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DNA methyltransferase 3B (DNMT3B) plays a crucial role in DNA methylation during mammalian development. Mutations in DNMT3B are associated with human genetic diseases, particularly immunodeficiency, centromere instability, facial anomalies (ICF) syndrome. Although ICF syndrome-related missense mutations in the DNMT3B have been identified, their precise impact on protein structure and function remains inadequately explored. Here, we delve into the impact of four ICF syndrome-linked mutations situated in the DNMT3B dimeric interface (H814R, D817G, V818M, and R823G), revealing that each of these mutations compromises DNA-binding and methyltransferase activities to varying degrees. We further show that H814R, D817G, and V818M mutations severely disrupt the proper assembly of DNMT3B homodimer, whereas R823G does not. We also determined the first crystal structure of the methyltransferase domain of DNMT3B-DNMT3L tetrameric complex hosting the R823G mutation showing that the R823G mutant displays diminished hydrogen bonding interactions around T775, K777, G823, and Q827 in the protein-DNA interface, resulting in reduced DNA-binding affinity and a shift in sequence preference of +1 to +3 flanking positions. Altogether, our study uncovers a wide array of fundamental defects triggered by DNMT3B mutations, including the disassembly of DNMT3B dimers, reduced DNA-binding capacity, and alterations in flanking sequence preferences, leading to aberrant DNA hypomethylation and ICF syndrome.

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G-quadruplex (G4) structures play integral roles in modulating biological functions and can be regulated by small molecules. The MYC gene is critical during tumor initiation and malignant progression, in which G4 acts as an important modulation motif. Herein, we reported the MYC promoter G4 recognized by a platinum(II) compound Pt-phen. Two Pt-phen-MYC G4 complex structures in 5 mM K+ were determined by NMR. The Pt-phen first strongly binds the 3'-end of MYC G4 to form a 1:1 3'-end binding complex and then binds 5'-end to form a 2:1 complex with more Pt-phen. In the complexes, the Pt-phen molecules are well-defined and stack over four bases at the G-tetrad for a highly extensive π-π interaction, with the Pt atom aligning with the center of the G-tetrad. The flanking residues were observed to rearrange and cover on top of Pt-phen to stabilize the whole complex. We further demonstrated that Pt-phen targets G4 DNA in living cells and represses MYC gene expression in cancer cells. Our work elucidated the structural basis of ligand binding to MYC promoter G4. The platinum compound bound G4 includes multiple complexes formation, providing insights into the design of metal ligands targeting oncogene G4 DNA.

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Silicon oxycarbide (SiOC) exhibits good retention and a reasonable specific capacity and is an alternative to silicon used as an anode material for high-performance lithium-ion batteries. However, SiOC generally shows a low Initial Coulombic Efficiency (ICE), wasting the lithium from the cathode. This work explores different sol-gel routes to synthesize SiOC from silanes and compares their performance. We found that the crushed bulk acid-catalyzed SiOC is simple and cost-effective but with excellent performance. Adding dimethyldimethoxysilane (DMDMS) by decreasing the oxygen content further enhances the battery performance. Building upon the excellent performance of SiOC, we further embed nano-silicon into SiOC. The Si/SiOC composites achieved a significantly higher specific capacity of 2185 mAhg-1 and an impressive ICE of 77 % with acceptable battery retention.

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BACKGROUND: The fusion rate, clinical efficacy, and complications of minimally invasive fusion surgery and open fusion surgery in the treatment of lumbar degenerative disease are still unclear. METHODS: We conducted a literature search using PubMed, Embase, Cochrane Library, CNKI, and WANFANG databases. RESULTS: This study included 38 retrospective studies involving 3097 patients. Five intervention modalities were considered: unilateral biportal endoscopic-lumbar interbody fusion (UBE-LIF), percutaneous endoscopic-lumbar interbody fusion (PE-LIF), minimally invasive-transforaminal lumbar interbody fusion (MIS-TLIF), transforaminal lumbar interbody fusion (TLIF), and posterior lumbar interbody fusion (PLIF). Quality assessment indicated that each study met acceptable quality standards. PE-LIF demonstrated reduced low back pain (Odds Ratio = 0.50, Confidence Interval: 0.38-0.65) and lower complication rate (Odds Ratio = 0.46, Confidence Interval: 0.25-0.87) compared to PLIF. However, in indirect comparisons, PE-LIF showed the lowest fusion rates, with the ranking as follows: UBE-LIF (83.2%) > MIS-TLIF (59.6%) > TLIF (44.3%) > PLIF (39.8%) > PE-LIF (23.1%). With respect to low back pain relief, PE-LIF yielded the best results, with the order of relief as follows: PE-LIF (96.4%) > MIS-TLIF (64.8%) > UBE-LIF (62.6%) > TLIF (23.0%) > PLIF (3.2%). Global and local consistency tests showed satisfactory results, and heterogeneity tests indicated good stability. CONCLUSIONS: Compared to conventional open surgery, minimally invasive fusion surgery offered better scores for low back pain and Oswestry Disability Index, lower complication rates, reduced bleeding, and shorter hospital stays. However, minimally invasive fusion surgery did not show a significant advantage in terms of fusion rate and had a longer operative time.

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High temperatures are a major stress factor that limit the growth of Pinellia ternata. WRKY proteins widely distribute in plants with the important roles in plant growth and stress responses. However, WRKY genes have not been identified in P. ternata thus far. In this study, five PtWRKYs with four functional subgroups were identified in P. ternata. One group III WRKY transcription factor, PtWRKY2, was strongly induced by high temperatures, whereas the other four PtWRKYs were suppressed. Analysis of transcription factor characteristics revealed that PtWRKY2 localized to the nucleus and specifically bound to W-box elements without transcriptional activation activity. Overexpression of PtWRKY2 increased the heat tolerance of Arabidopsis, as shown by the higher percentage of seed germination and survival rate, and the longer root length of transgenic lines under high temperatures compared to the wild-type. Moreover, PtWRKY2 overexpression significantly decreased reactive oxygen species accumulation by increasing the catalase, superoxide dismutase, and peroxidase activities. Furthermore, the selected heat shock-associated genes, including five transcription factors (HSFA1A, HSFA7A, bZIP28, DREB2A, and DREB2B), two heat shock proteins (HSP70 and HSP17.4), and three antioxidant enzymes (POD34, CAT1, and SOD1), were all upregulated in transgenic Arabidopsis. The study identifies that PtWRKY2 functions as a key transcriptional regulator in the heat tolerance of P. ternata, which might provide new insights into the genetic improvement of P. ternata.

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Objective: Our aim was to develop a nomogram that integrates clinical and radiological data obtained from computed tomography (CT) scans, enabling the prediction of chronic hydrocephalus in patients with aneurysmal subarachnoid hemorrhage (aSAH). Method: A total of 318 patients diagnosed with subarachnoid hemorrhage (SAH) and admitted to the Department of Neurosurgery at the Affiliated People's Hospital of Jiangsu University between January 2020 and December 2022 were enrolled in our study. We collected clinical characteristics from the hospital's medical record system. To identify risk factors associated with chronic hydrocephalus, we conducted both univariate and LASSO regression models on these clinical characteristics and radiological features, accompanied with penalty parameter adjustments conducted through tenfold cross-validation. All features were then incorporated into multivariate logistic regression analyses. Based on these findings, we developed a clinical-radiological nomogram. To evaluate its discrimination performance, we conducted Receiver Operating Characteristic (ROC) curve analysis and calculated the Area Under the Curve (AUC). Additionally, we employed calibration curves, and utilized Brier scores as an indicator of concordance. Additionally, Decision Curve Analysis (DCA) was performed to determine the clinical utility of our models by estimating net benefits at various threshold probabilities for both training and testing groups. Results: The study included 181 patients, with a determined chronic hydrocephalus prevalence of 17.7%. Univariate logistic regression analysis identified 11 potential risk factors, while LASSO regression identified 7 significant risk factors associated with chronic hydrocephalus. Multivariate logistic regression analysis revealed three independent predictors for chronic hydrocephalus following aSAH: Periventricular white matter changes, External lumbar drainage, and Modified Fisher Grade. A nomogram incorporating these factors accurately predicted the risk of chronic hydrocephalus in both the training and testing cohorts. The AUC values were calculated as 0.810 and 0.811 for each cohort respectively, indicating good discriminative ability of the nomogram model. Calibration curves along with Hosmer-Lemeshow tests demonstrated excellent agreement between predicted probabilities and observed outcomes in both cohorts. Furthermore, Brier scores (0.127 for the training and 0.09 for testing groups) further validated the predictive performance of our nomogram model. The DCA confirmed that this nomogram provides superior net benefit across various risk thresholds when predicting chronic hydrocephalus. The decision curve demonstrated that when an individual's threshold probability ranged from 5 to 62%, this model is more effective in predicting the occurrence of chronic hydrocephalus after aSAH. Conclusion: A clinical-radiological nomogram was developed to combine clinical characteristics and radiological features from CT scans, aiming to enhance the accuracy of predicting chronic hydrocephalus in patients with aSAH. This innovative nomogram shows promising potential in assisting clinicians to create personalized and optimal treatment plans by providing precise predictions of chronic hydrocephalus among aSAH patients.

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Background & aims: Macronutrients are the main part of the human diet and can affect multiple health outcomes. Nevertheless, associations between dietary macronutrient quality and asthenozoospermia risk have not been reported to date. Thus, this study aimed to be the first to explore the associations between macronutrient quality and asthenozoospermia risk using the novel multidimensional macronutrient quality index (MQI). Methods: A case-control study was conducted at infertility clinics of Shengjing Hospital of China Medical University during June and December 2020, including 552 asthenozoospermia cases and 585 normozoospermia controls. Data on diet were collected using a validated food frequency questionnaire. MQI was estimated according to the carbohydrate quality index (CQI), fat quality index (FQI), and protein quality index (PQI). Binary logistic regression models were performed to calculate the odds ratio (OR) with a 95% confidence interval (CI). Subgroup and interaction analyses were performed based on age, body mass index, physical activity, smoking, drinking, and education level. Dose-response relationships were evaluated by restricted cubic splines. Sensitivity analyses were performed in two ways. First, participants with a dietary change were excluded to lower potential reverse causation. Then, we used the healthy plate protein source quality index instead of PQI to redefine MQI. Results: No statistically significant association was observed between dietary MQI and asthenozoospermia risk (OR = 1.24, 95% CI: 0.88-1.73). The sub-indices of MQI, CQI, FQI, and PQI, failed to be identified as having a statistically significant association with asthenozoospermia risk (OR = 1.35, 95% CI: 0.92-1.97 for CQI; OR = 1.13, 95% CI: 0.84-1.53 for FQI; OR = 1.28, 95% CI: 0.92-1.78 for PQI). However, CQI showed a positive association with the risk of asthenozoospermia among non-drinkers (Ptrend < 0.05) and highly educated participants (OR = 1.82, 95% CI: 1.13-2.94; Ptrend < 0.05). Additionally, there was a multiplicative interaction between CQI and education level for asthenozoospermia risk (P < 0.05). Conclusions: Our findings demonstrated no association of MQI and its sub-indices with asthenozoospermia risk except for CQI. Although our findings are mostly non-significant, they contribute novel knowledge to this research field and lay the foundation for future studies.

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The rhizosphere is an important place for material exchange between medicinal plants and soil. Root exudates are the medium of material and signal exchange between plants and soil and are the key factors in the regulation of rhizosphere microecology. Rhizosphere microorganisms are an important part of the rhizosphere microecology of medicinal plants, and the interaction between root exudates and rhizosphere microorganisms has an important influence on the growth and quality formation of medicinal plants. Rational utilization of the interaction between root exudates and rhizosphere microorganisms of medicinal plants is one of the important ways to ensure the healthy growth of medicinal plants and promote the development of ecological planting of Chinese medicinal materials. In the paper, the research status of root exudates and rhizosphere microorganisms of medicinal plants in recent years was summarized. The interaction mechanism between root exudates and rhizosphere microorganisms of medicinal plants, as well as the influence of rhizosphere microorganisms on the growth of medicinal plants, were analyzed. In addition, the advantages and promoting effects of intercropping ecological planting mode on rhizosphere microecology of medicinal plants and quality improvement of Chinese medicinal materials were explained, providing a good basis for the study of the interaction among medicinal plants, microorganisms, and soil. Furthermore, it could produce important theoretical and practical significance for the ecological planting and sustainable utilization of medicinal plants.

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Pinellia ternata (Thunb.) Briet., a valuable herb native to China, is susceptible to the "sprout tumble" phenomenon because of high temperatures, resulting in a significant yield reduction. However, the molecular regulatory mechanisms underlying the response of P. ternata to heat stress are not well understood. In this study, we integrated transcriptome and miRNAome sequencing to identify heat-response genes, microRNAs (miRNAs), and key miRNA-target pairs in P. ternata that differed between heat-stress and room-temperature conditions. Transcriptome analysis revealed extensive reprogramming of 4,960 genes across various categories, predominantly associated with cellular and metabolic processes, responses to stimuli, biological regulation, cell parts, organelles, membranes, and catalytic and binding activities. miRNAome sequencing identified 1,597 known/conserved miRNAs that were differentially expressed between the two test conditions. According to the analysis, genes and miRNAs associated with the regulation of transcription, DNA template, transcription factor activity, and sequence-specific DNA binding pathways may play a major role in the resistance to heat stress in P. ternata. Integrated analysis of the transcriptome and miRNAome expression data revealed 41 high-confidence miRNA-mRNA pairs, forming 25 modules. MYB-like proteins and calcium-responsive transcription coactivators may play an integral role in heat-stress resistance in P. ternata. Additionally, the candidate genes and miRNAs were subjected to quantitative real-time polymerase chain reaction to validate their expression patterns. These results offer a foundation for future studies exploring the mechanisms and critical genes involved in heat-stress resistance in P. ternata.

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Pinellia ternata, a valuable Chinese herb, suffers yield reduction due to "sprout tumble" under high temperatures. However, the mechanisms underlying its high-temperature stress remain poorly understood. NAM, ATAF1/2, and CUC2 (NAC) transcription factors regulate plant tissue growth and abiotic stress. Hence, there has been no comprehensive research conducted on NAC transcription factors in P. ternata. We identified 98 PtNAC genes unevenly distributed across 13 chromosomes, grouped into 15 families via phylogenetic analysis. Gene expression analysis revealed diverse expression patterns of PtNAC genes in different tissue types. Further studies revealed that PtNAC5/7/17/35/43/47/57/66/86 genes were highly expressed in various tissues of P. ternata and induced by heat stress, among which PtNAC66 was up-regulated at the highest folds induced by heat temperature. PtNAC66 is a nuclear protein that can selectively bind to the cis-responsive region NACRS but lacks the ability to activate transcription in yeast. For further research, PtNAC66 was cloned and transgenic Arabidopsis was obtained. PtNAC66 overexpression increased high-temperature tolerance compared to wild-type plants. Transcriptome profiling demonstrated that overexpression of PtNAC66 led to significant modification of genes responsible for regulating binding, catalytic activity, transcription regulator activity and transporter activity response genes. Additionally, PtNAC66 was found to bind the promoters of CYP707A3, MYB102 and NAC055, respectively, and inhibited their expression, affecting the high-temperature stress response in Arabidopsis. Our research established the foundation for functional studies of PtNAC genes in response to high-temperature forcing by characterizing the P. ternata NAC gene family and examining the biological role of PtNAC66 in plant high-temperature tolerance.

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Thanks to the extensive efforts toward optimizing perovskite crystallization properties, high-quality perovskite films with near-unity photoluminescence quantum yield are successfully achieved. However, the light outcoupling efficiency of perovskite light-emitting diodes (PeLEDs) is impeded by insufficient light extraction, which poses a challenge to the further advancement of PeLEDs. Here, an anisotropic multifunctional electron transporting material, 9,10-bis(4-(2-phenyl-1H-benzo[d]imidazole-1-yl)phenyl) anthracene (BPBiPA), with a low extraordinary refractive index (ne) and high electron mobility is developed for fabricating high-efficiency PeLEDs. The anisotropic molecular orientations of BPBiPA can result in a low ne of 1.59 along the z-axis direction. Optical simulations show that the low ne of BPBiPA can effectively mitigate the surface plasmon polariton loss and enhance the photon extraction efficiency in waveguide mode, thereby improving the light outcoupling efficiency of PeLEDs. In addition, the high electron mobility of BPBiPA can facilitate balanced carrier injection in PeLEDs. As a result, high-efficiency green PeLEDs with a record external quantum efficiency of 32.1% and a current efficiency of 111.7 cd A-1 are obtained, which provides new inspirations for the design of electron transporting materials for high-performance PeLEDs.

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Pinellia ternata is an important natural medicinal herb in China. However, it is susceptible to withering when exposed to high temperatures during growth, which limits its tuber production. Mitochondria usually function in stress response. The P . ternata mitochondrial (mt) genome has yet to be explored. Therefore, we integrated PacBio and Illumina sequencing reads to assemble and annotate the mt genome of P . ternata . The circular mt genome of P . ternata is 876 608bp in length and contains 38 protein-coding genes (PCGs), 20 tRNA genes and three rRNA genes. Codon usage, sequence repeats, RNA editing and gene migration from chloroplast (cp) to mt were also examined. Phylogenetic analysis based on the mt genomes of P . ternata and 36 other taxa revealed the taxonomic and evolutionary status of P . ternata . Furthermore, we investigated the mt genome size and GC content by comparing P . ternata with the other 35 species. An evaluation of non-synonymous substitutions and synonymous substitutions indicated that most PCGs in the mt genome underwent negative selection. Our results provide comprehensive information on the P . ternata mt genome, which may facilitate future research on the high-temperature response of P . ternata and provide new molecular insights on the Araceae family.

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Mg-Sn alloy thin films have garnered significant attention for their outstanding thermoelectric (TE) properties and cost-effective elemental composition, making them potential candidates for wearable energy harvesting devices. While previous studies have explored the properties of these thin films, limited research has been conducted to identify physical factors that can further enhance their performance. In this study, we present a novel approach utilizing a convenient electron beam coevaporation technique to fabricate Mg-Sn alloy thin films. Experimental results revealed that controlling the tin content in the Mg-Sn thin films at 38.9% led to the formation of a mixed-phase structure, comprising Mg2Sn and Mg9Sn5. This dual-phase structure exhibited a notable advantage in enhancing the TE performance. The presence of the Mg9Sn5 phase significantly increased the carrier concentration, while maintaining the original Seebeck coefficient and mobility, thereby improving the conductivity of Mg2Sn. Theoretical calculations indicated that the Mg9Sn5 phase displayed 1D-like characteristics, leading to a highly effective valley degeneracy and consequently a high power factor. Overall, this work introduces a promising approach to fabricate high-performance Mg-Sn alloy thin films through electron beam coevaporation, opening up possibilities for their application in wearable energy harvesting devices.

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STUDY QUESTION: What is the mechanism behind cryoinjury in human sperm, particularly concerning the interplay between reactive oxygen species (ROS) and autophagy, and how does it subsequently affect sperm fate? SUMMARY ANSWER: The freeze-thaw operation induces oxidative stress by generating abundant ROS, which impairs sperm motility and activates autophagy, ultimately guiding the sperm toward programmed cell death such as apoptosis and necrosis, as well as triggering premature capacitation. WHAT IS KNOWN ALREADY: Both ROS-induced oxidative stress and autophagy are thought to exert an influence on the quality of frozen-thawed sperm. STUDY DESIGN, SIZE, DURATION: Overall, 84 semen specimens were collected from young healthy fertile males, with careful quality evaluation. The specimens were split into three groups to investigate the ROS-induced cryoinjury: normal control without any treatment, sperm treated with 0.5 mM hydrogen peroxide (H2O2) for 1 h, and sperm thawed following cryopreservation. Samples from 48 individuals underwent computer-assisted human sperm analysis (CASA) to evaluate sperm quality in response to the treatments. Semen samples from three donors were analyzed for changes in the sperm proteome after H2O2 treatment, and another set of samples from three donors were analyzed for changes following the freeze-thaw process. The other 30 samples were used for fluorescence-staining and western blotting. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm motility parameters, including progressive motility (PR %) and total motility (PR + NP %), were evaluated using the CASA system on a minimum of 200 spermatozoa. The proteomic profiles were determined with label-free mass spectrometry (MS/MS) and protein identification was performed via ion search against the NCBI human database. Subsequently, comprehensive bioinformatics was applied to detect significant proteomic changes and functional enrichment. Fluorescence-staining and western blot analyses were also conducted to confirm the proteomic changes on selected key proteins. The ROS level was measured using 2',7'-dichlorodihydrofluorescein diacetate labeling and the abundance of bioactive mitochondria was determined by evaluating the inner mitochondrial membrane potential (MMP) level. Molecular behaviors of sequestosome-1 (p62 or SQSTM1) and microtubule-associated proteins 1A/1B light chain 3 (LC3) were monitored to evaluate the state of apoptosis in human sperm. Fluorescent probes oxazole yellow (YO-PRO-1) and propidium iodide (PI) were utilized to monitor programmed cell death, namely apoptosis and necrosis. Additionally, gradient concentrations of antioxidant coenzyme Q10 (CoQ10) were introduced to suppress ROS impacts on sperm. MAIN RESULTS AND THE ROLE OF CHANCE: The CASA analysis revealed a significant decrease in sperm motility for both the H2O2-treatment and freeze-thaw groups. Fluorescence staining showed that high ROS levels were produced in the treated sperm and the MMPs were largely reduced. The introduction of CoQ10 at concentrations of 20 and 30 µM resulted in a significant rescue of progressive motility (P < 0.05). The result suggested that excessive ROS could be the major cause of sperm motility impairment, likely by damaging mitochondrial energy generation. Autophagy was significantly activated in sperm when they were under oxidative stress, as evidenced by the upregulation of p62 and the increased conversion of LC3 as well as the upregulation of several autophagy-related proteins, such as charged multivesicular body protein 2a, mitochondrial import receptor subunit TOM22 homolog, and WD repeat domain phosphoinositide-interacting protein 2. Additionally, fluorescent staining indicated the occurrence of apoptosis and necrosis in both H2O2-treated sperm and post-thaw sperm. The cell death process can be suppressed when CoQ10 is introduced, which consolidates the view that ROS could be the major contributor to sperm cryoinjury. The freeze-thaw process could also initiate sperm premature capacitation, demonstrated by the prominent increase in tyrosine phosphorylated proteins, verified with anti-phosphotyrosine antibody and immunofluorescence assays. The upregulation of capacitation-related proteins, such as hyaluronidase 3 and Folate receptor alpha, supported this finding. LARGE SCALE DATA: The data underlying this article are available in the article and its online supplementary material. LIMITATIONS, REASONS FOR CAUTION: The semen samples were obtained exclusively from young, healthy, and fertile males with progressive motility exceeding 60%, which might overemphasize the positive effects while possibly neglecting the negative impacts of cryoinjury. Additionally, the H2O2 treatment conditions in this study may not precisely mimic the oxidative stress experienced by sperm after thawing from cryopreservation, potentially resulting in the omission of certain molecular alterations. WIDER IMPLICATIONS OF THE FINDINGS: This study provides substantial proteomic data for a comprehensive and deeper understanding of the impact of cryopreservation on sperm quality. It will facilitate the design of optimal protocols for utilizing cryopreserved sperm to improve applications, such as ART, and help resolve various adverse situations caused by chemotherapy, radiotherapy, and surgery. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by grants from the Major Innovation Project of Research Institute of National Health Commission (#2022GJZD01-3) and the National Key R&D Program of China (#2018YFC1003600). All authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

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Objective To investigate the expression of circular-RNA DDX5(circ-DDX5)in breast cancer tissues and its relationship with the clinical stage of breast cancer patients,and to analyze the regulatory mechanism of circ-DDX5 on the proliferation and invasion of human breast cancer cell line.Methods The expression level of circ-DDX5 in breast cancer tissues and its correlation with the clinical stage of breast cancer patients were analyzed by TCGA database.Bioinformatics analysis and dual-luciferase reporter gene experiments verified the targeting rela-tionship between circ-DDX5 and miR-3940.The correlation between circ-DDX5 and miR-3940 expression in breast cancer tissues was analyzed by TCGA database.The expression level of circ-DDX5 in breast cancer SK-BR-3,MDA-MB-231,BT-549,MCF-7,and HCC-1937 cells was detected by RT-qPCR.The circ-DDX5 over-expression plasmid and negative control plasmid were transfected into MDA-MB-231 cells,which were named circ-DDX5 group and NC group,respectively.The proliferation and invasion of MDA-MB-231 cells in the circ-DDX5 group and the NC group were detected by colony formation assay and Transwell assay.The expressions of proliferation pheno-type protein and invasion phenotype protein of MDA-MB-231 cells were detected by Western blot.The expression level of miR-3940 in MDA-MB-231 cells of circ-DDX5 group and NC group was detected by RT-qPCR.Results The expression of circ-DDX5 in breast cancer tissues was lower than that in adjacent tissues(P＜0.01)and the ex-pression level of circ-DDX5 was negatively correlated with the clinical stage of breast cancer patients(P＜0.01).There was a targeting relationship between circ-DDX5 and miR-3940(P＜0.01).The expression of circ-DDX5 and miR-3940 in breast cancer tissue was negatively correlated(P＜0.01).The expression of circ-DDX5 in human breast cancer cell lines was lower than that in immortalized breast epithelial cells MCF-10A(P＜0.05 or P＜0.01).Compared with the NC group,the over-expression of circ-DDX5 could significantly inhibit the proliferation and in-vasion of MDA-MB-231 cells(P＜0.01),as well as the proliferation phenotype proteins(cyclin C,CDK3)and in-vasion phenotype proteins(Snail,vimentin)expression(P＜0.01)and miR-3940 expression(P＜0.01).Conclu-sions The expression of circ-DDX5 in breast cancer tissues and cells is low.circ-DDX5 inhibits the proliferation and invasion of breast cancer MDA-MB-231 cells by targeting the expression of miR-3940.

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Objective:To explore the impact of emergency response to public health emergencies on the efficiency of pre-hospital emergency work, and study the degree of impact on 120 ambulance dispatchers in Chongqing city during pre-periods and post-periods of the emergency intervention.Methods:Taking 120 phone answering and ambulance operation efficiency as the research subjects, we collected pre-hospital emergency case data from a city's emergency medical center, covering the period from November 10, 2021 to January 6, 2023. The cases were divided into groups according to the time periods of emergency response. A regression discontinuity design method was employed to compare the response of emergency intervention to the predictions (virtual cases) without the emergency intervention, obtaining the average intervention effect.Results:During the study period of 27 days, the number of 120 calls picked up within 10 seconds increased from 11 000 to 19 000, but the answering rate slightly decreased within 10 seconds. The vacancy rate of 120 ambulances during emergency response decreased from 0.39% to 0.20%, but the completion rate within 18 minutes decreased from 72% to 30%. In this particular emergency response period, the number of patient complaints (such as high fever and difficulty breathing) increased compared to the pre-period of emergency response.Conclusion:Emergency response significantly impacts pre-hospital emergency work such as emergency phone answering and ambulance operation efficiency. This study provides empirical research results and decision-making support for urban emergency medical services to respond to public health emergencies.

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BACKGROUND:Vitamin C,as an essential nutrient,has a wide range of biological effects and a variety of biological functions related to the pathogenesis of sarcopenia.Vitamin C supplementation is expected to be a novel prevention and treatment measure for sarcopenia. OBJECTIVE:To review recent research advances in the application of vitamin C in the pathogenesis and treatment of sarcopenia,and to discuss the potential role of vitamin C in the prevention and treatment of sarcopenia and possible mechanistic pathways based on published evidence. METHODS:The first author performed a computer search of PubMed,Web of Science,CNKI and other databases for relevant studies involving vitamin C in sarcopenia.The search keywords were"vitamin C,ascorbic acid,L-ascorbic acid,ascorbate,antioxidants,oxidative stress,sarcopenia,muscular atrophy,muscle weakness,muscle development,skeletal muscle regenerate,muscles,skeletal muscle"in English and Chinese,respectively.The search period was from each database inception to July 2023.After screening,85 articles were included for further review. RESULTS AND CONCLUSION:Ensuring adequate dietary vitamin C intake or maintaining normal circulating levels of vitamin C will help to reduce age-related muscle loss and decrease the prevalence of sarcopenia.In addition,vitamin C supplementation is also useful for improving skeletal muscle mass,strength and physical function with potential synergistic effects in exercise strategies for sarcopenia.The effects of vitamin C on sarcopenia may be via the following biological mechanisms:vitamin C limits the activation of the ubiquitin-proteasome pathway mainly by inhibiting oxidative stress and inflammatory responses in skeletal muscle,thus positively regulating protein metabolic homeostasis,and may enhance mitochondrial antioxidant defenses through its antioxidant effects to maintain healthy mitochondrial function.In addition,vitamin C affects myoblast proliferation,differentiation and myotube size,mainly by increasing the expression of myogenic regulatory factors and activating protein synthesis signaling pathways,which contribute to the promotion of muscle development as well as the repair and regeneration of damaged muscle tissue.The positive effects of vitamin C in sarcopenia need to be studied in large samples and with optimized designs for important influencing factors,such as the choice of supplementation dose and duration,the design of exercise prescription when vitamin C is combined with an exercise intervention,and the assessment of the redox status of the individual.It is recommended that future studies should be conducted in older patients with sarcopenia(<50 μmol/L)with suboptimal vitamin C status to investigate the efficacy of a combined intervention of long-term supplementation with 1 000 mg/d vitamin C(for 6 months or longer)with at least two or more types of multi-type combined exercise,with supplementation timed to take place at 1 hour after the end of the exercise,and with monitoring of markers of oxidative damage produced during the exercise such as malondialdehyde or protein hydroxyl levels were monitored.In conclusion,the optimal dose and timing of vitamin C supplementation for older adults with sarcopenia needs to be explored more,while the appropriate design of exercise prescriptions(especially the type and intensity of exercise)needs to be further determined.

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Objective In order to explore the influence and effect of case teaching method based on real patients in oto-rhinolaryngology on clinical practice ability of general practice.Methods 96 trainees of general practice in otolaryngology de-partment from January 2018 to January 2021 were randomly divided into two groups:a CBL group and a control group.In the CBL group,CBL teaching method was adopted based on real patients in Otorhinolaryngology.Conventional teaching method was used in the control group.Results The theoretical scores of written test and the examination of clinical skill operation scores of the CBL group and the control group were analyzed.There was significant difference between the two groups(P＜0.05).The students in CBL group were more satisfied with clinical thinking ability,analysis and problem solving ability,active learning abil-ity,learning efficiency,teacher-student interaction,doctor-patient communication ability and consultation skills than the control group.There was significant difference between the two groups(P＜0.05).Conclusion The CBL teaching method can obvi-ously improve the learning enthusiasm and clinical practice ability of general resident training doctors.The teaching quality has been significantly improved.It is of great value to cultivate excellent general practitioners.

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Objective:To evaluate the value of 18F-FDG PET metabolic parameters in predicting histopathological grade of soft tissue sarcoma (STS). Methods:From December 2012 to December 2021, 51 patients (26 males, 25 females, age range: 32-84 years) who underwent 18F-FDG PET/CT imaging before treatment and confirmed STS pathologically in the First Affiliated Hospital of Dalian Medical University were retrospectively collected. 18F-FDG PET metabolic parameters SUV max, metabolic tumor volume (MTV), total lesion glycolysis (TLG) and intertumoral FDG uptake heterogeneity (IFH) were measured. Kruskal-Wallis rank sum test was used to analyze the differences in metabolic parameters among different groups and Spearman rank correlation analysis was used to analyze the correlation of each metabolic parameter and histological grade. Logistic regression was used to screen and construct the prediction model for high-grade STS. ROC curve was plotted and Delong test was used to analyze the differences among AUCs. Results:The metabolic parameters SUV max, MTV, TLG and IFH were significantly different among French Federation of Cancer Centers Sarcoma Group (FNCLCC)Ⅰ( n=8), Ⅱ( n=10) and Ⅲ ( n=33) grade groups ( H values: 16.24, 10.52, 19.29 and 16.99, all P<0.05), and each metabolic parameter was positively correlated with histological grade ( rs values: 0.58, 0.45, 0.52, and 0.62, all P<0.05). Multivariate logistic regression analysis showed that SUV max(odds ratio ( OR)=1.27, 95% CI: 1.06-1.51, P=0.009) and IFH ( OR=6.83, 95% CI: 1.44-32.27, P=0.015) were independent risk indicators for high-grade STS. The prediction model constructed by combining SUV max and IFH had better diagnostic efficacy for differentiating high-grade STS with the AUC of 0.93, and the sensitivity of 93.9%(31/33) and the specificity of 16/18, respectively. The AUC of prediction model was significant different from SUV max, MTV, TLG and IFH (AUCs: 0.81, 0.78, 0.86 and 0.85; z values: 2.69, 2.53, 1.94 and 1.97, all P<0.05). Conclusions:The metabolic parameters SUV max, MTV, TLG and IFH are valuable predictors for histological grade of STS. The combination of SUV max and IFH may be a more meaningful method than using each of the above metabolic parameters alone.

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【Objective】 To investigate the safety and effectiveness of suctioning flexible ureteroscopy with intelligent pressure-control at different times after drainage for patients with urogenic sepsis complicated with upper urinary tract stones. 【Methods】 Clinical data of 59 patients treated in the Department of Urology, Affiliated Hospital of Nantong University during May 2022 and May 2023 were collected.The patients were divided into early lithotripsy (≤1 week) group (n=27) and late lithotripsy (>1 week) group (n=32).Baseline data, imaging data and postoperative data of the two groups were compared. 【Results】 There were no significant differences between the two groups in the stone-free rate, total incidence of complications, incidence of high-grade complications, length of stay after lithotripsy, hospitalization costs after lithotripsy and total hospitalization costs (P>0.05). 【Conclusion】 Both early lithotripsy (1 week) are safe and effective in the treatment of urogenic sepsis after drainage.