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Abstract Objectives To investigate the impact of COVID-19 pandemic measures on hospitalizations and the alterations and persistence of the epidemiological patterns of 12 common respiratory pathogens in children during the COVID-19 pandemic and after the cessation of the “zero-COVID-19” policy in southern China. Methods Respiratory specimens were collected from hospitalized children with acute respiratory infections at Shenzhen Children’s Hospital from January 2020 to June 2024. Twelve common respiratory pathogens were detected using multiplex PCR. Data on demographic characteristics, pathogen detection rates, epidemiological patterns, co-infections, and ICU admission rates were compared between the ‘during COVID-19’ period (Phase 1: January 2020 to December 2022) and the ‘post COVID-19’ period (Phase 2: January 2023 to June 2024). Results In Phase 2, there was a significant increase in average annual cases, with a higher median age of affected children, higher pathogen detection rates, and increased co-infection rates compared to Phase 1. The epidemiological patterns of most pathogens were altered by the COVID-19 pandemic. Human Parainfluenza Virus, Human Metapneumovirus, Human Bocavirus (HBOV), and Human Coronavirus remained active during Phase 1, while Mycoplasma pneumoniae (Mp) and Adenovirus (ADV) were low, and Respiratory Syncytial Virus (RSV) lacked a seasonal peak in 2022. In Phase 2, Mp, ADV, and RSV experienced outbreaks, with Mp’s high prevalence continuing into 2024. RSV showed out-of-season epidemics for two consecutive years. Influenza A (H1N1), Influenza A (H3N2), and InfB lost their seasonal patterns during Phase 1 but reemerged and regained their seasonal characteristics in 2023–2024. ICU admission rates did not significantly differ between the two phases, except for HBOV, which had higher rates in Phase 2. Conclusion The epidemiological patterns of various respiratory pathogens were affected by the COVID-19 pandemic to varying degrees. Pathogens suppressed during the pandemic experienced outbreaks or out-of-season epidemics after the lifting of non-pharmaceutical interventions, with Mp and RSV continuing into the second year and HBOV associated ICU admission rates increasing in the post-pandemic era. Continuous monitoring of these patterns is essential to understand the duration of these effects and to inform effective response strategies.

Abstract Background Glycerol-3-phosphate dehydrogenase 1 (GPD1) gene defect can cause hypertriglyceridemia (HTG), which usually occurs in infants. The gene defect has rarely been reported in adult HTG patients. In the present study, we described the clinical and functional analyses of a novel GPD1 missense variant in a Chinese adult patient with recurrent hypertriglyceridemia‑related acute pancreatitis (HTG-AP), consuming a high-fat diet and smoking heavily. Methods Exome sequencing was used to analyze the DNA of the adult patient’s blood sample. It was found that there was a new variant of GPD1 gene-p.K327N, which was verified by gold standard-sanger sequencing method. In vitro, the corresponding plasmid was constructed and transfected into human renal HEK-293T cells, and GPD1 protein levels were detected. A biogenic analysis was performed to study the population frequency, conservation, and electric potential diagram of the new variant p.K327N. Finally, the previously reported GPD1 variants were sorted and their phenotypic relationships were compared. Results A novel heterozygous variant of GPD1, p.K327N (c.981G > C), was found in the proband. Furthermore, the patient’s daughter carried this variant, whereas his wife did not carry the variant. The proband with obesity suffered eight episodes of HTG-AP from the age of 36 years, and each onset of AP was correlated to high-fat diet consumption and heavy smoking. In vitro, this variant exerted a relatively mild effect on GPD1 functions, which were associated with its effect upon secretion (~ 25% of secretion decreased compared with that of the wild-type); thus, eventually impairing protein synthesis. Additionally, 36 patients with GPD1 variants found in previous studies showed significant transient HTG in infancy. The proband carrying the GDP1 variant was the first reported adult with recurrent HTG-AP. Conclusion We identified a novel GPD1 variant, p.K327N, in a Chinese adult male patient with recurrent HTG-AP. The variant probably exerted a mild effect on GPD1 functions. The heterozygosity of this GPD1 variant, in addition to high-fat diet consumption and heavy smoking, probably triggered HTG-AP in the patient.

Abstract To investigate the effects of early-onset sepsis (EOS) on retinopathy of prematurity (ROP) in extremely premature infants (EPIs) by using propensity score matching (PSM). Clinical data of 591 EPIs admitted to NICU, Senior Department of Pediatric, PLA General Hospital from May 1, 2015 to May 1, 2022 were retrospectively analyzed. They were divided into an EOS group and a non-EOS group according to whether they had confirmed EOS or not. The incidence of ROP and severe ROP was compared between the two groups using the 1:1 PSM method. Of the 591 EPIs, 57 (9.6%) fell in the EOS group and the remaining 534 in the non-EOS group. There were statistical differences in artificial conception, cesarean section, bronchopulmonary dysplasia, duration of invasive mechanical ventilation, days of oxygen use, amniotic fluid contamination, and premature rupture of membranes between the two groups (all P 0.05). Of the 57 cases in the EOS group, 51 were successfully matched, in which the incidence of severe ROP was higher than that in the non-EOS group [47.1% (24/51) vs. 27.5% (14/51), OR 2.349,95% CI 1.030 to 5.360, P 0.05]. EOS didn’t seem to increase the incidence of ROP in EPIs, but was associated with an increase in the degree of ROP lesions. The progression of fundus lesions in EPIs with EOS during hospitalization should be closely monitored.

Abstract Introduction This study aimed to evaluate the accuracy of our own artificial intelligence (AI)‐generated model to assess automated segmentation and quantification of body composition‐derived computed tomography (CT) slices from the lumber (L3) region in colorectal cancer (CRC) patients. Methods A total of 541 axial CT slices at the L3 vertebra were retrospectively collected from 319 patients with CRC diagnosed during 2012–2019 at a single Australian tertiary institution, Western Health in Melbourne. A two‐dimensional U‐Net convolutional network was trained on 338 slices to segment muscle, visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT). Manual reading of these same slices of muscle, VAT and SAT was created to serve as ground truth data. The Dice similarity coefficient was used to assess the U‐Net‐based segmentation performance on both a validation dataset (68 slices) and a test dataset (203 slices). The measurement of cross‐sectional area and Hounsfield unit (HU) density of muscle, VAT and SAT were compared between two methods. Results The segmentation for muscle, VAT and SAT demonstrated excellent performance for both the validation (Dice similarity coefficients >0.98, respectively) and test (Dice similarity coefficients >0.97, respectively) datasets. There was a strong positive correlation between manual and AI segmentation measurements of body composition for both datasets (Spearman's correlation coefficients: 0.944–0.999, P

Objectives: The spread of CRE has been rapid on a global scale and represents a significant challenge in nosocomial infections worldwide. The aim is to evaluate the risk factors for CRE colonization and to describe the molecular and clinical characteristics of CRE colonization in pediatric inpatients in Shenzhen, China. Methods: We collected stool specimens from 2474 randomly selected pediatric inpatient hospitalized in 2 pediatric hospitals in Shenzhen between January 2023 and December 2023 for subsequent microbiological analysis, including microbial culture, species identification, antimicrobial sensitivity testing, genetic characterization and multilocus sequence typing (MLST). In addition, we conducted a case-control study to identify potential risk factors for gastrointestinal CRE colonization. Results: Of the 2474 non-replicating pediatric stool specimens collected, 3.6 % (n = 90) test positive for CRE. The most dominant CRE species were Escherichia coli (n = 67, 74.5 %), and Klebsiella pneumoniae (n = 17, 19.0 %). Multidrug resistance and carbapenemase production were observed in most CRE isolates. In CR E. coli and CR K. pneumoniae, the blaNDM was the predominant resistance gene, accounting for 95.5 % and 76.5 %, respectively. MLST showed considerable clonal diversity among the CR E. coli and CR K. pneumoniae isolates and the most common ST in CR E. coli was ST48 (n = 6, 9.0 %) and ST35 in CR K. pneumoniae (n = 4, 23.5 %). Conclusions: This study once again shows that pediatric inpatients in South China were colonized by a diversity of CRE strains, increasing the likelihood of difficult-to-treat infections. Hospitals and competent authorities should take appropriate public health measures, to prevent the further spread of CRE.

Ferroelectric thin films based on HfO2 have garnered increasing attention worldwide, primarily due to their remarkable compatibility with silicon and scalability, in contrast to traditional perovskite-structured ferroelectric materials. Nonetheless, significant challenges remain in their widespread commercial utilization, particularly concerning their notable wake-up effect and limited endurance. To address these challenges, we propose a novel strategy involving the inhomogeneous distribution of Hf/Zr elements within thin films and explore its effects on the ferroelectricity and endurance of Hf0.5Zr0.5O2 thin films. Through techniques such as grazing incidence X-ray diffraction, transmission electron microscopy, and piezoresponse force microscopy, we investigated the structural characteristics and domain switching behaviors of these materials. The experimental results indicate that the inhomogeneous distribution of Hf/Zr contributes to improving the frequency stability and endurance while maintaining a large remnant polarization in Hf0.5Zr0.5O2 ferroelectric thin films. By adjusting the distribution of Zr/Hf within the Hf0.5Zr0.5O2 thin films, significant enhancements in the remnant polarization (2Pr > 35 μC/cm2) and endurance (> 109) along with a reduced coercive voltage can be achieved. Additionally, the fabricated ferroelectric thin films also exhibit high dielectric tunability (≥ 26%) under a low operating voltage of 2.5 V, whether in the wake-up state or not. This study offers a promising approach to optimize both the ferroelectricity and endurance of HfO2-based thin films.

ABSTRACT Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease primarily transmitted by ticks. The development of encephalitis in SFTS patients significantly increases the risk of adverse outcomes. However, the understanding of SFTS‐associated encephalitis (SFTSAE) is still limited. This study aimed to identify the clinical characteristics of SFTSAE and develop a predictive model for early detection. Methods We retrospectively collected data from 220 SFTS patients admitted to Nanjing Drum Tower Hospital between May 2019 and January 2024. The patients were first randomly divided into a training set (154 people, 70%) and a validation set (66 people, 30%). The patients in the training set were divided into SFTSAE and non‐SFTSAE groups according to the presence of encephalitis. A prediction model was constructed using the training set: important clinical parameters were selected using univariate logistic regression, and then multivariate logistic regression was performed to determine the independent risk factors for SFTSAE. A prediction model was constructed using these independent risk factors. Finally, the validation set was used to verify the predictive ability of the model. Results Age, C‐reactive protein, d‐dimer, and viral load were independent risk factors for SFTSAE (p

Background: Although oxidative stress and malignancies are intimately connected, it is unknown how lung adenocarcinoma (LUAD) is affected by oxidative stress response-related genes (OSRGs).Our goal in this work was to create a genetic signature based on OSRGs that might both predict prognosis and hint to potential treatment options for LUAD. Methods: Clinicopathological and transcriptome information on LUAD patients was obtained from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A model for predicting risk was created using LASSO regression. The TCGA, GSE72094, and GSE41271 cohorts all demonstrated the risk model's prediction ability. Immune cell infiltration was measured using the CIBERSORT method, and the TIDE platform was implemented to evaluate the therapeutic efficacy of immune checkpoint inhibition (ICI). Chemotherapy sensitivity was predicted using drug activity data by the Genomics of Drug Sensitivity. An investigation into gene expression was conducted using qRT-PCR. CCK-8 and transwell assays were employed to look into how DKK1 affected the migration and proliferation of LUAD cells. Results: A gene signature consisting of ANLN, FAM83A, DKK1, LOXL2, RHOV, IGFBP1, CCR2, GNG7, and C11orf16 was efficiently determined and used to calculate a patient-specific risk score, this functioned as a stand-alone biomarker for prediction. Correlations were found between risk scores and immune cell infiltration frequency, ICI therapy response rate, estimated chemotherapeutic drug susceptibility and autophagy-related genes.Furthermore, DKK1 knockdown reduced the ability of LUAD cells to multiply and migrate. Conclusion: Our thorough transcriptome study of OSRGs generated a biological framework effective in forecasting outcome and responsiveness to therapy in LUAD patients.

Abstract Background Hepatocellular carcinoma (HCC) is a highly prevalent and deadly cancer, with limited treatment options for advanced-stage patients. Disulfidptosis is a recently identified mechanism of programmed cell death that occurs in SLC7A11 high-expressing cells due to glucose starvation-induced disintegration of the cellular disulfide skeleton. We aimed to explore the potential of disulfidptosis, as a prognostic and therapeutic marker in HCC. Methods We classified HCC patients into two disulfidptosis subtypes (C1 and C2) based on the transcriptional profiles of 31 disulfrgs using a non-negative matrix factorization (NMF) algorithm. Further, five genes (NEIL3, MMP1, STC2, ADH4 and CFHR3) were screened by Cox regression analysis and machine learning algorithm to construct a disulfidptosis scoring system (disulfS). Cell proliferation assay, F-actin staining and PBMC co-culture model were used to validate that disulfidptosis occurs in HCC and correlates with immunotherapy response. Results Our results suggests that the low disulfidptosis subtype (C2) demonstrated better overall survival (OS) and progression-free survival (PFS) prognosis, along with lower levels of immunosuppressive cell infiltration and activation of the glycine/serine/threonine metabolic pathway. Additionally, the low disulfidptosis group showed better responses to immunotherapy and potential antagonism with sorafenib treatment. As a total survival risk factor, disulfS demonstrated high predictive efficacy in multiple validation cohorts. We demonstrated the presence of disulfidptosis in HCC cells and its possible relevance to immunotherapeutic sensitization. Conclusion The present study indicates that novel biomarkers related to disulfidptosis may serve as useful clinical diagnostic indicators for liver cancer, enabling the prediction of prognosis and identification of potential treatment targets. Graphical Abstract

Abstract Background Combination therapy involving immune checkpoint blockade (ICB) and other drugs is a potential strategy for converting immune-cold tumors into immune-hot tumors to benefit from immunotherapy. To achieve drug synergy, we developed a homologous cancer cell membrane vesicle (CM)-coated metal-organic framework (MOF) nanodelivery platform for the codelivery of a TLR7/8 agonist with an epigenetic inhibitor. Methods A novel biomimetic codelivery system (MCM@UN) was constructed by MOF nanoparticles UiO-66 loading with a bromodomain-containing protein 4 (BRD4) inhibitor and then coated with the membrane vesicles of homologous cancer cells that embedding the 18 C lipid tail of 3M-052 (M). The antitumor immune ability and tumor suppressive effect of MCM@UN were evaluated in a mouse model of triple-negative breast cancer (TNBC) and in vitro. The tumor immune microenvironment was analyzed by multicolor immunofluorescence staining. Results In vitro and in vivo data showed that MCM@UN specifically targeted to TNBC cells and was superior to the free drug in terms of tumor growth inhibition and antitumor immune activity. In terms of mechanism, MCM@UN blocked BRD4 and PD-L1 to prompt dying tumor cells to disintegrate and expose tumor antigens. The disintegrated tumor cells released damage-associated molecular patterns (DAMPs), recruited dendritic cells (DCs) to efficiently activate CD8+ T cells to mediate effective and long-lasting antitumor immunity. In addition, TLR7/8 agonist on MCM@UN enhanced lymphocytes infiltration and immunogenic cell death and decreased regulatory T-cells (Tregs). On clinical specimens, we found that mature DCs infiltrating tumor tissues of TNBC patients were negatively correlated with the expression of BRD4, which was consistent with the result in animal model. Conclusion MCM@UN specifically targeted to TNBC cells and remodeled tumor immune microenvironment to inhibit malignant behaviors of TNBC.

Abstract Background Hartmann's reversal, a complex elective surgery, reverses and closes the colostomy in individuals who previously underwent a Hartmann's procedure due to colonic pathology like cancer or diverticulitis. It demands careful planning and patient optimisation to help reduce postoperative complications. Preoperative evaluation of body composition has been useful in identifying patients at high risk of short-term postoperative outcomes following colorectal cancer surgery. We sought to explore the use of our in-house derived Artificial Intelligence (AI) algorithm to measure body composition within patients undergoing Hartmann’s reversal procedure in the prediction of short-term postoperative complications. Methods A retrospective study of all patients who underwent Hartmann's reversal within a single tertiary referral centre (Western) in Melbourne, Australia and who had a preoperative Computerised Tomography (CT) scan performed. Body composition was measured using our previously validated AI algorithm for body segmentation developed by the Department of Surgery, Western Precinct, University of Melbourne. Sarcopenia in our study was defined as a skeletal muscle index (SMI), calculated as Skeletal Muscle Area (SMA) /height2

Noise profoundly affects the quality of electromagnetic data, and selecting the appropriate hyperparameters for machine learning models poses a significant challenge. Consequently, the current machine learning denoising techniques fall short in delivering precise processing of Wide Field Electromagnetic Method (WFEM) data. To eliminate the noise, this paper presents an electromagnetic data denoising approach based on the improved dung beetle optimized (IDBO) gated recurrent unit (GRU) and its application. Firstly, Spatial Pyramid Matching (SPM) chaotic mapping, variable spiral strategy, Levy flight mechanism, and adaptive T-distribution variation perturbation strategy were utilized to enhance the DBO algorithm. Subsequently, the mean square error is employed as the fitness of the IDBO algorithm to achieve the hyperparameter optimization of the GRU algorithm. Finally, the IDBO-GRU method is applied to the denoising processing of WFEM data. Experiments demonstrate that the optimization capacity of the IDBO algorithm is conspicuously superior to other intelligent optimization algorithms, and the IDBO-GRU algorithm surpasses the probabilistic neural network (PNN) and the GRU algorithm in the denoising accuracy of WFEM data. Moreover, the time domain of the processed WFEM data is more in line with periodic signal characteristics, its overall data quality is significantly enhanced, and the electric field curve is more stable. Therefore, the IDBO-GRU is more adept at processing the time domain sequence, and the application results also validate that the proposed method can offer technical support for electromagnetic inversion interpretation.

Citrus aurantium L., sometimes known as “sour orange,” is an important Chinese herb with young, immature fruits, or “zhishi,” that are high in synephrine. Synephrine is a commonly utilized natural chemical with promising applications in effectively increasing metabolism, heat expenditure, energy level, oxidative fat, and weight loss. However, little is known about the genes and pathways involved in synephrine production during the critical developmental stages of C. aurantium L., which limits the development of the industry. According to this study, the concentration of synephrine gradually decreased as the fruit developed. Transcriptome sequencing was used to examine the DEGs associated with synephrine connections and served as the foundation for creating synephrine-rich C. aurantium L. Comparisons conducted between different developmental stages to obtain DEGs, and the number of DEGs varied from 690 to 3,019. Tyrosine and tryptophan biosynthesis, glycolysis/gluconeogenesis, pentose phosphate pathway, phenylalanine, and tyrosine metabolism were the main KEGG pathways that were substantially enriched. The results showed that 25 genes among these KEGG pathways may be related to synephrine synthesis. The WGCNA and one-way ANOVA analysis adoption variance across the groups suggested that 11 genes might play a crucial role in synephrine synthesis and should therefore be further analyzed. We also selected six DEGs at random and analyzed their expression levels by RT-qPCR, and high repeatability and reliability were demonstrated by our finished RNA-seq study results. These results may be useful in selecting or modifying genes to increase the quantity of synephrine in sour oranges.

Background: Cancer associated fibroblasts (CAF), an important cancer-promoting and immunosuppressive component of the tumor immune microenvironment (TIME), have recently been found to infiltrate adult diffuse highest-grade gliomas (ADHGG) (gliomas of grade IV). Methods: Gene expression and clinical data of ADHGG patients were obtained from the CGGA and TCGA databases. Consensus clustering was used to identify CAF subtypes based on CAF key genes acquired from single-cell omics and spatial transcriptomomics. CIBERSORT, ssGSEA, MCPcounter, and ESTIMATE analyses were used to assess the TIME of GBM. Survival analysis, drug sensitivity analysis, TCIA database, TIDE and cMap algorithms were used to compare the prognosis and treatment response between patients with different CAF subtypes. An artificial neural network (ANN) model based on random forest was constructed to exactly identify CAF subtypes, which was validated in a real-world patient cohort of ADHGG. Results: Consensus clustering classified ADHGG into two CAF subtypes. Compared with subtype B, patients with ADHGG subtype A had a poorer prognosis, worse responsiveness to immunotherapy and radiotherapy, higher CAF infiltration in TIME, but higher sensitivity to temozolomide. Furthermore, patients with subtype A had a much lower proportion of IDH mutations. Finally, the ANN model based on five genes (COL3A1, COL1A2, CD248, FN1, and COL1A1) could exactly discriminate CAF subtypes, and the validation of the real-world cohort indicated consistent results with the bioinformatics analyses. Conclusion: This study revealed a novel CAF subtype to distinguish ADHGG patients with different prognosis and treatment responsiveness, which may be helpful for accurate clinical decision-making of ADHGG.

Abstract Background Narrative Medicine (NM), a contemporary medical concept proposed in the 21st century, emphasizes the use of narrative as a literary form in medicine. This study aims to explore the understanding about NM and willingness to learn NM among medical students in our hospital. Methods A questionnaire survey was conducted among 130 students at Xiangya Medical College of Central South University. Results The findings revealed that a small percentage of students (3.1%) were familiar with narrative medicine and its training methods. Knowledge about the treatment skills (77.7%) and core content (55.4%) of narrative medicine was limited among the students. Despite this, a majority (63.1%) expressed a lack of interest in further understanding and learning about narrative medicine. Surprisingly, the survey indicated that students possessed a high level of narrative literacy, even without formal training in narrative medicine. Additionally, over half of the surveyed students (61.5%) believed that narrative medicine could benefit their clinical practice. Conclusions This study serves as a preliminary basis for the future development of narrative medicine education in China. It highlights the need to prioritize medical humanities education and provide medical students with more opportunities to access information on narrative medicine. By doing so, we can strive to enhance the visibility and promote the integration of narrative medicine into medical humanities education in China.

Peach, an economically important model plant of the Rosaceae family, has been domesticated and cultivated in China for approximately 5 000 years. The Hexi Corridor, an important corridor connecting east-central China and the Tarim Basin, is the starting point of the Silk Road that links China and the Eurasian region. As a globally distributed fruit tree, the spread of peach was accomplished through historical trade routes in the Hexi Corridor and the Tarim Basin. However, knowledge of peach genetic diversity in these regions remains limited. In this study, we examined the relationships and the spread history of domesticated peaches through sequencing and genomic analysis of 161 peach accessions collected from Northwest China, including 43 from the Hexi Corridor and 104 from the Tarim Basin. The results indicate that peach landraces in the Hexi Corridor and the Tarim Basin are derivatives of peaches from the east and south of China (ESC). Notably, the genetic diversity of accessions from both the Hexi Corridor and the Tarim Basin was lower than that of ESC accessions. Reduction of diversity (ROD) and linkage disequilibrium (LD) analyses detected a genetic bottleneck in peaches from these regions. Additionally, these peaches have undergone varying degrees of selection from natural environment. Moreover, genes responsive to biotic and abiotic stresses were under selection, which could be the result of the climate change of Northwest China after the Last Glacial Maximum (LGM). Our findings provide a better understanding of the genetic basis of peach migration in Northwest China. Furthermore, this study expands the available genomic data for peaches and provides critical information for future peach breeding programs.

Abstract Acute respiratory distress syndrome (ARDS) is the primary cause of respiratory failure in critically ill patients. Despite remarkable therapeutic advances in recent years, ARDS remains a life-threatening clinical complication with high morbidity and mortality, especially during the global spread of the coronavirus disease 2019 (COVID-19) pandemic. Previous studies have demonstrated that mesenchymal stem cell (MSC)-based therapy is a potential alternative strategy for the treatment of refractory respiratory diseases including ARDS, while extracorporeal membrane oxygenation (ECMO) as the last resort treatment to sustain life can help improve the survival of ARDS patients. In recent years, several studies have explored the effects of ECMO combined with MSC-based therapies in the treatment of ARDS, and some of them have demonstrated that this combination can provide better therapeutic effects, while others have argued that some critical issues need to be solved before it can be applied to clinical practice. This review presents an overview of the current status, clinical challenges and future prospects of ECMO combined with MSCs in the treatment of ARDS.

The tumor metastasis suppressor gene CD82/KAI1 has been demonstrated to impact human trophoblast invasion and migration. Communication between trophoblasts and decidual stromal cells plays a crucial role in controlling the normal invasiveness of trophoblasts. However, whether CD82/KAI1 is involved in decidualization and what role it plays remain unclear. CD82/KAI1 demonstrates specific spatiotemporal expression patterns in stromal cells undergoing decidualization during pregnancy. This is observed in both naturally pregnant females post-implantation and pseudopregnant mice undergoing induced decidualization, as detected through in situ hybridization and immunofluorescence. CD82/KAI1 expression showed a significant time-dependent increase in cultured stromal cells after 24 and 48 h of progesterone (P4) and estrogen (E2) treatment. This was accompanied by a notable upregulation of decidualization markers, including cyclin D3 and PR. After transducing stromal cells with the adenovirus-overexpressing CD82/KAI1 for 48 h, the expression of cyclin D3 protein increased. Meanwhile, there was an attenuated expression of CD82/KAI1 due to an adenovirus siRNA knockdown, whereas cyclin D3 and PR expressions were not affected. Our findings suggest a potential role of CD82/KAI1 in regulating the process of decidualization, providing insights into stromal cell differentiation.

Bud dormancy facilitates the survival of meristems under harsh environmental conditions. To elucidate how molecular responses to chilling accumulation controlling dormancy in peach buds, chromatin immunoprecipitation sequencing to identify the H3K27me3 modifications and RNA sequencing of two peach cultivars with pronounced differences in chilling requirement were carried out, the results showed that genes associated with abscisic acid and gibberellic acid signal pathways play key roles in dormancy regulation. The results demonstrated that peach flower bud differentiation occurred continuously in both cultivars during chilling accumulation, which was correlated with the transcript abundance of key genes involved in phytohormone metabolism and flower bud development under adverse conditions. The more increased strength in high chilling-requirement cultivar along with the chilling accumulation at the genome-wide level. The function of the dormancy-associated MADS-box gene PpDAM6 was identified, which is involved in leaf bud break in peach and flower development in transgenic Nicotiana tabacum (NC89). In addition, PpDAM6 was positively regulated by PpCBF, and the genes of putative dormancy-related and associated with metabolic pathways were proposed. Taken together, these results constituted a theoretical basis for elucidating the regulation of peach bud dormancy transition.

ObjectiveTo estimate the trend in the coexistence of hypertension and diabetes mellitus (HTN-DM) among residents aged 35 – 74 years in Shanghai during 2002 – 2017 for the prevention and control of the comorbidity.MethodsThe study data were from four waves of surveillance on diabetes conducted in 2002, 2009, 2017 and on non-communicable chronic diseases in 2013 among totally 56 927 residents aged 35 – 74 years in Shanghai. The prevalence of HTN-DM and its annual percentage change (APC) among the residents were calculated to analyze the trend of HTN-DM during the period. ResultsThe detected prevalence rates of HTN-DM were 4.61%, 9.93%, 13.41% and 18.97% in the participants separately surveyed in 2002, 2009, 2013 and 2017, with a significantly increasing trend over the 16-year period (APC = 9.51%, P = 0.003). Further analyses revealed that the increasing trend in HTN-DM prevalence was significant in the participants of all subgroups stratified by gender, five-year age grouping, ethnicity, education, marital status, and residential area and the increasing trend was greater for the participants of male gender, aged 35 – 44 years, being Han ethnicity, with the education of high school and above, being married, and not residing in central urban area, with the APC of 9.66%, 11.49%, 9.53%, 10.56%, 9.94%, and 10.09%, respectively.ConclusionThe prevalence of HTN-DM showed an increasing trend among 35 – 74 years old residents in Shanghai over the period from 2002 to 2017, especially among those aged 35 – 44 years, being male, Han ethnicity, with the education of high school education and above, being married and not residing in central urban areas.

Abstract Objective Hypoxia, which can considerably affect the tumor microenvironment, hinders the use of immunotherapy in bladder cancer (BLCA). Therefore, we aimed to identify reliable hypoxia‐related biomarkers to guide clinical immunotherapy in BLCA. Methods Using data downloaded from TCGA‐BLCA cohort, we determined BLCA subtypes which divide 408 samples into different subtypes. Tumor immune infiltration levels of two clusters were quantified using ssGSEA, MCPcounter, EPIC, ESTIMATE, and TIMER algorithms. Next, we constructed a hypoxia score based on the expression of hypoxia‐related genes. The IMvigor210 cohort and SubMap analysis were used to predict immunotherapeutic responses in patients with different hypoxia scores. Hub genes were screened using cytoscape, immunohistochemistry (IHC), and multispectral immunofluorescence were used to detect the spatial distribution of immune markers. Results Patients with BLCA were categorized into cluster1 (n = 227) and Cluster2 (n = 181). Immune infiltration and expression of immune markers were higher in Cluster1. Immune infiltration was also more obvious in the high‐hypoxia score group which related to a better predicted response to immunotherapy. IHC, and multispectral immunofluorescence confirmed the importance of TLR8 in immune infiltration and immune phenotype. Conclusions BLCA subtype can evaluate the infiltration of immune cells in the tumor microenvironment of different patients. Hypoxia score in this study could effectively predict immunotherapeutic responses in patients with BLCA. TLR8 may be a potential target for clinical immunotherapy.

Abstract Background Doxorubicin (DOX)-induced cardiotoxicity (DIC) is a major impediment to its clinical application. It is indispensable to explore alternative treatment molecules or drugs for mitigating DIC. WGX50, an organic extract derived from Zanthoxylum bungeanum Maxim, has anti-inflammatory and antioxidant biological activity, however, its function and mechanism in DIC remain unclear. Methods We established DOX-induced cardiotoxicity models both in vitro and in vivo. Echocardiography and histological analyses were used to determine the severity of cardiac injury in mice. The myocardial damage markers cTnT, CK-MB, ANP, BNP, and ferroptosis associated indicators Fe2+, MDA, and GPX4 were measured using ELISA, RT-qPCR, and western blot assays. The morphology of mitochondria was investigated with a transmission electron microscope. The levels of mitochondrial membrane potential, mitochondrial ROS, and lipid ROS were detected using JC-1, MitoSOX™, and C11-BODIPY 581/591 probes. Results Our findings demonstrate that WGX50 protects DOX-induced cardiotoxicity via restraining mitochondrial ROS and ferroptosis. In vivo, WGX50 effectively relieves doxorubicin-induced cardiac dysfunction, cardiac injury, fibrosis, mitochondrial damage, and redox imbalance. In vitro, WGX50 preserves mitochondrial function by reducing the level of mitochondrial membrane potential and increasing mitochondrial ATP production. Furthermore, WGX50 reduces iron accumulation and mitochondrial ROS, increases GPX4 expression, and regulates lipid metabolism to inhibit DOX-induced ferroptosis. Conclusion Taken together, WGX50 protects DOX-induced cardiotoxicity via mitochondrial ROS and the ferroptosis pathway, which provides novel insights for WGX50 as a promising drug candidate for cardioprotection. Graphic abstract

Abnormal lung development can cause congenital pulmonary cysts, the mechanisms of which remain largely unknown. Although the cystic lesions are believed to result directly from disrupted airway epithelial cell growth, the extent to which developmental defects in lung mesenchymal cells contribute to abnormal airway epithelial cell growth and subsequent cystic lesions has not been thoroughly examined. In the present study using genetic mouse models, we dissected the roles of bone morphogenetic protein (BMP) receptor 1a (Bmpr1a)-mediated BMP signaling in lung mesenchyme during prenatal lung development and discovered that abrogation of mesenchymal Bmpr1a disrupted normal lung branching morphogenesis, leading to the formation of prenatal pulmonary cystic lesions. Severe deficiency of airway smooth muscle cells and subepithelial elastin fibers were found in the cystic airways of the mesenchymal Bmpr1a knockout lungs. In addition, ectopic mesenchymal expression of BMP ligands and airway epithelial perturbation of the Sox2-Sox9 proximal-distal axis were detected in the mesenchymal Bmpr1a knockout lungs. However, deletion of Smad1/5, two major BMP signaling downstream effectors, from the lung mesenchyme did not phenocopy the cystic abnormalities observed in the mesenchymal Bmpr1a knockout lungs, suggesting that a Smad-independent mechanism contributes to prenatal pulmonary cystic lesions. These findings reveal for the first time the role of mesenchymal BMP signaling in lung development and a potential pathogenic mechanism underlying congenital pulmonary cysts.

Efficient attribute reduction algorithm capable of handling high dimensional big data is one of the hot topics of rough set theory, and some related researchers have achieved with |C| jobs. In this paper, we present the definition of a marked reduction set and propose a more efficient attribute reduction algorithm (RA-MRS). The RA-MRS includes a batch processing phase and a vibration optimization phase, which reduce the number of jobs from |C| to log2|C|. Additionally, we provide an effective judgment strategy based on MapReduce, which supports the exception processing mechanism of Java to interrupt and advance the current job. Finally, the proposed algorithm is implemented in parallel based on Spark computing framework. The experimental results show that the proposed RA-MRS algorithm is over 99% faster than the classical PAAR_PR algorithm and 70% faster than the algorithm in the literature (Yin et al., 2021).

Development of low temperature catalytic pyrolysis technology for heated tobacco sheets is expected to increase the aroma of heated tobacco products and improve their overall smoking quality. In this study, the low temperature pyrolysis performances of heated tobacco sheets catalyzed by various anionic sodium salts were investigated using TG-DTG, Py-GC-MS technology and smoke routine chemical composition analysis. The results showed that the total weight loss between 100°C and 300°C increased by 7.8%–13.15% after adding various anionic sodium salts, among which, sodium acetate and sodium tartrate showed a relatively higher weight loss. The relative content of free hydroxyacetone, furfuryl alcohol, butyrolactone and megastigmatrienone in the pyrolysis gas increased, while the relative content of free nicotine decreased. With the change of anionic species, the catalytic decomposition ability of cellulose, lignin, and other substances may change, resulting in the distribution alteration of compounds in the pyrolysis gas. After adding sodium acetate and sodium citrate, the release of total particulate matter (TPM), glycerol, and nicotine in flue gas increased. Overall, the addition of sodium acetate and sodium citrate showed a higher low temperature pyrolysis performance of heated tobacco sheets. The research results in this paper provide data support for changing the low temperature catalytic pyrolysis performance of heated tobacco sheets by adjusting the type of anions in sodium salts.

This study investigated the influence of Cd (25 µM) on Zn accumulation in a hyperaccumulating (HE) and a non-hyperaccumulating (NHE) ecotype of Sedum alfredii Hance at short-term supply of replete (Zn5, 5 µM) and excess (Zn400, 400 µM) Zn. Cd inhibited Zn accumulation in both ecotypes, especially under Zn400, in organs with active metal sequestration, i.e. roots of NHE and shoots of HE. Direct biochemical Cd/Zn competition at the metal-protein interaction and changes in transporter gene expression contributed to the observed accumulation patterns in the roots. Specifically, in HE, Cd stimulated SaZIP4 and SaPCR2 under Zn5, but downregulated SaIRT1 and SaZIP4 under Zn400. However, Cd downregulated related transporter genes, except for SaNRAMP1, in NHE, irrespective of Zn. Cadmium stimulated casparian strip (CSs) development in NHE, as part of the defense response, while it had a subtle effect on the (CS) in HE. Moreover, Cd delayed the initiation of the suberin lamellae (SL) in HE, but stimulated SL deposition in NHE under both Zn5 or Zn400. Changes in suberization were mainly ascribed to suberin-biosynthesis-related genes and hormonal signaling. Altogether, Cd regulated Zn accumulation mainly via symplasmic and transmembrane transport in HE, while Cd inhibited both symplasmic and apoplasmic Zn transport in NHE.

Malignant tumor is still a major problem worldwide. During tumorigenesis or tumor development, tumor suppressor p53-binding protein 2 (TP53BP2), also known as apoptosis stimulating protein 2 of p53 (ASPP2), plays a critical role in p53 dependent and independent manner. Expression of TP53BP2 is highly correlated with the prognosis and survival rate of malignant tumor patients. TP53BP2 can interact with p53, NF-κB p65, Bcl-2, HCV core protein, PP1, YAP, CagA, RAS, PAR3, and other proteins to regulate cell function. Moreover, TP53BP2 can also regulate the proliferation, apoptosis, autophagy, migration, EMT and drug resistance of tumor cells through downstream signaling pathways, such as NF-κB, RAS/MAPK, mevalonate, TGF-β1, PI3K/AKT, aPKC-ι/GLI1 and autophagy pathways. As a potential therapeutic target, TP53BP2 has been attracted more attention. We review the role of TP53BP2 in tumorigenesis or tumor development and the signal pathway involved in TP53BP2, which may provide more deep insight and strategies for tumor treatment.

Abstract Nowadays, primary liver cancer is still a major threat to human health. Anoikis is a particular form of programed cell death that has an inhibitory effect on neoplasm metastasis. Although several prognostic models based on anoikis‐related genes for Hepatocellular carcinoma (HCC) have been established, signatures associated with anoikis‐related lncRNAs have not been identified. To fill this blank space, the authors built up a prognostic signature and appraised its value in guiding immunotherapy. Eleven prognostic anoikis‐related lncRNAs were identified through Least Absolute Shrinkage and Selection Operator Cox analysis. The accuracy of the risk signature in predicting prognosis was verified by K–M survival analysis and Receiver operating characteristic analysis. We further discovered that the high‐risk group was often enriched in signal pathways related to cell growth and death and immune response; in addition, in the low‐risk group, cells often undergo metabolic changes through gene set enrichment analysis. Finally, we realised that HCC patients in the high‐risk group were upregulated in immune‐checkpoint molecules and tend to have a higher tumour mutation burden level which indicated a higher sensitivity to immunotherapy. All in all, the anoikis‐related lncRNAs risk signature showed excellent ability in predicting prognosis and may guide the application of immunotherapy in future clinical practice.

At present, the optimization of public transportation networks and vehicle scheduling are carried out independently in stages. However, through analysis, it has been found that scheduling information such as route schedules is an important factor related to passenger route selection. Therefore, in order to further improve the optimization effect, this article proposes an innovative idea of simultaneously optimizing the line network and scheduling. Based on the construction of a real–virtual public transportation network, this article constructs a synchronous optimization model for the line network and scheduling by considering both passenger waiting and on-board time. To achieve the consideration of passengers for different route choices, a shortest path traversal algorithm based on Yen was proposed to analyze the number and weight of the shortest paths between the same OD, and a genetic algorithm was used to solve the model. Finally, the effectiveness of the model was verified through numerical examples, and the results showed that synchronous optimization was superior to phased optimization: the passenger time cost was reduced by 21.5%, the bus operation cost was reduced by 13.7%, and the total bus system cost was reduced by 18.0%.

Shallow gas was widely recognized in the coastal region, especially in the estuarine delta areas with high organic matter (OM) burial flux. In this study, the vertical variations of shallow gas and the related geochemical indicators from two boreholes in the coastal region of the East China Sea (ECS) were investigated. Two gas-bearing layers were identified in the sediments from the Holocene and late Pleistocene series. Both boreholes exhibit a “typical” and an “inverse” Sulfate Methane Transition Zone (SMTZ). The “typical” SMTZs (SMTZ1 and SMTZ3) were in the upper part of the gas-bearing layers, where sulfate levels decrease and methane levels increase with depth. Conversely, the “inverse” SMTZs (SMTZ2 and SMTZ4) were in the lower part of the gas-bearing layers, exhibiting an increase in sulfate levels and a decrease in methane levels with depth, a phenomenon rarely documented in previous research. The downward variations of pore water geochemical characteristics indicates that these ions were related to Anaerobic Oxidation of Methane (AOM) processes. The increase in Ca2+ and Ba2+ concentrations and the gradual decrease in sulfate at the SMTZ reflect a series of biogeochemical processes resulting from the dissolution of carbonate and other minerals by AOM. The research indicates that sulfate in AOM may originate from multiple sources. Through analyzing the vertical distribution of shallow gas and the geochemical properties of pore water, this study elucidates the shallow gas formation mechanism and the features of the SMTZ, laying the groundwork for further investigations.

Abstract Background Uterine corpus endometrial carcinoma (UCEC) is a gynecological malignant tumor with high incidence and poor prognosis. Although immunotherapy has brought significant survival benefits to advanced UCEC patients, traditional evaluation indicators cannot accurately identify all potential beneficiaries of immunotherapy. Consequently, it is necessary to construct a new scoring system to predict patient prognosis and responsiveness of immunotherapy. Methods CIBERSORT combined with weighted gene co-expression network analysis (WGCNA), non-negative matrix factorization (NMF), and random forest algorithms to screen the module associated with CD8+ T cells, and key genes related to prognosis were selected out by univariate, least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses to develop the novel immune risk score (NIRS). Kaplan–Meier (K-M) analysis was used to compare the difference of survival between high- and low- NIRS groups. We also explored the correlations between NIRS, immune infiltration and immunotherapy, and three external validation sets were used to verify the predictive performance of NIRS. Furthermore, clinical subgroup analysis, mutation analysis, differential expression of immune checkpoints, and drug sensitivity analysis were performed to generate individualized treatments for patients with different risk scores. Finally, gene set variation analysis (GSVA) was conducted to explore the biological functions of NIRS, and qRT-PCR was applied to verify the differential expressions of three trait genes at cellular and tissue levels. Results Among the modules clustered by WGCNA, the magenta module was most positively associated with CD8+ T cells. Three genes (CTSW, CD3D and CD48) were selected to construct NIRS after multiple screening procedures. NIRS was confirmed as an independent prognostic factor of UCEC, and patients with high NIRS had significantly worse prognosis compared to those with low NIRS. The high NIRS group showed lower levels of infiltrated immune cells, gene mutations, and expression of multiple immune checkpoints, indicating reduced sensitivity to immunotherapy. Three module genes were identified as protective factors positively correlated with the level of CD8+ T cells. Conclusions In this study, we constructed NIRS as a novel predictive signature of UCEC. NIRS not only differentiates patients with distinct prognoses and immune responsiveness, but also guides their therapeutic regimens.

Abstract Background The copper metabolism MURR1 domain (COMMD) protein family is involved in tumorigenicity of malignant tumors. However, as the member of COMMD, the role of COMMD2 in human tumors remains unknown. Methods We used The Cancer Genome Atlas (TCGA), Genotype Tissue Expression (GTEx), Human Protein Atlas (HPA) database, Cancer Cell Line Encyclopedia (CCLE) platform, univariate Cox regression analysis, Kaplan–Meier curve, cBioPortal, UALCAN database, Sangerbox online platform, GSCA database gene set enrichment analysis (GSEA), and GeneMANIA to analyze the expression of COMMD2, its prognostic values, genomic alteration patterns, and the correlation with tumor stemness, tumor mutational burden (TMB), microsatellite instability (MSI), and immune infiltrates, drug sensitivity, and gene function enrichment in pan‐cancer. qRT‐PCR, CCK‐8, EdU, wound healing, and transwell migration assays were performed to confirm the function of COMMD2. Results COMMD2 was strongly expressed in most cancer types. Elevated COMMD2 expression affects the prognosis, clinicopathological stage, and molecular or immune subtypes of various tumors. Moreover, promoter hypomethylation and mutations in the COMMD2 gene may be associated with its high expression and poor survival. Additionally, we discovered that COMMD2 expression was linked to tumor stemness, TMB, MSI, immune cell infiltration, immune‐checkpoint inhibitors, and drug sensitivity in pan‐cancer. Furthermore, the COMMD2 gene co‐expression network is constructed with GSEA analysis, displaying significant interaction of COMMD2 with E2F targets, G2‐M checkpoint, and mitotic spindle in bladder cancer (BLCA). Finally, RNA interference data showed suppression of COMMD2 prevented proliferation and migration of BLCA and uterine corpus endometrial carcinoma (UCEC) cells. Conclusion Our findings shed light on the COMMD2 functions in human cancers and demonstrate that it is a promising prognostic biomarker and therapeutic target in pan‐cancer.

Abstract Objective To compare post-treatment recurrence between ranibizumab injection and laser photocoagulation (LP) for type 1 retinopathy of prematurity (ROP), and explore the associated risk factors. Methods The clinical data of ROP infants treated with LP or ranibizumab in a NICU of China from October 2007 to November 2021 were retrospectively analyzed and compared, such as general condition, degree of ROP, therapeutic effectiveness and post-treatment recurrence. The dependent variable was recurrence after ROP treatment. Univariate and regression analysis of risk factors was performed. Results Of the 298 ROP infants (556 eyes), 58% of the eyes were treated with LP and the other 42% with ranibizumab. There was no significant difference in gestational age at birth, birth weight, sex, delivery mode, prenatal corticosteroids, ROP diagnosed before admission or after admission, and the duration of oxygen therapy between the two groups. However, the ratio of type 1 ROP and aggressive retinopathy of prematurity (A-ROP) in ranibizumab group was higher than that in LP group. The number of treatments, recurrence rate and recurrence interval in ranibizumab group were higher than those in LP group. However, there was no difference in the recurrence rate between the two groups after stratified analysis by the lesion area and the presence or absence of A-ROP. There was no significant difference in the final lesion regression between the two groups. Regression analysis showed that plus disease and ROP located in zone I were independent risk factors for post-treatment recurrence. Conclusion There is no significant difference in the recurrence rate of ROP between ranibizumab injection and LP, and recurrence is mainly related to the severity of ROP. In half of our patients treated with A-ROP recurrences occur.

ABSTRACTObjective: To explore the effect on empathy skills of integrating narrative medicine instruction into clinical internship undergraduate medical education.Methods: One hundred clinical undergraduate students who were transferred to gynecology and obstetrics in 2016 were selected as subjects and divided into two groups. The control group adopted the traditional practice teaching mode, while the experimental group adopted a narrative medicine integrated with traditional teaching mode. The impact of the narrative medicine course was evaluated using the Davis Empathy Scale, and the students’ acceptance of the course was investigated using a self-developed questionnaire.Results: After completion of the rotation, the empathy scores of the experimental group were higher than those of the control group (p

Purpose: Our study explored the effect of long noncoding RNA BBOX1-AS1 on colorectal cancer (CRC) radiosensitivity in vivo and in vitro. Methods: Differentially expressed lncRNAs in CRC were screened using a bioinformatics database and an online prediction website. The expression of BBOX1-AS1 in tissue samples was analyzed via real-time quantitative PCR (RT-qPCR). Subcellular localization of BBOX1-AS1 in CRC cells was analyzed using fluorescence in situ hybridization (FISH). The correlation between BBOX1-AS1 and PFK1 expression levels in CRC tissues was analyzed via Pearson's correlation coefficient. The effect of BBOX1-AS1 on PFK1 stability was investigated using RNA and protein stability testing. RNA Binding Protein Immunoprecipitation (RIP) and RNA pull-down assays were used to confirm the binding of BBOX1-AS1 to PFK1. Results: BBOX1-AS1 was highly expressed in CRC and associated with poor prognosis. Similarly, it was highly expressed in CRC tissues and CRC cell lines. In addition, BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells and inhibited apoptosis. RIP and RNA pull-down experiments confirmed that BBOX1-AS1 bound to PFK1. RNA stability and protein stability experiments showed that BBOX1-AS1 affected the stability of PFK1 mRNA and protein. Furthermore, we confirmed that BBOX1-AS1 increased radiation resistance through the regulation of PFK1 expression. Conclusions: BBOX1-AS1 promoted the proliferation, invasion, migration, and glycolysis of CRC cells through stabilization of the expression of PFK1. BBOX1-AS1 also inhibited CRC cell apoptosis and increased radiotherapy resistance in CRC cells.