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Abstract Depression, a widespread and highly heritable mental health condition, profoundly affects millions of individuals worldwide. Neuroimaging studies have consistently revealed volumetric abnormalities in subcortical structures associated with depression. However, the genetic underpinnings shared between depression and subcortical volumes remain inadequately understood. Here, we investigate the extent of polygenic overlap using the bivariate causal mixture model (MiXeR), leveraging summary statistics from the largest genome-wide association studies for depression (N = 674,452) and 14 subcortical volumetric phenotypes (N = 33,224). Additionally, we identify shared genomic loci through conditional/conjunctional FDR analyses. MiXeR shows that subcortical volumetric traits share a substantial proportion of genetic variants with depression, with 44 distinct shared loci identified by subsequent conjunctional FDR analysis. These shared loci are predominantly located in intronic regions (58.7%) and non-coding RNA intronic regions (25.4%). The 269 protein-coding genes mapped by these shared loci exhibit specific developmental trajectories, with the expression level of 55 genes linked to both depression and subcortical volumes, and 30 genes linked to cognitive abilities and behavioral symptoms. These findings highlight a shared genetic architecture between depression and subcortical volumetric phenotypes, enriching our understanding of the neurobiological underpinnings of depression.

Abstract Aims The present study aimed to investigate the relationship between mean platelet volume (MPV) and the risk of type 2 diabetes mellitus (T2DM), among women with and without a history of gestational diabetes mellitus (GDM). Methods Eight thousand one hundred eighty-one parous women of the ‘2007–2018 National Health and Nutrition Examination Survey (NHANES)’ were classified into GDM and non-GDM groups based on self-reported GDM history. We investigated the independent association between the MPV and the risk of T2DM in these groups via multivariable regression analysis. A subgroup analysis was done for the GDM group. Results After comprehensive adjustment for potential covariates, a significant positive correlation was observed between MPV and the risk of T2DM in women with a history of GDM (OR = 1.50, 95% CI 1.13–2.01, P = 0.006). There was a linear relationship between MPV and T2DM among women with a history of GDM, with each unit increase in MPV increasing the risk of T2DM by 50%. Subgroup analysis and interaction tests revealed a stronger significant effect on women with GDM history who had HbA1c ≥ 7%. Conclusions MPV is strongly associated with the incidence of T2DM among U.S. parous women with prior GDM, indicating that MPV may be a potential biomarker of T2DM among women with a history of GDM.

Abstract Objectives To investigate the clinical features and risk factors of Sjogren’s Syndrome (SS) patients suffering from oral candidiasis and to provide a foundation for the prevention and treatment of oral candidiasis in SS patients. Methods The medical records of 479 SS patients admitted to the Second Hospital of Shanxi Medical University from 2018 to 2020 were analysed to determine the clinical characteristics and risk factors that influence the occurrence of oral candidiasis infection in SS patients. Results Patients with oral candidiasis were older than those without oral candidiasis (P

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) has high mortality rates. The osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK)/Toll-like receptor 4 (TLR4) pathway and its potential role in SA-AKI pathogenesis remain to be fully understood. Herein, we addressed this issue using mouse models. Methods An SA-AKI mouse model was established using the cecal ligation and puncture method (CLP). Mice were grouped into sham, CLP model, CLP + recombinant RANKL, and CLP + anti-RANKL groups. Serum creatinine (Scr) and blood urea nitrogen (BUN) levels were measured to assess kidney function. ELISA was used to detect serum IL-1β, TNF-α, and IL-6 levels. Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of OPG, RANKL, RANK, and TLR4 in kidney tissues. HE staining was performed to evaluate the pathological changes. Results The CLP model group showed higher levels of Scr and BUN, indicating impaired kidney function in SA-AKI, compared to the sham group. Treatment with recombinant RANKL in the CLP + recombinant RANKL group reduced Scr and BUN levels, while anti-RANKL treatment in the CLP + anti-RANKL group elevated their levels. Moreover, the CLP model group had significantly increased IL-1β, TNF-α, and IL-6 than the sham group, indicating elevated inflammation in SA-AKI. The CLP + recombinant RANKL group demonstrated decreased cytokine levels, whereas the CLP + anti-RANKL group showed an increase. Additionally, the histopathological evaluation revealed distinct kidney tissue damage in the CLP model group. Recombinant RANKL treatment reduced this damage, while anti-RANKL treatment exacerbated it. Mechanically, the mRNA and protein expression of RANKL were significantly decreased, while those of OPG, RANK, and TLR4 were significantly increased in the CLP model group and the CLP + anti-RANKL group. Interestingly, treatment with recombinant RANKL reversed these changes, as evidenced by significantly increased RANKL but decreased OPG, RANK, and TLR4. Conclusion The OPG/RANKL/RANK/TLR4 pathway is involved in SA-AKI pathogenesis. Recombinant RANKL treatment attenuates the inflammatory response and kidney tissue damage in SA-AKI, possibly via regulating this pathway. This pathway shows promise as a therapeutic target for SA-AKI.

BackgroundRheumatoid arthritis (RA) patients suffering from chronic renal insufficiency tend to exhibit subtle manifestations at the beginning. Urine albumin to creatinine ratio (ACR) is a sensitive indicator for early assessment of renal function. However, it is unclear whether it serves as an independent risk factor influencing the prognosis of RA patients.MethodsNational Health and Nutrition Examination Survey (NHANES) data from 2009-2018 were included. Kaplan-Meier (K-M) curves were plotted to compare the cumulative survival probability of RA patients with different urinary albumin excretion. The association of ACR with mortality among RA patients was investigated with Cox regression model, restricted cubic spline (RCS) and stratified analyses. The prognostic efficacy of ACR and estimated glomerular filtration rate (eGFR) was evaluated by receiver operating characteristic (ROC) curves.ResultsThe Cox regression model adjusted with covariates showed a 53% (HR 1.53, 95% CI 1.06-2.21) increase in all-cause mortality and a statistically non-significant increase in cardiovascular disease (CVD) mortality in RA patients with microalbuminuria (30mg/g ≤ACR

Rheumatoid arthritis (RA) affects millions of people worldwide, but there are limited drugs available to treat it, so acquiring a more comprehensive comprehension of the underlying reasons and mechanisms behind inflammation is crucial, as well as developing novel therapeutic approaches to manage it and mitigate or forestall associated harm. It is evident that current in vitro models cannot faithfully replicate all aspects of joint diseases, which makes them ineffective as tools for disease research and drug testing. Organ-on-a-chip (OoC) technology is an innovative platform that can mimic the microenvironment and physiological state of living tissues more realistically than traditional methods by simulating the spatial arrangement of cells and interorgan communication. This technology allows for the precise control of fluid flow, nutrient exchange, and the transmission of physicochemical signals, such as bioelectrical, mechanical stimulation and shear force. In addition, the integration of cutting-edge technologies like sensors, 3D printing, and artificial intelligence enhances the capabilities of these models. Here, we delve into OoC models with a particular focus on Synovial Joints-on-a-Chip, where we outline their structure and function, highlighting the potential of the model to advance our understanding of RA. We integrate the actual evidence regarding various OoC models and their possible integration for multisystem disease study in RA research for the first time and introduce the prospects and opportunities of the chip in RA etiology and pathological mechanism research, drug research, disease prevention and human precision medicine. Although many challenges remain, OoC holds great promise as an in vitro model that approaches physiology and dynamics.

BackgroundRheumatoid arthritis (RA) is an autoimmune disease with various subtypes. Among these, seronegative rheumatoid arthritis (SnRA), distinguished by its distinctive seronegative antibody phenotype, presents clinical diagnosis and treatment challenges. This study aims to juxtapose the immunological features of SnRA with seropositive rheumatoid arthritis (SpRA) to investigate potential mechanisms contributing to differences in antibody production.MethodsThis study included 120 patients diagnosed with RA and 78 patients diagnosed with psoriatic arthritis (PsA), comprising 41 cases of SnRA and 79 cases of SpRA. Clinical, serological, and immune data were collected from all participants to systematically identify and confirm the most pivotal immunological distinctions between SnRA and SpRA.Results(1) SpRA demonstrates more pronounced T-helper 17 cells (Th17)/Regulatory T cells (Treg) dysregulation, vital immunological differences from SnRA. (2) SpRA exhibits higher inflammatory cytokine levels than SnRA and PsA. (3) Lymphocyte subset ratios and cytokine overall distribution in SnRA close to PsA. (4) Interleukin-4 (IL-4) emerges as the central immunological disparity marker between SnRA and SpRA.ConclusionTh17/Treg imbalance is one of the vital immunological disparities between SnRA and SpRA. Interestingly, PsA and SnRA display similar peripheral blood immunological profiles, providing immunological evidence for these two diseases’ clinical and pathological similarities. Furthermore, IL-4 emerges as the central immunological disparity marker between SnRA and SpRA, suggesting its potential role as a triggering mechanism for differential antibody production.

Abstract The thermal runaway issue represents a long‐standing obstacle that retards large‐scale applications of lithium metal batteries. Various approaches to inhibit thermal runaway suffer from some intrinsic drawbacks, either being irreversible or delayed thermal protection. Herein, this work has explored thermo‐responsive lower critical solution temperature (LCST) ionic liquid‐based electrolytes, which provides reversible overheating protection for batteries with warning and shut‐down stages, well corresponding to an initial stage of thermal runaway process. The batteries could function stably below 70 °C as a working mode, while demonstrating a warning mode above 80 °C with a noticeable reduction in specific capacitance to delay temperature increase of batteries. In terms of 110 °C as a critically dangerous temperature, a shut‐down mode is designed to minimize the thermal energy releasing as the batteries are barely chargeable and dischargeable. Dynamically growing polymeric particles above LCST contributed to such an intelligent and mild control on specific capacitance. Larger size will occupy larger surfaces of electrodes and close more pores of separators, enabling a gradual suppressing of Li+ transfer and reactions. The present work demonstrated a scientific design of thermoresponsive LCST electrolytes with a superiorly precise and intelligent control of electrochemical performances to achieve self‐adapted overheating protections.

Abstract This study aimed to analyze peripheral blood lymphocyte subsets in lupus nephritis (LN) patients and use machine learning (ML) methods to establish an effective algorithm for predicting co-infection in LN. This study included 111 non-infected LN patients, 72 infected LN patients, and 206 healthy controls (HCs). Patient information, infection characteristics, medication, and laboratory indexes were recorded. Eight ML methods were compared to establish a model through a training group and verify the results in a test group. We trained the ML models, including Logistic Regression, Decision Tree, K-Nearest Neighbors, Support Vector Machine, Multi-Layer Perceptron, Random Forest, Ada boost, Extreme Gradient Boosting (XGB), and further evaluated potential predictors of infection. Infected LN patients had significantly decreased levels of T, B, helper T, suppressor T, and natural killer cells compared to non-infected LN patients and HCs. The number of regulatory T cells (Tregs) in LN patients was significantly lower than in HCs, with infected patients having the lowest Tregs count. Among the ML algorithms, XGB demonstrated the highest accuracy and precision for predicting LN infections. The innate and adaptive immune systems are disrupted in LN patients, and monitoring lymphocyte subsets can help prevent and treat infections. The XGB algorithm was recommended for predicting co-infection in LN.

Abstract Background Patients with rheumatoid arthritis (RA) showed impaired immune tolerance characterized by reduced follicular regulatory T (Tfr) cells, and they also exhibited altered gut microbiotas and their metabolites in RA. However, the association of gut microbiotas and their metabolites with the immune tolerance mediated by Tfr cells in RA remains unclear. Methods Peripheral blood and stool samples were collected from 32 new-onset RA patients and 17 healthy controls (HCs) in the Second Hospital of Shanxi Medical University between January 2022 and June 2022. The peripheral blood was used to detect the circulating regulatory T (Treg), helper T(Th)17, Tfr, and follicular helper T (Tfh) cells by modified flow cytometry. The stool samples were used to analyze the gut microbiotas and their metabolites via 16S rDNA sequencing and metabolomic profiling. We aimed to characterize the gut microbiotas and their metabolites in RA and identified their association with Tfr cell-mediated immune tolerance. Results The new-onset RA demonstrated reduced Treg and Tfr cells, associated with the disease activity and autoantibodies. There were significant differences in gut microbiotas between the two groups as the results of β diversity analysis (P = 0.039) including 21 differential gut microbiotas from the phylum to genus levels. In which, Ruminococcus 2 was associated with the disease activity and autoantibodies of RA, and it was identified as the potential biomarker of RA [area under curve (AUC) = 0.782, 95% confidence interval (CI) = 0.636–0.929, P = 0.001]. Eleven differential metabolites were identified and participated in four main pathways related to RA. Arachidonic acid might be the potential biomarker of RA (AUC = 0.724, 95% CI = 0.595–0.909, P = 0.038), and it was the core metabolite as the positive association with six gut microbiotas enriched in RA. The reduced Tfr cells were associated with the altered gut microbiotas and their metabolites including the Ruminococcus 2, the arachidonic acid involved in the biosynthesis of unsaturated fatty acid pathway and the 3-methyldioxyindole involved in the tryptophan metabolism pathway. Conclusion The breakdown of immune tolerance mediated by reduced Tfr cells was associated with the altered gut microbiotas and their metabolites implying the possible mechanism of RA pathogenesis from the perspective of microecology-metabolism-immune.

Abstract Background Epidemiological studies have shown a close association between osteoarthritis (OA) and cardiovascular disease (CVD), but reliable evidence needs to be provided. We performed a two‐sample Mendelian randomization (MR) study to examine the potential causal effect between OA and CVD. Methods Exposures were self‐reported OA, knee osteoarthritis (KOA), and hip osteoarthritis (HOA). The outcomes were 12 CVDs, including heart failure, atrial fibrillation, coronary artery disease, pulmonary embolism, stroke and its subtypes, myocardial infarction, coronary heart disease, and primary hypertension. All outcomes were obtained from published genome‐wide association studies. The inverse‐variance weighted method was used as the primary MR analysis. Heterogeneity tests and sensitivity analyses were conducted to validate the accuracy of the MR results. Results Self‐reported OA increased the incidence of small vessel stroke (odds ratio [OR] = 1.25, 95% confidence interval [CI]: 1.02–1.52, p = 0.03) and primary hypertension (1.01 [1.00–1.02], p

Abstract Type VI secretion systems (T6SSs) deliver effectors into target cells. Besides structural and effector proteins, many other proteins, such as adaptors, co-effectors and accessory proteins, are involved in this process. MIX domains can assist in the delivery of T6SS effectors when encoded as a stand-alone gene or fused at the N-terminal of the effector. However, whether there are other conserved domains exhibiting similar encoding forms to MIX in T6SS remains obscure. Here, we scanned publicly available bacterial genomes and established a database which include 130,825 T6SS vgrG loci from 45,041 bacterial genomes. Based on this database, we revealed six domain families encoded within vgrG loci, which are either fused at the C-terminus of VgrG/N-terminus of T6SS toxin or encoded by an independent gene. Among them, DUF2345 was further validated and shown to be indispensable for the T6SS effector delivery and LysM was confirmed to assist the interaction between VgrG and the corresponding effector. Together, our results implied that these widely distributed domain families with similar genetic configurations may be required for the T6SS effector recruitment process.

Objective We aimed to assess the level of knowledge and awareness regarding the need for screening of early gastrointestinal cancer among residents of Sunan Yugur Autonomous County in China. Methods In this cross-sectional study, we conducted a survey among permanent residents of Sunan Yugur Autonomous County from January 2020 to January 2023 using a questionnaire to obtain data on knowledge regarding early gastrointestinal cancer screening. Results The survey included 12,000 residents. Among participants, 62.30% (7476/12,000) were aware of the need for early gastrointestinal cancer screening. Awareness about the need for early gastrointestinal cancer screening differed significantly based on participants’ sex, age, level of education, area of residence, and ethnicity. Conclusion The level of awareness regarding the need for early gastrointestinal cancer screening was relatively low in our study population. The government and medical institutions should provide information and promote early gastrointestinal cancer screening in the region to improve the health status and quality of life among the Yugur people.

BackgroundPsoriasis is a highly heterogeneous autoinflammatory disease. At present, heterogeneity in disease has not been adequately translated into concrete treatment options. Our aim was to develop and verify a new stratification scheme that identifies the heterogeneity of psoriasis by the integration of large-scale transcriptomic profiles, thereby identifying patient subtypes and providing personalized treatment options whenever possible.MethodsWe performed functional enrichment and network analysis of upregulated differentially expressed genes using microarray datasets of lesional and non-lesional skin samples from 250 psoriatic patients. Unsupervised clustering methods were used to identify the skin subtypes. Finally, an Xgboost classifier was utilized to predict the effects of methotrexate and commonly prescribed biologics on skin subtypes.ResultsBased on the 163 upregulated differentially expressed genes, psoriasis patients were categorized into three subtypes (subtypes A–C). Immune cells and proinflammatory-related pathways were markedly activated in subtype A, named immune activation. Contrastingly, subtype C, named stroma proliferation, was enriched in integrated stroma cells and tissue proliferation-related signaling pathways. Subtype B was modestly activated in all the signaling pathways. Notably, subtypes A and B presented good responses to methotrexate and interleukin-12/23 inhibitors (ustekinumab) but inadequate responses to tumor necrosis factor-α inhibitors and interleukin-17A receptor inhibitors. Contrastly, subtype C exhibited excellent responses to tumor necrosis factor-α inhibitors (etanercept) and interleukin-17A receptor inhibitors (brodalumab) but not methotrexate and interleukin-12/23 inhibitors.ConclusionsPsoriasis patients can be assorted into three subtypes with different molecular and cellular characteristics based on the heterogeneity of the skin's immune cells and the stroma, determining the clinical responses of conventional therapies.

Abstract Pericytes are the main cellular components of tiny arteries and capillaries. Studies have found that pericytes can undergo morphological contraction or relaxation under stimulation by cytokines, thus affecting the contraction and relaxation of microvessels and playing an essential role in regulating vascular microcirculation. Moreover, due to the characteristics of stem cells, pericytes can differentiate into a variety of inflammatory cell phenotypes, which then affect the immune function. Additionally, pericytes can also participate in angiogenesis and wound healing by interacting with endothelial cells in vascular microcirculation disorders. Here we review the origin, biological phenotype and function of pericytes, and discuss the potential mechanisms of pericytes in vascular microcirculation disorders, especially in pulmonary hypertension, so as to provide a sound basis and direction for the prevention and treatment of vascular microcirculation diseases.

Abstract Background Primary Sjogren’s Syndrome (pSS) is a lymphoproliferative disease with autoimmune characteristics, which is characterized by lymphocyte infiltration of exocrine glands and involvement and dysfunction of extraglandular organs. Renal tubular acidosis (RTA) is a common renal involvement in pSS. This study investigated the phenotypic characteristics of peripheral blood lymphocyte subsets and cytokines in pSS patients complicated with RTA (pSS-RTA). Method This retrospective study included 25 pSS patients complicated with RTA and 54 pSS patients without RTA (pSS-no-RTA). To examine the level of peripheral lymphocytes subsets, flow cytometry analysis was used. The level of serum cytokines were detected by flow cytometry bead array(CBA). The influencing factors related to the occurrence of pSS-RTA were identified through logistic regression analyze. Results The absolute number of CD4 + T cells and Th2 cells in peripheral blood were decreased in pSS-RTA patients than pSS-no-RTA patients. Moreover, the absolute number of NK cells and Treg cells were also decreased in pSS-RTA patients than pSS-no-RTA. The level of serum IL-2 was higher in pSS-RTA patients than pSS-no-RTA patients, and is negatively correlated with the number of NK cells, the number and percentage of Th17 cells, and Th17/Treg. Serum IL-2 level is also correlated with various cytokines. Multivariate logistic analysis proved that elevated ESR and ALP were risk factors for pSS complicated with RTA, while Treg was a protective factor. Conclusion The increase of serum IL-2 level and the decrease of peripheral blood NK cells and Treg cells may be the immune mechanism of the development of pSS-RTA disease.

Background: Internal capsule strokes often result in multidomain cognitive impairments across memory, attention, and executive function, typically due to disruptions in brain network connectivity. Our study examines these impairments by analyzing interactions within the triple-network model, focusing on both static and dynamic aspects. Methods: We collected resting-state fMRI data from 62 left (CI_L) and 56 right (CI_R) internal capsule stroke patients, along with 57 healthy controls (HC). Using independent component analysis to extract the default mode (DMN), executive control (ECN), and salience networks (SAN), we conducted static and dynamic functional network connectivity analyses (DFNC) to identify differences between stroke patients and controls. For DFNC, we used k-means clustering to focus on temporal properties and multilayer network analysis to examine integration and modularity Q, where integration represents dynamic interactions between networks, and modularity Q measures how well the network is divided into distinct modules. We then calculated the correlations between SFNC/DFNC properties with significant inter-group differences and cognitive scales. Results: Compared to HC, both CI_L and CI_R patients showed increased static FCs between SAN and DMN and decreased dynamic interactions between ECN and other networks. CI_R patients also had heightened static FCs between SAN and ECN and maintained a state with strongly positive FNCs across all networks in the triple-network model. Additionally, CI_R patients displayed decreased modularity Q. Conclusion: These findings highlight that stroke can result in the disruption of static and dynamic interactions in the triple network model, aiding our understanding of the neuropathological basis for multidomain cognitive deficits after internal capsule stroke.

Background: Subcortical stroke may significantly alter the cerebral cortical structure and affect attention function, but the details of this process remain unclear. The study aimed to investigate the neural substrates underlying attention impairment in patients with subcortical stroke. Materials and Methods: In this prospective observational study, two distinct datasets were acquired to identify imaging biomarkers underlying attention deficit. The first dataset consisted of 86 patients with subcortical stroke, providing a cross-sectional perspective, whereas the second comprised 108 patients with stroke, offering longitudinal insights. All statistical analyses were subjected to false discovery rate correction upon P

To investigate potential alterations of white matter hyperintensities (WMHs) on J-edited MR spectroscopy (MRS) measures of the primary inhibitory neurotransmitter γ-aminobutyric acid (GABA). Twenty-four WMHs patients and 20 healthy controls (HCs) were recruited to undergo magnetic resonance spectroscopy (MRS) scan at 3T from voxels in left centrum semiovale white matter, using the MEGA point resolved spectroscopy (MEGA-PRESS) technique with the MATLAB-based Gannet tool to estimate GABA+ co-edited macromolecule (GABA+) levels and using Tarquin software to estimate levels of glutamate + glutamine (Glx), total N-acetylaspartate (tNAA), total choline (tCho), and total creatine (tCr). Independent t-tests or Mann-Whitney U-tests were used to test group differences between WMHs and HCs. Additionally, WMHs patients were divided into mild and moderate-severe WMHs subgroup according to the Fazekas scale. Analysis of variance (ANOVA) and post-hoc tests were used among WMHs subgroups and HCs. We found there was a significant reduction in GABA+ levels (p = 0.018) in WMHs patients compared with healthy controls. In subgroup analyses, there was also a significant reduction of GABA+ levels in moderate-severe WMHs subgroup (p = 0.037) and mild WMHs subgroup (p = 0.047) when compared to HCs. Besides, the moderate-severe WMHs subgroup had significantly higher levels of tCho compared with healthy controls (p = 0.019). In conclusion, reduced GABA+ levels in WMHs patients and elevated tCho levels in moderate-severe WMHs were observed when compared with HCs. These results demonstrate that abnormalities of the GABAergic system and choline metabolism may contribute to the pathogenesis of WMHs.

IntroductionThe objective of this study was to characterize the alteration patterns of dynamic spatiotemporal activity in chronic subcortical stroke patients with varying motor outcomes, while investigating the imaging indicators relevant to the assessment of potential cognitive deficits in these patients.MethodsA total of 136 patients and 88 normal controls were included in the analysis of static and dynamic intrinsic brain activity, determined by amplitude of low-frequency fluctuations.ResultsThe findings unveiled that subcortical stroke patients exhibited significantly aberrant temporal dynamics of intrinsic brain activity, involving regions within multiple brain networks. These spatiotemporal patterns were found to be contingent upon the side of the lesion. In addition, these aberrant metrics demonstrated potential in discerning cognitive deficits in stroke patients with memory impairment, with the dynamic indices exerting more influence than the static ones. The observe findings may indicate that subcortical stroke can trigger imbalances in the segregation and integration of spatiotemporal patterns across the entire brain with multi-domain networks, especially in patients with poor motor outcomes.ConclusionIt suggests that the temporal dynamics indices of intrinsic brain activity could serve as potential imaging indicators for assessing cognitive impairment in patients with chronic subcortical stroke, which may be associated with the motor outcomes.

Abstract Background Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) is an under-recognized, emerging new entity of sporadic renal neoplasms, which is listed as a rare type of renal cell carcinoma in the 2022 WHO renal tumor classification. It is easily misdiagnosed because its characteristics are insufficiently understood. Case presentation We report one case of ESC-RCC, a 53-year-old female patient with a right kidney mass found during clinical examination. The patient experienced no discomforting symptoms. Computer-tomography imaging at our urinary department showed a round soft tissue density shadow around the right kidney. Microscopic examination revealed a tumor displaying a solid-cystic composition of eosinophilic cells with unique features, revealed by characteristic immunohistochemical markers (CK20-positive/CK7-negative), and a nonsense mutation in TSC2. Ten months after the renal tumor resection, the patient presented in good condition with no recurrence or metastasis. Conclusions The distinct morphological, immunophenotypic, and molecular characteristics of ESC-RCC we describe here, based on our case and the relevant literature, highlight the key points of the pathological and differential diagnosis of this novel renal neoplasm. Our findings will therefore deepen our understanding of this novel renal neoplasm and help reduce misdiagnosis.

Abstract Objective Rheumatoid arthritis (RA) is a typical, progressive autoimmune disease. Its occurrence and development are associated with dysregulation of T and B cell numbers. However, the specific immune characteristics of different RA courses remain incompletely defined. Here, we describe the peripheral blood lymphocyte subsets, particularly CD4 + T subsets, of different RA courses with a focus on early RA (Ea-RA). Methods In all, 131 patients with Ea-RA, 117 with advanced RA (Ad-RA), and 109 with treated RA (Tr-RA) were enrolled. We collected general clinical data. Whole blood samples obtained from the patients and 97 healthy controls (HCs) were analysed via flow cytometry. Results Decreased absolute NK cell numbers and increased CD4/CD8 T cell ratios were observed in different RA groups, including Ea-RA, compared to healthy controls. In Ea-RA patients, the Th17 and Treg cell numbers were similar to those in HCs. We performed k-means clustering based on the profiles of Th17 and Treg cells for patients with multi-stage of RA. We identified three patient types: type A characterised by relatively low Treg and Th17 cell numbers, type B with moderate levels of Treg cells and levels of Th17 cells similar to that of type C patients, and type C with high levels of Treg cells and levels of Th17 cells similar to that of type B patients. Conclusion The immune characteristics of Ea-RA patients differ from those of HCs; an immune system disorder is apparent although no differences in Th17 and Treg levels were evident between Ea-RA patients and HCs. We found distributional heterogeneities of Th17 and Treg cells in patients with multi-stage of RA. Stratified management based on such heterogeneity may serve as a useful novel immunotherapy allowing of early intervention.

Abstract. Background:. China bears the biggest atrial fibrillation (AF) burden in the world. However, little is known about the incidence and predictors of AF. This study aimed to investigate the current incidence of AF and its electrocardiographic (ECG) predictors in general community individuals aged over 60 years in China. Methods:. This was a prospective cohort study, recruiting subjects who were aged over 60 years and underwent annual health checkups from April to July 2015 in four community health centers in Songjiang District, Shanghai, China. The subjects were then followed up from 2015 to 2019 annually. Data on sociodemographic characteristics, medical history, and the resting 12-lead ECG were collected. Kaplan–Meier curve was used for showing the trends in AF incidence and calculating the predictors of AF. Associations of ECG abnormalities and AF incidence were examined using Cox proportional hazard models. Results:. This study recruited 18,738 subjects, and 351 (1.87%) developed AF. The overall incidence rate of AF was 5.2/1000 person-years during an observation period of 67,704 person-years. Multivariable Cox regression analysis indicated age (hazard ratio [HR], 1.07; 95% confidence interval [CI]: 1.06–1.09; P

Abstract Background Little is known on the association of types of grains with mortality and the moderating effect of lifestyle on this association. This study aims to evaluate the single or joint associations of types of grains and lifestyle with all-cause mortality among Chinese older adults. Methods Data were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018. Subjects aged ≥ 65 years were eligible. The types of grains included wheat, total rice, and coarse cereals. Lifestyle was derived using smoking, alcohol consumption, physical activity, and dietary pattern. All-cause mortality was the primary outcome. Results This study included 30275 participants with a mean age 87 ± 11 years and documented 19261 deaths during a mean follow-up of 4.8 years. Compared to wheat, in those with healthy and intermediate lifestyle, total rice was associated with a 13% (HR: 0.87, 95% CI 0.80, 0.93) and 6% (HR: 0.94, 95% CI 0.90, 1.00) lower risk of mortality, respectively, and coarse cereals were associated with a 14% (HR: 0.86, 95% CI 0.74, 1.00) and 12% (HR: 0.88, 95% CI 0.79, 0.97) lower risk of mortality, respectively. Meanwhile, an increase per SD in intakes of wheat and coarse cereals was associated with a 10% (HR: 1.10, 95% CI 1.03, 1.18) and 25% (HR: 1.25, 95% CI 1.08, 1.44) higher mortality rate in those with healthy lifestyle, and a 13% (HR: 1.13, 95% CI 1.08, 1.19) and 29% (HR: 1.29, 95% CI 1.17, 1.44) higher mortality in females but not males. In addition, a U-shaped association of intake of total grains with all- cause mortality was observed (P for non-linearity = 0.002), and a J-shaped association of intake of total rice with all- cause mortality was observed (P for non-linearity = 0.003). Conclusions Specific types of grains and lifestyle were separately or jointly associated with all-cause mortality. Compared to wheat, total rice and coarse cereals were advanced grains for participants with a relatively healthy lifestyle. Intake of total rice was related to all-cause mortality in a dose–response manner. Therefore, a combination of intermediate intake of total rice and healthy lifestyle should be encouraged in older adults.

Summary: Correlation between blood-oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) has been used as an index of neurovascular coupling. Hippocampal BOLD-CBF correlation is associated with neurocognition, and the reduced correlation is associated with neuropsychiatric disorders. We conducted the first genome-wide association study of the hippocampal BOLD-CBF correlation in 4,832 Chinese Han subjects. The hippocampal BOLD-CBF correlation had an estimated heritability of 16.2–23.9% and showed reliable genome-wide significant association with a locus at 3q28, in which many variants have been linked to neuroimaging and cerebrospinal fluid markers of Alzheimer’s disease. Gene-based association analyses showed four significant genes (GMNC, CRTC2, DENND4B, and GATAD2B) and revealed enrichment for mast cell calcium mobilization, microglial cell proliferation, and ubiquitin-related proteolysis pathways that regulate different cellular components of the neurovascular unit. This is the first unbiased identification of the association of hippocampal BOLD-CBF correlation, providing fresh insights into the genetic architecture of hippocampal neurovascular coupling.

The involvement of fine particulate matter (PM2.5) exposure in the progression of asthma has been extensively discussed in epidemiological and experimental evidence, which aroused widespread attention. Asthma is characterized by mucus hypersecretion. This study investigates the underlying toxic mechanism of traffic-related PM2.5 (TRPM2.5) and water-soluble extracts (WSE) on mucus hypersecretion in the lungs of rats with asthma and 16HBE cells. The ovalbumin-induced rats were administrated by instillation of TRPM2.5 and WSE in the trachea once three days for eight times. The results showed that TRPM2.5 and WSE had an adverse impact on mucus secretion. Specifically, conspicuous mucus stains and increased goblet cells in the bronchial epithelium by PAS staining were found in lung tissues of rats with asthma; MUC5AC gene and protein expression levels in lung tissues of rats with asthma and 16HBE cells were elevated. In addition, TRPM2.5 and WSE triggered oxidative damage via upregulation of malondialdehyde and myeloperoxidase as well as activation of the Sestrin2/Keap1/Nrf2 signaling pathway. Conversely, the knockdown of Sestrin2 effectively inhibited TRPM2.5 and WSE-induced mucus hypersecretion, oxidative stress, and Keap1/Nrf2 signaling pathway and its downstream target gene NQO1. Collectively, it was demonstrated that TRPM2.5 and WSE induced mucus hypersecretion mediated by the Sestrin2/Keap1/Nrf2 pathway.

Vascular endothelial polarity induced by blood flow plays crucial roles in the development of atherosclerosis. Loss of endothelial polarity leads to an increase in permeability and leukocyte recruitment, which are crucial hallmarks of atherosclerotic initiation. Endothelial cells exhibit a morphological adaptation to hemodynamic shear stress and possesses planar cell polarity to the direction of blood flow. However, the mechanism of how hemodynamic shear stress regulates endothelial planar cell polarity has not been firmly established. Here, we found that TET1s, a short isoform of Tet methylcytosine dioxygenase 1, was a mediator in the regulation of the planar cell polarity in endothelial cells in response to hemodynamic shear stress. In the process, low expression of TET1s induced by oscillatory shear stress led to the endothelial planar polarity damage through inhibition of F-actin polymerization. TET1s can regulate demethylation level of the sFRP-1 promoter to alter the expression of sFRP-1, which affects the interaction of sFRP-1/Fzd4 and F-actin polymerization. Our study revealed the mechanism of how TET1s mediates endothelial planar cell polarity in response to hemodynamic shear stress and provides a new insight for the prevention of atherosclerosis.

Abstract Design of hydrogels with superior flexible deformability, anti‐fracture toughness, and reliable environment adaption is fundamentally and practically important for diverse hydrogel‐based flexible devices. However, these features can hardly be compatible even in elaborately designed hydrogels. Herein soft hydrogel networks with superior anti‐fracture and deformability are proposed, which show good adaption to extremely harsh saline or alkaline environments. The hydrogel network is one‐step constructed via hydrophobic homogenous cross‐linking of poly (sodium acrylate), which is expected to provide hydrophobic associations and homogeneous cross‐linking for energy dissipation. The obtained hydrogels are quite soft and deformable (tensile modulus: ≈20 kPa, stretchability: 3700%), but show excellent anti‐fracture toughness (10.6 kJ m−2). The energy dissipation mechanism can be further intensified under saline or alkaline environments. The mechanical performance of the hydrophobic cross‐linking topology is inspired rather than weakened by extremely saline or alkaline environments (stretchability: 3900% and 5100%, toughness: 16.1 and 17.1 kJ m−2 under saturated NaCl and 6 mol L−1 NaOH environments, respectively). The hydrogel network also shows good performance in reversible deformations, ion conductivity, sensing strain, monitoring human motions, and freezing resistance under high‐saline environments. The hydrogel network show unique mechanical performance and robust environment adaption, which is quite promising for diverse applications.

Abstract Novel coronary Au@Bi nanospheres (NSs) are simply synthesized by sparkling gold nanoparticles (Au NPs) on the surface of bismuth (Bi) NSs and successfully used as highly impedance‐sensitive immunosensing platform to develop a new label‐free electrochemical immunosensor for the detection of carcinoembryonic antigen (CEA). Firstly, Bi NSs are prepared by one‐pot hydrothermal method, showing uniform sphere morphology with a dense oxide film formed outside Bi NSs due to the easy oxidation of Bi in the air. The oxide film significantly hinders the transmission of electrons and effectively improves the sensitivity of the proposed electrochemical impedance immunosensor. The surface functionalization of Bi NSs with Au NPs enhances the biocompatibility, stability, as well as active surface area of the produced Au@Bi NSs, preferable for the efficient loading of antibody molecules. The electrochemical impedance spectroscopy (EIS) is selected as the optical technique to measure CEA with the constructed immunosensor based on Au@Bi NSs. Because of the excellent impedance‐responsive performance, this new immunosensor displays highly sensitive detection toward CEA in a linear range of 50 fg mL−1–100 ng mL−1 with an extremely low detection limit of 9.83 fg mL−1 and could be potentially used in early clinical detection of cancer.

The risk for motor and cognitive impairment is increased in patients with chronic pontine infarction (PI). In this study, we attempted to explore the alterations of neurovascular coupling (NVC) in order to understand the neural basis of behavioral impairment after PI. Three-dimensional pseudo-continuous arterial spin labeling (3D-pcASL) and resting-state functional magnetic resonance imaging (rs-fMRI) were applied in 49 patients with unilateral PI (left-sided, n = 26; right-sided, n = 23) and 30 matched normal subjects to assess whole-brain cerebral blood flow (CBF) and functional connectivity strength (FCS). We evaluated NVC in each subject by calculating the correlation coefficient between the whole-brain CBF and FCS (CBF-FCS coupling) and the ratio between voxel-wise CBF and FCS (CBF/FCS ratio). The FCS maps were then divided into long-range and short-range FCS to identify the influence of connection distance. The results indicated that the CBF-FCS coupling in the whole-brain level was significantly interrupted in PI patients, and the CBF/FCS ratio in cognition-related brain regions was abnormal. Distance-dependent results demonstrated that PI had a more serious effect on long-range neurovascular coupling. Correlation analysis revealed that the changes in neurovascular coupling were correlated with working memory scores. These findings imply that disruption of neurovascular coupling in the remote-infarction brain regions may underlie the impaired cognitive functions in chronic PI.

Abstract Background Septic arthritis requires prompt diagnosis and treatments. Rare pathogens should be considered when patients respond poorly to the initial antibiotic treatments. Ureaplasma parvum is an opportunistic pathogen that commonly resides in the human urogenital tract. Its infection commonly causes hyperammonemia. Hyperammonemia from Ureaplasma parvum septic arthritis has never been reported previously. Case presentation A 65-year-old male presented with fever and left lower leg pain and swelling for more than ten days. Septic arthritis and sepsis were considered after laboratory tests and arthrocentesis. However, he responded poorly to the antibiotic treatments, including cefoperazone-sulbactam, imipenem-cilastatin, and linezolid. His mental status deteriorated rapidly with elevated blood ammonia levels with unremarkable liver function test and sonogram examination results. Despite the treatments with lactulose, L-ornithine L-aspartate, mannitol, and hemodialysis therapy to lower his ammonia level, his blood ammonia level remained persistently high. Finally, metagenomic sequencing of the left knee synovial fluid reported Ureaplasma parvum, which was considered to contribute to his hyperammonemia. Conclusion Ureaplasma parvum could cause septic arthritis with hyperammonemia. Genetic tests, such as polymerase chain reaction and next-generation sequencing techniques, could provide a sensitive and fast diagnosis of Ureaplasma parvum.

Peptide transporter 2 (PepT2) transports short peptides from the blood into bovine mammary epithelial cells (BMEC) to stimulate milk protein synthesis. Despite the fact that the effect of PepT2 is acknowledged in BMEC, little is known about its regulation. This study was completed to investigate the role of mammalian target of the rapamycin (mTOR) signaling in regulating the expression and function of PepT2 in BMEC. The regulation of PepT2 by mTOR in BMEC was studied in vitro using peptide transport assay, gene silencing, Western blot. The membrane expression of PepT2 and the uptake of β-Ala-Lys-N-7-amino-4-methylcoumarin-3-acetic acid (β-Ala-Lys-AMCA), a model dipeptide, in BMEC were reduced by rapamycin (a mTOR inhibitor) and silencing of either mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2), stimulated by DEP domain-containing mTOR-interacting protein (DEPTOR, endogenous inhibitor of mTORC1 and mTORC2) silencing. The trafficking of PepT2 to the membrane and the uptake of β-Ala-Lys-AMCA was promoted by neuronal precursor cell-expressed developmentally down-regulated 4 isoform 2 (Nedd4-2) silencing. The effects of knockdown of mTORC1, but not mTORC2, on cell membrane expression and transport activity of PepT2 was abolished by Nedd4-2 silencing. With immunofluorescence staining, PepT2 was identified to be interacting with Nedd4-2. The Nedd4-2 expression and the interaction between PepT2 and Nedd4-2 was increased through mTORC1 knockdown, indicating an increased ubiquitination of PepT2. The results revealed that mTORC1 can regulate the expression and function of PepT2 through Nedd4-2 in BMEC.

Background and objectiveThe cortico–hippocampal network is an emerging neural framework with striking evidence that it supports cognition in humans, especially memory; this network includes the anterior temporal (AT) system, the posterior medial (PM) system, the anterior hippocampus (aHIPPO), and the posterior hippocampus (pHIPPO). This study aimed to detect aberrant patterns of functional connectivity within and between large-scale cortico–hippocampal networks in first-episode schizophrenia patients compared with a healthy control group via resting-state functional magnetic resonance imaging (rs-fMRI) and to explore the correlations of these aberrant patterns with cognition.MethodsA total of 86 first-episode, drug-naïve schizophrenia patients and 102 healthy controls (HC) were recruited to undergo rs-fMRI examinations and clinical evaluations. We conducted large-scale edge-based network analysis to characterize the functional architecture of the cortico–hippocampus network and investigate between-group differences in within/between-network functional connectivity. Additionally, we explored the associations of functional connectivity (FC) abnormalities with clinical characteristics, including scores on the Positive and Negative Syndrome Scale (PANSS) and cognitive scores.ResultsCompared with the HC group, schizophrenia patients exhibited widespread alterations to within-network FC of the cortico–hippocampal network, with decreases in FC involving the precuneus (PREC), amygdala (AMYG), parahippocampal cortex (PHC), orbitofrontal cortex (OFC), perirhinal cortex (PRC), retrosplenial cortex (RSC), posterior cingulate cortex (PCC), angular gyrus (ANG), aHIPPO, and pHIPPO. Schizophrenia patients also showed abnormalities in large-scale between-network FC of the cortico–hippocampal network, in the form of significantly decreased FC between the AT and the PM, the AT and the aHIPPO, the PM and the aHIPPO, and the aHIPPO and the pHIPPO. A number of these signatures of aberrant FC were correlated with PANSS score (positive, negative, and total score) and with scores on cognitive test battery items, including attention/vigilance (AV), working memory (WM), verbal learning and memory (Verb_Lrng), visual learning and memory (Vis_Lrng), reasoning and problem-solving (RPS), and social cognition (SC).ConclusionSchizophrenia patients show distinct patterns of functional integration and separation both within and between large-scale cortico–hippocampal networks, reflecting a network imbalance of the hippocampal long axis with the AT and PM systems, which regulate cognitive domains (mainly Vis_Lrng, Verb_Lrng, WM, and RPS), and particularly involving alterations to FC of the AT system and the aHIPPO. These findings provide new insights into the neurofunctional markers of schizophrenia.

Bovine parvovirus (BPV) is a pathogen responsible for respiratory and digestive tract symptoms in calves and abortion and stillbirth in pregnant cows. In this study, we developed a colloidal gold immunochromatographic (GICG) strip with an enhanced signal for detecting BPV according to the double-antibody sandwich principle and an enzyme-based signal amplification system to amplify the signal. This system utilizes horseradish peroxidase reacting with a substrate solution containing 3,3′,5,5′-tetramethylbenzidine and dextran sulfate to obtain insoluble blue products on the test and control lines. We optimized different reaction conditions, including the amount of monoclonal antibodies (mAbs), pH of the colloidal gold solution, coating solution, blocking solution, sample pad treatment solution, antibody concentration in the control line, and antibody concentration in the detection line. The sensitivity of the signal-enhanced GICG strip showed that the minimum amount for detecting BPV was 102 TCID50, 10 times higher than that of the traditional GICG strip. The results of the specificity test showed that the signal-enhanced GICG strip had no cross-reactivity with BRV, BVDV, or BRSV. The results of the repeatability test showed that the coefficient of variation between and within batches was less than 5%, showing good repeatability. Moreover, for validation, PCR and the signal-enhanced GICG strip were used to detect 280 clinical bovine fecal samples. The concordance rate compared with PCR was 99.29%. Hence, the developed strip exhibited high sensitivity and specificity for the detection of BPV. Therefore, this strip could be a rapid, convenient, and effective method for the diagnosis of BPV infection in the field.

Abstract Though thermoresponsive lower critical solution temperature (LCST) hydrogels have attracted intense attention to be applied in smart windows, less efforts are paid on the LCST effect on the heat transfer process. Herein, the research mainly focuses on heat transfer process of thermoresponsive PNIPAm hydrogels. It is the first time reported that LCST behaviors can decrease thermal conductivity upon heating process. To be utilized as a smart window, thermal conduction flux is investigated yet the thermal conduction energy occupies little to manage the thermal transfer process in a model house. It is found that radiation thermal transfer predominates the heat transfer process for PNIPAm‐based smart windows. These results are meaningful to provide basic data for energy transfer in using thermoresponsive hydrogels.

Background: Urbanicity refers to the conditions that are particular to urban areas and is a growing environmental challenge that may affect hippocampus and neurocognition. This study aimed to investigate the effects of the average pre-adulthood urbanicity on hippocampal subfield volumes and neurocognitive abilities as well as the sensitive age windows of the urbanicity effects. Participants and methods: We included 5,390 CHIMGEN participants (3,538 females; age: 23.69 ± 2.26 years, range: 18–30 years). Pre-adulthood urbanicity of each participant was defined as the average value of annual night-time light (NL) or built-up% from age 0–18, which were extracted from remote-sensing satellite data based on annual residential coordinates of the participants. The hippocampal subfield volumes were calculated based on structural MRI and eight neurocognitive measures were assessed. The linear regression was applied to investigate the associations of pre-adulthood NL with hippocampal subfield volumes and neurocognitive abilities, mediation models were used to find the underlying pathways among urbanicity, hippocampus and neurocognition, and distributed lag models were used to identify sensitive age windows of urbanicity effect. Results: Higher pre-adulthood NL was associated with greater volumes in the left (β = 0.100, 95%CI: [0.075, 0.125]) and right (0.078, [0.052, 0.103]) fimbria and left subiculum body (0.045, [0.020, 0.070]) and better neurocognitive abilities in information processing speed (-0.212, [-0.240, −0.183]), working memory (0.085, [0.057, 0.114]), episodic memory (0.107, [0.080, 0.135]), and immediate (0.094, [0.065, 0.123]) and delayed (0.087, [0.058, 0.116]) visuospatial recall, and hippocampal subfield volumes and visuospatial memory showed bilateral mediations for the urbanicity effects. Urbanicity effects were greatest on the fimbria in preschool and adolescence, on visuospatial memory and information processing from childhood to adolescence and on working memory after 14 years. Conclusion: These findings improve our understanding of the impact of urbanicity on hippocampus and neurocognitive abilities and will benefit for designing more targeted intervention for neurocognitive improvement.

ObjectiveThe purpose of the study was to investigate the abnormality both of static spontaneous brain activity and dynamic temporal variances following a pontine infarction.MethodsForty-six patients with chronic left pontine infarction (LPI), thirty-two patients with chronic right pontine infarction (RPI), and fifty healthy controls (HCs) were recruited for the study. The static amplitude of low-frequency fluctuations (sALFF), static regional homogeneity (sReHo), dynamic ALFF (dALFF), and dynamic ReHo (dReHo) were employed to detect the alterations in brain activity induced by an infarction. The Rey Auditory Verbal Learning Test and Flanker task were used to evaluate the verbal memory and visual attention function, respectively. Receiver operating characteristic curve analysis was used to reveal the potential capacity of these metrics to distinguish the patients from HCs.ResultsThere were significant variations of these static and dynamic metrics in patients with chronic pontine infarction. The altered regions involved the supratentorial regions, including cortex and subcortical. Moreover, the altered metrics were significantly correlated with verbal memory and visual attention. In addition, these static and dynamic metrics also showed potential in distinguishing stroke patients with behavior deficits from HCs.ConclusionThe pontine infarction-induced cerebral activation changes are observed in both motor and cognitive systems, indicating the functional damage and reorganization across the global cerebral level in these patients with subtentorial infarction, and there is a reciprocal effect between motor and cognitive impairment and repair.

BackgroundThe increased risk of metabolic syndrome (MetS) during the menopausal transition might partly attribute to the changes in follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, few studies were conducted to examine the associations of FSH and LH concentrations with MetS at the full range of reproductive aging, especially in the US population. The aim of this study is to examine the associations of FSH, LH, and LH/FSH ratio with the risk of MetS and severity score in the US women.MethodsData were derived from the National Health and Nutrition Examination Survey. Women aged from 35 to 60 years were eligible. MetS was defined as having at least 3 of the following: a waist circumference ≥ 88 cm, a triglycerides level ≥ 150 mg/dL, a high density lipoprotein < 50 mg/dL, a systolic blood pressure ≥ 130 mm Hg or a diastolic blood pressure ≥ 85 mm Hg or taking hypertension medications, or a fasting plasma glucose level ≥100 mg/dL or taking diabetes medications. The MetS severity score was calculated according to race/ethnicity- specific equation.ResultsThere were 3,831 women included in this study. Increases in serum FSH and LH levels per 1 SD were separately linked to a 22.6% (OR: 0.774; 95% CI: 0.646, 0.929; and P= 0.006) and 18.5% (OR: 0.815; 95% CI: 0.690, 0.962; and P= 0.006) lower risk of MetS only in postmenopausal women. Meanwhile, increases in serum FSH and LH levels per 1SD were associated with a decrease of -0.157 (95% CI :-2.967, -2.034) and -0.078 (95% CI: -2.688, -1.806) MetS severity score in perimenopausal women and -0.195 (95% CI: -2.192, -1.023) and -0.098 (95% CI:-1.884, -0.733) in postmenopausal women. However, LH/FSH ratio had no connections with the risk of MetS and MetS severity score across the menopausal transition.ConclusionsElevated serum FSH and LH levels, but not LH/FSH ratio, were associated with a lower risk of MetS and MetS severity score, especially in postmenopausal women. Therefore, serum FSH and LH levels might be efficient predictors for screening and identifying women at risk of MetS across the menopausal transition.

Background and objectiveThe pathogenesis of schizophrenia (SCH) is related to the dysfunction of monoamine neurotransmitters, and the habenula participates in regulating the synthesis and release of dopamine. We examined the static functional connectivity (sFC) and dynamic functional connectivity (dFC) of habenula in first-episode schizophrenia patients using resting state functional magnetic resonance imaging (rs-fMRI) in this study.MethodsA total of 198 first-Episode, drug-Naïve schizophrenia patients and 199 healthy controls (HC) underwent rs-fMRI examinations. The sFC and dFC analysis with habenula as seed was performed to produce a whole-brain diagram initially, which subsequently were compared between SCH and HC groups. Finally, the correlation analysis of sFC and dFC values with the Positive and Negative Symptom Scale (PANSS) were performed.ResultsCompared with the HC groups, the left habenula showed increased sFC with the bilateral middle temporal gyrus, bilateral superior temporal gyrus, and right temporal pole in the SCH group, and the right habenula exhibited increased sFC with the left middle temporal gyrus, left superior temporal gyrus, and left angular gyrus. Additionally, compared with the HC group, the left habenula showed decreased dFC with the bilateral cuneus gyrus and bilateral calcarine gyrus in the SCH group. The PANSS negative sub-scores were positively correlated with the sFC values of the bilateral habenula with the bilateral middle temporal gyrus, superior temporal gyrus and angular gyrus. The PANSS general sub-scores were positively correlated with the sFC values of the right habenula with the left middle temporal gyrus and left superior temporal gyrus. The hallucination scores of PANSS were negatively correlated with the sFC values of the left habenula with the bilateral cuneus gyrus and bilateral calcarine gyrus; The anxiety scores of PANSS were positively correlated with the dFC values of the left habenula with the right temporal pole.ConclusionThis study provides evidence that the habenula of the first-episode schizophrenia patients presented abnormal static functional connectivity with temporal lobe and angular gyrus, and additionally showed weakened stability of functional connectivity in occipital lobe. This abnormality is closely related to the symptoms of hallucination and anxiety in schizophrenia, which may indicate that the habenula involved in the pathophysiology of schizophrenia by affecting the dopamine pathway.

BackgroundNeurobiological models to explain the vulnerability of autism spectrum disorders (ASDs) are scarce, and previous resting-state functional magnetic resonance imaging (rs-fMRI) studies mostly examined static functional connectivity (FC). Given that FC constantly evolves, it is critical to probe FC dynamic differences in ASD patients.MethodsWe characterized recurring phase-locking (PL) states during rest in 45 ASD patients and 47 age- and sex-matched healthy controls (HCs) using Leading Eigenvector Dynamics Analysis (LEiDA) and probed the organization of PL states across different fine grain sizes.ResultsOur results identified five different groups of discrete resting-state functional networks, which can be defined as recurrent PL state overtimes. Specifically, ASD patients showed an increased probability of three PL states, consisting of the visual network (VIS), frontoparietal control network (FPN), default mode network (DMN), and ventral attention network (VAN). Correspondingly, ASD patients also showed a decreased probability of two PL states, consisting of the subcortical network (SUB), somatomotor network (SMN), FPN, and VAN.ConclusionOur findings suggested that the temporal reorganization of brain discrete networks was closely linked to sensory to cognitive systems of the brain. Our study provides new insights into the dynamics of brain networks and contributes to a deeper understanding of the neurological mechanisms of ASD.

Abstract Objective To identify lymphocyte and CD4 + T cell subset characteristics, particularly regulatory T cells (Tregs), in active rheumatoid arthritis (RA) patients with coronary artery disease (CAD). Methods A total of 54 RA patients with CAD (RA-CAD group), 43 RA patients without CAD (pure RA group), and 43 healthy controls (HC group) were enrolled. The absolute number and frequency of lymphocyte subpopulations and CD4 + T cell subsets were analyzed by flow cytometry. Serum levels of cytokines were analyzed using a cytometric bead array. Clinical and laboratory data were collected retrospectively and their correlation with CD4 + T subsets were analyzed. Results There was a significant decrease in the absolute number of Treg cells (CD4 + CD25 + Foxp3 + T cells) in the RA-CAD group compared to the pure RA group (p

The hard-end is a disorder of pear fruit, however, the mechanisms underlying its development remain unknown. In this study, we found that the hard-end fruit contained a higher transcript abundance level of ethylene-response factor 1b-like (PpERF1b-like) and released more ethylene compared to normal pear. In the ethephon treated normal fruit, flesh tissues accumulated more lignin together with elevated expression of PpERF1b-like. Overexpressing PpERF1b-like transiently in fruit and stably in callus increased lignin accumulation and the expression of lignin biosynthesis genes; the opposite results were observed in fruit showing repressed expression of PpERF1b-like. These results confirmed the role of PpERF1b-like in promoting hard-end formation through promoting lignin synthesis. This study provided valuable information for further clarifying the regulation of hard-end formation in pear.

ObjectiveIn order to determine whether the immune balance of T helper 17(Th17)/regulatory T(Treg) is related to the pathogenesis of idiopathic retroperitoneal fibrosis (IRPF), we analyzed the differences in peripheral blood lymphocytes, CD4+T cell subsets and cytokines between patients with IRPF and healthy people to clarify the CD4+T cell subsets, especially Treg cell subsets, and the role of cytokines in the pathogenesis of IRPF.MethodsThis study included 22 patients with IRPF, 36 patients with IgG4-related diseases (IgG4-RD) without retroperitoneal fibrosis (RPF), and 28 healthy controls. The absolute numbers and percentage of peripheral blood lymphocyte subsets and CD4+T cell subsets in each group were detected by flow cytometry, and the serum cytokine level was detected by flow cytometric bead array (CBA).ResultsCompared with the healthy group, the absolute value of B cells in peripheral blood of IRPF patients was significantly decreased, and T, natural killer (NK), CD4+ and CD8+ were not significantly abnormal. The absolute numbers of Th2 cells were lower than healthy group(p=0.043). In particular, the absolute numbers of Treg cells were significantly lower than healthy group(p

Δ1-Pyrroline-5-carboxylate synthetase (P5CS) acts as the rate-limiting enzyme in the biosynthesis of proline in plants. Although P5CS plays an essential role in plant responses to environmental stresses, its biological functions remain largely unclear in pear (Pyrus betulifolia). In the present study, 11 putative pear P5CSs (PbP5CSs) were identified by comprehensive bioinformatics analysis and classified into five subfamilies. Segmental and tandem duplications contributed to the expansion and evolution of the PbP5CS gene family. Various cis-acting elements associated with plant development, hormone responses, and/or stress responses were identified in the promoters of PbP5CS genes. To investigate the regulatory roles of PbP5CS genes in response to abiotic and biotic stresses, gene expression patterns in publicly available data were explored. The tissue-specific expressional dynamics of PbP5CS genes indicate potentially important roles in pear growth and development. Their spatiotemporal expression patterns suggest key functions in multiple environmental stress responses. Transcriptome and real-time quantitative PCR analyses revealed that most PbP5CS genes exhibited distinct expression patterns in response to drought, waterlogging, salinity-alkalinity, heat, cold, and infection by Alternaria alternate and Gymnosporangium haraeanum. The results provide insight into the versatile functions of the PbP5CS gene family in stress responses. The findings may assist further exploration of the physiological functions of PbP5CS genes for the development and enhancement of stress tolerance in pear and other fruits.

Malus hupehensis is one of the most widely used apple rootstocks in china but is severely damaged by alkaline soil. Alkaline stress can cause more serious harmful effects on apple plants than salt stress because it also induces high pH stress except for ion toxicity, osmotic stress, and oxidative damage. Brassinolide (BL) plays important roles in plant responses to salt stress. However, its role and function mechanism in apple plants in response to alkaline stress has never been reported. This study showed that applying exogenous 0.2 mg/L BL significantly enhanced the resistance of M. hupehensis seedlings to alkaline stress. The main functional mechanisms were also explored. First, exogenous BL could decrease the rhizosphere pH and promote Ca2+ and Mg2+ absorption by regulating malic acid and citric acid contents and increasing H+ excretion. Second, exogenous BL could alleviate ion toxicity caused by alkaline stress through enhancing Na+ efflux and inhibiting K+ expel and vacuole compartmentalization. Last, exogenous BL could balance osmotic stress by accumulating proline and reduce oxidative damage through increasing the activities of antioxidant enzymes and antioxidants contents. This study provides an important theoretical basis for further analyzing the mechanism of exogenous BL in improving alkaline tolerance of apple plants.

Abstract Background Resveratrol (Res), a phytoalexin, has been widely reported to participate in plant resistance to fungal infections. However, little information is available on its role in abiotic stress, especially in iron deficiency stress. Malus baccata is widely used as apple rootstock in China, but it is sensitive to iron deficiency. Results In this study, we investigated the role of exogenous Res in M. baccata seedings under iron deficiency stress. Results showed that applying 100 μM exogenous Res could alleviate iron deficiency stress. The seedlings treated with Res had a lower etiolation rate and higher chlorophyll content and photosynthetic rate compared with the apple seedlings without Res treatment. Exogenous Res increased the iron content in the roots and leaves by inducing the expression of MbAHA genes and improving the H+-ATPase activity. As a result, the rhizosphere pH decreased, iron solubility increased, the expression of MbFRO2 and MbIRT1 was induced, and the ferric-chelated reductase activity was enhanced to absorb large amounts of Fe2+ into the root cells under iron deficiency conditions. Moreover, exogenous Res application increased the contents of IAA, ABA, and GA3 and decreased the contents of DHZR and BL for responding to iron deficiency stress indirectly. In addition, Res functioned as an antioxidant that strengthened the activities of antioxidant enzymes and thus eliminated reactive oxygen species production induced by iron deficiency stress. Conclusion Resveratrol improves the iron deficiency adaptation of M. baccata seedlings mainly by regulating iron absorption.

Although immunotherapy has made great strides in cancer therapy, its effectiveness varies widely among individual patients as well as tumor types, and there is an urgent need to develop biomarkers for effectively assessing immunotherapy response. In recent years, RNA methylation regulators have demonstrated to be novel potential biomarkers for prognosis as well as immunotherapy of cancers, such as N6-methyladenine (m6A) and 5-methylcytosine (m5C). N7-methylguanosine (m7G) is a prevalent RNA modification in eukaryotes, but the relationship between m7G regulators and prognosis as well as tumor immune microenvironment is still unclear. In this study, a pan-cancer analysis of 26 m7G regulators across 17 cancer types was conducted based on the bioinformatics approach. On the one hand, a comprehensive analysis of expression features, genetic variations and epigenetic regulation of m7G regulators was carried out, and we found that the expression tendency of m7G regulators were different among tumors and their aberrant expression in cancers could be affected by single nucleotide variation (SNV), copy number variation (CNV), DNA methylation and microRNA (miRNA) separately or simultaneously. On the other hand, the m7Gscore was modeled based on single sample gene set enrichment analysis (ssGSEA) for evaluating the relationships between m7G regulators and cancer clinical features, hallmark pathways, tumor immune microenvironment, immunotherapy response as well as pharmacotherapy sensitivity, and we illustrated that the m7Gscore exhibited tight correlations with prognosis, several immune features, immunotherapy response and drug sensitivity in most cancers. In conclusion, our pan-cancer analysis revealed that m7G regulators may exert critical roles in the tumor progression and immune microenvironment, and have the potential as biomarkers for predicting prognosis, immunotherapy response as well as candidate drug compounds for cancer patients.

Background and objectiveAs a key feature of schizophrenia, auditory verbal hallucination (AVH) is causing concern. Altered dynamic functional connectivity (dFC) patterns involving in auditory related regions were rarely reported in schizophrenia patients with AVH. The goal of this research was to find out the dFC abnormalities of auditory related regions in first-episode, drug-naïve schizophrenia patients with and without AVH using resting state functional magnetic resonance imaging (rs-fMRI).MethodsA total of 107 schizophrenia patients with AVH, 85 schizophrenia patients without AVH (NAVH) underwent rs-fMRI examinations, and 104 healthy controls (HC) were matched. Seed-based dFC of the primary auditory cortex (Heschl's gyrus, HES), auditory association cortex (AAC, including Brodmann's areas 22 and 42), and medial geniculate nucleus (MGN) was conducted to build a whole-brain dFC diagram, then inter group comparison and correlation analysis were performed.ResultsIn comparison to the NAVH and HC groups, the AVH group showed increased dFC from left ACC to the right middle temporal gyrus and right middle occipital gyrus, decreased dFC from left HES to the left superior occipital gyrus, left cuneus gyrus, left precuneus gyrus, decreased dFC from right HES to the posterior cingulate gyrus, and decreased dFC from left MGN to the bilateral calcarine gyrus, bilateral cuneus gyrus, bilateral lingual gyrus. The Auditory Hallucination Rating Scale (AHRS) was significantly positively correlated with the dFC values of cluster 1 (bilateral calcarine gyrus, cuneus gyrus, lingual gyrus, superior occipital gyrus, precuneus gyrus, and posterior cingulate gyrus) using left AAC seed, cluster 2 (right middle temporal gyrus and right middle occipital gyrus) using left AAC seed, cluster 1 (bilateral calcarine gyrus, cuneus gyrus, lingual gyrus, superior occipital gyrus, precuneus gyrus and posterior cingulate gyrus) using right AAC seed and cluster 2 (posterior cingulate gyrus) using right HES seed in the AVH group. In both AVH and NAVH groups, a significantly negative correlation is also found between the dFC values of cluster 2 (posterior cingulate gyrus) using the right HES seed and the PANSS negative sub-scores.ConclusionsThe present findings demonstrate that schizophrenia patients with AVH showed multiple abnormal dFC regions using auditory related cortex and nucleus as seeds, particularly involving the occipital lobe, default mode network (DMN), and middle temporal lobe, implying that the different dFC patterns of auditory related areas could provide a neurological mechanism of AVH in schizophrenia.

ObjectiveThis study aimed to analyze the application value of blood metagenomic next-generation sequencing (mNGS) in patients with connective tissue diseases (CTDs) to provide a reference for infection diagnosis and guidance for treatment.MethodsA total of 126 CTD patients with suspected infections who were hospitalized in the Department of Rheumatology, the Second Hospital of Shanxi Medical University from January 2020 to December 2021 were enrolled in this study. We retrospectively reviewed the results of mNGS and conventional diagnostic tests (CDTs).ResultsSystemic lupus erythematosus (SLE) and polymyositis/dermatomyositis (DM/PM) had the highest incidence of infections. The positive pathogen detection rates of mNGS were higher than those of CDT. The virus infections are the most common type in CTD patients with single or mixed infection, especially Human gammaherpesvirus 4 (EBV), Human betaherpesvirus 5 (CMV), and Human alphaherpesvirus 1. The incidence of prokaryote and eukaryote infections is secondary to viruses. Bloodstream infections of rare pathogens such as Pneumocystis jirovecii should be of concern. Meanwhile, the most common mixed infection was bacterial–virus coinfection.ConclusionmNGS has incremental application value in patients with CTD suspected of co-infection. It has a high sensitivity, and a wide detection range for microorganisms in CTD patients. Furthermore, the high incidence of opportunistic virus infections in CTD patients should be of sufficient concern.