Multimodal Connectivity-based Individual Parcellation and Analysis for Humans and Rhesus Monkeys.

Individual brains vary greatly in morphology, connectivity and organization. Individualized brain parcellation is capable of precisely localizing subject-specific functional regions. However, most individualization approaches examined single modality of data and have not generalized to nonhuman primates. The present study proposed a novel multimodal connectivity-based individual parcellation (MCIP) method, which optimizes within-region homogeneity, spatial continuity and similarity to a reference atlas with the fusion of personal functional and anatomical connectivity. Comprehensive evaluation demonstrated that MCIP outperformed state-of-the-art multimodal individualization methods in terms of functional and anatomical homogeneity, predictability of cognitive measures, heritability, reproducibility and generalizability across species. Comparative investigation showed a higher topographic variability in humans than that in macaques. Therefore, MCIP provides improved accurate and reliable mapping of brain functional regions over existing methods at an individual level across species, and could facilitate comparative and translational neuroscience research.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Current cancer vaccines using T cell epitopes activate antitumor T cell immunity through dendritic cell/macrophage-mediated antigen presentation, but they lack the ability to promote B/CD4 T cell crosstalk, limiting their anticancer efficacy. We developed antigen-clustered nanovaccine (ACNVax) to achieve long-term tumor remission by promoting B/CD4 T cell crosstalk. The topographic features of ACNVax were achieved using an iron nanoparticle core attached with an optimal number of gold nanoparticles, where the clusters of HER2 B/CD4 T cell epitopes were conjugated on the gold surface with an optimal intercluster distance of 5-10 nm. ACNVax effectively trafficked to lymph nodes and cross-linked with BCR, which are essential for stimulating B cell antigen presentation-mediated B/CD4 T cell crosstalk in vitro and in vivo. ACNVax, combined with anti-PD-1, achieved long-term tumor remission (>200 days) with 80% complete response in mice with HER2+ breast cancer. ACNVax not only remodeled the tumor immune microenvironment but also induced a long-term immune memory, as evidenced by complete rejection of tumor rechallenge and a high level of antigen-specific memory B, CD4, and CD8 cells in mice (>200 days). This study provides a cancer vaccine design strategy, using B/CD4 T cell epitopes in an antigen clustered topography, to achieve long-term durable anticancer efficacy through promoting B/CD4 T cell crosstalk.

Decoding and reconstructing disease relations between dry eye and depression: a multimodal investigation comprising meta-analysis, genetic pathways and Mendelian randomization.

INTRODUCTION: The clinical presentations of dry eye disease (DED) and depression (DEP) often comanifest. However, the robustness and the mechanisms underlying this association were undetermined. OBJECTIVES: To this end, we set up a three-segment study that employed multimodality results (meta-analysis, genome-wide association study [GWAS] and Mendelian randomization [MR]) to elucidate the association, common pathways and causality between DED and DEP. METHODS: A meta-analysis comprising 26 case-control studies was first conducted to confirm the DED-DEP association. Next, we performed a linkage disequilibrium (LD)-adjusted GWAS and targeted phenotype association study (PheWAS) in East Asian TW Biobank (TWB) and European UK Biobank (UKB) populations. Single-nucleotide polymorphisms (SNPs) were further screened for molecular interactions and common pathways at the functional gene level. To further elucidate the activated pathways in DED and DEP, a systemic transcriptome review was conducted on RNA sequencing samples from the Gene Expression Omnibus. Finally, 48 MR experiments were implemented to examine the bidirectional causation between DED and DEP. RESULTS: Our meta-analysis showed that DED patients are associated with an increased DEP prevalence (OR = 1.83), while DEP patients have a concurrent higher risk of DED (OR = 2.34). Notably, cross-disease GWAS analysis revealed that similar genetic architecture (rG = 0.19) and pleiotropic functional genes contributed to phenotypes in both diseases. Through protein-protein interaction and ontology convergence, we summarized the pleiotropic functional genes under the ontology of immune activation, which was further validated by a transcriptome systemic review. Importantly, the inverse variance-weighted (IVW)-MR experiments in both TWB and UKB populations (p value <0.001) supported the bidirectional exposure-outcome causation for DED-to-DEP and DEP-to-DED. Despite stringent LD-corrected instrumental variable re-selection, the bidirectional causation between DED and DEP remained. CONCLUSION: With the multi-modal evidence combined, we consolidated the association and causation between DED and DEP.

Response of Carbon-Fixing Bacteria to Patchy Degradation of the Alpine Meadow in the Source Zone of the Yellow River, West China.

This study aims to enlighten our understanding of the distribution of soil carbon-fixing bacteria (cbbL-harboring bacteria) and their community diversity in differently degraded patches at three altitudes. MiSeq high-throughput sequencing technology was used to analyze the soil carbon-fixing bacteria community diversity of degraded patches and healthy meadow at three altitudes. Redundancy analysis (RDA) and structural equation model (SEM) were used to analyze the correlation and influence path between environmental factors and carbon-fixing bacteria. The results showed that degradation reduced the relative abundance of Proteobacteria from 99.67% to 95.57%. Sulfurifustis, Cupriavidus, and Alkalispirillum were the dominant genera at the three altitudes. Hydrogenophaga and Ectothiorhodospira changed significantly with altitude. RDA results confirmed that available phosphorus (AP) was strongly and positively correlated with Proteobacteria. AP and total nitrogen (TN) were strongly and positively correlated with Hydrogenophaga. Grass coverage and sedge aboveground biomass were strongly and positively correlated with Sulfurifustis and Ectothiorhodospira, respectively. Elevation adversely affected the relative abundance of dominant carbon-fixing bacteria and diversity index by reducing the coverage of grass and soil volumetric moisture content (SVMC) indirectly, and also had a direct positive impact on the Chao1 index (path coefficient = 0.800). Therefore, increasing the content of nitrogen, phosphorus and SVMC and vegetation coverage, especially sedge and grass, will be conducive to the recovery of the diversity of soil carbon-fixing bacteria and improve the soil autotrophic microbial carbon sequestration potential in degraded meadows, especially in high-altitude areas.

Ferroptosis: a potential target for the treatment of atherosclerosis.

Atherosclerosis (AS), the main contributor to acute cardiovascular events, such as myocardial infarction and ischemic stroke, is characterized by necrotic core formation and plaque instability induced by cell death. The mechanisms of cell death in AS have recently been identified and elucidated. Ferroptosis, a novel iron-dependent form of cell death, has been proven to participate in atherosclerotic progression by increasing endothelial reactive oxygen species (ROS) levels and lipid peroxidation. Furthermore, accumulated intracellular iron activates various signaling pathways or risk factors for AS, such as abnormal lipid metabolism, oxidative stress, and inflammation, which can eventually lead to the disordered function of macrophages, vascular smooth muscle cells, and vascular endothelial cells. However, the molecular pathways through which ferroptosis affects AS development and progression are not entirely understood. This review systematically summarizes the interactions between AS and ferroptosis and provides a feasible approach for inhibiting AS progression from the perspective of ferroptosis.

FFCM-MRF: An accurate and generalizable cerebrovascular segmentation pipeline for humans and rhesus monkeys based on TOF-MRA.

PURPOSE: Cerebrovascular segmentation and quantification of vascular morphological features in humans and rhesus monkeys are essential for prevention, diagnosis, and treatment of brain diseases. However, current automated whole-brain vessel segmentation methods are often not generalizable to independent datasets, limiting their usefulness in real-world environments with their heterogeneity in participants, scanners, and species. MATERIALS AND METHODS: In this study, we proposed an automated, accurate and generalizable segmentation method for magnetic resonance angiography images called FFCM-MRF. This method integrated fast fuzzy c-means clustering and Markov random field optimization by vessel shape priors and spatial constraints. We used a total of 123 human and 44 macaque MRA images scanned at 1.5 T, 3 T, and 7 T MRI from 9 datasets to develop and validate the method. RESULTS: FFCM-MRF achieved average Dice similarity coefficients ranging from 69.16 % to 89.63 % across multiple independent datasets, with improvements ranging from 3.24 % to 7.3 % compared to state-of-the-art methods. Quantitative analysis showed that FFCM-MRF can accurately segment major arteries in the Circle of Willis at the base of the brain and small distal pial arteries while effectively reducing noise. Test-retest analysis showed that the model yielded high vascular volume and diameter reliability. CONCLUSIONS: Our results have demonstrated that FFCM-MRF is highly accurate and reliable and largely independent of variations in field strength, scanner platforms, acquisition parameters, and species. The macaque MRA data and user-friendly open-source toolbox are freely available at OpenNeuro and GitHub to facilitate studies of imaging biomarkers for cerebrovascular and neurodegenerative diseases.

A Study on the C, N, and P Contents and Stoichiometric Characteristics of Forage Leaves Based on Fertilizer-Reconstructed Soil in an Alpine Mining Area.

In this study, we analyzed the C, N, and P contents and stoichiometric characteristics of forage leaves of five species (Elymus breviaristatus cv. Tongde, Poa crymophila cv. Qinghai, Puccinellia tenuiflora cv. Qinghai, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai) in "fertilizer-reconstructed soil" through integrative soil amendment with parched sheep manure and granular organic fertilizer in an alpine mining area. A model is fitted in order to screen out the best forage species suitable for vegetation restoration in the alpine mining area and the most favorable fertilizer dosage to improve the nutrient content of forage leaves. The results showed that (1) increasing the dosages of granular organic fertilizer and sheep manure had little effect on the C content of the five types of forage grasses, but they could significantly increase the N and P contents and N/P of the manually restored grassland in the alpine mining area (p < 0.05). (2) The productivity and stability of the five species were ranked as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa pratensis cv. Qinghai > Poa crymophila cv. Qinghai. (3) According to the fitted least squares model and the willingness to maximize the C, N, and P contents of the leaves, the ranking of the five forage grasses was described by the Prediction Profiler as follows: Elymus breviaristatus cv. Tongde > Puccinellia tenuiflora cv. Qinghai > Festuca sinensis cv. Qinghai > Poa crymophila cv. Qinghai > Poa pratensis cv. Qinghai. (4) The predictive model suggested that the optimal contents of C, N, and P in Elymus breviaristatus cv. Tongde, Festuca sinensis cv. Qinghai, and Poa pratensis cv. Qinghai leaves could be achieved with the application of 3.6 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. For Poa crymophila cv. Qinghai leaves, the ideal content was attained by applying 0 kg/m2 of granular organic fertilizer and 45.0 kg/m2 of sheep manure. Lastly, the optimal C, N, and P contents in Puccinellia tenuiflora cv. Qinghai leaves could be obtained through the application of 3.6 kg/m2 of granular organic fertilizer combined with 0 kg/m2 of sheep manure. In conclusion, the study's results highlight the significant practical value of the fertilizer-reconstructed soil for vegetation restoration in alpine mining regions.

A gastrointestinal locally activating Janus kinase inhibitor to treat ulcerative colitis.

In this study, we integrated machine learning (ML), structure-tissue selectivity-activity-relationship (STAR), and wet lab synthesis/testing to design a gastrointestinal (GI) locally activating JAK inhibitor for ulcerative colitis treatment. The JAK inhibitor achieves site-specific efficacy through high local GI tissue selectivity while minimizing the requirement for JAK isoform specificity to reduce systemic toxicity. We used the ML model (CoGT) to classify whether the designed compounds were inhibitors or noninhibitors. Then we used the regression ML model (MTATFP) to predict their IC50 against related JAK isoforms of predicted JAK inhibitors. The ML model predicted MMT3-72, which was retained in the GI tract, to be a weak JAK1 inhibitor, while MMT3-72-M2, which accumulated in only GI tissues, was predicted to be an inhibitor of JAK1/2 and TYK2. ML docking methods were applied to simulate their docking poses in JAK isoforms. Application of these ML models enabled us to limit our synthetic efforts to MMT3-72 and MMT3-72-M2 for subsequent wet lab testing. The kinase assay confirmed MMT3-72 weakly inhibited JAK1, and MMT3-72-M2 inhibited JAK1/2 and TYK2. We found that MMT3-72 accumulated in the GI lumen, but not in GI tissue or plasma, but released MMT3-72-M2 accumulated in colon tissue with minimal exposure in the plasma. MMT3-72 achieved superior efficacy and reduced p-STAT3 in DSS-induced colitis. Overall, the integration of ML, the structure-tissue selectivity-activity-relationship system, and wet lab synthesis/testing could minimize the effort in the optimization of a JAK inhibitor to treat colitis. This site-specific inhibitor reduces systemic toxicity by minimizing the need for JAK isoform specificity.

N2-fixing bacteria are more sensitive to microtopography than nitrogen addition in degraded grassland.

Introduction: Soil bacteria play a crucial role in the terrestrial nitrogen (N) cycle by fixing atmospheric N2, and this process is influenced by both biotic and abiotic factors. The diversity of N2-fixing bacteria (NFB) directly reflects the efficiency of soil N fixation, and the diversity of NFB in degraded alpine meadow soil may change with different N fertilizing levels and varied slopes. However, how N addition affects the diversity of NFB in degraded alpine meadows, and whether this influence varies with slope, remain poorly understood. Methods: We conducted an N addition field experiment at three levels (2, 5, and 10 g N·m-2·a-1) to study the effects of N addition on soil NFB diversity on two different slopes in a degraded meadow on the Tibetan Plateau. Results: There were significant differences in the dominant bacterial species between the two slopes. The Chao1 index, species richness, and beta diversity of NFB did not differ significantly between slopes, but the Shannon index did. Interestingly, N addition had no effect on the diversity of NFB or the abundance of dominant bacteria. However, we did observe a significant change in some low-abundance NFB. The community composition and diversity of NFB were significantly positively correlated with slope and soil physicochemical properties (e.g., total potassium, pH, and total nitrogen). Conclusions: Our study highlights the variation in NFB communities among different slopes in degraded alpine meadows and their resilience to exogenous N addition. Our results also underscore the importance of considering the effects of micro-topography on soil microbial communities in future studies of alpine ecosystems.

Relationship between Species Diversity and Community Stability in Degraded Alpine Meadows during Bare Patch Succession.

Plant diversity plays an important role in maintaining the stability of ecosystem functioning. Based on field surveys and indoor analyses, this study investigated the relationship between species diversity and community stability at different stages of bare patch succession in degraded alpine meadow ecosystems. Results show that: (1) Using the ICV (the Inverse of the Coefficient of Variation) method to analyze changes in plant community stability, community stability was generally ranked as follows: Long-term recovered patches > Healthy alpine meadow > Degraded alpine meadow > Short-term recovered patch > Bare Patches. (2) Using factor analysis to construct an evaluation system, the stability ranking based on species diversity was as follows: Healthy alpine meadow > Long-term recovered patches > Degraded alpine meadow > Short-term recovered patches > Bare Patches. (3) The community stability index was significantly positively correlated with vegetation coverage, height, biomass, species richness, Shannon-Wiener diversity index, species evenness, and Simpson's diversity index (p < 0.05). Therefore, a positive correlation exists between plant diversity and community stability, such that plant communities with a higher species diversity tend to be more stable. To maintain the plant diversity and community stability of alpine meadow ecosystems, it is necessary to consider the characteristics of grassland plant composition and community structure, as well as their influencing factors, and promote the positive succession process of grasslands.

A multisectoral and multidisciplinary endeavor: a review of diabetes self-management apps in China.

BACKGROUND: While the use of self-management apps has considerable promise to efficiently reduce the diabetes burden that disproportionally affects low- and middle-income countries (LMICs), and the multisectoral and multidisciplinary approaches have been encouraged to be used in diabetes management, little is known about the status of the integration of these approaches in the existing diabetes self-management apps. This review examines the diabetes apps in China as an indication of the current status of integrating multisectoral and multidisciplinary approaches in diabetes mHealth care in LMICs. METHODS: Eligible diabetes apps were searched on major Chinese app stores up to December 23, 2022. The app comprehensiveness index (ranging 0-80) regarding the app functions and diabetes management domains was created. The multisectoral and multidisciplinary features were summarized using indices derived from current guidance. RESULTS: Sixty-six apps were reviewed, all developed by private companies. The average comprehensiveness score was 16, with many major self-management domains and functions not represented among the reviewed apps. Forty apps (61%) involved multiple sectoral entities, with public/private and private/private collaborations being the most common collaborative combinations. Thirty-seven apps (56%) involved multiple disciplines, among which endocrinology/metabolism, nutrition, and cardiovascular medicine were the top three most common disciplines. Compared to non-multidisciplinary apps, multidisciplinary apps tended to provide more comprehensive services in apps (6.14 vs. 5.18, p = 0.0345). Different sectors and disciplines tended to work independently, without robust interactions, in providing diabetes management services in the reviewed apps. CONCLUSION: Multisectoral and multidisciplinary features has presented in the current diabetes self-management apps in China; however, it is still in its infancy and significant limitations existed. More engagement of civil society organizations and community groups and innovative collaborations between sectors and disciplines are needed to provide comprehensive, continuous, and patient-centered mHealth care for patients with diabetes in LMICs like China. Clear guidance for integrating and evaluating the multisectoral and multidisciplinary efforts in self-management apps is necessary to ensure the effective use of mHealth solutions for diabetes management in LMICs.

Transaldolase inhibits CD36 expression by modulating glutathione-p38 signaling, exerting protective effects against macrophage foam cell formation.

In atherosclerosis, macrophage-derived foam cell formation is considered to be a hallmark of the pathological process; this occurs via the uptake of modified lipoproteins. In the present study, we aim to determine the role of transaldolase in foam cell formation and atherogenesis and reveal the mechanisms underlying its role. Bone marrow-derived macrophages (BMDMs) isolated from mice successfully form foam cells after treatment with oxidized low-density lipoprotein (80 µg/mL). Elevated transaldolase levels in the foam cell model are assessed by quantitative polymerase chain reaction and western blot analysis. Transaldolase overexpression and knockdown in BMDMs are achieved via plasmid transfection and small interfering RNA technology, respectively. We find that transaldolase overexpression effectively attenuates, whereas transaldolase knockdown accelerates, macrophage-derived foam cell formation through the inhibition or activation of cholesterol uptake mediated by the scavenger receptor cluster of differentiation 36 (CD36) in a p38 mitogen-activated protein kinase (MAPK) signaling-dependent manner. Transaldolase-mediated glutathione (GSH) homeostasis is identified as the upstream regulator of p38 MAPK-mediated CD36-dependent cholesterol uptake in BMDMs. Transaldolase upregulates GSH production, thereby suppressing p38 activity and reducing the CD36 level, ultimately preventing foam cell formation and atherosclerosis. Thus, our findings indicate that the transaldolase-GSH-p38-CD36 axis may represent a promising therapeutic target for atherosclerosis.

RNA-sequencing-based detection of human viral pathogens in cerebrospinal fluid and serum samples from children with meningitis and encephalitis.

Encephalitis and meningitis are notable global public health concerns, especially among infants or children. Metagenomic next-generation sequencing (mNGS) has greatly advanced our understanding of the viruses responsible for these diseases. However, the detection rate of the aetiology remains low. We conducted RNA sequencing and virome analysis on cerebrospinal fluid (CSF) and serum samples commonly used in the clinical diagnosis to detect viral pathogens. In total, 226 paired CSF and serum samples from 113 children with encephalitis and meningitis were enrolled. The results showed that the diversity of viruses was higher in CSF, with a total of 12 viral taxa detected, including one case each of herpesvirus, coronavirus and enterovirus, and six cases of adenovirus related to human diseases. In contrast, the Anelloviridae was the most abundant viral family detected in serum, and only a few samples contained human viral pathogens, including one case of enterovirus and two cases of adenovirus. The detection rate for human viral pathogens increases to 10.6 %(12/113) when both types of samples are used simultaneously, compared to CSF along 7.9 % (9/113) or serum alone 2.6 % (3/113). However, we did not detect these viruses simultaneously in paired samples from the same case. These results suggest that CSF samples still have irreplaceable advantages for using mNGS to detect viruses in patients with meningitis and encephalitis, and serum can supplement to improve the detection rate of viral encephalitis and meningitis. The findings of this study could help improve the etiological diagnosis, clinical management and prognosis of patients with meningitis and encephalitis in children.

Pyrosulfite-Involved Synthesis of Sulfides by Palladium-Catalyzed Decarboxylative Couplings.

The decarboxylative coupling using carboxylic acid and potassium metabisulfite, promoted by a palladium catalyst, is reported for the generation of sulfides. The coupling is performed using the easily available carboxylic acid and environmentally friendly inorganic sulfides as a divalent inorganic sulfur source. Not only aromatic acids but also aliphatic carboxylic acids are workable during the couplings. The method is applicable and practical to a scope of 20 examples and drug molecules.

Impact of deeper groundwater depth on vegetation and soil in semi-arid region of eastern China.

Introduction: Understanding the impact of deep groundwater depth on vegetation communities and soil in sand dunes with different underground water tables is essential for ecological restoration and the conservation of groundwater. Furthermore, this understanding is critical for determining the threshold value of groundwater depth that ensures the survival of vegetation. Method: This paper was conducted in a semi-arid region in eastern China, and the effects of deep groundwater depth (6.25 m, 10.61 m, and 15.26 m) on vegetation communities and soil properties (0-200 cm) across three dune types (mobile, semi-fixed, and fixed dunes) were evaluated in a sand ecosystem in the Horqin Sandy Land. Results: For vegetation community, variations in the same species are more significant at different groundwater depths. For soil properties, groundwater depth negatively influences soil moisture, total carbon, total nitrogen, available nitrogen, available phosphorus concentrations, and soil pH. Besides, groundwater depth also significantly affected organic carbon and available potassium concentrations. In addition, herb species were mainly distributed in areas with lower groundwater depth, yet arbor and shrub species were sparsely distributed in places with deeper groundwater depth. Discussion: As arbor and shrub species are key drivers of ecosystem sustainability, the adaptation of these dominant species to increasing groundwater depth may alleviate the negative effects of increasing groundwater depth; however, restrictions on this adaptation were exceeded at deeper groundwater depth.

[Response of Soil Microbial Diversity to Long-term Enclosure in Degraded Patches of Alpine Meadow in the Source Zone of the Yellow River].

The soil pH, water content, nutrients, and microbial community composition and diversity among one-year term (E1), short-term (E4), and long-term (E10) enclosures were analyzed for understanding the response of soil bacterial and fungal communities to long-term enclosure in degraded patches of alpine meadow in the source zone of the Yellow River, through determining the soil physicochemical properties and microbial diversity using high-throughput sequencing technology. The results showed that the E1 enclosure significantly decreased soil pH, whereas long-term and short-term enclosures increased soil pH. The long-term enclosure could significantly increase soil water content and total nitrogen content, and the short-term enclosure could significantly increase available phosphorus content. The long-term enclosure could significantly increase the bacterial Proteobacteria. The short-term enclosure could significantly increase the abundance of the bacteria Acidobacteriota. However, the abundance of the fungus Basidiomycota decreased in both long-term and short-term enclosures. With the extension of enclosure years, the Chao1 index and Shannon diversity index of bacteria showed an increasing trend, but there was no significant difference between long-term and short-term enclosures. The Chao1 index of fungi gradually increased, and the Shannon diversity index first increased and then decreased, but there was no significant difference between long-term and short-term enclosures. Redundancy analysis indicated that enclosure altered microbial community composition and structure mainly by changing soil pH and water content. Therefore, the E4 short-term enclosure could significantly improve the soil physicochemical properties and microbial diversity at the degraded patches of alpine meadow. The long-term enclosure is not necessary and will lead to the waste of grassland resources, reduction in biodiversity, and restriction of wildlife activities.

Predictive value of hyperglycemia on infection in critically ill patients with acute pancreatitis.

To analyze the predictive value of hyperglycemia on the extrapancreatic infection (EPI) and infected pancreatic necrosis (IPN) of severe patients with acute pancreatitis (AP). We enrolled 234 patients with acute pancreatitis admitted to the intensive care unit (ICU) of the Second Affiliated Hospital of Nanchang University from July 2017 to July 2022 for a retrospective cohort study. We collected maximum blood glucose values three times after admission to the ICU within 120 h (Glu1: 0-24 h, Glu2: 24-48 h, Glu3: 48-120 h), the levels of leucocyte, blood urea nitrogen (BUN), C-reactive protein (CRP), procalcitonin (PCT), and albumin within 24 h after admission to the ICU, and the BISAP and SIRS scores of all patients within 24 h. EPI was taken as the primary outcome indicator and IPN as the secondary outcome indicator. The accuracy of blood glucose values in predicting acute pancreatitis infection was measured by the area under the curve (AUC). A total of 56 patients appeared EPI. Univariate analysis showed that Glu3 was associated with IPN in critically ill patients with AP. Multivariate logistic regression analysis showed that Glu2, Glu3, and SIRS > 48 h were associated with EPI in critically ill patients with AP. The AUCs of Glu2 and Glu3 to predict EPI were 0.805(95%CI: 0.717-0.892) and 0.782(95%CI: 0.685-0.878), respectively, and the cutoff values were 12.60 mmol/L and 14.75 mmol/L, respectively. The AUC of Glu2 combined with Glu3 to predict EPI was 0.812(0.725-0.899). The maximum blood glucose on Day2-5 after admission to the ICU can predict infection in critically ill patients with AP. There are differences in etiology while glucose predicting infection. Patients with hypertriglyceridemia AP need to intervene blood glucose levels more actively and earlier, and control it more strictly.

Multifaceted role of ferroptosis in cardiovascular disease.

Ferroptosis is a newly identified form of non-apoptotic cell death characterised primarily by iron-dependent lipid peroxidation. It differs morphologically, biochemically, and genetically from other forms of cell death, such as apoptosis, autophagy, and necrosis. Although the molecular mechanism underlying ferroptosis remains unclear, multiple biological processes, such as iron metabolism, lipid peroxides, and systems, such as the glutathione system and the tetrahydrobiopterin/coenzyme Q10 system, appear to be involved. While the contribution of ferroptotic mechanisms to human diseases is not clear, recent studies have identified a number of ferroptosis-related genes. Cardiovascular diseases are the main cause of death globally. In this review, we outline the progress regarding the emerging role of ferroptosis in the pathogenesis of cardiac pathophysiological conditions and the association of ferroptosis with cardiomyopathy, myocardial ischemia-reperfusion injury, heart failure, and atherosclerosis. We further summarise newly discovered ferroptotic targets for the development of therapies for cardiovascular diseases. Finally, we discuss the current challenges and future research directions in cardiovascular disease treatments.

Hepatocyte-specific TMEM16A deficiency alleviates hepatic ischemia/reperfusion injury via suppressing GPX4-mediated ferroptosis.

Ischemia/reperfusion (I/R)-induced liver injury with severe cell death is a major complication of liver transplantation. Transmembrane member 16A (TMEM16A), a component of hepatocyte Ca2+-activated chloride channel, has been implicated in a variety of liver diseases. However, its role in hepatic I/R injury remains unknown. Here, mice with hepatocyte-specific TMEM16A knockout or overexpression were generated to examine the effect of TMEM16A on hepatic I/R injury. TMEM16A expression increased in liver samples from patients and mice with I/R injury, which was correlated with liver damage progression. Hepatocyte-specific TMEM16A knockout alleviated I/R-induced liver damage in mice, ameliorating inflammation and ferroptotic cell death. However, mice with hepatic TMEM16A overexpression showed the opposite phenotype. In addition, TMEM16A ablation decreased inflammatory responses and ferroptosis in hepatocytes upon hypoxia/reoxygenation insult in vitro, whereas TMEM16A overexpression promoted the opposite effects. The ameliorating effects of TMEM16A knockout on hepatocyte inflammation and cell death were abolished by chemically induced ferroptosis, whereas chemical inhibition of ferroptosis reversed the potentiated role of TMEM16A in hepatocyte injury. Mechanistically, TMEM16A interacted with glutathione peroxidase 4 (GPX4) to induce its ubiquitination and degradation, thereby enhancing ferroptosis. Disruption of TMEM16A-GPX4 interaction abrogated the effects of TMEM16A on GPX4 ubiquitination, ferroptosis, and hepatic I/R injury. Our results demonstrate that TMEM16A exacerbates hepatic I/R injury by promoting GPX4-dependent ferroptosis. TMEM16A-GPX4 interaction and GPX4 ubiquitination are therefore indispensable for TMEM16A-regulated hepatic I/R injury, suggesting that blockades of TMEM16A-GPX4 interaction or TMEM16A inhibition in hepatocytes may represent promising therapeutic strategies for acute liver injury.

[Effect of Nitrogen Addition on Soil Fungal Diversity in a Degraded Alpine Meadow at Different Slopes].

This study proposed nitrogen addition experiments to analyze the effects of exogenous nitrogen addition on soil fungal diversity in alpine meadow. All the experiments were performed in degraded alpine meadow with two different slopes (gentle slope and steep slope) in Guoluo Prefecture of the Sanjiangyuan Region, and the sequence and analysis of ITS of soil fungi were performed using MiSeq PE250 sequencing technology. Comparative analysis was carried out with three nitrogen addition levels on soil fungal diversity in degraded grassland with different slopes, which included low nitrogen (LN, 2 g·m-2), middle nitrogen (MN, 5 g·m-2), and high nitrogen (HN, 10 g·m-2). The results showed that:① the distribution groups of fungi in the soil were Ascomycota, Basidiomycota, Mortierellomycota, and Glomomycota, and the dominant bacteria was Ascomycota. ② The dominant genera were Mortierella and Archaeorhizomyces, and there were no differences in response to different slopes and nitrogen addition levels. ③ A total of 95 genera (Gibberellum, Preussia, etc.) were identified and significantly differed between two different slopes (P<0.05). ④ Bacteria with a relative abundance less than 1% had significant differences in nitrogen addition at different levels on the same slope (P<0.05). 5 In addition, the analyses of α and ß diversities showed that soil fungal community structure was stable under different slopes and nitrogen addition levels. Exogenous nitrogen supplementation significantly improved the relative abundance of non-dominant fungal communities without destroying soil fungal community structure.