Co2P/CoP embedded in N, P, S triply-doped hollow carbon towards enhanced oxygen electrocatalysis.

Simultaneously dispersing phosphide crystallites and multiple heteroatoms in hollow carbon is a significant yet challenging task for achieving high-performance oxygen electrocatalysts of zinc-air batteries. Herein, a simple wrapping-pyrolysis strategy is proposed to prepare Co2P/CoP embedded in N, P, S triply-doped hollow carbon (Co2P/CoP@NPS-HC). Co2P/CoP@NPS-HC composite features hollow polyhedral structure populated with numerous catalytically active Co2P/CoP nanoparticles and N, P, S heteroatoms. This optimized catalyst exhibits excellent activity for oxygen reduction reaction, with a half-wave potential of 0.82 V vs. RHE, and impressive enhancement for oxygen evolution reaction, indicated by an overpotential of 400 mV at 10 mA cm-2. Moreover, Co2P/CoP@NPS-HC catalyst exhibits greater durability and superior methanol tolerance compared to commercial Pt/C. The excellent bifunctional electrocatalytic performance of Co2P/CoP@NPS-HC catalyst is attributed to the synergistic effect of uniformly dispersed Co2P/CoP nanoparticles and N, P, S triply-doped hollow carbon structure. The former provides abundant catalytically active sites, while the latter offers a high accessible specific surface area, as well as enhances catalytic activity and electronic conductivity due to its altered charge distribution.

Hepatocyte growth factor-modified adipose-derived mesenchymal stem cells inhibit human hypertrophic scar fibroblast activation.

PURPOSE: Nucleoside-modified messenger RNA (modRNA) holds the potential for facilitating genetic enhancement of stem cells. In this study, modRNA encoding hepatocyte growth factor (modHGF) was used to chemically modify adipose-derived mesenchymal stem cells (ADSCs) and the effect of modified ADSCs on the activation of hypertrophic scar fibroblasts (HSFs) was evaluated. METHODS: CCK-8, wound healing, and transwell assays were utilized to evaluate the viability and migratory potential of modHGF-engineered ADSCs and their effect on HSF activation. Reverse transcription-polymerase chain reaction, western blot, and immunofluorescence staining were performed to detect the expression of collagen-I (Col I), collagen-III (Col III), alpha-smooth muscle actin (α-SMA), matrix metallopeptidase 1 (MMP-1), and MMP-3. RESULTS: Transfection of ADSCs with modHGF (HGF-ADSC) resulted in enhanced production of HGF. Meanwhile, modHGF modification enhanced the viability and migration of ADSCs. Notably, culture media from HGF-ADSCs exhibited a more potent inhibitory effect on the proliferation and migration of HSFs. In addition, culture media from HGF-ADSCs inhibited extracellular matrix synthesis of HSFs, as evidenced by reduced expression levels of Col I, Col III, and α-SMA, while increasing expression of MMP-1 and MMP-3. Conversely, neutralization experiments confirmed that these effects could be effectively alleviated by blocking HGF activity. CONCLUSION: modHGF modification optimizes the inhibitory effect of ADSCs on HSF activation, which provides a promising alternative for preventing and treating hyperplastic scars.

Iron deficiency anemia and platelet dysfunction: A comprehensive analysis of the underlying mechanisms.

AIMS: This research aimed to study the changes in platelet function and their underlying mechanisms in iron deficiency anemia. MAIN METHODS: Initially, we evaluated platelet function in an IDA mice model. Due to the inability to accurately reduce intracellular Fe2+ concentrations, we investigated the impact of Fe2+ on platelet function by introducing varying concentrations of Fe2+. To probe the underlying mechanism, we simultaneously examined the dynamics of calcium in the cytosol, and integrin αIIbß3 activation in Fe2+-treated platelets. Ferroptosis inhibitors Lip-1 and Fer-1 were applied to determine whether ferroptosis was involved in this process. KEY FINDINGS: Our study revealed that platelet function was suppressed in IDA mice. Fe2+ concentration-dependently facilitated platelet activation and function in vitro. Mechanistically, Fe2+ promoted calcium mobilization, integrin αIIbß3 activation, and its downstream outside-in signaling. Additionally, we also demonstrated that ferroptosis might play a role in this process. SIGNIFICANCE: Our data suggest an association between iron and platelet activation, with iron deficiency resulting in impaired platelet function, while high concentrations of Fe2+ contribute to platelet activation and function by promoting calcium mobilization, αIIbß3 activation, and ferroptosis.

[Characterization of Metal Elements in Atmospheric Fine Particulate Matter and Their Sources in Winter in the Southern Sichuan Urban Agglomeration].

To investigate the concentration characteristics and sources of metal elements in PM2.5 during winter heavy pollution in the southern Sichuan urban agglomeration (Zigong, Luzhou, Neijiang, and Yibin), the metal elements in PM2.5 were measured using membrane sampling methods from December 30, 2018 to January 14, 2019, and the enrichment factor method (EF) and positive matrix factorization(PMF) were applied to investigate the sources of metal elements. The metal element observation data of Zigong in the same period of 2015 were also used to investigate the changes in metal element pollution and enrichment in Zigong in the middle and end of the implementation of China's Air Pollution Prevention and Control Action Plan. The main findings were as follows:① The concentrations and percentages of metal elements in particulate matter in different cities did not differ significantly. The elements with higher concentrations in the four cities showed similarities, with Al, Sb, and Fe at the top. From the comparison of different observation periods in Zigong, the concentrations of all elements except Tl changed. ② The results of the enrichment factor calculation showed that the enrichment of the elements Cr (Zigong and Yibin), Ni, Cu, As, Se, Ag, Cd, Sb, Tl, and Pb in the urban agglomeration was high. The comparison of the enrichment levels of elements in Zigong for different observation periods showed that the enrichment levels of all elements, except Cu, tended to decrease in the winter observation period of 2018. ③ The results of PMF source analysis showed that the metal elements in each city mainly originated from dust sources, coal-fired sources, industrial sources, and traffic sources, whereas there was a mixed contribution among the sources. The contribution of the main sources differed among cities, in which Zigong was dominated by traffic dust sources and mixed sources, Luzhou was dominated by industrial sources, Neijiang had a similar contribution from different sources, and Yibin was dominated by traffic sources.

Supersulfides suppress type-â and type-â ¡ interferon responses by blocking JAK/STAT signaling in macrophages.

Interferons (IFNs) are cytokines produced and secreted by immune cells when viruses, tumor cells, and so forth, invade the body. Their biological effects are diverse, including antiviral, cell growth-inhibiting, and antitumor effects. The main subclasses of interferons include type-I (e.g., IFN-α and IFN-ß) and type-II (IFN-γ), which activate intracellular signals by binding to type-I and type-II IFN receptors, respectively. We have previously shown that when macrophages are treated with supersulfide donors, which have polysulfide structures in which three or more sulfur atoms are linked within the molecules, IFN-ß-induced cellular responses, including signal transducer and activator of transcription 1 (STAT1) phosphorylation and inducible nitric oxide synthase (iNOS) expression, were strongly suppressed. However, the subfamily specificity of the suppression of IFN signals by supersulfides and the mechanism of this suppression are unknown. This study demonstrated that supersulfide donor N-acetyl-L-cysteine tetrasulfide (NAC-S2) can inhibit IFN signaling in macrophages stimulated not only with IFN-α/ß but also with IFN-γ. Our data suggest that NAC-S2 blocks phosphorylation of Janus kinases (JAKs), thereby contributes to the inhibition of phosphorylation of STAT1. Under the current experimental conditions, hydrogen sulfide (H2S) donor NaHS failed to inhibit IFN signaling. Similar to NAC-S2, carbohydrate-based supersulfide donor thioglucose tetrasulfide (TGS4) was capable of strongly inhibiting tumor necrosis factor-αproduction, iNOS expression, and nitric oxide production from macrophages stimulated with lipopolysaccharide. Further understanding of molecular mechanisms how supersulfide donors exhibit their inhibitory actions towards JAK/STAT signaling is necessary basis for development of supersulfide-based therapeutic strategy against autoimmune disorders with dysregulated IFN signaling.

A global meta-analysis of yield-scaled N2 O emissions and its mitigation efforts for maize, wheat, and rice.

Maintaining or even increasing crop yields while reducing nitrous oxide (N2 O) emissions is necessary to reconcile food security and climate change, while the metric of yield-scaled N2 O emission (i.e., N2 O emissions per unit of crop yield) is at present poorly understood. Here we conducted a global meta-analysis with more than 6000 observations to explore the variation patterns and controlling factors of yield-scaled N2 O emissions for maize, wheat and rice and associated potential mitigation options. Our results showed that the average yield-scaled N2 O emissions across all available data followed the order wheat (322 g N Mg-1 , with the 95% confidence interval [CI]: 301-346) > maize (211 g N Mg-1 , CI: 198-225) > rice (153 g N Mg-1 , CI: 144-163). Yield-scaled N2 O emissions for individual crops were generally higher in tropical or subtropical zones than in temperate zones, and also showed a trend towards lower intensities from low to high latitudes. This global variation was better explained by climatic and edaphic factors than by N fertilizer management, while their combined effect predicted more than 70% of the variance. Furthermore, our analysis showed a significant decrease in yield-scaled N2 O emissions with increasing N use efficiency or in N2 O emissions for production systems with cereal yields >10 Mg ha-1 (maize), 6.6 Mg ha-1 (wheat) or 6.8 Mg ha-1 (rice), respectively. This highlights that N use efficiency indicators can be used as valuable proxies for reconciling trade-offs between crop production and N2 O mitigation. For all three major staple crops, reducing N fertilization by up to 30%, optimizing the timing and placement of fertilizer application or using enhanced-efficiency N fertilizers significantly reduced yield-scaled N2 O emissions at similar or even higher cereal yields. Our data-driven assessment provides some key guidance for developing effective and targeted mitigation and adaptation strategies for the sustainable intensification of cereal production.

Thioglucose-derived tetrasulfide, a unique polysulfide model compound.

Polysulfides have received increased interest in redox biology due to their role as the precursors of H2S and persulfides. However, the compounds that are suitable for biological investigations are limited to cysteine- and glutathione-derived polysulfides. In this work, we report the preparation and evaluation of a novel polysulfide derived from thioglucose, which represents the first carbohydrate-based polysulfide. This compound, thioglucose tetrasulfide (TGS4), showed excellent stability and water solubility. H2S and persulfide production from TGS4, as well as its associated antioxidative property were also demonstrated. Additionally, TGS4 was demonstrated to significantly induce cellular sulfane sulfur level increase, in particular for the formation of hydropersulfides/trisulfides. These results suggest that TGS4 is a useful tool for polysulfide research.

[Redox Biology Involved in the Toxicity of Enterohemorrhagic Escherichia coli Toxin SubAB].

AB5 toxins of pathogenic bacteria enter host cells and utilize the retrograde trafficking pathway to translocate to the cytoplasm and exert its pathogenesis. Cholera toxin and Shiga toxin reach the endoplasmic reticulum (ER), and the A subunit undergoes redox regulation by ER proteins to become active fragments, which pass through the ER membrane and translocate to the cytoplasm. By acting on molecular targets in the cytoplasm, the normal function of host cells are disrupted, causing diseases. ER chaperone proteins such as protein disulfide isomerase (PDI) and binding immunoglobulin protein (BiP) induce conformational changes triggered by the reduction of disulfide bonds in the A subunit. This is thought to be dependent on cysteine thiol-mediated redox regulation, but the detailed mechanism remains unclear. On the other hand, subtilase cytotoxin (SubAB), produced by enterohemorrhagic Escherichia coli (EHEC), localizes to the ER without translocating to the cytoplasm and cleaves BiP as a substrate. Therefore, it is thought that ER stress-based cytotoxicity and intestinal bleeding occur without translocating to the cytoplasm. We reported that PDI is involved in BiP cleavage through SubAB localization to the ER. Like other AB5 toxins, this indicates the involvement of redox regulation via chaperone proteins in the ER, but also suggests that SubAB does not translocate to the cytoplasm because it cleaves BiP. Although there are few reports on the redox state of ER protein thiols, it is suggested that polysulfidation, which is discussed in this symposium, may be involved.

Regulation of innate immune and inflammatory responses by supersulfides.

Innate immunity plays an important role in host defense against microbial infections. It also participates in activation of acquired immunity through cytokine production and antigen presentation. Pattern recognition receptors such as Toll-like receptors and nucleotide oligomerization domain-like receptors sense invading pathogens and associated tissue injury, after which inflammatory mediators such as pro-inflammatory cytokines and nitric oxide are induced. Supersulfides are molecular species possessing catenated sulfur atoms such as persulfide and polysulfide moieties. They have recently been recognized as important regulators in cellular redox homeostasis by acting as potent antioxidants and nucleophiles. In addition, recent studies suggested that supersulfides are critically involved in the regulation of innate immune and inflammatory responses. In this review, we summarize current knowledge of the chemistry and biology of supersulfides, with particular attention to their roles in regulation of innate immune, and inflammatory responses. Studies with animal models of infection and inflammation demonstrated the potent anti-inflammatory functions of supersulfides such as blocking pro-inflammatory signaling cascades, reducing oxidative stresses, and inhibiting replication of microbial pathogens including severe acute respiratory syndrome coronavirus 2. Precise understanding of how supersulfides regulate innate immune responses is the necessary requirement for developing supersulfide-based diagnostic as well as therapeutic strategies against inflammatory disorders.

Redox Regulation of Xenobiotics by Reactive Sulfur and Supersulfide Species.

Significance: Routine exposure to xenobiotics is unavoidable during our lifetimes. Certain xenobiotics are hazardous to human health, and are metabolized in the body to render them less toxic. During this process, several detoxification enzymes cooperatively metabolize xenobiotics. Glutathione (GSH) conjugation plays an important role in the metabolism of electrophilic xenobiotics. Recent Advances: Recent advances in reactive sulfur and supersulfide (RSS) analyses showed that persulfides and polysulfides bound to low-molecular-weight thiols, such as GSH, and to protein thiols are abundant in both eukaryotes and prokaryotes. The highly nucleophilic nature of hydropersulfides and hydropolysulfides contributes to cell protection against oxidative stress and electrophilic stress. Critical Issues: In contrast to GSH conjugation to electrophiles that is aided by glutathione S-transferase (GST), persulfides and polysulfides can directly form conjugates with electrophiles without the catalytic actions of GST. The polysulfur bonds in the conjugates are further reduced by perthioanions and polythioanions derived from RSS to form sulfhydrated metabolites that are no longer electrophilic but rather nucleophilic, and differ from metabolites that are formed via GSH conjugation. Future Directions: In view of the abundance of RSS in cells and tissues, metabolism of xenobiotics that is mediated by RSS warrants additional investigations, such as studies of the impact of microbiota-derived RSS on xenobiotic metabolism. Metabolites formed from reactions between electrophiles and RSS may be potential biomarkers for monitoring exposure to electrophiles and for studying their metabolism by RSS. Antioxid. Redox Signal. 40, 679-690.

Internalization, physiological responses and molecular mechanisms of lettuce to polystyrene microplastics of different sizes: Validation of simulated soilless culture.

Microplastics (MPs) exists widely in the environment, and the resulting pollution of MPs has become a global environmental problem. Plants can absorb MPs through their roots. However, studies on the mechanism of the effect of root exposure to different size MPs on vegetables are limited. Here, we use Polystyrene (PS) MPs with different particle sizes to investigate the internalization, physiological response and molecular mechanism of lettuce to MPs. MPs may accumulate in large amounts in lettuce roots and migrate to the aboveground part through the vascular bundle, while small particle size MPs (SMPs, 100 nm) have stronger translocation ability than large particle size MPs (LMPs, 500 nm). MPs can cause physiological and biochemical responses and transcriptome changes in lettuce. SMPs and LMPs resulted in reduced biomass (38.27 % and 48.22 % reduction in fresh weight); caused oxidative stress (59.33 % and 47.74 % upregulation of SOD activity in roots) and differential gene expression (605 and 907 DEGs). Signal transduction, membrane transport and alteration of synthetic and metabolic pathways may be the main causes of physiological toxicity of lettuce. Our study provides important information for understanding the behavior and fate of MPs in edible vegetables, especially the physiological toxicity of MPs to edible vegetables, in order to assess the potential threat of MPs to food safety and agricultural sustainable development.

PDIA6, which is regulated by TRPM2-AS/miR-424-5p axis, promotes endometrial cancer progression via TGF-beta pathway.

PDIA6 have been reported to be involved in a variety of cancers, however, the underlying role in endometrial cancer is still unclear. In this study, we aimed to study the function of PDIA6 in endometrial cancer. Firstly, we verified that PDIA6 was significantly upregulated in endometrial cancer, which was correlated with the progression of endometrial cancer patients. Furthermore, we identified PDIA6 significantly altered the ability of endometrial cancer cells to proliferate and metastasize. In addition, our result illustrated the oncogene effects of PDIA6 in promoting malignant biological behavior of endometrial cancer cells by regulating TGF-ß pathway and being modulated by TRPM2-AS/miR-424-5p axis for the first time. Taken together, this study suggested that PDIA6 may be a new candidate target for endometrial cancer therapy.

Turkish Plants, Including Quercetin and Oenothein B, Inhibit the HIV-1 Release and Accelerate Cell Apoptosis.

The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

Alkyl gallates inhibit serine O-acetyltransferase in bacteria and enhance susceptibility of drug-resistant Gram-negative bacteria to antibiotics.

A principal concept in developing antibacterial agents with selective toxicity is blocking metabolic pathways that are critical for bacterial growth but that mammalian cells lack. Serine O-acetyltransferase (CysE) is an enzyme in many bacteria that catalyzes the first step in l-cysteine biosynthesis by transferring an acetyl group from acetyl coenzyme A (acetyl-CoA) to l-serine to form O-acetylserine. Because mammalian cells lack this l-cysteine biosynthesis pathway, developing an inhibitor of CysE has been thought to be a way to establish a new class of antibacterial agents. Here, we demonstrated that alkyl gallates such as octyl gallate (OGA) could act as potent CysE inhibitors in vitro and in bacteria. Mass spectrometry analyses indicated that OGA treatment markedly reduced intrabacterial levels of l-cysteine and its metabolites including glutathione and glutathione persulfide in Escherichia coli to a level similar to that found in E. coli lacking the cysE gene. Consistent with the reduction of those antioxidant molecules in bacteria, E. coli became vulnerable to hydrogen peroxide-mediated bacterial killing in the presence of OGA. More important, OGA treatment intensified susceptibilities of metallo-ß-lactamase-expressing Gram-negative bacteria (E. coli and Klebsiella pneumoniae) to carbapenem. Structural analyses showed that alkyl gallate bound to the binding site for acetyl-CoA that limits access of acetyl-CoA to the active site. Our data thus suggest that CysE inhibitors may be used to treat infectious diseases caused by drug-resistant Gram-negative bacteria not only via direct antibacterial activity but also by enhancing therapeutic potentials of existing antibiotics.

Highly Antibacterial and Self-Healing Janus Fabric for Effective Body Moisture/Thermal Management and Durable Waterproof.

Despite the development of many functional fabrics, they are unable to meet practical needs due to their monolithic functions and low durability. Therefore, a multifunctional waterborne polyurethane nanodroplet containing disulfide bonds (WSPU) was synthesized using a simple and environmentally friendly approach. The functional WSPU nanodroplet coating endowed fabrics with a variety of properties, including exceptional hydrophobicity, antibacterial properties, self-healing at room temperature, directional transport, etc. The functionalized fabric demonstrated durable mechanical and chemical stabilities due to the combined effects of disulfide bond reconstruction and hydrophobic chain migration. It exhibited the ability to regain its hydrophobic properties at room temperature after 50 friction cycles were performed without requiring external stimulation. Furthermore, the fabric maintained a water contact angle above 140°, even after being subjected to washing, boiling, and immersion in acid and alkali solutions. In addition, as a result of the fabric's Janus-like wettability, it performed various functions in accordance with varying weather conditions, in terms of wearing comfort and breathability. In hot weather or during exercise, the Janus fabric with the hydrophilic side facing outward enhances the process of sweat-directed perspiration, resulting in a notable cooling effect. On rainy days, the Janus fabric, when positioned with the hydrophobic side facing outward, exhibited excellent waterproof performance. This study presents an opportunity to explore the development of multifunctional fabrics through the combined effects of several functions.

Extracorporeal membrane oxygenation for COVID-19 and influenza associated acute respiratory distress syndrome: a systematic review.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been used extensively for H1N1 influenza and coronavirus disease 2019 (COVID-19)-related acute respiratory distress syndrome (ARDS) to improve gas exchange and quickly correct hypoxemia and hypercapnia. This systematic review summarized the evidence on ECMO for the treatment of COVID-19 and influenza-associated ARDS. RESEARCH DESIGN AND METHODS: This is a systematic review and meta-analysis of studies to compare the efficacy and safety of ECMO with conventional mechanical ventilation in adults with COVID-19 and influenza-associated ARDS. The study performed a structured search on PubMed, Embase, Web of Science, Scopus and The Cochrane Library. The primary outcome was hospital mortality. RESULTS: The study included 15 observational studies with 5239 patients with COVID-19 and influenza-associated ARDS. The use of ECMO significantly reduced in-hospital mortality in COVID-19-associated ARDS (OR = 0.40; 95% CI = 0.27-0.58; P < 0.00001) but did not reduce influenza-related mortality (OR = 1.08; 95% CI = 0.41-2.87; P = 0.87). Moreover, ECMO treatment meaningfully increased the incidence of bleeding complications (OR = 7.66; 95% CI = 2.47-23.72; P = 0.0004). CONCLUSION: The use of ECMO significantly reduced in-hospital mortality in COVID-19- associated ARDS, which may be related to the advances in ECMO-related techniques and the increased experience of clinicians. However, the incidence of bleeding complications remains high. [Figure: see text].

AAV9-Tspyl2 gene therapy retards bleomycin-induced pulmonary fibrosis by modulating downstream TGF-ß signaling in mice.

Idiopathic pulmonary fibrosis (IPF) is a devastating fibrotic lung disease characterized by scarring and destruction of the lung architecture, with limited treatment options. Targeted gene therapy to restore cell division autoantigen-1 (CDA1) expression may be a potential treatment approach to delay the progression of pulmonary fibrosis (PF). Here, we focused on CDA1, which was significantly decreased in human IPF, in a mouse model of bleomycin (BLM)-induced PF, and in transforming growth factor (TGF-ß)-challenged lung fibroblasts. In vitro, CDA1 overexpression by lentivirus infection in human embryonic lung fibroblasts (HFL1 cells) inhibited the production of pro-fibrotic and pro-inflammatory cytokines, lung fibroblast-to-myofibroblast transition, and extracellular matrix protein expression induced by exogenous TGF-ß1 treatment, whereas CDA1 knockdown with small interfering RNA promoted this effect. CDA1 overexpression also inhibited cell proliferation and migration. In a mouse model of BLM-induced PF, we provided novel evidence that the intratracheal delivery of adeno-associated virus serotype 9 carrying the mouse Tspyl2 gene reduced lung tissue inflammation and fibrosis. Mechanistically, CDA1, as a transcription regulator, could repress the TGF-ß signal transduction in vivo and in vitro. In conclusion, our results show that Tspyl2 gene therapy plays an antifibrotic role by inhibiting the lung fibroblast-to-myofibroblast transition and downstream TGF-ß/Smad3 signaling transduction in BLM-induced PF in mice, suggesting that CDA1 is an appropriate and promising therapeutic target for PF.

Abandoned disposable masks become hot substrates for plastisphere, whether in soil, atmosphere or water.

A large number of surgical masks (SMs) to be discarded indiscriminately during the spread of COVID-19. The relationship between the changes of masks entering the environment and the succession of the microorganisms on them is not yet clear. The natural aging process of SMs in different environments (water, soil, and atmosphere) was simulated, the changes and succession of the microbial community on SMs with aging time were explored. The results showed that the SMs in water environment had the highest aging degree, followed by atmospheric environment, and SMs in soil had the lowest aging degree. The results of high-throughput sequencing demonstrated the load capacity of SMs for microorganisms, showed the important role of environment in determining microbial species on SMs. According to the relative abundance of microorganisms, it is found that compared with the water environment, the microbial community on SMs in water is dominated by rare species. While in soil, in addition to rare species, there are a lot of swinging strains on the SMs. Uncovering the ageing of SMs in the environment and its association with the colonization of microorganisms will help us understand the potential of microorganisms, especially pathogenic bacteria, to survive and migrate on SMs.

Interactions between genetic variants and environmental risk factors are associated with the severity of pelvic organ prolapse.

OBJECTIVE: Both environmental and genetic risk factors contribute to pelvic organ prolapse (POP). No genome-wide study has investigated the gene-environment (G × E) interactions. In this study, we aim to identify single nucleotide polymorphisms (SNPs) that may interact with the potential environmental factors, maximum birth weight, and age in Chinese women. METHODS: We recruited 576 women for phase 1 and 264 women for phase 2 with stages III and IV prolapse from six geographic regions of China. Genomic DNAs from blood samples were genotyped using Affymetrix Axiom Genome-Wide CHB1 Array of 640,674 SNPs for phase 1 and Illumina Infinium Asian Screening Array of 743,722 SNPs for phase 2. Meta-analysis was used to combine the two results. Interactions of genetic variants with maximum birth weight and age on POP severity were identified. RESULTS: In phase 1, 502,283 SNPs in 523 women passed quality control and 450 women had complete POP-quantification measurements. In phase 2, 463,351 SNPs in 257 women passed quality control with complete POP-quantification measurements. Three SNPs rs76662748 ( WDR59 , Pmeta = 2.146 × 10 -8 ), rs149541061 ( 3p26.1 , Pmeta = 9.273 × 10 -9 ), and rs34503674 ( DOCK9 , Pmeta = 1.778 × 10 -9 ) respectively interacted with maximum birth weight, and two SNPs rs74065743 ( LINC01343 , Pmeta = 4.386 × 10 -8 ) and rs322376 ( NEURL1B - DUSP1 , Pmeta = 2.263 × 10 -8 ), respectively, interacted with age. The magnitude of disease severity associated with maximum birth weight and age differed according to genetic variants. CONCLUSIONS: This study provided preliminary evidence that interactions between genetic variants and environmental risk factors are associated with POP severity, suggesting the potential use of combining epidemiologic exposure data with selected genotyping for risk assessment and patient stratification.