Soil microbial community composition and nitrogen enrichment responses to the operation of electric power substation.

The surge in global energy demand mandates a significant expansion of electric power substations. Nevertheless, the ecological consequences of electric power substation operation, particularly concerning the electromagnetic field, on soil microbial communities and nitrogen enrichment remain unexplored. In this study, we collected soil samples from six distinct sites at varying distances from an electric power substation in Xintang village, southeastern China, and investigated the impacts of electromagnetic field on the microbial diversity and community structures employing metagenomic sequencing technique. Our results showed discernible dissimilarities in the fungal community across the six distinct sites, each characterized by unique magnetic and electric intensities, whereas comparable variations were not evident within bacterial communities. Correlation analysis revealed a diminished nitrogen fixation capacity at the site nearest to the substation, characterized by low moisture content, elevated pH, and robust magnetic induction intensity and electric field intensity. Conversely, heightened nitrification processes were observed at this location compared to others. These findings were substantiated by the relative abundance of key genes associated with ammonium nitrogen and nitrate nitrogen production. This study provides insights into the relationships between soil microbial communities and the enduring operation of electric power substations, thereby contributing fundamental information essential for the rigorous environmental impact assessments of these facilities.

Application of tissue pneumoperitoneum technique around lymph nodes in thoracoscopic lung cancer resection.

Background: Thoracoscopic surgery is a primary treatment for lung cancer, with lobectomy and mediastinal lymph node dissection being the predominant surgical approaches for invasive lung cancer. While many thoracic surgeons can proficiently perform lobectomy, thorough and standardized lymph node dissection remains challenging. This study aimed to explore a safer and more efficient surgical method for mediastinal lymph node dissection in lung cancer. Methods: A prospective randomized controlled study was conducted, involving 100 patients with right lung cancer who were admitted to our hospital from January 2021 to April 2024 and met the inclusion criteria. These patients were randomly divided into an observation group (tissue pneumoperitoneum technique around lymph nodes group) and a control group (conventional surgery group). Thoracoscopic lobectomy and mediastinal lymph node dissection were performed. Intraoperative and postoperative related indicators were observed to validate the effectiveness and safety of the tissue pneumoperitoneum technique around lymph nodes. Results: The observation group showed a significantly shorter lymph node dissection surgery time compared to the control group, with a statistically significant difference (p < 0.05). The number of lymph nodes dissected in the observation group was significantly higher than that in the control group, with a statistically significant difference (p < 0.05). Although the observation group had slightly more mediastinal lymph node stations dissected than the control group, the difference was not statistically significant (p > 0.05). The total drainage volume within three days postoperatively was comparable between the two groups, with no statistically significant difference (p > 0.05). The observation group had shorter chest tube indwelling time and postoperative hospital stay than the control group, with statistically significant differences (p < 0.05). The incidence of surgical complications was similar between the two groups, and there were no perioperative deaths. Conclusion: The tissue pneumoperitoneum technique around lymph nodes is a more efficient method for mediastinal lymph node dissection in lung cancer, demonstrating safety and feasibility, and is worthy of promotion.

Increasing spillover of highly pathogenic avian influenza A (H5N1) virus to mammals.

•1.Increasing spillover of highly pathogenic avian influenza A (H5N1) virus to sea mammals.•2.Increasing spillover of highly pathogenic avian influenza A (H5N1) virus to fur mammals.•3.Increasing spillover of highly pathogenic avian influenza A (H5N1) virus to ruminant animals.•4.Cross-species transmission of highly pathogenic avian influenza A (H5N1) virus between ruminant animals and humans.•5.Highly pathogenic avian influenza A (H5N1) virus RNA was present in milk.

Conjugative transmission of virulence plasmid in Klebsiella pneumoniae mediated by a novel IncN-like plasmid.

Klebsiella pneumoniae (Kp) is increasingly recognized as a reservoir for a range of antibiotic resistance genes and a pathogen that frequently causes severe infections in both hospital and community settings. In this study, we have identified a novel mechanism of conjugative transfer of a non-conjugative virulence plasmid through the formation of a fusion plasmid between the virulence plasmid and a novel 59,162 bp IncN- plasmid. This plasmid was found to be a multidrug-resistance (MDR) plasmid and carried a T4SS cluster, which greatly facilitated the efficient horizontal transfer of the fusion plasmid between Kp strains. The fused virulence plasmid conferred the resistance of serum killing and macrophage phagocytosis to the transconjugants. Importantly, this plasmid was shown to be essential for Kp virulence in a mouse model. Mechanistic analysis revealed that the virulence factors encoded by this virulence plasmid contributed to resistance to in vivo clearance and induced a high level of proinflammatory cytokine IL-1ß, which acts as an inducer for more neutrophil recruitment. The transmission of the fusion plasmid in Kp has the potential to convert it into both MDR and hypervirulent Kp, accelerating its evolution, and posing a serious threat to human health. The findings of this study provide new insights into the rapid evolution of MDR and hypervirulent Kp in recent years.

Gasdermin D-mediated metabolic crosstalk promotes tissue repair.

The establishment of an early pro-regenerative niche is crucial for tissue regeneration1,2. Gasdermin D (GSDMD)-dependent pyroptosis accounts for the release of inflammatory cytokines upon various insults3-5. However, little is known about its role in tissue regeneration followed by homeostatic maintenance. Here, we show that macrophage GSDMD deficiency delayed tissue recovery, with little impact on the local inflammatory milieu or the lytic pyroptosis process. Metabolite secretome profiling of hyperactivated macrophages unveiled the non-canonical metabolite-secreting function of GSDMD. And we further identified 11,12-epoxyeicosatrienoic acid (11,12-EET) as a bioactive pro-healing oxylipin, secreted from hyperactive macrophages in a GSDMD-dependent manner. Indeed, accumulation of 11,12-EET by direct supplementation or deletion of its hydrolytic enzyme Ephx2 accelerated muscle regeneration. We further demonstrated that the Ephx2 level accumulated within aged muscle. And consecutive 11,12-EET treatment rejuvenated aged muscle. Mechanistically, 11,12-EET amplifies FGF-FGFR signaling by modulating FGF liquid-liquid phase separation, hence boosting the activation and proliferation of muscle stem cells (MuSCs). These data depict a GSDMD-guided metabolite crosstalk between macrophages and MuSCs that governs the repair process, which offers new therapeutic insights for the regeneration of injured or aged tissues.

Cellulose-based colorimetric/ratiometric fluorescence sensor for visual detecting amines and anti-counterfeiting.

Many amines with high toxicity always cause a serious threat to the ecological environment and human health; thus, their detection is important. Herein, a dual-mode colorimetric and ratiometric fluorescent sensor based on cellulose for detecting amines has been constructed by a new strategy. This sensor is made of a "negative response" indicator (Lum-MDI-CA) and a "positive response" indicator (perylene tetracarboxylic acid, PTCA). Lum-MDI-CA was obtained by attaching luminol onto cellulose chains, which emitted blue fluorescence and was quenched upon contact with amines. A possible mechanism of fluorescence quenching phenomenon is proposed by the intramolecular charge transfer (ICT) of Lum-MDI-CA. Subsequently, by simply mixing Lum-MDI-CA with PTCA, a dual-mode fluorescence sensor was designed for visual detection and classification of amines. When adding ammonia (NH3), morpholine (MOR), benzylamine (BNZ), diethylamine (DEA), and triethylamine (TEA), respectively, the dual-mode sensor showed visible different color changes under both UV light and daylight. In addition, owing to the excellent processibility and formability of cellulose acetate backbone, the prepared sensor can be easily processed into different material forms, including inks, coatings, films, and fibers, which still exhibit excellent fluorescence emission. Such sensors based on cellulose fluorescent materials are of great value in anti-counterfeiting and information encryption.

Structural basis for antibody-mediated NMDA receptor clustering and endocytosis in autoimmune encephalitis.

Antibodies against N-methyl-D-aspartate receptors (NMDARs) are most frequently detected in persons with autoimmune encephalitis (AE) and used as diagnostic biomarkers. Elucidating the structural basis of monoclonal antibody (mAb) binding to NMDARs would facilitate the development of targeted therapy for AE. Here, we reconstructed nanodiscs containing green fluorescent protein-fused NMDARs to label and sort individual immune B cells from persons with AE and further cloned and identified mAbs against NMDARs. This allowed cryo-electron microscopy analysis of NMDAR-Fab complexes, revealing that autoantibodies bind to the R1 lobe of the N-terminal domain of the GluN1 subunit. Small-angle X-ray scattering studies demonstrated NMDAR-mAb stoichiometry of 2:1 or 1:2, structurally suitable for mAb-induced clustering and endocytosis of NMDARs. Importantly, these mAbs reduced the surface NMDARs and NMDAR-mediated currents, without tonically affecting NMDAR channel gating. These structural and functional findings imply that the design of neutralizing antibody binding to the R1 lobe of NMDARs represents a potential therapy for AE treatment.

Sonographic features of uterine fibroids that predict the ablation rate and efficacy of high-intensity focused ultrasound.

Objective: This study aimed to identify the sonographic indicators that predict the ablation rate and efficiency of uterine fibroids during high-intensity focused ultrasound (HIFU) treatment. Methods: In this retrospective study, we analyzed the clinical data of patients with uterine fibroids who underwent HIFU treatment at Fujian Provincial Hospital between April 2019 and April 2022. Routine abdominal ultrasound examinations were performed to observe potential indicators before the HIFU treatment. After the treatment, enhanced magnetic resonance imaging (MRI) examination was performed within 2 weeks. The fibroid and non-perfused volumes (NPV) were determined, and the ablation rate and energy efficiency factor (EEF) were calculated. Results: A total of 75 patients (124 uterine fibroids) were included in this study. Uterine fibroids with a larger volume, high echogenicity, elliptical/diffuse leaf shape, and a posterior attenuation band had a higher HIFU ablation rate (p<0.05). Uterine fibroids with a larger volume and high echogenicity and without necrotic areas had a lower EEF (p<0.05). Multiple comparisons between fibroid types revealed statistically significant differences in EEF between subserosal and submucosal fibroids (p < 0.05) and between subserosal and mixed-type fibroids (p < 0.05). However, no statistically significant difference was observed between mixed-type and submucosal fibroids. The HIFU ablation rate and EEF showed no significant differences based on location within the wall and blood flow within the fibroids. Conclusion: Sonographic features of uterine fibroids can predict the rate and efficiency of HIFU ablation, providing useful guidance in selecting appropriate treatment for patients.

Recent advances in the potential of Phyllanthus emblica L. and its related foods for combating metabolic diseases through methylglyoxal trapping.

Methylglyoxal (MG) serves as the primary precursor for the nonenzymatic glycation of proteins and DNA, leading to advanced glycation end products (AGEs). Regular intake of dietary MG is strongly correlated with low-grade inflammation, potentially accelerating the pathogenesis of metabolic diseases, including obesity, diabetes, cancers, liver diseases, Alzheimer's disease, cardiovascular diseases, aging, and bone loss. Although pharmaceutical agents (pimagedine and candesartan) have been developed to inhibit MG formation, they often come with serious side effects (nausea, diarrhea, headache, gastrointestinal disturbance, symptomatic hypotension, abnormal renal and liver function tests, development of antinuclear antibody, pernicious-like anemia, and hyperkalemia), highlighting the need for an efficient and safe approach to scavenging MG. Phyllanthus emblica Linn fruit, a nutritious edible fruit, and medicinal plant contains over 300 bioactive compounds. Among twenty-three herbals, 100 µg/mL of the aqueous extract of Phyllanthus emblica fruit (APF) exhibits the highest potency in trapping MG, achieving an 87.3 % reduction under d-fructose induced BSA-AGEs formation. However, there are few reports detailing APF and its related foods' specific impact on disease prevention through MG trapping. This review summarizes the mechanisms through which MG is linked to the development of metabolic diseases and provides several strategies for reducing MG levels using APF and its bioactive compounds. The potential antiglycation properties of APF may offer new applications in the food industry and pharmacological research.

Analysis of complications of giant gastric ulcers induced by hepatic arterial infusion chemotherapy or combined immunotherapy: A report of three cases.

Primary liver cancer is a major public health issue in China, with high incidence and mortality rates. Notably, progress has been made in improving the surgical methods and hepatic arterial infusion chemotherapy (HAIC) regimens of liver cancer and the combination of HAIC with immunotherapy is expected to further increase the surgical conversion rate or objective response rate. However, patients with liver cancer often have underlying cirrhosis, which may lead to complications, such as esophageal varices and high-pressure gastric diseases. The present study describes three cases of giant gastric ulcers that occurred during the process of HAIC or combined immunotherapy. Notably, the causal relationship between HAIC and immunotherapy is unclear. In patients with tumors receiving immunotherapy, gastrointestinal adverse reactions are common, and some may develop serious complications, such as gastrointestinal perforation. The present study provides a detailed analysis of this issue and emphasizes the need for further clarification of its mechanisms and effective treatment methods.

High mortality of Acinetobacter baumannii infection is attributed to macrophage-mediated induction of cytokine storm but preventable by naproxen.

BACKGROUND: The continuous emergence of multidrug-resistant (MDR) Acinetobacter baumannii (Ab) strains poses further challenges in its control and clinical management. It is necessary to decipher the mechanisms underlying the high mortality of Ab infections to explore unconventional strategies for controlling outbreaks of drug-resistant infections. METHODS: The immune responses of Ab sepsis infection were investigated using flow cytometry, RNA-seq, qRT-PCR, and ELISA and scRNA-seq. The detailed pathways mediating Ab immune responses were also depicted and a specific therapy was developed based on the understanding of the mechanisms underlying Ab-induced cytokine storms. FINDINGS: The results highlighted the critical role of alveolar and interstitial macrophages as targets of Ab during the infection process. These cells were found to undergo polarization towards the M1 phenotype, triggering a cytokine storm that eventually caused the death of the host. The polarization and excessive inflammatory response mediated by macrophages were mainly regulated by the TLR2/Myd88/NF-κB signaling pathway. Suppression of Ab-triggered inflammatory responses and M1 polarization by the drug naproxen (NPXS) was shown to confer full protection of mice from lethal infections. INTERPRETATION: The findings in this work depict the major mechanisms underlying the high mortality rate of Ab infections and highlight the clinical potential application of anti-inflammatory drugs or immunosuppressants in reducing the mortality of such infections, including those caused by MDR strains. FUNDING: Funding sources are described in the acknowledgments section.

Artificial Neutrophil-Mediated CEBPA-saRNA Delivery to Ameliorate ALI/ARDS.

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) still faces great challenges due to uncontrollable inflammation disorders, complicated causes of occurrence, and high mortality. Small-activating RNA (saRNA) has emerged as a novel and powerful gene-activating tool that may be useful in the treatment of ALI/ARDS. However, effective saRNA therapy is still challenged by the lack of effective and safe gene delivery vehicles. In this study, we develop a type of artificial neutrophil that is used to deliver saRNAs for ALI/ARDS treatment. The saRNA targeting CCAAT-enhancer binding protein α (CEBPA-saRNA) is complexed with H1 histone and further camouflaged with neutrophil membranes (NHR). Interestingly, we are the first to find that the H1 histone possesses the most effective binding capability to saRNA, compared to other subtypes. The prepared NHR shows excellent physicochemical properties, effective cellular uptake by the inflammatory M1 macrophages, and efficient activation of CEBPA, leading to significant M2 polarization. NHR shows an extended circulation lifetime and high-level accumulation in the inflamed lungs. The in vivo experiments indicate that NHR ameliorates ALI in a mouse model. This type of artificial neutrophil shows powerful inflammatory inhibition both in vitro and in vivo, which opens a new avenue for the treatment of ALI/ARDS.

18F-DPA714 PET/MRI as a potential imaging tool for detecting possible antibody-negative autoimmune encephalitis: a prospective study.

BACKGROUND AND OBJECTIVES: Conventional magnetic resonance imaging (MRI) used for detecting possible antibody-negative autoimmune encephalitis (AIE) often fails to meet the diagnostic requirements of this disease. Positron emission tomography (PET) with a translocator protein radioligand can help visualize microglia distribution density in inflammation-related diseases, thereby offering potentially incremental value to conventional MRI for the in vivo assessment of possible antibody-negative AIE. METHODS: In this prospective study, 15 participants diagnosed with possible antibody-negative AIE and 10 healthy controls were enrolled (ClinicalTrials.gov: NCT05293405, dated March 15, 2022). All participants underwent hybrid 18F-DPA714 PET/MRI and evaluation for modified Rankin scale (mRS) score, clinical assessment scale for AIE (CASE), and appropriate antibodies. A positive finding was defined as the intensity of 18F-DPA714 uptake that was above a threshold of mean standardized uptake value ratio (SUVR) + two standard deviations of SUVR within the corresponding brain regions of healthy controls. RESULTS: The positive detection rate of 18F-DPA714 PET for possible antibody-negative AIE was significantly higher than that of brain MRI (10/15 [67%] vs. 3/15 [20%]; P = 0.039). In addition, both the intensity and extent of 18F-DPA714 uptake were significantly associated with the CASE score (P = 0.002 and 0.001). Meanwhile, SUVR levels in the cerebellar region were significantly higher in patients with ataxia than in those without ataxia (P = 0.006). Furthermore, 18F-DPA714 uptake decreased in 5/10 [50%] patients who underwent follow-up PET/MRI, which mirrored their symptom relief. CONCLUSION: 18F-DPA714 PET demonstrated its potentially incremental value to conventional MRI for detecting possible antibody-negative AIE.

Accurately predicting enzyme functions through geometric graph learning on ESMFold-predicted structures.

Enzymes are crucial in numerous biological processes, with the Enzyme Commission (EC) number being a commonly used method for defining enzyme function. However, current EC number prediction technologies have not fully recognized the importance of enzyme active sites and structural characteristics. Here, we propose GraphEC, a geometric graph learning-based EC number predictor using the ESMFold-predicted structures and a pre-trained protein language model. Specifically, we first construct a model to predict the enzyme active sites, which is utilized to predict the EC number. The prediction is further improved through a label diffusion algorithm by incorporating homology information. In parallel, the optimum pH of enzymes is predicted to reflect the enzyme-catalyzed reactions. Experiments demonstrate the superior performance of our model in predicting active sites, EC numbers, and optimum pH compared to other state-of-the-art methods. Additional analysis reveals that GraphEC is capable of extracting functional information from protein structures, emphasizing the effectiveness of geometric graph learning. This technology can be used to identify unannotated enzyme functions, as well as to predict their active sites and optimum pH, with the potential to advance research in synthetic biology, genomics, and other fields.

Sleep Disturbances in Autoimmune Neurological Diseases: Mechanisms, Clinical Characteristics, Assessment, and Treatment Strategies.

PURPOSE OF REVIEW: Sleep disturbances are a hallmark feature of various autoimmune neurological diseases (AINDs). However, limited awareness of these sleep manifestations exists among clinicians. We provide a comprehensive overview of assessment methods, characteristic sleep disturbances, the impact of specific antibodies on sleep patterns, and treatment strategies for sleep disturbances in AINDs. RECENT FINDINGS: Research advancements in sleep disturbances in autoimmune neurological disease focus primarily on four areas: mechanisms, clinical characteristics, assessment, and treatment. Regarding mechanisms, animal models for AINDs, particularly those involving specific antibodies like anti-NMDAR, anti-LGI1, and anti-IgLON5, have become more comprehensive. Recent advancements in animal models have led to the establishment of numerous models for AINDs; these models include a wide range of antibodies, including anti-NMDAR, anti-LGI1, and anti-IgLON5. Several studies using these models have revealed common mechanisms underlying sleep disturbances in these diseases. In terms of clinical characteristics, the identification of antibodies associated with recently discovered AINDs has expanded the spectrum of sleep disturbance symptoms observed compared to prior findings. A comprehensive evaluation system for the assessment of sleep disturbances has been established, including questionnaires, polysomnography, functional magnetic resonance imaging, and 18F-FDG PET/CT. Additionally, cardiopulmonary coupling shows promise as a novel assessment tool. Currently, no universally effective treatment exists for sleep disturbances in autoimmune neurological diseases, either through symptomatic treatment or immunosuppressive therapy. Further studies are needed to confirm the efficacy of new therapies and validate the benefits of existing treatments. Sleep disturbances are a hallmark feature of AINDs. Recent advancements have significantly expanded our understanding of their assessment and treatment. However, further studies are needed to address the remaining uncertainties in sleep disturbance management.

Dynamics of antimicrobial resistance and genomic characteristics of foodborne Vibrio spp. in Southern China (2013-2022).

Vibrio spp., known as significant marine pathogens, have become more prevalent due to global warming. Antibiotics released into the environment drive Vibrio resistance. The increasing consumption of seafood leads to more interactions between Vibrio and humans. Despite this concerning trend, there remains a lack of large-scale surveillance for Vibrio contamination across various types of food. This study isolated 4027 Vibrio strains, primarily comprising V. parahaemolyticus and V. alginolyticus, in 3581 fresh shrimp and meat products from 2013 to 2022. The Vibrio strains showed increased resistance to important antibiotics, especially ß-lactams used to treat foodborne bacterial infections. Whole genome sequencing of 591 randomly chosen strains showed a strong correlation between antibiotic resistance and genotypes in Vibrio. Notably, various ESBL genes have evolved over the past 8 years, with blaVEBs being the most dominant. Additionally, carbapenemase genes, such as blaNDM-1, have become increasingly prevalent in recent years. Various mobile genetic elements, including IncQ and IncA/C plasmids, recoverable in Vibrio, facilitate the transmission of crucial ß-lactamase genes. These data provide insights into the evolutionary traits of antimicrobial resistance in foodborne Vibrio strains over a decade. Policymakers should consider these findings when devising appropriate strategies to combat bacterial antimicrobial resistance and safeguard human health.

Unraveling the Long-term Natural History of Branch Duct Intraductal Papillary Mucinous Neoplasm: Beyond 10 years.

OBJECTIVE: To describe the long-term natural history of Branch duct intraductal papillary mucinous neoplasm (BD-IPMN). BACKGROUND: The BD-IPMN is a known precursor of pancreatic cancer, yet its long-term natural history is largely unknown. METHODS: We retrospectively reviewed patients with BD-IPMN who were followed at the Massachusetts General Hospital for at least ten years without surgical intervention. Patient and cyst characteristics, development of worrisome features (WF), need for surgery, and malignancy were recorded. The risk of pancreatic cancer in this cohort was compared with the general population by determining the Standardized Incidence Ratio (SIR). RESULTS: 316 patients with BD-IPMN who were followed for at least ten years without intervention were identified. The median age was 63 years, and the median follow-up was 13.5 years (range 10 - 28.8 years). Median cyst size at diagnosis was 1.2 cm (IQR 0.8 - 1.7), was 1.8 cm (IQR 1.2-2.6) at ten years, and increased to 2.0 cm (IQR 1.3 - 3.0) by the end of surveillance. At the 10-year mark, 24% of patients had WF, and by the end of surveillance, an additional 20% had developed WF or high-risk stigmata. 8.2% of patients developed pancreatic malignancy (high-grade dysplasia or invasive cancer). The SIR for pancreatic cancer was 9.28 (95%CI of 5.82 - 14.06), with almost two-thirds of invasive cancers occurring within the pancreatic cyst. CONCLUSIONS: After ten years of surveillance for BD-IPMN without intervention, the disease continues to progress and one of every 12 patients will develop malignancy. The risk of pancreatic cancer appears to be nine times higher than in the comparable age-matched population.

Assessing the inhibitory effects of some secondary amines, thioureas and 1,3-dimethyluracil conjugates of (-)-cytisine and thermopsine on the RNA-dependent RNA polymerase of SARS-CoV-1 and SARS-CoV-2.

SARS-CoV-2 causes COVID-19, with symptoms ranging from mild to severe, including pneumonia and death. This beta coronavirus has a 30-kilobase RNA genome and shares about 80 % of its nucleotide sequence with SARS-CoV-1. The replication/transcription complex, essential for viral RNA synthesis, includes RNA-dependent RNA polymerase (RdRp, nsp12) enhanced by nsp7 and nsp8. Antivirals like molnupiravir and remdesivir, which are RdRp inhibitors, treat severe COVID-19 but have limitations, highlighting the need for new therapies. This study assessed (-)-cytisine, methylcytisine, and thermopsine derivatives against SARS-CoV-1 and SARS-CoV-2 in vitro, focusing on their RdRp inhibition. Selected compounds from a previous study were evaluated using a SARS-CoV-2 RNA polymerase assay kit to investigate their structure-activity relationships. Compound 17 (1,3-dimethyluracil conjugate with (-)-cytisine and thermopsine) emerged as a potent inhibitor of SARS-CoV-1 and SARS-CoV-2 RdRp, with an IC50 value of 7.8 µM against SARS-CoV-2 RdRp. It showed a dose-dependent reduction in cytopathic effects in cells infected with SARS-CoV-1 and SARS-CoV-2 replicon-based single-round infectious particles (SRIPs) and significantly inhibited SARS-CoV N protein expression, with EC50 values of 0.12 µM for SARS-CoV-1 and 1.47 µM for SARS-CoV-2 SRIPs. Additionally, compound 17 reduced viral subgenomic RNA levels in a concentration-dependent manner in SRIP-infected cells. The structure-activity relationships of compound 17 with SARS-CoV-1 and SARS-CoV-2 RdRp were also investigated, highlighting it as a promising lead for developing antiviral agents against SARS and COVID-19.

Long-Term Exposure to Polystyrene Microspheres and High-Fat Diet-Induced Obesity in Mice: Evaluating a Role for Microbiota Dysbiosis.

BACKGROUND: Microplastics (MPs) have become a global environmental problem, emerging as contaminants with potentially alarming consequences. However, long-term exposure to polystyrene microspheres (PS-MS) and its effects on diet-induced obesity are not yet fully understood. OBJECTIVES: We aimed to investigate the effect of PS-MS exposure on high-fat diet (HFD)-induced obesity and underlying mechanisms. METHODS: In the present study, C57BL/6J mice were fed a normal diet (ND) or a HFD in the absence or presence of PS-MS via oral administration for 8 wk. Antibiotic depletion of the microbiota and fecal microbiota transplantation (FMT) were performed to assess the influence of PS-MS on intestinal microbial ecology. We performed 16S rRNA sequencing to dissect microbial discrepancies and investigated the dysbiosis-associated intestinal integrity and inflammation in serum. RESULTS: Compared with HFD mice, mice fed the HFD with PS-MS exhibited higher body weight, liver weight, metabolic dysfunction-associated steatotic liver disease (MASLD) activity scores, and mass of white adipose tissue, as well as higher blood glucose and serum lipid concentrations. Furthermore, 16S rRNA sequencing of the fecal microbiota revealed that mice fed the HFD with PS-MS had greater α-diversity and greater relative abundances of Lachnospiraceae, Oscillospiraceae, Bacteroidaceae, Akkermansiaceae, Marinifilaceae, Deferribacteres, and Desulfovibrio, but lower relative abundances of Atopobiaceae, Bifidobacterium, and Parabacteroides. Mice fed the HFD with PS-MS exhibited lower expression of MUC2 mucin and higher levels of lipopolysaccharide and inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß, and IL-17A] in serum. Correlation analyses revealed that differences in the microbial flora of mice exposed to PS-MS were associated with obesity. Interestingly, microbiota-depleted mice did not show the same PS-MS-associated differences in Muc2 and Tjp1 expression in the distal colon, expression of inflammatory cytokines in serum, or obesity outcomes between HFD and HFD + PS-MS. Importantly, transplantation of feces from HFD + PS-MS mice to microbiota-depleted HFD-fed mice resulted in a lower expression of mucus proteins, higher expression of inflammatory cytokines, and obesity outcomes, similar to the findings in HFD + PS-MS mice. CONCLUSIONS: Our findings provide a new gut microbiota-driven mechanism for PS-MS-induced obesity in HFD-fed mice, suggesting the need to reevaluate the adverse health effects of MPs commonly found in daily life, particularly in susceptible populations. https://doi.org/10.1289/EHP13913.

A natural language processing system for the efficient extraction of cell markers.

Single-cell RNA sequencing (scRNA-seq) has emerged as a pivotal tool for exploring cellular landscapes across diverse species and tissues. Precise annotation of cell types is essential for understanding these landscapes, relying heavily on empirical knowledge and curated cell marker databases. In this study, we introduce MarkerGeneBERT, a natural language processing (NLP) system designed to extract critical information from the literature regarding species, tissues, cell types, and cell marker genes in the context of single-cell sequencing studies. Leveraging MarkerGeneBERT, we systematically parsed full-text articles from 3702 single-cell sequencing-related studies, yielding a comprehensive collection of 7901 cell markers representing 1606 cell types across 425 human tissues/subtissues, and 8223 cell markers representing 1674 cell types across 482 mouse tissues/subtissues. Comparative analysis against manually curated databases demonstrated that our approach achieved 76% completeness and 75% accuracy, while also unveiling 89 cell types and 183 marker genes absent from existing databases. Furthermore, we successfully applied the compiled brain tissue marker gene list from MarkerGeneBERT to annotate scRNA-seq data, yielding results consistent with original studies. Conclusions: Our findings underscore the efficacy of NLP-based methods in expediting and augmenting the annotation and interpretation of scRNA-seq data, providing a systematic demonstration of the transformative potential of this approach. The 27323 manual reviewed sentences for training MarkerGeneBERT and the source code are hosted at https://github.com/chengpeng1116/MarkerGeneBERT .