Characterizing organophosphate esters and chlorinated paraffins in surface soils affected by diverse e-waste disassembling process in South China: Occurrence, distinct emission, and risk assessment.

E-waste recycling activities are a crucial emission source of organic pollutants, posing potential risks to the surrounding environment and human health. To understand the potential impact related to diverse e-waste dismantling activities, we investigated two categories of popular flame retardants (i.e., organophosphate esters (OPEs) and chlorinated paraffins (CPs) and their resultant possible ecological risk in 53 surface soil samples from Qingyuan, a well-known e-waste recycling region in South China. Varied concentrations of ΣOPEs (20.5-8720 ng/g) and ΣCPs (920-16800 ng/g) were observed at diverse dismantling sites, while relatively low levels of ΣOPEs (6.13-1240 ng/g) and ΣCPs (14.8-2870 ng/g) were found in surrounding soils. These results indicated that primitive e-waste dismantling processes were the primary emission source of OPEs and CPs in the studied area, with e-waste dumping and manual dismantling being the most important emission sources for OPEs and CPs. More importantly, CPs could be degraded/transformed into more toxic intermediates via dechlorination and decarbonization during the burning of e-waste. Furthermore, our results indicated the potential ecological risks posed by OPEs and CPs related to e-waste recycling.

Network medicine analysis for dissecting the therapeutic mechanism of consensus TCM formulae in treating hepatocellular carcinoma with different TCM syndromes.

Introduction: Hepatocellular carcinoma (HCC) is a major cause of cancer-related mortality worldwide. Traditional Chinese Medicine (TCM) is widely utilized as an adjunct therapy, improving patient survival and quality of life. TCM categorizes HCC into five distinct syndromes, each treated with specific herbal formulae. However, the molecular mechanisms underlying these treatments remain unclear. Methods: We employed a network medicine approach to explore the therapeutic mechanisms of TCM in HCC. By constructing a protein-protein interaction (PPI) network, we integrated genes associated with TCM syndromes and their corresponding herbal formulae. This allowed for a quantitative analysis of the topological and functional relationships between TCM syndromes, HCC, and the specific formulae used for treatment. Results: Our findings revealed that genes related to the five TCM syndromes were closely associated with HCC-related genes within the PPI network. The gene sets corresponding to the five TCM formulae exhibited significant proximity to HCC and its related syndromes, suggesting the efficacy of TCM syndrome differentiation and treatment. Additionally, through a random walk algorithm applied to a heterogeneous network, we prioritized active herbal ingredients, with results confirmed by literature. Discussion: The identification of these key compounds underscores the potential of network medicine to unravel the complex pharmacological actions of TCM. This study provides a molecular basis for TCM's therapeutic strategies in HCC and highlights specific herbal ingredients as potential leads for drug development and precision medicine.

Inhibition of TFEB deacetylation in proximal tubular epithelial cells (TECs) promotes TFEB activation and alleviates TEC damage in diabetic kidney disease.

The inhibition of the autophagolysosomal pathway mediated by transcription factor EB (TFEB) inactivation in proximal tubular epithelial cells (TECs) is a key mechanism of TEC injury in diabetic kidney disease (DKD). Acetylation is a novel mechanism that regulates TFEB activity. However, there are currently no studies on whether the adjustment of the acetylation level of TFEB can reduce the damage of diabetic TECs. In this study, we investigated the effect of Trichostatin A (TSA), a typical deacetylase inhibitor, on TFEB activity and damage to TECs in both in vivo and in vitro models of DKD. Here, we show that TSA treatment can alleviate the pathological damage of glomeruli and renal tubules and delay the DKD progression in db/db mice, which is associated with the increased expression of TFEB and its downstream genes. In vitro studies further confirmed that TSA treatment can upregulate the acetylation level of TFEB, promote its nuclear translocation, and activate the expression of its downstream genes, thereby reducing the apoptosis level of TECs. TFEB deletion or HDAC6 knockdown in TECs can counteract the activation effect of TSA on autophagolysosomal pathway. We also found that TFEB enhances the transcription of Tfeb through binding to its promoter and promotes its own expression. Our results, thus, provide a novel therapeutic mechanism for DKD that the alleviation of TEC damage by activating the autophagic lysosomal pathway through upregulating TFEB acetylation can, thus, delay DKD progression.

Exploring the mediating role of the ventral attention network and somatosensory motor network in the association between childhood trauma and depressive symptoms in major depressive disorders.

BACKGROUND: Childhood trauma is closely tied to adult depression, but the neurobiological mechanisms remain unclear. Previous studies suggested associations between depression and large-scale brain networks such as the Ventral Attention Network (VAN) and Somatosensory Motor Network (SMN). This study hypothesized that functional connectivity (FC) within and between these networks mediates the link between childhood trauma and adult depression. METHODS: The Childhood Trauma Questionnaire (CTQ) assessed developmental experiences, and the Hamilton Rating Scale for Depression (HAMD-17) gauged depressive symptoms. Resting-state functional magnetic resonance imaging (fMRI) analyzed FC within and between the VAN and SMN. RESULTS: Depression group exhibited significantly higher HAMD and CTQ scores, as well as elevated FC within the VAN and between the VAN and SMN (P < 0.05). Positive correlations were found between HAMD total score and FC within the VAN (P < 0.05, r = 0.35) and between the VAN and SMN (P < 0.05, r = 0.34), as well as with CTQ total score (P < 0.05, r = 0.27). Positive correlations were also observed between CTQ total score and FC within the VAN (P < 0.05, r = 0.31) and between the VAN and SMN (P < 0.05, r = 0.29). In the mediation model, FC within and between the VAN and SMN significantly mediated childhood trauma and depression. LIMITATIONS: The cross-sectional design limits causal inference. The sample size for different trauma types is relatively small, urging caution in generalizing findings. CONCLUSIONS: The study underscores the association between depression severity, VAN dysfunction, abnormal VAN-SMN FC, and childhood trauma. These findings contribute to understanding the neurobiological mechanisms underlying childhood trauma and depression.

Telitacicept: A novel horizon in targeting autoimmunity and rheumatic diseases.

BLyS and APRIL have the capability to bind to B cells within the body, allowing these cells to evade elimination when they should naturally be removed. While BLyS primarily plays a role in B cell development and maturation, APRIL is linked to B cell activation and the secretion of antibodies. Thus, in theory, inhibiting BLyS or APRIL could diminish the population of aberrant B cells that contribute to SLE and reduce disease activity in patients. Telitacicept functions by binding to and neutralizing the activities of both BLyS and APRIL, thus hindering the maturation and survival of plasma cells and fully developed B cells. The design of telitacicept is distinctive; it is not a monoclonal antibody but a TACI-Fc fusion protein generated through recombinant DNA technology. This fusion involves merging gene segments of the TACI protein, which can target BLyS/APRIL simultaneously, with the Fc gene segment of the human IgG protein. The TACI-Fc fusion protein exhibits the combined characteristics of both proteins. Currently utilized for autoimmune disease treatment, telitacicept is undergoing clinical investigations globally to assess its efficacy in managing various autoimmune conditions. This review consolidates information on the mechanistic actions, dosing regimens, pharmacokinetics, efficacy, and safety profile of telitacicept-a dual-targeted biological agent. It integrates findings from prior experiments and pharmacokinetic analyses in the treatment of RA and SLE, striving to offer a comprehensive overview of telitacicept's research advancements.

Synthesis of Etrasimod (APD334): Al2O3-Promoted Decarboxylative Rearrangements of Cyclopentenones with Stereochemical Inversion.

This study presents an efficient synthesis pathway for etrasimod, starting from (+)-cis-4-acetoxy-2-cyclopenten-1-ol, yielding 5.6% overall with 98% enantiomeric excess. The crucial intermediate, (4R)-anilinocyclopent-2-enone, was derived from the (S)-alcohol/isocyanate adduct through a concerted, Al2O3-promoted decarboxylative rearrangement, which inverted the configuration. A tetracyclic fused lactam was formed via a one-pot acylation-Michael addition, followed by keto α-arylation. Subsequent removal of the oxo group facilitated the synthesis of cyclopenta[b]indol-3-ylacetic acid through a series of reactions, including methanolysis, indoline oxidation, and hydrolysis.

SIRT6 prevent chronic cerebral hypoperfusion induced cognitive impairment by remodeling mitochondrial dynamics in a STAT5-PGAM5-Drp1 dependent manner.

Vascular dementia (VaD) is a prevalent form of dementia resulting from chronic cerebral hypoperfusion (CCH). However, the pathogenic mechanisms of VaD and corresponding therapeutic strategies are not well understood. Sirtuin 6 (SIRT6) has been implicated in various biological processes, including cellular metabolism, DNA repair, redox homeostasis, and aging. Nevertheless, its functional relevance in VaD remains unexplored. In this study, we utilized a bilateral common carotid artery stenosis (BCAS) mouse model of VaD to investigate the role of SIRT6. We detected a significant decrease in neuronal SIRT6 protein expression following CCH. Intriguingly, neuron-specific ablation of Sirt6 in mice exacerbated neuronal damage and cognitive deficits after CCH. Conversely, treatment with MDL-800, an agonist of SIRT6, effectively mitigated neuronal loss and facilitated neurological recovery. Mechanistically, SIRT6 inhibited excessive mitochondrial fission by suppressing the CCH-induced STAT5-PGAM5-Drp1 signaling cascade. Additionally, the gene expression of monocyte SIRT6 in patients with asymptomatic carotid stenosis showed a correlation with cognitive outcomes, suggesting translational implications in human subjects. Our findings provide the first evidence that SIRT6 prevents cognitive impairment induced by CCH, and mechanistically, this protection is achieved through the remodeling of mitochondrial dynamics in a STAT5-PGAM5-Drp1-dependent manner.

Potential and challenge in accelerating high-value conversion of CO2 in microbial electrosynthesis system via data-driven approach.

Microbial electrosynthesis for CO2 utilization (MESCU) producing valuable chemicals with high energy density has garnered attention due to its long-term stability and high coulombic efficiency. The data-driven approaches offer a promising avenue by leveraging existing data to uncover the underlying patterns. This comprehensive review firstly uncovered the potentials of utilizing data-driven approaches to enhance high-value conversion of CO2 via MESCU. Firstly, critical challenges of MESCU advancing have been identified, including reactor configuration, cathode design, and microbial analysis. Subsequently, the potential of data-driven approaches to tackle the corresponding challenges, encompassing the identification of pivotal parameters governing reactor setup and cathode design, alongside the decipheration of omics data derived from microbial communities, have been discussed. Correspondingly, the future direction of data-driven approaches in assisting the application of MESCU has been addressed. This review offers guidance and theoretical support for future data-driven applications to accelerate MESCU research and potential industrialization.

Surveillance of avian influenza viruses in Hebei Province of China from 2021 to 2023: Identification of a novel reassortant H3N3.

Avian influenza remains a global public health concern for its well-known point mutation and genomic segment reassortment, through which plenty of serum serotypes are generated to escape existing immune protection in animal and human populations. Some occasional cases of human infection of avian influenza viruses (AIVs) since 2020 posed a potential pandemic risk through human-to-human transmission. Both east-west and north-south migratory birds fly through and linger in the Hebei Province of China as a stopover habitat, providing an opportunity for imported AIVs to infect the local poultry and for viral gene reassortment to generate novel stains. In this study, we collected more than 6000 environmental samples (mostly feces) in Hebei Province from 2021 to 2023. Samples were screened using real-time RT-PCR, and virus isolation was performed using the chick embryo culture method. We identified 10 AIV isolates, including a novel reassortant H3N3 isolate. Sequencing analysis revealed these AIVs are highly homologous to those isolated in the Yellow River Basin. Our findings supported that AIVs keep evolving to generate new isolates, necessitating a continuous risk assessment of local avian influenza in wild waterfowl in Hebei, China.

ADS-J21 is a novel HIV-1 entry inhibitor targeting gp41.

HIV-1 envelope glycoprotein gp41 mediates fusion between HIV-1 and host cell membranes, making inhibitors of gp41 attractive anti-HIV drugs. We previously reported an efficient HIV-1 fusion inhibitor, ADS-J1, with a Y-shaped structure. Here, we discovered a new compound, ADS-J21, with a Y-shaped structure similar to that of ADS-J1 but with a lower molecular weight. Moreover, ADS-J21 exhibited effective anti-HIV-1 activity against divergent HIV-1 strains in vitro, including several HIV-1 laboratory-adapted strains and primary isolates with different subtypes (clades A to F) and tropisms (X4 or R5). Mechanistic studies have demonstrated that ADS-J21 blocks the formation of the gp41 six-helix bundle (6-HB) by targeting conserved amino acids Lys35 and Trp32. These findings suggest that ADS-J21 can be used as a new lead compound for further optimization in the development of a small-molecule fusion inhibitor.

Profiles, drivers, and prioritization of antibiotics in China's major rivers.

Through a systematic review of literature references from 2007 to 2022, we compiled a comprehensive national dataset comprising over 67,000 records and covering information on 129 antibiotics detected in the surface water and sediments of China's major rivers. Our analysis revealed notably high antibiotic concentrations in the Liaohe and Yellow Rivers. Among the antibiotics examined, sulfonamides, quinolones, and tetracyclines exhibited relatively high median concentrations in river water. Regional distribution analysis highlighted increased antibiotic levels in Shandong and Tianjin compared to other areas. Partial least squares path modeling revealed that animal production and pollution discharge positively influenced antibiotic levels in river water, whereas natural and socioeconomic factors had negative impacts. Based on the ecological risk assessment, we formulated a prioritized national list of antibiotics, with sulfonamides having the largest number of entries, followed by quinolones. Importantly, our analysis revealed a declining trend in antibiotic concentrations and the associated risk levels across China during the study period. This study not only enhances our understanding of antibiotic distribution in China's water systems, but also contributes to the development of a scientifically sound approach for prioritizing antibiotics. Ultimately, these findings will inform targeted antibiotic management and control strategies. ENVIRONMENTAL IMPLICATION: Antibiotics, posing threats to ecosystems and human health, exhibit pseudo-persistence in the environment. we compiled a national dataset of over 67,000 records on antibiotics, our study scrutinized antibiotic distribution in China's major river water and sediment. Through this analysis, we identified key factors influencing distribution patterns and crafted a national priority ranking for antibiotics. These findings deepen our understanding of antibiotic presence and contribute to the development of targeted management strategies aimed at minimizing environmental impact.

Genome-wide fine-mapping improves identification of causal variants.

Fine-mapping refines genotype-phenotype association signals to identify causal variants underlying complex traits. However, current methods typically focus on individual genomic segments without considering the global genetic architecture. Here, we demonstrate the advantages of performing genome-wide fine-mapping (GWFM) and develop methods to facilitate GWFM. In simulations and real data analyses, GWFM outperforms current methods in error control, mapping power and precision, replication rate, and trans-ancestry phenotype prediction. For 48 well-powered traits in the UK Biobank, we identify causal variants that collectively explain 17% of the SNP-based heritability, and predict that fine-mapping 50% of that would require 2 million samples on average. We pinpoint a known causal variant, as proof-of-principle, at FTO for body mass index, unveil a hidden secondary variant with evolutionary conservation, and identify new missense causal variants for schizophrenia and Crohn's disease. Overall, we analyse 600 complex traits with 13 million SNPs, highlighting the efficacy of GWFM with functional annotations.

Optimal nitrogen management for high yield and N use efficiency of ratoon sorghum.

Sorghum ratooning, a time and labor-saving cultivation practice, is increasingly being adopted by farmers in Southwest China as an alternative. Efficient N fertilizer management is critical for economical production of sorghum and the long-term protection of the environment. To investigate the impact of N management on grain yield and nitrogen use efficiencies (NUEs) of ratoon sorghum system, a three-year field experiment was conducted for Jinyunuo3 (a hybrid cultivar) and Guojiaohong1 (an inbred cultivar) using 12 combinations of N rates and splitting ratios. The results showed that increasing N rate and splitting application times led to improvements in various growth parameters such as dry matter weight, crop growth rate (CGR), leaf area index (LAI), and photosynthetic potential (PP). The main, ratoon, and annual yields increased with N rate increase, but there was no significant difference between 225 and 150 kg N ha-1 in the ratoon and annual yields. Splitting the application of N fertilizer enhanced grain yield compared to a single dose application method, especially three-split applications yielded higher than two-split applications. Compared with N rates of 225 and 150 kg ha-1, N rate of 75 kg ha-1 increased apparent recovery rate of applied nitrogen (REN), agronomic efficiency of applied nitrogen (AEN), and partial factor productivity from applied nitrogen (PFPN) in both main season and whole year. But through splitting application methods at high N rates could achieve similar or even higher levels of NUEs compared to all applied as basal fertilizer at low N rates. Therefore, it could be recommended that applying 150 kg N ha-1 with a basal-jointing-heading fertilizer ratio of 2:4:4 represented an efficient N management practice to synchronously obtain high grain yield and NUEs in ratoon sorghum system in Southwest China.

Biodegradation of organosulfur with extra carbon source: Insights into biofilm formation and bacterial metabolic processes.

Organosulfur compounds are prevalent in wastewater, presenting challenges for biodegradation, particularly in low-carbon environments. Supplementing additional carbon sources not only provides essential nutrients for microbial growth but also serves as regulators, influencing adaptive changes in biofilm and enhancing the survival of microorganisms in organosulfur-induced stress bioreactors. This study aims to elucidate the biodegradation of organosulfur under varying carbon source levels, placing specific emphasis on functional bacteria and metabolic processes. It has been observed that higher levels of carbon supplementation led to significantly improved total sulfur (TS) removal efficiencies, exceeding 83 %, and achieve a high organosulfur CH3SH removal efficiency of ~100 %. However, in the reactor with no external carbon source added, the oxidation end-product SO42- accumulated significantly, surpassing 120 mEq/m2-day. Furthermore, the TB-EPS concentration consistently increasedwith the ascending glucose concentration. The analysis of bacterial community reveals the enrichment of functional bacteria involved in sulfur metabolism and biofilm formation (e.g. Ferruginibacter, Rhodopeudomonas, Gordonia, and Thiobacillus). Correspondingly, the gene expressions related to the pathway of organosulfur to SO42- were notably enhanced (e.g. MTO increased by 27.7 %). In contrast, extra carbon source facilitated the transfer of organosulfur into amino acids in sulfur metabolism and promoted assimilation. These metabolic insights, coupled with kinetic transformation results, further validate distinct sulfur pathways under different carbon source conditions. The intricate interplay between bacteria growth regulation, pollutant biodegradation, and microbial metabolites underscores a complex network relationship that significantly contributes to efficient operation of bioreactors.

Could Ocular Glands Be Infected by SARS-CoV-2?

The aim of the study was to investigate the expression levels of ACE2 in ocular glands and to investigate the effect of S protein on them. Male C57BL/6J mice were used for the experiments. The expression levels of ACE2 are highest in the Meibomian glands, followed by the conjunctiva, the cornea, and the lacrimal glands. Co-immunoprecipitation assays confirmed direct binding between ACE2 and S protein in ocular surface epithelia and Meibomian glands. CD45+ cell infiltration was found in the S protein treatment group, which was accompanied by upregulation of inflammation-related cytokines. There was also prominent cell apoptosis in the S protein treatment group. In conclusion, not only the cornea and the conjunctiva, but also the Meibomian glands express ACE2, and S protein could induce ocular surface epithelial cell and Meibomian gland cell inflammation and apoptosis.

Evaluation of Phenazine Derivatives from the Lichen-Associated Streptomyces flavidovirens as Potent Antineuroinflammatory Agents In Vitro and In Vivo.

Eighteen nitrogen-containing compounds (1-18) were isolated from cultures of the lichen-associated Streptomyces flavidovirens collected from the Qinghai-Tibet Plateau, including seven phenazine derivatives with three new ones, named subphenazines A-C (2-4), two new furan pyrrolidones (8-9), and nine known alkaloids. The structures were elucidated by spectroscopic data analysis, and absolute configurations were determined by single-crystal X-ray diffraction and ECD calculations. The phenazine-type derivatives, in particular compound 3, exhibited significantly better antineuroinflammatory activity than other isolated compounds (8-18). Compound 3 inhibited the release of proinflammatory cytokines including IL-6, TNF-α, and PGE2, and the nuclear translocation of NF-κB; it also reduced the oxidative stress and activated the Nrf2 signaling pathway in LPS-induced BV2 microglia cells. In vivo anti-inflammatory activity in zebrafish indicated that 3 inhibited LPS-stimulated ROS generation. These findings suggested that compound 3 might be a potent antineuroinflammatory agent through the regulation of the NF-κB/Nrf2 signaling pathways.

Elevation of IL-8 secretion induced by PEDV infection via NF-κB signaling pathway.

Porcine epidemic diarrhea virus (PEDV) is associated with severe enteritis, which contributes to high mortality in piglets. The aim of this study was to describe molecular mechanisms associated with proinflammatory cytokine(s) production during PEDV infection. We showed that infection of porcine intestine epithelial cell clone J2 (IPEC-J2) with PEDV induces a gradual increase in interleukin 8 (IL-8) production at different time points, as well as infection of Vero E6 with PEDV. The secretion of IL-8 in these two cell lines infected with PEDV is related to the activation of NF-κB. Furthermore, the cells expressing PEDV M or E protein can induce the upregulation of IL-8. These findings suggest that the IL-8 production can be the initiator of inflammatory response by the host cells upon PEDV infection.

Comparative study of the clinical value of digital subtraction angiography via femoral and radial arterial paths.

OBJECTIVE: To evaluate the clinical efficacy of digital subtraction angiography (DSA) performed via femoral artery and radial artery approaches. METHODS: This retrospective study included 480 patients requiring cerebral vascular angiography at the First People's Hospital of Changde City from March 2020 to February 2022. Patients were divided into the femoral artery group (transfemoral approach, n=400) and the radial artery group (transradial approach, n=80) according to the surgical route. We compared perioperative metrics, success rates of selective angiography and puncture, and complication rates (including pseudoaneurysm, urinary retention, hematoma, vasospasm) between the groups. Multivariate logistic regression was used to analyze factors influencing the failure of angiography by each approach. RESULTS: The radial artery group exhibited shorter durations for puncture, hemostasis, exposure, operation, and postoperative recovery (all P<0.001). The success rate of selective angiography was higher in the radial artery group (93.75%) compared to the femoral artery group (85.25%) (χ2=4.168, P=0.041). No significant difference was found in puncture success rates between the groups (χ2=0.235, P=0.628). The overall complication rate was significantly lower in the radial artery group (2.50%) compared to the femoral artery group (9.25%) (χ2=4.069, P=0.044). Gender and low-density lipoprotein cholesterol levels were significant predictors of angiography failure in both approaches (both P<0.05). CONCLUSION: The transradial approach for DSA is safe and feasible, offering advantages in terms of operational time and complication rates, making it the preferred method in clinical settings.

Glucosamine sulfate-loaded nanofiber reinforced carboxymethyl chitosan sponge for articular cartilage restoration.

Cartilage is severely limited in self-repair after damage, and tissue engineering scaffold transplantation is considered the most promising strategy for cartilage regeneration. However, scaffolds without cells and growth factors, which can effectively avoid long cell culture times, high risk of infection, and susceptibility to contamination, remain scarce. Hence, we developed a cell- and growth factor-dual free hierarchically structured nanofibrous sponge to mimic the extracellular matrix, in which the encapsulated core-shell nanofibers served both as mechanical supports and as long-lasting carriers for bioactive biomass molecules (glucosamine sulfate). Under the protection of the nanofibers in this designed sponge, glucosamine sulfate could be released continuously for at least 30 days, which significantly accelerated the repair of cartilage tissue in a rat cartilage defect model. Moreover, the nanofibrous sponge based on carboxymethyl chitosan as the framework could effectively fill irregular cartilage defects, adapt to the dynamic changes during cartilage movement, and maintain almost 100 % elasticity even after multiple compression cycles. This strategy, which combines fiber freeze-shaping technology with a controlled-release method for encapsulating bioactivity, allows for the assembly of porous bionic scaffolds with hierarchical nanofiber structure, providing a novel and safe approach to tissue repair.