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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 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

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.

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.

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

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.

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.

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.

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).

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.

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.

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.

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.

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.

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 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

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.

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%.

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.

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.

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

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.

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.

Abstract Background Alternative splicing (AS) events are extensively involved in the progression of diverse tumors, but how serine/arginine-rich splicing Factor 10 (SRSF10) behaves in hepatocellular carcinoma (HCC) has not been sufficiently studied. We aimed to determine SRSF10 associated AS mechanisms and their effects on HCC progression. Methods The expression of SRSF10 in HCC tissues was examined, and the in vitro and in vivo functions of SRSF10 were investigated. The downstream AS targets were screened using RNA sequencing. The interaction between SRSF10 protein and exclusion of cell division cycle 25 A (CDC25A) mRNA was identified using RNA immunoprecipitation and crosslinking immunoprecipitation q-PCR. The effects of SRSF10 on CDC25A posttranslational modification, subcellular distribution, and protein stability were verified through coimmunoprecipitation, immunofluorescence, and western blotting. Results SRSF10 was enriched in HCC tissues and facilitated HCC proliferation, cell cycle, and invasion. RNA sequencing showed that SRSF10 promotes exon 6 exclusion of CDC25A pre-mRNA splicing. As a crucial cell cycle mediator, the exon-skipped isoform CDC25A(△E6) was identified to be stabilized and retained in the nucleus due to the deletion of two ubiquitination (Lys150, Lys169) sites in exon 6. The stabilized isoform CDC25A(△E6) derived from AS had stronger cell cycle effects on HCC tumorigenesis, and playing a more significant role than the commonly expressed longer variant CDC25A(L). Interestingly, SRSF10 activated the carcinogenesis role of CDC25A through Ser178 dephosphorylation to cause nuclear retention. Moreover, CDC25A(△E6) was verified to be indispensable for SRSF10 to promote HCC development in vitro and in vivo. Conclusions We reveal a regulatory pattern whereby SRSF10 contributes to a large proportion of stabilized CDC25A(△E6) production, which is indispensable for SRSF10 to promote HCC development. Our findings uncover AS mechanisms such as CDC25A that might serve as potential therapeutic targets to treat HCC.

Abstract Purpose Stereotactic radiosurgery (SRS) has become a standard approach for the treatment of patients with few metastatic brain lesions. However, the optimal treatment approach for the use radiotherapy in the treatment of non-small cell lung cancer (NSCLC) patients with brain metastases (BMs) remain unclear. This study aimed to compare the survival outcomes and intracranial local control in NSCLC patients with 1–4 BMs who are treated with SRS using linear accelerators (LINAC-SRS), whole-brain radiotherapy (WBRT), or WBRT plus radiotherapy boost (WBRT + RTB). Materials and methods We retrospectively analyzed 156 NSCLC patients with 1–4 BMs who received LINAC-SRS, WBRT, and WBRT + RTB. The median overall survival (OS), intracranial progression-free survival (iPFS), and distant brain failure-free survival (DBF-FS) and related prognostic factors were analyzed. Results The median follow-up period was 31.6 months. The median OS times in the LINAC-SRS, WBRT, and WBRT + RTB groups were not reached, 33.3 months and 27.9 months, respectively. The difference in survival rate was non-significant (P = 0.909). The 2-year iPFS and DBF-FS rates in the LINAC-SRS, WBRT and WBRT + RTB groups were 51.6% and 37.5%; 42.0% and 50.4%; and 51.1% and 56.1%, respectively. There was no significant difference in 2-year iPFS or DBF-FS among the three groups (P = 0.572 for iPFS, P = 0.628 for DBF-FS). Multivariate analysis showed that the independent adverse prognostic factors for OS, iPFS, and DBF-FS were neurological symptoms, recursive partitioning analysis (RPA) class, and targeted therapy. Conclusion LINAC-SRS did not result in significantly superior survival times or intracranial local control compared to WBRT or WBRT + RTB in the treatment of NSCLC patients with 1–4 BMs.

Abstract The fast conversion of hydrogen peroxide (H2O2) into reactive oxygen species (ROS) at tumor sites is a promising anticancer strategy by manipulating nanomedicines with near‐infrared light in the second region (NIR‐II). However, this strategy is greatly compromised by the powerful antioxidant capacity of tumors and the limited ROS generation rate of nanomedicines. This dilemma mainly stems from the lack of an effective synthesis method to support high‐density copper‐based nanocatalysts on the surface of photothermal nanomaterials. Herein, a multifunctional nanoplatform (MCPQZ) with high–density cuprous (Cu2O) supported molybdenum disulfide (MoS2) nanoflowers (MC NFs) is developed for the efficient killing of tumors via a potent ROS storm by an innovative method. Under NIR‐II light irradiation, the ROS intensity and maximum reaction velocity (Vmax) produced by MC NFs are 21.6 and 33.8 times that of the non–irradiation group in vitro, which is much higher than most current nanomedicines. Moreover, the strong ROS storm in cancer cells is efficiently formed by MCPQZ (increased by 27.8 times compared to the control), thanks to the fact that MCPQZ effectively pre–weakens the multiple antioxidant systems of cancer cells. This work provides a novel insight to solve the bottleneck of ROS‐based cancer therapy.

BackgroundSepsis-associated liver dysfunction (SALD) has high incidence and mortality in patients with intra-abdominal infection (IAI). The associations between acute gastrointestinal injury (AGI), gut microbiota, and SALD were evaluated in patients with IAI.MethodsA retrospective study was conducted to assess the relationship between AGI and SALD in patients with IAI. Patients were divided into non-SALD and sepsis-induced cholestasis (SIC) groups, which is a subtype of SALD. SIC was defined as total bilirubin >2 mg/dL. AGI incidences between the two groups were compared using Chi-square test. Subsequently, a prospective study was conducted to investigate the gut microbiota differences between patients without SALD and those with SIC. Fecal samples were collected on days 1, 3, and 7 after admission to analyze changes in gut microbiota using 16S ribosomal ribonucleic acid sequencing.ResultsOne hundred thirty-four patients with IAI were included retrospectively, with 77 SALD and 57 non-SALD cases. Among patients with SALD, 71 were diagnosed with SIC. Patients with SIC had a higher incidence of AGI compared to those without SALD (28.07% vs. 56.34%, p

Single fruit weight is an important goal of crop production and horticultural species domestication, but its genetic mechanism is still unclear. In this study, the fruits of different peach fruit types in their first rapid development period were used as materials. First, the differentially expressed genes were analyzed by RNA-seq data. Secondly, weighted gene co-expression network analysis (WGCNA) was used to calculate the correlation between genes and modules, the genes with different expression patterns were divided into 17 modules, the modules were correlated with the phenotype of single fruit, and a highly correlated blue module was obtained. Then, the possible differentially expressed genes and signal pathways among different fruit types were compared by gene set enrichment analysis (GSEA) and 43 significant pathways were obtained. Finally, 54 genes found to be repeatedly expressed in 3 of the methods were screened, and 11 genes involved in plant hormone signal transduction were selected for subsequent analysis according to their functional annotations. Combined with the changing trend of phenotype, three genes (Prupe.7G234800, Prupe.8G079200 and Prupe.8G082100) were obtained as candidate genes for single fruit weight traits. All three genes are involved in auxin signal transduction, with auxin playing an important role in plant growth and development. This discovery provides a new perspective for revealing the genetic law of single fruit weight in peach.

Post-harvest handling and ripening techniques have an impact on peach quality and shelf life, which has a big impact on consumer satisfaction and market competitiveness. This review paper examines recent advancements in ripening techniques and post-harvest technologies with the goal of improving peach fruit quality and sustainability. The factors impacting fruit quality after harvest and the physiological changes that occur throughout peach ripening are fully explained. For maintaining peach freshness and reducing losses, novel handling methods like modified atmosphere packaging (MAP) and controlled atmosphere storage (CAS) have been investigated. The study explores the possibilities of nanotechnology applications and low-temperature storage for prolonging shelf life while maintaining texture, flavor, and aroma. This study further analyzes the effectiveness and waste reduction potential of automation and mechanization in post-harvest activities. The paper also discusses ethylene-based and non-ethylene-based ripening agents, as well as innovative techniques including gene editing and RNAi technology for controlled and delayed ripening. Analyses are performed on how these technologies affect the sensory qualities and nutrient profiles of peaches. The study emphasizes the significance of sustainable practices in the peach industry by focusing on waste reduction, resource efficiency, and circular economy integration. Post-harvest technologies’ potential environmental consequences are taken into consideration, and the paper encourages more studies and cooperation to increase sustainability.

The montmorillonite-sodium alginate (MMT-SA) colon-targeting microcapsules have been designed as a WGX-50 encapsulation and controlled release vehicle used in oral administration. The MMT-SA microcapsule was formed from a cross-linking reaction, and the stable micropore in the microcapsule changed with a different MMT-SA mixed mass ratio. The MMT-SA microcapsule has a reinforced micropore structure and an enhanced swell–dissolution in SIF and SCF with alkaline environment, which is attributed to the incorporated MMT. The MMT-SA microcapsule exhibited a high WGX-50 encapsulation rate up to 98.81 ± 0.31% and an obvious WGX-50 controlled release in the simulated digestive fluid in vitro. The WGX-50 loaded with MMT-SA microcapsule showed a weak minimizing drug loss in SGF (Simulated Gastric Fluid) with an acidic environment, while it showed a strong maximizing drug release in SIF (Simulated Intestinal Fluid) and SCF (Simulated Colonic Fluid) with an alkaline environment. These features make the MMT-SA microcapsule a nominated vehicle for colon disease treatment used in oral administration.

Supercapacitors are extensively used in urban rail transit, electric vehicles, renewable energy storage, electronic products, and the military industry due to its long cycle life and high power density. Porous carbon materials are regarded as promising anode materials for supercapacitors due to their high specific surface areas and well-developed pore structures. However, the over-developed pore structure often results in poor conductivity and reduced cycle stability due to the destruction of a carbon skeleton. Herein, we introduce an advanced strategy for preparing porous carbon with high specific surface areas (3333 m2 g−1), high electrical conductivity (68.6 S m−1), and fast ion transport channels through secondary high-temperature carbonization treatment. As a result, the fabricated porous carbon anode delivers a high specific capacitance (199.2 F g−1 at 1 A g−1) and outstanding rate performance (136.3 F g−1 at 20 A g−1) in organic electrolyte. Furthermore, the assembled symmetrical supercapacitor achieves an energy density of 43.2 Wh kg−1 at 625.0 W kg−1, highlighting the potential of a secondary high-temperature carbonization strategy in practical applications.

Functional succinate dehydrogenase (SDH) complex is vital to mitochondrial homeostasis. Here the authors show that disruption of SDH assembly in the heart causes dilated cardiomyopathy via impairing the mitochondrial integrity and metabolism and that mitochondrial interventions can be an effective approach to ameliorate the disease progression.

Abstract Background Plant metabolites reshaped by nature and human beings are crucial for both their lives and human health. However, which metabolites respond most strongly to selection pressure at different evolutionary stages and what roles they undertake on perennial fruit crops such as peach remain unclear. Results Here, we report 18,052 significant locus-trait associations, 12,691 expression-metabolite correlations, and 294,676 expression quantitative trait loci (eQTLs) for peach. Our results indicate that amino acids accumulated in landraces may be involved in the environmental adaptation of peaches by responding to low temperature and drought. Moreover, the contents of flavonoids, the major nutrients in fruits, have kept decreasing accompanied by the reduced bitter flavor during both domestication and improvement stages. However, citric acid, under the selection of breeders’ and consumers’ preference for flavor, shows significantly different levels between eastern and western varieties. This correlates with differences in activity against cancer cells in vitro in fruit from these two regions. Based on the identified key genes regulating flavonoid and acid contents, we propose that more precise and targeted breeding technologies should be designed to improve peach varieties with rich functional contents because of the linkage of genes related to bitterness and acid taste, antioxidant and potential anti-cancer activity that are all located at the top of chromosome 5. Conclusions This study provides powerful data for future improvement of peach flavor, nutrition, and resistance in future and expands our understanding of the effects of natural and artificial selection on metabolites.

Abstract Purpose Extralevator (ELAPE) and abdominoperineal excision (APE) are two major surgical approaches for low rectal cancer patients. Although excellent short-term efficacy is achieved in patients undergoing ELAPE, the long-term benefits have not been established. In this study we evaluated the safety, pathological and survival outcomes in rectal cancer patients who underwent ELAPE and APE. Methods One hundred fourteen patients were enrolled, including 68 in the ELAPE group and 46 in the APE group at the Beijing Chaoyang Hospital, Capital Medical University from January 2011 to November 2020. The baseline characteristics, overall survival (OS), progression-free survival (PFS), and local recurrence-free survival (LRFS) were calculated and compared between the two groups. Results Demographics and tumor stage were comparable between the two groups. The 5-year PFS (67.2% versus 38.6%, log-rank P = 0.008) were significantly improved in the ELAPE group compared to the APE group, and the survival advantage was especially reflected in patients with pT3 tumors, positive lymph nodes or even those who have not received neoadjuvant chemoradiotherapy. Multivariate analysis showed that APE was an independent risk factor for OS (hazard ratio 3.000, 95% confidence interval 1.171 to 4.970, P = 0.004) and PFS (hazard ratio 2.730, 95% confidence interval 1.506 to 4.984, P = 0.001). Conclusion Compared with APE, ELAPE improved long-term outcomes for low rectal cancer patients, especially among patients with pT3 tumors, positive lymph nodes or those without neoadjuvant chemoradiotherapy.

Abstract Background Peach (Prunus persica) is an economically important stone fruit crop in Rosaceae and widely cultivated in temperate and subtropical regions, emerging as an excellent material to study the interaction between plant and environment. During its genus, there are four wild species of peach, all living in harsh environments. For example, one of the wild species, P. mira, originates from the Qinghai-Tibet Plateau (QTP) and exhibits strong cold/ultraviolet ray environmental adaptations. Although remarkable progresses in the gene discovery of fruit quality-related traits in peach using previous assembled genome were obtained, genomic basis of the response of these wild species to different geographical environments remains unclear. Results To uncover key genes regulating adaptability in different species and analyze the role of genetic variations in resistance formation, we performed de novo genome assembling of four wild relatives of peach (P. persica), P. mira, P. davidiana, P. kansuensis, and P. ferganensis and resequenced 175 peach varieties. The phylogenetic tree showed that the divergence time of P. mira and other wild relatives of peach was 11.5 million years ago, which was consistent with the drastic crustal movement of QTP. Abundant genetic variations were identified in four wild species when compared to P. persica, and the results showed that plant-pathogen interaction pathways were enriched in genes containing small insertions and deletions and copy number variations in all four wild relatives of peach. Then, the data were used to identify new genes and variations regulating resistance. For example, presence/absence variations which result from a hybridization event that occurred between P. mira and P. dulcis enhanced the resistance of their putative hybrid, P. davidiana. Using bulked segregant analysis, we located the nematode resistance locus of P. kansuensis in chromosome 2. Within the mapping region, a deletion in the promoter of one NBS-LRR gene was found to involve the resistance by regulating gene expression. Furthermore, combined with RNA-seq and selective sweeps analysis, we proposed that a deletion in the promoter of one CBF gene was essential for high-altitude adaptation of P. mira through increasing its resistance to low temperature. Conclusions In general, the reference genomes assembled in the study facilitate our understanding of resistance mechanism of perennial fruit crops, and provide valuable resources for future breeding and improvement.

IntroductionThe lack of systematic investigations of arbuscular mycorrhizal fungi (AMF) community composition is an obstacle to AMF biotechnological applications in antimony (Sb)- and arsenic (As)-polluted soil.MethodsMorphological and molecular identification were applied to study the AMF community composition in Sb- and As-contaminated areas, and the main influencing factors of AMF community composition in Sb- and As-contaminated areas were explored.Results(1) A total of 513,546 sequences were obtained, and the majority belonged to Glomeraceae [88.27%, 193 operational taxonomic units (OTUs)], followed by Diversisporaceae, Paraglomeraceae, Acaulosporaceae, Gigasporaceae, and Archaeosporaceae; (2) the affinity between AMF and plants was mainly related to plant species (F = 3.488, p = 0.022 < 0.050), which was not significantly correlated with the total Sb (TSb) and total As (TAs) in soil; (3) the AMF spore density was mainly related to the available nitrogen, available potassium, and total organic carbon; (4) The effect of soil nutrients on AMF community composition (total explanation: 15.36%) was greater than that of soil Sb and As content (total explanation: 5.80%); (5) the effect of TAs on AMF community composition (λ = −0.96) was more drastic than that of TSb (λ = −0.21), and the effect of As on AMF community composition was exacerbated by the interaction between As and phosphorus in the soil; and (6) Diversisporaceae was positively correlated with the TSb and TAs.DiscussionThe potential impact of As on the effective application of mycorrhizal technology should be further considered when applied to the ecological restoration of Sb- and As-contaminated areas.

Offshore Zhoushan sediments are a potential area for shallow gas resources in China, where authigenic pyrite is widely distributed. Pyrite content, size distribution, and morphology are influenced by depositional conditions and are sensitive to environmental changes. This study investigated the authigenic pyrites or gypsums of core JC-1 offshore of Zhoushan. Scanning electron microscopy was used to observe the pyrites and identify various aggregations. Changes in lithology, chlorine content, and stable isotope values of organic matter were analyzed to indicate the evolution of ancient marine, floodplain estuary, tidal flat environments, and shallow marine sedimentary facies. The morphology and microcrystalline structure of these types of pyrites can be divided into spherical framboid aggregates, sub-euhedral aggregates, and microcrystalline euhedral pyrites with different sedimentary facies. Gypsum minerals and the coexistence of pyrite and gypsum were found in the enriched authigenic pyrites at the SMTZs. The sources of sulfate formed by authigenic gypsums may originate from overlying seawater and pyrite oxidation, whereas calcium ions may come from the dissolution of carbonate or calcareous shells caused by local environmental acidification. The various aggregations of pyrites observed may be related to SO4-AOM in different environments. The findings suggest that authigenic gypsums form due to local environmental acidification and that the sources of the formed sulfate may be from overlying seawater and pyrite oxidation. This study provides a new perspective for understanding the responses of different sedimentary environments to sea level rise and climate change.

BackgroundThe main factors responsible for low-grade glioma (LGG)s’ poor prognosis and treatment effectiveness include recurrence and malignant progression. A specific type of programmed cell death, known as anoikis, which is crucial for tumor invasion and metastasis, however, has not yet been investigated in LGGs.MethodsWe downloaded data of 509 samples from the TCGA-LGG cohort, carried out cluster analysis for typing twice on the basis of 19 anoikis-associated genes, and the subtypes were evaluated the differences in clinicopathological and biological features. ESTIMATE and single-sample gene set enrichment analysis were employed to examine the immunological milieu of LGGs, and enrichment analysis was used to look into the underlying biological mechanisms in LGGs. Cox regression analysis and the Least Absolute Shrinkage and Selection Operator regression algorithm were used to create a prediction scoring system. The scoring system was used for classifying LGG into high- and low- anoikis riskscore (anoiS) groups. The impact of the anoiS on the prognosis, standard treatment, and immunotherapy of patients with LGG was assessed using survival analysis and drug sensitivity analysis. Cell experiments were employed for the verification of the differential expression between LGG cells and normal cells of the anoikis gene team that regard CCT5 as the core.ResultsBased on the expression profiles of the 19 anoikis-associated genes, all individuals with LGG were classified into four subtypes and two macrosubtypes. The different macrosubtypes had significantly different biological characteristics, and the anoirgclusterBD subtype manifested a significantly bad prognosis and a high immune level of infiltration. And subsequent secondary genotyping also showed good prognostic discrimination. We further constructed an anoikis scoring system, anoiS. LGG patients having a high anoiS had a worse prognosis in comparison to those having a low anoiS. The high anoiS group exhibited larger levels of immune infiltration and superior immunotherapy efficacy than the low anoiS group. The high anoiS group was also more susceptible to temozolomide (TMZ) than the low anoiS group, according to a drug sensitivity analysis of TMZ.ConclusionThis study constructed a scoring system for predicting the prognosis of patients with LGG and their responsive to TMZ and immunotherapy.

BackgroundAbnormalities in centrosome regulatory genes can induce chromosome instability, cell differentiation errors, and tumorigenesis. However, a limited number of comprehensive analyses of centrosome-related genes have been performed in low-grade gliomas (LGG).MethodsLGG data were extracted from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases. The ConsensusClusterPlus” R package was used for unsupervised clustering. We constructed a centrosome-related genes (CRGs) signature using a random forest model, lasso Cox model, and multivariate Cox model, and quantified the centrosome-related risk score (centS). The prognostic prediction efficacy of centS was evaluated using a Receiver Operating Characteristic (ROC) curve. Immune cell infiltration and genomic mutational landscapes were evaluated using the ESTIMATE algorithm, single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm, and “maftools” R package, respectively. Differences in clinical features, isocitrate dehydrogenase (IDH) mutation, 1p19q codeletion, O6-methylguanine-DNA methyltransferase promoter (MGMTp) methylation, and response to antitumor therapy between the high- and low-centS groups were explored. “pRRophetic” R packages were used for temozolomide (TMZ) sensitivity analysis. qRT-PCR verified the differential expression of the centrosomal gene team, the core of which is CEP135, between LGG cells and normal cells.ResultsTwo distinct CRG-based clusters were identified using consensus unsupervised clustering analysis. The prognosis, biological characteristics, and immune cell infiltration of the two clusters differed significantly. A well-performing centS signature was developed to predict the prognosis of patients with LGG based on 12 potential CRGs. We found that patients in the high-centS group showed poorer prognosis and lower proportion of IDH mutation and 1p19q codeletion compared to those in the low-centS group. Furthermore, patients in the high-centS group showed higher sensitivity to TMZ, higher tumor mutation burden, and immune cell infiltration. Finally, we identified a centrosomal gene team whose core was CEP135, and verified their differential expression between LGG cells and normal glial cells.ConclusionOur findings reveal a novel centrosome-related signature for predicting the prognosis and therapeutic responsiveness of patients with LGG. This may be helpful for the accurate clinical treatment of LGG.

IntroductionInnate lymphoid cells (ILCs) are key components of the immune system, yet the similarity and distinction of the properties across tissues under homeostasis, inflammation and tumor process remain elusive.MethodsHere we performed integrative inference of ILCs to reveal their transcriptional profiles and heterogeneity from single-cell genomics. We collected a large number of ILCs from human six different tissues which can represent unique immune niches (circulation, lymphoid tissue, normal and inflamed mucosa, tumor microenvironment), to systematically address the transcriptional imprinting.ResultsILCs are profoundly imprinted by their organ of residence, and tissue-specific distinctions are apparent under pathological conditions. In the hepatocellular carcinoma microenvironment, we identified intermediate c-kit+ ILC2 population, and lin-CD127- NK-like cells that expressed markers of cytotoxicity including CCL5 and IFNG. Additionally, CD127+CD94+ ILC1s were preferentially enriched in inflamed ileum from patients with Crohn’s disease.DiscussionThese analyses depicted a comprehensive characterization of ILC anatomical distribution and subset heterogeneity, and provided a base line for future temporal or spatial studies focused on tissue-specific ILC-mediated immunity.

Graphene is known to display a number of attractive mechanical properties. Here, anisotropy in the fracture toughness of graphene is investigated by in-situ mechanical testing, revealing weak anisotropy between armchair and zigzag directions.

Abstract Background Circular RNAs (circRNAs) have important functions in many fields of cancer biology. In particular, we previously reported that the oncogenic circRNA, circPRMT5, has a major role in bladder cancer progression. Therapy based on circRNAs have good prospects as anticancer strategies. While anti-circRNAs are emerging as therapeutics, the specific in vivo delivery of anti-circRNAs into cancer cells has not been reported and remains challenging. Methods Synthesized chrysotile nanotubes (SCNTs) with a relatively uniform length (~ 200 nm) have been designed to deliver an siRNA against the oncogenic circPRMT5 (si-circPRMT5) inhibit circPRMT5. In addition, the antitumor effects and safety evaluation of SCNTs/si-circPRMT5 was assessed with a series of in vitro and in vivo assays. Results The results showed that SCNTs/si-circPRMT5 nanomaterials prolong si-circPRMT5’s half-life in circulation, enhance its specific uptake by tumor cells, and maximize the silencing efficiency of circPRMT5. In vitro, SCNTs encapsulating si-circPRMT5 could inhibit bladder cancer cell growth and progression. In vivo, SCNTs/si-circPRMT5 inhibited growth and metastasis in three bladder tumor models (a subcutaneous model, a tail vein injection lung metastatic model, and an in situ model) without obvious toxicities. Mechanistic study showed that SCNTs/si-circPRMT5 regulated the miR-30c/SNAIL1/E-cadherin axis, inhibiting bladder cancer growth and progression. Conclusion The results highlight the potential therapeutic utility of SCNTs/si-circPRMT5 to deliver si-circPRMT5 to treat bladder cancer.

Abstract The wireless power transfer (WPT) system has been widely used in various fields such as household appliances, electric vehicle charging and sensor applications. A frequency reconfigurable magnetic resonant coupling wireless power transfer (MRCWPT) system with dynamically enhanced efficiency by using the frequency reconfigurable metamaterial is proposed in this paper. The reconfigurability is achieved by adjusting the capacitance value of the adjustable capacitor connected in the coil of the system. Finite element simulation results have shown that the frequency reconfigurable electromagnetic metamaterial can manipulate the direction of the electromagnetic field of the system due to its abnormal effective permeability. The ultra-thin frequency reconfigurable metamaterial is designed at different working frequencies of 14.1 MHz, 15 MHz, 16.2 MHz, 17.5 MHz, 19.3 MHz, 21.7 MHz and 25 MHz to enhance the magnetic field and power transfer efficiency (PTE) of the system. Frequency reconfigurable mechanism of the system with the frequency reconfigurable metamaterial is derived by the equivalent circuit theory. Finally, further measurement which verifies the simulation by reasonable agreement is carried out. PTE of the system by adding the metamaterial are 59%, 73%, 67%, 66%, 65%, 60% and 58% at different working frequencies. PTE of the system with and without the metamaterial is 72% and 49% at the distance of 120 mm and the frequency of 15 MHz, respectively.

In multilayer filter design, both the parasitic effects and the lack of fine-tunings may result in the error of component values, which has great influences on performance. In this paper, a design technique for multilayer filter composed of LC resonators is proposed. With this technique, influences of the error of component values may be reduced and the design procedure may be simplified. An elliptic filter composed of four LC resonators is used to demonstrate the proposed technique. Three experimental prototypes with different component values were fabricated for comparisons. Very good agreements between measured responses and designed responses can be observed. The measured parasitic resonances are higher than the third harmonic frequency. These facts show the effectiveness of the proposed technique.