Association of exposure to multiple perfluoroalkyl and polyfluoroalkyl substances and glucose metabolism in National Health and Nutrition Examination Survey 2017-2018.

Objective: To investigate the relationships between perfluoroalkyl and polyfluoroalkyl substances (PFASs) exposure and glucose metabolism indices. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 2017-2018 waves were used. A total of 611 participants with information on serum PFASs (perfluorononanoic acid (PFNA); perfluorooctanoic acid (PFOA); perfluoroundecanoic acid (PFUA); perfluorohexane sulfonic acid (PFHxS); perfluorooctane sulfonates acid (PFOS); perfluorodecanoic acid (PFDeA)), glucose metabolism indices (fasting plasma glucose (FPG), homeostasis model assessment for insulin resistance (HOMA-IR) and insulin) as well as selected covariates were included. We used cluster analysis to categorize the participants into three exposure subgroups and compared glucose metabolism index levels between the subgroups. Least absolute shrinkage and selection operator (LASSO), multiple linear regression analysis and Bayesian kernel machine regression (BKMR) were used to assess the effects of single and mixed PFASs exposures and glucose metabolism. Results: The cluster analysis results revealed overlapping exposure types among people with higher PFASs exposure. As the level of PFAS exposure increased, FPG level showed an upward linear trend (p < 0.001), whereas insulin levels demonstrated a downward linear trend (p = 0.012). LASSO and multiple linear regression analysis showed that PFNA and FPG had a positive relationship (>50 years-old group: ß = 0.059, p < 0.001). PFOA, PFUA, and PFHxS (≤50 years-old group: insulin ß = -0.194, p < 0.001, HOMA-IR ß = -0.132, p = 0.020) showed negative correlation with HOMA-IR/insulin. PFNA (>50 years-old group: insulin ß = 0.191, p = 0.018, HOMA-IR ß = 0.220, p = 0.013) showed positive correlation with HOMA-IR/insulin, which was essentially the same as results that obtained for the univariate exposure-response map in the BKMR model. Association of exposure to PFASs on glucose metabolism indices showed positive interactions between PFOS and PFHxS and negative interactions between PFOA and PFNA/PFOS/PFHxS. Conclusion: Our study provides evidence that positive and negative correlations between PFASs and FPG and HOMA-IR/insulin levels are observed, respectively. Combined effects and interactions between PFASs. Given the higher risk of glucose metabolism associated with elevated levels of PFAS, future studies are needed to explore the potential underlying mechanisms.

Analysis of relationship between mixed heavy metal exposure and early renal damage based on a weighted quantile sum regression and Bayesian kernel machine regression model.

BACKGROUND: Occupation, environmental heavy metal exposure, and renal function impairment are closely related. The relationship between mixed metal exposure and chronic renal injury is inadequately described, and the interaction between each metal is poorly explored. OBJECTIVE: This cross-sectional study assessed mixed heavy metal exposure in the general population and their relationship with early renal impairment, as well as possible interactions between metals. METHODS: The study was conducted in two communities in Taiyuan City in northern China. Multiple linear regression, weighted quantile sum (WQS) and bayesian kernel machine regression (BKMR) regression were used to explore the relationship of mixed heavy metal exposure with indicators of early kidney injury (N-acetyl-ß-D- glucosidase (UNAG), urinary albumin (UALB)). Meanwhile, BKMR was used to explore the possible interactions between mixed heavy metal and indicators of early kidney injury. RESULTS: Based on the WQS regression results, we observed adjusted WQS coefficient ß (ß-WQS) of 0.711 (95% CI: 0.543, 0.879). Notably, this change was primarily driven by As (35.6%) and Cd (22.5%). In the UALB model, the adjusted ß-WQS was 0.657 (95% CI: 0.567, 0.747), with Ni (30.5%), Mn (22.1%), Cd (21.2%), and As (18.6%) exhibiting higher weights in the overall effect. The BKMR results showed a negative interaction between As and other metals in the UNAG and UALB models, a positive interaction between Mn and Ni and other metals. No significant pairwise interaction was observed in the association of metals with indicators of early kidney injury. CONCLUSION: Through multiple linear regression, WQS regression, and BKMR analyses, we found that exposure to mixed heavy metals such as Cd, Cr, Pb, Mn, As, Co and Ni was positively correlated with UNAG and UALB. Moreover, there are complex interactions between two or more heavy metals in more than one direction.

Value of Contrast-Enhanced Microflow Imaging in Diagnosis of Breast Masses in Comparison with Contrast-Enhanced Ultrasound.

RATIONALE AND OBJECTIVES: To investigate the value of contrast-enhanced microflow imaging (CEUS-MFI) in distinguishing benign and malignant breast masses. METHODS: A total of 116 breast masses classified as Breast Imaging Reporting and Data System (BI-RADS) category 3-5 by ultrasound (US) were included. Both contrast-enhanced ultrasound (CEUS) and CEUS-MFI were performed before excision or biopsy, with features and diagnostic efficiency analyzed. The US and CEUS BI-RADS 4A masses were also re-assessed by CEUS-MFI. RESULTS: The features of CEUS-MFI including both interior and peripheral enlarged, twisted vessels (both P < 0.05), penetrating vessels (P = 0.007), and radial/spiculated vessels (P < 0.001) were more frequently detected in malignant masses, while peripheral annular vessels were mostly observed in benign masses (P < 0.001). Interestingly, a significant difference in the orientation of penetrating vessels between benign and malignant masses was found (P < 0.001), with parallel orientation mostly displayed in benign masses, while vertical or multiple-direction orientation mostly displayed in malignant masses. The microvascular architecture of breast masses was categorized into five patterns: avascular, line-like, tree-like, root hair-like, and crab claw-like pattern. Benign masses mainly displayed tree-like pattern (77.1% vs 10.9%, P < 0.05); malignant masses mainly displayed root hair-like (34.8% vs 5.7%, P < 0.05) and crab claw-like patterns (50.0% vs 1.4%, P < 0.05). The diagnostic efficiency of CEUS-MFI was higher relative to CEUS and US. In addition, CEUS-MFI decreased the biopsy rates of US and CEUS BI-RADS 4A masses without missing malignancies. CONCLUSION: CEUS-MFI could be a valuable and promising technique in diagnosis of breast masses, and could provide more diagnostic information for radiologists.

First trimester sCD40L levels associated with adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.

Backgrounds: It remained unclear whether isolated positive thyroid peroxidative antibodies (TPOAb) were associated with adverse maternal and neonatal outcomes. The purpose of this study was to observe adverse neonatal outcomes among euthyroid pregnant women with positive TPOAb and to investigate the underlying risk factors. Methods: Euthyroid pregnant women with TPOAb positivity were enrolled and followed up in our study. Adverse neonatal outcomes such as preterm birth, low birth weight, and fetal macrosomia were observed. Clinical data in the first trimester were collected and compared between groups with or without adverse neonatal outcomes. Maternal serum soluble CD40 ligand (sCD40L) was also measured at the same time. Results: A total of 176 euthyroid pregnant women with TPOAb positivity were finally enrolled and analyzed in our study. Thirty-nine (22.16%) euthyroid women with TPOAb positivity were found to have adverse neonatal outcomes. Thirteen participants received assisted reproductive technology (ART) in our study, and seven participants were in the adverse neonatal outcome group. Preterm birth, low birth weight, and fetal macrosomia were the most common comorbidities. The proportion of receiving ART and the levels of sCD40L and platelet were significantly higher in the adverse neonatal outcome group (all P < 0.05). Multivariate regression analysis showed that sCD40L and receiving ART were the independent risk factors for adverse neonatal outcomes. The odds ratio values of sCD40L higher than 5.625 ng/ml were 2.386 [95% confidence interval (CI) = 1.017 to 5.595; P = 0.046] for overall adverse neonatal outcome, 3.900 (95% CI = 1.194 to 12.738; P = 0.024) for preterm birth, and 3.149 (95% CI = 0.982 to 10.101; P = 0.054) for low birth weight. Conclusions: Approximately one of the four euthyroid women with TPOAb positivity might have adverse neonatal outcomes. Measurement of sCD40L in first trimester might have a predictive value for adverse neonatal outcomes in euthyroid pregnant women with positive TPOAb.

Chinese Community Home-Based Aging Institution Elders' Self-Management of Chronic Non-Communicable Diseases and Its Interrelationships with Social Support, E-Health Literacy, and Self Efficacy: A Serial Multiple Mediation Model.

Background: The Chinese population is aging, and chronic non-communicable diseases (NCDs) prevalence is correspondingly increasing, along with associated disability and healthcare costs. Although self-management has been associated with social support and is a recognized priority, its mediating variables have not been studied in detail, particularly among old people with chronic diseases. Purpose: To examine the mediating role of e-health literacy and general self-efficacy in the relationship between social support and self-management of chronic NCDs in Chinese community home-based aging institution residents. Patients and Methods: A random sample of 289 community home-based aging institution elders (≥60 years) with chronic NCDs in China was recruited. Questionnaire data were recorded on self-reported socio-demographics, self-management, social support, e-health literacy, and general self-efficacy. Pearson's correlation analysis identified the relationship between these factors and self-management. Serial multiple mediation model was used to test the hypothesized relationships. Results: The self-management mean (±SD) score was 29.39 ± 9.60, and the level of self-management was medium. Social support (r = 0.283; P < 0.001), e-health literacy (r = 0.566; P < 0.001), and general self-efficacy (r = 0.477; P < 0.001) were positively associated with self-management. Furthermore, social support indirectly influenced self-management through three pathways: independent mediation of e-health literacy (effect = 0.234, P < 0.001), independent mediation of general self-efficacy (effect = 0.515, P < 0.001), and chain mediation of e-health literacy and general self-efficacy (effect = 0.075, P < 0.001). Conclusion: In Chinese community home-based aging institution elders, the relationship between self-reported self-management and social support is positively affected by the independent mediating effect of e-health literacy and general self-efficacy and the serial mediating effect of e-health literacy and general self-efficacy. Targeted self-management programs for elders with chronic NCDs have theoretical support, which could improve the health status and quality of life in this population.

Phosphorus biorecovery from wastewater contaminated with multiple nitrogen species by a bacterial consortium.

Recovering finite and non-substitutable phosphorus from liquid waste streams through bio-mediated techniques has attracted increasing interest, but current approaches are incredibly dependent on ammonium. Herein, a process to recover phosphorus from wastewater under multiple nitrogen species conditions was developed. This study compared the effects of nitrogen species on the recovery of phosphorus resources by a bacterial consortium. It found that the consortium could not only efficiently utilize ammonium to enable phosphorus recovery but also utilize nitrate via dissimilatory nitrate reduction to ammonium (DNRA) to recover phosphorus. The characteristics of the generated phosphorus-bearing minerals, including magnesium phosphate and struvite, were evaluated. Furthermore, nitrogen loading positively influenced the stability of the bacterial community structure. The genus Acinetobacter was dominant under nitrate and ammonium conditions, with a relatively stable abundance of 89.01% and 88.54%, respectively. The finding may provide new insights into nutrient biorecovery from phosphorus-containing wastewater contaminated with multiple nitrogen species.

DRESS/DiHS syndrome induced by Propylthiouracil: a case report.

BACKGROUND: Drug reaction with eosinophilia and systemic symptoms (DRESS), also known as Drug-induced hypersensitivity syndrome (DiHS), is a severe adverse drug reaction. Propylthiouracil, a member of thiouracils group, is widely used in medical treatment of hyperthyroidism. Propylthiouracil is associated with multiple adverse effects such as rash, agranulocytosis hepatitis and antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, but rarely triggers DRESS/DiHS syndrome. Here, we describe a severe case of propylthiouracil-induced DRESS/DiHS syndrome. CASE PRESENTATION: A 38-year-old female was treated with methimazole for hyperthyroidism at first. 4 weeks later, the patient developed elevated liver transaminase so methimazole was stopped. After liver function improved in 2 weeks, medication was switched to propylthiouracil therapy. The patient subsequently developed nausea and rash followed by a high fever, acute toxic hepatitis and multiple organ dysfunction (liver, lung and heart), which lasted for 1 month after propylthiouracil was started. According to the diagnostic criteria, the patient was diagnosed of DRESS/DiHS syndrome which was induced by propylthiouracil. As a result, propylthiouracil was immediately withdrawn. And patient was then treated with adalimumab, systematic corticosteroids and plasmapheresis in sequence. Symptoms were finally resolved 4 weeks later. CONCLUSIONS: Propylthiouracil is a rare cause of the DRESS/DiHS syndrome, which typically consists of severe dermatitis and various degrees of internal organ involvement. We want to emphasize through this severe case that DRESS/DiHS syndrome should be promptly recognized to hasten recovery.

Development of quantitative wastewater surveillance models facilitated the precise epidemic management of COVID-19.

Wastewater surveillance serves as a promising approach to elucidate the silent transmission of SARS-CoV-2 in communities. To understand the decay of the coronavirus in sewage pipes, the decay of the coronavirus traveling over 20 km distance of pipeline was analyzed. Based on the decay model, a WWTP and a community model were then proposed for predicting COVID-19 cases in Xi'an and Nanchang city during the COVID-19 outbreak in 2021 and 2022. The results suggested that Monte Carol simulations estimated 23.3, 50.1, 127.3 and 524.2 infected persons in the Yanta district of Xi'an city on December 14th, 18th, 22nd and 26th of 2021, respectively, which is largely consistent with the clinical reports. Next, we further conducted wastewater surveillance in two WWTPs that covered the whole metropolitan region in Nanchang to validate the robustness of the WWTP model from December 2021 to April 2022. SARS-CoV-2 signals were detected in two WWTPs from March 15th to April 5th. Predicted infection numbers were in agreement with the actual infection cases, which promoted precise epidemic control. Finally, community wastewater surveillance was conducted for 40 communities that were not 100 % covered by massive nucleic acid testing in Nanchang city, which accurately identified the SARS-CoV-2 carriers not detected by massive nucleic acid testing. In conclusion, accurate prediction of COVID-19 cases based on WWTP and community models promoted precise epidemic control. This work highlights the viability of wastewater surveillance for outbreak evaluation and identification of hidden cases, which provides an extraordinary example for implementing precise epidemic control of COVID-19.

The involvement of hypoxia inducible factor-1α on the proportion of three types of haemocytes in Chinese mitten crab under hypoxia stress.

Hypoxia triggers diverse cell physiological processes, and the hypoxia inducible factors (HIFs) are a family of heterodimeric transcription factors that function as master regulators to respond to hypoxia in different cells. However, the knowledge about the hypoxic responses especially cell alteration mediated by HIFs under hypoxia stress is still limited in crustaceans. In the present study, a hypoxia-inducible factor-1α (HIF-1α) gene was identified (designed as EsHIF-1α). The relative mRNA expression level of EsHIF-1α was highest in hyalinocytes and lowest in granulocytes among three types of haemocytes in crabs. Hypoxia could significantly increase the EsHIF-1α protein expression level in haemocytes. Meanwhile, the proportion of hyalinocytes began to increase from 3 h post hypoxia treatment, and reached the highest level at 24 h. However, the opposite variation in proportion of granulocytes was observed under hypoxia stress. Further investigation showed that the inhibition of EsHIF-1α induced by KC7F2 (HIF-1α inhibitor) could lead to the significant decrease in the proportion of hyalinocytes under hypoxia stress, and also resulted in an increase of granulocytes proportion. While, after EsHIF-1α was activated by IOX4 (HIF-1α activator), the proportion of hyalinocytes was significantly up-regulated and the proportion of granulocytes was significantly down-regulated under post hypoxia treatment. These results collectively suggested that EsHIF-1α was involved in the regulation of proportion of three types of haemocytes induced by hypoxia stress, which provided vital insight into the understanding of the crosstalk between hypoxia and cell development in invertebrates.

Genomic analysis of a new type VI secretion system in Vibrio parahaemolyticus and its implications for environmental adaptation in shrimp ponds.

The type VI secretion system (T6SS) in Vibrio spp. is often used to kill heteroclonal neighbors by direct injection of toxic effectors, but its strategies in aquacultural environments receive limited attention. In this study, we conducted genomic analysis for a T6SS-harboring plasmid in V. parahaemolyticus strain VP157. Coculture assays were further conducted to verify its antibacterial function. The results showed that strain VP157 harbored a 132-kb plasmid, pVP157-1, which consists of two fragments: an 87.8-kb fragment identical to plasmid pTJ114-1 and a 44.2-kb T6SS gene cluster with only 4% DNA identity to T6SS1 in the V. parahaemolyticus reference genome. Gene-by-gene analysis of six genes representing core T6SS components suggested that each gene has distinct evolutionary origins. In vitro experimental evolution revealed that pVP157-1 can excise from the VP157 genome with an excision rate of 4%. A coculture assay suggested that strain VP157 had significantly higher antibacterial activity against Bacillus pumilus and V. cholerae than the strain without pVP157-1(VP157∆T6SS). In contrast, a rapid decline was observed for the proportion of VP157∆ T6SS in a mock microbial community, which decreased from 10.7% to 2.1% in 5 days. The results highlighted that the acquisition of T6SS fostered the fitness of V . parahaemolyticus in a complex environment.

Associations between e-health literacy and chronic disease self-management in older Chinese patients with chronic non-communicable diseases: a mediation analysis.

BACKGROUND: Chronic non-communicable diseases (CNCDs) are an urgent public health issue in China, especially among older adults. Hence, self-management is crucial for disease progression and treatment. Electronic health (e-health) literacy and self-efficacy positively correlate with self-management. However, we know little about their underlying mechanisms in older adults with CNCDs. OBJECTIVE: To explore the factors that influence chronic disease self-management (CDSM) and verify self-efficacy as the mediator between e-health literacy and self-management behavior in older patients with CNCDs. METHODS: This cross-sectional study included 289 older patients with CNCDs from Hunan province, China, between July and November 2021. E-health literacy, self-efficacy, social support, and CDSM data were collected through questionnaires. The influence of each factor on CDSM was explored with multiple linear regression analysis. Intermediary effects were computed via a structural equation model. RESULTS: The total CDSM score in the patients was 29.39 ± 9.60 and only 46 (15.92%) patients used smart healthcare devices. The regression analysis showed e-health literacy, self-efficacy, and social support were the factors that affected CDSM. Furthermore, the structural equation model revealed that self-efficacy directly affected CDSM (ß = 0.45, P < 0.01), whereas e-health literacy affected it directly (ß = 0.42, P < 0.01) and indirectly (ß = 0.429, P < 0.01) through self-efficacy. CONCLUSIONS: This study revealed that self-management among older patients with CNCDs is at a low level, and few of them use smart healthcare devices. Self-efficacy plays a partial intermediary role between e-health literacy and self-management in older patients with CNCDs. Thus, efforts to improve their CDSM by targeting e-health literacy may be more effective when considering self-efficacy.

sCD40L Is Increased and Associated with the Risk of Gestational Diabetes Mellitus in Pregnant Women with Isolated TPOAb Positivity.

Background: Autoimmune disorders are associated with gestational diabetes mellitus (GDM) in pregnant women who were positive for thyroid peroxidase antibody (TPOAb). Soluble CD40 ligand (sCD40L) and soluble interleukin-2 receptor (sCD25) are abnormally expressed in autoimmune diseases and are reliable markers of inflammation. The purpose of this study was to evaluate sCD40L and sCD25 in early pregnancy and investigate their correlation with GDM and TPOAb. Methods: A total of 126 pregnant women in the first trimester were enrolled for analysis: 93 were positive for TPOAb and 33 were negative for TPOAb. Demographical and clinical data in early pregnancy were collected. A total of 123 participants underwent a 75 g oral glucose tolerance test in the second trimester. Serum sCD40L and sCD25 levels were measured by ELISA. Results: The incidence of GDM was 24.4% in pregnant women with isolated TPOAb positivity in our study. Both sCD40L and sCD25 were positively correlated with TPOAb (r = 0.476, P < 0.001; r = 0.188, P < 0.05). sCD40L was highest in (P < 0.001) Ab-positive women with GDM group (P < 0.05). After adjusting for TPOAb, age, TSH, FT4, triglycerides, and low-density lipoprotein cholesterol, multivariate logistic regression analysis showed that sCD40L was an independent risk factor for GDM in pregnant women with TPOAb positivity (odds ratio = 3.235, 95% confidence interval 1.024-10.218, P < 0.05). Conclusions: About a quarter of pregnant women with isolated positive TPOAb might have GDM. sCD40L was an independent risk factor for GDM in women with isolated TPOAb positivity.

Construction of Z-scheme CdS/Ag/TiO2 NTs photocatalysts for photocatalytic dye degradation and hydrogen evolution.

The ternary CdS/Ag/TiO2 NTs photocatalysts with indirect Z-scheme heterojunctions were synthesized by the photoreduction deposition of Ag and successive ionic layer adsorption and reaction (SILAR) of CdS on TiO2 nanotube arrays (TiO2 NTs). The elemental composition, microstructure, photoresponse and photoelectrochemical property of the photocatalyst were systematically characterized. The results proved that compared with binary heterojunction, the light absorption range of the ternary CdS/Ag/TiO2 NTs photocatalyst was significantly extended, and the photoelectron transportation efficiency was improved. Under sunlight irradiation, the photocatalytic capacity was verified by investigating the photodegradation of MB and RhB dyes. The CdS/Ag/TiO2 NTs exhibited the optimal photocatalytic performance with the degradation efficiency of 82.24% for RhB and 100% for MB. The synthesized CdS/Ag/TiO2 NTs had high photocatalytic hydrogen evolution capacity and stability, and the hydrogen production reached 806.33 µmol·cm-2. Based on the results of electron spin resonance spectroscopy (ESR) and free radical trapping, the photocatalytic reaction mechanism was explained. The synthesis of ternary CdS/Ag/TiO2 NTs provides a practical reference and guidance for designing high-efficient photocatalysts with Z-scheme heterojunctions toward solar energy development for H2 generation, pollutant remediation and photoelectric conversion.

Horizontal transfer of antibiotic resistance genes within the bacterial communities in aquacultural environment.

Very little is known about how microbiome interactions shape the horizontal transfer of antibiotic resistance genes in aquacultural environment. To this end, we first conducted 16S rRNA gene amplicon sequencing to monitor the dynamics of bacterial community compositions in one shrimp farm from 2019 to 2020. Next, co-occurrence analysis was then conducted to reveal the interactions network between Vibrio spp. and other species. Subsequently, 21 V. parahaemolyticus isolates and 15 related bacterial species were selected for whole-genome sequencing (WGS). The 16S rDNA amplicon sequencing results identified a remarkable increase of Vibrio and Providencia in September-2019 and a significant rise of Enterobacter and Shewanella in Septtember-2020. Co-occurrence analysis revealed that Vibrio spp. positively interacted with the above species, leading to the sequencing of their isolates to further understand the sharing of the resistant genomic islands (GIs). Subsequent pan-genomic analysis of V. parahaemolyticus genomes identified 278 horizontally transferred genes in 10 GIs, most of which were associated with antibiotic resistance, virulence, and fitness of metabolism. Most of the GIs have also been identified in Providencia, and Enterobacter, suggesting that exchange of genetic traits might occur in V. parahaemolyticus and other cooperative species in a specific niche. No genetic exchange was found between the species with negative relationships. The knowledge generated from this study would greatly improve our capacity to predict and mitigate the emergence of new resistant population and provide practical guidance on the microbial management during the aquacultural activities.

Distinct dynamics of Vibrio parahaemolyticus populations in two farming models.

AIMS: Despite the recent prosperity of shrimp cultivation in China, very little is known about how different shrimp farming models influence the dynamics of Vibrio parahaemolyticus populations and the antibiotic resistance of this bacterium. METHODS AND RESULTS: To this end, we conducted continuous surveillance of V. parahaemolyticus on four farms over 3 years: two traditional shrimp farms with daily water exchange and two farms operated in the recirculating aquaculture systems (RAS). No antibiotics were used in these farms to exclude the potential impacts of antibiotics on the emergence of antibacterial resistance. Multilocus sequence typing was utilized to characterize the dynamics of V. parahaemolyticus populations. Whole-genome sequencing (WGS) was conducted to determine the representative sequence types (STs) at each farm. Results revealed that the population structure of V. parahaemolyticus remained stable over time in both RAS farms, with only nine and four STs observed at each. In contrast, annual replacement of V. parahaemolyticus populations was observed in traditional farms with 26 and 28 STs identified in rearing water. WGS of 50 isolates divided them into five clusters, of which ST917a isolates harboured a genomic island that disrupted the gene recA. Pair-wised genomic comparison of isolates from the same STs showed that they were genetically related but belonged to different clones associated with geographical distribution. CONCLUSIONS: These results suggested that RAS presented a specific ecological niche by minimizing the water exchanges with the external environment. In contrast, traditional farming might pose a food safety issue by introducing new V. parahaemolyticus populations with antibiotic resistance genes. SIGNIFICANCE AND IMPACT OF THE STUDY: Our results expose the potential food safety issue associated with conventional agriculture and should encourage the development of preventive strategies to reduce the emergence of resistant V. parahaemolyticus populations.

Quantitative Proteomic Analysis of Mouse Sciatic Nerve Reveals Post-injury Upregulation of ADP-Dependent Glucokinase Promoting Macrophage Phagocytosis.

Nerve injury induces profound and complex changes at molecular and cellular levels, leading to axonal self-destruction as well as immune and inflammatory responses that may further promote neurodegeneration. To better understand how neural injury changes the proteome within the injured nerve, we set up a mouse model of sciatic nerve injury (SNI) and conducted an unbiased, quantitative proteomic study followed by biochemical assays to confirm some of the changed proteins. Among them, the protein levels of ADP-dependent glucokinase (ADPGK) were significantly increased in the injured sciatic nerve. Further examination indicated that ADPGK was specifically expressed and upregulated in macrophages but not neurons or Schwann cells upon injury. Furthermore, culturing immortalized bone marrow-derived macrophages (iBMDMs) in vitro with the conditioned media from transected axons of mouse dorsal root ganglion (DRG) neurons induced ADPGK upregulation in iBMDMs, suggesting that injured axons could promote ADPGK expression in macrophages non-cell autonomously. Finally, we showed that overexpression of ADPGK per se did not activate macrophages but promoted the phagocytotic activity of lipopolysaccharides (LPS)-treated macrophages. Together, this proteomic analysis reveals interesting changes of many proteins within the injured nerve and our data identify ADPGK as an important in vivo booster of injury-induced macrophage phagocytosis.

Metagenomics combined with comprehensive validation as a public health risk assessment tool for urban and agricultural run-off.

Early detection of emerging and life-threatening pathogens circulating in complex environments is urgently required to combat infectious diseases. This study proposed a public health risk assessment workflow with three stages, pathogen screening, pathogen genotyping, and risk assessment. In stage one, pathogens were screened with metagenomic sequencing, microfluidic chip, and qPCR. In stage two, pathogens were isolated and genotyped with multi-locus sequence typing (MLST) or conventional PCR. Finally, virulence genes from metagenomic data were assessed for pathogenicity. Two regions (Donggang and Zhanjiang) with potential public health concerns were selected for evaluation, each of which comprised of one urban and one farming wastewater sampling location. Overall, metagenomic sequencing reflected the variation in the relative abundance of medically important bacteria. Over 90 bacterial pathogens were monitored in the metagenomic dataset, of which 56 species harbored virulence genes. In Donggang, a pathogenic Acinetobacter sp. reached high abundances in 2018 and 2020, whereas all pathogenic Vibrio spp. peaked in October 2019. In Zhanjiang, A. baumanni, and other Enterobacteriaceae species were abundantly present in 2019 and 2020, whereas Aeromonas and Vibrio spp. peaked in November-2017. Forty species were subsequently isolated and subtyped by MLST, half of which were prevalent genotypes in clinical data. Additionally, we identified the African Swine Fever Virus (ASFV) in water samples collected in 2017, ahead of the first reported ASFV outbreak in 2018 in China. RNA viruses like Hepatitis A virus (HAV) and Enterovirus 71 (EV71) were also detected, with concentrations peaking in April 2020 and April 2018, respectively. The dynamics of HAV and EV71 were consistent with local epidemic trends. Finally, based on the virulence gene profiles, our study identified the risk level in wastewater of two cities. This workflow illustrates the potential for an early warning of local epidemics, which helps to prioritize the preparedness for specific pathogens locally.

One health pathogen surveillance demonstrated the dissemination of gut pathogens within the two coastal regions associated with intensive farming.

BACKGROUND: Intensive aquaculture farming has caused significant degradation of coastal wetlands and has been proposed as a reservoir for pathogenic Vibrio spp. RESULTS: Gut pathogens including Vibrio spp., Salmonella spp., and Klebsiella spp. were isolated from bird feces, shrimp and wetland water in two typical coastal regions of China in 2015 and 2017 and were subsequently subjected to whole-genome sequencing. Meanwhile, local patient isolates were also selected to confirm the epidemiological links. Bacterial community composition analyses of the sediments that were sampled in 2015 and 2017 were conducted by the hypervariable region 4 of the 16S rRNA gene. Together with the local clinical isolates, we observed highly related Vibrio isolates from waterbirds, wetlands and shrimp. Phylogenetic genome comparisons also demonstrated that sequence types ST3 and ST2414 Vibrio parahaemolyticus isolates obtained from aquatic animals were clonally related to patient isolates. Likewise, three Salmonella typhimurium isolates were also genomically related to one clinical strain. The results showed that farming activities significantly altered the community composition and resulted in the emergence of several pathogens, including Acinetobacter, Mycobacterium and Legionella. CONCLUSIONS: In conclusion, our results demonstrated that intensive shrimp farming in wetlands has two devastating impacts: pathogen dissemination from aquatic animals into migratory birds and transmission of foodborne pathogens into local communities.

Continuous Genomic Surveillance Monitored the In Vivo Evolutionary Trajectories of Vibrio parahaemolyticus and Identified a New Virulent Genotype.

Our ability to predict evolutionary trajectories of pathogens is one of the promising leverages to fight against the pandemic disease, yet few studies have addressed this question in situ, due to the difficulty in monitoring the milestone evolutionary events for a given pathogen and in understanding the evolutionary strategies. In this study, we monitored the real-time evolution of Vibrio parahaemolyticus in response to successive antibiotic treatment in three shrimp farms in North China from 2011 to 2018 by whole-genome sequencing. Results showed that the stepwise emergence of resistance was associated with the antibiotic usage. Genomic analysis of resistant isolates showed that the acquisition of the resistant mobile genetic elements flanked by an insertion sequence (ISVal1) closely mirrored the antibiotics used in shrimp farms since 2014. Next, we also identified 50 insertion sites of ISVal1 in the chromosome, which facilitated the formation of pathogenicity islands (PAIs) and fitness islands in the following years. Further, horizontal transfers of a virulent trh-nik-ure genomic island (GI) and two GIs improving the fitness have been observed in two farms since 2016. In this case study, we proposed that the insertion sequence triggered four major evolutionary events during the outbreaks of shrimp disease in three farms, including horizontal transfer of transposon (HTT) (stage 1), the formation of resistance islands (stage 2) and the PAIs (stage 3), and horizontal transfer of the PAIs (stage 4). This study presented the first in vivo evolutionary trajectories for a given bacterial pathogen, which helps us to understand the emergence mechanisms of new genotypes.IMPORTANCE Most human infectious diseases originate from animals. Thus, how to reduce or prevent pandemic zoonoses before they emerge in people is becoming a critical issue. Continuous genomic surveillance of the evolutionary trajectories of potential human pathogens on farms is a promising strategy to realize early warning. Here, we conducted an 8-year surveillance of Vibrio parahaemolyticus in three shrimp farms. The results showed that the use of antibiotics and horizontal transfer of transposons (HTT) drove the evolution of V. parahaemolyticus, which could be divided into four stages: HTT, formation of resistance islands, formation of pathogenicity islands (PAIs), and horizontal transfer of PAIs. This study presented the first in vivo monitoring of evolutionary trajectories for a given bacterial pathogen, providing valuable information for the prevention of pandemic zoonoses.