Importantly, ZHPV16E61235 was applied in combination with HPV16 E7-binding affibody ZHPV16E7384 to simultaneously target the HPV16 E6/E7 oncoproteins, and this combination inhibited cell proliferation more potently than either modality alone. Mechanistic studies revealed that the synergistic antiproliferative activity depends primarily on the induction of cell apoptosis and senescence but not cell cycle arrest. Our findings provide strong evidence that three novel HPV16 E6-binding affibody molecules could form a novel basis for the development of rational strategies for molecular imaging and targeted therapy in HPV16-positive preneoplastic and neoplastic lesions.Mesenchymal stem cells (MSCs) help fight infection by promoting direct bacterial killing or indirectly by modulating the acute phase response, thereby decreasing tissue injury. Recent evidence suggests that extracellular vesicles (EVs) released from MSCs retain antimicrobial characteristics that may be enhanced by pretreatment of parent MSCs with the toll-like receptor 3 (TLR3) agonist poly(IC). Our aim was to determine whether poly(IC) priming can modify EV content of miRNAs and/or proteins to gain insight into the molecular mechanisms of their enhanced antimicrobial function. Human bone marrow-derived MSCs were cultured with or without 1 μg/ml poly(IC) for 1 h and then conditioned media was collected after 64 h of culture in EV-depleted media. Mass spectrometry and small RNA next-generation sequencing were performed to compare proteomic and miRNA profiles. Poly(IC) priming resulted in 49 upregulated EV proteins, with 21 known to be important in host defense and innate immunity. In contrast, EV miRNA content was not significantly altered. Functional annotation clustering analysis revealed enrichment in biological processes and pathways including negative regulation of endopeptidase activity, acute phase, complement and coagulation cascades, innate immunity, immune response, and Staphylococcus aureus infection. Several antimicrobial peptides identified in EVs remained unaltered by poly(IC) priming, including dermcidin, lactoferrin, lipocalin 1, lysozyme C, neutrophil defensin 1, S100A7 (psoriasin), S100A8/A9 (calprotectin), and histone H4. Although TLR3 activation of MSCs improves the proteomic profile of EVs, further investigation is needed to determine the relative importance of particular functional EV proteins and their activated signaling pathways following EV interaction with immune cells.Biophysical cues, such as mechanical properties, play a critical role in tissue growth and homeostasis. During organ development and tissue injury repair, compressive and tensional forces generated by cell-extracellular matrix or cell-cell interaction are key factors for cell fate determination. In the vascular system, hemodynamic forces, shear stress, and cyclic stretch modulate vascular cell phenotypes and susceptibility to atherosclerosis. Despite that emerging efforts have been made to investigate how mechanotransduction is involved in tuning cell and tissue functions in various contexts, the regulatory mechanisms remain largely unknown. One of the challenges is to understand the signaling cascades that transmit mechanical cues from the plasma membrane to the cytoplasm and then to the nuclei to generate mechanoresponsive transcriptomes. YAP and its homolog TAZ, the Hippo pathway effectors, have been identified as key mechanotransducers that sense mechanical stimuli and relay the signals to control transcriptional programs for cell proliferation, differentiation, and transformation. However, the upstream mechanosensors for YAP/TAZ signaling and downstream transcriptome responses following YAP/TAZ activation or repression have not been well characterized. Moreover, the mechanoregulation of YAP/TAZ in literature is highly context-dependent. In this review, we summarize the biomechanical cues in the tissue microenvironment and provide an update on the roles of YAP/TAZ in mechanotransduction in various physiological and pathological conditions.A distinguishing feature of meiotic DNA double-strand breaks (DSBs), compared to DSBs in somatic cells, is the fact that they are induced in a programmed and specifically orchestrated manner, which includes chromatin remodeling prior to DSB induction. In addition, the meiotic homologous recombination (HR) repair process that follows, is different from HR repair of accidental DSBs in somatic cells. For instance, meiotic HR involves preferred use of the homolog instead of the sister chromatid as a repair template and subsequent formation of crossovers and non-crossovers in a tightly regulated manner. An important outcome of this distinct repair pathway is the pairing of homologous chromosomes. Central to the initial steps in homology recognition during meiotic HR is the cooperation between the strand exchange proteins (recombinases) RAD51 and its meiosis-specific paralog DMC1. Despite our understanding of their enzymatic activity, details on the regulation of their assembly and subsequent molecular organization at meiotic DSBs in mammals have remained largely enigmatic. In this review, we summarize recent mouse data on recombinase regulation via meiosis-specific factors. Also, we reflect on bulk „omics” studies of initial meiotic DSB processing, compare these with studies using super-resolution microscopy in single cells, at single DSB sites, and explore the implications of these findings for our understanding of the molecular mechanisms underlying meiotic HR regulation.Hyperandrogenism is a key pathological feature of polycystic ovarian syndrome (PCOS). Excess androgen can lead to PCOS-like cell hypertrophy in the ovaries and adipose tissue of rodents. Here, we established a dihydrotestosterone (DHT)-induced hyperandrogenic mouse model to analyze the differences in gene expression and signaling pathways of the ovaries and gonad fat pads of mice treated with or without DHT by RNA microarray analysis. From the results, we focused on the overlapping differentially expressed gene-Col6a5-and the major differentially enriched signaling pathway-lipid metabolism. We employed DHT-induced mouse ovarian stromal cell, adipogenic 3T3-L1 cell and hepatic cell line NCTC1469 models to investigate whether androgens directly mediate lipid accumulation and hypertrophy. We found that DHT increased lipid droplet accumulation in ovarian stromal cells and adipogenic 3T3-L1 cells but not NCTC1469 cells. DHT significantly altered stromal cell cholesterol metabolism and steroidogenesis, as indicated by changes in cholesterol levels and the expression of related genes, but these effects were not observed in 3T3-L1 cells. Moreover, Col6a5 expression was significantly increased in ovaries and gonadal fat pads of DHT-treated mice, and Col6a5 inhibition alleviated DHT-induced excess lipid accumulation and hypertrophy of ovarian stromal cells and adipogenic 3T3-L1 cells, even improved lipid metabolism in overnourished NCTC1469 cells. Our results indicate that Col6a5 plays important roles in the pathogenesis of DHT-induced lipid metabolism disorder and the hypertrophy of ovarian stromal cells and adipocytes.Microglia are the resident immune cells of the adult brain that become activated in response to pathogen- or damage-associated stimuli. The acute inflammatory response to injury, stress, or infection comprises the release of cytokines and phagocytosis of damaged cells. Accumulating evidence indicates chronic microglia-mediated inflammation in diseases of the central nervous system, most notably neurodegenerative disorders, that is associated with disease progression. To understand microglia function in pathology, knowledge of microglia communication with their surroundings during normal state and the release of neurotrophins and growth factors in order to maintain homeostasis of neural circuits is of importance. Recent evidence shows that microglia interact with serotonin, the neurotransmitter crucially involved in adult neurogenesis, and known for its role in antidepressant action. In this chapter, we illustrate how microglia contribute to neuroplasticity of the hippocampus and interact with local factors, e.g., BDNF, and external stimuli that promote neurogenesis. We summarize the recent findings on the role of various receptors in microglia-mediated neurotransmission and particularly focus on microglia’s response to serotonin signaling. We review microglia function in neuroinflammation and neurodegeneration and discuss their novel role in antidepressant mechanisms. This synopsis sheds light on microglia in healthy brain and pathology that involves serotonin and may be a potential therapeutic model by which microglia play a crucial role in the maintenance of mood.Protein secretion in eukaryotic cells is a well-studied process, which has been known for decades and is dealt with by any standard cell biology textbook. However, over the past 20 years, several studies led to the realization that protein secretion as a process might not be as uniform among different cargos as once thought. While in classic canonical secretion proteins carry a signal sequence, the secretory or surface proteome of several organisms demonstrated a lack of such signals in several secreted proteins. Other proteins were found to indeed carry a leader sequence, but simply circumvent the Golgi apparatus, which in canonical secretion is generally responsible for the modification and sorting of secretory proteins after their passage through the endoplasmic reticulum (ER). These alternative mechanisms of protein translocation to, or across, the plasma membrane were collectively termed „unconventional protein secretion” (UPS). To date, many research groups have studied UPS in their respective model orgitic protists preceded by a brief overview of UPS in the mammalian cell model with a focus on IL-1β and FGF-2 as paradigmatic UPS substrates.BRD7 functions as a crucial tumor suppressor in numerous malignancies. However, the effects of BRD7 on colorectal cancer (CRC) progression are still unknown. Here, based on the BRD7 knockout (BRD7-/-) and BRD7 flox/flox (BRD7+/+) mouse models constructed in our previous work, we established an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse model. BRD7+/+ mice were found to be highly susceptible to AOM/DSS-induced colitis-associated CRC, and BRD7 significantly promoted cell proliferation and cell cycle G1/S transition but showed no significant effect on cell apoptosis. Furthermore, BRD7 interacted with c-Myc and stabilized c-Myc by inhibiting its ubiquitin-proteasome-dependent degradation. Moreover, restoring the expression of c-Myc in BRD7-silenced CRC cells restored cell proliferation, cell cycle progression, and tumor growth in vitro and in vivo. In addition, BRD7 and c-Myc were both significantly upregulated in CRC patients, and high expression of these proteins was associated with clinical stage and poor prognosis in CRC patients. Collectively, BRD7 functions as an oncogene and promotes CRC progression by regulating the ubiquitin-proteasome-dependent stabilization of c-Myc protein. Targeting the BRD7/c-Myc axis could be a potential therapeutic strategy for CRC.

Intracranial aneurysm is an abnormal expansion in the intracranial arteries, which is associated with growth and apoptosis of vascular smooth muscle cells. Circular RNAs (circRNAs) have implicated in the progression of intracranial aneurysms. The purpose of this paper is to study the function and mechanism of circRNA dedicator of cytokinesis 1 (circ_DOCK1) in regulating proliferation and apoptosis of human brain vascular smooth muscle cells (HBVSMCs).

HBVSMCs were exposed to hydrogen peroxide (H

O

). Cell proliferation and apoptosis were detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and flow cytometry, respectively. Circ_DOCK1, microRNA (miR)-409-3p, and myeloid cell leukemia sequence 1 (MCL1) levels were examined by quantitative reverse transcription polymerase chain reaction or western blotting. The target association was assessed by dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation assays.

Exposure to H

O

decreased proliferation and increased apoptosis of HBVSMCs. Circ_DOCK1 expression was reduced in H

O

-treated HBVSMCs. Circ_DOCK1 overexpression rescued H

O

-caused reduction of proliferation and PCNA expression and attenuated H

O

-induced apoptosis and expression of Bcl-2, Bax, and cleaved PARP. MiR-409-3p was targeted by circ_DOCK1 and upregulated in H

O

-treated HBVSMCs. MiR-409-3p upregulation mitigated the role of circ_DOCK1 in proliferation and apoptosis of H

O

-treated HBVSMCs. MCL1 was targeted

miR-409-3p and downregulated

H

O

treatment. Circ_DOCK1 overexpression enhanced MCL1 expression

modulating miR-409-3p. MiR-409-3p knockdown weakened H

O

-induced proliferation reduction and apoptosis promotion

regulating MCL1.

Circ_DOCK1 overexpression mitigated H

O

-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.

Circ_DOCK1 overexpression mitigated H2O2-caused proliferation inhibition and apoptosis promotion in HBVSMCs by modulating miR-409-3p/MCL1 axis.2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Because prestin is postnatally upregulated from the cochlear base toward the apex, we hypothesized that HPβCD ototoxicity would spread from the high-frequency base toward the low-frequency apex of the cochlea. Consistent with this hypothesis, cochlear hearing impairments and OHC loss rapidly spread from the high-frequency base toward the low-frequency apex of the cochlea when HPβCD administration shifted from postnatal day 3 (P3) to P28. HPβCD-induced histopathologies were initially confined to the OHCs, but between 4- and 6-weeks post-treatment, there was an unexpected, rapid and massive expansion of the lesion to include most inner hair cells (IHC), pillar cells (PC), peripheral auditory nerve fibers, and spiral ganglion neurons at location where OHCs were missing. The magnitude and spatial extent of HPβCD-induced OHC death was tightly correlated with the postnatal day when HPβCD was administered which coincided with the spatiotemporal upregulation of prestin in OHCs. A second, massive wave of degeneration involving IHCs, PC, auditory nerve fibers and spiral ganglion neurons abruptly emerged 4-6 weeks post-HPβCD treatment. This secondary wave of degeneration combined with the initial OHC loss results in a profound, irreversible hearing loss.

We aimed to develop and validate a comprehensive nomogram containing pre-treatment plasma HSP90AA1 to predict the risk of breast cancer onset and metastasis.

We assessed the expression of HSP90s in breast cancer patients using an online database. To verify the results, 677 patients diagnosed with breast cancer and 146 patients with benign breast disease between 2014 and 2019 were selected from our hospital and were divided into cancer risk and metastasis risk cohorts. We focused on HSP90AA1 to elucidate the risks of onset and metastasis in the cohorts.

Expression levels of

,

,

,

, and

were linked to disease progression. Survival analysis using the GEPIA and OncoLnc databases indicated that the upregulation of

and

was related to poor overall survival. In the cancer risk cohort, carcinoembryonic antigen (CEA), carbohydrate antigen 153 (CA153), HSP90AA1, T cells%, natural killer cells%, B cells%, neutrophil count, monocyte count, and d-dimer were incorporated into the nomogram. A high Harrell’s concordance index (C-index) value of 0.771 [95% confidence interval (CI), 0.725-0.817] could still be reached in the interval validation. In the metastasis risk cohort, predictors contained in the prediction nomogram included the use of CEA, CA153, HSP90AA1, carbohydrate antigen 125 (CA125), natural killer cells%, B cells%, platelet count, monocyte count, and d-dimer. The C-index was 0.844 (95% CI, 0.801-0.887) and it was well-calibrated. HSP90AA1 raised net clinical benefit of breast cancer onset and metastasis risk prediction nomogram in a range of risk thresholds (5-92%) and (1-90%).

Our study revealed that pretreatment plasma HSP90AA1 combined with other markers could conveniently predict the risk of breast cancer onset and metastasis.

Our study revealed that pretreatment plasma HSP90AA1 combined with other markers could conveniently predict the risk of breast cancer onset and metastasis.This study has analyzed sex-specific differences in pedestrian and cyclist accidents involving passenger cars. The most frequently injured body regions, types of injuries, which show sex-specific differences and the general accident parameters of females and males were compared. Accident data from three different European countries (Austria, Netherlands, Sweden) were analyzed. The current analysis shows that for both, females and males, pedestrian and cyclist injuries are sustained mainly to the body regions head, thorax, upper extremities and lower extremities. The results show that the odds for sustaining skeletal injuries to the lower extremities (incl. pelvis) in females are significantly higher. It was observed in all datasets, that the odds of females being involved in a rural accident or an accident at night are lower than for males. Elderly pedestrian and cyclist (≥60YO) tend to sustain more severe injuries (AIS2+ and AIS3+) than younger pedestrian and cyclists ( less then 60YO) in some of the datasets. The findings of this study highlight the differences in males and females in both, accident scenarios and sustained injuries. Further investigations are needed to distinguish between gender- and sex-specific differences causing the different injury patterns.To evaluate vehicle occupant injury risk, finite element human body models (HBMs) can be used in vehicle crash simulations. HBMs can predict tissue loading levels, and the risk for fracture can be estimated based on a tissue-based risk curve. A probabilistic framework utilizing an age-adjusted rib strain-based risk function was proposed in 2012. However, the risk function was based on tests from only twelve human subjects. Further, the age adjustment was based on previous literature postulating a 5.1% decrease in failure strain for femur bone material per decade of aging. The primary aim of this study was to develop a new strain-based rib fracture risk function using material test data spanning a wide range of ages. A second aim was to update the probabilistic framework with the new risk function and compare the probabilistic risk predictions from HBM simulations to both previous HBM probabilistic risk predictions and to approximate real-world rib fracture outcomes. Tensile test data of human rib cortical bonwithin the 2012 probabilistic framework.Phytic acid is an anti-nutritional compound able to chelate proteins and ions. For this reason, the food industry is looking for a convenient method which allows its degradation. Phytases are a class of enzymes that catalyze the degradation of phytic acid and are used as additives in feed-related industrial processes. Due to their industrial importance, our goal was to identify new activities that exhibit best performances in terms of tolerance to high temperature and acidic pH. As a result of an initial screening on 21 yeast species, we focused our attention on phytases found in Cyberlindnera jadinii, Kluyveromyces marxianus, and Torulaspora delbrueckeii. In particular, C. jadinii showed the highest secreted and cell-bound activity, with optimum of temperature and pH at 50°C and 4.5, respectively. These characteristics suggest that this enzyme could be successfully used for feed as well as for food-related industrial applications.This study aimed to utilize the enzymatic hydrolysis of leftover cooked rice (LCR) for fermentative ethanol production. Effect of glucoamylase volumes (V1 5 U/g, V2 25 U/g, and V3 50 U/g) on the performance of LCR hydrolysis was also evaluated. It was found that the highest chemical oxygen demand (COD) of 77.5 g/L and reducing sugar (RS) of 34.6 g/L were achieved at V3. The LCR hydrolyzate obtained from enzymatic hydrolysis was then used as feedstock for ethanol fermentation. Higher ethanol production was obtained when RS increased from 18.7 g/L (V1) to 23.2 g/L (V2). However, lower ethanol production was found when RS further increased to 34.6 g/L (V3) probably because too high RS concentration led to the inhibition on the yeast. The maximum ethanol production and yield were 21.1 g/L and 0.3 g ethanol/g LCR, respectively. The LCR could be a promising substrate for fermentative ethanol production for industrial application.An increasing need toward a more efficient expansion of adherent progenitor cell types arises with the advancements of cell therapy. The use of a dynamic expansion instead of a static planar expansion could be one way to tackle the challenges of expanding adherent cells at a large scale. Microcarriers are often reported as a biomaterial for culturing cells in suspension. However, the type of microcarrier has an effect on the cell expansion. In order to find an efficient expansion process for a specific adherent progenitor cell type, it is important to investigate the effect of the type of microcarrier on the cell expansion. Human periosteum-derived progenitor cells are extensively used in skeletal tissue engineering for the regeneration of bone defects. Therefore, we evaluated the use of different microcarriers on human periosteum-derived progenitor cells. In order to assess the potency, identity and viability of these cells after being cultured in the spinner flasks, this study performed several in vitro and in vivo analyses. The novelty of this work lies in the combination of screening different microcarriers for human periosteum-derived progenitor cells with in vivo assessments of the cells’ potency using the microcarrier that was selected as the most promising one. The results showed that expanding human periosteum-derived progenitor cells in spinner flasks using xeno-free medium and Star-Plus microcarriers, does not affect the potency, identity or viability of the cells. The potency of the cells was assured with an in vivo evaluation, where bone formation was achieved. In summary, this expansion method has the potential to be used for large scale cell expansion with clinical relevance.We develop here a novel hypothesis that may generate a general research framework of how autonomous robots may act as a future contingency to counteract the ongoing ecological mass extinction process. We showcase several research projects that have undertaken first steps to generate the required prerequisites for such a technology-based conservation biology approach. Our main idea is to stabilise and support broken ecosystems by introducing artificial members, robots, that are able to blend into the ecosystem’s regulatory feedback loops and can modulate natural organisms’ local densities through participation in those feedback loops. These robots are able to inject information that can be gathered using technology and to help the system in processing available information with technology. In order to understand the key principles of how these robots are capable of modulating the behaviour of large populations of living organisms based on interacting with just a few individuals, we develop novel mathematical mems. Only if the effects of autonomous robots onto the environment can be sufficiently well predicted can such robotic systems leave the safe space of the lab and can be applied in the wild to be able to unfold their ecosystem-stabilising potential.Natural products with novel chemistry are urgently needed to battle the continued increase in microbial drug resistance. Mushroom-forming fungi are underutilized as a source of novel antibiotics in the literature due to their challenging culture preparation and genetic intractability. However, modern fungal molecular and synthetic biology tools have renewed interest in exploring mushroom fungi for novel therapeutic agents. The aims of this study were to investigate the secondary metabolites of nine basidiomycetes, screen their biological and chemical properties, and then investigate the genetic pathways associated with their production. Of the nine fungi selected, Hypholoma fasciculare was revealed to be a highly active antagonistic species, with antimicrobial activity against three different microorganisms Bacillus subtilis, Escherichia coli, and Saccharomyces cerevisiae. Genomic comparisons and chromatographic studies were employed to characterize more than 15 biosynthetic gene clusters and resulted in the identification of 3,5-dichloromethoxy benzoic acid as a potential antibacterial compound. The biosynthetic gene cluster for this product is also predicted. This study reinforces the potential of mushroom-forming fungi as an underexplored reservoir of bioactive natural products. Access to genomic data, and chemical-based frameworks, will assist the development and application of novel molecules with applications in both the pharmaceutical and agrochemical industries.As a promising treatment option for cancer, immunotherapy can eliminate local and distant metastatic tumors and even prevent recurrence through boosting the body’s immune system. However, immunotherapy often encounters the issues of limited therapeutic efficacy and severe immune-related adverse events in clinical practices, which should be mainly due to the non-specific accumulations of immunotherapeutic agents. Activatable immunomodulatory agents that are responsive to endogenous stimuli in tumor microenvironment can afford controlled immunotherapeutic actions, while they still face certain extent of off-target activation. Since light has the advantages of noninvasiveness, simple controllability and high spatio-temporal selectivity, therapeutic agents that can be activated by light, particularly near-infrared (NIR) light with minimal phototoxicity and strong tissue penetrating ability have been programmed for cancer treatment. In this mini review, we summarize the recent progress of NIR photoactivatable immunomodulatory nanoparticles for combinational cancer immunotherapy. The rational designs, constructions and working mechanisms of NIR photoactivatable agents are first briefly introduced. The uses of immunomodulatory nanoparticles with controlled immunotherapeutic actions upon NIR photoactivation for photothermal and photodynamic combinational immunotherapy of cancer are then summarized. A conclusion and discussion of the existing challenges and further perspectives for the development and clinical translation of NIR photoactivatable immunomodulatory nanoparticles are finally given.Bacterial biofilms are responsible for the development of various chronic wound-related and implant-mediated infections and confer protection to the pathogenic bacteria against antimicrobial drugs and host immune responses. Hence, biofilm-mediated chronic infections have created a tremendous burden upon healthcare systems worldwide. The development of biofilms upon the surface of medical implants has resulted in the failure of various implant-based surgeries and therapies. Although different conventional chemical and physical agents are used as antimicrobials, they fail to kill the sessile forms of bacterial pathogens due to the resistance exerted by the exopolysaccharide (EPS) matrices of the biofilm. One of the major techniques used in addressing such a problem is to directly check the biofilm formation by the use of novel antibiofilm materials, local drug delivery, and device-associated surface modifications, but the success of these techniques is still limited. The immense expansion in the field of nanoscience and nanotechnology has resulted in the development of novel nanomaterials as biocidal agents that can be either easily integrated within biomaterials to prevent the colonization of microbial cells or directly approach the pathogen overcoming the biofilm matrix. The antibiofilm efficacies of these nanomaterials are accomplished by the generation of oxidative stresses and through alterations of the genetic expressions. Microorganism-assisted synthesis of nanomaterials paved the path to success in such therapeutic approaches and is found to be more acceptable for its „greener” approach. Metallic nanoparticles functionalized with microbial enzymes, silver-platinum nanohybrids (AgPtNHs), bacterial nanowires, superparamagnetic iron oxide (Fe3O4), and nanoparticles synthesized by both magnetotactic and non-magnetotactic bacteria showed are some of the examples of such agents used to attack the EPS.It is believed that ferroelectrics may serve as efficient photocatalysts as well as photovoltaic materials but for their large bandgaps which does not allow them to absorb a large part of the solar spectrum. We have explored theoretically within ab-initio density functional theory-based calculations, the efficacy of Cu and Te to co-dope BaTiO3 in reducing its bandgap while retaining its ferroelectric properties. Examining a dopant concentration of 11%, we find an insulating ground state being realized with a band gap reduction of 0.42 eV from the value for undoped BaTiO3 for some doping configurations. Ferroelectric distortions are found to survive even in the presence of doping suggesting possible applications in photocatalysis as well as photovoltaics.Two essential oils were isolated from discarded perfume lemon and leaves (Citrus limon (L.) Burm. F.) by hydro-distillation with good yield (0.044% for perfume lemon and 0.338% for leaves). Their biological activities were evaluated against five selected bacterial strains and Aedes albopictus (Ae. albopictus, Diptera Culicidae). Chemical composition indicated that both essential oils were rich in essential phytochemicals including hydrocarbons, monoterpenes and sesquiterpene. These constituents revealed some variability among the oils displaying interesting chemotypes (R)-(+)-limonene (12.29-49.63%), citronellal (5.37-78.70%) and citronellol (2.98-7.18%). The biological assessments proved that the two essential oils had similar effect against bacterial (inhibition zones diameter ranging from 7.27 ± 0.06 to 10.37 ± 0.15 mm; MICs and MBCs ranging from 1.6 to 6.4 mg/mL); against Ae. albopictus larvae (LC50 ranging from 384.81 to 395.09 ppm) and adult mosquito (LD50 ranging from 133.059 to 218.962 μg/cm2); the activity of the two chemotypes ((R)-(+)-limonene and citronellal) larvae (LC50 ranging from 267.08 to 295.28 ppm), which were all presented in dose-dependent manners. Through this work, we have showcased that recycling and reusing of agriculture by-products, such as discarded perfume lemon and leaves can produce eco-friendly alternatives in bacterial disinfectants and mosquito control product.Developing efficient N2 and O2 gas sensors is of great importance to our daily life and industrial technology. In this work, first-principles calculations are performed to study the N2 and O2 gas-sensing properties of pure and defected PtSe2. It is found that both N2 and O2 adsorb weakly on pure PtSe2, and adsorption of the molecules induces negligible changes in the electrical and optical properties. Whereas the Pt@Se anti-site defect significantly improves the N2 adsorption capacity of PtSe2 and induces notable changes in the electrical property. Similar results are also observed for the Pt and Se vacancies and Pt@Se anti-site defects when examining O2 adsorption. In addition, notable changes in the optical absorption spectra of the PtSe2 with Pt@Se defect are induced upon N2 adsorption, which also occurs for PtSe2 with Pt and Se vacancies and Pt@Se anti-site defects upon O2 adsorption. These results demonstrate that PtSe2 with the corresponding defects can be both excellent electrical and optical sensors for detecting N2 and O2 gases. Our work offers a new avenue for preparing efficient gas sensors.Detection of cancer at an early stage is one of the principal factors associated with successful treatment outcome. However, current diagnostic methods are not capable of making sensitive and robust cancer diagnosis. Nanotechnology based products exhibit unique physical, optical and electrical properties that can be useful in diagnosis. These nanotech-enabled diagnostic representatives have proved to be generally more capable and consistent; as they selectively accumulated in the tumor site due to their miniscule size. This article rotates around the conventional imaging techniques, the use of carbon based nanodots viz Carbon Quantum Dots (CQDs), Graphene Quantum Dots (GQDs), Nanodiamonds, Fullerene, and Carbon Nanotubes that have been synthesized in recent years, along with the discovery of a wide range of biomarkers to identify cancer at early stage. Early detection of cancer using nanoconstructs is anticipated to be a distinct reality in the coming years.A series of novel pyran-linked phthalazinone-pyrazole hybrids were designed and synthesized by a facile one-pot three-component reaction employing substituted phthalazinone, 1H-pyrazole-5-carbaldehyde, and active methylene compounds. Optimization studies led to the identification of L-proline and ethanol as efficient catalyst and solvent, respectively. This was followed by evaluation of anticancer activity against solid tumor cell lines of lung and cervical carcinoma that displayed IC50 values in the range of 9.8-41.6 µM. Molecular modeling studies were performed, and crucial interactions with the target protein were identified. The drug likeliness nature of the compounds and molecular descriptors such as molecular flexibility, complexity, and shape index were also calculated to understand the potential of the synthesized molecules to act as lead-like molecule upon further detailed biological investigations as well as 3D-QSAR studies.Knots have attracted scientists in mathematics, physics, biology, and engineering. Long flexible thin strings easily knot and tangle as experienced in our daily life. Similarly, long polymer chains inevitably tend to get trapped into knots. Little is known about their formation or function in proteins despite >1,000 knotted proteins identified in nature. However, these protein knots are not mathematical knots with their backbone polypeptide chains because of their open termini, and the presence of a „knot” depends on the algorithm used to create path closure. Furthermore, it is generally not possible to control the topology of the unfolded states of proteins, therefore making it challenging to characterize functional and physicochemical properties of knotting in any polymer. Covalently linking the amino and carboxyl termini of the deeply trefoil-knotted YibK from Pseudomonas aeruginosa allowed us to create the truly backbone knotted protein by enzymatic peptide ligation. Moreover, we produced and investigated backbone cyclized YibK without any knotted structure. Thus, we could directly probe the effect of the backbone knot and the decrease in conformational entropy on protein folding. The backbone cyclization did not perturb the native structure and its cofactor binding affinity, but it substantially increased the thermal stability and reduced the aggregation propensity. The enhanced stability of a backbone knotted YibK could be mainly originated from an increased ruggedness of its free energy landscape and the destabilization of the denatured state by backbone cyclization with little contribution from a knot structure. Despite the heterogeneity in the side-chain compositions, the chemically unfolded cyclized YibK exhibited several macroscopic physico-chemical attributes that agree with theoretical predictions derived from polymer physics.The serious shuttle effect, low conductivity, and large volume expansion have been regarded as persistent obstacles for lithium sulfur (Li-S) batteries in its practical application. Carbon materials, such as graphene, are considered as promising cathode hosts to alleviate those critical defects and be possibly coupled with other reinforcement methods to further improve the battery performance. However, the open structure of graphene and the weak interaction with sulfur species restrict its further development for hosting sulfur. Herein, a rational geometrical design of hierarchical porous graphene-like bubbles (PGBs) as a cathode host of the Li-S system was prepared by employing magnesium oxide (MgO) nanoparticles as templates for carbonization, potassium hydroxide (KOH) as activation agent, and car tal pitch as a carbon source. The synthesized PGBs owns a very thin carbon layer around 5 nm that can be comparable to graphite nanosheets. Its high content of mesoporous and interconnected curved structure can effectively entrap sulfur species and impose restrictions on their diffusion and shuttle effect, leading to a much stable electrochemical performance. The reversible capacity of PGBs@S 0.3 C still can be maintained at 831 mAh g-1 after 100 cycles and 512 mAh g-1 after 500 cycles.[This corrects the article DOI 10.3389/fpubh.2020.589359.].It took a white police officer’s knee on George Floyd’s neck before white people began to reckon with 400 years of slavery and its aftermath, the effects of which Black people have endured for generations. Monuments are being taken down, flags are being redesigned, and institutions that honored those who denied the humanity of Black people are being renamed. Unfortunately for Sandra Bland, Breonna Taylor, Sha-Asia Washington and countless other Black transgender people including those with capacity for pregnancy, there was no justice even prior to the global pandemic of SARS-Cov-2 or coronavirus; namely racism, violence, and the Black Maternal Health crisis that makes it less likely that Black women will survive pregnancy and childbirth. The purpose of this article is to situate the state of Black people with the capacity for pregnancy in the context of these existing crises to illuminate the myths that racism has perpetuated through science, health services provision and policy. The greatest of these is the an actionable roadmap to specifically disrupt the myth of the default human and dismantle racism in education, provision of care, research, policies, and public health praxis.Background There is increased interest in early intervention and prevention of mental health difficulties during adolescence; thus, we are seeing increased efforts to optimize well-being during this epoch. Positive emotional experiences are a central component of overall well-being. However, research exploring what adolescents perceive to be the cause(s) of their emotional difficulties is lacking. Improving understanding of this issue within non-clinical adolescent groups may provide useful insight into how to develop strategies to support young people as they navigate emotional difficulties. Objectives The aim of this research was to explore if meaningful categories of perceived cause(s) for emotional distress exist for non-clinical adolescent groups. Methods The data for this study were drawn from interviews across 6 sites in England conducted as part of the 5-year national evaluation of the HeadStart Learning Programme. The sample comprised of 32 young people aged 11-12 years from the first annual wave of qualitative data collection in 2017. Ideal type analysis-a qualitative form of person-centered analysis-was used to construct a typology of adolescents perceived cause(s) for emotional distress. Findings We identified five distinct categories of perceived cause (1) perceived lack of control; (2) unfair treatment; (3) others, their actions and judgements as the catalyst; (4) concerns for self and others; and, (5) self as cause. Conclusions Our findings illustrate that distinct categories for perceived cause of emotional distress exist among adolescents considered to be „at risk” of developing mental health difficulties, which provides a foundation for future necessary work seeking to investigate the possible link between perceived cause for emotional distress and help-seeking behavior among sub-clinical groups.Coronavirus disease 2019 (COVID-19) is caused by a new coronavirus, namely severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and is currently spreading all over the world. In this paper, we developed a practical model for identifying the features of cytokine storm, which is common in acute infectious diseases and harmful manifestation of COVID-19, by distinguishing major and minor clinical events. This model is particularly suitable for identifying febrile and infectious diseases like COVID-19. Based on this model, features of cytokine storm and pathogenesis of COVID-19 have been proposed to be a consequence of the disequilibrated cytokine network resulting from increased biological activity of transforming growth factor-β (TGF-β), which induces certain clinical manifestations such as fatigue, fever, dry cough, pneumonia, abatement and losing of olfactory, and taste senses in some patients. Research and clarification of the pathogenesis of COVID-19 will contribute to precision treatment. Various anti-TGF-β therapies may be explored as potential COVID-19 treatment. This novel model will be helpful in reducing the widespread mortality of COVID-19.Background Despite increasing calls for further spread of evidence-based collaborative care interventions (EBIs) in community-based settings, practitioner-driven efforts are often stymied by a lack of experience in addressing barriers to community-based implementation, especially for those not familiar with implementation science. The Michigan Mental Health Integration Partnership (MIP) is a statewide initiative that funds projects that support implementation and uptake of EBIs in community-based settings. MIP also provides an in situ implementation laboratory for understanding barriers to the uptake of EBIs across a variety of settings. We report findings from a statewide qualitative study of practitioners involved in MIP projects to garner their perspectives of best practices in the implementation of EBIs. Methods Twenty-eight semi-structured interviews of practitioners and researchers from six MIP Projects were conducted with individuals implementing various MIP EBI projects across Michigan, including staksuccessful uptake and evaluation. Our community-informed MIP Implementation Roadmap, offering generalized steps for reaching successful implementation, uses experiences from a diverse set of MIP teams to guide practitioners through the practices necessary for scaling up EBIs in community-based settings over pre-implementation, implementation and sustainability phases.Despite significant progress on the proportion of individuals who know their HIV status in 2020, Côte d’Ivoire (76%), Senegal (78%), and Mali (48%) remain far below, and key populations (KP) including female sex workers (FSW), men who have sex with men (MSM), and people who use drugs (PWUD) are the most vulnerable groups with a HIV prevalence at 5-30%. HIV self-testing (HIVST), a process where a person collects his/her own specimen, performs a test, and interprets the result, was introduced in 2019 as a new testing modality through the ATLAS project coordinated by the international partner organisation Solthis (IPO). We estimate the costs of implementing HIVST through 23 civil society organisations (CSO)-led models for KP in Côte d’Ivoire (N = 7), Senegal (N = 11), and Mali (N = 5). We modelled costs for programme transition (2021) and early scale-up (2022-2023). Between July 2019 and September 2020, a total of 51,028, 14,472, and 34,353 HIVST kits were distributed in Côte d’Ivoire, Senegal, and Mali, respectation of the HIVST programme into CSO activities, this model shows large potential for substantial economies of scale. Further research will assess the overall cost-effectiveness of this model.Background The pneumococcal vaccine has been considered as the most effective measure to prevent pneumococcal diseases. In 2013, Shanghai launched a major public health program to vaccinate people aged 60 years or older with 23-Valent Pneumococcal Polysaccharide Vaccine (PPSV-23) free of charge. By the end of June 2020, a total of 1.56 million old people had been vaccinated free of charge. Objective To evaluate the cost-effectiveness of PPSV-23 vaccination program in Shanghai from the health system perspective. Methods According to the actual number of people aged 60 years or older with PPSV-23 vaccination in Shanghai from 2013 to 2018, a multi-cohort Markov model for life-time was developed to compare health and economic outcomes of vaccinated people vs. if they were not vaccinated for PPSV-23. Cost effectiveness was reported as incremental cost effectiveness ratio (ICER). A 5% discount rate was used for both costs and health outcomes. In addition, one-way sensitivity analysis was used to test the model’s robustness. Results By the end of 2018, a total of 1,091,967 people aged 60 years or older were vaccinated with PPSV-23 in Shanghai, China. Comparing with the unvaccinated circumstances, PPSV-23 vaccination would cost US $19.62 million more and receive an additional 10,321.3 quality-adjusted life-year (QALY). PPSV-23 was associated with the ICER of $190.1 per QALY gained. The Results were sensitive to the variation of vaccine effectiveness against community-acquired pneumonia (CAP), and disease incidence, mortality, and costs of CAP. In all sensitivity analysis, the PPSV-23 was economical. Conclusion The PPSV-23 vaccination program in Shanghai was cost-effective. With the further development of the project, the administrative costs of the vaccine will be reduced, making it more cost-effective.Glyphosate is the most commonly used herbicide around the world, which led to its accumulation in the environment and consequent ubiquitous human exposure. Glyphosate is marketed in numerous glyphosate-based herbicide formulations (GBHs) that include co-formulants to enhance herbicidal effect of the active ingredient, but are declared as inert substances. However, these other ingredients can have biologic activity on their own and may interact with the glyphosate in synergistic toxicity. In this study, we focused to compare the cytogenetic effect of the active ingredient glyphosate and three marketed GBHs (Roundup Mega, Fozat 480, and Glyfos) by investigating cytotoxicity with fluorescent co-labeling and WST-1 cell viability assay as well as genotoxicity with cytokinesis block micronucleus assay in isolated human mononuclear white blood cells. Glyphosate had no notable cytotoxic activity over the tested concentration range (0-10,000 μM), whereas all the selected GBHs induced significant cell death from 1,000 e fact that GBHs are still currently in use, the toxicity of which rivals that of POEA-containing formulations (e.g., Glyfos) already banned in Europe. Hence, it is advisable to subject them to further comprehensive toxicological screening to assess the true health risks of exposed individuals, and to reconsider their free availability to any users.Introduction Social or physical distancing has been an effective measure for reducing the spread of COVID-19 infections. Investigating the determinants of adherence to social distancing can inform public health strategies to improve the behaviour. However, there is a lack of data in various populations. This study investigates the degree to which South Africans complied with social distancing during the country’s COVID-19 lockdown and identifies the determinants associated with being in close contact with large numbers of people. Materials and Methods Data was collected from a South African national online survey on a data free platform, supplemented with telephone interviews. The survey was conducted from 8 to 29 April 2020. The primary outcome was the number of people that participants came into close contact with (within a 2-metre distance) the last time they were outside their home during the COVID-19 lockdown. Multivariate multinomial regression investigated the socio-demographic, psychosocial and househistancing regulations. Public health communication, interventions and policy can be tailored to address these determinants of social distancing.Although many studies have addressed the consequences of cyberbullying on mental health in secondary school, there is a lack of research in primary education. Moreover, most students who are cybervictims also suffer from traditional bullying, and studies on cyberbullying do not always control for the effects of the latter. The aim of our study is therefore to address the possible effects of cyberbullying on different aspects of the life and behavior of students in Years 3 to 6 of primary school. The sample consisted of 636 students attending 38 schools, as well as their parents. Children responded to a bullying and a cyberbullying questionnaire (the EBIPQ and ECIPQ, respectively), and their parents responded to three questionnaires the Strengths and Difficulties Questionnaire (SDQ), a sociodemographic questionnaire, and one on children’s experiences related to bullying and cyberbullying. The results reveal that 14.4% of the children, mostly boys, had suffered at least one online aggression in the previous 2 months. Most of them were also victims of traditional bullying. In this latter group, no differences were found between the SDQ scores reported by cybervictims and those reported by non-cybervictims. In contrast, those cybervictims who were not victims of traditional bullying displayed more difficulties in relation to Conduct problems, Externalizing problems, Home-life impact, and Total difficulties on the SDQ scales. Our results show that cyberbullying affects children’s lives as early as primary school, and especially boys, even in children who do not suffer from traditional bullying.Objective Fetus-in-fetu (FIF) is an extremely rare disease, and most prior publications are single case reports. Here, we describe the clinical characteristics, imaging manifestations, and the treatment and related complications of FIF from a large tertiary pediatric referral center. Materials After institutional review board approval, patients with a diagnosis of FIF between January 2010 and November 2019 were further selected and reexamined. We analyzed the general clinical characteristics, imaging manifestations, treatment, and prognosis of the patients. Results A total of seven (four male and three female) patients with FIF were included in the study. All patients were diagnosed with FIF during the antenatal ultrasound examination along with an abnormal increase in alpha fetoprotein, and it was confirmed by subsequent pathological examination. The median gestation period when FIF was first diagnosed was 25 (range 22-32) weeks. Ultrasound, computed tomography, and magnetic resonance imaging were the main pre-operative diagnostic techniques used.