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The immersive experience and diverse interaction modes provided by virtual digital technology match the spatial sensitivity and practical ability required in the field of architectural teaching, and its technological advantages can significantly enhance teaching outcomes. However, in the field of architecture teaching, there has been a lack of discussion on the suitability of different virtual technologies and teaching scenarios for historical buildings. Therefore, this study constructed a comprehensive adaptive evaluation system for virtual technology and selected 360-degree panoramic technology (360-degree PT), Immersive Virtual Reality (IVR) technology, and Desktop Virtual Reality (DVR) technology as representatives for empirical study. The research method used in this experiment is a questionnaire survey, involving a total of 60 students majoring in architecture and planning, with a certain foundation in historical architecture knowledge. Multiple statistical methods are employed to analyze the data. The experimental data indicates that IVR technology performs the best in terms of learning outcomes, learning autonomy, and sense of presence, making it suitable for immersive and interactive learning needs. 360-degree PT demonstrates the best perception of architectural features, catering to the demand for visual effects. DVR technology exhibits the highest learning efficiency, meeting the need for simplicity, efficiency, and widespread application. On the other hand, augmented reality (AR) technology and mixed reality (MR) technology have lower adaptability and do not meet the learning requirements for immersive spatial experiences. This study is expected to provide a new technical pathway for teaching historical buildings and serve as a systematic reference for selecting specific technologies.

Abstract Objective To explore the differences in the effectiveness of various teaching methods combining online and offline modes in paediatric medical education. Methods Fourth-year medical paediatric students at our university in 2020 were randomly divided into three groups: a control group, experimental group 1, and experimental group 2, with 30 students in each group. The control group received traditional teaching, experimental group 1 received a combination of online and offline teaching using two methods simultaneously, and experimental group 2, in addition to the methods used in experimental group 1, engaged in real-case teaching in the ward. The teaching outcomes were evaluated through theoretical exams, clinical skills assessments, and questionnaires. Results Experimental groups 1 and 2 were superior to the control group concerning theoretical examination and overall scores (P

Abstract Optical aberrations hinder fluorescence microscopy of thick samples, reducing image signal, contrast, and resolution. Here we introduce a deep learning-based strategy for aberration compensation, improving image quality without slowing image acquisition, applying additional dose, or introducing more optics. Our method (i) introduces synthetic aberrations to images acquired on the shallow side of image stacks, making them resemble those acquired deeper into the volume and (ii) trains neural networks to reverse the effect of these aberrations. We use simulations and experiments to show that applying the trained ‘de-aberration’ networks outperforms alternative methods, providing restoration on par with adaptive optics techniques; and subsequently apply the networks to diverse datasets captured with confocal, light-sheet, multi-photon, and super-resolution microscopy. In all cases, the improved quality of the restored data facilitates qualitative image inspection and improves downstream image quantitation, including orientational analysis of blood vessels in mouse tissue and improved membrane and nuclear segmentation in C. elegans embryos.

Abstract Background Cardiovascular disease carries the highest mortality rate among diseases, and pharmacological interventions have limited efficacy. Baicalin (Bai) promotes biological metabolic processes, eliminates oxygen free radicals, and is anti-inflammatory. This study aimed to investigate the effect of Bai on the cardiac injury model induced by isoproterenol in mice. Methods and Result In this study, all groups except the control received intraperitoneal injections of isoproterenol (ISO) to induce a cardiac injury model, with the drug administered continuously for 14 days. hematoxylin and eosin staining and Masson’s trichrome staining revealed that Bai significantly mitigated ISO-induced pathological changes in mouse heart tissue and alleviated myocardial hypertrophy. Echocardiography assessments demonstrated that Bai preserved cardiac function in ISO-treated mice. Furthermore, our findings indicated that Bai activated the Nrf2 signaling pathway in vivo and in vitro. To delve deeper, mice were further treated with ML385 (ML) via intraperitoneal injection to inhibit the Nrf2 pathway. Results showed that ML385 blocked the cardioprotective effects of Bai in mouse heart tissue. Conclusion Bai protects against ISO-induced cardiac injury, and its mechanism is related to activating the Nrf2/HO-1 signaling pathway to regulate cardiac ferroptosis and improve cardiac remodeling.

Laser power bed fusion (LPBF) as a widely used laser additive manufacturing, which has demonstrated a promising capability in the simultaneous formation of high-performance composites with unique microstructure. In order to further meet the urgent needs of aerospace sophisticated equipment, this work investigated the laser additive manufacturing of CrFeNb particles reinforced Ni-based superalloy composites with grain refinement and superior performance. A few CrFeNb particles were added to IN718 superalloy powder. The CrFeNb particles as a center of heterogeneous nucleation effectively facilitated to produce fine equiaxed grains and did not introduce significant residual stress in the as-deposited IN718 with CrFeNb composites. The stress concentration of the heat-treated IN718 with 4 wt% CrFeNb composites was significantly reduced. The grain orientation was not along the and tended towards random. The particle size of as-deposited IN718 with 4 wt% CrFeNb composites was refined and the average size was 13.46 μm. The unmelted CrFeNb particles were dissolved and diffused into the γ matrix during heat treatment. A hard brittle phase was rich in Nb and Mo elements along the grain boundary. Under the combined effect of three strengthening mechanisms, the mechanical properties of the IN718 with 4 wt% CrFeNb composites at room temperature were improved. The yield strength, tensile strength and microhardness of the heat-treated IN718 with 4 wt% CrFeNb composites reached to 1194 MPa, 1426 MPa and 521 HV, respectively. This study provides a new method and foundation for the preparation and application of IN718 composites with excellent performance.

Layered MAX phases possess distinctive chemical, physical, electrical, and mechanical properties due to their amalgamation of metallic and ceramic characteristics. Understanding the corrosion mechanisms of MAX phases in various extreme environments is crucial. This paper commenced by scrutinizing synthesis techniques for MAX phase powders, thin films, and bulk materials, with a focus on fabrication processes and formation mechanisms. Subsequently, it delved into corrosion & oxidation mechanisms in diverse environments, emphasized their unique self-healing properties, and outlined future research directions. This comprehensive and systematic review aims to furnish researchers with effective guidance for selecting MAX phases based on different application environments.

Abstract Background Exogenous gonadotropin-controlled ovarian stimulation is the critical step in animal reproductive management, such as pig, sheep, bovine and other species. It helps synchronize ovulation or stimulate multiple ovulations. However, a number of evidence indicated an unexpected decrease in pregnancy outcomes following ovarian stimulation. This study aimed to explore the underlying mechanism of the pregnancy defect and develop a practical rescue strategy. Results Compared with those in the control group, gilts that underwent ovarian stimulation showed a decrease in pregnancy rate, farrowing rate, and total number of piglets born. Stimulated gilts also showed an increase in estradiol (E2) levels. The supraphysiological E2 level was correlated with the decrease in the number of piglets born. Furthermore, we found that high levels of E2 impair uterine receptivity, as shown by the overproliferation of endometrial epithelial cells. In vitro mechanistic studies demonstrated that high levels of E2 hyperactivate FGF-FGFR-ERK signaling cascade in the uterine endometrium, and in turn induces overproliferation of endometrial epithelial cells. Of note, N-acetyl-L-cysteine (NAC) supplementation effectively inhibits ERK hyperphosphorylation and ameliorates endometrial epithelial overproliferation. Importantly, in vivo experiments indicated that dietary NAC supplementation, compared with ovarian stimulation group, improves the uterine receptivity in gilts, and significantly increases the pregnancy rate and total number of piglets born. Conclusions Ovarian stimulation-induced supraphysiological levels of E2 impairs uterine receptivity by hyperactivating FGF-FGFR-ERK signaling cascade, thereby reducing pregnancy rate and litter size. Supplementing NAC to a conventional diet for gilts ameliorates hyperactivated ERK signaling and improves uterine receptivity, thus rescuing adverse pregnancy outcomes following ovarian stimulation. Graphical Abstract

Streptococcus thermophilus is one of the most prevalent species in stool samples of westernized populations due to continuous exposure to fermented dairy products. However, few studies have explored the effect on host physiology by multiple S. thermophilus strains and considered the inter-strain differences in regulating host. In the present study, we investigated how four S. thermophilus strains influenced the gut microbiota, mucin changes, and host metabolism after 28 days of intervention in conventional mice. The results indicated that the consumption of S. thermophilus affected the host with strain specificity. Among four S. thermophilus strains, DYNDL13-4 and DQHXNQ38M61, especially DQHXNQ38M61, had more effect on host physiology by modulating gut microbiota and host metabolism than LMD9 and 4M6. Ingestion of strains DYNDL13-4 and DQHXNQ38M61 resulted in more remarkable changes in amino acid metabolism and lipid metabolism than that of strains LMD9 and 4M6, which may be related to the elevation of intestinal Bifi dobacterium by DYNDL13-4 and DQHXNQ38M61. The enriched Coriobacteriaceae UCG-002, Rikenellaceae RC9 gut group, and Lactobacillus only in the DQHXNQ38M61 group, had a close relationship with the prominent effect of DQHXNQ38M61 on regulating amino acid and lipid metabolism. In addition, DQHXNQ38M61 had a strong influence on degrading colonic mucin fucose by decreased α-fucosidase activity in feces, and improving mucin sulfation by upregulated Gal3ST2 expression. Comparative genomic analysis revealed that the four S. thermophilus strains belonged to different branches in the phylogenetic tree, and DYNDL13-4 and DQHXNQ38M61 had more genes involved in carbohydrate metabolism, amino acid metabolism, membrane transport, and signal transduction, which may confer the capacity of nutrient utilization and gastrointestinal adaptation of the strains and be associated with their strong regulation in host. Our study provides valuable information for understanding the regulation of host metabolism after consuming different S. thermophilus strains and could facilitate potential personalized applications of S. thermophilus based on strain varieties.

Abstract Background This study aimed to identify the roles of L-tryptophan (Trp) and its rate-limiting enzymes on the receptivity of bovine endometrial epithelial cells. Real-time PCR was conducted to analyze the differential expression of genes between different groups of bovine endometrial epithelial cells. Western blot was performed to detect Cyclooxygenase-2 (COX2) expression after treatment with Trp or kynurenine (the main metabolites of Trp). The kynurenine assay was used to examine if Trp or prostaglandin E2 (PGE2) can increase the production of kynurenine in the bovine endometrial epithelial cells. Results Trp significantly stimulates insulin growth factor binding protein 1 (IGFBP1) expression, a common endometrial marker of conceptus elongation and uterus receptivity for ruminants. When bovine endometrial epithelial cells are treated with Trp, tryptophan hydroxylase-1 remains unchanged, but tryptophan 2,3-dioxygenase 2 (TDO2) is significantly increased, suggesting tryptophan is mainly metabolized through the kynurenine pathway. Kynurenine significantly stimulates IGFBP1 expression. Furthermore, Trp and kynurenine significantly increase the expression of aryl hydrocarbon receptor (AHR). CH223191, an AHR inhibitor, abrogates the induction of Trp and kynurenine on IGFBP1. PGE2 significantly induces the expression of TDO2, AHR, and IGFBP1. Conclusions The regulation between Trp / kynurenine and PGE2 may be crucial for the receptivity of the bovine uterus.

Abstract The rapid variation of influenza challenges vaccines and treatments, which makes an urgent task to develop the high-efficiency and low-toxicity new anti-influenza virus drugs. Selenium is one of the essential trace elements for the human body that possesses a good antiviral activity. In this study, we assessed anti-influenza A virus (H1N1) activity of polyethylene glycol (PEG)-modified gray selenium nanoparticles (PEG-SeNPs) on Madin-Darby Canine Kidney (MDCK) cells in vitro. CCK-8 assay showed that PEG-SeNPs had a protective effect on H1N1-infected MDCK cells. Moreover, PEG-SeNPs significantly reduced the mRNA level of H1N1. TUNEL-DAPI test showed that DNA damage reached a high level but effectively prevented after PEG-SeNPs treatment. Meanwhile, JC-1, Annexin V-FITC and cell cycle assay demonstrated the apoptosis induced by H1N1 was reduced greatly when treated with PEG-SeNPs. Furthermore, the downregulation of p-ATM, p-ATR and P53 protein, along with the upregualation of AKT protein indicated that PEG-SeNPs could inhibit H1N1-induced cell apoptosis through reactive oxygen species (ROS)-mediated related signaling pathways. Finally, Cytokine detection demonstrated PEG-SeNPs inhibited the production of pro-inflammatory factors after infection, including IL-1β, IL-5, IL-6, and TNF-α. To sum up, PEG-SeNPs might become a new potential anti-H1N1 influenza virus drug due to its antiviral and anti-inflammatory activity.

Abstract Colorectal cancer is a common malignant tumor of the digestive system. Its morbidity and mortality rank among the highest in the world. Cancer development is associated with aberrant signaling pathways. Autophagy is a process of cell self-digestion that maintains the intracellular environment and has a bidirectional regulatory role in cancer. Apoptosis is one of the important death programs in cancer cells and is able to inhibit cancer development. Studies have shown that a variety of substances can regulate autophagy and apoptosis in colorectal cancer cells through signaling pathways, and participate in the regulation of autophagy on apoptosis. In this paper, we focus on the relevant research on autophagy in colorectal cancer cells based on the involvement of related signaling pathways in the regulation of apoptosis in order to provide new research ideas and therapeutic directions for the treatment of colorectal cancer.

This is an article in the field of mining engineering. The deep sand gravel type pore brine in Qaidam Basin belongs to the unsaturated chloride type brine with high calcium, high sodium and low potassium. 480 kg of gravel-type pore brine at 1000～2000 meters underground in Dalangtan mining area was selected for the test, and evaporated and crysta-llized in the natural state in summer. The distribution law of ions in the solid and liquid phases, the salt crystallization law and crystal morphology were analyzed, and the main precipitation characteristics of potassium were studied. The results show when evaporating in the outdoor natural state, the salt precipitation process is mainly divided into four stages: halite→carnallite→bischofite→tachyhydrite. The salt evolution law in the halite stage conforms to the phase diagram of Na+, K+, Mg2+//Cl-—H2O at 25 ℃, and that in carnallite and bischofite stages conforms to the phase diagram of K+, Ca2+, Mg2+//Cl-—H2O system at 25 ℃. There is a separate precipitation stage of potassium, at which potassium is mainly precipitated in the form of carnallite, and the recovery rate of potassium is 85.76%. The K+content in the potassium mixed salt can reach 9.27%, which is a high quality raw material for the production of potassium fertilizer. Calcium precipitates after the brucite stage. The experimental results can provide references for the development and utilization of this type of brine.

BackgroundDextrocardia is a rare congenital condition, affecting approximately 1 in 10,000–12,000 individuals. When combined with atrial fibrillation (AF), it becomes even rarer. “One-stop” surgery, including combined radiofrequency ablation (RFA) and left atrial appendage occlusion (LAAO), has become a common clinical treatment for patients with AF who develop cerebral infarction despite regular oral anticoagulants. To date, no cases have been reported of patients with AF and dextrocardia undergoing the “one-stop” procedure, making this surgery particularly challenging.Case presentationAn 85-year-old dextrocardia male with total visceral inversion and persistent AF developed cerebral infarction despite regular oral anticoagulation therapy. He was referred to our hospital for RFA of AF and LAAO. The procedure was successfully performed using a three-dimensional electroanatomical mapping system (Carto3, Biosense Webster, Diamond Bar, CA, USA), intracardiac echocardiography (ICE), and x-ray, with no complications.ConclusionThis is the first reported case of a “one-stop” surgery for dextrocardia with AF. This procedure is safe and feasible with the assistance of advanced technologies such as ICE and the VIZIGO bidirectional adjustable bent sheath.

BackgroundThis review systematically evaluates the efficacy and safety of the combined treatment of glucocorticoids (GC) and cyclophosphamide (CTX) in patients with membranous nephropathy (MN).MethodsAs of June 2024, a comprehensive literature search was performed utilizing several reputable databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and Wanfang. A meta-analysis was then carried out using Review Manager 5.4 and STATA/SE-15 software.ResultsThis research evaluated a total of 22 articles involving 1,971 patients. The findings revealed that patients with MN receiving combined GC and CTX therapy had significantly higher complete remission rates (odds ratio = 1.78, p = 0.02) and total remission rates (odds ratio = 2.14, p = 0.01) when the follow-up period exceeded 12 months. Additionally, this treatment demonstrated greater efficacy in lowering serum creatinine levels compared to the control group (standardized mean difference = −0.19, p = 0.04), while its relapse rate was also lower than that of the control group (odds ratio = 0.51, p = 0.009). However, it has a high incidence of serious adverse effects (odds ratio = 2.32, p = 0.03).ConclusionOur systematic review highlights that the combination of GC and CTX demonstrates superior long-term effectiveness and reduced relapse rates in managing membranous nephropathy (MN). Furthermore, this drug combination is considered the optimal choice for normalizing serum creatinine levels. Data on the effectiveness and safety of glucocorticoids alone versus other drugs alone, and the treatment of secondary membranous nephropathy (SMN), are limited.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=566477, identifier CRD42024566477.

Abstract [11C]Carfentanil ([11C]CFN) is the only selective carbon-11 labeled radiotracer currently available for positron emission tomography (PET) imaging of mu opioid receptors (MORs). Though used extensively in clinical research, [11C]CFN has not been thoroughly characterized as a tool for preclinical PET imaging. As we were occasionally observing severe vital sign instability in rat [11C]CFN studies, we set out to investigate physiological effects of CFN mass and to explore its influence on MOR quantification. In anesthetized rats (n = 15), significant dose-dependent PCO2 increases and heart rate decreases were observed at a conventional tracer dose range (IV, > 100 ng/kg). Next, we conducted baseline and retest [11C]CFN PET scans over a wide range of molar activities. Baseline [11C]CFN PET studies (n = 27) found that nondisplaceable binding potential (BPND) in the thalamus was positively correlated to CFN injected mass, demonstrating increase of MOR availability at higher injected CFN mass. Consistently, when CFN injected mass was constrained

Background and objective Neoantigen reactive T cell (NRT) has the ability to inhibit the growth of tumors expressing specific neoantigens. However, due to the difficult immune infiltration and the inhibition of tumor microenvironment, the therapeutic effect of NRT in solid tumors is limited. In this study, we designed NRT cells (7×19 NRT) that can express both interleukin-7 (IL-7) and chemokine C-C motif ligand 19 (CCL19) in mouse lung cancer cells, and evaluated the difference in anti-tumor effect between 7×19 NRT cells and conventional NRT cells. Methods We performed next-generation sequencing and neoantigen prediction for mouse Lewis lung carcinoma (LLC), prepared RNA vaccine, cultured NRT cells, constructed retroviral vectors encoding IL-7 and CCL19, transduced NRT cells and IL-7 and CCL19 were successfully expressed, and 7×19 NRT was successfully obtained. The anti-tumor effect was evaluated in vivo and in vitro in mice. Results The 7×19 NRT cells significantly enhanced the proliferation and invasion ability of T cells by secreting IL-7 and CCL19, achieved significant tumor inhibition in the mouse lung cancer and extended the survival period of mice. The T cell infiltration into tumor tissue and the necrosis of tumor tissue increased significantly after 7×19 NRT treatment. In addition, both 7×19 NRT treatment and conventional NRT treatment were safe. Conclusion The anti-solid tumor ability of NRT cells is significantly enhanced by the arming of IL-7 and CCL19, which is a safe and effective genetic modification of NRT.

Abstract The loss of dopaminergic neurons in the substantia nigra is a hallmark of pathology in Parkinson’s disease (PD). Dimethylarginine dimethylaminohydrolase-1 (DDAH-1) is the critical enzyme responsible for the degradation of asymmetric dimethylarginine (ADMA) which inhibits nitric oxide (NO) synthase and has been implicated in neurodegeneration. Mitochondrial dysfunction, particularly in the mitochondria-associated endoplasmic reticulum membrane (MAM), plays a critical role in this process, although the specific molecular target has not yet been determined. This study aims to examine the involvement of DDAH-1 in the nigrostriatal dopaminergic pathway and PD pathogenesis. The distribution of DDAH-1 in the brain and its colocalization with dopaminergic neurons were observed. The loss of dopaminergic neurons and aggravated locomotor disability after rotenone (ROT) injection were showed in the DDAH-1 knockout rat. l-arginine (ARG) and NO donors were employed to elucidate the role of NO respectively. In vitro, we investigated the effects of DDAH-1 knockdown or overexpression on cell viability and mitochondrial functions, as well as modulation of ADMA/NO levels using ADMA or ARG. MAM formation was assessed by the Mitofusin2 oligomerization and the mitochondrial ubiquitin ligase (MITOL) phosphorylation. We found that DDAH-1 downregulation resulted in enhanced cell death and mitochondrial dysfunctions, accompanied by elevated ADMA and reduced NO levels. However, the recovered NO level after the ARG supplement failed to exhibit a protective effect on mitochondrial functions and partially restored cell viability. DDAH-1 overexpression prevented ROT toxicity, while ADMA treatment attenuated these protective effects. The declines of MAM formation in ROT-treated cells were exacerbated by DDAH-1 downregulation via reduced MITOL phosphorylation, which was reversed by DDAH-1 overexpression. Together, the abundant expression of DDAH-1 in nigral dopaminergic neurons may exert neuroprotective effects by maintaining MAM formation and mitochondrial function probably via ADMA, indicating the therapeutic potential of targeting DDAH-1 for PD.

Abstract Background Glioblastoma is an aggressive brain tumor linked to significant angiogenesis and poor prognosis. Anti-angiogenic therapies with vascular endothelial growth factor receptor 2 (VEGFR2) inhibition have been investigated as an alternative glioblastoma treatment. However, little is known about the effect of VEGFR2 blockade on glioblastoma cells per se. Methods VEGFR2 expression data in glioma patients were retrieved from the public database TCGA. VEGFR2 intervention was implemented by using its selective inhibitor Ki8751 or shRNA. Mitochondrial biogenesis of glioblastoma cells was assessed by immunofluorescence imaging, mass spectrometry, and western blot analysis. Results VEGFR2 expression was higher in glioma patients with higher malignancy (grade III and IV). VEGFR2 inhibition hampered glioblastoma cell proliferation and induced cell apoptosis. Mass spectrometry and immunofluorescence imaging showed that the anti-glioblastoma effects of VEGFR2 blockade involved mitochondrial biogenesis, as evidenced by the increases of mitochondrial protein expression, mitochondria mass, mitochondrial oxidative phosphorylation (OXPHOS), and reactive oxygen species (ROS) production, all of which play important roles in tumor cell apoptosis, growth inhibition, cell cycle arrest and cell senescence. Furthermore, VEGFR2 inhibition exaggerated mitochondrial biogenesis by decreased phosphorylation of AKT and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), which mobilized PGC1α into the nucleus, increased mitochondrial transcription factor A (TFAM) expression, and subsequently enhanced mitochondrial biogenesis. Conclusions VEGFR2 blockade inhibits glioblastoma progression via AKT-PGC1α-TFAM-mitochondria biogenesis signaling cascade, suggesting that VEGFR2 intervention might bring additive therapeutic values to anti-glioblastoma therapy.

Abstract Difluoromethyl pyridines have gained significant attention in medicinal and agricultural chemistry. The direct C−H-difluoromethylation of pyridines represents a highly efficient economic way to access these azines. However, the direct meta-difluoromethylation of pyridines has remained elusive and methods for site-switchable regioselective meta- and para-difluoromethylation are unknown. Here, we demonstrate the meta-C−H-difluoromethylation of pyridines through a radical process by using oxazino pyridine intermediates, which are easily accessed from pyridines. The selectivity can be readily switched to para by in situ transformation of the oxazino pyridines to pyridinium salts upon acid treatment. The preparation of various meta- and para-difluoromethylated pyridines through this approach is presented. The mild conditions used also allow for the late-stage meta- or para-difluoromethylation of pyridine containing drugs. Sequential double functionalization of pyridines is presented, which further underlines the value of this work.

Fast homogenization without incipient melting is the key to designing solution heat treatment (SHT) process for single crystal superalloys. In this paper, a multicomponent phase-field model coupled with solidus temperature is developed for dynamically tracking incipient melting temperature, TIM, of alloy during SHT. The simulation process runs completely automatically only by inputting the composition information of as-cast specimen. Based on the obtained TIM-time profile, the holding temperature and the time of SHT are determined. Applying this approach to Co–30Ni–11Al–4W–1Ta–4Ti–5Cr single crystal specimen, a gradual increased TIM from 1247 °C to 1293 °C within 72,000 s is obtained, and thus a stepwise SHT process with a short time of less than 20 h is designed. The experimental verification shows that after SHT, the segregation coefficient of the slowest diffusing element W decreased from more than 2 to 1.065, the content of harmful secondary phase has decreased to below 0.1%, and no incipient melting occurs.

【Objective】Auxin response factors (ARF) are key transcription factors engaged in the auxin signaling system and play significant roles in plant flower and fruit development, organ morphogenesis, hormone control, and stress responses. The study aims to investigate the biological functions of AsARF gene in Aquilaria sinensis (Lour.) Gilg during the aroma formation process.【Method】The AsARF genes in A. sinensis at genome-wide level were identified and analyzed by bioinformatics approaches. The expression patterns of ARF family members in response to mechanical damage in A. sinensis were revealed through transcriptome data analysis.【Result】Twenty-one AsARF genes were identified at the genome-wide level, and the systematic bioinformatics analysis results showed that these 21 AsARF genes were divided into five groups, with gene sequences within the same group sharing similar gene structures and conserved protein domains, while different groups of AsARF genes exhibited significant variations in the number of exons and introns. Furthermore, cis-acting element analysis revealed that the promoter regions of ARF genes in A. sinensis contained numerous sequences associated with sunlight, anaerobic conditions, gibberellin and other response elements. Gene duplication and collinearity analysis indicated that fragment duplication events played a crucial role in the evolution and expansion of the A. sinensis ARF gene family. Comparing with rice ARF genes, it revealed there was a closer relationship between A. sinensis and Arabidopsis thaliana ARF genes. Additionally, transcriptome data analysis demonstrated a significant decrease in expression levels of AsARF5, AsARF6, AsARF19, AsARF20, and AsARF21 genes in response to mechanical damage in A. sinensis.【Conclusion】The study conducted the first genome-wide identification of the AsARF gene family and offered a comprehensive analysis on their physicochemical properties, systematic evolution, gene structure, conserved protein domains, promoter cis-acting elements, gene duplication, and collinearity. Furthermore, the potential mechanisms of AsARF genes in the aroma formation process of A. sinensis were explored through RNA-seq analysis. The results suggested that some AsARF genes may be involved in the defense and dynamic balance of aroma formation in A. sinensis. These findings provided important theoretical basis for a deeper understanding of the aroma formation mechanism in A. sinensis.

Objective To study the changes in related parameters after secondary preparation of blood components, in order to further improve the quality of blood components. Methods Different centrifugation conditions were selected for the preparation of primary blood component red blood cells in additive solution leukocytes reduced, and the quality was tested. Then, using the red blood cells in additive solution leukocytes reduced as the initial blood for secondary preparation, and the red blood cells were washed through the Haemonetics ACP 215 device, and the quality was tested. The preparation parameters of blood components were observed, compared and optimized. Results Under comparable centrifugation effects of different centrifugation conditions, the quality control items, which of primary blood components of red blood cells in additive solution leukocytes reduced and frozen plasma prepared by the separation, such as volume, hemoglobin, hematocrit and residual white blood cells met the relevant national standards. And the quality control items of secondary blood components of washed red blood cells such as the hemoglobin and superalbumin content both met the relevant national standards, while volume exceeded the standard by 7-14 mL, which can be operated to the standard range. In addition, the recovery rate of red blood cells and the clearance rate of plasma protein could reach 75% and 99% respectively. Conclusion There is a certain correlation between primary and secondary preparation of blood components, but the relevant parameters of secondary preparation of blood components can be flexibly adjusted according to the actual situation to ensure that the quality of prepared blood component products meet the national standards, thus ensuring clinical treatment effect and safety.

In the context of the digital era, e-learning has become an innovative and indispensable component of the educational sector. With the continuous advancement of technology and the widespread adoption of the internet, e-learning has demonstrated its key role in maintaining educational continuity and supporting remote teaching. However, despite the extensive applications and significant advantages of e-learning, the willingness of college students to continue using e-learning platforms is not always high, presenting a challenge for educators and technology developers. Based on the Expectation Confirmation Model, this study examines the influence of perceived educational and emotional support on the continuance intention of e-learning among college students. The researchers conducted a survey using a structured questionnaire randomly among 379 university students from three universities in Henan Province to measure their self-reported responses on six constructs: perceived educational support, perceived emotional support, perceived usefulness, confirmation, satisfaction, and continuance intention. The study uses the Structural Equation Modeling—Artificial Neural Network (SEM-ANN) method to elucidate the non-compensatory and non-linear relationships between predictive factors and e-learning continuance intention. Except for the direct effects of perceived educational support and perceived emotional support on perceived usefulness, which were not significant, all other hypotheses were confirmed. Moreover, according to the normalized importance obtained from the multilayer perceptron, satisfaction (100%) was found to be the most critical predictive factor, followed by confirmation (29.8%), perceived usefulness (28.2%), perceived educational support (22.7%), and perceived emotional support (21.8%). All constructs together accounted for 62.0% of the total variance in college students’ e-learning continuance intention. This study’s adoption of a two-stage analysis approach improved the depth and accuracy of data processing and expanded the methodological scope of educational technology research. It provides direction for future in-depth studies in various environments and cultural contexts.

ObjectivesWe aim to investigate the prevalence of respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) among pediatric patients with acute respiratory tract illness (ARTI) in southern China both pre- and post-COVID-19 pandemic, as well as identify associated risk factors for severe infections.MethodsThe study conducted a real-time PCR analysis on hospitalized children with ARTI from 2012 to 2023, specifically targeting RSV, hMPV, and other respiratory pathogens. Additionally, demographic data was collected during this analysis.ResultsThe prevalence of RSV occurs triennially, and likewise, the temporal pattern of hMPV outbreaks mirrors that of RSV. The peak infection rates of RSV and hMPV occurred during and following the implementation of COVID-19 epidemic prevention and control measures. The incidence of RSV infection exhibited bimodal peaks in 2022, while hMPV demonstrated seasonal peaks during the spring, fall, and winter periods post-COVID-19 pandemic. After the COVID-19 outbreak, there has been an upward trend in the proportion of female patients and patients aged one year and older presenting with ARTI, RSV infections, and hMPV infections. Infant (OR = 4.767, 95%CI: [3.888–5.846], p < 0.0001), presence of co-infection (OR = 0.540, 95%CI: [0.404–0.722], p < 0.0001), and existence of comorbidities (OR = 1.582, 95%CI: [1.285–1.949], p < 0.0001) was the risk ratio for the severity of RSV infection. Children infected with hMPV under the age of 1 year (OR = 0.322, 95%CI: [0.180 – 0.575], p < 0.0001), as well as those with comorbidities (OR = 8.809, 95%CI: [4.493 – 17.272], p < 0.0001), have a higher risk of developing severe illness.ConclusionThe changing epidemiological patterns have the potential to lead to widespread severe outbreaks among children, particularly those with underlying medical conditions who may experience more severe symptoms. Conducting surveillance for pneumoviridae viruses in children is an imperative measure to establish a robust foundation for future epidemic prevention and treatment strategies.

BackgroundChemicals may lead to acute liver injuries, posing a serious threat to human health. Achieving the precise safety profile of a compound is challenging due to the complex and expensive testing procedures. In silico approaches will aid in identifying the potential risk of drug candidates in the initial stage of drug development and thus mitigating the developmental cost.MethodsIn current studies, QSAR models were developed for hepatotoxicity predictions using the ensemble strategy to integrate machine learning (ML) and deep learning (DL) algorithms using various molecular features. A large dataset of 2588 chemicals and drugs was randomly divided into training (80%) and test (20%) sets, followed by the training of individual base models using diverse machine learning or deep learning based on three different kinds of descriptors and fingerprints. Feature selection approaches were employed to proceed with model optimizations based on the model performance. Hybrid ensemble approaches were further utilized to determine the method with the best performance.ResultsThe voting ensemble classifier emerged as the optimal model, achieving an excellent prediction accuracy of 80.26%, AUC of 82.84%, and recall of over 93% followed by bagging and stacking ensemble classifiers method. The model was further verified by an external test set, internal 10-fold cross-validation, and rigorous benchmark training, exhibiting much better reliability than the published models.ConclusionThe proposed ensemble model offers a dependable assessment with a good performance for the prediction regarding the risk of chemicals and drugs to induce liver damage.

Leukemia is a malignant tumor with high heterogeneity and a complex evolutionary process. It is difficult to resolve the heterogeneity and clonal evolution of leukemia cells by applying traditional bulk sequencing techniques, thus preventing a deep understanding of the mechanisms of leukemia development and the identification of potential therapeutic targets. However, with the development and application of single-cell sequencing technology, it is now possible to investigate the gene expression profile, mutations, and epigenetic features of leukemia at the single-cell level, thus providing a new perspective for leukemia research. In this article, we review the recent applications and advances of single-cell sequencing technology in leukemia research, discuss its potential for enhancing our understanding of the mechanisms of leukemia development, discovering therapeutic targets and personalized treatment, and provide reference guidelines for the significance of this technology in clinical research.

Background: Colorectal cancer is a major cause of mortality among the prevalent malignant tumors of the gastrointestinal tract. Although chemotherapy is a standard treatment for colorectal cancer, its efficacy is limited by chemoresistance. Recent studies have investigated targeting tumor stem cells as a potential new therapeutic approach for addressing chemoresistance in colorectal cancer. Colorectal cancer frequently relapses, with tumor stem cells often representing one of the leading causes of treatment failure. Purpose: Understanding drug resistance in colorectal cancer stem cells is crucial for improving treatment outcomes. By focusing on developing targeted therapies that specifically address drug resistance in colorectal cancer stem cells, there is potential to make significant advancements in the treatment of colorectal cancer.This approach may lead to more effective and lasting outcomes in patients battling colorectal cancer. Research Design: In this review, a comprehensive overview of recent research on colorectal cancer stem cell treatment resistance is presented.Results: Elucidating the key underlying mechanisms. This review also highlights the potential benefits of targeted therapies in overcoming colorectal cancer resistance to treatment. Conclusions: CCSCs are key players in drug resistance of CRC, indicating their potential as targets for effective therapy. Elucidating their role in this process could aid in discovering tailored treatment strategies.The significance of signaling pathways, TME, and miRNA in regulating drug resistance in CCSCs is been highlighted.

Abstract Pure self-management model, pure aggregation business model and Self-support + aggregation model are three commonly used business modes on ride-hailing platforms. We use an analytical model to study these three business models and give the optimal business model decision of the platform. The research shows that the heterogeneity ratio of drivers, the cost of the platform under the Self-support model, the franchise fee received by the platform under the aggregation model and the dissatisfaction of the original users on the platform play a key role in the selection of the platform’s business model. When the difference between the franchise fee under the aggregation mode and the platform cost under the Self-support mode fails to generate positive feedback on the platform profit, the platform should choose the pure Self-support mode. When riders are more sensitive to the heterogeneity of service quality of the platform and user stickiness can be ensured, the platform should choose the pure aggregation business model. When user stickiness can be guaranteed and the cost of the platform under the self-run model is controllable, the platform should choose the Self-support + aggregation business model.

Lipid metabolism disorders commonly occur during menopause. Estrogen deficiency has been shown to lead to excessive energy intake and abnormal lipid metabolism in ovariectomized rats, resulting in obesity. Probiotics exhibit anti-obesity properties, and their underlying mechanism has been widely reported. In this study, we demonstrated the metabolic benefits of Lactobacillus plantarum CCFM1180 in suppressing appetite, controlling body weight, correcting obesity-induced abnormalities, enhancing liver lipid metabolism, and protecting liver function in estrogen-deficient rats. The mechanisms associated with the anti-obesity and antidyslipidemia effects of CCFM1180 on estrogen-deficient rats were clarified. The results showed that CCFM1180 dramatically reduced food intake by activating the expression of estrogen receptor alpha (ERα) and increasing the level of leptin in abdominal adipose tissue. These changes, combined with the increased butyrate concentration and recovered bile acid structure, helped enhance lipid metabolism. Additionally, CCFM1180 treatment was found to be safer than exogenous estrogen supplementation. Thus, L. plantarum CCFM1180 could be considered a new therapeutic strategy for preventing and alleviating menopausal lipid abnormalities.

The gut microbiota-brain axis has emerged as a novel target for Alzheimer's disease (AD), a neurodegenerative disease characterised by behavioural and cognitive impairment. However, most previous microbiome-based intervention studies have focused on single factors and yielded only modest cognitive improvements. Here, we proposed a multidomain intervention strategy that combined Bifidobacterium breve treatment with environmental enrichment (EE) training. In this study, we found that compared with EE or B. breve treatment alone, B. breve intervention combined with EE amplified its neuroprotective effects on AD mice, as reflected by improved cognition, inhibited neuroinflammation and enhanced synaptic function. Moreover, using microbiome and metabolome profiling, we found that the combination of B. breve and EE treatment restored AD-related gut microbiota dysbiosis and reversed microbial metabolite changes. Finally, by integrating behavioural and neurological data with metabolomic profiles, we revealed that the underlying mechanism may involve the modulation of microbiota-derived glutamine metabolism via gut-brain interactions. Collectively, combined B. breve intervention with EE treatment can alleviate AD-related cognitive impairment and improve brain function by regulating glutamine metabolism of the gut microbiome. Our findings provide a promising multidomain intervention strategy, with a combination of dietary microbiome-based and lifestyle-targeted interventions, to promote brain function and delay the progression of AD.

Abstract Background Small intestinal monomorphic–epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare aggressive T-cell lymphoma originating in the gastrointestinal tract. This study aimed to investigate the clinicopathological features, immunophenotypes, and molecular genetic changes of MEITL. Methods The clinicopathological data for three patients with surgically resected MEITL of the small intestine were collected. Next, immunohistochemical labeling, Epstein–Barr virus (EBV) in situ hybridization, assessment of clonal rearrangement of T-cell receptor (TCR) genes, and next-generation sequencing (NGS) were performed. Results Of the three patients, two were male and one was female, with ages of 61, 67, and 73 years, respectively. Clinical manifestations were predominantly abdominal pain and distension. Histopathology revealed infiltrative growth of small-to-medium-sized lymphocytes with a consistent morphology between the intestinal walls, accompanied by an obvious pro-epithelial phenomenon. The expression of CD3, CD8, CD43, CD56, TIA-1, CD103, H3K36me3, and Bcl-2 was detected, and the Ki-67 proliferation index ranged from 50% to 80%. All three patients tested negative for EBER. However, monoclonal rearrangement of the TCR gene was detected in them. NGS testing showed a JAK3 mutation in all three cases. Further, STAT5B, SETD2, and TP53 mutations were each observed in two cases, and a BCOR mutation was found in one case. All patients were treated with chemotherapy after surgery. Two patients died 7 and 15 month post-operation, and one patient survived for 5 months of follow-up. Conclusions Our findings demonstrate that mutations in JAK3 and STAT5B of the JAK/STAT pathway and inactivation of the oncogene SETD2 markedly contribute to the lymphomagenesis of MEITL.

This paper aimed to explore the correlation between the physical and chemical indicators of sauce-flavor Daqu with different sensory characteristics and the community of molds, six physical and chemical indicators of WQ, YQ and BQ were tested, the mold of Daqu were separated and identified, the correlation between the physical and chemical indicators and mold community in three kinds of Daqu were analyzed by redundancy analysis. The results showed that the liquefaction power of YQ was higher, and YQ and BQ showed the higher fermentation power and esterification power, respectively: 1.56 U, 22.63 U and 1.51 U, 22.48 U. A total of 78 strains of 13 species of molds belonging to 6 genera were isolated and identified from three kinds of Daqu, including 7 species in WQ, namely Paecilomyces subglobosus, Paecilomyces variotii, Lichtheimia corymbifera, Lichtheimia ornata, Penicillium tardochrysogenum, Penicillium chrysogenum, Epicoccum endophytica. 6 Species were isolated from YQ, namely Lichtheimia ramosa, Lichtheimia corymbifera, Paecilomyces variotii, Lichtheimia hongkongensis, Lichtheimia ornata, Aspergillus intermedius. 7 Species were isolated from BQ, namely Paecilomyces variotii, Paecilomyces subglobosus, Lichtheimia ramosa, Scopulariopsis brevicaulis, Lichtheimia corymbifera, Aspergillus sydowii, Aspergillus quadrilineatus. Through redundancy analysis, it was concluded that Lichtheimia was the main strain affecting the saccharification and esterification of Daqu. This study provides a basis for the research and application of molds in sauce-flavored Daqu and provides data support for improving the fermentation performance of sauce-flavored Daqu.

Volcanic activity is often associated with the development of faulted lacustrine basins. Organic-rich shale in such basins usually contains abundant volcanic material. The influence of volcanic input on organic-rich shale deposition in the basin studied has not been discussed in detail. Based on the ten shale samples from three wells, this study analyzed the depositional environment of the Yingcheng Formation shale in the Lishu Fault Depression area of the Songliao Basin by using interpretation of logging, total organic carbon analysis, gas chromatography mass spectrometry analysis, and trace element analysis. The impact of fault break to basement and volcanic materials on the organic matter enrichment was evaluated. The results show that the organic matter of Ying 1 (Y1), the First Member of the Yingcheng Formation, in the Lishu Fault Depression is characterized mainly by type I kerogen. The shale of the Y1 Member, having high total organic carbon content, is laterally continuous and could be considered as a potential target for shale oil exploration. The shale with high total organic carbon was deposited in a freshwater deep lake under an anoxic environment. There is a significant input of volcanic material, especially around the Su2 well near the Sangshutai Fault. This study has established a sedimentary model of organic-rich shale in the faulted lacustrine basin affected by volcanic activity, which has significance for the exploration of shale oil in faulted lacustrine basins.

Abstract Background Moyamoya disease (MMD) is a rare and complex cerebrovascular disorder characterized by the progressive narrowing of the internal carotid arteries and the formation of compensatory collateral vessels. The etiology of MMD remains enigmatic, making diagnosis and management challenging. The MOYAOMICS project was initiated to investigate the molecular underpinnings of MMD and explore potential diagnostic and therapeutic strategies. Methods The MOYAOMICS project employs a multidisciplinary approach, integrating various omics technologies, including genomics, transcriptomics, proteomics, and metabolomics, to comprehensively examine the molecular signatures associated with MMD pathogenesis. Additionally, we will investigate the potential influence of gut microbiota and brain-gut peptides on MMD development, assessing their suitability as targets for therapeutic strategies and dietary interventions. Radiomics, a specialized field in medical imaging, is utilized to analyze neuroimaging data for early detection and characterization of MMD-related brain changes. Deep learning algorithms are employed to differentiate MMD from other conditions, automating the diagnostic process. We also employ single-cellomics and mass cytometry to precisely study cellular heterogeneity in peripheral blood samples from MMD patients. Conclusions The MOYAOMICS project represents a significant step toward comprehending MMD’s molecular underpinnings. This multidisciplinary approach has the potential to revolutionize early diagnosis, patient stratification, and the development of targeted therapies for MMD. The identification of blood-based biomarkers and the integration of multiple omics data are critical for improving the clinical management of MMD and enhancing patient outcomes for this complex disease.

Abstract Reinforcement learning (RL) stands as one of the three fundamental paradigms within machine learning and has made a substantial leap to build general-purpose learning systems. However, using traditional electrical computers to simulate agent-environment interactions in RL models consumes tremendous computing resources, posing a significant challenge to the efficiency of RL. Here, we propose a universal framework that utilizes a photonic integrated circuit (PIC) to simulate the interactions in RL for improving the algorithm efficiency. High parallelism and precision on-chip optical interaction calculations are implemented with the assistance of link calibration in the hybrid architecture PIC. By introducing similarity information into the reward function of the RL model, PIC-RL successfully accomplishes perovskite materials synthesis task within a 3472-dimensional state space, resulting in a notable 56% improvement in efficiency. Our results validate the effectiveness of simulating RL algorithm interactions on the PIC platform, highlighting its potential to boost computing power in large-scale and sophisticated RL tasks.

The energy storage adjustment strategy of source and load storage in a DC microgrid is very important to the economic benefits of a power grid. Therefore, a multi-timescale energy storage optimization method for direct current (DC) microgrid source-load storage based on a virtual bus voltage control is studied. It uses a virtual damping compensation strategy to control the stability of virtual bus voltage and establishes a virtual energy storage model by combining different types of distributed capability units. The design of an optimization process for upper-level daily energy storage has the objective function of maximizing the economic benefits of microgrids to cope with unplanned fluctuations in power. A real-time energy-adjustment scheme for the lower level is introduced, and a real-time energy-adjustment scheme based on virtual energy storage for the short-term partition of the source-load storage is designed to improve the reliability of microgrid operations. The experiment shows that, in response to the constant amplitude oscillation of the power grid after a sudden increase in power, this method introduces a virtual damping compensation strategy at 20 s, which can stabilize the virtual bus voltage. From 00:00 to 09:00, the battery power remains at around 4 MW, and from 12:00 to 21:00, the battery exits the discharge state. The economic benefits from applying this method are significantly higher than before. This method can effectively adjust the source-load energy storage in real time. During peak electricity price periods, the SOC value of supercapacitors is below 0.4, and during normal electricity price periods, the SOC value of supercapacitors can reach up to 1.0, which can make the state of the charge value of supercapacitors meet economic requirements.

Objective and rationale: Hospital-acquired falls are common and serious adverse events in medical institutions, with high incidence and injury rates. Studying the occurrence patterns of hospital-acquired falls is important for preventing falls in hospitalized patients. However, the effect of meteorological factors on hospital-acquired falls has not been elucidated. Therefore, this study explored the impact of meteorological parameters on hospital-acquired falls in Chongqing, China, and provided new ideas for the clinical prevention of falls in patients. Methods: Correlation analysis and distributed lag nonlinear models were employed to analyze the relationship between 3890 cases of hospital-acquired falls and meteorological data in 13 hospitals in 11 districts and counties in Chongqing from January 2013 to April 2023. Results: The number of hospital-acquired falls demonstrated a nonlinear correlation with the daily average relative humidity and negatively correlated with sunshine duration; however, temperature, air pressure, and wind speed were not correlated. Compared to the reference humidity (87 %), the immediate effects of daily average relative humidity (65–68 % and 90–97 %) increased the risk of hospital-acquired falls on the same day (relative risk [RR]:1.027–1.243). When the daily average relative humidity was 95–97 %, lags of 0–1 d and 8–12 d had greater effects on falls (RR:1.073–1.243). The daily average relative humidities of 62–74 % and 91–97 % were statistically significant at cumulative relative risk (CRR)of 4, 7, 10, and 14 d with a cumulative lag (CRR: 1.111–4.277). On sex and age stratification, the lag and cumulative effects of relative humidity more significantly impacted falls in women and patients aged ≥65 years. Conclusion: Daily average relative humidity had a nonlinear correlation and lag effect on hospital-acquired falls; therefore, medical institutions should pay attention to the effect of relative humidity on hospital-acquired falls in patients, especially old and female patients.

Background: Labor epidural analgesia (LEA) may influence gut microbiota. We explored the association between LEA and gut microbiota for both mothers and their newborns. Methods: In this prospective cohort study, parturients aged 25–35 years with a gestational age of 37–42 weeks and planned vaginal delivery were recruited. Twenty-one parturients received LEA (the LEA group), and 24 did not (the control group). Maternal and neonatal fecal samples were collected, and the gut microbiota profiles were analyzed using the 16S rRNA gene sequencing. The impact of LEA on gut microbiota was assessed using the general liner models. Results: We showcased the gut microbiota profile from the phyla to species levels based on data on 45 mother-newborn dyads. The results of α- and β-diversity suggested significant changes in gut microbiota between the LEA and control groups. After adjusting for baseline confounders, the administration of LEA had positive correlations with R. ilealis (β = 91.87, adjusted P = 0.007) in mothers; LEA also had negative correlations with A. pittii (β = −449.36, adjusted P = 0.015), P. aeruginosa (β = −192.55, adjusted P = 0.008), or S. maltophilia (β = −142.62, adjusted P = 0.001) in mothers, and with Muribaculaceae (β = −2702.77, adjusted P = 0.003) in neonates. Conclusion: LEA was associated with changes in maternal and neonatal gut microbiota, and future studies are still required to assess their impact on clinical outcomes and explore the mechanisms.