Standardized framework for assessing soil quality at antimony smelting site by considering microbial-induced resilience and heavy metal contamination.

Antimony smelting activities damage the soil and vegetation surroundings while generating economic value. However, no standardized methods are available to diagnose the extent of soil degradation at antimony smelting sites. This study developed a standardized framework for assessing soil quality by considering microbial-induced resilience and heavy metal contamination at Xikuangshan antimony smelting site. The soil resilience index (SRI) and soil contamination index (SCI) were calculated by Minimum Data Set and geo-accumulation model, respectively. After standardized by a multi-criteria quantitative procedure of modified Nemerow's pollution index (NPI), the integrated assessment of soil quality index (SQI), which is the minimum of SRINPI and SCINPI, was achieved. The results showed that Sb and As were the prominent metal(loid) pollutants, and significant correlations between SQI and SRI indicated that the poor soil quality was mainly caused by the low level of soil resilience. The primary limiting factors of SRI were Fungi in high and middle contaminated areas, and Skermanella in low contaminated area, suggesting that the weak soil resilience was caused by low specific microbial abundances. Microbial regulation and phytoremediation are greatly required to improve the soil quality at antimony smelting sites from the perspectives of pollution control and resilience improvement. This study improves our understanding of ecological effects of antimony smelting sites and provides a theoretical basis for ecological restoration and sustainable development of mining areas.

Deciphering the Dynamics of EGFR-TKI Resistance in Lung Cancer: Insights from Bibliometric Analysis.

Background: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries. Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics. Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as "Lung Cancer", are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation. Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, "chemo+" treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.

CoNglyPred: Accurate Prediction of N-Linked Glycosylation Sites Using ESM-2 and Structural Features With Graph Network and Co-Attention.

N-Linked glycosylation is crucial for various biological processes such as protein folding, immune response, and cellular transport. Traditional experimental methods for determining N-linked glycosylation sites entail substantial time and labor investment, which has led to the development of computational approaches as a more efficient alternative. However, due to the limited availability of 3D structural data, existing prediction methods often struggle to fully utilize structural information and fall short in integrating sequence and structural information effectively. Motivated by the progress of protein pretrained language models (pLMs) and the breakthrough in protein structure prediction, we introduced a high-accuracy model called CoNglyPred. Having compared various pLMs, we opt for the large-scale pLM ESM-2 to extract sequence embeddings, thus mitigating certain limitations associated with manual feature extraction. Meanwhile, our approach employs a graph transformer network to process the 3D protein structures predicted by AlphaFold2. The final graph output and ESM-2 embedding are intricately integrated through a co-attention mechanism. Among a series of comprehensive experiments on the independent test dataset, CoNglyPred outperforms state-of-the-art models and demonstrates exceptional performance in case study. In addition, we are the first to report the uncertainty of N-linked glycosylation predictors using expected calibration error and expected uncertainty calibration error.

PBLD promotes IRF3 mediated the type I interferon (IFN-I) response and apoptosis to inhibit viral replication.

Recent studies have implicated the phenazine biosynthesis-like domain-containing protein (PBLD) in the negative regulation of the development and progression of various cancers. However, its function in viral infection remains unknown. In this study, we found that PBLD plays important roles in multiple virus infections including BPIV3, SeV, VSV, and HSV-1. Our study revealed that PBLD enhances the expression of type I interferon (IFN-I) and ISGs through interferon regulatory factor 3 (IRF3). Further study indicated that PBLD promotes transcriptional phosphorylation of IRF3 (S385/386), thereby facilitating virus-induced IFN-I production. Interestingly, PBLD mediates virus-triggered mitochondrial apoptosis through its dependence on IRF3 (K313/315). Mechanistically, PBLD facilitated virus-induced apoptosis by recruiting the Puma protein to the mitochondria via IRF3. Additionally, we performed mutational analyses of IRF3, showing that its loss of either transcriptional or apoptotic function markedly increased viral replication. Moreover, macrophages with PBLD deficiency during viral infection exhibited decreased the IFN-I and ISGs expression, exacerbating viral infection. Importantly, mice deficient in PBLD exhibited increased viral replication and susceptibility to SeV infection, leading to decreased survival. Notably, Cedrelone, a chemical activator of PBLD, has the ability to reduce SeV replication. Collectively, we first discovered the new function of PBLD in viral infection, broadening our understanding of potential therapeutic targets and offering new insights for antiviral drug development.

The mediating effect of social connectedness between internet gaming disorder and somatic symptoms in adolescents: a large sample cross-sectional study.

BACKGROUND: Previous studies have indicated that social connectedness can serve as a protective buffer against negative outcomes associated with online victimization. However, the role of social connectedness between Internet gaming disorder and somatic symptoms is still unclear. This study aims to examine the mediating effect of social connectedness on the association between Internet gaming disorder and somatic symptoms. METHODS: A cross-sectional design was utilized, using questionnaires for data collection and multi-stage stratified cluster sampling. The general demographic questionnaire, Nine-Item Internet Gaming Disorder Scale-Short Form, Social Connectedness Scale-Revised and Patient Health Questionnaire Physical Symptoms were used to collect data. We adopted Pearson's correlation analysis and the PROCESS Macro Model in regression analysis to explore the relationships among Internet gaming disorder, social connectedness and somatic symptoms. RESULTS: Internet gaming disorder was positively correlated with somatic symptoms (r = 0.20, P < 0.001), while network (r=-0.08, P < 0.001) and real-life social connectedness (r=-0.31, P < 0.001) negatively affected somatic symptoms. The network social connectedness and the real-life social connectedness played a chain mediating role in the development of Internet gaming disorder to somatic symptoms [95%CI: 0.073, 0.088], explaining 45.25% of the total effect value. The difference of real-life social connectedness and network social connectedness played a partial mediating role between Internet gaming disorder and somatic symptoms [95% CI:0.050, 0.062], accounting for 31.28% of the total effect value. CONCLUSIONS: Real-life social connectedness, network social connectedness, and their disparity all mediated the relationship between Internet gaming disorder and somatic symptoms. Real-life social connectedness acted as a protective factor, while network social connectedness served as a risk factor. Encouraging offline activities and guiding teenagers to use the internet responsibly may help prevent and reduce physical symptoms linked to Internet gaming disorder.

The relationship between the tertiary lymphoid structure and immune-infiltrating cells in gastrointestinal cancers: A systematic review and meta-analysis.

OBJECTIVES: This study systematically evaluated the relationship between tertiary lymphoid structures (TLS) and clinical pathological features as well as immune infiltrating cells in gastrointestinal cancers. METHODS: We searched Web of science, Pubmed, Embase, and Cochrane Library for studies that met the requirements as of July 1, 2023, and the odds ratio, the corresponding 95% confidence interval or mean and standard deviation, were included in the analysis. FINDINGS: We eventually included 20 studies, involving a total of 4856 patients. TLS were found to be significantly associated with T stage, N stage, TNM stage, and tumor size. Moreover, patients with positive TLS showed significantly elevated expression of T-cell related markers, including CD3, CD4, CD8, CD45RO; B-cell related markers, such as CD11c and CD20; and dendritic cell-related marker CD103. On the other hand, positive TLS correlated significantly with low expression of FOXP3 and CD68. Additionally, there was a significant positive association between TLS and overall infiltration of tumor-infiltrating lymphocytes. CONCLUSION: The presence of TLS is significantly correlated with the infiltration of various immune cells in gastrointestinal cancers. To determine the ideal balance between the presence of mature TLS and appropriate immune cell infiltration, further high-quality and multicenter clinical studies need to be conducted.

Differential response of subterranean microbiome to exogenous organic matter input in a cave ecosystem.

As a recurrent climatic phenomenon in the context of climate change, extreme rainstorms induce vertical translocation of organic matter and increase moisture content in terrestrial ecosystems. However, it remains unclear whether heavy rainstorms can impact microbial communities in the deep biosphere by modulating organic matter input. In this study, we present findings on the different responses of bacterial and fungal communities in a subsurface cave to rainstorms and moisture variations through field surveys and microcosm experiments. During periods of rainstorms, the influx of dissolved organic matter (DOM) from soil overlying the cave into cave sediments significantly enhanced the correlation between core bacteria and environmental factors, particularly fluorescence spectral indices. The resource utilization of core bacteria was diminished, while the functional diversity of core fungi remained relatively unaltered. We also performed simulated experiments with restricted external DOM inputs, in which DOM content was observed to decrease and microbial diversity increase in response to artificially increased moisture content (MC). The niche breadth of core bacteria decreased and became more closely associated with DOM as the MC increased, while the niche breadth of core fungi remained predominantly unchanged. Compared to fungi, cave bacteria exhibited higher sensitivity towards variations in DOM. The core microbiome can efficiently utilize the available organic matter and participate in nitrogen- and sulfur-related metabolic processes. The study systematically revealed distinct microbial responses to rainstorm events, thereby providing valuable insights for future investigations into energy utilization within deep biospheres.

Nasopharyngeal carriage of Streptococcus pneumoniae among children aged 30 days to <60 months in Beijing and Shenzhen, China (2018-2021) during pneumococcal conjugate vaccine introduction and the coronavirus disease (COVID-19) pandemic.

Objectives: To describe the carriage rate, serotype distribution, and antimicrobial susceptibility patterns of Streptococcus pneumoniae (S. pneumoniae) nasopharyngeal (NP) isolates among healthy children aged 30 days to <60 months in the cities of Beijing and Shenzhen during 2018-2021. Methods: A NP swab sample was collected among four annual cohorts of healthy children at routine well-child visits. S. pneumoniae was identified by culture, optochin sensitivity and bile solubility, serotypes determined by latex agglutination and Quellung, and antimicrobial susceptibility testing performed using E-test strips. Results: S. pneumoniae NP carriage was 13.1% (645/4,911), with the highest S. pneumoniae carriage prevalence (15.3%) observed in 25 to <60 months. The carriage prevalence was 15.1% in children 13-24 months, 13.2% in children 7-12 months, and 8.2% in children 30 days to 6 months (P < 0.01). Living with siblings [20.0% vs. 9.4%: OR: 2.42 (95% CI: 2.05-2.87)] or attending day-care [31.8% vs. 11.3%: OR: 3.67 (95% CI: 2.94-4.57)] increased the risk (P < 0.01). During the period (January 2020-April 2021) of strict non-pharmaceutical interventions to prevent and control the COVID-19 pandemic, the proportion of children with S. pneumoniae colonization declined from 16.0% (94/587) to 5.8% (108/1,848) in Beijing while increasing from 14.5% (64/443) to 18.6% (379/2,033) in Shenzhen. Among S. pneumoniae isolates, 36.7% (237/645) belonged to 13-valent pneumococcal conjugate vaccine (PCV13) serotypes, 64.3% (408/645) were non-PCV13 serotypes, including 20.8% (134/645) non-serotypeable S. pneumoniae (NST). A total of 158/644 isolates (24.5%) were MDR. For the PCV13 isolates, MDR was detected in 36.3% (86/237) of isolates; in comparison, 17.6% (72/407) of non-PCV13 serotypes, including NST, were MDR (P < 0.01). S. pneumoniae NP carriage was detected in 10.7% of children with previous pneumococcal vaccination (PCV7 or PCV13 only) compared with 14.9% in children without previous pneumococcal vaccination. Conclusions: The highest S. pneumoniae carriage prevalence were found in the oldest age group (25 to <60 months) and in children living with siblings or attending day-care. Vaccination with PCV7 or PCV13 was associated with lower PCV13-serotype colonization. In Beijing, S. pneumoniae carriage significantly declined during the COVID-19 pandemic.

Bacterial Epidemiology and Antimicrobial Resistance Profiles of Bloodstream Infections Caused by Negative Bacteria in Children's: A Multicenter Study in China (2016-2022).

Objective: Aim to investigate the pathogens distribution and drug resistance of gram-negative bacteria causing bloodstream infection (BSIs) in Infectious Disease Surveillance of Pediatric from 2016 to 2022. The prevalence of four important drug resistance phenotypes was studied: difficult-to-treat resistance, fluoroquinolone resistance, carbapenem resistance, and extended-spectrum cephalosporin resistance, and to provide reference basis for preventing and treating BSIs diseases in children. Methods: Strain identification and antimicrobial susceptibility tests were independently performed at each hospital. Data were analyzed using Whonet 5.6 and GraphPad Prism 8 software. The Mann-Whitney U-test was used to examine and compare temporal changes. Results: A total of 39977 BSIs strains were isolated, with 27.1% of the negative bacteria causing BSIs (10824 strains). The highest bacteria detected were E. coli and S. maltophilia in the neonatal and pediatric groups. The detection rate of carbapenem-resistant-K. pneumoniae (CRKPN) in neonate group was 31.4%, significantly increased compared with pediatric group, whose detection rate was 24.7%. The rates of resistance to levofloxacin and trimethoprim/sulfamethoxazole were significantly lower in neonatal groups than pediatric groups in BSIs caused by K. pneumoniae. To imipenem and meropenem were 3.6% and 3.9% among neonatal isolates, which was lower than 4.7% and 5.8 among pediatric BSIs caused by E. coli. Isolated from neonatal BSIs caused by A. baumannii showed lower resistance ratios to all the agents tested than those from pediatric. However, only the prevalence of piperacillin/tazobactam resistance was statistically lower than that in pediatric BSIs caused by P. aeruginosa. The average detection rates of carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance for K. pneumoniae and E. coli were 28.1%,41.4%,11.6% and 4.0%,24.3%,31.1%, respectively. Conclusion: The detection rate of gram-negative pathogens showed an increasing trend among the bloodstream infection. The detection rate of CRKPN assumed a downward trend in 2018. There are differences types of pathogens between the neonatal group and the pediatric group, The detection rate of CRKPN in the neonate group was significantly higher than pediatric group. The first average detection rates for carbapenem resistance, extended-spectrum cephalosporin resistance, and fluoroquinolone resistance were obtained for A. baumannii, K. pneumoniae, and Escherichia coli, respectively. Those data showed a high level of antimicrobial resistance, which has posed an urgent threat to Children's health, suggested that effective monitoring of antimicrobial resistance and antimicrobial stewardship among children in China are required.

Development and applications of graduate outcome-based curriculum for basic medical education.

Introduction: Outcome-based education (OBE) leads to revolutionary change in medical education, but each medical school is acknowledged to develop suited framework based on specific positioning, educational philosophy and expected outcomes. Methods: Based on the graduate outcomes of basic medical education in China released by Working Committee for the Accreditation of Medical Education (WCAME) which officially recognized by World Federation for Medical Education (WFME), Taizhou University re-documented the overall organization of the curriculum and classified the courses as "Crucial, Supporting and Associated (CSA)" categories to connect the graduate outcomes and course objectives. Results: We redefined the standard for graduates in Taizhou University Medical School including 34 items in four domains and redesigned the curriculum with 76 courses classified as CSA. Empirical data reveals a substantial improvement in students' performance on Standardized Competence Test for Clinical Medicine Undergraduates in China (SCTCMU) by implementing the CSA system between 2022 and 2023. Notably, in 2023, Taizhou University's students achieved pass rates more than 20 percentage points higher than the national average, demonstrating a profound and unprecedented impact. Conclusion: The CSA classification system provides a notably clear and structured framework for categorizing courses based on their direct or indirect relevance to educational objectives, which provides clarity to educators and empowers students with a more purposeful approach to their studies.