Mycolic acid methyl esters were extracted from Mycobacterium avium by a mild saponification protocol, designed to preserve labile components. The resulting mixture of α-, keto- and wax ester mycolates was accompanied by some degraded ω-carboxymycolic acid dimethyl esters, whose overall structures were found to support previous studies. Chromatography of the mono-carboxylic mycolates gave an inseparable mixture of keto- and wax ester mycolates and separate α-mycolates. Reduction of the ketomycolate components allowed isolation and characterisation of intact wax ester mycolates for the first time. Minor α- and ω-carboxymycolates were detected in which methyl branches were located on either the proximal or distal sides of trans-alkene groups.Among the structurally diverse collection of lipids that comprise the membrane lipidome, polyunsaturated phospholipids are particularly vulnerable to oxidation. The role of α-tocopherol (vitamin E) is to protect this influential class of membrane phospholipid from oxidative damage. Whether lipid-lipid interactions play a role in supporting this function is an unanswered question. Here, we compare the molecular organization of polyunsaturated 1-[2H31]palmitoyl-2-docosahexaenoylphosphatidylethanolamine (PDPE-d31) and, as a control, monounsaturated 1-[2H31]palmitoyl-2-oleoylphosphatidylethanolamine (POPE-d31) mixed with sphingomyelin (SM) and α-tocopherol (α-toc) (221 mol) by solid-state 2H NMR spectroscopy. In both cases the effect of α-tocopherol appears similar. Spectral moments reveal that the main chain melting transition of POPE-d31 and PDPE-d31 is broadened beyond detection. A spectral component attributed to the formation of inverted hexagonal HII phase in coexistence with lamellar Lα phase by POPE-d31 (20 %) and PDPE-d31 (18 %) is resolved following the addition of α-toc. Order parameters in the remaining Lα phase are increased slightly more for POPE-d31 (7%) than PDPE-d31 (4%). Preferential interaction with polyunsaturated phospholipid is not apparent in these results. The propensity for α-toc to form phase structure with negative curvature that is more tightly packed at the membrane surface, nevertheless, may restrict the contact of free radicals with lipid chains on phosphatidylethanolamine molecules that accumulate polyunsaturated fatty acids.Endothelial progenitor cells (EPCs) are important to tissue repair and regeneration especially after ischemic injury, and very heterogeneous in phenotypes and biological features. Reactive oxygen species are involved in regulating EPC number and function. N-acetylcysteine (NAC) inhibits ischemia-induced reactive oxygen species formation and promotes ischemic limb recovery. This study was to evaluate the effect of NAC on EPC subpopulations in bone marrow (BM) and blood in mice with limb ischemia. Limb ischemia was induced by femoral artery ligation in male C57BL/6 mice with or without NAC treatment. EPC subpopulations, intracellular reactive oxygen species production, cell proliferation and apoptosis in BM and blood cells were analyzed at baseline, day 3 (acute ischemia) and 21 (chronic) after ligation. c-Kit+/CD31+, Sca-1+/Flk-1+, CD34+/CD133+, and CD34+/Flk-1+ were used to define EPC subpopulations. Limb blood flow, function, muscle structure, and capillary density were evaluated with laser Doppler perfusion imaging, treadmill test, and immunohistochemistry, respectively, at day 3, 7, 14 and 21 post ischemia. Reactive oxygen species production in circulating and BM mononuclear cells and EPCs populations were significantly increased in BM and blood in mice with acute and chronic ischemia. NAC treatment effectively blocked ischemia-induced reactive oxygen species production in circulating and BM mononuclear cells, and selectively increased EPC population in circulation, not BM, with preserved proliferation in mice with chronic ischemia, and enhanced limb blood flow and function recovery, while preventing acute ischemia-induced increase in BM and circulating EPCs. These data demonstrated that NAC selectively enhanced circulating EPC population in mice with chronic limb ischemia.Species often interact with multiple mutualistic partners that provide functionally different benefits and/or that interact with different life-history stages. These functionally different partners, however, may also interact directly with one another in other ways, indirectly altering net outcomes and persistence of the mutualistic system as a whole. We present a population dynamical model of a three-species system involving antagonism between species sharing a mutualist partner species with two explicit life stages. We find that, regardless of whether the antagonism is predatory or non-consumptive, persistence of the shared mutualist is possible only under a restrictive set of conditions. As the rate of antagonism between the species sharing the mutualist increases, indirect rather than direct interactions increasingly determine species’ densities and sometimes result in complex, oscillatory dynamics for all species. Surprisingly, persistence of the mutualistic system is particularly dependent upon the degree to which each of the two mutualistic interactions is specialized. Our work investigates a novel mechanism by which changing ecological conditions can lead to extinction of mutualist partners and provides testable predictions regarding the interactive roles of mutualism and antagonism in net outcomes for species’ densities.Background and aims Cold snare polypectomy (CSP) of small colorectal polyps is widely used. However, the technique is still troubled with insufficient resection depth, which may prevent precise pathological evaluation. In this study, we investigated whether submucosal injection of saline solution helps to achieve deeper resection in CSP. Methods The study was a single center, prospective, randomized trial (UMIN000037980). Patients with small (3-10 mm diameter) nonpedunculated adenomatous or sessile serrated colorectal polyps were randomly allocated to either conventional CSP (C-CSP) or CSP with submucosal injection (CSP-SI). Primary outcome was the rate of complete muscularis mucosae (MM) resection, defined by the proportion of MM under the tumor more than 80% of the tumor’s horizontal dimension. Secondary outcomes were the rates of negative lateral and vertical margins, fragmentation of resected specimens, conversion to hot-snare mucosal resection, intraprocedural bleeding, delayed bleeding, and perforation. Results Two hundred fourteen patients were randomly assigned to CSP-SI (n=107) or C-CSP (n=107). The rate of complete MM resection was 43.9% in the CSP-SI group and 53.3% in the C-CSP group, a statistically insignificant difference. The rates of negative lateral margin and vertical margin (42.3% and 56.7%, respectively) in the CSP-SI group were significantly lower than those (58% and 76%) in the C-CSP group (p=0.03 and p=0.006, respectively). There was no polypectomy-related major bleeding or perforation. Conclusions Saline solution injection into the submucosa did not improve the resection depth of CSP of small colorectal polyps, and the method resulted in lower rates of negative lateral and vertical margins of resected lesions.Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels belong to the superfamily of voltage-gated potassium (Kv) and cyclic nucleotide-gated (CNG) channels. HCN channels contain the glycine-tyrosine-glycine (GYG) sequence that forms part of the selectivity filter, a similar structure than some potassium channels; however, they permeate both sodium and potassium, giving rise to an inward current. Yet a second amino acid sequence, leucine-cysteine-isoleucine (LCI), next to GYG, is well-preserved in all HCNs but not in the selective potassium channels. In this study we used site-directed mutagenesis and electrophysiology in frog oocytes to determine whether the LCI sequence affects the kinetics of HCN2 currents. Permeability and voltage dependence were evaluated, and we found a role of LCI in the gating mechanism combined with changes in ion permeability. The I residue resulted critical to this function.We propose a simple model for chromatin organization based on the interaction of the chromatin fibers with lamin proteins along the nuclear membrane. Lamin proteins are known to be a major factor that influences chromatin organization and hence gene expression in the cells. We provide a quantitative understanding of lamin-associated chromatin organization in a crowded macromolecular environment by systematically varying the heteropolymer segment distribution and the strength of the lamin-chromatin attractive interaction. Our minimal polymer model reproduces the formation of lamin-associated-domains and provides an in silico tool for quantifying domain length distributions for different distributions of heteropolymer segments. We show that a Gaussian distribution of heteropolymer segments, coupled with strong lamin-chromatin interactions, can qualitatively reproduce observed length distributions of lamin-associated-domains. Further, lamin-mediated interaction can enhance the formation of chromosome territories as well as the organization of chromatin into tightly packed heterochromatin and the loosely packed gene-rich euchromatin regions.Protein diffusion in lower-dimensional spaces is used for various cellular functions. For example, sliding on DNA is essential for proteins searching for their target sites, and protein diffusion on microtubules is important for proper cell division and neuronal development. On the one hand, these linear diffusion processes are mediated by long-range electrostatic interactions between positively charged proteins and negatively charged biopolymers and have similar characteristic diffusion coefficients. On the other hand, DNA and microtubules have different structural properties. Here, using computational approaches, we studied the mechanism of protein diffusion along DNA and microtubules by exploring the diffusion of both protein types on both biopolymers. We found that DNA-binding and microtubule-binding proteins can diffuse on each other’s substrates; however, the adopted diffusion mechanism depends on the molecular properties of the diffusing proteins and the biopolymers. On the protein side, only DNA-binding proteins can perform rotation-coupled diffusion along DNA, with this being due to their higher net charge and its spatial organization at the DNA recognition helix. By contrast, the lower net charge on microtubule-binding proteins enables them to diffuse more quickly than DNA-binding proteins on both biopolymers. On the biopolymer side, microtubules possess intrinsically disordered, negatively charged C-terminal tails that interact with microtubule-binding proteins, thus supporting their diffusion. Thus, although both DNA-binding and microtubule-binding proteins can diffuse on the negatively charged biopolymers, the unique molecular features of the biopolymers and of their natural substrates are essential for function.STAC3 is a soluble protein essential for skeletal muscle excitation-contraction (EC) coupling. Through its tandem SH3 domains, it interacts with the cytosolic II-III loop of the skeletal muscle voltage-gated calcium channel. STAC3 is the target for a mutation (W284S) that causes Native American myopathy, but multiple other sequence variants have been reported. Here, we report a crystal structure of the human STAC3 tandem SH3 domains. We analyzed the effect of five disease-associated variants, spread over both SH3 domains, on their ability to bind to the CaV1.1 II-III loop and on muscle EC coupling. In addition to W284S, we find the F295L and K329N variants to affect both binding and EC coupling. The ability of the K329N variant, located in the second SH3 domain, to affect the interaction highlights the importance of both SH3 domains in association with CaV1.1. Our results suggest that multiple STAC3 variants may cause myopathy.Bacteria belonging to the Lachnospiraceae family are abundant, obligate anaerobic members of the microbiota in healthy humans. Lachnospiraceae impact their hosts by producing short-chain fatty acids, converting primary to secondary bile acids, and facilitating colonization resistance against intestinal pathogens. To increase our understanding of genomic and functional diversity between members of this family, we cultured 273 Lachnospiraceae isolates representing 11 genera and 27 species from human donors and performed whole-genome sequencing assembly and annotation. This analysis revealed substantial inter- and intra-species diversity in pathways that likely influence an isolate’s ability to impact host health. These differences are likely to impact colonization resistance through lantibiotic expression or intestinal acidification, influence host mucosal immune cells and enterocytes via butyrate production, or contribute to synergism within a consortium by heterogenous polysaccharide metabolism. Identification of these specific functions could facilitate development of probiotic bacterial consortia that drive and/or restore in vivo microbiome functions.Regulatory T cells maintain immunological tolerance and dampen inflammatory responses. Administering regulatory T cells can prevent the immune-mediated tissue destruction of graft-versus-host disease, which frequently accompanies hematopoietic stem cell transfer. Neutralizing the T cell-specific kinase, protein kinase C theta, which promotes T cell effector functions and represses regulatory T cell differentiation, augments regulatory T cell immunosuppression and stability. We used a synthetic, cell-penetrating peptide mimic to deliver antibodies recognizing protein kinase C theta into primary human CD4 T cells. When differentiated ex vivo into induced regulatory T cells, treated cells expressed elevated levels of the regulatory T cell transcriptional regulator forkhead box P3, the surface-bound immune checkpoint receptor programmed death receptor-1, and pro-inflammatory interferon gamma, previously ascribed to a specific population of stable, highly suppressive human induced regulatory T cells. The in vitro suppressive capacity of these induced regulatory T cells was 10-fold greater than that of T cells differentiated without antibody delivery. When administered at the time of graft-versus-host disease induction, using a humanized mouse model, antibody-treated regulatory T cells were superior to non-treated T cells in attenuating lethal outcomes. This antibody delivery approach may overcome obstacles currently encountered using patient-derived regulatory T cells as a cell-based therapy for immune modulation.Post-tetanic potentiation (PTP) is an attractive candidate mechanism for hippocampus-dependent short-term memory. Although PTP has a uniquely large magnitude at hippocampal mossy fiber-CA3 pyramidal neuron synapses, it is unclear whether it can be induced by natural activity and whether its lifetime is sufficient to support short-term memory. We combined in vivo recordings from granule cells (GCs), in vitro paired recordings from mossy fiber terminals and postsynaptic CA3 neurons, and „flash and freeze” electron microscopy. PTP was induced at single synapses and showed a low induction threshold adapted to sparse GC activity in vivo. PTP was mainly generated by enlargement of the readily releasable pool of synaptic vesicles, allowing multiplicative interaction with other plasticity forms. PTP was associated with an increase in the docked vesicle pool, suggesting formation of structural „pool engrams.” Absence of presynaptic activity extended the lifetime of the potentiation, enabling prolonged information storage in the hippocampal network.ObjectiveLong-acting reversible contraception (LARC) is the most effective form of reversible contraception, but its use in Australia is low compared with other countries. The aim of this study was to evaluate the economic effect of an increase in LARC uptake to international rates.MethodsAn economic model was designed to assess two scenarios, namely increasing the current rate of LARC uptake of 12.5% to the international benchmark of 14.8% among (1) women currently using the oral contraceptive pill (OCP); and (2) women at risk of pregnancy and not using contraception. Model inputs included cost of contraceptive methods, discontinuation rates and abortion and miscarriage costs associated with unintended pregnancies.ResultsWomen who switch from an OCP to LARC would save A$114-157 per year. Those not currently using any contraception who adopt LARC would incur costs of A$36-194 per year, but would reap savings from the reduction in unintended pregnancies. Over 5 years there would be a net saving of A$74.4 million for Scenario 1 and A$2.4 million for Scenario 2.ConclusionGreater use of LARC would result in a net gain in economic benefits to Australia. These benefits are largely driven by women switching from an OCP to LARC who have reduced costs, as well as women wishing to avoid pregnancy who choose to use LARC rather than no method. This evidence will support women making an informed contraceptive choice and policy makers in increasing the accessibility of LARC.What is known about the topic?LARC is the most effective form of reversible contraception, but uptake in Australia is relatively low.What does this paper add?There are economic benefits to society for women who switch from an OCP to LARC, as well as for women who switch from no contraception to LARC.What are the implications for practitioners?The findings of this study will support women in making an informed contraceptive choice and policy makers in increasing the accessibility of LARC.Objective The aim of this study was to explore the features of sustainable antimicrobial stewardship (AMS) programs in Australian rural hospitals and develop recommendations on incorporating these features into rural hospitals’ AMS programs. Methods Lead AMS clinicians with knowledge of at least one AMS program sustained for >2 years in a health service in rural Australia were recruited to the study. A series of interviews was conducted and the transcripts analysed thematically using a framework method. Results Fifteen participants from various professional disciplines were interviewed. Key features that positively affected the sustainability of AMS programs in rural hospitals included a hospital executive who provided strong governance and accountability, dedicated resources, passionate local champions, area-wide arrangements and adaptability to engage in new partnerships. Challenges to building AMS programs with these features were identified, particularly in engaging hospital executive to allocate AMS reso implications for practitioners? Recommended actions to boost the sustainability of AMS programs in rural hospitals are required. These include using accreditation as a mechanism to drive direct resource allocation, explicit staffing recommendations for rural hospitals, greater support to develop network arrangements and support to create integrated AMS programs across acute, aged and primary care.Objective The aim of this study was to explore whether a relationship exists between the number of disasters a jurisdiction has experienced and the presence of disaster-specific pharmacy legislation. Methods Pharmacy legislation specific to disasters was reviewed for five countries Australia, Canada, UK, US and New Zealand. A binary logistic regression test using a generalised estimating equation was used to examine the association between the number of disasters experienced by a state, province, territory or country and whether they had disaster-specific pharmacy legislation. Results Three of six models were statistically significant, suggesting that the odds of a jurisdiction having disaster-specific pharmacy legislation increased as the number of disasters increased for the period 2007-17 and 2013-17. There was an association between the everyday emergency supply legislation and the presence of the extended disaster-specific emergency supply legislation . Conclusions It is evident from this review that thewever, this is likely to be only one of many factors affecting the political decisions of when and what legislation is passed in relation to pharmacists’ roles in disasters. What are the implications for practitioners? Pharmacists are well situated in the community to be of assistance during disasters. However, their ability to help patients with chronic disease management or providing necessary vaccinations in disasters is limited by the legislation in their jurisdiction. Releasing pharmacists’ full potential in disasters could alleviate the burden of low-acuity patients on other healthcare services. This could subsequently free up other healthcare professionals to treat high-acuity patients and emergencies.The American alligator, Alligator mississippiensis, is an opportunistic carnivore that experiences an ontogenetic shift in food and feeding habits with an increase in body size. Alligators frequently feed on invertebrates and small fish as neonates and transition to feeding less frequently on larger vertebrates as they grow. We hypothesized that alligators experience an ontogenetic shift in the regulation of intestinal performance-modest regulation with frequent feeding early in life and wider regulation with less frequent feeding as they increase in body size. We tested this hypothesis by comparing postprandial responses in metabolic rate, organ masses, intestinal histology, digestive hydrolase activities, and intestinal nutrient uptake rates among neonate, juvenile, and subadult alligators. With feeding, alligators of all three age classes experienced a rapid increase in metabolic rate that peaked within 2 d and thereafter declined more slowly to prefeeding rates. Specific dynamic action increased with bodys, the modest regulation of digestive performance with feeding and fasting for alligators appears to be ontogenetically conserved.Purpose The purpose of this study was to explore and describe the features of Individualized Education Plans (IEPs) for a cohort of students with traumatic brain injury (TBI) to help elucidate current special education practices for students with TBI. Method We obtained permission from administrators of a local school district of 41,000 students in a Midwestern state to review de-identified IEP records of students verified with TBI. We examined demographic information (i.e., cause and age at time of injury), IEP services and intensity, IEP goal categories, and previous verification status. Results Descriptive results support that intervention services were more intense for students with TBI with greater lengths of time postinjury. Target behaviors within goals were more often related to math and reading than to the cognitive processes that govern these skills, such as attention, memory, and executive functioning. Finally, more than a third of our sample had been verified with a disability and were receiving special education services via an IEP prior to their TBI. Conclusions This work represents an important first step in understanding the special education services for students with TBI. Future research should explore interventions that are ecologically valid for school-based settings and are developed to address the idiosyncratic deficits of students with TBI, particularly interventions that focus on the underlying cognitive processes experienced by these students.Purpose The purpose of this study was to determine how quality of life (QoL) is measured in people with dementia involved in interventions designed to improve well-being and to explore how those measures align with principles of person-centered care. Method A systematic literature review was conducted utilizing PsychInfo, CINAHL, and PubMed and combinations of the search terms „dementia,” „outcome measure,” „creative engagement,” „creative intervention,” „TimeSlips,” „art,” „quality of life,” and „well-being.” The search was limited to studies published in peer-reviewed journals that reported outcomes for people with dementia in response to a creative intervention. Results Across the 24 reviewed studies, 30 different outcome measures were reported including eight self-reported, nine observational, and 13 proxy-reported measures. Self-report of QoL was elicited 16 times, observational measures were reported 17 times, and proxy-reported measures were used 28 times. All measures were used with participants across the dementia severity spectrum. Conclusion Current clinical practice of QoL evaluation does not align well with person-centered care principles of self-determination based on the low proportion of self-report. The previously reported limitations of proxy-report have been in part confirmed with this study. Implications of the findings for speech-language pathologists are discussed.The Outcomes Related to COVID-19 treated with Hydroxychloroquine among In-patients with symptomatic Disease (ORCHID) trial is a multicenter, blinded, randomized trial of hydroxychloroquine versus placebo for the treatment of adults hospitalized with COVID-19. This document provides the rationale and background for the trial and highlights key design features. We discuss five novel challenges to the design and conduct of a large, multi-center, randomized trial during a pandemic, including 1) widespread, off-label use of the study drug before the availability of safety and efficacy data; 2) the need to adapt traditional procedures for documentation of informed consent during an infectious pandemic; 3) developing a flexible and robust Bayesian analysis incorporating significant uncertainty about the disease, outcomes, and treatment; 4) obtaining indistinguishable drug and placebo without delaying enrollment; and 5) rapidly obtaining administrative and regulatory approvals. Our goals in describing how the ORCHID trial progressed from study conception to enrollment of the first patient in 15 days are to inform the development of other high-quality, multi-center trials targeting COVID-19. We describe lessons learned to improve the efficiency of future clinical trials, particularly in the setting of pandemics. The ORCHID trial will provide high-quality, clinically relevant data on the safety and efficacy of hydroxychloroquine for the treatment of COVID-19 among hospitalized adults. This trial was registered with ClinicalTrials.gov (NCT04332991) prior to enrollment of the first patient on April 2, 2020.Salts with asymmetric (fluorosulfonyl)(trifluoromethanesulfonyl)imide (FTFSI) anions have recently been shown to suppress crystallization of water-in-salt electrolytes, enabling low-temperature operation of high-voltage aqueous rechargeable batteries. To clarify the underlying mechanism for the kinetic suppression of crystallization, we investigate the local solution structures and dynamic behaviors of water-in-salt electrolytes based on the asymmetric FTFSI anion and its symmetric anion analogues by Raman spectroscopy and molecular dynamics simulations. We find that monodentate coordination of FTFSI to cations leads to high rotational mobility of the uncoordinated SO2CF3 group. We conclude that the peculiar, coordination-dependent, local dynamics in the asymmetric FTFSI anion, manifested by enhanced intramolecular bond rotation, enables the strong supercooling behavior.While the properties of surfaces and interfaces are crucial to modern devices, they are commonly difficult to explore since the signal from the bulk often masks the surface contribution. Here we introduce a methodology based on scanning electron microscopy (SEM) coupled with a pulsed laser source, which offers the capability to sense the topmost layer of materials, to study the surface photovoltage (SPV) related effects. This method relies on a pulsed optical laser to transiently induce an SPV and a continuous primary electron beam to produce secondary electron (SE) emission and monitor the change of the SE yield under laser illumination. We observe contrasting behaviors of the SPV-induced SE yield change on n-type and p-type semiconductors. We further study the dependence of the SPV-induced SE yield on the primary electron beam energy, the optical fluence, and the modulation frequency of the optical excitation, which reveal the details of the dynamics of the photocarriers in the presence of the surface built-in potential. This fast, contactless, and bias-free technique offers a convenient and robust platform to probe surface electronic phenomena, with great promise to probe nanoscale effects with a high spatial resolution. Our result further provides a basis to understand the contrast mechanisms of emerging time-resolved electron microscopic techniques, such as the scanning ultrafast electron microscopy.Here we use triple-cation metal-organic halide perovskite single crystals for the transistor channel of a flash memory device. Moreover, we design and demonstrate a 10 nm thick single-layer nanofloating gate. It consists of a ternary blend of two organic semiconductors, a p-type polyfluorene and an n-type fullerene that form a donoracceptor interpenetrating network that serves as the charge storage unit, and of an insulating polystyrene that acts as the tunneling dielectric. Under such a framework, we realize the first non-volatile flash memory transistor based on a perovskite channel. This simplified, solution-processed perovskite flash memory displays unique performance metrics such as a large memory window of 30 V, an on/off ratio of 9 × 107, short write/erase times of 50 ms, and a satisfactory retention time exceeding 106 s. The realization of the first flash memory transistor using a single-crystal perovskite channel could be a valuable direction for perovskite electronics research.Leucosceptroids are sesterterpenoids with potent antifeedant and antifungal activities. An efficient stereoselective construction of the highly congested [5,6,5] tricyclic framework of leucosceptroid H is presented. This framework bearing eight contiguous stereogenic centers, including three tetrasubstituted ones, could serve as a common intermediate for the collective total synthesis of the leucosceptroid family of natural products.The organocatalytic enantio- and diastereoselective cycloetherification of 1,3-cyclohexanedione-bearing enones involving the in situ generation of chiral cyanohydrins was developed. This transformation offers the first catalytic asymmetric approach to oxadecalin derivatives containing contiguous tetrasubstituted chiral carbons at the bridge heads of the fused ring systems. Depending on substituents, both cis- and trans-decalin-type scaffolds were synthesized with good to excellent stereoselectivities, and a range of functional groups accumulated on the chiral quaternary carbon moieties of the trans-oxadecalin derivatives.A novel nanohybrid composite of TiO2, SiO2, γ-Fe2O3, and reduced graphene oxide (TiO2@SiFerGO) is fabricated by the sol-gel method. The properties of the coated film were examined by structural and self-cleaning analyses using simulated discoloration/soiling and roofing tests. The fabricated transparent TiO2@SiFerGO composite showed excellent photoactivity and wettability, behaving well in self-cleaning applications. The addition of SiO2 improved the crystalline structure and surface hydroxylation of TiO2 nanoparticles. γ-Fe2O3 decreased the recombination rate of e-/h+ pairs, and significantly improved photocatalytic activity under visible light. Moreover, rGO sheets as excellent electron acceptors and transporters also reduced recombination, as well as affected wettability, achieving superhydrophilicity under irradiation. The coated substrate showed excellent resistance to simulated acid rain and significantly preserved the substrate from soiling in roofing tests.Atomic edge sites on two-dimensional (2D) nanomaterials display striking catalytic behavior, whereas edge engineering for 2D metal nanocatalysts remains an insurmountable challenge. Here we advance a one-pot synthesis of ultrathin 2D PdPtCu trimetallic nanosheets and nanorings with escalating low-coordinated edge proportions from 11.74% and 23.11% to 45.85% as cutting-edge ethanol oxidation reaction (EOR) electrocatalysts. This in situ edge enrichment hinges on a competitive surface capping and etching strategy with integrated manipulation of the reaction kinetics. Electrocatalysis tests demystify an edge-relied EOR performance, where the edge-richest 9.0 nm-Pd61Pt22Cu17 nanorings attain an exceptional activity (12.42 A mg-1Pt+Pd, 20.2 times that of commercial Pt/C) with substantially improved durability. Molecularly mechanistic studies certify that the unsaturated edge sites on these 2D catalysts prevail, triggering the C-C bond scission and succeeding CO removal to facilitate a 12-electron-transferring EOR process. This study introduces the „metal-edge-driven” concept and enables the „edge sites on 2D multimetallic nanocatalysts” technique to design versatile heterocatalysts.Free-energy perturbation (FEP) methods are commonly used in drug design to calculate relative binding free energies of different ligands to a common host protein. Alchemical ligand transformations are usually performed in multiple steps which need to be chosen carefully to ensure sufficient phase-space overlap between neighboring states. With one-step or single-step FEP techniques, a single reference state is designed that samples phase-space not only representative of a full transformation but also ideally resembles multiple ligand end states and hence allows for efficient multistate perturbations. Enveloping distribution sampling (EDS) is one example for such a method in which the reference state is created by a mathematical combination of the different ligand end states based on solid statistical mechanics. We have recently proposed a novel approach to EDS which enables efficient barrier crossing between the different end states, termed accelerated EDS (A-EDS). In this work, we further simplify the parametrization of the A-EDS reference state and demonstrate the automated calculation of multiple free-energy differences between different ligands from a single simulation in three different well-described drug design model systems.Peptide methionine sulfoxide reductases (Msrs) are enzymes that repair ROS-damage to sulfur-containing amino acids such as methionine, ensuring functional integrity of cellular proteins. Here we have shown that unlike the majority of pro- and eukaryotic Msrs, the peptide methionine sulfoxide reductase (MsrAB) from the human pathobiont Haemophilus influenzae (Hi) is required for the repair of hypochlorite damage to cell envelope proteins, but more importantly, we were able to demonstrate that MsrAB plays a role in modulating the host immune response to Hi infection. Loss of MsrAB resulted in >1000-fold increase in sensitivity of Hi to HOCl-mediated killing, and also reduced biofilm formation and in-biofilm survival. Expression of msrAB was also induced by hydrogen peroxide and paraquat, but a Hi2019ΔmsrAB strain was not susceptible to killing by these ROS in vitro. Hi2019ΔmsrAB fitness in infection models was low, with a 3-fold reduction in intracellular survival in bronchial epithelial cells, increased susceptibility to neutrophil killing, and a 10-fold reduction in survival in a mouse model of lung infection. Interestingly, infection with Hi2019ΔmsrAB led to specific changes in the antibacterial response of human host cells, with genes encoding antimicrobial peptides (BPI, CAMP) upregulated between 4 and 9 fold compared to infection with Hi2019WT, and reduction in expression of two proteins with antiapoptotic functions (BIRC3, XIAP). Modulation of host immune responses is a novel role for an enzyme of this type and provides first insights into mechanisms by which MsrAB supports Hi survival in vivo.Ultrasonic transducers with large output power have attracted extensive attentions due to their widespread applications in sonar, acoustic levitation, ultrasonic focusing, and so forth. However, the traditional transducer has almost no heat-dissipation capability itself, strictly relying on the assistant coolant system. Introducing high-performance heat-dissipation component is thus highly necessary. Herein, an embedded porcelain radiator component was designed by combining the excellent thermal conductivity of vertically oriented graphene (VG) with the outstanding heat-dissipation characteristics of thermosensitive ceramics, and a new-type transducer with an embedded VG/ceramic-hybrid radiator was constructed to show high heat-dissipation efficiency (up to ∼5 °C/min). Remarkably, prominent heat-dissipation effectiveness (temperature decline of ∼12 °C), enhanced amplitude and vibration uniformity were also achieved for the new-type transducer along with stabilized operating states. This research should pave ways for extending the applications of VG/ceramic hybrids to heat-dissipation scenarios and provide newfangled thoughts for the performance upgrade of multitudinous high-power devices.Understanding molecular principles underlying chaperone-based modulation of kinase client activity is critically important to dissect functions and activation mechanisms of many oncogenic proteins. The recent experimental studies have suggested that phosphorylation sites in the Hsp90 and Cdc37 proteins can serve as conformational communication switches of chaperone regulation and kinase interactions. However, a mechanism of allosteric coupling between phosphorylation sites in the Hsp90 and Cdc37 during client binding is poorly understood, and the molecular signatures underpinning specific roles of phosphorylation sites in the Hsp90 regulation remain unknown. In this work, we employed a combination of evolutionary analysis, coarse-grained molecular simulations together with perturbation-based network modeling and scanning of the unbound and bound Hsp90 and Cdc37 structures to quantify allosteric effects of phosphorylation sites and identify unique signatures that are characteristic for communication switches of kinase-specific client binding. By using network-based metrics of the dynamic intercommunity bridgeness and community centrality, we characterize specific signatures of phosphorylation switches involved in allosteric regulation. Through perturbation-based analysis of the dynamic residue interaction networks, we show that mutations of kinase-specific phosphorylation switches can induce long-range effects and lead to a global rewiring of the allosteric network and signal transmission in the Hsp90-Cdc37-kinase complex. We determine a specific group of phosphorylation sites in the Hsp90 where mutations may have a strong detrimental effect on allosteric interaction network, providing insight into the mechanism of phosphorylation-induced communication switching. The results demonstrate that kinase-specific phosphorylation switches of communications in the Hsp90 may be partly predisposed for their regulatory role based on preexisting allosteric propensities.A large number of nonadiabatic dynamical studies have been applied to reveal the nature of carrier transport in organic semiconductors with different approximations. We present here a „nearly exact” graphical-process-unit-based finite-temperature time-dependent density matrix renormalization group (TD-DMRG) method to evaluate the carrier mobility in organic semiconductors, as described by the electron-phonon model, in particular, in rubrene crystal, one of the prototypical organic semiconductors, with parameters derived from first-principles. We find that (i) TD-DMRG is a general and robust method that can bridge the gap between hopping and band pictures, covering a wide range of electronic coupling strengths and (ii) with realistic parameters, TD-DMRG is able to account for the experimentally observed „band-like” transport behavior (∂μ/∂T less then 0) in rubrene. We further study the long-standing puzzle of the isotope effect for charge transport and unambiguously demonstrate that the negative isotope effect (∂μ/∂m less then 0 where m is the atomic mass) should be universal.Reaction of [Li(THF)]4[L] (L = Me8-calix[4]pyrrole]) with 0.5 equiv of [UVIO2Cl2(THF)2]2 results in formation of the oxidized calix[4]pyrrole product, [Li(THF)]2[LΔ] (1), concomitant with formation of reduced uranium oxide byproducts. Complex 1 can also be generated by reaction of [Li(THF)]4[L] with 1 equiv of I2. We hypothesize that formation of 1 proceeds via formation of a highly oxidizing cis-uranyl intermediate, [Li]2[cis-UVIO2(calix[4]pyrrole)]. To test this hypothesis, we explored the reaction of 1 with either 0.5 equiv of [UVIO2Cl2(THF)2]2 or 1 equiv of [UVIO2(OTf)2(THF)3], which affords the isostructural uranyl complexes, [Li(THF)][UVIO2(LΔ)Cl(THF)] (2) and [Li(THF)][UVIO2(LΔ)(OTf)(THF)] (3), respectively. In the solid state, 2 and 3 feature unprecedented uranyl-η5-pyrrole interactions, making them rare examples of uranyl organometallic complexes. In addition, 2 and 3 exhibit some of the smallest O-U-O angles reported to date (2 162.0(7) and 162.7(7)°; 3 164.5(5)°). Importantly, the O-U-O bending observed in these complexes suggests that the oxidation of [Li(THF)]4[L] does indeed occur via an unobserved cis-uranyl intermediate.Two-dimensional ferroelectrics is attractive for synaptic device applications because of its low power consumption and amenability to high-density device integration. Here, we demonstrate that tin monosulfide (SnS) films less than 6 nm thick show optimum performance as a semiconductor channel in an in-plane ferroelectric analogue synaptic device, whereas thicker films have a much poorer ferroelectric response due to screening effects by a higher concentration of charge carriers. The SnS ferroelectric device exhibits synaptic behaviors with highly stable room-temperature operation, high linearity in potentiation/depression, long retention, and low cycle-to-cycle/device-to-device variations. The simulated device based on ferroelectric SnS achieves ∼92.1% pattern recognition accuracy in an artificial neural network simulation. By switching the ferroelectric domains partially, multilevel conductance states and the conductance ratio can be obtained, achieving high pattern recognition accuracy.Organic-inorganic hybrid halide perovskites are promising semiconductors with tailorable optical and electronic properties. The choice of A-site cation to support a three-dimensional (3D) perovskite structure AMX3 (where M is a metal and X is a halide) is limited by the geometric Goldschmidt tolerance factor. However, this geometric constraint can be relaxed in two-dimensional (2D) perovskites, providing us an opportunity to understand how various A-site cations modulate the structural properties and thereby the optoelectronic properties. Here, we report the synthesis and structures of single-crystal (BA)2(A)Pb2I7 where BA = butylammonium and A = methylammonium (MA), formamidinium (FA), dimethylammonium (DMA), or guanidinium (GA), with a series of A-site cations varying in size. Single-crystal X-ray diffraction reveals that the MA, FA, and GA structures crystallize in the same Cmcm space group, while the DMA imposes the Ccmb space group. We observe that as the A-site cation becomes larger, the Pb-I bond continuously elongates, expanding the volume of the perovskite cage, equivalent to exerting „negative pressure” on the perovskite structures. Optical studies and DFT calculations show that the Pb-I bond length elongation reduces the overlap of the Pb s- and I p-orbitals and increases the optical bandgap, while Pb-I-Pb tilting angles play a secondary role. Raman spectra show lattice softening with increasing size of the A-site cation. These structural changes with enlarged A cations result in significant decreases in photoluminescence intensity and lifetime, consistent with a more pronounced nonradiative decay. Transient absorption microscopy results suggest that the PL drop may derive from a higher concentration of traps or phonon-assisted nonradiative recombination. The results highlight that extending the range of Goldschmidt tolerance factors for 2D perovskites is achievable, enabling further tuning of the structure-property relationships in 2D perovskites.Rhenium disulfide (ReS2) which possessed a unique direct band gap from bulk to monolayer played a very important role in the establishing optoelectronic devices, while the rapid recombination of electron-hole pair might hinder its further applications. Therefore, in order to improve its photocurrent performance, a bimetallic co-chamber feeding atomic layer deposition (ALD) with a precise dose regulation strategy was used to fabricate MoS2-ReS2 heterojunctions with controllable Mo-to-Re ratio in this work. Furthermore, because of the controlled addition of Mo atoms, the electron transfer capacity, carrier mobility and photocurrent response of these heterojunctions were significantly improved, among which the sample obtained under 100 super cycles (one super cycle for this sample consists of the followings in turn 1 ReCl5 pulse, 1 H2S pulse, 1 ReCl5 pulse and 1 MoCl5 pulse, 1 H2S pulse, the real Mo-to-Re ratio Rr=57.9%) exhibited the best photocurrent response. Due to the significant improvement in optoelectronic performance, photoelectrochemical (PEC) biosensor with the basis of the above optimized sample could achieve ultrasensitive detection of cancer-related miRNA-21 ranging from 10 aM to 1 nM with a low detection limit of 2.8 aM.Group IV color centers in diamond (Si, Ge, Sn, and Pb) have recently emerged as promising candidates for realization of scalable quantum photonics. However, their synthesis in nanoscale diamond is still in its infancy. In this work we demonstrate controlled synthesis of selected group IV defects (Ge and Sn) into nanodiamonds and nanoscale single crystal diamond membranes by microwave plasma chemical vapor deposition. We take advantage of inorganic salts to prepare the chemical precursors that contain the required ions that are then incorporated into the growing diamond. Photoluminescence measurements confirm that the selected group IV emitters are present in the diamond without degrading its structural quality. Our results are important to expand the versatile synthesis of color centers in diamond.Dysfunction of the glymphatic system may play a significant role in the development of neurodegenerative diseases. However, in vivo imaging of the glymphatic system is challenging. In this study, we describe an unconventional MRI method for imaging the glymphatic system based on chemical exchange saturation transfer, which we tested in an in vivo porcine model of impaired glymphatic function. The blood, lymph, and cerebrospinal fluid (CSF) from one pig were used for testing the MRI effect in vitro at 7 Tesla (T). Unilateral deep cervical lymph node ligation models were then performed in 20 adult male Sprague-Dawley rats. The brains were scanned in vivo dynamically after surgery using the new MRI method. Behavioral tests were performed after each scanning session and the results were tested for correlations with the MRI signal intensity. Finally, the pathological assessment was conducted in the same brain slices. The special MRI effect in the lymph was evident at about 1.0 ppm in water and was distinguishable from those of blood and CSF. In the model group, the intensity of this MRI signal was significantly higher in the ipsilateral than in the contralateral hippocampus. The correlation between the signal abnormality and the behavioral score was significant (Pearson’s, R2 = 0.9154, p less then 0.005). We conclude that the novel MRI method can visualize the glymphatic system in vivo.Alzheimer’s disease (AD) is a severe neurodegenerative disorder caused by abnormal accumulation of toxic amyloid plaques of the amyloid-beta (Aβ) or the tau proteins in the brain. The plaque deposition leading to the collapse of the cellular integrity is responsible for a myriad of surface phenomena acting at the neuronal lipid interface. Recent years have witnessed dysfunction of the blood-brain barriers (BBB) associated with AD. Several studies support the idea that BBB acts as a platform for the formation of misfolded Aβ peptide, promoting oligomerization and fibrillation, compromising the overall integrity of the central nervous system. While the amyloid plaque deposition has been known to be responsible for the collapse of the BBB membrane integrity, the causal effect relationship between BBB and Aβ amyloidogenesis remains unclear. In this study, we have used physiologically relevant synthetic model membrane systems to gain atomic insight into the functional aspects of the lipid interface. Here, we have used a minimalist BBB mimic, POPC/POPG/cholesterol/GM1, to compare with the native BBB (total lipid brain extract (TLBE)), to understand the molecular events occurring in the membrane-induced Aβ40 amyloid aggregation. Our study showed that the two membrane models accelerated the Aβ40 aggregation kinetics with differential secondary structural transitions of the peptide. The observed structural transitions are defined by the lipid compositions, which in turn undermines the differences in lipid surface phenomena, leading to peptide induced cellular toxicity in the neuronal membrane.The ability to dictate the assembly of quantum dots (QDs) is critical for their integration into solid-state electronic and optoelectronic devices. However, assembly methods that enable efficient electronic communication between QDs, facilitate access to the reactive surface, and retain the native quantum confinement characteristics of the QD are lacking. Here we introduce a universal and facile electrochemical gelation method for assembling metal chalcogenide QDs (as demonstrated for CdS, ZnS, and CdSe) into macroscale 3-D connected pore-matter nanoarchitectures that remain quantum confined and in which each QD is accessible to the ambient. Because of the redox-active nature of the bonding between QD building blocks in the gel network, the electrogelation process is reversible. We further demonstrate the application of this electrogelation method for a one-step fabrication of CdS gel gas sensors, producing devices with exceptional performance for NO2 gas sensing at room temperature, thereby enabling the development of low-cost, sensitive, and reliable devices for air quality monitoring.Spontaneously exfoliated pristine graphene is used as a surfactant to template the formation of electrically conductive filters for the adsorption of an organic dye from water. In contrast to other reported graphene-based adsorption materials, our system provides a continuous approach to water treatment rather than a batch approach, and uses pristine graphene instead of the more costly and environmentally challenging graphene oxide. The use of self-assembled graphene also results in our filters being electrically conductive, providing a convenient route to clean the filters by resistive heating. An investigation of the mechanism of formation and filtration by these filters, templated by self-assembled two-dimensional pristine graphene, is presented. The thermodynamically driven exfoliation of natural flake graphite at a high-energy monomer/water interface produces water-in-oil emulsions stabilized by a thin layer of overlapping graphene sheets. Subsequent polymerization of the continuous monomer phase produces polymer foams with cells lined by graphene.