Search

Abstract Background Promoting patient participation stands as a global priority in nursing care. Currently, there is a lack of a standardized tool to assess the culture of patient participation from the perspective of nurses in China. Aims To translate and examine the validity and reliability of the Patient Participation Culture Tool for healthcare workers (PaCT-HCW) on general hospital wards in Chinese nursing context. Methods A cross-sectional research study was conducted among 812 nurses. Brislin's recommendations were adhered to during the translation of the scale. Validity was assessed using construct validity, content validity, and face validity. Split-half reliability, test–retest reliability, and internal consistency reliability were used to evaluate dependability. The study was guided and reported following the STROBE checklist and recommendations for reporting the results of studies of instrument and scale development and testing. Results The Chinese version of PaCT-HCW (the PaCT-HCW-C) exhibits good face validity and content validity. A rigorous exploratory factor analyse verified a six-factor (competence, support, perceived lack of time, information sharing and dialogue, response to questions and acceptance of a new role) scale structure with a cumulative variance contribution of the factors with 44 items of 68.840%. With a Cronbach's α coefficient of 0.962, split-half reliability of 0.866, and intraclass correlation coefficients of 0.989, the instrument demonstrates great reliability. Confirmatory factor analysis results validated the consistency of the six factors with the structure of the PaCT-HCW-C scale. Conclusions The 44-item PaCT-HCW-C is a valid and reliable instrument with satisfactory psychometric properties. It could serve as a tool for assessing the effectiveness of international programs aimed at fostering patient participation from the perspective of nurses, while also providing insights from China's practical experiences.

Abstract Li metal batteries have been widely expected to break the energy‐density limits of current Li‐ion batteries, showing impressive prospects for the next‐generation electrochemical energy storage system. Although much progress has been achieved in stabilizing the Li metal anode, the current Li electrode still lacks efficiency and safety. Moreover, a practical Li metal battery requires a thickness‐controllable Li electrode to maximally balance the energy density and stability. However, due to the stickiness and fragile nature of Li metal, manufacturing Li ingot into thin electrodes from conventional approaches has historically remained challenging, limiting the sufficient utilization of energy density in Li metal batteries. Aiming at the practical application of Li metal anode, the current issues and their initiation mechanism are comprehensively summarized from the stability and processability perspectives. Recent advances in robust and ultra‐thin Li metal anode are outlined from methodology innovation to provide an overall insight. Finally, challenges and prospective developments regarding this burgeoning field are critically discussed to afford future outlooks. With the development of advanced processing and modification technology, we are optimistic that a truly great leap will be achieved in the foreseeable future toward the industrial application of Li metal batteries.

Abstract The inactivation of natural enzymes by radiation poses a great challenge to their applications for radiotherapy. Single-atom nanozymes (SAzymes) with high structural stability under such extreme conditions become a promising candidate for replacing natural enzymes to shrink tumors. Here, we report a CuN3-centered SAzyme (CuN3-SAzyme) that exhibits higher peroxidase-like catalytic activity than a CuN4-centered counterpart, by locally regulating the coordination environment of single copper sites. Density functional theory calculations reveal that the CuN3 active moiety confers optimal H2O2 adsorption and dissociation properties, thus contributing to high enzymatic activity of CuN3-SAzyme. The introduction of X-ray can improve the kinetics of the decomposition of H2O2 by CuN3-SAzyme. Moreover, CuN3-SAzyme is very stable after a total radiation dose of 500 Gy, without significant changes in its geometrical structure or coordination environment, and simultaneously still retains comparable peroxidase-like activity relative to natural enzymes. Finally, this developed CuN3-SAzyme with remarkable radioresistance can be used as an external field-improved therapeutics for enhancing radio-enzymatic therapy in vitro and in vivo. Overall, this study provides a paradigm for developing SAzymes with improved enzymatic activity through local coordination manipulation and high radioresistance over natural enzymes, for example, as sensitizers for cancer therapy.

Abstract Evolution of SARS-CoV-2 variants emphasizes the need for multivalent vaccines capable of simultaneously targeting multiple strains. SCTV01E is a tetravalent COVID-19 vaccine derived from the spike protein of SARS-CoV-2 variants Alpha, Beta, Delta, and Omicron BA.1. In this double-blinded placebo-controlled pivotal efficacy trial (NCT05308576), the primary endpoint was vaccine efficacy (VE) against COVID-19 seven days post-vaccination in individuals without recent infection. Other endpoints included evaluating safety, immunogenicity, and the VE against all SARS-CoV-2 infections in individuals meeting the study criteria. Between December 26, 2022, and January 15, 2023, 9,223 individuals were randomized at a 1:1 ratio to receive SCTV01E or a placebo. SCTV01E showed a VE of 69.4% (95% CI: 50.6, 81.0) 7 days post-vaccination, with 75 cases in the placebo group and 23 in the SCTV01E group for the primary endpoint. VEs were 79.7% (95% CI: 51.0, 91.6) and 82.4% (95% CI: 57.9, 92.6), respectively, for preventing symptomatic infection and all SARS-CoV-2 infections 14 days post-vaccination. SCTV01E elicited a 25.0-fold higher neutralizing antibody response against Omicron BA.5 28 days post-vaccination compared to placebo. Reactogenicity was generally mild and transient, with no reported vaccine-related SAE, adverse events of special interest (AESI), or deaths. The trial aligned with the shift from dominant variants BA.5 and BF.7 to XBB, suggesting SCTV01E as a potential vaccine alternative effective against present and future variants.

The forecast of the global numerical weather prediction model is often used as the background field to drive the regional mesoscale weather models, and its forecast quality has an important impact on the prediction skill of regional models. The mesoscale operational model in Central China uses the Global Forecast Field (NCEP GFS) of the US Center for Environmental Prediction as the background field, and its forecast accuracy needs to be improved. This paper proposes a method to improve the initial field of the model by using the three-dimensional variational method to assimilate the high-quality European Centre for Medium-range Weather Forecasts (ECMWF) fine-grid forecast field to improve the short-term forecasting ability of the model. At first, the error characters of the 12 h forecast products of NCEP GFS and ECMWF were analyzed by using sounding observations. The RMSE (root mean square error) of temperature, horizontal wind field and relative humidity of ECMWF 12 h forecast are smaller than those of NCEP GFS forecast. Second, sensitivity experiments of ECMWF forecast field assimilation with different resolutions were conducted. Finally, 1°×1° resolution was selected based on the sensitivity experiments and a series of the data assimilation experiments with 1°×1° resolution was performed for August 2021. The results are as follows. (1) The assimilation forecast of heavy rain from 11 to 13 August 2021 shows that after 12 hours of spin-up, the forecast error of the element field has been significantly improved, especially at the bottom of the model. The TS score of 12-36 h, 36-60 h and 60-84 h cumulative precipitation has a certain improvement, especially the forecast of rainstorm magnitude. (2) ECMWF forecast field assimilation sensitivity experiments with different resolutions show that the forecast effect of ECMWF forecast field with 1°×1° resolution is better than 0.5°×0.5° and 0.25°×0.25°. (3) A series of the data assimilation experiments for August 2021 shows that the assimilation of ECMWF 12 h 1°×1° predicted variables has a lower RMSE of the 12 h, 36 h and 60 h forecasted temperature, humidity and wind field in the vertical direction than the control experiments, and the TS score was significantly improved, especially for 50 mm heavy rain precipitation, with an increase of 13.33%, which can effectively improve the forecast skills of the Wuhan Mesoscale Model.

Abstract Background Q fever, caused by the zoonotic pathogen Coxiella burnetii, exhibits a worldwide prevalence. In China, Q fever is not recognized as a notifiable disease, and the disease is overlooked and underestimated in clinical practice, leading to diagnostic challenges. Case presentation We present a case series of three patients diagnosed with persistent Q fever between 2022 and 2023. The average age of our three cases was 63.33 years old, consisting of two males and one female. The medical history of the individuals included previous valve replacement, aneurysm followed by aortic stent-graft placement and prosthetic hip joint replacement. At the onset of the disease, only one case exhibited acute fever, while the remaining two cases were devoid of any acute symptoms. The etiology was initially overlooked until metagenomic next-generation sequencing test identified Coxiella burnetii from the blood or biopsy samples. Delayed diagnosis was noted, with a duration ranging from three months to one year between the onset of the disease and its confirmation. The epidemiological history uncovered that none of the three cases had direct exposure to domestic animals or consumption of unpasteurized dairy products. Case 1 and 2 resided in urban areas, while Case 3 was a rural resident engaged in farming. All patients received combination therapy of doxycycline and hydroxychloroquine, and no recurrence of the disease was observed during the follow-up period. Conclusion Q fever is rarely diagnosed and reported in clinical practice in our country. We should be aware of persistent Q fever in high-risk population, even with unremarkable exposure history. Metagenomic next-generation sequencing holds great potential as a diagnostic tool for identifying rare and fastidious pathogens such as Coxiella burnetii.

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

This study was conducted to evaluate the effects of Monascus purpureus M-32 fermented soybean meal (MFSM) on growth, immunity, intestinal morphology, intestinal microbiota, and intestinal metabolome of Pacific white shrimp (Litopenaeus vannamei). Four groups of diets were formulated, including control group (30% fish meal and 30% soybean meal [SBM] included in the basal diet) and three experimental groups which MFSM replaced 20% (MFSM20), 40% (MFSM40), and 60% (MFSM60) of SBM in control group, respectively. Results showed that the soluble proteins larger than 49 kDa in MFSM were almost completely degraded. Meanwhile, the crude protein, acid-soluble protein, and amino acid in MFSM were increased. The results of shrimp culture experiment showed that the replacement of SBM with MFSM decreased FCR (P

Multiple myeloma (MM) is the second most prevalent hematological malignancy. Current MM treatment strategies are hampered by systemic toxicity and suboptimal therapeutic efficacy. This study addressed these limitations through the development of a potent MM-targeting chemotherapy strategy, which capitalized on the high binding affinity of alendronate for hydroxyapatite in the bone matrix and the homologous targeting of myeloma cell membranes, termed T-PB@M. The results from our investigations highlight the considerable bone affinity of T-PB@M, both in vitro and in vivo. Additionally, this material demonstrated a capability for drug release triggered by low pH conditions. Moreover, T-PB@M induced the generation of reactive oxygen species and triggered cell apoptosis through the poly(ADP-ribose) polymerase 1 (PARP1)–Caspase-3–B-cell lymphoma-2 (Bcl-2) pathway in MM cells. Notably, T-PB@M preferentially targeted bone-involved sites, thereby circumventing systemic toxic side effects and leading to prolonged survival of MM orthotopic mice. Therefore, this designed target-MM nanocarrier presents a promising and potentially effective platform for the precise treatment of MM.

Abstract Background Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne infectious disease, and its morbidity and mortality are increasing. At present, there is no specific therapy available. An exacerbated IFN-I response and cytokine storm are related to the mortality of patients with SFTS. Ruxolitinib is a Janus kinase (JAK) 1/2 inhibitor that can block proinflammatory cytokines and inhibit the type I IFN pathway. We aimed to explore the use of ruxolitinib plus standard of care for severe SFTS. Methods We conducted a prospective, single-arm study of severe SFTS. We recruited participants aged 18 years or older who were admitted to the hospital with laboratory-confirmed severe SFTS and whose clinical score exceeded 8 points within 6 days of symptom onset. Participants received oral ruxolitinib (10 mg twice a day) for up to 10 days. The primary endpoint was 28-day overall survival. The secondary endpoints included the proportion of participants who needed intensive care unit (ICU) admission, total cost, changes in neurologic symptoms and clinical laboratory parameters, and adverse events (AEs) within 28 days. A historical control group (HC group, n = 26) who met the upper criteria for inclusion and hospitalized from April 1, 2021, to September 16, 2022, was selected and 1:1 matched for baseline characteristics by propensity score matching. Results Between Sep 16, 2022, and Sep 16, 2023, 26 participants were recruited into the ruxolitinib treatment group (RUX group). The 28-day overall mortality was 7.7% in the RUX group and 46.2% in the HC group (P = 0.0017). There was a significantly lower proportion of ICU admissions (15.4% vs 65.4%, p

Abstract Charge loss at grain boundaries of kesterite Cu2ZnSn(S, Se)4 polycrystalline absorbers is an important cause limiting the performance of this emerging thin-film solar cell. Herein, we report a Pd element assisted reaction strategy to suppress atomic vacancy defects in GB regions. The Pd, on one hand in the form of PdSe x compounds, can heterogeneously cover the GBs of the absorber film, suppressing Sn and Se volatilization loss and the formation of their vacancy defects (i.e. VSn and VSe), and on the other hand, in the form of Pd(II)/Pd(IV) redox shuttle, can assist the capture and exchange of Se atoms, thus contributing to eliminating the already-existing VSe defects within GBs. These collective effects have effectively reduced charge recombination loss and enhanced p-type characteristics of the kesterite absorber. As a result, high-performance kesterite solar cells with a total-area efficiency of 14.5% (certified at 14.3%) have been achieved.

Carbon nanotubes (CNTs), as a kind of nanopowder, can be used as reinforcing powder to improve various properties of coatings because of their good self-lubricating properties and three-dimensional structure. However, CNTs are difficult to mix uniformly with other powders due to their easily disrupted microstructure and extremely low density. Therefore, CoCrFeNiMn HEA and 2 wt% CNTs were mixed by a new mixing method—alcohol stirring and ball-less ball mill mixing methods. CoCrFeNiMn/2 wt% CNTs coatings prepared by laser cladding (LC). The phase composition, microstructure, wear resistance, and corrosion resistance of the HEA/CNTs coating were analyzed by various characterization techniques. The results showed that grain refinement occurred in the coatings after adding CNTs, generating fine carbides. It was calculated that the densification percentage of the HEA/CNTs coating increased and the porosity decreased. Compared with the HEA coating, the microhardness of the HEA/CNTs coating increased by 101.66%, and the friction coefficient and wear rate of the HEA/CNTs coating were only 63.30% and 6.22% of the HEA coating. The more positive Ecorr and smaller Icorr indicated that the HEA/CNTs coating has better corrosion resistance.

Abstract Self-powered skin attachable and detachable electronics are under intense development to enable the internet of everything and everyone in new and useful ways. Existing on-demand separation strategies rely on complicated pretreatments and physical properties of the adherends, achieving detachable-on-demand in a facile, rapid, and universal way remains challenging. To overcome this challenge, an ingenious cellulose nanofiber-mediated manifold dynamic synergy strategy is developed to construct a supramolecular hydrogel with both reversible tough adhesion and easy photodetachment. The cellulose nanofiber-reinforced network and the coordination between Fe ions and polymer chains endow the dynamic reconfiguration of supramolecular networks and the adhesion behavior of the hydrogel. This strategy enables the simple and rapid fabrication of strong yet reversible hydrogels with tunable toughness ((Value max -Value min )/Value max of up to 86%), on-demand adhesion energy ((Value max -Value min )/Value max of up to 93%), and stable conductivity up to 12 mS cm−1. We further extend this strategy to fabricate different cellulose nanofiber/Fe3+-based hydrogels from various biomacromolecules and petroleum polymers, and shed light on exploration of fundamental dynamic supramolecular network reconfiguration. Simultaneously, we prepare an adhesive-detachable triboelectric nanogenerator as a human-machine interface for a self-powered wireless monitoring system based on this strategy, which can acquire the real-time, self-powered monitoring, and wireless whole-body movement signal, opening up possibilities for diversifying potential applications in electronic skins and intelligent devices.

Bacteriocins from lactic acid bacteria are kinds of natural proteins or peptides with antibacterial activities produced by lactic acid bacteria in the process of metabolism. They have the advantages of non-drug resistance, biodegradation, good antibacterial activity, etc., which have broad application prospects in food, medicine and feed fields. Based on bibliometrics, the literatures related to bacteriocins from lactic acid bacteria are searched in CNKI database and Web of Science (WOS) core collection database from 2000 to 2023, obtains 627 Chinese literatures and 2543 English literatures. CiteSpace software is used to analyze the research status and hot spots in this field from the perspective of annual number of published papers, core countries, authors, institutions and journals, highly cited literatures, keyword co-occurrence and co-clustering, etc.. The results show that the number of literatures has an increasing trend from 2000 to 2022. Spain, India and China are the top three countries in terms of number of literatures. The authors with the highest number of publications in CNKI database and WOS database are LI Pinglan from China Agricultural University and Todorov SD from University of Sao Paulo in Brazil, respectively. The journals with the highest number of publications are “Science and Technology of Food Industry” and “Journal of Appled Micbiogy”. In the CNKI database, keyword analysis reveals that most of the literatures are isolated, screened and identified from different food samples to obtain bacteriocin-producing lactic acid bacteria, and further evaluates the antibacterial activity of bacteriocins, and discusses the application in the food industry. The analysis of burst words shows that the focus of current research are antibacterial mechanism of bacteriocin and the relationship between bacteriocin and probiotics. In WOS database, the keywords of "gastrointestinal tract", "genetic characteristics", "Listeria mononucleogenes" and "antibacterial activity" appears more frequently. The main focus is the mining of bacteriocins from lactic acid bacteria toward antibiotic-resistant bacteria, and analysis of the genetic characteristics. The comprehensive analysis provides a reference and help for Chinese scientific researchers to engage in related research and predict the future development trend of the industry.

Abstract The manipulation of excitation modes and resultant emission colors in luminescent materials holds pivotal importance for encrypting information in anti-counterfeiting applications. Despite considerable achievements in multimodal and multicolor luminescent materials, existing options generally suffer from static monocolor emission under fixed external stimulation, rendering them vulnerability to replication. Achieving dynamic multimodal luminescence within a single material presents a promising yet challenging solution. Here, we report the development of a phosphor exhibiting dynamic multicolor photoluminescence (PL) and photo-thermo-mechanically responsive multimodal emissions through the incorporation of trace Mn2+ ions into a self-activated CaGa4O7 host. The resulting phosphor offers adjustable emission-color changing rates, controllable via re-excitation intervals and photoexcitation powers. Additionally, it demonstrates temperature-induced color reversal and anti-thermal-quenched emission, alongside reproducible elastic mechanoluminescence (ML) characterized by high mechanical durability. Theoretical calculations elucidate electron transfer pathways dominated by intrinsic interstitial defects and vacancies for dynamic multicolor emission. Mn2+ dopants serve a dual role in stabilizing nearby defects and introducing additional defect levels, enabling flexible multi-responsive luminescence. This developed phosphor facilitates evolutionary color/pattern displays in both temporal and spatial dimensions using readily available tools, offering significant promise for dynamic anticounterfeiting displays and multimode sensing applications.

Abstract Background Timely and accurate identification of pathogens is crucial for appropriate treatment and prognosis of infectious diseases. As an increasingly popular pathogen detection method, the performance of metagenomic next-generation sequencing (mNGS) in detecting pathogens in febrile patients with suspected infection requires further exploration. Methods This study included 368 febrile patients with suspected infections who were admitted to the Infectious Disease Department of Qilu Hospital, Shandong University between January 5, 2021 and April 14, 2023. Both mNGS testing and conventional culture were performed in all patients. Clinical data of enrolled patients were collected, and the diagnostic performances of mNGS and culture were compared. Results Of the 368 enrolled patients, 231 were finally diagnosed with infection and 137 were with diseases other than infection. The sensitivity (58.01% vs. 21.65%, p

Abstract Based on the advantages of laser high brightness, a high-temperature mechanical property measuring device has been developed, which can measure the high-temperature strength of C/SiC composites under the condition of short-term high-temperature rise rate and solve the problem of over-oxidation of materials in conventional high-temperature mechanical properties experiments. The experimental results show that the maximum temperature rise rate is 260 ℃/s at the initial heating stage, and the test time is controlled within 35 s. The tensile strength of the prepared C/SiC composites decreased first and then increased at high temperatures and laser-induced high temperatures. The experimental results are similar to those in the literature under the inert atmosphere. Oxidation has less of an effect on the mechanical characteristics of materials under conditions of rapid temperature rise. The system can be used to test the mechanical properties of composite materials at high temperatures and as a simulation platform for the thermal response of specific thermal protection systems subjected to a constant heat flux. This study can provide a new idea for testing ultra-high temperature mechanical properties of C/SiC materials and provide key technical support for the engineering application and high-temperature testing of C/SiC materials in high-temperature environments.

Abstract The structural modeling of open-high-low-close (OHLC) data contained within the candlestick chart is crucial to financial practice. However, the inherent constraints in OHLC data pose immense challenges to its structural modeling. Models that fail to process these constraints may yield results deviating from those of the original OHLC data structure. To address this issue, a novel unconstrained transformation method, along with its explicit inverse transformation, is proposed to properly handle the inherent constraints of OHLC data. A flexible and effective framework for structurally modeling OHLC data is designed, and the detailed procedure for modeling OHLC data through the vector autoregression and vector error correction model are provided as an example of multivariate time-series analysis. Extensive simulations and three authentic financial datasets from the Kweichow Moutai, CSI 100 index, and 50 ETF of the Chinese stock market demonstrate the effectiveness and stability of the proposed modeling approach. The modeling results of support vector regression provide further evidence that the proposed unconstrained transformation not only ensures structural forecasting of OHLC data but also is an effective feature-extraction method that can effectively improve the forecasting accuracy of machine-learning models for close prices.

Objectives: This study aimed to investigate the association between drug exposure and adverse events (AEs) during the standardized multidrug-resistant tuberculosis (MDR-TB) treatment, as well as to identify predictive drug exposure thresholds. Methods: We conducted a prospective, observational multicenter study among participants receiving standardized MDR-TB treatment between 2016 and 2019 in China. AEs were monitored throughout the treatment and their relationships to drug exposure (e.g., the area under the drug concentration-time curve from 0 to 24 h, AUC0-24 h) were analyzed. The thresholds of pharmacokinetic predictors of observed AEs were identified by boosted classification and regression tree (CART) and further evaluated by external validation. Results: Of 197 study participants, 124 (62.9%) had at least one AE, and 15 (7.6%) experienced serious AEs. The association between drug exposure and AEs was observed including bedaquiline, its metabolite M2, moxifloxacin and QTcF prolongation (QTcF >450 ms), linezolid and mitochondrial toxicity, cycloserine and psychiatric AEs. The CART-derived thresholds of AUC0-24 h predictive of the respective AEs were 3.2 mg·h/l (bedaquiline M2); 49.3 mg·h/l (moxifloxacin); 119.3 mg·h/l (linezolid); 718.7 mg·h/l (cycloserine). Conclusions: This study demonstrated the drug exposure thresholds predictive of AEs for key drugs against MDR-TB treatment. Using the derived thresholds will provide the knowledge base for further randomized clinical trials of dose adjustment to minimize the risk of AEs.

Multi-functional triply periodic minimal surface (TPMS) structures have been widely studied and proven to have significant importance. Most studies are based on several typical TPMSs. However, some research suggests that the hybrid forms of the TPMSs can exhibit superior mechanical properties. The challenge lies in the unpredictability of the hybrid TPMS property. In this study, an approach is proposed for precisely identify the hybrid TPMS using fully connected neural network (FCNN) and particle swarm optimization (PSO) algorithm. A design space of four TPMSs hybridization is introduced and used to generate over 8000 samples. Stiffness constants obtained using the homogenization method is used in elastic characterization. The hybrid TPMSs is proved to lack common cubic symmetry but possess wide rotational symmetry. Indirect stiffness constant-based way exhibits better predictions for optimal stiffness and elastic isotropy than direct property parameter-based one. The approach successfully identified useful structures: quasi-elastic-isotropic ones and a ultra-stiff one that is ∼ 9 % stronger than the currently strongest TPMS. The method offers comprehensive guidance for stiffness constant-based TPMS design using DL technique.

Introduction: Numerous studies have explored the treatment outcomes of Nirmatrelvir-Ritonavir and Azvudine in older patients with COVID-19. However, direct comparisons between these two drugs are still relatively limited. This study aims to compare the safety and effectiveness of these two drugs in Chinese older patients with early infection to provide strategies for clinical treatment.Methods: Older COVID-19 patients (age ≥65) hospitalized during the winter 2022 epidemic in China were included and divided into Nirmatrelvir-Ritonavir and Azvudine. Demographics, medication information, laboratory parameters, and treatment outcomes were collected. All-cause 28-day mortality, delta cycle threshold (ΔCt), nucleic acid negative conversion time, and incidence of adverse events were defined as outcomes. Propensity score matching (PSM), Kaplan-Meier, Cox proportional hazards model, subgroup analysis, and nomograms were selected to evaluate the outcomes.Results: A total of 1,508 older COVID-19 patients were screened. Based on the inclusion and exclusion criteria, 1,075 patients were eligible for the study. After PSM, the final number of older COVID-19 patients included in the study was 375, and there were no significant differences in demographic characteristics between the two groups (p > 0.05). Compared to the Azvudine group, the Nirmatrelvir-Ritonavir group showed a higher incidence of multiple adverse events (12.8% vs 5.2%, p = 0.009). The incidence of adverse events related to abnormal renal function was higher in the Nirmatrelvir-Ritonavir group compared to the Azvudine group (13.6% vs 7.2%, p = 0.045). There were no significant differences between the two groups in terms of all-cause 28-day mortality (HR = 1.020, 95% CI: 0.542 - 1.921, p = 0.951), whereas there were significant differences in nucleic acid negative conversion time (HR = 1.659, 95% CI: 1.166 - 2.360, p = 0.005) and ΔCt values (HR = 1.442, 95% CI: 1.084 - 1.918, p = 0.012).Conclusion: Azvudine and Nirmatrelvir-Ritonavir have comparable effectiveness in reducing mortality risk. Azvudine may perform better in nucleic acid negative conversion time and virus clearance and shows slightly better safety in older patients. Further studies with a larger sample size were needed to validate the result.

Defective oocyte maturation is a common cause of female infertility. The loss of the zona pellucida (ZP) represents a specific condition of impaired oocyte maturation. The extracellular matrix known as the ZP envelops mammalian oocytes and preimplantation embryos, exerting significant influence on oogenesis, fertilization, and embryo implantation. However, the genetic factors leading to the loss of the ZP in oocytes are not well understood. This study focused on patients who underwent oocyte retrieval surgery after ovarian stimulation and were found to have abnormal oocyte maturation without the presence of the ZP. Ultrasonography was performed during the surgical procedure to evaluate follicle development. Peripheral blood samples from the patient were subjected to exome sequencing. Here, a novel, previously unreported heterozygous mutation in the ZP1 gene was identified. Within the ZP1 gene, we discovered a novel heterozygous mutation (ZP1 NM_207341.4:c.785A>G (p.Y262C)), specifically located in the trefoil domain. Bioinformatics comparisons further revealed conservation of the ZP1-Y262C mutation across different species. Model predictions of amino acid mutations on protein structure and cell immunofluorescence/western blot experiments collectively confirmed the detrimental effects of the ZP1-Y262C mutation on the function and expression of the ZP1 protein. The ZP1-Y262C mutation represents the novel mutation in the trefoil domain of the ZP1 protein, which is associated with defective oocyte maturation in humans. Our report enhances comprehension regarding the involvement of ZP-associated genes in female infertility and offers enriched understanding for the genetic diagnosis of this condition.

Background The association between gut bacteria and the response to immune checkpoint inhibitors (ICI) in hepatocellular carcinoma (HCC) has been studied; however, multi-kingdom gut microbiome alterations and interactions in ICI-treated HCC cohorts are not fully understood.Methods From November 2018 to April 2022, patients receiving ICI treatment for advanced HCC were prospectively enrolled. Herein, we investigated the multi-kingdom microbiota characterization of the gut microbiome, mycobiome, and metabolome using metagenomic, ITS2, and metabolomic data sets of 80 patients with ICI-treated HCC.Results Our findings demonstrated that bacteria and metabolites differed significantly between the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups, whereas the differences were smaller for fungi. The overall diversity of bacteria and fungi before treatment was higher in the DCB group than in the NDB group, and the difference in diversity began to change with the use of immunotherapy after 6–8 weeks. We also explored the alterations of gut microbes in the DCB and NDB groups, established 18 bacterial species models as predictive biomarkers for predicting whether immunotherapy is of sustained benefit (area under the curve=75.63%), and screened two species of bacteria (Actinomyces_sp_ICM47, and Senegalimassilia_anaerobia) and one metabolite (galanthaminone) as prognostic biomarkers for predicting survival in patients with HCC treated with ICI.Conclusions In this study, the status and characterization of the multi-kingdom microbiota, including gut bacteria, fungi, and their metabolites, were described by multiomics sequencing for the first time in patients with HCC treated with ICI. Our findings demonstrate the potential of bacterial taxa as predictive biomarkers of ICI clinical efficacy, and bacteria and their metabolites as prognostic biomarkers.

ObjectivesUnder the system of health decentralization, there are differences in the level of expenditure decentralization at different levels of government, and their impact on residents’ health may also be different. This paper is one of the first to evaluate the effect of decentralization of health services at the municipal level from a multi-dimensional health perspective.Data and methodsThis paper uses the data of expenditure decentralization of health services at the municipal level to match the panel data from the China Household Panel Survey (CFPS) from 2010 to 2018, and uses the logit model, ordered logit model and two-way fixed effects model to empirically analyze the impact of health decentralization at the municipal level on health outcomes.ResultsBased on the perspective of multi-dimensional health, from the three aspects of physical health, depression status and cognitive ability, the six sub-indicators of self-rated health, BMI standards, depression scores (summation method), depression scores (factor method), phrase test scores and mathematics test scores are discussed separately. The results show that the decentralization of health services at the municipal level has a significant promotion effect on the multi-dimensional health of residents.ConclusionThe decentralization of health services at the municipal level has important theoretical significance for promoting the reasonable division of medical and health powers and expenditure responsibilities between provincial and municipal governments, improving the efficiency of health expenditure funds, and establishing a fiscal system that matches financial resources.

Abstract This article uses ultra‐high performance concrete (UHPC) to repair damaged concrete and analyzes the durability performance of the repaired concrete. Among them, three erosion solutions with a mass concentration of 2.8% NaCl + 0.29% Na2SO4, 5% NaCl, and 5% NaCl + 10% Na2SO4 were designed to soak the concrete specimens for 1 to 3 months. Taking the SWC test group as an example, when the concrete test block undergoes 30 dry wet cycles and the erosion depth is 20 mm, the difference in chloride ion concentration under different diffusion dimensions is not significant. After 90 dry wet cycles, at a depth of 20 mm, the chloride ion concentration inside the concrete in the three‐dimensional diffusion state reached 3 times that of one‐dimensional diffusion, and the chloride ion concentration in the two‐dimensional diffusion state also reached 2 times that of one‐dimensional diffusion. At a depth of 30 mm, a small amount of chloride ion content was also found in the two‐dimensional diffusion and three‐dimensional diffusion.

Consumers rely on flavor characteristics to distinguish different types of Qingke Baijiu (QKBJ). Clarifying QKBJ's traits enhances its recognition and long-term growth. Thus, this study analyzed eight QKBJ samples from different regions of Tibet (Lhasa, Sannan, Shigatse, and Qamdo) using GC–MS, electronic nose and electronic tongue. The radar charts of the electronic tongue and electronic nose revealed highly similar profiles for all eight samples. Fifteen common compounds were found in all samples, with the main alcohol compounds being 3-Methyl-1-butanol, 1-hexanol, isobutanol, 1-butanol, 1-nonanol, and phenylethyl alcohol, imparting fruity, floral, and herbal aromas. However, the Sannan samples had higher total alcohol content than total ester content, emphasizing bitterness. Lhasa1 exhibited the most prominent sweetness, Lhasa2 the most noticeable sourness, and Qamdo the most pronounced umami. Lhasa3 and Lhasa4 had total acid content second only to total ester content. Tyd had the highest alkanes, while Lhasa had most aldehydes among samples.

Microbial composition plays an important role in the quality and flavor of bacon. The aims of this study were to detect bacterial community succession using high-throughput sequencing (HTS) and volatile flavor compound changes using gas chromatography-ion mobility spectrometry (GC-IMS) during the production of Zhenba bacon. The results showed that a total of 70 volatile compounds were detected. Among them, ketones, hydrocarbons, aldehydes, esters and alcohols were the main substances in the curing and smoking stages. In addition, the fungal abundance was greater than the bacterial abundance, and there was obvious succession of the microbial community with changes in fermentation time and processing technology. The main functional bacterial genera in the curing and smoking stages were Staphylococcus, Psychrobacter and Latilactobacillus, and the main fungal genera were Fusarium and Debaryomyces. Through correlation analysis, we found that pyrrole, 2-pentanol, methyl isobutyl ketone (MIBK) and ethyl acetate (EA) were significantly correlated with Staphylococcus, Psychrobacter, Pseudomonas and Myroides (p

Abstract Background Providing informal care for individuals with dementia is frequently a challenging and demanding experience that can have detrimental effects on the psychological well-being of caregivers. Regrettably, community-based caregiver services often prove inadequate, highlighting the necessity for innovative approaches to support caregivers. Aim To test the efficacy of e-bibliotherapy in improving the psychological well-being of informal caregivers of people with dementia. Method The study is divided into two phases. In phase 1, the research team will co-design the e-bibliotherapy app with caregivers. In phase 2, a randomized controlled trial will be conducted among 192 informal caregivers of people with dementia in Hong Kong. Caregivers will be randomly assigned to either the e-bibliotherapy group or the control group using simple randomization. Outcome measures will encompass caregivers’ psychological well-being, caregiving appraisal, mental health, saliva cortisol levels as an indicator of stress, and health-related quality of life for caregivers. Data will be collected at baseline, immediately post intervention, and 3 months and 6 months post intervention. General linear mixed model will be employed to analyze intervention effects. Qualitative interviews will be undertaken to explore caregiver experiences within this study and evaluate intervention acceptability using conventional content analysis methods. Discussion This study represents a pioneering effort in utilizing e-bibliotherapy to enhance the psychological well-being of informal caregivers of individuals with dementia, addressing the existing gap in caregiver services and facilitating knowledge dissemination within the community. Trial registration The trial has been registered on ClinicalTrial.gov (Ref: NCT05927805).

Abstract Polymerization degree plays a vital role in material properties. Previous methodologies of molecular weight control generally cannot suppress or alleviate batch-to-batch variations in device performance, especially in polymer solar cells. Herein, we develop an in-situ photoluminescence system in tandem with a set of analysis and processing procedures to track and estimate the polymerization degree of organic photovoltaic materials. To support the development of this protocol, we introduce polymer acceptor PYT constructed by near-infrared Y-series small molecule acceptors via Stille polymerization, and shed light on the correlations between molecular weight, spectral parameters, and device efficiencies that enable the design of the optical setup and confirm its feasibility. The universality is verified in PYT derivatives with stereoregularity and fluoro-substitution as well as benzo[1,2-b:4,5-b’]dithiophene-based polymers. Overall, our result provides a tool to tailor suitable conjugated oligomers applied to polymer solar cells and other organic electronics for industrial scalability and desired cost reduction.

Abstract Background The peroxisome is a dynamic organelle with variety in number, size, shape, and activity in different cell types and physiological states. Recent studies have implicated peroxisomal homeostasis in ferroptosis susceptibility. Here, we developed a U-2OS cell line with a fluorescent peroxisomal tag and screened a target-selective chemical library through high-content imaging analysis. Methods U-2OS cells stably expressing the mOrange2-Peroxisomes2 tag were generated to screen a target-selective inhibitor library. The nuclear DNA was counterstained with Hoechst 33342 for cell cycle analysis. Cellular images were recorded and quantitatively analyzed through a high-content imaging platform. The effect of selected compounds on ferroptosis induction was analyzed in combination with ferroptosis inducers (RSL3 and erastin). Flow cytometry analysis was conducted to assess the level of reactive oxygen species (ROS) and cell death events. Results Through the quantification of DNA content and peroxisomal signals in single cells, we demonstrated that peroxisomal abundance was closely linked with cell cycle progression and that peroxisomal biogenesis mainly occurred in the G1/S phase. We further identified compounds that positively and negatively regulated peroxisomal abundance without significantly affecting the cell cycle distribution. Some compounds promoted peroxisomal signals by inducing oxidative stress, while others regulated peroxisomal abundance independent of redox status. Importantly, compounds with peroxisome-enhancing activity potentiated ferroptosis induction. Conclusions Our findings pinpoint novel cellular targets that might be involved in peroxisome homeostasis and indicate that compounds promoting peroxisomal abundance could be jointly applied with ferroptosis inducers to potentiate anticancer effect. Graphical Abstract

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

Abstract Background Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI) plays an important role in the diagnosis and treatment of breast cancer. However, obtaining complete eight temporal images of DCE-MRI requires a long scanning time, which causes patients’ discomfort in the scanning process. Therefore, to reduce the time, the multi temporal feature fusing neural network with Co-attention (MTFN) is proposed to generate the eighth temporal images of DCE-MRI, which enables the acquisition of DCE-MRI images without scanning. In order to reduce the time, multi-temporal feature fusion cooperative attention mechanism neural network (MTFN) is proposed to generate the eighth temporal images of DCE-MRI, which enables DCE-MRI image acquisition without scanning. Methods In this paper, we propose multi temporal feature fusing neural network with Co-attention (MTFN) for DCE-MRI Synthesis, in which the Co-attention module can fully fuse the features of the first and third temporal image to obtain the hybrid features. The Co-attention explore long-range dependencies, not just relationships between pixels. Therefore, the hybrid features are more helpful to generate the eighth temporal images. Results We conduct experiments on the private breast DCE-MRI dataset from hospitals and the multi modal Brain Tumor Segmentation Challenge2018 dataset (BraTs2018). Compared with existing methods, the experimental results of our method show the improvement and our method can generate more realistic images. In the meanwhile, we also use synthetic images to classify the molecular typing of breast cancer that the accuracy on the original eighth time-series images and the generated images are 89.53% and 92.46%, which have been improved by about 3%, and the classification results verify the practicability of the synthetic images. Conclusions The results of subjective evaluation and objective image quality evaluation indicators show the effectiveness of our method, which can obtain comprehensive and useful information. The improvement of classification accuracy proves that the images generated by our method are practical.

In order to study the effect of physical synergistic enzymatic treatment on the structural characteristics of highland barley starch, ultrasonic and pressure heat were combined with pullulanase to treat highland barley starch. The particle morphology, crystal structure, functional group structure and particle size of treated samples were determined. The results showed that the contents of resistant starch and amylose were increased while amylopectin was decreased. The original structure of starch granules of highland barley was seriously damaged by the modification, showing a clumped structure, rough surface, full of wrinkles, cracks and holes, and the polarized cross disappeared. It was also found that the average particles size of highland barley starch and the number of large particles increased. Meanwhile, the crystallinity of highland barley starch changed from A-type crystal to B-, C- and V-type which lead to the crystallinity increased. The modified treatment did not produce new chemical groups and chemical bonds, but changed the internal structure of barley starch rearrangement. In addition, compared to untreated, the order degree (DO) of the modified barley starch increased, and the value of DO treated with pullulanase was the largest. The modification treatment made the starch molecules into smaller particles then formed more denser and larger starch crystals.

Wireless communications are increasingly used today. Despite such use, there is a significant perception of risk which makes exposure monitoring a significant concern today. The work described in this article was carried out within the framework of the European SEAWave project and the French Beyond5G project. The exposure assessment was evaluated using a personal exposimeter (MVG EMF Spy) whose compactness and ease of use make it more suitable and portable than a system combining measuring probes and spectrum analyzers. Measurements were carried out on the cellular frequency bands used by 2G, 3G, 4G, and 5G, as well as that of Wi-Fi, in different modes of public transportation (RER, metro, tramway, bus, and train) circulating in the Paris region. The measurements have been analyzed by frequency band, type of public transportation, and type of environment encountered. For each set of measurements (e.g., metro lines, tramways), the mean, standard deviation, skewness, and kurtosis were evaluated and analyzed. For all exposure measurements taken in the 700, 800, 900, 1800, 2100, 2600, and 3500 MHz frequency bands, the overall average values are 0.39, 0.43, 0.30, 0.21, 0.18, 0.24 and 0.18 V/m, respectively. These measurements have, in all cases, a significant dispersion as shown by the ratios of standard deviations to mean values. The well-known K-means clustering technique was applied to these four parameters for different subsets of data. The number of clusters k = 3 has been chosen based on the analysis of the optimal value of k for the current dataset. Our analysis indicates that the first group’s members display the highest mean values with moderate variance and the lowest values for the third and fourth moments. The second cluster is distinguished by points with large mean and variance, accompanied by moderate skewness and kurtosis. Conversely, the third group comprises points with the smallest mean and variance values, yet the largest measurements for the third and fourth moments.

Abstract Background Microsatellite instability-high (MSI-H) is a unique genomic status in many cancers. However, its role in the genomic features and immunotherapy in cholangiocarcinoma (CCA) is unclear. This study aimed to systematically investigate the genomic characterization and immunotherapy efficacy of MSI-H patients with CCA. Methods We enrolled 887 patients with CCA in this study. Tumor samples were collected for next-generation sequencing. Differences in genomic alterations between the MSI-H and microsatellite stability (MSS) groups were analyzed. We also investigated the survival of PD-1 inhibitor-based immunotherapy between two groups of 139 patients with advanced CCA. Results Differential genetic alterations between the MSI-H and MSS groups included mutations in ARID1A, ACVR2A, TGFBR2, KMT2D, RNF43, and PBRM1 which were enriched in MSI-H groups. Patients with an MSI-H status have a significantly higher tumor mutation burden (TMB) (median 41.7 vs. 3.1 muts/Mb, P

Recently, the monitoring of the radiofrequency electromagnetic field (RF-EMF) exposure induced by cellular networks has received a great deal of attention. In this work, a set of 70 microenvironments (MEs) located in urban and rural areas are selected in France under, on the one hand, the French Beyond5G project, and on the other hand, the 5G expOsure, causaL effects and rIsk perception through citizen engagement (GOLIAT) EU project. The purpose of this study is to assess the RF-EMF DL exposure in residential areas, downtowns, business areas, train stations, and public transport rides. For that, we employ the personal ExpoM-RF4 dosimeter placed inside a backpack to perform the measurements in different MEs. To take into consideration the effect of the presence of the human body near the dosimeter, we propose a correction approach that is mainly based on comparing the measurements given by ExpoM-RF4 to the ones provided by a reference system using the Tektronix real-time spectrum analyzer (RTSA) far from the body. Then, we use metrics, such as the quadratic mean, standard deviation, and median of the electric (E) field to carry out a comparative study between different MEs with different RF bands. It was found that the RF-EMF exposure levels for all MEs are well below the maximum allowable exposure limit prescribed by the International Commission on Non-Ionizing Radiation Protection (ICNIRP). In addition, we perform clustering analyses using the K-Means technique to group the MEs with comparable exposure levels. The results show that the exposure level is low, but generally higher in MEs located in Paris than in the other considered areas (i.e., Massy and three villages, namely Igny, Bures-sur-Yvette and Gif-Sur-Yvette). For example, we observe that outdoor MEs can be grouped into three clusters, where the average total E fields (ATEFs) are 0.77 V/m, 0.35 V/m, and 0.08 V/m for the MEs belonging to the first, second and third clusters, respectively. Note that the first cluster here mainly contains the MEs located in Paris. This can be explained by the important number of antennas deployed in that area to serve the huge amount of users. We also observe few locations with exceptions confirming the presence of heterogeneous environments in the vicinity of some areas. For instance, three MEs in Paris among fifteen have an exposure level similar to Massy MEs in outdoor

Abstract Background Social frailty (SF) is associated with multiple adverse health outcomes, yet there has been an inadequate focus on social frailty. The convoy model portrays the social networks through the perspective of the life course, thus providing a framework to explain the occurrence of social frailty. This study aimd to figure out the prevalence of social frailty and loneliness among community-dwelling older adults and to explore their correlations based on convoy model. Methods This was a cross-sectional study, and 295 older adults from 10 communities of Zhengzhou in Henan Province participated in the study. Social frailty and loneliness were assessed separately with the Social Frailty Scale and University of California at Los Angeles-Loneliness Scale. The scores of social frailty of the older adults in different characteristic communities were compared by independent sample t-test and single factor analysis of variance. The influencing factors of social frailty were analysed by multiple stepwise linear regression and the structural equation model. The correlation between social frailty and loneliness was analysed by Pearson correlation analysis. Results The total scores of social frailty and loneliness of the older adults in the community were (2.09 ± 1.53) and (43.19 ± 8.91), respectively. There was a moderate positive correlation between social frailty and loneliness (r = 0.621, P

Abstract Background Talaromyces marneffei is endemic to eastern India, Southeast Asia, and Guangdong and Guangxi provinces in China. It is common in immunocompromised individuals, especially in HIV-infected patients. Case presentation A 66-year-old male who had a history of hypertension and resided in Shandong Province (Northern China) was admitted for recurrent fever for one month. The patient had recurrent fever, multiple lymphadenopathies, hepatosplenomegaly, a back rash, and a progressive decrease in white blood cells and platelets. Talaromyces marneffei was isolated from peripheral blood and bone marrow after admission, and suspected fungal cells were found via lymph node pathology. The patient’s infection secondary to haemophagocytic syndrome continued to worsen despite antifungal, anti-inflammatory, and symptomatic treatment, leading to death due to multiple-organ failure. Conclusion Although rare, infection due to Talaromyces marneffei in HIV-negative patients has been increasing in recent years, and we should be vigilant about “new” infections in nonendemic areas.

Abstract Background Clonidine stimulation test has been widely used in the diagnosis of growth hormone deficiency in children with short stature with a high level of reliability. However, it may cause hypotension, which usually appears as headache, dizziness, bradycardia, and even syncope. It is well known that elevating the beds to make patients’ feet above their cardiac level might relieve this discomfort. However, the real efficiency of this method remains to be proved while the best angle for the elevated bed is still unclear. Methods A total of 1200 children with short stature were enrolled in this retrospective cross-sectional study. Age, gender, weight, and basic systolic and diastolic blood pressure were collected. Blood pressure at 1, 2, 3, and 4 h after stimulation tests were recorded. The participants were divided into 3 groups based on the angles of the elevated foot of their beds named 0°, 20°, and 40° groups. Results At one hour after the commencement of the tests, participants lying on the elevated beds showed a higher mean increase on the change of pulse pressure. The difference in the angles of the elevated beds did not show statistical significance compared with those who did not elevate their beds (0.13 vs. 2.83, P = 0.001; 0.13 vs. 2.18, P = 0.005; 2.83 vs. 2.18, P = 0.369). When it came to 4 h after the tests began, participants whose beds were elevated at an angle around 20° had a significantly higher mean increase in the change of pulse pressure values compared with those whose beds were elevated at an angle around 40° (1.46 vs. -0.05, P = 0.042). Conclusion Elevating the foot of the beds of the patients who are undergoing clonidine stimulation tests at an angle of 20°might be a good choice to alleviate the hypotension caused by the tests.

Decellularized extracellular matrix (dECM), with its distinct biological properties, has gained significant attention as a natural biomaterial. Leveraging its potentials, we successfully developed a three-dimensional matrix-based oriented nerve graft by encapsulating a fibrous scaffold with multilayered conformationally intact and biologically active human bone marrow mesenchymal stem cell-derived decellularized extracellular matrix (hBMSC-dECM). Convincingly, the hBMSC-dECM group exhibited comparable functional recoveries to the autograft group by postoperative week 12. In the comprehensive analysis, the molecular regulations in the hBMSC-dECM group were more intricate and nuanced compared to the autograft group. Nevertheless, both groups displayed similar molecular regulatory processes in terms of vascularization and extracellular matrix. Notably, the hBMSC-dECM group demonstrated sustained high levels of regulation in axon and myelin regeneration at week 12, while the immunomodulation returned to the normal levels after peaking at week 2. Collectively, our findings illustrated the satisfactory construction of a cell-matrixed nerve graft that established a microenvironment conducive to nerve regeneration, and elucidated the distinct molecular regulation patterns and characteristics associated with different repair modes.

Abstract Background We conducted a large-scale epidemiological analysis to investigate the associations between systemic inflammation markers and hypertension prevalence. Our aim is to identify potential biomarkers for early detection of hypertension. Methods A cross-sectional study with 119664 individuals from the National Health and Nutrition Examination Survey was performed. We investigated the associations between three systemic inflammation markers, namely the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and the prevalence of hypertension. Results The prevalence rates of hypertension gradually increased with increasing logSII, logSIRI, and logAISI quartiles. In continuous analyses, each unit increase in logSII, logSIRI, and logAISI was associated with a 20.3%, 20.1%, and 23.7% increased risk of hypertension. Compared to those in the lowest quartiles, the hypertension risks for subjects in the highest logSII, logSIRI, and logAISI quartiles were 1.114-fold,1.143-fold, and 1.186-fold. The restricted cubic splines (RCS) analysis revealed a non-linear relationship between the elevation of systemic inflammation markers and hypertension prevalence. Specifically, a per standard deviation increase in any of these variables is associated with a respective 9%, 16%, and 11% increase in hypertension prevalence. Conclusion Our cross-sectional study reveals significant positive correlations between SII, SIRI, and AISI with the prevalence of hypertension.

Abstract Human cancer cell lines have long served as tools for cancer research and drug discovery, but the presence and the source of intra-cell-line heterogeneity remain elusive. Here, we perform single-cell RNA-sequencing and ATAC-sequencing on 42 and 39 human cell lines, respectively, to illustrate both transcriptomic and epigenetic heterogeneity within individual cell lines. Our data reveal that transcriptomic heterogeneity is frequently observed in cancer cell lines of different tissue origins, often driven by multiple common transcriptional programs. Copy number variation, as well as epigenetic variation and extrachromosomal DNA distribution all contribute to the detected intra-cell-line heterogeneity. Using hypoxia treatment as an example, we demonstrate that transcriptomic heterogeneity could be reshaped by environmental stress. Overall, our study performs single-cell multi-omics of commonly used human cancer cell lines and offers mechanistic insights into the intra-cell-line heterogeneity and its dynamics, which would serve as an important resource for future cancer cell line-based studies.

Cancer poses a major threat to human health worldwide. The development of anti-tumor materials provides new modalities for cancer diagnosis and treatment. In this review, we comprehensively summarize the research progress and clinical applications of anti-tumor materials. First, we introduce the etiology and pathogenesis of cancer, and the significance and challenges of anti-tumor materials research. Then, we classify anti-tumor materials and discuss their mechanisms of action. After that, we elaborate the research advances and clinical applications of anti-tumor materials, including those targeting tumor cells and therapeutic instruments. Finally, we discuss the future perspectives and challenges in the field of anti-tumor materials. This review aims to provide an overview of the current status of anti-tumor materials research and application, and to offer insights into future directions in this rapidly evolving field, which holds promise for more precise, efficient and customized treatment of cancer.

Cytochromes P450 monooxygenases (CYP450s) constitute the largest enzymic protein family that is widely present in plants, animals, and microorganisms, participate in numerous metabolic pathways, and play diverse roles in development, metabolism, and defense. Rapeseed (Brassica napus) is an important oil crop worldwide and have many versions of reference genome. However, there is no systemically comparative genome-wide analysis of CYP450 family genes in rapeseed and its parental species B. rapa and B. oleracea. In this study, we identified 765, 293 and 437 CYP450 genes in B. napus, B. rapa and B. oleracea, respectively, which were unevenly located in A01-A10 and/or C01-C09 chromosomes in corresponding species. Phylogenetic relationship analysis indicated that 1745 CYP450 proteins from three Brassica species and Arabidopsis were divided into 4 groups. Whole genome duplication (WGD) or segmental duplication resulted in gene expansion of CYP450 family in three Brassica species. There were 33–83 SSR loci in CYP450 genes of three Brassica species, and numerous transcription factor binding sites were identified in their promoters. A total of 459–777 miRNAs were predicted to target 174–426 CYP450 genes in three Brassica species. Based on transcriptome data, BnCYP450s, BrCYP450s and BoCYP450s were differentially expressed in various tissues. There existed numerous BnCYP450 DEGs in response to pathogens and abiotic stresses. Besides, many BnCYP450 DEGs were involved in the regulation of important traits, such as seed germination, seed ALA content, and yellow-seed. The qRT-PCR experiment confirmed the transcriptome analysis results by validating two representative Sclerotinia-responsive BnCYP450 DEGs as an example. Three BnCYP450s genes (CYP707A1, CYP81F1, CYP81H1) might be regulated by seed-specific transcription factors BnTT1 and BnbZIP67 to participate in the development and metabolism of seed coat and embryo by undertaking related metabolic reactions.

Aim: To assesses the cost–effectiveness of sotagliflozin for the treatment of patients hospitalized with heart failure and comorbid diabetes. Materials & methods: A de novo cost–effectiveness model with a Markov structure was created for patients hospitalized for heart failure with comorbid diabetes. Outcomes of interest included hospital readmissions, emergency department visits and all-cause mortality measured over a 30-year time horizon. Baseline event frequencies were derived from published real-world data studies; sotagliflozin’s efficacy was estimated from SOLOIST-WHF. Health benefits were calculated quality-adjusted life years (QALYs). Costs included pharmaceutical costs, rehospitalization, emergency room visits and adverse events. Economic value was measured using the incremental cost–effectiveness ratio (ICER). Results: Sotagliflozin use decreased annualized rehospitalization rates by 34.5% (0.228 vs 0.348, difference: -0.120), annualized emergency department visits by 40.0% (0.091 vs 0.153, difference: -0.061) and annualized mortality by 18.0% (0.298 vs 0.363, difference: -0.065) relative to standard of care, resulting in a net gain in QAYs of 0.425 for sotagliflozin versus standard of care. Incremental costs using sotagliflozin increased by $19,374 over a 30-year time horizon of the patient, driven largely by increased pharmaceutical cost. Estimated ICER for sotagliflozin relative to standard of care was $45,596 per QALY. Conclusion: Sotagliflozin is a cost-effective addition to standard of care for patients hospitalized with heart failure and comorbid diabetes.

Abstract Porous aromatic framework 1 (PAF‐1) is an extremely representative nanoporous organic framework owing to its high stability and exceptionally high surface area. Currently, the synthesis of PAF‐1 is catalyzed by the Ni(COD)2/COD/bpy system, suffering from great instability and high cost. Herein, we developed an in situ reduction of the Ni(II) catalytic system to synthesize PAF‐1 in low cost and high yield. The active Ni(0) species produced from the NiCl2/bpy/NaI/Mg catalyst system can effectively catalyze homocoupling of tetrakis(4‐bromophenyl)methane at the room temperature to form PAF‐1 with high Brunauer–Emmett–Teller (BET)‐specific surface area up to 4948 m2 g−1 (Langmuir surface area, 6785 m2 g−1). The possible halogen exchange and dehalogenation coupling mechanisms for this new catalytic process in PAF's synthesis are discussed in detail. The efficiency and universality of this innovative catalyst system have also been demonstrated in other PAFs' synthesis. This work provides a cheap, facile, and efficient method for scalable synthesis of PAFs and explores their application for high‐pressure storage of Xe and Kr.