MRI-based axis-referenced morphometric model corresponding to lamellar organization for assessing hippocampal atrophy in dementia.

Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an "axis-referenced coordinate system" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer's disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.

Luteolin enhances drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in paclitaxel­resistant esophageal squamous cell carcinoma.

Drug resistance is a key factor underlying the failure of tumor chemotherapy. It enhances the stem­like cell properties of cancer cells, tumor metastasis and relapse. Luteolin is a natural flavonoid with strong anti­tumor effects. However, the mechanism(s) by which luteolin protects against paclitaxel (PTX)­resistant cancer cell remains to be elucidated. The inhibitory effect of luteolin on the proliferation of EC1/PTX and EC1 cells was detected by cell counting kit­8 assay. Colony formation and flow cytometry assays were used to assess clonogenic capacity, cell cycle and apoptosis. Wound healing and Transwell invasion tests were used to investigate the effects of luteolin on the migration and invasion of EC1/PTX cells. Western blotting was used to detect the protein levels of EMT­related proteins and stem cell markers after sphere formation. Parental cells and drug­resistant cells were screened by high­throughput sequencing to detect the differential expression of RNA and differential genes. ELISA and western blotting were used to verify the screened PI3K/Akt signaling pathway, key proteins of which were explored by molecular docking. Hematoxylin and eosin staining and TUNEL staining were used to observe tumor xenografts on morphology and apoptosis in nude mice. The present study found that luteolin inhibited tumor resistance (inhibited proliferation, induced cell cycle arrest and apoptosis and hindered migration invasion, EMT and stem cell spherification) in vitro in PTX­resistant esophageal squamous cell carcinoma (ESCC) cells. In addition, luteolin enhanced drug sensitivity and promoted the apoptosis of drug­resistant ESCC cells in combination with PTX. Mechanistically, luteolin may inhibit the PI3K/AKT signaling pathway by binding to the active sites of focal adhesion kinase (FAK), Src and AKT. Notably, luteolin lowered the tumorigenic potential of PTX­resistant ESCC cells but did not show significant toxicity in vivo. Luteolin enhanced drug chemosensitivity by downregulating the FAK/PI3K/AKT pathway in PTX­resistant ESCC and could be a promising agent for the treatment of PTX­resistant ESCC cancers.

MICAL1 promotes the proliferation in acute myeloid leukemia and is associated with clinical prognosis and immune infiltration.

Acute myeloid leukemia (AML) is one of the most common hematopoietic malignancies that has a poor prognosis and a high rate of relapse. Dysregulated metabolism plays an important role in AML progression. This study aimed to conduct a comprehensive analysis of MRGs using TCGA and GEO datasets and further explore the potential function of critical MRGs in AML progression. In this study, we identified 17 survival-related differentially expressed MRGs in AML using TCGA and GEO datasets. The 150 AML samples were divided into three molecular subtypes using 17 MRGs, and we found that three molecular subtypes exhibited a different association with ferroptosis, cuproptosis and m6A related genes. Moreover, a prognostic signature that comprised nine MRGs and had good predictive capacity was established by LASSO-Cox stepwise regression analysis. Among the 17 MRGs, our attention focused on MICAL1 which was highly expressed in many types of tumors, including AML and its overexpression was also confirmed in several AML cell lines. We also found that the expression of MICAL1 was associated with several immune cells. Moreover, functional experiments revealed that knockdown of MICAL1 distinctly suppressed the proliferation of AML cells. Overall, this study not only contributes to a deeper understanding of the molecular mechanisms underlying AML but also provides potential targets and prognostic markers for AML treatment. These findings offer robust support for further research into therapeutic strategies and mechanisms related to AML, with the potential to improve the prognosis and quality of life for AML patients. Nevertheless, further research is needed to validate these findings and explore more in-depth molecular mechanisms.

[A multicenter clinical study of critically ill patients with sepsis complicated with acute kidney injury in Beijing: incidence, clinical characteristics and outcomes].

OBJECTIVE: To investigate the epidemiological characteristics and prognosis of critically ill patients with sepsis combined with acute kidney injury (AKI) in intensive care unit (ICU) in Beijing, and to analyze the risk factors associated with in-hospital mortality among these critically ill patients. METHODS: Data were collected from the Beijing AKI Trial (BAKIT) database, including 9 049 patients consecutively admitted to 30 ICUs in 28 tertiary hospitals in Beijing from March 1 to August 31, 2012. Patients were divided into non-AKI and non-sepsis group, AKI and non-sepsis group, non-AKI and sepsis group, AKI and sepsis group. Clinical data recorded included demographic characteristics, primary reasons for ICU admission, comorbidities, sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II(APACHE II) within 24 hours of ICU admission, physiological and laboratory indexes, treatment in the ICU, AKI staging based on the Kidney Disease: Improving Global Outcomes (KDIGO), as well as the prognostic indicators including length of stay in ICU, length of stay in hospital, ICU and in-hospital mortality. The primary endpoint was discharge or in-hospital death. Multivariate Logistic regression analysis was used to investigate the risk factors for hospital death in ICU patients. Kaplan-Meier survival curve was drawn to analyze the cumulative survival of ICU patients during hospitalization. RESULTS: A total of 3 107 critically ill patients were ultimately enrolled, including 1 259 cases in the non-AKI and non-sepsis group, 931 cases in the AKI and non-sepsis group, 264 cases in the non-AKI and sepsis groups, and 653 cases in the AKI and sepsis group. Compared with the other three group, patients in the AKI and sepsis group were the oldest, had the lowest mean arterial pressure (MAP), and the highest APACHE II score, SOFA score, blood urea nitrogen (BUN), and serum creatinine (SCr) levels, and they also had the highest proportion of receiving mechanical ventilation, requiring vasopressor support, and undergoing renal replacement therapy (RRT), all P < 0.01. Of these 3 107 patients, 1 584 (51.0%) were diagnosed with AKI, and the incidence of AKI in patients with sepsis was significantly higher than in those without sepsis [71.2% (653/917) vs. 42.5% (931/2 190), P < 0.01]. The highest proportion of KDIGO 0 stage was observed in the non-sepsis group (57.5%), while the highest proportion of KDIGO 3 stage was observed in the sepsis group (32.2%). Within the same KDIGO stage, the mortality of patients with sepsis was significantly higher than that of non-sepsis patients (0 stage: 17.8% vs. 3.1%, 1 stage: 36.3% vs. 7.4%, 2 stage: 42.7% vs. 17.1%, 3 stage: 54.6% vs. 28.6%, AKI: 46.1% vs. 14.2%). The ICU mortality (38.7%) and in-hospital mortality (46.1%) in the AKI and sepsis group were significantly higher than those in the other three groups. Kaplan-Meier survival curves further showed that the cumulative survival rate of patients with AKI and sepsis during hospitalization was significantly lower than that of the other three groups (53.9% vs. 96.9%, 85.8%, 82.2%, Log-Rank: χ 2 = 379.901, P < 0.001). Subgroup analysis showed that among surviving patients, length of ICU stay and total length of hospital stay were significantly longer in the AKI and sepsis group than those in the other three groups (both P < 0.01). Multivariate regression analysis showed that age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, sepsis, and AKI combined with sepsis were independent risk factors for ICU mortality in patients (all P < 0.05). After adjusting for covariates, AKI, sepsis, and sepsis combined with AKI were significantly associated with higher ICU and in-hospital mortality, with the highest ICU mortality [adjusted odds ratio (OR) = 14.82, 95% confidence interval (95%CI) was 8.10-27.12; Hosmer-Lemeshow test: P = 0.816] and in-hospital mortality (adjusted OR = 7.40, 95%CI was 4.94-11.08; Hosmer-Lemeshow test: P = 0.708) observed in patients with sepsis combined with AKI. CONCLUSIONS: The incidence of AKI is high in sepsis patients, and those with both AKI and sepsis have a higher disease burden, more abnormalities in physiological and laboratory indicators, and significantly increased ICU and in-hospital mortality. Among surviving patients, the length of ICU stay and total length of hospital stay are also longer in the AKI and sepsis group. Age, APACHE II score and SOFA score within 24 hours of ICU admission, coronary heart disease, AKI, and sepsis are independent risk factors for in-hospital mortality in ICU patients.

Interferon-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level.

Background: The correlation between metabolic syndrome (MetS) and hepatitis B surface antigen (HBsAg) loss remains to be further elucidated, particularly in patients receiving pegylated interferon-α (PEG-IFN) treatment. Methods: 758 patients with low HBsAg quantification who had received nucleos(t)ide analog (NUC) therapy for at least one year and subsequently switched to or add on PEG-IFN therapy over an unfixed course were enrolled. 412 patients were obtained with baseline data matched. A total of 206 patients achieved HBsAg loss (cured group) within 48 weeks. Demographic and biochemical data associated with MetS were gathered for analysis. HepG2.2.15 cell line was used in vitro experiments to validate the efficacy of interferon-α (IFN-α). Results: The proportion of patients with diabetes or hypertension in the uncured group was significantly higher than in the cured group. The levels of fasting blood glucose (FBG) and glycated albumin remained elevated in the uncured group over the 48 weeks. In contrast, the levels of blood lipids and uric acid remained higher in the cured group within 48 weeks. Triglycerides levels and liver steatosis of all patients increased after PEG-IFN therapy. Baseline elevated uric acid levels and hepatic steatosis may be beneficial for HBsAg loss. IFN-α could induce hepatic steatosis and indirectly promote HBsAg loss by increasing triglyceride level through upregulation of acyl-CoA synthetase long-chain family member 1(ACSL1). Conclusions: IFN-α could induce liver steatosis to promote HBsAg loss by increasing triglyceride level through upregulation of ACSL1. Comorbid diabetes may be detrimental to obtaining HBsAg loss with PEG-IFN therapy in CHB patients.

Bio-inspired gradient poly(lactic acid) nanofibers for active capturing of PM0.3 and real-time respiratory monitoring.

The concept of bio-inspired gradient hierarchies, in which the well-defined MOF nanocrystals serve as active nanodielectrics to create electroactive shell at poly(lactic acid) (PLA) nanofibers, is introduced to promote the surface activity and electroactivity of PLA nanofibrous membranes (NFMs). The strategy enabled significant refinement of PLA nanofibers during coaxial electrospinning (∼40 % decline of fiber diameter), accompanied by remarkable increase of specific surface area (nearly 1.5 m2/g), porosity (approximately 85 %) and dielectric constants for the bio-inspired gradient PLA (BG-PLA) NFMs. It largely boosted initial electret properties and electrostatic adsorption capability of BG-PLA NFMs, as well as charge regeneration by TENG mechanisms even under high-humidity environment. The BG-PLA NFMs thus featured exceptionally high PM0.3 filtration efficiencies with well-controlled air resistance (94.3 %, 163.4 Pa, 85 L/min), in contrast to the relatively low efficiency of only 80.0 % for normal PLA. During the application evaluation of outdoor air purification, excellent long-term filtering performance was demonstrated for the BG-PLA for up to 4 h (nearly 98.0 %, 53 Pa), whereas normal PLA exhibited a gradually declined filtration efficiency and an increased pressure drop. Moreover, the BG-PLA NFMs of increased electroactivity were ready to generate tribo-output currents as driven by respiratory vibrations, which enabled real-time monitoring of electrophysiological signals. This bio-inspired gradient strategy opens up promising pathways to engender biodegradable nanofibers of high surface activity and electroactivity, which has significant implications for intelligent protective membranes.

Structure and pharmacokinetics/pharmacodynamics of the anticoagulant tetradecasaccharide oHG-14 as an intrinsic tenase inhibitor.

The intrinsic tenase complex (iXase) is an attractive antithrombotic target to treat or prevent pathological thrombosis with negligible bleeding risk. Fucosylated glycosaminoglycan (FG) is a promising anticoagulant by inhibiting iXase. A depolymerized FG (dHG-5) as an anticoagulant has been approved for clinical trials. Given that dHG-5 is a multi-component drug candidate consisting of a homologous series of oligosaccharides, it is difficult to predict a clear pharmacokinetics. Here, as a major oligosaccharide component, the tetradecasaccharide (oHG-14) was purified from dHG-5 and its structure was defined as L-Fuc3S4S-α(1,3)-L-Δ4,5GlcA-α(1,3)-{D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ß(1,3)-}3-D-GalNAc4S6S-ß(1,4)-[L-Fuc3S4S-α(1,]3)-D-GlcA-ol. oHG-14 showed potent iXase inhibitory activity in vitro and antithrombotic effect in vivo comparable to dHG-5. After single subcutaneous administration of oHG-14 at 8, 14.4 and 32.4 mg/kg to rats, the absolute bioavailability was 71.6 %-80.9 % determined by the validated bioanalytical methods. The maximum concentration (Cmax) was 3.73, 8.07, and 11.95 µg/mL, respectively, and the time reaching Cmax (Tmax) was about 1 h. oHG-14 was mainly excreted by kidney as the parent compound with the elimination kinetics of first-order linear model. Anticoagulant activity of oHG-14 was positively correlated with its concentration in rat plasma. The pharmacokinetics/pharmacodynamics (PK/PD) of oHG-14 is similar to that of dHG-5. This study could provide supportive data for the clinical trial of dHG-5 and further development of pure oligosaccharide as an antithrombotic drug candidate.

Synergistic immunochemotherapy targeted SAMD4B-APOA2-PD-L1 axis potentiates antitumor immunity in hepatocellular carcinoma.

Targeted and immunotherapy combined with interventional therapy can improve the prognosis of advanced cancer patients, and it has become a hot spot to find the new therapeutic schemes, but most of which are not satisfactory. Single-cell RNA sequencing was performed in PDX mouse models with or without TCC therapy. 2-'O-Methylation modification and multiplex immunofluorescence staining were used to explore the function and mechanism of SAMD4B in the immune context of HCC. Here, we propose for the first time a synergistic immunochemotherapy that exerts a potent antitumour effect for patients with advanced hepatocellular carcinoma (HCC) in clinical practice based on three common antitumour drugs and found that HCC patients with new synergistic immunochemotherapy had better three-year overall survival (p = 0.004) and significantly higher survival ratio (increased by 2.3 times) than the control group. We further reveal the immunoregulatory mechanism of synergistic immunochemotherapy through 2'-O-Methylation modification mediated by SAMD4B, a tumour suppressor gene. Mechanistically, SAMD4B, increased by the reduced mutations of upstream genes NOTCH1 and NOTCH2, affected the instability of APOA2 mRNA by 2-'O-Methylation modification of the C-terminus. The decreased APOA2 further attenuated programmed death ligand 1 (PD-L1) level with a direct interaction pattern. The high-SAMD4B tumour tissues contained fewer native CD29+CD8+ T cells, which improved immune microenvironment to achieve the effect of antitumour effect. Overall, we developed a potent synergistic immunochemotherapy strategy that exerts an efficient anti-HCC effect inducing SAMD4B-APOA2-PD-L1 axis to inhibit tumour immune evasion.

Surface engineering of zinc plate by self-growth three-dimensional-interconnected zinc silicate nanosheets effectively guiding the deposition of zinc ion for aqueous Zn metal battery.

Among battery technologies, aqueous zinc ion batteries (AZIBs) have hit between the eyes in the next generation of extensive energy storage devices due to their outstanding superiority. The main problem that currently restricts the development of AZIBs is how to obtain stable Zn anodes. In this study, taking the improvement of a series of problems caused by the physically attached artificial interfacial layer on Zn anode as a starting point, a nanosheet morphology of ZnSiO3 (denoted as ZnSi) is constructed by self-growth on Zn foil (Zn@ZnSi) by a simple hydrothermal reaction. The ZnSi nano-interfacial layer effectively slices the surface of the Zn foil into individual microscopic interfacial layers, constructing abundant pores. The nanosheets of Zn@ZnSi construct rich nanoscale Zn2+ transport channels, which provide higher electron and ion transport paths, thus achieving the effect of effectively homogenizing the electric field distribution and decreasing the local current density. Thanks to its inherent and structural properties, the Zn@ZnSi anode has a high specific capacity and good cycling stability compared with the Zn electrode. The lifetime of the Zn@ZnSi//Zn@ZnSi symmetric cell is much higher than that of the Zn//Zn symmetric cell at 1 mA cm-2. The capacity of the Zn@ZnSi//NH4V4O10 full cell can still reach 98 mAh g-1 after 1000 cycles at 1 A/g. The low-cost and scalable synthesis of ZnSi nano-interfacial layer on Zn is expected to provide new perspectives on interfacial engineering for Zn anodic protection.

Geodesic shape regression based deep learning segmentation for assessing longitudinal hippocampal atrophy in dementia progression.

Longitudinal hippocampal atrophy is commonly used as progressive marker assisting clinical diagnose of dementia. However, precise quantification of the atrophy is limited by longitudinal segmentation errors resulting from MRI artifacts across multiple independent scans. To accurately segment the hippocampal morphology from longitudinal 3T T1-weighted MR images, we propose a diffeomorphic geodesic guided deep learning method called the GeoLongSeg to mitigate the longitudinal variabilities that unrelated to diseases by enhancing intra-individual morphological consistency. Specifically, we integrate geodesic shape regression, an evolutional model that estimates smooth deformation process of anatomical shapes, into a two-stage segmentation network. We adopt a 3D U-Net in the first-stage network with an enhanced attention mechanism for independent segmentation. Then, a hippocampal shape evolutional trajectory is estimated by geodesic shape regression and fed into the second network to refine the independent segmentation. We verify that GeoLongSeg outperforms other four state-of-the-art segmentation pipelines in longitudinal morphological consistency evaluated by test-retest reliability, variance ratio and atrophy trajectories. When assessing hippocampal atrophy in longitudinal data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), results based on GeoLongSeg exhibit spatial and temporal local atrophy in bilateral hippocampi of dementia patients. These features derived from GeoLongSeg segmentation exhibit the greatest discriminatory capability compared to the outcomes of other methods in distinguishing between patients and normal controls. Overall, GeoLongSeg provides an accurate and efficient segmentation network for extracting hippocampal morphology from longitudinal MR images, which assist precise atrophy measurement of the hippocampus in early stage of dementia.

Towards Stem/Progenitor Cell-Based Therapies for Retinal Degeneration.

Retinal degeneration (RD) is a leading cause of blindness worldwide and includes conditions such as retinitis pigmentosa (RP), age-related macular degeneration (AMD), and Stargardt's disease (STGD). These diseases result in the permanent loss of vision due to the progressive and irreversible degeneration of retinal cells, including photoreceptors (PR) and the retinal pigment epithelium (RPE). The adult human retina has limited abilities to regenerate and repair itself, making it challenging to achieve complete self-replenishment and functional repair of retinal cells. Currently, there is no effective clinical treatment for RD. Stem cell therapy, which involves transplanting exogenous stem cells such as retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs), or activating endogenous stem cells like Müller Glia (MG) cells, holds great promise for regenerating and repairing retinal cells in the treatment of RD. Several preclinical and clinical studies have shown the potential of stem cell-based therapies for RD. However, the clinical translation of these therapies for the reconstruction of substantial vision still faces significant challenges. This review provides a comprehensive overview of stem/progenitor cell-based therapy strategies for RD, summarizes recent advances in preclinical studies and clinical trials, and highlights the major challenges in using stem/progenitor cell-based therapies for RD.

Multiomics-based molecular subtyping based on the commensal microbiome predicts molecular characteristics and the therapeutic response in breast cancer.

The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called "challenging BC". Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in "challenging BC" patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in "challenging BC" patients.

Biomass hydrothermal carbonization solution-assisted synthesis of intercalation-expanded core-shell structured molybdenum disulfide for efficient adsorption of Cr (VI) in electroplating wastewater treatment.

Cr (VI) is a common heavy metal pollutant in electroplating wastewater. This study introduces the liquid-phase product from the hydrothermal reaction of coffee grounds (CGHCL) into the synthesis process of molybdenum disulfide, assisting in the fabrication of an intercalated, expanded core-shell structured molybdenum disulfide adsorbent (C-MoS2), designed for the adsorption and reduction of Cr (VI) from electroplating wastewater. The addition of CGHCL significantly enhances the adsorption performance of MoS2. Furthermore, C-MoS2 exhibits exceedingly high removal efficiency and excellent regenerative capability for Cr (VI)-containing electroplating wastewater. The core-shell structure effectively minimizes molybdenum leaching to the greatest extent, while the oleophobic interface is unaffected by oily substances in water, and the expanded interlayer structure ensures the long-term stability of C-MoS2 in air (90 days). This study provides a viable pathway for the resource utilization of biomass and the application of molybdenum disulfide-based materials in wastewater treatment.

Characterization of acute-on-chronic liver diseases: A multicenter prospective cohort study.

BACKGROUND: Acute-on-chronic liver disease (AoCLD) accounts for the majority of patients hospitalized in the Department of Hepatology or Infectious Diseases. AIM: To explore the characterization of AoCLD to provide theoretical guidance for the accurate diagnosis and prognosis of AoCLD. METHODS: Patients with AoCLD from the Chinese Acute-on-Chronic Liver Failure (ACLF) study cohort were included in this study. The clinical characteristics and outcomes, and the 90-d survival rate associated with each clinical type of AoCLD were analyzed, using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 3375 patients with AoCLD were enrolled, including 1679 (49.7%) patients with liver cirrhosis acute decompensation (LC-AD), 850 (25.2%) patients with ACLF, 577 (17.1%) patients with chronic hepatitis acute exacerbation (CHAE), and 269 (8.0%) patients with liver cirrhosis active phase (LC-A). The most common cause of chronic liver disease (CLD) was HBV infection (71.4%). The most common precipitants of AoCLD was bacterial infection (22.8%). The 90-d mortality rates of each clinical subtype of AoCLD were 43.4% (232/535) for type-C ACLF, 36.0% (36/100) for type-B ACLF, 27.0% (58/215) for type-A ACLF, 9.0% (151/1679) for LC-AD, 3.0% (8/269) for LC-A, and 1.2% (7/577) for CHAE. CONCLUSION: HBV infection is the main cause of CLD, and bacterial infection is the main precipitant of AoCLD. The most common clinical type of AoCLD is LC-AD. Early diagnosis and timely intervention are needed to reduce the mortality of patients with LC-AD or ACLF.

Prevalence survey and psychometric measurement of vertigo and dizziness in individuals with obstructive sleep apnoea: A cross-sectional study.

INTRODUCTION: This study aimed to evaluate the prevalence and psychometric properties of vertigo and dizziness in an obstructive sleep apnoea (OSA) population. METHODS: Five hundred and twelve OSA patients and 53 controls were enroled. All eligible subjects were asked to complete the basic information questionnaire, the Chinese version of Vestibular Disorders Activities of Daily Living (VADL-C), the Dizziness Handicap Inventory (DHI) and the Activities-Specific Balance Confidence (ABC) scale. RESULTS: Among 512 enroled OSA patients, a 22.46% (115) prevalence of vertigo and dizziness was found. The scores of the VADL-C, DHI and ABC of the study group were significantly worse (p < .001) than those of the control group, while the abnormal rates of the three scales in the study group were higher than those of the control group. In the study group, the results of the VADL-C were correlated with those of the DHI (r = .55, p < .001) and inversely correlated with those of the ABC (r = -.50, p < .001), and the results of the DHI were inversely correlated with those of the ABC (r = -.60, p < .001). CONCLUSIONS: A high prevalence of vertigo and dizziness in the OSA population was detected. Psychometric results showed that vertigo and dizziness in OSA patients led to changes in activities of daily living, increased frequency of somatic symptoms, and reduced balance confidence. In the diagnosis and treatment of OSA patients, the occurrence of vertigo and dizziness is worth clinicians' attention.

Alternations in the human skin, gut and vaginal microbiomes in perimenopausal or postmenopausal Vulvar lichen sclerosus.

Vulvar lichen sclerosus (VLS) is a chronic and progressive dermatologic condition that can cause physical dysfunction, disfigurement, and impaired quality of life. However, the etiology of VLS remains unknown. The vulvar skin, intestinal and vaginal microbiomes have been postulated to play important roles in the pathogenesis of this disease. The aim of this study was to compare the compositional characteristics of the vulvar skin, vagina, and gut microbiota between perimenopausal or postmenopausal VLS patients and healthy controls. The study involved six perimenopausal or postmenopausal VLS patients which were based on characteristic clinical manifestations and histologic confirmation and five healthy controls. The pruritus severity of each patient was evaluated using the NRS scale, and the dermatology-specific health-related quality of life was assessed using the Skindex-16. Metagenomic sequencing was performed, and the results were analyzed for alpha and beta diversity. LEfSe analysis were used to investigate the microbial alterations in vulvar skin, gut and vagina. KEGG databases were used to analyze differences in functional abundance. The study found significant differences in alpha diversity between the two groups in stool and vaginal samples (P < 0.05). Patients with VLS had a higher abundance of Enterobacter cloacae, Flavobacterium_branchiophilum, Mediterranea_sp._An20, Parabacteroides_johnsoniiand Streptococcus_bovimastitidis on the vulvar skin, while Corynebacterium_sp._zg-913 was less abundant compared to the control group. The relative abundance of Sphingomonas_sp._SCN_67_18, Sphingobium_sp._Ant17, and Pontibacter_sp_BT213 was significantly higher in the gut samples of patients with VLS.Paenibacillus_popilliae,Gemella_asaccharolytica, and Coriobacteriales_bacterium_DNF00809 compared to the control group. Additionally, the vaginal samples of patients with VLS exhibited a significantly lower relative abundance of Bacteroidales_bacterium_43_8, Bacteroides_sp._CAG:20, Blautia_sp._AM28-10, Fibrobacter_sp._UWB16, Lachnospiraceae_bacterium_AM25-39, Holdemania_filiformis, Lachnospiraceae_bacterium_GAM79, and Tolumonas_sp. Additionally, the butyrate-producing bacterium SS3/4 showed a significant difference compared to the controls. The study found a negative relationship between Sphingobium_sp._Ant17 in stool and Skindex-16 (P < 0.05), while Mediterranea_sp._An20 had a positive correlation with Skindex-16 (P < 0.05) in the skin. Additionally, our functional analysis revealed alterations in Aminoacyl_tRNA_biosynthesis, Glutathione_metabolism, the pentose phosphate pathway, and Alanine__aspartate_and_glutamate_metabolism in the VLS patient group. The study suggests that perimenopausal or postmenopausal patients with VLS have a modified microbiome in the vulvar skin, gut, and vagina. This modification is linked to abnormal energy metabolism, increased oxidative stress, and abnormal amino acid metabolism.

Coronary artery calcification in Takayasu's arteritis: clinical characteristics and risk factors.

OBJECTIVES: Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC. METHODS: This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups. RESULTS: Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors. CONCLUSIONS: We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.

Variations and Interseasonal Changes in the Gut Microbial Communities of Seven Wild Fish Species in a Natural Lake with Limited Water Exchange during the Closed Fishing Season.

The gut microbiota of fish is crucial for their growth, development, nutrient uptake, physiological balance, and disease resistance. Yet our knowledge of these microbial communities in wild fish populations in their natural ecosystems is insufficient. This study systematically examined the gut microbial communities of seven wild fish species in Chaohu Lake, a fishing-restricted area with minimal water turnover, across four seasons. We found significant variations in gut microbial community structures among species. Additionally, we observed significant seasonal and regional variations in the gut microbial communities. The Chaohu Lake fish gut microbial communities were predominantly composed of the phyla Firmicutes, Proteobacteria(Gamma), Proteobacteria(Alpha), Actinobacteriota, and Cyanobacteria. At the genus level, Aeromonas, Cetobacterium, Clostridium sensu stricto 1, Romboutsia, and Pseudomonas emerged as the most prevalent. A co-occurrence network analysis revealed that C. auratus, C. carpio, and C. brachygnathus possessed more complex and robust gut microbial networks than H. molitrix, C. alburnus, C. ectenes taihuensis, and A. nobilis. Certain microbial groups, such as Clostridium sensu stricto 1, Romboutsia, and Pseudomonas, were both dominant and keystone in the fish gut microbial network. Our study offers a new approach for studying the wild fish gut microbiota in natural, controlled environments. It offers an in-depth understanding of gut microbial communities in wild fish living in stable, limited water exchange natural environments.

Comparison of Transcriptome Differences between Two Rice Cultivars Differing in Cadmium Translocation from Spike-Neck to Grain.

At present, the mechanism of varietal differences in cadmium (Cd) accumulation in rice is not well understood. Two rice cultivars, ZZY (high translocation-high grain Cd) and SJ18 (low translocation-low grain Cd), were used to analyze transcriptome differences in the spike-neck tissue in field trials. The results showed that, compared with ZZY, 22,367 differentially expressed genes (DEGs) were identified in SJ18, including 2941 upregulated and 19,426 downregulated genes. GO analysis enriched 59 downregulated terms, concerning 24 terms enriched for more than 1000 DEGs, including cellular and metabolic processes, biological regulation, localization, catalytic activity, transporter activity, signaling, etc. KEGG enrichment identified 21 significant downregulated pathways, regarding the ribosome, metabolic pathways, biosynthesis of secondary metabolism, signaling transduction, cell membrane and cytoskeleton synthesis, genetic information transfer, amino acid synthesis, etc. Weighted gene co-expression network analysis (WGCNA) revealed that these DEGs could be clustered into five modules. Among them, the yellow module was significantly related to SJ18 with hub genes related to OsHMA and OsActin, whereas the brown module was significantly related to ZZY with hub genes related to mitogen-activated protein kinase (MAPK), CBS, and glutaredoxin. This suggests that different mechanisms are involved in the process of spike-neck-grain Cd translocation among varieties. This study provides new insights into the mechanisms underlying differences in Cd transport among rice varieties.

Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis.

The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.