SO3-COF@Al2O3 modified cathode electrode materials enhance the cycling ability of lithium sulfur batteries.

Herein, a covalent organic framework (SO3-COF) containing sulfonic acid groups has been developed on the surface of alumina by a one-step method, labeled as SO3-COF@Al2O3. The experimental results show that SO3-COF@Al2O3 can effectively inhibit the shuttle effect of soluble lithium polysulfide (LiPSs) in LSBs after loading the active material sulfur, and exhibits better cycling behavior than the initial polymer SO3-COF. The initial discharge specific capacity of this electrode material at 0.05C is as high as 1141 mA h g-1, and the capacity can be maintained at 466 mA h g-1 after 500 cycles with a capacity decay rate of 0.08% per cycle.

Structure and antitumor activity of a polysaccharide from Rosa roxburghii.

It is proverbial that Rosa roxburghii, as a homology of medicine and food, is rich in polysaccharides. To discover bioactive macromolecules for combating cancer, the polysaccharides in R. roxburghii were investigated, leading to the purification of a polysaccharide (RRTP80-1). RRTP80-1 was measured to have an average molecular weight of 8.65 × 103 g/mol. Monosaccharide composition analysis revealed that RRTP80-1 was formed from three types of monosaccharides including arabinose, glucose, and galactose. Combination of methylation and GC-MS analysis suggested that the backbone of RRTP80-1 consisted of →5)-α-l-Araf-(1→, →6)-α-d-Glcp-(1→, →2,5)-α-l-Araf-(1→, →4,6)-ß-d-Galp-(1→, and →3)-α-l-Araf-(1→, with branch chains, α-l-Araf-(1→. In vivo studies indicated that RRTP80-1 exhibited inhibitory activity against the growth and proliferation of neoplasms in the zebrafish tumor xenograft model by suppressing angiogenesis. Additionally, RRTP80-1 was found to upregulate reactive oxygen species (ROS) and nitric oxide (NO) production levels in zebrafish models. All these studies suggest that RRTP80-1 activates the immune system to inhibit tumors. The potential role of the newly discovered homogeneous polysaccharide RRTP80-1 in cancer treatment was preliminarily clarified in this study.

Disulfidptosis-Related LncRNA Signatures for Prognostic Prediction in Kidney Renal Clear Cell Carcinoma.

INTRODUCTION BACKGROUND: Disulfidptosis is a prevalent apoptotic mechanism, intrinsically linked to cancer prognosis. However, the specific involvement of disulfidptosis-related long non-coding RNA (DRLncRNAs) in Kidney renal clear cell carcinoma (KIRC) remains incompletely understood. This study aims to elucidate the potential prognostic significance of disulfidptosis-related LncRNAs in KIRC. MATERIALS AND METHODS: Expression profiles and clinical data of KIRC patients were retrieved from the TCGA database to discern differentially expressed DRLncRNAs correlated with overall survival. Cox univariate analysis, Lasso Regression, and Cox multivariate analysis were used to construct a clinical prediction model. RESULTS: Six signatures, namely FAM83C.AS1, AC136475.2, AC121338.2, AC026401.3, AC254562.3, and AC000050.2, were established to evaluate overall survival (OS) in the context of Kidney renal clear cell carcinoma (KIRC) in this study. Survival analysis and ROC curves demonstrated the strong predictive performance of the associated signature. The nomogram exhibited accurate prognostic predictions for overall patient survival, offering substantial clinical utility. Gene set enrichment analysis revealed that risk signals were enriched in various immune-related pathways. Furthermore, the risk features exhibited significant correlations with immune cells, immune function, immune cell infiltration, and immune checkpoints. CONCLUSION: This study has unveiled, for the first time, six disulfdptosis-related LncRNA signatures, laying a solid foundation for enhanced and precise prognostic predictions in KIRC.

Variation and interrelationships in the growth, yield, and lodging of oat under different planting densities.

Background: Oat is a dual-purpose cereal used for grain and forage. The demand of oat has been increasing as the understanding of the nutritional, ecological, and economic values of oat increased. However, the frequent lodging during the growing period severely affect the high yielding potential and the quality of the grain and forage of oat. Methods: Therefore, we used the lodging-resistant variety LENA and the lodging-sensitive variety QY2 as materials, implementing four different planting densities: 2.25×106 plants/ha (D1), 4.5×106 plants/ha (D2), 6.75×106 plants/ha (D3), and 9×106 plants/ha (D4). At the appropriate growth and development stages, we assessed agronomic traits, mechanical characteristics, biochemical compositions, yield and its components. The study investigated the impact of planting density on the growth, lodging, and yield of oat, as well as their interrelationships. Additionally, we identified the optimal planting density to establish a robust crop structure. The research aims to contribute to the high-yield and high-quality cultivation of oat. Results: We observed that with increasing planting density, plant height, grass and grain yields of both varieties first increased and then decreased; root fresh weight, stem diameter, stem wall thickness, stem puncture strength, breaking strength, compressive strength, lignin and crude fiber contents, and yield components decreased; whereas the lodging rate and lodging coefficient increased. Planting density affects lodging by regulating plant height, height of center of gravity, stem wall thickness, internode length, and root fresh weight of oat. Additionally, it can impact stem mechanical strength by modulating the synthesis of lignin and crude fiber, which in turn affecting lodging resistance. Plant height, height of center of gravity, stem wall thickness, internode length, root fresh weight, breaking strength, compressive strength, lignin and crude fiber content, single-plant weight, grain yield and 1,000-grain weight can serve as important indicators for evaluating oat stem lodging resistance. We also noted that planting density affected grain yield both directly and indirectly (by affecting lodging); high density increased lodging rate and decreased grain yield, mainly by reducing 1,000-grain weight. Nonetheless, there was no significant relationship between lodging and grass yield. As appropriate planting density can increase the yield while maintaining good lodging resistance, in this study, 4.5×106 plants/ha (D2) was found to be the best planting density for oat in terms of lodging resistance and grass and grain yield. These findings can be used as a reference for oat planting.

The impact of mixed planting of Poaceae species in the Qinghai-Tibet plateau region on forage yield, soil nutrients, and soil microbial communities.

Establishing cultivated grassland in the Qinghai-Tibet Plateau region is an effective method to address the conflict between vegetation and livestock. However, the high altitude, low temperature, and arid climate in the region result in slow regeneration and susceptibility to degradation of mixed cultivation grassland containing perennial legumes and gramineous plants. Therefore, we aim to through field experiments, explore the feasibility of establishing mixed cultivation grassland of Poaceae species in the region by utilizing two grass species, Poa pratensis L. and Puccinellia tenuiflora. By employing a mixture of P. pratensis and P. tenuiflora to establish cultivated grassland, we observed significant changes in forage yield over time. Specifically, during the 3rd to 6th years of cultivation, the yield in the mixed grassland was higher than in monocultures. It exceeded the yield of monoculture P. tenuiflora by 19.38% to 29.14% and surpassed the monoculture of P. pratensis by 17.18% to 62.98%. Through the analysis of soil physicochemical properties and soil microbial communities in the cultivated grassland, the study suggests that the mixed grassland with Poaceae species can enhance soil enzyme activity and improve soil microbial communities. Consequently, this leads to increased soil nutrient levels, enhanced nitrogen fixation efficiency, and improved organic phosphorus conversion efficiency. Therefore, establishing mixed grasslands with Poaceae species in the Qinghai-Tibet Plateau region is deemed feasible.

The role of grid management in community risk governance: a case study in Yuelu, China.

Objective: In this study, we aim to provide a comprehensive analysis of the effectiveness of the risk prevention and control mechanism within the grid management model for community risk prevention. We emphasize the importance of thoroughly examining the risk prevention and control mechanism to enhance risk management efforts in urban communities, particularly in response to unforeseen outbreaks such as COVID-19. Methods: Case studies are widely acknowledged as one of the most effective approaches to examine governance in China. In this study, the "Yuelu Model" serves as an illustrative example to demonstrate the application and effectiveness of grid management in community risk governance. To ensure the validity of the case study, it is imperative to adhere to the principle of representativeness. The collection of case data involves a combination of primary and secondary sources, and supplementary information is obtained through follow-up investigations conducted via WeChat, telephone, and other means, thereby enhancing the comprehensiveness and accuracy of the data. Results: Our analysis reveals significant findings regarding the impact of the grid management model, fulfilling a triple role as a "Social Safety Valve" in the management process: (1) Community stress reduction function, (2) Community alarm function, and (3) Community integration function. Furthermore, we explore the adaptability of the grid management mechanism in addressing community risks, highlighting its effectiveness and potential for broader application. Discussion: The findings of this study suggest that: Firstly, it is crucial to establish a shared information repository among different departments on a big data platform. Secondly, a dynamic government public information internal network should be established through collaborative efforts among multiple departments. Thirdly, implementing a regular (or periodic) early warning mechanism is essential. Lastly, the establishment of a high-quality talent team for power grid management is highly recommended. Our research provides valuable insights to enhance community risk governance.

A novel approach for sludge deep-dewatering via flowing-out enhancement but not relying on cell lysis and bound water release.

Effective deep-dewatering is crucial for wastewater sludge management. Currently, the dominant methods focus on promoting cell lysis to release intracellular water, but these techniques often lead to secondary pollution and require stringent conditions, limiting their practical use. This study explores an innovative method using a commercially available complex quaternary ammonium salt surfactant, known as G-agent. This agent remarkably reduces the sludge water content from 98.6 % to 56.8 % with a low dosage (50 mg/g DS) and under neutral pH conditions. This approach surpasses Fenton oxidation in terms of dewatering efficiency and avoids the necessity for cell lysis and bound water release, thereby reducing the risk of secondary pollution in the filtrate, including heavy metals, nitrogen, phosphorus, and other contaminants. The G-agent plays a significant role in destabilizing flocs and enhancing flocculation during the conditioning and initial dewatering stages, effectively reducing the solid-liquid interfacial affinity of the sludge. In the compression filtration stage, the agent's solidification effect is crucial in forming a robust skeleton that improves pore connectivity within the filter cake, leading to increased water permeability, drainage performance and water flow-out efficiency. This facilitates deep dewatering of sludge without cell lysis. The study reveals that the G-agent primarily improves water flow-out efficiency rather than water flowability, indicating that cell lysis and bound water release are not indispensable prerequisites for sludge deep-dewatering. Furthermore, it presents an encouraging prospect for overcoming the limitations associated with conventional sludge deep-dewatering processes.

A fungal polysaccharide from Fomitopsis officinalis as a multi-target molecule to combat cancer.

Some macrofungi have a long history of being used as traditional or folk medicines, making significant contributions to human health. To discover bioactive molecules with potential anticancer properties, a homogeneous heteropolysaccharide (FOBP90-1) was purified from the medicinal macrofungus Fomitopsis officinalis. FOBP90-1 was found to have a molecular weight of 2.87 × 104 g/mol and mainly consist of →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, →6)-ß-d-Glcp-(1→, α-d-Manp-(1→, and 3-O-Me-α-l-Fucp-(1→ according to UV, FT-IR, methylation analysis, and NMR data. In addition to its structural properties, FOBP90-1 displayed anticancer activity in zebrafish models. The following mechanistic analysis discovered that the in vivo antitumor effect was linked to immune activation and angiogenesis inhibition. These effects were mediated by the interactions of FOBP90-1 with TLR-2, TLR-4, PD-L1, and VEGFR-2, as determined through a series of experiments involving cells, transgenic zebrafish, molecular docking simulations, and surface plasmon resonance (SPR). All the experimental findings have demonstrated that FOBP90-1, a purified fungal polysaccharide, is expected to be utilized as a cancer treatment agent.

Camelus knoblochi genome reveals the complex evolutionary history of Old World camels.

Extant Old World camels (genus Camelus) contributed to the economic and cultural exchanges between the East and West for thousands of years.1,2 Although many remains have been unearthed,3,4,5 we know neither whether the prevalent hybridization observed between extant Camelus species2,6,7 also occurred between extinct lineages and the ancestors of extant Camelus species nor why some populations became extinct while others survived. To investigate these questions, we generated paleogenomic and stable isotope data from an extinct two-humped camel species, Camelus knoblochi. We find that in the mitochondrial phylogeny, all C. knoblochi form a paraphyletic group that nests within the diversity of modern, wild two-humped camels (Camelus ferus). In contrast, they are clearly distinguished from both wild and domesticated (Camelus bactrianus) two-humped camels on the nuclear level. Moreover, the divergence pattern of the three camel species approximates a trifurcation, because the most common topology is only slightly more frequent than the two other possible topologies. This mito-nuclear phylogenetic discordance likely arose due to interspecific gene flow between all three species, suggesting that interspecific hybridization is not exclusive to modern camels but a recurrent phenomenon throughout the evolutionary history of the genus Camelus. These results suggest that the genomic complexity of Old World camels' evolutionary history is underestimated when considering data from only modern species. Finally, we find that C. knoblochi populations began declining prior to the last glacial maximum and, by integrating palaeoecological evidence and stable isotope data, suggest that this was likely due to failure to adapt to a changing environment.

Enhanced Prediction of Malignant Cerebral Edema in Large Vessel Occlusion with Successful Recanalization through Automated Weighted Net Water Uptake.

BACKGROUND AND PURPOSE: Malignant cerebral edema (MCE) is associated with both net water uptake (NWU) and infarct volume. We hypothesized that NWU weighted by the affected ASPECTS regions could serve as a quantitative imaging biomarker of aggravated edema development in acute ischemic stroke with large vessel occlusion (LVO). The aim of this study was to evaluate the performance of weighted NWU (wNWU) to predict MCE in patients with mechanical thrombectomy (MT). MATERIALS AND METHODS: We retrospectively analyzed consecutive patients who underwent MT due to LVO. NWU was computed from nonenhanced CT scans upon admission using automated ASPECTS software. wNWU was derived by multiplying NWU with the number of affected ASPECTS regions in the ischemic hemisphere. Predictors of MCE were assessed through multivariate logistic regression analysis and receiver operating characteristic curves. RESULTS: NWU and wNWU were significantly higher in MCE patients than that in non-MCE patients. Vessel recanalization status influenced the performance of wNWU in predicting MCE. In patients with successful recanalization, wNWU was an independent predictor of MCE (adjusted OR 1.61; 95%CI 1.24-2.09; P < 0.001). The model integrating wNWU, NIHSS, and collateral score exhibited an excellent performance in predicting MCE (AUC 0.80; 95%CI 0.75-0.84). Among patients with unsuccessful recanalization, wNWU did not influence the development of MCE (adjusted OR 0.99; 95%CI 0.60-1.62; P = 0.953). CONCLUSION: This study revealed that wNWU at admission can serve as a quantitative predictor of MCE in LVO with successful recanalization after MT and may contribute to the decision for early intervention.

Soil microbial community are more sensitive to ecological regions than cropping systems in alpine annual grassland of the Qinghai-Tibet Plateau.

Introduction: Modern agriculture emphasizes the design of cropping systems using ecological function and production services to achieve sustainability. The functional characteristics of plants (grasses vs. legumes) affect changes in soil microbial communities that drive agroecosystem services. Information on the relationship between legume-grass mixtures and soil microorganisms in different ecological zones guides decision-making toward eco-friendly and sustainable forage production. However, it is still poorly understood how cropping patterns affect soil microbial diversity in alpine grasslands and whether this effect varies with altitude. Methods: To fill this gap in knowledge, we conducted a field study to investigate the effects of growing oats (Avena sativa L.), forage peas (Pisum sativum L.), common cornflower (Vicia sativa L.), and fava beans (Vicia faba L.) in monocultures and mixtures on the soil microbial communities in three ecological zones of the high alpine zone. Results: We found that the fungal and bacterial community structure differed among the cropping patterns, particularly the community structure of the legume mixed cropping pattern was very different from that of monocropped oats. In all ecological zones, mixed cropping significantly (p < 0.05) increased the α-diversity of the soil bacteria and fungi compared to oat monoculture. The α-diversity of the soil bacteria tended to increase with increasing elevation (MY [2,513 m] < HZ [2,661 m] < GN [3,203 m]), while the opposite was true for fungi (except for the Chao1 index in HZ, which was the lowest). Mixed cropping increased the abundance of soil fungi and bacteria across ecological zones, particularly the relative abundances of Nitrospira, Nitrososphaera, Phytophthora, and Acari. Factors affecting the bacterial community structure included the cropping pattern, the ecological zone, water content, nitrate-nitrogen, nitrate reductase, and soil capacity, whereas factors affecting fungal community structure included the cropping pattern, the ecological zone, water content, pH, microbial biomass nitrogen, and catalase. Discussion: Our study highlights the variation in soil microbial communities among different in alpine ecological regions and their resilience to cropping systems. Our results also underscore that mixed legume planting is a sustainable and effective forage management practice for the Tibetan Plateau.

Genetic Background of Blood ß-Hydroxybutyrate Acid Concentrations in Early-Lactating Holstein Dairy Cows Based on Genome-Wide Association Analyses.

Ketosis is a common metabolic disorder in the early lactation of dairy cows. It is typically diagnosed by measuring the concentration of ß-hydroxybutyrate (BHB) in the blood. This study aimed to estimate the genetic parameters of blood BHB and conducted a genome-wide association study (GWAS) based on the estimated breeding value. Phenotypic data were collected from December 2019 to August 2023, comprising blood BHB concentrations in 45,617 Holstein cows during the three weeks post-calving across seven dairy farms. Genotypic data were obtained using the Neogen Geneseek Genomic Profiler (GGP) Bovine 100 K SNP Chip and GGP Bovine SNP50 v3 (Illumina Inc., San Diego, CA, USA) for genotyping. The estimated heritability and repeatability values for blood BHB levels were 0.167 and 0.175, respectively. The GWAS result detected a total of ten genome-wide significant associations with blood BHB. Significant SNPs were distributed in Bos taurus autosomes (BTA) 2, 6, 9, 11, 13, and 23, with 48 annotated candidate genes. These potential genes included those associated with insulin regulation, such as INSIG2, and those linked to fatty acid metabolism, such as HADHB, HADHA, and PANK2. Enrichment analysis of the candidate genes for blood BHB revealed the molecular functions and biological processes involved in fatty acid and lipid metabolism in dairy cattle. The identification of novel genomic regions in this study contributes to the characterization of key genes and pathways that elucidate susceptibility to ketosis in dairy cattle.

Unveiling the role of FTO polymorphisms in predicting response to immune checkpoint inhibitors: A retrospective study.

BACKGROUND: Identifying patients who can benefit from immune checkpoint inhibitors (ICIs) is a critical challenge in immunotherapy. This study aimed to investigate the association between fat mass and obesity-associated protein (FTO) polymorphisms and ICIs treatment outcomes. METHOD: This retrospective study was conducted on 371 patients with malignant tumors who received ICIs treatment and were followed-up for a minimum duration of 12 months. Seven variants in FTO gene were genotyped using the Sequenome MassARRAY platform, and their associations with ICIs treatment outcomes were analyzed. RESULTS: Pharmacogenomic research revealed that individuals carrying the rs11075995AT/TT genotype were more likely to benefit from ICIs treatment compare to TT genotype. Cox regression analysis showed that rs1125338TT carriers exhibited a shorter progression-free survival (PFS, hazard ratio (HR) = 1.72, 95 % confidence interval (CI) = 1.12-2.46), while rs12596638GG carriers experienced extended PFS (HR = 0.71, 95 % CI = 0.50-0.99). Multiple Cox regression analysis indicated that rs12596638GG (HR = 6.81, 95 %CI = 1.20-38.56) and rs1125338CC (HR = 1.78, 95 %CI = 0.07-0.45), rs12600192CC (HR = 0.13, 95 %CI = 0.037-0.44) genotypes were independently associated with overall survival (OS) after adjusting clinical characteristics. Furthermore, patients with rs12600192CC genotype had a lower risk of severe irAEs compared to those with GG/GC genotypes (P < 0.01). CONCLUSION: We identified FTO gene polymorphisms associated with treatment outcomes of ICI treatment in patients with multiple solid cancers, which might serve as potential predictive biomarkers.

ZLN005 alleviates PBDE-47 induced impairment of mitochondrial translation and neurotoxicity through PGC-1α/ERRα axis.

Recent studies are identified the mitochondria as critical targets of 2, 2', 4, 4'-tetrabromodiphenyl ether (PBDE-47) induced neurotoxicity. This study aimed at examining the impact of PBDE-47 exposure on mitochondrial translation, and its subsequent effect on PBDE-47 neurotoxicity. The Sprague-Dawley (SD) rat model and neuroendocrine pheochromocytoma (PC12) cells were adopted for the measurements of mitochondrial ATP levels, mitochondrial translation products, and expressions of important mitochondrial regulators, such as required meiotic nuclear division 1 (RMND1), estrogen-related receptor α (ERRα), and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). To delve into the role of PGC-1α/ERRα axis in mitochondrial translation, 2-(4-tert-butylphenyl) benzimidazole (ZLN005) was employed. Both cellular and animal model results shown that PBDE-47 impeded PGC-1α/ERRα axis and mitochondrial translation. PBDE-47 suppressed mitochondrial function in rat hippocampus and PC12 cells by decreasing relative mitochondrial DNA (mtDNA) content, mitochondrial translation products, and mitochondrial ATP levels. Particularly, ZLN005 reversed PBDE-47 neurotoxicity by enhancing mitochondrial translation through activation of PGC-1α/ERRα axis, yet suppressing PGC-1α with siRNA attenuates its neuroprotective effect in vitro. In conclusion, this work highlights the importance of mitochondrial translation in PBDE-47 neurotoxicity by presenting results from cellular and animal models and suggests a potential therapeutic approach through activation of PGC-1α/ERRα axis. ENVIRONMENTAL IMPLICATION: PBDEs have attracted extensive attention because of their high lipophilicity, persistence, and detection levels in various environmental media. Increasing evidence has shown that neurodevelopmental disorders in children are associated with PBDE exposure. Several studies have also found that perinatal PBDE exposure can cause long-lasting neurobehavioral abnormalities in experimental animals. Our recent studies have also demonstrated the impact of PBDE-47 exposure on mitochondrial biogenesis and dynamics, leading to memory and neurobehavioral deficits. Therefore, we explore whether the pathological mechanism of PBDE-47-induced neurotoxicity involves the regulation of mitochondrial translation through the PGC-1α/ERRα axis.

An antitumor fungal polysaccharide from Fomitopsis officinalis by activating immunity and inhibiting angiogenesis.

Macrofungi, a class of unique natural resources, are gaining popularity owing to their potential therapeutic benefits and edibility. From Fomitopsis officinalis, a medicinal macrofungus with anticancer activity, a homogeneous heteropolysaccharide (FOBP50-1) with a molecular weight of 2.21 × 104 g/mol has been extracted and purified. FOBP50-1 was found to be composed of 3-O-methylfucose, fucose, mannose, glucose, and galactose with a ratio of 1: 6.5: 4.4: 8.1: 18.2. The sugar fragments and structure of FOBP50-1 were investigated, which included →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, α-d-Glcp-(1→, →3)-ß-d-Manp-(1→, →6)-ß-d-Manp-(1→, 3-O-Me-α-l-Fucp-(1→, according to the UV, FT-IR, GC-MS, and NMR data. Besides the structure elucidation, FOBP50-1 showed promising antitumor activity in the zebrafish assays. The following mechanism examination discovered that FOBP50-1 interacted with TLR-4, PD-1, and VEGF to activate immunity and inhibit angiogenesis according to a series of cell, transgenic zebrafish, and surface plasmon resonance (SPR) experiments. The KD values indicating the association of FOBP50-1 with TLR-4, PD-1, and VEGF, were 4.69 × 10-5, 7.98 × 10-6, 3.04 × 10-6 M, respectively, in the SPR experiments. All investigations have demonstrated that the homogenous fungal polysaccharide FOBP50-1 has the potential to be turned into a tumor immunotherapy agent.

Molecular mechanism of infectious spleen and kidney necrosis virus in manipulating the hypoxia-inducible factor pathway to augment virus replication.

Infectious spleen and kidney necrosis virus (ISKNV), a member of the genus Megalocytivirus in the family Iridoviridae, can infect over 50 fish species and cause significant economic losses in Asia. Our previous study showed that hypoxia triggers the hypoxia-inducible factor pathway (HIF-pathway), leading to increased replication of ISKNV through promoting the upregulation of viral hypoxic response genes like orf077r. This study delved into the molecular mechanism of how ISKNV manipulates the HIF-pathway to enhance its replication. In vitro and in vivo experiments confirmed that ISKNV infection activated the HIF-pathway, which in turn promoted ISKNV replication. These findings suggest that ISKNV actively manipulates the HIF-pathway. Co-immunoprecipitation experiments revealed that the ISKNV-encoded protein VP077R interacts with the Von Hippel-Lindau (VHL) protein at the HIF-binding region, competitively inhibiting the interaction of HIF-1α with VHL. This prevents HIF degradation and activates the HIF-pathway. Furthermore, VP077R interacts with factor-inhibiting HIF (FIH), recruiting FIH and S-phase kinase-associated protein 1 (Skp1) to form an FIH - VP077R - Skp1 complex. This complex promotes FIH protein degradation via ubiquitination, further activating the HIF-pathway. These findings indicated that ISKNV takes over the HIF-pathway by releasing two "brakes" on this pathway (VHL and FIH) via VP077R, facilitating virus replication. We speculate that hypoxia initiates a positive feedback loop between ISKNV VP077R and the HIF pathway, leading to the outbreak of ISKNV disease. This work offers valuable insights into the complex interactions between the environment, host, and virus.

TRPV4 antagonist suppresses retinal ganglion cell apoptosis by regulating the activation of CaMKII and TNF-α expression in a chronic ocular hypertension rat model.

Glaucoma is characterized by a progressive loss of retinal ganglion cells (RGCs), leading to irreversible visual function impairment. Sustained increase in intraocular pressure represents a major risk factor for glaucoma, yet the underlying mechanisms of RGC apoptosis induced by intraocular pressure remains unclear. This study aims to investigate the role of TRPV4 in RGC apoptosis in a rat model of chronic ocular hypertension (COH) and the underlying molecular mechanism. In the COH rat models, we evaluated the visual function, retinal pathological changes and RGC apoptosis. TRPV4 expression and downstream signaling molecules were also detected. We found that RGC density decreased and RGC apoptosis was induced in COH eyes compared with control eyes. TRPV4 expression increased significantly in response to elevated IOP. TRPV4 inhibition by the TRPV4 antagonist HC-067047 (HC-067) suppressed RGC apoptosis and protected visual function. HC-067 treatment upregulated the phosphorylation of CaMKII in both control and COH eyes. Finally, HC-067 treatment suppressed the production of TNF-α induced by ocular hypertension. The TRPV4 antagonist HC-067 might suppress RGC apoptosis by regulating the activation of CaMKII and inhibiting the production of TNF-α in the COH model. This indicated that TRPV4 antagonists may be a potential and novel therapeutic strategy for glaucoma.

Research hotspots and frontiers of alcohol and epilepsy: A bibliometric analysis.

PURPOSE: Alcohol is implicated in epileptogenesis and seizures attack. An increasing number of studies about alcohol and epilepsy have been published. We aimed to assess research trends and hot spots in the field of alcohol and epilepsy. PATIENTS AND METHODS: Literature concerning alcohol and epilepsy was systemically searched through the Web of Science database. Collaborative maps were quantitatively analyzed by using the VOSviewer and CiteSpace tools. RESULTS: A total of 1578 papers about the field of alcohol and epilepsy were taken into analysis, which was written by 6840 authors from 2153 institutions in 85 countries, published in 676 journals, and cited 79 667 references from 10 750 journals. The United States was the leading country and had close ties with others. The University of Toronto was the most productive institution. Alcoholism-clinical and experimental research was the fastest-growing journal. Richard J. Bodnar was the author contributing the most literature. Analysis of keywords showed epilepsy, alcohol, seizures, alcohol withdrawal, and management were common themes. CONCLUSION: The presented study conducted the first bibliometric analysis of the field of alcohol and epilepsy, which will provide insights into the latest progress, evolution paths, frontier research hot spots, and future research trends in the field.

Prediction of potential distributions of Morina kokonorica and Morina chinensis in China.

Changes in the habitats of species can provide insights into the impact of climate change on their habitats. Species in the genus Morina (Morinoideae) are perennial herbaceous plants that are mainly distributed in the South Asian Mountains and Eastern Mediterranean. In China, there are four species and two varieties of this genus distributed across the Yunnan, Sichuan, Qinghai, and Gansu provinces. This study used the optimal MaxEnt model to simulate past, current, and future potentially suitable habitats of Morina kokonorica and Morina chinensis. Seventy data of M. kokonorica occurrences and 3 of M. chinensis were used in the model to predict potentially suitable habitats. The model prediction results indicated that both M. kokonorica and M. chinensis exhibited trends of northward migration to higher latitudes and westward migration along the Himalayas to higher elevations, suggesting that the northern valleys of Hengduan Mountains and northern and eastern parts of the Himalayas were potential refugia for M. kokonorica, and the potential refugia for M. chinensis was located in the eastern part of Qinghai-Tibet Plateau. The results of this niche analysis showed that the two species had higher levels of interspecific competition and that the environmental adaptability of M. chinensis was stronger. This research could help further understand the response pattern of Morina to environmental change, to understand the adaptability of species to the environment, and promote the protection of species.