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Abstract Background This study was to explore the relationship between cardiovascular health (CVH) and the risk of all-cause mortality in patients with osteoarthritis (OA). Methods This cohort study retrieved the data of 3642 patients with OA aged ≥ 20 years from the 2007—2018 National Health and Nutrition Examination Survey (NHANES). CVH was evaluated based on Life’s Essential 8 (LE8) includes diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. The outcome of all-cause mortality was assessed using the death certificate records of participants from the National Death Index. Variables that might affect all-cause mortality were used as covariates. The weighted univariate COX proportional hazards model was used to explore the association between each covariate and all-cause mortality. The weighted univariate and multivariate COX proportional hazards models were used to explore the association between different CVH levels and all-cause mortality. A restricted cubic spline (RCS) curve was plotted to show the association between different CVH levels and all-cause mortality in OA patients. Hazard ratio (HR) and 95% confidence interval (CI) were calculated. Results Findings show that people with moderate CVH (HR = 0.67, 95% CI = 0.45—0.98) and high CVH (HR = 0.47, 95% CI = 0.26—0.87) were associated with reduced risk of all-cause mortality in patients with OA. The HR of all-cause mortality in patients with OA decreased by 0.12 as per 10 points increase of LE8 score (HR = 0.81, 95% CI = 0.73—0.90). The RCS curve revealed that the HR of all-cause mortality decreased with the increase in LE8 score. The survival probability of patients in the high CVH group was higher than the moderate CVH group and low CVH group (p = 0.002). Conclusion Moderate-to-high CVH is associated with a decreased risk of all-cause mortality in patients with OA. These findings might provide a reference for the formulation of prognosis improvement strategies for the management of patients with OA.

Abstract Renal interstitial fibrosis (RIF) is a prevalent consequence of chronic renal diseases, characterized by excessive extracellular matrix (ECM) deposition. A Disintegrin and Metalloprotease 17 (ADAM17), a transmembrane metalloproteinase, plays a central role in driving renal fibrosis progression by activating Notch 1 protein and the downstream TGF-β signaling pathway. Our study investigated potential therapeutic interventions for renal fibrosis, focusing on human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hucMSC-EVs). We found that hucMSC-EVs inhibit ADAM17, thereby impeding renal fibrosis progression. Analysis of hucMSC-EVs miRNA profiles revealed significant enrichment of miR-13474, which effectively targeted and inhibited ADAM17 mRNA expression, subsequently suppressing Notch1 activation, TGF-β signaling, and collagen deposition. Overexpression of miR-13474 enhanced hucMSC-EVs' inhibitory effect on renal fibrosis, while its downregulation abolished this protective effect. Our findings highlight the efficacy of hucMSC-EVs overexpressing miR-13474 in mitigating renal fibrosis via ADAM17 targeting. These insights offer potential therapeutic strategies for managing renal fibrosis.

Abstract Background Cardiac dysfunction, including arrhythmias, may be one of the main clinical manifestations of Becker muscular dystrophy (BMD). Amiodarone is widely used to treat arrhythmia. However, multi-systemic toxicity caused by amiodarone, especially hepatotoxicity, should not be neglected. Here, we introduce a novel case of multi-systemic amiodarone toxicity involving the liver, renal and coagulation in BDM patient with ABCB4 gene mutation. Case presentation We present a case of a 16-year-old boy admitted with heart failure and atrial fibrillation (AF). He was diagnosed with Becker muscular dystrophy (BMD) and gene testing showed comorbid mutations in gene DMD, ABCB4 and DSC2. Amiodarone was prescribed to control the paroxysmal atrial fibrillation intravenously. However, his liver enzyme levels were sharply elevated, along with cardiac shock, renal failure and coagulation disorders. After bedside continuous renal replacement therapy, the patient’s liver function and clinical status rehabilitated. Conclusions ABCB4 gene mutation might be involved in amiodarone-induced hepatotoxicity. Studies in a cohort might help to prove this hypothesis in the future.

Abstract The CRISPR/Cas9 system has shown great potential for treating human genetic diseases through gene therapy. However, there are concerns about the safety of this system, specifically related to the use of guide-free Cas9. Previous studies have shown that guide-free Cas9 can induce genomic instability in vitro. However, the in vivo safety risks associated with guide-free Cas9 have not been evaluated, which is necessary for the development of gene therapy in clinical settings. In this study, we used doxycycline-inducible Cas9-expressing pigs to evaluate the safety risks of guide-free Cas9 in vivo. Our findings demonstrated that expression of guide-free Cas9 could induce genomic damages and transcriptome changes in vivo. The severity of the genomic damages and transcriptome changes were correlate with the expression levels of Cas9 protein. Moreover, prolonged expression of Cas9 in pigs led to abnormal phenotypes, including a significant decrease in body weight, which may be attributable to genomic damage-induced nutritional absorption and metabolic dysfunction. Furthermore, we observed an increase in whole-genome and tumor driver gene mutations in pigs with long-term Cas9 expression, raising the risk of tumor occurrence. Our in vivo evaluation of guide-free Cas9 in pigs highlights the necessity of considering and monitoring the detrimental effects of Cas9 alone as genome editing via the CRISPR/Cas9 system is implemented in clinical gene therapy. This research emphasizes the importance of further study and implementation of safety measures to ensure the successful and safe application of the CRISPR/Cas9 system in clinical practice.

Abstract Data sources The Global Burden of Diseases, Injuries, and Risk Factors study (GBD) 2019. Background To describe burden, and to explore cross-country inequalities according to socio-demographic index (SDI) for stroke and subtypes attributable to diet. Methods Death and years lived with disability (YLDs) data and corresponding estimated annual percentage changes (EAPCs) were estimated by year, age, gender, location and SDI. Pearson correlation analysis was performed to evaluate the connections between age-standardized rates (ASRs) of death, YLDs, their EAPCs and SDI. We used ARIMA model to predict the trend. Slope index of inequality (SII) and relative concentration index (RCI) were utilized to quantify the distributive inequalities in the burden of stroke. Results A total of 1.74 million deaths (56.17% male) and 5.52 million YLDs (55.27% female) attributable to diet were included in the analysis in 2019.Between 1990 and 2019, the number of global stroke deaths and YLDs related to poor diet increased by 25.96% and 74.76% while ASRs for death and YLDs decreased by 42.29% and 11.34% respectively. The disease burden generally increased with age. The trends varied among stroke subtypes, with ischemic stroke (IS) being the primary cause of YLDs and intracerebral hemorrhage (ICH) being the leading cause of death. Mortality is inversely proportional to SDI (R = -0.45, p

Abstract Investigating the anti‐inflammatory effects of bioactive components present in cold‐pressed rapeseed oil through the use of network pharmacology and molecular docking methods. The components of cold‐pressed rapeseed oil were identified by liquid chromatography‐mass spectrometry. We then conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis using bioinformatics databases on overlapping targets affected by active components and inflammation. Finally, molecular docking was used to predict the interactions between core components and key targets. Analysis identified 13 phenols, four steroids, and one retinoid in cold‐pressed rapeseed oil, with 143 overlapping targets related to inflammation. Bioinformatics analysis revealed that 25‐Hydroxycholesterol, Rosmarinic acid, 9‐cis‐Retinoic acid, Soyasapogenol B and α‐Tocopherol in cold‐pressed rapeseed oil could play a positive role in treating inflammation. They achieved this by regulating key targets (MMP9, EGFR, AKT1, ESR1, and PTGS2) involved in the peroxisome proliferator‐activated receptor signaling pathway and other related pathways. The molecular docking binding energy of the core components and the key targets were less than −5.0 kcal/mol, indicating that the components and the targets can be stably bound. This result indicated that the active components found in cold‐pressed rapeseed oil may exert an anti‐inflammatory effect through a synergistic mechanism involving multicomponent, multitarget and multipathway interactions.

Abstract Background The primary objective of this study is to comparatively assess the safety of nasogastric (NG) feeding versus nasojejunal (NJ) feeding in patients with acute pancreatitis (AP), with a special focus on the initiation of these feeding methods within the first 48 h of hospital admission. Methods Studies were identified through a systematic search in PubMed, EMbase, Cochrane Central Register of Controlled Trials, and Web of Science. Four studies involving 217 patients were included. This systematic review assesses the safety and efficacy of nasogastric versus nasojejunal feeding initiated within 48 h post-admission in moderate/severe acute pancreatitis, with a specific focus on the timing of initiation and patient age as influential factors. Results The results showed that the mortality rates were similar between NG and NJ feeding groups (RR 0.86, 95% CI 0.42 to 1.77, P = 0.68). Significant differences were observed in the incidence of diarrhea (RR 2.75, 95% CI 1.21 to 6.25, P = 0.02) and pain (RR 2.91, 95% CI 1.50 to 5.64, P = 0.002) in the NG group. The NG group also showed a higher probability of infection (6.67% vs. 3.33%, P = 0.027) and a higher frequency of multiple organ failures. Subgroup analysis for early intervention (within 48 h) showed a higher risk of diarrhea in the NG group (RR 2.80, P = 0.02). No significant differences were found in the need for surgical intervention, parenteral nutrition, or success rates of feeding procedures. Conclusion This meta-analysis highlights the importance of considering the method and timing of nutritional support in acute pancreatitis. While NG feeding within 48 h of admission increases the risk of certain complications such as diarrhea and infection, it does not significantly impact mortality or the need for surgical intervention.

Abstract Diabetic kidney disease (DKD), a chronic kidney disease, is characterized by progressive fibrosis caused due to persistent hyperglycemia. The development of fibrosis in DKD determines the patient prognosis, but no particularly effective treatment. Here, small extracellular vesicles derived from mesenchymal stem cells (MSC-sEV) have been used to treat DKD fibrosis. Single-cell RNA sequencing was used to analyze 27,424 cells of the kidney, we have found that a novel fibrosis-associated TGF-β1 +Arg1+ macrophage subpopulation, which expanded and polarized in DKD and was noted to be profibrogenic. Additionally, Actin+Col4a5+ mesangial cells in DKD differentiated into myofibroblasts. Multilineage ligand-receptor and cell-communication analysis showed that fibrosis-associated macrophages activated the TGF-β1/Smad2/3/YAP signal axis, which promotes mesangial fibrosis-like change and accelerates renal fibrosis niche. Subsequently, the transcriptome sequencing and LC-MS/MS analysis indicated that MSC-sEV intervention could restore the levels of the kinase ubiquitin system in DKD and attenuate renal interstitial fibrosis via delivering CK1δ/β-TRCP to mediate YAP ubiquitination degradation in mesangial cells. Our findings demonstrate the unique cellular and molecular mechanisms of MSC-sEV in treating the DKD fibrosis niche at a single-cell level and provide a novel therapeutic strategy for renal fibrosis.

Abstract Communication is crucial in constructing the relationship between students and advisers, ultimately bridging interpersonal interactions. Only a few studies however explore the communication between postgraduate students and advisers. To fill the gaps in the empirical researches, this study uses functional near-infrared spectroscopy (FNIRS) techniques to explore the neurophysiology differences in brain activation of postgraduates with different adviser-advise relationships during simulated communication with their advisers. Results showed significant differences in the activation of the prefrontal cortex between high-quality and the low-quality students during simulating and when communicating with advisers, specifically in the Broca's areas, the frontal pole, and the orbitofrontal and dorsolateral prefrontal cortices. This further elucidated the complex cognitive process of communication between graduate students and advisers.

Abstract Background Many efforts have been made to improve the precision of Cas9-mediated gene editing through increasing knock-in efficiency and decreasing byproducts, which proved to be challenging. Results Here, we have developed a human exonuclease 1-based genome-editing tool, referred to as exonuclease editor. When compared to Cas9, the exonuclease editor gave rise to increased HDR efficiency, reduced NHEJ repair frequency, and significantly elevated HDR/indel ratio. Robust gene editing precision of exonuclease editor was even superior to the fusion of Cas9 with E1B or DN1S, two previously reported precision-enhancing domains. Notably, exonuclease editor inhibited NHEJ at double strand breaks locally rather than globally, reducing indel frequency without compromising genome integrity. The replacement of Cas9 with single-strand DNA break-creating Cas9 nickase further increased the HDR/indel ratio by 453-fold than the original Cas9. In addition, exonuclease editor resulted in high microhomology-mediated end joining efficiency, allowing accurate and flexible deletion of targeted sequences with extended lengths with the aid of paired sgRNAs. Exonuclease editor was further used for correction of DMD patient-derived induced pluripotent stem cells, where 30.0% of colonies were repaired by HDR versus 11.1% in the control. Conclusions Therefore, the exonuclease editor system provides a versatile and safe genome editing tool with high precision and holds promise for therapeutic gene correction.

This investigation was conducted to explore the impact of extrusion temperature on the microstructure, mechanical properties, and osteogenic differentiation of the as-extruded Mg-1Ho alloy. The Mg-1Ho alloy was extruded at three different temperatures, i.e., 320, 350, and 380 °C, leading to variation in its grain size and texture intensity. With decreasing extrusion temperature, a significant increase was achieved in its room-temperature ultimate tensile strength (UTS) and yield strength (YS). After being subjected to an extrusion temperature of 320 °C, furthermore, Mg-1Ho alloy can effectively promote osteogenic proliferation and differentiation, anti-inflammatory, along with osteogenic gene expression. Our findings emphasized that adding extract from Mg-1Ho alloy extruded at 320 °C enhanced the ability of osteogenesis, demonstrating its potential as a biomaterial to improve cell performance and fate.

Abstract Background Prime editing enables precise base substitutions, insertions, and deletions at targeted sites without the involvement of double-strand DNA breaks or exogenous donor DNA templates. However, the large size of prime editors (PEs) hampers their delivery in vivo via adeno-associated virus (AAV) due to the viral packaging limit. Previously reported split PE versions provide a size reduction, but they require intricate engineering and potentially compromise editing efficiency. Results Herein, we present a simplified split PE named as CC-PE, created through non-covalent recruitment of reverse transcriptase to the Cas9 nickase via coiled-coil heterodimers, which are widely used in protein design due to their modularity and well-understood sequence-structure relationship. We demonstrate that the CC-PE maintains or even surpasses the efficiency of unsplit PE in installing intended edits, with no increase in the levels of undesired byproducts within tested loci amongst a variety of cell types (HEK293T, A549, HCT116, and U2OS). Furthermore, coiled-coil heterodimers are used to engineer SpCas9-NG-PE and SpRY-PE, two Cas9 variants with more flexible editing scope. Similarly, the resulting NG-CC-PE and SpRY-CC-PE also achieve equivalent or enhanced efficiency of precise editing compared to the intact PE. When the dual AAV vectors carrying CC-PE are delivered into mice to target the Pcsk9 gene in the liver, CC-PE enables highly efficient precise editing, resulting in a significant reduction of plasma low-density lipoprotein cholesterol and total cholesterol. Conclusions Our innovative, modular system enhances flexibility, thus potentially facilitating the in vivo applicability of prime editing.

Colorectal cancer (CRC) presents a complex landscape, characterized by both inter-tumor and intra-tumor heterogeneity. RUNX1, a gene implicated in modulating tumor cell growth, survival, and differentiation, remains incompletely understood regarding its impact on CRC prognosis. In our investigation, we discerned a positive correlation between elevated RUNX1 expression and aggressive phenotypes across various CRC subtypes. Notably, knockdown of RUNX1 demonstrated efficacy in restraining CRC proliferation both in vitro and in vivo, primarily through inducing apoptosis and impeding cell proliferation. Mechanistically, we unveiled a direct regulatory link between RUNX1 and cholesterol synthesis, mediated by its control over HMGCR expression. Knockdown of RUNX1 in CRC cells triggered HMGCR transcriptional activation, culminating in elevated cholesterol levels that subsequently hindered cancer progression. Clinically, heightened RUNX1 expression emerged as a prognostic marker for adverse outcomes in CRC patients. Our findings underscore the pivotal involvement of RUNX1 in CRC advancement and its potential as a therapeutic target. The unique influence of RUNX1 on cholesterol synthesis and HMGCR transcriptional regulation uncovers a novel pathway contributing to CRC progression.

IntroductionAtopic dermatitis (AD) is a common, chronic, recurrent inflammatory skin disease. To date, no meta-analysis have been conducted on the prevalence and risk factors of AD in children aged 1–7 years in Mainland China.MethodsWe conducted a meta-analysis of the prevalence and risk factors of AD among children aged 1–7 years in China. Chinese and English publications were searched in Chinese and English databases on AD epidemiology published between 1999 and 2023. Two researchers independently screened the literature, extracted the data, and evaluated their quality. A meta-analysis was performed using a random-effects model (I2 > 50%) with 95% confidence intervals (CIs) for the forest plots. Data were processed using the RevMan 5.3.ResultsNineteen studies (data from 127,660 samples) met the inclusion criteria. The pooled prevalence of AD in Chinese children aged 1–7 years was 8%. Over the last decade, the prevalence of AD has increased. The prevalence of AD among children in southern China was higher than that in northern China and was the highest at the provincial level in Zhejiang, Shanxi, and Anhui. The prevalence of AD was dependent on the family history of allergy, passive smoking, households with pets, plush toys, and residential area.DiscussionThe prevalence of AD in children (age 1–7 years) in China has increased. Further studies are needed to monitor the prevalence of AD in Chinese children. Therefore, early prevention and screening should be performed for children with a family history of AD, and their living environment should be improved to reduce allergen stimulation, thus reducing the development of AD.

Background The band and loop space maintainer is used to maintain the missing space of deciduous molars which are lost early. When the second deciduous molar is lost prematurely, the stress on the first permanent molar during different degrees of development may vary when it is the abutment. The design and use of the space maintainer may also lead to damage of the loop. The purpose of this article is to use the finite element method to study the stress on the first permanent molar and the loop with or without occlusal contact, with the first permanent molar of four different degrees of development serving as the abutment. We aimed to guide the clinical design and use of the space maintainer. Methods We developed finite element models of the mandibular first permanent molar and the band and loop space maintainer, and simulated alveolar bone, periodontal ligament (PDL), enamel and dentin. The four developmental stages were 1/2 (I), 2/3 (II), 3/4 (III) and full development (IV). Ansys Workbench was used to analyze the effects of root development and occlusal contact between the loop and the opposite jaw on abutment teeth and the loop. Abutment teeth were statically loaded vertically and obliquely with a force of 70 N. The loop was statically loaded vertically with a force of 14 N. The stress on all structures and the displacement trends of the loop were calculated. Results The stress on enamel, dentin, PDL and alveolar bone were similar, and the concentration was consistent. But if there was occlusal contact, the loop produced maximum displacement at the near middle edge of contact with the anterior teeth. When the loop was in occlusal contact with the opposing occlusal tooth, the peak value of the equivalent stress on the space maintainer under vertical load was: group I > group IV > group III > group II, and the maximum principal stress peak change was: group I > group III > group II > group IV. The change of the equivalent stress peak value of the loop under oblique load was: group I > group III > group IV > group II, and the maximum principal stress peak change was: group III > group I > group II > group IV. When the loop was not in occlusal contact with the opposing occlusal tooth, the peak value of the equivalent stress on the space maintainer under vertical load was: group IV > group I > group II > group III, and the maximum principal stress peak change was: group IV > group I > group II > group III. The change of the equivalent stress peak value of the space maintainer under oblique load was: group I > group IV > group II > group III, and the maximum principal stress peak change was: group I > group IV > group II > group III. Conclusions Our results suggested that whenever possible, choosing the teeth with nearly complete root development as the abutment of the space maintainer is advisable. The design and use of the band and loop space maintainer should avoid occlusal contact with the occlusal teeth to prevent deformation of the loop.

IntroductionThe outbreak of the COVID-19 pandemic has disrupted people’s routine, bringing uncertainty and stress, leading to mental health issues. This situation is particularly acute among Chinese prospective graduates in higher education stage as they cannot predict the outcomes of their studies, graduation, and career development, and therefore experience career-related stress.MethodsThis study included 4041 prospective graduates in higher education stage (using handy sampling) recruited in March 2020 as participants (MAge = 22.56, SD = 1.865), utilizing a Sparse Gaussian Graphical Model for regularized partial correlation network analysis of depression symptoms (by PHQ-9), anxiety symptoms (by GAD-7), and career-related stress, which aims to explore the role of career-related stress in the symptom networks of depression and anxiety among prospective graduates in their final semester.ResultsThe results revealed that fatigue, sad mood, and psychomotor symptoms in depression, as well as uncontrollable worry and trouble relaxing in anxiety, were central symptoms in the network. Additionally, sad mood and guilt belonging to depressive symptoms, and feeling afraid, restlessness, and irritability belonging to anxiety symptoms, served as bridge symptoms connecting symptom communities. Specifically, guilt as a depressive symptom showed a strong association with employment stress in career-related stress. There were no significant differences in network structure and global strength based on participants’ gender. However, despite no significant differences in network structure, the global strength of prospective graduates from Wuhan was significantly lower than samples from non-Hubei provinces, possibly indicative of a Typhoon Eye Effect.DiscussionThe findings of this study can inspire psychological professionals in higher education institutions to provide support for mental interventions and therapies for prospective graduates, and addressing career development issues.

Abstract M2‐polarized tumor‐associated macrophages (M2 TAMs) promote cancer progression. Exosomes mediate cellular communication in the tumor microenvironment (TME). However, the roles of exosomes from M2 TAMs in gastric cancer progression are unclear. Herein, it is reported that M2 TAMs‐derived exosomes induced aerobic glycolysis in gastric cancer cells and enhanced their proliferation, metastasis, and chemoresistance in a glycolysis‐dependent manner. It is identified that MALAT1 (metastasis‐associated lung adenocarcinoma transcript 1) is enriched in M2 TAM exosomes and confirmed that MALAT1 transfer from M2 TAMs to gastric cancer cells via exosomes mediates this effect. Mechanistically, MALAT1 interacted with the δ‐catenin protein and suppressed its ubiquitination and degradation by β‐TRCP. In addition, MALAT1 upregulated HIF‐1α expression by acting as a sponge for miR‐217‐5p. The activation of β‐catenin and HIF‐1α signaling pathways by M2 TAM exosomes collectively led to enhanced aerobic glycolysis in gastric cancer cells. Finally, a dual‐targeted inhibition of MALAT1 in both gastric cancer cells and macrophages by exosome‐mediated delivery of siRNA remarkably suppressed gastric cancer growth and improved chemosensitivity in mouse tumor models. Taken together, these results suggest that M2 TAMs‐derived exosomes promote gastric cancer progression via MALAT1‐mediated regulation of glycolysis. The findings offer a potential target for gastric cancer therapy.

Background and aimsPatients with relapsed/refractory aggressive B-cell lymphoma(r/r aBCL)who progressed after CD19-specific chimeric antigen receptor T-cell therapy (CD19CART) had a poor prognosis. Application of CAR T-cells targeting a second different antigen (CD20) expressed on the surface of B-cell lymphoma as subsequent anti-cancer salvage therapy (CD20-SD-CART) is also an option. This study aimed to evaluate the survival outcome of CD20-SD-CART as a salvage therapy for CD19 CART treatment failure.MethodsThis retrospective cohort study enrolled patients with aBCL after the failure of CD19 CART treatment at Beijing Gobroad Boren Hospital from December 2019 to May 2022. Patients were subsequently treated with CD20CART therapy or non-CART therapy (polatuzumab or non-polatuzumab).ResultsA total of 93 patients were included in the study, with 54 patients receiving CD20-SD-CART therapy. After a median follow-up of 18.54 months, the CD20-SD-CART group demonstrated significantly longer median progression-free survival (4.04 months vs. 2.27 months, p=0.0032) and median overall survival (8.15 months vs. 3.02 months, p

In environmental epidemiological research, extensive non-random environmental exposures and complex confounding biases pose significant challenges when attempting causal inference. In recent years, the introduction of causal inference methods into observational studies has provided a broader range of statistical tools for causal inference research in environmental epidemiology. The instrumental variable (IV) approach, as a causal inference technique for effectively controlling unmeasured confounding factors, has gradually found application in the field of environmental epidemiological research. This article reviewed the basic principles of IV and summarized the current research progress and limitations of applying IV for causal inference in environmental epidemiology. IV application in the field of environmental epidemiology is still in the initial stage. Rational use of IV and effective integration with other causal inference methods will become the focus of the development of causal inference in environmental epidemiology. The aim of this paper is to provide a methodological reference and basis for future studies involving causal inference to target population health effects of environmental exposures in China.

Abstract Objective Evaluation of the accuracy and effectiveness of 3D printed guides to assist femoral tunnel preparation in individualised reconstruction of the anterior cruciate ligament. Methods Sixty patients who attended the Affiliated Hospital of Binzhou Medical College for autologous hamstring single bundle reconstruction of the anterior cruciate ligament from October 2018 to October 2020 were selected and randomly divided into two groups, including 31 cases in the 3D printing group (14 males and 17 females, mean age 41.94 ± 10.15 years) and 29 cases in the control group (13 males and 16 females, mean age 37.76 ± 10.34 years). Patients in both groups were assessed for intraoperative femoral tunnel accuracy, the number of intraoperative positioning and the time taken to prepare the femoral tunnel, the length of the anteromedial approach incision, the pre-planned bone tunnel length and intraoperative bone tunnel length in the 3D printed group, IKDC score and Lysholm score preoperatively and at 3, 6 and 12 months postoperatively, the Lachman、pivot-shift test preoperatively and at 6 months postoperatively, gait analysis to assess internal and external rotation in flexion of the knee at 12 months postoperatively and postoperative complications in both groups. Results There was no statistical difference in functional knee scores and anteromedial approach incision length between the 3D printed and control groups (p > 0.05), while there was a statistical difference in the accuracy of tunnel positioning, the time taken to prepare the femoral bone tunnel and the degree of external rotation of the knee in flexion between the two groups (p 0.05). Complications: One case in the 3D printing group developed intermuscular vein thrombosis in the affected lower limb after surgery, which disappeared after treatment, while three cases in the control group developed intermuscular vein thrombosis in the affected lower limb. No complications such as bone tunnel rupture, deep vein thrombosis in the lower limb and infection occurred in either group. Conclusion 3D printed guides assisted with individualized ACL reconstruction may improve the accuracy of femoral tunnel positioning, which is safe and effective, while reducing the operative time and the number of intraoperative positioning, without increasing the length of incision, and may obtain higher functional scores and rotational stability of the knee joint, which is in line with the concept of individualized ACL reconstruction.

Abstract The association between surgical approach and prognosis in patients with spontaneous supratentorial deep intracerebral hemorrhage is unclear. We aimed to explore the association between surgical approach and prognosis in these patients. A retrospective cohort of 311 patients from 3 centers who were treated with surgery 24 h after ictus was recruited. The surgical procedure involved removing the intracerebral hematoma using an aspirator through either the cortical approach or Sylvian fissure approach, assisted by an endoscope or microscope. The primary outcome was the one-year modified Rankin scale (mRS) score. The association between the surgical approach and the one-year mRS score was explored by using ordinal logistic regression and binary logistic regression. Baseline characteristics were balanced by propensity score matching and inverse propensity score weighting. In the adjusted analysis, compared with the cortex approach group, the Sylvian fissure approach group had better one-year mRS scores when analyzed as an ordinal variable (3.00 [2.00–4.00] vs. 4.00 [3.00–5.00]; adjusted odds ratio, 3.15; 95% CI, 1.78–5.58; p 0.999) or three-month mortality (Fisher's exact test, p > 0.999). Inverse probability weighted regression analysis showed better one-year mRS scores when analyzed as an ordinal variable (adjusted odds ratio, 3.03; 95% CI, 2.17–4.17; p

Abstract Aims Circulating biomarkers can provide important information for the diagnosis and prognosis of dilated cardiomyopathy (DCM). We explored novel biomarkers for the diagnosis and prognosis of DCM to improve clinical decision‐making. Methods and results A total of 238 DCM patients and 65 control were consecutively enrolled at Zhongshan Hospital between January 2017 and January 2019. In the screening set, four DCM patients and four controls underwent measurements of serum proteomic analysis. Seventy‐six differentially expressed circulating proteins were screened by data‐independent acquisition proteomics, and three of these proteins (S100A4, S100A8/A9, and S100A12) were validated by multiple‐reaction monitoring‐mass spectrometry. In the validation set, subsequently, a total of 234 DCM patients and 61 control subjects were evaluated by enzyme‐linked immunosorbent assay. Circulating S100A4, S100A8/A9, and S100A12 were significantly increased in DCM patients (P 0.05). Cox proportional hazards regression analysis revealed that S100A4 [≥75th percentile vs.

Abstract Introduction This study aimed to characterize the morbidity, hospitalization, and mortality rates among patients with adult-onset Still’s disease (AOSD) affected by coronavirus disease 2019 (COVID-19) and explore the impact of COVID-19 on the disease activity of AOSD. Methods Data on the clinical and demographic characteristics, COVID-19-related symptoms, and outcomes were retrospectively collected. Patients were stratified according to COVID-19 severity and associations between risk factors and outcomes were analyzed using multivariate logistic regression. The disease activity of patients with AOSD flares after COVID-19 was described. Results A total of 188 patients with AOSD were followed up, of whom 75.5% (n = 142) had a confirmed or highly suspected COVID-19. Patients on medium or high-dose oral glucocorticoids or Janus kinase (JAK) inhibitors were at increased risk of developing moderate to severe COVID-19. Six patients suffered flares of AOSD following COVID-19 in a short period; however, the relapse rate was not statistically increased compared with patients without COVID-19. Conclusion Patients with AOSD receiving medium or high-dose glucocorticoid therapy or JAK inhibitors had worse COVID-19 outcomes. Further work is needed to explore risk factors affecting COVID-19 outcomes and the impact of COVID-19 on disease activity in AOSD.

Abstract The impairment of sperm maturation is one of the major pathogenic factors in male subfertility, a serious medical and social problem affecting millions of global couples. Regrettably, the existing research on sperm maturation is slow, limited, and fragmented, largely attributable to the lack of a global molecular view. To fill the data gap, we newly established a database, namely the Sperm Maturation Database (SperMD, http://bio-add.org/SperMD ). SperMD integrates heterogeneous multi-omics data (170 transcriptomes, 91 proteomes, and five human metabolomes) to illustrate the transcriptional, translational, and metabolic manifestations during the entire lifespan of sperm maturation. These data involve almost all crucial scenarios related to sperm maturation, including the tissue components of the epididymal microenvironment, cell constituents of tissues, different pathological states, and so on. To the best of our knowledge, SperMD could be one of the limited repositories that provide focused and comprehensive information on sperm maturation. Easy-to-use web services are also implemented to enhance the experience of data retrieval and molecular comparison between humans and mice. Furthermore, the manuscript illustrates an example application demonstrated to systematically characterize novel gene functions in sperm maturation. Nevertheless, SperMD undertakes the endeavor to integrate the islanding omics data, offering a panoramic molecular view of how the spermatozoa gain full reproductive abilities. It will serve as a valuable resource for the systematic exploration of sperm maturation and for prioritizing the biomarkers and targets for precise diagnosis and therapy of male subfertility.

Abstract Renal interstitial fibrosis (RIF) is a fundamental pathological feature of chronic kidney disease (CKD). However, toxicity and poor renal enrichment of fibrosis inhibitors limit their further applications. In this study, a platform for CKD therapy is developed using superparamagnetic iron oxide nanoparticles (SPION) decorated mesenchymal stem cells derived extracellular vesicles with carboxyl terminus of Hsc70-interacting protein (CHIP) high expression (SPION-EVs) to achieve higher renal-targeting antifibrotic therapeutic effect. SPION-EVs selectively accumulate at the injury renal sites under an external magnetic field. Moreover, SPION-EVs deliver CHIP to induce Smad2/3 degradation in renal tubular cells which alleviates Smad2/3 activation-mediated fibrosis-like changes and collagen deposition. The extracellular vesicle engineering technology provides a potential nanoplatform for RIF therapy through CHIP-mediated Smad2/3 degradation.

Abstract Background Transcription factors bind DNA in specific sequence contexts. In addition to distinguishing one nucleobase from another, some transcription factors can distinguish between unmodified and modified bases. Current models of transcription factor binding tend not to take DNA modifications into account, while the recent few that do often have limitations. This makes a comprehensive and accurate profiling of transcription factor affinities difficult. Results Here, we develop methods to identify transcription factor binding sites in modified DNA. Our models expand the standard A/C/G/T DNA alphabet to include cytosine modifications. We develop Cytomod to create modified genomic sequences and we also enhance the MEME Suite, adding the capacity to handle custom alphabets. We adapt the well-established position weight matrix (PWM) model of transcription factor binding affinity to this expanded DNA alphabet. Using these methods, we identify modification-sensitive transcription factor binding motifs. We confirm established binding preferences, such as the preference of ZFP57 and C/EBPβ for methylated motifs and the preference of c-Myc for unmethylated E-box motifs. Conclusions Using known binding preferences to tune model parameters, we discover novel modified motifs for a wide array of transcription factors. Finally, we validate our binding preference predictions for OCT4 using cleavage under targets and release using nuclease (CUT&RUN) experiments across conventional, methylation-, and hydroxymethylation-enriched sequences. Our approach readily extends to other DNA modifications. As more genome-wide single-base resolution modification data becomes available, we expect that our method will yield insights into altered transcription factor binding affinities across many different modifications.

Abstract Background Adult-onset Still’s disease (AOSD) is a systemic autoinflammatory disease characterized by innate immune system activation, with a high risk for macrophage activation syndrome (MAS). MAS development is associated with monocyte/macrophage activation and cytokine storm. Monocytes consist of three different subsets, classical monocytes (CMs, CD14brightCD16 −), intermediate monocytes (IMs, CD14brightCD16 +), and non-classical monocytes (NCMs, CD14dimCD16 +), each has distinct roles in inflammatory regulation. However, the frequencies and regulatory mechanism of monocyte subsets in AOSD patients have not been identified. Methods We performed flow cytometry, RNA sequencing, phagocytosis analysis, and enzyme-linked immunosorbent assay to evaluate monocyte subsets, cell functions, and potential biomarkers. The effect of neutrophil extracellular traps (NETs) on monocytes was determined by evaluating mRNA levels of DNA sensors, surface CD16 expression, and inflammasome pathway activation. Results Higher proportions of intermediate monocytes (IMs) were identified in active AOSD patients. IMs displayed higher expression of CD80, CD86, HLA-DR, and CD163 than CMs and NCMs. CD163 upregulation was noted on AOSD IMs, accompanied by increased phagocytic activity and elevated cytokine/chemokine production, including IL-1β, IL-6, CCL8, and CXCL10. The frequencies of IMs were correlated with disease activity and higher in AOSD patients with MAS (AOSD-MAS). CCL8 and CXCL10 were highly expressed in RNA sequencing of monocytes from AOSD-MAS patients and plasma CXCL10 level could serve as a potential biomarker for AOSD-MAS. Moreover, DNA-sensing pathway was activated in monocytes from AOSD-MAS patients. Stimulation with NETs derived from AOSD induced DNA sensor expression, the expansion of IMs, and inflammasome pathway activation. These effects can be abrogated by DNase I treatment. Conclusions Our results demonstrated that the proportions of IMs were elevated in AOSD and associated with MAS. The DNA component in NETs from AOSD plays an important role in the formation of IMs, shedding new light for the therapeutic target.

AbstractContext Punicalagin has myocardial protection; the mechanism of punicalagin on ventricular remodeling (VR) after acute myocardial infarction (AMI) remains unclear.Objective These studies explore the role and mechanism of punicalagin in preventing and treating VR after AMI.Materials and methods Molecular docking was used to predict the targets of punicalagin. After 2 weeks of AMI model, the SD rats were randomly divided into model, and punicalagin (200, 400 mg/kg, gavage) groups for 4 weeks. Thoracotomy with perforation but no ligature was performed on rats in control group. The protein expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis speck-like protein (ASC), caspase-1, gasdermin D (GSDMD), and GSDMD-N, the mRNA expression of NLRP3, caspase-1, GSDMD, interleukin-1β (IL-1β) and IL-18 were evaluated.Results Punicalagin had binding activities with NLRP3 (Vina score, −5.8), caspase-1 (Vina score, −6.7), and GSDMD (Vina score, −6.7). Punicalagin could improve cardiac function, alleviate cardiac pathological changes, minimize the excessive accumulation of collagen in the left ventricular myocardium (p

Background: The diagnostic yield of radial endobronchial ultrasound (r-EBUS) for the diagnosis of peripheral pulmonary lesions (PPLs) varies between studies and is affected by multiple factors. We aimed to evaluate the efficacy and safety of r-EBUS, and to explore the factors influencing the diagnostic yield of r-EBUS in patients with PPLs. Methods: The PubMed, Web of Science, and EMBASE databases were searched to identify relevant studies that used r-EBUS for diagnosing PPLs from the date of inception to Dec 2022. Meta-analysis was conducted using Review Manager 5.4 and Stata 15.1. Results: An analysis of 46 studies with a total of 7252 PPLs was performed. The pooled diagnostic yield of r-EBUS was 73.4 % (95 % CI: 69.9%–76.7 %), with significant heterogeneity detected among studies (I2 = 90 %, P 2 cm in size, malignant in type, solid in appearance on computerized tomography (CT), present in bronchus sign, the within probe location, and the addition of rapid on-site evaluation (ROSE) were associated with increased diagnostic yield, whereas use of a guide sheath (GS), bronchoscopy type, and a multimodality approach failed to influence the outcome. The pooled incidence rates of overall complications, pneumothorax and moderate and severe bleeding were 3.1 % (95 % CI: 2.1%–4.3 %), 0.4 % (95 % CI: 0.1%–0.7 %) and 1.1 % (95 % CI: 0.5%–2.0 %), respectively. Conclusions: r-EBUS has an appreciable diagnostic yield and an excellent safety manifestation when used to deal with PPLs.

BackgroundNo standardized criteria for surgical resection of parasagittal sinus meningiomas (PSM) have been established, and different surgical strategies have been proposed. The aim of the present study was to investigate the efficacy and safety of a “radical” surgical strategy in the treatment of PSM.MethodsThe clinical histories, radiological findings, pathologic features, and surgical records of 53 patients with PSM admitted by the same surgical team using the “radical” surgical strategy were retrospectively analyzed between 2018 and 2023.ResultsAmong the 53 PSM cases, 16 (30.2%) had a patent sinus proper, 28 (52.8%) had partial obstruction of the sinus proper, and 9 (17.0%) had complete obstruction of the sinus proper before the operation. During operation, Simpson grade I resection was performed in 34 (64.2%) cases and Simpson grade II in 19 (35.8%) cases. Postoperative pathologic examination suggested tumors of WHO grade I in 47 (88.7%) cases, WHO grade II in 4 (7.5%) cases, and WHO grade III in 2 (3.8%) cases. Postoperative complications primarily included a small amount of delayed intracerebral hemorrhage in 3 (5.7%) cases, exacerbation of cerebral edema in 3 (5.7%) cases, exacerbation of motor and sensory deficits in 4 (7.5%) cases, and intracranial infection in 2 (3.8%) cases. There were no cases of death or new-onset neurological dysfunction. Dizziness and headache symptoms improved to varying degrees, and a seizure-free status was achieved postoperatively. Excluding one case lost to follow-up, the average follow-up period was 33 months, and there were no cases of recurrence.ConclusionA “radical” strategy for the surgical management of PSM is effective, safe, and simple to perform, provided that the sagittal sinus is properly managed and its associated veins are protected.

Rapidly expanding urban areas constitute places of high-intensity energy consumption and, hence, major carbon emissions. There is an urgent need to systematically review the relationship between urban spatial expansion and carbon emissions at the city level, especially for cities in western China where development lags behind compared to other parts of the country, and differences among resource availability exist. Here, we conducted a systematic comparative analysis of carbon emissions and urban expansion indicators for urban spatial development. We introduce and apply an extension of the STIRPAT model to quantify the impact of urban spatial expansion on carbon emissions for the cities of Xi’an and Chengdu located in western China. The model findings indicate that both cities have reached the absolute and relative goal of carbon emissions, although they experienced a sprawling pattern. Moreover, population density for both cities displayed a negative relationship with carbon emissions, whereas road area per capita displayed a positive relationship. Since western cities have a later starting point for development, the empirical research on influencing variables of carbon emissions for western cities is important to local and regional urban spatial planning and governance. We propose further empirical studies regarding the gaps of existing urban spatial structure and low-carbon urban areas, in order to construct a systematic and scientifically sound approach to further low-carbon strategies in urban development.

Summary: Background: Azvudine and nirmatrelvir/ritonavir are approved to treat mild-to-moderate coronavirus disease 2019 (COVID-19) in adults with a high risk for progression to severe infection. We sought to compare the antiviral effectiveness and clinical outcomes of elderly severe patients with COVID-19 receiving these two antiviral agents. Methods: In this observational study, we identified 249 elderly patients with severe COVID-19 infection who were admitted to the Second Medical Center of the People's Liberation Army General Hospital from December 2022 to January 2023, including 128 azvudine recipients, 66 nirmatrelvir/ritonavir recipients and 55 patients not received antiviral treatments. We compared the cycle threshold (Ct) value dynamic change of all three groups. The primary outcome was a composite outcome of disease progression, including all-cause death, intensive care unit admission, and initiation of invasive mechanical ventilation. The outcomes of all enrolled patients were followed up from the electronic medical record system. Kaplan–Meier and Cox risk proportional regression analyses were used to compare the clinical outcomes of all three groups. To more directly compare the effectiveness of the two antiviral drugs, we performed propensity-score matching between the two antiviral groups and compared antiviral efficacy and clinical outcomes in the matched population. Findings: Among 249 patients (mean age, 91.41 years), 77 patients died during the follow-up period. When compared to patients who did not receive any antivirals, neither nirmatrelvir/ritonavir nor azvudine demonstrated a survival benefit. The Cox analysis of the all-cause death of the three groups showed that the risk of death was 0.730 (0.423–1.262) in the azvudine group 0.802 (0.435–1.480) and in the nirmatrelvir/ritonavir group compared with the non-antiviral group. After propensity score matching, we included 58 azvudine recipients and 58 nirmatrelvir/ritonavir recipients. The fitted curve of the Ct value after matching illustrated that the rate of viral decline in the early stage of nirmatrelvir/ritonavir treatment seems to surpass that of azvudine, but there was no statistical significance. Azvudine was seemly associated with a lower risk of composite outcomes (HR:1.676, 95% CI:0.805–3.488) and short-term all-cause death (HR: 1.291, 95%CI: 0.546–3.051). Interpretation: Patients who received azvudine have a similar antiviral effectiveness and survival curve trend compared to nirmatrelvir/ritonavir. In this limited series, antiviral treatment was not associated with a significant clinical benefit. This lack of clinical benefit might be attributed to potential bias. Funding: This study was supported by the “National Key R&D Program of China” (Funding No. 2020YFC2008900) and the National Defense Science and Technology Innovation Special Zone Project (223-CXCY-N101-07-18-01).

Abstract Conditional gene regulation systems can control gene expression in predefined tissues or organs at a desired time. Site‐specific recombinase systems and chemically induced gene expression systems are the two most widely used approaches for creating genetically modified (GM) animals with conditional regulation of gene expression. Generation of GM pigs with controllable elements, usually involving multiple gene editing, used to be a major challenge due to a lack of germ line‐competent pluripotent stem cells. With the emergence of artificial endonuclease‐mediated gene editors, a variety of GM pigs with recombinase‐specific recognition elements or chemically induced elements for conditional regulation of gene expression have been generated by the combination of site‐directed knock‐in of somatic cells and somatic cell nuclear transfer technology, allowing conditional deletion of endogenous genes or overexpression of exogenous genes in pigs. These inducible tool pig models will greatly facilitate the production of GM pigs and broaden the applications of transgenic pigs in biomedicine and agriculture fields. In this paper, we review the progress in the construction and application of pigs with controllable elements using gene editing techniques.

Abstract Objectives Cardiac involvement is one of the most serious complications of idiopathic inflammatory myopathy (IIM) that indicates poor prognosis. However, there is a lack of effective biomarkers for the identification of cardiac involvement and the prediction of prognosis in IIM. Here, we aimed to explore the value of different cardiac biomarkers in IIM patients. Methods A total of 142 IIM patients in the Department of Rheumatology and Immunology, Ruijin Hospital from July 2019 to October 2022 were included in this study. The clinical characteristics, laboratory tests, treatments and prognosis were recorded. The disease activity was assessed according to the core set measures. The correlations of the serum cardiac biomarkers levels with disease activity were analyzed by the Spearman correlation test. Risk factors for cardiac involvement were evaluated by multivariate logistic regression analysis. Results Higher high-sensitivity cardiac troponin I (hs-cTnI) levels were associated with cardiac involvement (n = 41) in IIM patients [adjusted OR 7.810 (95% CI: 1.962–31.097); p = 0.004], independent of other serum cardiac biomarkers. The abnormal hs-cTnI had the highest AUC for distinguishing of cardiac involvement in IIM patients (AUC = 0.848, 95% CI: 0.772,0.924; p

Abstract Background The absence of thyroid transcription factor 1 (TTF‐1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF‐1 expression on the clinical response to EGFR‐tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD. Methods The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed. Results A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF‐1‐negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF‐1 expression significantly correlated with male sex (68.8% vs. 42.3%, p

Abstract Background Young migrant workers living in low- and middle-income countries often experience barriers and inadequate access to HIV prevention and treatment services. This study examines the prevalence of HIV testing, associated factors, and reasons for obtaining and not obtaining HIV testing among young sexually active women migrant workers in an industrial zone in Hanoi, Vietnam. Methods A cross-sectional study was conducted among 512 sexually active young women migrant workers (aged 18 to 29) working in the Thang Long industrial zone in Hanoi, Vietnam. Data was collected via a face-to-face interview from January 2020 to June 2021. Multivariable logistic regression analysis was used to explore factors associated with ever-testing for HIV among sexually active participants. Results The study found a low level of HIV testing and high rates of unprotected sex. Among those who reported being sexually active, only 23.7% of participants (n = 126) reported having ever been tested for HIV. Among those who reported never having tested for HIV, 38.2% reported not using condoms during their most recent sexual encounter. Factors associated with engaging in HIV testing included being older (25–29 years), having greater knowledge about HIV, past use of sexual and reproductive health and HIV services, and familiarity with HIV testing locations. Conclusions Overall, a low level of HIV testing, high rates of unprotected sex, and low perceived risks regarding HIV among the study participants point to a need to implement targeted HIV interventions that can improve both safe sex practices and perceptions of and knowledge about risky sexual behaviors. Such interventions should use insights from this study to address factors facilitating HIV testing among industrial zones’ women migrant workers.

The present work reports the creep behavior and microstructural evolution of the sand-cast Mg–14Gd–0.4Zr alloy (wt.%) prepared by the differential pressure casting machine. Their compressive creep tests at 250 °C were performed under various applied stresses (i.e., 60, 80 and 100 MPa). Among them, the sand-cast Mg–14Gd–0.4Zr samples examined under 250 °C/80 MPa for 39 and 95 h, respectively, were chosen to systemically analyze their creep mechanisms using high-angle annular dark field-scanning transmission electron microscopy (HAADF-STEM). The obtained results showed that the enhancement of creep resistance can be mainly attributed to the coherent β' and β'F phases with an alternate distribution, effectively impeding the basal dislocations movement. However, with the creep time increasing, the fine β'+β'F precipitate chains coarsened and transformed to semi-coherent β1 phase and even to large incoherent β phase (surrounded by precipitate-free areas) in grain interiors. The precipitate-free zones (PFZs) at grain boundaries (GBs) were formed, and they could expand during creep deformation. Apart from the main cross-slip of basal and prismatic dislocations, type dislocations were activated and tended to distribute near the GBs. The aforementioned phenomena induced the stress concentrations, consequently leading to the increment of the creep strain.

Abstract Plant disease is a threat to global food security. Breeding crops carrying broad-spectrum resistance loci is an effective way to control infectious disease. Disease-resistant mutants are valuable resources for deciphering the underlying mechanisms of plant immunity and could provide genetic loci to generate disease-resistant crops. Here, we identified a rice mutant, rbr7 (rice blast resistance 7), that confers resistance against different strains of Magnaporthe oryzae. Disease-mimicking necrotic lesions started to appear on the leaves of rbr7 four weeks after sowing. Histochemical analysis revealed reactive oxygen species accumulation and cell death accompanied by spontaneous lesion formation in rbr7. Map-based cloning and bulk segregation analysis showed a 2855 bp fragment deletion on chromosome 5, leading to the disruption of the LOC_Os05g28480-coding protein. Transgenic rbr7 complementation plants showed compromised resistance to rice blast, indicating that LOC_Os05g28480, or Rbr7, regulates the rice immune response. Rbr7 encodes a small protein of unknown function with 85 amino acids. Transcriptomic analysis revealed that disruption of RBR7 led to the upregulation of genes responding to salicylic acid, systemic acquired resistance and pathogenesis-related genes. Taken together, our findings reveal insights into a novel small protein involved in regulating plant resistance to rice blast and provide a potential target for crop breeding.

This study systematically investigates the effect of Al2O3 insertions on the thermal stability of [Pt(1)/Al2O3(t)/Co(0.4)]3 films (unit: nm). The interdiffusion of Pt and Co was limited by inserting a thin Al2O3 at the Pt/Co interface for film after annealing. The increased perpendicular magnetic anisotropy (PMA) and decreased coercivity (Hc) were observed for the films with Al2O3 insertions after annealing at 400 °C. X-ray diffraction results show that CoPt3(111) is formed. Simultaneously, oxygen from the Al2O3 insertions combined with Co to form Co oxides that strengthened the PMA. The annealed film with the Al2O3 insertions has better CoPt3(111) crystallinity, lower Hc, and higher amount of Co oxides than those without Al2O3 insertions. To meet the application requirements for magnetic tunnel junction electrodes, it is critical to maintain strong PMA during the 400°C-annealing process, which can be achieved by inserting Al2O3 in the [Pt/Co]n multilayers.

PurposeThis study measured three of the psychological stages of dying in patients with cancer and explored the differences in proximal and intimacy-related defense mechanisms at each stage.Patients and methodsA total of 220 cancer patients were recruited for this study; 168 patients met the inclusion criteria and were included in the data analysis. The participants were divided into three groups using the “Death Attitudes Questionnaire Revised” (1994) and then completed the Death-Thought Accessibility Test, Self-Control Questionnaire, Rumination Reflection Questionnaire, Attachment Type Test, Intimacy Test, External Control Test, and Positive and Negative Affect Scale.ResultsIn the death avoidance stage, which represents a defense stage without cognitive processes, patients are in an irrational state with the highest level of self-control and the lowest level of external control; they tend to prefer close relationships with many people while experiencing high levels of fear and depression. In the bargaining stage, which represents a biased cognitive defense stage, the level of rationality increases, the level of fear and depression decreases, and patients tend to prefer relationships with many people that do not involve intimacy. In the neutral death acceptance stage, which represents a defense stage without cognitive bias, self-control is lowest, external control is highest, patients tend to prefer intimate relationships with a few people, and experience the lowest levels of fear and depression.ConclusionThree psychological stages of death exist in cancer patients, with differences in proximal and intimacy-related defense mechanisms in each stage. The findings have theoretical and practical implications for psychological interventions for cancer patients.

BackgroundThere is an escalating concern about the rising levels of anxiety and depression among college students, especially during the post-pandemic era. A thorough examination of the various dimensions of social support and their impact on these negative emotions in college students is imperative.AimThis study aimed to determine if a perceived loss of control mediates the relationship between social support and levels of anxiety and depression among college students during the post-pandemic era. Additionally, it examined whether family socioeconomic status moderates this mediated relationship.MethodsWe administered an online cross-sectional survey in China, securing responses from 502 participants. The sample comprised home-isolated college students impacted by COVID-19. Established scales were employed to assess social support, anxiety, depression, perceived loss of control, and family socioeconomic status. Analytical techniques included descriptive statistics, correlation analysis, and a bootstrap method to investigate mediating and moderating effects.ResultsSocial support was found to negatively affect anxiety and depression in college students, with perceived loss of control partially mediating this relationship. In addition, family socio-economic status was shown to moderate this moderating process. Furthermore, family socioeconomic status influenced this mediation, with higher socioeconomic families exhibiting a stronger moderating effect on perceived loss of control across different dimensions of social support.ConclusionThis study may help to develop strategies to mitigate the impact of anxiety and depression in the lives and studies of university students during unexpected public health crises, and to promote better mental health among college students.

Amid the landscape of digital literacies and frameworks is a common assumption that contemporary youth, frequently dubbed “digital natives,” intuitively understand and use online technologies. While their use of these technologies may be frequent and highly skilled in some respects (e.g., communicating with friends), their use and abilities in other areas, such as those valued in school settings and the workforce, may differ. This survey of 350 college students examines how they use an array of online platforms for everyday life information-seeking purposes, including the frequency with which they engage in different networked knowledge activities. Findings show that while students often use platforms associated with personal networking, such as Instagram, professional platforms like LinkedIn are less commonly used. Students are much more likely to engage in passive online activities than active ones. In particular, skills related to tagging, writing, and creation are infrequently used. Additionally, about half of these college students do not believe social media, which fosters these networked knowledge activities, is relevant to their careers. These findings show opportunities for better developing college students’ digital skill sets, with guidance for skills that might be targeted, taught together, and supported through learning activities in online spaces to prepare college students for digital information tasks in the workplace.

This study explores how online instructors use different instructional strategies to engage learners, and the active learning indicators that they look for among their students. Additionally, it examines how modality—synchronous versus asynchronous—and instructor learner-centeredness relate to instructional strategy choices. Using a mixed methods approach with a concurrent triangulation design, 101 higher education online instructors were surveyed and 11 were interviewed. Findings show that the use of learner-centered strategies, particularly discussion, occurs at a high rate regardless of an instructor’s learner-centeredness or modality. Interestingly, instructors with high learner-centeredness reported greater use of lectures as a percentage of both synchronous and asynchronous courses than instructors with low learner-centeredness. This finding was counterbalanced by the high learner-centeredness group reporting significantly higher importance for having learners speak and post messages during class.

Abstract Medical devices are commonly implanted underneath the skin, but how to real‐time noninvasively monitor their migration, integrity, and biodegradation in human body is still a formidable challenge. Here, the study demonstrates that benzyl violet 4B (BV‐4B), a main component in the FDA‐approved surgical suture, is found to produce fluorescence signal in the first near‐infrared window (NIR‐I, 700–900 nm) in polar solutions, whereas BV‐4B self‐assembles into highly crystalline aggregates upon a formation of ultrasmall nanodots and can emit strong fluorescence in the second near‐infrared window (NIR‐II, 1000–1700 nm) with a dramatic bathochromic shift in the absorption spectrum of ≈200 nm. Intriguingly, BV‐4B‐involved suture knots underneath the skin can be facilely monitored during the whole degradation process in vivo, and the rupture of the customized BV‐4B‐coated silicone catheter is noninvasively diagnosed by NIR‐II imaging. Furthermore, BV‐4B suspended in embolization glue achieves hybrid fluorescence‐guided surgery (hybrid FGS) for arteriovenous malformation. As a proof‐of‐concept study, the solid‐state BV‐4B is successfully used for NIR‐II imaging of surgical sutures in operations of patients. Overall, as a clinically translatable solid‐state dye, BV‐4B can be applied for in vivo monitoring the fate of medical devices by NIR‐II imaging.

Abstract Aberrant coagulation and thrombosis are associated with severe COVID-19 post-SARS-CoV-2 infection, yet the underlying mechanism remains obscure. Here we show that serum levels of SARS-CoV-2 envelope (E) protein are associated with coagulation disorders of COVID-19 patients, and intravenous administration of the E protein is able to potentiate thrombosis in mice. Through protein pull-down and mass spectrometry, we find that CD36, a transmembrane glycoprotein, directly binds with E protein and mediates hyperactivation of human and mouse platelets through the p38 MAPK-NF-κB signaling pathway. Conversely, the pharmacological blockade of CD36 or p38 notably attenuates human platelet activation induced by the E protein. Similarly, the genetic deficiency of CD36, as well as the pharmacological inhibition of p38 in mice, significantly diminishes E protein-induced platelet activation and thrombotic events. Together, our study reveals a critical role for the CD36-p38 axis in E protein-induced platelet hyperactivity, which could serve as an actionable target for developing therapies against aberrant thrombotic events related to the severity and mortality of COVID-19.

Abstract Purpose Traumatic brain injury (TBI) patients admitted to the intensive care unit (ICU) are at a high risk of infection and sepsis. However, there are few studies on predicting secondary sepsis in TBI patients in the ICU. This study aimed to build a prediction model for the risk of secondary sepsis in TBI patients in the ICU, and provide effective information for clinical diagnosis and treatment. Methods Using the MIMIC IV database version 2.0 (Medical Information Mart for Intensive Care IV), we searched data on TBI patients admitted to ICU and considered them as a study cohort. The extracted data included patient demographic information, laboratory indicators, complications, and other clinical data. The study cohort was divided into a training cohort and a validation cohort. In the training cohort, variables were screened by LASSO (Least absolute shrinkage and selection operator) regression and stepwise Logistic regression to assess the predictive ability of each feature on the incidence of patients. The screened variables were included in the final Logistic regression model. Finally, the decision curve, calibration curve, and receiver operating character (ROC) were used to test the performance of the model. Results Finally, a total of 1167 patients were included in the study, and these patients were randomly divided into the training (N = 817) and validation (N = 350) cohorts at a ratio of 7:3. In the training cohort, seven features were identified as key predictors of secondary sepsis in TBI patients in the ICU, including acute kidney injury (AKI), anemia, invasive ventilation, GCS (Glasgow Coma Scale) score, lactic acid, and blood calcium level, which were included in the final model. The areas under the ROC curve in the training cohort and the validation cohort were 0.756 and 0.711, respectively. The calibration curve and ROC curve show that the model has favorable predictive accuracy, while the decision curve shows that the model has favorable clinical benefits with good and robust predictive efficiency. Conclusion We have developed a nomogram model for predicting secondary sepsis in TBI patients admitted to the ICU, which can provide useful predictive information for clinical decision-making.

Abstract Objectives The HFA-PEFF score has been validated to hold great diagnostic and prognostic utility for heart failure with preserved ejection fraction (HFpEF). Idiopathic inflammatory myopathy (IIM) is recognized as one of the potential etiologies underlying HFpEF. Here, we intended to investigate the real prevalence of HFpEF in IIM via the HFA-PEFF score and explore the prognostic value of this score. Methods Two hundred twenty IIM patients were enrolled for assessment. The cohort was divided into low, intermediate and high tertiles of the HFA-PEFF score. Spearman’s correlation analysis was used to explore the association between the score and disease activity. Chi-square test was applied to investigate the distribution discrepancy of HFA-PEFF tertiles among patients with different myositis-specific antibodies (MSAs) or myositis-associated antibodies (MAAs). Univariate and multivariate ordinal regression analyses were performed to screen risk factors for high HFA-PEFF scores. Survival curves were obtained using the Kaplan–Meier method and log-rank tests. Results In total, 79 (35.9%), 107 (48.6%) and 34 (15.5%) patients were rated low, intermediate and high probability of HFpEF, respectively. The HFA-PEFF score correlated well with disease activity. Patients with positive AMA-M2 scored higher in the HFA-PEFF score (p = 0.011). During follow-up, patients with positive AMA-M2 or anti-SRP antibody developed an inclination towards concentric hypertrophy on echocardiography. Additionally, palpitation symptom, AMA-M2 positivity and elevated serum levels of LDH, cTnI were independent risk factors for high HFA-PEFF scores. Finally, a high-tertile HFA-PEFF score was related to lower overall survival rate (p

The visceral white nodules disease in the internal organs of Larimichthys crocea has caused significant harm in the aquaculture of this species, with Pseudomonas plecoglossicida considered one of the core pathogens causing this disease. In this study, we designed three pairs of specific nested PCR primers targeting the sctU gene of P. plecoglossicida, a crucial component of the Type III secretion system (T3SS), which is instrumental in bacterial pathogenesis and virulence. Through the optimization of PCR reaction conditions, specificity testing, and sensitivity determination, a method was established for the accurate detection of P. plecoglossicida. This method yielded single amplification products, exhibited a false positive rate of zero for reference bacteria, and achieved a detection sensitivity of a minimum of 2.62 copies/reaction for the target sequence. Using the detection method, we conducted analyses on the diseased populations of L. crocea, involving a total of 64 screened fishes along the southeast coast of China from 2021 to 2023. The results revealed that the infection rate of P. plecoglossicida in diseased L. crocea exceeded over 90% in March and April, while in other months, the maximum recorded infection rate was merely 10%. The detection method developed in this study shows potential for early warning and routine monitoring of visceral white nodules disease in the internal organs of species such as L. crocea.

Little is known about the independent and joint effects of the energy-adjusted dietary inflammatory index (E-DII) and dietary diversity score (DDS) on sarcopenia and its components (low muscle mass, low muscle strength, and low physical performance). A total of 155,669 UK Biobank participants with ≥1 (maximum 5) 24 h dietary assessments were included in this cross-sectional analysis. We used logistic regression models to investigate the associations of E-DII and DDS with sarcopenia and its three components. We further examined the joint effects of E-DII and DDS on sarcopenia and its components using additive and multiplicative interaction analyses. We observed that lower E-DII and higher DDS were associated with lower odds of sarcopenia and its components. There were significant joint associations of E-DII and DDS with sarcopenia and low physical performance (p-interaction < 0.05) on the multiplicative interactive scale. Our study suggests that lower dietary inflammatory potential and higher dietary diversity might be important protective factors against sarcopenia and its components. More cases of sarcopenia and low physical performance might be preventable by adherence to a more anti-inflammatory diet combined with a higher dietary diversity.

Previous studies have reported that exposure to forest landscapes has many benefits on human physiological and psychological health, as well as effectiveness in reducing stress and improving mood depending on different types of landscape. This study examined the effects of different types of forest landscapes for indirect visual experiences on the physical and mental health of college students (N = 33). Three types of landscape images were selected, in which forest landscapes included vegetated landscapes and water features, and as a control, we set up images of urban landscapes without natural elements. Physiological and psychological assessment was performed before the experiment for each student, followed by each student being exposed consecutively to nine landscape images for 3 min (each type) and assessed after each exposure. The results showed that both forest landscapes decreased stress (p < 0.05 for all) and improved mood and self-esteem (p < 0.01 for all). In contrast, water landscapes showed a slightly higher impact on physical and mental health than vegetated landscapes, but there was no significant difference. Conversely, only for self-esteem, the response after viewing vegetated landscapes (VL, SD = 29.06 ± 3.38) was better than after water views (WL, SD = 28.21 ± 2.48). Despite significant differences between the two types of forest landscapes not being found in our findings, the benefits of forest landscapes were observed through understanding the health-promoting capacities of different forest landscapes.