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Abstract The triglyceride-glucose (TyG) index and the Atherogenic Index of Plasma (AIP) are both predictors of cardiovascular diseases (CVD). However, their combined and individual contributions to CVD risk are not well understood. This study evaluate the joint and individual associations of the TyG index and AIP with CVD events in middle-aged and older Chinese adults. This nationwide, retrospective cohort study utilized data from CHARLS. The diagnosis of CVD in this study was determined based on self-reported information provided by participants regarding their medical history( heart disease and/or stroke). Cross-sectional analyses in 2011 and longitudinal analyses over a 9-year follow-up were conducted to assess these associations. In the cross-sectional analysis, 8,531 participants were included at baseline. The odds ratio (OR) for TyG alone was 1.06 (95% CI 0.96–1.22) for CVD, while the OR for AIP alone was 1.16 (95% CI 1.02–1.33). Combined analysis showed that compared to the low TyG & low AIP group, the OR for the high TyG & high AIP group was 1.23 (95% CI 1.07–1.42) for CVD. In the survival Analysis, the hazard ratio (HR) for TyG alone was 1.19 (95% CI 1.04–1.35) for CVD, while the HR for AIP alone was 1.25 (95% CI 1.09–1.43). Combined analysis showed that compared to the low TyG & low AIP group, the HR for the high TyG & high AIP group was 1.27 (95% CI 1.10–1.43) for CVD. The findings underscore the significant coexposure effects of the TyG index and AIP on CVD, particularly in middle-aged adults.

Abstract Background Previous studies have identified sarcopenia as a significant risk factor for cardiovascular disease (CVD). However, these studies primarily focused on sarcopenia status at baseline, without considering changes in sarcopenia status during follow-up. The aim of this study is to investigate the association between changes in sarcopenia status and the incidence of new-onset cardiovascular disease. Methods This study utilized prospective cohort data from the China Health and Retirement Longitudinal Study (CHARLS). Sarcopenia status was assessed using the 2019 Asian Working Group for Sarcopenia (AWGS) algorithm and categorized as non-sarcopenia, possible sarcopenia, or sarcopenia. Changes in sarcopenia status were evaluated based on assessments at baseline and at the second follow-up survey 2 years later. CVD was identified through self-reported physician diagnoses of heart disease, including angina, myocardial infarction, congestive heart failure, and other heart problems, or stroke. Cox proportional hazards models were employed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for potential confounding factors. Results Based on the inclusion and exclusion criteria, a total of 7499 CHARLS participants were included in the analysis, with 50.8% being female and an average age of 58.5 years. Compared to participants with stable non-sarcopenia status, those who progressed from non-sarcopenia to possible sarcopenia or sarcopenia exhibited a significantly increased risk of new-onset CVD (HR 1.30, 95% CI 1.06–1.59). Conversely, participants who recovered from sarcopenia to non-sarcopenia or possible sarcopenia had a significantly reduced risk of new-onset CVD compared to those with stable sarcopenia status (HR 0.61, 95% CI 0.37–0.99). Among participants with baseline possible sarcopenia, those who recovered to non-sarcopenia had a significantly lower risk of new-onset CVD compared to those with stable possible sarcopenia status (HR 0.67, 95% CI 0.52–0.86). Conclusions Changes in sarcopenia status are associated with varying risks of new-onset CVD. Progression in sarcopenia status increases the risk, while recovery from sarcopenia reduces the risk of developing cardiovascular disease. Graphical Abstract

Abstract Axis inhibition protein 1 (AXIN1), a scaffold protein interacting with various critical molecules, plays a vital role in determining cell fate. However, its impact on the antiviral innate immune response remains largely unknown. Here, we identify that AXIN1 acts as an effective regulator of antiviral innate immunity against both DNA and RNA virus infections. In the resting state, AXIN1 maintains the stability of the transcription factor interferon regulatory factor 3 (IRF3) by preventing p62-mediated autophagic degradation of IRF3. This is achieved by recruiting ubiquitin-specific peptidase 35 (USP35), which removes lysine (K) 48-linked ubiquitination at IRF3 K366. Upon virus infection, AXIN1 undergoes a phase separation triggered by phosphorylated TANK-binding kinase 1 (TBK1). This leads to increased phosphorylation of IRF3 and a boost in IFN-I production. Moreover, KYA1797K, a small molecule that binds to the AXIN1 RGS domain, enhances the AXIN1-IRF3 interaction and promotes the elimination of various highly pathogenic viruses. Clinically, patients with HBV-associated hepatocellular carcinoma (HCC) who show reduced AXIN1 expression in pericarcinoma tissues have low overall and disease-free survival rates, as well as higher HBV levels in their blood. Overall, our findings reveal how AXIN1 regulates IRF3 signaling and phase separation-mediated antiviral immune responses, underscoring the potential of the AXIN1 agonist KYA1797K as an effective antiviral agent.

Abstract Approximately 70% of treatment failures in nasopharyngeal carcinoma (NPC) patients are attributed to distant metastasis, yet the underlying mechanisms remain unclear. RNA 5-methylcytosine (m5C) is an emerging regulatory modification that controls gene expression and plays a critical role in tumor progression. However, there is little information on the potential roles of RNA m5C modification in NPC metastasis. In this study, we found that the m5C reader Aly/REF export factor (ALYREF) is significantly upregulated in NPC, whereby its high expression is associated with metastasis and poor prognosis. ALYREF overexpression was found to promote tumor metastasis of NPC cells in vitro and in vivo. Mechanistically, m5C-modified NOTCH1 mRNA was identified as a target of ALYREF. Moreover, ALYREF was found to upregulate NOTCH1 expression by enhancing its RNA stability in an m5C modification-dependent manner, thereby promoting the activation of the NOTCH signaling pathway and facilitating NPC metastasis. Overall, our data reveal the crucial role of ALYREF in NPC metastasis and provide a potential therapeutic target for NPC.

Aim: Retinal photochemical damage (RPD) plays a significant role in the development of various ocular diseases, with Caspase-1 being a key contributor. This study investigates the protective effects of Caspase-1 gene-mediated pyroptosis against RPD. Methods: Differentially expressed genes (DEGs) associated with RPD were identified through the analysis of two expression profiles from the GEO database. Correlation analysis was used to pinpoint pyroptosis-related genes (PRGs) linked to RPD. A Caspase-1 knockout 661 W cell line was generated via CRISPR-Cas9 gene editing, and single-cell colonies were screened and purified. Validation of knockout cells was performed through RT-qPCR, gene sequencing, and Western blot analysis. Comparative assays on cell proliferation, intracellular reactive oxygen species (ROS), and cytotoxicity were conducted between wild-type and Caspase-1 knockout cells under light exposure. Further RT-qPCR and Western blot experiments examined changes in the mRNA and protein levels of key pyroptosis pathway components. Results: Significant alterations in Caspase-1 expression were observed among PRGs. Homozygous Caspase-1 knockout cell lines were confirmed through RT-qPCR, genomic PCR product sequencing, and Western blot analysis. Compared to wild-type 661 W cells, Caspase-1 knockout cells exhibited higher viability and proliferation rates after 24 h of light exposure, alongside reduced LDH release. The expression of downstream pyroptosis factors at both the mRNA and protein levels was markedly decreased in the knockout group. Conclusion: CRISPR/Cas9-mediated Caspase-1 knockout enhanced the resistance of 661 W cells to photochemical damage, suggesting that Caspase-1 may serve as a potential therapeutic target for RPD-related diseases.

Lately, the inclusion of oleogels has emerged as an alternative strategy for the preparation of chocolate. The present study used Lycium barbarum seed oil-based oleogel through a combination of glyceryl monostearate and vegetable wax as gelling factor, and partially replaced cocoa butter for the preparation of chocolate. To further explore the storage stability of the oleogel chocolate, we measured the white index of the chocolate every five days, and also observed the surface morphology of the chocolate using 3D laser focusing microscopy. Then, we characterized the stability of resulting oleogel-chocolate stored at different temperature conditions using differential scanning calorimetry and X-ray diffraction. Our data showed that the polycrystalline morphology of the chocolate changed during storage, and the temperature differences led to variations in white index and surface roughness. The presence of oleogel attenuated the migration of liquid oils and fats in the chocolate system, and increased the stability of the chocolate system as well as relatively improved the frosting phenomenon of the chocolate. This study provides innovative avenue for the preparation of chocolates with lower saturated fatty acid content, higher storage stability, and improved nutritional value.

Background The role of B cells in antitumor immunity remains controversial, with studies suggesting the protumor and antitumor activity. This controversy may be due to the heterogeneity in B cell populations, as the balance among the subtypes may impact tumor progression. The immunosuppressive regulatory B cells (Breg) release interleukin 10 (IL-10) but only represent a minor population. Additionally, tumor-specific antibodies (Abs) also exhibit antitumor and protumor functions dependent on the Ab isotype. Transcription factor c-Maf has been suggested to contribute to the regulation of IL-10 in Breg, but the role of B cell c-Maf signaling in antitumor immunity and regulating Ab responses remains unknown.Methods Conditional B cell c-Maf knockout (KO) and control mice were used to establish a KPC pancreatic cancer model and B16.F10 melanoma model. Tumor progression was evaluated. B cell and T cell phenotypes were determined by flow cytometry, mass cytometry, and cytokine/chemokine profiling. Differentially expressed genes in B cells were examined by using RNA sequencing (RNA-seq). Peripheral blood samples were collected from healthy donors and patients with melanoma for B cell phenotyping.Results Compared with B cells from the spleen and lymph nodes (LN), B cells in the pancreas exhibited significantly less follicular phenotype and higher IL-10 production in naïve mice. c-Maf deficiency resulted in a significant reduction of CD9+ IL-10-producing Breg in the pancreas. Pancreatic ductal adenocarcinoma (PDAC) progression resulted in the accumulation of circulating B cells with the follicular phenotype and less IL-10 production in the pancreas. Notably, B cell c-Maf deficiency delayed PDAC tumor progression and resulted in proinflammatory B cells. Further, tumor volume reduction and increased effective T cells in the tumor-draining LN were observed in B cell c-Maf KO mice in the B16.F10 melanoma model. RNA-seq analysis of isolated B cells revealed that B cell c-Maf signaling modulates immunoglobulin-associated genes and tumor-specific Ab production. We furthermore demonstrated c-Maf-positive B cell subsets and an increase of IL-10-producing B cells after incubation with IL-4 and CD40L in the peripheral blood of patients with melanoma.Conclusion Our study highlights that B cell c-Maf signaling drives tumor progression through the modulation of Breg, inflammatory responses, and tumor-specific Ab responses.

In this paper, we describe Ixeridium nujiangense, a novel species identified in southwestern Yunnan, China. Two populations have been found along the riverbanks of the Nujiang River in Yongde and Zhenkang Counties. Morphologically, I. nujiangense is most similar to the recently described I. malingheense, but it can be readily distinguished by its mostly divided basal leaves, narrower non-clasping cauline leaves, notably shorter corolla tube, pale brown anthers, and considerably longer beak of achenes.

Different sagittal and vertical malocclusions exhibit different characteristics in the growth, development, and final morphology of the temporomandibular joint. Different skeletal malocclusions affect the spatial and morphological characteristics of the final temporomandibular joint through different growth and development mechanisms. These mechanisms have important guiding significance for determining the etiology and guiding treatment plans of maxillofacial malocclusion in children and adolescents in clinical practice. This article summarized and analyzed morphological differences of the temporomandibular joint fossa and condyle in different sagittal and vertical malocclusions, as well as the relative position of the condyle in the fossa. It is found that there is a connection between different maxillofacial malocclusions and the characteristics of the temporomandibular joint, with the vertical direction having a more significant impact on the temporomandibular joint than the sagittal direction;the impact of vertical malocclusion on the temporomandibular joint is mainly reflected in the shape of the joint fossa and the position of the condyle in the fossa. The joint fossa of hyperdivergent malocclusion is often relatively low and flat, with the condyle located in the anterior upper position of the fossa. The joint fossa of hypodivergent is relatively narrow and deep, and the condyle is relatively backward and lower in the joint fossa. The possible mechanisms were also elaborated, providing reference for clinicians’ comprehensive diagnosis and treatment.

The coronary artery constitutes a vital vascular system that sustains cardiac function, with its primary role being the conveyance of indispensable nutrients to the myocardial tissue. When coronary artery disease occurs, it will affect the blood supply of the heart and induce myocardial ischemia. Therefore, it is of great significance to numerically simulate the coronary artery and evaluate its blood supply capacity. In this article, the coronary artery lumped parameter model was derived based on the relationship between circuit system parameters and cardiovascular system parameters, and the blood supply capacity of the coronary artery in healthy and stenosis states was studied. The aortic root pressure calculated by the aortic valve fluid-structure interaction (AV FSI) simulator was employed as the inlet boundary condition. To emulate the physiological phenomenon of sudden pressure drops resulting from an abrupt reduction in blood vessel radius, a head loss model was connected at the coronary artery's entrance. For each coronary artery outlet, the symmetric structured tree model was appended to simulate the terminal impedance of the missing downstream coronary arteries. The particle swarm optimization (PSO) algorithm was used to optimize the blood flow viscous resistance, blood flow inertia, and vascular compliance of the coronary artery model. In the stenosis states, the relative flow and fractional flow reserve (FFR) calculated by numerical simulation corresponded to the published literature data. It was anticipated that the proposed model can be readily adapted for clinical application, serving as a valuable reference for diagnosing and treating patients.

IntroductionLong non-coding RNAs (lncRNAs) play crucial roles in genetic markers, genome rearrangement, chromatin modifications, and other biological processes. Increasing evidence suggests that lncRNA functions are closely related to their subcellular localization. However, the distribution of lncRNAs in different subcellular localizations is imbalanced. The number of lncRNAs located in the nucleus is more than ten times that in the exosome.MethodsIn this study, we propose a new oversampling method to construct a predictive dataset and develop a predictive model called LncSTPred. This model improves the Adaboost algorithm for subcellular localization prediction using 3-mer, 3-RF sequence, and minimum free energy structure features.Results and DiscussionBy using our improved Adaboost algorithm, better prediction accuracy for lncRNA subcellular localization was obtained. In addition, we evaluated feature importance by using the F-score and analyzed the influence of highly relevant features on lncRNAs. Our study shows that the ANA features may be a key factor for predicting lncRNA subcellular localization, which correlates with the composition of stems and loops in the secondary structure of lncRNAs.

Abstract Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein‐Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV‐ (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC‐associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene‐edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV‐coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV‐ and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

In this paper, we describe a new species, Melanoseris penghuana, from Mt. Jiaozi Xueshan located in North-central Yunnan, China. Despite its morphological similarities to M. likiangensis, M. penghuana exhibits distinct differences in leaf texture, shape of terminal lobes, indumentum of leaves, peduncles, and involucres, as well as the length of the achenes. Additionally, the conservation status of this species is classified as Vulnerable through data analysis from two field surveys.

The Low-Energy X-ray Polarization Detector (LPD) is one of the payloads in the POLAR-2 experiment, which is planned as an external payload for deployment on the China Space Station in 2026. The LPD is specifically designed to observe the polarization of gamma-ray burst prompt emissions in the energy range of 2–10 keV, with a preliminary design featuring a wide field-of-view (FOV) of ±45°. This observation is achieved using an array of X-ray photoelectric polarimeters. Because of the wide FOV design of the detector, nearly all photons impinge on the detector off-axis. This paper investigates the polarization reconstruction of a photoelectric polarimeter for off-axis photons. It was found that the reconstruction of the emission azimuthal angles of photoelectron tracks is the main factor affecting the shape of the modulation function for off-axis radiation. Therefore, a modulation function correction method based on Monte Carlo (MC) simulation is proposed. This MC simulation-based method is applied to both simulated and experimental data to correct the modulation function for off-axis radiation. The reconstruction results demonstrate that this method can accurately determine the polarization degree and polarization angle of photons under different conditions. While we tested up to 45° off-axis angles due to our ±45° FOV, the method is theoretically applicable to off-axis angles up to ∼90°.

Designing photocatalysts with p-n heterojunction structures is an effective way to boost the separation of photogenerated carriers and stimulate the photocatalytic degradation activity. Herein, an efficient visible-light responsive AgI/BiSI p-n heterojunction photocatalyst was successfully constructed. X-ray photoelectron spectroscopy (XPS), photoluminescence (PL) spectroscopy, and electrochemical measurements confirmed that the AgI/BiSI p-n heterojunction structure was beneficial to the separation and transfer of photogenerated carriers, promoting the generation of main active species (•O2− and h+). Furthermore, the photocatalytic degradation rate constants of Acid Red 1 (0.4699 min−1) and metronidazole (0.0730 min−1) over the optimal AgI/BiSI were about 8.4 and 3.0 times higher than those over pure AgI, respectively. This work provides a heterojunction engineering strategy to design high-efficient photocatalysts for the degradation of refractory organic pollutants.

AIM: To evaluate the effect of lens surgery on health-related quality of life (HRQoL) of preschool children with congenital ectopia lentis (CEL). METHODS: A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center. Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study. All of them completed the child and proxy (parental) PedsQL™ 4.0 before and after the surgery. Their preoperative scores were compared to their postoperative ones. Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children. RESULTS: Thirty-two children with CEL successfully underwent surgery without any complications, among whom 8 had monocular surgery and 24 had binocular surgery. Preoperative and postoperative questionnaires were completed by 32 child-parent pairs. Surgical intervention could significantly improve the vision of affected children (P

Apigenin, a natural flavonoid has been reported against a variety of cancer types. However, it is unclear whether apigenin can promote autophagy and ferroptosis in Ishikawa cells. There are few reports on the mechanism of apigenin on autophagy and ferroptosis of endometrial cancer Ishikawa cells. We found that iron accumulation, lipid peroxidation, glutathione consumption, p62, HMOX1, and ferritin were increased, while, solute carrier family 7 member 11 and glutathione peroxidase 4 were decreased. Ferrostatin-1, an iron-death inhibitor could reverse the effects of apigenin in Ishikawa cells. On the other hand, apigenin could promote autophagy via up-regulating Beclin 1, ULK1, ATG5, ATG13, and LC3B and down-regulating AMPK, mTOR, P70S6K, and ATG4. Furthermore, apigenin could inhibit tumor tissue proliferation and restrict tumor growth via ferroptosis in vivo.

Melanoseris kangdingensis, a new species native to western Sichuan, China, is firstly described and illustrated, and its conservation status is also assessed. It bears resemblance to M. macrantha and M. bracteata in terms of morphology; however, there are distinguishing characteristics in terms of their leaf structure, presence of bracts, hairiness of involucre, number of florets, and length of both stamen tube and achene’s beak.

Abstract Background FLT-PET/CT can accurately identify and locate functional bone marrow (FBM) with hematopoietic capability, the FBM were divided into two levels as FBM1 (strongest hemopoietic ability region)and FBM2 (moderate hemopoietic ability region) via FLT-PET/CT. The purpose of this study was to explore the relationship between dose-volume parameters of pelvic FBM and hematologic toxicity (HT) during radiotherapy with or without concurrent chemotherapy for uterine cervical/endometrial cancer. Methods From December 2016 to September 2021, ninety-seven uterine cervical/endometrial cancer patients received intensity-modulated radiation therapy were prospectively recruited in this single-arm, prospective, phase II trial. Blood counts were reviewed weekly during radiotherapy. Single- and multifactor regression methods were used to analyze the relationships between dose-volume parameters of FBM1/2 and grade ≥ 2 HT. ROC curves were used to determine the cutoff values for the dose-volume parameters of FBM1/2. Results The incidence of grade ≥ 2 leukopenia, neutropenia, thrombocytopenia and anemia in patients during radiotherapy was 63.9%, 45.4%, 19.6% and 38.8% respectively, and the median occurrence time was the 29th, 42th, 35th and 31th day, respectively. Multivariate regression analysis showed that the Dmax of FBM1 was significantly related to grade ≥ 2 leukopenia (OR = 1.277 95% CI 1.067–1.528, P = 0.008), Dmean of FBM2 was significantly related to grade ≥ 2 thrombocytopenia (OR = 1.262 95% CI 1.066–1.494, P = 0.007), and V10 of FBM1 was significantly related to grade ≥ 2 anemia (OR = 1.198 95% CI 1.003–1.431, P = 0.046). The incidence of grade ≥ 2 leukopenia for patients with FBM1 Dmax < 53 Gy was lower than that for patients with FBM1 Dmax ≥ 53 Gy (53.4% vs. 95.8%, P

Objective: Prenatal hyperandrogenism, characterized by elevated androgen levels during pregnancy, has significant multisystem impacts on offspring health. This review systematically examines the effects of prenatal hyperandrogenism on the cardiovascular, metabolic, reproductive, and behavioral health of offspring. By analyzing existing research, this review aims to provide a comprehensive understanding of the long-term health impacts of prenatal hyperandrogenism, offering insights for clinical management and prevention of related diseases. Mechanism: A comprehensive search was performed in PubMed database with the key words: “hyperandrogenemia and child”, “hyperandrogenemia and offspring”, “androgen excess and child”, “androgen excess and offspring”, “prenatal hyperandrogenism”, “prenatal androgen excess”, and a combination of these terms to find quality articles published from 1995 to 2024. Findings in Brief: Elevated prenatal androgen levels disrupt normal fetal development, leading to long-term consequences such as cardiovascular dysfunction, including hypertension and cardiac hypertrophy, and metabolic abnormalities such as insulin resistance and metabolic syndrome. It has a significant impact on the long-term health of the offspring’s reproductive system, with potential links to conditions such as polycystic ovary syndrome (PCOS). Furthermore, prenatal hyperandrogenism is associated with increased risks of neuropsychiatric disorders, including autism spectrum disorder (ASD) and anxiety. Conclusions: Elevated prenatal androgen levels disrupt normal fetal development, leading to long-term cardiovascular, metabolic, reproductive, and neuropsychiatric disorders. The underlying mechanisms involve hormonal regulation, placental function, oxidative stress, gene expression alterations, and metabolic programming. Further research is needed to develop effective interventions to mitigate these adverse effects.

The objective of this study was to investigate the effects of ultrasonically emulsified palm oil (UE-PA), peanut oil (UE-PE), and sunflower oil (UE-SU) on the whiteness, textural, rheological, and microstructural properties of surimi gels from silver carp. Three ultrasonically emulsified oils had different specific fatty acids and oil droplet sizes of 300-400 nm. Compared with the control group, low addition of UE-SU (2.5 g/100 g) showed the highest water-holding capacity (WHC), storage modulus (G’), and hydrogen bond in surimi gels. The low addition of UE-PE (2.5 g/100 g) increased disulfide bond, β-sheet, and β-turn of surimi gel, so had higher hardness and chewiness values, comparing to those with other emulsified oils. As ultrasonically emulsified oil addition increased in surimi gels (2.5–7.5 g/100 g), hardness, chewiness, WHC, G’ were decreased, while whiteness was increased (p

Abstract Sustained activation of DNA damage response (DDR) signaling has been demonstrated to play vital role in chemotherapy failure in cancer. However, the mechanism underlying DDR sustaining in cancer cells remains unclear. In the current study, we found that the expression of the DDUP microprotein, encoded by the CTBP1-DT lncRNA, drastically increased in cisplatin-resistant ovarian cancer cells and was inversely correlated to cisplatin-based therapy response. Using a patient-derived human cancer cell model, we observed that DNA damage-induced DDUP foci sustained the RAD18/RAD51C and RAD18/PCNA complexes at the sites of DNA damage, consequently resulting in cisplatin resistance through dual RAD51C-mediated homologous recombination (HR) and proliferating cell nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. Notably, treatment with an ATR inhibitor disrupted the DDUP/RAD18 interaction and abolished the effect of DDUP on prolonged DNA damage signaling, which resulted in the hypersensitivity of ovarian cancer cells to cisplatin-based therapy in vivo. Altogether, our study provides insights into DDUP-mediated aberrant DDR signaling in cisplatin resistance and describes a potential novel therapeutic approach for the management of platinum-resistant ovarian cancer.

IntroductionCircadian 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.MethodsA 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