MicroRNAs in metabolic dysfunction-associated diseases: Pathogenesis and therapeutic opportunities.

Metabolic dysfunction-associated diseases often refer to various diseases caused by metabolic problems such as glucose and lipid metabolism disorders. With the improvement of living standards, the increasing prevalence of metabolic diseases has become a severe public health problem, including metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-related liver disease (ALD), diabetes and obesity. These diseases are both independent and interdependent, with complex and diverse molecular mechanisms. Therefore, it is urgent to explore the molecular mechanisms and find effective therapeutic targets of these diseases. MicroRNAs (miRNAs) have emerged as key regulators of metabolic homoeostasis due to their multitargets and network regulatory properties within the past few decades. In this review, we discussed the latest progress in the roles of miRNA-mediated regulatory networks in the development and progression of MASLD, ALD, diabetes and obesity.

Identifying potential key ferroptosis-related genes and therapeutic drugs in sepsis-induced ARDS by bioinformatics and experimental verification.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a serious pathological process with high mortality. Ferroptosis is pivotal in sepsis, whose regulatory mechanisms in sepsis-induced ARDS remains unknown. We aimed to determine key ferroptosis-related genes in septic ARDS and investigate therapeutic traditional Chinese medicine (TCM). METHOD: Sepsis-induced ARDS dataset obtained from Gene Expression Omnibus (GEO) was analyzed to identify ferroptosis-related differentially expressed genes (FRDEGs). Enrichment analysis and protein-protein interaction (PPI) network construction were performed to identify hub genes. Immune cells infiltration was analyzed and competitive endogenous RNA (ceRNA) network was constructed. The diagnostic value of hub genes in septic ARDS was analyzed and the occurrence of ferroptosis and the expression of hub genes were detected. TCM targeting hub genes was predicted via SymMap database and was verified. RESULTS: 16 FRDEGs were obtained, among which the top four genes (IL1B, TXN, MAPK3, HSPB1) were selected as hub genes, which may be potential diagnostic markers of septic ARDS. Immunoassay showed that sepsis-induced ARDS and hub genes were closely related to immune cells. The ceRNA network showed 26 microRNAs and 38 long noncoding RNA (lncRNAs). Ferroptosis occurred and the expressions of IL1B, MAPK3 and TXN were increased in septic ARDS mice and LPS-challenged human pulmonary alveolar epithelial cells (HPAEpiCs). Sea buckthorn alleviated septic lung injury and affected hub genes expression. CONCLUSIONS: Ferroptosis-related genes of IL1B, MAPK3 and TXN serve as potential diagnostic genes for sepsis-induced ARDS. Sea buckthorn may be therapeutic medication for ARDS. This study provides a new direction for septic ARDS treatment.

Investigating the efficacy of acupuncture in treating patients with metabolic-associated fatty liver disease: a protocol for a randomised controlled clinical trial.

INTRODUCTION: Acupuncture is widely used for metabolic-associated fatty liver disease (MAFLD) treatment; however, the clinical efficacy has not been confirmed due to the lack of high-level evidence-based clinical practice. The purpose of this study is to design a research protocol that will be used to determine the efficacy of acupuncture versus sham acupuncture (SHA) for MAFLD treatment. METHODS AND ANALYSIS: This will be a multicentre, randomised and sham-controlled trial. Ninety-eight participants with MAFLD will be enrolled in this trial. Participants will be randomly assigned in a 1:1 ratio to receive acupuncture or SHA for 12 weeks. The primary outcome is the rate of patients with a 30% relative decline in liver fat after 12 weeks of treatment in MRI-proton density fat fraction (MRI-PDFF), which will be obtained by quantitative chemical shift imaging such as the multipoint Dixon method at 0, 12 and 24 weeks. Secondary outcomes include the changes in the relative liver fat content measured by MRI-PDFF, magnetic resonance elastography, liver function, lipid metabolism, homeostatic model assessment for insulin resistance (HOMA-IR) and serum high sensitivity C reactive protein, which will be obtained at 0, 6, 12 and 24 weeks. Body measurement indicators (body mass index, waist circumference, hip circumference and waist-to-hip ratio) will be obtained at 0, 3, 6, 9, 12 and 24 weeks. The alteration in the gut microbiota composition and its metabolism will be assessed by 16S ribosomal RNA sequencing and liquid chromatography-mass spectrometry at 0 and 12 weeks. ETHICS AND DISSEMINATION: This study protocol has been approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (2023-1347-114-01). The results of this study will be published in a peer-reviewed journal and presented at academic conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300075701.

The biphasic role of Hspb1 on ferroptotic cell death in Parkinson's disease.

Rationale: Ferroptosis-driven loss of dopaminergic neurons plays a pivotal role in the pathogenesis of Parkinson's disease (PD). In PD patients, Hspb1 is commonly observed at abnormally high levels in the substantia nigra. The precise consequences of Hspb1 overexpression in PD, however, have yet to be fully elucidated. Methods: We used human iPSC-derived dopaminergic neurons and Coniferaldehyde (CFA)-an Nrf2 agonist known for its ability to cross the blood-brain barrier-to investigate the role of Hspb1 in PD. We examined the correlation between Hspb1 overexpression and Nrf2 activation and explored the transcriptional regulation of Hspb1 by Nrf2. Gene deletion techniques were employed to determine the necessity of Nrf2 and Hspb1 for CFA's neuroprotective effects. Results: Our research demonstrated that Nrf2 can upregulate the transcription of Hspb1 by directly binding to its promoter. Deletion of either Nrf2 or Hspb1 gene abolished the neuroprotective effects of CFA. The Nrf2-Hspb1 pathway, newly identified as a defense mechanism against ferroptosis, was shown to be essential for preventing neurodegeneration progression. Additionally, we discovered that prolonged overexpression of Hspb1 leads to neuronal death and that Hspb1 released from ruptured cells can trigger secondary cell death in neighboring cells, exacerbating neuroinflammatory responses. Conclusions: These findings highlight a biphasic role of Hspb1 in PD, where it initially provides neuroprotection through the Nrf2-Hspb1 pathway but ultimately contributes to neurodegeneration and inflammation when overexpressed. Understanding this dual role is crucial for developing therapeutic strategies targeting Hspb1 and Nrf2 in PD.

Loading Lewis Acid/Base Pair on Metal Nanocluster for Catalytic Ugi Reaction.

Constructing structurally robust and catalytically active metal nanoclusters for catalyzing multi-component reactions is an interesting while challenging task. Inspired by Lewis acid and Lewis base catalysis, we realized the combination of both Lewis acid and Lewis base sites on the surface of a stable gold nanocluster Au35Cd2. The catalytic potential of Au35Cd2 in four-component Ugi reaction was explored, demonstrating high activity and exceptional recyclability. In-depth mechanism studies indicate that the catalytic synergy of the Lewis acid/base pair is crucial for the high efficiency of Au35Cd2-catalyzed Ugi reaction. Bearing the stable structure, multiple activation sites and hierarchical chirality, Au35Cd2 is expected to display further interesting catalytic performance such as asymmetric catalysis.

LONP1 alleviates ageing-related renal fibrosis by maintaining mitochondrial homeostasis.

Mitochondrial dysfunction is a pivotal event contributing to the development of ageing-related kidney disorders. Lon protease 1 (LONP1) has been reported to be responsible for ageing-related renal fibrosis; however, the underlying mechanism(s) of LONP1-driven kidney ageing with respect to mitochondrial disturbances remains to be further explored. The level of LONP1 was tested in the kidneys of aged humans and mice. Renal fibrosis and mitochondrial quality control were confirmed in the kidneys of aged mice. Effects of LONP1 silencing or overexpression on renal fibrosis and mitochondrial quality control were explored. In addition, N6-methyladenosine (m6A) modification and methyltransferase like 3 (METTL3) levels, the relationship between LONP1 and METTL3, and the impacts of METTL3 overexpression on mitochondrial functions were confirmed. Furthermore, the expression of insulin-like growth factor 2 mRNA binding protein 2 (IGF2BP2) and the regulatory effects of IGF2BP2 on LONP1 were confirmed in vitro. LONP1 expression was reduced in the kidneys of aged humans and mice, accompanied by renal fibrosis and mitochondrial dysregulation. Overexpression of LONP1 alleviated renal fibrosis and maintained mitochondrial homeostasis, while silencing of LONP1 had the opposite effect. Impaired METTL3-m6A signalling contributed at least in part to ageing-induced LONP1 modification, reducing subsequent degradation in an IGF2BP2-dependent manner. Moreover, METTL3 overexpression alleviated proximal tubule cell injury, preserved mitochondrial stability, inhibited LONP1 degradation, and protected mitochondrial functions. LONP1 mediates mitochondrial function in kidney ageing and that targeting LONP1 may be a potential therapeutic strategy for improving ageing-related renal fibrosis.

The development of a digital intelligence quotient scale: A new measuring instrument for primary school students in China.

The development of a Digital Intelligence Quotient (DQ) scale for primary school students is the basis for research on the DQ of primary school students, which helps to scientifically diagnose the level and the current average DQ among Chinese primary school students. This study developed and validated a scale applicable to the assessment of DQ in Chinese primary school students where, the initial scale was first constructed; Then 1109 valid datasets were collected through purposive sampling and divided into Sample A and Sample B; Sample A was subjected to exploratory factor analysis and Sample B was tested by confirmatory factor analysis; The final validated scale consists of 22 items in 7 dimensions: digital identity, digital use, digital safety, digital security, digital emotional intelligence, digital literacy and digital rights. The scale has high reliability and validity and thus can be used as a reliable instrument for assessing DQ in Chinese primary school students.

[Effect of Pterostilbene Regulating Nuclear Factor E2-Related Factor 2 on Apoptosis of Colon Cancer Cells in Vitro].

Objective To investigate the effects of pterostilbene on human colon cancer LoVo cells and study the regulatory mechanism of nuclear factor E2-related factor 2 (Nrf2) in the process of pterostilbene acting on LoVo cells. Methods LoVo cells were treated with different concentrations (5,10,20,40,60,80,100 µmol/L) of pterostilbene.Cell viability,migration,invasion,and apoptosis were examined by CCK-8,scratch,Transwell,and TUNEL assays,respectively.The mitochondrial membrane potential was measured by the mitochondrial membrane potential assay kit with JC-1.The reactive oxygen species level was measured by 2',7'-dichlorofluorescein diacetate.The protein levels of Nrf2,phosphorylated Nrf2,heme oxygenase 1,and apoptotic proteins (Bcl2 and Bax) were determined by Western blotting.In addition,cell viability,Nrf2 expression,and apoptosis rate were determined after co-application of the Nrf2-specific agonist sulforaphane. Results Compared with the control group,40,60,80,100 µmol/L pterostilbene reduced the viability of LoVo cells (P=0.014,P<0.001,P<0.001,P<0.001).Pterostilbene at 5,10,20 µmol/L did not show effects on cell viability but inhibited cell migration (P=0.008,P<0.001,P<0.001) and invasion (all P<0.001).Pterostilbene at 40,60,80 µmol/L increased apoptosis (P=0.014,P<0.001,P<0.001),promoted mitochondrial membrane potential depolarization (P=0.026,P<0.001,P<0.001) and reactive oxygen species accumulation (all P<0.001),and down-regulated the expression of phosphorylated Nrf2 (P=0.030,P<0.001,P<0.001),heme oxygenase 1 (P=0.015,P<0.001,P<0.001),and Bcl2 (P=0.039,P<0.001,P<0.001) in LoVo cells.Pterostilbene at 60,80 µmol/L down-regulated Nrf2 expression (P=0.001,P<0.001) and up-regulated Bax expression (both P<0.001).The application of sulforaphane reversed the effects of pterostilbene on cell viability (P<0.001),apoptosis (P<0.001),and Nrf2 expression (P=0.022). Conclusion Pterostilbene is a compound that can effectively inhibit colon cancer cells by inhibiting the Nrf2 pathway.

Selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids.

A novel selenium dioxide promoted selenylation/cyclization of leucosceptrane sesterterpenoids was reported. Two types of leucosceptrane derivatives with different valence states of selenium atoms (Se2+ and Se4+) were obtained. The mechanisms of these two processes were proposed, and the selenium-containing derivates may serve as intermediates of Riley oxidation that could be trapped with appropriate substrates. Immunosuppressive activity screening revealed that 10 and 11 had obvious inhibitory effects on IFN-γ production, with IC50 values of 5.29 and 17.60 µM, respectively, which were more active than their precursor leucosceptroid A.

Transgenic poplar (Populus davidiana×P. bolleana Loucne) expressing dsRNA of insect chitinase gene: lines identification and resistance assay.

Poplar is a valuable tree species that is distributed all over the world. However, many insect pests infest poplar trees and have caused significant damage. To control poplar pests, we transformed a poplar species, Populus davidiana × P. bolleana Loucne, with the dsRNA of the chitinase gene of a poplar defoliator, Clostera anastomosis (Linnaeus) (Lepidoptera: Notodontidae), employing an Agrobaterium-mediated approach. The transgenic plant has been identified by cloning the T-DNA flanking sequences using TAIL-PCR and quantifying the expression of the dsRNA using qPCR. The toxicity assay of the transgenic poplar lines was carried out by feeding the target insect species (C. anastomosis). The results showed that, in C. anastomosis, the activity of chitinase was significantly decreased, consistent with the expression on mRNA levels, and the larval mortality was significantly increased. These results suggested that the transgenic poplar of dsRNA could be used for pest control.

LncRNA XIST/miR-455-3p/HOXC4 axis promotes breast cancer development by activating TGF-ß/SMAD signaling pathway.

Breast cancer is the second primary cause of cancer death among women. Long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) is a central regulator for X chromosome inactivation, and its abnormal expression is a primary feature of breast cancer. So far, the mechanism of XIST in breast cancer has not been fully elucidated. We attempted to illustrate the mechanism of XIST in breast cancer. The expressions of XIST, microRNA-455-3p (miR-455-3p) in breast cancer were measured using quantitative real-time PCR. The expressions of homeobox C4 (HOXC4) were assessed with immunohistochemical and Western blot. Also, the functions of XIST in breast cancer were assessed by Cell Counting Kit-8 analysis, colony formation assay, flow cytometry, Western blot, Transwell, and cell scratch assays. Meanwhile, the mechanism of XIST in breast cancer was validated using database analysis and dual-luciferase reporter assay. Furthermore, the function of XIST in breast cancer in vivo was estimated by tumor xenograft model, immunohistochemical assay, and hematoxylin-eosin staining. XIST and HOXC4 expressions were increased, but miR-455-3p expressions were decreased in breast cancer tissues and cells. Knocking down XIST restrained breast cancer cell proliferation, invasion, migration, epithelial-mesenchymal transformation (EMT), and induced cell cycle arrest at G0/G1. Meanwhile, XIST interacted with miR-455-3p, while miR-455-3p interacted with HOXC4. XIST knockdown repressed breast cancer cell proliferation, invasion, and EMT, while miR-455-3p inhibitor or HOXC4 overexpression abolished those impacts. HOXC4 overexpression also blocked the impacts of miR-455-3p mimic on breast cancer cell malignant behavior. In vivo experimental data further indicated that XIST knockdown repressed breast cancer cell tumorigenic ability, and decreased HOXC4 and p-SMAD3 (TGF-ß/SMAD-related protein) expressions.XIST/miR-455-3p/HOXC4 facilitated breast cancer development by activating the TGF-ß/SMAD pathway.

Factors Affecting the Formation and Transformation of the Intermediates in Pd(II)-Catalyzed Aromatic C-H Activation: A Comprehensive Study with the Pd(II)/LA Platform.

How the factors affecting the formation and transformation of the intermediates in Pd(II)-catalyzed aromatic C-H activation: A comprehensive study with the Pd(II)/LA platform. Using the Pd(II)/Lewis acid (LA)-catalyzed C-H activation of electron-rich acetanilides as a platform, the C-H activation intermediates, including the precomplex η2-intermediate, the agostic hydrogen intermediate, and the palladacycle compound have been well-characterized. This work presents how the catalyst source, substrate, and solvent affect the formation of the η2-intermediate and its equilibrium with the agostic hydrogen intermediate, and the transformation of the agostic hydrogen intermediate to the palladacycle compound through C-H activation. The findings disclosed above are provided as a guideline for the catalyst design of the oxidative olefination of acetanilide with dioxygen, and the catalytic efficiency matched well with the mechanistic findings.

Leaching behavior of microplastics during sludge mechanical dewatering and its effect on activated sludge.

Dewatering is an indispensable link in sludge treatment, but its effect on the microplastics (MPs) remains inadequately understood. This study investigated the physicochemical changes and leaching behavior of MPs during the mechanical dewatering of sludge, as well as the impact of MP leachates on activated sludge (AS). After sludge dewatering, MPs exhibit rougher surfaces, decreased sizes and altered functional groups due to the addition of dewatering agents and the application of mechanical force. Meanwhile, plastic additives, depolymerization products, and derivatives of their interactions are leached from MPs during sludge dewatering process. The concentration of MP-based leachates in sludge is 2-25 times higher than that in water. The enhancement of pH and ionic strength caused by dewatering agents induces the release of MP leachates enriched with protein-like, fulvic acid-like, and soluble microbial by-product-like substances. The reflux of MP leachates in sludge dewatering liquor to the wastewater treatment system negatively impacts AS, leading to a decrease in COD removal rate and inhibition of the extracellular polymeric substances secretion. More importantly, MP leachates cause oxidative stress to microbial cells and alter the microbial community structure of AS at the phylum and genus levels. These findings confirm that MPs undergo aging and leaching during sludge dewatering process, and MP leachates may negatively affect the wastewater treatment system.

From phenotyping to genetic mapping: identifying water-stress adaptations in legume root traits.

BACKGROUND: Climate change induces perturbation in the global water cycle, profoundly impacting water availability for agriculture and therefore global food security. Water stress encompasses both drought (i.e. water scarcity) that causes the drying of soil and subsequent plant desiccation, and flooding, which results in excess soil water and hypoxia for plant roots. Terrestrial plants have evolved diverse mechanisms to cope with soil water stress, with the root system serving as the first line of defense. The responses of roots to water stress can involve both structural and physiological changes, and their plasticity is a vital feature of these adaptations. Genetic methodologies have been extensively employed to identify numerous genetic loci linked to water stress-responsive root traits. This knowledge is immensely important for developing crops with optimal root systems that enhance yield and guarantee food security under water stress conditions. RESULTS: This review focused on the latest insights into modifications in the root system architecture and anatomical features of legume roots in response to drought and flooding stresses. Special attention was given to recent breakthroughs in understanding the genetic underpinnings of legume root development under water stress. The review also described various root phenotyping techniques and examples of their applications in different legume species. Finally, the prevailing challenges and prospective research avenues in this dynamic field as well as the potential for using root system architecture as a breeding target are discussed. CONCLUSIONS: This review integrated the latest knowledge of the genetic components governing the adaptability of legume roots to water stress, providing a reference for using root traits as the new crop breeding targets.

Deciphering interleukin-18 in diabetes and its complications: Biological features, mechanisms, and therapeutic perspectives.

Interleukin-18 (IL-18), a potent and multifunctional pro-inflammatory cytokine, plays a critical role in regulating ß-cell failure, ß-cell death, insulin resistance, and various complications of diabetes mellitus (DM). It exerts its effects by triggering various signaling pathways, enhancing the production of pro-inflammatory cytokines and nitric oxide (NO), as well as promoting immune cells infiltration and ß-cells death. Abnormal alterations in IL-18 levels have been revealed to be strongly associated with the onset and development of DM and its complications. Targeting IL-18 may present a novel and promising approach for DM therapy. An increasing number of IL-18 inhibitors, including chemical and natural inhibitors, have been developed and have been shown to protect against DM and diabetic complications. This review provides a comprehensive understanding of the production, biological functions, action mode, and activated signaling pathways of IL-18. Next, we shed light on how IL-18 contributes to the pathogenesis of DM and its associated complications with links to its roles in the modulation of ß-cell failure and death, insulin resistance in various tissues, and pancreatitis. Furthermore, the therapeutic potential of targeting IL-18 for the diagnosis and treatment of DM is also highlighted. We hope that this review will help us better understand the functions of IL-18 in the pathogenesis of DM and its complications, providing novel strategies for DM diagnosis and treatment.

Complete mitochondrial genome assembly of Zizania latifolia and comparative genome analysis.

Zizania latifolia (Griseb.) Turcz. ex Stapf has been cultivated as a popular aquatic vegetable in China due to its important nutritional, medicinal, ecological, and economic values. The complete mitochondrial genome (mitogenome) of Z. latifolia has not been previously studied and reported, which has hindered its molecular systematics and understanding of evolutionary processes. Here, we assembled the complete mitogenome of Z. latifolia and performed a comprehensive analysis including genome organization, repetitive sequences, RNA editing event, intercellular gene transfer, phylogenetic analysis, and comparative mitogenome analysis. The mitogenome of Z. latifolia was estimated to have a circular molecule of 392,219 bp and 58 genes consisting of three rRNA genes, 20 tRNA genes, and 35 protein-coding genes (PCGs). There were 46 and 20 simple sequence repeats (SSRs) with different motifs identified from the mitogenome and chloroplast genome of Z. latifolia, respectively. Furthermore, 49 homologous fragments were observed to transfer from the chloroplast genome to the mitogenome of Z. latifolia, accounting for 47,500 bp, presenting 12.1% of the whole mitogenome. In addition, there were 11 gene-containing homologous regions between the mitogenome and chloroplast genome of Z. latifolia. Also, approximately 85% of fragments from the mitogenome were duplicated in the Z. latifolia nuclear genome. Selection pressure analysis revealed that most of the mitochondrial genes were highly conserved except for ccmFc, ccmFn, matR, rps1, and rps3. A total of 93 RNA editing sites were found in the PCGs of the mitogenome. Z. latifolia and Oryza minuta are the most closely related, as shown by collinear analysis and the phylogenetic analysis. We found that repeat sequences and foreign sequences in the mitogenomes of Oryzoideae plants were associated with genome rearrangements. In general, the availability of the Z. latifolia mitogenome will contribute valuable information to our understanding of the molecular and genomic aspects of Zizania.

Enhanced delivery of CRISPR/Cas9 system based on biomimetic nanoparticles for hepatitis B virus therapy.

The persistent presence of covalently closed circular DNA (cccDNA) in hepatocyte nuclei poses a significant obstacle to achieving a comprehensive cure for hepatitis B virus (HBV). Current applications of CRISPR/Cas9 for targeting and eliminating cccDNA have been confined to in vitro studies due to challenges in stable cccDNA expression in animal models and the limited non-immunogenicity of delivery systems. This study addresses these limitations by introducing a novel non-viral gene delivery system utilizing Gemini Surfactant (GS). The developed system creates stable and targeted CRISPR/Cas9 nanodrugs with a negatively charged surface through modification with red blood cell membranes (RBCM) or hepatocyte membranes (HCM), resulting in GS-pDNA@Cas9-CMs complexes. These GS-pDNA complexes demonstrated complete formation at a 4:1 w/w ratio. The in vitro transfection efficiency of GS-pDNA-HCM reached 54.61%, showing homotypic targeting and excellent safety. Additionally, the study identified the most effective single-guide RNA (sgRNA) from six sequences delivered by GS-pDNA@Cas9-HCM. Using GS-pDNA@Cas9-HCM, a significant reduction of 96.47% in in vitro HBV cccDNA and a 52.34% reduction in in vivo HBV cccDNA were observed, along with a notable decrease in other HBV-related markers. The investigation of GS complex uptake by AML-12 cells under varied time and temperature conditions revealed clathrin-mediated endocytosis (CME) for GS-pDNA and caveolin-mediated endocytosis (CVME) for GS-pDNA-HCM and GS-pDNA-RBCM. In summary, this research presents biomimetic gene-editing nanovectors based on GS (GS-pDNA@Cas9-CMs) and explores their precise and targeted clearance of cccDNA using CRISPR/Cas9, demonstrating good biocompatibility both in vitro and in vivo. This innovative approach provides a promising therapeutic strategy for advancing the cure of HBV.

Physical Activity Modifies the Risk of Incident Cardiac Conduction Disorders Upon Inflammation: A Population-Based Cohort Study.

BACKGROUND: Emerging evidence suggests a central role for inflammation in cardiac conduction disorder (CCD). It is unknown whether habitual physical activity could modulate the inflammation-associated risks of incident CCD in the general population. METHODS AND RESULTS: This population-based cohort was derived from the China Kailuan study, including a total of 97 192 participants without prior CCD. The end points included incident CCD and its subcategories (atrioventricular block and bundle-branch block). Systemic inflammation was indicated by the monocyte-to-lymphocyte ratio (MLR). Over a median 10.91-year follow-up, 3747 cases of CCD occurred, with 1062 cases of atrioventricular block and 2697 cases of bundle-branch block. An overall linear dose-dependent relationship was observed between MLR and each study end point (all P-nonlinearity≥0.05). Both higher MLR and physical inactivity were significantly associated with higher risks of conduction block. The MLR-associated risks of developing study end points were higher in the physically inactive individuals than in those being physically active, with significant interactions between MLR levels and physical activity for developing CCD (P-interaction=0.07) and bundle-branch block (P-interaction<0.05) found. Compared with those in MLR quartile 2 and being physically active, those in the highest MLR quartile and being physically inactive had significantly higher risks for all study end points (1.42 [95% CI, 1.24-1.63], 1.62 [95% CI, 1.25-2.10], and 1.33 [95% CI, 1.13-1.56], respectively, for incident CCD, atrioventricular block, and bundle-branch block). CONCLUSIONS: MLR should be a biomarker for the risk assessment of incident CCD. Adherence to habitual physical activity is favorable for reducing the MLR-associated risks of CCD.

Associations of 24-Hour Central Systolic Blood Pressure With Multiorgan Damage in Nondialysis Patients With Chronic Kidney Disease.

BACKGROUND: Multiple target-organ damages (TODs) in the same patient are common and further increase the risk of cardiovascular disease. However, the relationship between ambulatory central systolic blood pressure (SBP) and multiple TODs has yet to be explored. METHODS AND RESULTS: MobilO-Graph PWA was used to monitor the participants' ambulatory blood pressure, and the presence of left ventricular hypertrophy, carotid hypertrophy, and kidney injury were used to define TOD. Logistic regression analyses and receiver operating characteristic analyses were used to explore the correlation between SBP and TOD. Overall, 2018 nondialysis patients with chronic kidney disease were included and 580 (28.74%) had multiple TODs. Twenty-four-hour central SBP with c2 calibration exhibited a stronger correlation with the increasing number of TOD compared with 24-hour brachial SBP in ordinal logistic regression analyses. In the multivariable analyses with the presence of multiple TODs, the odds ratios were 1.786 (95% CI, 1.474-2.165; P<0.001) for 24-hour brachial SBP and 1.949 (95% CI, 1.605-2.366; P<0.001) for 24-hour central SBP with c2 calibration. The receiver operating characteristic analyses also showed that 24-hour central SBP with c2 calibration had higher discrimination than 24-hour brachial SBP regarding multiple TODs (P<0.001). In addition, using 130/135 mm Hg as the threshold for 24-hour brachial SBP/central SBP with c2 calibration to cross-classify, the prevalence of multiple TODs was greater in cases of concordant hypertension compared with cases of isolated brachial hypertension and concordant normotension, with no difference between the latter 2 conditions. CONCLUSIONS: Twenty-four-hour central SBP with c2 calibration was more associated with the presence of multiple TODs compared with 24-hour brachial SBP and was helpful in risk classification of multiple TODs among nondialysis patients with chronic kidney disease.

A user-friendly method for estimating discrete choice land-use model in a panel data setting.

Land-use modeling stands as a pivotal tool in shaping sustainable development policies. With the rapid advancement of remote-sensing technology and the widespread adoption of satellite imagery-based land cover products, these datasets have emerged as primary sources for understanding land-use dynamics due to their high spatial and temporal resolutions. Yet, it remains challenging to effectively integrate such rich panel data into nonlinear econometric land-use models. This paper introduces a method to seamlessly incorporate land cover panel data into econometric models, enabling comprehensive utilization of temporal information within a single framework.-By capturing dynamic land-use patterns, the method enhances prediction accuracy while mitigating issues such as autocorrelated error terms commonly encountered in panel data analysis.-The method is straightforward to implement and applicable to many nonlinear models, making it particularly suitable for datasets with large sample sizes.