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Ross Bray opublikował 1 rok, 3 miesiące temu
Condensins play a key role in higher order chromosome organization. In budding yeast Saccharomyces cerevisiae, a condensin complex consists of five subunits two conserved structural maintenance of chromosome subunits, Smc2 and Smc4, a kleisin Brn1, and two HEAT repeat subunits, Ycg1, which possesses a DNA binding activity, and Ycs4, which can transiently associate with Smc4 and thereby disrupt its association with the Smc2 head. We characterized here DNA binding activity of the non-SMC subunits using an agnostic, model-independent approach. To this end, we mapped the DNA interface of the complex using sulfo-NHS biotin labeling. Besides the known site on Ycg1, we found a patch of lysines at the C-terminal domain of Ycs4 that were protected from biotinylation in the presence of DNA. Point mutations at the predicted protein-DNA interface reduced both Ycs4 binding to DNA and the DNA stimulated ATPase activity of the reconstituted condensin, whereas overproduction of the mutant Ycs4 was detrimental for yeast viability. Notably, the DNA binding site on Ycs4 partially overlapped with its interface with SMC4, revealing an intricate interplay between DNA binding, engagement of the Smc2-Smc4 heads, and ATP hydrolysis and suggesting a mechanism for ATP-modulated loading and translocation of condensins on DNA.Many bacterial mechanisms for highly specific and sensitive detection of heavy metals and other hazards have been reengineered to serve as sensors. In some cases, these sensors have been implemented in cell-free expression systems, enabling easier design optimization and deployment in low-resource settings through lyophilization. Here, we apply the advantages of cell-free expression systems to optimize sensors based on three separate bacterial response mechanisms for arsenic, cadmium, and mercury. We achieved detection limits below the World Health Organization-recommended levels for arsenic and mercury and below the short-term US Military Exposure Guideline levels for all three. The optimization of each sensor was approached differently, leading to observations useful for the development of future sensors (1) there can be a strong dependence of specificity on the particular cell-free expression system used, (2) tuning of relative concentrations of the sensing and reporter elements improves sensitivity, and (3) sensor performance can vary significantly with linear vs plasmid DNA. In addition, we show that simply combining DNA for the three sensors into a single reaction enables detection of each target heavy metal without any further optimization. This combined approach could lead to sensors that detect a range of hazards at once, such as a panel of water contaminants or all known variants of a target virus. For low-resource settings, such „all-hazard” sensors in a cheap, easy-to-use format could have high utility.Implementation of hydrogel precursors in two-photon polymerization (2PP) technology provides promising opportunities in the tissue engineering field thanks to their soft characteristics and similarity to extracellular matrix. Most of the hydrogels, however, are prone to post-fabrication deformations, leading to a mismatch between the computer-aided design and the printed structure. In the present work, we have developed novel synthetic hydrogel precursors to overcome the limitations associated with 2PP processing of conventional hydrogel precursors such as post-processing deformations and a narrow processing window. The precursors are based on a poly(ethylene glycol) backbone containing urethane linkers and are, on average, functionalized with six acrylate terminal groups (three on each terminal group). As a benchmark material, we exploited a precursor with an identical backbone and urethane linkers, albeit functionalized with two acrylate groups, that were reported as state-of-the-art. An in-depth characterization of the hexafunctional precursors revealed a reduced swelling ratio (36 MPa Young’s modulus) compared to their difunctional analogs. The superior physical properties of the newly developed hydrogels lead to 2PP-based fabrication of stable microstructures with excellent shape fidelity at laser scanning speeds up to at least 90 mm s-1, in contrast with the distorted structures of conventional difunctional precursors. The hydrogel films and microscaffolds revealed a good cell interactivity after functionalization of their surface with a gelatin methacrylamide-based coating. The proposed synthesis strategy provides a one-pot and scalable synthesis of hydrogel building blocks that can overcome the current limitations associated with 2PP fabrication of hydrogel microstructures.Dietary ethanolamine plasmalogen (PlsEtn) has been reported to have several health benefits; however, its functional role during colon pathophysiology remains elusive. The present study investigated the anticolitis effect of dietary ethanolamine glycerophospholipids (EtnGpls) with high PlsEtn from ascidian muscle (86.2 mol %) and low PlsEtn from porcine liver (7.7 mol %) in dextran sulfate sodium (DSS)-induced colitis in mice. Dietary EtnGpls lowered myeloperoxidase activity, thiobarbituric acid-reactive substances, proinflammatory cytokines and proapoptosis-related protein levels in colon mucosa after 16 days of DSS treatment, with ascidian muscle (0.1% EtnGpl in diet) showing higher suppression than porcine liver (0.1% EtnGpl in diet). Moreover, dietary EtnGpls suppressed DSS symptoms after 38 days of DSS treatment as evidenced by increased body weight, colon length, and ameliorated colon mucosa integrity. Additionally, dietary EtnGpls elevated short-chain fatty acid production in DSS-treated mice. Altogether, these results indicate the potential of utilizing diets with abundant PlsEtn for the prevention of colon inflammation-related disorders.Nickel serves critical roles in the metabolism of E. coli and many prokaryotes. Many details of nickel trafficking are unestablished, but a nonproteinaceous low-molecular-mass (LMM) labile nickel pool (LNiP) is thought to be involved. The portion of the cell lysate that flowed through a 3 kDa cutoff membrane, which ought to contain this pool, was analyzed by size-exclusion and hydrophilic interaction chromatographies (SEC and HILIC) with detection by inductively coupled plasma (ICP) and electrospray ionization (ESI) mass spectrometries. Flow-through-solutions (FTSs) contained 11-15 μM Ni, which represented most Ni in the cell. Chromatograms exhibited 4 major Ni-detected peaks. MS analysis of FTS and prepared nickel complex standards established that these peaks arose from Ni(II) coordinated to oxidized glutathione, histidine, aspartate, and ATP. Surprisingly, Ni complexes with reduced glutathione or citrate were not members of the LNiP under the conditions examined. Aqueous Ni(II) ions were absent in the FTS. Detected complexes were stable in chelator-free buffer but were disrupted by treatment with 1,10-phenanthroline or citrate. Titrating FTS with additional NiSO4 suggested that the total nickel-binding capacity of cytosol is approximately 20-45 μM. Members of the LNiP are probably in rapid equilibrium. Previously reported binding constants to various metalloregulators may have overestimated the relevant binding strength in the cell because aqueous metal salts were used in those determinations. The LNiP may serve as both a Ni reservoir and buffer, allowing cells to accommodate a range of Ni concentrations. The composition of the LNiP may change with cellular metabolism and nutrient status.Hyaluronic acid (HA) based hydrogels are one of most functional natural biomaterials in the field of cartilage tissue engineering (CTE). Even with the promising advantages of HA hydrogels, the complicated mechanical properties of the native cartilage have not been realized, and fabricating HA hydrogels with excellent mechanical properties to make them practical in CTE still remains a current challenge. Here, a strategy that integrates hydrogels and nanomaterials is shown to form a HA hydrogel with sufficient mechanical loading for cartilage tissue production and recombination. Cellulose nanofibrils (CNFs) are promising nanomaterial candidates as they possess high mechanical strength and excellent biocompatibility. In this study, we developed methacrylate-functionalized CNFs that are able to photo-crosslink with methacrylated HA to fabricate HA/CNF nanocomposite hydrogels. The present composite hydrogels with a compressive modulus of 0.46 ± 0.05 MPa showed adequate compressive strength (0.198 ± 0.009 MPa) and restorability, which can be expected to employ as a stress-bearing tissue such as articular cartilage. Besides, this nanocomposite hydrogel could provide a good microenvironment for bone marrow mesenchymal stem cell proliferation, as well as chondrogenic differentiation, and exhibit prominent repair effect in the full-thickness cartilage defect model of SD rats. These results suggest that the HA/CNF nanocomposite hydrogel creates a new possibility for fabricating a scaffold in CTE.The free energy for hydride transfer reactions of transition metal hydrides is known to be influenced by solvent effects. The first-row transition metal hydride [HNi(dmpe)2][BF4] (dmpe = 1,2-bis(dimethylphosphino)ethane) has starkly different hydride transfer reactivities with CO2 in different solvents. A binary mixture of water and acetonitrile was used to tune the hydride transfer reactivity of HNi(dmpe)2+ with CO2 so that the free energy for this reaction approached zero. Various mole fractions of water were tested and a linear relationship between the hydride transfer free energy and solvent composition was established for 0-0.24 mole fraction of water. A deviation from linearity was found upon moving toward higher mole fractions of water. The tuning of the free energy for hydride transfer allowed HNi(dmpe)2+ to be used as a catalyst for the hydrogenation of CO2. The optimized catalyst conditions produced 58 turnovers at room temperature in 0.082 mole fraction of water using 60 atm of a 11 mixture of H2 to CO2 gas.Colorimetric reporter enzymes are useful for generating eye-readable biosensor readouts that do not require a device to interpret, an attractive property for applications in remote or developing parts of the world. The use of cell-free gene expression further facilitates such applications via amenability to lyophilization and incorporation into materials like paper. Currently, detection of multiple analytes simultaneously with these systems requires multiple reactions or a device. Here we evaluate seven enzymes and 15 corresponding substrates for functionality in a particular cell-free expression system known as PURE. We report eight enzyme/substrate pairs spanning four enzymes that are compatible with PURE. Of the four enzymes, three pairings exhibit no cross-reactivity. We finally show that at least one pairing can be used to create a third color when both are present, highlighting the potential use of these reporters for multiplex sensing.Layered double hydroxides (LDHs) are potential low-cost filter materials for use in fluoride removal from drinking water, but molecular-scale defluoridation mechanisms are lacking. In this research, we employed 19F solid-state NMR spectroscopy to identify fluoride sorption products on 21 MgAl LDH and to reveal the relationship between fluoride sorption and the LDH structure. A set of six 19F NMR peaks centered at -140, -148, -156, -163, -176, and -183 ppm was resolved. Combining quantum chemical calculations based on density function theory (DFT) and 19F27Al transfer of populations in double resonance (TRAPDOR) analysis, we could assign the peaks at -140, -148, -156, and -163 ppm to Al-F (F coordinated to surface Al) and those at -176 and -183 ppm to Mg-F (F coordinated to surface Mg only). Interestingly, the spectroscopic data reveal that the formation of Al-F is the predominant mode of F- sorption at low pH, whereas the formation of Mg-F is predominant at high pH (or a higher Mg/Al ratio). This finding supports the fact that the F- uptake of 21 MgAl LDH was nearly six times that of activated alumina at pH 9. Overall, we explicitly revealed the different roles of the surface >MgOH and >AlOH sites of LDHs in defluoridation, which explained why the use of classic activated alumina for defluoridation is limited at high pH. The findings from this research may also provide new insights into material screening for potential filters for F- removal under alkaline conditions.Selectively colonized microbial communities and enriched antibiotic resistance genes (ARGs) in (micro)plastics in aquatic and soil environments make the plastisphere a great health concern. Although microplastics (MPs) are distributed in indoor environments in high abundance, information on the effect of MPs on a microbial community in an indoor environment is lacking. Here, we detected polymers (containing MPs and natural polymers), bacterial communities, and 18 kinds of ARGs in collected indoor dust samples. A significant correlation by Procrustes analysis between bacterial community composition and the abundance of MPs was observed, and correlation tests and redundancy analysis identified specific associations between MP polymers and bacterial taxa, such as polyamide and Actinobacteria. In addition, the abundance of MPs showed a positive correlation with the relative abundance of the ARGs (to 16S RNA), while natural polymers, such as cellulosics, showed positive correlations with the absolute abundance of ARGs and 16S rRNA. Simulated experiments verified that significantly higher bacterial biomasses and ARGs were observed on the surface of cotton, hair, and wool than on MPs, while a higher relative abundance of ARGs was detected on MPs. However, a significantly higher amount of ARG was found on MPs of poly(lactic acid), the biodegradable plastics with the highest yield. In addition to the plastisphere in water and soil environments, MPs in an indoor environment may also affect the bacterial community and specifically enrich ARGs. Moreover, degradable MPs and nondegradable MPs may result in different health hazards due to their distinct effects on bacterial community.Fluensulfone (FSF) becomes increasingly popular because of its nonfumigation application method. However, studies on the metabolic mechanism of FSF in plants are lacking. Here, tomato seedling was cultivated in hydroponic media to investigate the connection among FSF’s metabolism in tomato, the regulation of tomato endogenous glycosides, and the elimination of hydrogen peroxide in tomato cells. The accumulation of FSF was only detected in the lower stems of tomatoes; FSF was mainly metabolized into S-glycosylated conjugates in the roots, and the roots were the tissues with the highest metabolite content; and no FSF and metabolites were detected in the upper leaves. In response to FSF stress (2 mg/L for 7 d), the content of sugar and glycosides in the stems of tomato seedlings significantly increased. The amount of some compounds on the pathway related to glucose was affected by FSF. The three precursor compounds (homomethioine, isoleucine, and l-tyrosine) in the pathway of glucosinolate biosynthesis increased significantly under the stress of FSF, which indicates that FSF may compete with them for UGT74B1. Besides, FSF-induced flavonoid glycosides may play a role in the process of removing hydrogen peroxide. This research provides inspiration for the fate of many xenobiotics containing sulfonyl groups in plants.Modulating the tumor immune microenvironment to activate immune cells has been investigated to convert cold to hot tumors. Here, we report that metal-lipid hybrid nanoparticle (MLN)-mediated gene editing of transforming growth factor-β (TGF-β) can restructure the tumor microenvironment to an „immune activated” state for subsequent immunotherapy. MLNs with cationic lipids and elemental metallic Au inside were designed to deliver plasmid DNA encoding TGF-β single guide RNA and Cas9 protein (pC9sTgf) and to convert near-infrared light (NIR) to heat. Upon NIR irradiation, MLNs induced photothermal anticancer effects and calreticulin exposure on B16F10 cancer cells. Lipoplexes of pC9sTgf and MLN (pC9sTgf@MLN) provided gene editing of B16F10 cells and in vivo tumor tissues. In mice treated with pC9sTgf@MLNs and NIR irradiation, the tumor microenvironment showed increases in mature dendritic cells, cytotoxic T cells, and interferon-γ expression. In B16F10 tumor-bearing mice, intratumoral injection of pC9sTgf@MLNs and NIR irradiation resulted in ablation of primary tumors. Application of pC9sTgf@MLNs and NIR irradiation prevented the growth of secondarily challenged B16F10 cells at distant sites and B16F10 lung metastasis. Combined TGF-β gene editing and phototherapy is herein supported as a modality for restructuring the tumor immune microenvironment and preventing tumor recurrence.Mainstream anaerobic wastewater treatment has received increasing attention for the recovery of methane-rich biogas from biodegradable organics, but subsequent mainstream nitrogen and dissolved methane removal at low temperatures remains a critical challenge in practical applications. In this study, granular sludge coupling n-DAMO with Anammox was employed for mainstream nitrogen removal, and the dissolved methane removal potential of granular sludge at low temperatures was investigated. A stable nitrogen removal rate (0.94 kg N m-3 d-1 at 20 °C) was achieved with a high-level effluent quality ( less then 3.0 mg TN L-1) in a lab-scale membrane granular sludge reactor (MGSR). With decreasing temperature, the nitrogen removal rate dropped to 0.55 kg N m-3 d-1 at 10 °C, while the effluent concentration remained less then 1.0 mg TN L-1. The granular sludge with an average diameter of 1.8 mm proved to retain sufficient biomass (27 g VSS L-1), which enabled n-DAMO and Anammox activity at a hydraulic retention time as low as 2.16 h even at 10 °C. 16S rRNA gene sequencing and scanning electron microscopy revealed a stable community composition and compact structure of granular sludge during long-term operation. Energy recovery could be maximized by recovering most of the dissolved methane in mainstream anaerobic effluent, as only a small amount of dissolved methane was capable of supporting denitrifying methanotrophs in granular sludge, which enabled high-level nitrogen removal.Modulating the crystal field environment around the emitting ions is an effective strategy to improve the luminescence performance of the practical effective phosphor materials. Here, smaller Y3+ ions are introduced into substituting the Gd3+ sites in Ba2GdNbO6Mn4+ phosphor to modify the optical properties, including the enhanced luminescence intensity, redshift, and longer lifetime of the Mn4+ ions. The substitution of smaller Y3+ ions leads to lattice contraction and then strengthens pressure on the local structure, enhances lattice rigidity, and suppresses nonradiative transition. Moreover, the prototype phosphor-converted light-emitting diode (LED) demonstrates a continuous change photoelectric performance with a correlated color temperature of 4883-7876 K and a color rendering index of 64.1-83.2, suggesting that it can be one of the most prospective fluorescent materials applied as a warm red component for white LEDss. Thus, the smaller ion partial substitution can provide a concise approach to modulate the crystal field environment around the emitting ions for excellent luminescence properties of phosphors toward the modern artificial light.Phytoestrogens are strongly recommended for treating osteoporosis. Our previous study showed that naringin, a citrus flavonoid, can enhance the bone mass in ovariectomized rats. In this study, we further elucidated the mechanisms of naringin-induced osteoblast maturation and bone healing. Treatment of human osteoblasts with naringin increased cell viability and proliferation. In parallel, exposure to naringin enhanced translocation of estrogen receptor alpha (ERα) to nuclei and its transactivation activity. Sequentially, naringin induced alkaline phosphatase (ALP) mRNA and protein expression and its enzyme activity. Pretreatment with methylpiperidinopyrazole (MPP), a specific inhibitor of ERα, attenuated naringin-induced augmentations in ERα transactivation activity, ALP gene expression, and cell mineralization. The beneficial effects of naringin were also confirmed in mouse MC3T3-E1 cells. Moreover, administration of mice with a bone defect with naringin increased levels of ERα and ALP in damaged sites and simultaneously enhanced the healing rate and bone strength. Nevertheless, treatment with MPP weakened naringin-triggered expression of ERα and ALP and improved bone healing and mass. Therefore, naringin could improve osteoblast mineralization and bone healing via regulating ERα-dependent ALP gene expression. Naringin can be clinically applied for treatment of osteoporosis-related bone diseases.Thin films of amorphous alumina (a-Al2O3) have recently been found to deform permanently up to 100% elongation without fracture at room temperature. If the underlying ductile deformation mechanism can be understood at the nanoscale and exploited in bulk samples, it could help to facilitate the design of damage-tolerant glassy materials, the holy grail within glass science. Here, based on atomistic simulations and classification-based machine learning, we reveal that the propensity of a-Al2O3 to exhibit nanoscale ductility is encoded in its static (nonstrained) structure. By considering the fracture response of a series of a-Al2O3 systems quenched under varying pressure, we demonstrate that the degree of nanoductility is correlated with the number of bond switching events, specifically the fraction of 5- and 6-fold coordinated Al atoms, which are able to decrease their coordination numbers under stress. In turn, we find that the tendency for bond switching can be predicted based on a nonintuitive structural descriptor calculated based on the static structure, namely, the recently developed „softness” metric as determined from machine learning. Importantly, the softness metric is here trained from the spontaneous dynamics of the system (i.e., under zero strain) but, interestingly, is able to readily predict the fracture behavior of the glass (i.e., under strain). That is, lower softness facilitates Al bond switching and the local accumulation of high-softness regions leads to rapid crack propagation. These results are helpful for designing glass formulations with improved resistance to fracture.A simple one-step method is presented for fabricating inorganic nanosponges with a kaolinite [Al2Si2O5(OH)4] structure. The nanosponges were synthesized by the hydrothermal treatment of aluminosilicate gels in an acidic medium (pH = 2.6) at 220 °C without using organic cross-linking agents, such as cyclodextrin or polymers. The formation of the nanosponge morphology was confirmed by scanning electron microscopy, and the assignment of the synthesized aluminosilicates to the kaolinite group was confirmed by X-ray diffraction and infrared spectroscopy. The effect of the synthesis conditions, in particular, the nature (HCl, HF, NaOH, and H2O) and pH of the reaction medium (2.6, 7, and 12), as well as the duration of the synthesis (3, 6, and 12 days), on the morphology of aluminosilicates of the kaolinite group was studied. The sorption capacity of aluminosilicate nanosponges with respect to cationic (e.g., methylene blue) and anionic (e.g., azorubine) dyes in aqueous solutions was studied. The pH sensitivity of the surface ζ potential of the synthesized nanosponges was demonstrated. The dependence of the hemolytic activity (the ability to destroy erythrocytes) of aluminosilicate nanoparticles on the particle morphology (platy, spherical, and nanosponge) has been identified for the first time. Aluminosilicate nanosponges were not found to exhibit hemolytic activity. The prospects of using aluminosilicate nanosponges to prepare innovative functional materials for ecology and medicine applications, in particular, as matrices for drug delivery systems, were identified.Through rational chemical design, and thanks to the hybrid nature of metal-organic frameworks (MOFs), it is possible to prepare molecule-based 2D magnetic materials stable at ambient conditions. Here, we illustrate the versatility of this approach by changing both the metallic nodes and the ligands in a family of layered MOFs that allows the tuning of their magnetic properties. Specifically, the reaction of benzimidazole-type ligands with different metal centers (MII = Fe, Co, Mn, Zn) in a solvent-free synthesis produces a family of crystalline materials, denoted as MUV-1(M), which order antiferromagnetically with critical temperatures that depend on M. Furthermore, the incorporation of additional substituents in the ligand results in a novel system, denoted as MUV-8, formed by covalently bound magnetic double layers interconnected by van der Waals interactions, a topology that is very rare in the field of 2D materials and unprecedented for 2D magnets. These layered materials are robust enough to be mechanically exfoliated down to a few layers with large lateral dimensions. Finally, the robustness and crystallinity of these layered MOFs allow the fabrication of nanomechanical resonators that can be used to detect─through laser interferometry─the magnetic order in thin layers of these 2D molecule-based antiferromagnets.Achieving biosensors of high sensitivity and reliability is extremely significant for early diagnosis and treatment of tumor diseases. Herein, a novel organic field-effect transistor (OFET)-based biosensor was developed and applied for carcinoembryonic antigen (CEA) bioassay. This OFET-based biosensor can respond sensitively to the antigen-antibody immune-recognition reaction under illumination and darkness, respectively, thereby generating electrical signal changes of source-drain current (IDS) and threshold voltage (Vth). The OFET-based biosensor exhibits detection limits for CEA detection of 0.5 and 0.2 pM, respectively, using IDS and Vth as the response signals under darkness. When a specific intensity of light is applied, light will influence the charge-carrier transport process in the conductive channel, thus causing biosignals to turn into higher electrical signal changes of photocurrent and threshold voltage under illumination. Compared with the detection results in the dark, the biosensor exhibits higher sensitivity for CEA detection under illumination with detection limits of 13.5 and 16.9 fM. Also, multisignal outputs effectively improve the reliability of the biosensor for CEA detection. Consequently, with powerful detection functions, this OFET-based biosensor is expected to become a high-performance biosensing platform for the detection of various biological substances in the future.The metabolic fate of a newly developed herbicide, epyrifenacil, (ethyl[(3-2-chloro-4-fluoro-5-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-3,6-dihydropyrimidin-1(2H)-yl]phenoxypyridin-2-yl)oxy]acetate, S-3100), in rats was determined using 14C-labeled epyrifenacil. When it was administered orally to rats at 1 mg/kg, around 73-74% of the dose was absorbed, metabolized, and mainly excreted into feces within 48 h. The elimination of radioactivity in plasma and tissues was rapid, suggesting that exposure of epyrifenacil and metabolites is small. Metabolite analysis revealed that epyrifenacil was rapidly ester-cleaved to M1 and then mainly excreted into bile or further metabolized. No parent was detected in plasma, tissues, and urine. Remarkably, M1 was mainly distributed in the liver (at a concentration of 70-112 times higher than in plasma at a low dose). Furthermore, a significant sex-related difference was observed in urinary excretion of M1. Considering the above observations with those in the literature, the organic anion-transporting polypeptide (OATP) likely plays a role on the active transport of M1 in the liver and kidney.Tendon adhesion formation is associated with the aberrant expression of many genes, and interfering with the expression of these genes can prevent adhesion and promote tendon repair. Recent studies have found that silencing the transforming growth factor β-1 (TGF-β1) gene can reduce the occurrence of tendon adhesions. The development of tissue engineering and three-dimensional (3D) printing technology have provided new solutions for tendon repair. In this study, TGF-β1 gene silencing microRNA (miRNA) based RNAi plasmid was loaded on a 3D tendon scaffold using 3D printing technology. In vitro experiments confirmed the sustained release of plasmid and the good biocompatibility of the printed tendon scaffold. Subsequently, the TGF-β1 gene silencing plasmid loaded tendon scaffold was implanted in a chicken tendon defect model to evaluate the effect of the scaffold in vivo. The results from biomechanical tests and histological examinations showed that the scaffold not only promoted tendon regeneration but also prevented tendon adhesion, which was conducive to the recovery of biofunction. Evaluation of protein expression showed that the loaded plasmids prevented tendon adhesion and promoted tendon functional repair via silencing of the TGF-β1 gene.Bone cancer pain (BCP) is a distinct pain state showing characteristics of both neuropathic and inflammatory pain. On average, almost 46% of cancer patients exhibit BCP with numbers flaring up to as high as 76% for terminally ill patients. Patients suffering from BCP experience a compromised quality of life, and the unavailability of effective therapeutics makes this a more devastating condition. In every individual cancer patient, the pain is driven by different mechanisms at different sites. The mechanisms behind the manifestation of BCP are very complex and poorly understood, which creates a substantial barrier to drug development. Nevertheless, some of the key mechanisms involved have been identified and are being explored further to develop targeted molecules. Developing a multitarget approach might be beneficial in this case as the underlying mechanism is not fixed and usually a number of these pathways are simultaneously dysregulated. In this review, we have discussed the role of recently identified novel modulators and mechanisms involved in the development of BCP. They include ion channels and receptors involved in sensing alteration of temperature and acidic microenvironment, immune system activation, sodium channels, endothelins, protease-activated receptors, neurotrophins, motor proteins mediated trafficking of glutamate receptor, and some bone-specific mechanisms. Apart from this, we have also discussed some of the novel approaches under preclinical and clinical development for the treatment of bone cancer pain.The replacement of dressings may cause secondary damage to the wounds; thus, the real-time monitoring of the state of wound dressings is crucial for evaluating wound care processes. Herein, we report a smart dressing to self-monitor residue nanomedicine on it during the application. We load aminobenzeneboronic acid (ABA)-modified gold nanoclusters (A-GNCs) on bacterial cellulose (BC) membranes as an antibacterial wound dressing to display the amount of residual nanomedicine (A-GNCs) by in situ colorimetry during the application in remedying multi-drug-resistant (MDR) bacteria-infected wounds. A-GNCs emit bright orange fluorescence under UV light, whereas the BC membrane is transparent at a humidified state on the wounds. Thus, the BC-A-GNCs nanocomposite (BGN) shows decreasing intensity of orange fluorescence with the release of the A-GNCs, indicating the appropriate time points for the replacement of the dressing. The BGN, which can realize accurate self-monitoring in a simple, low-cost, and efficient way, thus holds great promise for broad clinical applications.Textiles are materials that are extensively used in everyday life; textile-based sensors can, therefore, be regarded as ideal devices for a health monitor. However, previously reported textile sensors have limited prospects due to their single function or incompatibility. Traditional textile sensors generally focus on signal detection, which has not been able to be combined with an actuator to provide real-time health status feedback. Thus, to date, there are no well-established health monitoring systems based on intelligent textiles. Herein, we present a wearable batch-prepared graphene-based textile based on laser-scribing and thermal-transfer technology. Integrated with four functions of strain sensing, pressure sensing, physiological electrical sensing, and sound emitting, the GT is able to detect human body signals and transduce them to sound signals when the user is in an abnormal physical state. Moreover, the GT has high linearity for both strain and pressure sensing; the coefficients of determination exceed 99.3% and 98.2%, respectively. The performance of the device remains stable up to a pressure of 1000 kPa. The response time of the GT possession reaches as low as 85 ms at 4.2 Pa pressure. Therefore, due to their diversified functions and good performance, the research on GT is expected to extend to the fields of health monitoring, sports monitoring, and so forth.A novel dissolution method that allows for the total solvation of high-concentration, high-molecular-weight polyaniline (PANi) doped with (+)-camphor-10-sulfonic acid (CSA) is reported. Preparation of 12-16 wt % 65,000 Da PANi solutions in N,N-dimethylformamide is achievable using a simple one-pot method. Doped polyaniline solutions in common organic solvents were processed into nanofibers using a convenient single-nozzle electrospinning technique. The electrospinning of PANi-CSA into nanofibrous membranes generated substrates that were subsequently employed in colorimetric gas sensing. These substrates demonstrated linearity of resistivity upon exposure to 50-5500 ppm ammonia at ambient (50 ± 10% RH) and high (80% RH) humidity.Electrochemical reduction of nitrate (NO3-) to ammonia (NH3) provides a promising route for recycling nitrate from wastewater to balance the nitrogen cycle and sustainable production of ammonia. Among various catalytic materials for NO3- electroreduction, Cu shows a favorable selectivity to NH3. However, Cu can be easily oxidized, while the effect of the Cu oxidation state on NO3- reduction remains to be elucidated. Here, we report that oxidic Cu formed on a Cu electrode can enhance its activity and selectivity for NO3- reduction to NH3. We first used a polished Cu foil as a model catalyst for NO3- reduction and found that a brief exposure of the Cu electrode to air could increase its yield rate and Faradaic efficiency for NH3 production. The improved catalytic performance was attributed to the formed Cu+ sites that can reduce the energy barrier for NO3- reduction to NH3 and suppress the competing HER reaction. Based on this finding, an oxide-derived Cu (OD-Cu) electrode was prepared by annealing a Cu foil in O2 gas followed by electroreduction, which exhibited superior performance for NO3- reduction to NH3, with a Faradaic efficiency of 92% and a yield rate of 1.1 mmol h-1 cm-2 for NH3 production at -0.15 V versus reversible hydrogen electrode. Moreover, an OD-Cu foam electrode was similarly developed to demonstrate NO3- recycling from a low-concentration NO3- solution, which showed a nearly 100% conversion of NO3- to NH3 using a circulating flow cell.Exosomes are cell-derived structures packaged with lipids, proteins, and nucleic acids. They exist in diverse bodily fluids and are involved in physiological and pathological processes. Although their potential for clinical application as diagnostic and therapeutic tools has been revealed, a huge bottleneck impeding the development of applications in the rapidly burgeoning field of exosome research is an inability to efficiently isolate pure exosomes from other unwanted components present in bodily fluids. To date, several approaches have been proposed and investigated for exosome separation, with the leading candidate being microfluidic technology due to its relative simplicity, cost-effectiveness, precise and fast processing at the microscale, and amenability to automation. Notably, avoiding the need for exosome labeling represents a significant advance in terms of process simplicity, time, and cost as well as protecting the biological activities of exosomes. Despite the exciting progress in microfluidic strategies for exosome isolation and the countless benefits of label-free approaches for clinical applications, current microfluidic platforms for isolation of exosomes are still facing a series of problems and challenges that prevent their use for clinical sample processing. This review focuses on the recent microfluidic platforms developed for label-free isolation of exosomes including those based on sieving, deterministic lateral displacement, field flow, and pinched flow fractionation as well as viscoelastic, acoustic, inertial, electrical, and centrifugal forces. Further, we discuss advantages and disadvantages of these strategies with highlights of current challenges and outlook of label-free microfluidics toward the clinical utility of exosomes.Lanthanide-based upconversion (UC) allows harvesting sub-bandgap near-infrared photons in photovoltaics. In this work, we investigate UC in perovskite solar cells by implementing UC single crystal BaF2Yb3+, Er3+ at the rear of the solar cell. Upon illumination with high-intensity sub-bandgap photons at 980 nm, the BaF2Yb3+, Er3+ crystal emits upconverted photons in the spectral range between 520 and 700 nm. When tested under terrestrial sunlight representing one sun above the perovskite’s bandgap and sub-bandgap illumination at 980 nm, upconverted photons contribute a 0.38 mA/cm2 enhancement in the short-circuit current density at lower intensity. The current enhancement scales non-linearly with the incident intensity of sub-bandgap illumination, and at higher intensity, 2.09 mA/cm2 enhancement in current was observed. Hence, our study shows that using a fluoride single crystal like BaF2Yb3+, Er3+ for UC is a suitable method to extend the response of perovskite solar cells to near-infrared illumination at 980 nm with a subsequent enhancement in current for very high incident intensity.Lithium-sulfur (Li-S) batteries hold great promise for next-generation electronics owing to their high theoretical energy density, low cost, and eco-friendliness. Nevertheless, the practical implementation of Li-S batteries is hindered by the shuttle effect and sluggish reaction kinetics of polysulfides. Herein, the spray drying and chemical etching strategies are implemented to fabricate hierarchically porous MXene microspheres as a multifunctional sulfur electrocatalyst. The interconnected skeleton offers uniform sulfur distribution and prevents the restacking of MXene sheets, while the abundant edges endow the nanosheet-like Ti3C2 with rich active sites and regulated a d-band center of Ti atoms, leading to strong lithium polysulfide (LiPS) adsorption. The unsaturated Ti on edge sites can further act as multifunctional sites for chemically anchoring LiPS and lowering Li-ion migration barriers, accelerating LiPS conversion. Owing to these structural advantages, excellent cycling and rate performances of the sulfur cathode can be obtained, even under a raised sulfur loading and lean electrolyte content.Flexible wearable pressure sensors have attracted great interest from researchers in recent years because of their important applications in human-machine interaction, human behavior detection, medical diagnosis, and other fields. At present, integrating multiple functions such as pressure and temperature sensing and self-cleaning into a single material remains a challenging task. Here, by in situ reduction of graphene oxide (GO) grown on a sponge surface and deposition of polypyrrole (PPy) nanoparticles, we have built a highly sensitive, stable, and multifunctional rGO/PPy/poly(dimethylsiloxane) (PDMS) polyurethane (PU) sponge (GPPS) sensor for the detection of pressure, water level, and temperature. This multifunctional sensor shows excellent pressure-sensing performance, ultrasensitive loading sensing of a leaf (98 mg), and outstanding reproducibility over 5000 cycles. Due to the stability of the superhydrophobic surface water contact angle (WCA) = 153.3°, our sensor can work in an underwater environment, which can sense water levels from 1 cm (∼98 Pa) to 40 cm and also a variety of underwater behaviors (knock, ultrasonication, blow, etc.) with high stability. In addition, the sensor can be integrated into a circuit for the water level and pressure detection. The sensor can also be used as a smart underwater-temperature sensor; it shows a linear temperature coefficient of resistance (TCR) of 0.48% °C-1 in a temperature range of 35-80 °C. This multifunctional sensor shows potential application prospects in wearable electronic devices for sensing.Unification of the techniques of ultrafast science and scanning tunneling microscopy (STM) has the potential of tracking electronic motion in molecules simultaneously in real space and real time. Laser pulses can couple to an STM junction either in the weak-field or in the strong-field interaction regime. The strong-field regime entails significant modification (dressing) of the tunneling barrier of the STM junction, whereas the weak-field or the photon-driven regime entails perturbative interaction. Here, we describe how photons carried in an ultrashort pulse interact with an STM junction, defining the basic fundamental framework of ultrafast photon-induced tunneling microscopy. Selective dipole coupling of electronic states by photons is shown to be controllable by adjusting the DC bias at the STM junction. An ultrafast tunneling microscopy involving photons is established. Consolidation of the technique calls for innovative approaches to detect photon-induced tunneling currents at the STM junction. We introduce and characterize here three techniques involving dispersion, polarization, and frequency modulation of the laser pulses to lock-in detect the laser-induced tunneling current. We show that photon-induced tunneling currents can simultaneously achieve angstrom scale spatial resolution and sub-femtosecond temporal resolution. Ultrafast photon-induced tunneling microscopy will be able to directly probe electron dynamics in complex molecular systems, without the need of reconstruction techniques.Lithium (Li) metal has emerged as a promising electrode material for high-energy-density batteries. However, serious Li dendrite issues during cycling have plagued the safety and cyclability of the batteries, thus limiting the practical application of Li metal batteries. Herein, we prepare a novel metal-organic-framework-based (MOF-based) succinonitrile electrolyte, which enables homogeneous and fast Li-ion (Li+) transport for dendrite-free Li deposition. Given the appropriate aperture size of the MOF skeleton, the targeted electrolyte can allow only small-size Li+ to pass through its pores, which effectively guides uniform Li+ transport. Specially, Li ions are coordinated by the C═N of the MOF framework and the C≡N of succinonitrile, which could accelerate Li+ migration jointly. These characteristics afford an excellent quasi-solid-state electrolyte with a high ionic conductivity of 7.04 × 10-4 S cm-1 at room temperature and a superior Li+ transference number of 0.68. The Li/LiFePO4 battery with the MOF-based succinonitrile electrolyte exhibits dendrite-free Li deposition during the charge process, accompanied by a high capacity retention of 98.9% after 100 cycles at 0.1C.Measurement of interfacial properties between thin films and elastomers is investigated. As a prototype, the interface adhesion between a graphite nanoflake and an elastic polymer is determined by topography imaging of the induced graphite buckles using atomic force microscopy. A theoretical analysis is carried out to establish the relationship among interface adhesion, elastic strain energy, and buckle surface area. The strain energy of the graphite is obtained by employing an elastic plate deflection theory. To introduce the buckles, different methods are applied, including thermal contraction, bending, and stretching, and different substrate materials, namely, polydimethylsiloxane and polystyrene, are used. The uncertainty in measuring the interface adhesion is discussed. These investigations provide a promising approach to characterize the interfacial properties of multilayer samples.Molybdenum dioxide (MoO2), considering its near-metallic conductivity and surface plasmonic properties, is a great material for electronics, energy storage devices and biosensing. Yet to this day, room-temperature synthesis of large area MoO2, which allows deposition on arbitrary substrates, has remained a challenge. Due to their reactive interfaces and specific solubility conditions, gallium-based liquid metal alloys offer unique opportunities for synthesizing materials that can meet these challenges. Herein, a substrate-independent liquid metal-based method for the room temperature deposition and patterning of MoO2 is presented. By introducing a molybdate precursor to the surrounding of a eutectic gallium-indium alloy droplet, a uniform layer of hydrated molybdenum oxide (H2MoO3) is formed at the interface. This layer is then exfoliated and transferred onto a desired substrate. Utilizing the transferred H2MoO3 layer, a laser-writing technique is developed which selectively transforms this H2MoO3 into crystalline MoO2 and produces electrically conductive MoO2 patterns at room temperature. The electrical conductivity and plasmonic properties of the MoO2 are analyzed and demonstrated. The presented metal oxide room-temperature deposition and patterning method can find many applications in optoelectronics, sensing, and energy industries.Transition metal dichalcogenide (TMD) nanoflake thin films are attractive electrode materials for photoelectrochemical (PEC) solar energy conversion and sensing applications, but their photocurrent quantum yields are generally lower than those of bulk TMD electrodes. The poor PEC performance has been primarily attributed to enhanced charge carrier recombination at exposed defect and edge sites introduced by the exfoliation process. Here, a single nanoflake PEC approach reveals how an alternative effect, doping heterogeneity, limits ensemble-level PEC performance. Photocurrent mapping and local photocurrent-potential (i-E) measurements of MoS2 nanoflakes exfoliated from naturally occurring bulk crystals revealed the presence of n- and p-type domains within the same nanoflake. Interestingly, the n- and p-type domains in the natural MoS2 nanoflakes were equally efficient for iodide oxidation and tri-iodide reduction (IQE values exceed 80%). At the single domain-level, the natural MoS2 nanoflakes were nearly as efficient as nanoflakes exfoliated from synthetic n-type MoS2 crystals. Single domain-level i-E measurements explain why natural MoS2 nanoflakes exhibit an n-type to p-type photocurrent switching effect in ensemble-level measurements the n- and p-type diode currents from individual domains oppose each other upon illuminating the entire nanoflake, resulting in zero photocurrent at the switching potential. The doping heterogeneity effect is likely due to nonideal stoichiometry, where p-type domains are S-rich according to XPS measurements. Although this doping heterogeneity effect limits photoanode or photocathode performance, these findings open the possibility to synthesize efficient TMD nanoflake photocatalysts with well-defined lateral p- and n-type domains for enhanced charge separation.Colloidal lead halide perovskite nanocrystals (NCs) have recently emerged as one of the most promising light-emitting materials for optoelectronic devices with outstanding performance. However, the facile detachment of surface capping organic ligands from these NCs leads to very poor colloidal stability and durability. This is mainly due to the weak interfacial interactions between the inorganic perovskite core and ligands, high density of surface defect states, and aggregation of NCs. Here, using a combination of time-resolved laser spectroscopy and density functional theory (DFT) calculations, we explored the major impact of surface orientations and terminations for both CsPbBr3 and Cs4PbBr6 NCs not only on the interfacial binding affinities with organic ligands but also on surface defect formation and NC aggregation. By rationalizing that surface trap states are responsible for the decrease in photoluminescence (PL) upon fabrication and purification, we propose a powerful ligand-engineering strategy for elious compositions and to achieve more efficient and stable light-harvesting devices.To enable smart homes and relative applications, the floor monitoring system with embedded triboelectric sensors has been proven as an effective paradigm to capture the ample sensory information from our daily activities, without the camera-associated privacy concerns. Yet the inherent limitations of triboelectric sensors such as high susceptibility to humidity and long-term stability remain a great challenge to develop a reliable floor monitoring system. Here we develop a robust and smart floor monitoring system through the synergistic integration of highly reliable triboelectric coding mats and deep-learning-assisted data analytics. Two quaternary coding electrodes are configured, and their outputs are normalized with respect to a reference electrode, leading to highly stable detection that is not affected by the ambient parameters and operation manners. Besides, due to the universal electrode pattern design, all the floor mats can be screen-printed with only one mask, rendering higher facileness and cost-effectiveness. Then a distinctive coding can be implemented to each floor mat through external wiring, which permits the parallel-array connection to minimize the output terminals and system complexity. Further integrating with deep-learning-assisted data analytics, a smart floor monitoring system is realized for various smart home monitoring and interactions, including position/trajectory tracking, identity recognition, and automatic controls. Hence, the developed low-cost, large-area, reliable, and smart floor monitoring system shows a promising advancement of floor sensing technology in smart home applications.Cytokine immunotherapy represents an attractive strategy to stimulate robust immune responses for renal injury repair in ischemic acute kidney injury (AKI). However, its clinical application is hindered by its nonspecificity to kidney, short circulation half-life, and severe side effects. An ideal cytokine immunotherapy for AKI requires preferential delivery of cytokines with accurate dosage to the kidney and sustained-release of cytokines to stimulate the immune responses. Herein, we developed a DNA nanoraft cytokine by precisely arranging interleukin-33 (IL-33) nanoarray on rectangle DNA origami, through which IL-33 can be preferentially delivered to the kidney for alleviation of AKI. A nanoraft carrying precisely quantified IL-33 predominantly accumulated in the kidney for up to 48 h. Long-term sustained-release of IL-33 from nanoraft induced rapid expansion of type 2 innate lymphoid cells (ILC 2s) and regulatory T cells (Tregs) and achieved better treatment efficiency compared to free IL-33 treatment. Thus, our study demonstrates that a nanoraft can serve as a structurally well-defined delivery platform for cytokine immunotherapy in ischemic AKI and other renal diseases.


