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Min Gao,1,2,* Wenhua Sang,1,3,4,* Kun Mi,1,3,4 Jiancong Liu,1,3,4 Yudong Liu,1,3,4 Wenge Zhen,1,3,4 Bang An2 1Department of Affective Disorders II, Hebei Provincial Mental Health Center, Baoding, People’s Republic of China; 2Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China; 3Hebei Key Laboratory of Major Mental and Behavioral Disorders, Baoding, People’s Republic of China; 4The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wenhua Sang, Department of Affective Disorders II, Hebei Provincial Mental Health Center, Hebei Key Laboratory of Major Mental and Behavioral Disorders, The Sixth Clinical Medical College of Hebei University, Baoding, People’s Republic of China, Email whsang997169@163.com Bang An, Xianyang Central Hospital, Xianyang Mental Health Center, Xianyang, People’s Republic of China, Email xyanbang@163.comObjective: Only about one-third of depressed patients respond to initial antidepressant treatment. Therefore, it is crucial to find effective predictors of antidepressants. The purpose of our study was to learn the relationship between EEG theta power, theta asymmetry, and the efficacy of escitalopram.Methods: The study included 34 patients with depression. Before and after each patient’s course of treatment, EEG data was gathered. Both the Hamilton Anxiety Scale (HAMA) and the 17-item Hamilton Depression Scale (HAMD-17) were evaluated simultaneously. The natural logarithm of right frontal theta power minus left frontal theta power was used to calculate inter-electrode theta asymmetry (AT).Results: First, our study found no statistically significant difference between intra-electrode theta power and inter-electrode AT before and after treatment (P ≥ 0.05). When we later looked at the data regarding treatment effects, the findings revealed that patients (n = 9) who did not respond to treatment had lower baseline theta power at C4 [6.190 (2.000, 12.990) vs 15.800 (7.255, 22.330), z = − 2.166, P = 0.030]. The two groups had no difference in other electrodes (P ≥ 0.05). The AT of C3/C4 in non-responders (n = 9) was lower [0.012 (0.795) vs 0.733 (0.539), t = − 3.224, P = 0.005]. However, there was no difference in inter-electrode AT between the two groups in F3/F4 and F7/F8 (P ≥ 0.05). We finally show that the theta power at C4 was negatively correlated with HAMD scores before treatment (r = − 0.346, P = 0.045).Conclusion: Our findings determined that increased theta power and positive asymmetry in the right frontal-central area correlate with favourable escitalopram treatment, providing a basis for finding predictive markers for antidepressants.Keywords: depression, EEG, theta power, theta asymmetry, treatment effect

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Proteoglycans are glycosylated proteins that play a number of structural and signalling functions. Here, Corti, Wang et al. show that the N-terminal sequence of proteoglycan Syndecan-2 selectively increases 6-O sulfation of its heparan sulfate chains, and that this promotes formation of a ternary Sdc2/VEGFA/VEGFR2 complex leading to increased angiogenesis.

Abstract Fasting plasma lactate concentrations are elevated in individuals with metabolic disease. The aim of this study was to determine if the variance in fasting lactate concentrations were associated with factors linked with cardiometabolic health even in a young, lean cohort. Young (age 22 ± 0.5; N = 30) lean (BMI (22.4 ± 0.4 kg/m2) women were assessed for waist‐to‐hip ratio, aerobic capacity (VO2peak), skeletal muscle oxidative capacity (near infrared spectroscopy; fat oxidation from muscle biopsies), and fasting glucose and insulin (HOMA‐IR). Subjects had a mean fasting lactate of 0.9 ± 0.1 mmol/L. The rate of deoxygenation of hemoglobin/myoglobin (R2 = .23, p = .03) in resting muscle and skeletal muscle homogenate fatty acid oxidation (R2 = .72, p = .004) were inversely associated with fasting lactate. Likewise, cardiorespiratory fitness (time to exhaustion during the VO2peak test) was inversely associated with lactate (R2 = .20, p = .05). Lactate concentration was inversely correlated with HDL:LDL (R2 = .57, p = .02) and positively correlated with the waist to hip ratio (R2 = .52, p = .02). Plasma lactate was associated with various indices of cardiometabolic health. Thus, early determination of fasting lactate concentration could become a common biomarker used for identifying individuals at early risk for metabolic diseases.

VEGFR2 is a central regulator of angiogenesis. Here Zhou et al. report that SUMOylation of VEGFR2 regulates its subcellular localisation and activity, and that endothelial-specific knockout of the SUMO endopeptidase SENP1 protects against VEGFR2-mediated pathological angiogenesis.

Hyperoxia contributes to lung injury in bronchopulmonary dysplasia. The authors show that hyperoxia increases miR-34a expression in human neonates and in mouse models, and that pathology is ameliorated by miR-34a inhibition or by administration of its target angiopoietin-1

BackgroundFibronectin in endothelial basement membranes promotes endothelial inflammatory activation and atherosclerosis but also promotes plaque stability and vascular remodeling. The fibronectin receptor α5 subunit is proinflammatory through binding to and activating phosphodiesterase 4D5, which inhibits anti‐inflammatory cyclic adenosine monophosphate and protein kinase A. Replacing the α5 cytoplasmic domain with that of α2 resulted in smaller atherosclerotic plaques. Here, we further assessed plaque phenotype and compensatory vascular remodeling in this model. Methods and Resultsα5/2 mice in the hyperlipidemic apolipoprotein E null background had smaller plaques in the aortic root, with reduced endothelial NF‐κB activation and inflammatory gene expression, reduced leukocyte content, and much lower metalloproteinase expression. However, smooth muscle cell content, fibrous cap thickness, and fibrillar collagen were unchanged, indicating no shift toward vulnerability. In vivo knockdown of phosphodiesterase 4D5 also decreased endothelial inflammatory activation and atherosclerotic plaque size. α5/2 mice showed improved recovery from hindlimb ischemia after femoral artery ligation. ConclusionsBlocking the fibronectin‐Integrin α5 pathway reduces atherosclerotic plaque size, maintains plaque stability, and improves compensatory remodeling. This pathway is therefore a potential therapeutic target for treatment of atherosclerosis.

Abstract Angiogenic growth factors have recently been linked to tissue metabolism. We have used genetic gain‐ and loss‐of function models to elucidate the effects and mechanisms of action of vascular endothelial growth factor‐B (VEGF‐B) in the heart. A cardiomyocyte‐specific VEGF‐B transgene induced an expanded coronary arterial tree and reprogramming of cardiomyocyte metabolism. This was associated with protection against myocardial infarction and preservation of mitochondrial complex I function upon ischemia‐reperfusion. VEGF‐B increased VEGF signals via VEGF receptor‐2 to activate Erk1/2, which resulted in vascular growth. Akt and mTORC1 pathways were upregulated and AMPK downregulated, readjusting cardiomyocyte metabolic pathways to favor glucose oxidation and macromolecular biosynthesis. However, contrasting with a previous theory, there was no difference in fatty acid uptake by the heart between the VEGF‐B transgenic, gene‐targeted or wildtype rats. Importantly, we also show that VEGF‐B expression is reduced in human heart disease. Our data indicate that VEGF‐B could be used to increase the coronary vasculature and to reprogram myocardial metabolism to improve cardiac function in ischemic heart disease.

The original version of this Article contained errors in Figures 1, 3 and 4. In panels b and d of Figure 1, the labels ‘Sdc4-/-’ were inadvertently replaced by ‘Sdc4+/+‘. In panels c and d of Figure 3, the labels ‘Sdc4-/-’ were replaced by ‘Sdc2-/-’. In panel f of Figure 3, the labels ‘FGF2’ were replaced by ‘VEGFA165’. In panel e of Figure 6, a ‘Sdc2-/-‘ label was inadvertently included. This has now been corrected in the PDF and HTML versions of the Article.

The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (

BackgroundCOVID-19 convalescent plasma (CCP), from donors recovered from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection, is one of the limited therapeutic options currently available for the treatment of critically ill patients with COVID-19. There is growing evidence that CCP may reduce viral loads and disease severity; and reduce mortality. However, concerns about the risk of transfusion-transmitted infections (TTI) and other complications associated with transfusion of plasma, remain. Amotosalen/UVA pathogen reduction treatment (A/UVA-PRT) of plasma offers a mitigation of TTI risk, and when combined with pooling has the potential to increase the diversity of the polyclonal SARS-CoV-2 neutralizing antibodies.Study design and methodsThis study assessed the impact of A/UVA-PRT on SARS-CoV-2 antibodies in 42 CCP using multiple complimentary assays including antigen binding, neutralizing, and epitope microarrays. Other mediators of CCP efficacy were also assessed.ResultsA/UVA-PRT did not negatively impact antibodies to SARS-CoV-2 and other viral epitopes, had no impact on neutralizing activity or other potential mediators of CCP efficacy. Finally, immune cross-reactivity with other coronavirus antigens was observed raising the potential for neutralizing activity against other emergent coronaviruses.ConclusionThe findings of this study support the selection of effective CCP combined with the use of A/UVA-PRT in the production of CCP for patients with COVID-19.

Titanium alloys have promising potential for applications in marine nuclear power systems owing to their exceptional mechanical and corrosion properties. Nevertheless, their radiation resistivity is a determining factor for their extensive use as structural materials in nuclear energy systems. In this study, the radiation resistivity of Ti–5Al–3V–3Zr–Cr (Ti-5331) alloys with three different microstructures was examined using a combination of characterization techniques including positron annihilation Doppler broadening spectroscopy (DBS), Elastic Recoil Detection Analysis (ERDA), Transmission Electron Microscope (TEM), Small-Angle X-ray scattering (SAXS) and nanoindentation. The results reveal that the equiaxed structure, bimodal structure, and Widmanstatten structure of Ti-5331 alloy obtained through different annealing processes exhibit differences in the number of interfaces and the content of the β phase. The α/β interfaces can significantly enhance the radiation resistance of titanium alloys by inhibiting the diffusion of helium atoms after helium ion irradiation. Notably, the alloy with a bimodal structure exhibited the best overall radiation resistivity, showing small defect size, low hardening effect, and low swelling rate of 0.003%. Moreover, the size of helium bubbles of the bimodal structure is half of that in the equiaxed structure and Widmanstatten structure. Thus, the bimodal structure of the Ti-5331 alloy possesses superior radiation resistivity.

Abstract Background When compared to open surgery, laparoscopic common bile duct exploration (LCBDE) is known to cause less discomfort and a faster recovery. This study examines the effect of the Enhanced Recovery After Surgery (ERAS) strategy on LCBDE outcomes. Methods In March 2021 to May 2024, 400 patients with LCBDE participated in randomized research. The six patient groups were: Multimodal Pain Management (n = 50), Standard Pain Management (n = 50), ERAS (n = 50), Preoperative Assessment (n = 100), Standard Preoperative Assessment (n = 100), and Standard Care (n = 50). The patient’s satisfaction, long-term recovery, pain, anxiety, and complication rates were among the outcomes that were measured. Results After the intervention, the mean anxiety level of the ERAS group was significantly lower (P

Abstract Anther development involves a series of important biological events that are precisely regulated by many genes. Although several important genes involved in rice anther development have been identified, the regulatory network involved in tapetal development and pollen wall formation is still largely unclear. PERSISTENT TAPETAL CELL 1 (PTC1) encodes a PHD-Finger protein, which plays a critical role in the regulation of tapetal cell death and pollen development in rice. Here, we report the isolation and characterization of a new allele ptc1-2 with 2-base deletion in the third exon, causing the absent of the PHD domain due to the sequence change. Cytological analysis revealed delayed tapetal PCD, defective pollen exine formation and abnormal ubisch bodies development. Transcriptome analysis revealed that genes related to pollen wall formation (secondary metabolism, phenylalanine synthesis, and cutin and wax biosynthesis pathways), cell death (cysteine and methionine metabolism and DNA repair pathways), and carbohydrate synthesis (starch and sucrose metabolism pathways) were significantly altered in ptc1-2 mutant. A total of 13 reported anther development genes exhibited significant expression changes in the ptc1-2 mutant. Yeast two-hybrid and BiFC analyses showed that PTC1 could interact with API5, an inhibitor of apoptosis, and the citrin-binding enzyme EDT1. This work is helpful in deepening the understanding of the regulatory network of male reproductive development in rice.

Abstract Aim Explore the effects of mitochondrial transplantation (MT) after cardiopulmonary resuscitation (CPR) on the polarization of microglia/macrophages (MG/MΦ) and neurological function. Methods Seventy-five Sprague-Dawley rats were randomly divided into five groups: sham, normal saline (NS), vehicle, mitochondria (Mito), and non-functional mitochondria (N-Mito) group. Rats in sham group underwent surgical procedures without cardiac arrest, while the other four groups underwent cardiac arrest and CPR, and then received NS, respiration buffer, mitochondrial suspension or non-functional mitochondria, immediately after the restoration of spontaneous circulation (ROSC). The number of mitochondria in the hippocampus, the morphology and structure of mitochondria in MG/MΦ, the phenotype of MG/MΦ, and hippocampal tissue injury, neuroinflammation, and neuronal apoptosis were detected on days 1 and 3 after ROSC. Neurodeficit score (NDS) was performed on days 1, 3, 7, 15 and 30 after ROSC. Results Compared with other groups, the number of mitochondria in the hippocampus was increased, and the morphology and structure of mitochondria in MG/MΦ were significantly improved in the Mito group. Our results show higher expression of M2-type markers in MG/MΦ and decreased hippocampal tissue damage in the Mito group. Levels of NSE and S100β in serum, and TNF-α, IL-6 in the hippocampus were decreased, while the levels of TGF-β and IL-10 were increased in the Mito group. Apoptosis rate of neurons in the Mito group was decreased and the NDS of the Mito group was higher than the other groups. Conclusions Exogenous MT can improve neurological function after CPR by promoting the polarization of MG/MΦ to M2-type cells, and this could be a potential method for brain protection after CPR.

Abstract This study explores the relationship between surface roughness and characteristic scale through theoretical analyses and experimental data. Considering the concavity and convexity of cycloidal gear tooth profile curvatures, a curved surface contact coefficient model suitable for both inner and outer contacts, with either equal or unequal curvatures, has been developed. Moreover, a fractal contact model is constructed for cycloidal pinwheels. This model considers scale correlation and analyzes the influence of microscopic parameters on the elastic-plastic critical grade and the behavior of the contact area. Additionally, the influence of the micro-convex body frequency index on surface contact performance is explored to provide theoretical insights for improving the elastic contact ratio and reducing wear on contact surfaces.

Abstract Background Assessing the methodological quality of case reports and case series is challenging due to human judgment variability and time constraints. We evaluated the agreement in judgments between human reviewers and GPT-4 when applying a standard methodological quality assessment tool designed for case reports and series. Methods We searched Scopus for systematic reviews published in 2023–2024 that cited the appraisal tool by Murad et al. A GPT-4 based agent was developed to assess the methodological quality using the 8 signaling questions of the tool. Observed agreement and agreement coefficient were estimated comparing published judgments of human reviewers to GPT-4 assessment. Results We included 797 case reports and series. The observed agreement ranged between 41.91% and 80.93% across the eight questions (agreement coefficient ranged from 25.39 to 79.72%). The lowest agreement was noted in the first signaling question about selection of cases. The agreement was similar in articles published in journals with impact factor

Abstract Electrocatalysts are extensively employed to suppress the shuttling effect in lithium-sulfur (Li-S) batteries. However, it remains challenging to probe the sulfur redox reactions and mechanism at the electrocatalyst/LiPS interface after the active sites are covered by the solid discharge products Li2S/Li2S2. Here, we demonstrate the intrinsic autocatalytic activity of the Li2S (100) plane towards lithium polysulfides on single-atom nickel (SANi) electrocatalysts. Guided by theoretical models and experimental data, it is concluded that LiPS dissociates into Li2S2 and short-chain LiPS on the Li2S (100) plane. Subsequently, Li2S2 undergoes further lithiation to Li2S on the Li2S (100) surface, generating a new Li2S (100) layer, thus enabling the autocatalytic formation of a new Li2S (100) surface. Benefiting from the autocatalytic growth of Li2S, the concentration of LiPS in the electrolyte remains at a lower level, enabling Li-S batteries under high loading and low electrolyte conditions to exhibit superior electrochemical performance.

Abstract Background Colorectal cancer (CRC) is the most common gastrointestinal malignancy worldwide, with obesity-induced lipid metabolism disorders playing a crucial role in its progression. A complex connection exists between gut microbiota and the development of intestinal tumors through the microbiota metabolite pathway. Metabolic disorders frequently alter the gut microbiome, impairing immune and cellular functions and hastening cancer progression. Methods This study thoroughly examined the gut microbiota through 16S rRNA sequencing of fecal samples from 181 CRC patients, integrating preoperative Low-density lipoprotein cholesterol (LDL-C) levels and RNA sequencing data. The study includes a comparison of microbial diversity, differential microbiological analysis, exploration of the associations between microbiota, tumor microenvironment immune cells, and immune genes, enrichment analysis of potential biological functions of microbe-related host genes, and the prediction of LDL-C status through microorganisms. Results The analysis revealed that differences in α and β diversity indices of intestinal microbiota in CRC patients were not statistically significant across different LDL-C metabolic states. Patients exhibited varying LDL-C metabolic conditions, leading to a bifurcation of their gut microbiota into two distinct clusters. Patients with LDL-C metabolic irregularities had higher concentrations of twelve gut microbiota, which were linked to various immune cells and immune-related genes, influencing tumor immunity. Under normal LDL-C metabolic conditions, the protective microorganism Anaerostipes_caccae was significantly negatively correlated with the GO Biological Process pathway involved in the negative regulation of the unfolded protein response in the endoplasmic reticulum. Both XGBoost and MLP models, developed using differential gut microbiota, could forecast LDL-C levels in CRC patients biologically. Conclusions The intestinal microbiota in CRC patients influences the LDL-C metabolic status. With elevated LDL-C levels, gut microbiota can regulate the function of immune cells and gene expression within the tumor microenvironment, affecting cancer-related pathways and promoting CRC progression. LDL-C and its associated gut microbiota could provide non-invasive markers for clinical evaluation and treatment of CRC patients.

High-repetition-rate free-electron lasers impose stringent requirements on the thermal deformation of beamline optics. The Shanghai HIgh-repetition-rate XFEL aNd Extreme light facility (SHINE) experiences high average thermal power and demands wavefront preservation. To deeply study the thermal field of the first reflection mirror M1 at the FEL-II beamline of SHINE, thermal analysis under a photon energy of 400 eV was executed by fluid and solid heat transfer method. According to the thermal analysis results and the reference cooling water temperature of 30 °C, the temperature of the cooling water at the flow outlet is raised by 0.15 °C, and the wall temperature of the cooling tube increases by a maximum of 0.5 °C. The maximum temperature position of the footprint centerline in the meridian direction deviates away from the central position, and this asymmetrical temperature distribution will directly affect the thermal deformation of the mirror and indirectly affect the focus spot of the beam at the sample.

Abstract In multiple physical fields, the mutual influence among these fields can significantly impact material elastoplasticity. This paper proposes a thermodynamic-based constitutive model that incorporates the mutual influence of multiple physical fields. Rather than treating physical field characteristics as adjustable “parameters” affecting material coefficients, the proposed model employs a thermodynamic dissipation potential derived from the Onsager reciprocity relations, accounting for thermodynamic forces coupling. This dissipation potential ensures that the thermodynamic flow in the stress field is influenced by both stress field and other physical fields thermodynamic forces, which describes the plastic flow under multiple physical fields, while preserving thermodynamic duality. The paper begins with the formulation of a generalized thermodynamic model applicable to diverse materials and types of coupled fields, which is then degraded to a specific model for AA5182-O AlMg alloy under the influence of temperature and strain rate fields coupling. Given the universal applicability of the generalized model, such degradation provides a structured approach framework for developing thermodynamics-based constitutive models. For different materials encountered in practical engineering, new thermodynamic forces can be introduced to describe their unique mechanical properties while preserving the overarching thermodynamics-based model framework, thereby facilitating model scalability. The paper concludes with a validation example, showing that within the Portevin-Le Chatelie (PLC) regime, the plastic flow stress of AA5182-O AlMg alloy decreases with increasing strain rate at low temperatures but increases at high temperatures. The accurate simulation of these distinct strain rate effects crucially relies on integrating the mutual influence of temperature field and strain rate field.

Abstract Background The current practice in guideline development is to use the control group event rate (CR) as a surrogate of baseline risk and to assume portability of the relative treatment effect across populations with low, moderate and high baseline risk. We sought to emulate this practice in a very large sample of meta-analyses. Methods We retrieved data from all meta-analyses published in the Cochrane Database of Systematic Reviews (2003–2020) that evaluated a binary outcome, reported 2 × 2 data for each individual study and included at least 4 studies. We excluded studies with no events. We conducted meta-analyses with odds ratios and relative risks and performed subgroup analyses based on tertiles of CR. In sensitivity analyses, we evaluated the use of total event rate (TR) instead of CR and using quartiles instead of tertiles. Results The analysis included 2,531 systematic reviews (27,692 meta-analyses, 226,975 studies, 25,669,783 patients).The percentages of meta-analyses with statistically significant interaction (P

Very low frequency(VLF) electromagnetic wave provides a reliable method for cross-medium communication in polar sea environments due to its ability to penetrate seawater. In order to solve the problem of polar VLF electromagnetic wave propagation across the ice layer, a multilayer dielectric propagation model based on the transmission matrix was established in this paper. The attenuation characteristics of VLF electromagnetic waves in air-ice layer-seawater and the influence of incident angle were studied by using the two-port network equivalent circuit method. Through simulation and field experiment data, the attenuation law of VLF electromagnetic wave field intensity in the ice layer was quantified for the first time, revealing the important discovery that the attenuation of VLF electromagnetic wave field intensity in the ice layer was less than 1 dB per meter. The effect of sea ice on VLF communication in polar regions was evaluated. The results show that sea ice had less loss on VLF electromagnetic waves and was not the main factor affecting VLF communication.

Abstract Introduction Noninvasive ventilation (NIV) is widely used for sequential extubation in patients with chronic obstructive pulmonary disease (COPD). However, NIV may cause many adverse events such as claustrophobia, facial skin compression, air leakage, bloating, and even reflux aspiration, resulting in poor patient compliance/tolerance and high failure rate, especially for older adults who are at high risk of communication difficulties and consciousness disorder. High-flow nasal cannula (HFNC) oxygen therapy is a new alternative support to NIV, but whether it can effectively reduce the rate of re-intubation after extubation in elderly patients with COPD remains controversial. The purpose of this study is to explore the safety and efficacy of HFNC versus NIV for elderly COPD patients after extubation. Methods and analysis This study is an investigator-initiated, single-center, prospective, non-inferior, randomized controlled trial. Elderly patients (age > 65 years) who have received invasive ventilation and was diagnosed with COPD will be randomly assigned to HFNC group or NIV group immediately after extubation with a planned enrollment of 168 patients. The primary outcomes will be reintubation rates at 72 h and 7 days after extubation. Secondary outcomes will include treatment failure, post-extubation vital signs and arterial blood gases, the scores of compliance and comfort of patients, duration of respiratory support after extubation, respiratory support related adverse events, sleep quality scores, usage of sedative and analgesic drugs after extubation, and the incidence of delirium. Additionally, clinical outcomes such as ventilator-free days at 28 days post-randomization, tracheotomy rate, duration of intensive care unit (ICU) and hospital stay, ICU and hospital mortality will be evaluated. Ethics and dissemination This study has been approved by the Ethics Committee of West China Hospital of Sichuan University (2023–2284). Informed consent is required. It is expected that a follow-up randomized controlled trial will be conducted. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences. Trial registration The study was retrospectively registered at ClinicalTrials.gov (ChiCTR2400087312).

Abstract Background Elucidating the dynamics of gene expression across developmental stages, including the genomic characteristics of brain expression during infancy, is pivotal in deciphering human psychiatric and neurological disorders and providing insights into developmental disorders. Results Leveraging comprehensive human GWAS associations with temporal and spatial brain expression data, we discovered a distinctive co-expression cluster comprising 897 genes highly expressed specifically during infancy, enriched in functions related to the neuronal system. This gene cluster notably harbors the highest ratio of genes linked to psychiatric and neurological disorders. Through computational analysis, MYT1L emerged as a potential central transcription factor governing these genes. Remarkably, the infancy-specific expressed genes, including SYT1, exhibit prominent colocalization within human accelerated regions. Additionally, chromatin state analysis unveiled prevalent epigenetic markers associated with enhancer-specific modifications. In addition, this cluster of genes has demonstrated to be specifically highly expressed in cell-types including excitatory neurons, medial ganglionic eminence and caudal ganglionic eminence. Conclusions This study comprehensively characterizes the genomics and epigenomics of genes specifically expressed during infancy, identifying crucial hub genes and transcription factors. These findings offer valuable insights into early detection strategies and interventions for psychiatric and neurological disorders.

Abstract Background Obesity in humans can lead to chronic diseases such as diabetes and cardiovascular disease. Similarly, subcutaneous fat (SCF) in pigs affects feed utilization, and excessive SCF can reduce the feed efficiency of pigs. Therefore, identifying factors that suppress fat deposition is particularly important. Numerous studies have implicated the gut microbiome in pigs’ fat deposition, but research into its suppression remains scarce. The Lulai black pig (LL) is a hybrid breed derived from the Laiwu pig (LW) and the Yorkshire pig, with lower levels of SCF compared to the LW. In this study, we focused on these breeds to identify microbiota that regulate fat deposition. The key questions were: Which microbial populations reduce fat in LL pigs compared to LW pigs, and what is the underlying regulatory mechanism? Results In this study, we identified four different microbial strains, Eubacterium siraeum, Treponema bryantii, Clostridium sp. CAG:413, and Jeotgalibaca dankookensis, prevalent in both LW and LL pigs. Blood metabolome analysis revealed 49 differential metabolites, including tanshinone IIA and royal jelly acid, known for their anti-adipogenic properties. E. siraeum was strongly correlated with these metabolites, and its genes and metabolites were enriched in pathways linked to fatty acid degradation, glycerophospholipid, and glycerolipid metabolism. In vivo mouse experiments confirmed that E. siraeum metabolites curb weight gain, reduce SCF adipocyte size, increase the number of brown adipocytes, and regulate leptin, IL-6, and insulin secretion. Finally, we found that one important pathway through which E. siraeum inhibits fat deposition is by suppressing the phosphorylation of key proteins in the PI3K/AKT signaling pathway through the reduction of tyrosine. Conclusions We compared LW and LL pigs using fecal metagenomics, metabolomics, and blood metabolomics, identifying E. siraeum as a strain linked to fat deposition. Oral administration experiments in mice demonstrated that E. siraeum effectively inhibits fat accumulation, primarily through the suppression of the PI3K/AKT signaling pathway, a critical regulator of lipid metabolism. These findings provide a valuable theoretical basis for improving pork quality and offer insights relevant to the study of human obesity and related chronic metabolic diseases. Video Abstract

Abstract Chimeric Antigen Receptor T (CAR-T) cell therapy has significantly advanced in treating B-cell acute lymphoblastic leukemia (B-ALL) and has shown efficacy in managing relapsed B-ALL after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Donor-derived CAR-T cell offer both high efficacy and rapid response. Although promising results exist, current research lacks definitive evidence of long-term survival benefits for patients treated with donor-derived CAR-T therapy. We report the long-term survival of 32 patients with post-transplant relapsed B-ALL treated with donor-derived CD19 CAR-T cell, achieving either complete Remission (CR) or CR with incomplete peripheral blood recovery (CRi). The median follow-up was 42 months, with 2-year overall survival (OS) and event-free survival (EFS) rates of 56.25% and 50.0%, respectively. The 5-year OS and EFS rates were 53.13% and 46.88%, with no new long-term adverse events observed. These findings demonstrate good long-term safety, supporting donor-derived CAR-T cell as a recommended treatment option for relapsed B-ALL patients post-transplantation. Trial registration: https://www.chictr.org.cn/showproj.html?proj=14315 . Registration number: ChiCTR-OOC-16008447.

Abstract Observational studies and clinical trials have suggested the relationship between the gut microbiome and respiratory diseases, but the causality between them remains unclear. Firstly, we selected eight respiratory diseases Genome-wide association study (GWAS) datasets mainly from the FinnGen collaboration as outcomes. The exposure was based on GWAS statistics about the gut microbiome, sourced from the MiBioGen consortium, including gut microbial taxa. The causal link between the gut microbiome and respiratory illnesses was then estimated using a Two-sample Mendelian randomization (MR) analysis, including the inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode. To ensure reliability, F-statistics and sensitivity tests were conducted. Furthermore, we performed a reverse MR analysis of the pre-Mendelian positive findings to possible reverse causality. For the 196 gut microbe taxa, the IVW analysis suggested 88 potential associations with eight clinically prevalent respiratory diseases. Among them, 30 causal associations were found in more than one MR method. Multiple statistical corrections have confirmed three causal associations: genus Holdemanella was a risk factor for chronic obstructive pulmonary disease (COPD) (P = 1.3 × 10−4, OR = 1.18), family FamilyXIII was a protective factor for COPD (P = 1.3 × 10−3, OR = 0.75), and genus Oxalobacter was a risk factor for asthma (P = 2.1 × 10−4, OR = 1.09). Our MR analysis results indicate that there would be a causal relationship between the gut microbiome and respiratory diseases, contributing to the gut-lung axis. This finding offers new insights into the gut microbiome’s roles in respiratory diseases’ clinical prevention, pathogenesis, and improvement of clinical symptoms. Further randomized controlled trials are necessary to clarify the protective effect of probiotics and fecal microbial transplantation on respiratory health.

Abstract Recent advancements of quantum technologies have triggered tremendous interest in exploring practical quantum advantage. The simulation of fluid dynamics, a highly challenging problem in classical physics but vital for practical applications, emerges as a potential direction. Here, we report an experiment on the digital simulation of unsteady flows with a superconducting quantum processor. The quantum algorithm is based on the Hamiltonian simulation using the hydrodynamic formulation of the Schrödinger equation. With the median fidelities of 99.97% and 99.67% for parallel single- and two-qubit gates respectively, we simulate the dynamics of a two-dimensional (2D) compressible diverging flow and a 2D decaying vortex with ten qubits. Note that the former case is an inviscid potential flow, and the latter one is an artificial vortical flow with an external body force. The experimental results well capture the temporal evolution of averaged density and momentum profiles, and qualitatively reproduce spatial flow fields with moderate noises. This work demonstrates the potential of quantum computing in simulating more complex flows, such as turbulence, for practical applications.