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Abstract Runoff and evapotranspiration (ET) are pivotal constituents of the water, energy, and carbon cycles. This research presents a 5-km monthly gridded runoff and ET dataset for 1998–2017, encompassing seven headwaters of Tibetan Plateau rivers (Yellow, Yangtze, Mekong, Salween, Brahmaputra, Ganges, and Indus) (hereinafter TPRED). The dataset was generated using the advanced cryosphere-hydrology model WEB-DHM, yielding a Nash coefficient ranging from 0.77 to 0.93 when compared to the observed discharges. The findings indicate that TPRED’s monthly runoff notably outperforms existing datasets in capturing hydrological patterns, as evidenced by robust metrics such as the correlation coefficient (CC) (0.944–0.995), Bias (−0.68-0.53), and Root Mean Square Error (5.50–15.59 mm). Additionally, TPRED’s monthly ET estimates closely align with expected seasonal fluctuations, as reflected by a CC ranging from 0.94 to 0.98 when contrasted with alternative ET products. Furthermore, TPRED’s annual values exhibit commendable concordance with operational products across multiple dimensions. Ultimately, the TPRED will have great application on hydrometeorology, carbon transport, water management, hydrological modeling, and sustainable development of water resources.

Abstract Although bone dehiscence may occur during orthodontic tooth movement into the narrow alveolar ridge, a non-invasive prevention method is yet to be fully established. We show for the first time prevention of bone dehiscence associated with orthodontic tooth movement by prophylactic injection of bone anabolic agents in mice. In this study, we established a bone dehiscence mouse model by applying force application and used the granular type of scaffold materials encapsulated with bone morphogenetic protein (BMP)-2 and OP3-4, the receptor activator of NF-κB ligand (RANKL)-binding peptide, for the prophylactic injection to the alveolar bone. In vivo micro-computed tomography revealed bone dehiscence with decreased buccal alveolar bone thickness and height after force application, whereas no bone dehiscence was observed with the prophylactic injection after force application, and alveolar bone thickness and height were kept at similar levels as those in the control group. Bone histomorphometry analyses revealed that both bone formation and resorption parameters were significantly higher in the injection with force application group than in the force application without the prophylactic injection group. These findings suggest that the prophylactic local delivery of bone anabolic reagents can prevent bone dehiscence with increased bone remodelling activity.

Abstract Obesity is accompanied by multiple known health risks and increased morbidity, and obese men display reduced reproductive health. However, the impact of obesity on the testes at the molecular levels remain inadequately explored. This is partially attributed to the lack of monitoring tools for tracking alterations within cell clusters in testes associated with obesity. Here, we utilized single-cell RNA sequencing to analyze over 70,000 cells from testes of obese and lean mice, and to study changes related to obesity in non-spermatogenic cells and spermatogenesis. The Testicular Library encompasses all non-spermatogenic cells and spermatogenic cells spanning from spermatogonia to spermatozoa, which will significantly aid in characterizing alterations in cellular niches and the testicular microenvironment during high-fat diet (HFD)-induced obesity. This comprehensive dataset is indispensable for studying how HFD disrupts cell-cell communication networks within the testis and impacts alterations in the testicular microenvironment that regulate spermatogenesis. Being the inaugural dataset of single-cell RNA-seq in the testes of diet-induced obese (DIO) mice, this holds the potential to offer innovative insights and directions in the realm of single-cell transcriptomics concerning male reproductive injury associated with HFD.

Abstract Oral poisoning can trigger diverse physiological reactions, determined by the toxic substance involved. One such consequence is hyperchloremia, characterized by an elevated level of chloride in the blood and leads to kidney damage and impairing chloride ion regulation. Here, we conducted a comprehensive genome-wide analysis to investigate genes or proteins linked to hyperchloremia. Our analysis included functional enrichment, protein–protein interactions, gene expression, exploration of molecular pathways, and the identification of potential shared genetic factors contributing to the development of hyperchloremia. Functional enrichment analysis revealed that oral poisoning owing hyperchloremia is associated with 4 proteins e.g. Kelch-like protein 3, Serine/threonine-protein kinase WNK4, Serine/threonine-protein kinase WNK1 and Cullin-3. The protein–protein interaction network revealed Cullin-3 as an exceptional protein, displaying a maximum connection of 18 nodes. Insufficient data from transcriptomic analysis indicates that there are lack of information having direct associations between these proteins and human-related functions to oral poisoning, hyperchloremia, or metabolic acidosis. The metabolic pathway of Cullin-3 protein revealed that the derivative is Sulfonamide which play role in, increasing urine output, and metabolic acidosis resulted in hypertension. Based on molecular docking results analysis it found that Cullin-3 proteins has the lowest binding energies score and being suitable proteins. Moreover, no major variations were observed in unbound Cullin-3 and all three peptide bound complexes shows that all systems remain compact during 50 ns simulations. The results of our study revealed Cullin-3 proteins be a strong foundation for the development of potential drug targets or biomarker for future studies.

Aiming at the problem of uncertainty and complexity of battlefield situation, which leads to the poor accuracy of risk prediction in the process of research and judgment, it is proposed to build a situation-risk model and construct the risk possibility distribution in order to realize the accurate prediction of risk. Firstly, the risk prediction index system is established from the enemy situation, our situation and the battlefield environment situation research and judgment content; secondly, the role of situation information on the risk is analyzed, and the risk model such as exponential, Z-type, tangent and so on is constructed and the risk value interval is calculated; then, based on the fuzzy function constructing method in the possibility theory, and relying on the weighting difference and uncertainty measurement, the risk possibility distribution is constructed within the risk value interval. Finally, an example of a defense mission is used to verify the feasibility and reasonableness of the proposed method by combining the expert system and cloud modeling methods in an experiment. The results show that the proposed method can fully take into account the uncertainty of situational information in risk prediction, which provides an important basis for subsequent planning decision-making.

Similar to other RNA viruses, grass carp reovirus, the causative agent of the hemorrhagic disease, replicates in cytoplasmic viral inclusion bodies (VIBs), orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of GCRV VIBs are poorly understood. This work demonstrates that GCRV manipulates grass carp oxysterol binding protein 1 (named as gcOSBP1) and vesicle-associated membrane protein–associated protein A/B (named as gcVAP-A/B), 3 components of cholesterol transport pathway, to generate VIBs. By siRNA-mediated knockdown, we demonstrate that gcOSBP1 is an essential host factor for GCRV replication. We reveal that the nonstructural proteins NS80 and NS38 of GCRV interact with gcOSBP1, and that the gcOSBP1 is recruited by NS38 and NS80 for promoting the generation of VIBs. gcOSBP1 increases the expression of gcVAP-A/B and promotes the accumulation of intracellular cholesterol. gcOSBP1 also interacts with gcVAP-A/B for forming gcOSBP1-gcVAP-A/B complexes, which contribute to enhance the accumulation of intracellular cholesterol and gcOSBP1-mediated generation of VIBs. Inhibiting cholesterol accumulation by lovastatin can completely abolish the effects of gcOSBP1 and/or gcVAP-A/B in promoting GCRV infection, suggesting that cholesterol accumulation is vital for gcOSBP1- and/or gcVAP-A/B-mediated GCRV replication. Thus, our results, which highlight that gcOSBP1 functions in the replication of GCRV via its interaction with essential viral proteins for forming VIBs and with host gcVAP-A/B, provide key molecular targets for obtaining anti-hemorrhagic disease grass carp via gene editing technology.

Abstract Background Deep venous thrombosis (DVT) is the common clinical cardiovascular disease, and easily develops into post-thrombotic syndrome (PTS). The study aimed to examine the clinical value of long non-coding RNA NORAD gene in the development of DVT and PTS. In vitro, the underlying mechanism was explored. Methods Serum levels of lncRNA NORAD gene in 85 DVT cases and 85 healthy individuals were tested. The role of lncRNA NORAD gene in human umbilical vein endothelial cells (HUVECs) proliferation, migration and inflammation was examined. The candidate downstream target gene was predicted via bioinformatic analysis. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were done for the function annotation and pathway enrichment. Results LncRNA NORAD gene was at high expression in the serum of DVT patients, it can distinguish DVT patients from healthy controls with the area under the curve of 0.919. Elevated expression of lncRNA NORAD gene in PTS patients was detected, DVT cases with high expression of lncRNA NORAD gene were more susceptible to PTS. LncRNA NORAD gene knockdown promoted HUVECs’ proliferation, migration while suppressing cell apoptosis and inflammation. MiR-93-5p served as a target of lncRNA NORAD gene, and its overexpression reversed the role of lncRNA NORAD gene in the biological function of HUVECs. The target genes of miR-93-5p were enriched in HIF-1 signaling, TGF-beta signaling and PI3K-Akt signaling, protein-protein interaction (PPI) network indicated STAT3, MAPK1 to be the key targets. Conclusions Upregulation of expression of lncRNA NORAD gene was a potential diagnostic biomarker for DVT and related to the development of PTS. LncRNA NORAD/miR-93-5p axis was involved in the progress of DVT through regulating endothelial cell function.

Objective: To investigate the effects of a high-fat diet (HFD) on the gut bacterium Roseburia intestinalis and butyric acid levels, and to assess their impact on ovarian function and epigenetic markers in mice. Methods: A total of 20 female ICR mice aged 4 weeks were randomly assigned to two groups and fed either a control diet (CD) or an HFD for 36 weeks. Post-intervention, ileal contents were analyzed for the quantification of butyric acid using ELISA, while feces were obtained for Roseburia intestinalis expression assessment via qPCR. Histological evaluations of intestinal and ovarian tissues included H&E and Alcian Blue-Periodic Acid Schiff (AB-PAS) staining, alongside immunohistochemical analysis for F4/80, and immunofluorescent detection of Occludin, ZO-1, 5 mC, and H3K36me3. Ovarian health was assessed through follicle counts and morphological evaluations. Statistical analyses were performed using GraphPad Prism 8.0, with P

ABSTRACT The unexpected foodborne outbreak in Singapore in 2015 has accentuated Group B Streptococcus (GBS, Streptococcus agalactiae) sequence type 283 as an emerging foodborne pathogen transmitted via the consumption of contaminated raw freshwater fish. Isolation-based workflows utilizing conventional microbiological and whole-genome sequencing methods are commonly used to support biosurveillance efforts critical for the control management of this emerging foodborne pathogen. However, these isolation-based workflows tend to have relatively long turnaround times that hamper a timely response for implementing risk mitigation. To address this gap, we have developed a metagenomics-based workflow for the simultaneous detection and genomic characterization of GBS in raw freshwater fish. Notably, our validation results showed that this metagenomics-based workflow could achieve comparable accuracy and potentially better detection limits while halving the turnaround time (from 2 weeks to 5 days) relative to an isolation-based workflow. The metagenomics-based workflow was also successfully adapted for use on a portable long-read nanopore sequencer, demonstrating its potential applicability for real-time point-of-need testing. Using GBS in freshwater fish as an example, this work represents a proof-of-concept study that supports the feasibility and validity of metagenomics as a rapid and accurate test methodology for the detection and genomic characterization of foodborne pathogens in complex food matrices.IMPORTANCEThe need for a rapid and accurate food microbiological testing method is apparent for a timely and effective foodborne outbreak response. This is particularly relevant for emerging foodborne pathogens such as Group B Streptococcus (GBS) whose associated food safety risk might be undercharacterized. By using GBS in raw freshwater fish as a case example, this study describes the development of a metagenomics-based workflow for rapid food microbiological safety testing and surveillance. This study can inform as a working model for various foodborne pathogens in other complex food matrices, paving the way for future methodological development of metagenomics for food microbiological safety testing.

Abstract The prevalence of infertility caused by endometrial defects is steadily increasing, posing a significant challenge to women's reproductive health. In this study, injectable “homing‐like” bioactive decellularized extracellular matrix short‐fibers (DEFs) of porcine skin origin are innovatively designed for endometrial and fertility restoration. The DEFs can effectively bind to endometrial cells through noncovalent dipole interactions and release bioactive growth factors in situ. In vitro, the DEFs effectively attracted endometrial cells through the “homing‐like” effect, enabling cell adhesion, spreading, and proliferation on their surface. Furthermore, the DEFs effectively facilitated the proliferation and angiogenesis of human primary endometrial stromal cells (HESCs) and human umbilical vein endothelial cells (HUVECs), and inhibited fibrosis of pretreated HESCs. In vivo, the DEFs significantly accelerated endometrial restoration, angiogenesis, and receptivity. Notably, the deposition of endometrial collagen decreased from 41.19 ± 2.16% to 14.15 ± 1.70% with DEFs treatment. Most importantly, in endometrium‐injured rats, the use of DEFs increased the live birth rate from 30% to an impressive 90%, and the number and development of live births close to normal rats. The injectable “homing‐like” bioactive DEFs system can achieve efficient live births and intrauterine injection of DEFs provides a new promising clinical strategy for endometrial factor infertility.

PurposeThe prevalence of comorbid pain and Bipolar Disorder in clinical practice continues to be high, with an increasing number of related publications. However, no study has used bibliometric methods to analyze the research progress and knowledge structure in this field. Our research is dedicated to systematically exploring the global trends and focal points in scientific research on pain comorbidity with bipolar disorder from 2003 to 2023, with the goal of contributing to the field.MethodsRelevant publications in this field were retrieved from the Web of Science core collection database (WOSSCC). And we used VOSviewer, CiteSpace, and the R package “Bibliometrix” for bibliometric analysis.ResultsA total of 485 publications (including 360 articles and 125 reviews) from 66 countries, 1019 institutions, were included in this study. Univ Toront and Kings Coll London are the leading research institutions in this field. J Affect Disorders contributed the largest number of articles, and is the most co-cited journal. Of the 2,537 scholars who participated in the study, Stubbs B, Vancampfort D, and Abdin E had the largest number of articles. Stubbs B is the most co-cited author. “chronic pain,” “neuropathic pain,” “psychological pain” are the keywords in the research.ConclusionThis is the first bibliometric analysis of pain-related bipolar disorder. There is growing interest in the area of pain and comorbid bipolar disorder. Focusing on different types of pain in bipolar disorder and emphasizing pain management in bipolar disorder are research hotspots and future trends. The study of pain related bipolar disorder still has significant potential for development, and we look forward to more high-quality research in the future.

Purpose: To evaluate the feasibility of rib fracture detection in low-dose computed tomography (CT) images with a RetinaNet-based approach and to evaluate the potential of lowdose CT for rib fracture detection compared with regular-dose CT images. Materials and methods: The RetinaNet-based deep learning model was trained using 7300 scans with 50,410 rib fractures that were used as internal training datasets from four multicenter. The external test datasets consisted of both regular-dose and low-dose chest-abdomen CT images of rib fractures; the MICCAI 2020 RibFrac Challenge Dataset was used as the public dataset. Radiologists' interpretations were used as reference standards. The performance of the model in rib fracture detection was compared with the radiologists’ interpretation. Results: In total, 728 traumatic rib fractures of 100 patients [60 men (60 %); mean age, 53.45 ± 11.19 (standard deviation (SD)); range, 18–77 years] were assessed in the external datasets. In these patients, the regular-dose group had a mean CT dose index volume (CTDIvol) of 7.18 mGy (SD: 2.22) and a mean dose length product (DLP) of 305.38 mGy cm (SD: 95.31); the low-dose group had a mean CTDIvol of 2.79 mGy (SD: 1.11) and a mean DLP of 131.52 mGy cm (SD: 55.58). The sensitivity of the RetinaNet-based model and that of the radiologists was 0.859 and 0.721 in the low-dose CT images and 0.886 and 0.794 in the regular-dose CT images, respectively. Conclusions: These findings indicate that the RetinaNet-based model can detect rib fractures in low-dose CT images with a robust performance, indicating its feasibility in assisting radiologists with rib fracture diagnosis.

Objective: Bendamustine was approved for treating chronic lymphocytic leukemia and indolent B-cell non-Hodgkin lymphoma. Despite its therapeutic benefits, the long-term safety of bendamustine in a large population remains inadequately understood. This study evaluates the adverse events (AEs) associated with bendamustine, using a real-world pharmacovigilance database to support its clinical application.Methods: We conducted a post-marketing risk analysis to assess the association between bendamustine and its AEs. Data were extracted from the US FDA’s Adverse Event Reporting System (FAERS), covering the period from January 2017 to September 2023. The characteristics of bendamustine-associated AEs and the onset time were further analyzed. Statistical analysis was performed using MYSQL 8.0, Navicat Premium 15, Microsoft EXCEL 2016, and Minitab 21.0.Results: 9,461,874 reports were collected from the FAERS database, 9,131 identified bendamustine as the “primary suspected” drug. We identified 331 significant disproportionality preferred terms (PTs). Common AEs included pyrexia, neutropenia, infusion site reaction, progressive multifocal leukoencephalopathy (PML), injection site vasculitis, and pneumonia—all documented on bendamustine’s label. Notably, 16 unexpected and significant AEs were discovered, including hypogammaglobulinemia, which is concerning due to its potential to increase infection susceptibility following bendamustine treatment. Other significant findings were anaphylactic reactions, PML, and cutaneous malignancies, suggesting updates to the drug’s label may be necessary. Physicians should monitor for neurological and skin changes in patients and discontinue treatment if PML is suspected. Moreover, the median onset time for bendamustine-associated AEs was 13 days, with an interquartile range [IQR] of 0–59 days, predominantly occurring on the first day post-initiation. The β of bendamustine-related AEs suggested risk reduction over time.Conclusion: Our study uncovered some potential pharmacovigilance signals for bendamustine, providing important insights for its safe and effective clinical use.

Abstract Background Anterior column realignment (ACR) is a novel surgical method for correcting spinal sagittal balance. meanwhile, oblique lumbar interbody fusion (OLIF) and anterior lumbar interbody fusion (ALIF) are considered minimally invasive surgical methods through natural anatomical space. This study aimed to explore the corrective effects and clinical outcomes of OLIF or ALIF combined with ACR technology in patients with adult spinal deformity (ASD). Methods We retrospectively analyzed patients with sagittal imbalance who received OLIF and/or ALIF and ACR treatment from 2018 to 2021. Surgical time and intraoperative bleeding volume are recorded, the corrective effect is determined by the intervertebral space angle (IVA), lumbar lordosis (LL), the sagittal vertical axis (SVA), clinical outcome is evaluated by preoperative and final follow-up visual analog pain score (VAS), Japanese orthopedic association scores (JOA) and complications. Results Sixty-four patients were enrolled in the study, average age of 65.1(range, 47–82) years. All patients completed 173 fusion segments, for 150 segments of ACR surgery. The operation time of ALIF-ACR was 50.4 ± 22.1 min; The intraoperative bleeding volume was 50.2 ± 23.6 ml. The operation time and intraoperative bleeding volume of single-segment OLIF-ACR was 66.2 ± 19.4 min and 70.2 ± 31.6 ml. At the follow-up of 6 months after surgery, the intervertebral space angle correction for OLIF-ACR and ALIF-ACR is 9.2° and 12.2°, the preoperative and postoperative lumbar lordosis were 16.7° ± 6.4°and 47.1° ± 3.6° (p

To improve the processing efficiency and extend the tuning range of 3D isotropic fabrication, we apply the simultaneous spatiotemporal focusing (SSTF) technique to a high-repetition-rate femtosecond (fs) fiber laser system. In the SSTF scheme, we propose a pulse compensation scheme for the fiber laser with a narrow spectral bandwidth by building an extra-cavity pulse stretcher. We further demonstrate truly 3D isotropic microfabrication in photosensitive glass with a tunable resolution ranging from 8 µm to 22 µm using the SSTF of fs laser pulses. Moreover, we systematically investigate the influences of pulse energy, writing speed, processing depth, and spherical aberration on the fabrication resolution. As a proof-of-concept demonstration, the SSTF scheme was further employed for the fs laser-assisted etching of complicated glass microfluidic structures with 3D uniform sizes. The developed technique can be extended to many applications such as advanced photonics, 3D biomimetic printing, micro-electromechanical systems, and lab-on-a-chips.

Abstract Background There are limited real-world data regarding the use of droperidol for antiemetic prophylaxis in intravenous patient-controlled analgesia (IV-PCA). This study aimed to evaluate the antiemetic benefits and sedation effects of droperidol in morphine-based IV-PCA. Methods Patients who underwent major surgery and used morphine-based IV-PCA at a medical center from January 2020 to November 2022 were retrospectively analyzed. The primary outcome was the rate of any postoperative nausea and/or vomiting (PONV) within 72 h after surgery. Propensity score matching was used to match patients with and without the addition of droperidol to IV-PCA infusate in a 1:1 ratio. Multivariable conditional logistic regression models were used to calculate adjusted odds ratios (aORs) with 95% confidence intervals (CIs). Results After matching, 1,104 subjects were included for analysis. The addition of droperidol to IV-PCA reduced the risk of PONV (aOR: 0.49, 95% CI: 0.35–0.67, p

Polarization (P), angular index (l), and radius index (p) are three independent degrees of freedom (DoFs) of vector vortex beams, which have found extensive applications in various domains. While efficient sorting of a single DoF has been achieved successfully, simultaneous sorting of all these DoFs in a compact and efficient manner remains a challenge. In this study, we propose a beam sorter that simultaneously handles all the three DoFs using a diffractive deep neural network (D2NN), and demonstrate the robust sorting of 120 Laguerre–Gaussian (LG) modes experimentally in the visible spectrum. Our proposed beam sorter underscores the considerable potential of D2NN in optical field manipulation and promises to enhance the diverse applications of vector vortex beams.

Abstract Obstructive sleep apnoea (OSA)-induced chronic intermittent hypoxia (CIH) has been considered a risk factor for severe asthma. Airway remodelling, which could be modulated by autophagy, plays a key role in severe asthma. However, the extent of autophagy’s involvement in CIH-potentiated airway remodelling remains largely unexplored. Furthermore, we had found that angiotensin-(1-7) [Ang-(1-7)] has therapeutic effects on airway remodelling in asthma, but the underlying mechanism is either unclear. This study aimed to explore how CIH aggravates asthma and mechanism of protective effects of Ang-(1-7) on airway remodelling, with a focus on autophagy. We observed that CIH promoted epithelial-to-mesenchymal transition (EMT), indicated by elevated EMT and fibrotic markers such as Snail and Collagen IV, both in vitro and in vivo. CIH intensified cell autophagy, evident from increased LC3B expression and reduced p62 levels. Ang-(1-7) reversed the CIH-enhanced expression of Snail, Collagen IV, and LC3B. To explore how CIH enhanced autophagy in cellular and animal model of asthma, overexpression of hypoxia-inducible factor 1-alpha (HIF-1α) and Thrombospondin 1 (THBS1) were identified in CIH-exposure mice lung compared with normal mice lung tissues from the GEO database. Finally, through chromatin immunoprecipitation and immunoprecipitation assays, we verified that Ang-(1-7) inhibits CIH-induced binding of HIF-1α to the promoter of THBS1, and also disrupts the protein-protein interaction between THBS1 and the autophagy-associated protein Beclin 1 (BECN1), ultimately leading to autophagy inhibition. Our findings suggest that exogenous Ang-(1-7) can inhibit autophagy via HIF-1α/THBS1/BECN1 axis, thereby alleviating CIH-enhanced airway remodelling in asthma. These findings imply the potential therapeutic effect of Ang-(1-7) in asthma with OSA.

The deposition of micron particles in gas pipelines has always been an important problem in ultra-clean ventilation technology in the modern laser fusion, precision electronics, aerospace, and biomedical fields. Combining the mathematical expression of the migration, collision, and deposition of micron particles in a gas pipeline with a simulation of flow fields, a two-parameter particle probability deposition model based on vinl, θcr and collision probability coefficient PP is established, and the distribution law of particle deposition, considering two deposition targets of the pipe wall and deposition layer, is given. Combined with an experiment on particle migration and deposition in a gas pipeline, an interpretation and verification of the particle deposition distribution law are given, and the difference between the model and experiment is discussed through particle deposition efficiency mass distribution. Studies have shown the following: Under the premise of two kinds of deposition targets, different particle sizes in the gas pipeline present different deposition laws; the deposit morphology is a spot deposit of 10 µm particles and a flake deposit of 40 µm particles; the deposit position shows a uniform distribution and a lower wall dominance; and the deposit concentration area of 40 µm shows a more significant distribution. The results are very important for the selection and optimization of gas pipelines for clean spaces.

Introduction: Gastric Cancer (GC) refers to a prevalent malignant cancer accompanied by a weak prognosis. The APOBEC3 family genes and lncRNAs are linked with cancer progression. Nevertheless, there is still a scarcity of data concerning the prognostic value of APOBEC3-related lncRNAs in GC. Methods: We extracted the data from GC samples, including transcriptome as well as clinical data, obtained from the TCGA database. Then, we screened for lncRNAs that were correlated with the APOBEC3 family genes and constructed an APOBEC3-related lncRNA prognostic signature (LPS) by utilizing univariate Cox and lasso regression analysis. Furthermore, we validated our constructed signature and evaluated it thoroughly, including analysis of its function, immunity, mutations, and clinical applications via multiple methods, including Metascape, GSEA, and analyses including TIC and TME, immune checkpoints, CNV and SNPs, Kaplan-Meier survival curves, nomogram, decision tree and drug prediction analysis. Finally, we overexpressed LINC01094 to evaluate the impacts on the proliferation as well as migration with regards to KATO-2 cells. Results: We selected eight lncRNAs for our APOBEC3-related LPS, which is demonstrated as a valuable tool in predicting the individual GC patients’ prognosis. Subsequently, we segregated the samples into subgroups of high-as well as low-risk relying on the risk score with regards to APOBEC3-related LPS. By performing functional analysis, we have shown that immune-as well as tumor-related pathways were enriched in high- and low-risk GC patients. Furthermore, immune analysis revealed a robust correlation between the APOBEC3-related LPS and immunity. We found that immune checkpoints were significantly associated with the APOBEC3-related LPS and were greatly exhibited in GC tumor and high-risk samples. Mutational analysis suggested that the mutational rate was greater in low-risk samples. Furthermore, we predicted small molecular drugs displayed greater sensitivity in patients categorized as high-risk. Moreover, the immune response was also better in high-risk patients. Of these drugs, dasatinib was significant in both methods and might be considered a potential novel drug for treating high-risk GC patients. Finally, we found that LINC01094 has the potential to enhance the migration, proliferation as well as inhibit apoptosis of KATO-2 in GC cells. And Dasatinib has an inhibitory effect on the migration as well as proliferation in GC cells. Conclusion: We created a novel APOBEC3-related LPS in predicting the prognosis with regards to individual GC patients. Importantly, this APOBEC3-related LPS was closely associated with immunity and might guide clinical treatment.

BackgroundThe persistence of symptoms or the development of new symptoms following a diagnosis of SARS-CoV-2 has given rise to a multifaceted clinical condition referred to as “long COVID” (LC). The understanding of LC among China’s non-hospitalized population continues to be insufficient. This investigation was designed to evaluate the protracted consequences amongst this demographic, as well as to identify the associated risk factors.MethodsThis research constitutes a prospective cohort study focusing on non-hospitalized individuals, aged between 18 and 59, who have been positively diagnosed with COVID-19. Each participant was subjected to a sequence of questionnaire-based surveys, designed to evaluate symptoms as well as the status of depression and anxiety. A logistic regression model, adjusted for multiple variables, was employed to scrutinize the correlation between demographic elements, lifestyle attributes, and health-related risk factors in relation to conditions and symptoms post COVID-19 infection.ResultsA total of 706 individuals participated in the 3 months follow-up, with 620 continuing on to the 6 months follow-up. The median age was 35 (28, 43) years, and 597 (85%) are female. Upon follow-up, Compared with patients without LC, patients with LC have a higher proportion of females (420 (87%) vs. 177 (79%); p = 0.010), were older (35 (29, 44) years vs. 33 (27, 41) years; p = 0.010) and have more comorbidities. Out of all participants, 483 (68.4%) reported experiencing at least one symptom at the 3 months mark, while 49.7% reported symptoms persisting at the 6 months mark. At the 3 months follow-up, the most prevalent persistent symptoms were cough (46%), fatigue (38%), and shortness of breath (34%). By the 6 months follow-up, fatigue (25%), shortness of breath (22%), and sleep disorders (16%) were the most commonly reported symptoms. Anxiety and depression were consistently reported as prevalent symptoms throughout the follow-up period. Most patient symptoms fade over time, with the quickest decreases observed in cough (from 46 to 9%), expectoration (from 26 to 6.3%), smell disorder (from 16 to 3.9%), and taste disorder (from 18 to 3.5%). Male and those possessing advanced educational qualifications exhibit a decreased susceptibility to the sustained incidence of coughing. Conversely, older age and the presence of comorbidities were identified as risk factors for persistent fatigue and shortness of breath.ConclusionIn the after of COVID-19, it has been observed that the majority of patient symptoms tend to decrease over time. The primary residual symptoms noticed after a 6 month follow-up were fatigue, dyspnea, and sleep disturbances. However, it’s noteworthy that the risk factors associated with these symptoms exhibit subtle variations. Furthermore, psychological sequelae, namely depression and anxiety, are frequently reported among COVID-19 survivors.

In this paper, through the collection and analysis of data, the art of Guangling paper-cutting is theoretically researched, and the general features and shapes of Guangling paper-cutting are summarized. In order to overcome the limitations of traditional algorithms in the extraction of features of Guangling paper-cutting, the combination of spatial pyramid matching and context-dependent histogram methods are used to extract the shape features of paper-cutting images with stronger differentiation. The support vector machine is used to solve the problem of recognizing and classifying the image patterns in the digitized display. The design of the digital promotion of the Shanxi Guangling paper-cutting brand is carried out. Research variables are designed to analyze the effect of digital transformation and promotion of paper-cutting brands. The results show that the discrepancy of Guangling paper-cutting features extracted by the algorithm in this paper is very low, the e1 difference is maintained within 0.1, and the total recognition rate of SVM on Guangling paper-cutting features can reach 88.06%, and the overall effect is more satisfactory, and the regression equation of the influence of paper-cutting = −0.807+0.111*history+0.122* style+0.234*paper-cutting+0.216*display+0.136 * linkage, and propose strategies to enhance the influence of paper-cutting brand. The technical methods used in this study guarantee the quality of the digital transformation of Guangdong paper-cutting from the source.

Aims: Autophagy plays a significant role in the development of acute myocardial infarction (AMI), and cardiomyocyte autophagy is of major importance in maintaining cardiac function. We aimed to identify key genes associated with autophagy in AMI through bioinformatics analysis and verify them through clinical validation. Materials and Methods: We downloaded an AMI expression profile dataset GSE166780 from Gene Expression Omnibus (GEO). Autophagy-associated genes potentially differentially expressed in AMI were screened using R software. Then, to identify key autophagy-related genes, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, protein-protein interaction (PPI) analysis, Receiver Operating Characteristic (ROC) curve analysis, and correlation analysis were performed on the differentially expressed autophagy-related genes in AMI. Finally, we used quantificational real-time polymerase chain reaction (qRT-PCR) to verify the RNA expression of the screened key genes. Results: TSC2, HSPA8, and HIF1A were screened out as key autophagy-related genes. qRT-PCR results showed that the expression levels of HSPA8 and TSC2 in AMI blood samples were lower, while the expression level of HIF1A was higher than that in the healthy controls. Conclusions: TSC2, HSPA8, and HIF1A were identified as key autophagy-related genes in this study. They may influence the development of AMI through autophagy. These findings may help deepen our understanding of AMI and may be useful for the treatment of AMI.

Color blindness is a retinal disease that mainly manifests as a color vision disorder, characterized by achromatopsia, red-green color blindness, and blue-yellow color blindness. With the development of technology and progress in theory, extensive research has been conducted on the genetic basis of color blindness, and various approaches have been explored for its treatment. This article aims to provide a comprehensive review of recent advances in understanding the pathological mechanism, clinical symptoms, and treatment options for color blindness. Additionally, we discuss the various treatment approaches that have been developed to address color blindness, including gene therapy, pharmacological interventions, and visual aids. Furthermore, we highlight the promising results from clinical trials of these treatments, as well as the ongoing challenges that must be addressed to achieve effective and long-lasting therapeutic outcomes. Overall, this review provides valuable insights into the current state of research on color blindness, with the intention of informing further investigation and development of effective treatments for this disease.

Abstract Programmable metasurfaces present significant capabilities in manipulating electromagnetic waves, making them a promising candidate for simultaneous wireless information and power transfer (SWIPT), which has the potential to enable sustainable wireless communication in complex electromagnetic environments. However, challenges remain in terms of maximum power transmission distance and stable phase manipulation with high-power scattered waves. Additionally, waveform limitations restrict average scattered power and rectifier conversion efficiency, affecting data transmission rates and energy transmission distance. Here we show an amplifying programmable metasurface (APM) and a joint modulation method to address these challenges. The APM mitigates the peak-to-average power ratio and improves maximum power, phase response stability, average output power, and rectifier conversion efficiency. Through experimental validation, we demonstrate the feasibility of the SWIPT system, showcasing simultaneous LED array powering and movie video transmission. This innovative SWIPT system holds promise for diverse applications, including 6 G wireless communications, IoT, implanted devices, and cognitive radio networks.

The performance and reliability of lithium thionyl chloride (Li/SOCl2) batteries are significantly affected by temperature, but the reliability level and failure mechanisms of Li/SOCl2 batteries remain unclear. In this study, Weibull distribution statistics were used to infer the life expectancy of Li/SOCl2 batteries at different temperatures. Additionally, the battery failure mechanism was analyzed using electrochemical impedance spectroscopy (EIS). It is found that under the discharge condition of 7.5 kΩ load, the mean time between failures (MTBF) and reliable life of the battery decreased with increasing operating temperature. Under the discharge condition of 750 Ω load, the MTBF of the battery peaked at 60 °C. Furthermore, the influence of temperature on the voltage output characteristics of Li/SOCl2 batteries and the voltage hysteresis were analyzed. Both the battery output voltage and the hysteresis effect increased with rising temperature. This is because high temperature accelerates internal battery reactions, thus altering the formation process of the passivation film on the lithium metal negative electrode.

Abstract Metastasis involves epithelial‐to‐mesenchymal transition (EMT), a process that is regulated by complex gene networks, where their deliberate disruption may yield a promising outcome. However, little is known about mechanisms that coordinate these metastasis‐associated networks. To address this gap, hub genes with broad engagement across various human cancers by analyzing the transcriptomes of different cancer cell types undergoing EMT are identified. The oncogenic signaling adaptor protein tyrosine 3‐monooxygenase/tryptophan 5‐monooxygenase activation protein gamma (YWHAG) is ranked top for its clinical relevance and impact. The cellular kinome and transcriptome data are surveyed to construct the regulome of YWHAG, revealing stress responses and metabolic processes during cancer EMT. It is demonstrated that a YWHAG‐dependent cytoprotective mechanism in the regulome is embedded in EMT‐associated networks to protect cancer cells from oxidative catastrophe through enhanced autophagy during EMT. YWHAG deficiency results in a rapid accumulation of reactive oxygen species (ROS), delayed EMT, and cell death. Tumor allografts show that metastasis potential and overall survival time are correlated with the YWHAG expression level of cancer cell lines. Metastasized tumors have higher expression of YWHAG and autophagy‐related genes than primary tumors. Silencing YWHAG diminishes primary tumor volumes, prevents metastasis, and prolongs the median survival period of the mice.

Digital metasurfaces define a novel methodology for metasurface designs by adopting discrete coding meta‐atoms to engineer electromagnetic waves in programmable ways. Herein, a novel field‐reorganizable digital metasurface (FRDM) that can be used to enhance the indoor non‐line‐of‐sight (NLOS) millimeter‐wave (mmWave) signal coverage is presented. The passive binary supercells which can be reorganized with an in situ optimization characteristic to deflect the incoming mmWaves into the blind area with adjustable angles are proposed. The indoor L‐shaped corridor signal coverage simulated by the ray‐tracing technique confirms that the NLOS blind area is effectively communicated using the passive FRDM. Practical environment experiments using FRDMs with different coding sequences are conducted, indicating that the averaged signal intensity is increased by over 10 dB in the NLOS blind area in a wide operating frequency band from 26 to 30 GHz by reorganizing the passive digital metasurfaces. The results suggest that the proposed FRDM enabled by the reorganizable binary supercells is a highly flexible, low‐cost, and extensible solution for B5G and 6G mmWave wireless communications.

In order to make direct memory access (DMA) high-speed transmission while ensuring the security and integrity of data, the traditional Secure Hash Algorithm (SHA) is improved from the algorithm model and hardware architecture level by adopting the methods of data synchronization preprocessing and multi-block multi-output, and a dual-channel design with instant data comparison and data error correction functions adapted to high-speed DMA is achieved. The simulation results show that the maximum clock frequency of the DMA controller is 120 MHz and the throughput rate is up to 3.8 Gbps. The improved comparison channel can output the message summary at an interval of 0.56 μs, whereas the traditional algorithm needs to wait five times as long as the data handling time. The error correction channel also implements multi-block output and error block indexing. The results show that the improved dual-channel design based on the SHA algorithm can be highly adapted to DMA controllers and has good application prospects.

Introduction: There is conflicting evidence for the association between antihypertensive medications and colorectal cancer risk, possibly reflecting methodological limitations of previously conducted studies. Here, we aimed to clarify associations between commonly prescribed antihypertensive medication classes and colorectal cancer risk in a large, retrospective, cohort study.Methods: Using linked administrative data between 1996 and 2017 from British Columbia, we identified a cohort of 1,693,297 men and women who were 50 years of age or older, initially cancer-free and nonusers of antihypertensive medications. Medication use was parameterized as ever use, cumulative duration, and cumulative dose. Cox proportional hazard models were used to estimate hazard ratios (HRs) and associated 95% confidence intervals (95% CIs) for associations of time-varying medication use [angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs), beta-blockers (BBs), calcium channel blockers (CCBs), and diuretics] with colorectal cancer risk.Results: There were 28,460 incident cases of colorectal cancer identified over the follow-up period (mean = 12.9 years). When medication use was assessed as ever/never, diuretics were associated with increased risk of colorectal cancer (HR 1.08, 95% CI 1.04–1.12). However, no similar association was observed with cumulative duration or cumulative dose of diuretics. No significant associations between the other four classes of medications and colorectal cancer risk were observed.Conclusion: No compelling evidence of associations between antihypertensive medications and colorectal cancer were observed.

The taxonomic status of the Pieris napi-complex and similar species which occur in China are revised. Relevant species distributed in the adjacent regions were included to clarify the status of Chinese species and were briefly revised. All those species are described and illustrated and new synonyms are established. A molecular phylogenetic analysis is also performed on the species group including similar species, to investigate the phylogenetic relationships between taxa. Species of the Pieris napi-complex that occur in China and adjacent regions are redefined, with four similar species excluded (P. melaina, P. extensa, P. chumbiensis gyantsensis and P. melete). A distribution map and keys of the complex including similar species are provided. The taxon P. mihon Yakovlev, 2006 stat. nov. is raised from subspecies to species status; P. narina Verity, 1908 stat. rev. is confirmed as a distinct species rather than a subspecies of P. ochsenheimeri; Pieris euorientis Verity, 1908 stat. rev. is recovered as a distinct species sister to P. dulcinea. Two taxa, ssp. sauron and ssp. bryonides are moved from subspecies of P. euorientis and P. bryoniae, respectively, to P. napi, i.e. P. napi sauron Yakovlev, 2004 comb. nov and P. napi bryonides Sheljuzhko, 1910 comb. rev. A new synonym is proposed: Pieris ochsenheimeri tianshansis Tadokoro, Shinkawa & Wang, 2014, new synonym of P. mihon Yakovlev, 2006. A new mistaken identification is proposed: Pieris dulcinea kneitzi is a misidentification of Pieris erutae kneitzi Eitschberger, 1983 comb. rev. Five Chinese species belonging to the Pieris napi-complex were confirmed, namely P. narina, P. mihon, P. latouchei, P. dulcinea, and P. erutae. Among them, two species, P. mihon Yakovlev, 2006 and Pieris narina Verity, 1908, are newly recorded from China. The taxonomic status of Pieris steinigeri Eitschberger, 1983 and Pieris bryoniae sifanica Grum-Grshimailo, 1895 is also discussed.

Abstract Background Conventional differential expression (DE) testing compares the grouped mean value of tumour samples to the grouped mean value of the normal samples, and may miss out dysregulated genes in small subgroup of patients. This is especially so for highly heterogeneous cancer like Hepatocellular Carcinoma (HCC). Methods Using multi-region sampled RNA-seq data of 90 patients, we performed patient-specific differential expression testing, together with the patients’ matched adjacent normal samples. Results Comparing the results from conventional DE analysis and patient-specific DE analyses, we show that the conventional DE analysis omits some genes due to high inter-individual variability present in both tumour and normal tissues. Dysregulated genes shared in small subgroup of patients were useful in stratifying patients, and presented differential prognosis. We also showed that the target genes of some of the current targeted agents used in HCC exhibited highly individualistic dysregulation pattern, which may explain the poor response rate. Discussion/conclusion Our results highlight the importance of identifying patient-specific DE genes, with its potential to provide clinically valuable insights into patient subgroups for applications in precision medicine.

The Chinese named entity recognition (NER) is a critical task in natural language processing, aiming at identifying and classifying named entities in text. However, the specificity of domain texts and the lack of large-scale labelled datasets have led to the poor performance of NER methods trained on public domain corpora on domain texts. In this paper, a named entity recognition method incorporating sentence semantic information is proposed, mainly by adaptively incorporating sentence semantic information into character semantic information through an attention mechanism and a gating mechanism to enhance entity feature representation while attenuating the noise generated by irrelevant character information. In addition, to address the lack of large-scale labelled samples, we used data self-augmentation methods to expand the training samples. Furthermore, we introduced a Weighted Strategy considering that the low-quality samples generated by the data self-augmentation process can have a negative impact on the model. Experiments on the TCM prescriptions corpus showed that the F1 values of our method outperformed the comparison methods.

This paper proposes a hybrid current predictive deadbeat tracking control method to address the problem that a conventional deadbeat current tracking control has evolved into a deadbeat control in the digital implementation process. First, the reference current prediction link provides in advance the harmonic compensation reference current at two sampling periods by adopting adaptive forward linear prediction and repetitive prediction algorithms. It realizes the switching between the two current prediction algorithms by setting load dynamic occurrence discriminant conditions. Second, the inverter output current historical and harmonic compensation reference current data is used to predict the output current of the inverter. It can effectively predict the output current of the inverter while considering measurement noise suppression. The problems of the deadbeat control method are its strong mathematics model dependence and weak ability to resist high-frequency interference. Therefore, this study analyzes the robust stability of the control system under the uncertainties of the output filter inductor and equivalent resistance parameters of the active power filter and the measurement noise transmission in the system. Finally, the simulation and experimental results indicate that the proposed method based on hybrid current prediction has a high steady-state compensation accuracy and a fast dynamic response speed under steady-state and load mutation conditions. Thus, the proposed method can still effectively compensate the harmonic current under the condition of uncertain output filter inductor and its equivalent resistance parameters.

Background Combination therapy with radioembolization (yttrium-90)-resin microspheres) followed by nivolumab has shown a promising response rate of 30.6% in a Phase II trial (CA209-678) for advanced hepatocellular carcinoma (HCC); however, the response mechanisms and relevant biomarkers remain unknown.Methods By collecting both pretreatment and on-treatment samples, we performed multimodal profiling of tissue and blood samples and investigated molecular changes associated with favorable responses in 33 patients from the trial.Results We found that higher tumor mutation burden, NCOR1 mutations and higher expression of interferon gamma pathways occurred more frequently in responders. Meanwhile, non-responders tended to be enriched for a novel Asian-specific transcriptomic subtype (Kaya_P2) with a high frequency of chromosome 16 deletions and upregulated cell cycle pathways. Strikingly, unlike other cancer types, we did not observe any association between T-cell populations and treatment response, but tumors from responders had a higher proportion of CXCL9+/CXCR3+ macrophages. Moreover, biomarkers discovered in previous immunotherapy trials were not predictive in the current cohort, suggesting a distinctive molecular landscape associated with differential responses to the combination therapy.Conclusions This study unraveled extensive molecular changes underlying distinctive responses to the novel treatment and pinpointed new directions for harnessing combination therapy in patients with advanced HCC.

ObjectiveTo determine whether the peak serum estradiol (E2) level during ovarian stimulation affects the cumulative live birth rate (CLBR) and obstetric outcomes in freeze-all cycles.MethodsThis retrospective cohort study involved patients who underwent their first cycle of in vitro fertilization followed by a freeze-all strategy and frozen embryo transfer cycles between January 2014 and June 2019 at a tertiary care center. Patients were categorized into four groups according to quartiles of peak serum E2 levels during ovarian stimulation (Q1-Q4). The primary outcome was CLBR. Secondary outcomes included obstetric and neonatal outcomes of singleton and twin pregnancies. Poisson or logistic regression was applied to control for potential confounders for outcome measures, as appropriate. Generalized estimating equations were used to account for multiple cycles from the same patient for the outcome of CLBR.Result(s)A total of 11237 patients were included in the analysis. Cumulatively, live births occurred in 8410 women (74.8%). The live birth rate (LBR) and CLBR improved as quartiles of peak E2 levels increased (49.7%, 52.1%, 54.9%, and 56.4% for LBR; 65.1%, 74.3%, 78.4%, and 81.6% for CLBR, from the lowest to the highest quartile of estradiol levels, respectively, P

Abstract Background and Aim Thiopurines are recommended for maintenance of steroid‐free remission (SFR) in inflammatory bowel disease (IBD). Thiopurine metabolite monitoring (MM) is increasingly used in the West but remains novel in Singapore, with limited information on its therapeutic and economic benefits. Hence, this study aims to investigate MM's clinical utility and its impact on healthcare resource utilization in Singaporean IBD patients. Methods A retrospective observational study was conducted at Singapore General Hospital outpatient IBD Centre. Patients with IBD, baseline MM during 2014–2017, and weight‐based thiopurine doses for ≥4 weeks were followed up for 1 year. Actions were taken to optimize therapy, and metabolite levels before and after the first action were documented. Outcomes assessed included SFR, no therapy escalation or surgery, healthcare resource utilization, and direct healthcare costs. Results Ninety IBD patients (50 Crohn's disease, 40 ulcerative colitis) were included. Among them, 40% had baseline metabolite levels within therapeutic range, 31.1% sub‐therapeutic, 21.1% supra‐therapeutic, and 7.8% shunters. Repeated MM with subsequent dose optimization helped 67.2% of patients achieve therapeutic levels after 1 year. Overall, 87.8% of patients achieved SFR and 90% had no therapy escalation or surgery. Despite greater outpatient visits and laboratory investigations with MM, the median total healthcare costs at 1 year only increased marginally (S$6407.66 [shunters] vs S$5215.20 [supra‐therapeutic] vs S$4970.80 [sub‐therapeutic] vs S$4370.48 [control (within therapeutic range)], P = 0.592). Conclusion MM guided timely therapy escalation for non‐responders, identification of non‐adherence, and reversal of shunting. Therefore, it is a useful clinical tool to optimize thiopurines without significantly increasing healthcare costs.

Introduction: Tri-Generational HomeCare (TriGen) is a student-initiated home visit programme for patients with a key focus on undergraduate interprofessional education (IPE). We sought to validate the Readiness for Interprofessional Learning Scale (RIPLS) and evaluate TriGen’s efficacy by investigating healthcare undergraduates’ attitude towards IPE. Methods: Teams of healthcare undergraduates performed home visits for patients fortnightly over six months, trained by professionals from a regional hospital and a social service organisation. The RIPLS was validated using exploratory factor analysis. Evaluation of TriGen’s efficacy was performed via the administration of the RIPLS pre- and post-intervention, analysis of qualitative survey results and thematic analysis of written feedback. Results: 79.6% of 226 undergraduate participants from 2015-2018 were enrolled. Exploratory factor analysis revealed four factors accounting for 64.9% of total variance. One item loaded poorly and was removed. There was no difference in pre- and post-intervention RIPLS total and subscale scores. 91.6% of respondents agreed they better appreciated the importance of interprofessional collaboration (IPC) in patient care, and 72.8% said MDMs were important for their learning. Thematic analysis revealed takeaways including learning from and teaching one another, understanding one’s own and other healthcare professionals’ role, teamwork, and meeting undergraduates from different faculties. Conclusion: We validated the RIPLS in Singapore and demonstrated the feasibility of an interprofessional, student-initiated home visit programme. While there was no change in RIPLS scores, the qualitative feedback suggests that there are participant-perceived benefits for IPE after undergoing this programme, even with the perceived barriers to IPE. Future programmes can work on addressing these barriers to IPE.

Background & Aims: Lifestyle and environmental-related exposures are important risk factors for hepatocellular carcinoma (HCC), suggesting that epigenetic dysregulation significantly underpins HCC. We profiled 30 surgically resected tumours and the matched adjacent normal tissues to understand the aberrant epigenetic events associated with HCC. Methods: We identified tumour differential enhancers and the associated genes by analysing H3K27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) and Hi-C/HiChIP data from the resected tumour samples of 30 patients with early-stage HCC. This epigenome dataset was analysed with previously reported genome and transcriptome data of the overlapping group of patients from the same cohort. We performed patient-specific differential expression testing using multiregion sequencing data to identify genes that undergo both enhancer and gene expression changes. Based on the genes selected, we identified two patient groups and performed a recurrence-free survival analysis. Results: We observed large-scale changes in the enhancer distribution between HCC tumours and the adjacent normal samples. Many of the gain-in-tumour enhancers showed corresponding upregulation of the associated genes and vice versa, but much of the enhancer and gene expression changes were patient-specific. A subset of the upregulated genes was activated in a subgroup of patients’ tumours. Recurrence-free survival analysis revealed that the patients with a more robust upregulation of those genes showed a worse prognosis. Conclusions: We report the genomic enhancer signature associated with differential prognosis in HCC. Findings that cohere with oncofoetal reprogramming in HCC were underpinned by genome-wide enhancer rewiring. Our results present the epigenetic changes in HCC that offer the rational selection of epigenetic-driven gene targets for therapeutic intervention or disease prognostication in HCC. Impact and Implications: Lifestyle and environmental-related exposures are the important risk factors of hepatocellular carcinoma (HCC), suggesting that tumour-associated epigenetic dysregulations may significantly underpin HCC. We profiled tumour tissues and their matched normal from 30 patients with early-stage HCC to study the dysregulated epigenetic changes associated with HCC. By also analysing the patients’ RNA-seq and clinical data, we found the signature genes – with epigenetic and transcriptomic dysregulation – associated with worse prognosis. Our findings suggest that systemic approaches are needed to consider the surrounding cellular environmental and epigenetic changes in HCC tumours.

BackgroundPrevious clinical randomized controlled trials (RCTs) have demonstrated that immune checkpoint inhibitors (ICIs) cause various toxicities during cancer treatment, but the effects of different inhibitors in combination with chemotherapy for cardiotoxicity remain controversial. The aim of the present study was to assess cardiotoxicity caused by programmed cell death protein 1 (PD-1), programmed cell death-Ligand 1 (PD-L1), and cytotoxic T lymphocyte associate protein-4 (CTLA-4) in combination with chemotherapy to treat lung cancer.MethodsThe following ICIs were included in the present study: durvalumab, avelumab, ipilimumab, atezolizumab, pembrolizumab, cemiplimab, and nivolumab. The relevant information was extracted using a predefined data extraction table, and the risk of bias was assessed in randomized controlled trials using the Cochrane Bias Risk tool. The main outcomes were hypertension, heart failure, pericardial effusion, and other adverse cardiac events. The random effects model was used to conduct a paired meta-analysis, and a random effects network meta-analysis was then performed within a Bayesian framework.ResultsIn total, 17 RCTs were included in the present study. There were 11,063 individuals in the experimental and control groups, with an average age greater than 60 years. Based on the evaluation of all drug classes in RCTs, CTLA-4+chemotherapy (RR, -0.69 [95% CI, 2.91-1.52] and PD-L1 (RR, -0.21 [95% CI, -1.03-0.60]) were less cardiotoxic than the control arm, which indicated they were safer options for adverse cardiac events. PD-L1 alone was less cardiotoxic than PD-1 alone (RR, -0.57 [95% CI, -1.96-0.82]). Further, the dual immunotarget inhibitor, PD-1+CTLA-4, had the lowest SUCRA value and had the highest cardiotoxicity (SUCRA=9).ConclusionWhen classified according to drug type, CTLA-4+chemotherapy is associated with fewer cardiac adverse events compared to other treatments. Dual immunotarget inhibitors are more likely to have adverse cardiac reactions. Therefore, clinicians should consider this evidence when developing an ICI immunotherapy regimen for lung cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier CRD42023360931.

Vascular remodeling is the pathological basis for the development of many cardiovascular diseases. The mechanisms underlying endothelial cell dysfunction, smooth muscle cell phenotypic switching, fibroblast activation, and inflammatory macrophage differentiation during vascular remodeling remain elusive. Mitochondria are highly dynamic organelles. Recent studies showed that mitochondrial fusion and fission play crucial roles in vascular remodeling and that the delicate balance of fusion-fission may be more important than individual processes. In addition, vascular remodeling may also lead to target-organ damage by interfering with the blood supply to major body organs such as the heart, brain, and kidney. The protective effect of mitochondrial dynamics modulators on target-organs has been demonstrated in numerous studies, but whether they can be used for the treatment of related cardiovascular diseases needs to be verified in future clinical studies. Herein, we summarize recent advances regarding mitochondrial dynamics in multiple cells involved in vascular remodeling and associated target-organ damage.

Using information technology to extract emergency decision-making knowledge from emergency plan documents is an essential means to enhance the efficiency and capacity of emergency management. To address the problems of numerous terminologies and complex relationships faced by emergency knowledge extraction of water diversion project, a multi-feature graph convolutional network (PTM-MFGCN) based on pre-trained model is proposed. Initially, through the utilization of random masking of domain-specific terminologies during pre-training, the model's comprehension of the meaning and application of such terminologies within specific fields is enhanced, thereby augmenting the network's proficiency in extracting professional terminologies. Furthermore, by introducing a multi-feature adjacency matrix to capture a broader range of neighboring node information, thereby enhancing the network's ability to handle complex relationships. Lastly, we utilize the PTM-MFGCN to achieve the extraction of emergency entity relationships in water diversion project, thus constructing a knowledge graph for water diversion emergency management. The experimental results demonstrate that PTM-MFGCN exhibits improvements of 2.84% in accuracy, 4.87% in recall, and 5.18% in F1 score, compared to the baseline model. Relevant studies can effectively enhance the efficiency and capability of emergency management, mitigating the impact of unforeseen events on engineering safety.

Introduction: O-linked β-D-N-acetylglucosamine (O-GlcNAc) modification is a post-translational modification in which a single O-GlcNAc is added to serine or threonine residues in nuclear, cytoplasmic, and mitochondrial proteins, and is involved in a variety of physiological processes. Objectives: In the present study, the role of O-GlcNAcylation in embryo implantation was evaluated. Furthermore, whether O-GlcNAcylation is involved in orchestrating glucose metabolism to influence endometrial cell physiological functions was investigated. Methods: Different endometrial tissues were detected using immunohistochemistry. Pregnant mouse models were established to verify molecular expression. O-GlcNAc transferase and aquaporin 3 (AQP3) knockdown were used to detect embryo implantation efficiency in vitro and in vivo. Western blotting and immunofluorescence were used to detect protein expression and stability. Dual luciferase reporter assay and chromatin immunoprecipitation (ChIP) were used to verify the binding transcription factor. Glycolysis was detected using bioenergy analyzer, and metabolites were analyzed using isotope 13C-labeled LC-MS. Metabolic-related genes were determined using RNA sequencing. Results: Activation of endometrial hexosamine biosynthetic pathway (HBP) caused elevated O-GlcNAcylation during the window of implantation, affecting endometrial cell function and embryo implantation. Specifically, elevated O-GlcNAcylation increased glucose uptake via glucose transporter 1 (GLUT1) leading to glucose metabolic flow into the pentose phosphate pathways and HBP, which regulate the metabolic reprogramming of endometrial cells. Furthermore, O-GlcNAcylation mediated the intracellular transport of glycerol to support and compensate for glycolysis through regulation of AQP3. Unexpectedly, elevated AQP3 also increased glucose uptake via GLUT1. These processes maintained higher metabolic requirements for endometrial physiology. Furthermore, the transcription factor SP1 specifically bound to the AQP3 promoter region, and O-GlcNAcylation of SP1 increased its stability and transcriptional regulation of AQP3 which is associated with O-GlcNAcylation of SP1. Conclusion: Overall, O-GlcNAcylation regulated glucose metabolism in endometrial cells, and AQP3-mediated compensation provides new insights into the communication between glycolysis and O-GlcNAcylation.

Abstract Background Gastric cancer (GC), the most commonly diagnosed cancer worldwide with poor 5-year survival rate in advanced stages. Although immune-related and survival-related biomarkers, which typically comprise aberrantly expressed long non-coding RNAs (lncRNAs) and genes, have been identified, there are no reports of immune-related lncRNA pair (IRLP) signatures for GC. Methods In this study, we acquired lncRNA expression profiles from The Cancer Genome Atlas (TCGA) and used the least absolute shrinkage and selection operator (LASSO) Cox proportional hazards model (iteration = 1000) to develop a IRLP prognostic signature. The area under curve (AUC) was used to assess the prognosis predictive power. The multivariate Cox regression analysis was performed to identify whether this signature was an independent prognostic factor. The immune cell infiltration analysis was performed between the two risk groups. Last, molecular experiments were performed to explore LINC01082 is involved in the development of GC. Results We acquired lncRNA expression profiles and used the LASSO Cox model to develop an 18-IRLP signature with a strong prognostic predictive power. The 5-year AUC values of the training, validation, and overall TCGA datasets were 0.77, 0.86, and 0.80, respectively. The different prognostic outcomes between the high- and low-risk groups were determined using our 18-IRLP signature. Moreover, our 18-IRLP signature was an independent prognostic factor as per the multivariate Cox regression analysis, and showed better prognostic evaluation than the traditional TNM staging system as well as other clinical features. We also found differences in cancer-associated fibroblast and macrophage M2 infiltration and the expression of PD-L1, CTLA4, LAG3, and HLA were also observed between the two risk groups (P

Abstract Background Insulin resistance (IR) contributes to ovarian dysfunctions in polycystic ovarian syndrome (PCOS) patients. Serum amyloid A1 (SAA1) is an acute phase protein produced primarily by the liver in response to inflammation. In addition to its role in inflammation, SAA1 may participate in IR development in peripheral tissues. Yet, expressional regulation of SAA1 in the ovary and its role in the pathogenesis of ovarian IR in PCOS remain elusive. Methods Follicular fluid, granulosa cells and peripheral venous blood were collected from PCOS and non-PCOS patients with and without IR to measure SAA1 abundance for analysis of its correlation with IR status. The effects of SAA1 on its own expression and insulin signaling pathway were investigated in cultured primary granulosa cells. Results Ovarian granulosa cells were capable of producing SAA1, which could be induced by SAA1 per se. Moreover, the abundance of SAA1 significantly increased in granulosa cells and follicular fluid in PCOS patients with IR. SAA1 treatment significantly attenuated insulin-stimulated membrane translocation of glucose transporter 4 and glucose uptake in granulosa cells through induction of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) expression with subsequent inhibition of Akt phosphorylation. These effects of SAA1 could be blocked by inhibitors for toll-like receptors 2/4 (TLR 2/4) and nuclear factor kappa light chain enhancer of activated B (NF-κB). Conclusions Human granulosa cells are capable of feedforward production of SAA1, which significantly increased in PCOS patients with IR. Excessive SAA1 reduces insulin sensitivity in granulosa cells via induction of PTEN and subsequent inhibition of Akt phosphorylation upon activation of TLR2/4 and NF-κB pathway. These findings highlight that elevation of SAA1 in the ovary promotes the development of IR in granulosa cells of PCOS patients.

Background: The (R)-CDOP combination regimen, based on pegylated liposomal doxorubicin, is increasingly used for elderly patients with non-Hodgkin’s lymphoma. However, the cardiotoxicity and efficacy of the (R)-CDOP regimen compared with conventional anthracyclines have not been demonstrated in the general population. Therefore, this systematic review and meta-analysis evaluated the risk of cardiotoxicity and efficacy associated with the (R)-CDOP regimen in patients with non-Hodgkin’s lymphoma.Methods: PubMed, Embase, Cochrane Library, CNKI, WanFang Database, and VIP were searched. The search covered the period from the start of the clinical use of (R)-CDOP to April 2022. We searched the literature for cardiovascular adverse events associated with (R)-CDOP in non-Hodgkin’s lymphoma. The data were analyzed using R 4.2.0 and Stata 12.0.Results: From the included studies, the important findings were as follows: total cardiovascular event rate, 7.45% (95% confidence interval [CI] = 4.86%–10.44%); non-serious cardiovascular adverse event rate, 6.48% (95% CI = 3.70%–9.8%); serious cardiovascular adverse event rate, 0.67% (95% CI = 0.00%–2.12%); heart failure rate, 0.55% (95% CI = 0.00%–1.93%); rate of treatment discontinuation attributable to left ventricular dysfunction or heart failure, 0.02% (95% CI = 0.00%–0.57%); and cardiovascular death rate, 0.00% (95% CI = 0.00%–0.37%). Compared with the (R)-CHOP regimen, the (R)-CDOP regimen reduced the risk of cardiovascular events, including total cardiovascular adverse events (odds ratio [OR] = 0.161, 95% CI = 0.103–0.251, p < 0.001, and NNT = 3.7), non-serious cardiovascular adverse events (OR = 0.171, 95% CI = 0.093–0.314, p < 0.001, and NNT = 3.6), serious cardiovascular adverse events (OR = 0.252, 95% CI = 0.119–0.535, p < 0.001, and NNT = 6.8), and heart failure (OR = 0.294, 95% CI = 0.128–0.674, p = 0.004, and NNT = 9.5). To evaluate the survival benefits, we compared (R)-CDOP and (R)-CHOP regimens. We found that the (R)-CDOP regimen was no less efficacious, including complete remission (CR) (OR = 1.398, 95% CI = 0.997–1.960, and p = 0.052), partial response (PR) (OR = 1.631, 95% CI = 1.162–2.289, and p = 0.005), objective response rate (ORR) (OR = 2.236, 95% CI = 1.594–3.135, and p < 0.001), stable disease (SD) (OR = 0.526, 95% CI = 0.356–0.776, and p = 0.001), and progressive disease (PD) (OR = 0.537, 95% CI = 0.323–0.894, and p = 0.017).Conclusion: Our findings suggested that the (R)-CDOP regimen had a lower risk of cardiovascular adverse events in non-Hodgkin’s lymphoma than the (R)-CHOP regimen, demonstrating its safety with regard to cardiotoxicity. In addition, this study found the (R)-CDOP regimen was no less efficacious than the (R)-CHOP regimen in the treatment of non-Hodgkin’s lymphoma. These findings need to be validated by higher-quality research because of the limited number and quality of included studies.

Higher-order sensory thalamic nuclei are densely connected with multiple cortical and subcortical areas, yet the role of these nuclei remains elusive. The posteromedial thalamic nucleus (POm), the higher-order thalamic nucleus in the rodent somatosensory system, is an anatomical hub broadly connected with multiple sensory and motor brain areas yet weakly responds to passive sensory stimulation and whisker movements. To understand the role of POm in sensory perception, we developed a self-initiated, two-alternative forced-choice task in freely moving mice during active sensing. Using optogenetic and chemogenetic manipulation, we show that POm plays a significant role in sensory perception and the projection from the primary somatosensory cortex to POm is critical for the contribution of POm in sensory perception during active sensing.

Abstract Objectives We aimed to understand the barriers experienced by physicians when prescribing for older adults with multimorbidity in specialist outpatient clinics in Singapore. Methods A modified Delphi study was conducted via email with 20 panel experts in the field of geriatric medicine. Barriers identified from an earlier scoping review were presented as statements to the panel. Results Eleven barrier statements reached consensus with high importance according to the Delphi panel. Of these statements, seven (64%) belong to the domain of Environmental context and resources in the Theoretical Domains Framework (TDF), while the remaining barriers belong to the domains of skills, knowledge, intentions, and professional/social role and identity. The barriers are further linked to intervention functions in the Behaviour Change Wheel (BCW). Conclusion Linking the TDF domains to intervention functions revealed strategic directions for the development of an intervention to address the barriers and optimize prescribing.