Multi-omics analysis reveals the impact of gut microbiota on antipsychotic-induced weight gain in schizophrenia.

Emerging evidence indicates that gut microbial dysbiosis is associated with the development of antipsychotic-induced weight gain in schizophrenia (SZ). However, the exact taxonomic composition and functionality that constitute the "obesogenic" microbial profile remain elusive. Our retrospective survey identified two groups of the SZ population separated by BMI, with 1/3 of patients developing overweight/obesity after chronic antipsychotic treatment. Based on multi-omics analysis, we observed altered gut microbiota in SZ patients with overweight/obesity, characterized by a reduction in several beneficial bacteria genera, including Bacteroides, Parabacteroides, Akkermansia, and Clostridium. This microbial dysbiosis was accompanied by disrupted energy expenditure and nutritional metabolism, worsened metabolic indices, and reduced levels of beneficial metabolites, e.g. indole-3-carboxylic acid and propionic acid. Moreover, leveraging data from first-episode drug-naïve schizophrenia (FSZ) patients at one-month and one-year follow-up, both artificial neural network and random forest classifier-based prediction models demonstrated a strong ability of microbial profiles to predict antipsychotic-induced weight gain. Importantly, FSZ patients with higher relative abundance of Parabacteria distasonis were less susceptible to antipsychotic-induced weight gain. Thus, gut microbiota could serve as a noninvasive approach to predict antipsychotic-induced weight gain, guiding clinical antipsychotics administration and developing novel therapeutic strategies for weight management in SZ.

Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis.

BACKGROUND: Cholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated. METHODS: Extrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8+ T cells were performed to study the immune-suppressive effect of phenotypic-altered neutrophils. Clinical samples collected from colorectal cancer patients with liver metastasis and cholestasis were applied to RNA-Seq. RESULTS: Compared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-ß-muricholic acid (Tß-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8+ T cells, indicating that the immunosuppressive phenotype of neutrophils was directly induced by BAs. Importantly, targeting BA anabolism with Obeticholic acid (OCA) under cholestasis effectively suppressed liver metastasis progression, enhanced the efficacy of immune checkpoint blockade, and prolonged survival of mice. CONCLUSIONS: Our study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism.

Porphyrin-Based Organic Nanoparticles with NIR-IIa Fluorescence for Orthotopic Glioblastoma Theranostics.

The development of efficient theranostic nanoagents for the precise diagnosis and targeted therapy of glioblastoma (GBM) remains a big challenge. Herein, we designed and developed porphyrin-based organic nanoparticles (PNP NPs) with strong emission in the near-infrared IIa window (NIR-IIa) for orthotopic GBM theranostics. PNP NPs possess favorable photoacoustic and photothermal properties, high photostability, and low toxicity. After modification with the RGD peptide, the obtained PNPD NPs exhibited enhanced blood-brain barrier (BBB) penetration capability and GBM targeting ability. NIR-IIa imaging was employed to monitor the in vivo biodistribution and accumulation of the nanoparticles, revealing a significant enhancement in penetration depth and signal-to-noise ratio. Both in vitro and in vivo results demonstrated that PNPD NPs effectively inhibited the proliferation of tumor cells and induced negligible side effects in normal brain tissues. In general, the work presented a kind of brain-targeted porphyrin-based NPs with NIR-IIa fluorescence for orthotopic glioblastoma theranostics, showing promising prospects for clinical translation.

Characterization of winter PM2.5 source contributions and impacts of meteorological conditions and anthropogenic emission changes in the Sichuan Basin, 2002-2020.

In this study, the Weather Research and Forecasting (WRF) model and Community Multiscale Air Quality-Integrated Source Apportionment Method (CMAQ-ISAM) were utilized, which were integrated with the Multiresolution Emission Inventory for China (MEIC) emission inventory, to simulate winter PM2.5 concentrations, regional transport, and changes in emission source contributions in the Sichuan basin (SCB) from 2002 to 2020, considering variations in meteorological conditions and anthropogenic emissions. The results indicated a gradual decrease in the basin's winter average PM2.5 concentration from 300 µg/m3 to 120 µg/m3, with the most significant decrease occurring after 2014, reflecting the actual impact of China's air pollution control measures. Spatially, the main pollution area shifted from Chongqing to Chengdu and the western basin. The sources of PM2.5 at the eastern and western margins of the basin have remained stable and have been dominated by local emissions for many years, while the sources of PM2.5 in the central part of the basin have evolved from a multiregional co-influenced source during the early period to a high proportion of local emissions; except for boundary condition sources, residential sources were the main PM2.5 sources in the basin (approximately 29.70 %), followed by industrial sources (approximately 14.11 %). Industrial sources exhibited higher contributions in Chengdu and Chongqing and gradually stabilized with residential sources over the years, while residential sources dominated in the eastern and western parts of the basin and exhibited a declining trend. Meteorological conditions exacerbated pollution in the whole basin from 2008 to 2014, especially in the west (21-40 µg/m3). The eastern basin and Chongqing exhibited more years with alleviated meteorological pollution, including a 40+ µg/m3 decrease in Chongqing from 2002 to 2005. Reduced anthropogenic emissions alleviated annual pollution levels, with a greater reduction (> -20 µg/m3) after 2011 due to pollution control measures.

Fabricating a high-performance anode by coating a carbon layer on a yolk-shell bimetallic selenide microsphere for enhanced lithium storage.

The rational synthesis of an electrode material with a highly active and stable architecture is very critical to achieving high-performance electrochemical energy storage. Herein, N-doped carbon restricting yolk-shell CoSe2/Ni3Se4 (CoSe2/Ni3Se4@NC) flower-like microspheres were successfully synthesized from solid CoNi-glycerate microspheres using a coating technology as an anode material for lithium-ion batteries (LIBs). The unique yolk-shell CoSe2/Ni3Se4@NC microspheres with hierarchical pores can increase the contact area with the electrolyte and provide enough transfer channels for the diffusion of Li+. The carbon layer on the surface of CoSe2/Ni3Se4@NC can not only improve the conductivity of the electrode but also provide the protective effect of active nanosheets during the process of synthesis, avoiding the overall structure collapse during the charge/discharge process of LIBs. Benefiting from the high conductivity, hollow structure, and elastic NC shell bestowed by the unique architecture, the yolk-shell CoSe2/Ni3Se4@NC anode shows excellent lithium storage performances, such as an excellent reversible specific capacity of 319 mA h g-1 at a current density of 1000 mA g-1 after 500 cycles and excellent cycling stability. This synthesis strategy provides a new way to optimize the lithium storage performance of transition metal compound electrode materials, which is helpful to the design of the next generation of high-performance LIBs.

Multi-omic characterization of allele-specific regulatory variation in hybrid pigs.

Hybrid mapping is a powerful approach to efficiently identify and characterize genes regulated through mechanisms in cis. In this study, using reciprocal crosses of the phenotypically divergent Duroc and Lulai pig breeds, we perform a comprehensive multi-omic characterization of regulatory variation across the brain, liver, muscle, and placenta through four developmental stages. We produce one of the largest multi-omic datasets in pigs to date, including 16 whole genome sequenced individuals, as well as 48 whole genome bisulfite sequencing, 168 ATAC-Seq and 168 RNA-Seq samples. We develop a read count-based method to reliably assess allele-specific methylation, chromatin accessibility, and RNA expression. We show that tissue specificity was much stronger than developmental stage specificity in all of DNA methylation, chromatin accessibility, and gene expression. We identify 573 genes showing allele specific expression, including those influenced by parent-of-origin as well as allele genotype effects. We integrate methylation, chromatin accessibility, and gene expression data to show that allele specific expression can be explained in great part by allele specific methylation and/or chromatin accessibility. This study provides a comprehensive characterization of regulatory variation across multiple tissues and developmental stages in pigs.

H-Net: Heterogeneous Neural Network for Multi-Classification of Neuropsychiatric Disorders.

Clinical studies have proved that both structural magnetic resonance imaging (sMRI) and functional magnetic resonance imaging (fMRI) are implicitly associated with neuropsychiatric disorders (NDs), and integrating multi-modal to the binary classification of NDs has been thoroughly explored. However, accurately classifying multiple classes of NDs remains a challenge due to the complexity of disease subclass. In our study, we develop a heterogeneous neural network (H-Net) that integrates sMRI and fMRI modes for classifying multi-class NDs. To account for the differences between the two modes, H-Net adopts a heterogeneous neural network strategy to extract information from each mode. Specifically, H-Net includes an multi-layer perceptron based (MLP-based) encoder, a graph attention network based (GAT-based) encoder, and a cross-modality transformer block. The MLP-based and GAT-based encoders extract semantic features from sMRI and features from fMRI, respectively, while the cross-modality transformer block models the attention of two types of features. In H-Net, the proposed MLP-mixer block and cross-modality alignment are powerful tools for improving the multi-classification performance of NDs. H-Net is validate on the public dataset (CNP), where H-Net achieves 90% classification accuracy in diagnosing multi-class NDs. Furthermore, we demonstrate the complementarity of the two MRI modalities in improving the identification of multi-class NDs. Both visual and statistical analyses show the differences between ND subclasses.

Risk factors for acute kidney injury and kidney relapse in patients with lupus podocytopathy.

Background: Patients with lupus podocytopathy show a high incidence of acute kidney injury (AKI) and relapse, but the risk factors and mechanisms were unclear. This study analysed the clinicopathological features and risk factors for AKI and relapse in lupus podocytopathy patients. Methods: The cohort of lupus podocytopathy was generated by screening the biopsies of patients with lupus nephritis (LN) from 2002 to 2022 and was divided into the mild glomerular lesion (MGL) and focal segmental glomerulosclerosis (FSGS) groups based on glomerular morphological characteristics. The acute (ATI) and chronic (CTI) tubulointerstitial lesions were semi-quantitatively scored. Logistic and Cox regressions were employed to identify the risk factors for AKI and relapse, respectively. Results: Among 6052 LN cases, 98 (1.6%) were diagnosed as lupus podocytopathy, with 71 in the MGL group and 27 in the FSGS group. All patients presented with nephrotic syndrome and 33 (34.7%) of them had AKI. Seventy-seven (78.6%) patients achieved complete renal response (CRR) within 12 weeks of induction treatment, in which there was no difference in the CRR rate between glucocorticoid monotherapy and combination therapy with glucocorticoids plus immunosuppressants. Compared with the MGL group, patients in the FSGS group had significantly higher incidences of hypertension and haematuria; in addition, they had higher Systemic Lupus Erythematosus Disease Activity Index 2000, ATI and CTI scores but a significantly lower CRR rate. Urinary protein ≥7.0 g/24 h and serum C3 ≤0.750 g/l were independent risk factors for AKI. During a median follow-up of 78 months, 57 cases (60.0%) had relapse and none reached the kidney endpoint. Failure to achieve CRR within 12 weeks, maintenance with glucocorticoid monotherapy and AKI at onset were independent risk factors for kidney relapse. Conclusions: In this study, histological subtypes of lupus podocytopathy were found to be associated with clinical features and treatment response. In addition, several risk factors associated with AKI occurrence and kidney relapse were identified.

The management pattern and outcomes of chronic thromboembolic pulmonary hypertension: rationale and design for a Chinese real-world study.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive pulmonary vascular disorder with substantial morbidity and mortality, also a disease underdiagnosed and undertreated. It is potentially curable by pulmonary endarterectomy (PEA) in patients with surgically accessible thrombi. Balloon pulmonary angioplasty (BPA) and targeted medical therapy are options for patients with distal lesions or persistent/recurrent pulmonary hypertension after PEA. There is an urgent need to increase the awareness of CTEPH. Qualified CTEPH centers are still quite limited. Baseline characteristics, management pattern and clinical outcome of CTEPH in China needs to be reported. METHODS AND DESIGN: The CHinese reAl-world study to iNvestigate the manaGEment pattern and outcomes of chronic thromboembolic pulmonary hypertension (CHANGE) study is designed to provide the multimodality treatment pattern and clinical outcomes of CTEPH in China. Consecutive patients who are ≥ 14 year-old and diagnosed with CTEPH are enrolled. The diagnosis of CTEPH is confirmed in right heart catheterization and imaging examinations. The multimodality therapeutic strategy, which consists of PEA, BPA and targeted medical therapy, is made by a multidisciplinary team. The blood sample and tissue from PEA are stored in the central biobank for further research. The patients receive regular follow-up every 3 or 6 months for at least 3 years. The primary outcomes include all-cause mortality and changes in functional and hemodynamic parameters from baseline. The secondary outcomes include the proportion of patients experiencing lung transplantation, the proportion of patients experiencing heart and lung transplantation, and changes in health-related quality of life. Up to 31 December 2023, the study has enrolled 1500 eligible patients from 18 expert centers. CONCLUSIONS: As a real-world study, the CHANGE study is expected to increase our understanding of CTEPH, and to fill the gap between guidelines and the clinical practice in the diagnosis, assessment and treatment of patients with CTEPH. REGISTRATION NUMBER IN CLINICALTRIALS.GOV: NCT05311072.

Quantification of urinary podocyte-derived migrasomes for the diagnosis of kidney disease.

Migrasomes represent a recently uncovered category of extracellular microvesicles, spanning a diameter range of 500 to 3000 nm. They are emitted by migrating cells and harbour a diverse array of RNAs and proteins. Migrasomes can be readily identified in bodily fluids like serum and urine, rendering them a valuable non-invasive source for disease diagnosis through liquid biopsy. In this investigation, we introduce a streamlined and effective approach for the capture and quantitative assessment of migrasomes, employing wheat germ agglutinin (WGA)-coated magnetic beads and flow cytometry (referred to as WBFC). Subsequently, we examined the levels of migrasomes in the urine of kidney disease (KD) patients with podocyte injury and healthy volunteers using WBFC. The outcomes unveiled a substantial increase in urinary podocyte-derived migrasome concentrations among individuals with KD with podocyte injury compared to the healthy counterparts. Notably, the urinary podocyte-derived migrasomes were found to express an abundant quantity of phospholipase A2 receptor (PLA2R) proteins. The presence of PLA2R proteins in these migrasomes holds promise for serving as a natural antigen for the quantification of autoantibodies against PLA2R in the serum of patients afflicted by membranous nephropathy. Consequently, our study not only pioneers a novel technique for the isolation and quantification of migrasomes but also underscores the potential of urinary migrasomes as a promising biomarker for the early diagnosis of KD with podocyte injury.

EHHADH deficiency regulates pexophagy and accelerates tubulointerstitial injury in diabetic kidney disease.

Peroxisomal L-bifunctional enzyme (EHHADH) plays a role in the classic peroxisomal fatty acid ß-oxidation pathway; however, the relationship between EHHADH expression and diabetic kidney disease has not been well understood. Here, we found that endogenous EHHADH levels were strongly correlated with the progression and severity of diabetic nephropathy in T2D patients. EHHADH knockout mice exhibited worsened renal tubular injury in diabetic mice. Furthermore, EHHADH is a modulator of pexophagy. In renal tubular epithelial cells (RTECs) in vitro, the knockdown of EHHADH induced a dramatic loss of peroxisomes. The loss of peroxisomes in EHHADH-deficient RTECs was restored by either an autophagic inhibitor 3-methyladenine or bafilomycin A1 both in vitro and in vivo. NBR1 was required for pexophagy in EHHADH-knockdown cells, where the level of reactive oxygen species (ROS) was increased, while inhibition of ROS blocked pexophagy. In summary, our findings revealed EHHADH deficiency accelerated renal injury in DKD as a modulator of pexophagy.

Scalable drop-casting construction of light-addressable photoelectrochemical biosensor on laser-induced graphene electrode arrays for high-throughput drug screening.

A drop-casting method for the scalable construction of a solar cell-type light-addressable photoelectrochemical (PEC) sensor on commercial phenol resin (PR) plates is reported. The sensor was fabricated by laser writing of addressable laser-induced graphene (LIG) electrode arrays on PR plates with ring-disc dual-electrode cell configurations using a 405 nm laser machine. Beneficial from the good hydrophilicity of PR-based LIG and the excellent film formation of bismuth sulfide nanorods (Bi2S3 NRs), uniform Bi2S3 photovoltaic films can be reproducibly deposited onto the LIG disc photoanode array via drop casting modification, which show a sensitive photocurrent response toward thiocholine (TCl) when the ring cathode array was coated with Ag/AgCl. An acetylcholinesterase (AChE)-based PEC biosensor was therefore constructed by a similar drop-casting modification method. The resulting biosensor exhibits good sensitivity toward an AChE inhibitor, i.e., galantamine hydrobromide (GH), with a calibration range of 10-300 µM and a detection limit of 7.33 µM (S/N = 3). Moreover, the biosensor possesses good storage stability, which can achieve the high-throughput screening of AChE inhibitor drugs from traditional Chinese medicines (TCMs). The present work thus demonstrates the promising application of LIG technology in constructing light-addressable PEC sensing devices with high performance and low cost.

Screening of potential drugs for the treatment of diabetic kidney disease using single-cell transcriptome sequencing and connectivity map data.

OBJECTIVE: To explore the feasibility of screening potential drugs for the treatment of diabetic kidney disease (DKD) using a single-cell transcriptome sequencing dataset and Connectivity Map (CMap) database screening. METHODS: A DKD single-nucleus transcriptome sequencing dataset was analyzed using Seurat 4.0 to obtain specific podocyte subclusters and differentially expressed genes (DEGs) related to DKD. These DEGs were subsequently subjected to a search against the CMap database to screen for drug candidates. Cell and animal experiments were conducted to evaluate the efficacy of the top 3 drug candidates. RESULTS: Initially, we analyzed the DKD single-nucleus transcriptome sequencing dataset to obtain intrinsic renal cells such as podocytes, endothelial cells, mesangial cells, proximal tubular cells, collecting duct cells and immune cells. Podocytes were further divided into four subclusters, among which the proportion of POD_1 podcytes was significantly greater in DKD kidneys than in control kidneys (34.0 % vs. 3.4 %). The CMap database was searched using the identified DEGs in the POD_1 subcluster, and the drugs, including tozasertib, paroxetine, and xylazine, were obtained. Cell-based experiments showed that tozasertib, paroxetine and xylazine had no significant podocyte toxicity in the concentration range of 0.01-50 µM. Tozasertib, paroxetine, and xylazine all reversed the advanced glycation end products (AGEs)-induced decrease in podocyte marker levels, but the effect of paroxetine was more prominent. Animal experiments showed that paroxetine decreased urine ALB/Cr levels in DKD model mice by approximately 51.5 % (115.7 mg/g vs. 238.8 mg/g, P < 0.05). Histopathological assessment revealed that paroxetine attenuated basement membrane thickening, restored the number of foot processes of podocytes, and reduced foot process fusion. In addition, paroxetine also attenuated renal tubular-interstitial fibrosis. Mechanistically, paroxetine inhibited the expression of GRK2 and NLRP3, decreased the phosphorylation level of p65, restored NRF2 expression, and relieved inflammation and oxidative stress. CONCLUSION: This strategy based on single-cell transcriptome sequencing and CMap data can facilitate the identification and aid the rapid development of clinical DKD drugs. Paroxetine, screened by this strategy, has excellent renoprotective effects.

Influence of the PET-PTFE Separator Pore Structure on the Performance of Lithium Metal Batteries.

The separator is a crucial component in lithium batteries, as it physically separates the cathode and the anode while allowing ion transfer through the internal channel. The pore structure of the separator significantly influences the performance of lithium batteries, particularly lithium metal batteries. In this study, we investigate the use of a Janus separator composed of poly(ethylene terephthalate) (PET)-polytetrafluoroethylene (PTFE) fibers in lithium metal batteries. This paper presents a comprehensive analysis of the impact of this asymmetric material on the cycling performance of the battery alongside an investigation into the influence of two different substrates on lithium-ion deposition behavior. The research findings indicate that when the rigid PET side faces the lithium metal anode and the soft PTFE side faces the cathode, it significantly extends the cycling lifespan of lithium metal batteries, with an impressive 82.6% capacity retention over 2000 cycles. Furthermore, this study demonstrates the versatility of this separator type in lithium metal batteries by assembling the lithium metal electrode with high cathode-loading capacities (4 mA h/cm2). In conclusion, the results suggest that the design of asymmetric separators can serve as an effective engineering strategy with substantial potential for enhancing the lifespan of lithium metal batteries.

Inhibition of receptor interacting protein kinase-1 (RIPK1) in the treatment of murine lupus.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a type of autoimmune disease that involves multiple organs involved as well as cytokine dysregulation. The treatment of SLE is still challenging due to the side effects of the different drugs used. Receptor-interacting protein kinase 1 (RIPK1) is a kinase involved in T cell homeostasis and autoinflammation. Although clinical trials have shown that RIPK1 inhibition exhibits significant efficacy in different autoimmune diseases, its role in SLE remains unclear. METHODS: MRL/lpr lupus-prone mice received RIPK1 inhibitor ZJU37 or vehicle intraperitoneally for 10 weeks. A BM12-induced chronic graft-versus-host-disease (cGVHD) lupus-like model was introduced in RIPK1 D138N mice or C57BL/6 mice. Nephritis, serum autoantibody levels, dysregulation of adaptive immune response and cytokines were compared in treated and untreated mice. RESULTS: ZJU37 alleviated the clinical features of the MRL/lpr mice including nephritis and anti-dsDNA antibody production. In addition, ZJU37 treatment reduced the proportion of double-negative T cells in the spleen and the cytokines of TNFα, IFN-γ, IL-6, IL-17 and IL-1ß in the serum. Moreover, RIPK1 D138N mice were able to prevent the cGVHD lupus-like model from SLE attack, manifesting as anti-dsDNA antibody production, the proliferation of germinal centre B cells, plasma cells, and T follicular helper cells as well as IgG and C3 deposits in kidneys. CONCLUSION: RIPK1 inhibition has a protective effect in the mouse model of SLE and can potentially become a new therapeutic target for SLE in humans.

Sequencing of the Complete Mitochondrial Genome of the Big Brown Mactra Clam, Mactra grandis (Venerida: Mactridae).

Mitochondrial genomes are playing an increasingly important role in molluscan taxonomy, germplasm, and evolution studies. The first complete mitochondrial genome of the commercial big brown mactra clam, Mactra grandis, was characterized using Illumina next-generation sequencing in this study. The 17,289 bp circular genome has a typical gene organization of 13 protein-coding genes (PCGs), 2 rRNAs, and 22 tRNAs, with an obvious (A + T)-bias of 64.54%. All PCGs exhibited a homogeneous bias in nucleotide composition with a (A + T)-bias, a positive GC skew, and a negative AT skew. Results of phylogenetic analysis showed that Mactra grandis was most closely related to Mactra cygnus. The functional gene arrangement of the two species was identical but different from other Mactra species. The congeneric relationships among Mactra species were demonstrated by genetic distance analysis. Additionally, the selective pressure analysis suggested that cox1 was highly efficient for discriminating closely related species in genus Mactra, while nad2 was the most appropriate marker for population genetic analysis.

The association between circadian syndrome and chronic kidney disease in an aging population: a 4-year follow-up study.

Introduction: Circadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed. Methods: A national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR <60 mL.min-1/1.73/m2 were diagnosed with CKD. Multivariate binary logistic regression was used to assess the cross-sectional association between CircS and CKD. Subgroup and interactive analyses were performed to determine the interactive effects of covariates. In the sensitivity analysis, the obese population was excluded and another method for calculating the eGFR was used to verify the robustness of previous findings. In addition, participants without CKD at baseline were followed up for four years to investigate the longitudinal relationship between CircS and CKD. Results: A total of 6355 participants were included in this study. In the full model, CircS was positively associated with CKD (OR = 1.28, 95% CI = 1.04-1.59, P < 0.05). As per one increase of CircS components, there was a 1.11-fold (95% CI = 1.04-1.18, P < 0.05) risk of prevalent CKD in the full model. A significant interactive effect of hyperuricemia in the CircS-CKD association (P for interaction < 0.01) was observed. Sensitivity analyses excluding the obese population and using the 2009 CKD-EPI creatinine equation to diagnose CKD supported the positive correlation between CircS and CKD. In the 2011-2015 follow-up cohort, the CircS group had a 2.18-fold risk of incident CKD (95% CI = 1.33-3.58, P < 0.01) in the full model. The OR was 1.29 (95% CI = 1.10-1.51, P < 0.001) with per one increase of CircS components. Conclusion: CircS is a risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

High-Speed Electro-Optic Modulators Based on Thin-Film Lithium Niobate.

Electro-optic modulators (EOMs) are pivotal in bridging electrical and optical domains, essential for diverse applications including optical communication, microwave signal processing, sensing, and quantum technologies. However, achieving the trifecta of high-density integration, cost-effectiveness, and superior performance remains challenging within established integrated photonics platforms. Enter thin-film lithium niobate (LN), a recent standout with its inherent electro-optic (EO) efficiency, proven industrial performance, durability, and rapid fabrication advancements. This platform inherits material advantages from traditional bulk LN devices while offering a reduced footprint, wider bandwidths, and lower power requirements. Despite its recent introduction, commercial thin-film LN wafers already rival or surpass established alternatives like silicon and indium phosphide, benefitting from decades of research. In this review, we delve into the foundational principles and technical innovations driving state-of-the-art LN modulator demonstrations, exploring various methodologies, their strengths, and challenges. Furthermore, we outline pathways for further enhancing LN modulators and anticipate exciting prospects for larger-scale LN EO circuits beyond singular components. By elucidating the current landscape and future directions, we highlight the transformative potential of thin-film LN technology in advancing electro-optic modulation and integrated photonics.