Clinical Outcomes and Prognostic Factors in Stage III C Cervical Cancer Patients Treated with Radical Radiotherapy or Radiochemotherapy.

Objective: Since the update of the 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria, there have been few reports on the prognosis of stage III C cervical cancer. Moreover, some studies have drawn controversial conclusions, necessitating further verification. This study aims to evaluate the clinical outcomes and determine the prognostic factors for stage III C cervical cancer patients treated with radical radiotherapy or radiochemotherapy. Methods: The data of 117 stage III C cervical cancer patients (98 III C1 and 19 III C2) who underwent radical radiotherapy or radiochemotherapy were retrospectively analyzed. We evaluated 3-year overall survival (OS) and disease-free survival (DFS) using the Kaplan-Meier method. Prognostic factors were analyzed using the Log-rank test and Cox proportional hazard regression model. The risk of para-aortic lymph node metastasis (LNM) in all patients was assessed through Chi-squared test and logistic regression analysis. Results: For stage III C1 and III C2 patients, the 3-year OS rates were 77.6% and 63.2% (P = .042), and the 3-year DFS rates were 70.4% and 47.4% (P = .003), respectively. The pretreatment location of pelvic LNM, histological type, and FIGO stage was associated with OS (P = .033, .003, .042, respectively); the number of pelvic LNM and FIGO stage were associated with DFS (P = .015, .003, respectively). The histological type was an independent prognostic indicator for OS, and the numbers of pelvic LNM and FIGO stage were independent prognostic indicators for DFS. Furthermore, a pelvic LNM largest short-axis diameter ≥ 1.5 cm and the presence of common iliac LNM were identified as high-risk factors influencing para-aortic LNM in stage III C patients (P = .046, .006, respectively). Conclusions: The results of this study validated the 2018 FIGO staging criteria for stage III C cervical cancer patients undergoing concurrent chemoradiotherapy. These findings may enhance our understanding of the updated staging criteria and contribute to better management of patients in stage III C.

FLOURY ENDOSPERM24, a heat shock protein 101 (HSP101), is required for starch biosynthesis and endosperm development in rice.

Endosperm is the main storage organ in cereal grain and determines grain yield and quality. The molecular mechanisms of heat shock proteins in regulating starch biosynthesis and endosperm development remain obscure. Here, we report a rice floury endosperm mutant flo24 that develops abnormal starch grains in the central starchy endosperm cells. Map-based cloning and complementation test showed that FLO24 encodes a heat shock protein HSP101, which is localized in plastids. The mutated protein FLO24T296I dramatically lost its ability to hydrolyze ATP and to rescue the thermotolerance defects of the yeast hsp104 mutant. The flo24 mutant develops more severe floury endosperm when grown under high-temperature conditions than normal conditions. And the FLO24 protein was dramatically induced at high temperature. FLO24 physically interacts with several key enzymes required for starch biosynthesis, including AGPL1, AGPL3 and PHO1. Combined biochemical and genetic evidence suggests that FLO24 acts cooperatively with HSP70cp-2 to regulate starch biosynthesis and endosperm development in rice. Our results reveal that FLO24 acts as an important regulator of endosperm development, which might function in maintaining the activities of enzymes involved in starch biosynthesis in rice.

Intelligent Detection and Odor Recognition of Cigarette Packaging Paper Boxes Based on a Homemade Electronic Nose.

The printing process of box packaging paper can generate volatile organic compounds, resulting in odors that impact product quality and health. An efficient, objective, and cost-effective detection method is urgently needed. We utilized a self-developed electronic nose system to test four different cigarette packaging paper samples. Employing multivariate statistical methods like Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA), Statistical Quality Control (SQC), and Similarity-based Independent Modeling of Class Analogy (SIMCA), we analyzed and processed the collected data. Comprehensive evaluation and quality control models were constructed to assess sample stability and distinguish odors. Results indicate that our electronic nose system rapidly detects odors and effectively performs quality control. By establishing models for quality stability control, we successfully identified samples with acceptable quality and those with odors. To further validate the system's performance and extend its applications, we collected two types of cigarette packaging paper samples with odor data. Using data augmentation techniques, we expanded the dataset and achieved an accuracy rate of 0.9938 through classification and discrimination. This highlights the significant potential of our self-developed electronic nose system in recognizing cigarette packaging paper odors and odorous samples.

Effects of Streptomyces sp. HU2014 inoculation on wheat growth and rhizosphere microbial diversity under hexavalent chromium stress.

Wheat (Triticum aestivum L.) is a major foodstuff for over 40% of the world's population. However, hexavalent chromium [Cr(VI)] in contaminated soil significantly affects wheat production and its ecological environment. Streptomyces sp. HU2014 was first used to investigate the effects of Cr (VI) stress on wheat growth. We analyzed the Cr(VI) concentration, physicochemical properties of wheat and soil, total Cr content, and microbial community structures during their interactions. HU2014 reduced the toxicity of Cr(VI) and promoted wheat growth by increasing total nitrogen, nitrate nitrogen, total phosphorus, and Olsen-phosphorus in Cr(VI)-contaminated soil. These four soil variables had strong positive effects on two bacterial taxa, Proteobacteria and Bacteroidota, in the HU2014 treatments. In addition, the level of the dominant Proteobacteria positively correlated with the total Cr content in the soil. Among the fungal communities, which had weaker correlations with soil variables compared with bacterial communities, Ascomycota was the most abundant. Our findings suggest that HU2014 can promote the phytoremediation of Cr(VI)-contaminated soil.

Effect of bioaugmentation on gas production and microbial community during anaerobic digestion in a low-temperature fixed-bed reactor.

Low temperature is one of the limiting factors for anaerobic digestion in cold regions. To improve the efficiency of anaerobic digestion for methane production in stationary reactors under low-temperature conditions, and to improve the structure of the microbial community for anaerobic digestion at low temperatures. We investigated the effects of different concentrations of exogenous Methanomicrobium (10, 20, 30%) and different volumes of carbon fiber carriers (0, 10, 20%) on gas production and microbial communities to improve the performance of low-temperature anaerobic digestion systems. The results show that the addition of 30% exogenous microorganisms and a 10% volume of carbon fiber carrier led to the highest daily (128.15 mL/g VS) and cumulative (576.62 mL/g VS) methane production. This treatment effectively reduced the concentrations of COD and organic acid, in addition to stabilizing the pH of the system. High-throughput sequencing analysis revealed that the dominant bacteria under these conditions were Acidobacteria and Firmicutes and the dominant archaea were Candidatus_Udaeobacter and Methanobacterium. While the abundance of microorganisms that metabolize organic acids was reduced, the functional abundance of hydrogenophilic methanogenic microorganisms was increased. Therefore, the synergistic effect of Methanomicrobium bioaugmentation with carbon fiber carriers can significantly improve the performance and efficiency of low-temperature anaerobic fermentation systems.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Physiological and transcriptomic responses of seawater halobios to micro/nano-scale polystyrene-cadmium exposure in a marine food web.

Micro/nano-plastics (MPs/NPs) represent an emerging contaminant, posing a significant threat to oceanic halobios. While the adverse effects of joint pollutants on marine organisms are well-documented, the potential biological impacts on the food chain transmission resulting from combinations of MPs/NPs and heavy metals (HMs) remain largely unexplored. This study exposed the microbial loop to combined contaminants (MPs/NPs + HMs) for 48h, bacteria and contaminants are washed away before feeding to the traditional food chain, employing microscopic observation, biochemical detection, and transcriptome analysis to elucidate the toxicological mechanisms of the top predator. The findings revealed that MPs/NPs combined with Cd2+ could traverse both the microbial loop and classical food chain. Acute exposure significantly affected the carbon biomass of the top predator Tigriopus japonicus (75.8% lower). Elevated antioxidant enzyme activity led to lipid peroxidation, manifesting in increased malondialdehyde levels. Transcriptome sequencing showed substantial differential gene expression levels in T. japonicus under various treatments. The upregulation of genes associated with apoptosis and inflammatory responses, highlighting the impact of co-exposure on oxidative damage and necroptosis within cells. Notably, NPs-Cd exhibited stronger toxicity than MPs-Cd. NPs-Cd led to a greater decrease in the biomass of top predators, accompanied by lower activities of GSH, SOD, CAT, and GSH-PX, resulting in increased production of lipid peroxidation product MDA and higher oxidative stress levels. This investigation provides novel insights into the potential threats of MPs/NPs combined with Cd2+ on the microbial loop across traditional food chain, contributing to a more comprehensive assessment of the ecological risks associated with micro/nano-plastics and heavy metals.

IL-33 aggravates extranodal NK/T cell lymphoma aggressiveness and angiogenesis by activating the Wnt/ß-catenin signaling pathway.

Extranodal NK/T cell lymphoma (ENKTCL) is an extremely aggressive form of lymphoma and lacks of specific diagnostic markers. The study intended to unearth the role of interleukin-33 (IL-33) in ENKTCL. RT-qPCR was conducted to assess mRNA levels of ENKTCL tissues and cells, while western blot assay was performed for evaluating protein levels. Plate cloning experiment and transwell assay were employed to measure aggressiveness of ENKTCL. Tube formation assay was executed to determine the angiogenesis ability. Mice ENKTCL xenograft model was designed to probe the impacts of IL-33 in vivo. IL-33 and suppression of tumorigenicity 2 receptor (ST2, receptor of IL-33) were enhanced in ENKTCL. IL-33 inhibition suppressed viability, migration, and invasion of ENKTCL cells. Moreover, IL-33 knockdown restricted angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, Wnt/ß-catenin pathway associated proteins (ß-catenin, c-myc, and cyclin D1) were downregulated by loss of IL-33. However, these impacts were overturned by Wnt/ß-catenin signaling agonist lithium chloride (LiCl). Additionally, IL-33 silencing exerted anti-tumor effect via Wnt/ß-catenin pathway in vivo. Silencing of IL-33 inhibited ENKTCL tumorigenesis and angiogenesis by inactivating Wnt/ß-catenin signaling pathway. As such, IL-33 might be a prospective treatment target for ENKTCL.

High glucose promotes atherosclerosis by regulating miRNA let7d-5p level.

BACKGROUND: MiRNA let7d-5p has been recently reported to be abnormally expressed in diabetes-associated atherosclerosis (AS). However, it still remains unknown how let7d-5p contributes to the process of atherosclerosis. METHODS: Twenty fresh tissues and a total of 28 wax block specimens from carotid endarterectomy procedures were obtained from the Luoyang Central Hospital affiliated to Zhengzhou University. The expression of let7d-5p was assessed using quantitative RT-PCR (qRT-PCR). A series of in vitro experiments was used to determine the roles of let7d-5p knockdown and overexpression in vascular smooth muscle cells (VSMCs). RESULTS: We discovered that the carotid plaques from diabetic patients had lower expression levels of miR let7d-5p. In VSMCs, the expression of miRNA let7d-5p was significantly lower in high glucose conditions compared with low glucose situations. The proliferation and migration of VSMCs were also inhibited by the overexpression of let7d-5p, whereas the opposite was true when let7d-5p was inhibited, according to gain and loss of function studies. Mechanically, let7d-5p might activate the GSK3ß/ß-catenin signaling pathway via binding to the high mobility group AT-Hook 2 (HMGA2) mRNA in VSMCs. Additionally, GLP-1RA liraglutide may prevent the migration and proliferation of VSMCs by raising let7d-5p levels. CONCLUSIONS: High glucose stimulated the proliferation and migration of VSMCs by regulating the let7d-5p/HMGA2/GSK3ß/ß-catenin pathway, and liraglutide may slow atherosclerosis by increasing the levels of miR let7d-5p.

Mechanisms of the novel pesticide sodium dodecyl benzene sulfonate in the mitigation of protozoan ciliated pathogens during microalgal cultivation.

Protozoan ciliates represent a common biological contaminant during microalgae cultivation, which will lead to a decline in microalgae productivity. This study investigated the effectiveness of sodium dodecyl benzene sulfonate (SDBS) in controlling ciliate populations within microalgae cultures. SDBS concentrations of 160 mg/L and 100 mg/L were found to effectively manage the representative species of ciliates contamination by Euplotes vannus and Uronema marinum during the cultivation of Synechococcus and Chlorella, and the growth vitality of microalgae has been restored. Additionally, SDBS at these concentrations reduced oxidative stress resistance and induced membrane damage to remove biological pollutants by modulating enzyme activity, affecting lipid, energy, amino acid metabolism pathways, and processes such as translation and protein folding. This research provides insights into the mechanisms through which SDBS effectively combats protozoan ciliates during the microalgal cultivation. This contributes to reduce biological pollution, ensure the overall productivity and healthy and sustainable management of microalgae ecosystems.

Seroprevalence of Anti-SARS-CoV-2 Remained Extremely Low in Taiwan Until the Vaccination Program Was Implemented.

Background: The Taiwanese government made a concerted effort to contain a coronavirus disease 2019 (COVID-19) nosocomial outbreak of variant B.1.429, shortly before universal vaccination program implementation. This study aimed to investigate seroprevalence in the highest-risk regions. Methods: Between January and February 2021, we retrieved 10 000 repository serum samples from blood donors to examine for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid (N) and spike (S) antigens. A positive result was confirmed if anti-N and anti-S antibodies were positive. Overall, 2000 donors residing in the highest-risk district and donating blood in January 2021 were further examined for SARS-CoV-2 RNA. We estimated seroprevalence and compared the epidemic curve between confirmed COVID-19 cases and blood donors with positive antibodies or viral RNA. Results: Twenty-one cases with COVID-19 were confirmed in the nosocomial cluster, with an incidence of 1.27/100 000 in the COVID-affected districts. Among 4888 close contacts of the nosocomial cases, 20 (0.4%) became confirmed cases during isolation. Anti-SARS-CoV-2 was detected in 2 of the 10000 blood donors, showing a seroprevalence of 2/10000 (95% CI, 0.55-7.29). None of the 2000 donors who underwent tests for SARS-CoV-2 RNA were positive. The SARS-CoV-2 infection epidemic curve was observed sporadically in blood donors compared with the nosocomial cluster. Conclusions: In early 2021, an extremely low anti-SARS-CoV-2 seroprevalence among blood donors was observed. Epidemic control measures through precise close contact tracing, testing, and isolation effectively contained SARS-CoV-2 transmission before universal vaccination program implementation.

Connective tissue inspired elastomer-based hydrogel for artificial skin via radiation-indued penetrating polymerization.

Robust hydrogels offer a candidate for artificial skin of bionic robots, yet few hydrogels have a comprehensive performance comparable to real human skin. Here, we present a general method to convert traditional elastomers into tough hydrogels via a unique radiation-induced penetrating polymerization method. The hydrogel is composed of the original hydrophobic crosslinking network from elastomers and grafted hydrophilic chains, which act as elastic collagen fibers and water-rich substances. Therefore, it successfully combines the advantages of both elastomers and hydrogels and provides similar Young's modulus and friction coefficients to human skin, as well as better compression and puncture load capacities than double network and polyampholyte hydrogels. Additionally, responsive abilities can be introduced during the preparation process, granting the hybrid hydrogels shape adaptability. With these unique properties, the hybrid hydrogel can be a candidate for artificial skin, fluid flow controller, wound dressing layer and many other bionic application scenarios.

Toxic effects on ciliates under nano-/micro-plastics coexist with silver nanoparticles.

Owing to the degradation of plastics, microplastics (MPs) and nanoplastics (NPs) have remained the focus of global attention. Silver nanoparticles (AgNPs) could adversely affect marine organisms due to their broad application. So far, the combined effects of MPs/NPs (strong adsorbents) with AgNPs on marine organisms are scant. Thus, four sizes polystyrene beads (80 nm, 220 nm, 1.07 µm, and 2.14 µm) combined with AgNPs (30 nm) were assessed using ciliated protozoa Uronema marinum. Results showed that MPs/NPs dramatically decrease the abundance, biovolume, and carbon biomass of U. marinum. And, exposure could cause changes of antioxidant enzyme activity and antioxidant content on U. marinum. The combined toxicity of MPs/NPs with AgNPs to ciliates showed an enhanced effect compared to exposure alone. Additionally, the negative effects under exposure of NPs plus AgNPs were more significant than those of MPs plus AgNPs. Transcriptome sequencing showed that co-exposure could affect the energy metabolism and lipid metabolism of ciliates, even cause DNA and protein damage. Our study provided a novel insight and first-hand basic data for the understanding of combined toxicity of MPs /NPs with AgNPs on the basic trophic level ciliated protozoa in marine ecosystems.

Guided by the goal of "double carbon", what is the carbon emission reduction effect of the promotion and application of green technology in China?

"Carbon peaking and carbon neutralization" is an important measure to promote China's ecological and environmental protection and high-quality economic development, and the innovation and application of green technology are critical factors in achieving the "double carbon" goal. Based on the number of citations of green patents of listed enterprises in 30 provinces in China from 2011 to 2020, this paper uses GGDP to replace traditional GDP and calculate carbon emission intensity. Based on the relevant panel data at the provincial level, this paper constructs a spatial Durbin model to analyze the impact mechanism of whether the promotion and application of green technologies promote regional carbon emission reduction. The specific research results are as follows: (1) Through regression of the core explanatory variables with a one-stage lag, it is verified that the promotion and application of green technology has a significant positive promoting effect on regional carbon emission reduction, and there are significant spatial spillover effects and "learning by doing" effects. (2) In the part of heterogeneity test, the impact of green technology promotion and application on carbon emission reduction presents apparent regional heterogeneity and factor endowment heterogeneity. (3) The mediating effect test verifies the mediating effect of energy structure and industrial structure on the influence of green technology promotion and application on regional carbon emission reduction. (4) In the part moderating effect test, it is verified that marketization level and new infrastructure construction have a positive moderating effect in their influencing process, financial development, and government support will weaken the influence of green technology promotion and application on carbon emission reduction effect, and human capital level has a nonlinear regulating effect. The research conclusions of this paper provide necessary enlightenment for the coordination and unification of China's economic transition to innovation-driven and green and low-carbon development.

Unraveling the Activity Trends and Design Principles of Single-Atom Catalysts for Nitrate Electrocatalytic Reduction.

Electrocatalytic nitrate (NO3-) reduction represents one of the most promising approaches to mitigate NO3- pollution and yield NH3, but it is still challenged by the atomic economy and selectivity issues of substantial active sites. Here, we describe a comprehensive investigation on a series of single-atom catalysts (SACs) using nitrogen-doped carbon as substrate (metal/NC). The essence of activity is related to the extent of the electron transfer capacity (SAs → NO3-). Among these examined SACs, the Cu/NC presents good performance toward NH3 synthesis, i.e., a maximum NH3 Faradaic efficiency of 100% with a high NH3 yield rate of up to 32,300 µg h-1 mgcat.-1. X-ray absorption fine structure spectra and density functional theory calculations provide evidence that the electronic structure of Cu-N4 coordination prohibits the formation of N2, N2O, and H2 and facilitates the orbital hybridization between the 2p orbitals of NO3- and 3d orbitals of Cu single-atom sites. Our study is believed to provide fundamental guidance for the future design of highly efficient electrocatalysts in NO3- reduction to NH3.

Understanding the Activity Trends in Electrocatalytic Nitrate Reduction to Ammonia on Cu Catalysts.

Cu-based catalysts possess great potential in the electrocatalytic nitrate (NO3-) reduction reaction for ammonia (NH3) synthesis. However, the low atomic economy limits their further application. Here we report a Cu single-atom (SA) incorporated in nitrogen-doped carbon (Cu SA/NC) with high atomic economy, which exhibits superior NH3 Faradaic efficiency (FE) of 100% along with an impressive NH3 yield rate of 7480 µg h-1 mgcat.-1. As counterparts, Cus+n/NC, with mixed SA and nanoparticles (NPs), shows decreasing NH3 FE with decreasing SA content, but the production of N2 and N2O increases gradually, which reaches the maximum on pure Cu NPs. In situ characterizations and theoretical calculations reveal that a higher NH3 FE of Cu SA/NC is ascribed to a lower free energy of the rate-limiting step (HNO* → N*) and effective inhibition for the N-N coupled process. This work provides the intuitive activity trends of Cu-based catalysts, opening an avenue for subsequent catalysts design.

Efficacy Analysis of Physical Therapy in Treating Chronic Prostatitis: Unblocking Obstructed Glandular Ducts Could Be a Novel Treatment Strategy.

Objective: This study investigates the efficacy of physical therapy in treating chronic prostatitis grounded on the glandular duct blockage theory. Methods: The study includes patients who were diagnosed and treated for chronic prostatitis between November 2022 and July 2023 at Renhui clinic in Jiangmen, Guangdong and Renhui frontline clinic in Shenzhen Guangdong. The recorded data includes the frequency of physical therapies including prostate massages, rectal probe high-frequency vibration treatment, and low-intensity extracorporeal shockwave therapy (Li-ESWT). Post-treatment urine sediment was collected for microscopic examination, and the scores of each patient on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) and the Premature Ejaculation Diagnostic Tool (PEDT) were recorded pre- and post-treatment in order to calculate the effectiveness rate. Results: The study involved a total of 48 patients, of which 26 were diagnosed with premature ejaculation. On average, each patient received 2.1 prostate massages, underwent 4.1 rectal probe high-frequency vibration treatments, and 8.3 Li-ESWT sessions. Following treatment, the initial microscopic examination of the urine sediment revealed aged white blood cell clusters, prostate calculi clusters, and inactive sperm clusters, all appearing in the shape of glandular tubes. The mean NIH-CPSI scores pre- and post-treatment were 27.2±6.9 and 18.0±6.6, respectively, indicating an effectiveness rate of 81.3%. The average PEDT scores pre- and post-treatment were 14.5±3.5 and 10.5±4.2, respectively, with an effectiveness rate of 53.8%. Conclusion: Unblocking obstructed glandular ducts might provide a novel therapeutic strategy for treating chronic prostatitis.

CiRS-7 Enhances the Liquid-liquid Phase Separation of miRISC and Promotes DNA Damage Repair.

Noncoding RNAs have been found to play important roles in DNA damage repair, whereas the participation of circRNA remains undisclosed. Here, we characterized ciRS-7, a circRNA containing over 70 putative miR-7-binding sites, as an enhancer of miRISC condensation and DNA repair. Both in vivo and in vitro experiments confirmed the condensation of TNRC6B and AGO2, two core protein components of human miRISC. Moreover, overexpressing ciRS-7 largely increased the condensate number of TNRC6B and AGO2 in cells, while silencing ciRS-7 reduced it. Additionally, miR-7 overexpression also promoted miRISC condensation. Consistent with the previous report that AGO2 participated in RAD51-mediated DNA damage repair, the overexpression of ciRS-7 significantly promoted irradiation-induced DNA damage repair by enhancing RAD51 recruitment. Our results uncover a new role of circRNA in liquid-liquid phase separation and provide new insight into the regulatory mechanism of ciRS-7 on miRISC function and DNA repair.

Liquid-liquid phase separation in DNA double-strand breaks repair.

DNA double-strand breaks (DSBs) are the fatal type of DNA damage mostly induced by exposure genome to ionizing radiation or genotoxic chemicals. DSBs are mainly repaired by homologous recombination (HR) and nonhomologous end joining (NHEJ). To repair DSBs, a large amount of DNA repair factors was observed to be concentrated at the end of DSBs in a specific spatiotemporal manner to form a repair center. Recently, this repair center was characterized as a condensate derived from liquid-liquid phase separation (LLPS) of key DSBs repair factors. LLPS has been found to be the mechanism of membraneless organelles formation and plays key roles in a variety of biological processes. In this review, the recent advances and mechanisms of LLPS in the formation of DSBs repair-related condensates are summarized.

Cardiovascular and microvascular outcomes according to vitamin D level and genetic variants among individuals with prediabetes: a prospective study.

BACKGROUND: Whether serum vitamin D mediate vascular diseases in prediabetic populations remains unclear. This study aimed to determine the associations between circulating 25-hydroxyvitamin D [25(OH)D] levels and vitamin D receptor (VDR) polymorphisms with the risk of macrovascular complications, including myocardial infarction and stroke, and microvascular complications such as diabetic nephropathy and retinopathy, among adults with prediabetes. METHODS: Participants with prediabetes in UK Biobank were included (N = 56,387). Multivariable dose-response and Cox proportion models were used to explore the relationship of serum 25(OH)D status and the risks of vascular complications. The interaction of VDR polymorphisms with serum 25(OH)D level on risks of vascular events was also assessed. RESULTS: During a median follow-up of 12 years, higher levels of 25(OH)D were significantly and nonlinearly associated with a lower risk of macrovascular diseases among prediabetic individuals. The adjusted hazard ratios (95% confidential interval) of serum 25(OH)D levels of ≥ 75.0 nmol/L versus < 25 nmol/L were 0.75 (0.63-0.88) for myocardial infarction, 0.74 (0.55-1.00) for stroke, 1.02 (0.60-1.74) for diabetic nephropathy, and 1.30 (0.92-1.84) for diabetic retinopathy, respectively. The rs2228570 (FokI) polymorphisms significantly interacted with 25(OH)D on incident myocardial infarction (P-interaction = 0.042) and stroke (P-interaction = 0.033). The individuals with serum 25(OH)D level of 50.0-74.9 nmol/L and rs2228570 (FokI) homozygotes had the lowest risks of vascular complications. CONCLUSIONS: Lower serum 25(OH)D levels are significantly and nonlinearly associated with an increased risk of cardiocerebrovascular diseases in prediabetic individuals, with VDR polymorphisms of rs2228570 (FokI) modify such associations. Monitoring a safe 25(OH)D concentration is suggested to prevent the vascular complications for prediabetes.