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Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.

Abstract Acute asthma exacerbation refers to the progressive deterioration of asthma symptoms that is always triggered by virus infection represented by respiratory syncytial virus (RSV). After RSV infection, exaggerated Th2‐mediated pulmonary inflammation is the critical pathological response of asthmatic patients with acute exacerbation. Significantly, airway epithelial cells, being the primary targets of RSV infection, play a crucial role in controlling the pulmonary inflammatory response by releasing airway epithelial cell‐derived exosomes (AEC‐Exos), which potentially influence the development of asthma. However, the specific role of AEC‐Exos in acute asthma exacerbation after RSV infection remains obscure. The purpose of this study was to determine the distinct function of AEC‐Exos in exacerbating acute asthma following RSV infection. Blockade of exosomes by GW reduce the enhanced pulmonary inflammation significantly. Specifically, the enhanced Th2 inflammation was induced by AEC‐Exos thorough transportation of hsa‐miR‐155‐5p–Sirtuin 1 (SIRT1) pathway during acute asthma exacerbation. Targeted inhibition of hsa‐miR‐155‐5p blocks the exaggerated Th2 inflammation effectively in mice with acute asthma exacerbation. In summary, our study showed that during acute asthma exacerbation after RSV infection, AEC‐Exos promote the enhanced Th2 inflammation through transportation of increased hsa‐miR‐155‐5p, which was mediated partly through SIRT1‐mediated pathway. hsa‐miR‐155‐5p is a potential biomarker for early prediction of acute asthma exacerbation.

Abstract Coffee, a widely consumed beverage, has shown benefits for human health but lacks sufficient basic and clinical evidence to fully understand its impacts and mechanisms. Here, we conducted a cross‐sectional observational study of coffee consumption and a 1‐month clinical trial in humans. We found that coffee consumption significantly reshaped the immune system and metabolism, including reduced levels of inflammatory factors and a reduced frequency of senescent T cells. The frequency of senescent T cells and the levels of the senescence‐associated secretory phenotype were lower in both long‐term coffee consumers and new coffee consumers than in coffee nondrinking subjects, suggesting that coffee has anti‐immunosenescence effects. Moreover, coffee consumption downregulated the activities of the The Janus kinase/signal transduction and activator of transcription (JAK/STAT) and mitogen‐activated protein kinases (MAPK) signaling pathways and reduced systemic proinflammatory cytokine levels. Mechanistically, coffee‐associated metabolites, such as 1‐methylxanthine, 3‐methylxanthine, paraxanthine, and ceramide, reduced the frequency of senescent CD4+CD57+ T cells in vitro. Finally, in vivo, coffee intake alleviated inflammation and immunosenescence in imiquimod‐induced psoriasis‐like mice. Our results provide novel evidence of the anti‐inflammatory and anti‐immunosenescence effects of coffee, suggesting that coffee consumption could be considered a healthy habit.

Abstract Elasticity, featured by a recoverable strain, refers to the ability that materials can return to their original shapes after deformation. Typically, the elastic strains of most metals are well‐known 0.2%. In shape memory alloys and high entropy alloys, the elastic strains can be several percent, as called superelasticity, which are all triggered by external stresses. A superelasticity induced by magnetic field, termed as magneto‐superelasticity, is extremely important for contactless work of materials and for developing brand‐new large stroke actuators and high efficiency energy transducers. In magnetic shape memory alloys, the twin boundary motion driven by magnetic field can output a strain of several percent. However, this strain is unrecoverable when removing the magnetic field and hence it is not magneto‐superelasticity. Here, a giant magneto‐superelasticity of 5% in a Ni34Co8Cu8Mn36Ga14 single crystal is reported by introducing arrays of ordered dislocations to form preferentially oriented martensitic variants during the magnetically induced reverse martensitic transformation. This work provides an opportunity to achieve high performance in functional materials by defect engineering.

Breaking the poor permeability of immune checkpoint inhibitors (ICIs) caused by the stromal barrier and reversing the immunosuppressive microenvironment are significant challenges in pancreatic cancer immunotherapy. In this study, we synthesized core-shell Fe3O4@TiO2 nanoparticles to act as carriers for loading VISTA monoclonal antibodies to form Fe3O4@TiO2@VISTAmAb (FTV). The nanoparticles are designed to target the overexpressed ICIs VISTA in pancreatic cancer, aiming to improve magnetic resonance imaging-guided sonodynamic therapy (SDT)-facilitated immunotherapy. Laser confocal microscopy and flow cytometry results demonstrate that FTV nanoparticles are specifically recognized and phagocytosed by Panc-2 cells. In vivo experiments reveal that ultrasound-triggered TiO2 SDT can induce tumor immunogenic cell death (ICD) and recruit T-cell infiltration within the tumor microenvironment by releasing damage-associated molecular patterns (DAMPs). Furthermore, ultrasound loosens the dense fibrous stroma surrounding the pancreatic tumor and increases vascular density, facilitating immune therapeutic efficiency. In summary, our study demonstrates that FTV nanoparticles hold great promise for synergistic SDT and immunotherapy in pancreatic cancer.

BackgroundMalnutrition is strongly correlated with worsened treatment outcomes, reduced standard of living, and heightened mortality rates among individuals with cancer. Our research explores how the Geriatric Nutritional Risk Index (GNRI), a measure of nutritional status, relates to all-cause mortality, cancer-specific, and non-cancer mortality among middle-aged and older adult cancer patients.MethodsWe enrolled 3,253 participants aged 40 and above who were diagnosed with cancer. The data was obtained from the National Health and Nutrition Examination Survey (NHANES) dataset covering the period from 2001 to 2018, with a median follow-up duration of 83 months. According to the GNRI levels, patients in the study were classified into two distinct groups: the group with a low GNRI (

BackgroundThe prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients.MethodsA total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms.ResultsPatients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25–7.72; p

Epiphyas postvittana, commonly known as the light brown apple moth (LBAM), is native to Australia and has a restricted global distribution. Its polyphagous nature and the recent surge in interceptions have emphasized the need for focused risk assessments to guide effective measures to curb the entry of this pest into new countries. This study aimed to perform a detailed global invasion risk assessment using an optimized MaxEnt model that incorporated 19 bioclimatic variables and elevation. The predictive outcomes underscored the significance of key variables, specifically the minimum temperature of the coldest month (bio6), precipitation of the driest month (bio14), and precipitation of the coldest quarter (bio19), in shaping the potential geographical distribution of LBAM. Regions beyond the existing range, including the southeastern United States, southern Brazil, eastern Argentina, Uruguay, southern Chile, and various Western European countries, were identified as susceptible to invasion and establishment by LBAM. An increase in suitability was observed above 45°N and 40°S under future climate scenario. With respect to climate change, LBAM would expand its potential range in Western Europe and the United States, especially under SSP5-8.5, in the 2050s. An upward trend in the latitudinal suitability gradient for LBAM in mid-high latitude areas implies that amid changing climate conditions, LBAM may find favorable habitats in these regions. For countries and regions with invasion risk, it is imperative to implement corresponding inspections and quarantine measures to thwart the introduction of LBAM, particularly in countries with established trade ties with invaded regions.

Summary: Xeroderma pigmentosum (XP) is caused by defective nucleotide excision repair of DNA damage. This results in hypersensitivity to ultraviolet light and increased skin cancer risk, as sunlight-induced photoproducts remain unrepaired. However, many XP patients also display early-onset neurodegeneration, which leads to premature death. The mechanism of neurodegeneration is unknown. Here, we investigate XP neurodegeneration using pluripotent stem cells derived from XP patients and healthy relatives, performing functional multi-omics on samples during neuronal differentiation. We show substantially increased levels of 5′,8-cyclopurine and 8-oxopurine in XP neuronal DNA secondary to marked oxidative stress. Furthermore, we find that the endoplasmic reticulum stress response is upregulated and reversal of the mutant genotype is associated with phenotypic rescue. Critically, XP neurons exhibit inappropriate downregulation of the protein clearance ubiquitin-proteasome system (UPS). Chemical enhancement of UPS activity in XP neuronal models improves phenotypes, albeit inadequately. Although more work is required, this study presents insights with intervention potential.

Pecan (Carya illinoensis), an economically important deciduous tree, bears commercially valuable nutritional nuts. Spring freezes in April can severely injure pecan buds, decreasing bloom, and fruit set. This study determined how low temperatures affect pecan buds/flowers at different growth stages in several pecan scion/rootstock combinations. This study focused on three pecan scion/rootstock combinations: Pawnee/Peruque (PP), Kanza/Giles (KG), and Maramec/Colby (MC), grown at the Cimarron Valley Research Station, Perkins, Oklahoma. Branches at three different growth stages, i.e., outer bud scale shed, one week after bud break, and early bloom stages were collected from PP, MC, and KG. Branches were held in a Conviron E8 freezing unit at 4 temperatures (-2, 0, 2, and 4°C) for 4 and 8 hours; A total of 8 treatments. One sample set was kept as an untreated control. After 2–3 weeks, branch samples from all the temperature treatments were observed and categorized into two groups. Group one with number of branches had healthy buds/formation of healthy leaves/flowers and group two with number of dead branches. The carbohydrate content reserved from dormant was analyzed using an Anthrone reagent. Visual observations and carbohydrate analyses revealed differences in damage and carbohydrate content among the scion/rootstock combinations, low-temperature treatments, and growth stages. The MC combination had minimum visual damage to leaves, buds, and flowers and significantly lower soluble sugars and starch in bark phloem as well as significantly lower soluble sugars in woody tissue xylem. The KG combination had maximum visual damage and significantly higher soluble sugars and starches in the bark, and soluble sugars in the woody tissues. These results indicate the MC combination is more tolerant to spring freeze damage at all three growth stages compared to the other two pecan scion/rootstock combinations. The results also demonstrate the MC combination is using more non-structural carbohydrates, soluble sugars and starches, suggesting this is a possible mechanism in its freeze tolerance.

BackgroundInsomnia is one of the most common symptoms among breast cancer patients, which can be present throughout all stages of breast cancer. As a non-pharmacological alternative treatment, acupuncture has been suggested to improve sleep situations in patients with cancer suffering from insomnia. However, there is a lack of well-designed, high-quality clinical evidence regarding the efficacy of acupuncture in the treatment of breast cancer-related insomnia. This study is conducted to evaluate the efficacy and safety of acupuncture treatment for breast cancer-related insomnia.MethodsThis study was designed as a multicenter, randomized, sham-controlled clinical trial. A total of 264 eligible patients with breast cancer-related insomnia will be randomized into an acupuncture group and a sham acupuncture group in a 1:1 ratio. In the trial, patients in the acupuncture and sham acupuncture groups will receive 12 sessions over a consecutive 4-week period. The primary outcome will be the treatment response rate of Insomnia Severity Index (ISI) at week 4; secondary outcomes include treatment remission rate of ISI, Sleep Efficiency (SE) obtained by the use of Sleep diary, treatment response rate of ISI at 8th and 16th weeks of follow-up, the mean changes of ISI, Generalized Anxiety Disorder Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Quality of Life Questionnaire - Core 30 (QLQ-C30), sleep parameters recorded in Actigraphy and weekly usage of remedial drugs. Adverse events will be recorded throughout the study. All analyses will be based on the ITT principle and performed with SAS 9.4 statistical software.DiscussionThis trial will evaluate the clinical efficacy and safety of acupuncture for breast cancer-related insomnia. If proven effective, acupuncture will provide an effective option for patients with breast cancer-related insomnia, which will play a positive role in helping patients reduce their use of sleeping medications.Clinical trial registrationClinicalTrials.gov, identifier NCT05510700.

Background: Absent in melanoma 2 (AIM2) is implicated in inflammatory processes. We measured serum AIM2 with intent to unveil its predictive significance for stroke-associated pneumonia (SAP) and functional prognosis following acute intracerebral hemorrhage (ICH). Methods: In this prospective cohort study, serum AIM2 concentrations of 163 ICH patients were gauged upon admission and 57 of them also consented for measurements at days 1, 3, 5, 7, 10 and 14. Coupled with 57 individuals without health conditions, dynamic change of serum AIM2 levels were uncovered. National Institutes of Health Stroke Scale (NIHSS) scores and hematoma volume were identified as the dual indicators of severity. Poststroke six-month modified Rankin Scale (mRS) scores ranging from 3 to 6 indicated an unfavorable outcome. SAP was observed during the first seven days after ICH. Sequential univariate and multivariate analyses were performed to discern predictors of SAP and adverse prognosis. Results: The serum levels of AIM2 in patients exhibited a marked elevation upon admission, reaching peak levels on the third and fifth days, and remained notably elevated until day 14 compared to those of the control group. Serum AIM2 levels showed independent correlations with both NIHSS scores and the volume of hematoma. Additionally, AIM2 concentrations were independently associated with a poor prognosis and SAP at the six-month mark. Within the framework of restricted cubic spline analysis, serum AIM2 concentrations exhibited a linear correlation with the likelihood of developing SAP and experiencing a poor prognosis. In the context of receiver operating characteristic (ROC) curve analysis, serum AIM2 concentrations effectively differentiated risks of SAP and poor prognosis. By employing segmented analysis, serum AIM2 concentrations showed negligible interactions with several traditional variables, such as age, gender, smoking habits, alcohol consumption, and more. The integrated model incorporating serum AIM2, NIHSS scores, and the volume of hematoma was depicted by employing a nomogram and demonstrated strong predictive performance for poor prognosis or SAP across various evaluation metrics, including ROC curve analysis, calibration curve analysis, and decision curve analysis. Conclusion: Serum AIM2 levels show a marked increase shortly after intracerebral hemorrhage (ICH), which may accurately reflect stroke severity, and effectively predict SAP and poor neurological outcomes, and therefore serum AIM2 stands out as an encouraging predictive indicator for ICH.

Abstract Cell-free RNAs (cfRNAs) offer an opportunity to detect diseases from a transcriptomic perspective, however, existing techniques have fallen short in generating a comprehensive cell-free transcriptome profile. We develop a sensitive library preparation method that is robust down to 100 µl input plasma to analyze cfRNAs independent of their 5’-end modifications. We show that it outperforms adapter ligation-based method in detecting a greater number of cfRNA species. We perform transcriptome-wide characterizations in 165 lung cancer, 30 breast cancer, 37 colorectal cancer, 55 gastric cancer, 15 liver cancer, and 133 cancer-free participants and demonstrate its ability to identify transcriptomic changes occurring in early-stage tumors. We also leverage machine learning analyses on the differentially expressed cfRNA signatures and reveal their robust performance in cancer detection and classification. Our work sets the stage for in-depth study of the cfRNA repertoire and highlights the value of cfRNAs as cancer biomarkers in clinical applications.

Abstract Background Laparoscopic nephrectomy is a commonly utilized surgical approach for the management of renal cancer. Despite its widespread acceptance, postoperative pain management remains a significant challenge for many patients undergoing this procedure. Traditional pain management techniques, including opioid and nonsteroidal anti-inflammatory drug administration, may not provide adequate pain relief and may result in adverse effects. In recent years, erector spinae plane block (ESPB) has emerged as a promising regional anesthesia technique due to its simplicity, safety, and potential efficacy in reducing postoperative pain. ESPB has demonstrated effectiveness in reducing postoperative pain in various surgical procedures. However, the efficacy of ESPB in laparoscopic nephrectomy for renal cancer has not been extensively studied. As such, further investigation is necessary to determine the potential benefits of ESPB in this context. The addition of adjuvants such as dexmedetomidine and dexamethasone to nerve blocks has been shown to improve both the duration and quality of the block. Multiple studies have demonstrated the safety and efficacy of these adjuvants in reducing postoperative pain and opioid consumption and improving patient satisfaction. The use of dexmedetomidine and dexamethasone as adjuvants for nerve blocks represents a promising approach for enhancing regional anesthesia and analgesia. In light of these findings, we have incorporated dexmedetomidine and dexamethasone into our nerve block protocol. Methods This study is a randomized controlled trial conducted at a single center, with 50 participants being randomized in a 1:1 ratio to either the ESPB group or the control group. The trial aims to investigate the efficacy of ESPB in patients diagnosed with kidney cancer who are scheduled for laparoscopic nephrectomy. The primary outcome measure is the total consumption of intraoperative sufentanil. Secondary outcomes include the VAS score at rest and during coughing at 1 h, 6 h, 12 h, 24 h, and 48 h after surgery; total intraoperative remifentanil consumption; the number of times rescue analgesia is required; and the incidence of nausea and vomiting in the first 24 h after surgery. This study is registered for a duration of 1 year and is being conducted in China. Discussion The objective of our study is to evaluate the potential benefits of erector spinae plane block (ESPB) in patients undergoing laparoscopic nephrectomy, with a focus on the impact of dexmedetomidine and dexamethasone as adjuvants on the quality and duration of the block, as well as postoperative pain and opioid consumption. By investigating the effects of these adjuvants in the context of ESPB, we hope to contribute to the growing body of literature on the use of adjuvants in nerve blocks and provide further insight into the potential benefits of this approach for improving patient outcomes following laparoscopic nephrectomy. This trial was approved by the Ethics Committee of the Second Affiliated Hospital of Army Medical University. Trial registration China Clinical Trial Register ChiCTR2300068578 . Registered on 20 February 2023.

Abstract Background The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. Methods In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. Results The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13–1.33), 34% (internal test cohort, 95%CI = 1.11–1.62), and 35% (external validation cohort, 95%CI = 1.14–1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22–1.71; internal test cohort, HR = 1.62, 95%CI = 1.12–2.36; external validation cohort, HR = 1.61, 95%CI = 1.15–2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05–4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42–3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52–4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24–2.55] in patients with cancer cachexia. Conclusion The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Abstract Background Immune checkpoint inhibitors (ICIs) have contributed to a significant advancement in the treatment of cancer, leading to improved clinical outcomes in many individuals with advanced disease. Both preclinical and clinical investigations have shown that ICIs are associated with atherosclerosis and other cardiovascular events; however, the exact mechanism underlying this relationship has not been clarified. Methods Patients diagnosed with stages III or IV non-small cell lung cancer (NSCLC) at the Wuhan Union Hospital from March 1, 2020, to April 30, 2022, were included in this retrospective study. Coronary artery calcium (CAC) volume and score were assessed in a subset of patients during non-ECG-gated chest CT scans at baseline and 3, 6, and 12 months after treatment. Propensity score matching (PSM) was performed in a 1:1 ratio to balance the baseline characteristics between the two groups. Results Overall, 1458 patients (487 with ICI therapy and 971 without ICI therapy) were enrolled in this cardiovascular cohort study. After PSM, 446 patients were included in each group. During the entire period of follow-up (median follow-up 23.1 months), 24 atherosclerotic cardiovascular disease (ASCVD) events (4.9%) occurred in the ICI group, and 14 ASCVD events (1.4%) in the non-ICI group, before PSM; 24 ASCVD events (5.4%) occurred in the ICI group and 5 ASCVD events (1.1%) in the non-ICI group after PSM. The CAC imaging study group comprised 113 patients with ICI therapy and 133 patients without ICI therapy. After PSM, each group consisted of 75 patients. In the ICI group, the CAC volume/score increased from 93.4 mm3/96.9 (baseline) to 125.1 mm3/132.8 (at 12 months). In the non-ICI group, the CAC volume/score was increased from 70.1 mm3/68.8 (baseline) to 84.4 mm3/87.9 (at 12 months). After PSM, the CAC volume/score was increased from 85.1 mm3/76.4 (baseline) to 111.8 mm3/121.1 (12 months) in the ICI group and was increased from 74.9 mm3/76.8 (baseline) to 109.3 mm3/98.7 (12 months) in the non-ICI group. Both cardiovascular events and CAC progression were increased after the initiation of ICIs. Conclusions Treatment with ICIs was associated with a higher rate of ASCVD events and a noticeable increase in CAC progression.

Pregnancy complications significantly impact women and pose potential threats to the developing child’s health. Early identification of these complications is imperative for life-saving interventions. The manual analysis of cardiotocography (CTG) tests, a conventional practice among obstetricians, is both labor-intensive and unreliable. Consequently, the development of efficient fetal health classification models becomes crucial for optimizing medical resources and saving time.This study addresses the imperative for advanced fetal health classification through the application of machine learning (ML) techniques. The objective is to explore, develop, and analyze ML models capable of accurately classifying fetal health based on CTG data. The overarching goal is to enhance diagnostic precision and facilitate timely interventions.Utilizing a freely available cardiotocography data set, despite its relatively small size, the research acknowledges its rich characteristics. Various ML models, including Random Forests, Logistic Regression, Decision Trees, Support Vector Classifiers, Voting Classes, and K-Nearest Neighbors, are deployed on the data set. The analysis involves rigorous training and testing of these models to assess their efficacy in classifying fetal health.The study yields promising outcomes, with the implemented ML models achieving a notable accuracy level of 93%, surpassing previous methods. This underscores the effectiveness of the proposed models in elevating the precision of fetal health classification based on CTG data.The findings advocate for the integration of ML models into routine clinical practices, streamlining fetal health assessments. The study not only underscores the significance of early complication detection but also demonstrates the potential of ML in optimizing medical resource allocation and time efficiency. Further research is warranted to refine and expand ML applications in the context of fetal health assessment, promising advancements in prenatal care.

Abstract Designing high-performance thermal catalysts with stable catalytic sites is an important challenge. Conventional wisdom holds that strong metal-support interactions can benefit the catalyst performance, but there is a knowledge gap in generalizing this effect across different metals. Here, we have successfully developed a generalizable strong metal-support interaction strategy guided by Tammann temperatures of materials, enabling functional oxide encapsulation of transition metal nanocatalysts. As an illustrative example, Co@BaAl2O4 core@shell is synthesized and tracked in real-time through in-situ microscopy and spectroscopy, revealing an unconventional strong metal-support interaction encapsulation mechanism. Notably, Co@BaAl2O4 exhibits exceptional activity relative to previously reported core@shell catalysts, displaying excellent long-term stability during high-temperature chemical reactions and overcoming the durability and reusability limitations of conventional supported catalysts. This pioneering design and widely applicable approach has been validated to guide the encapsulation of various transition metal nanoparticles for environmental tolerance functionalities, offering great potential to advance energy, catalysis, and environmental fields.

Abstract With the increase of aging population and prevalence of obesity, the incidence of cardiovascular disease (CVD) and cancer has also presented an increasing tendency. These two different diseases, which share some common risk factors. Relevant studies in the field of reversing Cardio-Oncology have shown that the phenotype of CVD has a significant adverse effect on tumor prognosis, which is mainly manifested by a positive correlation between CVD and malignant progression of concomitant tumors. This distal crosstalk and the link between different diseases makes us aware of the importance of diagnosis, prediction, management and personalized treatment of systemic diseases. The circulatory system bridges the interaction between CVD and cancer, which suggests that we need to fully consider the systemic and holistic characteristics of these two diseases in the process of clinical treatment. The circulating exosome-miRNAs has been intrinsically associated with CVD -related regulation, which has become one of the focuses on clinical and basic research (as biomarker). The changes in the expression profiles of cardiovascular disease-associated miRNAs (Cardio-miRNAs) may adversely affect concomitant tumors. In this article, we sorted and screened CVD and tumor-related miRNA data based on literature, then summarized their commonalities and characteristics (several important pathways), and further discussed the conclusions of Cardio-Oncology related experimental studies. We take a holistic approach to considering CVD as a risk factor for tumor malignancy, which provides an in-depth analysis of the various regulatory mechanisms or pathways involved in the dual attribute miRNAs (Cardio-/Onco-miRNAs). These mechanisms will be key to revealing the systemic effects of CVD on tumors and highlight the holistic nature of different diseases. Therefore, the Cardio-miRNAs should be given great attention from researchers in the field of CVD and tumors, which might become new targets for tumor treatment. Meanwhile, based on the principles of precision medicine (such as the predictive preventive personalized medicine, 3PM) and reverse Cardio-oncology to better improve individual outcomes, we should consider developing personalized medicine and systemic therapy for cancer from the perspective of protecting cardiovascular function.

Introduction: It has been reported that rapamycin inhibited inflammation in renal interstitial diseases. We therefore hypothesized that rapamycin could attenuate inflammation in polycystic kidney disease (PKD). Methods: Han:SPRD rats were treated with rapamycin by daily gavage from 4 weeks to 12 weeks of age at the dosage of 0.5 mg/kg/day (low dose) or 1 mg/kg/day (high dose). WT9-12 human PKD cells were treated with various concentrations of rapamycin. Results: Two-kidney/total body weight ratio and cystic index in Cy/+ kidneys were significantly reduced with the treatment of low-dose rapamycin and further reduced by the treatment with high-dose rapamycin. However, the renal function of Cy/+ rats was equally improved by the treatment with either low-dose or high-dose rapamycin. The renal cell proliferation was significantly decreased in Cy/+ kidneys with the treatment of low-dose rapamycin and was further decreased with the treatment of high-dose rapamycin as examined by Ki67 staining. The phosphorylation of S6K in cystic kidneys was decreased by low-dose rapamycin and further decreased by high-dose rapamycin. Both low-dose and high-dose rapamycin treatment decreased macrophage infiltration and the expression of complement factor B (CFB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) to a similar level. The expression of CFB, MCP-1, and TNF-α and phosphorylation of S6K were inhibited in WT9-12 cells treated with 10 nm rapamycin at 24 h and 48 h, respectively. Moreover, the phosphorylation of Akt was not increased by 1 nm and 10 nm of rapamycin and enhanced by 1 μm rapamycin treatment. Interestingly, WT9-12 cell proliferation could be inhibited by 1 μm rapamycin. Conclusion: Low dose of rapamycin could inhibit inflammation and protect renal function in PKD. Inflammation is more sensitive than cell proliferation in response to rapamycin treatment in PKD.

Graphene nanoplatelets (GNPs)/copper composites containing nano-Ti addition were prepared using the vacuum hot-pressing sintering process. The effect of Nano-Ti on microstructure and mechanical properties of GNPs/copper composite was investigated. Before the sintering of the composite powders, the massive nano-Ti particles decorated on the GNPs surface. The GNPs/Ti chemical reaction occurred during the sintering, and then formed abundant TiC particles. Hardness and strength of bulk GNPs/copper composites were enhanced evidently by nano-Ti addition, which increased with nano-Ti increasing. The nano-Ti addition achieved simultaneous strength-ductility enhancement of GNPs/copper composites. The hardness, tensile yield strength, ultimate tensile strength and tensile elongation of the composite with 3.0 wt% nano-Ti addition demonstrated respectively 128.2 %, 199.6 %, 125.9 %, and 30.6 % enhancement comparing with no nano-Ti added sample. The nano Ti addition can effectively improve the wear resistance of GNPs/copper composites. The relevant structural formation, strengthening-toughening and wear mechanisms of GNPs/copper composites with nano-Ti addition were discussed.

Over the past two decades, advances in arthroscopic and minimally invasive surgical techniques have led to significant growth in sports medicine surgery. Implants such as suture anchors, interference screws, and endo-buttons are commonly used in these procedures. However, traditional implants made of metal or inert materials are not absorbable, leading to complications that affect treatment outcomes. To address this issue, absorbable materials with excellent mechanical properties, good biocompatibility, and controlled degradation rates have been developed and applied in clinical practice. These materials include absorbable polymers, absorbable bioceramics, and absorbable metals. In this paper, we will provide a comprehensive summary of these absorbable materials from the perspective of clinicians, and discuss their clinical applications and related research in sport medicine.

Using colloid water as a covering for explosives can improve the energy efficiency for explosive welding, while its effects on bonding properties remain unclear. Here, by employing titanium/steel as a model system, the effect of covering thickness on microstructures and mechanical properties of the bonding interface was systematically investigated. It was found that all the welds displayed wavy interfaces, and the wave size increased with increasing covering thickness. Vortices characterized by solidified melt zones surrounded by strongly deformed parent materials, were only formed for the welds performed with a covering. Moreover, with increasing covering thickness, both the tensile strength and the elongation of the titanium/steel plate decreased, and the failure mode changed from ductile to cleavage fracture, gradually. In the tensile-shear tests, all the fractures took place in titanium matrix without separation at interface, indicating that the titanium/steel interfaces had an excellent bonding strength. The micro-hardness decreased with increasing distance from the interface, and this trend was more remarkable for a thicker covering. The micro-hardness inside the solidified melt zones was far higher than that observed in strain-hardened layers of the parent metal, due to formation of hard intermetallic compounds.

Abstract Background Malnutrition is associated with poor overall survival (OS) in breast cancer patients; however, the most predictive nutritional indicators for the prognosis of patients with breast cancer are not well-established. This study aimed to compare the predictive effects of common nutritional indicators on OS and to refine existing nutritional indicators, thereby identifying a more effective nutritional evaluation indicator for predicting the prognosis in breast cancer patients. Methods This prospective study analyzed data from 776 breast cancer patients enrolled in the “Investigation on Nutritional Status and its Clinical Outcome of Common Cancers” (INSCOC) project, which was conducted in 40 hospitals in China. We used the time-dependent receiver operating characteristic curve (ROC), Kaplan–Meier survival curve, and Cox regression analysis to evaluate the predictive effects of several nutritional assessments. These assessments included the patient-generated subjective nutrition assessment (PGSGA), the global leadership initiative on malnutrition (GLIM), the controlling nutritional status (CONUT), the nutritional risk index (NRI), and the prognostic nutritional index (PNI). Utilizing machine learning, these nutritional indicators were screened through single-factor analysis, and relatively important variables were selected to modify the PNI. The modified PNI, termed the cholesterol-modified prognostic nutritional index (CPNI), was evaluated for its predictive effect on the prognosis of patients. Results Among the nutritional assessments (including PGSGA, GLIM, CONUT, NRI, and PNI), PNI showed the highest predictive ability for patient prognosis (time-dependent ROC = 0.58). CPNI, which evolved from PNI, emerged as the superior nutritional index for OS in breast cancer patients, with the time-dependent ROC of 0.65. It also acted as an independent risk factor for mortality (p

Abstract Background and aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered a new biomarker for atherosclerosis, but its ability to predict cardiovascular outcomes has been controversial. This study aimed to address the lack of data on PCSK9, coronary heart disease (CHD) severity, and major cardiovascular events (MACEs) in patients with type 2 diabetes mellitus (T2DM). Methods A total of 2984 T2DM patients underwent selective coronary angiography, and their serum PCSK9 levels were measured using enzyme-linked immunosorbent assay. Correlation and logistic regression analyses were performed to investigate the association between PCSK9 expression and CHD severity. This study used Cox regression analysis to assess the association between circulating PCSK9 levels and the risk of MACEs. Results Circulating PCSK9 levels were significantly higher in the CHD group than in the non-CHD group [554.62 (265.11) ng/mL vs. 496.86 (129.05) ng/mL, p

High-order coal has the characteristics of weak water absorption due to the development of micropores. From the perspective of micropores, it is of great significance to study the improvement effect of different types of surfactants on the wettability of high-end coal, which is of great significance for dust prevention and dust reduction of high-end coal. Taking the high-order coal of Zhaozhuang Mine in Shanxi Province and Nuodong Mine in Guizhou as the research object, the low-field nuclear magnetic resonance (LNMR) measurement system was used to carry out the coal sample sedimentation experiment and the coal sample-solution permeation pore water distribution determination experiment, and analyze the improvement law of micropore wettability of surfactant solution on high-order coal samples under different compound ratios. The results show that: In the sedimentation of eight surfactant monomer solutions, the sedimentation rate of coal samples in surfactant solution gradually increased with the increase of mass fraction, and the sedimentation rate of coal samples in each solution tended to balance at 0.5% mass fraction, among which the sedimentation effect of Trolatong X-100 (X-100), fatty alcohol polyoxyethylene ether (JFC-U) and sodium dodecyl benzene sulfonate (SDBS) was faster than that of other surfactant solutions. Based on the low-field NMR experiment T2 spectroscopy, a dual quantitative evaluation method was established, and it was found that when the three preferred surfactant solutions were compounded with volume ratios of 1∶1, 1∶2 and 2∶1 under the condition that the mass fraction was 0.5%, the compound solution played a synergistic role in the wettability of the micropores of high-order coal, and the wetting improvement effect of the compound surfactant solution was higher than that of the surfactant monomer solution. When the volume ratio of the nonionic surfactant JFC-U solution and the anionic surfactant SDBS solution were compounded 2∶1, the effect on improving the wetting of high-order coal was obvious. In the compound solution of nonionic and nonionic surfactants, the wetting improvement effect of compound surfactant solution on coal samples was positively correlated with the content of JFC-U. The research results can provide a reference for the selection of surfactant types and the research methods of coal sample wettability during wet dust control in coal mines.

Abstract Background The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. Methods This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG‐PS). Survival data were analysed using univariate and multivariate Cox regression analyses. Results The area under the curve, concordance index and survival analysis showed that C‐reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non‐cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08–5.32); high CAR, HR (95% CI) = 2.92 (1.88–4.55); high CRP, HR (95% CI) = 3.12 (2.08–4.67)] indicated a worse prognosis, compared with non‐cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65–3.16); high CAR, HR (95% CI) = 2.36 (1.71–3.25); high CRP, HR (95% CI) = 2.58 (1.85–3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG‐PS 2, HR (95% CI) = 1.61 (1.04–2.50); ECOG‐PS 3/4, HR (95% CI) = 2.91 (1.69–5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG‐PS 2, HR (95% CI) = 1.28 (0.90–1.81); ECOG‐PS 3/4, HR (95% CI) = 2.41 (1.32–4.39]). Patients with CRC cachexia with an ECOG‐PS score of 2 or 3–4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG‐PS score of 0/1 and a low inflammation. Conclusions The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG‐PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG‐PS in patients with CRC cachexia could provide a simple survival prediction.

Abstract Background Involuntary weight loss (WL) is a common symptom in cancer patients and is associated with poor outcomes. However, there is no standardized definition of WL, and it is unclear what magnitude of weight loss should be considered significant for prognostic purposes. This study aimed to determine an individualized threshold for WL that can be used for prognostic assessment in cancer patients. Methods Univariate and multivariate analyses of overall survival (OS) were performed using Cox proportional hazard models. The Kaplan–Meier method was performed to estimate the survival distribution of different WL levels. Logistic regression analysis was used to determine the relationship between WL and 90‐day outcomes. Restricted cubic splines with three knots were used to examine the effects of WL on survival under different body mass index (BMI) conditions. Results Among the 8806 enrolled patients with cancer, median survival time declined as WL increased, from 25.1 to 20.1, 17.8 and 16.4 months at

Abstract The pandemic of coronavirus disease 2019 (COVID-19) caused by the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a significant impact on the economy and public health worldwide. Therapeutic options such as drugs and vaccines for this newly emerged disease are eagerly desired due to the high mortality. Using the U.S. Food and Drug Administration (FDA) approved drugs to treat a new disease or entirely different diseases, in terms of drug repurposing, minimizes the time and cost of drug development compared to the de novo design of a new drug. Drug repurposing also has some other advantages such as reducing safety evaluation to accelerate drug application on time. Carvedilol, a non-selective beta-adrenergic blocker originally designed to treat high blood pressure and manage heart disease, has been shown to impact SARS-CoV-2 infection in clinical observation and basic studies. Here, we applied computer-aided approaches to investigate the possibility of repurposing carvedilol to combat SARS-CoV-2 infection. The molecular mechanisms and potential molecular targets of carvedilol were identified by evaluating the interactions of carvedilol with viral proteins. Additionally, the binding affinities of in vivo metabolites of carvedilol with selected targets were evaluated. The docking scores for carvedilol and its metabolites with RdRp were − 10.0 kcal/mol, − 9.8 kcal/mol (1-hydroxyl carvedilol), − 9.7 kcal/mol (3-hydroxyl carvedilol), − 9.8 kcal/mol (4-hydroxyl carvedilol), − 9.7 kcal/mol (5-hydroxyl carvedilol), − 10.0 kcal/mol (8-hydroxyl carvedilol), and − 10.1 kcal/mol (O-desmethyl carvedilol), respectively. Using the molecular dynamics simulation (100 ns) method, we further confirmed the stability of formed complexes of RNA-dependent RNA polymerase (RdRp) and carvedilol or its metabolites. Finally, the drug-target interaction mechanisms that contribute to the complex were investigated. Overall, this study provides the molecular targets and mechanisms of carvedilol and its metabolites as repurposed drugs to fight against SARS-CoV-2 infection.

Abstract The notion of topological insulators (TIs), characterized by an insulating bulk and conducting topological surface states, can be extended to higher-order topological insulators (HOTIs) hosting gapless modes localized at the boundaries of two or more dimensions lower than the insulating bulk. In this work, by performing high-resolution angle-resolved photoemission spectroscopy (ARPES) measurements with submicron spatial and spin resolution, we systematically investigate the electronic structure and spin texture of quasi-one-dimensional (1D) HOTI candidate Bi4Br4. In contrast to the bulk-state-dominant spectra on the (001) surface, we observe gapped surface states on the (100) surface, whose dispersion and spin-polarization agree well with our ab-initio calculations. Moreover, we reveal in-gap states connecting the surface valence and conduction bands, which is a signature of the hinge states inside the (100) surface gap. Our findings provide compelling evidence for the HOTI phase of Bi4Br4. The identification of the higher-order topological phase promises applications based on 1D spin-momentum locked current in electronic and spintronic devices.

Introduction Studies on economic evaluations of the 13-valent pneumococcal conjugate vaccine (PCV13) have been increasing over the last decade. No systematic reviews have synthesized the evidence of economic evaluations of the PCV13. Areas covered We systematically searched the literature which published on peer-reviewed journals from January 2010 to June 2022. The literature search was conducted in the following electronic databases: PubMed, Web of Science, Embase, the Cochrane Library, CNKI, Wanfang database, VIP database. We identified 1827 records from the database search. After excluding 511 duplicates, 1314 records were screened, of which 156 records were retained for the full-text reviews. A total of 44 studies were included in the review. Among the included studies, 33 studies were economic evaluations of PCV13 among children, and 11 studies were conducted among adults. The literature search initiated in April, 2022, and updated in June 2022. Expert opinion Vaccination with PCV13 was found to significantly reduce the mortality and morbidity of pneumococcal diseases and was cost-effective compared to no vaccine or several other pneumococcal vaccines (e.g. PCV10, PPV23). Future research is advised to expand economic evaluations of PCV13 combined with dynamic model to enhance methodologic rigor and prediction accuracy.

Abstract Both learner-generated drawing and retrieval practice methods are effective to enhance science learning. To compare the impact of combining different drawing methods (representational drawing vs. abstract drawing) with retrieval practice on the carbon cycle learning, 136 Chinese high school students enrolled in a geography course were assigned randomly to six learning conditions: students built their mental models of the carbon cycle by either generating sketches with or without access to the text learning material introducing the carbon cycle (i.e., generative sketching vs. retrieval sketching), or by creating concept maps with or without access to the learning material (i.e., generative concept mapping vs. retrieval concept mapping), or students just freely recalled on what they have learned from the learning material by paragraphing (i.e., retrieval practice), or restudied the learning material with note-taking (i.e., restudy). Students’ learning outcomes were assessed by immediate and one-week delayed tests. Results revealed that no difference was found between the six conditions on the immediate test, whereas students in the retrieval practice condition with paragraphing significantly outperformed those who did not practice retrieval on the one-week delayed test. However, there was no difference between the two drawing conditions regardless of whether they were adopted with or without retrieval practice. Furthermore, the same pattern was found on the factual knowledge questions in both tests, but no main effect of condition was found on both the immediate and the delayed tests for the application questions. We conclude that retrieval-based drawing could be adopted for climate change education at the high school level.

Abstract Objective The primary objective of this study was to evaluate the efficacy and safety of pulsed field ablation in individuals diagnosed with atrial fibrillation. Methods A total of 36 patients diagnosed with atrial fibrillation were enrolled in the pulsed field ablation group, while another 36 patients diagnosed with atrial fibrillation were included in the radiofrequency ablation group. Among the study participants, 15 patients in the pulsed field ablation group and 17 patients in the radiofrequency ablation group had persistent atrial fibrillation. Comprehensive comparisons were made between the two groups, including baseline data, underlying diseases, medication usage, intraoperative parameters, and atrial fibrillation recurrence rates at 1, 3, and 6 months during the postoperative follow-up period. Results (1) There were no significant differences observed between the two groups concerning baseline data and antiarrhythmic drug usage (P > 0.05); (2) the effective ablation time for both left and right pulmonary veins in the pulsed field ablation group was markedly shorter compared to the radiofrequency ablation group (P 0.05). Conclusion During the 6-month follow-up period, pulsed field ablation demonstrated comparable efficacy to radiofrequency ablation with respect to recurrence rates for both paroxysmal and persistent atrial fibrillation. Moreover, pulsed field ablation exhibited high safety levels, excellent surgical efficiency, and a notably brief learning curve, affirming its viability as a therapeutic option for these conditions.

Abstract. Long-chain acyl-coenzyme A (CoA) synthase 4 (ACSL4) is an enzyme that esterifies CoA into specific polyunsaturated fatty acids, such as arachidonic acid and adrenic acid. Based on accumulated evidence, the ACSL4-catalyzed biosynthesis of arachidonoyl-CoA contributes to the execution of ferroptosis by triggering phospholipid peroxidation. Ferroptosis is a type of programmed cell death caused by iron-dependent peroxidation of lipids; ACSL4 and glutathione peroxidase 4 positively and negatively regulate ferroptosis, respectively. In addition, ACSL4 is an essential regulator of fatty acid (FA) metabolism. ACSL4 remodels the phospholipid composition of cell membranes, regulates steroidogenesis, and balances eicosanoid biosynthesis. In addition, ACSL4-mediated metabolic reprogramming and antitumor immunity have attracted much attention in cancer biology. Because it facilitates the cross-talk between ferroptosis and FA metabolism, ACSL4 is also a research hotspot in metabolic diseases and ischemia/reperfusion injuries. In this review, we focus on the structure, biological function, and unique role of ASCL4 in various human diseases. Finally, we propose that ACSL4 might be a potential therapeutic target.

The knowledge of the deposition fate of ambient polycyclic aromatic hydrocarbons (PAHs) on plant leaves is limited. To fill in this knowledge gap, this study strives to observe the intermolecular complex between the polycyclic aromatic hydrocarbons and epicuticular wax of plant leaves using laser scanning microscopy. Epicuticular wax refers to a type of organic mixture that covers the outermost layer of leaves. The leaves of 20 tree species were collected in Beijing in July 2023. The concentrations of 31 PAHs were quantified by gas chromatography–mass spectrometry. Furthermore, the intermolecular complexes of polycyclic aromatic hydrocarbons and epicuticular wax were found with a fluorescence spectrofluorometer and laser scanning microscopy. The levels of total PAHs across 20 tree species ranged from 12.4 ng g−1 to 68.4 ng g−1. Differences in the amounts of total PAHs across tree leaves were observed, which may be ascribed to the differences in leaf surface across tree types. The higher concentration of low-molecular-weight PAHs was found in leaves compared to high-molecular-weight PAHs. The fluorescence spectrofluorometer identified the formation of a new intermolecular complex with fluorescence emission at an excitation wavelength of 340 nm between PAHs and epicuticular wax relative to PAHs. We used laser scanning microscopy with a 405 nm laser for excitation to observe the new intermolecular complex of PAHs and epicuticular wax on the stomata and epicuticular wax of leaves. This study found the intermolecular complex of PAHs on the surface of leaves in situ, which provides important information about the deposition fate of ambient PAHs.

In ex vivo heart perfusion (EVHP), the control of aortic pressure (AoP) is critical for maintaining the heart’s physiologic aerobic metabolism. However, the complexity of and variability in cardiac parameters present a challenge in achieving the rapid and accurate regulation of AoP. In this paper, we propose a method of AoP control based on deep reinforcement learning for EVHP in Langendorff mode, which can adapt to the variations in cardiac parameters. Firstly, a mathematical model is developed by coupling the coronary artery and the pulsatile blood pump models. Subsequently, an aortic pressure control method based on the Deep Deterministic Policy Gradient (DDPG) algorithm is proposed. This method enables the regulation of the blood pump and the realization of closed-loop control. The control performance of the proposed DDPG method, the traditional proportional–integral–derivative (PID) method, and the fuzzy PID method are compared by simulating single and mixed changes in mean aortic pressure target values and coronary resistance. The proposed method exhibits superior performance compared to the PID and fuzzy PID methods under mixed factors, with 68.6% and 66.4% lower settling times and 70.3% and 54.1% lower overshoot values, respectively. This study demonstrates that the proposed DDPG-based method can respond more rapidly and accurately to different cardiac conditions than the conventional PID controllers.

The small-signal S parameters of the fabricated double-finger gate AlGaN/GaN high electron mobility transistors (HEMTs) were measured at various direct current quiescent operating points (DCQOPs). Under active bias conditions, small-signal equivalent circuit (SSEC) parameters such as Rs and Rd, and intrinsic parameters were extracted. Utilizing fT and the SSEC parameters, the effective electron velocity (νe−eff) and intrinsic electron velocity (νe−int) corresponding to each gate bias (VGS) were obtained. Under active bias conditions, the influence mechanism of VGS on νe−eff was systematically studied, and an expression was established that correlates νe−eff, νe−int, and bias-dependent parasitic resistances. Through the analysis of the main scattering mechanisms in AlGaN/GaN HEMTs, it has been discovered that the impact of VGS on νe−eff should be comprehensively analyzed from the aspects of νe−int and parasitic resistances. On the one hand, changes in VGS influence the intensity of polar optical phonon (POP) scattering and polarization Coulomb field (PCF) scattering, which lead to changes in νe−int dependent on VGS. The trend of νe−int with changes in VGS plays a dominant role in determining the trend of νe−eff with changes in VGS. On the other hand, both POP scattering and PCF scattering affect νe−eff through their impact on parasitic resistance. Since there is a difference in the additional scattering potential corresponding to the additional polarization charges (APC) between the gate-source/drain regions and the region under the gate, the mutual effects of PCF scattering on the under-gate electron system and the gate-source/drain electron system should be considered when adjusting the PCF scattering intensity through device structure optimization to improve linearity. This study contributes to a new understanding of the electron transport mechanisms in AlGaN/GaN HEMTs and provides a novel theoretical basis for improving device performance.

Foot-and-mouth disease (FMD) is one of the most infectious viral transboundary diseases of livestock, which causes devastating global economic losses. Different enzyme-linked immunosorbent assays (ELISAs) are used for sero-surveillance of the foot-and-mouth disease virus (FMDV). However, more sensitive, accurate, and convenient ELISAs are still required to detect antibodies against FMDV serotypes. The primary goal of this study was to establish serotype-specific monoclonal antibody (mAb)-based blocking ELISAs (mAb-bELISAs) that would provide better performance characteristics or be equivalent in performance characteristics compared with a conventional polyclonal antibody (pAb)-based competitive ELISA (pAb-cELISA). Four mAb-bELISAs were developed using FMDV serotype-specific mAbs for the detection of anti-FMDV/O/A/Asia1/SAT2 antibodies. Using a 50% cut-off, all four mAb-bELISAs exhibited species-independent 99.74%, 98.01%, 96.59%, and 98.55% diagnostic specificity (DSp) and 98.93%, 98.25%, 100%, and 87.50% diagnostic sensitivity (DSe) for FMDV serotypes O, A, Asia1, and SAT2, respectively. In addition, a 100% DSe of serotypes O- and SAT2-specific mAb-bELISAs was observed for porcine sera when the cut-off was 30%. All mAb-bELISAs developed in this study displayed high repeatability/reproducibility without cross-reactivity. Finally, the diagnostic performance of mAb-bELISAs was found to be better than or equivalent to compared with pAb-cELISAs, suggesting that mAb-bELISAs can be used to replace existing pAb-ELISAs for the detection of antibodies against these four FMDV serotypes.

Public open spaces make crucial contributions to the livability of communities and promote physical and mental health. Soundscapes play an important role in the overall physical comfort of public open spaces. However, owing to insufficient studies of high-density situations, soundscapes are ignored in public open spaces in high-density residential areas. This paper presents a case study of a soundscape in the overseas Chinese town (OCT) of Shenzhen, China. Through in situ observation, four distinct soundscapes were easily identified by performing soundscape conceptualization according to the ISO. In terms of the four identified soundscape areas, subjective evaluations of acoustic comfort and annoyance and their influencing factors were thoroughly explored. The results reveal that the natural soundscape had the best evaluations, whereas the artificial one did not have the worst result. It is interesting to note that acoustic factors do not always significantly influence a soundscape’s evaluation. A non-acoustic factor such as the spatial function may play a role as it is related to the context of an individual perceiving an acoustic environment. This study provides first-hand empirical evidence for understanding soundscapes and the influencing factors present in high-density residential public open spaces. The results provide useful knowledge for enhancing soundscape quality in such spaces.

Abstract Background Declining oocyte quality in women with advanced age has been a major impediment to assisted reproductive treatments’ (ART) success rate. However, aging is often accompanied by a diminished ovarian reserve (DOR). Cumulus cells (CCs) are known to play an important role in the development and maturation of oocytes, and the quality of CCs actually reflects the quality of the oocyte. In this study, CCs were used to investigate the real reasons for the decline in oocyte quality in older women. Methods Ninety-nine CC samples were subdivided into 4 different groups according to the different age and ovarian reserve status. Other than clinical ART results, transcriptional expression profiles were performed in CCs to detect the differences. Results The results were that DOR, no matter in young or advanced age group, was found to be significantly associated with adverse ART outcomes. Of note, there were no statistically significant changes in ART outcomes in the group at advanced age with normal ovarian reserve (NOR), compared to the young with NOR. DOR induced a series of transcriptional variations in CCs commonly enriched in oxygen metabolism. Conclusion Our results revealed that the ART outcomes in advanced patients were attributable to the DOR. The oxygen metabolic changes may interfere with CCs’ function of supporting oocytes. This study can provide guidance for ART practice that not age but ovarian reserve status is the main predictor for ART outcomes, and ovarian reserve status should be timely assessed when the clinical manifestations are still mild in elderly women.

Non-alcoholic fatty liver disease (NAFLD) is the leading chronic liver disease worldwide, with a progressive form of non-alcoholic steatohepatitis (NASH). It may progress to advanced liver diseases, including liver fibrosis, cirrhosis, and hepatocellular carcinoma. NAFLD/NASH is a comorbidity of many metabolic disorders such as obesity, insulin resistance, type 2 diabetes, cardiovascular disease, and chronic kidney disease. These metabolic diseases are often accompanied by systemic or extrahepatic inflammation, which plays an important role in the pathogenesis and treatment of NAFLD or NASH. Metabolites, such as short-chain fatty acids, impact the function, inflammation, and death of hepatocytes, the primary parenchymal cells in the liver tissue. Cholangiocytes, the epithelial cells that line the bile ducts, can differentiate into proliferative hepatocytes in chronic liver injury. In addition, hepatic non-parenchymal cells, including liver sinusoidal endothelial cells, hepatic stellate cells, and innate and adaptive immune cells, are involved in liver inflammation. Proteins such as fibroblast growth factors, acetyl-coenzyme A carboxylases, and nuclear factor erythroid 2-related factor 2 are involved in liver metabolism and inflammation, which are potential targets for NASH treatment. This review focuses on the effects of metabolic disease-induced extrahepatic inflammation, liver inflammation, and the cellular and molecular mechanisms of liver metabolism on the development and progression of NAFLD and NASH, as well as the associated treatments.

Prescription data is an important focus and breakthrough in the study of clinical treatment rules, and the complex multidimensional relationships between Traditional Chinese medicine (TCM) prescription data increase the difficulty of extracting knowledge from clinical data. This paper proposes a complex prescription recognition algorithm (MTCMC) based on the classification and matching of TCM prescriptions with classical prescriptions to identify the classical prescriptions contained in the prescriptions and provide a reference for mining TCM knowledge. The MTCMC algorithm first calculates the importance level of each drug in the complex prescriptions and determines the core prescription combinations of patients through the Analytic Hierarchy Process (AHP) combined with drug dosage. Secondly, a drug attribute tagging strategy was used to quantify the functional features of each drug in the core prescriptions; finally, a Bidirectional Long Short-Term Memory Network (BiLSTM) was used to extract the relational features of the core prescriptions, and a vector representation similarity matrix was constructed in combination with the Siamese network framework to calculate the similarity between the core prescriptions and the classical prescriptions. The experimental results show that the accuracy and F1 score of the prescription matching dataset constructed based on this paper reach 94.45% and 94.34% respectively, which is a significant improvement compared with the models of existing methods.

Abstract This study aimed to evaluate the diagnostic performances of dual-layer CT (DLCT) for the identification of positive lymph nodes (LNs) in patients with lymphoma and retrospectively included 1165 LNs obtained by biopsy from 78 patients with histologically proven lymphoma, who underwent both pretreatment DLCT and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). According to 18F-FDG PET/CT findings as a reference standard, cases were categorized into the LN-negative and LN-positive groups. LNs were then randomly divided at a ratio of 7:3 into the training (n = 809) and validation (n = 356) cohorts. The patients’ clinical characteristics and quantitative parameters including spectral curve slope (λHU), iodine concentration (IC) on arterial phase (AP) and venous phase (VP) images were compared between the LN-negative and LN-positive groups using Chi-square test, t-test or Mann–Whitney U test for categorical variables or quantitative parameters. Multivariate logistic regression analysis with tenfold cross-validation was performed to establish the most efficient predictive model in the training cohort. The area under the curve (AUC) was used to evaluate the diagnostic value of the predictive model, and differences in AUC were determined by the DeLong test. Moreover, the predictive model was validated in the validation cohort. Repeatability analysis was performed for LNs using intraclass correlation coefficients (ICCs). In the training cohort, long diameter (LD) had the highest AUC as an independent factors compared to other parameter in differentiating LN positivity from LN negativity (p = 0.006 to p 0.75). The combination of DLCT with morphological and functional parameters may represent a potential imaging biomarker for detecting LN positivity in lymphoma.

Abstract Background To clarify the relationship between p53 immunohistochemistry (IHC) staining and TP53 alterations (including mutations and deletions) in large B-cell lymphomas (LBCLs) and to explore the possibility of p53 IHC expression patterns as surrogate markers for TP53 alterations. Methods A total of 95 patients diagnosed with LBCLs were selected, and paraffin samples were taken for TP53 gene sequencing, fluorescence in situ hybridization and p53 IHC staining. The results were interpreted by experienced pathologists and molecular pathologists. Results Forty-three nonsynonymous TP53 mutations and p53 deletions were detected in 40 cases, whereas the remaining 55 cases had wild-type TP53 genes. The majority of TP53 mutations (34/43, 79.1%) occurred in exons 4-8, and R248Q was the most common mutation codon (4/43, 9.3%). The highest frequency single nucleotide variant was C > T (43.6%). p53 expression was interpreted as follows: Pattern A: p53 staining was positive in 0%-3% of tumor cells, Pattern B: p53 staining was positive in 4-65% of tumor cells, Pattern C: more than 65% of tumor cells were stained positive for p53. The p53 IHC expression patterns were associated with TP53 alterations. Gain of function variants and wild-type TP53 tended to exhibit type C and B p53 expression patterns, but loss of function variants were exclusively seen in type A cases. Additionally, interpretation of the staining by various observers produced significant reproducibility. Conclusions The p53 IHC expression patterns can be used to predict TP53 alterations and are reliable for diverse alteration types, making them possible surrogate biomarkers for TP53 alterations in LBCLs.

Abstract To evaluate myocardial strain in patients with different coronary artery disease-reporting and data system (CAD-RADS) levels using the computed tomography (CT) feature tracking technology and to investigate the relationship of myocardial strain with coronary artery calcium scores (CACs) and the degree of coronary artery stenosis. We prospectively enrolled 237 consecutive patients to undergo coronary CT angiography. The participants were divided into the following groups: control (n = 87), CAD-RADS 1 (n = 43), CAD-RADS 2 (n = 43), CAD-RADS 3 (n = 38), and CAD-RADS 4 and above (n = 26). Myocardial strains were analyzed by commercial software, and CACs and coronary stenosis were assessed on post-processing stations. Differences between multiple groups were analyzed using one-way analysis of variance or the Kruskal–Wallis test. Logistic regression were used to analyze the effects of dichotomous variables. As the CAD-RADS level increased, the global circumferential strain (GCS), global longitudinal strain (GLS) and global radial strain (GRS) of the left ventricle based on CT gradually decreased. A significant correlation was observed between global myocardial strain and CACs (GRS: r = − 0.219, GCS: r = 0.189, GLS: r = 0.491; P

Abstract Background The original weight loss grading system (WLGS) was developed in western population, which did not perform effectively in cancer patients from China. This study aimed to develop and validate the modified WLGS (mWLGS) in the prognostic assessment of cancer patients in China. Methods A prospective multicentre real‐world cohort study involving 16 842 patients diagnosed with cancer was conducted. Cox regression was used to calculate the hazard ratios for overall survival. Logistic linear regression was used to assess the odds ratio for 90‐day outcomes. Results We calculated survival risks for the 25 mWLGS groups and clustered the approximate survival risks. Finally, we revised the prognostic grading system for mWLGS to include five grades of 0–4. Compared with the original WLGS, the mWLGS had a better prognostic differentiation effect in predicting the prognosis of patients with cancer. The survival rate gradually deteriorated with increasing grade of mWLGS, with the survival rate of grade 0 decreasing from 76.4% to 48.2% for grade 4 (76.4 vs. 72.8 vs. 66.1 vs. 57.0 vs. 48.2%, respectively). The mWLGS provides effective prognostic stratification for most site‐specific cancers, especially lung and gastrointestinal cancers. High‐grade mWLGS is independently associated with an increased risk of poor quality of life and adverse 90‐day outcomes. Multivariate Cox regression analysis showed that the mWLGS was an independent prognostic factor for cancer patients in the validation cohorts. Conclusions Compared with the original WLGS, the mWLGS can better stratify the prognosis of cancer patients. mWLGS is a useful tool for predicting survival, 90‐day outcomes, and quality of life in patients with cancer. These analyses may provide new insights into the application of WLGS in cancer patients in China.

Abstract Autophagy of endoplasmic reticulum (ER-phagy) selectively removes damaged ER through autophagy-lysosome pathway, acting as an adaptive mechanism to alleviate ER stress and restore ER homeostasis. However, the role and precise mechanism of ER-phagy in tubular injury of diabetic kidney disease (DKD) remain obscure. In the present study, we demonstrated that ER-phagy of renal tubular cells was severely impaired in streptozocin (STZ)-induced diabetic mice, with a decreased expression of phosphofurin acidic cluster sorting protein 2 (PACS-2), a membrane trafficking protein which was involved in autophagy, and a reduction of family with sequence similarity 134 member B (FAM134B), one ER-phagy receptor. These changes were further aggravated in mice with proximal tubule specific knockout of Pacs-2 gene. In vitro, transfection of HK-2 cells with PACS-2 overexpression plasmid partially improved the impairment of ER-phagy and the reduction of FAM134B, both of which were induced in high glucose ambience; while the effect was blocked by FAM134B siRNA. Mechanistically, PACS-2 interacted with and promoted the nuclear translocation of transcription factor EB (TFEB), which was reported to activate the expression of FAM134B. Collectively, these data unveiled that PACS-2 deficiency aggravates renal tubular injury in DKD via inhibiting ER-phagy through TFEB/FAM134B pathway.

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.

Abstract M6A methylation is the most prevalent and abundant RNA modification in mammals. Although there are many studies on the regulatory role of m6A methylation in the immune response, the m6A regulators in the pathogenesis of acute ST-segment elevation myocardial infarction (STEMI) remain unclear. We comprehensively analysed the role of m6A regulators in STEMI and built a predictive model, revealing the relationship between m6A methylations and the immune microenvironment. Differential analysis revealed that 18 of 24 m6A regulators were significantly differentially expressed, and there were substantial interactions between the m6A regulator. Then, we established a classifier and nomogram model based on 6 m6A regulators, which can easily distinguish the STEMI and control samples. Finally, two distinct m6A subtypes were obtained and significantly differentially expressed in terms of infiltrating immunocyte abundance, immune reaction activity and human leukocyte antigen genes. Three hub m6A phenotype related genes (RAC2, RELA, and WAS) in the midnightblue module were identified by weighted gene coexpression network analysis, and were associated with immunity. These findings suggest that m6A modification and the immune microenvironment play a key role in the pathogenesis of STEMI.