A Universal Strategy to Enhance Polarization Performance and Anode Reversal Tolerance by Polyaniline-Coated Carbon Support for Proton Exchange Membrane Fuel Cells.

Anode cell reversal typically leads to severe carbon corrosion and catalyst layer collapse, which significantly compromises the durability of proton exchange membrane fuel cells. Herein, three types of commercial carbon supports with various structures are facilely coated by polyaniline (PANI) and subsequently fabricated into reversal-tolerant anodes (RTAs). Consequently, the optimized PANI-coated catalyst RTAs demonstrate enhanced polarization performance and improved reversal tolerance compared to their uncoated counterparts, thus confirming the universality of this coating strategy. Essentially, the surface engineering introduced by PANI coating incorporates abundant N-groups and enhances coulombic interactions with ionomer side chains, which in turn reduces lower carbon exposure, promotes more uniform Pt deposition, and ensures better ionomer distribution. Accordingly, the membrane-electrode-assembly containing the Pt/PANI/XC-72R-1+IrO2 RTA presents a 100 mV (at 2500 mA cm-2) polarization performance improvement and 26-fold reduction in the degradation rate compared to the uncoated counterpart. This work provides a universal strategy for developing durable anodes and lays the groundwork for the practical fabrication of high-performance, low-degradation RTA.

Itaconate to treat acute lung injury: recent advances and insights from preclinical models.

Acute lung injury (ALI) is defined as the acute onset of diffuse bilateral pulmonary infiltration, leading to PaO2/FiO2 ≤ 300 mmHg without clinical evidence of left atrial hypertension. Acute respiratory distress syndrome (ARDS) involves more severe hypoxemia (PaO2/FiO2 ≤ 200 mmHg). Treatment of ALI and ARDS has received renewed attention as the incidence of ALI caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has increased. Itaconate and its derivatives have shown therapeutic potential against ALI. This review provides an in-depth summary of the mechanistic research of itaconate in the field of acute lung injury, including inducing autophagy, preventing ferroptosis and pyroptosis, shifting macrophage polarization to an anti-inflammatory M2 phenotype, inhibiting neutrophil activation, regulating epigenetic modifications, and repressing aerobic glycolysis. These compounds merit further consideration in clinical trials. We anticipate that the clinical translation of itaconate-based drugs can be accelerated.

Elevated meteorin-like protein from high-intensity interval training improves heart function via AMPK/HDAC4 pathway.

High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

Intermittent Fasting-Induced Orm2 Promotes Adipose Browning via the GP130/IL23R-p38 Cascade.

Intermittent fasting (IF) plays a critical role in mitigating obesity, yet the precise biological mechanisms require further elucidation. Here Orosomucoid 2 (Orm2) is identified as an IF-induced hepatokine that stimulates adipose browning. IF induced Orm2 expression and secretion from the liver through peroxisome proliferator-activated receptor alpha (PPARα). In adipose tissue, Orm2 bound to glycoprotein 130/interleukin 23 receptor (GP130/IL23R) and promoted adipose browning through the activation of p38 mitogen-activated protein kinases (p38-MAPK). In obese mice, Orm2 led to a significant induction of adipose tissue browning and subsequent weight loss, an effect that is not replicated by a mutant variant of Orm2 deficient in GP130/IL23R binding capability. Crucially, genetic association studies in humans identified an obesity-associated Orm2 variant (D178E), which shows decreased GP130/IL23R binding and impaired browning capacity in mice. Overall, the research identifies Orm2 as a promising therapeutic target for obesity, mediating adipose browning through the GP130/IL23R-p38 signalling pathway.

Association between perioperative hemoglobin decrease and outcomes of transfusion in patients undergoing on-pump cardiac surgery: An observational study from two Chinese heart centers.

Background: It is unclear how perioperative hemoglobin decrease (ΔHb) influences the balance between risks and benefits of red blood cell transfusion after cardiac surgery. Methods: We retrospectively analyzed data on 8186 adults who underwent valve surgery and/or coronary artery bypass grafting under cardiopulmonary bypass at two large cardiology centers. We explored the potential association of ΔHb, defined relative to the preoperative level and postoperative nadir, with a composite outcome of in-hospital mortality, myocardial infarction, stroke, and acute kidney injury using multivariable logistic regression, restricted cubic spline, and piecewise-linear models. Results: Among 6316 patients without preoperative anemia, ΔHb ≥ 50 % was associated with an elevated risk of the composite outcome [adjusted odds ratio (aOR) 1.95, 95 % confidence interval (CI) 1.81-2.35]. Among 869 patients without preoperative anemia and with ΔHb ≥ 50 %, postoperative transfusion of no more than four units of red blood cell appeared to decrease the risk of the composite outcome, whereas transfusion of more than six units increased risk. Among 5447 patients without preoperative anemia and with ΔHb < 50 %, postoperative transfusion appeared not to decrease the risk of the composite outcome. Among 1870 patients with preoperative anemia, ΔHb ≥ 30 % significantly increased the risk of the composite outcome (aOR 1.61, 95 % CI 1.23-2.10), and this risk might be moderated by postoperative transfusion of no more than four units of red blood cell, but increased by transfusion of more than six units. Conclusions: ΔHb may influence the balance between risks and benefits of red blood cell transfusion after cardiac surgery.

An Inhalable Nanoshield for Effective Prevention of Influenza Virus Infections.

Influenza virus (IV) infection currently poses a serious and continuing threat to the global public health. Developing effective prevention strategies is important to defend against infection and spread of IV. Here, we developed a triple-protective nanoshield against IV infection in the lungs, formed by self-assembling DSPE-PEG amphiphilic polymers encapsulating the flu-preventive antiviral drug Arbidol internally. The preventive effect of the nanoshield against virus infection includes increasing the viscosity in the surrounding environment to physically defend against viral entry, forming a hydrated layer to block the interaction between viruses and cells, and inhibiting virus replication. Our finding suggested that a single inhalation of the nanoshield provides effective protection against IV infection for at least 8 h. Thus, this nanoshield may be a potential pandemic protection agent against IV, especially in viral environments, where no prophylactic or therapeutic measures are available.

Distribution and drivers of co-hosts of antibiotic and metal(loid) resistance genes in the fresh-brackish-saline groundwater.

Groundwater is an essential source of drinking water and agricultural irrigation water, and its protection has become a global goal for public health. However, knowledge about heavy metal(loid) resistance genes (MRGs) in groundwater and the potential co-selection of antibiotic resistance genes (ARGs) have seldom been developed. Here, during the wet and dry seasons, we collected 66 groundwater samples (total dissolved solids = 93.9-9530 mg/L) adjacent to Baiyangdian Lake in Northern China, which presented the few metal(loid) and antibiotic contamination. We identified 160 MRGs whose composition exhibited significant seasonal variation, and dissolved metal(loid)s (particularly Ba) played a determinative role in promoting the MRGs proliferation though with relatively low concentrations, suggesting the relatively vulnerable groundwater ecosystems. Moreover, 27.4% of MRG-carrying metagenome-assembled genomes (MAGs) simultaneously carried ARGs, with the most frequently detected MRG types of Cu, Hg, and As, and ARG types of multidrug and bacitracin. Physicochemical variables, variables related to total dissolved solids, metal(loid)s, and antibiotics synthetically shaped the variation of MRG-ARG hosts in groundwater. We found that the increase of MRG-ARG hosts was critically responsible for the spread of MRGs and ARGs in groundwater. Our findings revealed the widespread co-occurrence of MRGs and ARGs in few-contaminated groundwater and highlighted the crucial roles of salinity in their propagation and transmission.

A Rechargeable Urea-Assisted Zn-Air Battery with High Energy Efficiency and Fast-Charging Enabled by Engineering High-Energy Interfacial Structures.

Electrochemical urea oxidation reaction (UOR) offers a promising alternative to the oxygen evolution reaction (OER) in clean energy conversion and storage systems. Nickel-based catalysts are highly regarded as promising electrocatalysts for the UOR. However, their effectiveness is significantly hindered by the unavoidable self-oxidation reaction of nickel species during UOR. To address this challenge, we proposed an interface chemistry modulation strategy to boost UOR kinetics by creating a high-energy interfacial heterostructure. This heterostructure features the incorporation of Ag at the CoOOH@NiOOH heterojunction interface. Strong interactions significantly promote the electron exchanges in the heterointerface between the -OH and -O. Consequently, the improved electron delocalization led to the formation of stronger bonds between Co sites and urea CO(NH2)2, promoting a preference for urea to occupy Co active sites over OH*. The resulting catalyst, Ag-CoOOH@NiOOH, affords an ultrahigh UOR activity with a low potential of 1.33 V at 100 mA cm-2. The fabricated catalyst exhibits a mass activity exceeding that of initial cobalt oxyhydroxide by over 11.9 times. The rechargeable urea-assisted zinc-air batteries (ZABs) achieves a record-breaking energy efficiency of 74.56% at 1 mA cm-2, remarkable durability (1000 hours at even a current density of 50 mA cm-2), and quick charge performances.

Identification of genetic basis of brain imaging by group sparse multi-task learning leveraging summary statistics.

Brain imaging genetics is an evolving neuroscience topic aiming to identify genetic variations related to neuroimaging measurements of interest. Traditional linear regression methods have shown success, but their reliance on individual-level imaging and genetic data limits their applicability. Herein, we proposed S-GsMTLR, a group sparse multi-task linear regression method designed to harness summary statistics from genome-wide association studies (GWAS) of neuroimaging quantitative traits. S-GsMTLR directly employs GWAS summary statistics, bypassing the requirement for raw imaging genetic data, and applies multivariate multi-task sparse learning to these univariate GWAS results. It amalgamates the strengths of conventional sparse learning methods, including sophisticated modeling techniques and efficient feature selection. Additionally, we implemented a rapid optimization strategy to alleviate computational burdens by identifying genetic variants associated with phenotypes of interest across the entire chromosome. We first evaluated S-GsMTLR using summary statistics derived from the Alzheimer's Disease Neuroimaging Initiative. The results were remarkably encouraging, demonstrating its comparability to conventional methods in modeling and identification of risk loci. Furthermore, our method was evaluated with two additional GWAS summary statistics datasets: One focused on white matter microstructures and the other on whole brain imaging phenotypes, where the original individual-level data was unavailable. The results not only highlighted S-GsMTLR's ability to pinpoint significant loci but also revealed intriguing structures within genetic variations and loci that went unnoticed by GWAS. These findings suggest that S-GsMTLR is a promising multivariate sparse learning method in brain imaging genetics. It eliminates the need for original individual-level imaging and genetic data while demonstrating commendable modeling and feature selection capabilities.

Bridging gaps and seeding futures: A synthesis of soil salinization and the role of plant-soil interactions under climate change.

Soil salinization, exacerbated by climate change, poses significant threats to agricultural productivity, land restoration, and ecosystem resilience. This study reviews current knowledge on plant-soil interactions as a strategy to mitigate soil salinization induced by climate change, focusing on their role in soil salinity dynamics and tolerance mechanisms. The review examines how alterations in hydrological and temperature regimes impact soil salinity and how plant-soil mechanisms-such as salt exclusion, compartmentalization, and plant-microbe interactions-contribute to salinity mitigation. This, in turn, enhances soil quality, fertility, microbial diversity, and ecosystem services. The analysis identifies a growing body of research and highlights key themes and emerging trends, including drought, microbial communities, and salt tolerance strategies. This study underscores the critical role of plant-soil interactions in sustainable salinity management and identifies knowledge gaps and future research priorities, advocating for plant-soil interactions as a crucial pathway for improving ecosystem resilience to salinity stress amid climate change.

A Novel Multi-Dimensional Joint Search Method for the Compression of Medical Image Segmentation Models.

Due to the excellent results achieved by transformers in computer vision, more and more scholars have introduced transformers into the field of medical image segmentation. However, the use of transformers will make the model's parameters very large, which occupies a large amount of the computer's resources, making them very time-consuming during training. In order to alleviate this disadvantage, this paper explores a flexible and efficient search strategy that can find the best subnet from a continuous transformer network. The method is based on a learnable and uniform L1 sparsity constraint, which contains factors that reflect the global importance of the continuous search space in different dimensions, while the search process is simple and efficient, containing a single round of training. At the same time, in order to compensate for the loss of accuracy caused by the search, a pixel classification module is introduced into the model to compensate for the loss of accuracy in the model search process. Our experiments show that the model in this paper compresses 30% of the parameters and FLOPs used, while also showing a slight increase in the accuracy of the model on the Automatic Cardiac Diagnosis Challenge (ACDC) dataset.

Molecular cloning and functional characterization in response to saline-alkali stress of the MhZEP gene in Arabidopsis thaliana.

Soil salinization is one of the major environmental factors that restrict plant growth and development. Zeaxanthin epoxidase (ZEP) functions in ABA biosynthesis and the xanthophyll cycle and has a vital role in plant responses to various environmental stresses. It was found by quantitative real-time PCR (qRT-PCR) that MhZEP responded to saline-alkali stress and showed the highest expression at 48 h of saline-alkali stress, which was 14.53-fold of 0 h. The MhZEP gene was cloned from the apple rootstock begonia (Malus halliana Koehne) and its protein physicochemical properties were analyzed. Subsequently, the functional characterization of MhZEP (ID: 103403091) was further investigated in Arabidopsis thaliana. The MhZEP contained a complete open reading frame with a length of 1998 bp, and encoded 665 amino acids with an isoelectric point of 7.18. Phylogenetic tree analysis showed that MhZEP was the most homologous and closely related to Glycine max. Compared with wild-type, transgenic plants grew better under saline-alkali stress and the MhZEP-OE line showed higher chlorophyll content, carotenoid content, enzyme activities (POD, SOD, CAT and APX) and K+ content, whereas they had lower chlorosis and Na+ content than the wild type (WT), which indicated that they had strong resistance to stress. The expression levels of saline-alkali stress-related genes in A. thaliana MhZEP-OE were examined by qRT-PCR, and it was found that the MhZEP improved the tolerance of A. thaliana to saline-alkali stress tolerance by regulating the expression of carotenoid synthesis genes (MhPSY, MhZDS, MhLYCB and MhVDE) and ABA biosynthesis genes (MhNCED5, MhABI1 and MhCYP707A2). And the potassium-sodium ratio in the cytoplasm was increased to maintain ionic homeostasis by modulating the expression of Na+ transporter genes (MhCHX15 and MhSOS1) and K+ transporter genes (MhHKT1;1, MhNHX1 and MhSKOR1). Moreover, the expression of H+-ATPase genes (MhAHA2 and MhAHA8) was increased to reduce the oxidative damage caused by saline-alkali stress. In summary, MhZEP acted as an essential role in plant resistance to saline-alkali stress, which lays the foundation for further studies on its function in apple.

Revealing Different Pathways for Influenza A Virus To Reach Microtubules after Endocytosis by Quantum Dot-Based Single-Virus Tracking.

Actin- and microtubule (MT)-based transport systems are essential for intracellular transport. During influenza A virus (IAV) infection, MTs provide long tracks for virus trafficking toward the nucleus. However, the role of the actin cytoskeleton in IAV entry and especially the transit process is still ambiguous. Here, by using quantum dot-based single-virus tracking, it was revealed that the actin cytoskeleton was crucial for the virus entry via clathrin-mediated endocytosis (CME). After entry via CME, the virus reached MTs through three different pathways: the virus (1) was driven by myosin VI to move along actin filaments to reach MTs (AF); (2) was propelled by actin tails assembled by an Arp2/3-dependent mechanism to reach MTs (AT); and (3) directly reached MTs without experiencing actin-related movement (NA). Therefore, the NA pathway was the main one and the fastest for the virus to reach MTs. The AT pathway was activated only when plenty of viruses entered the cell. The viruses transported by the AF and AT pathways shared similar moving velocities, durations, and displacements. This study comprehensively visualized the role of the actin cytoskeleton in IAV entry and transport, revealing different pathways for IAV to reach MTs after entry. The results are of great significance for globally understanding IAV infection and the cellular endocytic transport pathway.

Huaxi integrated blood management reduces the red blood cell transfusion for on-pump cardiac surgery: A quasi-experimental study.

OBJECTIVE: As many as half of patients undergoing on-pump cardiac surgery require red blood cell transfusion, emphasizing the need for effective strategies that can reduce this need. We conducted this analysis to assess the effectiveness of Huaxi Integrated Blood Management strategy at our medical center. DESIGN: Before and after study. PARTICIPANTS: Patients who underwent on-pump cardiac surgery were included from January 2019 to December 2021. Two cohorts were compared, one before implementation of the strategy (1 January 2019 until 31 May 2020) and one after implementation (1 June 2020 until 31 December 2021). MEASUREMENTS: We evaluated temporal trends in blood transfusion, safety, and efficacy of this strategy. Primary outcomes were the incidence and volume of intra- and postoperative blood transfusions of packed red blood cells. Secondary outcomes are intraoperative and postoperative transfusion of other blood products, all-cause mortality during hospitalization, and incidence of new-onset complications. MAIN RESULTS: Our results demonstrated that this integrated strategy effectively decreased both the perioperative packed red blood cell transfusion volume and incidence for patients who underwent the on-pump cardiac surgery. Following the implementation, the incidence of packed red blood cell transfusions decreased by 8.1% during the intraoperative period and by 12.3% during the postoperative period. The mean volume of such transfusions decreased by 0.28 units during the intraoperative period and by 0.49 units during the postoperative period. Hemoglobin concentrations were significantly higher after implementation, and the maximal mean increase was 4.72 g/l on postoperative day 1. Similar benefit of the strategy was observed across subgroups of patients who underwent different types of surgery. CONCLUSIONS: The Huaxi Integrated Blood Management strategy may be effective at reducing the need for packed red blood cell transfusion and enhancing patient care.

Engineered Microbial Consortium for De Novo Production of Sclareolide.

Sclareolide, a natural product with bioactive and fragrant properties, is not only utilized in the food, healthcare, and cosmetics industries but also serves as a precursor for the production of ambroxide and some bioactive compounds. Currently, there are three primary methods for producing sclareolide: direct extraction from plants, chemical synthesis using sclareol as a precursor, and the biotransformation of sclareol. Here, we established a platform for producing sclareolide through a modular coculture system with Saccharomyces cerevisiae and Cryptococcus albidus ATCC 20918. S. cerevisiae was engineered for de novo sclareol biosynthesis from glucose, while C. albidus enabled the production of sclareolide via sclareol biotransformation. To enhance the supply of sclareol, a recombinant yeast strain was constructed through metabolic engineering to produce 536.2 mg/L of sclareol. Further improvement of the coculture system for sclareolide production was achieved by incorporating Triton X-100 facilitated intermediate permeability, inoculation proportion adjustment, and culture temperature optimization. These refinements culminated in a sclareolide yield of 626.3 mg/L. This study presents a novel streamlined and efficient approach for sclareolide preparation, showcasing the potential of the microbial consortium in sustainable bioproduction.

Nitrogen fertilization and soil nitrogen cycling: Unraveling the links among multiple environmental factors, functional genes, and transformation rates.

Anthropogenic nitrogen (N) inputs substantially influence the N cycle in agricultural ecosystems. However, the potential links among various environmental factors, nitrogen functional genes, and transformation rates under N fertilization remain poorly understood. Here, we conducted a five-year field experiment and collected 54 soil samples from three 0-4 m boreholes across different treatments: control, N-addition (nitrogen fertilizer) and NPK-addition (combined application of nitrogen, phosphorus and potassium fertilizers) treatments. Our results revealed pronounced variations in soil physiochemical parameters, metal concentrations and antibiotic levels under both N and NPK treatments. These alternations induced significant shifts in bacterial and fungal communities, altered NFG abundance and composition, and greatly enhanced rates of nitrate reduction processes. Notably, nutrients, antibiotics and bacteria exerted a more pronounced influence on NFGs and nitrate reduction under N treatment, whereas nutrients, metals, bacteria and fungi had a significant impact under NPK treatment. Furthermore, we established multidimensional correlations between nitrate reduction gene profiles and the activity rates under N and NPK treatments, contrasting with the absence of significant relationships in the control treatment. These findings shed light on the intricate relationships between microbial genetics and ecosystem functions in agricultural ecosystem, which is of significance for predicting and managing metabolic processes effectively.

Quantitatively Dissecting Triple Roles of Dynactin in Dynein-Driven Transport of Influenza Virus by Quantum Dot-Based Single-Virus Tracking.

After entering host cells by endocytosis, influenza A virus (IAV) is transported along microfilaments and then transported by dynein along microtubules (MTs) to the perinuclear region for genome release. Understanding the mechanisms of dynein-driven transport is significant for a comprehensive understanding of IAV infection. In this work, the roles of dynactin in dynein-driven transport of IAV were quantitatively dissected in situ using quantum dot-based single-virus tracking. It was revealed that dynactin was essential for dynein to transport IAV toward the nucleus. After virus entry, virus-carrying vesicles bound to dynein and dynactin before being delivered to MTs. The attachment of dynein to the vesicles was dependent on dynactin and its subunits, p150Glued and Arp1. Once viruses reached MTs, dynactin-assisted dynein initiates retrograde transport of IAV. Importantly, the retrograde transport of viruses could be initiated at both plus ends (32%) and other regions on MTs (68%). Subsequently, dynactin accompanied and assisted dynein to persistently transport the virus along MTs in the retrograde direction. This study revealed the dynactin-dependent dynein-driven transport process of IAV, enhancing our understanding of IAV infection and providing important insights into the cell's endocytic transport mechanism.

RSSI-WSDE: Wireless Sensing of Dynamic Events Based on RSSI.

Wireless sensing is a crucial technology for building smart cities, playing a vital role in applications such as human monitoring, route planning, and traffic management. Analyzing the data provided by wireless sensing enables the formulation of more scientific decisions. The wireless sensing of dynamic events is a significant branch of wireless sensing. Sensing the specific times and durations of dynamic events is a challenging problem due to the dynamic event information is concealed within static environments. To effectively sense the relevant information of event occurrence, we propose a wireless sensing method for dynamic events based on RSSI, named RSSI-WSDE. RSSI-WSDE utilizes variable-length sliding windows and statistical methods to process original RSSI time series, amplifying the differences between dynamic events and static environments. Subsequently, z-score normalization is employed to enhance the comparability of the sensing effects for different dynamic events. Furthermore, by setting the adaptive threshold, the occurrence of dynamic event is sensed and the relevant information is marked on the original RSSI time series. In this study, the sensing performance of RSSI-WSDE was tested in indoor corridors and outdoor urban road environments. The wireless sensing of dynamic events, including walking, running, cycling, and driving, was conducted. The experimental results demonstrate that RSSI-WSDE can accurately sense the occurrence of dynamic events, marking the specific time and duration with millisecond-level precision. Moreover, RSSI-WSDE exhibits robust performance in wireless sensing of dynamic events in both indoor and outdoor environments.

Effect of Raloxifene Treatment on Apolipoproteins and Lipoprotein(a) Concentrations in Postmenopausal Women: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND AND AIM: Although various randomized controlled trials (RCTs) have evaluated the effect of raloxifene on apolipoproteins and lipoprotein(a) concentrations in postmenopausal women, the results have been inconsistent and inconclusive. Therefore, we conducted this meta-analysis of RCTs to investigate the effect of raloxifene administration on apolipoproteins and lipoprotein(a) [Lp(a)] concentrations in postmenopausal women. METHODS: Two independent researchers systematically searched the scientific literature (including PubMed/Medline, Scopus, Web of Science, and EMBASE) for English-language randomized controlled trials (RCTs) published up to June 2024. We included RCTs reporting the impact of raloxifene on apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB), and Lp(a) levels in postmenopausal women. The primary outcome of interest was change in Lp(a), and the secondary outcomes were changes in ApoA-I and ApoB. FINDINGS: The present meta-analysis incorporated 12 publications with 14 RCT arms. The comprehensive outcomes derived from the random-effects model revealed a statistically significant increase in ApoA-I (WMD: 6.06 mg/dL, 95% CI: 4.38, 7.75, P < 0.001) and decrease in ApoB concentrations (WMD: -8.48 mg/dL, 95% CI: -10.60, -6.36, P < 0.001) and Lp(a) (WMD: -3.02 mg/dL, 95% CI: -4.83, -1.21, P < 0.001) following the administration of raloxifene in postmenopausal women. In the subgroup analyses, the increase in ApoA-I and the decrease in ApoB and Lp(a) levels were greater in RCTs with a mean participant age of ≥60 years and a duration of ≤12 weeks. IMPLICATIONS: The current meta-analysis of RCTs demonstrates that treatment with raloxifene reduces ApoB and Lp(a) levels while increasing ApoA-I levels in postmenopausal women. Since these effects on lipid components are associated with a reduced risk of cardiovascular disease (CVD), raloxifene could be a suitable therapy for postmenopausal women who are at an increased risk of CVD and have other medical indications for raloxifene administration.

Contrasting Multi-Source Temporal Knowledge Graphs for Biomedical Hypothesis Generation.

Hypothesis Generation (HG) aims to expedite biomedical researches by generating novel hypotheses from existing scientific literature. Most existing studies focused on modeling static snapshots of the corpus, neglecting the temporal evolution of scientific terms. Despite recent efforts to learn term evolution from Knowledge Bases (KBs) for HG, the temporal information from multi-source KBs is still overlooked, which contains important, up-to-date knowledge. In this paper, an innovative Temporal Contrastive Learning (TCL) framework is introduced to uncover latent associations between entities by jointly modeling their co-evolution across multi-source temporal KBs. Specifically, we first construct a temporal relation graph based on PubMed papers and a biomedical relation database (such as Comparative Toxicogenomics Database (CTD)). Then the constructed temporal relation graph and a temporal concept graph (such as Medical Subject Headings (MeSH)) are used to train two GCN-based recurrent networks for learning the entity temporal evolutional embeddings, respectively. Finally, a cross-view temporal prediction task is designed for learning knowledge enriched temporal embeddings by contrasting the temporal embeddings learned from the two Temporal Knowledge Graphs (TKGs). Findings from experiments conducted on three real-world biomedical term relationship datasets demonstrate that the proposed approach is clearly superior to approaches based on single TKG, achieving the state-of-the-art performance.