Immunomics in one health: understanding the human, animal, and environmental aspects of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic underscores the critical need to integrate immunomics within the One Health framework to effectively address zoonotic diseases across humans, animals, and environments. Employing advanced high-throughput technologies, this interdisciplinary approach reveals the complex immunological interactions among these systems, enhancing our understanding of immune responses and yielding vital insights into the mechanisms that influence viral spread and host susceptibility. Significant advancements in immunomics have accelerated vaccine development, improved viral mutation tracking, and broadened our comprehension of immune pathways in zoonotic transmissions. This review highlights the role of animals, not merely as carriers or reservoirs, but as essential elements of ecological networks that profoundly influence viral epidemiology. Furthermore, we explore how environmental factors shape immune response patterns across species, influencing viral persistence and spillover risks. Moreover, case studies demonstrating the integration of immunogenomic data within the One Health framework for COVID-19 are discussed, outlining its implications for future research. However, linking humans, animals, and the environment through immunogenomics remains challenging, including the complex management of vast amounts of data and issues of scalability. Despite challenges, integrating immunomics data within the One Health framework significantly enhances our strategies and responses to zoonotic diseases and pandemic threats, marking a crucial direction for future public health breakthroughs.

Shaping the immune landscape: Multidimensional environmental stimuli refine macrophage polarization and foster revolutionary approaches in tissue regeneration.

In immunology, the role of macrophages extends far beyond their traditional classification as mere phagocytes; they emerge as pivotal architects of the immune response, with their function being significantly influenced by multidimensional environmental stimuli. This review investigates the nuanced mechanisms by which diverse external signals ranging from chemical cues to physical stress orchestrate macrophage polarization, a process that is crucial for the modulation of immune responses. By transitioning between pro-inflammatory (M1) and anti-inflammatory (M2) states, macrophages exhibit remarkable plasticity, enabling them to adapt to and influence their surroundings effectively. The exploration of macrophage polarization provides a compelling narrative on how these cells can be manipulated to foster an immune environment conducive to tissue repair and regeneration. Highlighting cutting-edge research, this review presents innovative strategies that leverage the dynamic interplay between macrophages and their environment, proposing novel therapeutic avenues that harness the potential of macrophages in regenerative medicine. Moreover, this review critically evaluates the current challenges and future prospects of translating macrophage-centered strategies from the laboratory to clinical applications.

High casein concentration induces diarrhea through mTOR signal pathway inhibition in post-weaning piglets.

Weaning is one of the most challenging periods in a pig's life, during which piglets suffer from nutrition and other issues. Post-weaning diarrhea is one of the major health problems in the pig industry, leading to high morbidity and mortality rates. Previous studies have demonstrated that both the source and concentration of proteins are closely associated with post-weaning diarrhea in piglets. This study was conducted to prevent and control post-weaning diarrhea by selecting different dietary protein concentrations. To eliminate interference from other protein sources, casein was used as the only protein source in this study. Fourteen piglets (weighing 8.43 ± 0.3 kg, weaned on the 28th day) were randomly assigned to two dietary protein groups: a low-protein group (LP, containing 17% casein) and a high-protein group (HP, containing 30% casein). The experiment lasted 2 weeks, during which all piglets had ad libitum access to food and water. Diarrhea was scored on a scale from 1 to 3 (where 1 indicates normal stools and 3 indicates watery diarrhea), and growth performance measurements were recorded daily. The results showed that the piglets in the HP group had persistent diarrhea during the whole study, whereas no diarrhea was observed among piglets in the control group. The body weights and feed intake were significantly lower in piglets in the HP group compared to those in the LP group (p < 0.05). The gastrointestinal pH was significantly higher in piglets in the HP group than those in the LP group (p < 0.05). The intestinal tract microorganisms of the piglets in both groups were significantly affected by the protein concentration of the diet. A diet with high casein concentration significantly reduced the microbiota diversity. Compared to the LP group, the 30% casein diet decreased the abundance of Firmicutes, Bacteroidetes, and Actinobacteria at the phylum level and the relative abundance of Ruminococcus at the genus level. Diarrhea-related mRNA abundances were analyzed by the real-time polymerase chain reaction (PCR) in the intestine of piglets, and the results showed that the HP concentration markedly decreased the expression of solute carriers (SLC, p < 0.05). The mammalian target of rapamycin-mTOR signaling pathway (p < 0.01) was activated in the HP group. In conclusion, a high-protein diet induced post-weaning diarrhea, decreased growth performance, increased gastrointestinal pH, and reduced expression of solute carrier proteins. However, the relationship between high dietary casein feed and post-weaning diarrhea remains unclear and needs to be explored further.

Air pollution exposure, chemical compositions, and risk of expiratory airflow limitation in youth in Northeast China.

BACKGROUND: Expiratory airflow limitation (EAL) is closely associated with respiratory health in youth and adulthood. Owing to limited evidence, we aim to estimate the association between air pollutants, both individually and in combination, along with their chemical compositions, and the risk of EAL in youth based on data obtained from Northeast China Biobank. METHODS: Pulmonary function was evaluated using a medical-grade pulmonary function analyzer, with EAL defined as a forced expiratory flow in 1 s/ forced vital capacity ratio of < 0.8. Land use regression models were used to predict exposure to six air pollutants. Air pollution score (APS) for each participant was constructed as combined exposure. The chemical composition of particulate matter with an aerodynamic diameter of ≤ 2.5 µm (PM2.5) was determined using a validated machine-learning algorithm. Logistic regression models were employed to estimate effect sizes, and odds ratio (OR) and 95 % confidence intervals (CI) were calculated. RESULTS: In total, 905 EAL cases were identified among the 4301 participants, with a prevalence of 21.04 %. Each inter-quartile range increase in APS was associated with a 25 % higher risk of EAL (OR = 1.25, 95 % CI: 1.12, 1.39). Among the pollutants analyzed, PM2.5 exposure had the strongest association with the risk of EAL (OR = 1.33, 95 % CI: 1.18, 1.52). Out of the five chemical components, sulfate (SO2-4) (OR = 1.39, 95 % CI: 1.24, 1.57) and ammonium (NH+4) (OR = 1.39, 95 % CI: 1.23, 1.57) exhibited the strongest associations with the risk of EAL. CONCLUSIONS: Overall, combined effects of air pollution increased the risk of EAL in youth, with SO2-4 and NH+4 emerging as the predominant contributing chemical components in Northeast China.

Information sharing and channel encroachment in biomass supply chains.

To guarantee the sustainable development of the biomass raw material supply chain, researchers are increasingly focusing on the issue of information asymmetry between biomass power plants and upstream supply chain members. This paper investigates the optimal information sharing strategy for a biomass power plant where farmers choose whether to encroach on the biomass feedstock supply. Using a game theory model, we analyze eight different information sharing scenarios, and the results show that when the encroachment occurs in supply chain channels, information sharing can significantly increase the profits of the entire supply chain. In this case, the power plant should share its demand information with all upstream players to promote the overall benefit of the supply chain. In contrast, when the power plant shares its information only with the middleman, it can maximize its profits, which, however, may not be conducive to the long-term stability of the supply chain. Furthermore, surprisingly, in the absence of channel encroachment, the power plant sharing information with upstream members may harm their profits. This suggests that power plants may need to consider the scope of information sharing more carefully when the farmers choose not to encroach. Finally, we also examine the impact of channel competition intensity on information sharing strategies, and find that when channel competition intensity is low, transparent demand information helps the power plant maximize expected returns. However, in a highly competitive market environment, the power plant should carefully handle information sharing with farmers to avoid damaging their profits.

Single-cell sequencing reveals the heterogeneity of pancreatic neuroendocrine tumors under genomic instability and histological grading.

Histological grading is the key factors affecting the prognosis and instructive in guiding treatment and assessing recurrence in non-functional pancreatic neuroendocrine tumor (NF-Pan-NET). Approximately one-third of patients without copy number variation (CNV) alteration and the prognosis of these patients are better than that of patients with CNV alteration. However, the difference between CNV and histological grading is unclear. Here, we analyzed the heterogeneity of tumor cells according to two classification criteria, genomic instability (including CNV alteration and tumor mutation burden) and histological grading. We revealed that the activated core pathways of tumor cells were significantly different under different histological grading's and genomic instability patterns. We also found that tip cells, lymphatic endothelial cells, macrophages, CD1A + dendritic cell, Treg, MAIT, ILC, and CAFs might participate in the process of hepatic metastases, which will facilitate the understanding of the patterns to decode the malignant potential and of NF-Pan-NET.

Patho-immunological mechanisms of atopic dermatitis: The role of the three major human microbiomes.

Atopic dermatitis (AD) is a genetically predisposed allergic inflammatory dermatosis with chronic, pruritic, and recurrent features. Patients with AD have dry and itchy skin, often accompanied by chronic eczematous lesions, allergic rhinitis, or asthma, which has a considerable impact on their daily lives. With advances in genome sequencing technology, it has been demonstrated that microorganisms are involved in this disease, and the microorganisms associated with AD are attracting considerable research attention. An increasing number of studies conducted in recent years have demonstrated that an imbalanced microbiome in AD patients has substantial impact on disease prognosis, and the causes are closely tied to various immune mechanisms. However, the involvement of microorganisms in the pathogenesis of AD remains poorly understood. In this paper, we review the advances in research on the immunological mechanisms of the skin microbiome, intestinal microbiome, and lung microbiome that are related to AD prognosis and immunotherapy protocols. It is hoped that this approach will lay the foundation for exploring the pathogenesis of and emerging treatments for AD.

Network pharmacology-based study on the mechanism of action of Trollius chinensis capsule in the treatment of upper respiratory tract infection.

BACKGROUND: Upper respiratory tract infection (URTI), one of the most common respiratory diseases, has a high annual incidence. Trollius chinensis capsule has been used to treat URTI in China. However, the underlying-mechanisms remain unclear. METHODS: Network pharmacology was used to explore the potential mechanism of action of Trollius chinensis capsule in URTI treatment. The active compounds in Trollius chinensis were obtained from the TCMSP, SymMap, and ETCM databases. The TCMSP, PubChem, and SwissTargetPrediction databases were used to predict potential targets of Trollius chinensis. URTI-associated targets were gathered from GeneCards and DisGeNET databases. The key targets and signaling pathways associated with URTI were selected by network topology, GO, and KEGG pathway enrichment analysis. Molecular docking was used to verify the binding activity between active compounds and key targets. RESULTS: Quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are major active compounds in Trollius chinensis capsule. Eighty one candidate therapeutic targets were confirmed to be involved in protection of Trollius chinensis capsule against URTI. Among them, 7 key targets (TP53, IL6, AKT1, CASP3, CXCL8, MMP9, and EGFR) were verified to have good binding affinities to the main active compounds. Furthermore, enrichment analyses suggested that inflammatory response, virus infection and oxidative stress related biological processes and pathways were possibly the potential mechanism. CONCLUSION: Overall, the present study clarified that quercetin, pectolinarigenin, beta-sitosterol, acacetin and cirsimaritin are proved to be the main effective compounds of Trollius chinensis capsule treating URTI, possibly by acting on the targets of IL6, AKT1, CASP3, CXCL8, MMP9 and EGFR to play anti-infectious, anti-viral, and anti-oxidative effects. This study provides a new understanding of the active compounds and mechanisms of Trollius chinensis capsule in URTI treatment from the perspective of network pharmacology.

Deubiquitinase USP18 inhibits hepatic stellate cells activation and alleviates liver fibrosis via regulation of TAK1 activity.

BACKGROUND & AIMS: Activation of hepatic stellate cells (HSCs) is the key process underlying liver fibrosis. Unveiling its molecular mechanism may provide an effective target for inhibiting liver fibrosis. Protein ubiquitination is a dynamic and reversible process. Deubiquitinases (DUBs) catalyze the removal of ubiquitin chains from substrate proteins, thereby inhibiting the biological processes regulated by ubiquitination signals. However, there are few studies revealing the role of deubiquitination in the activation of HSCs. METHODS & RESULTS: Single-cell RNA sequencing (scRNA-seq) revealed significantly decreased USP18 expression in activated HSCs when compared to quiescent HSCs. In mouse primary HSCs, continuous activation of HSCs led to a gradual decrease in USP18 expression whilst restoration of USP18 expression significantly inhibited HSC activation. Injection of USP18 lentivirus into the portal vein of a CCl4-induced liver fibrosis mouse model confirmed that overexpression of USP18 can significantly reduce the degree of liver fibrosis. In terms of mechanism, we screened some targets of USP18 in mouse primary HSCs and found that USP18 could directly bind to TAK1. Furthermore, we demonstrated that USP18 can inhibit TAK1 activity by interfering with the K63 ubiquitination of TAK1. CONCLUSIONS: Our study demonstrated that USP18 inhibited HSC activation and alleviated liver fibrosis via modulation of TAK1 activity; this may prove to be an effective target for inhibiting liver fibrosis.

Seeking the optimal gestational weight gain according to the pre-pregnancy body mass index: a cross-sectional study from Shanghai, China.

OBJECTIVES: Maternal nutritional status is closely related to fetal intrauterine development and an abnormal birth weight increases various disease risks across life stages. To better guide pregnancy weight gain, we aimed to explore the optimal weight gain for pregnant women with different body mass indexes (BMIs). METHODS: This retrospective cohort study included 68,981 women with singleton live birth between January 2017 and October 2021 in maternity centres in Shanghai, China. The fluctuations of the incidence of small and large for gestational age (small for gestational age (SGA) and LGA, respectively) were recorded at different maternal pre-pregnancy BMI (p-BMI) and different gestational weight gain (GWG) groups to find the lowest point of abnormal fetal weight incidence. The optimal GWG was then determined using a linear regression equation. RESULT: The lowest risk of LGA/SGA was associated with a maternal p-BMI of 19.46 kg/m2. For pregnant women with maternal p-BMI below 24 kg/m2, we confirmed an optimal GWG linear equation: opt GWG (kg) = -1.94 × p-BMI (kg/m²) + 51, which showed an excellent degree of fit. Women who were overweight and obese could not achieve the lowest risk of LGA/SGA despite controlling their GWG; hence, their BMI should be normalized before pregnancy. CONCLUSION: By merely using the pre-pregnancy BMI, this study has established the optimal GWG equation, with the goal of achieving the appropriate fetal gestational age. It is a practical measure to ensure desirable pregnancy outcomes and meet the health economics requirements.

STING Agonist Delivered by Neutrophil Membrane-Coated Gold Nanoparticles Exerts Synergistic Tumor Inhibition with Radiotherapy.

Radiotherapy (RT) is one of the major treatments for cancers and a promising initiator of immune response. Gold nanoparticles are a promising radiosensitizer. In this study, we sought to optimize the drug delivery efficiency of gold nanoparticles and explore their function in delivering stimulator of interferon genes (STING) agonists with or without RT. Gold nanoparticles covalent to MSA-2 (MSA-Au) were mixed with cRGD-modified neutrophil membranes to obtain M-Au@RGD-NM. We explored the treatment efficiency of M-Au@RGD-NM combined with RT. Immune cell regulation and STING pathway activation were detected. We successfully prepared M-Au@RGD-NM with significant tumor suppression by induction of ROS and the resulting DNA damage. In vivo dynamic imaging showed that M-Au@RGD-NM was mainly targeted to radiated tumors. Tumor-bearing mice showed significant tumor inhibition following a combination therapy. M-Au@RGD-NM significantly activated the STING pathway and regulated the whole-body immune response. Locally radiated tumors showed dendritic cells mature, CD8+ T cells upregulation, and M1 polarization, with systematic immune response demonstrated by CD8+ T cell infiltration in abscopal tumors. In this study, we synthesized M-Au@RGD-NM loading MSA-2. Following characterization, we found that RT-based M-Au@RGD-NM treatment achieved good antitumor effects, tumor RT enhancement, and induction of an immune response via STING activation.

Stabilizing the Interphase in an Ultra-High-Nickel Cathode Enabling High-Performance Lithium-Ion Batteries.

High-nickel (Ni ≥ 90%) cathodes which have a high specific capacity hold great potential for next-generation lithium-ion batteries (LIBs). However, their practical application is restricted by their high interfacial reactivity because of the presence of residual lithium (Li) compounds on the surface. Herein, the LiNi0.9Co0.06Mn0.04O2 (NCM90) cathode is surface-modified with sulfur (S) via a simple and feasible dry mixing and low-temperature heat treatment, converting the residual lithium compound on the surface into inactive lithium sulfate (Li2SO4). This induces the formation of a stable inorganic enriched electrode-electrolyte interface on the cathode surface and inhibits the occurrence of side reactions, ultimately inhibiting lattice collapse and the dissolution of transition metal ions. After modifying, the capacity retention rates of NCM90/Li and NCM90/graphite cells are both greatly enhanced after long cycling. This work provides a new idea for the rational design of the electrode-electrolyte interface of high-nickel cathodes.

Fabrication of Anti-Fatigue Double-Wrapped Yarns with Excellent Mechanical Properties for Generating Compression Fabrics.

Elastic yarns are the key component of high-performance compression garments. However, it remains a challenge to fabricate anti-fatigue yarns with high mechanical force and long elongation for generating compression garments with prolonged wear. In this paper, we report the development of anti-fatigue double-wrapped yarns with excellent mechanical properties by wrapping high-denier Spandex with nylon filaments in opposite twists. In particular, high-denier (560 D) Spandex as the core was untwisted, which can maximally reduce the interaction between the core and wrapping filaments, enabling high elongation of double-wrapped yarns. In addition, we chose 70 D nylon filaments with a tensile force of 3.87 ± 0.09 N as the wrapping materials to provide sufficient force for double-wrapped yarns. Notably, opposite twists were induced for the inner and outer wrapping filaments to achieve a balanced stable yarn structure. By systematically optimizing manufacturing parameters, including inner wrapping density, outer wrapping density, take-up ratio, and drafting ratio, we obtained double-wrapped yarn with excellent tensile stress (32.59 ± 0.82 MPa) and tensile strain (357.28% ± 9.10%). Notably, the stress decay rate of optimized yarns was only 12.0% ± 2.2%. In addition, the optimized yarn was used as the weft-lining yarn for generating weft-lined fabrics. The elastic recovery rate of the obtained fabric was decreased by only 2.6% after five cyclic stretches, much lower than the control fabric. Our design of anti-fatigue double-wrapped yarns could be widely used for fabricating high-performance compression garments.

Circadian rhythms and breast cancer: from molecular level to therapeutic advancements.

BACKGROUND AND OBJECTIVES: Circadian rhythms, the endogenous biological clocks that govern physiological processes, have emerged as pivotal regulators in the development and progression of breast cancer. This comprehensive review delves into the intricate interplay between circadian disruption and breast tumorigenesis from multifaceted perspectives, encompassing biological rhythms, circadian gene regulation, tumor microenvironment dynamics, and genetic polymorphisms. METHODS AND RESULTS: Epidemiological evidence underscores the profound impact of external factors, such as night shift work, jet lag, dietary patterns, and exercise routines, on breast cancer risk and progression through the perturbation of circadian homeostasis. The review elucidates the distinct roles of key circadian genes, including CLOCK, BMAL1, PER, and CRY, in breast cancer biology, highlighting their therapeutic potential as molecular targets. Additionally, it investigates how circadian rhythm dysregulation shapes the tumor microenvironment, fostering epithelial-mesenchymal transition, chronic inflammation, and immunosuppression, thereby promoting tumor progression and metastasis. Furthermore, the review sheds light on the association between circadian gene polymorphisms and breast cancer susceptibility, paving the way for personalized risk assessment and tailored treatment strategies. CONCLUSIONS: Importantly, it explores innovative therapeutic modalities that harness circadian rhythms, including chronotherapy, melatonin administration, and traditional Chinese medicine interventions. Overall, this comprehensive review emphasizes the critical role of circadian rhythms in the pathogenesis of breast cancer and highlights the promising prospects for the development of circadian rhythm-based interventions to enhance treatment efficacy and improve patient outcomes.

Variability in Lipid Profiles During Young Adulthood and the Risk of Coronary Artery Calcium Incidence in Midlife: Insights From the CARDIA Study.

BACKGROUND: Intraindividual variability in lipid profiles is recognized as a potential predictor of cardiovascular events. However, the influence of early adulthood lipid profile variability along with mean lipid levels on future coronary artery calcium (CAC) incidence remains unclear. METHODS: A total of 2395 participants (41.6% men; mean±SD age, 40.2±3.6 years) with initial CAC =0 from the CARDIA study (Coronary Artery Risk Development in Young Adults) were included. Serial lipid measurements were obtained to calculate mean levels and variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), and triglycerides. CAC incidence was defined as CAC >0 at follow-up. RESULTS: During a mean follow-up of 9.0 years, 534 individuals (22.3%) exhibited CAC incidence. Higher mean levels of total cholesterol, LDL-C, and non-HDL-C were associated with a greater risk of future CAC incidence. Similarly, 1-SD increment of lipid variability, as assessed by variability independent of the mean, was associated with an increased risk of CAC incidence (LDL-C: hazard ratio, 1.139 [95% CI, 1.048-1.238]; P=0.002; non-HDL-C: hazard ratio, 1.102 [95% CI, 1.014-1.198]; P=0.022; and triglycerides: hazard ratio, 1.480 [95% CI, 1.384-1.582]; P<0.001). Combination analyses demonstrated that participants with both high lipid levels and high variability in lipid profiles (LDL-C and non-HDL-C) faced the greatest risk of CAC incidence. Specifically, elevated variability of LDL-C was associated with an additional risk of CAC incidence even in low mean levels of LDL-C (hazard ratio, 1.396 [95% CI, 1.106-1.763]; P=0.005). These findings remained robust across a series of sensitivity and subgroup analyses. CONCLUSIONS: Elevated variability in LDL-C and non-HDL-C during young adulthood was associated with an increased risk of CAC incidence in midlife, especially among those with high mean levels of atherogenic lipoproteins. These findings highlight the importance of maintaining consistently low levels of atherogenic lipids throughout early adulthood to reduce subclinical atherosclerosis in midlife. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00005130.

The stability of FKBP9 maintained by BiP is crucial for glioma progression.

FK506-binding protein 9 (FKBP9) is involved in tumor malignancy by resistance to endoplasmic reticulum (ER) stress, and the up-regulation of FKBP9 is associated with patients' poor prognosis. The current knowledge of the molecular mechanisms is still limited. One previous study showed that FKBP9 could confer glioblastoma cell resistance to ER stress through ASK1-p38 signaling. However, the upstream regulatory mechanism of FKBP9 expression is still indistinct. In this study, we identified the FKBP9 binding proteins using co-immunoprecipitation followed by mass spectrometry. Results showed that FKBP9 interacted with the binding immunoglobulin protein (BiP). BiP bound directly to FKBP9 with high affinity. BiP prolonged the half-life of the FKBP9 protein and stabilized the FKBP9 protein. BiP and FKBP9 protein levels were positively correlated in patients with glioma, and patients with high expression of BiP and FKBP9 showed a worse prognosis. Further studies showed that FKBP9 knockout in genetically engineered mice inhibited intracranial glioblastoma formation and prolonged survival by decreasing cellular proliferation and ER stress-induced CHOP-related apoptosis. Moreover, normal cells may depend less on FKBP9, as shown by the absence of apoptosis upon FKBP9 knockdown in a non-transformed human cell line and overall normal development in homozygous knockout mice. These findings suggest an important role of BiP-regulated FKBP9-associated signaling in glioma progression and the BiP-FKBP9 axis may be a potential therapeutic target for glioma.

Prevalence and Antibiotic Resistance Patterns of Methicillin-Resistant Staphylococcus aureus (MRSA) in a Hospital Setting: A Retrospective Study from 2018 to 2022.

Methicillin-resistant Staphylococcus aureus (MRSA) is a highly infectious pathogen that poses a serious threat to human life and health. This study aimed to provide a scientific basis for the rational clinical use of antimicrobial drugs for treating MRSA infections and inform the development of preventive and control measures by analyzing the clinical distribution and resistance characteristics of MRSA in a hospital in Hebei China. To accomplish this, bacterial identification and drug sensitivity experiments were performed with 1858 Staphylococcus aureus (S. aureus) strains collected from a hospital from January 2018 to December 2022 using a phoenixTM-100 bacterial identification drug sensitivity analyzer. The experimental data were analyzed using WHONET 5.6 software, and the MRSA strains detected were analyzed for their clinical distribution and drug resistance. Of the 1858 S. aureus strains isolated, 429 were MRSA. Sputum samples had the highest MRSA detection rates (52.45%). Critical care medicine had the highest rate of MRSA (12.59%), followed by dermatology (9.79%). MRSA resistance to tetracycline increased by 13.9% over 5 years; resistance to quinupristin/dalfopristin also increased but remained low (1.9%). Resistance decreased to gentamicin, rifampicin, ciprofloxacin, and cotrimoxazole, though most significantly to erythromycin and clindamycin, exceeding 77% and 83%, respectively. No strains were resistant to vancomycin, teicoplanin, or linezolid, and drug resistance was most prevalent in patients ≥ 60 years old. This study will aid in improving the diagnosis and treatment of MRSA infections.

OSR1 suppresses oral squamous cell carcinoma proliferation and migration via the AXIN2/ß-catenin pathway.

OBJECTIVES: The odd-skipped related transcription factor 1 (OSR1) gene exerts distinct regulatory effects on tumorigenesis and development in various cancer types. However, the precise role of OSR1 in oral squamous cell carcinoma (OSCC) remains to be elucidated. METHODS: GEPIA 2 and TCGA databases were utilized to analyze the OSR1 expression in head and neck squamous cell carcinoma (HNSC) patients and its impact on prognosis. Hematoxylin-eosin staining, immunohistochemistry, immunofluorescence, western blotting, and RT-qPCR were employed to detect the OSR1 expression in OSCC tissues and cells. Lentivirus transfection was utilized for overexpression and downexpression of OSR1 in OSCC. CCK8 cell proliferation assay, colony formation and cell scratch assay were conducted to investigate the effects of OSR1 on biological behavior of OSCC cells. Western blotting and RT-qPCR were applied to investigate the regulatory mechanism of OSR1 on AXIN2/ß-catenin signaling pathway. RESULTS: OSR1 expression was significantly decreased in HNSC patients, OSCC tissues and cells, leading to a decrease in 5-year survival rate. OSR1 overexpression inhibited the proliferation and migration of OSCC cells, and the AXIN2/ß-catenin signaling pathway was inhibited. Silencing OSR1 had the opposite effect. CONCLUSIONS: OSR1 functioned as a tumor suppressor gene in OSCC proliferation and migration by regulating the AXIN2/ß-catenin signaling pathway.

Blocking lactate regulation of the Grhl2/SLC31A1 axis inhibits trophoblast cuproptosis and preeclampsia development.

PURPOSE: Abnormal cell death due to superficial trophoblast dysfunction caused by placental hypoxia plays a vital role in the development of preeclampsia (PE). Lactic acid stimulates gene transcription in chromatin through lactate modification of histone lysine. Nevertheless, the content and function of lactate in PE development remains largely unclear. METHODS: The contents of lactic acid and copper in 30 PE and 30 normal placentas were determined by kit colorimetry. Real-time quantitative fluorescent PCR (qRT-PCR) and Western blot were used to detect the expression of SLC31A1 in cells and tissues. Cell proliferation, apoptosis, and invasion were detected by cell counting kit 8 (CCK-8), MTS assay, colony formation assay, and Transwell assay. The transcriptional regulation between Grhl2 and SLC31A was verified by the luciferase reporter gene method and ChIP. The H3K18la modification level was detected by ChIP-PCR. RESULTS: Herein, we detected increased lactic acid levels in the PE placental tissue, which inhibit the proliferation and invasion of trophoblasts. Interestingly, lactic acid increases intracellular copper content by enhancing the expression of SLC31A1, a key protein of copper ion transporters. Lentivirus knockdown of SLC31A1 blocked the lactate-induced proliferation and invasion of trophoblasts by inhibiting cell cuproptosis. Mechanically, we identified that Grhl2 mediated SLC31A1 expression through transcription and participated in SLC31A1-inhibited proliferation, invasion, and cuproptosis of trophoblasts. Furthermore, the high lactate content increased Grhl2 expression by enhancing lactate modification of histone H3K18 in the Grhl2 promoter region. CONCLUSIONS: Blocking the lactate-regulated Grhl2/SLC31A1 axis and trophoblastic cuproptosis may be a potential approach to prevent and treat PE.

Divergent input patterns to the central lateral amygdala play a duet in fear memory formation.

Somatostatin (SOM)-expressing neurons in the central lateral amygdala (CeL) are responsible for fear memory learning, but the circuit and molecular mechanisms underlying this biology remain elusive. Here, we found that glutamatergic neurons in the lateral parabrachial nucleus (LPB) directly dominated the activity of CeLSOM neurons, and that selectively inhibiting the LPBGlu→CeLSOM pathway suppressed fear memory acquisition. By contrast, inhibiting CeL-projecting glutamatergic neurons in the paraventricular thalamic nucleus (PVT) interfered with consolidation-related processes. Notably, CeLSOM-innervating neurons in the LPB were modulated by presynaptic cannabinoid receptor 1 (CB1R), and knock down of CB1Rs in LPB glutamatergic neurons enhanced excitatory transmission to the CeL and partially rescued the impairment in fear memory induced by CB1R activation in the CeL. Overall, our study reveals the mechanisms by which CeLSOM neurons mediate the formation of fear memories during fear conditioning in mice, which may provide a new direction for the clinical research of fear-related disorders.