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Abstract Learning to associate cues, both directly and indirectly, with biologically significant events is essential for survival. Second-order conditioning (SOC) involves forming an association between a previously reinforced conditioned stimulus (CS1) and a new conditioned stimulus (CS2) without the presence of an unconditioned stimulus (US). The neural substrates mediating SOC, however, remain unclear. Parabrachial Calca neurons, which react to the noxious US, also respond to a CS after pairing with a US, suggesting that Calca neurons mediate SOC. We established an aversive SOC behavioral paradigm in mice and monitored Calca neuron activity via single-cell calcium imaging during conditioning and subsequent recall phases. These neurons were activated by both CS1 and CS2 after SOC. Chemogenetically inhibiting Calca neurons during CS1-CS2 pairing attenuated SOC. Thus, reactivation of the US pathway by a learned CS plays an important role in forming the association between the old and a new CS, promoting the formation of second-order memories.

Abstract Purpose Investigate the clinical characteristics of splenomegaly secondary to acute pancreatitis (SSAP) and construct a nomogram prediction model based on Lasso-Logistic regression. Methods A retrospective case-control study was conducted to analyze the laboratory parameters and computed tomography (CT) imaging of acute pancreatitis (AP) patients recruited at Xuanwu Hospital from December 2014 to December 2021. Lasso regression was used to identify risk factors, and a novel nomogram was developed. The performance of the nomogram in discrimination, calibration, and clinical usefulness was evaluated through internal validation. Results The prevalence of SSAP was 9.2% (88/950), with the first detection occurring 65(30, 125) days after AP onset. Compared with the control group, the SSAP group exhibited a higher frequency of persistent respiratory failure, persistent renal failure, infected pancreatic necrosis, and severe AP, along with an increased need for surgery and longer hospital stay (P

Abstract Extreme cold exposure has been widely considered as a cardiac stress and may result in cardiac function decompensation. This study was to examine the risk factors that contribute to changes in cardiovascular indicators of cardiac function following extreme cold exposure and to provide valuable insights into the preservation of cardiac function and the cardiac adaptation that occur in real‐world cold environment. Seventy subjects were exposed to cold outside (Mohe, mean temperature −17 to −34°C) for one day, and were monitored by a 24‐h ambulatory blood pressure device and underwent echocardiography examination before and after extreme cold exposure. After exposure to extreme cold, 41 subjects exhibited an increase in ejection fraction (EF), while 29 subjects experienced a decrease. Subjects with elevated EF had lower baseline coefficients of variation (CV) in blood pressure compared to those in the EF decrease group. Additionally, the average real variability (ARV) of blood pressure was also significantly lower in the EF increase group. Multivariate regression analysis indicated that both baseline CV and ARV of blood pressure were independent risk factors for EF decrease, and both indicators proved effective for prognostic evaluation. Correlation analysis revealed a correlation between baseline blood pressure CV and ARV, as well as EF variation after exposure to extreme cold environment. Our research clearly indicated that baseline cardiovascular indicators were closely associated with the changes in EF after extreme cold exposure. Furthermore, baseline blood pressure variability could effectively predict alterations in left cardiac functions when individuals were exposed to extreme cold environment.

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.

Abstract Background Metabolic dysfunction-associated steatotic liver disease(MASLD) is the most common cause of chronic liver disease. Clinical evidences have demonstrated the link between MASLD and the increased risk of cardiovascular disease (CVD) development. We aimed to investigate the relationship between Life’s Essential 8 (LE8), an enhanced approach to assessing cardiovascular health(CVH), and MASLD. Methods Data were extracted from the National Health and Nutrition Examination Survey (NHANES) in 2017–2020 cycles. MASLD was assessed by the latest diagnostic criteria. LE8 scores (range 0–100) were obtained from measurements based on American Heart Association definitions, divided into health factor and health behavior scores. Multivariable logistic and restricted cubic spline models were used to assess the associations. Results 5646 participants were included based on the inclusion and exclusion criteria, 2616 (46.33%) participants were diagnosed with MASLD. After adjusting for confounding variables, higher LE8 scores were associated with a lower risk of MASLD (OR = 0.19, 95%CI 0.17–0.21; P

Abstract Background Acute thrombotic events play a major role in various cardiovascular diseases. Therefore, direct thrombus imaging can be proved beneficial for early diagnosis and prompt therapy of thrombosis. Our study investigated targeted dual‐modality cyclic arginine‐glycine‐aspartic micro bubbles (cRGD‐MBs) for direct imaging of thrombi by fluorescence and ultrasound. Methods cRGD‐MBs were prepared by mechanical vibration and chemical chelation methods. Results Coulter counter analysis demonstrated that the cRGD‐MBs were well dispersed, with diameters ranging from 1 to 3 μm. They emitted bright red fluorescence under an excitation wavelength of 660 nm. In vivo fluorescence and ultrasound imaging revealed that cRGD‐MBs accumulated at the site of thrombus in the carotid artery with significant fluorescence and ultrasonic signal. Conclusions This study showed that novel microbubble cRGD‐MBs were successfully synthesized, and that these could potentially be used as contrast agents for immediate diagnosis of acute thrombus in vivo.

Abstract Background Ischemic cardio-cerebrovascular disease is the leading cause of mortality worldwide. However, studies focusing on elderly and very elderly patients are scarce. Hence, our study aimed to characterize and investigate the long-term prognostic implications of ischemic cardio-cerebrovascular diseases in elderly Chinese patients. Methods This retrospective cohort study included 1026 patients aged ≥ 65 years who were categorized into the mono ischemic cardio-cerebrovascular disease (MICCD) (either coronary artery disease or ischemic stroke/transient ischemic attack) (n = 912) and the comorbidity of ischemic cardio-cerebrovascular disease (CICCD) (diagnosed with both coronary artery disease and ischemic stroke/transient ischemic attack at admission) (n = 114). The primary outcome was all-cause death. The mortality risk was evaluated using the Cox proportional hazards risk model with multiple adjustments by conventional and propensity-score-based approaches. Results Of the 2494 consecutive elderly patients admitted to the hospital, 1026 (median age 83 years [interquartile range]: 76.5–86.4; 94.4% men) met the inclusion criteria. Patients with CICCD consisted mostly of very elderly (79.2% vs. 66.1%, P

BackgroundGastric cancer (GC) remains a malignancy with high incidence and mortality rates worldwide. Although branched-chain amino acids (BCAAs) play a crucial role in various physiological and pathological processes, their specific relationship with risk of GC remains unclear.MethodsWe conducted a large-scale prospective cohort from UK Biobank database. We evaluated the relationship between BCAA levels and risk of GC using Cox regression, Kaplan–Meier survival curves, the accelerated failure time (AFT) model, and restricted cubic spline (RCS) analysis.ResultsDuring the follow-up of 12 years, 247,753 participants were included in the study. And the Cox regression analysis revealed that higher levels of isoleucine (HR = 0.65, 95% CI 0.48–0.89; p = 0.007), leucine (HR = 0.57, 95% CI 0.42–0.79; p

Background: Acupressure has proven efficacy in symptoms management, making it valuable in clinical practice and patient care. Given the rising number of increasing publications on acupressure, we aimed to analyze the literature from the past 20 years and provided current trends and hotspot for future research directions. Methods: Publications on acupressure from January 1, 2004 through May 1, 2024 were retrieved from the Web of Science database. The extracted records underwent thorough analysis based on publication year, research area, journal, countries/regions, organization, authors, and keywords. The bibliometric analysis was conducted using Citespace and Microsoft Excel software. Results: Of the 1,929 screened records, 770 publications were identified. The annual number of acupressure has gradually increased, with the 45 % of the total publication occurring from 2020 to 2024. Among countries and institutions, China (252 articles) and Hong Kong Polytechnic University (41 articles) have the highest number of publications. Notably, USA and Hong Kong Polytechnic University exhibits the highest centrality score in cooperative network among countries/regions and institutions. Chao Hsing Yeh from the Cizik School of Nursing, University of Texas Health Science Center, was the most prolific author with 22 papers. Evidence-Based Comple Alt, with 53 articles, is the journal with the most publications. According to the keyword, timeline diagram and prominence mapping analysis, we believe that “insomnia”, “labor”, “waist circumference”, “reliability” and “vagus nerve stimulation” related clusters may be new hotspots in the field of acupressure. Conclusion: This study presents the research trajectory of acupressure over the past 20 years, providing a foundation for future research and highlighting the significant contributions of nursing researchers. By analyzing research trends and hotsport, nursing professionals can integrate acupressure more effectively into holistic patient care, improving quality of life, and contributing to traditional Chinese medicine.

Wastewater treatment plants (WWTPs), including both domestic and industrial facilities, are key contributors to antibiotic resistance genes (ARGs) and human pathogens in the environment. However, the characteristics and dissemination mechanisms of ARGs in domestic (SD) and industrial (SI) wastewater treatment systems remain unclear, leading to uncertainties in risk assessment. Based on metagenomic analysis, we observed significant differences in the compositions of resistome (ARGs and metal resistance genes, MRGs), mobilome (mobile genetic elements, MGEs), and bacterial community between SD and SI. SI exhibited lower diversity of ARGs but higher abundance of MRGs compared to SD. The removal efficiency of resistome was lower in the SI than that in the SD. MGEs emerged as the primary driver of ARG dissemination in the WWTPs, followed by the bacterial community. Environmental conditions (physicochemical parameters, heavy metals, and antibiotics) indirectly influenced the variation of resistome. Significantly, environmental conditions and MGEs highly influenced the composition of resistome in the SI, while bacterial community more associated with resistome in the SD. Additionally, we identified 36 human bacterial pathogens as potential hosts of ARGs, MRGs, and MGEs in wastewater samples. This study provides new insights on the dissemination mechanisms and risk assessment of antimicrobial resistance in the different types of WWTPs.

Abstract This study investigates the gas–liquid two-phase counter-current flow through a vertical annulus, a phenomenon prevalent across numerous industrial fields. The presence of an inner pipe and varying degrees of eccentricity between the inner and outer pipes often blur the clear demarcation of flow regime boundaries. To address this, we designed a vertical annulus with adjustable eccentricity (outer and inner diameters of 125 mm and 75 mm, respectively). We conducted gas–liquid counter-current flow experiments under specific conditions: gas superficial velocity ranging from 0.06 to 5.04 m/s, liquid superficial velocity from 0.01 to 0.25 m/s, and five levels of eccentricity (e = 0, 0.25, 0.5, 0.75, 1). We collected differential pressure data at two distinct height distances (DP1: 50 mm and DP2: 1000 mm). We used vectors, composed of both the probability density functions (PDFs) of the differential pressure signals and the power spectral density (PSD) reduced via Principal Component Analysis, as features. Using the CFDP clustering algorithm—based on local density—we clustered the flow regimes of the experimental data, thereby achieving an objective and consistent identification of the flow regime of gas–liquid two-phase counter-current flow in a vertical annulus. Our analysis reveals that for DP1, the main differences in the PSD of various flow regimes occur within the 0.5–1 Hz range. Among the three flow regimes involved, the slug flow exhibits the highest power intensity, followed by the bubbly flow, with the churn flow having the least. In terms of differential pressure distribution, the bubbly and churn flows have a concentrated distribution, while the slug flow is more dispersed. For DP2, the PSD differences primarily exist within the 0.5–2 Hz range. The churn flow has the highest power intensity, followed by the slug flow, with the bubbly flow being the weakest. Here, the bubbly flow's differential pressure distribution is concentrated, while the slug and churn flows are more dispersed. Based on the results of the flow regime classification, we generated a flow regime map and analyzed the influence of annulus eccentricity on the flow regime. We found that in most cases, pipe eccentricity does not significantly affect the flow regime. However, in the transition region—such as the bubbly to slug flow transition zone—flows with medium eccentricity values (e = 0.5, 0.75) are more likely to transition to slug flow. We compared the visual recognition results of flow regimes with the clustering results. 4.04% of the total samples showed different results from visual recognition and clustering, primarily located in the flow regime transition area. Since visually distinguishing flow regimes in these areas is typically challenging, our methodology offers an objective classification approach for gas–liquid two-phase counter-current flow in a vertical annulus.

Abstract Considering that neutralizing antibody levels induced by two doses of the inactivated vaccine decreased over time and had fallen to low levels by 6 months, and homologous and heterologous booster immunization programs have been implemented in adults in China. The booster immunization of recombinant COVID-19 vaccine (ZF2001) after priming with inactivated vaccine in healthy children and adolescents has not been reported. We performed an open-labeled, single-arm clinical trial to evaluate the safety and immunogenicity of heterologous booster immunization with ZF2001 after priming with inactivated vaccine among 240 population aged 3-17 years in China. The primary outcome was immunogenicity, including geometric mean titers (GMTs), geometric mean ratios (GMRs) and seroconversion rates of SARS-CoV-2 neutralizing antibodies against prototype SARS-CoV-2 and Omicron BA.2 variant at 14 days after vaccination booster. On day 14 post-booster, a third dose booster of the ZF2001 provided a substantial increase in antibody responses in minors, and the overall occurrence rate of adverse reactions after heterologous vaccination was low and all adverse reactions were mild or moderate. The results showed that the ZF2001 heterologous booster had high immunogenicity and good safety profile in children and adolescents, and can elicit a certain level of neutralizing antibodies against Omicron. Trial registration NCT05895110 (Retrospectively registered, First posted in ClinicalTrials.gov date: 08/06/2023)

Enhancement in the visible light absorption and efficient interfacial charge transfer is crucial for optimizing photocatalytic efficiency in the degradation of pollutants such as methyl orange (MO) and formaldehyde. This study focuses on the properties of a TiO2/C/g-C3N4 hybrid efficient photocatalyst, which is developed using an air calcination method to deposit graphitic nitride (g-C3N4) onto a carbon-modified TiO2 surface. The characterization techniques, including high-resolution transmission electron Microscopy (HRTEM), X-ray diffraction (XRD), Raman spectroscopy, thermogravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS), were used to provide a comprehensive understanding of the material’s structural, morphological, thermal, and chemical properties. This hybrid catalyst is specifically engineered for the efficient decomposition of methyl orange (MO) and formaldehyde, demonstrating a significant increase in photocatalytic activity. The TiO2/C/g-C3N4 photocatalyst also exhibits an enhanced specific surface area of 181.2 m2/g, which facilitates increased physical adsorption and photo-catalytic active sites. Experimental results confirm that this catalyst effectively adsorbs MO physically even in the dark without degradation. Combining physical and photo-catalytic functions, this catalyst degrades 94 % of MO within 180 min with the initial concentration 0.2 mol/L of MO, and achieves almost 100 % decolorization of MO under visible light irradiation. Notably, the catalyst retains its high activity after 4 cycles of MO degradation, underscoring its durability and consistent performance. Additionally, the hybrid catalyst features a staggered type-II energy level configuration, which effectively enhances charge separation and boosts photocatalytic efficacy. The incorporation of an ultrafine carbon layer further augments electron mobility towards the surface, crucial for effective catalytic reactions. This study paves the way for future development of highly efficient photocatalytic materials for environmental purification.

Adagrasib (MRTX849), an approved and promising KRAS G12C inhibitor, has shown the promising results for treating patients with advanced non-small cell lung cancer (NSCLC) or colorectal cancer (CRC) harboring KRAS-activating mutations. However, emergence of the acquired resistance limits its long-term efficacy and clinical application. Further understanding of the mechanism of the acquired resistance is crucial for developing more new effective therapeutic strategies. Herein, we firstly found a new connection between the acquired resistance to MRTX849 and nuclear factor erythroid 2-related factor 2 (Nrf2). The expression levels of Nrf2 and GLS1 proteins were substantially elevated in different CRC cell lines with the acquired resistance to MRTX849 in comparison with their corresponding parental cell lines. Next, we discovered that RA-V, one of natural cyclopeptides isolated from the roots of Rubia yunnanensis, could restore the response of resistant CRC cells to MRTX849. The results of molecular mechanisms showed that RA-V suppressed Nrf2 protein through the ubiquitin-proteasome-dependent degradation, leading to the induction of oxidative and ER stress, and DNA damage in CRC cell lines. Consequently, RA-V reverses the resistance to MRTX849 by inhibiting the Nrf2/GLS1 axis, which shows the potential for further developing into one of novel adjuvant therapies of MRTX849.

BackgroundHypoalbuminemia and cognitive impairment (CI) each independently increase the mortality risk in older adults. However, these two geriatric syndromes can occur simultaneously. In community-dwelling older adults, is the combination of hypoalbuminemia and CI linked to a higher mortality risk than either condition alone?ObjectiveWe aimed to investigate the association between plasma albumin, cognitive function, and their synergistic effect on mortality in Chinese community-dwelling older adults.MethodsData from the Chinese Longitudinal Healthy Longevity Survey (2012) included 1,858 participants aged ≥65. Baseline assessments comprised albumin levels and cognitive status. All-cause mortality was confirmed through 2014–2018 surveys. Cox proportional hazards models assessed associations, and restricted cubic splines explored albumin-mortality relationship.ResultsDuring a median follow-up of 48.85 months, 921 deaths. Albumin≥35 g/L vs

ABSTRACT Chronic obstructive pulmonary disease (COPD) is one of the primary causes of mortality and morbidity worldwide. The gut microbiome, particularly the bacteriome, has been demonstrated to contribute to the progression of COPD. However, the influence of gut virome on the pathogenesis of COPD is rarely studied. Recent advances in viral metagenomics have enabled the rapid discovery of its remarkable role in COPD. In this study, deep metagenomics sequencing of fecal virus-like particles and bacterial 16S rRNA sequencing was performed on 92 subjects from China to characterize alterations of the gut virome in COPD. Lower richness and diversity of the gut virome were observed in the COPD subjects compared with the healthy individuals. Sixty-four viral species, including Clostridium phage, Myoviridae sp., and Synechococcus phage, showed positive relationships with pulmonary ventilation functions and had markedly declined population in COPD subjects. Multiple viral functions, mainly involved in bacterial susceptibility and the interaction between bacteriophages and bacterial hosts, were significantly declined in COPD. In addition, COPD was characterized by weakened viral-bacterial interactions compared with those in the healthy cohort. The gut virome showed diagnostic performance with an area under the curve (AUC) of 88.7%, which indicates the potential diagnostic value of the gut virome for COPD. These results suggest that gut virome may play an important role in the development of COPD. The information can provide a reference for the future investigation of diagnosis, treatment, and in-depth mechanism research of COPD.IMPORTANCEPrevious studies showed that the bacteriome plays an important role in the progression of chronic obstructive pulmonary disease (COPD). However, little is known about the involvement of the gut virome in COPD. Our study explored the disease-specific virome signatures of patients with COPD. We found the diversity and compositions altered of the gut virome in COPD subjects compared with healthy individuals, especially those viral species positively correlated with pulmonary ventilation functions. Additionally, the declined bacterial susceptibility, the interaction between bacteriophages and bacterial hosts, and the weakened viral-bacterial interactions in COPD were observed. The findings also suggested the potential diagnostic value of the gut virome for COPD. The results highlight the significance of gut virome in COPD. The novel strategies for gut virome rectifications may help to restore the balance of gut microecology and represent promising therapeutics for COPD.

Abstract Ingenious design and fabrication of advanced carbon‐based sulfur cathodes are extremely important to the development of high‐energy lithium‐sulfur batteries, which hold promise as the next‐generation power source. Herein, for the first time, we report a novel versatile hyphae‐mediated biological assembly technology to achieve scale production of hyphae carbon fibers (HCFs) derivatives, in which different components including carbon, metal compounds, and semiconductors can be homogeneously assembled with HCFs to form composite networks. The mechanism of biological adsorption assembly is also proposed. As a representative, reduced graphene oxides (rGOs) decorated with hollow carbon spheres (HCSs) successfully co‐assemble with HCFs to form HCSs@rGOs/HCFs hosts for sulfur cathodes. In this unique architecture, not only large accommodation space for sulfur but also restrained volume expansion and fast charge transport paths are realized. Meanwhile, multiscale physical barriers plus chemisorption sites are simultaneously established to anchor soluble lithium polysulfides. Accordingly, the designed HCSs@rGOs/HCFs‐S cathodes deliver a high capacity (1189 mA h g−1 at 0.1 C) and good high‐rate capability (686 mA h g−1 at 5 C). Our work provides a new approach for the preparation of high‐performance carbon‐based electrodes for energy storage devices.

Abstract Since thermoelectric materials have different physical and chemical properties, the design of contact layers requires dedicated efforts, and the welding temperatures are distinctly different. Therefore, a general interface design and connection technology can greatly facilitate the development of thermoelectric devices. Herein, we proposed a screening strategy for the contact materials based on the calculation of phase diagram method, and Mg2Ni has been identified as a matched contact layer for n-type Mg3Sb2-based materials. And this screening strategy can be effectively applied to other thermoelectric materials. By adopting the low-temperature sintering silver nanoparticles technology, the Zintl phase thermoelectric device can be fabricated at low temperature but operate at medium temperature. The single-leg n-type Mg3.15Co0.05SbBi0.99Se0.01 device achieves an efficiency of ~13.3%, and a high efficiency of ~11% at the temperature difference of 430 K has been realized for the Zintl phase thermoelectric device comprised together with p-type Yb0.9Mg0.9Zn1.198Ag0.002Sb2. Additionally, the thermal aging and thermal cycle experiments proved the long-term reliability of the Mg2Ni/Mg3.15Co0.05SbBi0.99Se0.01 interface and the nano-silver sintering joints. Our work paves an effective avenue for the development of advanced devices for thermoelectric power generation.

Abstract Background The number and proportion of the elderly population have been continuously increasing in China, leading to the elevated prevalence of chronic diseases and multimorbidity, which ultimately brings heavy burden to society and families. Meanwhile, the status of multimorbidity tends to be more complex in elderly inpatients than community population. In view of the above concerns, this study was designed to investigate the health status of elderly inpatients by analyzing clinical data in Chinese People's Liberation Army (PLA) General Hospital from 2008 to 2019, including the constitution of common diseases, comorbidities, the status of multimorbidity, in-hospital death and polypharmacy among elderly inpatients, so as to better understand the diseases spectrum and multimorbidity of elderly inpatients and also to provide supporting evidence for targeted management of chronic diseases in the elderly. Methods A clinical inpatients database was set up by collecting medical records of elderly inpatients from 2008 to 2019 in Chinese PLA General Hospital, focusing on diseases spectrum and characteristics of elderly inpatients. In this study, we collected data of inpatients aged ≥ 65 years old, and further analyzed the constitution of diseases, multimorbidity rates and mortality causes in the past decade. In addition, the prescriptions were also analyzed to investigate the status of polypharmacy in elderly inpatients. Results A total of 210,169 elderly patients were hospitalized from January 1st, 2008 to December 31st, 2019. The corresponding number of hospitalizations was 290,833. The average age of the study population was 72.67 years old. Of the total population, 73,493 elderly patients were re-admitted within one year, with the re-hospitalization rate of 25.27%. Malignant tumor, hypertension, ischemic heart disease, diabetes mellitus and cerebrovascular disease were the top 5 diseases. Among the study population, the number of patients with two or more long-term health conditions was 267,259, accounting for 91.89%, with an average of 4.68 diseases. In addition, the average number of medications taken by the study population was 5.4, among which, the proportion of patients taking more than 5 types of medications accounted for 55.42%. Conclusions By analyzing the constitution of diseases and multimorbidity, we found that multimorbidity has turned out to be a prominent problem in elderly inpatients, greatly affecting the process of healthy aging and increasing the burden on families and society. Therefore, multidisciplinary treatment should be strengthened to make reasonable preventive and therapeutic strategies to improve the life quality of the elderly. Meanwhile, more attention should be paid to reasonable medications for elderly patients with multimorbidity to avoid preventable side effects caused by irrational medication therapy.

Background: The SYNTAX score II (SS II) has earned widespread recognition for use on individuals with coronary artery disease (CAD) due to its reliable predictions of 4-year all-cause mortality (ACM). This research focuses on substantiating the prognostic significance of using the SS II for patients experiencing concurrent chronic renal insufficiency (CRI) and CAD who have undergone percutaneous coronary intervention (PCI). Methods: This study retrospectively examined 2468 patients with concurrent CAD and CRI who underwent PCI. Based on their SS II, these participants were sorted into low-, medium-, and high-risk groups and monitored over a median of three years. The evaluation of the predictive precision of different SYNTAX scores for clinical outcomes in patients with CRI after PCI involved using time-dependent receiver operating characteristic (ROC) curves. These included the standard SS (SS), SS II, clinical SS (CSS), and residual SS (rSS). The primary outcomes were ACM and cardiac mortality (CM), while the secondary outcomes covered major adverse cardiovascular and cerebrovascular events (MACCEs), stroke, unplanned revascularization, and myocardial infarction (MI). Results: Higher 5-year cumulative incidences of MACCEs, MI, CM, and ACM were observed significantly in patients in the high SS II category relative to those in the low and medium SS II categories. Multivariable Cox regression analysis confirmed that the SS II independently predicts ACM, CM, MI, and MACCEs as a prognostic marker. Additionally, the analysis of the time-dependent ROC curve demonstrated that the areas under the curve (AUC) for predicting CM and ACM were 0.772 and 0.767, respectively, which are superior to those of other SYNTAX scores (p < 0.05). Conclusions: As an independent predictor, the SS II is notable for its ability to forecast long-term adverse outcomes, including MACCEs, CM, ACM, and MI. For patients with coexisting CAD and CRI undergoing PCI, it provides significantly improved prognostic accuracy for 5-year ACM and CM compared to other SYNTAX scores.

Accessible and superior electrocatalysts to overcome the sluggish oxygen evolution reaction (OER) are pivotal for sustainable and low-cost hydrogen production through electrocatalytic water splitting. The iron and nickel oxohydroxide complexes are regarded as the most promising OER electrocatalyst attributed to their inexpensive costs, easy preparation, and robust stability. In particular, the Fe-doped NiOOH is widely deemed to be superior constituents for OER in an alkaline environment. However, the facile construction of robust Fe-doped NiOOH electrocatalysts is still a great challenge. Herein, we report the facile construction of Fe-doped NiOOH on Ni(OH)2 hierarchical nanosheet arrays grown on nickel foam (FeNi@NiA) as efficient OER electrocatalysts through a facile in-situ electrochemical activation of FeNi-based Prussian blue analogues (PBA) derived from Ni(OH)2. The resultant FeNi@NiA heterostructure shows high intrinsic activity for OER due to the modulation of the overall electronic energy state and the electrical conductivity. Importantly, the electrochemical measurement revealed that FeNi@NiA exhibits a low overpotential of 240 mV at 10 mA/cm2 with a small Tafel slope of 62 mV dec−1 in 1.0 M KOH, outperforming the commercial RuO2 electrocatalysts for OER.

Summary: Pain that persists beyond the time required for tissue healing and pain that arises in the absence of tissue injury, collectively referred to as nociplastic pain, are poorly understood phenomena mediated by plasticity within the central nervous system. The parabrachial nucleus (PBN) is a hub that relays aversive sensory information and appears to play a role in nociplasticity. Here, by preventing PBN Calca neurons from releasing neurotransmitters, we demonstrate that activation of Calca neurons is necessary for the manifestation and maintenance of chronic pain. Additionally, by directly stimulating Calca neurons, we demonstrate that Calca neuron activity is sufficient to drive nociplasticity. Aversive stimuli of multiple sensory modalities, such as exposure to nitroglycerin, cisplatin, or lithium chloride, can drive nociplasticity in a Calca-neuron-dependent manner. Aversive events drive nociplasticity in Calca neurons in the form of increased activity and excitability; however, neuroplasticity also appears to occur in downstream circuitry.

Introduction The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct.Methods and analysis This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests.Ethics and dissemination The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi’an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal.Trial registration number NCT05523778.

Aimed at the problem that a large number of hyperspectral remote sensing images were rich in spectral and spatial information, and the labeled samples available for image classification were far less than unlabeled samples, a semisupervised spectral-spatial classification algorithm was proposed by fusing spectral measure-based label transfer and Tri-training.A spectral measure-based label transfer method was proposed for our algorithm.The transferred labels and predicted labels for Tri-training algorithm were used to predict the labels of expanded unlabeled samples, which can promoted the prediction accuracies of labels for expanded unlabeled samples.Meanwhile, our algorithm selectel expanded samples based on spatial correlation, and used spectral and spatial features to improve the accuracy of image classification.Experimental study was executed on two public hyperspectral remote sensing image datasets, and the results showed that the proposed algorithm outperform tri-training algorithm.

Atherosclerosis (AS) is a leading cause of the life-threatening cardiovascular disease (CVD), creating an urgent need for efficient, biocompatible therapeutics for diagnosis and treatment. Biomimetic nanomedicines (bNMs) are moving closer to fulfilling this need, pushing back the frontier of nano-based drug delivery systems design. This review seeks to outline how these nanomedicines (NMs) might work to diagnose and treat atherosclerosis, to trace the trajectory of their development to date and in the coming years, and to provide a foundation for further discussion about atherosclerotic theranostics.

Abstract The incidence and mortality rate of gastric cancer (GC) have remained high worldwide. Although some progress has been made in immunotargeted therapy, the treatment effect remains limited. With more attention has been paid to the immune potential of tumor-associated macrophages (TAMs), but the specific mechanisms of tumor immunity are still unclear. Thus, we screened marker genes in TAMs differentiation (MDMs) through single-cell RNA sequencing, and combined with GC transcriptome data from TCGA and GEO databases, the clinical and TME characteristics, prognostic differences, immune infiltration, and drug sensitivity among different subtypes of patients with GC in different data sets were analyzed. A prognostic model of GC was constructed to evaluate the prognosis and immunotherapy response of patients with GC. In this study, we extensively studied the mutations in MDMs such as CGN, S100A6, and C1QA, and found differences in the infiltration of immune cells and immune checkpoints including M2 TAMs, T cells, CD274, and CTLA4 in different GC subtypes. In the model, we constructed a predictive scoring system with high accuracy and screened out key MDMs-related genes associated with prognosis and M2 TAMs, among which VKORC1 may be involved in GC progression and iron death in tumor cells. Therefore, this study explores the therapeutic strategy of TAMs reprogramming in-depth, providing new ideas for the clinical diagnosis, treatment, and prognosis assessment of GC.

Abstract Background Severe peripheral nerve injury (PNI) often leads to significant movement disorders and intractable pain. Therefore, promoting nerve regeneration while avoiding neuropathic pain is crucial for the clinical treatment of PNI patients. However, established animal models for peripheral neuropathy fail to accurately recapitulate the clinical features of PNI. Additionally, researchers usually investigate neuropathic pain and axonal regeneration separately, leaving the intrinsic relationship between the development of neuropathic pain and nerve regeneration after PNI unclear. To explore the underlying connections between pain and regeneration after PNI and provide potential molecular targets, we performed single-cell RNA sequencing and functional verification in an established rat model, allowing simultaneous study of the neuropathic pain and axonal regeneration after PNI. Results First, a novel rat model named spared nerve crush (SNC) was created. In this model, two branches of the sciatic nerve were crushed, but the epineurium remained unsevered. This model successfully recapitulated both neuropathic pain and axonal regeneration after PNI, allowing for the study of the intrinsic link between these two crucial biological processes. Dorsal root ganglions (DRGs) from SNC and naïve rats at various time points after SNC were collected for single-cell RNA sequencing (scRNA-seq). After matching all scRNA-seq data to the 7 known DRG types, we discovered that the PEP1 and PEP3 DRG neuron subtypes increased in crushed and uncrushed DRG separately after SNC. Using experimental design scRNA-seq processing (EDSSP), we identified Adcyap1 as a potential gene contributing to both pain and nerve regeneration. Indeed, repeated intrathecal administration of PACAP38 mitigated pain and facilitated axonal regeneration, while Adcyap1 siRNA or PACAP6-38, an antagonist of PAC1R (a receptor of PACAP38) led to both mechanical hyperalgesia and delayed DRG axon regeneration in SNC rats. Moreover, these effects can be reversed by repeated intrathecal administration of PACAP38 in the acute phase but not the late phase after PNI, resulting in alleviated pain and promoted axonal regeneration. Conclusions Our study reveals that Adcyap1 is an intrinsic protective factor linking neuropathic pain and axonal regeneration following PNI. This finding provides new potential targets and strategies for early therapeutic intervention of PNI.

Metal-ion (Li-, Na-, Zn-, K-, Mg-, and Al-ion) batteries (MIBs) play an important role in realizing the goals of “emission peak and carbon neutralization” because of their green production techniques, lower pollution, high voltage, and large energy density. Carbon-based materials are indispensable for developing MIBs and are widely adopted as active or auxiliary materials in the anodes and cathodes. For example, carbon-based materials, including graphite, Si/C and hard carbon, have been used as anode materials for Li- and Na-ion batteries. Carbon can also be used as a conductive coating for cathodes, such as in LiFePO4/C, to achieve better performance. In addition, as new high-valence MIBs (Zn-, Al-, and Mg-ion) have emerged, a growing number of novel carbon-based materials have been utilized to construct high-performance MIBs. Herein, we discuss the recent development trends in advanced carbon-based materials for MIBs. The impact of the structure properties of advanced carbon-based materials on energy storage is addressed, and a perspective on their development is also proposed.

Disulfidptosis, a newly identified mode of programmed cell death, is yet to be comprehensively elucidated with respect to its multi-omics characteristics in tumors, specific pathogenic mechanisms, and antitumor functions in liver cancer. This study included 10,327 tumor and normal tissue samples from 33 cancer types. In-depth analyses using various bioinformatics tools revealed widespread dysregulation of disulfidptosis-related genes (DRGs) in pan-cancer and significant associations with prognosis, genetic variations, tumor stemness, methylation levels, and drug sensitivity. Univariate and multivariate Cox regression and LASSO regression were used to screen and construct prognosis-related hub DRGs and predictive models in the context of liver cancer. Subsequently, single cell analysis was conducted to investigate the subcellular localization of RPN1, a hub DRG, in various solid tumors. Western blotting was performed to validate the expression of RPN1 at both cellular and tissue levels. Additionally, functional experiments, including CCK8, EdU, clone, and transwell assays, indicated that RPN1 knockdown promoted the proliferative and invasive capacities of liver cancer cells. Therefore, this study elucidated the multi-omics characteristics of DRGs in pan-cancer and established a prognostic model for liver cancer. Additionally, this study revealed the molecular functions of RPN1 in liver cancer, suggesting its potential as a therapeutic target for this disease.

Bacteriophages (phages) represent promising alternative treatments against multidrug-resistant Acinetobacter baumannii (MDRAB) infections. The application of phages as antibacterial agents is limited by their generally narrow host ranges, so changing or expanding the host ranges of phages is beneficial for phage therapy. Multiple studies have identified that phage tail fiber protein mediates the recognition and binding to the host as receptor binding protein in phage infection. However, the tail tubular-dependent host specificity of phages has not been studied well. In this study, we isolated and characterized a novel lytic phage, vB_Ab4_Hep4, specifically infecting MDRAB strains. Meanwhile, we identified a spontaneous mutant of the phage, vB_Ab4_Hep4-M, which revealed an expanded host range compared to the wild-type phage. A single mutation of G to C was detected in the gene encoding the phage tail tubular protein B and thus resulted in an aspartate to histidine change. We further demonstrated that the host range expansion of the phage mutant is driven by the spontaneous mutation of guanine to cytosine using expressed tail tubular protein B. Moreover, we established that the bacterial capsule is the receptor for phage Abp4 and Abp4-M by identifying mutant genes in phage-resistant strains. In conclusion, our study provided a detailed description of phage vB_Ab4_Hep4 and revealed the tail tubular-dependent host specificity in A. baumannii phages, which may provide new insights into extending the host ranges of phages by gene-modifying tail tubular proteins.

Urban forests can absorb carbon dioxide for urban CO2 emission mitigation. However, the potential capacity of urban forest carbon sequestration (CS) and its drivers remain unclear in urban agglomerations under rapid urbanization. In our study, the net primary productivity (NPP) of built-up areas was reconstructed in the Harbin-Changchun urban agglomeration (HCUA) from 2000 to 2020 to reflect urban forest CS, and the drivers of spatial urban forest CS patterns were further explored using the Geodetector model. Our results showed that the HCUA has experienced rapid urbanization over the past 20 years. Across the urbanization gradient, the CS capacity was higher in new developing built-up areas than in the old developed built-up areas for all years. The CS capacity of urban forests increased gradually from 2000 to 2020, especially in large built-up areas. The urban forest CS was skewed toward low (300 g·m−2) show an overall increasing trend from 2000 to 2020, especially in small, low-altitude and old developed built-up areas. The total CS of built-up areas increased from 0.35 Mt·C·yr−1 in 2000 to 2.06 Mt·C·yr−1 in 2020, and the urban forests in the HCUA could offset approximately 2.23 % of urban carbon emissions in 2000, increasing to 5.08 % in 2020. Natural factors, such as temperature, mainly determined changes of the spatial urban forest CS distribution. In addition, we found that urban morphology factors, such as urban build-up area, construction height, population density, and gross national product, can significantly influence urban forest CS. We further found there may exist the threshold of urban built-up area and gross national product significantly affecting urban forest CS variation. The interaction between natural and anthropogenic factors had stronger explanatory power for the spatial variation of CS. Our study can help city managers formulate low-carbon development strategies to address the negative impacts of climate change and realize the low-carbon development of cities.

Due to the nonlinearity and underactuation of bipedal robots, developing efficient jumping strategies remains challenging. To address this, a multiobjective collaborative deep reinforcement learning algorithm based on the actor‐critic framework is presented. Initially, two deep deterministic policy gradient (DDPG) networks are established for training the jumping motion, each focusing on different objectives and collaboratively learning the optimal jumping policy. Following this, a recovery experience replay mechanism, predicated on dynamic time warping, is integrated into the DDPG to enhance sample utilization efficiency. Concurrently, a timely adjustment unit is incorporated, which works in tandem with the training frequency to improve the convergence accuracy of the algorithm. Additionally, a Markov decision process is designed to manage the complexity and parameter uncertainty in the dynamic model of the bipedal robot. Finally, the proposed method is validated on a PyBullet platform. The results show that the method outperforms baseline methods by improving learning speed and enabling robust jumps with greater height and distance.

This study presents a novel approach to analysing environmental governance by Chinese governments through the lens of a tripartite evolutionary game model. The key novelty of our research lies in the explicit incorporation of a reputation mechanism into the evolutionary game analysis, which significantly influences government decision-making, environmental governance strategies, and the dynamics of the relationship between government and polluting enterprises. By assessing the marginal effects of conventional governance and mobilization-based governance on the environmental mechanism, as well as the collusion behaviours between government and polluting enterprises, our study sheds light on previously unexplored aspects of environmental governance. Our findings indicate that the reputation mechanism plays a crucial role within the evolutionary game system of environmental governance, exerting a substantial impact on government decision-making. Furthermore, we demonstrate that policy interventions, such as increasing the cost of penalties under regulatory policies, can encourage compliance strategies among enterprises. Additionally, our research highlights the high sensitivity of reputation signals towards local government's environmental governance strategies, directly impacting their credibility and influencing the adoption of proactive environmental governance strategies. Moreover, we emphasize the role of the central environmental inspection system as a means to facilitate the transmission of environmental governance pressures between central and local governments, ultimately fostering a green development concept and promoting coordinated development between the economy and ecological civilization. Overall, this study provides valuable insights into the intricacies of environmental governance in China and underscores the importance of reputation mechanisms and policy interventions in promoting sustainable development.

Aim: To compare all-cause and acute lymphoblastic leukemia (ALL)-related healthcare resource utilization (HCRU) and costs among patients receiving inotuzumab ozogamicin (InO) and blinatumomab (Blina) for ALL in the first relapsed/refractory (R/R) setting. Patients & methods: We studied retrospective claims for adult commercial and Medicare Advantage enrollees with ALL receiving InO (n = 29) or Blina (n = 23) from 1 January 2015 to 16 February 2021. Mean per-patient-per-month (PPPM) HCRU and total costs were described and multivariable-adjusted PPPM total all-cause and ALL-related predicted costs were calculated. Results: Mean monthly ALL-related hospitalizations were the same for patients receiving InO and Blina (PPPM = 0.8 stays); however, the length of ALL-related hospital stay was almost twice as long among patients receiving Blina versus InO (ALL-related: InO = 7.6 days; Blina = 14.1 days; p = 0.346). In multivariable models, total ALL-related costs were 43% lower for InO compared with Blina (PPPM costs: InO = $93,767; Blina = $163,470; p = 0.021). Conclusion: In the first R/R setting, patients who used InO had significantly lower all-cause and ALL-related costs compared with patients who used Blina, in part driven by hospitalization patterns.

ABSTRACTAlthough changes in gut microbiome have been associated with the development of T2D and its complications, the role of the gut virome remains largely unknown. Here, we characterized the gut virome alterations in T2D and its complications diabetic nephropathy (DN) by metagenomic sequencing of fecal viral-like particles. Compared with controls, T2D subjects, especially those with DN, had significantly lower viral richness and diversity. 81 viral species were identified to be significantly altered in T2D subjects, including a decrease in some phages (e.g. Flavobacterium phage and Cellulophaga phaga). DN subjects were depleted of 12 viral species, including Bacteroides phage, Anoxybacillus virus and Brevibacillus phage, and enriched in 2 phages (Shigella phage and Xylella phage). Multiple viral functions, particularly those of phage lysing host bacteria, were markedly reduced in T2D and DN. Strong viral-bacterial interactions in healthy controls were disrupted in both T2D and DN. Moreover, the combined use of gut viral and bacterial markers achieved a powerful diagnostic performance for T2D and DN, with AUC of 99.03% and 98.19%, respectively. Our results suggest that T2D and its complication DN are characterized by a significant decrease in gut viral diversity, changes in specific virus species, loss of multiple viral functions, and disruption of viral-bacterial correlations. The combined gut viral and bacterial markers have diagnostic potential for T2D and DN.

Abstract Flexible thermoelectric generators can power wearable electronics by harvesting body heat. However, existing thermoelectric materials rarely realize high flexibility and output properties simultaneously. Here we present a facile, cost-effective, and scalable two-step impregnation method for fabricating a three-dimensional thermoelectric network with excellent elasticity and superior thermoelectric performance. The reticular construction endows this material with ultra-light weight (0.28 g cm−3), ultra-low thermal conductivity (0.04 W m−1 K−1), moderate softness (0.03 MPa), and high elongation (>100%). The obtained network-based flexible thermoelectric generator achieves a pretty high output power of 4 μW cm−2, even comparable to state-of-the-art bulk-based flexible thermoelectric generators.

Abstract Background Estimated pulse wave velocity (ePWV) has revealed excellent performance in predicting cardiovascular disease (CVD) risk. However, whether ePWV predicts all-cause mortality and CVD mortality in populations with obesity remains elusive. Methods We performed a prospective cohort including 49,116 participants from the National Health and Nutrition Examination Survey from 2005 to 2014. Arterial stiffness was evaluated by ePWV. Weighted univariate, multivariate Cox regression and receiver operating characteristic curve (ROC) analysis was used to assess the effects of ePWV on the risk of all-cause and CVD mortality. In addition, the two-piecewise linear regression analysis was used to describe the trend of ePWV affecting mortality and identify the thresholds that significantly affect mortality. Results A total of 9929 participants with obesity with ePWV data and 833 deaths were enrolled. Based on the multivariate Cox regression results, the high ePWV group had a 1.25-fold higher risk of all-cause mortality and a 5.76-fold higher risk of CVD mortality than the low-ePWV group. All-cause and CVD mortality risk increased by 123% and 44%, respectively, for every 1 m/s increase in ePWV. ROC results showed that ePWV had an excellent accuracy in predicting all-cause mortality (AUC = 0.801) and CVD mortality (AUC = 0.806). Furthermore, the two-piecewise linear regression analysis exhibited that the minimal threshold at which ePWV affected participant mortality was 6.7 m/s for all-cause mortality and 7.2 m/s for CVD mortality. Conclusions ePWV was an independent risk factor for mortality in populations with obesity. High ePWV levels were associated with an increased all-cause and CVD mortality. Thus, ePWV can be considered a novel biomarker to assess mortality risk in patients with obesity.

In order to further optimize the microstructure and mechanical properties of TiB/TiAl composites, the individual and synergistic effects of Ta and Mn were investigated in this study. Ti43Al6Nb1.6B-xTa-yMn (x + y = 1, at%) composites, termed as TNB, TNB-1Ta, TNB-1Mn and TNB-0.5Ta0.5Mn, were fabricated by vacuum arc melting. X-ray diffraction results showed that the diffraction peak of B2 phase appeared in TNB-1Ta and TNB-1Mn composites, while it was not obvious in TNB-0.5Ta0.5Mn counterpart, which indicated that higher content of B2 phase formed with individual 1% Ta or 1% Mn addition. According to the solidified microstructures, Ta and/or Mn addition changed the α2/γ lamellar colonies from elongated to equiaxed morphology, which was due to the constitutional undercooling by Ta and/or Mn addition. Compressive results showed that individual and synergistic addition of Ta and Mn all increased the compressive strength and strain at room temperature, while the highest compressive properties were obtained in TNB-0.5Ta0.5Mn, which were 2142 MPa and 25.7%, respectively. Compared with individual addition of Ta or Mn, the synergistic addition of 0.5% Ta and 0.5% Mn not only induced less brittle B2 phase, but also had a stronger solid solution strengthening effect, because Ta atoms existed in TiB phase and Mn atoms existed in α2/γ lamellae. Therefore, the enhanced properties of TNB-0.5Ta0.5Mn resulted from the refinement of α2/γ lamellar colonies, solid solution strengthening of Ta and Mn, and lower content of brittle B2 phase.

Background: The objective of this study is to estimate the causal relationship between plasma proteins and myocardial infarction (MI) through Mendelian randomization (MR), predict potential target-mediated side effects associated with protein interventions, and ensure a comprehensive assessment of clinical safety. Methods: From 3 proteome genome-wide association studies (GWASs) involving 9775 European participants, 331 unique blood proteins were screened and chosed. The summary data related to MI were derived from a GWAS meta-analysis, incorporating approximately 61,000 cases and 577,000 controls. The assessment of associations between blood proteins and MI was conducted through MR analyses. A phenome-wide MR (Phe-MR) analysis was subsequently employed to determine the potential on-target side effects of protein interventions. Results: Causal mediators for MI were identified, encompassing cardiotrophin-1 (CT-1) (odds ratio [OR] per SD increase: 1.16; 95% confidence interval [CI]: 1.13–1.18; p = 1.29 × 10-31), Selenoprotein S (SELENOS) (OR: 1.16; 95% CI: 1.13–1.20; p = 4.73 × 10-24), killer cell immunoglobulin-like receptor 2DS2 (KIR2DS2) (OR: 0.93; 95% CI: 0.90–0.96; p = 1.08 × 10-5), vacuolar protein sorting-associated protein 29 (VPS29) (OR: 0.92; 95% CI: 0.90–0.94; p = 8.05 × 10-13), and histo-blood group ABO system transferase (NAGAT) (OR: 1.05; 95% CI: 1.03–1.07; p = 1.41 × 10-5). In the Phe-MR analysis, memory loss risk was mediated by CT-1, VPS29 exhibited favorable effects on the risk of 5 diseases, and KIR2DS2 showed no predicted detrimental side effects. Conclusions: Elevated genetic predictions of KIR2DS2 and VPS29 appear to be linked to a reduced risk of MI, whereas an increased risk is associated with CT-1, SELENOS, and NAGAT. The characterization of side effect profiles aids in the prioritization of drug targets. Notably, KIR2DS2 emerges as a potentially promising target for preventing and treating MI, devoid of predicted detrimental side effects.

Backgrounds and aims: Carcinogenesis is characterized by an unlimited growth of cells exacerbated by Cox-2 overexpression. Cox-2 inhibitors have been proven effective in preventing and treating tumors. In our previous studies, we found that 4-Amino-2-Trifluoromethylphenyl Retinate (ATPR) induces cell apoptosis and inhibits cell proliferation to exhibit anti-cancer properties. The use of ATRA as well as Cox-2 inhibitors in clinical settings can cause adverse reactions. It is unknown what the effects and mechanisms of co-administration of ATPR and Cox-2 inhibitors are. Results: A combination of ATPR and Cox-2 inhibitors, Celecoxib, inhibited pharyngeal cancer cell proliferation in vitro and induced apoptosis. The cell cycle was arrested at G0/G1 by activating P53 and CDNA1. By activating MAPK/JNK pathways, ATPR and Celecoxib led to intrinsic and extrinsic apoptosis in pharyngeal cancer cells. ATPR/Celecoxib combined treatment suppressed tumor growth in the pharyngeal cancer cell-derived xenograft mouse model by increasing the number of apoptotic cells. The expression of the RARA and PTGS2 genes was significantly increased in tumor tissue compared to non-tumor tissue in the clinical analysis of the head and neck squamous cell carcinoma dataset. An association was found between this and the level of intrinsic apoptotic signals. Furthermore, a survival analysis conducted over a period of five years indicated that higher levels of RARA expression were associated with a better clinical outcome. Conclusion: ATPR and celecoxib inhibit the proliferation of cancer cells as well as induce apoptosis. Co-administration of ATPR and Cox-2 inhibitors has the potential to be a novel treatment plan for cancer.

BackgroundNumerous studies have revealed associations between gut microbiota and adipose tissue. However, the specific functional bacterial taxa and their causal relationships with adipose tissue production in different regions of the body remain unclear.MethodsWe conducted a bidirectional two-sample Mendelian Randomization (MR) study using aggregated data from genome-wide association studies (GWAS) for gut microbiota and adipose tissue. We employed methods such as inverse variance weighted (IVW), MR Egger, weighted median, simple mode, and weighted mode to assess the causal relationships between gut microbiota and subcutaneous adipose tissue (SAT) as well as visceral adipose tissue (VAT). Cochran’s Q test, MR-Egger regression intercept analysis, and MR-PRESSO were used to test for heterogeneity, pleiotropy, and outliers of the instrumental variables, respectively. Reverse MR was employed to evaluate the reverse causal relationships between SAT, VAT, and gut microbiota with significant associations.ResultsIVW results demonstrated that Betaproteobacteria were protective factors for SAT production (OR = 0.88, 95% CI: 0.80–0.96, p = 0.005) and VAT production (OR = 0.91, 95% CI: 0.83–0.99, p = 0.030). Various bacterial taxa including Ruminococcaceae UCG002 (OR = 0.94, 95% CI: 0.89–0.99, p = 0.017), Methanobacteria class (OR = 0.96, 95% CI: 0.92–1.00, p = 0.029), and Burkholderiales (OR = 0.90, 95% CI: 0.83–0.98, p = 0.012) were associated only with decreased SAT production. Rikenellaceae RC9 gut group (OR = 1.05, 95% CI: 1.02–1.10, p = 0.005), Eubacterium hallii group (OR = 1.08, 95% CI: 1.01–1.15, p = 0.028), Peptococcaceae (OR = 1.08, 95% CI: 1.01–1.17, p = 0.034), and Peptococcus (OR = 1.05, 95% CI: 1.00–1.10, p = 0.047) were risk factors for SAT production. Meanwhile, Eubacterium fissicatena group (OR = 0.95, 95% CI: 0.91–0.99, p = 0.019), Turicibacter (OR = 0.93, 95% CI: 0.88–0.99, p = 0.022), and Defluviitaleaceae UCG011 (OR = 0.94, 95% CI: 0.89–0.99, p = 0.024) were protective factors for VAT production. Furthermore, Bacteroidetes (OR = 1.09, 95% CI: 1.01–1.17, p = 0.018), Eubacterium eligens group (OR = 1.09, 95% CI: 1.01–1.19, p = 0.037), Alloprevotella (OR = 1.05, 95% CI: 1.00–1.10, p = 0.038), and Phascolarctobacterium (OR = 1.07, 95% CI: 1.00–1.15, p = 0.042) were associated with VAT accumulation. Additionally, reverse MR revealed significant associations between SAT, VAT, and Rikenellaceae RC9 gut group (IVW: OR = 1.57, 95% CI: 1.18–2.09, p = 0.002) as well as Betaproteobacteria (IVW: OR = 1.14, 95% CI: 1.01–1.29, p = 0.029), both acting as risk factors. Sensitivity analyzes during bidirectional MR did not identify heterogeneity or pleiotropy.ConclusionThis study unveils complex causal relationships between gut microbiota and SAT/VAT, providing novel insights into the diagnostic and therapeutic potential of gut microbiota in obesity and related metabolic disorders.

Background: Cuproptosis, as a recently discovered type of programmed cell death, occupies a very important role in hepatocellular carcinoma (HCC) and provides new methods for immunotherapy; however, the functions of cuproptosis in HCC are still unclear.Methods: We first analyzed the transcriptome data and clinical information of 526 HCC patients using multiple algorithms in R language and extensively described the copy number variation, prognostic and immune infiltration characteristics of cuproptosis related genes (CRGs). Then, the hub CRG related genes associated with prognosis through LASSO and Cox regression analyses and constructed a prognostic prediction model including multiple molecular markers and clinicopathological parameters through training cohorts, then this model was verified by test cohorts. On the basis of the model, the clinicopathological indicators, immune infiltration and tumor microenvironment characteristics of HCC patients were further explored via bioinformation analysis. Then, We further explored the key gene biological function by single-cell analysis, cell viability and transwell experiments. Meantime, we also explored the molecular docking of the hub genes.Results: We have screened 5 hub genes associated with HCC prognosis and constructed a prognosis prediction scoring model. And the model results showed that patients in the high-risk group had poor prognosis and the expression levels of multiple immune markers, including PD-L1, CD276 and CTLA4, were higher than those patients in the low-risk group. We found a significant correlation between risk score and M0 macrophages and memory CD4+ T cells. And the single-cell analysis and molecular experiments showed that BEX1 were higher expressed in HCC tissues and deletion inhibited the proliferation, invasion and migration and EMT pathway of HCC cells. Finally, it was observed that BEX1 could bind to sorafenib to form a stable conformation.Conclusion: The study not only revealed the multiomics characteristics of CRGs in HCC but also constructed a new high-accuracy prognostic prediction model. Meanwhile, BEX1 were also identified as hub genes that can mediate the cuproptosis of hepatocytes as potential therapeutic targets for HCC.

Background:. Pancreaticoduodenectomy (PD) has been widely applied in general hospitals in China; however, there is still a lack of unified standards for each surgical technique and procedure. This survey is intended to investigate the current status of digestive tract reconstruction after PD in university hospitals in China. Method:. A cross-sectional survey was conducted among the members of the Young Elite Pancreatic Surgery Club of China by using the Questionnaire for Digestive Tract Reconstruction after Pancreaticoduodenectomy. The questionnaire was disseminated and collected by point-to-point communication via WeChat public platforms. Results:. A total of 73 valid questionnaires were returned from 65 university hospitals in 28 provincial divisions of mainland China. The respondents who performed PD surgery with an annual volume of over 100 cases accounted for 63%. Generally, laparoscopic PD was performed less often than open PD. Child and Whipple reconstructions accounted for 70% and 26%, respectively. The sequence of pancreatoenteric, biliary-enteric, and gastrointestinal reconstruction accounted for 84% of cases. In pancreatoenteric anastomosis, double-layer anastomosis is the most commonly employed type, accounting for approximately 67%, while single-layer anastomosis accounts for 30%. Of the double-layer anastomoses, duct-to-mucosa/dunking (94%/4%) pancreatojejunostomy was performed with duct-mucosa using the Blumgart method (39%) and Cattel-Warren (29%), with continuous/interrupted sutures in the inner layer (69%/31%) and continuous/interrupted sutures in the outer layer (53%/23%). In single-layer anastomosis, continuous/interrupted sutures accounted for 41%/45%. In hepatojejunostomy, single-layer/double-layer suture accounted for 79%/4%, and continuous/interrupted suture accounted for 75%/9%. Forty-six percent of the responding units had not applied double-layer biliary-intestinal anastomosis in the last 3 years, 75% of the responding surgeons chose the anastomosis method according to bile duct diameter, with absorbable/non-absorbable suture accounting for 86%/12%. PD/pylorus-preserving PD accounted for 79%/11% of gastrojejunostomy (GJ) cases, the distance between GJ and hepaticojejunostomy < 30, 30–50, and > 50 cm were 11%, 75%, and 14%, respectively. Antecolic/retrocolic GJ accounted for 71%/23% of cases. Twenty-two percent of GJ cases employed Braun anastomosis, while 55% and 19% of GJ cases used linear cutting staplers/tube-type staplers, respectively; 60%/14% were reinforced/not reinforced via manual suturing after stapler anastomosis. Manual anastomosis in GJ surgery employed absorbable/non-absorbable sutures (91%/9%). Significant differences in reconstruction techniques were detected between different volumes of PD procedures (100/year), regions with different economic development levels, and between north and south China. Conclusion:. Digestive tract reconstruction following PD exists heterogeneity in Chinese university hospitals. Corresponding prospective clinical studies are needed to determine the consensus on pancreatic surgery that meets the clinical reality in China.

As a highly efficient thermodynamic cycle formed by pure natural fluid and using aerothermal energy, transcritical CO2 technology has huge advantages in terms of energy consumption, equivalent carbon content and environmental benefits, and is an important technological means for global carbon neutrality and renewable energy structure transformation. After reviewing the development history of refrigerants and the basic principle of transcritical CO2 technology, the technical characteristics, research status and development trend of the transcritical CO2 cooling/heating technology in the fields of vehicle air conditioning, building heating, hot water supply, drying industry, commercial cold chain and other fields are comprehensively summarized in details. The main problems in the development of transcritical CO2 technology was summarized regarding different applications with their unique operating conditions and requirements, while corresponding structural modification and thermodynamic parameter optimization schemes have been briefly summarized. As results, it has been proved that CO2 refrigerant has become one of the most important solutions in various applications, and this historical trend has been almost irreversible. Therefore, the future development of the transcritical CO2 technologies, including the system intelligentization and expansion work recovery techniques such as expander, ejector and vortex tube, were carefully analyzed. In summary, the explosive development of the transcritical CO2 technology will be significant for mitigating the contemporary environmental challenges and respecting the regulations on the progressive ban of hydrofluorocarbons (HFCs), so relevant contents are detailed in this paper for providing reference for its further engineering and industrialization.

Cannabidiol (CBD) is the major functional component in hemp and has a broad range of pharmacological applications, such as analgesic, anti-epileptic, anti-anxiety, etc. Currently, CBD is widely used in pharmaceuticals, cosmetics, and food. To ensure the quality and safety of the products containing CBD, more and more related sample testing is being conducted, and the demand for CBD-certified reference material (CRM) has also sharply increased. However, there is currently a lack of relevant reference materials. In this paper, a simple method for preparing CBD CRM was established based on preparative liquid chromatography using crude hemp extract as a raw material. A qualitative analysis of CBD was performed using techniques such as ultraviolet absorption spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), nuclear magnetic resonance spectroscopy (NMR), and differential scanning calorimetry (DSC). High-performance liquid chromatography (HPLC) was used for the homogeneity and stability tests, and the data were analyzed using an F-test and a T-test, respectively. Then, eight qualified laboratories were chosen for the determination of a certified value using HPLC. The results show that the CBD CRM had excellent homogeneity and good stability for 18 months. The certified value was 99.57%, with an expanded uncertainty of 0.24% (p = 0.95, k = 2). The developed CBD CRM can be used for the detection and quality control of cannabidiol products.

The intermetallic PtBi/MgO/Mg monolithic catalyst was first prepared using non-equilibrium plasma electrolytic oxidation (PEO) technology. Spherical aberration-corrected transmission electron microscope (ACTEM) observation confirms the successful synthesis of the PtBi intermetallic structure. The efficiency of PtBi/Mg/MgO catalysts in catalyzing the reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) in the presence of NaBH4 was demonstrated. The activity factor for the catalyst is 31.8 s−1 g−1, which is much higher than reported values. In addition, the resultant catalyst also exhibits excellent catalytic activity in the organic pollutant reaction of p-nitrobenzoic acid (p-NBA) and methyl orange (MO). Moreover, benefiting from ordered atomic structures and the half-embedded PtBi nanoparticles (NPs), the catalyst demonstrates excellent stability and reproducibility in the degradation of 4-NP. This study provides an example of a simple method for the preparation of intermetallic structures as catalysts for organic pollutant degradation.