T cell exhaustion in human cancers.

T cell exhaustion refers to a progressive state in which T cells become functionally impaired due to sustained antigenic stimulation, which is characterized by increased expression of immune inhibitory receptors, but weakened effector functions, reduced self-renewal capacity, altered epigenetics, transcriptional programme and metabolism. T cell exhaustion is one of the major causes leading to immune escape of cancer, creating an environment that supports tumor development and metastatic spread. In addition, T cell exhaustion plays a pivotal role to the efficacy of current immunotherapies for cancer. This review aims to provide a comprehensive view of roles of T cell exhaustion in cancer development and progression. We summerized the regulatory mechanisms that involved in T cell exhaustion, including transcription factors, epigenetic and metabolic reprogramming events, and various microenvironmental factors such as cytokines, microorganisms, and tumor autocrine substances. The paper also discussed the challenges posed by T cell exhaustion to cancer immunotherapies, including immune checkpoint blockade (ICB) therapies and chimeric antigen receptor T cell (CAR-T) therapy, highlightsing the obstacles encountered in ICB therapies and CAR-T therapies due to T cell exhaustion. Finally, the article provides an overview of current therapeutic options aimed to reversing or alleviating T cell exhaustion in ICB and CAR-T therapies. These therapeutic approaches seek to overcome T cell exhaustion and enhance the effectiveness of immunotherapies in treating tumors.

Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential.

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health.

Factors affecting the effectiveness and safety of polymyxin B in the treatment of Gram-negative bacterial infections: A meta-analysis of 96 articles.

PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI]: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

Hernandezine acts as a CDK4 suppressor inhibiting tumor growth by the CDK4/PKM2/NRF2 axis in colon cancer.

BACKGROUND: The cyclin-dependent kinase 4 (CDK4) interacts with its canonical and non-canonical substrates modulating the cell cycle in tumor cells. However, the potential substrates and the beyond-cell-cycle-regulated functions of CDK4 in colon cancer (CC) are still unknown. Hernandezine (HER) is previously verified to induce G0/G1 phase arrest and autophagic cell death in human cancer cells, which implies that HER might target G0/G1 phase-related proteins, including CDK4. PURPOSE: The present study tried to investigate the glycolytic metabolism and oxidative stress functions of CDK4 in colon cancer. Furthermore, the inhibitory effects and potential binding sites of HER on CDK4, as well as its anti-tumor activity were investigated in CC cells. METHODS: The mass spectrometry assay was performed to identify potential endogenous substrates of CDK4 and the correlation between glycolytic metabolic rate and CDK4 level in COAD patient tissues. Meanwhile, after inhibiting the activity or the expression of CDK4, the binding capacity of CDK4 to PKM2 and NRF2 and the latter two protein distributions in cytoplasm and nucleus were detected in CC cells. In vitro, the regulatory effects of the CDK4-PKM2-NRF2 axis on glycolysis and oxidative stress were performed by ECAR, OCR, and ROS assay. The inhibitory effect of HER on CDK4 activity was explored in CC cells and the potential binding sites were predicted and testified in vitro. Furthermore, tumor growth inhibition of HER by suppressing the CDK4-PKM2-NRF2 axis was also investigated in vitro and in vivo. RESULTS: PKM2 and NRF2 were identified as endogenous substrates of CDK4 and, high-expressed CDK4 was associated with low-level glycolysis in COAD. In vitro, inactivated CDK4 facilitated CDK4-PKM2-NRF2 complex formation which resulted in 1) inhibited PKM2 activity and retarded the glycolytic rate; 2) cytoplasm-detained NRF2 failed to transcript anti-oxidative gene expressions and induced oxidant stress. Additionally, as a CDK4 inhibitor, HER developed triple anti-tumor effects including induced G0/G1 phase arrest, suppressed glycolysis, and disrupted the anti-oxidative capacity of CC cells. CONCLUSION: The results first time revealed that CDK4 modulated glycolytic and anti-oxidative capacity of CC cells via bound to its endogenous substrates, PKM2 and NRF2. Additionally, 140Asp145Asn amino acid sites of CDK4 were potential targets of HER. HER exerts anti-tumor activity by inhibited the activity of CDK4, promoted the CDK4-PKM2-NRF2 complex formation in the CC cells.

Roles of Thermosensitive Transient Receptor Channels TRPV1 and TRPM8 in Paclitaxel-Induced Peripheral Neuropathic Pain.

Paclitaxel, a microtubule-stabilizing chemotherapy drug, can cause severe paclitaxel-induced peripheral neuropathic pain (PIPNP). The roles of transient receptor potential (TRP) ion channel vanilloid 1 (TRPV1, a nociceptor and heat sensor) and melastatin 8 (TRPM8, a cold sensor) in PIPNP remain controversial. In this study, Western blotting, immunofluorescence staining, and calcium imaging revealed that the expression and functional activity of TRPV1 were upregulated in rat dorsal root ganglion (DRG) neurons in PIPNP. Behavioral assessments using the von Frey and brush tests demonstrated that mechanical hyperalgesia in PIPNP was significantly inhibited by intraperitoneal or intrathecal administration of the TRPV1 antagonist capsazepine, indicating that TRPV1 played a key role in PIPNP. Conversely, the expression of TRPM8 protein decreased and its channel activity was reduced in DRG neurons. Furthermore, activation of TRPM8 via topical application of menthol or intrathecal injection of WS-12 attenuated the mechanical pain. Mechanistically, the TRPV1 activity triggered by capsaicin (a TRPV1 agonist) was reduced after menthol application in cultured DRG neurons, especially in the paclitaxel-treated group. These findings showed that upregulation of TRPV1 and inhibition of TRPM8 are involved in the generation of PIPNP, and they suggested that inhibition of TRPV1 function in DRG neurons via activation of TRPM8 might underlie the analgesic effects of menthol.

Current and future invasion risk of tomato red spider mite under climate change.

Tomato red spider mite Tetranychus evansi Baker and Pritchard (Acari: Tetranychidae) is a phytophagous pest that causes severe damage to Solanaceous plants worldwide, resulting in significant economic losses. In this study, the maximum entropy model was used to predict the potential current (1970-2000) and future (2021-2060) global distribution of the species based on its past occurrence records and high-resolution environmental data. The results showed that the mean values of the area under the curve were all >0.96, indicating that the model performed well. The three bioclimatic variables with the highest contributions were the coldest quarterly mean temperature (bio11), coldest monthly minimum temperature (bio6), and annual precipitation (bio12). A wide range of suitable areas was found across continents except Antarctica, both currently and in the future, with a much larger distribution area in South America, Africa, and Oceania (Australia), dominated by moderately and low suitable areas. A comparison of current and future suitable areas reveals a general trend of north expansion and increasing expansion over time. This study provides information for the prevention and management of this pest mite in the future.

Distribution patterns of Phytoseiulus persimilis in response to climate change.

BACKGROUND: The biological control agent Phytoseiulus persimilis is a commercialized specialist predator of two agricultural pest mite species Tetranychus urticae and Tetranychus evansi. Biocontrol of these pest species by P. persimilis has achieved success in biological control in some areas. However, the lack of precise information about the influence of global climate change on the worldwide distribution of this biocontrol agent hampers international efforts to manage pest mites with P. persimilis. With 276 occurrence records and 19 bioclimatic variables, this study investigated the potential global distribution of P. persimilis. RESULTS: The results demonstrated that the Maximum Entropy (MaxEnt) model performed well, with the area under the curve being 0.956, indicating the high accuracy of this model. Two variables, the minimum temperature of the coldest month (Bio_6) and precipitation of the coldest quarter (Bio_19) were the most important environmental variables that influenced the distribution of P. persimilis, contributing more than 30% to the model, respectively. The suitable area currently occupies 21.67% of the world's land area, spanning latitudes between 60°S and 60°N. Under shared socio-economic pathway (SSP) 5-8.5 (high-carbon emissions), the low suitable area would increase by 1.31% until the 2050s. CONCLUSION: This study successfully identified that south-eastern China, parts of countries in the Mediterranean coastal regions, including Libya, Algeria, Portugal, Spain, and France, are climatically favorable regions for P. persimilis, providing valuable information about the potential areas where it can be effectively exploited as biocontrol agents in classical biological control programs to manage pest spider mites environmentally friendly. © 2024 Society of Chemical Industry.

BCAT1 alleviates early brain injury by inhibiting ferroptosis through PI3K/AKT/mTOR/GPX4 pathway after subarachnoid hemorrhage.

Regulation of the redox system by branched-chain amino acid transferase 1 (BCAT1) is of great significance in the occurrence and development of diseases, but the relationship between BCAT1 and subarachnoid hemorrhage (SAH) is still unknown. Ferroptosis, featured by iron-dependent lipid peroxidation accompanied by the depletion of glutathione peroxidase 4 (GPX4), has been implicated in the pathological process of early brain injury after subarachnoid hemorrhage. This study established SAH model by endovascular perforation and adding oxyhemoglobin (Hb) to HT22 cells and delved into the mechanism of BCAT1 in SAH-induced ferroptotic neuronal cell death. It was found that SAH-induced neuronal ferroptosis could be inhibited by BCAT1 overexpression (OE) in rats and HT22 cells, and BCAT1 OE alleviated neurological deficits and cognitive dysfunction in rats after SAH. In addition, the effect of BCAT1 could be reversed by the Ly294002, a specific inhibitor of the PI3K pathway. In summary, our present study indicated that BCAT1 OE alleviated early brain injury EBI after SAH by inhibiting neuron ferroptosis via activation of PI3K/AKT/mTOR pathway and the elevation of GPX4. These results suggested that BCAT1 was a promising therapeutic target for subarachnoid hemorrhage.

HMGA1 sensitizes esophageal squamous cell carcinoma to mTOR inhibitors through the ETS1-FKBP12 axis.

Esophageal carcinoma is amongst the prevalent malignancies worldwide, characterized by unclear molecular classifications and varying clinical outcomes. The PI3K/AKT/mTOR signaling, one of the frequently perturbed dysregulated pathways in human malignancies, has instigated the development of various inhibitory agents targeting this pathway, but many ESCC patients exhibit intrinsic or adaptive resistance to these inhibitors. Here, we aim to explore the reasons for the insensitivity of ESCC patients to mTOR inhibitors. We assessed the sensitivity to rapamycin in various ESCC cell lines by determining their respective IC50 values and found that cells with a low level of HMGA1 were more tolerant to rapamycin. Subsequent experiments have supported this finding. Through a transcriptome sequencing, we identified a crucial downstream effector of HMGA1, FKBP12, and found that FKBP12 was necessary for HMGA1-induced cell sensitivity to rapamycin. HMGA1 interacted with ETS1, and facilitated the transcription of FKBP12. Finally, we validated this regulatory axis in in vivo experiments, where HMGA1 deficiency in transplanted tumors rendered them resistance to rapamycin. Therefore, we speculate that mTOR inhibitor therapy for individuals exhibiting a reduced level of HMGA1 or FKBP12 may not work. Conversely, individuals exhibiting an elevated level of HMGA1 or FKBP12 are more suitable candidates for mTOR inhibitor treatment.

Biological and physiological effects in Bemisia tabaci feeding on tomatoes endophytically colonized by Beauveria bassiana.

BACKGROUND: Entomopathogenic fungi (EPF) treatment of plants may affect the survival and feeding preferences of herbivorous pests. However, comprehensive studies on the fitness across their entire life cycle, feeding behavior, and physiological changes in herbivores consuming EPF-treated plants within the tripartite interactions of EPF, plants, and pests are still limited. In this study, we utilized life tables, electrical penetration graph (EPG), and metabolomics to uncover the biological and physiological characteristics of Bemisia tabaci on tomato plants inoculated with Beauveria bassiana through root irrigation. RESULTS: Our study indicated that Beauveria bassiana Bb252 can penetrate the entire tissue from the point of inoculation, primarily colonizing the intercellular spaces and vascular tissue. However, this colonization is temporary, lasting no more than 35 days. Moreover, the population fitness and feeding behavior of Bemisia tabaci on tomato plants treated with Beauveria bassiana via root irrigation were significantly affected, showing a substantial 41.4% decrease in net reproductive rate (R0), a notable reduction in watery salivation, and shortened phloem ingestion. Lastly, we observed a significant decrease in hormones and amino acids of whiteflies that fed on Beauveria bassiana-treated tomato plants by root irrigation. CONCLUSIONS: Our results indicated that the endophyte, Beauveria bassiana Bb252, reduced demographic fitness of Bemisia tabaci by altering its hormones and amino acids levels. These findings enhance our understanding of multitrophic interactions in integrated pest management. © 2024 Society of Chemical Industry.

Cancer-associated fibroblasts secrete FGF5 to inhibit ferroptosis to decrease cisplatin sensitivity in nasopharyngeal carcinoma through binding to FGFR2.

Cisplatin (DDP)-based chemoradiotherapy is one of the standard treatments for nasopharyngeal carcinoma (NPC). However, the sensitivity and side effects of DDP to patients remain major obstacles for NPC treatment. This research aimed to study DDP sensitivity regulated by cancer-associated fibroblasts (CAFs) through modulating ferroptosis. We demonstrated that DDP triggered ferroptosis in NPC cells, and it inhibited tumor growth via inducing ferroptosis in xenograft model. CAFs secreted high level of FGF5, thus inhibiting DDP-induced ferroptosis in NPC cells. Mechanistically, FGF5 secreted by CAFs directly bound to FGFR2 in NPC cells, leading to the activation of Keap1/Nrf2/HO-1 signaling. Rescued experiments indicated that FGFR2 overexpression inhibited DDP-induced ferroptosis, and CAFs protected against DDP-induced ferroptosis via FGF5/FGFR2 axis in NPC cells. In vivo data further showed the protective effects of FGF5 on DDP-triggered ferroptosis in NPC xenograft model. In conclusion, CAFs inhibited ferroptosis to decrease DDP sensitivity in NPC through secreting FGF5 and activating downstream FGFR2/Nrf2 signaling. The therapeutic strategy targeting FGF5/FGFR2 axis from CAFs might augment DDP sensitivity, thus decreasing the side effects of DDP in NPC treatment.

Maternal Care Behavior and Its Consequences in Competition.

Parental care behavior has evolved as a life history strategy to improve reproductive success, particularly in organisms facing challenging environments. However, the variation in maternal care, such as egg-guarding behavior in response to the social environment and the associated ecological consequence of competition, remains largely unknown. This study addresses a gap in current knowledge by examining the plasticity of maternal care behavior in the predatory mite C. eruditus and its impact on offspring survival and intra- and interspecific competition. Our results demonstrated that the reproductive females frequently exhibit egg-guarding behaviors, with enhanced maternal care efforts when the interspecific competitor is present. Egg masses are significantly more vulnerable to predation in the absence of maternal care. Guarding females increased egg survival rates and adversely influenced the survival of both con- and heterospecific competitors, with higher mortality rates being detected. Our findings highlight the ecological significance of maternal care behaviors and suggest that releasing C. eruditus and Neoseiulus cucumeris (Oudemans) together is not recommended for pest management in storage products.

BdTTLL3B-mediated polyglycylation is involved in the spermatogenesis in Bactrocera dorsalis.

Polyglycylation is a post-translational modification that generates glycine side chains in the C-terminal domains of both α- and ß-tubulins. To date, the patterns and significance of polyglycylation across insect species remain largely unknown. The TTLL3B was thought to be a polyglycylase and be essential for polyglycylation in dipteran insects. In this study, the TTLL3B of Bactrocera dorsalis (BdTTLL3B) was identified and characterized. The BdTTLL3B expressed remarkably higher in adult males, especially in testes. The spatio-temporal patterns of polyglycylation were consistent with that of BdTTLL3B. Along with spermatogenesis, the intensity of polyglycylation was enhanced steadily and concentrated in elongated flagella. The expression of recombinant BdTTLL3B in Hela cells, which are genetically deficient in polyglycylation, catalyzed intracellular polyglycylation, validating the identity of BdTTLL3B as a polyglycylase. Knockout of BdTTLL3B significantly suppressed polyglycylation in testes and impaired male fertility, probably due to abnormal morphology of mitochondrial derivatives and over-accumulation of paracrystalline. Taken together, these findings indicated that the BdTTLL3B-mediated polyglycylation is involved in the spermatogenesis and play an important role in fertility of adult B. dorsalis. Therefore, the BdTTLL3B can be considered as a candidate target gene for the management of B. dorsalis, such as developing gene silencing/knockout-based sterile insect technology (SIT).

Development of high-concentration labeled colloidal gold immunochromatographic test strips for detecting african swine fever virus p30 protein antibodies.

African Swine Fever (ASF), caused by the African swine fever virus (ASFV), has inflicted significant economic losses on the pig industry in China. The key to mitigating its impact lies in accurate screening and strict biosecurity measures. In this regard, the development of colloidal gold immunochromatographic test strips (CGITS) has proven to be an effective method for detecting ASFV antibodies. These test strips are based on the ASFV p30 recombinant protein and corresponding monoclonal antibodies. The design of the test strip incorporates a high-concentration colloidal gold-labeled p30 recombinant protein as the detection sensor, utilizing Staphylococcal Protein A (SPA) as the test line (T line), and p30 monoclonal antibody as the control line (C line). The sensitivity and specificity of the test strip were evaluated after optimizing the labeling concentration, pH, and protein dosage. The research findings revealed that the optimal colloidal gold labeling concentration was 0.05 %, the optimal pH was 8.4, and the optimal protein dosage was 10 µg/mL. Under these conditions, the CGITS demonstrated a detection limit of 1:512 dilution of ASFV standard positive serum, without exhibiting cross-reactivity with antibodies against other viral pathogens. Furthermore, the test strips remained stable for up to 20 days when stored at 50 °C and 4 °C. Comparatively, the CGITS outperformed commercial ELISA kits, displaying a sensitivity of 90.9 % and a specificity of 96.2 %. Subsequently, 108 clinical sera were tested to assess its performance. The data showed that the coincidence rate between the CGITS and ELISA was 93.5 %. In conclusion, the rapid colloidal gold test strip provides an efficient and reliable screening tool for on-site clinical detection of ASF in China. Its accuracy, stability, and simplicity make it a valuable asset in combating the spread of ASF and limiting its impact on the pig industry.

[Hydrochemical Characteristics and Formation Mechanism of Groundwater in the Western Region of Hepu Basin, Beihai City].

Beihai City is a typical coastal city where groundwater provides a strong support for social and economic development. Studies on the hydrochemical characteristics and formation mechanism in Beihai City play an important role in the scientific management of water resources and coastal ecological environment protection. In this study, we revealed the main hydrogeochemical processes controlling groundwater quality by means of groundwater survey and water sample collection in the western region of Hepu Basin, Beihai City, combined with hydrochemistry and isotope theories and methods. The results showed that groundwater had the remarkable features of low pH value and low mineralization degree. For pore water, hydrochemistry type by primarily NO3 type water and concentrations of Na+ and Cl- were modestly increased along the flow path. Ca-HCO3, Ca-Cl·HCO3, Ca·Na-HCO3, and Na-Cl·HCO3 types were predominant in fissure water. The groundwater was of meteoric origin, hydrogeochemical evolutions were mainly affected by water-rock interactions, cation exchange, and anthropogenic activities. Na+, K+, and Cl- were mainly derived from evaporite and silicate rocks; Ca2+, Mg2+, HCO3-, and SO42- were from carbonatite and evaporite; and NO3- principally arose from anthropogenic activities. This study suggests that the groundwater pollution prevention and control should be carried out as soon as possible in the area where the NO3 type water occurs to avoid the further deterioration of water quality.

Nasopharyngeal carcinoma: current views on the tumor microenvironment's impact on drug resistance and clinical outcomes.

The incidence of nasopharyngeal carcinoma (NPC) exhibits significant variations across different ethnic groups and geographical regions, with Southeast Asia and North Africa being endemic areas. Of note, Epstein-Barr virus (EBV) infection is closely associated with almost all of the undifferentiated NPC cases. Over the past three decades, radiation therapy and chemotherapy have formed the cornerstone of NPC treatment. However, recent advancements in immunotherapy have introduced a range of promising approaches for managing NPC. In light of these developments, it has become evident that a deeper understanding of the tumor microenvironment (TME) is crucial. The TME serves a dual function, acting as a promoter of tumorigenesis while also orchestrating immunosuppression, thereby facilitating cancer progression and enabling immune evasion. Consequently, a comprehensive comprehension of the TME and its intricate involvement in the initiation, progression, and metastasis of NPC is imperative for the development of effective anticancer drugs. Moreover, given the complexity of TME and the inter-patient heterogeneity, personalized treatment should be designed to maximize therapeutic efficacy and circumvent drug resistance. This review aims to provide an in-depth exploration of the TME within the context of EBV-induced NPC, with a particular emphasis on its pivotal role in regulating intercellular communication and shaping treatment responses. Additionally, the review offers a concise summary of drug resistance mechanisms and potential strategies for their reversal, specifically in relation to chemoradiation therapy, targeted therapy, and immunotherapy. Furthermore, recent advances in clinical trials pertaining to NPC are also discussed.

Associations between ALDOB polymorphisms and intrahepatic cholestasis of pregnancy susceptibility in the Chinese Han population.

OBJECTIVES: To research the associations between fructose-bisphosphate aldolase B (ALDOB) gene polymorphisms and intrahepatic cholestasis of pregnancy (ICP) risk. MATERIAL AND METHODS: Whole-genome sequencing (WGS) was performed to detect ALDOB polymorphisms. Five web-available tools were employed to predict the effect of the site variant on the protein. Protein structure comparisons between the reference and ALDOB-modified samples were performed by SWISS-MODEL and Chimera 1.14rc, respectively. RESULTS: We identified 28 genetic variants in the ALDOB gene. When the cut-off value of minor allele frequency (MAF) of loci was 0.001 in four databases, five missense variants, including rs747604233, rs759204107, rs758242037, rs371526091 and rs77718928, were reserved for subsequent analysis. These variants were absent from the 1029 control individuals. The influence of all five variants on protein function was predicted to be damaging by the abovementioned five prediction software programs. Bioinformatics analysis demonstrated that these five missense variants were highly conserved among vertebrates. Compared to the wild-type protein structure, all five mutated protein structures showed a slight change in the chemical bond lengths of the enzyme activity domains. The combined clinical data indicate that the variant group had a significantly older age (p = 0.038), a higher level of indirect bilirubin (IDBIL, p = 0.033), and lower counts of white blood cells (WBCs, p = 7.38E-05) and platelets (PLTs, p = 0.018) than the wild-type group. CONCLUSIONS: This is the first study to examine the associations between ALDOB polymorphisms and ICP disease in 249 Chinese patients with ICP. Our present study expands the understanding of the pathogenesis of ICP.

Life table and cold tolerance of laboratory-reared Penthaleus major (Acari: Penthaleidae).

Penthaleus major (Dugés) is a significant agricultural pest that attacks various pasture, vegetable, and crop plants. Temperature plays a critical role in the life history of P. major. However, there is limited understanding of its life table at different temperatures and cold tolerance. This study aimed to elucidate the performance of P. major by constructing life tables at 6, 9, 12, 15, 18, 21, and 24 °C. The results showed that P. major successfully developed at 9‒21 °C. However, no adults emerged at 6°C, and no eggs hatched at 24 °C. The highest intrinsic rate of increase (r), finite rate of increase (λ), net reproductive rate (R0), and gross reproductive rate (GRR) were observed at 12 °C. The supercooling point (SCP) exhibited significant variations at different developmental stages. The highest SCP (‒9.75 °C) was recorded in 10-day-old female adults, while the lowest SCP (‒24.37 °C) was observed in larvae. For female adult mites of 2, 6, and 10 days old, the low lethal temperatures (LLT50) were ‒14.63, ‒12.03, and ‒11.08 °C, respectively. This study provided valuable insights for modeling and predicting the population dynamics of P. major in the field and offered implications for developing successful management strategies.

Analyzing the correlation between quinolone-resistant Escherichia coli resistance rates and climate factors: A comprehensive analysis across 31 Chinese provinces.

BACKGROUND: The increasing problem of bacterial resistance, particularly with quinolone-resistant Escherichia coli (QnR eco) poses a serious global health issue. METHODS: We collected data on QnR eco resistance rates and detection frequencies from 2014 to 2021 via the China Antimicrobial Resistance Surveillance System, complemented by meteorological and socioeconomic data from the China Statistical Yearbook and the China Meteorological Data Service Centre (CMDC). Comprehensive nonparametric testing and multivariate regression models were used in the analysis. RESULT: Our analysis revealed significant regional differences in QnR eco resistance and detection rates across China. Along the Hu Huanyong Line, resistance rates varied markedly: 49.35 in the northwest, 54.40 on the line, and 52.30 in the southeast (P = 0.001). Detection rates also showed significant geographical variation, with notable differences between regions (P < 0.001). Climate types influenced these rates, with significant variability observed across different climates (P < 0.001). Our predictive model for resistance rates, integrating climate and healthcare factors, explained 64.1% of the variance (adjusted R-squared = 0.641). For detection rates, the model accounted for 19.2% of the variance, highlighting the impact of environmental and healthcare influences. CONCLUSION: The study found higher resistance rates in warmer, monsoon climates and areas with more public health facilities, but lower rates in cooler, mountainous, or continental climates with more rainfall. This highlights the strong impact of climate on antibiotic resistance. Meanwhile, the predictive model effectively forecasts these resistance rates using China's diverse climate data. This is crucial for public health strategies and helps policymakers and healthcare practitioners tailor their approaches to antibiotic resistance based on local environmental conditions. These insights emphasize the importance of considering regional climates in managing antibiotic resistance.

Akkermansia muciniphila protects the intestine from irradiation-induced injury by secretion of propionic acid.

Intestinal dysbiosis frequently occurs in abdominal radiotherapy and contributes to irradiation (IR)-induced intestinal damage and inflammation. Akkermansia muciniphila (A. muciniphila) is a recently characterized probiotic, which is critical for maintaining the dynamics of the intestinal mucus layer and preserving intestinal microbiota homeostasis. However, the role of A. muciniphila in the alleviation of radiation enteritis remains unknown. In this study, we reported that the abundance of A. muciniphila was markedly reduced in the intestines of mice exposed to abdominal IR and in the feces of patients who received abdominal radiotherapy. Abundance of A. muciniphila in feces of radiotherapy patients was negatively correlated with the duration of diarrhea in patients. Administration of A. muciniphila substantially mitigated IR-induced intestinal damage and prevented mouse death. Analyzing the metabolic products of A. muciniphila revealed that propionic acid, a short-chain fatty acid secreted by the microbe, mediated the radioprotective effect. We further demonstrated that propionic acid bound to G-protein coupled receptor 43 (GRP43) on the surface of intestinal epithelia and increased histone acetylation and hence enhanced the expression of tight junction proteins occludin and ZO-1 and elevated the level of mucins, leading to enhanced integrity of intestinal epithelial barrier and reduced radiation-induced intestinal damage. Metformin, a first-line agent for the treatment of type II diabetes, promoted intestinal epithelial barrier integrity and reduced radiation intestinal damage through increasing the abundance of A. muciniphila. Together, our results demonstrated that A. muciniphila plays a critical role in the reduction of abdominal IR-induced intestinal damage. Application of probiotics or their regulators, such as metformin, could be an effective treatment for the protection of radiation exposure-damaged intestine.