Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Relationship between Vitamin D Concentration and Lipid Concentration in Patients with NAFLD in the Hulunbuir Region of China.

BACKGROUND: We aimed to characterize the relationship between the serum 25-hydroxyvitamin D concentration and the circulating lipid concentrations of patients with NAFLD in the Hulunbuir region of China. METHODS: One hundred fifty-six patients, who were diagnosed with NAFLD in the Physical Examination Department of the Second Clinical College of Inner Mongolia University for the Nationalities between January 2021 and March 2023, were recruited as NAFLD group, and 160 healthy people were recruited as a control group during the same period. The serum 25(OH)VitD, TBIL, TG, TC, LDL-C, HDL-C, AST, ALT, GGT, and FPG activities of the participants were measured, and hepatic ultrasonography was performed. RESULTS: The BMI of the NAFLD group was higher than of the control group (p < 0.05). The serum 25(OH)VitD3 (p < 0.05) and the HDL-C concentrations of the NAFLD group were lower than those of the normal control group. However, the AST (p < 0.05), ALT (p < 0.05), and GGT (p < 0.05) activities, and the serum TG (p < 0.05), TC (p < 0.05), LDL-C (p < 0.05), and the fasting glucose (p < 0.05) concentrations of the NAFLD group were higher than those of the normal control group. The serum 25(OH)VitD3 concentrations of the NAFLD group significantly cor-related negatively with BMI (r = -0.302, p < 0.01), TG (r = -0.221, p < 0.05), and fasting glucose (r = -0.236, p < 0.05). The BMI, TG, and fasting glucose of vitamin D-deficient participants were higher than of the participants with adequate or insufficient levels of vitamin D (p < 0.05). Finally, the BMI of vitamin D-deficient participants was higher than of those with an adequate vitamin D status (p < 0.05). CONCLUSIONS: A deficiency of 25(OH)VitD is more common in people from the Hulunbuir region of China than elsewhere. In addition, the vitamin D status is significantly associated with NAFLD; as the serum vitamin D concentration decreases, patients with NAFLD show greater dyslipidemia and hyperglycemia and a higher BMI.

Exosomes derived from cord blood Treg cells promote diabetic wound healing by targeting monocytes.

Chronic nonhealing diabetic wounds are a critical clinical challenge. Regulatory T cells (Tregs) are immunosuppressive modulators affecting wound healing progression by controlling the inflammatory response. The current study attempted to investigate whether the exosomes derived from cord blood (CB) Tregs can accelerate the healing process. Exosomes were isolated from CB-Treg cultures using ultracentrifugation and validated with different specific markers of exosomes. The purified CB-Treg-derived exosomes were co-cultured with peripheral blood mononuclear cells (PBMCs) and CD14+ monocytes. The migration-promoting effect of CB-Treg-derived exosomes on fibroblasts and endothelial cells was investigated. We used thermosensitive Pluronic F-127 hydrogel (PF-127) loaded with CB-Treg-derived exosomes in a diabetic wound healing mouse model. CB-Treg-derived exosomes with 30-120 nm diameters revealed exosome-specific markers, such as TSG101, Alix, and CD63. CB-Treg-derived exosomes were mainly bound to the monocytes when co-cultured with PBMCs, and promoted monocyte polarization to the anti-inflammatory phenotype (M2) in vitro. CB-Treg-derived exosomes enhanced the migration of endothelial cells and fibroblasts. Furthermore, CB-Treg-derived exosomes treatment accelerated wound healing by downregulating inflammatory factor levels and upregulating the M2 macrophage ratio in vivo. Our findings indicated that CB-Treg-derived exosomes could be a promising cell-free therapeutic strategy for diabetic wound healing, partly by targeting monocytes.

Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

Identification of formation mechanism and key elements of quality geriatric care behavior of nursing assistants in nursing homes: a grounded theory study.

Objectives: This study aimed to identify the key elements and develop a formation mechanism model of quality geriatric care behavior for nursing assistants. Methods: This qualitative research employed the strategy of grounded theory proposed by Strauss and Corbin. Furthermore, the data was collected by participatory observation and semi-structured interviews. A total of 12 nursing managers, 63 nursing assistants, and 36 older people from 9 nursing homes in 6 cities were interviewed, whereas for the observatory survey, participants were recruited from 2 nursing homes. Results: The comparative and analysis process revealed 5 key elements of quality geriatric care behavior, including holistic care, personalized care, respect, positive interaction, and empowerment. Based on the Capability-Opportunity-Motivation-Behavior (COM-B) model, key elements and the 3 stages of quality geriatric care behavior (negative behavior cognition stage, practice exchange run-in stage, and positive behavior reinforcement stage), the theoretical framework of the formation mechanism was established. Conclusion: The results indicated that nursing assistants' capabilities, motivation, and organizational and environmental support are vital for quality care behaviors. The theoretical framework established in this study provides theoretical support and practical reference to policymakers, institutional administrators, and healthcare professionals for improving nursing assistant's care behaviors.

Role of mitophagy in pulmonary hypertension: Targeting the mechanism and pharmacological intervention.

Mitophagy, a crucial pathway in eukaryotic cells, selectively eliminates dysfunctional mitochondria, thereby maintaining cellular homeostasis via mitochondrial quality control. Pulmonary hypertension (PH) refers to a pathological condition where pulmonary arterial pressure is abnormally elevated due to various reasons, and the underlying pathogenesis remains elusive. This article examines the molecular mechanisms underlying mitophagy, emphasizing its role in PH and the progress in elucidating related molecular signaling pathways. Additionally, it highlights current drug regulatory pathways, aiming to provide novel insights into the prevention and treatment of pulmonary hypertension.

Lnc PVT1 facilitates TGF-ß1-induced human cardiac fibroblast activation in vitro and ISO-induced myocardial fibrosis in vivo through regulating MYC.

Cardiac fibrosis is a commonly seen pathophysiological process in various cardiovascular disorders, such as coronary heart disorder, hypertension, and cardiomyopathy. Cardiac fibroblast trans-differentiation into myofibroblasts (MFs) is a key link in myocardial fibrosis. LncRNA PVT1 participates in fibrotic diseases in multiple organs; however, its role and mechanism in cardiac fibrosis remain largely unknown. Human cardiac fibroblasts (HCFs) were stimulated with TGF-ß1 to induce myofibroblast; Immunofluorescent staining, Immunoblotting, and fluorescence in situ hybridization were used to detect the myofibroblasts phenotypes and lnc PVT1 expression. Cell biological phenotypes induced by lnc PVT1 knockdown or overexpression were detected by CCK-8, flow cytometry, and Immunoblotting. A mouse model of myocardial fibrosis was induced using isoproterenol (ISO), and the cardiac functions were examined by echocardiography measurements, cardiac tissues by H&E, and Masson trichrome staining. In this study, TGF-ß1 induced HCF transformation into myofibroblasts, as manifested as significantly increased levels of α-SMA, vimentin, collagen I, and collagen III; the expression level of lnc PVT1 expression showed to be significantly increased by TGF-ß1 stimulation. The protein levels of TGF-ß1, TGFBR1, and TGFBR2 were also decreased by lnc PVT1 knockdown. Under TGF-ß1 stimulation, lnc PVT1 knockdown decreased FN1, α-SMA, collagen I, and collagen III protein contents, inhibited HCF cell viability and enhanced cell apoptosis, and inhibited Smad2/3 phosphorylation. Lnc PVT1 positively regulated MYC expression with or without TGF-ß1 stimulation; MYC overexpression in TGF-ß1-stimulated HCFs significantly attenuated the effects of lnc PVT1 knockdown on HCF proliferation and trans-differentiation to MFs. In the ISO-induced myocardial fibrosis model, lnc PVT1 knockdown partially reduced fibrotic area, improved cardiac functions, and decreased the levels of fibrotic markers. In addition, lnc PVT1 knockdown decreased MYC and CDK4 levels but increased E-cadherin in mice heart tissues. lnc PVT1 is up-regulated in cardiac fibrosis and TGF-ß1-stimulated HCFs. Lnc PVT1 knockdown partially ameliorates TGF-ß1-induced HCF activation and trans-differentiation into MFs in vitro and ISO-induced myocardial fibrosis in vivo, potentially through interacting with MYC and up-regulating MYC.

Identification of candidate genes controlling cold tolerance at the early seedling stage from Dongxiang wild rice by QTL mapping, BSA-Seq and RNA-Seq.

BACKGROUND: The cold tolerance of rice is closely related to its production and geographic distribution. The identification of cold tolerance-related genes is of important significance for developing cold-tolerant rice. Dongxiang wild rice (Oryza rufipogon Griff.) (DXWR) is well-adapted to the cold climate of northernmost-latitude habitats ever found in the world, and is one of the most valuable rice germplasms for cold tolerance improvement. RESULTS: Transcriptome analysis revealed genes differentially expressed between Xieqingzao B (XB; a cold sensitive variety) and 19H19 (derived from an interspecific cross between DXWR and XB) in the room temperature (RT), low temperature (LT), and recovery treatments. The results demonstrated that chloroplast genes might be involved in the regulation of cold tolerance in rice. A high-resolution SNP genetic map was constructed using 120 BC5F2 lines derived from a cross between 19H19 and XB based on the genotyping-by-sequencing (GBS) technique. Two quantitative trait loci (QTLs) for cold tolerance at the early seedling stage (CTS), qCTS12 and qCTS8, were detected. Moreover, a total of 112 candidate genes associated with cold tolerance were identified based on bulked segregant analysis sequencing (BSA-seq). These candidate genes were divided into eight functional categories, and the expression trend of candidate genes related to 'oxidation-reduction process' and 'response to stress' differed between XB and 19H19 in the RT, LT and recovery treatments. Among these candidate genes, the expression level of LOC_Os12g18729 in 19H19 (related to 'response to stress') decreased in the LT treatment but restored and enhanced during the recovery treatment whereas the expression level of LOC_Os12g18729 in XB declined during recovery treatment. Additionally, XB contained a 42-bp deletion in the third exon of LOC_Os12g18729, and the genotype of BC5F2 individuals with a survival percentage (SP) lower than 15% was consistent with that of XB. Weighted gene coexpression network analysis (WGCNA) and modular regulatory network learning with per gene information (MERLIN) algorithm revealed a gene interaction/coexpression network regulating cold tolerance in rice. In the network, differentially expressed genes (DEGs) related to 'oxidation-reduction process', 'response to stress' and 'protein phosphorylation' interacted with LOC_Os12g18729. Moreover, the knockout mutant of LOC_Os12g18729 decreased cold tolerance in early rice seedling stage signifcantly compared with that of wild type. CONCLUSIONS: In general, study of the genetic basis of cold tolerance of rice is important for the development of cold-tolerant rice varieties. In the present study, QTL mapping, BSA-seq and RNA-seq were integrated to identify two CTS QTLs qCTS8 and qCTS12. Furthermore, qRT-PCR, genotype sequencing and knockout analysis indicated that LOC_Os12g18729 could be the candidate gene of qCTS12. These results are expected to further exploration of the genetic mechanism of CTS in rice and improve cold tolerance of cultivated rice by introducing the cold tolerant genes from DXWR through marker-assisted selection.

Nucleus Accumbens Corticotropin-Releasing Hormone Neurons Projecting to the Bed Nucleus of the Stria Terminalis Promote Wakefulness and Positive Affective State.

The nucleus accumbens (NAc) plays an important role in various emotional and motivational behaviors that rely on heightened wakefulness. However, the neural mechanisms underlying the relationship between arousal and emotion regulation in NAc remain unclear. Here, we investigated the roles of a specific subset of inhibitory corticotropin-releasing hormone neurons in the NAc (NAcCRH) in regulating arousal and emotional behaviors in mice. We found an increased activity of NAcCRH neurons during wakefulness and rewarding stimulation. Activation of NAcCRH neurons converts NREM or REM sleep to wakefulness, while inhibition of these neurons attenuates wakefulness. Remarkably, activation of NAcCRH neurons induces a place preference response (PPR) and decreased basal anxiety level, whereas their inactivation induces a place aversion response and anxious state. NAcCRH neurons are identified as the major NAc projection neurons to the bed nucleus of the stria terminalis (BNST). Furthermore, activation of the NAcCRH-BNST pathway similarly induced wakefulness and positive emotional behaviors. Taken together, we identified a basal forebrain CRH pathway that promotes the arousal associated with positive affective states.

Exosomal LncRNAs and CircRNAs in lung cancer: Emerging regulators and potential therapeutic targets.

Lung cancer remains one of the most prevalent and lethal malignancies globally, characterized by high incidence and mortality rates among all cancers. The delayed diagnosis of lung cancer at intermediate to advanced stages frequently leads to suboptimal treatment outcomes. To improve the management of this disease, it is imperative to identify new, highly sensitive prognostic and diagnostic biomarkers. Exosomes, extracellular vesicles with a lipid-bilayer structure and a size range of 30-150 nm, are pivotal in intercellular communication and play significant roles in lung cancer progression. Non-coding RNAs (ncRNAs), including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), are highly prevalent within exosomes and play a crucial role in various pathophysiological processes mediated by these extracellular vesicles. Beyond their established functions in miRNA and protein sequestration, these ncRNAs are involved in regulating translation and interactions within exosomes. Numerous studies have highlighted the importance of exosomal lncRNAs and circRNAs in influencing epithelial-mesenchymal transition (EMT), angiogenesis, proliferation, invasion, migration, and metastasis in lung cancer. Due to their unique functional characteristics, these molecules are promising therapeutic targets and biomarkers for diagnosis and prognosis. This review provides a succinct summary of the formation of exosomal lncRNAs and circRNAs, clarifies their biological roles, and thoroughly explains the mechanisms by which they participate in the progression of lung cancer. Finally, we discuss the potential clinical applications and challenges associated with exosomal lncRNAs and circRNAs in lung cancer.

Association of hydration status and in-hospital mortality in critically ill patients with ischemic stroke: Data from the MIMIC-IV database.

BACKGROUND: Hydration plays a critical role in the pathophysiological progression of ischemic stroke. However, the impact of extreme hydration on the mortality of critically ill patients with ischemic stroke remains unclear. Therefore, our objective was to evaluate the association between hydration, as indicated by the blood urea nitrogen to creatinine ratio (UCR), and in-hospital mortality in critically ill patients with ischemic stroke. METHODS: Data from the Medical Information Mart for Intensive Care (MIMIC-IV) database were utilized. Patients with ischemic stroke admitted to the Intensive Care Unit (ICU) for the first time were identified. The exposure variable was the hydration state represented by the UCR. The study outcome measure was in-hospital mortality. The primary analytical approach involved multivariate Cox regression analysis. Kaplan-Meier curves were constructed, and subgroup analyses with interaction were performed. RESULTS: A total of 1539 patients, with a mean age of 69.9 years, were included in the study. Kaplan-Meier curves illustrated that patients in higher UCR tertiles exhibited increased in-hospital mortality. Accordingly, the risk of in-hospital mortality significantly rose by 29 % with every 10 units increase in UCR. Subgroup analysis indicated a robust association between UCR and in-hospital mortality in each subgroup, with no statistically significant interactions observed. CONCLUSION: Hydration status is significantly associated with in-hospital all-cause mortality in critically ill patients with ischemic stroke. This finding underscores the importance of closely monitoring critically ill patients for adequate hydration and implementing appropriate rehydration strategies.

A metabolic atlas of blood cells in young and aged mice identifies uridine as a metabolite to rejuvenate aged hematopoietic stem cells.

Aging of hematopoietic stem cells (HSCs) is accompanied by impaired self-renewal ability, myeloid skewing, immunodeficiencies and increased susceptibility to malignancies. Although previous studies highlighted the pivotal roles of individual metabolites in hematopoiesis, comprehensive and high-resolution metabolomic profiles of different hematopoietic cells across ages are still lacking. In this study, we created a metabolome atlas of different blood cells across ages in mice. We reveal here that purine, pyrimidine and retinol metabolism are enriched in young hematopoietic stem and progenitor cells (HSPCs), whereas glutamate and sphingolipid metabolism are concentrated in aged HSPCs. Through metabolic screening, we identified uridine as a potential regulator to rejuvenate aged HSPCs. Mechanistically, uridine treatment upregulates the FoxO signaling pathway and enhances self-renewal while suppressing inflammation in aged HSCs. Finally, we constructed an open-source platform for public easy access and metabolomic analysis in blood cells. Collectively, we provide a resource for metabolic studies in hematopoiesis that can contribute to future anti-aging metabolite screening.

Kiwifruit-Agaricus blazei intercropping effectively improved yield productivity, nutrient uptake, and rhizospheric bacterial community.

Intercropping systems have garnered attention as a sustainable agricultural approach for efficient land use, increased ecological diversity in farmland, and enhanced crop yields. This study examined the effect of intercropping on the kiwifruit rhizosphere to gain a deeper understanding of the relationships between cover plants and kiwifruit in this sustainable agricultural system. Soil physicochemical properties and bacterial communities were analyzed using the Kiwifruit-Agaricus blazei intercropping System. Moreover, a combined analysis of 16S rRNA gene sequencing and metabolomic sequencing was used to identify differential microbes and metabolites in the rhizosphere. Intercropping led to an increase in soil physicochemical and enzyme activity, as well as re-shaping the bacterial community and increasing microbial diversity. Proteobacteria, Bacteroidota, Myxococcota, and Patescibacteria were the most abundant and diverse phyla in the intercropping system. Expression analysis further revealed that the bacterial genera BIrii41, Acidibacter, and Altererythrobacter were significantly upregulated in the intercropping system. Moreover, 358 differential metabolites (DMs) were identified between the monocropping and intercropping cultivation patterns, with fatty acyls, carboxylic acids and derivatives, and organooxygen compounds being significantly upregulated in the intercropping system. The KEGG metabolic pathways further revealed considerable enrichment of DMs in ABC transporters, histidine metabolism, and pyrimidine metabolism. This study identified a significant correlation between 95 bacterial genera and 79 soil metabolites, and an interactive network was constructed to explore the relationships between these differential microbes and metabolites in the rhizosphere. This study demonstrated that Kiwifruit-Agaricus blazei intercropping can be an effective, labor-saving, economic, and sustainable practice for reshaping bacterial communities and promoting the accumulation and metabolism of beneficial microorganisms in the rhizosphere.

Identification of novel dual-target 4-hydroxyphenylpyruvate dioxygenase & phytoene dehydrogenase inhibitors via multiple virtual screening.

Two important plant enzymes are 4-hydroxyphenylpyruvate dioxygenase (HPPD; EC 1.13.11.27), which is necessary for biosynthesis of plastoquinone and tocopherols, and phytoene dehydrogenase (PDS; EC 1.3.99.26), which plays an important role in colour rendering. Dual-target proteins that inhibit pigment synthesis will prevent resistant weeds and improve the spectral characteristics of herbicides. This study introduces virtual screening of pharmacophores based on the complex structure of the two targets. A three-dimensional database was established by screening 1,492,858 compounds based on the Lipinski principle. HPPD&PDS dual-target receptor-ligand pharmacophore models were then constructed, and nine potential dual-target inhibitors were obtained through pharmacophore modeling, molecular docking, and molecular dynamics simulations. Ultimately, ADMET prediction software yielded three compounds with high potential as dual-target herbicides. The obtained nine inhibitors were stable when combined with both HPPD and PDS proteins. This study offers guidance for the development of HPPD&PDS dual-target inhibitors with novel skeletons.

Ultrahigh proton conductivity of four ionic hydrogen-bonded organic frameworks based on functionalized terephthalates.

Recently, the utilization of hydrogen-bonded organic frameworks (HOFs) with high crystallinity and inherent well-defined H-bonding networks in the field of proton conduction has received increasing attention, but obtaining HOFs with excellent water stability and prominent proton conductivity (σ) remains challenging. Herein, by employing functionalized terephthalic acids, 2,5-dihydroxyterephthalic acid, 2-hydroxyterephthalic acid, 2-nitro terephthalic acid, and terephthalic acid, respectively, four highly water-stable ionic HOFs (iHOFs), [(C8H5O6)(Me2NH2)]∙2H2O (iHOF 1), [(C8H5O5)(Me2NH2)] (iHOF 2), [(C8H4NO6)(Me2NH2)] (iHOF 3) and [(C8H5O4)(Me2NH2)] (iHOF 4) were efficiently prepared by a straightforward synthesis approach in DMF and H2O solutions. The alternating-current (AC) impedance testing in humid conditions revealed that all four iHOFs were temperature- and humidity-dependent σ, with the greatest value reaching 10-2 S·cm-1. As expected, the high density of free carboxylic acid groups, crystallization water, and protonated [Me2NH2]+ units offer adequate protons and hydrophilic environments for effective proton transport. Furthermore, the σ values of these iHOFs with different functional groups were compared. It was discovered that it dropped in the following order under 100 °C and 98 % relative humidity (RH): σ iHOF 1 (1.72 × 10-2 S·cm-1) > σ iHOF 2 (4.03 × 10-3 S·cm-1) > σ iHOF 3 (1.46 × 10-3 S·cm-1) > σ iHOF 4 (4.86 × 10-4 S·cm-1). Finally, we investigated the causes of the above differences and the proton transport mechanism inside the framework using crystal structure data, water contact angle tests, and activation energy values. This study provides new motivation to develop highly proton-conductive materials.

Photothermal Iron-Based Riboflavin Microneedles for the Treatment of Bacterial Keratitis via Ion Therapy and Immunomodulation.

Bacterial biofilm formation protects bacteria from antibiotics and the immune system, excessive inflammation further complicates treatment. Here, iron-based metal-organic framework (MIL-101)-loaded riboflavin nanoparticles are designed for the therapeutic challenge of biofilm infection and hyperinflammation in bacterial keratitis. Specifically, MIL-101 produces a thermal effect under exogenous near-infrared light irradiation, which synergizes with ferroptosis-like bacterial death induced by iron ions to exert an effective biofilm infection eradication effect. On the other hand, the disintegration of MIL-101 sustains the release of riboflavin, which inhibits the pro-inflammatory response of macrophage over-activation by modulating their phenotypic switch. In addition, to solve the problems of short residence time, poor permeability, and low bioavailability of corneal medication, the MR@MN microneedle patch is further prepared by loading nanoparticles into SilMA hydrogel, which ultimately achieves painless, transepithelial, and highly efficient drug delivery. In vivo and ex vivo experiments demonstrate the effectiveness of this approach in eliminating bacterial infection and promoting corneal healing. Therefore, the MRMN patch, acting as an ocular drug delivery system with the ability of rapid corneal healing, promises a cost-effective solution for the treatment of bacterial keratitis, which may also lead to a new approach for treating bacterial keratitis in clinics.

Geomagnetic Disturbances and Pulse Amplitude Anomalies Preceding M > 6 Earthquakes from 2021 to 2022 in Sichuan-Yunnan, China.

Compelling evidence has shown that geomagnetic disturbances in vertical intensity polarization before great earthquakes are promising precursors across diverse rupture conditions. However, the geomagnetic vertical intensity polarization method uses the spectrum of smooth signals, and the anomalous waveforms of seismic electromagnetic radiation, which are basically nonstationary, have not been adequately considered. By combining pulse amplitude analysis and an experimental study of the cumulative frequency of anomalies, we found that the pulse amplitudes before the 2022 Luding M6.8 earthquake show characteristics of multiple synchronous anomalies, with the highest (or higher) values occurring during the analyzed period. Similar synchronous anomalies were observed before the 2021 Yangbi M6.4 earthquake, the 2022 Lushan M6.1 earthquake and the 2022 Malcolm M6.0 earthquake, and these anomalies indicate migration from the periphery toward the epicenters over time. The synchronous changes are in line with the recognition of previous geomagnetic anomalies with characteristics of high values before an earthquake and gradual recovery after the earthquake. Our study suggests that the pulse amplitude is effective for extracting anomalies in geomagnetic vertical intensity polarization, especially in the presence of nonstationary signals when utilizing observations from multiple station arrays. Our findings highlight the importance of incorporating pulse amplitude analysis into earthquake prediction research on geomagnetic disturbances.

Low Remnant Cholesterol and In-Hospital Bleeding Risk After Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: Bleeding risk brought by intensive lipid-lowering therapy and low low-density lipoprotein cholesterol is concerning, while evidence regarding the relationship between remnant cholesterol and bleeding is frightening. This study aimed to investigate the association between remnant cholesterol at admission and an in-hospital bleeding event after acute ischemic stroke or transient ischemic attack (TIA). METHODS AND RESULTS: A total of 3222 eligible patients admitted to Shanghai Huashan Hospital between 2015 and 2021 with complete lipid data were analyzed. Patients were classified into low (<20.0 mg/dL), moderate (20.0-29.9 mg/dL), and high (≥30 mg/dL) groups by remnant cholesterol. The mean age of patients was 63.0± 13.1 years, including 2301 (71.4%) men and 651 (20.2%) with TIA. The median (interquartile range) of remnant cholesterol was 18.6 (13.5-25.9) mg/dL. After adjustment for confounding variables, patients with low remnant cholesterol had a higher risk of bleeding events (odds ratio, 2.56 [95% CI, 1.12-6.67]) than those with moderate remnant cholesterol. The high remnant cholesterol group was not significantly associated with bleeding risk. Combined assessment of low-density lipoprotein cholesterol and remnant cholesterol further identified patients with the highest risk of bleeding events. CONCLUSIONS: Low remnant cholesterol levels were associated with bleeding events during the acute stage of ischemic stroke and TIA. The assessment of remnant cholesterol could inform the bleeding risk during hospitalization both for patients and physicians in clinical practice.

A high-quality chromosome-level genome assembly of the endangered tree Kmeria septentrionalis.

Kmeria septentrionalis is a critically endangered tree endemic to Guangxi, China, and is listed on the International Union for Conservation of Nature's Red List. The lack of genetic information and high-quality genome data has hindered conservation efforts and studies on this species. In this study, we present a chromosome-level genome assembly of K. septentrionalis. The genome was initially assembled to be 2.57 Gb, with a contig N50 of 11.93 Mb. Hi-C guided genome assembly allowed us to anchor 98.83% of the total length of the initial contigs onto 19 pseudochromosomes, resulting in a scaffold N50 of 135.08 Mb. The final chromosome-level genome, spaning 2.54 Gb, achieved a BUSCO completeness of 98.9% and contained 1.67 Gb repetitive elements and 35,927 coding genes. This high-quality genome assembly provides a valuable resource for understanding the genetic basis of conservation-related traits and biological properties of this endangered tree species. Furthermore, it lays a critical foundation for evolutionary studies within the Magnoliaceae family.

Physiological Mechanisms by Which the Functional Ingredients in Beer Impact Human Health.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.