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Background: More research is needed to solidify the basis for reasonable metronomic chemotherapy regimens due to the inconsistent clinical outcomes from studies on metronomic chemotherapy with antineoplastic agents, along with signs of a nonlinear dose-response relationship at low doses. The present study therefore explored the dose-response relationships of representative antineoplastic agents in low dose ranges and their underlying mechanisms., Methods: Cyclophosphamide (CPA) and 5-fluorouracil (5-Fu) were employed to observe the effects of the frequent administration of low-dose antineoplastic agents on tumor growth, tumor angiogenesis, and bone-marrow-derived cell (BMDC) mobilization in mouse models. The effects of antineoplastic agents on tumor and endothelial cell functions with or without BMDCs were analyzed in vitro ., Results: Tumor growth and metastasis were significantly promoted after the administration of CPA or 5-Fu at certain low dose ranges, and were accompanied by enhanced tumor angiogenesis and proangiogenic factor expression in tumor tissues, increased proangiogenic BMDC release in the circulating blood, and augmented proangiogenic BMDC retention in tumor tissues. Low concentrations of CPA or 5-Fu were found to significantly promote tumor cell migration and invasion, and enhance BMDC adhesion to endothelial cells in vitro ., Conclusion: These results suggest that there are risks in empirical metronomic chemotherapy using low-dose antineoplastic agents and the optimal dosage and administration schedule of antineoplastic agents need to be determined through further research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 You, Zhao, Zhao, Zheng, Ma, Cheng, Li, Kou and Feng.)

Developing more effective bioactive ingredients of natural origin is imperative for promoting wound healing. Sea cucumbers have long enjoyed a good reputation as both food delicacies and traditional medicines. In this study, we heterogeneously expressed a Apostichopus japonicus derived novel protein AjPSPLP-3, which exhibits a theoretical molecular weight of 13.034 kDa, through fusion with maltose binding protein (MBP). AjPSPLP-3 contains a strict CXXCXC motif, nine extremely conserved cysteine residues and two highly conserved cysteine residues. The predicted structure of AjPSPLP-3 consists of random coil and nine β-sheets, Cys 30 -Cys 67 , Cys 38 -Cys 58 , Cys 53 -Cys 90 , Cys 56 -Cys 66 , and Cys 81 -Cys 102 participating in the formation of five pairs of disulfide bonds. In vitro experiments conducted on HaCaT cells proved that AjPSPLP-3 and MBP-fused AjPSPLP-3 significantly contribute to HaCaT cells proliferation and migration without exhibiting hemolytic activity on murine erythrocytes. Specifically, treatment with 10 μmol/L MBP-fused AjPSPLP-3 protein increased the viability of HaCaT cells by 12.28 % (p < 0.001), while treatment with 10 μmol/L AjPSPLP-3 protein increased viability of HaCaT cells by 6.01 % (p < 0.01). Furthermore, wound closure of MBP-fused AjPSPLP-3 and AjPSPLP-3 were 22.51 % (p < 0.01) and 7.32 % (p < 0.05) higher than that of the control groups in HaCaT cells following 24 h of incubation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: This study sought to develop and assess an exploratory model of how demographic and psychosocial attributes, and drug use or acquisition behaviors interact to affect opioid-involved overdoses., Design: We conducted exploratory and confirmatory factor analysis (EFA/CFA) to identify a factor structure for ten drug acquisition and use behaviors. We then evaluated alternative structural equation models incorporating the identified factors, adding demographic and psychosocial attributes as predictors of past-year opioid overdose., Setting and Participants: We used interview data collected for two studies recruiting opioid-misusing participants receiving services from a community-based syringe services program. The first investigated current attitudes toward drug-checking (N = 150). The second was an RCT assessing a telehealth versus in-person medical appointment for opioid use disorder treatment referral (N = 270)., Measurements: Demographics included gender, age, race/ethnicity, education, and socioeconomic status. Psychosocial measures were homelessness, psychological distress, and trauma. Self-reported drug-related risk behaviors included using alone, having a new supplier, using opioids with benzodiazepines/alcohol, and preferring fentanyl. Past-year opioid-involved overdoses were dichotomized into experiencing none or any., Findings: The EFA/CFA revealed a two-factor structure with one factor reflecting drug acquisition and the second drug use behaviors. The selected model (CFI = .984, TLI = .981, RMSEA = .024) accounted for 13.1% of overdose probability variance. A latent variable representing psychosocial attributes was indirectly associated with an increase in past-year overdose probability (β = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (β = .683, p < .001) and drug use (β = .567, p = .001). Drug use behaviors (β = .287, p = .04) but not drug acquisition (β = .105, p = .461) also had a significant, positive direct effect on past-year overdose. No demographic attributes were significant direct or indirect overdose predictors., Conclusions: Psychosocial attributes, particularly homelessness, increase the probability of an overdose through associations with risky drug acquisition and drug-using behaviors. Further research is needed to replicate these findings with populations at high-risk of an opioid-related overdose to assess generalizability and refine the metrics used to assess psychosocial characteristics., (© 2024. The Author(s).)

Excessive formation of neutrophil extracellular traps (NETs) may lead to myositis-related interstitial lung disease (ILD). There is evidence that NETs can directly injure vascular endothelial cells and play a pathogenic role in the inflammatory exudation of ILD. However, the specific mechanism is unclear. This study aimed to investigate the specific mechanism underlying NET-induced injury to human pulmonary microvascular endothelial cells (HPMECs). HPMECs were stimulated with NETs (200 ng/ml) in vitro. Cell death was detected by propidium iodide staining. The morphological changes of the cells were observed by transmission electron microscopy (TEM). Pyroptosis markers were detected by western blot, immunofluorescence, and quantitative real-time polymerase chain reaction, and the related inflammatory factor Interleukin-1β (IL-1β) was verified by enzyme-linked immunosorbent assay (ELISA). Compared with the control group, HPMECs mortality increased after NET stimulation, and the number of pyroptosis vacuoles in HPMECs was further observed by TEM. The pulmonary microvascular endothelial cells (PMECs) of the experimental autoimmune myositis mouse model also showed a trend of pyroptosis in vivo. Cell experiment further confirmed the significantly high expression of the NLRP3 inflammasome and pyroptosis-related markers, including GSDMD and inflammatory factor IL-1β. Pretreated with the NLRP3 inhibitor MCC950, the activation of NLRP3 inflammasome and pyroptosis of HPMECs were effectively inhibited. Our study confirmed that NETs promote pulmonary microvascular endothelial pyroptosis by activating the NLRP3 inflammasome, suggesting that NETs-induced pyroptosis of PMECs may be a potential pathogenic mechanism of inflammatory exudation in ILD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Purpose: Chloride, the predominant anion in extracellular fluid from humans, is essential to maintaining homeostasis. One important metric for thoroughly assessing kidney function is the estimated glomerular filtration rate (eGFR). However, the relationship between variations in serum chloride concentration and eGFR in general populations has been poorly studied. Therefore, the purpose of this study is to elucidate the correlation between serum chloride levels and eGFR within the United States' adult population., Methods: This cohort study was conducted using data from the National Health and Nutrition Examination Survey (NHANES), which covered the years 1999-2018. We employed multiple linear regression analysis and subgroup analysis to evaluate the correlation between serum chloride concentration and eGFR. To examine the nonlinear association between serum chloride levels and eGFR, restricted cubic spline analyses were employed., Results: Data from 49,008 participants in this cohort study were used for the chloride analysis. In the comprehensively adjusted model, a noteworthy inverse relationship was discovered between chloride plasma concentration and eGFR. Restricted cubic spline analyses revealed a significant nonlinear relationship between chloride levels and eGFR (P for overall < 0.001 and P for nonlinear < 0.001). A significant interaction was observed between eGFR and plasma chloride concentration (all P < 0.001 for interaction) among the subgroups characterized by sex, household income to poverty ratio, BMI, hypertension, and diabetes., Conclusion: Our findings suggest that higher levels of chloride plasma concentration were linked to decreased eGFR. These findings underscore the significance of monitoring chloride plasma concentration as a potential indicator for identifying individuals at risk of developing chronic kidney disease (CKD)., (© 2024. The Author(s).)

Jingfang Granule (JFG), a traditional Chinese medicine, is frequently employed in clinical settings for the treatment of infectious diseases. Nevertheless, the anti-aging and anti-infection effects of JFG remain uncertain. In the present study, these effects were evaluated using the Caenorhabditis elegans (C. elegans) N2 as a model organism. The results demonstrated that JFG significantly increased the median lifespan of C. elegans by 31.2% at a dosage of 10 mg/mL, without any discernible adverse effects, such as alterations in the pharyngeal pumping rate or nematode motility. Moreover, JFG notably increased oviposition by 11.3%. Subsequent investigations revealed that JFG enhanced oxidative stress resistance in C. elegans by reducing reactive oxygen species levels and significantly improved survival rates in nematodes infected with Pseudomonas aeruginosa ATCC 9027. These findings suggest that JFG delays reproductive senescence in C. elegans and protects them from oxidative stress, thereby extending their lifespan. Additionally, JFG improves the survival of P. aeruginosa-infected nematodes. Consequently, JFG has potential as a candidate for the development of anti-aging and anti-infection functional medicines., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Histone acetylation modifications in filamentous fungi play a crucial role in epigenetic gene regulation and are closely linked to the transcription of secondary metabolite (SM) biosynthetic gene clusters (BGCs). Histone deacetylases (HDACs) play a pivotal role in determining the extent of histone acetylation modifications and act as triggers for the expression activity of target BGCs. The genus Chaetomium is widely recognized as a rich source of novel and bioactive SMs. Deletion of a class I HDAC gene of Chaetomium olivaceum SD-80A, g7489, induces a substantial pleiotropic effect on the expression of SM BGCs. The C. olivaceum SD-80A ∆g7489 strain exhibited significant changes in morphology, sporulation ability, and secondary metabolic profile, resulting in the emergence of new compound peaks. Notably, three polyketides (A1-A3) and one asterriquinone (A4) were isolated from this mutant strain. Furthermore, our study explored the BGCs of A1-A4, confirming the function of two polyketide synthases (PKSs). Collectively, our findings highlight the promising potential of molecular epigenetic approaches for the elucidation of novel active compounds and their biosynthetic elements in Chaetomium species. This finding holds great significance for the exploration and utilization of Chaetomium resources. KEY POINTS: • Deletion of a class I histone deacetylase activated secondary metabolite gene clusters. • Three polyketides and one asterriquinone were isolated from HDAC deleted strain. • Two different PKSs were reported in C. olivaceum SD-80A., (© 2024. The Author(s).)

A pair of new quinolone alkaloid enantiomers, ( Ra )-(-)-viridicatol ( 1 ) and ( Sa )-(+)-viridicatol ( 4 ), and seven known compounds, namely, 2 , 3 and 5 - 9 , were isolated from Penicillium christenseniae SD.84. The structures of 1 and 4 were determined using NMR and HRESIMS data. Theoretical calculations through CD and ECD confirmed 1 and 4 as a pair of enantiomers. The MIC values of 4 against Staphylococcus aureus and methicillin-resistant S. aureus were 12.4 and 24.7 μM, respectively, compound 1 had no inhibitory activity. Antimicrobial assays of 2 , 3 , and 5 - 7 showed a moderate activity against S. aureus and methicillin-resistant S. aureus . This study demonstrated the remarkable potential of Penicillium sp. to produce new drug-resistant leading compounds, thereby advancing the mining for new sources of antimicrobial agents.

The CRISPR sensing and detection technology has the advantages of cheap, simple, portable, high sensitivity, and high specificity, therefore is regarded as the "next-generation molecular diagnostic technology". Due to the specific recognition, cis -cleavage and nonspecific trans -cleavage capabilities, CRISPR-Cas systems have been implemented for the detection of nucleic acid targets (DNA and RNA) as well as non-nucleic acid targets (e.g., proteins, exosomes, cells, and small molecules). This review summarizes the current CRISPR sensing and detection technologies in terms of the activity characteristics of different Cas proteins, with the aim to understand the advantages and development history of different CRISPR sensing and detection technologies, as well as promote its development and application. Moreover, this review summarizes the applications of various CRISPR sensing and detection technologies according to the types of detection targets, hoping to facilitate the development of novel CRISPR sensing detection technology.

To easily load Pt on smoothy graphene synthesized by cathodic exfoliation method and achieve adjacent plane distribution of Pt, carbon dots (CDs) are used to construct anchoring points to load highly dispersed Pt species due to strong interaction between CDs and Pt species. The composite of Pt-CDs/graphene is synthesized via a continuous process of cathodic exfoliation-hydrothermal-impregnation-reduction. Characterization results indicate the distribution configuration of Pt varies from coated structure of CDs@Pt to dispersed configuration of CDs&Pt or Pt&CDs, then to wrapping configuration of Pt@CDs with increased amount of CDs. It's found that suitable introduction of CDs promotes the adjacent plane distribution of Pt species. The obtained best Pt-4CDs/G shows the low overpotential of 36 mV (10 mA⋅cm -2 ) and high mass activity of 3747.8 mA mg -1 at -40 mV towards electrocatalytic hydrogen evolution reaction (HER), 9.2 times more active than that of Pt/C (406.2 mA mg -1 ). The superior HER performance of Pt-4CDs/G is attributed to its relatively adjacent plane distribution of Pt, which supports high electrochemically active surface area and more adjacent Pt sites for H* adsorption. Benefitting from that, the HER process for Pt-4CDs/G favorably follows the Tafel pathway, resulting in low hydrogen adsorption free energy and excellent HER activity., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The excessive formation of neutrophil extracellular traps (NETs) has been demonstrated to be a pathogenic mechanism of idiopathic inflammatory myopathy (IIM)-associated interstitial lung disease (ILD). This study aimed to answer whether an experimental autoimmune myositis (EAM) model can be used to study IIM-ILD and whether NETs participate in the development of EAM-ILD. An EAM mouse model was established using skeletal muscle homogenate and pertussis toxin (PTX). The relationship between NETs and the ILD phenotype was determined via histopathological analysis. As NETs markers, serum cell-free DNA (cfDNA) and serum citrullinated histone 3 (Cit-H3)-DNA were tested. The healthy mouse was injected with PTX intraperitoneally to determine whether PTX intervention could induce NETs formation in vivo. Neutrophils isolated from the peripheral blood of healthy individuals were given different interventions to determine whether PTX and skeletal muscle homogenate can induce neutrophils to form NETs in vitro. EAM-ILD had three pathological phenotypes similar to IIM-ILD. Cit-H3, neutrophil myeloperoxidase, and neutrophil elastase were overexpressed in the lungs of EAM model mice. The serum cfDNA level and Cit-H3-DNA complex level were significantly increased in EAM model mice. Serum cfDNA levels were increased significantly in vivo intervention with PTX in mice. Both PTX and skeletal muscle homogenate-induced neutrophils to form NETs in vitro. EAM-ILD pathological phenotypes are similar to IIM-ILD, and NETs are involved in the development of ILD in a murine model of EAM. Thus, the EAM mouse model can be used as an ideal model targeting NETs to prevent and treat IIM-ILD., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: Community engagement is key to the success of sustainable public health interventions. This review highlights recent published studies that describe the use of community-engaged methods in sexually transmitted infection (STI) prevention research., Recent Findings: We organized the findings using a socio-ecological model. At the individual level, communities were engaged through participation in formative research, short-term consultations and community advisory board participation, as well as co-creation activities. At the interpersonal level, studies reviewed described peer-led interventions that leverage the influence and guidance of peers, patient-led interventions in the form of patient navigation and notification, as well as those that mobilize social networks and the power of social relationships to promote health. At the organizational and community level, multisectoral, multifacility collaborations between community, government, and academic stakeholders were highlighted. At the policy and population level, communities were engaged through community dialogues to disseminate research findings, as well as in developing strategic frameworks and clinical guidelines. Digital tools have also been leveraged for effective community engagement., Summary: Communities have an effective role to play in STI prevention and can be engaged at multiple levels. Future efforts may consider the use of community engagement tools highlighted in this review, including digital technologies that have the potential to reach more diverse end-users., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Antimicrobial peptides (AMPs) offer an opportunity to overcome multidrug resistance. Here, novel peptides were designed based on AMP fragments derived from sea cucumber hemolytic lectin to enhance anti-methicillin-resistant Staphylococcus aureus (MRSA) activity with less side effects. Two designed peptides, CGS19 (LARVARRVIRFIRRAW-NH2) and CGS20 (RRRLARRLIFFIRRAW-NH2), exhibited strong antibacterial activities against clinically isolated MRSA with MICs of 3-6 μM, but no obvious cytotoxicity was observed. Consistently, CGS19 and CGS20 exerted rapid bactericidal activity and effectively induced 5.9 and 5.8 log reduction of MRSA counts in mouse subeschar, respectively. Further, CGS19 and CGS20 kill bacteria not only through disturbing membrane integrity but also by binding formate-tetrahydrofolate ligase, a key enzyme in the folate metabolism pathway, thereby inhibiting the folate pathway of MRSA. CGS19 and CGS20 are promising lead candidates for drug development against MRSA infection. The dual mechanisms on the identical peptide sequence or scaffold might be an underappreciated manner of treating life-threatening pathogens.

Background: This study aims to identify the current status and factors influencing self-management of knee discomfort in middle-aged and elderly people in China., Methods: A stratified multistage cluster sampling method was used to select participants from communities in China from January 15 to May 31, 2020. A cross-sectional survey was conducted using the general information questionnaire and the Knee Joint Discomfort Self-management Scale. Univariate analysis and a generalized linear model were used to analyze the factors influencing self-management., Results: The prevalence of knee discomfort was 77%. Moderate to severe discomfort accounted for 30.5%. The average item score of self-management in 9640 participants was 1.98 ± 0.76. The highest and lowest levels were: 'daily life management' and 'information management'. Gender, ethnicity, education level, economic source, chronic disease, knee pain in the past month, and the degree of self-reported knee discomfort were significant predictors of self-management., Conclusion: The self-management of knee discomfort in middle-aged and elderly people is poor, and the degree of discomfort is a significant predictor. Healthcare providers should consider socioeconomic demographic and clinical characteristics to help these individuals improve their self-management skills. Attention should also be given to improving their ability to access health information and making them aware of disease risks., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Supercontinuum sources with high compactness are essential for applications such as optical sensing, airborne detection and communication systems. In the past decades, the adoption of bulky optical parametric amplifier to pump various chalcogenide glass waveguides are widely reported for on-chip mid-infrared supercontinuum generation, but this usually leads to a large volume of the whole system, and is not practical. Therefore, integrating advanced femtosecond fiber lasers with optical waveguides using nano-fabrication technology are highly desired. However, the scarcity of compact pump sources and the dispersion-matched high-nonlinearity waveguide in short wavelength regions have hindered the advancement of integrated supercontinuum source performances in the near and mid-infrared region. In this study, we demonstrate a broadband supercontinuum source from As 2 S 3 waveguide pumped by a compact dual-femtosecond solitons pulse source. The laser is completely fiber structured, and its wavelength can be readily tuned from 2 to 2.3 µm using Raman soliton self-frequency shift technology in a Tm 3+ -doped fiber amplifier. Furthermore, the As 2 S 3 waveguide is designed with controllable dispersion and high nonlinearity for a broadband supercontinuum generation. These results will advance the development of on-chip supercontinuum sources based on chalcogenide waveguides.

Idiopathic inflammatory myopathies (IIMs) are a group of systemic autoimmune diseases characterized by immune-mediated muscle injury. Abnormal neutrophil extracellular traps (NETs) can be used as a biomarker of IIM disease activity, but the mechanism of NET involvement in IIMs needs to be elucidated. Important components of NETs, including high-mobility group box 1, DNA, histones, extracellular matrix, serum amyloid A, and S100A8/A9, act as damage-associated molecular patterns (DAMPs) to promote inflammation in IIMs. NETs can act on different cells to release large amounts of cytokines and activate the inflammasome, which can subsequently aggravate the inflammatory response. Based on the idea that NETs may be proinflammatory DAMPs of IIMs, we describe the role of NETs, DAMPs, and their interaction in the pathogenesis of IIMs and discuss the possible targeted treatment strategies in IIMs., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Gemcitabine is an antimetabolite drug approved for the treatment of various cancers. However, its use is limited due to several issues such as stability, toxicity and drug resistance. Herein, we present the design and synthesis of a series of gemcitabine prodrugs with modifications on the 4- N -amino group by employing an acetylated l- or d-lysine moiety masked by different substitutions. Prodrugs 1-3 and 6-8 showed up to 2.4 times greater anticancer activity than gemcitabine in A549 lung cells, while they exhibited potent activity against BxPC-3 pancreatic cells with IC 50 values in the range of 7-40 nM. Moreover, prodrugs 2-3 and 7-8 were found to be less potent against CTSL low expression Caco-2 cells and at least 69-fold less toxic towards human normal HEK-293T cells compared to gemcitabine, leading to improved selectivity and safety profiles. Further stability studies showed that representative prodrugs 2 and 7 exhibited enhanced metabolic stability in human plasma, human liver microsomes and cytidine deaminase. Prodrug 1 can be cleaved by tumor cell-enriched CTSL to release parent drug gemcitabine. Overall, these results demonstrated that acetylated lysine conjugated gemcitabine prodrugs could serve as promising leads for further evaluation as new anticancer drugs., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Eosinophil-derived neurotoxin (EDN), an eosinophil degranulation product, is a good biomarker for eosinophilic inflammation of the airway. Several articles have shown that EDN levels are higher in patients with asthma than in controls, and EDN levels are correlated with the percentage of predicted forced expiratory volume in the first second (FEV 1 %) in patients with asthma. Their results were inconclusive. Methods: A comprehensive meta-analysis was performed to assess EDN levels between patients with asthma and controls, and the correlations between EDN and FEV 1 % in the patients with asthma. Fourteen relevant articles were identified from electronic data bases. Pooled standardized mean difference (SMD) with a 95% confidence interval (CI) for the difference of EDN levels between the patients with asthma and controls, and pooled coefficient (r) values with 95% CI for the correlations between EDN and FEV 1 %, respectively, were calculated. Results: A total of 14 articles were selected. Among the included reports, six articles related to the difference and eight essays on the correlation. Pooled effect size showed that EDN levels were higher in patients with asthma than in controls (SMD 2.85 [95% CI, 1.92-3.78]). Furthermore, the pooled effect size showed that EDN levels were negatively correlated with FEV 1 % in patients with asthma (r -0.21 [95% CI, -0.28 to -0.14]). Conclusion: EDN levels increased in the patients with asthma compared with in the controls. They were correlated with FEV 1 % in the patients with asthma, which indicated that EDN could be a reliable marker to monitor asthma's therapeutic effects.

The selection of base liquor plays a crucial role in the flavor of soaked greengage wine. This study aimed to investigate the effects of different base liquor treatments on the physicochemical characteristics and aroma composition of greengage wine. We carried out a comprehensive analysis using HPLC for the determination of organic acids and GC-MS for the determination of volatile aroma compounds, combined with sensory evaluation. The results showed that the red and yellow colors were the darkest in the high-alcohol group, while the citric acid content was the highest in the sake group (21.95 ± 2.19 g/L). In addition, the greengage wine steeped in 50% edible alcohol had more terpenes, a significantly higher concentration of acid-lipid compounds, and a more intense aroma compared to that of the low-alcohol group, whose typical aroma compounds were greatly reduced. The sensory results showed that the greengage wine treated with baijiu had a distinct alcoholic flavor, while almond flavors were more intense in the greengage wine treated with 15% edible alcohol. In this study, base liquor was used as the main influencing factor to provide new research ideas for the flavor optimization of soaked greengage wine.

HIV self-testing (HIVST) is recommended as a promising way to increase HIV testing uptake among MSM. MSM sometimes used HIVST kits together with their sexual partners or friends. However, limited data was reported on MSM's testing together behaviors with sexual partners and non-sexual contacts. Data were collected among MSM in China from June 2018 to June 2019. Eligible participants (referred to as "index participants") finished a baseline survey and applied for HIVST kits. They were encouraged to distribute the kits to other people (referred to as "alters"). Index participants finished a 3-month follow-up survey on the distribution and usage of the kits. Alters finished an online survey on the usage of HIVST kits after they returned the photographed testing results. Results were reported based on index participants and alters, respectively. Based on follow-up data, 138 index participants successfully motivated others for HIVST, most of them (77.5%) tested together with at least one alter. Around half of alters (52.3%) reported testing together with index participants. Index participants distributed more HIVST kits to friends than sexual partners. MSM who had ever tested for HIV were more likely to test together. Our study demonstrated that the testing together behaviors during HIVST distribution among sexual partners and social network contacts were common. The social network-based approach is essential in promoting testing together and HIV status disclosure among MSM., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

High-resolution mass spectrometry was extensively applied in molecular composition and transformation pathways of dissolved organic matter (DOM) in wastewater sludge treatments. Sample pretreatment methods and electrospray ionization (ESI) modes significant affect the accuracy of molecular characterization for DOM. This study investigated the effects of pretreatment methods (styrene divinyl benzene polymer (PPL), octadecyl (C18), and electrodialysis (ED)) on molecular characteristics of DOM in two typical wastewater sludges (waste activated sludge (WAS) and anaerobic digestion sludge (ADS)) analyzed by FT-ICR MS in both positive ESI (ESI (+)) and negative ESI (ESI (-)) modes. The results indicated that ED pretreatment exhibited the highest recovery rate of 70% ‒ 95% for sludge-derived DOM. ED and PPL performed well in recovering the different sludge-derived DOM with a high similarity of molecular characteristics (e.g., lipids, proteins/aliphatic, and lignins/CRAM-like), and the C18 method was ineffective in extracting carbohydrates, unsaturated hydrocarbons, and amino sugars. In addition, compared with single ESI (-) analysis mode, the molecular number identified by ESI (+) analysis mode was increased by 200%, especially, more unsaturated hydrocarbons and N-containing compounds were detected. Except for biogenic DOM, plenty of emerging containments (ECs) in sludge-derived DOM were identified; ESI (-) mode was more effectively in recognizing the alkyl benzene sulfonic acids (e.g., anionic surfactants); and ESI (+) mode was more effectively for plasticizers identification, for example, dioctyl terephthalate and dibutyl phthalate. This study illustrated that ED pretreatment coupled with FT-ICR MS in dual ESI modes could give more insights in complexed molecular information for DOM in wastewater sludge, and provides a theoretical basis for subsequent sludge treatments and disposals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Orsellinic acid (2,4-dihydroxy-6-methylbenzoic acid, OA) and its structural analog o-Orsellinaldehyde, have become widely used intermediates in clinical drugs synthesis. Although the research on the biosynthesis of such compounds has made significant progress, due to the lack of suitable hosts, there is still far from the industrial production of such compounds based on synthetic biology., Results: With the help of genome mining, we found a polyketide synthase (PKS, HerA) in the genome of the Hericium erinaceus, which shares 60% amino acid sequence homology with ArmB from Armillaria mellea, an identified PKS capable of synthesizing OA. To characterize the function of HerA, we cloned herA and heterologously expressed it in Aspergillus oryzae, and successfully detected the production of OA. Subsequently, the introduction of an incomplete PKS (Pks5) from Ustilago maydis containing only three domains (AMP-ACP-R), which was into herA-containing A. oryzae, the resulted in the production of o-Orsellinaldehyde. Considering the economic value of OA and o-Orsellinaldehyde, we then optimized the yield of these compounds in A. oryzae. The screening showed that when maltose was used as carbon source, the yields of OA and o-Orsellinaldehyde were 57.68 mg/L and 15.71 mg/L respectively, while the yields were 340.41 mg/Kg and 84.79 mg/Kg respectively in rice medium for 10 days., Conclusions: Herein, we successfully expressed the genes of basidiomycetes using A. oryzae heterologous host. As a fungus of ascomycetes, which not only correctly splices genes of basidiomycetes containing multiple introns, but also efficiently produces their metabolites. This study highlights that A. oryzae is an excellent host for the heterologous production of fungal natural products, and has the potential to become an efficient chassis for the production of basidiomycete secondary metabolites in synthetic biology., (© 2023. The Author(s).)

Recovering high-value biomaterials from anaerobic digestion sludge (ADS) has attracted considerable attention. However, the molecular features and biological effects of abundant dissolved organic matters (DOMs) in ADS are still unclear, which limits the efficient recycling and application of these bioproducts. This study investigated the molecular composition and transformation of DOMs recovered from ADS through a mild-temperature alkali-hydrothermal treatment (AHT) with ultrahigh-resolution mass spectrometry and energy spectroscopy, and the fertilizing effects of DOMs were evaluated by rice hydroponics. The results indicated that AHT processes significantly promoted the solubilization and release of DOMs from ADS, where most of DOMs molecules remained unchanged and mainly consisted of N-containing compounds with 1-3 N atoms, featuring aromatic or N-heterocyclic rings. Furthermore, AHT processes at pH of 9-10 induced the hydrolysis of partial protein-like substances in DOMs, which was accompanied by formation of heterocyclic-N compounds. Under AHT at pH of 11-12, protein-like and heterocyclic-N substances were increasingly decomposed into amino-N compounds containing 1 or 5 N atoms, while numerous oxygenated aromatic substances with phytotoxicity were degraded and removed from DOMs. Rice hydroponic test verified that ADS-derived DOMs recovered by AHT process at pH of 12 exhibited the highest bioactivity for rice growth, which was attributed to the abundance of amino compounds and humic substances. This study proposed a novel process for the recovery of high-quality liquid organic fertilizer from ADS through AHT process, which can further enrich the technical options available for the safe utilization of sludge resources., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Multiple regimens have been widely used in the eradication treatment of Helicobacter pylori infection in children. However, there is a lack of comparison and evaluation of their effectiveness in different regions of the world., Methods: Randomized controlled trials were retrieved. Review Manager 5.4, Stata SE 15 and R 4.0.4 statistical software were used to analyze date. The ranking probability is assessed according to the surfaces under cumulative ranking (SUCRA)., Results: 163 studies were eligible for this study, involving 336 arms and 18,257 children, and 10 different interventions. The results showed that the eradication rates of sequential therapy with probiotics (SP), bismuth-containing quadruple (Quadruple) therapy, concomitant therapy and PCN therapy were at least 90%. Cumulative ranking showed that SP therapy had the best eradication effect (SUCRA 92.7%) whereas Bismuth-containing triple therapy (B) had the worst (SUCRA 3.5%). Subgroup analysis suggested that SP therapy ranked first in China and other regions, and the ranking of Triple therapy with probiotics therapy (TP) was equally stable (SUCRA 72.0% vs 76.4% respectively). The security of the SP and TP therapy had great advantages., Conclusions: As for the eradication treatment of Helicobacter pylori infection in children, SP therapy ranks highest. SP and TP therapies are most safe., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liang, Zhu, Zhao, Zhu, Shi and Yuan.)

Introduction: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation., Method: We modulated the PI3K-AKT pathway in TIL isolated from cervical and ovarian cancer by application of AKT or PI3K inhibitors or CRISPR knockout of AKT1 and/or AKT2, and characterized their effects on TIL phenotype and effector function. Mechanistic study was further performed with RNA-seq analysis of AKT1/2 KO TIL in comparison to control TIL., Result: The inhibition of either PI3K or AKT led to an increase in the population of effector CD8 + T cells with upregulation of activation markers, elevated CD39 - CD69 - memory T cells, and significantly enhanced cytotoxicity when cocultured with tumor cell lines and patient-derived tumor samples. Moreover, dual knockout of AKT1 and AKT2 largely phenocopies the functional impact of AKT or PI3K inhibition on TIL. This result was further validated by RNA-seq analysis indicating that AKT1/2 ablation primarily regulates T cell differentiation and function-related programs., Conclusion: Modulation of PI3K-AKT signaling represents a promising strategy to enhance TIL stemness and cytotoxicity and improve the clinical outcome of current TIL-based therapy to treat solid tumors., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: The aim of this study was to describe the knee joint discomfort, self-management behavior, and quality of life (QoL) in the middle-aged and elderly people in China and to clarify the relationship between the knee joint discomfort, self-management behavior, and QoL., Methods: It is a cross-sectional study and in this study, a stratified multistage random sampling method was used to collect data on the three factors such as knee joint discomfort, self-management behavior, and QoL among the middle-aged and elderly people in the Hunan Province. Spearman's correlation analysis was used to test the relationship between the knee joint discomfort, self-management behavior, and QoL., Results: The results of the present study showed that among them, the prevalence of knee pain was the highest (52.1%), followed by knee weakness (42.5%), numbness (41.8%), cold feeling (40.0%), tenderness (38.3%), and distension feeling (37.5%). Average score of self-management of knee joint discomfort in the middle-aged and elderly people was 2.14 ± 0.67. The level of self-management in each dimension ranged from high to low as emotional management, daily management, symptoms management, and information management. The average scores of physical component summary (PCS) and mental component summary (MCS) were 42.85 ± 5.34 and 43.62 ± 8.43, respectively. The occurrence, frequency, and severity of discomfort symptoms were positively correlated with the symptoms management, daily management, information management, and self-management behaviors, and negatively correlated with the emotional management, PCS and MSC, except for the occurrence of discomfort symptoms ( P < 0.05)., Conclusion: Knee joint discomfort was prevalent in the middle-aged and elderly people. In addition, they displayed a low level of self-management behavior and poor QoL. The middle-aged and elderly people faced knee discomfort symptoms, the more frequent and severe symptoms, the higher level of symptom management, daily management, and information management, and the lower level of emotional management and QoL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Su, Zhou, Zhao, Zeng and Zhou.)

In recent years, there has been a significant rise in the importance of sustainability in business and personal life. Unsustainable techniques are used throughout the whole lifecycle of the clothing and textiles business, from the time it is made to the time it is recycled or thrown away. The garment sector and its customers must be ready for a more sustainable future as the government, corporations, and society turn their focus toward it. An investigation of how the apparel design industry (ADI) might adhere to the global value chain (GVC) in light of sustainable economic development (SED) and their relevance in China. This study analyzes the ADI moves up from one functional level to another within the global apparel value chain and what factors allow them to break into the global market. Researchers demonstrate that the existing sustainable operations in the AD industry are a long way from attaining the aims of economic development going hand in hand with the goals of economic sustainability by studying both the relevant literature and the industrial practices in the sector. This study relies on various case studies, proposes the "apparel global value chain" of governance-based sustainability, explores the implications of these models for areas with very varied degrees of development and diverse AD structures, and considers their implications for regional development and sustainability. As a development of a better knowledge of how fashion design contributes to economic sustainability. The study aims to examine how ADI uses economically sustainable techniques and how designers contribute to the creation of environmentally friendly goods., Competing Interests: The authors declare that they have no known conflicts of financial interest or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Dan Yu and Peipei Zhao.)

Aims: There is emerging evidence that antineoplastic agents and the cytotoxic effects on tumor tissues attenuate the benefits of chemotherapy due to tumor microenvironment changes. Nevertheless, the actual relationship between chemotherapy and recurrent tumors in which the genotypes differ from the original tumor after chemotherapy is unclear., Materials and Methods: Bone marrow transplantation, flow cytometer, immune inhibition and immunofluorescence will be utilized to investigate the effect of antineoplastic agents on bone-marrow-derived cells (BMDCs) release and recruitment, and to explore the pathways and mechanisms of antineoplastic agents in promoting tumor growth., Key Findings: Tumor growth and angiogenesis were significantly enhanced in the mouse model after treatment with antineoplastic agents such as cyclophosphamide, 5-fluorouracil, or cisplatin, along with large increases in proangiogenic vascular endothelial growth factor receptor-2 (VEGFR2 + ), β 3 + , CD11b + Gr-1 + , and VEGFR2 + β 3 + BMDCs in circulating blood. BMDC recruitment and VEGFR2 and β 3 mRNA transcription in tumor tissues were also enhanced by antineoplastic agents. Antineoplastic-agent-treated BMDCs markedly augmented tumor and endothelial cell proliferation, and β 3 mRNA transcription in endothelial cells (ECs)., Significance: The results suggested that antineoplastic-agent treatment augmented the tumor microenvironment by mobilizing proangiogenic BMDCs, enhancing BMDC recruitment and angiogenesis, and increasing BMDC-mediated tumor and EC functions. These results led to tumor growth and angiogenesis aggravation. It is paramount to elucidate the potential mechanism by which the cellular and molecular effects triggered by the antineoplastic agents attenuate the effects of cancer therapy, and thereafter to explore possible methods for improving tumor treatment efficacy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

The sperm DNA fragmentation index (DFI) is an objective indicator of male fertility. Currently, effective treatments for high sperm DFI are limited and traditional Chinese medicine (TCM) has certain advantages in this aspect. Yishen Tongluo formula (YSTL), a TCM formula, has been found to reduce DFI in patients. To better understand the mechanisms underlying its activity, we used transcriptomics and proteomics to analyse the potential target gene YSTL repairing tripterygium glycosides (TGs)-mediated sperm DNA damage in rats, followed by validation analyses using RT-qPCR and western blotting, which showed that relative to the control group, DFI was markedly elevated in the TGs group, but markedly lower in the YSTL group relative to the TGs group. KEGG pathway analysis of 119 differentially expressed genes and 158 DEPs identified using trend analysis revealed that they were enriched for apoptosis and base excision repair at the transcriptomic level and for microRNAs in cancer and complement and coagulation cascades at the proteomic level. Ttr and Pnpla2 were identified as potential target genes for YSTL. Our data show that YSTL can protect rat sperm DNA from TGs-induced damage, which may be related to apoptosis, DNA repair and other pathways, and the possible target genes are Ttr and Pnpla2., (© 2022 Wiley-VCH GmbH.)

Heavy metals in indoor dust are associated with health risks in humans. However, in Shijiazhuang, a city in northern China with severe haze, no research has been published on this topic. To determine the content, distribution characteristics, and sources of heavy metals in indoor dust in the city of Shijiazhuang, indoor dust samples from 33 sampling points in the main urban area of Shijiazhuang were collected and tested. Concentrations of Cu, Ni, Cr, Zn, Cd, and Pb were 87.0, 35.1, 104.4, 568.0, 1.980, and 187.6 mg·kg -1 , respectively; their levels have been discussed statistically in comparison with the reported values in other cities in China. The sources of heavy metals were analyzed using enrichment factor, correlation coefficient, and principal component analysis. The results showed that the levels of all six elements in indoor dust in Shijiazhuang exceeded the background values of soil in Hebei Province. Among these, Cd, Pb, and Zn were significantly enriched. The enrichment factors of Cu, Ni, and Cr were below 10, and their levels at different sampling points were similar, indicating their geogenic source. The corresponding pollution levels of Cd, Pb, and Zn were relatively high, and their levels at different points were significantly different and correlated, indicating that they were derived mainly from transportation. Additionally, the level of Zn was significantly affected by the indoor environment. Our findings provide a basis for conducting health risk assessments in the future., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Necroptosis and inflammation are closely related to the pathogenesis of respiratory syncytial virus (RSV). Acteoside (AC), a natural phenylpropanoid glycoside from Kuding Tea, has significant anti-RSV effect. However, the roles of AC on RSV-induced lung necroptosis and inflammation are yet to be elucidated. Methods: The effects of AC were investigated in BALB/c mice and A549 cells. Lung histopathology was observed through H&E staining. The viral titer was assessed via plaque assay. The RSV-F expression was determined by RT-qPCR and immunohistochemistry assay. The levels of cytokines were detected by ELISA and RT-qPCR. The necroptosis rate and mitochondrial membrane potential were evaluated via flow cytometry. The expressions of HMGB1/NF-κB and RIP1/RIP3/MLKL/PGAM5/DRP1 were detected by western blot. Additionally, untargeted metabolomics was conducted to investigate the metabolic profiles and related metabolic pathways via Gas Chromatography-Mass Spectrometry. Results: The results showed that compared with the RSV-infected group, AC treatment significantly attenuated lung pathological damage, virus replication, and cytokines levels. AC also alleviated RSV-induced necroptosis and mitochondrial dysfunction in vitro and in vivo . Moreover, AC treatment down-regulated the expression of HMGB1, p-Iκbα/Iκbα, p-p65/p65, RIP1, RIP3, MLKL, PGAM5, and DRP1. Furthermore, metabolomic analyses suggested that the perturbations in major metabolites of AC therapy were related to variations in amino acid and energy metabolism. Conclusion: Our findings validated the beneficial effects of AC in suppressing necroptosis and regulating metabolism, suggesting AC may be a new drug candidate for RSV infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ling, Zhou, Jin, Xu, Sun, Li, Ding, Liang, Zhu, Zhao, Hu, Yuan, Xie and Tao.)

Sustainable agricultural practices (SAPs) are conducive to increasing agricultural productivity and income while reducing resource and environmental stress. However, due to credit constraints in traditional financial markets, the adoption rate of SAPs remains low among smallholder farmers in rural China. Recently, the emergence of digital finance provides small farmers with a new way to obtain credit and alleviate their credit constraints, which may exert an impact on the adoption of SAPs. To verify this conjecture, this paper examines the impact and mechanism of digital finance use on SAPs adoption among smallholder farmers in China based on survey data collected from 903 apple growers. Empirical results showed that digital finance use significantly increases the number of SAPs adopted by smallholder farmers. Alleviating credit constraints, promoting information acquisition, and facilitating social interactions are the pathways through which digital finance use influences small farmers' SAPs adoption. Heterogeneity analysis showed that farmers with higher education level, smaller farming size, and who have received extension services adopt more SAPs with the use of digital finance. Therefore, it is suggested that the government should strengthen the construction of rural network infrastructure and provide training to promote smallholder farmers' access to digital financial services in a cost-effective and secure manner., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Chaetomium fungi produce a diversity of bioactive compounds. Chaetomium cochliodes SD-280 possesses 91 secondary metabolite gene clusters and exhibits strong antibacterial activity. One of the active compounds responsible for that activity, chetomin, has a minimum inhibitory concentration (MIC) for anti-methicillin-resistant Staphylococcus aureus (MRSA) of 0.05 μg/mL (vancomycin: 0.625 μg/mL). This study demonstrated that the addition of glutathione (GSH) can enhance chetomin yield dramatically, increasing its production 15.43-fold. Following genome sequencing, cluster prediction, and transcriptome and proteome analyses of the fungus were carried out. Furthermore, a relatively complete chetomin biosynthetic gene cluster was proposed, and the coding sequences were acquired. In the cluster of GSH-treated cells, proteome analysis revealed two up-regulated proteins that are critical enzymes for chetomin biosynthesis. One of these enzymes, a nonribosomal peptide synthetase (NRPS), was heterologously expressed in Aspergillus nidulans, and one of its metabolites was determined to be an intermediate in the chetomin biosynthetic pathway. We present here, to our knowledge, the first experimental evidence that chetomin exhibits strong bioactivity against MRSA. Our work also provides extensive insights into the biosynthetic pathway of chetomin, in particular identifying two key enzymes (glutathione S-transferase (CheG) and NRPS (CheP)) that substantially up-regulate chetomin. These mechanistic insights into chetomin biosynthesis will provide the foundation for further investigation into the anti-pathogenic properties and applications of chetomin. KEY POINTS: • Chetomin exhibits strong anti-MRSA activity with MIC of 0.05 μg/mL. • Addition of glutathione improved the yield of chetomin by 15.43-fold. • CheG and CheP involved in the chetomin biosynthesis were revealed for the first time., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with a poor prognosis. To date, the mechanism of TNBC's aggressive phenotype is still unclear. Based on metabolome analysis, we found that glutamine (Gln) metabolism plays a key role in the difference between TNBC and non-TNBC. We identified a 21-amino-acid survival-associated micropeptide XBP1SBM, encoded by the lncRNA MLLT4-AS1, which was upregulated in TNBC tissues and Gln-deprived TNBC cell lines. We showed that XBP1SBM expression was upregulated by Gln-deprivation-induced XBP1s transcriptional promotion, and in turn retained XBP1s in the nuclear to enhance the expression of VEGF. Using human endothelial cells, mouse xenograft models and mouse spontaneous BC models, we found that XBP1SBM improved Gln levels and promoted angiogenesis and metastasis in TNBC. Our study showed that a TNBC-specific nutrient deficiency adaption results in aggressive TNBC, and this mechanism provides a novel potential prognostic biomarker and therapeutic target in TNBC., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Immune and targeted therapy are becoming the first-line treatment for renal cell carcinoma (RCC). However, therapeutic outcomes are limited due to the low efficiency and side effect. Here, it is found that helicenes are able to exhibit an anticancer capability through changing the molecular structure from planar to nonplanar. Furthermore, the cytotoxicity in vitro and cancer inhibition ability of nonplanar helicenes increase with its aromatic rings' number. It is further demonstrated that benzo[4]helicenium shows the specific killing efficiency against the RCC cancer as compared to normal kidney cells. This is majorly originated from a more selective damage of benzo[4]helicenium for mitochondria and DNA in RCC cancer cells, not the normal kidney. The selective killing ability of benzo[4]helicenium makes it have potential to be used as a targeted drug for the precise treatment of RCC., (© 2021 Wiley-VCH GmbH.)

High-sensitivity gas sensor is a crucial online monitoring device to ensure the safe operation of the transformer. In this paper, based on density functional theory, an Ag-MoSe 2 monolayer system was established by investigating four different positions of Ag doping to adsorb the dissolved gas (H 2 , C 2 H 2 , CH 4 , CO and CO 2 ) in transformer oil. The sensing properties of adsorption system for different dissolved gas were studied via the analysis of adsorption energy ( E ad ), charge transfer, density of state, energy band, lowest unoccupied molecular orbit, highest occupied molecular orbit, and desorption time. Finally, Ag-MoSe 2 had good adsorption and desorption properties for CO and CH 4 at room temperature, and could be used as a sensor material for the two gases detection. It had strong adsorption and poor desorption performances for C 2 H 2 at room temperature, which could serve as C 2 H 2 scavenger, and simultaneously had good adsorption and desorption performance at a temperature of 358 K, therefore it could be used as a candidate material to detect C 2 H 2 at high temperatures. Ag-MoSe 2 had a weak interaction with H 2 and CO 2 , thus was not suitable for detecting the two gases. The results indicated that Ag-MoSe 2 had excellent potential in detecting dissolved gases in transformer oil., (© 2021 IOP Publishing Ltd.)

Fungi are important resources for drug development, as they have a diversity of genes, that can produce novel secondary metabolites with effective bioactivities. Here, five depsidone-based analogs were isolated from the rice media of Chaetomium brasiliense SD-596. Their structures were elucidated using NMR and mass spectrometry analysis. Five compounds, including three new depsidone analogs, mollicellin S (1), mollicellin T (2), and mollicellin U (3), and two known compounds, mollicellin D (4) and mollicellin H (5), exhibited significant inhibition against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA), with MIC values ranging from 6.25 to 12.5 μg ml -1 . Herein, we identified the predicted plausible biosynthetic cluster of the compounds and discussed the structure-activity relationship. Finally, we found that the introduction of aldehyde and methoxyl groups provide marked improvement for the inhibition against MRSA.

This study is aimed at investigating the awareness of and preferences for oral and long-acting injectable HIV preexposure prophylaxis (PrEP) and their associated factors among men who have sex with men (MSM) at high risk of HIV infection in southern China. A cross-sectional survey was conducted among 603 MSM who were recruited through a cohort study called the T2T Study at three sexual health clinics in Guangzhou, Shenzhen, and Wuxi, China, from 2017 to 2018. We collected information on HIV-negative participants' awareness of and willingness to use PrEP and its potential correlations. Univariate and multivariate logistic regressions were used for data analyses. A total of 550 HIV-negative MSM were enrolled in the study. Less than half of at-risk MSM (43.1%) had heard of PrEP before, and the rate of overall willingness to use PrEP was 65.8%, while MSM were more willing to use daily oral PrEP than long-acting injectable- (LAI-) PrEP (62.2% vs. 38.5%). MSM who had university degrees or above (aOR = 1.55, 95% CI: 1.01-2.37), used condoms during last anal sex (1.52, 1.01-2.29), and tested 3 times or more for HIV (2.45, 1.10-5.47) were more likely to be aware of PrEP. MSM who had use of gay dating apps (1.51, 1.02-2.23), ever participated in HIV- or sexually transmitted disease (STD-) related studies (1.91, 1.24-2.94), and had heard of PrEP (3.06, 2.06-4.54) were more willing to use any regimen of PrEP. MSM at high risk of HIV infection had low awareness of PrEP and moderate willingness to use PrEP. Further studies of the implementation and promotion of PrEP targeting at-risk MSM should be performed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Weiying Chen et al.)

Emerging evidence shows that type II protein arginine methyltransferase 5 (PRMT5) serves as an oncoprotein and plays a critical role in many types of human cancer. However, the precise role and function of PRMT5 in human colorectal cancer (CRC) growth and epithelial-mesenchymal transition (EMT) are still unclear, and the related molecular mechanism and signaling axis remains largely obscure. Here, we show that PRMT5 is highly expressed in CRC cell lines and tissues. Using PRMT5 stable depletion cell lines and specific inhibitor, we discover that down-regulation of PRMT5 by shRNA or inhibition of PRMT5 activity by specific inhibitor GSK591 markedly suppresses CRC cell proliferation and cell cycle progression, which is closely associated with PRMT5 enzyme activity. Moreover, PRMT5 regulates CRC cell growth and cycle progression via activation of Akt, but not through ERK1/2, PTEN, and mTOR signaling pathway. Further study shows that PRMT5 controls EMT of CRC cells by activation of EGFR/Akt/GSK3β signaling cascades. Collectively, our results reveal that PRMT5 promotes CRC cell proliferation, cell cycle progression, and EMT via regulation of EGFR/Akt/GSK3β signaling cascades. Most importantly, our findings also suggest that PRMT5 may be a potential therapeutic target for the treatment of human colorectal cancer.

Aim: To research the influence and mechanism of gold nanoparticles (AuNPs) with different size for HK-2 cells (kidney normal cells) and 786-0 cells (kidney cancer cells). Materials & methods: HK-2 cells and 786-0 cells were treated with 5 and 200 nm AuNPs at 1 and 10 μg/ml. The cell viability, intracellular reactive oxygen species levels, cell apoptosis, cell autophagy, and related cell signaling pathways were analyzed. Results: In HK-2 cells, AuNPs reduced the activity of Akt and mTOR and upregulated the expression of LC3 II. In 786-0 cells, the activity of p38 was upregulated, which leaded to the increase of caspase 3 and initiated apoptosis. Conclusion: AuNPs of 5 and 200 nm at 10 μg/ml exerted antitumor effect by prompting apoptosis and inhibiting proliferation, while autophagy was activated to protect HK-2 cells from AuNPs-induced cytotoxicity.

MicroRNAs (miRNAs) therapy has shown to have great promise for the treatment of androgen-independent prostate cancer (AIPC) due to the low efficiency of hormonal therapy. However, instability of RNA and inefficiency of RNA therapy limit the use of miRNAs in the treatment of AIPC. Here, we report a pH/ATP-activated nanocomplexes for increasing cytosolic delivery of miR146a which can effectively inhibit the expression of epidermal growth factor receptor (EGFR) in AIPC. The nanocomplexes show identical suppressing effect in invasion, colony formation, migration ability, and growth of DU145 cells compared with Lipofectamine 2000 (lipo). But for in vivo experiments, the nanocomplexes vigorously suppress the growth of tumor volumes comparing to lipo group after five weeks' treatment. These results demonstrate the potential of the pH/ATP-activated nanocarriers for AIPC gene therapy.

Increasing attention has recently been focused on complex symbiotic associations, for instance coral and its symbionts. Sea cucumber, harboring diverse fungi, has also attracted more and more attention for their functional diversity. Here, secondary metabolites produced by Chaetomium globosum associated with sea cucumber, Apostichopus japonicus, were investigated using gene mining with third-generation sequencing technology (PacBio SMRT). Nine compounds, including one new compound cytoglobosin X (1), were isolated from cultures of Chaetomium globosum. Compound 1 was identified based on NMR data, HRESIMS, and ECD, and the absolute configurations were identified as 3S, 4R, 7S, 8R, 9R, 16S, 19S, 20S, and 23S. In an antimicrobial assay, compound 4 showed moderate activity against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus with MICs of 47.3 and 94.6 μM, respectively. Our results suggest that the microbiomes associated with sea cucumber could be an important resource for biodiversity and structural novelty, and the bioactive compounds may protect the host from pathogen microbial.

Cycloaddition reactions such as intramolecular Diels-Alder (IMDA) are extremely important in constructing multicyclic scaffolds with diverse bioactivities. Using MycB as a biomarker, three new polyketides - Chaetolivacines A ( 1 ), B ( 3 ), and C ( 4 ) - with one known compound Myceliothermophin E ( 2 ) comprising of decalin and 4-hydroxy-2-pyridones were obtained from the culture of Chaetomium olivaceum SD-80A under the guidance of gene mining. The structures of these compounds were established using detailed 1D, 2D NMR, and high-resolution electron spray ionization mass spectroscopy (HRESIMS) analysis. The relative and absolute configurations of the compounds 1 , 3 , and 4 were elucidated by NOESY and ECD. The biosynthesis pathways of these compounds were proposed, which involves in three key genes ChaA [polyketide synthase-non-ribosomal peptide synthetases (PKS-NRPS)], ChaB , and ChaC . Compounds 1 - 4 were tested for their antimicrobial activities, and compounds 2 and 3 showed moderate bioactivity against Staphylococcus aureus (SA) and methicillin-resistant S. aureus (MRSA) with MIC values of 15.8 and 27.1 μM. The results showed that configuration of C-21 in 3 and 4 is important for anti-SA and anti-MRSA activities. This study reveals the significant potential of the genus Chaetomium in producing new PKS-NRPS, therefore increasing the speed in the mining for new sources of antimicrobial agents., (Copyright © 2020 Wang, Zhao, Liu, Qi, Zhao, Liu, Li, Hu, Yin, Liu, Liao, Zhang and Xia.)

The rapid increase of Methicillin-resistant Staphylococcus aureus (MRSA) infections and the cross-resistance of MRSA to other antibiotics create an urgent demand for new therapeutic agents. Antimicrobial peptides (AMPs) are one of the most promising options for next-generation antibiotics. In this study, novel peptides were designed based on antimicrobial peptide fragments derived from Aristicluthys nobilia interferon-I to promote anti-MRSA activity and decrease adverse effects. Design strategies included substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote amphipathicity. Two designed peptides, P5 (YIRKIRRFFKKLKKILKK-NH2) and P9 (SYERKINRHFKTLKKNLKKK-NH2), showed potent antimicrobial activities against both sensitive Staphylococcus aureus clinical isolates and MRSA strains without significant hemolysis or cytotoxicity to human hemocytes and renal epithelial cells. Scanning Electronic Microscopy (SEM) and qRT-PCR were employed to investigate the effects of P5 and P9 on S. aureus biofilm formation, morphology, and virulence-related gene expression. P5 and P9 significantly inhibited the biofilm and destroyed the cell membrane integrity, in addition to down-regulating several virulence factor genes and biofilm formation-related genes including spa, hld, and sdrC. P5 and P9 could be promising candidate antibacterial agents for the treatment of MRSA infections., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

SSZ-13 zeolite has been widely used in catalysis and adsorption because of good hydrothermal stability and pore structure. However, long crystallization time is the main challenge limiting its industry application. As increased emissions and ineffective treatment, coal gangue not only occupies land, but also pollutes the waterbody and farmland. Using coal gangue as raw material to synthetize zeolite has been considered as an environmentally friendly and effective alternative to solve the issues of accumulation and pollution, which also improves the added value of coal gangue. The ultrasonic assistance has been proven to be one of the potential pretreatment methods to promote the dissolution of crystalline silicon aluminum and reduce the crystallization time of molecular sieve. In this work, SSZ-13 was synthesized by coal gangue via ultrasonic pretreatment combined with hydrothermal growth method. The ultrasonic frequency and power were 20 kHz and 120 W, respectively. The synthesized samples were characterized by XRD, SEM, EDS, BET. The results showed that the crystallization time was shorten to 18 h, which was about 12 h lower than the same conditions of conventional chemicals synthesis. Furthermore, the specific surface area of the synthesized sample was more than 620 m 2 /g, which also indicated over 95% NO x conversion across a broad range from 180 to 400 °C and over 94% NO x conversion at 200-400 °C after hydrothermal treatment 6 h. This study provides a reference for the environmentally friendly utilization of coal gangue and the low-cost rapid synthesis and application of SSZ-13., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Men who have sex with men (MSM), including both gay and bisexual men, have a high prevalence of HIV and sexually transmitted infections (STIs) in China. However, healthcare seeking behaviors and engagement in clinical services among MSM are often suboptimal. Global evidence shows that embedding online HIV or sexual health services into gay social networking applications holds promise for facilitating higher rates of healthcare utilization among MSM. We developed a prototype of a gay-friendly health services platform, designed for integration within a popular gay social networking app (Blued) in China., Objective: The purpose of this study was to evaluate the acceptability of the platform and ask for user feedback through focus group interviews with young MSM in Guangzhou and Shenzhen, cities in Southern China., Methods: The prototype was developed through an open, national crowdsourcing contest. Open crowdsourcing contests solicit community input on a topic in order to identify potential improvements and implement creative solutions. The prototype included a local, gay-friendly, STI physician finder tool and online psychological consulting services. Semistructured focus group discussions were conducted with MSM to ask for their feedback on the platform, and a short survey was administered following discussions. Thematic analysis was used to analyze the data in NVivo, and we developed a codebook based on the first interview. Double coding was conducted, and discrepancies were discussed with a third individual until consensus was reached. We then carried out descriptive analysis of the survey data., Results: A total of 34 participants attended four focus group discussions. The mean age was 27.3 years old (SD 4.6). A total of 32 (94%) participants obtained at least university education, and 29 (85%) men had seen a doctor at least once before. Our survey results showed that 24 (71%) participants had interest in using the online health services platform and 25 (74%) thought that the system was easy to use. Qualitative data also revealed that there was a high demand for gay-friendly healthcare services which could help with care seeking. Men felt that the platform could bridge gaps in the existing HIV or STI service delivery system, specifically by identifying local gay-friendly physicians and counselors, providing access to online physician consultation and psychological counseling services, creating space for peer support, and distributing pre-exposure prophylaxis and sexual health education., Conclusions: Crowdsourcing can help develop a community-centered online platform linking MSM to local gay-friendly HIV or STI services. Further research on developing social media-based platforms for MSM and evaluating the effectiveness of such platforms may be useful for improving sexual health outcomes., (©Dan Wu, Wenting Huang, Peipei Zhao, Chunyan Li, Bolin Cao, Yifan Wang, Shelby Stoneking, Weiming Tang, Zhenzhou Luo, Chongyi Wei, Joseph Tucker. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 08.10.2019.)

Although men who have sex with men (MSM) are disproportionately affected by HIV and other sexually transmissible infections, sexual health services for MSM in low- and middle-income countries (LMIC) remain under-resourced and are poorly understood. A scoping review of literature on MSM sexual health in LMIC was conducted in order to identify key clinical services and gaps in knowledge. Three databases were searched, in addition to hand-reviewing key journals and bulletins, to identify literature with a focus on MSM sexual health. Key services related to providing care to MSM in LMIC that emerged from our review are described. These services include creation of safe and confidential clinic environments, HIV testing services, behavioural interventions, HIV pre-exposure prophylaxis (PrEP), rapid antiretroviral therapy (ART) initiation and STI services. Compared with high-income settings, major differences in LMIC include lack of diagnostic technology, unfavourable legal environments and lack of funding for MSM health. Innovative approaches to healthcare delivery, such as harnessing mobile technology, self-testing and crowdsourcing interventions, can improve health services among MSM in LMIC. There are gaps in the evidence about how best to provide sexual health services for MSM in LMIC settings. Implementation research and scale-up of existing biomedical and behavioural interventions, such as HIV/STI testing services, PrEP and early antiretroviral initiation are urgently needed in LMIC.

Brain ischemia, including cerebral ischemia and cerebrovascular ischemia, leads to poor oxygen supply or cerebral hypoxia, and causes brain tissue death or cerebral infarction/ischemic stroke. The troxerutin and cerebroprotein hydrolysate injection (TCHI), is widely applied in China to improve blood supply in ischemic brain tissues and to enhance neuroprotective effects in clinical practice. However, the benefits and detailed underlying mechanism elaborating the effectiveness of TCHI in cerebrovascular diseases require further investigation. Therefore, in the present study, experimental in vivo and in vitro models were employed to investigate the potential mechanisms of TCHI on cerebral ischemic injury. The results demonstrated that TCHI increased the lactate dehydrogenase levels in the brain homogenate and conversely decreased lactic acid levels. TCHI was further observed to significantly increase superoxide dismutase activity and decrease malondialdehyde levels in ischemic brain tissues. In addition, TCHI significantly induced vascular maturation processes, including proliferation, adhesion, migration and tube formation in cultured human umbilical vein endothelial cells. Additionally, TCHI significantly stimulated microvessel formation in the rat aortic ring and chick chorioallantoic membrane assays. Taken together, these results provided strong evidence that TCHI stimulated angiogenesis at multiple steps, and indicated that TCHI attenuated cerebral ischemic damage through the amelioration of oxidative stress and promotion of angiogenesis.