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Abstract Background Rice blast is a devastating disease caused by Magnaporthe grisea, and it is not well controlled globally. As a Traditional Chinese Medicine, Artemisia argyi has been proven to have inhibitory effects on a variety of phytopathogenic fungi. Here, we used bioactivity-guided isolation method and transcriptomics to clarify the antifungal active compounds in A. argyi and their antifungal mechanisms. Results In vitro studies showed that the absolute ethanol extract (AEE) of A. argyi had a strong inhibitory effect on the growth of M. grisea, with a low EC50 value of 1.156 mg/mL, and could cause the destruction of hyphae cell membrane and the leakage of cell contents. To identify the active constituents, we fractionated the AEE using macroporous adsorption resin and silica gel column chromatography. The active fraction (Fr.F-1) was fractionated and had even higher antifungal activity than AEE. The results showed that both AEE and Fr.F-1 could impact primary metabolic pathways and reactive oxygen species homeostasis of M. grisea, decrease the content of reducing sugars and downregulate the expression of genes related to starch and sucrose metabolism. Further fractionation of Fr.F-1 led to the identification of two polymethoxylated flavonoids (eupatilin and 3,5,3ʹ-trihydroxy-7,8,4ʹ-trimethoxyflavone), both of which had antifungal activity and they worked synergistically in Fr.F-1. Finally, we also investigated the effect of AEE, Fr.F-1 and eupatilin on rice blast control. The results showed that AEE, Fr.F-1 and eupatilin application strongly enhanced rice resistance to M. grisea. Conclusion In brief, these findings indicate that Fr.F-1 subfraction from A. argyi and its main components polymethoxylated flavonoids confer inhibiting activities to M. grisea. This discovery can effectively alleviate the degradation pressure of A. argyi by-products, promote the healthy development of its industry, and provide new a strategy for the development of new botanical fungicides to control rice blast. Graphical Abstract

Abstract Background Workplace may not only increase the risk of heat-related illnesses and injuries but also compromise work efficiency, particularly in a warming climate. This study aimed to utilize machine learning (ML) and deep learning (DL) algorithms to quantify the impact of temperature discomfort on productivity loss among petrochemical workers and to identify key influencing factors. Methods A cross-sectional face-to-face questionnaire survey was conducted among petrochemical workers between May and September 2023 in Fujian Province, China. Initial feature selection was performed using Lasso regression. The dataset was divided into training (70%), validation (20%), and testing (10%) sets. Six predictive models were evaluated: support vector machine (SVM), random forest (RF), extreme gradient boosting (XGBoost), Gaussian Naive Bayes (GNB), multilayer perceptron (MLP), and logistic regression (LR). The most effective model was further analyzed with SHapley Additive exPlanations (SHAP). Results Among the 2393 workers surveyed, 58.4% (1,747) reported productivity loss when working in high temperatures. Lasso regression identified twenty-seven predictive factors such as educational level and smoking. All six models displayed strong prediction accuracy (SVM = 0.775, RF = 0.760, XGBoost = 0.727, GNB = 0.863, MLP = 0.738, LR = 0.680). GNB model showed the best performance, with a cutoff of 0.869, accuracy of 0.863, precision of 0.897, sensitivity of 0.918, specificity of 0.715, and an F1-score of 0.642, indicating its efficacy as a predictive tool. SHAP analysis showed that occupational health training (SHAP value: -3.56), protective measures (-2.61), and less physically demanding jobs (-1.75) were negatively associated with heat-attributed productivity loss, whereas lack of air conditioning (1.92), noise (2.64), vibration (1.15), and dust (0.95) increased the risk of heat-induced productivity loss. Conclusions Temperature discomfort significantly undermined labor productivity in the petrochemical sector, and this impact may worsen in a warming climate if adaptation and prevention measures are insufficient. To effectively reduce heat-related productivity loss, there is a need to strengthen occupational health training and implement strict controls for occupational hazards, minimizing the potential combined effects of heat with other exposures.

Abstract Background Metabolic syndrome (MetS) and coronary artery stenosis (CAS) independently increase the risk of cardiovascular events, while the impact of CAS on left ventricular (LV) function and deformation in MetS patients remains unclear. This study investigates how varying degrees of CAS exacerbate LV function and myocardial deformation in MetS patients. Methods One hundred thirty-one MetS patients who underwent CMR examinations were divided into two groups: the MetS(CAS−) group (n = 47) and the MetS(CAS+) group (n = 84). The MetS(CAS+) group was divided into MetS with non-obstructive CAS(NOCAS+) (n = 30) and MetS with obstructive CAS(OCAS+) group (n = 54). Additionally, 48 age- and sex-matched subjects were included as a control group. LV functional and deformation parameters were measured and compared among subgroups. The determinants of decreased LV global peak strains in all MetS patients were identified using linear regression. The receiver operating characteristic (ROC) curve and logistic regression model (LRM) evaluated the diagnostic accuracy of the degree of CAS for identifying impaired LV strain. Results Compared to MetS(CAS−), MetS(NOCAS+) showed a significantly increased LV mass index (p

Abstract Background The phenylalanine ammonia-lyase (PAL) gene, a well-studied plant defense gene, is crucial for growth, development, and stress resistance. The PAL gene family has been studied in many plants. Citrus is among the most vital cash crops worldwide. However, the PAL gene family has not been comprehensively studied in most Citrus species, and the biological functions and specific underlying mechanisms are unclear. Results We identified 41 PAL genes from nine Citrus species and revealed different patterns of evolution among the PAL genes in different Citrus species. Gene duplication was found to be a vital mechanism for the expansion of the PAL gene family in citrus. In addition, there was a strong correlation between the ability of PAL genes to respond to stress and their evolutionary duration in citrus. PAL genes with shorter evolutionary times were involved in more multiple stress responses, and these PAL genes with broad-spectrum resistance were all single-copy genes. By further integrating the lignin and flavonoid synthesis pathways in citrus, we observed that PAL genes contribute to the synthesis of lignin and flavonoids, which enhance the physical defense and ROS scavenging ability of citrus plants, thereby helping them withstand stress. Conclusions This study provides a comprehensive framework of the PAL gene family in citrus, and we propose a hypothetical model for the stress resistance mechanism in citrus. This study provides a foundation for further investigations into the biological functions of PAL genes in the growth, development, and response to various stresses in citrus.

Abstract Background Mutation of MMACHC gene causes cobalamin C disease (cblC), an inherited metabolic disorder, which presents as combined methylmalonic aciduria (MMA-uria) and hyperhomocysteinaemia in clinical. Renal complications may also be present in patients with this inborn deficiency. The most common histological change is thrombotic microangiopathy (TMA). However, to our acknowledge, renal tubular injury in the late-onset presentation of cblC is rarely been reported. This study provides a detailed description of the characteristics of kidney disease in cblC deficiency, aiming to improve the early recognition of this treatable disease for clinical nephrologists. Case presentation Here we described three teenage patients who presented with hematuria, proteinuria, and hypertension in clinical presentation. They were diagnosed with renal involvement due to cblC deficiency after laboratory tests revealing elevated serum and urine homocysteine, renal biopsy showing TMA and tubular injury, along with genetic testing showing heterogeneous compound mutations in MMACHC. Hydroxocobalamin, betaine, and L-carnitine were administered to these patients. All of them got improved, with decreased homocysteine, controlled blood pressure, and kidney outcomes recovered. Conclusions The clinical diagnosis of cblC disease associated with kidney injury should be considered in patients with unclear TMA accompanied by a high concentration of serum homocysteine, even in teenagers or adults. Early diagnosis and timely intervention are vital to improving the prognosis of cobalamin C disease. Clinical Trial Number Not applicable.

Abstract Background Breast cancer (BRCA) remains to be among the main causes of cancer-associated mortality in women globally. HGH1 homolog (HGH1) has been reported to be associated with tumor immunity. However, the function of HGH1 in BRCA remains unclear. Therefore, the present study examined the potential role of HGH1 in BRCA. Methods The Cancer Genome Atlas (TCGA) databases and Gene Expression Omnibus (GEO) were used to obtain RNA-seq data for BRCA. A protein localization of HGH1 was determined by using the Human Protein Atlas (HPA), and immunohistochemistry (IHC) staining revealed an upregulation in the expression of HGH1 in clinical BRCA tissues. Xenograft mice were used to test tumor growth and HGH1 expression in breast cancer cells. The protein interaction information of HGH1 was analyzed using the GeneMANIA website. Based on univariate Cox regression and Kaplan-Meier methods, we evaluated the role of HGH1 in BRCA prognosis. HGH1-related differentially expressed genes were analyzed using GO, KEGG, and GSEA. We also examined the relationship between HGH1 expression, immune checkpoints, and immune infiltration. CCK-8, EdU, and colony formation assays were used to measure cell proliferation, and western blot analysis was used to evaluate HGH1’s role in BRCA. Results IHC results showed that the expression of HGH1 was significantly upregulated in BRCA tissues compared to normal tissues. High levels of HGH1 expression was associated with worse clinical features and a worse prognosis. HGH1 expression was an independent predictor of BRCA outcomes in both univariate and multivariate analyses. Functionally, western blot analysis showed that HGH1 is implicated in cell cycle. As well, knocking down HGH1 significantly reduced BRCA cells’ proliferative abilities. Crucially, HGH1 expression levels were positively correlated with Th2 cell infiltration and negatively correlated with Tcm cell infiltration. Conclusion Biomarkers such as HGH1 can reliably predict prognosis in BRCA patients.

Prodrug nanoparticles have been explored as an effective means for drug delivery because of controlled drug release in a stimulus-responsive manner. Organellar-targeted drug delivery could enhance the efficacy of cancer therapy. Herein, pH and light dual responsive mitochondrial targeted prodrug nanoparticles were designed to deliver both chemotherapeutic drugs and photosensitisers for enhanced antitumour efficacy. The prodrug nanoparticles (TPP-PEI-PheoA/ALG=DOX NPs, TPPAD NPs) are composed of a light-responsive mitochondrial targeted prodrug (triphenylphosphonium and pheophorbide A modified polyethyleneimine, TPP-PEI-PheoA) and a pH-responsive prodrug (doxorubicin conjugated alginate with Schiff's base bond, ALG=DOX). TPPAD NPs were prepared through electrostatic interaction. TPPAD NPs could simultaneously deliver DOX and PheoA to the tumour site by passive targeting effect, release drugs in a designed mode and deliver drugs to the target organelles. Moreover, TPPAD NP-based PDT could induce immunogenic cell death of tumour cells, thereby activating the immune system. TPPAD NPs greatly enhanced antitumour efficacy by combinational therapy. Taken together, this prodrug nanoparticle platform has appeared to be a simple and smart nanomedicine for targeted tumour combinational treatment.

Abstract Background tRNA-derived small RNAs (tsRNAs) are newly discovered non-coding RNA, which are generated from tRNAs and are reported to participate in several biological processes in diseases, especially cancer; however, the mechanism of tsRNA involvement in colorectal cancer (CRC) and 5-fluorouracil (5-FU) is still unclear. Methods RNA sequencing was performed to identify differential expression of tsRNAs in CRC tissues. CCK8, colony formation, transwell assays, and tumor sphere assays were used to investigate the role of tsRNA-GlyGCC in 5-FU resistance in CRC. TargetScan and miRanda were used to identify the target genes of tsRNA-GlyGCC. Biotin pull-down, RNA pull-down, luciferase assay, ChIP, and western blotting were used to explore the underlying molecular mechanisms of action of tsRNA-GlyGCC. The MeRIP assay was used to investigate the N(7)-methylguanosine RNA modification of tsRNA-GlyGCC. Results In this study, we uncovered the feature of tsRNAs in human CRC tissues and confirmed a specific 5’ half tRNA, 5’tiRNA-Gly-GCC (tsRNA-GlyGCC), which is upregulated in CRC tissues and modulated by METTL1-mediated N(7)-methylguanosine tRNA modification. In vitro and in vivo experiments revealed the oncogenic role of tsRNA-GlyGCC in 5-FU drug resistance in CRC. Remarkably, our results showed that tsRNA-GlyGCC modulated the JAK1/STAT6 signaling pathway by targeting SPIB. Poly (β-amino esters) were synthesized to assist the delivery of 5-FU and tsRNA-GlyGCC inhibitor, which effectively inhibited tumor growth and enhanced CRC sensitive to 5-FU without obvious adverse effects in subcutaneous tumor. Conclusions Our study revealed a specific tsRNA-GlyGCC-engaged pathway in CRC progression. Targeting tsRNA-GlyGCC in combination with 5-FU may provide a promising nanotherapeutic strategy for the treatment of 5-FU-resistance CRC. Graphical Abstract

Abstract Ketamine has gained attention for its effective treatment for patients with major depressive disorder (MDD) and suicidal ideation; Despite numerous studies presenting the rapid efficacy, long-term benefit in real-world populations remains poorly characterized. This is a retrospective cohort study using TriNetX US Collaborative Network, a platform aggregating electronic health records (EHRs) data from 108 million patients from 62 health care organizations in the US, and the study population includes 514,988 patients with a diagnosis of recurrent MDD who were prescribed relevant treatment in their EHRs. The prescription of ketamine was associated with significantly decreased risk of suicidal ideation compared to the prescription of other common antidepressants: HR = 0.63 (95% CI: 0.53–0.76) at 1 day – 7 days, 0.67 (95% CI: 0.59–0.77) at 1 day – 30 days, 0.69 (95% CI: 0.62–0.77) at 1 day – 90 days, 0.74 (95% CI: 0.67–0.81) at 1 day – 180 days, and 0.78 (95% CI: 0.69–0.83) at 1 day – 270 days. This trend was especially robust among adults over 24 years of age, females, males, and White patients with recurrent MDD. This study provides real-world evidence that ketamine has long-term benefits in mitigating suicidal ideation in patients with recurrent MDD. Future work should focus on optimizing dosage regimens for ketamine, understanding the mechanism, and the difference in various demographic subpopulations.

Coronaviruses (CoVs) pose a threat to human health globally, as highlighted by severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS) and the COVID-19 pandemic. Bats from the Greater Mekong Subregion (GMS) are an important natural reservoir for CoVs. Here we report the differential prevalence of CoVs in bats within Yunnan Province across biological and ecological variables. We also show the coexistence of CoVs in individual bats and identify an additional putative host for SARS-related CoV, with higher dispersal capacity than other known hosts. Notably, 11 SARS-related coronaviruses (SARSr-CoVs) were discovered in horseshoe bats (family Rhinolophidae) and a Chinese water myotis bat (Myotis laniger) by pan-CoV detection and Illumina sequencing. Our findings facilitate an understanding of the fundamental features of the distribution and circulation of CoVs in nature as well as zoonotic spillover risk in the One health framework.

Immunotherapy has recently attracted considerable attention. However, currently, a thorough analysis of the trends associated with the epithelial-mesenchymal transition (EMT) and immunotherapy is lacking. In this study, we used bibliometric tools to provide a comprehensive overview of the progress in EMT-immunotherapy research. A total of 1,302 articles related to EMT and immunotherapy were retrieved from the Web of Science Core Collection (WOSCC). The analysis indicated that in terms of the volume of research, China was the most productive country (49.07%, 639), followed by the United States (16.89%, 220) and Italy (3.6%, 47). The United States was the most influential country according to the frequency of citations and citation burstiness. The results also suggested that Frontiers in Immunotherapy can be considered as the most influential journal with respect to the number of articles and impact factors. “Immune infiltration,” “bioinformatics analysis,” “traditional Chinese medicine,” “gene signature,” and “ferroptosis” were found to be emerging keywords in EMT-immunotherapy research. These findings point to potential new directions that can deepen our understanding of the mechanisms underlying the combined effects of immunotherapy and EMT and help develop strategies for improving immunotherapy.

PurposeThis study aimed to develop a model to predict the risk of axillary lymph node (ALN) metastasis in breast cancer patients, using gray-scale ultrasound and clinical pathological features.MethodsA retrospective analysis of 212 breast cancer patients who met the inclusion criteria from January 2011 to December 2021 was carried out. Clinical and pathological characteristics, including age, tumor size, pathological type, molecular subtype, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and proliferation cell nuclear antigen (Ki-67), were examined. Preoperative ultrasound examinations were performed, and ultrasound radiomics features of breast cancer lesions were extracted using Pyradiomics software. The data was divided into training (70%) and testing (30%) sets. A predictive model for axillary lymph node metastasis (ALNM) was established by combining clinical and ultrasound features. The diagnostic performance of the model was evaluated using receiver operating characteristic (ROC) curves and five-fold cross-validation.ResultsThe rate of lymph node metastasis was 41.51%. Using LASSO algorithm, 17 features linked to ALN metastasis were extracted from a comprehensive databank of 8 clinical features and 1314 ultrasound radiomic attributes. Of these, four were clinical-pathological features (tumor size, tumor type, age, and expression levels of the Ki-67 protein), and 13 were radiomic features. And the following features exhibited both high weights and correlation coefficients: tumor size (R=0.29, weight=0.071), tumor type (R=-0.24, weight=-0.048), wavelet-LH_glcm_Imc1 (R=0.28, weight=0.029363), wavelet-LH_glszm_SZNUN (R=-0.20, weight=-0.028507), and squareroot_ firstorder_ Minimum (R= -0.25, weight= -0.059). The ROC area under the curve for the model in the training and testing sets was 0.882 (95% CI: 0.830-0.935) and 0.853 (95% CI: 0.762-0.945), respectively. The predictive model demonstrated a sensitivity of 87.5% on the training set and 79.2% on the test set, with corresponding specificities of 75.0% and 77.5%, accuracy of 80.4% and 78.1%, respectively. When evaluated using 5-fold cross-validation, the model achieved an average test set area under the curve (AUC) of 0.799 and a training set AUC of 0.852.ConclusionThe clinical-radiomic model has the potential to predict axillary lymph node metastasis in breast cancer.

Abstract Most deaths in breast cancer patients are attributed to metastasis, and lung metastasis is associated with a particularly poor prognosis; therefore it is imperative to identify potential target for intervention. The transforming growth factor‐β (TGF‐β) pathway plays a vital role in breast cancer metastasis, in which Smad3 is the key mediator and performs specific functions by binding with different cofactors. However, Smad3 cofactors involved in lung metastasis have not yet been identified. This study first establishes the interactome of Smad3 in breast cancer cells and identifies ZNF8 as a novel Smad3 cofactor. Furthermore, the results reveal that ZNF8 is closely associated with breast cancer lung metastasis prognosis, and specifically facilitates TGF‐β pathway‐mediated breast cancer lung metastasis by participating in multiple processes. Mechanistically, ZNF8 binds with Smad3 to enhance the H3K4me3 modification and promote the expression of lung metastasis signature genes by recruiting SMYD3. SMYD3 inhibition by BCI121 effectively prevents ZNF8‐mediated lung metastasis. Overall, the study identifies a novel cofactor of TGF‐β/Smad3 that promotes lung metastasis in breast cancer and introduces potential therapeutic strategies for the early management of breast cancer lung metastasis.

A case of Bowen's disease of toe is reported. A 39-year-old woman presented with red asymptomatic lesion on the medial side of the left big toe for over a month. Topical treatment with glucocorticoid was not effective. A similar rash appeared on the same area 5 to 6 years ago, and was surgically removed. Clinical examination revealed a demarcated red plaque 1.5 cm×1.5 cm in diameter, with dark red crust in the center, on her big left toe. The histopathological examination of the skin lesion showed heteroplasia of the squamous epithelium in the epidermis. The diagnosis was Bowen's disease. Following removal of lesion with electrocauterization, 5-aminolevulinic acid photodynamic (ALA-PDT) was given 4 times. The lesion completely subsided with no recurrence during 1-year telephone follow-up.

To meet the requirements of explosives in military and civilian fields, researchers are committed to improving the comprehensive performance of explosives. The performance of explosive crystals can be significantly improved by regulating the structure and morphology of single-compound explosive crystals as well as compounding explosive crystals. According to the related research on explosive crystals at home and abroad from 2022 to now, the development of explosive crystal composites and single-compound explosives' crystal morphology, particle size, and crystal form regulation study were reviewed. The explosive crystal composites encompass both the complex consisting of a single-compound explosive and the complex consisting of two separate types of explosives. Simultaneously, the main problems encountered in the development of explosive crystals were also analyzed, such as the deficiency of systematic and broadly applicable regulation methods and theories. Finally, the future development direction of explosive crystal research was envisioned, with the aim of providing guidance for the production, handling, and application of explosives.

Abstract Background Analyzing distance-dependent functional connectivity density (FCD) yields valuable insights into patterns of brain activity. Nevertheless, whether alterations of FCD in non-acute stroke patients are associated with the anatomical distance between brain regions remains unclear. This study aimed to explore the distance-related functional reorganization in non-acute stroke patients following left and right hemisphere subcortical lesions, and its relationship with clinical assessments. Methods In this study, we used resting-state fMRI to calculate distance-dependent (i.e., short- and long-range) FCD in 25 left subcortical stroke (LSS) patients, 22 right subcortical stroke (RSS) patients, and 39 well-matched healthy controls (HCs). Then, we compared FCD differences among the three groups and assessed the correlation between FCD alterations and paralyzed motor function using linear regression analysis. Results Our findings demonstrated that the left inferior frontal gyrus displayed distance-independent FCD changes, while the bilateral supplementary motor area, cerebellum, and left middle occipital gyrus exhibited distance-dependent FCD alterations in two patient subgroups compared with HCs. Furthermore, we observed a positive correlation between increased FCD in the bilateral supplementary motor area and the motor function of lower limbs, and a negative correlation between increased FCD in the left inferior frontal gyrus and the motor function of both upper and lower limbs across all stroke patients. These associations were validated by using a longitudinal dataset. Conclusions The FCD in the cerebral and cerebellar cortices shows distance-related changes in non-acute stroke patients with motor dysfunction, which may serve as potential biomarkers for predicting motor outcomes after stroke. These findings enhance our comprehension of the neurobiological mechanisms driving non-acute stroke. Trial registration All data used in the present study were obtained from a research trial registered with the ClinicalTrials.gov database (NCT05648552, registered 05 December 2022, starting from 01 January 2022).

Objective To analyze the correlation between frailty and living conditions in the elderly. Methods A convenience sampling method was used to select 4 869 elderly people who underwent physical examination and hospitalization in 20 medical institutions in hospitals,communities and nursing homes from August 2021 to February 2022.According to the Fried frailty diagnostic criteria,the research subjects were divided into a non-frailty group(2 904 cases),pre-frailty group(1 284 cases) and frailty group(681 cases).Multivariate logistic regression was used to analyze the correlation between living conditions and frailty. Results The total prevalence of frailty was 14.0%(95% CI:13.0-15.0),and the prevalence of men and women was compared(11.9% and 16.3%),and the difference was statistically significant(P

Abstract Alcohol use disorders are among the top causes of the global burden of disease, yet therapeutic interventions are limited. Reduced desire to drink in patients treated with semaglutide has raised interest regarding its potential therapeutic benefits for alcohol use disorders. In this retrospective cohort study of electronic health records of 83,825 patients with obesity, we show that semaglutide compared with other anti-obesity medications is associated with a 50%-56% lower risk for both the incidence and recurrence of alcohol use disorder for a 12-month follow-up period. Consistent reductions were seen for patients stratified by gender, age group, race and in patients with and without type 2 diabetes. Similar findings are replicated in the study population with 598,803 patients with type 2 diabetes. These findings provide evidence of the potential benefit of semaglutide in AUD in real-world populations and call for further randomized clinical trials.

Abstract Background Fear of childbirth (FOC) can influence both maternal and child health. Research on FOC in China is scarce, especially on rural women. This study aimed to assess pre- and postpartum FOC and its predictors among Chinese rural women. Methods This was a prospective correlation study. A total of 569 women completed the prenatal questionnaire in the third trimester, and 477 of them completed the postpartum questionnaire within three days after childbirth. Maternal socio-demographic information, clinical information, childbirth self-efficacy and prenatal and postpartum FOC were investigated. FOC was evaluated using the Wijma Childbirth Expectancy/ Experience Questionnaire (WDEQ). Descriptive, bivariate, multivariate linear regression analysis, univariate and multivariate logistic regression analyses were performed. Results The mean pre- and postpartum FOC scores were 64.5 (standard deviation: 25.1) and 64.3 (standard deviation: 23.9), respectively, with 20.8% of women reporting severe fear before childbirth and 18.2% after childbirth. Multivariate linear regression analysis revealed predictors for higher levels of prenatal FOC including higher education level, nullipara, higher monthly household income, lower family support, and lower childbirth self-efficacy (p

Abstract Background WHO stated the environment is an important factor affecting the development of hospice care. The environment is the sum of factors affecting behavior besides the individual factors. Currently, a scale to comprehensively assess the hospice environment of nurse is still lacking. This study aimed to develop an instrument to investigate the environmental factors affecting hospice care of nurses. Methods Literature review and a semi-structured interview were conducted to form the items pool of the Hospice Care Environment Scale. Two rounds of Delphi expert consultation were conducted by 16 experts to revise the scale dimensions and entries to form the Hospice Care Environment Scale. A psychometric evaluation was then performed among 530 oncology nurses in a large tertiary oncology hospital in Hubei Province. The 500 valid questionnaires were randomly divided into two groups in a 1:1 ratio, sample 1 (n1 = 250) for item screening and sample 2 (n2 = 250) for quality evaluation of the resulting scale. Item analysis, reliability analysis, validity analysis and acceptability analysis were performed. Result The Hospice Care Environment Scale consists of two dimensions and 13 entries. The Cronbach’s α coefficient of the Hospice Care Environment Scale was 0.970, and the Cronbach’s α coefficient of the two dimensions were 0.952 and 0.969, respectively, with the Item-content validity index and average Scale- content validity index of the scale was both 1.000. The validation factor analysis showed the standardized path coefficients of each item were basically above 0.5, and the factor structure model was stable and suitable. The average completion time of the scale was about 3 min, which had good feasibility. Conclusion The Hospice Care Environment Scale to assess the environment of hospice care services, has good content and construct validity and reliability. This scale can provide guidance to evaluate the hospice care environment.

Abstract Chemokines, cytokines, and inflammatory cells mediate the onset and progression of many diseases through the induction of an inflammatory response. LncRNAs have emerged as important regulators of gene expression and signaling pathways. Increasing evidence suggests that lncRNAs are key players in the inflammatory response, making it a potential therapeutic target for various diseases. From the perspective of lncRNAs and inflammatory factors, we summarized the expression level and regulatory mechanisms of lncRNAs in human inflammatory diseases, such as cardiovascular disease, osteoarthritis, sepsis, chronic obstructive pulmonary disease, asthma, acute lung injury, diabetic retinopathy, and Parkinson’s disease. We also summarized the functions of lncRNAs in the macrophages polarization and discussed the potential applications of lncRNAs in human inflammatory diseases. Although our understanding of lncRNAs is still in its infancy, these data will provide a theoretical basis for the clinical application of lncRNAs.

Abstract Electrochemical-mechanical coupling poses enormous challenges to the interfacial and structural stability but create new opportunities to design innovative all-solid-state batteries from scratch. Relying on the solid-solid constraint in the space-limited domain structure, we propose to exploit the lithiation-induced stress to drive the active materials creep, thereby improving the structural integrity. For demonstration, we fabricate the creep-type all-solid-state cathode using creepable Se material and an all-in-one rigid ionic/electronic conducting Mo6Se8 framework. As indicated by the in-situ experiment and numerical simulation, this cathode presents unique capabilities in improving interparticle contact and avoiding particle fracture, leading to its superior electrochemical performance, including a superior long-cycle life of more than 3000 cycles at 0.5 C and a high volumetric energy density of 2460 Wh/L at the cathode level. We believe this innovative strategy to utilize mechanics to boost the electrochemical performance could shed light on the future design of all-solid-state batteries for practical applications.

Abstract Purpose To evaluate short-term visual and refractive outcomes after implantation of a diffractive trifocal intraocular lens (IOL) in cataract patients with phacoemulsification (PHACO) and femtosecond laser assisted cataract surgery (FLACS). Setting Department of Ophthalmology, Shanghai Aier Eye Hospital, China. Design A retrospective, observational study. Methods Patients who underwent cataract surgery combined with Acrysoft IQ PanOptix trifocal IOL implantation were enrolled and divided into three groups: PHACO group, LAstig-FLACS group (astigmatism less then 1D) and HAstig-FLACS group (astigmatism more than 1D). Logarithm of the minimum angle of resolution (logMAR) visual acuity of uncorrected distance (UDVA), intermediate (UIVA), near visual (UNVA), defocus curve, surgically induced astigmatism (SIA) were evaluated in 1 months postoperatively and wavefront aberrations were evaluated in 6 months. Results 101 eyes of 60 patients were included with 31 eyes in PHACO group, 45 eyes in LAstig-FLACS group and 25 eyes in HAstig-FLACS group. Significant difference was found of internal Strehl Ratio (SR) between PHACO and LAstig-FLACS group (P = 0.026). In PHACO group, 79.31%, 86.21%, 72.41% of eyes gain visual acuity LogMAR 0.1 or more in UDVA, UIVA and UNVA, while 83.72%, 93.02%, 93.02% of those in LAstig-FLACS group and 92.00%, 84.00%, 76.00% in HAstig-FLACS group. Conclusions Panoptix diffractive trifocal IOL provides satisfied visual outcome in no matter FLACS or PHACO. Besides, trifocal IOL implantation via FLACS can provide a better accumulative visual acuity outcome at all distance than PHACO in 1 month. Femtosecond laser assisted limbal relaxing incisions (FLLRIs) is an excellent way to reduce a patient’s corneal astigmatism.

Urban heat island (UHI) has posed a threat to sustainable development, and the identification of the spatial characteristics of UHI is a prerequisite for the mitigation of UHI effects. Taking Kunming City and Guiyang City in the karst region of Southwest China as two examples, this study utilized spatial econometric modeling and random forest regression to identify and compare the spatial distribution and impact of urban heat islands related to topographic and urban morphology. The results indicated that the UHI in Kunming and Guiyang mainly monocentrically and polycentrically distributed, respectively, and the urban heat island intensity (UHII) in Kunming was significantly higher than that in Guiyang. The spatial error model effectively reflected the influence of topography and urban form on UHII, and the random forest regression model objectively measured the contribution of different influencing factors to UHII. Enhanced vegetation index (EVI), population density (PD), percentage of impervious surface (PIS), ground sky view factor (GSVF), building density (BD) and percentage of water bodies (PW) had similar effects and contributions to the UHII in the two cities, while urban surface roughness (USR) contributed less than topographic slope (SLOPE) on UHII in Kunming, and the SLOPE contributed less than USR in Guiyang. In the karst ecologically fragile zone, the morphology of Kunming and Guiyang are mainly shaped by the topography, which can be characterized as monocentric and polycentric, respectively. And the UHI distribution and UHII were also closely related to topographic patterns. EVI, SLOPE and PW, all showed inhibitory effects on UHII, and EVI contributed the most. PD, PIS, USR and BD, exacerbate the UHII, with PD contributing the most. The above conclusions can provide a reference for policymakers and urban planners to optimize urban morphology and mitigate urban heat island.

Abstract l‐2‐Hydroxyglutarate (l‐2‐HG) is a functionally compartmentalized metabolite involved in various physiological processes. However, its subcellular distribution and mitochondrial transport remain unclear owing to technical limitations. In the present study, an ultrasensitive l‐2‐HG biosensor, sfLHGFRH, composed of circularly permuted yellow fluorescent protein and l‐2‐HG‐specific transcriptional regulator, is developed. The ability of sfLHGFRH to be used for analyzing l‐2‐HG metabolism is first determined in human embryonic kidney cells (HEK293FT) and macrophages. Then, the subcellular distribution of l‐2‐HG in HEK293FT cells and the lower abundance of mitochondrial l‐2‐HG are identified by the sfLHGFRH‐supported spatiotemporal l‐2‐HG monitoring. Finally, the role of the l‐glutamate transporter SLC1A1 in mitochondrial l‐2‐HG uptake is elucidated using sfLHGFRH. Based on the design of sfLHGFRH, another highly sensitive biosensor with a low limit of detection, sfLHGFRL, is developed for the point‐of‐care diagnosis of l‐2‐HG‐related diseases. The accumulation of l‐2‐HG in the urine of patients with kidney cancer is determined using the sfLHGFRL biosensor.

Background: BET family proteins are important epigenetic and transcriptional regulators involved in the control of tumorigenesis and development and have become important targets for cancer therapy. However, there is no systematic bibliometric analysis in this field. A visual analysis of the research hotspots and trends of BET is helpful to understand the future development direction. Method: We used CiteSpace, VOSviewer, and Excel to visualize and analyze the trends regarding authors, journals, countries or regions, highly cited papers, and keywords in the field. Result: The results included a total of 946 publications. There are many more papers on BET proteins published since 2013. The papers are mainly from 44 countries, led by the U.S. and China. A total of 7381 authors were identified, among which Bradner, J.E. had the greatest number of articles and the greatest influence. Cancer Discovery was the journal with the most citations per article. Our analysis identified the most influential papers in the field, including highly cited papers and citation burst references. The most frequent keywords included ‘expression’, ‘c-Myc’, ‘cancer’, ‘BRD4’, ‘BET inhibition’, ‘resistance’, ‘differentiation’, and ‘JQ1’, which represent the focus of current and developing research fields. Conclusion: Research on BET is thriving. Collaboration and exchanges between countries and institutions must be strengthened in the future, and the mechanisms of BET-related pathways, the relationship between BET and various diseases, and the development of new BET inhibitors have become the major focus of current research and the trend of future research.

IntroductionIndividuals with diabetes mellitus (DM) are at an increased risk of Mycobacterium tuberculosis (Mtb) infection and progressing from latent tuberculosis (TB) infection to active tuberculosis disease. TB in the DM population is more likely to go undiagnosed due to smear-negative results.MethodsExhaled breath samples were collected and analyzed using high-pressure photon ionization time-of-flight mass spectrometry. An eXtreme Gradient Boosting (XGBoost) model was utilized for breathomics analysis and TB detection.ResultsXGBoost model achieved a sensitivity of 88.5%, specificity of 100%, accuracy of 90.2%, and an area under the curve (AUC) of 98.8%. The most significant feature across the entire set was m106, which demonstrated a sensitivity of 93%, specificity of 100%, and an AUC of 99.7%.DiscussionThe breathomics-based TB detection method utilizing m106 exhibited high sensitivity and specificity potentially beneficial for clinical TB screening and diagnosis in individuals with diabetes.

Background: CD20 is a membrane protein extensively expressed on the surface of B cells at various stages of development and differentiation. Herein, we conducted a bibliometrics analysis of the literature on CD20-targeting antibody therapy in lymphoma. Methods: A total of 6663 articles were downloaded from the web of science core collection (WOSCC) from 1999 to July 23, 2022. Bibliometric.com was used for citation and annual publications analysis. VOSviewer was used to map countries/institutions/authors/journals nodes and links, extract hotspot keywords, and analyze the time trend of keywords. Citespace was employed to recognize the turning points based on the centrality value of countries, define the topic distribution of academics according to the map of dual-map overlay of journals, and characterize the emerging topics or landmark articles in a field based on references citation bursts. Results: All articles were cited 225,032 times, averaging 33.77. The number of articles increased from 1999 to 2002, while the growth rate entered the platform after 2002. The USA was the most publication country, and China was the largest emerging country. Hotspots in this field still focus on the efficacy of rituximab in treating non-Hodgkin's lymphoma and the pathogenesis of lymphoma Application of generation CD-20 antibodies or molecule inhibitors in clinical research and cellular therapy/immunotherapy, such as CAR-T and PDL1/PD1 were the emerging research topics. Conclusion: This study provides essential information and the tendency of the CD20-targeting antibody therapy in lymphoma by using bibliometric and visual methods, which would provide helpful references for clinical experiments and basic scientific research.

BackgroundAngiomatoid fibrous histiocytoma (AFH) is a clinically rare, low-grade malignant soft tissue tumor that occasionally metastasizes. It accounts for 0.3% of all soft tissue tumors and most frequently occurs in the extremities, followed by the trunk, and the head and neck. Primary angiomatoid fibrous histiocytoma (PAFH) of the pulmonary bronchus is rare. In this paper, the clinical and imaging data of a case of PAFH of the pulmonary bronchus are reported, and the literature is reviewed.Case descriptionA 57-year-old female patient presented with a six-month history of cough without apparent cause, characterized by paroxysmal dry cough, chest tightness, and shortness of breath, which worsened with activity. She did not experience fever, chills, chest pain, hemoptysis, or night sweats. Laboratory tests revealed an elevated C-reactive protein and ferritin levels, while tumor markers such as AFP, CEA, CA199, CA125, CA50, and T-SPOT were negative. A chest CT scan showed bronchial obstruction, atelectasis, and a soft tissue density in the right middle lobe of the lung. The enhanced scan demonstrated uneven enhancement of endobronchial nodules. An 18F-FDG PET/CT scan revealed a nodular soft tissue density shadow in the right lung bronchus with uneven density, clear boundaries, and increased 18F-FDG uptake, with a maximum standard uptake value (SUVmax) of 11.2. Bronchoscopy revealed a nodular or polypoid mass that was yellow and tough. Based on imaging findings, the preoperative diagnosis favored lung cancer. However, the postoperative pathological diagnosis confirmed primary angiomatoid fibrous histiocytoma (PAFH) of the pulmonary bronchus.ConclusionThe incidence of primary angiomatoid fibrous histiocytoma (PAFH) is very low, and its clinical manifestations and imaging findings lack specificity, with the final diagnosis relying on pathology. PET/CT imaging has a certain value in the diagnosis of PAFH and holds significant application value in preoperative staging, postoperative efficacy evaluation, and follow-up monitoring. In conclusion, this case report further expands the spectrum of lung and bronchial tumors.

BackgroundFatigue is a prevalent symptom among individuals with active systemic lupus erythematosus (SLE). We aimed to investigate the status quo and influencing factors of fatigue in patients with SLE, to provide insights to the clinical SLE treatment and care.MethodsWe conducted a longitudinal survey on the fatigue of active SLE patients from June 2022 to November 2023 in our hospital. Fatigue severity scale (FSS), Self-rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used for data collection. Pearson correlation and multiple stepwise regression analysis were conducted to analyze the relevant factors affecting the fatigue level of patients with SLE.ResultsA total of 212 active SLE patients were included, the incidence of fatigue in active SLE patients was 55.66%. There were statistical differences in the fatigue score between SLE patients with different age and course of SLE (all p

Abstract Background The single-pool model urea clearance index (single-pool Kt/Vurea; spKt/V) is the most commonly used method for dialysis adequacy assessment. However, only a few studies have examined the relationship between spKt/V values and parameters related to sarcopenia and nutritional status. This study aimed to evaluate whether the spKt/V is an indicator of sarcopenia and nutritional status in patients undergoing maintenance hemodialysis (MHD). Methods A total of 142 patients were included in this single-center, cross-sectional study. Venous blood samples were collected shortly before the hemodialysis session. The adequacy of dialysis in patients receiving MHD was assessed using spKt/V. Sarcopenia was identified according to the Asian Working Group for Sarcopenia (2019) definition. Receiver operating characteristic curve and area under the curve were used to evaluate the predictive value of spKt/V in sarcopenia. Univariate and multivariate binary logistic regression analyses were used to determine the association between spKt/V and sarcopenia and nutritional status. Results The mean spKt/V level was 1.3 ± 0.2, the prevalence of sarcopenia was 15.5% in patients on MHD. The best cutoff value of spKt/V in sarcopenia was 1.45 for both sexes, 1.33 and 1.45 for men and women, respectively (P

Abstract Single-atom catalysts show excellent catalytic performance because of their coordination environments and electronic configurations. However, controllable regulation of single-atom permutations still faces challenges. Herein, we demonstrate that a polarization electric field regulates single atom permutations and forms periodic one-dimensional Au single-atom arrays on ferroelectric Bi4Ti3O12 nanosheets. The Au single-atom arrays greatly lower the Gibbs free energy for CO2 conversion via Au-O=C=O-Au dual-site adsorption compared to that for Au-O=C=O single-site adsorption on Au isolated single atoms. Additionally, the Au single-atom arrays suppress the depolarization of Bi4Ti3O12, so it maintains a stronger driving force for separation and transfer of photogenerated charges. Thus, Bi4Ti3O12 with Au single-atom arrays exhibit an efficient CO production rate of 34.15 µmol·g−1·h−1, ∼18 times higher than that of pristine Bi4Ti3O12. More importantly, the polarization electric field proves to be a general tactic for the syntheses of one-dimensional Pt, Ag, Fe, Co and Ni single-atom arrays on the Bi4Ti3O12 surface.

Abstract Background Deep vein thrombosis (DVT) has been one of the most dangerous complications in total hip arthroplasty (THA). If a patient’s pre-surgical DVT is overlooked, it can easily be mistaken for a post-operative thrombus and lead to an increased risk of DVT during and after surgery. This retrospective study was to explore the incidence and associated risk factors of deep vein thrombosis (DVT) in non-fracture patients before total hip arthroplasty (THA). Methods From September 2015 to September 2020, 1242 patients admitted for THA were enrolled with 1120 patients (90.2%) for primary THA and 122 patients (9.8%) for revision THA. An experienced sonographer performed a bedside ultrasound to detect DVT in bilateral lower limbs preoperatively. Univariate and logistic regression analysis was performed to identify the independent risk factors. Results 38 patients (3.1%) were detected with preoperative DVT. Univariate analysis showed that age (P

Two novel Comoclathris species were identified from dicotyledonous plants (Clematis sp. and Xanthoceras sorbifolium) in China. The results were supported by morphological characters and Maximum Likelihood (ML) and Bayesian Inference (BI) analyses. Multi-gene phylogenetic analyses of the ITS, LSU, SSU and rpb2 sequences revealed two new species Comoclathris clematidis and C. xanthoceratis, which are phylogenetically distinct. The new species are phylogenetically closely related to C. arrhenatheri. However, they are distinguishable from C. arrhenatheri by having comparatively larger asci and ascospores. This study improves our knowledge of Comoclathris as no species has been previously described from China. This suggests such taxa may be rare and it is likely that new taxa will be discovered from hosts and environments that have not yet been extensively investigated.

Abstract Both lytic and apoptotic cell death remove senescent and damaged cells in living organisms. However, they elicit contrasting pro- and anti-inflammatory responses, respectively. The precise cellular mechanism that governs the choice between these two modes of death remains incompletely understood. Here we identify Gasdermin E (GSDME) as a master switch for neutrophil lytic pyroptotic death. The tightly regulated GSDME cleavage and activation in aging neutrophils are mediated by proteinase-3 and caspase-3, leading to pyroptosis. GSDME deficiency does not alter neutrophil overall survival rate; instead, it specifically precludes pyroptosis and skews neutrophil death towards apoptosis, thereby attenuating inflammatory responses due to augmented efferocytosis of apoptotic neutrophils by macrophages. In a clinically relevant acid-aspiration-induced lung injury model, neutrophil-specific deletion of GSDME reduces pulmonary inflammation, facilitates inflammation resolution, and alleviates lung injury. Thus, by controlling the mode of neutrophil death, GSDME dictates host inflammatory outcomes, providing a potential therapeutic target for infectious and inflammatory diseases.

Constructing tissue/organ analogs with natural structures and cell types in vitro offers a valuable strategy for the in situ repair of damaged tissues/organs. Three-dimensional (3D) bioprinting is a flexible method for fabricating these analogs. However, extrusion-based 3D bioprinting faces the challenge of balancing the use of soft bioinks with the need for high-fidelity geometric shapes. To address these challenges, recent advancements have introduced various suspension mediums based on gelatin, agarose, and gellan gum microgels. The emergence of these gel-based suspension mediums has significantly advanced the fabrication of tissue/organ constructs using 3D bioprinting. They effectively stabilize and support soft bioinks, enabling the formation of complex spatial geometries. Moreover, they provide a stable, cell-friendly environment that maximizes cell viability during the printing process. This minireview will summarize the properties, preparation methods, and potential applications of gel-based suspension mediums in constructing tissue/organ analogs, while also addressing current challenges and providing an outlook on the future of 3D bioprinting.

BackgroundPrimary splenic angiosarcoma (PSA) is a rare neoplasm. It is a malignant tumor derived from endothelial cells of the splenic sinuses. PSA has an unknown etiology, a high degree of malignancy, easy early metastasis, atypical clinical symptoms and imaging findings, and difficult early diagnosis. This paper reports the 18F-FDG PET/CT findings of a case of PSA with intrahepatic metastasis; summarizes its clinical, imaging, and pathological data; and reviews the literature.Case descriptionA 64-year-old male patient presented with left lower abdominal distending pain without obvious causes on 13 March 2022. The pain was persistent and dull and worsened after sitting and eating. Blood routine examination results were RBC ↓ 3.33 × 1012/L, WBC ↑ 12.32 × 109/L, and PLT ↓ 40 × 109/L. The tumor markers indicated CA125 ↑ 47.0 U/ml, AFP (−), CEA (−), CA199 (−), and CA724 (−). Non-contrast-enhanced CT scan of the abdomen showed that the spleen was significantly enlarged in volume and irregular in shape and had multiple nodules and clumpy low-density shadows, unclear boundaries, uneven density, and multiple necrotic areas. Enhanced CT showed diffuse uneven mild enhancement of the spleen, and the degree of enhancement increased with time. Multiple nodular low-density shadows were seen in the liver, which were slightly enhanced by the enhanced scan.18F-FDG PET/CT showed multiple nodular and massive lesions in the spleen with multiple necrotic areas. There were multiple nodular lesions in the liver, the level of FDG metabolism increased, the SUVmax of the spleen lesions was 9.0, and the SUVmax of the liver lesions was 5.6. The 18F-FDG PET/CT diagnosis was splenic malignancy with liver metastasis. Finally, after a multidisciplinary discussion, it was decided to perform laparoscopic total splenectomy and portal vein infusion chemotherapy. Pathological examination showed that the tumor cells were round, oval, or fusiform, with obvious atypia, arranged into a cable or anastomosed vascular lumen. The final diagnosis was primary splenic angiosarcoma with massive necrosis. After surgery, the patient received antitumor combined therapy and died 5 months later.ConclusionThe incidence of PSA is very low, and its clinical and radiological manifestations lack specificity. 18F-FDG PET/CT imaging has a certain diagnostic value for PSA and significant utility in preoperative staging, guiding biopsy procedures, evaluating postoperative treatment response, and monitoring disease recurrence. PSA should be considered in the presence of a space-occupying lesion within the spleen that exhibits necrotic areas, shows progressive enhancement on contrast-enhanced scans, and demonstrates heterogeneous increases in FDG uptake.

Abstract The surface properties of oxidic supports and their interaction with the supported metals play critical roles in governing the catalytic activities of oxide‐supported metal catalysts. When metals are supported on reducible oxides, dynamic surface reconstruction phenomena, including strong metal–support interaction (SMSI) and oxygen vacancy formation, complicate the determination of the structural–functional relationship at the active sites. Here, we performed a systematic investigation of the dynamic behavior of Au nanocatalysts supported on flame‐synthesized TiO2, which takes predominantly a rutile phase, using CO oxidation above room temperature as a probe reaction. Our analysis conclusively elucidated a negative correlation between the catalytic activity of Au/TiO2 and the oxygen vacancy at the Au/TiO2 interface. Although the reversible formation and retracting of SMSI overlayers have been ubiquitously observed on Au/TiO2 samples, the catalytic consequence of SMSI remains inconclusive. Density functional theory suggests that the electron transfer from TiO2 to Au is correlated to the presence of the interfacial oxygen vacancies, retarding the catalytic activation of CO oxidation.

Objective We established an orthopedic ward fracture liaison services (OWFLS) model and evaluated its role in improving detection rates of bone metabolic markers, treatment rates, and long-term treatability. Methods This observational retrospective cohort study included 120 patients aged >50 years hospitalized for primary osteoporotic fracture from January 2018 to January 2019 (group A: not included in OWFLS). Group B (included in OWFLS) comprised 120 patients from February 2019 to February 2020. We compared rates of bone metabolic index testing, treatment, and adherence; symptomatic improvement; and recurrent fracture between groups. Results Rates of bone metabolism index testing (50% vs. 0%) and medication use (94.2% vs. 64.2%) were significantly higher after OWFLS implementation. There was no significant difference in adherence rates at 3 months between groups (97.3% vs. 93.5%). Adherence rates at 1 and 3 years were better in group B than A (73.5% vs. 51.9%; 57.5% vs. 26%, respectively). Recurrence of bone pain at 1 and 3 years was significantly lower in group B than A (20.4% vs. 46.8%; 45.1% vs. 76.6%, respectively). Conclusions OWFLS improved the detection rate of bone metabolism indicators, treatment rate, and patient adherence and reduced recurrence of bone pain. OWFLS may be suitable for settings lacking human resources.

Diabetic retinopathy (DR) is the most common ocular fundus disease in diabetic patients. Chronic hyperglycemia not only promotes the development of diabetes and its complications, but also aggravates the occurrence of senescence. Previous studies have shown that DR is associated with senescence, but the specific mechanism has not been fully elucidated. Here, we first detected the differentially expressed genes (DEGs) and cellular senescence level of db/db mouse retinas by bulk RNA sequencing. Then, we used single-cell sequencing (scRNA-seq) to identify the main cell types in the retina and analyzed the DEGs in each cluster. We demonstrated that p53 expression was significantly increased in retinal endothelial cell cluster of db/db mice. Inhibition of p53 can reduce the expression of SA-β-Gal and the senescence-associated secretory phenotype (SASP) in HRMECs. Finally, we found that p53 can promote FoxO3a ubiquitination and degradation by increasing the expression of the ubiquitin-conjugating enzyme UBE2L6. Overall, our results demonstrate that p53 can accelerate the senescence process of endothelial cells and aggravate the development of DR. These data reveal new targets and insights that may be used to treat DR.

Abstract Background Gadolinium-enhanced cardiovascular magnetic resonance (CMR) is the most widely used approach for diagnosing myocardial fibrosis with late gadolinium enhancement (LGE) in cardiomyopathy associated with Duchenne muscular dystrophy. Given the limitations and safety of gadolinium use, we wanted to develop and evaluate multi-parametric pre-contrast CMR models for the diagnosis of LGE and investigate whether they could be utilised as surrogates for LGE in DMD patients. Methods A total of 136 DMD patients were prospectively recruited and separated into LGE − and LGE + groups. In the first subset of patients (derivation cohort), regression models for the diagnosis of LGE were built by logistic regression using pre-contrast sequence parameters. In a validation cohort of other patients, the models’ performances were evaluated. Results EF, native T1 and longitudinal strain alone, as well as their combinations form seven models. The model that included EF, native T1 and longitudinal strain had the best diagnostic value, but there was no significant difference in diagnostic accuracy among the other models except EF. In the validation cohort, the diagnosis outcomes of models were moderate consistent with the existence of LGE. The longitudinal strain outperformed the other models in terms of diagnostic value (sensitivity: 83.33%, specificity: 54.55%). Conclusions Pre-contrast sequences have a moderate predictive value for LGE. Thus, pre-contrast parameters may be considered only in a specific subset of DMD patients who cannot cooperate for long-time examinations and have contradiction of contrast agent to help predict the presence of LGE. Trial registration number (TRN) ChiCTR1800018340 Date of registration 20180107

AbstractBackground Teachers with high educational levels significantly impact the health-related knowledge and attitudes of young students and their family members. This study aimed to investigate the coronavirus disease 2019 (COVID-19) vaccine hesitancy and associated factors, and compare the differences between decision-makers and non-decision-makers among college teachers.Methods A cross-sectional online survey was administered across mainland China from 4 to 7 August 2021. Overall, 251 college teachers were included using snowball sampling. A multivariable logistic regression model was applied to explore the association between decision-makers and hesitancy to receive a COVID-19 vaccine.Results Overall, 42.2% of the teachers were hesitant to being vaccinated against COVID-19. The hesitancy rate was lower among primary decision-makers than that among non-decision-makers (34.8% vs. 60.3%, p

Abstract Human rhinovirus B (HRV-B) is a major human viral pathogen that can be responsible for various kinds of infections. Due to the health risks associated with HRV-B, it is therefore crucial to explore a rapid, specific, and sensitive method for surveillance. Herein, we exploited a novel detection method for HRV-B by combining reverse-transcription recombinase polymerase amplification (RT-RPA) of nucleic acids isothermal amplification and the trans-cleavage activity of Cas12a. Our RT-RPA-Cas12a-based fluorescent assay can be completed within 35–45 min and obtain a lower detection threshold to 0.5 copies/µL of target RNA. Meanwhile, crRNA sequences without a specific protospacer adjacent motif can effectively activate the trans-cleavage activity of Cas12a. Moreover, our RT-RPA-Cas12a-based fluorescent method was examined using 30 clinical samples, and exhibited high accuracy with positive and negative predictive agreement of 90% and 100%, respectively. Taken together, a novel promising, rapid and effective RT-RPA-Cas12a-based detection method was explored and shows promising potential for on-site HRV-B infection in resource-limited settings.

Abstract The Centers for Disease Control and Prevention announced in January 2023 a potential connection between administration of the Pfizer novel coronavirus disease-2019 (COVID-19) bivalent vaccine booster and ischemic stroke (IS). A retrospective cohort study was conducted to compare the hazard of IS in patients aged 65 years and over administered the Pfizer bivalent booster versus those administered the Pfizer/Moderna monovalent or Moderna bivalent boosters. De-identified patient electronic health data were collected from TriNetX, a cloud-based analytics platform that includes data from over 90 million unique patients in the United States. Patients aged 65 years and over at the time of administration of a Pfizer bivalent, Moderna bivalent, or Pfizer/Moderna monovalent booster were included for analysis. Cohorts were propensity-score matched. The hazard ratios (HR) and 95% confidence intervals (CI) for IS between matched cohorts at 1–21 and 22–42 days after booster administration were calculated. There was reduced hazard of IS in the Pfizer bivalent cohort compared to the monovalent cohort at both timepoints: 1–21 days after vaccination (HR: 0.54, 95% CI: 0.47–0.62), and 22–42 days after vaccination (HR: 0.62, 95% CI: 0.54–0.72) (n = 79,036 patients per cohort). There was reduced hazard of IS in the Pfizer bivalent cohort compared to the Moderna bivalent cohort at 1–21 days after vaccination (HR: 0.75, 95% CI: 0.58–0.96) (n = 26,962 patients per cohort). This analysis provides no evidence that the Pfizer bivalent vaccine is associated with increased hazard of IS compared to the monovalent or Moderna bivalent vaccines.

Abstract Background Understanding the mechanism behind immune cell plasticity in cancer metastasis is crucial for identifying key regulators. Previously we found that mitotic factors regulate epithelial-mesenchymal transition, but how these factors convert to metastatic players in the tumor microenvironment (TME) is not fully understood. Methods The clinical importance of mitotic factors was analyzed by heatmap analysis, a KM plot, and immunohistochemistry in lung adenocarcinoma (LUAD) patients. Immunoprecipitation, LC–MS/MS, kinase assay, and site-directed mutagenesis were performed for the interaction and phosphorylation. A tail-vein injection mouse model, Transwell-based 3D culture, microarray analysis, coculture with monocytes, and chromatin immunoprecipitation assays were used to elucidate the function of phosphorylated FoxM1 in metastasis of TME. Results The phosphorylated FoxM1 at Ser25 by PLK1 acquires the reprogramming ability to stimulate the invasive traits in cancer and influence immune cell plasticity. This invasive form of p-FoxM1 upregulates the expression of IL1A/1B, VEGFA, and IL6 by direct activation, recruiting monocytes and promoting the polarization of M2d-like tumor-associated macrophages (TAMs). Upregulation of PD-L1 in LUAD having phosphomimetic FoxM1 facilitates immune evasion. In invasive LUAD with phosphomimetic FoxM1, IFITM1 is the most highly expressed through the activation of the STING-TBK1-IRF3 signaling, which enhances FoxM1-mediated signaling. Clinically, higher expression of FOXM1, PLK1, and IFITM1 is inversely correlated with the survival rate of advanced LUAD patients, providing a promising therapeutic strategy for the treatment of LUAD. Conclusion FoxM1-based therapy would be a potential therapeutic strategy for LUAD to reduce TAM polarization, immune escape, and metastasis, since FoxM1 functions as a genetic reprogramming factor reinforcing LUAD malignancy in the TME.

Abstract Background The composition of the bone marrow immune microenvironment in patients with acute myeloid leukaemia (AML) was analysed by single-cell sequencing and the evolutionary role of different subpopulations of T cells in the development of AML and in driving drug resistance was explored in conjunction with E3 ubiquitin ligase-related genes. Methods To elucidate the mechanisms underlying AML-NR and Ara-C resistance, we analyzed the bone marrow immune microenvironment of AML patients by integrating multiple single-cell RNA sequencing datasets. When compared to the AML disease remission (AML-CR) cohort, AML-NR displayed distinct cellular interactions and alterations in the ratios of CD4+T, Treg, and CD8+T cell populations. Results Our findings indicate that the E3 ubiquitin ligase RNF149 accelerates AML progression, modifies the AML immune milieu, triggers CD8+T cell dysfunction, and influences the transformation of CD8+ Navie.T cells to CD8+TExh, culminating in diminished AML responsiveness to chemotherapeutic agents. Experiments both in vivo and in vitro revealed RNF149’s role in enhancing AML drug-resistant cell line proliferation and in apoptotic inhibition, fostering resistance to Ara-C. Conclusion In essence, the immune microenvironments of AML-CR and AML-NR diverge considerably, spotlighting RNF149’s tumorigenic function in AML and cementing its status as a potential prognostic indicator and innovative therapeutic avenue for countering AML resistance. Graphical Abstract

Osteoporosis (OP) is a systemic bone disease in which bone density and quality decrease and bone fragility increases due to a variety of causes, making it prone to fractures. The development of OP is closely related to oxidative stress. Uric acid (UA) is the end product of purine metabolism in the human body. Extracellular UA has antioxidant properties and is thought to have a protective effect on bone metabolism. However, the process of UA degradation can lead to intracellular oxidative stress, which together with UA-induced inflammatory factors, leads to increased bone destruction. In addition, UA can inhibit vitamin D production, resulting in secondary hyperparathyroidism and further exacerbating UA-associated bone loss. This review summarizes the relationship between serum UA levels and bone mineral density, bone turnover markers, and so on, in the hope of providing new insights into the pathogenesis and treatment of OP.

There are currently no prophylactic vaccines licensed to protect against Lassa fever caused by Lassa virus (LASV) infection. The Emergent BioSolutions (EBS) vaccine candidate, EBS-LASV, is being developed for the prevention of Lassa fever. EBS-LASV is a live-attenuated recombinant Vesicular Stomatitis Virus (rVSV)-vectored vaccine encoding the surface glycoprotein complex (GPC) from LASV and has two attenuating vector modifications: a gene shuffle of the VSV N gene and a deletion of the VSV G gene. Preclinical studies were performed to evaluate EBS-LASV’s neurovirulence potential following intracranial (IC) injection and to determine the biodistribution and vector replication following intramuscular (IM) inoculation in mice. In addition, the potential EBS-LASV toxicity was assessed using repeated-dose IM EBS-LASV administration to rabbits. All mice receiving the IC injection of EBS-LASV survived, while mice administered the unattenuated control vector did not. The vaccine was only detected in the muscle at the injection site, draining lymph nodes, and the spleen over the first week following IM EBS-LASV injection in mice, with no detectable plasma viremia. No toxicity was observed in rabbits receiving a three-dose regimen of EBS-LASV. These studies demonstrate that EBS-LASV is safe when administered to animals and supported a first-in-human dose-escalation, safety, and immunogenicity clinical study.

Background: Although observational studies have reported several common biomarkers related to coronary artery disease (CAD) and cancer, there is a shortage of traditional epidemiological data to establish causative linkages. Thus, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis to systematically investigate the causal associations of 109 traits with both CAD and cancer to identify their shared risk and protective factors. Methods: The genetic association datasets pertaining to exposure and outcomes were reviewed using the most recent and public genome-wide association studies (GWAS). Inverse variance weighting (IVW), weighted median (WM), and MR-Egger strategies were implemented for the MR analyses. The heterogeneity and pleiotropy were measured utilizing leave-one-out sensitivity testing, MR-PRESSO outlier detection, and Cochran’s Q test. Results: The IVW analyses revealed that genetic-predicted mean sphered cell volume (MSCV) is a protective factor for CAD, and weight is a risk factor. MSCV and weight also show similar effects on cancer. Furthermore, our study also identified a set of risk and protective factors unique to CAD and cancer, such as telomere length. Conclusions: Our Mendelian randomization study sheds light on shared and unique risk and protective factors for CAD and cancer, offering valuable insights that could guide future research and the development of personalized strategies for preventing and treating these two significant health issues.

Abstract Cancer cachexia is characterized by weight loss and skeletal muscle wasting. Based on the up-regulation of catabolism and down-regulation of anabolism, here we showed genetic mutation-mediated metabolic reprogramming in the progression of cancer cachexia by screening for metabolites and investigating their direct effect on muscle atrophy. Treatment with 93 μM D-2-hydroxyglutarate (D2HG) resulted in reduced myotube width and increased expression of E3 ubiquitin ligases. Isocitrate Dehydrogenase 1 (IDH1) mutant patients had higher D2HG than non-mutant patients. In the in vivo murine cancer cachexia model, mutant IDH1 in CT26 cancer cells accelerated cachexia progression and worsened overall survival. Transcriptomics and metabolomics revealed a distinct D2HG-induced metabolic imbalance. Treatment with the IDH1 inhibitor ivosidenib delayed the progression of cancer cachexia in murine GL261 glioma model and CT26 colorectal carcinoma models. These data demonstrate the contribution of IDH1 mutation mediated D2HG accumulation to the progression of cancer cachexia and highlight the individualized treatment of IDH1 mutation associated cancer cachexia.