Community engagement tools in HIV/STI prevention research.

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.

Neutrophil extracellular traps are involved in the occurrence of interstitial lung disease in a murine experimental autoimmune myositis model.

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.

Neutrophil extracellular traps induce pyroptosis of pulmonary microvascular endothelial cells by activating the NLRP3 inflammasome.

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-1ß (IL-1ß) 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-1ß. 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.

Novel heterologously expressed protein, AjPSPLP-3, derived from Apostichopus japonicus exhibits cell proliferation and migration activities.

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 ß-sheets, Cys30-Cys67, Cys38-Cys58, Cys53-Cys90, Cys56-Cys66, and Cys81-Cys102 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.

Screening and heterologous expression of an antimicrobial peptide SCAK33 with broad-spectrum antimicrobial activity resourced from sea cucumber proteome.

Antimicrobial peptides (AMPs) are a family of short defense proteins that are naturally produced by all organisms and have great potential as effective substitutes for small-molecule antibiotics. The present study aims to excavate AMPs from sea cucumbers and achieve their heterologous expression in prokaryotic Escherichia coli. Using MytC as a probe, a cysteine-stabilized peptide SCAK33 with broad-spectrum antimicrobial activity was discovered from the proteome of Apostichopus japonicas. The SCAK33 showed inhibitory effects on both gram positive and gram negative bacteria with MICs of 3-28 µM, and without significant hemolysis activity in rat blood erythrocyte. Especially, it exhibited good antimicrobial activity against Bacillus megaterium, B. subtilis, and Vibrio parahaemolyticus with the MIC of 3, 7, and 7 µM, respectively. After observation by scanning electronic microscopy (SEM) and confocal laser scanning microscope (CLSM), it was found that the cell membrane of bacteria was severely damaged. Furthermore, the recombinant SCAK33 (reSCAK33) was heterologously expressed by fusion with SUMO tag in E. coli BL21(DE3), and the protein yield reached 70 mg/L. The research will supplement the existing quantity of sea cucumber AMPs and provide data support for rapid mining and biological preparation of sea cucumber AMPs.

Activation of secondary metabolite gene clusters in Chaetomium olivaceum via the deletion of a histone deacetylase.

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.

Associations among drug acquisition and use behaviors, psychosocial attributes, and opioid-involved overdoses.

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 (ß = .234, p = .001), as mediated by the EFA/CFA identified latent variables: drug acquisition (ß = .683, p < .001) and drug use (ß = .567, p = .001). Drug use behaviors (ß = .287, p = .04) but not drug acquisition (ß = .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.

A gene cluster encoding a nonribosomal peptide synthetase-like enzyme catalyzes γ-aromatic butenolides.

Sea cucumber-derived fungi have attracted much attention due to their capacity to produce an incredible variety of secondary metabolites. Genome-wide information on Aspergillus micronesiensis H39 obtained using third-generation sequencing technology (PacBio-SMRT) showed that the strain contains nonribosomal peptide synthetase (NRPS)-like gene clusters, which aroused our interest in mining its secondary metabolites. 11 known compounds (1-11), including two γ-aromatic butenolides (γ-AB) and five cytochalasans, were isolated from A. micronesiensis H39. The structures of the compounds were determined by NMR and ESIMS, and comparison with those reported in the literature. From the perspective of biogenetic origins, the γ-butyrolactone core of compounds 1 and 2 was assembled by NRPS-like enzyme. All of the obtained compounds showed no inhibitory activity against drug-resistant bacteria and fungi, as well as compounds 1 and 2 had no anti-angiogenic activity against zebrafish.

The role of neutrophil extracellular traps and proinflammatory damage-associated molecular patterns in idiopathic inflammatory myopathies.

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.

Supercontinuum generation in As2S3 chalcogenide waveguide pumped by all-fiber structured dual-femtosecond solitons.

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 As2S3 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 Tm3+-doped fiber amplifier. Furthermore, the As2S3 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.

Investigation of anti-aging and anti-infection properties of Jingfang Granules using the Caenorhabditis elegans model.

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.

High-efficient production of mushroom polyketide compounds in a platform host Aspergillus oryzae.

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.

Testing Together Behaviors in Secondary Distribution of HIV/Syphilis Self-testing Program Among Men Who have Sex with Men in China.

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.

Current status and influencing factors of self-management in knee joint discomfort among middle-aged and elderly people: a cross-sectional study.

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.

Association of EDN levels in patients with asthma and correlation with FEV1%: A meta-analysis.

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 (FEV1%) 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 FEV1% 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 FEV1%, 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 FEV1% 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 FEV1% in the patients with asthma, which indicated that EDN could be a reliable marker to monitor asthma's therapeutic effects.

Investigation of chetomin as a lead compound and its biosynthetic pathway.

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.

Transcriptomics and proteomics analysis to explore the mechanism of Yishen Tongluo formula repairing sperm DNA damage in rats.

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.

Levels, distribution characteristics, and sources of heavy metals in indoor dust in Shijiazhuang, China.

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.

[Effects of Yishen Tongluo Prescription on the PI3K-Akt-MTOR pathway and the protein and mRNA expressions of CatSper-1 and HSPA2 in the testis tissue of oligoasthenospermia rats].

OBJECTIVE: To study the effect of Yishen Tongluo Prescription (YTP) on the testis tissue of the male rats with oligoasthenospermia (OAS) and its action mechanism based on the PI3K-AKT-mTOR pathway. METHODS: We randomly divided 48 SPF male SD rats into 8 groups: normal control, OAS model control, L-carnitine (LC), high-dose YTP, low-dose YTP, Omipalisib inhibitor (OI), OI + high-dose YTP, and OI + low-dose YTP, with 6 rats in each group. We established a model of OAS in the latter 7 groups by intragastric administration of tripterygium wilfordii polyside, followed by intervention with corresponding drugs. After treatment, we obtained semen parameters from the rats, observed pathological changes in the testis tissue by HE staining, and determined the expressions of the PI3K-AKT-mTOR signaling pathway-related proteins and mRNA by Western blot and real-time fluorescence quantitative PCR (qRT-PCR). RESULTS: Sperm concentration and total sperm motility were significantly improved in the LC and YTP groups compared with those in the OAS model control group (P < 0.001). HE staining showed irregularly arranged spermatogenic cells and narrowed lumina and widened gaps of seminiferous tubules in the OAS model controls, as well as similar pathological changes in the LC, YTP and OI + YTP groups. Significant up-regulation was observed in the protein expressions of p-Akt, CatSper-1 and HSPA2 in the LC group (P < 0.05), those of p-Akt, mTOR, catsper-1 and HSP2 in the low-dose YTP group (P < 0.05) and that of PI3K in the high-dose YTP group (P < 0.05) compared with those in the model controls. There were no statistically significant differences in the expressions of PI3K, mTOR and catsper-1 between the OI and model control groups (P > 0.05), nor in those of PI3K, p-Akt, mTOR, CatSper-1 and HSPA2 between the OI + YTP and the former two groups (P > 0.05). The mRNA expressions of PI3K, mTOR, CatSper-1 and HSPA2 were remarkably higher in the LC and YTP groups than in the model control (P< 0.05), with those of catsper-1 and PI3K even more significantly up-regulated in the high-dose than in the low-dose YTP group (P< 0.001; P< 0.05). Statistically significant differences were not observed in the mRNA expressions of PI3K, mTOR, CatSper-1 and HSPA2 between the model control and OI groups (P > 0.05), nor in those of PI3K, mTOR, catsper-1 and HSPA2 between the model control and OI + YTP groups (P > 0.05). CONCLUSION: Yishen Tongluo Prescription can improve sperm quality and pathological changes of the testis tissue in rats with Tripterygium glycoside-induced OAS, which might be attributed to its ability of up-regulating the expressions of the PI3K Akt mTOR pathway-related proteins and mRNA in the testis tissue.

Chaetoglobosins and azaphilones from Chaetomium globosum associated with Apostichopus japonicus.

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.