Methylation entropy landscape of Chinese long-lived individuals reveals lower epigenetic noise related to human healthy aging.

The transition from ordered to noisy is a significant epigenetic signature of aging and age-related disease. As a paradigm of healthy human aging and longevity, long-lived individuals (LLI, >90 years old) may possess characteristic strategies in coping with the disordered epigenetic regulation. In this study, we constructed high-resolution blood epigenetic noise landscapes for this cohort by a methylation entropy (ME) method using whole genome bisulfite sequencing (WGBS). Although a universal increase in global ME occurred with chronological age in general control samples, this trend was suppressed in LLIs. Importantly, we identified 38,923 genomic regions with LLI-specific lower ME (LLI-specific lower entropy regions, for short, LLI-specific LERs). These regions were overrepresented in promoters, which likely function in transcriptional noise suppression. Genes associated with LLI-specific LERs have a considerable impact on SNP-based heritability of some aging-related disorders (e.g., asthma and stroke). Furthermore, neutrophil was identified as the primary cell type sustaining LLI-specific LERs. Our results highlight the stability of epigenetic order in promoters of genes involved with aging and age-related disorders within LLI epigenomes. This unique epigenetic feature reveals a previously unknown role of epigenetic order maintenance in specific genomic regions of LLIs, which helps open a new avenue on the epigenetic regulation mechanism in human healthy aging and longevity.

Leukocyte Ig-like receptor B4 (Lilrb4a) alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation.

BACKGROUND: Heart failure (HF) is usually accompanied by the activation of the sympathetic nerve, and the excessive activation of the sympathetic nerve also promotes cardiac remodeling and cardiac dysfunction. In the isoproterenol (ISO) induced animal model, it is often accompanied by myocardial hypertrophy, fibrosis, and inflammation. Leukocyte immunoglobulin-like receptor B4a (Lilrb4a) is an immunosuppressive regulatory receptor and plays a vital role in cardiovascular disease. However, the effect of Lilrb4a on ventricular arrhythmias from ISO-induced mice model remains unclear. OBJECTIVE: The purpose of this study was to explore the role and molecular mechanism of Lilrb4a in ISO-induced arrhythmogenic remodeling. METHODS: Lilrb4a knockout mice and Lilrb4a overexpression mice were infused with ISO (15 mg/kg/24h, 4 weeks). Echocardiography and Histology were used to evaluate myocardial hypertrophy and cardiac structural remodeling. Surface ECG and Electrophysiological examination were used to evaluate cardiac electrical remodeling and the susceptibility to ventricular arrhythmias (VAs). qRT-PCR and Western Blotting were used to detect the expression levels of ion channel proteins and signal pathway proteins. RESULTS: The results discovered that ISO induced cardiac hypertrophy, fibrosis, and inflammation, and led to electrical remodeling and the occurrence of VAs. Lilrb4a alleviated cardiac structural and electrical remodeling and protected against the occurrence of VAs in ISO-induced mice by gain- or loss-of-function approaches. The mechanism is that Lilrb4a inhibited NF-kB signaling and p38 signaling activation medicated by TAK1. CONCLUSIONS: Lilrb4a alleviates cardiac dysfunction and isoproterenol-induced arrhythmogenic remodeling associated with cardiac fibrosis and inflammation through the regulation of NF-kB signaling and p38 signaling activation.

Protective Effect of Resveratrol Combined with Levodopa Against Oxidative Damage in Dopaminergic Neurons.

Levodopa (L-3,4-dihydroxyphenylalanine, L-Dopa) alleviates the symptoms of Parkinson's disease (PD), yet prolonged usage may give rise to severe adverse effects. Resveratrol (RSV) is a potent antioxidant, anticancer and anti-inflammatory agent. And a variety of polyphenol antioxidant compounds derived from RSV combined with levodopa have demonstrated neuroprotective activity against neuronal cell death. The purpose of this study was to examine the impact of this combination of RSV and L-Dopa on the survival rate, growth status, and reactive oxygen species (ROS) of MES23.5 dopamine (DA) neuron cells. In this study, we induced MPP+ in MES23.5 dopamine neuron cells and observed their survival rate, growth status, ROS content, as well as the effect of RSV combined with L-Dopa on cell survival. We also measured malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels as indicators of mitochondrial function, oxidative stress, and oxidative damage in the cells. Our results indicated that the MES23.5 dopamine neurons had decreased survival, poor growth status, and increased ROS content after MPP+ induction. Moreover, we found that MDA levels were elevated, and SOD activity levels were decreased, suggesting that the cells experienced abnormal mitochondrial function. However, when RSV was combined with L-Dopa, the cells showed a reduced level of MPP + -induced oxidative damage, with a more significant inhibitory effect observed in the RSV group at a concentration of 50 µmol/L. In conclusion, we found that the effects of co-administration of RSV with L-Dopa (100 µmol/L) was more effective than L-Dopa administered at the high dose. Thus, we found that RSV has the potential to reduce the dose of L-Dopa required to improve PD symptoms.

Crystal-Phase-Engineered High-Entropy Alloy Aerogels for Enhanced Ethylamine Electrosynthesis from Acetonitrile.

Crystal-phase engineering that promotes the rearrangement of active atoms to form new structural frameworks achieves excellent result in the field of electrocatalysis and optimizes the performance of various electrochemical reactions. Herein, for the first time, it is found that the different components in metallic aerogels will affect the crystal-phase transformation, especially in high-entropy alloy aerogels (HEAAs), whose crystal-phase transformation during annealing is more difficult than medium-entropy alloy aerogels (MEAAs), but they still show better electrochemical performance. Specifically, PdPtCuCoNi HEAAs with the parent phase of face-centered cubic (FCC) PdCu possess excellent 89.24% of selectivity, 746.82 mmol h-1 g-1 cat. of yield rate, and 90.75% of Faraday efficiency for ethylamine during acetonitrile reduction reaction (ARR); while, maintaining stability under 50 h of long-term testing and ten consecutive electrolysis cycles. The structure-activity relationship indicates that crystal-phase regulation from amorphous state to FCC phase promotes the atomic rearrangement in HEAAs, thereby optimizing the electronic structure and enhancing the adsorption strength of reaction intermediates, improving the catalytic performance. This study provides a new paradigm for developing novel ARR electrocatalysts and also expands the potential of crystal-phase engineering in other application areas.

Hyperbaric oxygen therapy promotes the browning of white fat and contributes to the healing of diabetic wounds.

Non-healing wounds are one of the chronic complications of diabetes and have remained a worldwide challenge as one of the major health problems. Hyperbaric oxygen (HBO) therapy is proven to be very successful for diabetic wound treatment, for which the molecular basis is not understood. Adipocytes regulate multiple aspects of repair and may be therapeutic for inflammatory diseases and defective wound healing associated with aging and diabetes. Endothelial cell-derived extracellular vesicles could promote wound healing in diabetes. To study the mechanism by which HBO promotes wound healing in diabetes, we investigated the effect of HBO on fat cells in diabetic mice. A diabetic wound mouse model was established and treated with HBO. Haematoxylin and eosin (H&E) staining and immunofluorescence were used for the analysis of wound healing. To further explore the mechanism, we performed whole-genome sequencing on extracellular vesicles (EVs). Furthermore, we conducted in vitro experiments. Specifically, exosomes were collected from human umbilical vein endothelial cell (HUVEC) cells after HBO treatment, and then these exosomes were co-incubated with adipose tissue. The wound healing rate in diabetic mice treated with HBO was significantly higher. HBO therapy promotes the proliferation of adipose precursor cells. HUVEC-derived exosomes treated with HBO significantly promoted fat cell browning. These data clarify that HBO therapy may promote vascular endothelial cell proliferation and migration, and promote browning of fat cells through vascular endothelial cells derived exosomes, thereby promoting diabetic wound healing. This provides new ideas for the application of HBO therapy in the treatment of diabetic trauma.

Prolonged oral intake of green tea polyphenols attenuates delirium-like behaviors in mice induced by anesthesia/surgery.

Postoperative delirium (POD) is a severe postoperative complication characterized by delirium-like symptoms. So far, no effective preventable strategy for POD prevention has been identified. Reports show that the consumption of green tea polyphenols (GTP) is associated with better cognitive function by modulating the composition of gut microbiota. Whether GTP also play a role in alleviating POD through gut microbiota is unknown. Herein, we studied the effect of prolonged (eight weeks) GTP intake on postoperative delirium in C57BL/6 mice with laparotomies under isoflurane anesthesia (anesthesia/surgery). We subsequently investigated anesthesia/surgery caused behavioral changes and increased the expression of malondialdehyde (MAD), an oxidative stress marker, and the activities of superoxide dismutase (SOD), an antioxidant marker, in the mice at 6 h after anesthesia/surgery. However, GTP administration reversed these changes and alleviated anesthesia/surgery-induced decrease in the abundance of gut bacterial genera, Roseburia. Further, fecal microbiota transplant demonstrated that compared with mice in the control group, treatment of C57BL/6 mice with feces from GTP-treated mice had a slight effect on the behavioral changes of mice. These data suggest that daily consumption of GTP could protect against anesthesia/surgery-induced behavioral changes, which is closely associated with gut microbiota modification by GTP.

Acute urinary retention due to corpus cavernosum penile metastasis from lung adenocarcinoma after targeted therapy: a case report and review of the literature.

Background: Metastasis in penile corpus cavernosum from adenocarcinoma of lung is a rare but fatal disease, which was reported in cases without series studies. It causes various clinical symptoms seriously affecting the quality of life. Case presentation: A 72-year-old male smoker patient, who had a history of adenocarcinoma of lung after targeted therapy 36 months before, was admitted to Jiangxi Cancer Hospital because of presenting with aggressive dysuria and penis pain for one hour. A Foley catheter was inserted into the patient's bladder with difficulty. Immediately do a bladder puncture. Emergency pelvic computed tomography (CT): a soft tissue nodule of 1.1 cm×1.4 cm was found in the cavernous area of the middle part of the penis, and the proximal urethra was dilated with a wide diameter of about 1.5 cm. The diagnosis of metastatic lung adenocarcinoma from the primary was made by CT-guided biopsy. Conclusion: The penis may be a site of metastasis from primary lung cancer, especially for old patient. Metastasis to the penis usually indicates that the primary lung cancer is at an advanced stage and the prognosis is very poor. More research is necessary to understand the underlying mechanism of adenocarcinoma of lung metastasis.

DL-3-n-butylphthalide attenuates doxorubicin-induced acute cardiotoxicity via Nrf2/HO-1 signaling pathway.

Doxorubicin (DOX) is a widely used chemotherapeutic drug known to cause dose-dependent myocardial toxicity, which limits its clinical potential. DL-3-n-butylphthalide (NBP), a substance extracted from celery seed species, has a number of pharmacological properties, such as antioxidant, anti-inflammatory, and anti-apoptotic actions. However, whether NBP can protect against DOX-induced acute myocardial toxicity is still unclear. Therefore, this study was designed to investigate the potential protective effects of NBP against DOX-induced acute myocardial injury and its underlying mechanism. By injecting 15 mg/kg of DOX intraperitoneally, eight-week-old male C57BL6 mice suffered an acute myocardial injury. The treatment group of mice received 80 mg/kg NBP by gavage once daily for 14 days. To mimic the cardiotoxicity of DOX, 1uM DOX was administered to H9C2 cells in vitro. In comparison to the DOX group, the results showed that NBP improved cardiac function and decreased serum levels of cTnI, LDH, and CK-MB. Additionally, HE staining demonstrated that NBP attenuated cardiac fibrillar lysis and breakage in DOX-treated mouse hearts. Western blotting assay and immunofluorescence staining suggested that NBP attenuated DOX-induced oxidative stress, apoptosis, and inflammation both in vivo and in vitro. Mechanistically, NBP significantly upregulated the Nrf2/HO-1 signaling pathway, while the Nrf2 inhibitor ML385 prevented NBP from protecting the myocardium from DOX-induced myocardial toxicity in vitro. In conclusion, Our results indicate that NBP alleviates DOX-induced myocardial toxicity by activating the Nrf2/HO-1 signaling pathway.

New insights into functional divergence and adaptive evolution of uncultured bacteria in anammox community by complete genome-centric analysis.

Anaerobic ammonium-oxidation (anammox) bacteria play a crucial role in global nitrogen cycling and wastewater nitrogen removal, but they share symbiotic relationships with various other microorganisms. Functional divergence and adaptive evolution of uncultured bacteria in anammox community remain underexplored. Although shotgun metagenomics based on short reads has been widely used in anammox research, metagenome-assembled genomes (MAGs) are often discontinuous and highly contaminated, which limits in-depth analyses of anammox communities. Here, for the first time, we performed Pacific Biosciences high-fidelity (HiFi) long-read sequencing on the anammox granule sludge sample from a lab-scale bioreactor, and obtained 30 accurate and complete metagenome-assembled genomes (cMAGs). These cMAGs were obtained by selecting high-quality circular contigs from initial assemblies of long reads generated by HiFi sequencing, eliminating the need for Illumina short reads, binning, and reassembly. One new anammox species affiliated with Candidatus Jettenia and three species affiliated with novel families were found in this anammox community. cMAG-centric analysis revealed functional divergence in general and nitrogen metabolism among the anammox community members, and they might adopt a cross-feeding strategy in organic matter, cofactors, and vitamins. Furthermore, we identified 63 mobile genetic elements (MGEs) and 50 putative horizontal gene transfer (HGT) events within these cMAGs. The results suggest that HGT events and MGEs related to phage and integration or excision, particularly transposons containing tnpA in anammox bacteria, might play important roles in the adaptive evolution of this anammox community. The cMAGs generated in the present study could be used to establish of a comprehensive database for anammox bacteria and associated microorganisms. These findings highlight the advantages of HiFi sequencing for the studies of complex mixed cultures and advance the understanding of anammox communities.

Composite of formamidinium lead bromide perovskite FAPbBr3 with reduced graphene oxide (rGO) for efficient H2 evolution from HBr splitting.

Solar hydrobromic acid (HBr) splitting using perovskite photocatalysts provides an attractive avenue to store solar energy into hydrogen (H2) and bromine (Br2), while an efficient photocatalytic system is still demanded. As for the semiconductor photocatalyst, formamidinium perovskites show some superiorities in structural stability, light adsorption and charge dynamics compared to their methylammonium counterparts, which are fitter for the photocatalysis process. Herein, the composite of formamidinium lead bromide perovskite (FAPbBr3) with reduced graphene oxide (rGO) is prepared using a facile photoreduction method. Under simulated sunlight irradiation (AM1.5G, 100 mW cm-2), this FAPbBr3/rGO composite (100 mg) demonstrates a noteworthy enhancement in photocatalytic H2 evolution activity of 386.7 µmol h-1, and it exhibits a notable stability with no significant decrease after 50 h of repeated tests. The single particle PL (photoluminescence) microscope is employed to study the charge dynamics, revealing that rGO in the composite effectively promotes the carrier separation. This work provides a highly efficient and stable photocatalyst for HBr splitting, and offers an effective modification strategy on lead bromide perovskites.

Oligodendrocytes in central nervous system diseases: the effect of cytokine regulation.

Cytokines including tumor necrosis factor, interleukins, interferons, and chemokines are abundantly produced in various diseases. As pleiotropic factors, cytokines are involved in nearly every aspect of cellular functions such as migration, survival, proliferation, and differentiation. Oligodendrocytes are the myelin-forming cells in the central nervous system and play critical roles in the conduction of action potentials, supply of metabolic components for axons, and other functions. Emerging evidence suggests that both oligodendrocytes and oligodendrocyte precursor cells are vulnerable to cytokines released under pathological conditions. This review mainly summarizes the effects of cytokines on oligodendrocyte lineage cells in central nervous system diseases. A comprehensive understanding of the effects of cytokines on oligodendrocyte lineage cells contributes to our understanding of central nervous system diseases and offers insights into treatment strategies.

Canagliflozin combined with aerobic exercise protects against chronic heart failure in rats.

To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function. In rats treated with canagliflozin combined with aerobic exercise, the expression of cytochrome P450 (CYP) 4A3, CYP4A8, COL1A1, COL3A1, and FN1 was reduced, while the expression of CYP26B1, ALDH1A2, and CYP1A1 increased significantly. Additionally, canagliflozin combined with aerobic exercise decreased the phosphorylation of AKT and ERK1/2. Canagliflozin combined with aerobic exercise has a positive effect on the development of CHF via the regulation of retinol metabolism and the AKT/ERK signaling pathway.

Efficacy of polyethylene glycol loxenatide for type 2 diabetes mellitus patients: a systematic review and meta-analysis.

Objective: Some studies have proved that polyethylene glycol loxenatide (PEG-Loxe) has significant effects on controlling blood glucose and body weight in patients with type 2 diabetes mellitus (T2DM), but there is still some controversy over the improvement of blood lipid profiles (BLP) and blood pressure (BP), and more evidences are needed to verify such effects. Therefore, this study was conducted to provide a comprehensive evaluation of the efficacy of PEG-Loxe in improving blood glucose (BG), BLP, BP, body mass index (BMI), and body weight (BW) in patients with T2DM for clinical reference. Methods: Randomized controlled trials (RCT) in which PEG-Loxe was applied to treat T2DM were retrieved by searching PubMed, Cochrane Library, Embase, Medline, Scopus, Web of Science, China National Knowledge Infrastructure, China Scientific Journal, Wanfang Data, and SinoMed databases. Outcome measures included BG, BLP, BP, BMI, and BW. RevMan 5.3 software was used to perform data analysis. Results: Eighteen trials were identified involving 2,166 patients. In experimental group 1,260 patients received PEG-Loxe alone or with other hypoglycemic agents, while in control group 906 patients received placebo or other hypoglycemic agents. In the overall analysis, PEG-Loxe significantly reduced the levels of glycosylated hemoglobin (HbA1c), fasting plasma glucose (FPG), 2-h postprandial blood glucose (2-h PBG), BMI, and BW compared with control group. However, it had no obvious effect on total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Conclusion: PEG-Loxe has better hypoglycemic effects compared with placebo in patients with T2DM, but could not significantly improved TG, LDL-C, HDL-C, SBP, and DBP. And the combination of conventional hypoglycemic drugs (CHD) and PEG-Loxe could more effectively improve the levels of HbA1c, FPG, 2-h PBG, TC, TG, BMI, and BW compared with CHD in T2DM patients. Systematic Review Registration: www.inplasy.com, identifier INPLASY202350106.

Re-oligotrophication and warming stabilize phytoplankton networks.

Phytoplankton taxa are strongly interconnected as a network, which could show temporal dynamics and non-linear responses to changes in drivers at both seasonal and long-term scale. Using a high quality dataset of 20 Danish lakes (1989-2008), we applied extended Local Similarity Analysis to construct temporal network of phytoplankton communities for each lake, obtained sub-network for each sampling month, and then measured indices of network complexity and stability for each sub-network. We assessed how lake re-oligotrophication, climate warming and grazers influenced the temporal dynamics on network complexity and stability of phytoplankton community covering three aspects: seasonal trends, long-term trends and detrended variability. We found strong seasonality for the complexity and stability of phytoplankton network, an increasing trend for the average degree, modularity, nestedness, persistence and robustness, and a decreasing trend for connectance, negative:positive interactions and vulnerability. Our study revealed a cascading effect of lake re-oligotrophication, climate warming and zooplankton grazers on phytoplankton network stability through changes in network complexity characterizing diversity, interactions and topography. Network stability of phytoplankton increased with average degree, modularity, nestedness and decreased with connectance and negative:positive interactions. Oligotrophication and warming stabilized the phytoplankton network (enhanced robustness, persistence and decreased vulnerability) by enhancing its average degree, modularity, nestedness and by reducing its connectance, while zooplankton richness promoted stability of phytoplankton network through increases in average degree and decreases in negative interactions. Our results further indicate that the stabilization effects might lead to more closed, compartmentalized and nested interconnections especially in the deeper lakes, in the warmer seasons and during bloom periods. From a temporal dynamic network view, our findings highlight stabilization of the phytoplankton community as an adaptive response to lake re-oligotrophication, climate warming and grazers.

The novel TERF2::PDGFRB fusion gene enhances tumorigenesis via PDGFRB/STAT5 signalling pathways and sensitivity to TKI in ph-like ALL.

Patients with Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like ALL) often face a grim prognosis, with PDGFRB gene fusions being commonly detected in this subgroup. Our study has unveiled a newfound fusion gene, TERF2::PDGFRB, and we have found that patients carrying this fusion gene exhibit sensitivity to dasatinib. Ba/F3 cells harbouring the TERF2::PDGFRB fusion display IL-3-independent cell proliferation through activation of the p-PDGFRB and p-STAT5 signalling pathways. These cells exhibit reduced apoptosis and demonstrate sensitivity to imatinib in vitro. When transfused into mice, Ba/F3 cells with the TERF2::PDGFRB fusion gene induce tumorigenesis and a shortened lifespan in cell-derived graft models, but this outcome can be improved with imatinib treatment. In summary, we have identified the novel TERF2::PDGFRB fusion gene, which exhibits oncogenic potential both in vitro and in vivo, making it a potential therapeutic target for tyrosine kinase inhibitors (TKIs).

Landscape of T cell epitopes displays hot mutations of SARS-CoV-2 variant spikes evading cellular immunity.

The continuous evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been accompanied by the emergence of viral mutations that pose a great challenge to existing vaccine strategies. It is not fully understood with regard to the role of mutations on the SARS-CoV-2 spike protein from emerging viral variants in T cell immunity. In the current study, recombinant eukaryotic plasmids were constructed as DNA vaccines to express the spike protein from multiple SARS-CoV-2 strains. These DNA vaccines were used to immunize BALB/c mice, and cross-T cell responses to the spike protein from these viral strains were quantitated using interferon-γ (IFN-γ) Elispot. Peptides covering the full-length spike protein from different viral strains were used to detect epitope-specific IFN-γ+ CD4+ and CD8+ T cell responses by fluorescence-activated cell sorting. SARS-CoV-2 Delta and Omicron BA.1 strains were found to have broad T cell cross-reactivity, followed by the Beta strain. The landscapes of T cell epitopes on the spike protein demonstrated that at least 30 mutations emerging from Alpha to Omicron BA.5 can mediate the escape of T cell immunity. Omicron and its sublineages have 19 out of these 30 mutations, most of which are new, and a few are inherited from ancient circulating variants of concerns. The cross-T cell immunity between SARS-CoV-2 prototype strain and Omicron strains can be attributed to the T cell epitopes located in the N-terminal domain (181-246 aa [amino acids], 271-318 aa) and C-terminal domain (1171-1273 aa) of the spike protein. These findings provide in vivo evidence for optimizing vaccine manufacturing and immunization strategies for current or future viral variants.

[Determination of 35 antibiotics and four ß-receptor agonists in teenagers and analysis of exposure status].

Antibiotics are mainly used for disease treatment and prevention, and ß-receptor agonists are mainly used in the clinical treatment of respiratory diseases. Both types of drugs are also widely used in animal husbandry and aquaculture to promote animal growth and prevent disease. These drugs enter the human body through many routes and cause harm to human health. Teenagers are in a critical period of growth and development, and long-term antibiotic exposure may have adverse effects on their bodies. In this study, 442 teenagers aged 11-15 years were recruited from a middle school to investigate the body burden of various antibiotics and ß-receptor agonists. The seven categories of antibiotics, including five macrolides, four tetracyclines, 10 quinolones, 11 sulfonamides, three ß-lactams, one quinoxaline, and one lincosamide, and four ß-receptor agonists were determined by isotope dilution and solid phase extraction coupled with ultra performance liquid chromatography-tandem mass spectrometry. Analyte levels were corrected using urine creatinine, and detection rates were used for data analysis. Pearson's chi-squared test was used to analyze the correlations between detection rate and gender, age, or body mass index (BMI). Logistic regression was used to evaluate the correlation between detection rate and different groups after adjusting for confounding factors. The results showed that 397 teenagers had at least one antibiotic or ß-receptor agonist in their urine, with a total detection rate of 89.8%. A total of 29 antibiotics and ß-receptor agonists were detected, and the detection rate of each compound ranged from 0.2% to 59.0%. Doxycycline, oxytetracycline, and azithromycin were the top three drugs with the highest detection rates (59.0%, 56.1%, and 34.6%, respectively). Tetracyclines and macrolides were the two antibiotic categories detected most often, with detection rates of 81.9% and 42.3%, respectively. Among the antibiotics investigated, preferred veterinary antibiotics (PVAs) had the highest detection rate (85.1%), followed by human antibiotics (HAs) (41.0%). The overall detection rate of ß-receptor agonists was 2.7%. Statistical analysis showed that the male was prone to be exposed to tetracycline antibiotics (odds ratio (OR)=2.17). The detection rates of macrolides differed among the different age groups and were higher in those aged 12-13 years than in those aged 11 years. As the BMI of the teenagers increased, the detection rate of macrolides gradually increased. After adjusting for age and gender, teenagers with obesity were found to be 2.35 times more likely to be exposed to macrolides than those with a normal weight. The findings suggest that teenagers are generally exposed to low levels of antibiotics, that food and the environment may be the main sources of antibiotic exposure in teenagers, and that macrolide exposure may be associated with adolescent obesity.

Mediating Role of Liver Dysfunction in the Association between Arsenic Exposure and Diabetes in Chinese Adults: A Nationwide Cross-Sectional Study of China National Human Biomonitoring (CNHBM) 2017-2018.

Inconsistent results have been reported regarding the association between low-to-moderate arsenic (As) exposure and diabetes. The effect of liver dysfunction on As-induced diabetes remains unclear. The cross-sectional study included 10,574 adults from 2017-2018 China National Human Biomonitoring. Urinary total As (TAs) levels were analyzed as markers of As exposure. Generalized linear mixed models and restricted cubic splines models were used to examine the relationships among TAs levels, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) concentrations, and diabetes prevalence. Mediating analysis was performed to assess whether liver dysfunction mediated the association between TAs and diabetes. Overall, the OR (95% CI) of diabetes in participants in the second, third, and fourth quartiles of TAs were 1.08 (0.88, 1.33), 1.17 (0.94, 1.45), and 1.52 (1.22, 1.90), respectively, in the fully adjusted models compared with those in the lowest quartile. Serum ALT was positively associated with TAs and diabetes. Additionally, mediation analyses showed that ALT mediated 4.32% of the association between TAs and diabetes in the overall population and 8.86% in the population without alcohol consumption in the past year. This study suggested that alleviating the hepatotoxicity of As could have implications for both diabetes and liver disease.