Differentiation of bone marrow mesenchymal stem cells into Leydig-like cells with testicular extract liquid in vitro.

Differentiation of Leydig cells plays a key role in male reproductive function. Bone marrow mesenchymal stem cells (BMSCs) have emerged as a potential cell source for generating Leydig-like cells due to their multipotent differentiation capacity and accessibility. This study aimed to investigate the morphological and genetic expression changes of BMSCs during differentiation into Leydig-like cells. Testicular extract liquid, which simulates the microenvironment in vivo, induced the third passage BMSCs differentiated into Leydig-like cells. Changes in cell morphology were observed by microscopy, the formation of lipid droplets of androgen precursor was identified by Oil Red Staining, and the expression of testicular specific genes 3ß-HSD and SF-1 in testicular stromal cells was detected by RT-qPCR. BMSCs isolated from the bone marrow of Sprague-Dawley (SD) rats were cultured for 3 generations and identified as qualified BMSCs in terms of morphology and cell surface markers. After 14 days of induction with testicular tissue lysate, lipid droplets appeared in the cytoplasm of P3 BMSCs by Oil Red O staining. RT-qPCR detection was performed on BMSCs on the 3rd, 7th, 14th, and 21st day after induction. Relative expression levels of 3ß-HSD mRNA significantly increased after 14 days of induction, while the relative expression of SF-1 mRNA increased after 14 days of induction but was not significant. BMSCs can differentiate into testicular interstitial cells with reserve androgen precursor lipid droplets after induction by testicular tissue lysate. The differentiation ability of BMSCs provides the potential to reconstruct the testicular microenvironment and is expected to fundamentally improve testicular function and provide new treatment options for abnormal spermatogenesis diseases.

The influence of cortisol co-secretion on clinical characteristics and postoperative outcomes in unilateral primary aldosteronism.

Context: The prevalence of unilateral primary aldosteronism (UPA) with cortisol co-secretion varies geographically. Objective: To investigate the prevalence and clinical characteristics of UPA with cortisol co-secretion in a Chinese population. Design: Retrospective cohort study. Methods: We recruited 580 patients with UPA who underwent cosyntropin stimulation test (CST) after the 1-mg dexamethasone suppression test (DST) and retrospectively analyzed the clinical characteristics and postoperative outcomes of UPA with and without cortisol co-secretion. Results: UPA with cortisol co-secretion (1 mg DST>1.8 ug/dL) was identified in 65 of 580 (11.2%) patients. These patients were characterized by older age, longer duration of hypertension, higher concentration of plasma aldosterone and midnight cortisol, lower adrenocorticotropic hormone (ACTH) and dehydroepiandrosterone sulfate (DHEAS), larger tumor diameter, and more history of diabetes mellitus. Cortisol and aldosterone levels were higher and DHEAS level was lower in UPA with cortisol co-secretion at 0-120 min after CST. Among 342 UPA patients with KCNJ5 gene sequencing and follow-up results, the complete clinical success rate was lower in UPA with cortisol co-secretion (33.3% vs. 56.4%, P<0.05); the complete biochemical success rate and KCNJ5 mutation did not differ between the two groups. Age, tumor size, and ACTH were independent predictors of UPA with cortisol co-secretion. Sex, BMI, duration of hypertension, KCNJ5 mutation, and cortisol co-secretion were independent predictors for complete clinical success in UPA after surgery. Conclusions: UPA with cortisol co-secretion is not uncommon in China, but the clinical features were distinctly different from those without co-secretion. Cortisol co-secretion is an independent risk factor for incomplete clinical success after surgery in UPA.

Hidden hotspots of amphibian biodiversity in China.

Identifying and protecting hotspots of endemism and species richness is crucial for mitigating the global biodiversity crisis. However, our understanding of spatial diversity patterns is far from complete, which severely limits our ability to conserve biodiversity hotspots. Here, we report a comprehensive analysis of amphibian species diversity in China, one of the most species-rich countries on Earth. Our study combines 20 y of field surveys with new molecular analyses of 521 described species and also identifies 100 potential cryptic species. We identify 10 hotspots of amphibian diversity in China, each with exceptional species richness and endemism and with exceptional phylogenetic diversity and phylogenetic endemism (based on a new time-calibrated, species-level phylogeny for Chinese amphibians). These 10 hotspots encompass 59.6% of China's described amphibian species, 49.0% of cryptic species, and 55.6% of species endemic to China. Only four of these 10 hotspots correspond to previously recognized biodiversity hotspots. The six new hotspots include the Nanling Mountains and other mountain ranges in South China. Among the 186 species in the six new hotspots, only 9.7% are well covered by protected areas and most (88.2%) are exposed to high human impacts. Five of the six new hotspots are under very high human pressure and are in urgent need of protection. We also find that patterns of richness in cryptic species are significantly related to those in described species but are not identical.

Use of 3D echocardiography facilitates analysis of thrombolytic efficacy in patients with persistent atrial fibrillation.

ABSTRACT: This study seeks to identify the anticoagulant efficacy of rivaroxaban treatment on thrombi detected using echocardiography of the left atrial appendage in 275 patients with persistent atrial fibrillation (AF). During follow-up after 9 to 24 weeks of Rivaroxaban treatment, patients were divided into 'effective group' (n = 143) and 'ineffective group' (n = 132) according to the thrombolytic effect of the drug. Left atrial diameter (LAD), left atrial ejection fraction (LAEF), left ventricular ejection fraction (LVEF), mean diameter of left atrial appendage (LAADmean), angle between left atrial appendage and left atrial (LAA-A), velocity of blood flow in left atrial appendage (LAA-v) and thrombus size were compared before and after drug administration. Following treatment, LAEF, LVEF and LAA-v values were greater and LAD and LAADmean values were lower in the effective (P<0.05). Logistic regression analysis showed significant correlations of LAD, LAEF, LVEF, LAA-A and LAA-v with anticoagulant efficacy (P<0.05). The efficacy of Rivaroxaban in treatment of left atrial auricular thrombosis in patients with persistent AF was correlated with LAD, LAEF, LVEF, LAA-A and LAA-v. Multivariate logistic regression analysis further revealed LAEF (OR 1.7, 95% CI 0.45-16.9, P=0.008), 3D-EF (OR 6.4, 95% CI 1.06-16.9, P=0.039), and left ventricular global longitudinal strain (GLS) (OR 18.0, 95% CI 1.38-35.68, P=0.028) as factors related to left atrial appendage thrombus. Echocardiography with global longitudinal strain assessment could be effectively utilized to evaluate the functional parameters of LAA and thus aid in predicting the safety of Rivaroxaban as an anticoagulation agent.

Elevated expression of LCN13 through FXR activation ameliorates hepatocellular lipid accumulation and inflammation.

BACKGROUND: Lipocalin 13 (LCN13) is a member of the lipocalin family that consists of numerous secretory proteins. LCN13 high-expression has been reported to possess anti-obesity and anti-diabetic effects. Although metabolic dysfunction-associated steatotic liver diseases (MASLD) including metabolic dysfunction-associated steatohepatitis (MASH) are frequently associated with obesity and insulin resistance, the functional role of endogenous LCN13 and the therapeutic effect of LCN13 in MASH and related metabolic deterioration have not been evaluated. METHODS: We employed a methionine-choline deficient diet model and MASH cell models to investigate the role of LCN13 in MASH development. We sought to explore the effects of LCN13 on lipid metabolism and inflammation in hepatocytes under PA/OA exposure using Western blotting, real-time RT-PCR, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, oil red O staining. Using RNA sequencing, chromatin immunoprecipitation assay, and luciferase reporter assays to elucidate whether farnesoid X receptor (FXR) regulates human LCN13 transcription as a transcription factor. RESULTS: Our study found that LCN13 was down-regulated in MASH patients, MASH mouse and cell models. LCN13 overexpression in hepatocyte cells significantly inhibited lipid accumulation and inflammation in vitro. Conversely, LCN13 downregulation significantly exacerbated lipid accumulation and inflammatory responses in vivo and in vitro. Mechanistically, we provided the first evidence that LCN13 was transcriptionally activated by FXR, representing a novel direct target gene of FXR. And the key promoter region of LCN13 binds to FXR was also elucidated. We further revealed that LCN13 overexpression via FXR activation ameliorates hepatocellular lipid accumulation and inflammation in vivo and in vitro. Furthermore, LCN13-down-regulated mice exhibited aggravated MASH phenotypes, including increased hepatic lipid accumulation and inflammation. CONCLUSION: Our findings provide new insight regarding the protective role of LCN13 in MASH development and suggest an innovative therapeutic strategy for treating MASH or related metabolic disorders.

Ginsenoside Rg1 relieves rat intervertebral disc degeneration and inhibits IL-1ß-induced nucleus pulposus cell apoptosis and inflammation via NF-κB signaling pathway.

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.

Dissociating the Influence of Limb Posture and Visual Feedback Shifts on the Adaptation to Novel Movement Dynamics.

Accurate movements of the upper limb require the integration of various forms of sensory feedback (e.g., visual and postural information). The influence of these different sensory modalities on reaching movements has been largely studied by assessing endpoint errors after selectively perturbing sensory estimates of hand location. These studies have demonstrated that both vision and proprioception make key contributions in determining the reach endpoint. However, their influence on motor output throughout movement remains unclear. Here we used separate perturbations of posture and visual information to dissociate their effects on reaching dynamics and temporal force profiles during point-to-point reaching movements. We tested human subjects (N = 32) and found that vision and posture modulate select aspects of reaching dynamics. Specifically, altering arm posture influences the relationship between temporal force patterns and the motion-state variables of hand position and acceleration, whereas dissociating visual feedback influences the relationship between force patterns and the motion-state variables of velocity and acceleration. Next, we examined the extent these baseline motion-state relationships influence motor adaptation based on perturbations of movement dynamics. We trained subjects using a velocity-dependent force-field to probe the extent arm posture-dependent influences persisted after exposure to a motion-state dependent perturbation. Changes in the temporal force profiles due to variations in arm posture were not reduced by adaptation to novel movement dynamics, but persisted throughout learning. These results suggest that vision and posture differentially influence the internal estimation of limb state throughout movement and play distinct roles in forming the response to external perturbations during movement.

Incidence rate and implications of splenic ischemia during sleeve gastrectomy and its related procedure.

Splenic ischemia (SI) is a common finding during sleeve gastrectomy (SG) procedures; however, reports are still lacking. In this study, we retrospectively analyzed our SG patients to understand better the incidence rate and implications of SI. Patients' data from the beginning of the year 2021 until December 2022 that underwent bariatric surgery at our university hospital were retrospectively analyzed. Patient surgery video was reviewed by all the authors to investigate the incidence of SI. Thereafter, the corresponding patient age, height, weight, BMI, and their postoperative day 1 (POD1) temperature and blood routine test results (patients were routinely discharged at POD2) were collected and analyzed. 204 patients were included in this study. The mean age and preoperative BMI were 31.7 ±â€…7.4 years old and 38.8 ±â€…5.6 kg/m2, respectively. SI was observed in 18 cases (8.8%). 30-day readmission rate was seen in 3 patients (1.5%, all without SI during the primary surgery). There was no statistical difference with regard to the POD1 temperature and blood test results between the patients with and without SI. The incidence of SI during sleeve gastrectomy-related procedures is a common finding in our study. We did not observe significant differences postoperatively between the patients with and without SI before discharge. Further study is needed to understand the mechanism for the incidence of SI during SG.

Effect of intensity of sedimentary cover deformation on hydrocarbon accumulation in Dongying Sag, Bohai Bay Basin, China.

The developmental phase of the fault deformation zone denotes the zone of weak deformation (with strong concealment) that evolves within the sedimentary cover of the basin. Recent studies have unveiled the objectively existing tectonic phenomenon of weakly deformed tectonic belts within the sedimentary basin cover, closely intertwined with oil and gas accumulation. To elucidate the deformation intensity and hydrocarbon accumulation scale within the cap cover deformation zone, a pivotal concern in oil and gas geology, this study focuses on the Dongying Sag. The structural physical simulation experiment method, incorporating variable caprock thickness and variable shear strength, is employed to scrutinize the impact of basement fault strike-slip activity on the development of faults in the sedimentary caprock of the basin and dyed oil is charged. In conjunction with sag examples, Early R shear single-channel migration-isolated aggregation, Early and mid-term R shear main channel migration-geese and beaded aggregation, P shear main channel migration-intermittent zonal aggregation, Full channel migration-continuous belt aggregation accumulation models of basement faults are established. It is emphasized that the R shear pressurized deformation section and the R and P shear intersection section in the deformation zone are favorable target areas for oil and gas exploration.

Motion state-dependent motor learning based on explicit visual feedback has limited spatiotemporal properties compared with adaptation to physical perturbations.

We recently showed that subjects can learn motion state-dependent changes to motor output (temporal force patterns) based on explicit visual feedback of the equivalent force field (i.e., without the physical perturbation). Here, we examined the spatiotemporal properties of this learning compared with learning based on physical perturbations. There were two human subject groups and two experimental paradigms. One group (n = 40) experienced physical perturbations (i.e., a velocity-dependent force field, vFF), whereas the second (n = 40) was given explicit visual feedback (EVF) of the force-velocity relationship. In the latter, subjects moved in force channels and we provided visual feedback of the lateral force exerted during the movement, as well as the required force pattern based on movement velocity. In the first paradigm (spatial generalization), following vFF or EVF training, generalization of learning was tested by requiring subjects to move to 14 untrained target locations (0° to ±135° around the trained location). In the second paradigm (temporal stability), following training, we examined the decay of learning over eight delay periods (0 to 90 s). Results showed that learning based on EVF did not generalize to untrained directions, whereas the generalization for the vFF was significant for targets ≤ 45° away. In addition, the decay of learning for the EVF group was significantly faster than the FF group (a time constant of 2.72 ± 1.74 s vs. 12.53 ± 11.83 s). Collectively, our results suggest that recalibrating motor output based on explicit motion state information, in contrast to physical disturbances, uses learning mechanisms with limited spatiotemporal properties.NEW & NOTEWORTHY Adjustment of motor output based on limb motion state information can be achieved based on explicit information or from physical perturbations. Here, we investigated the spatiotemporal characteristics of short-term motor learning to determine the properties of the respective learning mechanisms. Our results suggest that adjustments based on physical perturbations are more temporally stable and applied over a greater spatial range than the learning based on explicit visual feedback, suggesting largely separate learning mechanisms.

Effects of ohmic heating with different voltages on the quality and microbial diversity of cow milk during thermal treatment and subsequent cold storage.

Ohmic heating (OH), an innovative heating technology, presents potential applications in the pasteurization of liquid foods. Therefore, the study was conducted to evaluate the effect of OH at various voltage gradients (10 V/cm, 12.5 V/cm, and 15 V/cm) and water bath (WB) on microbial inactivation, physicochemical and sensory properties and microbial flora of pasteurized milk. Results indicated that OH with higher voltage could effectively inactivate microorganisms in milk, requiring less heating time and energy. Moreover, OH treatment at higher voltages could decelerate lipid oxidation and better maintain the sensory quality and essential amino acids content of milk. Additionally, all treatments significantly altered the microbial community, and during storage, the microbial community in milk treated with 10 V/cm and 12.5 V/cm OH remained relatively stable. OH treatments with voltage gradients exceeding 12.5 V/cm could effectively inactive microorganisms and maintain the quality attributes of milk.

Responses of lettuce (Lactuca sativa L.) growth and soil properties to conventional non-biodegradable and new biodegradable microplastics.

Residual plastic films in soils are posing a potential threat to agricultural ecosystem. However, little is known about the impacts of microplastics (MPs) derived from biodegradable and non-biodegradable plastic films on plant-soil systems. Here, we carried out a pot experiment using soil-cultivated lettuce treated by two types of MPs, degradable poly(butylene adipate-co-terephthalate) (PBAT-MPs) and non-biodegradable polyethylene (PE-MPs). MPs resulted in different degrees of reduction in shoot biomass, chlorophyll content, photosynthetic parameters, and leaf contents of nitrogen (N), phosphorus (P), and potassium (K), accelerated accumulation of hydrogen peroxide and superoxide, and increased malondialdehyde content in lettuce leaves. Moreover, MPs obviously decreased contents of total N, nitrate, ammonium, and available K in soils, and increased available P, thus altering soil nutrient availability. MPs also significantly decreased proportions of macroaggregates, and decreased soil electrical conductivity and microbial activity. PBAT-MPs had significantly greater impacts on oxidative damage, photosynthetic rate, soil aggregation, microbial activity, and soil ammonium than those of PE-MPs. Our results suggested that MPs caused oxidative damages, nutrient uptake inhibition, soil properties alteration, ultimately leading to growth reduction, and PBAT-MPs exhibited stronger impacts. Therefore, it is urgent to further study the ecological effects of MPs, especially biodegradable MPs, on soil-plant systems.

Clinical Outcomes of Surgical Crown Reattachment as Treatment for Complicated Crown-Root Fractures: A Retrospective Study.

This retrospective study evaluated the clinical outcomes of surgical crown reattachment in the treatment of complicated crown-root fractures in permanent teeth in 35 patients. Treatments were defined as follows: surgical crown reattachment combined with internal fixation with a fiberreinforced core post, ostectomy, and reattachment of the original crown fragment. Patients were examined to record the periodontal pocket depth (PD), marginal bone loss, tooth migration, and coronal fragment looseness or loss. In most cases, the fracture lines on the palatal aspect were located below the alveolar crest. About 20% to 30% of teeth had periodontal pockets ≥ 3 mm present at least 1 year after surgery. Significant PD differences were observed between the traumatized teeth and adjacent untraumatized teeth at 6 months. The available evidence suggests that surgical crown reattachment is a feasible and effective technique for managing complicated crown-root fractures in permanent teeth.

SORC: an integrated spatial omics resource in cancer.

The interactions between tumor cells and the microenvironment play pivotal roles in the initiation, progression and metastasis of cancer. The advent of spatial transcriptomics data offers an opportunity to unravel the intricate dynamics of cellular states and cell-cell interactions in cancer. Herein, we have developed an integrated spatial omics resource in cancer (SORC, http://bio-bigdata.hrbmu.edu.cn/SORC), which interactively visualizes and analyzes the spatial transcriptomics data in cancer. We manually curated currently available spatial transcriptomics datasets for 17 types of cancer, comprising 722 899 spots across 269 slices. Furthermore, we matched reference single-cell RNA sequencing data in the majority of spatial transcriptomics datasets, involving 334 379 cells and 46 distinct cell types. SORC offers five major analytical modules that address the primary requirements of spatial transcriptomics analysis, including slice annotation, identification of spatially variable genes, co-occurrence of immune cells and tumor cells, functional analysis and cell-cell communications. All these spatial transcriptomics data and in-depth analyses have been integrated into easy-to-browse and explore pages, visualized through intuitive tables and various image formats. In summary, SORC serves as a valuable resource for providing an unprecedented spatially resolved cellular map of cancer and identifying specific genes and functional pathways to enhance our understanding of the tumor microenvironment.

FOXO3-Activated HOTTIP Sequesters miR-615-3p away from COL2A1 to Mitigate Intervertebral Disc Degeneration.

In this study, knockout of FOXO3 was found to impair intervertebral disc maturation and homeostasis in postnatal mice as well as facilitating extracellular matrix degradation. RNA sequencing can uncover disease-related gene expression and investigate disease pathophysiology. High-throughput transcriptome sequencing and experimental validations were used to identify the essential gene and mechanism involved in intervertebral disc degeneration (IDD). Nucleus pulposus (NP) tissue samples were collected from the mice with conditional knockout of FOXO3 (FOXO3 KO) for high-throughput sequencing, followed by screening of differentially expressed lncRNAs and mRNAs. The mRNAs were subjected to GO and KEGG enrichment analyses. Interactions among FOXO3, HOTTIP, miR-615-3p, and COL2A1 were analyzed. NP cells were subjected to a series of mimics, inhibitors, overexpression plasmids, and shRNAs to validate the mechanisms of FOXO3 in controlling HOTTIP/miR-615-3p/COL2A1 in IDD. Mechanistically, FOXO3 transcriptionally activated HOTTIP, facilitated the competitive HOTTIP binding to miR-615-3p, and increased the expression of the miR-615-3p target gene COL2A1. Thus, NP cell proliferation was induced, cell apoptosis was diminished, resulting in delayed development of IDD. Based on these data, the transcription factor FOXO3 may decrease miR-615-3p binding to COL2A1 and up-regulate COL2A1 expression by activating HOTTIP transcription, which in turn inhibits NP cell apoptosis and promotes its proliferation, to prevent the degradation of intervertebral disc matrix and maintain the normal physiological function of intervertebral disc, thereby preventing the occurrence and development of IDD.

Cushing Syndrome Is Associated With Gut Microbial Dysbiosis and Cortisol-Degrading Bacteria.

CONTEXT: Cushing syndrome (CS) is a severe endocrine disease characterized by excessive secretion of cortisol with multiple metabolic disorders. While gut microbial dysbiosis plays a vital role in metabolic disorders, the role of gut microbiota in CS remains unclear. OBJECTIVE: The objective of this work is to examine the alteration of gut microbiota in patients with CS. METHODS: We performed shotgun metagenomic sequencing of fecal samples from 78 patients with CS and 78 healthy controls matched for age and body mass index. Furthermore, we verify the cortisol degradation capacity of Ruminococcus gnavus in vitro and identify the potential metabolite by LC-MC/MS. RESULTS: We observed significant differences in microbial composition between CS and controls in both sexes, with CS showing reduced Bacteroidetes (Bacteroides vulgatus) and elevated Firmicutes (Erysipelotrichaceae_bacterium_6_1_45) and Proteobacteria (Enterobacter cloacae). Despite distinct causes of hypercortisolism in ACTH-dependent and ACTH-independent CS, we found no significant differences in metabolic profiles or gut microbiota between the 2 subgroups. Furthermore, we identified a group of gut species, including R. gnavus, that were positively correlated with cortisol levels in CS. These bacteria were found to harbor cortisol-degrading desAB genes and were consistently enriched in CS. Moreover, we demonstrated the efficient capacity of R. gnavus to degrade cortisol to 11-oxygenated androgens in vitro. CONCLUSION: This study provides evidence of gut microbial dysbiosis in patients with CS and identifies a group of CS-enriched bacteria capable of degrading cortisol. These findings highlight the potential role of gut microbiota in regulating host steroid hormone levels, and consequently host health.

Effects of sleep duration and changes in body mass index on diabetic kidney disease: a prospective cohort study.

Aims: To examine the associations of sleep duration and changes in BMI with the onset of diabetic kidney disease (DKD). Materials and methods: 2,959 participants with type 2 diabetes were divided into three groups based on sleep duration: short (<7 h/day), intermediate (7-9 h/day), or long (>9 h/day). Changes in BMI during follow-up were trisected into loss, stable, or gain groups. DKD was defined as either the urinary albumin/creatinine ratio (UACR) ≥ 3.39 mg/mmol or the estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m², or both. Cox regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs). Results: During a mean follow-up of 2.3 years, DKD occurred in 613 participants (20.7%). A J-shaped curve was observed between sleep duration and DKD. Compared to intermediate sleep duration, long sleep duration was associated with higher risks of DKD (HR 1.47; 95% CI: 1.19-1.81). In the joint analyses, compared to participants with intermediate sleep duration and stable BMI, long sleep duration with BMI gain had the highest risks of DKD (HR 2.04; 95% CI: 1.48-2.83). In contrast, short or intermediate sleep duration accompanied by decrease in BMI was associated with a reduced risk of DKD, with HRs of 0.50 (95% CI: 0.31-0.82) and 0.61 (95% CI:0.47-0.80), respectively. Conclusions: Long sleep duration is significantly associated with an increased risk of DKD, which is further amplified by obesity or BMI gain. These findings suggest that both proper sleep duration and weight control are essential to preventing DKD.