Metagenomic perspectives on antibiotic resistance genes in tap water: The environmental characteristic, potential mobility and health threat.

As an emerging environmental contaminant, antibiotic resistance genes (ARGs) in tap water have attracted great attention. Although studies have provided ARG profiles in tap water, research on their abundance levels, composition characteristics, and potential threat is still insufficient. Here, 9 household tap water samples were collected from the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) in China. Additionally, 75 sets of environmental sample data (9 types) were downloaded from the public database. Metagenomics was then performed to explore the differences in the abundance and composition of ARGs. 221 ARG subtypes consisting of 17 types were detected in tap water. Although the ARG abundance in tap water was not significantly different from that found in drinking water plants and reservoirs, their composition varied. In tap water samples, the three most abundant classes of resistance genes were multidrug, fosfomycin and MLS (macrolide-lincosamide-streptogramin) ARGs, and their corresponding subtypes ompR, fosX and macB were also the most abundant ARG subtypes. Regarding the potential mobility, vanS had the highest abundance on plasmids and viruses, but the absence of key genes rendered resistance to vancomycin ineffective. Generally, the majority of ARGs present in tap water were those that have not been assessed and are currently not listed as high-threat level ARG families based on the World Health Organization Guideline. Although the current potential threat to human health posed by ARGs in tap water is limited, with persistent transfer and accumulation, especially in pathogens, the potential danger to human health posed by ARGs should not be ignored.

Achilles tendinopathy treatment via circadian rhythm regulation.

INTRODUCTION: Achilles tendinopathy (AT) is a prevalent musculoskeletal disorder closely linked to oxidative stress. Existing evidence suggests a potential link between circadian clock rhythms and oxidative stress. However, the precise role of the circadian clock in the progression and treatment of AT remains unclear. OBJECTIVE: The purpose of this study was to investigate the role of the Achilles tendon circadian clock in AT pathology and explore the potential use of biomaterials for modulating the circadian clock in the treatment of AT. METHODS: We utilized in vivo and in vitro models to investigate the alterations of the circadian clock within the Achilles tendon during the progression of AT, as well as its impact on disease development. Additionally, we fabricated Nb2C@CeO2 composites featuring a Schottky heterojunction for regulating the circadian rhythm and validated its therapeutic efficacy and molecular mechanism of AT through both in vivo and in vitro experiments. RESULTS: The Achilles tendon functioned as a peripheral oscillator with an independent and self-sustained time-keeping system. The rhythm of the Achilles tendon clock was disrupted during the development of AT, as indicated by the decreased amplitude of Bmal1 and Nrf2 rhythm expression. Mechanistically, the knockdown of Bmal1 disrupted the Achilles tendon clock, thereby destroying the Bmal1-Nrf2 axis dependent molecular defense mechanism, and exacerbating the inflammatory response, whereas overexpression of Bmal1 had a protective effect. Nb2C@CeO2 composites with Schottky heterojunctions enhance intercellular electrical signaling, boosting Bmal1 expression and mitigating AT's pathological changes. Importantly, enhancing Bmal1 expression during its peak, rather than its trough, was more effective. CONCLUSION: This study identified the protective role of the circadian clock against oxidative stress and inflammation in the Achilles tendon. Achilles tendon circadian clock-targeted therapy represents a promising strategy for AT treatment.

The fate of Cd in Soils with Various Particle Sizes: Characteristics, Speciation Distribution and Influencing Factors.

This study investigated the distribution of Cd in soil water-stable aggregate particles of varying sizes, revealing that smaller particles have higher total Cd content as well as different forms of Cd content, with the clay particle showing a greater tendency to accumulate Cd. However, the proportion of high activity Cd is lower in clay particles, posing a lower environmental risk of Cd transformation compared to silt particles. Adsorption experiments indicated that the clay particle exhibits the strongest adsorption capacity and highest adsorption rate. Additionally, correlation and principal component analyses identified Fe-Mn oxides and organic matter as the primary influencing factors on Cd distribution characteristics, with pH playing a secondary role. These findings provide valuable insights for the remediation of heavy metal-contaminated soil.

The Impact of Infection Control Policies on Hospital Acquired Infections by MDROs from 2016 to 2023.

Purpose: Hospital-acquired infections (HAIs) caused by multidrug-resistant organisms (MDROs) pose a significant challenge to healthcare systems. The present study aimed to evaluate the impact of the infection policy to COVID-19 on the incidence of HAIs caused by MDROs. Methods: We conducted an eight-years retrospective analysis at a hospital in Shanghai, China. Bloodstream, sputum, and urinary tract cultures of MDROs obtained 48h after admission were collected monthly from January 2016 to Dec 2023. Occupied bed days (OBDs) were used to generate monthly HAI incidences per 10,000 OBDs. The study period was divided into pre-control, in-control, and post-control cohorts, in January 2020 and January 2022. The incidence was compared using interrupted time-series regression. Results: In total, 6763 MDRO cultures were identified, comprising 1058 bloodstream, 4581 sputum, and 1124 urine cultures derived from 4549 patients. The incidence rates of all HAIs were 8.68 per 10,000 OBDs in the pre-control cohort, 9.76 per 10,000 OBDs in the in-control cohort and 12.58 per 10,000 OBDs in the post-control cohorts, respectively. A downward trend in the incidence of HAI was observed in the post-control cohort (p<0.05). Conclusion: This study demonstrates that while the COVID-19 pandemic poses a significant challenge to infection control within hospitals, it provides a unique opportunity to enhance infection control measures and evaluate their effectiveness. In addition, these findings highlight the need for more targeted prevention and control strategies against different pathogens in future epidemics.

Maize-Tripsacum-Teosinte allopolyploid (MTP), a novel dwarf mutant inducer tool in maize.

Dwarf plant architecture facilitates dense planting, and increased planting densities boost the maize yield. However, breeding applications of dwarfing materials for maize are currently limited. There is an urgent need remove the obstacles to applying dwarf resources. Here, we innovated a new method to add a novel maize dwarf germplasm through the distant hybridization of Maize-Tripsacum-Teosinte allopolyploid (MTP) with maize. We identified ten independent dwarf families with unique characteristics. Five germplasms in our library were controlled by their respective dwarf genes. However, no allele was controlled by Br2. Subsequently, d024 in the library was successfully fine mapped, revealing its linkage to indel-4 in ZmCYP90D1. The indel-4 polymorphism regulates the expression of ZmCYP90D1 and is controlled by an upstream transcription factor (ZmBES1/BZR1-5). The indel-4 of ZmCYP90D1 allele, which reduces plant height, originated from Tripsacum, a wild variety of maize. However, d024 exhibits sensitivity to brassinosteroids (BRs), with lower castasterone levels in the internodes than that in the wild type. Furthermore, ZmCYP90D1 interacted with ZmFDXs and ZmNAD(P)H to positively regulate the downstream BR synthesis pathway. Additionally, we showed that introgressing the indel-4 of the Tripsacum allele into modern hybrids ensures yield potential and improves the harvest index under high-density conditions. Overall, as we begin to manufacture highly engineered dwarf materials using the MTP, this approach will solve the problems faced by corn dwarfs.

Yr29 combined with QYr.nwafu-4BL.3 confers durable resistance to stripe rust in wheat cultivar Jing 411.

KEY MESSAGE: The combination of a QTL on chromosome arm 4BL and Yr29 provides durable resistance with no significant yield penalty. Wheat stripe rust or yellow rust (YR), caused by Puccinia striiformis f. sp. tritici (Pst), causes substantial yield reductions globally, but losses can be minimized by using resistance genes. Chinese wheat cultivar Jing 411 (J411) has continued to display an acceptable level of adult-plant resistance (APR) to YR in varied field conditions since its release in the 1990s. A recombinant inbred line (RIL) population comprising 187 lines developed from a cross of J411 and Kenong 9204 (KN9204) was evaluated in multiple environments to identify genomic regions carrying genes for YR resistance. A total of five quantitative trait loci (QTL) on chromosome arm 1BL, 3BS, 4BL, 6BS, and 7BL from J411 and two QTL on 3DS and 7DL from KN9204 were detected using inclusive composite interval mapping with the wheat 660 K SNP array. QYr.nwafu-1BL.5 and QYr.nwafu-4BL.3 from J411 were robust and showed similar effects in all environments. QYr.nwafu-1BL.5 was likely the pleiotropic gene of Yr29/Lr46. QYr.nwafu-4BL.3 was located within a 1.0 cM interval delimited by KASP markers AX-111609222 and AX-89755491. Based on haplotype analysis, Yr29 and QYr.nwafu-4BL.3 were identified as genetic components of quantitative resistance in a number of wheat cultivars. Moreover, RILs with Yr29 and QYr.nwafu-4BL.3 individually or when combined showed higher resistance to YR in rust nurseries compared with RILs without them, and there was no negative effect of their presence on agronomic traits under rust-free conditions. These results suggest that effective polymerization strategy is important for breeding high yielding and durable resistance cultivars.

Novel framework-confined Cu@ 13X catalyst with excellent resistance to toxic SO2 as an eco-friendly substitute for hazardous V-based NH3-SCR catalyst.

V2O5-WO3/TiO2 (VWTi) catalyst has long been utilized in fixed source flue gases to purify harmful NO gas. However, VWTi is classified as a hazardous material because of its harm to human health and environment. To address this issue, a low-cost green Cu-based zeolite catalyst (Cu@13X) with a wide temperature range was synthesized using an in-situ hydrothermal method. This method is intended to control the adsorption capacity of toxic SO2 by regulating the location of Cu species. UV-Vis DRS and EXAFS analyses revealed that a significant amount of Cu was encapsulated within the 12-membered ring pores of the 13X molecular sieve. SO2-TPD and DFT calculations further indicated that Cu@ 13X exhibits reduced SO2 chemical adsorption capacity. Consequently, this green catalyst demonstrated superior catalytic performance, maintaining superior NOx conversion for over 70 h in the mixture gas containing 250 ppm SO2; while the Cu/13X catalyst lacked NH3-SCR catalytic activity under the same conditions. Moreover, Cu@ 13X catalyst also has excellent NH3-SCR catalytic performance in low temperature flue gas below 250 °C, which is significantly better than the hazardous VWTi catalyst. Characterization techniques such as NH3-TPD, H2-TPR, and XPS confirmed that the Cu@ 13X catalyst possesses excellent acidity, robust redox capabilities, and abundant surface defects. In-situ DRIFT spectra further illustrated that the NH3-SCR reaction on the catalyst surface adheres to the Eley-Rideal mechanism both before and after the introduction of toxic SO2. This study offers a fresh perspective on the development of framework-confined NH3-SCR catalysts and elucidates the mechanism behind the sulfur resistance of these catalysts. And the green Cu@ 13X catalyst is anticipated to serve as an effective alternative to the hazardous VWTi catalyst.

Resting-state brain networks alterations in adolescents with Internet Gaming Disorder associate with cognitive control impairments.

Objective: Research indicates that cognitive control is compromised in individuals with internet gaming disorder (IGD). However, the neural mechanisms behind it are still unclear. This study aims to investigate alterations in resting-state brain networks in adolescents with IGD and the potential neurobiological mechanisms underlying cognitive dysfunction. Materials and methods: A total of 44 adolescent IGD subjects (male/female: 38/6) and 50 healthy controls (male/female: 40/10) were enrolled. Participants underwent demographic assessments, Young's Internet Addiction Scale, Barratt Impulsiveness Scale 11 Chinese Revised Version, the Chinese Adolescents' Maladaptive Cognitions Scale, exploratory eye movement tests, and functional magnetic resonance imaging (fMRI). FMRI data were analyzed using the GIFT software for independent component analysis, focusing on functional connectivity within and between resting-state brain networks. Results: In comparison to the control group, impulsivity in adolescent IGD subjects showed a positive correlation with the severity of IGD (r=0.6350, p < 0.001), linked to impairments in the Executive Control Network (ECN) and a decrease in functional connectivity between the Salience Network (SN) and ECN (r=0.4307, p=0.0021; r=-0.5147, p=0.0034). Decreased resting state activity of the dorsal attention network (DAN) was associated with attentional dysregulation of IGD in adolescents (r=0.4071, p=0.0017), and ECN increased functional connectivity with DAN. The degree of IGD was positively correlated with enhanced functional connectivity between the ECN and DAN (r=0.4283, p=0.0037). Conclusions: This research demonstrates that changes in the ECN and DAN correlate with heightened impulsivity and attentional deficits in adolescents with IGD. The interaction between cognitive control disorders and resting-state brain networks in adolescent IGD is related.

Automated data collection tool for real-world cohort studies of chronic hepatitis B: Leveraging OCR and NLP technologies for improved efficiency.

Background: Collecting and standardizing clinical research data is a very tedious task. This study is to develop an intelligent data collection tool, named CHB-EDC, for real-world cohort studies of chronic hepatitis B (CHB), which can assist in standardized and efficient data collection. Methods: CHB_EDC is capable of automatically processing various formats of data, including raw data in image format, using internationally recognized data standards, OCR, and NLP models. It can automatically populate the data into eCRFs designed in the REDCap system, supporting the integration of patient data from electronic medical record systems through commonly used web application interfaces. This tool enables intelligent extraction and aggregation of data, as well as secure and anonymous data sharing. Results: For non-electronic data collection, the average accuracy of manual collection was 98.65 %, with an average time of 63.64 min to collect information for one patient. The average accuracy CHB-EDC was 98.66 %, with an average time of 3.57 min to collect information for one patient. In the same data collection task, CHB-EDC achieved a comparable average accuracy to manual collection. However, in terms of time, CHB-EDC significantly outperformed manual collection (p < 0.05). Our research has significantly reduced the required collection time and lowered the cost of data collection while ensuring accuracy. Conclusion: The tool has significantly improved the efficiency of data collection while ensuring accuracy, enabling standardized collection of real-world data.

Extracellular vesicles from a novel Lactiplantibacillus plantarum strain suppress inflammation and promote M2 macrophage polarization.

Background: Lactiplantibacillus plantarum (L. plantarum) is known for its probiotic properties, including antioxidant and anti-inflammatory effects. Recent studies have highlighted the role of extracellular vesicles (EVs) from prokaryotic cells in anti-inflammatory effects. Objective: This study aims to investigate the anti-inflammatory effects of extracellular vesicles derived from a newly isolated strain of L. plantarum (LP25 strain) and their role in macrophage polarization. Methods: The LP25 strain and its extracellular vesicles were isolated and identified through genomic sequencing, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA). RAW 264.7 cells were treated with lipopolysaccharide (LPS) and/or LP25-derived extracellular vesicles (LEV). Morphological changes in the cells were observed, and the expression levels of pro-inflammatory cytokines (TNF-α, IL-6)、iNOS and anti-inflammatory cytokines (IL-10) 、Arg-1 were measured using quantitative real-time PCR (qPCR). Flow cytometry was used to detect the expression of Arg-1 in the treated cells. Results: Treatment with LP25 EVs led to significant morphological changes in RAW 264.7 cells exposed to LPS. LP25 EVs treatment resulted in increased expression of Arg-1 and anti-inflammatory cytokines IL-10, and decreased expression of iNOS and surface markers protein CD86. Flow cytometry confirmed the increased expression of the M2 macrophage marker Arg-1 in the LP25 EVs-treated group. Conclusion: Extracellular vesicles from Lactiplantibacillus plantarum LP25 can suppress inflammatory responses and promote the polarization of macrophages toward the anti-inflammatory M2 phenotype. These findings provide new evidence supporting the anti-inflammatory activity of L. plantarum-derived EVs.

Role of Enterococcus mundtii in gut of the tomato leaf miner (Tuta absoluta) to detoxification of Chlorantraniliprole.

Chlorantraniliprole (CAP) is applied worldwide for the control of caterpillars (Lepidoptera). However, with the overuse of CAP, the resistance problem in pest control is becoming increasingly serious. Recent studies have indicated a central role of the gut symbiont in insect pest resistance to pesticides and these may apply to the tomato leaf miner Tuta absoluta, is one of the most destructive insects worldwide. Here, we successfully isolated seven strains of tolerant CAP bacterium from the CAP-resistant T. absoluta gut, of which Enterococcus mundtii E14 showed the highest CAP tolerance, with a minimum inhibitory concentration (MIC) of 1.6 g/L and CAP degradation rate of 42.4%. Through transcriptomics and metabolism analysis, we studied the detoxification process of CAP by the E. mundtii E14, and found that CAP can be degraded by E. mundtii E14 into non-toxic compounds, such as 3,4-dihydroxy-2-(5-hydroxy-3,7-dimethylocta-2,6-dien-1-yl) benzoic acid and 2-pyridylacetic acid. Additionally, 2-pyridylacetic acid was detected both intracellular and extracellular in E. mundtii E14 treated with CAP. Meanwhile, we identified 52 up-regulated genes, including those associated with CAP degradation, such as RS11670 and RS19130. Transcriptome results annotated using KEGG indicated significant enrichment in up-regulated genes related to the glyoxylate cycle, nitrogen metabolism, and biosynthesis of secondary metabolites. Additionally, we observed that reinfection with E. mundtii E14 may effectively enhance resistance of T. absoluta to CAP. The LC50 values of the antibiotic treatment population of T. absoluta reinfection with E. mundtii E14 is 0.6122 mg/L, which was 18.27 folds higher than before reinfection. These findings offer new insights into T. absoluta resistance to CAP and contribute to a better understanding of the relationship between insecticide resistance and gut symbionts of T. absoluta, which may play a pivotal role in pest management.

Synthesis and Biological Evaluation of Novel Furopyridone Derivatives as Potent Cytotoxic Agents against Esophageal Cancer.

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC50 was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds.

Landsat data reveal lake deoxygenation worldwide.

Dissolved oxygen (DO) is a fundamental requirement for the survival of aquatic organisms, which plays a crucial role in shaping the structure and functioning of aquatic ecosystems. However, the long-term DO change in global lakes remains unknown due to limited available data. To address this gap, we integrate Landsat data and geographic features to develop DO estimation models for global lakes using machine learning approaches. The results demonstrated that the trained random forest (RF) model has better performance (R2 = 0.72, and RMSE = 1.24 mg/L) than artificial neural network (ANN) (R2 = 0.66, and RMSE = 1.39 mg/L), support vector machine regression (SVR) (R2 = 0.62, and RMSE = 1.45 mg/L) and extreme gradient boosting (XGBoost) (R2 = 0.72, and RMSE = 1.29 mg/L). Then, we used the trained RF model to reveal the DO long-term (1984-2021) change in surface water (epilimnetic) of 351,236 global lakes with water area ≥ 0.1 km2. The results show that the average epilimnetic DO concentration of global lake was 9.72 ± 1.07 mg/L, with higher DO in the polar regions (latitude > 66.56 °) (10.87 ± 0.54 mg/L) and lower in the equatorial regions (-5 ° < latitude < 5 °) (6.29 ± 0.63 mg/L). We also find widespread deoxygenation in surface water of global lakes, with a rate of - 0.036 mg/L per decade. Meanwhile, the number of lakes and surface area that experiencing DO stress are continuously increasing, with rate of 39 and 212.85 km2, respectively. Our results offer a comprehensive dataset of DO variation spanning nearly 40 years, furnishing valuable insights for formulating effective management strategies, and enhancing the maintenance of the health of aquatic ecosystems.

DDP-FedFV: A Dual-Decoupling Personalized Federated Learning Framework for Finger Vein Recognition.

Finger vein recognition methods, as emerging biometric technologies, have attracted increasing attention in identity verification due to their high accuracy and live detection capabilities. However, as privacy protection awareness increases, traditional centralized finger vein recognition algorithms face privacy and security issues. Federated learning, a distributed training method that protects data privacy without sharing data across endpoints, is gradually being promoted and applied. Nevertheless, its performance is severely limited by heterogeneity among datasets. To address these issues, this paper proposes a dual-decoupling personalized federated learning framework for finger vein recognition (DDP-FedFV). The DDP-FedFV method combines generalization and personalization. In the first stage, the DDP-FedFV method implements a dual-decoupling mechanism involving model and feature decoupling to optimize feature representations and enhance the generalizability of the global model. In the second stage, the DDP-FedFV method implements a personalized weight aggregation method, federated personalization weight ratio reduction (FedPWRR), to optimize the parameter aggregation process based on data distribution information, thereby enhancing the personalization of the client models. To evaluate the performance of the DDP-FedFV method, theoretical analyses and experiments were conducted based on six public finger vein datasets. The experimental results indicate that the proposed algorithm outperforms centralized training models without increasing communication costs or privacy leakage risks.

Colorimetric and Fluorometric Determination of Fluoride in Tetrahydrofuran and Dimethyl Sulfoxide Using a 4-Hydroxypyrene Probe.

F- ions (fluoride ions) are crucial in various chemical waste and environmental safety contexts. However, excessive fluoride exposure can pose a threat to human well-being. In this study, a simple 4-substituted pyrene derivative known as 4-hydroxypyrene (4-PyOH) was designed as a colorimetric probe for detecting F- through the formation of hydrogen bonds between F- and a hydroxyl group. The probe 4-PyOH exhibited exceptional sensitivity and selectivity towards F- ions and was successfully utilized as test strips for detecting F- ions in organic solvents. The detection limit reached an impressively low level of 3.06 × 10-7 M in the organic solvent. The recognition mechanism was confirmed through 1H NMR titration.

Essential features of weak current for excellent enhancement of NOx reduction over monoatomic V-based catalyst.

Human society is facing increasingly serious problems of environmental pollution and energy shortage, and up to now, achieving high NH3-SCR activity at ultra-low temperatures (<150 °C) remains challenging for the V-based catalysts with V content below 2%. In this study, the monoatomic V-based catalyst under the weak current-assisted strategy can completely convert NOx into N2 at ultra-low temperature with V content of 1.36%, which shows the preeminent turnover frequencies (TOF145 °C = 1.97×10-3 s-1). The improvement of catalytic performance is mainly attributed to the enhancement catalysis of weak current (ECWC) rather than electric field, which significantly reduce the energy consumption of the catalytic system by more than 90%. The further mechanism research for the ECWC based on a series of weak current-assisted characterization means and DFT calculations confirms that migrated electrons mainly concentrate around the V single atoms and increase the proportion of antibonding orbitals, which make the V-O chemical bond weaker (electron scissors effect) and thus accelerate oxygen circulation. The novel current-assisted catalysis in the present work can potentially apply to other environmental and energy fields.

Elevational distribution patterns and drivers factors of fungal community diversity at different soil depths in the Abies georgei var. smithii forests on Sygera Mountains, southeastern Tibet, China.

Introduction: Soil fungal communities play a crucial role in maintaining the ecological functions of alpine forest soil ecosystems. However, it is currently unclear how the distribution patterns of fungal communities in different soil layers of alpine forests will change along the elevational gradients. Material and methods: Therefore, Illumina MiSeq sequencing technology was employed to investigate fungal communities in three soil layers (0-10, 10-20, and 20-30 cm) along an elevational gradient (3500 m to 4300 m) at Sygera Mountains, located in Bayi District, Nyingchi City, Tibet. Results and discussion: The results indicated that: 1) Soil depth had a greater impact on fungal diversity than elevation, demonstrating a significant reduction in fungal diversity with increased soil depth but showing no significant difference with elevation changes in all soil layers. Within the 0-10 cm soil layer, both Basidiomycota and Ascomycota co-dominate the microbial community. However, as the soil depth increases to 10-20 and 20-30 cm soil layers, the Basidiomycota predominantly dominates. 2) Deterministic processes were dominant in the assembly mechanism of the 0-10 cm fungal community and remained unchanged with increasing elevation. By contrast, the assembly mechanisms of the 10-20 and 20-30 cm fungal communities shifted from deterministic to stochastic processes as elevation increased. 3) The network complexity of the 0-10 cm fungal community gradually increased with elevation, while that of the 10-20 and 20-30 cm fungal communities exhibited a decreasing trend. Compared to the 0-10 cm soil layer, more changes in the relative abundance of fungal biomarkers occurred in the 10-20 and 20-30 cm soil layers, indicating that the fungal communities at these depths are more sensitive to climate changes. Among the key factors driving these alterations, soil temperature and moisture soil water content stood out as pivotal in shaping the assembly mechanisms and network complexity of fungal communities. This study contributes to the understanding of soil fungal community patterns and drivers along elevational gradients in alpine ecosystems and provides important scientific evidence for predicting the functional responses of soil microbial ecosystems in alpine forests.

Hypoxia-inducible factor-1α promotes macrophage functional activities in protecting hypoxia-tolerant large yellow croaker (Larimichthys crocea) against Aeromonas hydrophila infection.

The immune system requires a high energy expenditure to resist pathogen invasion. Macrophages undergo metabolic reprogramming to meet these energy requirements and immunologic activity and polarize to M1-type macrophages. Understanding the metabolic pathway switching in large yellow croaker (Larimichthys crocea) macrophages in response to lipopolysaccharide (LPS) stimulation and whether this switching affects immunity is helpful in explaining the stronger immunity of hypoxia-tolerant L. crocea. In this study, transcript levels of glycolytic pathway genes (Glut1 and Pdk1), mRNA levels or enzyme activities of glycolytic enzymes [hexokinase (HK), phosphofructokinase (PFK), pyruvate kinase (PK), and lactate dehydrogenase A (LDHA)], aerobic respiratory enzymes [pyruvate dehydrogenase (PDH), isocitrate dehydrogenase (IDH), and succinate dehydrogenase (SDH)], metabolites [lactic acid (LA) and adenosine triphosphate (ATP)], levels of bactericidal products [reactive oxygen species (ROS) and nitric oxide (NO)], and transcripts and level changes of inflammatory factors [IL1ß, TNFα, and interferon (IFN) γ] were detected in LPS-stimulated L. crocea head kidney macrophages. We showed that glycolysis was significantly induced, the tricarboxylic acid (TCA) cycle was inhibited, and metabolic reprogramming occurred, showing the Warburg effect when immune cells were activated. To determine the potential regulatory mechanism behind these changes, LcHIF-1α was detected and found to be significantly induced and transferred to the nucleus after LPS stimulation. LcHif-1α interference led to a significant reduction in glycolytic pathway gene transcript expression, enzyme activity, metabolites, bactericidal substances, and inflammatory factor levels; a significant increase in the aerobic respiration enzymes; and decreased migration, invasion, and phagocytosis. Further ultrastructural observation by electron microscopy showed that fewer microspheres contained phagocytes and that more cells were damaged after LcHif-1α interference. LcHif-1α overexpression L. crocea head kidney macrophages showed the opposite trend, and promoter activities of Ldha and Il1ß were significantly enhanced after LcHif-1α overexpression in HEK293T cells. Our data showed that LcHIF-1α acted as a metabolic switch in L. crocea macrophages and was important in polarization. Hypoxia-tolerant L. crocea head kidney showed a stronger Warburg effect and inhibited the TCA cycle, higher metabolites, and bactericidal substance levels. These results collectively revealed that LcHif-1α may promote the functional activities of head kidney macrophages in protecting hypoxia-tolerant L. crocea from Aeromonas hydrophila infection.

[The surgical outcomes in management of jugular foramen paragangliomas with tension free anterior rerouting of the facial never and tunnel packing of the inferior petrous sinus].

Objective:The aim of this study is to evaluate the safety and efficacy of surgical interventions ofjugular foramen paragangliomas（JFP） utilizing modified surgical techniques, tensionfree anterior rerouting of the facial nerve and tunnel-packing or push-packing of the inferior petrous sinus. Methods:A retrospective analysis was conducted on a cohort of 88 patients diagnosed with JFP and treated at the Eye Ear Nose and Throat Hospital of Fudan University（in Shanghai, China） from October 2010 to June 2021. The surgical outcomes were analyzed for tumor classification, intraoperative conditions, and function of the postoperative facial nerve（FN） and lower cranial nerve（LCN）. Results:The study included a total of 88 patients, gross total resection was achieved in 70 patients（79.5%）, near total resection was obtained in 17 patients（19.3%）, and one patient undergoing subtotal resection. The average of intraoperative blood loss was 448.3 mL. Additionally, 24 patients underwent surgical total anterior rerouting（TAR）, 18 patients underwent surgical total FN tension free anterior rerouting（TF-TAR）, and 18 patients underwent surgical FN partial FN tension free anterior rerouting（TF-PAR）. Good postoperative FN function（House-Brackmann Ⅰ-Ⅱ） was achieved in 62.5% of TAR group. In the TF-TAR and PF_TAR groups, good postoperative FN function was demonstrated in 88.9% patients. It showed a significantly improvement of the FN function following application of tension-free FN anterior rerouting technique（P=0.007）. Twenty patients（22.7%） suffered from at least one LCN deficit in the preoperative evaluation. The postoperative LCN deficits was correlated with the Fisch classification of tumors, which showed a lower incidence of LCN dysfunction in classes C1-C2（4.9%, 2/41cases） and poorer outcomes of LCN dysfunction in classes C3-D（8.5%,4/47cases ）, it was likely less impacted the LCN function in the early stage tumor. Conclusion:The application of modified surgical techniques of FN tension-free anterior rerouting and tunnel-packing of the inferior petrous sinus has been shown to effectively preserve the function of the FN and LCN, decrease intraoperative blood loss, and ultimately improve patients' postoperative quality of life.

Regulation of post-translational modification of PD-L1 and associated opportunities for novel small-molecule therapeutics.

PD-L1 is overexpressed on the surface of tumor cells and binds to PD-1, resulting in tumor immune escape. Therapeutic strategies to target the PD-1/PD-L1 pathway involve blocking the binding. Immune checkpoint inhibitors have limited efficacy against tumors because PD-L1 is also present in the cytoplasm. PD-L1 of post-translational modifications (PTMs) have uncovered numerous mechanisms contributing to carcinogenesis and have identified potential therapeutic targets. Therefore, small molecule inhibitors can block crucial carcinogenic signaling pathways, making them a potential therapeutic option. To better develop small molecule inhibitors, we have summarized the PTMs of PD-L1. This review discusses the regulatory mechanisms of small molecule inhibitors in carcinogenesis and explore their potential applications, proposing a novel approach for tumor immunotherapy based on PD-L1 PTM.

[Box: see text].