Search

Abstract Background Zika virus (ZIKV) primarily spreads through mosquito bites and can lead to microcephaly in infants and Guillain-Barre syndrome in adults. It is noteworthy that ZIKV can persist in the semen of infected males for extended periods and can be sexually transmitted. Infection with ZIKV has severe pathological manifestations on the testicular tissues of male mice, resulting in reduced sperm motility and fertility. However, there are no approved prophylactic vaccines or therapeutics available to treat Zika virus infection. Methods Using a male type I and II interferon receptor-deficient (ifnar1(-/-) ifngr1(-/-)) C57BL/6 (AG6) mouse model infected with ZIKV as a representative model, we evaluated the degree of testicular damage and viral replication in various organs in mice treated with EVs derived from MSC-stimulated with IFN-β (IFNβ-EVs) and treated with controls. We measured testicle size, detected viral load in various organs, and analyzed gene expression to assess treatment efficacy. Results Our findings demonstrated that intravenous administration of IFNβ-EVs effectively suppressed ZIKV replication in the testes. Investigation with in-depth RNA sequencing analysis found that IFN-β treatment changed the cargo miRNA of EVs. Notably, miR-431-5p was identified to be significantly enriched in IFNβ-EVs and exhibited potent antiviral activity in vitro. We showed that CD95 was a direct downstream target for miR-431-5p and played a role in facilitating ZIKV replication. miR-431-5p effectively downregulated the expression of CD95 protein, consequently promoted the phosphorylation and nuclear localization of NF-kB, which resulted in the activation of anti-viral status, leading to the suppression of viral replication. Conclusions Our study demonstrated that the EVs produced by IFNβ-treated MSCs could effectively convey antiviral activity.

Abstract Millions of new cases of cancer are diagnosed worldwide each year, making it a serious public health concern. Developments in customized therapy and early detection have significantly enhanced treatment for and results from cancer. Therefore, it is important to investigate new molecular biomarkers. In this study, we created an efficient transient receptor potential melastatin (TRPM) family members-related TRPM-Score for 17 solid tumors. CCNE1, produced from TRPM-Score, was found to be an exceptional biomarker through several sophisticated machine learning and deep learning computational techniques. TRPM-Score and CCNE1 immunotherapeutic prediction, immunological characteristics, and predictive value were thoroughly assessed. In most cancer types, CCNE1 was a substantially dangerous marker. Additional in vitro tests validated CCNE1’s immunomodulatory properties, demonstrating that silencing impeded macrophage movement and decreased PD-L1 expression. Additionally, CCNE1 may accurately predict responses to cancer immunotherapy. These findings indicate that the TRPM family—particularly CCNE1, which is associated with TRPM—is a significant player in the pan-cancer domain and can be utilized as a therapeutic target and prognostic biomarkers, especially in immuno-oncology. The thorough characterization of the TRPM family and the discovery of CCNE1 as a crucial downstream effector mark important developments in our comprehension of pan-cancer biology.

Abstract The close spatial and temporal connection between osteogenesis and angiogenesis around type H vasculature is referred as “osteogenesis-angiogenesis coupling”, which is one of the basic mechanisms of osteogenesis. Endothelial cells (ECs), bone marrow mesenchymal stem cells (BMSCs), and their specific lineage constitute important cluster that participate in the regulation of osteogenesis and angiogenesis in bone microenvironment. However, the regulatory mechanism of osteogenesis-angiogenesis coupling under the condition of bone healing has not been unveiled. In this study, we demonstrated that the exosome derived from ECs (EC-exo) is an initiator of type H blood vessels formation, and EC-exo acts as a mediator in orchestrating osteogenesis-angiogenesis coupling by enhancing BMSC osteogenic differentiation and EC angiogenesis both in monolayer and stereoscopic co-culture system of primary human cells. The transcriptome array indicated that zinc finger and BTB domain containing 16 (ZBTB16) is a key gene in EC-exo-mediated osteogenesis, and ZBTB16 is indispensable in EC-exo-initiated osteogenesis-angiogenesis coupling. Mechanistically, EC-exo up-regulated the expression of ZBTB16 in BMSCs, thereby promoting osteoprogenitor phenotype transformation; the osteoprogenitors further promote ECs which constitute type H vessel (H-ECs) generation by activating HIF-1α pathway; and the H-ECs conversely promotes osteogenic differentiation of BMSCs. The crosstalk between BMSCs and ECs triggered by EC-exo constitutes a positive feedback loop that enhances osteogenesis-angiogenesis coupling. This study demonstrates that EC-exo can become an effective therapeutic tool to promote bone regeneration and repair. Graphical Abstract

Abstract Bacterial stem and root rot (BSRR) in sweetpotato caused by Dickeya dadantii is one of the ten major diseases of sweetpotatoes in China. However, the molecular mechanism underlying the resistance of sweetpotato to D. dadantii remains unclear. This study adopted a resistance identification assay that conformed Guangshu87 (GS87) as BSRR-resistant and Xinxiang (XX) as susceptible. Compared to XX, GS87 effectively prevented the invasion and dissemination of D. dadantii in planta. An RNA sequencing (RNA-seq) analysis identified 54,844 expressed unigenes between GS87 and XX at four different stages. Further, it revealed that GS87 was more able to regulate the expressions of more unigenes after the inoculation with D. dadantii, including resistance (R) and transcription factors (TF) genes. Moreover, content measurements of disease resistance-related phytohormones showed that both jasmonic acids (JAs) and salicylic acids (SAs) accumulated in D. dadantii-inoculated sweetpotatoes, and JAs may negatively regulate sweetpotato resistance against D. dadantii and accumulated faster than SAs. Meanwhile, determinations of ROS production rate and relevant enzymatic/non-enzymatic activity highlighted the vital roles of reactive oxygen species (ROS) and superoxide dismutase (SOD) in confering GS87 resistance against D. dadantii. Additionally, several hub genes with high connectivity were highlighted through Protein–Protein interaction (PPI) network analysis. In summary, the findings in this study contribute to the understanding of the different responses of resistant and susceptible sweetpotato cultivars to D. dadantii infection, and it also provide the first insight into the relevant candidate genes and phytohormones involved in the resistance of sweetpotato to D. dadantii.

Highlights 1. This is the first report identifying SCUBE1 and RNF103-CHMP3 as therapeutic targets for diabetic foot ulcers (DFU). 2. Our study found that SCUBE1 and RNF103-CHMP3 were significantly downregulated in patients who were cured of DFU. 3. This study discovered that SCUBE1 and RNF103-CHMP3 are associated with extracellular interactions. 4. Our findings indicate that SCUBE1 and RNF103-CHMP3 are related to immune cell infiltration. 5. This study provides new theoretical foundations and molecular targets for the diagnosis and treatment of DFU.

Abstract Background The zoonotic infectious diseases of poverty (zIDPs) are a group of diseases contributing to global poverty, with significant impacts on a substantial population. This study aims to describe the global, regional, and national burden of zIDPs—schistosomiasis, cystic echinococcosis, cysticercosis, and food-borne trematodiases (FBTs)—to support policy making and resource allocation for their control and elimination. Methods Data of zIDPs from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 were retrieved from 1990 to 2021. The age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life-year (DALY) rate were described and the estimated annual percentage changes (EAPCs) were calculated to quantify their burden and temporal trends. Spearman correlation analysis was conducted to examine the relationship between age-standardized rates and Socio-demographic Index (SDI). Results In 2021, these zIDPs exhibited a certain level of ASPRs and age-standardized DALY rates, while maintaining relatively low ASMRs. Noticeably, schistosomiasis presented the highest ASPR of 1914.299 (95% UI: 1378.920, 2510.853 per 100,000 population) and an age-standardized DALY rate of 21.895 (95% UI: 12.937, 37.278 per 100,000 population) among the zIDPs. The tapestry of burden—woven predominantly through low and lower-middle SDI regions—stretched across Africa, Latin America, and parts of Asia. From 1990 to 2021, a kaleidoscopic shift was observed globally as ASPRs, ASMRs, and age-standardized DALY rates declined significantly, as reflected by the EAPC values. Negative correlations were observed between the ASPRs, ASMRs, age-standardized DALY rates of schistosomiasis (r value = − 0.610, − 0.622 and − 0.610), cystic echinococcosis (− 0.676 of ASMR, − 0.550 of age-standardized DALYs), cysticercosis (− 0.420, − 0.797 and − 0.591) and the SDI. In contrast, a slight positive correlation was noted between the ASPR, age-standardized DALY rates of FBTs and SDI with r value of 0.221 and 0.213, respectively. Conclusion The burden of zIDPs declined across almost all endemic regions from 1990 to 2021, yet still predominated in low and low-middle SDI regions. Substantial challenges exist to achieve the goal of control and elimination of zIDPs, and integrated approaches based on One Health need to be strengthened to improve health outcomes. Graphical Abstract

Abstract Background Premature ovarian insufficiency (POI) is an immune-related condition. Dihydroberberine (dhBBR) plays a regulatory role in maintaining the T-helper 17 (Th17)/regulatory T (Treg) cell balance. This study aimed to explore the action mechanisms of dhBBR on POI. Methods In vivo, female BALB/c mice were used as POI models, treated with dhBBR, or injected with recombinant interleukin (rIL)-17 and anti-CD25 monoclonal antibody. Hematoxylin and eosin staining was used to validate the model and assess the therapeutic effects of dhBBR. mRNA expression levels of cytochrome P450 (Cyp)-17a1, Cyp19a1, Cyp11a1, steroidogenic acute regulatory protein, and luteinizing hormone receptor in mouse ovaries were quantified via quantitative polymerase chain reaction (qPCR). Enzyme-linked immunosorbent assay was used to determine the cytokine and sex hormone levels. Immunohistochemical staining for cleaved-caspase 3 and Ki-67 were performed to assess ovarian cell apoptosis and proliferation. Flow cytometry was used to analyze the Th17/Treg cell balance in the ovary and spleen. In vitro cytotoxicity of dhBBR was measured using the cell counting kit-8 assay. GTP-Ras homolog enriched in brain (Rheb) activity was determined via immunofluorescence assay. Co-immunoprecipitation was performed to assess Rheb activity, Th17 or Treg induction, and binding between Rheb and mammalian target of rapamycin (mTOR) after dhBBR treatment. Flow cytometry and qPCR assays were used to verify the effect of dhBBR on CD4 + cell differentiation. Finally, Rheb/mTOR pathway activation was confirmed via western blotting of proteins, including mTOR, p-mTOR, p70S6K, p-p70S6K, 4E-BP1, and p-4E-BP1. Results dhBBR improved the ovarian function in a dose-dependent manner. It also decreased ovarian cell apoptosis and increased cell proliferation. It decreased Th1 and Th17 cell proportions but increased Treg cell proportions in the ovaries and spleens of POI model mice. Cell experiments revealed that dhBBR promoted CD4 + cell differentiation into Treg cells. Co-immunoprecipitation revealed Rheb as the dhBBR target that bound to mTOR. However, MHY1485 restored dhBBR-induced changes in forkhead box P3, IL-10, transforming growth factor-β1, IL-17, IL-22, retinoic acid-related orphan receptor-γt and p-mTOR levels in Th17- and Treg-induced CD4 + cells. Conclusion Overall, dhBBR targeted the Rheb/mTOR pathway to promote CD4 + cell differentiation into Treg cells and alleviate POI.

Abstract Gliomas are one of the most frequent primary brain tumors and pose a serious threat to people’s lives and health. Platelets, a crucial component of blood, have been applied as drug delivery carriers for disease diagnosis and treatment. In this study, we designed engineered nanoplatelets for targeted delivery of therapeutic miR-375 and temozolomide (TMZ, a first-line glioma treatment agent) to enhance glioma therapy. Nanoplatelets were prepared through mild ultrasound, TMZ and miR-375 were co-loaded through ultrasound and electrostatic interactions, respectively, to combine chemotherapy with gene therapy against glioma. To improve the blood brain barrier (BBB) crossing efficiency and glioma targeting ability, the nanoplatelets were modified with central nervous system-specific rabies viral glycoprotein peptide (RVG) through thiol-maleimide click reaction. The RVG modified nanoplatelets co-loaded TMZ and miR-375 (NR/TMZ/miR-375) not only inherited the good stability and remarkable biocompatibility of platelets, but also promoted the cellular uptake and penetration of glioma tissues, and effectively induced cell apoptosis to enhance the therapeutic effect of drugs. In vivo studies showed that NR/TMZ/miR-375 significantly increased the circulation time of TMZ, and exhibited superior combined antitumor effects. In summary, this multifunctional ‘natural’ nanodrug delivery system provides a potent, scalable, and safety approach for platelet-based combined cancer chemotherapy and gene therapy.

Abstract Single-cell transcriptome sequencing (scRNA-seq) is a powerful tool for describing the transcriptome dynamics of plant development but has not yet been utilized to analyze the tissue ontology of sweetpotato. This study established a stable method for isolating single protoplast cells for scRNA-seq to reveal the cell heterogeneity of sweetpotato root tip meristems at the single-cell level. The study analyzed 12,172 single cells and 27,355 genes in the root tips of the sweetpotato variety Guangshu 87, which were distributed into 15 cell clusters. Pseudo-time analysis showed that there were transitional cells in the apical development trajectory of mature cell types from stem cell niches. Furthermore, we identified novel development regulators of sweetpotato tubers via trajectory analysis. The transcription factor IbGATA4 was highly expressed in the adventitious roots during the development of sweetpotato root tips, where it may regulate the development of sweetpotato root tips. In addition, significant differences were observed in the transcriptional profiles of cell types between sweetpotato, Arabidopsis thaliana, and maize. This study mapped the single-cell transcriptome of sweetpotato root tips, laying a foundation for studying the types, functions, differentiation, and development of sweetpotato root tip cells.

Abstract Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a ‘hot’ tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.

Abstract N6-methyladenosine (m6A) is a prevalent mRNA modification known for its implications in various cancer types, yet its role in chromophobe renal cell carcinoma (chRCC) remains largely unexplored. In this study, we performed m6A-SEAL-seq and RNA-seq analyses on tissues from three chRCC subjects, aiming to uncover m6A alterations in chRCC. Our findings revealed reduced expression levels of four m6A regulators in chRCC tissues and highlighted differences in m6A levels compared to normal tissues. Furthermore, we identified specific genes and cancer-related pathways affected by these differences, including notable candidates like NOTCH1 and FGFR1, implicated in chRCC development. Additionally, we developed a predictive model based on the expression level of m6A associated genes, demonstrating promising prognostic capabilities for patient survival prediction. Overall, our study provides valuable insights into the role of m6A in chRCC and its potential as a prognostic indicator.

Abstract Background The increasing incidence of diabetes mellitus has established diabetic cataracts (DC) as a significant worldwide public health issue. The mechanisms underlying DC remain unknown, and effective prevention and treatment strategies are lacking. Accordingly, we aimed to explore the role and mechanism behind N6-methyladenosine (m6A) in DC progression. Methods Methyltransferase-like 3 (METTL3), p21, Beclin1, LC3, and p62 expression levels were measured in human tissues. This study assessed total m6A levels and common m6A-regulated biomarkers in both in vitro and in vivo DC models. Autophagy flux was detected in vitro through Ad-mCherry-GFP-LC3B and Monodansylcadaverine (MDC) staining. Cellular senescence was assessed utilizing the senescence-associated β-galactosidase (SA-β-Gal) assay. Furthermore, the effect of METTL3 on SIRT1 mRNA modification was demonstrated, and its mechanism was elucidated using RT-qPCR, western blot, RNA stability assays, and RIP analysis. Results METTL3, p21, and p62 expression levels were elevated in lens epithelial cells (LECs) from DC patients, while Beclin1 and LC3 levels were reduced. Silencing METTL3-mediated m6A modifications restored high-glucose-induced autophagy inhibition and prevented premature senescence in LECs. Notably, SIRT1720 and Metformin significantly enhanced autophagosome generation and delayed cellular senescence. The m6A-reading protein YTHDF2 bound to m6A modifications, and YTHDF2 silencing significantly reduced METTL3-mediated SIRT1 inactivation. Conclusions METTL3 induces senescence in DC by destabilizing SIRT1 mRNA in an m6A-YTHDF2-dependent manner. The METTL3-YTHDF2-SIRT1 axis is a key target and potential pathogenic mechanism in DC.

Abstract Background Influenza remains a global public health concern. Understanding the vaccination-induced response in an aging population, which is susceptible and at high risk, is essential for disease prevention and control. Here, we report findings on the safety and immunogenicity of a quadrivalent influenza split-virion vaccine (15 µg/subtype/0.5 ml/dose) (hereinafter referred to as the “quadrivalent influenza vaccine”) in a population aged ≥ 60 years. Methods This open-label, pragmatic post-marketing trial enrolled 1399 older adults to receive one dose of an approved commercially available quadrivalent influenza vaccine manufactured by Hualan Biological Bacterin Inc. (hereinafter referred to as “Hualan Bio”). Participants with contraindications for the vaccine were excluded, while poor health condition was acceptable. All vaccinated subjects experienced adverse events collection within 30 days and serious adverse events within 180 days post-vaccination. 25% subjects, selected randomly, underwent venous blood sampling pre-vaccination and 30 days after post-vaccination, for detecting antibody titers against each subtype of influenza virus by hemagglutination inhibition assay. The incidences of adverse events and antibody titers against each subtype of influenza virus were statistically analyzed using SAS 9.4. Results No grade 3 adverse reactions occurred within 30 days post-vaccination. The incidences of overall adverse reactions, local adverse reactions and systemic adverse reactions were 3.79%, 2.86% and 1.00%, respectively. No serious adverse reactions occurred within 180 days post-vaccination. There were 350 subjects who completed venous blood sampling pre-vaccination, among whom 348 subjects completed venous blood sampling at 30 days post-vaccination for immunogenicity assessment. With respect to hemagglutination inhibition antibodies against influenza viruses H1N1, H3N2, BV and BY subtypes, at 30 days post-vaccination, the seroconversion rates were 87.64%, 75.57%, 73.28% and 78.74%, respectively; the seropositive rates were 93.97%, 98.56%, 79.31% and 95.40%, respectively; and the geometric mean increase (GMI) in post-immunization/pre-immunization antibodies was 24.80, 7.26, 10.39 and 7.39, respectively. Conclusion One 15 µg/subtype dose of the vaccine had a good safety profile and elicited favorable immunogenicity among subjects aged ≥ 60 years. The results of this study indicate that Hualan Bio quadrivalent influenza vaccine strike balance between safety and immunogenicity, supporting unnecessity to increase dosage or inoculation frequency for further enhancing immunogenicity. Trial registration Registered on ClinicalTrials.gov. Registration number: NCT06334510. Registered on 28/03/2024 (retrospectively registered).

Abstract Background The objectives of this study were twofold: (1) to compare gait characteristics between cerebral small vessel disease (CSVD) patients with low-risk oral frailty (OF) and high-risk OF, particularly during dual-task walking (DTW); (2) to investigate the association of OF, the gait characteristics of DTW, and falls among older adults patients with CSVD. Methods A total of 126 hospitalized patients diagnosed with CSVD were recruited and classified into a low-risk group (n = 90) and a high-risk group (n = 36) based on OF status in our study. Comprehensive data pertaining to basic parameters (cadence, as well as stride time, velocity and length), variability, asymmetry, and coordination were gathered during both single-task walking (STW) and DTW. Additionally, the number of falls was calculated. Subsequently, t-test or chi-squared test was used for comparison between the two groups. Furthermore, linear regression analysis was employed to elucidate the association of the OF index-8 score and gait parameters during cognitive DTW. Also, logistic regression models were utilized to assess the independent association of OF risk and falls. Results During cognitive DTW, the high-risk group demonstrated inferior performance in terms of basic parameters (p

Abstract Background Loss-of-function mutations of ZBTB24 cause immunodeficiency, centromeric instability, and facial anomalies syndrome 2 (ICF2). ICF2 is a rare autosomal recessive disorder with immunological defects in serum antibodies and circulating memory B cells, resulting in recurrent and sometimes fatal respiratory and gastrointestinal infections. The genotype–phenotype correlation in patients with ICF2 indicates an essential role of ZBTB24 in the terminal differentiation of B cells. Methods We used the clustered regularly interspaced short palindromic repeats (CRISPER)/Cas9 technology to generate B cell specific Zbtb24-deficient mice and verified the deletion specificity and efficiency by quantitative polymerase chain reaction (Q-PCR) and western blotting analyses in fluorescence-activated cell sorting (FACS)-sorted cells. The development, phenotype of B cells and in vivo responses to T cell dependent or independent antigens post immunization were analyzed by flow cytometry and enzyme-linked immunosorbent assay (ELISA). Adoptive transfer experiment in combination with in vitro cultures of FACS-purified B cells and RNA-Seq analysis were utilized to specifically determine the impact of Zbtb24 on B cell biology as well as the underlying mechanisms. Results Zbtb24 is dispensable for B cell development and maintenance in naive mice. Surprisingly, B cell specific deletion of Zbtb24 does not evidently compromise germinal center reactions and the resulting primary and secondary antibody responses induced by T cell dependent antigens (TD-Ags), but significantly inhibits T cell independent antigen-elicited antibody productions in vivo. At the cellular level, Zbtb24-deficiency specifically impedes the plasma cell differentiation of B1 cells without impairing their survival, activation and proliferation in vitro. Mechanistically, Zbtb24-ablation attenuates heme biosynthesis partially through mTORC1 in B1 cells, and addition of exogenous hemin abrogates the differentiation defects of Zbtb24-null B1 cells. Conclusions Zbtb24 seems to regulate antibody responses against TD-Ags B cell extrinsically, but it specifically promotes the plasma cell differentiation of B1 cells via heme synthesis in mice. Our study also suggests that defected B1 functions contribute to recurrent infections in patients with ICF2.

Abstract Background Certain infectious diseases are caused by specific bacterial pathogens, including syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, leprosy, and tuberculosis. These diseases significantly impact global health, contributing heavily to the disease burden. The study aims to thoroughly evaluate the global burden of syphilis, gonorrhea, typhoid and paratyphoid fever, diphtheria, pertussis, tetanus, and leprosy. Methods Leveraging the Global Burden of Disease (GBD) study 2021, age-specific and Socio-demographic Index (SDI)-specific incidence, disability-adjusted life-years (DALYs), and death for eight specific bacterial infections across 204 countries and territories from 1990 to 2021 were analyzed. Percentage changes in age-standardized incidence rate (ASIR), DALY rate, and mortality rate (ASMR) were also examined, with a focus on disease distribution across different regions, age groups, genders, and SDI. Results By 2021, among the eight diseases, gonococcal infection had the highest global ASIR [1096.58 per 100,000 population, 95% uncertainty interval (UI): 838.70, 1385.47 per 100,000 population], and syphilis had the highest global age-standardized DALY rate (107.13 per 100,000 population, 95% UI: 41.77, 212.12 per 100,000 population). Except for syphilis and gonococcal infection, the age-standardized DALY rate of the remaining diseases decreased by at least 55% compared to 1990, with tetanus showing the largest decrease by at least 90%. Globally, significant declines in the ASIR, age-standardized DALY rate, and ASMR for these eight bacterial infections have been observed in association with increases in the SDI. Regions with lower SDI, such as sub-Saharan Africa, experienced a relatively higher burden of these eight bacterial infections. Conclusions Although there has been an overall decline in these eight diseases, they continue to pose significant public health challenges, particularly in low SDI regions. To further reduce this burden in these areas, targeted intervention strategies are essential, including multi-sectoral collaboration, policy support, improved WASH management, and enhanced research efforts. Graphical Abstract

Abstract Objective To compile a scale of Chinese college students’ perception of teachers’ differential behavior and to provide a reference for college students to establish correct life values, promote college students’ physical and mental health, and reduce teachers’ differential treatment. Methods Open-ended questionnaires and expert interviews were used to conduct interviews and correspondence with 58 college students, ten psychologists, and six psychologists to form an initial questionnaire. Then, the scale’s exploratory factor analysis, confirmatory factor analysis, and reliability and validity test were conducted on 7053 college students from 18 universities in 6 provinces (municipalities directly under the Central Government). Results The Chinese college students’ perception of teachers’ differential behavior scale has two dimensions: teacher prejudice and preference. Each dimension includes three aspects: emotional feedback, behavior orientation, and opportunity privilege, and each aspect have a total of 4 items. The consistency test coefficients of each dimension and each factor of the prepared scale are all above 0.7, and the split-half reliability is above 0.6. Confirmatory factor analysis shows that the six-factor structural model fits well (χ 2/df = 4.287, RMSEA = 0.066, CFI = 0.950, TLI = 0.919). Using the generalized anxiety disorder scale and the patient health questionaire-9items as empirical criteria, each factor in the scale demonstrated significant correlations with both the GAD scale and the patient health questionaire-9items. Conclusions The Chinese college students’ perception of teachers’ differential behavior scale has a two-dimensional six-factor structure and has good reliability and validity. It can be used as an effective tool to measure Chinese college students’ perceived teacher differential behavior.

Abstract Background Plant growth-promoting rhizobacteria (PGPR), as a group of environmentally friendly bacteria growing in the rhizosphere of plants, play an important role in plant growth and development and resistance to environmental stresses. However, their limited understanding has led to the fact that their large-scale use in agriculture is still scarce, and the mechanisms by which beneficial bacteria are selected by plants and how they interact with them are still unclear. Method In this study, we investigated the interaction between the auxin-producing strain Bacillus aryabhattai LAD and maize roots, and performed transcriptomic and metabolomic analyses of Bacillus aryabhattai LAD after treatment with maize root secretions(RS). Results Our results show that there is a feedback effect between the plant immune system and bacterial auxin. Bacteria activate the immune response of plant roots to produce reactive oxygen species(ROS), which in turn stimulates bacteria to synthesize IAA, and the synthesized IAA further promotes plant growth. Under the condition of co-culture with LAD, the main root length, seedling length, root surface area and root volume of maize increased by 197%, 107%, 89% and 75%, respectively. In addition, the results of transcriptome metabolome analysis showed that LAD was significantly enriched in amino acid metabolism, carbohydrate metabolism and lipid metabolism pathways after RS treatment, including 93 differentially expressed genes and 45 differentially accumulated metabolites. Conclusion Our findings not only provide a relevant model for exploring the effects of plant-soil microbial interactions on plant defense functions and thereby promoting plant growth, but also lay a solid foundation for the future large-scale use of PGPR in agriculture for sustainable agricultural development.

Abstract Recent observational studies suggest that gut microorganisms are involved in the onset and development of coronavirus disease 2019 (COVID-19), but the potential causal relationship behind them remains unclear. Exposure data were derived from the MiBioGen consortium, encompassing 211 gut microbiota (n = 18,340). The outcome data were sourced from the COVID-19 host genetics initiative (round 7), including COVID-19 severity (n = 1,086,211), hospitalization (n = 2,095,324), and susceptibility (n = 2,597,856). First, a two-sample Mendelian randomization (TSMR) was performed to investigate the causal effect between gut microbiota and COVID-19 outcomes. Second, a two-step MR was used to explore the potential mediators and underlying mechanisms. Third, several sensitivity analyses were performed to verify the robustness of the results. Five gut microbes were found to have a potential causality with COVID-19 severity, namely Betaproteobacteria (beta = 0.096, p = 0.034), Christensenellaceae (beta = -0.092, p = 0.023), Adlercreutzia (beta = 0.072, p = 0.048), Coprococcus 1 (beta = 0.089, p = 0.032), Eisenbergiella (beta = 0.064, p = 0.024). Seven gut microbes were found to have a potential causality with COVID-19 hospitalization, namely Victivallaceae (beta = 0.037, p = 0.028), Actinomyces (beta = 0.047, p = 0.046), Coprococcus 2 (beta = -0.061, p = 0.031), Dorea (beta = 0.067, p = 0.016), Peptococcus (beta = -0.035, p = 0.049), Rikenellaceae RC9 gut group (beta = 0.034, p = 0.018), and Proteobacteria (beta = -0.069, p = 0.035). Two gut microbes were found to have a potential causality with COVID-19 susceptibility, namely Holdemanella (beta = -0.024, p = 0.023) and Lachnospiraceae FCS020 group (beta = 0.026, p = 0.027). Multi-omics mediation analyses indicate that numerous plasma proteins, metabolites, and immune factors are critical mediators linking gut microbiota with COVID-19 outcomes. Sensitivity analysis suggested no significant heterogeneity or pleiotropy. These findings revealed the causal correlation and potential mechanism between gut microbiota and COVID-19 outcomes, which may improve our understanding of the gut-lung axis in the etiology and pathology of COVID-19 in the future.

Abstract Background The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. Methods A multiple sensitive nano-delivery system comprising β-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. Results Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. Conclusions We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand. Graphical Abstract

Abstract Purpose Glioma-associated epilepsy affects a significant proportion of glioma patients, contributing to disease progression and diminished survival rates. However, the lack of a reliable preoperative seizure predictor hampers effective surgical planning. This study investigates the potential of Alpha B crystallin protein (CRYAB) plasma levels as a predictive biomarker for epilepsy seizures in glioma patients. Methods Plasma samples were obtained from 75 participants, including 21 glioma patients with pre-operative epilepsy, 14 glioma patients without pre-operative epilepsy, and 21 age- and sex-matched control subjects. Additionally, 11 idiopathic epilepsy patients and 8 intractable epilepsy patients served as positive disease control groups. The study utilized ELISA to accurately quantify the circulating levels of CRYAB in the plasma samples of all participants. Results The analysis revealed a significant reduction in plasma CRYAB levels in glioma patients with pre-operative epilepsy and idiopathic epilepsy. The receiver operating characteristic (ROC) curve analysis displayed an impressive performance, indicating an AUC of 0.863 (95% CI, 0.810–0.916) across the entire patient cohort. Furthermore, plasma CRYAB levels exhibited a robust diagnostic capability, with an AUC of 0.9135, a sensitivity of 100.0%, and a specificity of 73.68%, effectively distinguishing glioma patients with preoperative epilepsy from those without epilepsy. The Decision Curve Analysis (DCA) underscored the clinical relevance of plasma CRYAB levels in predicting pre-operative epilepsy in glioma. Conclusion The findings imply that the reduced levels of CRYAB may assist in prediction of seizure occurrence in glioma patients, although future large-scale prospective studies are warranted.

Abstract Objective The Center for Neurologic Study Bulbar Function Scale (CNS-BFS) was specifically designed as a self-reported measure of bulbar function. The purpose of this research was to validate the Chinese translation of the CNS-BFSC as an effective measurement for the Chinese population with ALS. Methods A total of 111 ALS patients were included in this study. The CNS-BFSC score, three bulbar function items from the ALSFRS-R, and visual analog scale (VAS) score for speech, swallowing and salivation were assessed in the present study. Forty-six ALS patients were retested on the same scale 5–10 days after the first evaluation. Results The CNS-BFSC sialorrhea, speech and swallowing subscores were separately correlated with the VAS subscores (p 0.05). The Cronbach’s α of the CNS-BFSC was 0.972. Conclusion The Chinese version of the CNS-BFSC has acceptable efficacy and reliability for the assessment of bulbar dysfunction in ALS patients.

Abstract It remains a substantial challenge to balance treatment efficacy and toxicity in geriatric patients with multiple myeloma (MM), primarily due to the dynamic nature of frailty. Here, we conducted a prospective study to evaluate the feasibility and benefits of dynamic frailty-tailored therapy (DynaFiT) in elderly patients. Patients with newly diagnosed MM (aged ≥ 65 years) received eight induction cycles of bortezomib, lenalidomide, and dexamethasone (daratumumab was recommended for frail patients), with treatment intensity adjusted according to longitudinal changes in the frailty category (IMWG-FI) at each cycle. Of 90 patients, 33 (37%), 16 (18%), and 41 (45%) were fit, intermediate fit, and frail at baseline, respectively. Of 75 patients who had geriatric assessment at least twice, 28 (37%) experienced frailty category changes at least once. At analysis, 15/26 (58%) frail patients improved (27% became fit and 31% became intermediate fit), 4/15 (27%) intermediate fit patients either improved or deteriorated (two for each), and 6/30 (20%) fit patients deteriorated. During induction, 34/90 (38%) patients discontinued treatment, including 10/33 (30%) fit, 4/16 (25%) intermediate fit, and 20/41 (49%) frail; 14/40 (35%) frail patients discontinued treatment within the first two cycles, mainly because of non-hematologic toxicity (mostly infections). For fit, intermediate-fit, and frail patients, the overall response rate was 100%, 93%, and 73%, respectively; one-year overall survival was 90%, 75%, and 54%, respectively. Therefore, the individualized DynaFiT is feasible and promising for heterogeneous elderly patients.

Abstract Photothermal therapy (PTT) is a promising cancer treatment method due to its ability to induce tumor-specific T cell responses and enhance therapeutic outcomes. However, incomplete PTT can leave residual tumors that often lead to new metastases and decreased patient survival in clinical scenarios. This is primarily due to the release of ATP, a damage-associated molecular pattern that quickly transforms into the immunosuppressive metabolite adenosine by CD39, prevalent in the tumor microenvironment, thus promoting tumor immune evasion. This study presents a photothermal nanomedicine fabricated by electrostatic adsorption among the Fe-doped polydiaminopyridine (Fe-PDAP), indocyanine green (ICG), and CD39 inhibitor sodium polyoxotungstate (POM-1). The constructed Fe-PDAP@ICG@POM-1 (FIP) can induce tumor PTT and immunogenic cell death when exposed to a near-infrared laser. Significantly, it can inhibit the ATP-adenosine pathway by dual-directional immunometabolic regulation, resulting in increased ATP levels and decreased adenosine synthesis, which ultimately reverses the immunosuppressive microenvironment and increases the susceptibility of immune checkpoint blockade (aPD-1) therapy. With the aid of aPD-1, the dual-directional immunometabolic regulation strategy mediated by FIP can effectively suppress/eradicate primary and distant tumors and evoke long-term solid immunological memory. This study presents an immunometabolic control strategy to offer a salvage option for treating residual tumors following incomplete PTT.

Abstract Background Cucurbita pepo cv Dayangua (CPD) is an edible plant with diverse pharmacological properties. The current research on CPD has primarily focused on initial investigations of its chemical composition and pharmacological effects, and no comprehensive toxicity assessment has been conducted to date. Methods In the present study, the toxicity of CPD was evaluated through both acute and sub-chronic oral toxicity tests in mice. 16S rDNA sequencing was used to analyze the composition of the gut microbiota of mice at different time points to observe the effect of CPD on these microbial communities. Results In the acute toxicity test, CPD exhibited low toxicity, with a median lethal dose (LD50) > 2000 mg/kg. The sub-chronic toxicity test indicated that CPD administration at doses of 200, 400, and 600 mg/kg did not cause mortality or significant organ damage in mice. Furthermore, analysis of the gut microbiota after gavage administration of CPD at 400 and 600 mg/kg revealed an improved abundance of some beneficial gut bacteria. Conclusions In summary, no acute or sub-chronic toxic effects were observed in mice following the oral administration of CPD. CPD did not affect the structure and diversity of the gut microbiota and may contribute to an increase in the number of beneficial gut bacteria.

Abstract Background Previous observational studies have indicated a potential link between insomnia and bladder cancer, yet the underlying causal relationship remains uncertain. The current study employed a bidirectional two-sample Mendelian randomization (MR) analysis to investigate this association. Methods A two-sample MR analysis was conducted utilizing publicly available summary data from genome-wide association studies (GWAS) on insomnia and bladder cancer. Various regression methods including the inverse variance weighted (IVW), weighted median, MR-Egger, weighted mode, and simple mode methods were employed for the MR analysis. The presence of pleiotropy and heterogeneity in the MR results was also assessed. Furthermore, additional sensitivity tests were performed to mitigate potential biases. Results No significant causal relationship was detected between insomnia and bladder cancer using IVW method (OR = 0.761, 95% CI 0.996–1.005; P = 0.76). Similarly, the IVW model did not reveal any causal effect of bladder cancer on the risk of insomnia (OR = 1.47, 95% CI 0.772–2.799; P = 0.24). Consistent results were obtained from the other four methods employed. There was no evidence of horizontal pleiotropy or heterogeneity in our MR analysis (P > 0.05). The sensitivity analyses further supported the reliability of the estimated causal effects. Conclusions This study presents no evidence for a causal relationship between insomnia and bladder cancer.

Abstract Background Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers. Methods This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored. Results Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy. Conclusions Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.

Abstract Herpes simplex virus type 1 (HSV-1) infection of the eyes results in herpes simplex keratitis (HSK), which has led to vision loss and even blindness in patients. However, the rate of drug resistance in HSV is on the rise; therefore, new antiviral agents with sufficient safety profiles must be developed. At present, we assessed the anti-HSV-1 activity of 502 natural compounds and their ability to reduce the HSV-1-induced cytopathic effect. We chose harmol for further studies because it exhibited the highest antiviral activity. We found that harmol inhibited both HSV-1 F and HSV-1/153 (a clinical drug-resistant strain) replication, with an EC50 of 9.34 µM and 5.84 µM, respectively. Moreover, harmol reduced HSV-1 replication in corneal tissues and viral progeny production in tears, and also alleviated early corneal surface lesions related to HSK. For example, harmol treatment preserved corneal thickness and nerve density in HSK mice. Interestingly, harmol also showed a promising antiviral effect on HSV-1/153 induced HSK in mouse model. Furthermore, harmol combined with acyclovir (ACV) treatment showed a greater antiviral effect than either one alone in vitro. Therefore, harmol may be a promising therapeutic agent for managing HSK.

Abstract Background Insulin resistance (IR) and obesity are established risk factors for hypertension, with triglyceride-glucose (TyG) serving as a recognized surrogate marker for IR. The aim of this study was to investigate the association between TyG-BMI and hypertension in the general population. Methods A total of 60,283 adults aged ≥18 years who underwent face-to-face questionnaires, anthropometric measurements, and laboratory examination were included in this study. Multivariable logistic regression models and receiver operating characteristic curve (ROC) were used to determine the association between TyG-BMI and hypertension. The restricted cubic spline model was used for the dose-response analysis. Results After fully adjusting for confounding variables, multivariate logistic regression model showed a stable positive association between TyG-BMI and hypertension (OR: 1.61 per SD increase; 95% CI: 1.55–1.67; P-trend

Abstract Background Interleukin-17 (IL-17) has been hypothesized to be involved in ischemic cardiovascular disease (ICVD). However, the association of IL-17 with ICVD remained unclear. The aim of this study was to systematically analyze the available evidence regarding the association between IL-17 and ICVD. Methods We searched the PubMed, Web of Science, Cochrane Library, and Embase databases up to October 2023 to identify publications on the association between IL-17 and ICVD. The merged results were analyzed using a random effects model for meta-analysis and subgroup analysis. Results A total of 955 publications were initially identified in our search and screened; six studies were eventually included in the analysis. The average age of study participants was 60.3 ± 12.6 years and 65.5% were men. There was a high degree of heterogeneity among studies. The results showed that IL-17 level were higher in the case group than those in the control group (standardized mean difference, SMD = 1.60, 95% confidence interval (95% CI): 0.53–2.66, P = 0.003). In sensitivity analysis, the merged results showed good robustness. Additionally, subgroup analysis showed that race and ethnicity, sample size, and detection methods were significant factors influencing heterogeneity in the published studies. Conclusion Our finding revealed that increased IL-17 level contributed to the development of ICVD, suggesting IL-17 as a potential risk marker. Further research is needed to establish IL-17 as a therapeutic biomarker of ICVD.

Abstract Background As one major symptom of Alzheimer’s disease (AD), anterograde amnesia describes patients with an inability in new memory formation. The crucial role of the entorhinal cortex in forming new memories has been well established, and the neuropeptide cholecystokinin (CCK) is reported to be released from the entorhinal cortex to enable neocortical associated memory and long-term potentiation. Though several studies reveal that the entorhinal cortex and CCK are related to AD, it is less well studied. It is unclear whether CCK is a good biomarker or further a great drug candidate for AD. Methods mRNA expressions of CCK and CCK-B receptor (CCKBR) were examined in two mouse models, 3xTg AD and CCK knock-out (CCK−/−) mice. Animals’ cognition was investigated with Morris water maze, novel object recognition test and neuroplasticity with in-vitro electrophysiological recording. Drugs were given intraperitoneally to animals to investigate the rescue effects on cognitive deficits, or applied to brain slices directly to explore the influence in inducement of long-term potentiation. Results Aged 3xTg AD mice exhibited reduced CCK mRNA expression in the entorhinal cortex but reduced CCKBR expression in the neocortex and hippocampus, and impaired cognition and neuroplasticity comparable with CCK−/− mice. Importantly, the animals displayed improved performance and enhanced long-term potentiation after the treatment of CCKBR agonists. Conclusions Here we provide more evidence to support the role of CCK in learning and memory and its potential to treat AD. We elaborated on the rescue effect of a promising novel drug, HT-267, on aged 3xTg AD mice. Although the physiological etiology of CCK in AD still needs to be further investigated, this study sheds light on a potential pharmaceutical candidate for AD and dementia.

Abstract Background Anemia is a common complication of HIV/AIDS, particularly in adolescents and young adults across various countries and regions. However, little is known about the changing prevalence trends of anemia impairment in this population over time. Methods Data on anemia in adolescents and young adults with HIV/AIDS from 1990 to 2019 were collected from the Global Burden of Disease. Prevalence was calculated by gender, region, and country for individuals aged 10–24, and trends were measured using estimating annual percentage changes (EAPC). Results Globally, the prevalence of adolescents and young adults with HIV/AIDS increased from 103.95 per 100,000 population in 1990 to 203.78 in 2019. However, anemia impairment has decreased over the past three decades, with a global percentage decreasing from 70.6% in 1990 to 34.7% in 2019, mainly presenting as mild to moderate anemia and significantly higher in females than males. The largest decreases were observed in Central Sub-Saharan Africa, North America, and Eastern Sub-Saharan Africa, with EAPCs of -2.8, -2.34, and -2.17, respectively. Tajikistan (78.76%) and Madagascar (74.65%) had the highest anemia impairment percentage in 2019, while China (16.61%) and Iceland (13.73%) had the lowest. Anemia impairment was closely related to sociodemographic index (SDI) levels, with a high proportion of impairment in low SDI regions but a stable decreasing trend (EAPC = -0.37). Conclusion Continued anemia monitoring and management are crucial for patients with HIV, especially in high-prevalence regions and among females. Public health policies and interventions can improve the quality of life and reduce morbidity and mortality.

Abstract Background Accumulating evidences indicate that the specific alternative splicing (AS) events are linked to the occurrence and prognosis of gastric cancer (GC). Nevertheless, the impact of AS is still unclear and needed to further elucidation. Methods The expression profile of GC and normal samples were downloaded from TCGA. AS events were achieved from SpliceSeq database. Cox regression together with LASSO analysis were employed to identify survival-associated AS events (SASEs) and calculate risk scores. PPI and pathway enrichment analysis were implemented to determine the function and pathways of these genes. Kaplan-Meier (K-M) analysis and Receiver Operating Characteristic Curves were used to evaluate the clinical significance of genes of SASEs. Q-PCR were applied to validate the hub genes on the survival prognosis in 47 GC samples. Drug sensitivity and immune cell infiltration analysis were conducted. Results In total, 48 140 AS events in 10 610 genes from 361 GC and 31 normal samples were analyzed. Through univariate Cox regression, 855 SASEs in 763 genes were screened out. Further, these SASEs were analyzed by PPI and 17 hub genes were identified. Meanwhile, using Lasso and multivariate Cox regression analysis, 135 SASEs in 132 genes related to 7 AS forms were further screened and a GC prognostic model was constructed. K-M curves indicates that high-risk group has poorer prognosis. And the nomogram analysis on the basis of the multivariate Cox analysis was disclosed the interrelationships between 7 AS forms and clinical parameters in the model. Five key genes were then screened out by PPI analysis and Differential Expression Gene analysis based on TCGA and Combined-dataset, namely STAT3, RAD51B, SOCS2, POLE2 and TSR1. The expression levels of AS in STAT3, RAD51B, SOCS2, POLE2 and TSR1 were all significantly correlated with survival by qPCR verification. Nineteen drugs were sensitized to high-risk patients and eight immune cells showed significantly different infiltration between the STAD and normal groups. Conclusions In this research, the prognostic model constructed by SASEs can be applied to predict the prognosis of GC patients and the selected key genes are expected to become new biomarkers and therapeutical targets for GC treatment.

Abstract Background Epidemiological evidence links a close correlation between long-term exposure to air pollutants and autoimmune diseases, while the causality remained unknown. Methods Two-sample Mendelian randomization (TSMR) was used to investigate the role of PM10, PM2.5, NO2, and NOX (N = 423,796–456,380) in 15 autoimmune diseases (N = 14,890–314,995) using data from large European GWASs including UKB, FINNGEN, IMSGC, and IPSCSG. Multivariable Mendelian randomization (MVMR) was conducted to investigate the direct effect of each air pollutant and the mediating role of common factors, including body mass index (BMI), alcohol consumption, smoking status, and household income. Transcriptome-wide association studies (TWAS), two-step MR, and colocalization analyses were performed to explore underlying mechanisms between air pollution and autoimmune diseases. Results In TSMR, after correction of multiple testing, hypothyroidism was causally associated with higher exposure to NO2 [odds ratio (OR): 1.37, p = 9.08 × 10–4] and NOX [OR: 1.34, p = 2.86 × 10–3], ulcerative colitis (UC) was causally associated with higher exposure to NOX [OR: 2.24, p = 1.23 × 10–2] and PM2.5 [OR: 2.60, p = 5.96 × 10–3], rheumatoid arthritis was causally associated with higher exposure to NOX [OR: 1.72, p = 1.50 × 10–2], systemic lupus erythematosus was causally associated with higher exposure to NOX [OR: 4.92, p = 6.89 × 10–3], celiac disease was causally associated with lower exposure to NOX [OR: 0.14, p = 6.74 × 10–4] and PM2.5 [OR: 0.17, p = 3.18 × 10–3]. The risky effects of PM2.5 on UC remained significant in MVMR analyses after adjusting for other air pollutants. MVMR revealed several common mediators between air pollutants and autoimmune diseases. Transcriptional analysis identified specific gene transcripts and pathways interconnecting air pollutants and autoimmune diseases. Two-step MR revealed that POR, HSPA1B, and BRD2 might mediate from air pollutants to autoimmune diseases. POR pQTL (rs59882870, PPH4=1.00) strongly colocalized with autoimmune diseases. Conclusion This research underscores the necessity of rigorous air pollutant surveillance within public health studies to curb the prevalence of autoimmune diseases. Graphical abstract (Built by the Biorender)

Abstract Background The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. Results In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. Conclusions Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.

Abstract Background Mobile health (mHealth) may be an ideal solution for breast cancer (BC) patients in China to access weight management interventions. User retention and engagement are the main challenges faced by mHealth applications. A user persona, which is a user-centered design process, can lead to the development of mHealth that is more acceptable to the needs of target users. This study aimed to investigate the variety of experiences in weight management and the behavioral preferences of BC patients receiving chemotherapy to develop users’ personal information and persona development for the design and implementation of mHealth interventions. Methods Sixteen individual semi-structured in-depth interviews were conducted with BC patients receiving chemotherapy. We employed the thematic analysis method to analyze the interview transcripts in NVivo 11 software. The themes obtained from the analysis were used as the subdomains of personas. A proforma was designed to extract each participant’s experience in each subdomain. Patients who exhibited similar experience in subdomains were grouped into a persona using affinity diagrams. The personas were named according to their prominent features. A questionnaire survey was conducted to validate the personas and to test whether the personas that were generated from the qualitative interview data were applicable to the Chinese population with BC. Results Four themes were identified as subdomains of weight management personas: the perception of weight management while undergoing chemotherapy, symptoms and emotional disturbance, changes in diet and exercise, and health literacy and information seeking. Five personas were ultimately obtained: (1) positive weight controllers, (2) patients who were inactive due to fatigue, (3) young patients who avoided communication, (4) overweight patients with treatment priority, and (5) patients who engaged in irregular exercise. Finally, the quantitative study showed that 51.58% of patients chose one of these five personas to represent themselves in weight management. None of the patient reported selecting options that were not explicitly outlined in the questionnaire and provided personalized descriptions of their weight management characteristics. Conclusions The selected personas were developed from in-depth interviews on biopsychosocial areas. They highlight different weight management patterns in Chinese BC patients and provide implications for both the design of mHealth systems and traditional interventions.

Abstract Background Chimeric antigen receptor (CAR) T-cells have demonstrated significant efficacy in targeting hematological malignancies, and their use continues to expand. Despite substantial efforts spent on the optimization of protocols for CAR T-cell manufacturing, critical parameters of cell culture such as pH or oxygenation are rarely actively monitored during cGMP CAR T-cell generation. A comprehensive understanding of the role that these factors play in manufacturing may help in optimizing patient-specific CAR T-cell therapy with maximum benefits and minimal toxicity. Methods This retrospective study examined cell culture supernatants from the manufacture of CAR T-cells for 20 patients with B-cell malignancies enrolled in a phase 1/2 clinical trial of anti-CD22 CAR T-cells. MetaFLEX was used to measure supernatant pH, oxygenation, and metabolites, and a Bio-Plex assay was used to assess protein levels. Correlations were assessed between the pH of cell culture media throughout manufacturing and cell proliferation as well as clinical outcomes. Next-generation sequencing was conducted to examine gene expression profiles of the final CAR T-cell products. Results A pH level at the lower range of normal at the beginning of the manufacturing process significantly correlated with measures of T-cell expansion and metabolism. Stable or rising pH during the manufacturing process was associated with clinical response, whereas a drop in pH was associated with non-response. Conclusions pH has potential to serve as an informative factor in predicting CAR T-cell quality and clinical outcomes. Thus, its active monitoring during manufacturing may ensure a more effective CAR T-cell product.

Abstract Background Cardiovascular disease (CVD) is a major global health threat, particularly in China, contributing to over 40% of deaths. While sleep behaviors, sedentary behaviors, and physical activities are recognized as independent lifestyle risk factors for CVD, there remains limited understanding of specific movement behavior patterns and their CVD risks, especially considering sex-specific differences. This study examines movement behavior patterns among Chinese adults (40–75) and their associations with cardiovascular risk, with a focus on sleep, physical activity (PA), and sedentary behavior (SB). Methods Data pertaining to 13,465 male participants and 15,613 female participants, collected from the Chronic Disease and Risk Factor Surveillance Survey in Nanjing from February 2020 to December 2022. The latent class analysis method was employed to identify underlying movement patterns across sexes. Multinomial logistic regression models assessed CVD risk, and the China-PAR model calculated 10-year risk. Results Three male and four female movement patterns emerged. Active Movers (17.10% males, 5.93% females) adhered to PA recommendations but had poorer sleep quality. Moderate Achievers (61.42% males, 45.32% females) demonstrated moderate behavior. Sedentary Sleepers (21.48% males, 10.20% females) exhibited minimal PA but good sleep. Female Moderate Physical Activity (MPA) Dominant Movers demonstrated a prevalent adherence to recommended MPA levels. Active movers had the lowest CVD risk. After adjusting for potential confounders, moderate achievers (OR = 1.462, 95% CI 1.212, 1.764) and sedentary sleepers (OR = 1.504, 95% CI 1.211, 1.868) were both identified as being associated with a high-risk of cardiovascular diseases (CVDs) compared to active movers in males, demonstrating a similar trend for intermediate risk. Such associations were not statistically significant among females. Conclusions Our study revealed sex-specific movement patterns associated with CVD risks among middle-aged Chinese adults. We suggest that adopting an active movement behavior pattern, characterized by meeting or exceeding recommended levels of vigorous physical activity (VPA) and reducing sedentary behavior, is beneficial for all middle-aged adults, particularly males. An active lifestyle could help counteract the adverse effects of relatively poor sleep quality on the risk of developing CVD in this population. Integrating sleep, PA, and SB information provides a holistic framework for understanding and mitigating CVD risks.

Abstract Background Nonalcoholic fatty liver disease (NAFLD) is on the rise globally, and past research suggests a significant association with various blood cell components. Our goal is to explore the potential correlation between whole blood cell indices and NAFLD risk using Mendelian randomization (MR). Methods We analyzed data from 4,198 participants in the 2017–2018 National Health and Nutrition Examination Survey to investigate the link between blood cell indicators and NAFLD. Using various methods like weighted quantile sum and multivariate logistic regression, we assessed the association. Additionally, two-sample Mendelian randomization were employed to infer causality for 36 blood cell indicators and NAFLD. Results Multivariate logistic regression identified 10 NAFLD risk factors. Weighted quantile sum revealed a positive correlation (p = 6.03e-07) between total blood cell indices and NAFLD, with hemoglobin and lymphocyte counts as key contributors. Restricted cubic spline analysis found five indicators with significant nonlinear correlations to NAFLD. Mendelian randomization showed a notable association between reticulocyte counts and NAFLD using the inverse-variance weighted method. Conclusions Hematological markers pose an independent NAFLD risk, with a positive causal link found for reticulocyte count. These results emphasize the importance of monitoring NAFLD and investigating specific underlying mechanisms further.

Abstract Background The protein annexin A6 (AnxA6) is involved in numerous membrane-related biological processes including cell migration and invasion by interacting with other proteins. The dysfunction of AnxA6, including protein expression abundance change and imbalance of post-translational modification, is tightly related to multiple cancers. Herein we focus on the biological function of AnxA6 SUMOylation in hepatocellular carcinoma (HCC) progression. Methods The modification sites of AnxA6 SUMOylation were identified by LC-MS/MS and amino acid site mutation. AnxA6 expression was assessed by immunohistochemistry and immunofluorescence. HCC cells were induced into the epithelial-mesenchymal transition (EMT)-featured cells by 100 ng/mL 12-O-tetradecanoylphorbol-13-acetate exposure. The ability of cell migration was evaluated under AnxA6 overexpression by transwell assay. The SUMO1 modified AnxA6 proteins were enriched from total cellular proteins by immunoprecipitation with anti-SUMO1 antibody, then the SUMOylated AnxA6 was detected by Western blot using anti-AnxA6 antibody. The nude mouse xenograft and orthotopic hepatoma models were established to determine HCC growth and tumorigenicity in vivo. The HCC patient’s overall survival versus AnxA6 expression level was evaluated by the Kaplan–Meier method. Results Lys579 is a major SUMO1 modification site of AnxA6 in HCC cells, and SUMOylation protects AnxA6 from degradation via the ubiquitin-proteasome pathway. Compared to the wild-type AnxA6, its SUMO site mutant AnxA6K579R leads to disassociation of the binding of AnxA6 with RHOU, subsequently RHOU-mediated p-AKT1ser473 is upregulated to facilitate cell migration and EMT progression in HCC. Moreover, the SENP1 deSUMOylates AnxA6, and AnxA6 expression is negatively correlated with SENP1 protein expression level in HCC tissues, and a high gene expression ratio of ANXA6/SENP1 indicates a poor overall survival of patients. Conclusions AnxA6 deSUMOylation contributes to HCC progression and EMT phenotype, and the combination of AnxA6 and SENP1 is a better tumor biomarker for diagnosis of HCC grade malignancy and prognosis.

Abstract Background Alzheimer’s disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized. Results Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition. Conclusions Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration.

Abstract Background The efficacy of subsequent therapy after poly-ADP-ribose polymerase (PARP) inhibitor maintenance treatment has raised concerns. Retrospective studies show worse outcomes for platinum-based chemotherapy after progression of PARP inhibitor-maintenance therapy, especially in BRCA-mutant patients. We aimed to describe subsequent therapy in ovarian cancer patients after PARP inhibitor-maintenance therapy and evaluate their response to treatment. We focused on chemotherapy for patients with a progression-free interval (PFI) of ≥ 6 months after prior platinum treatment, based on BRCA status. Methods We analyzed real-world data from Peking University Cancer Hospital, subsequent therapy after progression to PARP inhibitor-maintenance therapy for epithelial ovarian cancer between January 2016 and December 2022. Clinicopathological characteristics and treatment outcomes were extracted from medical records. The last follow-up was in May 2023. Results A total of 102 patients were included, of which 29 (28.4%) had a germline BRCA1/2 mutation and 73 (71.6%) exhibited BRCA1/2 wild-type mutations. The PARP inhibitors used were Olaparib (n = 62, 60.8%), Niraparib (n = 35, 34.3%), and others (n = 5, 4.9%). The overall response rate (ORR) was 41.2%, and the median time to second progression (mTTSP) was 8.1 months (95%CI 5.8–10.2). Of 91 platinum-sensitive patients (PFI ≥ 6 months) after progression to PARP inhibitor-maintenance therapy, 65 patients subsequently received platinum regimens. Among them, 30 had received one line of chemotherapy before PARP inhibitor-maintenance therapy. Analysis of these 30 patients by BRCA status showed an ORR of 16.7% versus 33.3% and mTTSP of 7.1 (95% CI 4.9–9.1) versus 6.2 months (95% CI 3.7–8.3, P = 0.550), for BRCA-mutant and wild-type patients, respectively. For the remaining 35 patients who had received two or more lines of chemotherapy before PARP inhibitor-maintenance therapy, ORR was 57.1% versus 42.9%, and mTTSP was 18.0 (95% CI 5.0–31.0) versus 8.0 months (95% CI 4.9–11.1, P = 0.199), for BRCA-mutant and wild-type patients, respectively. Conclusion No differences in survival outcomes were observed among patients with different BRCA statuses. Furthermore, for patients who had undergone two or more lines of chemotherapy before PARP inhibitor maintenance therapy, no negative effects of PARP inhibitors on subsequent treatment were found, regardless of BRCA status.

Abstract Background To report a case of a 4-year-old patient with Goldenhar syndrome. Case presentation The author presents a rare case report involving a 4-year-old boy with multiple malformations. A comprehensive examination showed that the patient primarily had a limbal dermoid. He also has bilateral microtia and ear canal deformities. The skull CT scan and spine X-ray showed Maxillofacial Abnormalities and scoliosis. Whole Exome Sequencing revealed potential gene variations related to microtia. Although certain circumstances prevented us from initiating follow-up treatment for the patient, we have provided a detailed account of the diagnostic methodologies used for this condition. Conclusions Goldenhar syndrome is a congenital condition, predominantly presenting as sporadic cases. Its diagnosis and management typically necessitate the involvement of multiple disciplines, including otolaryngology and craniofacial surgery. The syndrome encompasses a variety of craniofacial features, which can facilitate early diagnosis and guide subsequent therapeutic interventions.

Abstract Background To explore the feasibility and effectiveness of applying CBL teaching method and SEGUE Framework in the doctor-patient communication skills of resident physicians in the department of otolaryngology. Methods This is an observational study to compare the score changes in doctor-patient communication skills of 120 resident physicians, before and after using CBL combined SEGUE Framework teaching method. The effects of gender, age, grade, educational background and marital status on SEGUE score were analyzed. Results Through the combined application of CBL teaching method and SEGUE Framework, the SEGUE score of 120 resident physicians was significantly improved. There was no significant difference in SEGUE score among different sex and marital status of resident physicians. SEGUE score is positively correlated with age; Different grades and educational backgrounds have significant effects on SEGUE score. Conclusion The combination of CBL teaching method and SEGUE Framework is feasible and effective in the education program of doctor-patient communication skills for resident physicians in the department of otolaryngology, and worthy of popularization and application in other medical specialties.

Abstract Systemic therapies using programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors have demonstrated commendable efficacy in some patients with advanced hepatocellular carcinoma (HCC); however, other individuals do not respond favorably. Hence, identifying the biomarkers, the prognostic factors, and their underlying mechanisms is crucial. In this review, we summarized the latest advancements in this field. Within the tumor microenvironment, PD-L1 expression is commonly utilized to predict response. Moreover, the characteristics of tumor-infiltrating lymphocytes are associated with the effectiveness of immunotherapy. Preclinical studies have identified stimulatory dendritic cells, conventional dendritic cells, and macrophages as potential biomarkers. The emergence of single-cell sequencing and spatial transcriptomics has provided invaluable insights into tumor heterogeneity through the lens of single-cell profiling and spatial distribution. With the widespread adoption of next-generation sequencing, certain genomic characteristics, including tumor mutational burden, copy number alterations, specific genes (TP53, CTNNB1, and GZMB), and signaling pathways (WNT/β-catenin) have been found to correlate with prognosis. Furthermore, clinical features such as tumor size, number, and metastasis status have demonstrated prognostic value. Notably, common indicators such as the Child-Pugh score and Eastern Cooperative Oncology Group score, which are used in patients with liver diseases, have shown potential. Similarly, commonly employed laboratory parameters such as baseline transforming growth factor beta, lactate dehydrogenase, dynamic changes in alpha-fetoprotein (AFP) and abnormal prothrombin, CRAFITY score (composed of C-reactive protein and AFP), and immune adverse events have been identified as predictive biomarkers. Novel imaging techniques such as EOB-MRI and PET/CT employing innovative tracers also have potential. Moreover, liquid biopsy has gained widespread use in biomarker studies owing to its non-invasive, convenient, and highly reproducible nature, as well as its dynamic monitoring capabilities. Research on the gut microbiome, including its composition, dynamic changes, and metabolomic analysis, has gained considerable attention. Efficient biomarker discovery relies on continuous updating of treatment strategies. Next, we summarized recent advancements in clinical research on HCC immunotherapy and provided an overview of ongoing clinical trials for contributing to the understanding and improvement of HCC immunotherapy.

Abstract Background The association of longitudinal uric acid (UA) changes with cardiac conduction block risk is unclear. We aimed to identify the trajectories of UA and explore its association with cardiac conduction block. Methods A total of 67,095 participants with a mean age of 53.12 years were included from the Kailuan cohort in Tangshan, China, who were free of cardiac conduction block and with repeated measurements of UA from 2006 to 2012. UA trajectories during 2006 to 2012 were identified by group-based trajectory modeling. Cox proportional hazard regression models were used to assess the association of UA trajectories with cardiac conduction block. Results We categorized three observed discrete trajectories of UA during 2006–2012 period: low-stable, moderate-stable, and high-stable. Over a median follow-up of 6.19 years, we identified 1405 (2.09%) incident cardiac conduction block. Compared to those in the low-stable trajectory, the adjusted hazard ratios (HRs) (95% confidence interval [CI]) of cardiac conduction block in the moderate-stable and high-stable trajectory were 1.30 (1.16–1.47) and 1.86 (1.56–2.22), and HRs of atrioventricular block were 1.39 (1.12–1.72) and 2.90 (2.19–3.83), and HRs of bundle branch blocks were 1.27 (1.10–1.47) and 1.43 (1.13–1.79). Notably, although the average UA level in the moderate-stable UA trajectory group is within the normal range, the risk of cardiac conduction block has increased. Conclusions The moderate-stable and high-stable trajectories are associated with increased risk for new-onset cardiac conduction block. Monitoring UA trajectories may assist in identifying subpopulations at higher risk for cardiac conduction block.

Abstract The clinical application of cell therapies is becoming increasingly important for the treatment of cancer, congenital immune deficiencies, and hemoglobinopathies. These therapies have been primarily manufactured and used at academic medical centers. However, cell therapies are now increasingly being produced in centralized manufacturing facilities and shipped to medical centers for administration. Typically, these cell therapies are produced from a patient’s own cells, which are the critical starting material. For these therapies to achieve their full potential, more medical centers must develop the infrastructure to collect, label, cryopreserve, test, and ship these cells to the centralized laboratories where these cell therapies are manufactured. Medical centers must also develop systems to receive, store, and infuse the finished cell therapy products. Since most cell therapies are cryopreserved for shipment and storage, medical centers using these therapies will require access to liquid nitrogen product storage tanks and develop procedures to thaw cell therapies. These services could be provided by the hospital pharmacy or transfusion service, but the latter is likely most appropriate. Another barrier to implementing these services is the variability among providers of these cell therapies in the processes related to handling cell therapies. The provision of these services by medical centers would be facilitated by establishing a national coordinating center and a network of apheresis centers to collect and cryopreserve the cells needed to begin the manufacturing process and cell therapy laboratories to store and issue the cells. In addition to organizing cell collections, the coordinating center could establish uniform practices for collecting, labeling, shipping, receiving, thawing, and infusing the cell therapy.

Abstract Background This study aimed to assess the global, regional, and national burden of liver cirrhosis and other chronic liver diseases between 1990 and 2019, considering five etiologies (hepatitis B, hepatitis C, alcohol use, NAFLD and other causes), age, gender, and sociodemographic index (SDI). Methods Data on liver cirrhosis and other chronic liver diseases mortality, incidence, and disability-adjusted life years (DALYs) were collected from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2019. Results In 2019, liver cirrhosis and other chronic liver diseases accounted for 1,472,011 (95% UI 1,374,608-1,578,731) deaths worldwide, compared to 1,012,975 (948,941-1,073,877) deaths in 1990. Despite an increase in absolute deaths, the age-standardized death rate declined from 24.43 (22.93–25.73) per 100,000 population in 1990 to 18.00 (19.31–16.80) per 100,000 population in 2019. Eastern sub-Saharan Africa exhibited the highest age-standardized death rate (44.15 [38.47–51.91] per 100,000 population), while Australasia had the lowest rate (5.48 [5.05–5.93] deaths per 100,000 population in 2019). The age-standardized incidence rate of liver cirrhosis and other chronic liver diseases attributed to hepatitis B virus has declined since 1990, but incidence rates for other etiologies have increased. Age-standardized death and DALYs rates progressively decreased with higher SDI across different GBD regions and countries. Mortality due to liver cirrhosis and other chronic liver diseases increased with age in 2019, and the death rate among males was estimated 1.51 times higher than that among females globally. Conclusion Liver cirrhosis and other chronic liver diseases continues to pose a significant global public health challenge. Effective disease control, prevention, and treatment strategies should account for variations in risk factors, age, gender, and regional disparities.

Abstract Background An English version of the Patient Perception of Patient-Centeredness (PPPC) scale was recently revised, and it is necessary to test this instrument in different primary care populations. Aim This study aimed to assess the validity and reliability of a Chinese version of the PPPC scale. Design A mixed method was used in this study. The Delphi method was used to collect qualitative and quantitative data to address the content validity of the PPPC scale by calculating the Content Validity Index, Content Validity Ratio, the adjusted Kappa, and the Item Impact Score. Confirmatory factor analysis (CFA) and exploratory factor analysis (EFA) were used to assess the construct validity of the PPPC scale through a cross-sectional survey. The internal consistency was also assessed. Setting/participants In the Delphi consultation, seven experts were consulted through a questionnaire sent by email. The cross-sectional survey interviewed 188 outpatients in Guangzhou city and 108 outpatients in Hohhot City from community health service centers or stations face-to-face. Results The 21 items in the scale were relevant to their component. The Item-level Content Validity Index for each item was higher than 0.79, and the average Scale-level content validity index was 0.97 in each evaluation round. The initial proposed 4-factor CFA model did not fit adequately. Still, we found a 3-factor solution based on our EFA model and the validation via the CFA model (model fit: $${\chi }^{2}=294.573$$ χ 2 = 294.573 , P

Abstract Background Studies have revealed that acute myeloid leukemia (AML) patients are prone to combined cardiac injury. We aimed to identify hematological risk factors associated with cardiac injury in newly diagnosed AML patients before chemotherapy and develop a personalized predictive model. Methods The population baseline, blood test, electrocardiogram, echocardiograph, and genetic and cytogenetic data were collected from newly diagnosed AML patients. The data were subdivided into training and validation cohorts. The independent risk factors were explored by univariate and multivariate logistic regression analysis respectively, and data dimension reduction and variable selection were performed using the least absolute shrinkage and selection operator (LASSO) regression models. The nomogram was generated and the reliability and generalizability were verified by receiver operating characteristic (ROC) curves, the area under the curve (AUC) and calibration curves in an external validation cohort. Results Finally, 499 AML patients were included. After univariate logistic regression, LASSO regression and multivariate logistic regression analysis, abnormal NT-proBNP, NPM1 mutation, WBC, and RBC were independent risk factors for cardiac injury in AML patients (all P