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Abstract With the emergence of computer‐aided diagnostic (CAD) systems, the speed of histopathological image analysis and the accuracy of cancer detection have considerably improved. However, the appearance of histopathological slides can vary depending on the consistency of tissue thickness, stain concentrations, and equipment, thus affecting the judgment of CAD systems. This study proposes a palette‐based colour normalization method for histopathology images is proposed to solve the problem of colour differences between histopathology images. The method builds a graphical user interface based on an improved palette generation algorithm and colour transfer definitions, through which the user can complete the corresponding colour modification to achieve colour normalization. The evaluation of the metrics on histopathological images shows that our method is able to achieve higher image quality and better preservation of structural information of the source image compared with four other colour normalization algorithms. The peak signal‐to‐noise ratio values obtained by the proposed method on two publicly available datasets were 24.1914 and 21.3666, and the structural similarity index matrix values were 0.9871 and 0.9760. The proposed method provides new ideas for the development and design of CAD systems.

Abstract The abounding variations in wild rice provided potential reservoirs of beneficial genes for rice breeding. Maintaining stable and high yields under environmental stresses is a long-standing goal of rice breeding but is challenging due to internal trade-off mechanisms. Here, we report wild rice GL12 W improves grain length and salt tolerance in both indica and japonica genetic backgrounds. GL12 W alters cell length by regulating grain size related genes including GS2, and positively regulates the salt tolerance related genes, such as NAC5, NCED3, under salt stresses. We find that a G/T variation in GL12 promoter determined its binding to coactivator GIF1 and transcription factor WRKY53. GIF1 promotes GL12 W expression in young panicle and WRKY53 represses GL12 W expression under salt stresses. The G/T variation also contributes to the divergence of indica and japonica subspecies. Our results provide useful resources for modern rice breeding and shed insights for understanding yield and salt tolerance trade-off mechanism.

In advanced hepatocellular carcinoma (HCC) tissues, M2-like tumor-associated macrophages (TAMs) are in the majority and promotes HCC progression. Contrary to the pro-tumor effect of M2-like TAMs, M1-like TAMs account for a small proportion and have anti-tumor effects. Since TAMs can switch from one type to another, reprogramming TAMs may be an important treatment for HCC therapy. However, the mechanisms of phenotypic switch and reprogramming TAMs are still obscure. In this study, we analyzed differential genes in normal macrophages and TAMs, and found that loss of MANF in TAMs accompanied by high levels of downstream genes negatively regulated by MANF. MANF reprogrammed TAMs into M1 phenotype. Meanwhile, loss of MANF promoted HCC progression in HCC patients and mice HCC model, especially tumor neovascularization. Additionally, macrophages with MANF supplement suppressed HCC progression in mice, suggesting MANF supplement in macrophage was an effective treatment for HCC. Mechanistically, MANF enhanced the HSF1–HSP70-1 interaction, restricted HSF1 in the cytoplasm of macrophages, and decreased both mRNA and protein levels of HSP70-1, which in turn led to reprogramming TAMs, and suppressing neovascularization of HCC. Our study contributes to the exploration the mechanism of TAMs reprogramming, which may provide insights for future therapeutic exploitation of HCC neovascularization.

Abstract To assist the visually impaired in their daily lives and solve the problems associated with poor portability, high hardware costs, and environmental susceptibility of indoor object-finding aids for the visually impaired, an improved YOLOv5 algorithm was proposed. It was combined with a RealSense D435i depth camera and a voice system to realise an indoor object-finding device for the visually impaired using a Raspberry Pi 4 B device as its core. The algorithm uses GhostNet instead of the YOLOv5s backbone network to reduce the number of parameters and computation of the model, incorporates an attention mechanism (coordinate attention), and replaces the YOLOv5 neck network with a bidirectional feature pyramid network to enhance feature extraction. Compared to the YOLOv5 model, the model size was reduced by 42.4%, number of parameters was reduced by 47.9%, and recall rate increased by 1.2% with the same precision. This study applied the improved YOLOv5 algorithm to an indoor object-finding device for the visually impaired, where the searched object was input by voice, and the RealSense D435i was used to acquire RGB and depth images to realize the detection and ranging of the object, broadcast the specific distance of the target object by voice, and assist the visually impaired in finding the object.

Abstract Aims The benefits of lowering heart rate (HR) in heart failure (HF) with preserved ejection fraction (HFpEF) patients are still a matter of debate. This study aimed to investigate the relationship between changes in HR during hospitalization and cardiovascular (CV) events and all‐cause death in hospitalized HFpEF patients. Methods and results Hospitalized HF patients between January 2017 and December 2021 were consecutively enrolled in a national, multicentred, and prospective registry database, the China Cardiovascular Association Database‐HF Center Registry. HF patients with a left ventricular ejection fraction of ≥50% were defined as HFpEF patients. The study analysed admission/discharge HR, change in HR during hospitalization (∆HR), and ∆HR ratio (∆HR/admission HR). The patients were categorized into three groups: no HR dropping group (ΔHR ratio > 0.0%), moderate HR dropping group (−15%

Abstract Background Exploring the physiological and molecular mechanisms underlying goat sexual maturation can enhance breeding practices and optimize reproductive efficiency and is therefore substantially important for practical breeding purposes. As an essential neuroendocrine organ in animals, the hypothalamus is involved in sexual development and other reproductive processes in female animals. Although microRNAs (miRNAs) have been identified as significant regulators of goat reproduction, there is a lack of research on the molecular regulatory mechanisms of hypothalamic miRNAs that are involved in the sexual development of goats. Therefore, we examined the dynamic changes in serum hormone profiles and hypothalamic miRNA expression profiles at four developmental stages (1 day (neonatal, D1, n = 5), 2 months (prepubertal, M2, n = 5), 4 months (sexual maturity, M4, n = 5), and 6 months (breeding period, M6, n = 5)) during sexual development in Jining grey goats. Results Transcriptome analysis revealed 95 differentially expressed miRNAs (DEMs) in the hypothalamus of goats across the four developmental stages. The target genes of these miRNAs were significantly enriched in the GnRH signalling pathway, the PI3K-Akt signalling pathway, and the Ras signalling pathway (P

Abstract Background The efficiency of controlling nutritional status (CONUT) score in detecting the prognosis of head and neck cancer (HNC) patients has been investigated in some works, but no consistent findings are obtained. Therefore, this work focused on evaluating the precise prognostic role of CONUT for HNC patients through meta-analysis. Methods The effect of CONUT on predicting the prognosis of HNC patients was evaluated through calculating combined hazard ratios (HRs) as well as 95% confidence intervals (CIs). The correlations of CONUT with clinicopathological features of HNC patients were investigated through combined odds ratios (ORs) and 95%CIs. This study used the random-effects model in the case of significant heterogeneity; or else, we selected the fixed-effects model. Results There were eight articles involving 1,478 patients enrolled for the current meta-analysis. We adopted the fixed-effects model for OS and DFS analysis because of the non-significant heterogeneity. As demonstrated by our combined findings, high CONUT score could significantly predict the poor overall survival (OS) (HR = 1.94, 95%CI = 1.55–2.44, p

Abstract Recent studies have highlighted the potential of ferroptosis in treating breast cancer. However, the efficacy of ferroptosis induction in the most common subtype, estrogen receptor-positive (ER + ) breast cancer, remains inadequately explored. This study unveils that both short-term and long-term treatment with ER-targeted endocrine agents sensitizes ER+ breast cancer cells to ferroptosis inducers, particularly the GPX4 inhibitor, revealing a non-mutational sensitization mechanism. Based on this finding, we introduce a 55-gene signature score (FERscore) tailored to assess ferroptosis susceptibility in breast cancer. Data from cell lines and primary tumors demonstrate significant lower FERscores in ER+ breast cancer compared to other subtypes; however, FERscores dramatically increase in endocrine-resistant ER+ tumor cells and residual tumors post-endocrine therapy. Furthermore, FERscore correlates positively with mesenchymal traits, stemness, immune cell infiltration, and cancer-associated fibroblasts enrichment, while inversely correlating with estrogen responsiveness and DNA repair capacity. Additionally, the FERscore proves effective in predicting therapeutic responses to anti-ER, anti-HER2, poly (ADP-ribose) polymerase inhibitor, and anti-angiogenesis therapies in breast cancer. In summary, ferroptosis induction emerges as a promising avenue in breast cancer therapy. The FERscore offers an innovative tool for identifying patients who may benefit from ferroptosis-inducing therapies, especially those responsive to GPX4 inhibitors.

Abstract Objective To explore the effect of Balint Group in improving stress, negative mood and empathy of psychiatric nurses. Method In March 2022-March 2023, 150 psychiatric nurses from four hospitals in Lanzhou were selected for the study, randomly grouped into experimental group and control groups (75 per group), the experimental group participated the Balint Group activities biweekly, the control group only attended mental health knowledge lectures. Job stress, negative emotion and empathy of the two groups before and after the intervention were evaluated and compared by using job stressor Scale, coping style Assessment Scale, self-assessment scale for depression, self-assessment Scale for anxiety and Jefferson Empathy Scale. Results After intervention, the job stressor scale and coping style evaluation of nurses in the two groups were significantly decreased, and the experimental group was lower than the control group (P

Abstract Psoriasis is characterized by keratinocyte (KC) hyperproliferation and inflammatory cell infiltration, but the mechanisms remain unclear. In an imiquimod-induced mouse psoriasiform model, p38 activity is significantly elevated in KCs and p38α specific deletion in KCs ameliorates skin inflammation. p38α signaling promotes KC proliferation and psoriasis-related proinflammatory gene expression during psoriasis development. Mechanistically, p38α enhances KC proliferation and production of inflammatory cytokines and chemokines by activating STAT3. While p38α signaling in KCs does not affect the expression of IL-23 and IL-17, it substantially amplifies the IL-23/IL-17 pathogenic axis in psoriasis. The therapeutic effect of IL-17 neutralization is associated with decreased p38 and STAT3 activities in KCs and targeting the p38α-STAT3 axis in KCs ameliorates the severity of psoriasis. As IL-17 also highly activates p38 and STAT3 in KCs, our findings reveal a sustained signaling circuit important for psoriasis development, highlighting p38α-STAT3 axis as an important target for psoriasis treatment.

Existing studies have evidenced that mobile-assisted vocabulary learning, which allows students to create artefacts and engage in productive skills, can help them in vocabulary learning. However, there remains little research and validated approaches for designing seamless vocabulary learning experiences for young learners. In this paper, a seamless vocabulary learning system was specifically designed for young learners. The study involved three classes of primary 2 students to investigate the learning effectiveness of seamless vocabulary learning, with a focus on analyzing student-generated artefacts. The results validated the effectiveness of seamless vocabulary learning for young learners, emphasizing the importance of strengthening the connection between home-based learning and classroom-based learning. The study also indicated the pivotal role of providing students with opportunities to improve their artefacts constantly across different learning contexts.

Abstract The ovaries and uterus are crucial reproductive organs in mammals, and their coordinated development ensures the normal development of sexual maturity and reproductive capacity. This study aimed to comprehensively capture the different physiological stages of the goat’s sexual maturation by selecting four specific time points. We collected samples of ovarian and uterine tissues from five female Jining Gray goats at each time point: after birth (D1), 2-month-old (M2), 4-month-old (M4), and 6-month-old (M6). By combining transcriptomic sequencing of 40 samples (including rRNA-depleted RNA-seq libraries with 3607.8 million reads and miRNA-seq libraries with 444.0 million reads) and metabolomics analysis, we investigated the transcriptomic mechanisms involved in reproductive regulation in the ovary and uterus during sexual maturation, as well as the changes in metabolites and their functional potential. Additionally, we analyzed blood hormone indices and uterine tissue sections to examine temporal changes. These datasets will provide a valuable reference for the reproductive regulation of the ovary and uterus, as well as the regulation of metabolites during sexual maturation in goats.

Abstract Myelodysplastic syndromes (MDS) are clonal hematopoietic malignancies and seriously threaten people’s health. Current therapies include bone marrow transplantation and several hypomethylating agents. However, many elderly patients cannot benefit from bone marrow transplantation and many patients develop drug resistance to hypomethylating agents, making it urgent to explore novel therapy. RSL3 can effectively induce ferroptosis in various tumors and combination of RSL3 and hypomethylating agents is promising to treat many tumors. However, its effect in MDS was unknown. In this study, we found that RSL3 inhibited MDS cell proliferation through inducing ROS-dependent apoptosis. RSL3 inhibited Bcl-2 expression and increased caspase 3 and PARP cleavage. RNA-seq analysis revealed that MYB may be a potential target of RSL3. Rescue experiments showed that overexpression of MYB can rescue MDS cell proliferation inhibition caused by RSL3. Cellular thermal shift assay showed that RSL3 binds to MYB to exert its function. Furthermore, RSL3 inhibited tumor growth and decreased MYB and Bcl-2 expression in vivo. More importantly, RSL3 decreased the viability of bone marrow mononuclear cells (BMMCs) isolated from MDS patients, and RSL3 had a synergistic effect with DAC in MDS cells. Our studies have uncovered RSL3 as a promising compound and MYB/Bcl-2 signaling pathway as a potential target for MDS treatment.

Abstract Background Ischemic stroke presents a significant threat to human health due to its high disability rate and mortality. Currently, the clinical treatment drug, rt-PA, has a narrow therapeutic window and carries a high risk of bleeding. There is an urgent need to find new effective therapeutic drugs for ischemic stroke. Icariin (ICA), a key ingredient in the traditional Chinese medicine Epimedium, undergoes metabolism in vivo to produce Icaritin (ICT). While ICA has been reported to inhibit neuronal apoptosis after cerebral ischemia-reperfusion (I/R), yet its underlying mechanism remains unclear. Methods PC-12 cells were treated with 200 µM H2O2 for 8 h to establish a vitro model of oxidative damage. After administration of ICT, cell viability was detected by Thiazolyl blue tetrazolium Bromide (MTT) assay, reactive oxygen species (ROS) and apoptosis level, mPTP status and mitochondrial membrane potential (MMP) were detected by flow cytometry and immunofluorescence. Apoptosis and mitochondrial permeability transition pore (mPTP) related proteins were assessed by Western blotting. Middle cerebral artery occlusion (MCAO) model was used to establish I/R injury in vivo. After the treatment of ICA, the neurological function was scored by ZeaLonga socres; the infarct volume was observed by 2,3,5-Triphenyltetrazolium chloride (TTC) staining; HE and Nissl staining were used to detect the pathological state of the ischemic cortex; the expression changes of mPTP and apoptosis related proteins were detected by Western blotting. Results In vitro: ICT effectively improved H2O2-induced oxidative injury through decreasing the ROS level, inhibiting mPTP opening and apoptosis. In addition, the protective effects of ICT were not enhanced when it was co-treated with mPTP inhibitor Cyclosporin A (CsA), but reversed when combined with mPTP activator Lonidamine (LND). In vivo: Rats after MCAO shown cortical infarct volume of 32–40%, severe neurological impairment, while mPTP opening and apoptosis were obviously increased. Those damage caused was improved by the administration of ICA and CsA. Conclusions ICA improves cerebral ischemia-reperfusion injury by inhibiting mPTP opening, making it a potential candidate drug for the treatment of ischemic stroke. Graphical Abstract

Studies on epistemic beliefs in L2 research are in a nascent stage. Acknowledging deeply rooted and complex intersections between prevalent cultural norms within a society, individually held beliefs, and mutually shared opinions among members of a social group, this Q methodological study explored Chinese university students’ rationales for holding particular language-related epistemic beliefs. Twenty students learning English as a foreign language participated in post Q-sorting interviews, where they explained the rationales for holding certain sets of beliefs about knowing and learning the English language. We analyzed the data using Card Content Analysis (CCA), a particularly suitable approach for the Q methodology. The findings revealed that the students held fairly sophisticated epistemic beliefs, and these beliefs were culturally rooted. The students placed a high premium on making a conscientious effort to learn English; they prioritized commitment and perseverance over having a special talent for learning languages. The respondents also believed that English, as any language, is evolving over time. Notably, while respecting their language instructors, the students realized that teachers, or even people for whom English is the mother tongue, might occasionally make linguistic errors. Several students stated that there are many sources from which one can learn English, and they also asserted the importance of being able to gage the veracity of the linguistic information one receives. The article concludes by drawing some pedagogical implications.

The phyllospheric microbial composition of tobacco plants is influenced by multiple factors. Disease severity level is one of the main influencing factors. This study was designed to understand the microbial community in tobacco wildfire disease with different disease severity levels. Tobacco leaves at disease severity level of 1, 5, 7, and 9 (L1, L5, L7, and L9) were collected; both healthy and diseased leaf tissues for each level were collected. The community structure and diversity in tobacco leaves with different disease severity levels were compared using high-throughput technique and Biolog Eco. The results showed that in all healthy and diseased tobacco leaves, the most dominant bacterial phylum was Proteobacteria with a high prevalence of genus Pseudomonas; the relative abundance of Pseudomonas was most found at B9 diseased samples. Ascomycota represents the most prominent fungal phylum, with Blastobotrys as the predominant genus. In bacterial communities, the Alpha diversity of healthy samples was higher than that of diseased samples. In fungal community, the difference in Alpha diversity between healthy and diseased was not significant. LEfSe analysis showed that the most enriched bacterial biomarker was unclassified_Gammaproteobacteria in diseased samples; unclassified_Alcaligenaceae were the most enrich bacterial biomarker in healthy samples. FUNGuild analysis showed that saprotroph was the dominated mode in health and lower diseased samples, The abundance of pathotroph–saprotroph and pathotroph–saprotroph–symbiotroph increases at high disease levels. PICRUSt analysis showed that the predominant pathway was metabolism function, and most bacterial gene sequences seem to be independent of the disease severity level. The Biolog Eco results showed that the utilization rates of carbon sources decrease with increasing disease severity level. The current study revealed the microbial community’s characteristic of tobacco wildfire disease with different disease severity levels, providing scientific references for the control of tobacco wildfire disease.

Ovalbumin (OVA) is the primary allergenic protein, associated with T helper 2 (Th2)-mediated allergy reactions. Here, we studied OVA’s conformational structure, digestibility, and allergenic potency upon galactomannan (Man) conjugation along with transglutaminase-catalyzed crosslinking (TG-Man/OVA) and tyrosinase/caffeic acid-catalyzed crosslinking (Tyr-Man/OVA). Enzymatic glycosylation altered OVA’s conformation and enhanced the gastrointestinal digestibility. Stimulation of bone marrow-derived dendritic cells (BMDCs) with enzymatically glycosylated OVA reduced the expression of CD40, CD80, CD86 and MHC class II molecules. Furthermore, glycosylated OVA increased IL-10 production while suppressing proinflammatory cytokine production in BMDCs. In an OVA-induced mouse asthma model, TG-Man/OVA and Tyr-Man/OVA upregulated IFN-γ and IL-10 expression and downregulated IL-4, IL-5, and IL-13 in lungs. Crosslinked OVA diminished infiltrated cells in bronchoalveolar lavage fluid and lung and attenuated eosinophilic airway inflammation. These findings offer valuable insights into the development of a novel product with improved hypoallergenic and immunomodulatory properties and hold promise in attenuating allergic diseases.

Chronic hepatitis B virus (HBV) infection is a leading cause of liver cirrhosis and hepatocellular carcinoma, representing a global health problem for which a functional cure is difficult to achieve. The HBV core protein (HBc) is essential for multiple steps in the viral life cycle. It is the building block of the nucleocapsid in which viral DNA reverse transcription occurs, and its mediation role in viral-host cell interactions is critical to HBV infection persistence. However, systematic studies targeting HBc-interacting proteins remain lacking. Here, we combined HBc with the APEX2 to systematically identify HBc-related host proteins in living cells. Using functional screening, we confirmed that proteasome activator subunit 1 (PSME1) is a potent HBV-associated host factor. PSME1 expression was up-regulated upon HBV infection, and the protein level of HBc decreased after PSME1 knockdown. Mechanistically, the interaction between PSME1 and HBc inhibited the degradation of HBc by the 26S proteasome, thereby improving the stability of the HBc protein. Furthermore, PSME1 silencing inhibits HBV transcription in the HBV infection system. Our findings reveal an important mechanism by which PSME1 regulates HBc proteins and may facilitate the development of new antiviral therapies targeting PSME1 function.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1’s molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotransferase, CHAC1 degrades glutathione, affecting calcium signaling and mitochondrial function. Its regulation involves transcription factors like ATF4 and ATF3, which control CHAC1 mRNA expression. CHAC1 is crucial for maintaining redox balance and regulating cell death pathways in cancer. Its elevated levels are associated with poor prognosis in many cancers, indicating its potential as a biomarker and therapeutic target. Additionally, CHAC1 influences non-cancerous diseases such as neurodegenerative and cardiovascular disorders. Therapeutically, targeting CHAC1 could increase cancer cell sensitivity to ferroptosis, aiding in overcoming resistance to standard treatments. This review compiles current knowledge and recent discoveries, emphasizing CHAC1’s vital role in human diseases and its potential in diagnostic and therapeutic applications.

Streptococcus pneumoniae is a pathogenic bacterium that causes infections such as pneumonia, meningitis, otitis media, and bacteremia. The prevention of pneumococcal disease by vaccination has become more urgent due to increased antibiotic resistance. Pneumococcal capsular polysaccharides (CPS) are effective vaccine antigens that stimulate the host to produce protective antibodies. S. pneumoniae serotype 14 is one of most prevalent types in Latin America and across the world. However, the yield of S. pneumoniae serotype 14 CPS from existing fermentation processes remains low and requires improvement. In this study, various aspects of the fermentation process were optimized to improve pneumococcal growth and polysaccharide productivity, including feed medium, cultivation gas environment, fermentation pH, and temperature. A simplified purification method was also developed to obtain pure CPS, including ultrafiltration, acid and ethanol precipitation, diafiltration, and lyophilization. These fermentation optimizations significantly enhanced the optical density of pneumococcal bacterial cultures and increased fermentation yields to 2.4–2.6 g/L—significantly higher than previously achieved. Furthermore, the test results of pure CPS could meet the requirements in the European Pharmacopoeia (11th edition). These optimizations provide valuable insights into the nutritional requirements and impact of varying fermentation process parameters on pneumococcal growth and CPS productivity, thus contributing to the development of a more efficient and cost-effective method for the production of pneumococcal CPS—essential for manufacturing vaccines against pneumococcal infections.

Abstract Oligodendrocyte precursor cells (OPCs) migrate extensively using blood vessels as physical scaffolds in the developing central nervous system. Although the association of OPCs with the vasculature is critical for migration, the regulatory mechanisms important for OPCs proliferative and oligodendrocyte development are unknown. Here, a correlation is demonstrated between the developing vasculature and OPCs response during brain development. Deletion of endothelial stimulator of interferon genes (STING) disrupts angiogenesis by inhibiting farnesyl‐diphosphate farnesyltransferase 1 (FDFT1) and thereby reducing cholesterol synthesis. Furthermore, the perturbation of metabolic homeostasis in endothelial cells increases interleukin 17D production which mediates the signal transduction from endothelial cells to OPCs, which inhibits oligodendrocyte development and myelination and causes behavioral abnormalities in adult mice. Overall, these findings indicate how the endothelial STING maintains metabolic homeostasis and contributes to oligodendrocyte precursor cells response in the developing neocortex.

Increasing the energy efficiency of existing buildings is the major strategy to reach carbon neutral targets, given that the building sector is a major emitter. In particular, one major part of building energy usage is the building heating, ventilation and air-cooling system, which are highly depending on the thermal performance of building envelope and increase the challenge of selecting optimal packages of energy efficiency measures. This paper thereby presents a method for optimizing the building envelope and heating, ventilation and air-cooling system. The simulation-based NSGA-III approach developed in this paper is based on coupling the dynamic simulation models created in EnergyPlus software with the non-dominated sorting genetic algorithm, as the engine that performs an optimization process. A large domain of energy efficiency packages combined with heating, ventilation and air-cooling systems and building envelope are investigated to minimize energy consumption, retrofit cost and thermal discomfort in indoor environments, which including ideal loads air system, four pipe fan coil system and variable refrigerant flow system, insulation materials and insulation thickness for external walls and roof, different types of external windows, and window-wall ratio. An office building in Chongqing was chosen as a case study to demonstrate the practical implementation of the proposed method. The results show that the four pipe fan coil system was superior in the diversity and performance of the Pareto front. Then, the optimal packages were generated by a synthetic method, which have 58.57 kWh/m2 of energy consumption, 30.76 CNY/m2 of retrofit cost and 40.67 % of the percentage of thermal discomfort hours. The results also indicate that the yearly energy savings rates are 17.30 %, 23.05 % and 21.10 % separately for ideal loads air system, four pipe fan coil system and variable refrigerant flow system after performing optimization. These results highlight the importance and necessity of performing an optimization procedure for existing buildings to select the optimal retrofit measures.

Theanine (N-ethyl-γ-glutamine), as a unique non-protein amino acid, plays vital roles in abiotic stress resistance, while its roles in biotic stress resistance are still unclear. Gray mold caused by Botrytis cinerea is a major disease in strawberries. Effects of theanine on the development of gray mold, cell-wall and phenylpropanoid metabolisms in strawberries were investigated in this study. Results showed that 5 mmol L−1 theanine treatment reduced disease incidence and severity of gray mold in strawberries with antifungal activity in vitro. Meanwhile, theanine treatment enhanced the accumulation of phenolic compounds and lignin, especially ellagic acid, cyanidin, and quercetin, which was associated with increased phenylpropanoid pathway related enzyme activities. Moreover, theanine induced callose deposition and suppressed cell- wall disassembling enzymes, accompanied by higher levels of water insoluble pectin, hemicellulose and cellulose. Therefore, theanine treatment could alleviate decay of B. cinerea-inoculated strawberries by regulating phenylpropanoid and cell-wall metabolisms, maintaining higher levels of phenolic compounds and cell-wall components, thereby contributing to disease resistance and cell-wall structure integrity.

Abstract The abundant genetic variation harbored by wild rice (Oryza rufipogon) has provided a reservoir of useful genes for rice breeding. However, the genome of wild rice has not yet been comprehensively assessed. Here, we report the haplotype-resolved gapless genome assembly and annotation of wild rice Y476. In addition, we develop two sets of chromosome segment substitution lines (CSSLs) using Y476 as the donor parent and cultivated rice as the recurrent parents. By analyzing the gapless reference genome and CSSL population, we identify 254 QTLs associated with agronomic traits, biotic and abiotic stresses. We clone a receptor-like kinase gene associated with rice blast resistance and confirm its wild rice allele improves rice blast resistance. Collectively, our study provides a haplotype-resolved gapless reference genome and demonstrates a highly efficient platform for gene identification from wild rice.

Abstract In recent years, knowledge graph technology has been widely applied in various fields such as intelligent auditing, urban transportation planning, legal research, and financial analysis. In traditional auditing methods, there are inefficiencies in data integration and analysis, making it difficult to achieve deep correlation analysis and risk identification among data. Additionally, decision support systems in the auditing process may face issues of insufficient information interpretability and limited predictive capability, thus affecting the quality of auditing and the scientificity of decision-making. However, knowledge graphs, by constructing rich networks of entity relationships, provide deep knowledge support for areas such as intelligent search, recommendation systems, and semantic understanding, significantly improving the accuracy and efficiency of information processing. This presents new opportunities to address the challenges of traditional auditing techniques. In this paper, we investigate the integration of intelligent auditing and knowledge graphs, focusing on the application of knowledge graph technology in auditing work for power engineering projects. We particularly emphasize mainstream key technologies of knowledge graphs, such as data extraction, knowledge fusion, and knowledge graph reasoning. We also introduce the application of knowledge graph technology in intelligent auditing, such as improving auditing efficiency and identifying auditing risks. Furthermore, considering the environment of cloud-edge collaboration to reduce computing latency, knowledge graphs can also play an important role in intelligent auditing. By integrating knowledge graph technology with cloud-edge collaboration, distributed computing and data processing can be achieved, reducing computing latency and improving the response speed and efficiency of intelligent auditing systems. Finally, we summarize the current research status, outlining the challenges faced by knowledge graph technology in the field of intelligent auditing, such as scalability and security. At the same time, we elaborate on the future development trends and opportunities of knowledge graphs in intelligent auditing.

Abstract In response to the low real-time performance and accuracy of traditional sports injury monitoring, this article conducts research on a real-time injury monitoring system using the SVM model as an example. Video detection is performed to capture human movements, followed by human joint detection. Polynomial fitting analysis is used to extract joint motion patterns, and the average of training data is calculated as a reference point. The raw data is then normalized to adjust position and direction, and dimensionality reduction is achieved through singular value decomposition to enhance processing efficiency and model training speed. A support vector machine classifier is used to classify and identify the processed data. The experimental section monitors sports injuries and investigates the accuracy of the system’s monitoring. Compared to mainstream models such as Random Forest and Naive Bayes, the SVM utilized demonstrates good performance in accuracy, sensitivity, and specificity, reaching 94.2%, 92.5%, and 96.0% respectively.

Objective: We aimed to systematically evaluate the efficacy and safety of bone marrow mesenchymal stem cells (BMMSCs) in the treatment of ischemic stroke. Methods: Six Chinese and English databases were searched for related randomized controlled trials from the establishment of the databases to 28 February 2023. Two investigators performed screening and a comprehensive analysis and evaluated the quality of the studies. They extracted information from the included studies, and managed and analzsed the data using RevMan 5.4.1 software (The First College of Clinical Medical Science, China Three Gorges University). Finally, they performed meta and heterogeneity analyses and created a risk-of-bias map. Results: A total of 13 high-quality articles were included. The National Institute of Health Stroke Scale (NIHSS) scores of the experimental group differed significantly from those of the control group at 3 months (I2 50%, MD = 15.94, P < 0.001), 3 months (I2 >50%, MD = 12.71, P < 0.001), and 6 months (I2 >50%, MD = 13.76, P < 0.001) after treatment, and the overall difference (I2 >50%, MD = 14.38, P ≤ 0.001) was significant. The functional independence measure (FIM) scores were significantly different from that of the control group at 1 month (I2 >50%, MD = 20.04, P = 0.02), 3 months (I2 >50%, MD = 15.51, P < 0.001), and 6 months (I2 >50%, MD = 13.46, P = 0.03). There was no significant increase in adverse events compared with the traditional treatment regimen. Conclusion: To some extent, BMMSC transplantation can improve the neurological deficit, motor function, and daily living ability of patients with ischemic stroke.

Abstract. Diabetic cardiomyopathy is defined as abnormal structure and function of the heart in the setting of diabetes, which could eventually develop heart failure and leads to the death of the patients. Although blood glucose control and medications to heart failure show beneficial effects on this disease, there is currently no specific treatment for diabetic cardiomyopathy. Over the past few decades, the pathophysiology of diabetic cardiomyopathy has been extensively studied, and an increasing number of studies pinpoint that impaired mitochondrial energy metabolism is a key mediator as well as a therapeutic target. In this review, we summarize the latest research in the field of diabetic cardiomyopathy, focusing on mitochondrial damage and adaptation, altered energy substrates, and potential therapeutic targets. A better understanding of the mitochondrial energy metabolism in diabetic cardiomyopathy may help to gain more mechanistic insights and generate more precise mitochondria-oriented therapies to treat this disease.

Abstract Angelman syndrome (AS) is a neurodevelopmental disorder caused by abnormal expression of the maternal ubiquitin protein ligase E3A gene (UBE3A). As one of the most challenging symptoms and important focuses of new treatment, sleep disturbance is reported to occur in 70–80% of patients with AS and has a serious impact on the lives of patients and their families. Although clinical studies and animal model studies have provided some clues, recent research into sleep disorders in the context of AS is still very limited. It is generally accepted that there is an interaction between neurodevelopment and sleep; however, there is no recognized mechanism for sleep disorders in AS patients. Accordingly, there are no aetiologically specific clinical treatments for AS-related sleep disorders. The most common approaches involve ameliorating symptoms through methods such as behavioural therapy and symptomatic pharmacotherapy. In recent years, preclinical and clinical studies on the targeted treatment of AS have emerged. Although precision therapy for restoring the UBE3A level and the function of its signalling pathways is inevitably hindered by many remaining obstacles, this approach has the potential to address AS-related sleep disturbance.

Abstract Goats can provide meat, milk and skins for humans and are livestock with high economic benefits. However, despite their economic significance, the comprehensive analysis of goats’ serum metabolic profile and its intricate alterations throughout their developmental journey remains conspicuously absent. To investigate the stage-specificity and dynamic change characteristics of metabolites during the growth and development of goats, this study compared the alterations in serum hormone levels and serum biochemical markers across different developmental stages of female goats (1, 60, 120 and 180 days old; n = 5). Additionally, a serum untargeted LC–MS metabolomics analysis was conducted. A total of 504 DAMs were identified with age. The results indicated that PE, PC, Lyso-PE, Lyso-PC and FAFHA may play important roles in lipid metabolism in goats after birth. Weighted gene co-expression network analysis (WGCNA) identified two metabolite modules (Turquoise and Yellow) and key metabolites within these modules that were significantly associated with phenotypic features. l-carnitine may be a metabolite related to muscle development in goats. The findings of this study demonstrate notable variations in serum metabolites across distinct developmental phases in goats. Lipids and organic acids play important roles in different developmental stages of goats.

Abstract Due to continuing mining activities, Cd(II) and As(III) contamination in acid mine drainage (AMD) has become a major environmental challenge. Currently, there is increasing focus on the use of biochar to mitigate AMD pollution. However, the impact of biochar on the process of Fe(II) oxidation by Acidithiobacillus ferrooxidans (A. ferrooxidans) in AMD systems has not been determined. In this study, we investigated the effects of introducing biochar and biochar-leachate on Fe(II) biooxidation by A. ferrooxidans and on the removal of Cd(II) and As(III) from an AMD system. The results showed that the biochar-leachate had a promoting effect on Fe(II) biooxidation by A. ferrooxidans. Conversely, biochar inhibited this process, and the inhibition increased with increasing biochar dose. Under both conditions (c(A. ferrooxidans) = 1.4 × 107 copies mL–1, m(FeSO4·7H2O):m(biochar) = 20:1; c(A. ferrooxidans) = 7.0 × 107 copies mL–1, m(FeSO4·7H2O):m(biochar) = 5:1), the biooxidation capacity of A. ferrooxidans was severely inhibited, with Fe(II) oxidation efficiency reaching a value of only ~ 20% after 84 h. The results confirmed that this inhibition might have occurred because a large fraction of the A. ferrooxidans present in the system adsorbed to the biochar, which weakened bacterial activity. In addition, mineral characterization analysis showed that the introduction of biochar changed the A. ferrooxidans biooxidation products from schwertmannite to jarosite, and the specific surface area increased after the minerals combined with biochar. Coprecipitation experiments of As(III) and Cd(II) showed that Cd(II) was adsorbed by the biochar over the first 12 h of reaction, with a removal efficiency of ~ 26%. As(III) was adsorbed by the generated schwertmannite over 24 h, with a removal efficiency of ~ 100%. These findings have positive implications for the removal of As(III) and Cd(II) from AMD. Graphical Abstract

Metasurface significantly enriches the light-matter interaction and promotes the development of planar optics. In recent years, with the rapid advancements of terahertz (THz) technology, THz devices with switchable and reconfigurable functions have been intensively pursued. Liquid crystal (LC), a unique soft matter that combines the fluidity of liquids and the order of crystals, is now indispensable in displays and spatial light modulations. LC is integrated with metasurfaces to realize dynamic THz devices and apparatuses as well. This review summarizes the research progress in LC based THz metadevices in three different respects: LC planar THz devices, LC integrated metal metasurfaces, and LC integrated dielectric metasurfaces. Various technologies for fabrications of LC microstructures and integrations of LCs with metal or dielectric metasurfaces are presented. The obtained LC metadevices exhibit excellent responsiveness to external stimulus such as electric fields, magnetic fields, heat, and light. By this means, the amplitude, frequency, phase as well as polarization of THz waves are dynamically manipulated. The LC based tunable THz metadevices will significantly improve THz applications in imaging, communication, and sensing.

BackgroundQianggu Concentrate (QGHJ), a traditional Chinese medicine, is extensively used to treat Type 2 Diabetic Osteoporosis (T2DOP). Despite its widespread use, research on its therapeutic mechanisms within T2DOP is notably scarce.ObjectiveTo explore QGHJ’s osteoprotection in T2DOP rats and BMSCs, focusing on the antioxidant activation of SIRT1/NRF2/HO-1 and NRF2 nuclear migration.MethodsQGHJ constituent analysis was performed using UPLC-HRMS. Safety, bone-health efficacy, and glucose metabolic effects in T2DOP rats were evaluated via general condition assessments, biomarker profiling, micro-CT, biomechanics, staining methods, and ELISA, supplemented by RT-qPCR and Western blot. BMSCs’ responses to QGHJ under oxidative stress, including viability, apoptosis, and osteogenic differentiation, were determined using CCK-8, flow cytometry, ALP/ARS staining, and molecular techniques. The modulation of the SIRT1/NRF2/HO-1 pathway by QGHJ was explored through oxidative stress biomarkers, immunofluorescence, and Western blot assays.ResultsUPLC-HRMS identified flavonoids, monoterpenes, and isoflavones as QGHJ’s key compounds. In vivo, QGHJ proved safe and effective for T2DOP rats, enhancing bone mineral density, microenvironment, and biomechanical properties without impairing vital organs. It modulated bone markers PINP, TRACP 5b, RUNX2 and PPARγ, favoring bone anabolism and reduced catabolism, thus optimizing bone integrity. QGHJ also regulated glycemia and mitigated insulin resistance. In vitro, it preserved BMSCs’ viability amidst oxidative stress, curbed apoptosis, and fostered osteogenesis with regulated RUNX2/PPARγ expression. Mechanistic insights revealed QGHJ activated the SIRT1/NRF2/HO-1 pathway, augmented NRF2 nuclear translocation, and enhanced the antioxidative response, promoting bone health under stress.ConclusionIn T2DOP rat and BMSCs oxidative stress models, QGHJ’s bone protection is anchored in its antioxidative mechanisms via the SIRT1/NRF2/HO-1 pathway activation and NRF2 nuclear translocation.

Under the sufficient nitrogen supply, it is of great significance to investigate the law of biomass allocation, root morphological traits, and the salt absorption capacity of euhalophytes to evaluate their biological desalination in saline soil. Although the curvilinear responses of biomass accumulation and root morphology in response to soil salinity have been recognized, these perceptions are still confined to the descriptions of inter-treatment population changes and lack details on biomass allocation in organs at an individual level. In this study, Suaeda salsa was grown in root boxes across a range of soil salt levels. The study showed that their growth and development were significantly affected by soil soluble salts. The law of biomass allocation was described as follows: increased soil soluble salts significantly increased the leaf mass ratio and decreased the stem mass ratio, and slightly increased the root mass ratio among treatments. For individuals at each treatment, leaf mass ratio > stem mass ratio > root mass ratio, except in the control treatment at the flower bud and fruit stages. Biomass responses of the control treatment indicated that salt was not rigorously required for Suaeda salsa in the presence of an adequate nitrogen supply, as verified by the correlation between biomass, nitrogen, and soil soluble salt. Salt could significantly inhibit the growth of Suaeda salsa (P

Abstract Energy loss in perovskite grain boundaries (GBs) is a primary limitation toward high‐efficiency perovskite solar cells (PSCs). Two critical strategies to address this issue are high‐quality crystallization and passivation of GBs. However, the established methods are generally carried out discretely due to the complicated mechanisms of grain growth and defect formation. In this study, a combined method is proposed by introducing 3,4,5‐Trifluoroaniline iodide (TFAI) into the perovskite precursor. The TFAI triggers the union of nano‐sized colloids into microclusters and facilitates the complete phase transition of α‐FAPbI3 at room temperature. The controlled chemical reactivity and strong steric hindrance effect enable the fixed location of TFAI and suppress defects at GBs. This combination of well‐crystallized perovskite grains and effectively passivated GBs leads to an improvement in the open circuit voltage (Voc) of PSCs from 1.08 V to 1.17 V, which is one of the highest recorded Voc without interface modification. The TFAI‐incorporated device achieved a champion PCE of 24.81%. The device maintained a steady power output near its maximum power output point, showing almost no decay over 280 h testing without pre‐processing.

The hypothalamus is an essential neuroendocrine area in animals that regulates sexual development. Long non-coding RNAs (lncRNAs) are hypothesized to regulate physiological processes related to animal reproduction. However, the regulatory mechanism by which lncRNAs participate in sexual maturity in goats is poorly known, particularly from birth to sexual maturation. In this study, RNAseq analysis was conducted on the hypothalamus of four developmental stages (1day (D1, n = 5), 2 months (M2, n = 5), 4 months (M4, n = 5), and 6 months (M6, n = 5)) of Jining grey goats. The results showed that a total of 237 differentially expressed lncRNAs (DELs) were identified in the hypothalamus. Among these, 221 DELs exhibited cis-regulatory effects on 693 target genes, while 24 DELs demonstrated trans-regulatory effects on 63 target genes. The target genes of these DELs are mainly involved in biological processes related to energy metabolism, signal transduction and hormone secretion, such as sphingolipid signaling pathway, adipocytokine signaling pathway, neurotrophic signaling pathway, glutamatergic synapse, P53 signaling pathway and GnRH signaling pathway. In addition, XR_001918477.1, TCONS_00077463, XR_001918760.1, and TCONS_00029048 and their potential target genes may play a crucial role in the process of goat sexual maturation. This study advances our understanding of lncRNA in hypothalamic tissue during sexual maturation in goats and will give a theoretical foundation for improving goat reproductive features.

Objectives The relationship between Ki-67 expression and the prognosis of patients with oesophageal squamous cell carcinoma (ESCC) has been extensively studied. However, their findings were inconsistent. Consequently, the present meta-analysis was performed to identify the precise value of Ki-67 in predicting the prognosis of ESCC.Design The current meta-analysis was carried out in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses.Data sources Electronic databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched until 26 September 2023.Statistical methods Pooled HRs and corresponding 95% CIs were calculated to estimate the role of Ki-67 in predicting overall survival (OS) and disease-free survival (DFS) in ESCC. Between-study heterogeneity was evaluated using Cochrane’s Q test and I2 statistics. Specifically, significant heterogeneities were identified based on p50% so the random-effects model should be used; otherwise, the fixed-effects model should be used. The relationship between Ki-67 and clinicopathological characteristics of ESCC was evaluated by combining ORs with their corresponding 95% CIs.Results 11 articles with 1124 patients were included in the present meta-analysis. Based on our analysis, increased Ki-67 expression was markedly associated with poor OS (HR 1.62, 95% CI 1.15 to 2.28, p=0.006) and DFS (HR 1.72, 95% CI 1.22 to 2.43, p=0.002) in ESCC. Moreover, subgroup analysis revealed that Ki-67 upregulation significantly predicted OS and DFS when a Ki-67 threshold of >30% was used. Nonetheless, Ki-67 was not significantly associated with sex, T stage, N stage, TNM stage, tumour differentiation or tumour location.Conclusions In the present meta-analysis, high Ki-67 expression significantly predicted OS and DFS in patients with ESCC, especially when Ki-67>30% was used as the threshold. These results suggest that Ki-67 could serve as an effective and reliable prognostic indicator for ESCC.

Ideally, optimal emergency resource allocation would have been vital for effective relief work during the COVID-19 outbreak. However, the suddenness of the epidemic and uncertainty of its spread added some difficulties to distributing emergency resources. First, this study introduces triangular fuzzy numbers to describe the uncertainty of supply and demand of emergency resources, and interval numbers to describe the time required for resource transportation under disaster conditions. To minimize the total delivery time and difference in the total satisfaction rate, this study constructs an optimal model for emergency resource distribution under uncertain conditions that considers both efficiency and equity. Subsequently, an improved genetic algorithm (IMGA) is proposed to obtain the optimal decision scheme. Finally, a case study on emergency resource distribution during the COVID-19 pandemic is conducted for model verification. The results demonstrate that the proposed model can improve the efficiency and effect of emergency resource distribution. The model allocates some emergency resources to each demand site during each emergency period, which can help avoid large losses caused by extreme shortages of resources at a certain demand point. The emergency resource allocation scheme considers the transportation time and degree of impact, which is beneficial for enhancing the flexibility of decision-making and practical applicability of distribution operations. A comparative analysis of the algorithms shows that the proposed IMGA is an effective method for managing emergency resource distribution optimization problems because it has higher solving efficiency, better convergence, and stronger stability. These findings can provide decision support for the optimal distribution of large-scale, multiperiod emergency resources during the COVID-19 pandemic.

This study investigates the valuation and real effects of the mandatory disclosure of greenhouse gas (GHG) emission costs from the perspective of “double materiality.” We consider a firm with a Cobb-Douglas production function that combines GHG-related and non-GHG-related investments to produce short-term and long-term returns. In particular, the GHG-related investment entails short-term and long-term social costs of GHG emissions, including corporate costs and negative externalities. We demonstrate how the mandatory disclosure of the long-term costs of GHG emissions affects capital market valuations and corporate investment decisions relative to a non-disclosure regime. The social welfare in an accounting regime hinges on three parameters: the persistence of the short-term investment return, the ratio of the productivity of GHG-related investment to that of non-GHG-related investment, and the social cost parameter for GHG emissions. Our findings suggest that disclosing the long-term costs of GHG emissions may be detrimental to social welfare. Specifically, the non-disclosure regime results in higher social welfare than the disclosure regime for high values of these parameters.

Pepper (Capsicum spp.) belongs to the genus Capsicum in the Solanaceae family and is widely cultivated around the world as a vegetable and spice crop. In addition to its application as a cooking ingredient and spice, pepper also has a wide range of uses in the pharmaceutical and cosmetic fields. Carotenoids are a class of natural pigments involved in many important metabolic processes in plants, such as photosynthesis, photoprotection, photomorphogenesis and growth and development. Carotenoid is one of the main nutrients of pepper fruit, which has various biological activities. To cultivate varieties with higher carotenoid content, it is necessary to understand its biosynthesis and molecular mechanism of regulation. The development of molecular biology and biotechnology has promoted the identification of carotenoid biosynthesis genes, providing opportunities for breeding new varieties of pepper with higher carotenoid content. In this review, the physiological role of carotenoid, carotenoid and pepper fruit color, carotenoid biosynthesis pathway, structural genes and regulatory factors of carotenoid biosynthesis pathway, molecular genetics of pepper fruit color and QTL sites related to pepper fruit color are described. GGPS, PSY, PDS, ZDS, LCY, CCS are port enzymes and rate-limiting enzymes in the carotenoid biosynthesis pathway of pepper, and the expression abundance and activity of them directly regulate the carotenoid content in pepper. Transcription factors such as MYB306, DIVARICATA1 and BBX20 are involved in the regulation of carotenoid biosynthesis in pepper. The diversity of carotenoid biosynthesis and regulatory genes determines the amount and content of carotenoid monomer and affects the color of pepper fruit. Based on the current research progress, future research on carotenoid metabolism of pepper is prospected in order to provide new ideas for breeding new varieties of biofortified pepper rich in carotenoids in the future.

Abstract The scientific allocation of emergency resources is crucial to ensure the success of COVID-19 relief operations. However, the heterogeneity of epidemic areas has an important impact on the allocation of emergency resources. Although it is a crucial topic, there has been limited research that considers the heterogeneity of affected areas in the emergency resource allocation. To bridge the gap, this study proposes a multi-period optimal allocation model of emergency resources considering the heterogeneity of affected areas, which aims to make the allocation of resources more equitable, efficient and economical. Then, a typical and representative case of emergency medical resource allocation in Hubei Province, China (where the epidemic occurred earlier and was seriously affected by COVID-19), was selected for a simulation study to verify the effectiveness and feasibility of the proposed model and method. The study finds that considering the heterogeneity such as disaster coefficient and demand urgency in different disaster stricken areas in emergency resource allocation can minimize the negative impact of resource shortfalls, especially in the early period of relief operations with insufficient resource supply. In addition, the proposed model can optimize multi-period emergency resource allocation by simultaneously considering time (efficiency criterion), cost (economic criterion), and loss(equity criterion), which is in line with the actual needs of emergency rescue to the COVID-19 epidemic. The results of this study can be effectively applied to the multi-period optimal allocation of emergency resources for large-scale public health emergencies, and providing insights for the government and relevant management departments to formulate emergency resource allocation policies and plans.

Abstract The paper proposes a SOC (State of Charge) estimation method for lead–carbon batteries based on the GA-MIUKF algorithm. The GA-MIUKF algorithm combines GA (Genetic Algorithm) for global search and optimization with the MI-UKF (Multi-innovation Unscented Kalman Filter) algorithm for estimating the SOC of lead–carbon batteries. By establishing an equivalent circuit model for the battery, the GA is employed to globally search and optimize the battery model parameters and the noise variance parameters in the MI-UKF algorithm. Comparative analyses with the UKF (Unscented Kalman Filter) algorithms and MI-UKF algorithms reveal that the SOC estimation method based on the GA-MIUKF algorithm yields more accurate results for lead–carbon battery SOC estimation, with an average estimation error of 2.0%. This highlights the efficacy of the proposed approach in enhancing SOC estimation precision.

Abstract Background Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of heart failure cases. The molecular mechanisms by which HFpEF leads to impaired diastolic function of the heart have not been clarified, nor have the drugs that target the clinical symptoms of HFpEF patients. Methods HFpEF chip data (GSE180065) was downloaded from the National Center for Biotechnology Information (NCBI) database. Differentially expressed genes (DEGs) were filtered by the limma package in R and processed for GO and KEGG pathway analyses. Then, ferroptosis-related genes in HFpEF were identified by taking the intersection between DEGs and ferroptosis-related genes. CytoHubba and MCODE were used to screen ferroptosis-related hub DEGs in the protein–protein interaction (PPI) network. Establishment of a mouse HFpEF model to validate the transcript levels of ferroptosis-related hub DEGs and ferroptosis-related phenotypes. Transcript levels of ferroptosis-related hub DEGs and HFpEF phenotypic changes in the hearts of HFpEF mice were further examined after the use of ferroptosis inhibitors. Results GO and KEGG enrichment analyses suggested that the DEGs in HFpEF were significantly enriched in ferroptosis-related pathways. A total of 24 ferroptosis-related DEGs were identified between the ferroptosis gene dataset and the DEGs. The established PPI network was further analyzed by CytoHubba and MCODE modules, and 11 ferroptosis-related hub DEGs in HFpEF were obtained. In animal experiments, HFpEF mice showed significant abnormal activation of ferroptosis. The expression trends of the 11 hub DEGs associated with ferroptosis, except for Cdh1, were consistent with the results of the bioinformatics analysis. Inhibition of ferroptosis alters the transcript levels of 11 ferroptosis-related hub DEGs and ameliorates HFpEF phenotypes. Conclusions The present study contributes to a deeper understanding of the specific mechanisms by which ferroptosis is involved in the development of HFpEF and suggests that inhibition of ferroptosis may mitigate the progression of HFpEF. In addition, eleven hub genes were recognized as potential drug binding targets.

Abstract Background and aims Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by progressive biliary inflammation and bile duct injury. Berberine (BBR) is a bioactive isoquinoline alkaloid found in various herbs and has multiple beneficial effects on metabolic and inflammatory diseases, including liver diseases. This study aimed to examine the therapeutic effect of BBR on cholestatic liver injury in a PSC mouse model (Mdr2−/− mice) and elucidate the underlying mechanisms. Methods Mdr2−/−mice (12–14 weeks old, both sexes) received either BBR (50 mg/kg) or control solution daily for eight weeks via oral gavage. Histological and serum biochemical analyses were used to assess fibrotic liver injury severity. Total RNAseq and pathway analyses were used to identify the potential signaling pathways modulated by BBR in the liver. The expression levels of key genes involved in regulating hepatic fibrosis, bile duct proliferation, inflammation, and bile acid metabolism were validated by qRT-PCR or Western blot analysis. The bile acid composition and levels in the serum, liver, small intestine, and feces and tissue distribution of BBR were measured by LC–MS/MS. Intestinal inflammation and injury were assessed by gene expression profiling and histological analysis. The impact on the gut microbiome was assessed using 16S rRNA gene sequencing. Results BBR treatment significantly ameliorated cholestatic liver injury, evidenced by decreased serum levels of AST, ALT, and ALP, and reduced bile duct proliferation and hepatic fibrosis, as shown by H&E, Picro-Sirius Red, and CK19 IHC staining. RNAseq and qRT-PCR analyses indicated a substantial inhibition of fibrotic and inflammatory gene expression. BBR also mitigated ER stress by downregulating Chop, Atf4 and Xbp-1 expression. In addition, BBR modulated bile acid metabolism by altering key gene expressions in the liver and small intestine, resulting in restored bile acid homeostasis characterized by reduced total bile acids in serum, liver, and small intestine and increased fecal excretion. Furthermore, BBR significantly improved intestinal barrier function and reduced bacterial translocation by modulating the gut microbiota. Conclusion BBR effectively attenuates cholestatic liver injury, suggesting its potential as a therapeutic agent for PSC and other cholestatic liver diseases.

Improving the reversibility of anionic redox and inhibiting irreversible oxygen evolution are the main challenges in the application of high reversible capacity Li-rich Mn-based cathode materials. A facile synchronous lithiation strategy combining the advantages of yttrium doping and LiYO2 surface coating is proposed. Yttrium doping effectively suppresses the oxygen evolution during the delithiation process by increasing the energy barrier of oxygen evolution reaction through strong Y–O bond energy. LiYO2 nanocoating has the function of structural constraint and protection, that protecting the lattice oxygen exposed to the surface, thus avoiding irreversible oxidation. As an Li+ conductor, LiYO2 nanocoating can provide a fast Li+ transfer channel, which enables the sample to have excellent rate performance. The synergistic effect of Y doping and nano-LiYO2 coating integration suppresses the oxygen release from the surface, accelerates the diffusion of Li+ from electrolyte to electrode and decreases the interfacial side reactions, enabling the lithium ion batteries to obtain good electrochemical performance. The lithium-ion full cell employing the Y-1 sample (cathode) and commercial graphite (anode) exhibit an excellent specific energy density of 442.9 Wh kg−1 at a current density of 0.1C, with very stable safety performance, which can be used in a wide temperature range (60 to −15 °C) stable operation. This result illustrates a new integration strategy for advanced cathode materials to achieve high specific energy density.

The Pseudomonas promysalinigenes strain RL-WG26, which was previously isolated from the rhizosphere of Sea Rice 86 (SR86), could promote the plant growth and alleviate the plant salt stress of SR86 by regulating the ion concentration in plants, increasing the dry weight and chlorophyll content of plants, and reducing the proline and malondialdehyde content in roots. Here, we report the complete genome sequence of Pseudomonas promysalinigenes strain RL-WG26 to lay a foundation for deciphering the molecular mechanisms of strain RL-WG26-mediated plant salt tolerance and to further the application potential of this strain. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background This prospective study aims to investigate the efficacy and safety of pyrotinib (P) combined with 4 cycles of epirubicin and cyclophosphamide followed by 4 cycles of taxane and trastuzumab (P + EC-TH) regimen as neoadjuvant therapy for human epidermal growth factor receptor 2 (HER2) positive breast cancer and to investigate the predictive value of p53, p63, and epidermal growth factor receptor (EGFR) status for neoadjuvant efficacy. Methods A total of 138 HER2-positive breast cancer patients who received neoadjuvant therapy and underwent surgery were included. Case group: 55 patients received P + EC-TH regimen. Control group: 83 patients received EC-TH regimen. The chi-square test, Fisher’s exact test, and logistic regression analysis were applied. The primary endpoint was total pathologic complete response (tpCR), and the secondary endpoints were breast pathologic complete response (bpCR), overall response rate (ORR), and adverse events (AEs). Results In the case group, the tpCR rate was 63.64% (35/55), the bpCR rate was 69.09% (38/55), and the ORR was 100.00% (55/55). In the control group, the tpCR rate was 39.76% (33/83), the bpCR rate was 44.58% (37/83), and the ORR was 95.18% (79/83). The case group had significantly higher tpCR and bpCR rates than those of the control group (P 0.05). The tpCR was associated with the status of estrogen receptor (ER), progesterone receptor (PR), and androgen receptor (AR), and the patients with any negative ER, PR, AR, or combined, were more likely to achieve tpCR than those with positive results (P

Abstract Biallelic mutations of the chromatin regulator SMARCAL1 cause Schimke Immunoosseous Dysplasia (SIOD), characterized by severe growth defects and premature mortality. Atherosclerosis and hyperlipidemia are common among SIOD patients, yet their onset and progression are poorly understood. Using an integrative approach involving proteomics, mouse models, and population genetics, we investigated SMARCAL1’s role. We found that SmarcAL1 interacts with angiopoietin-like 3 (Angptl3), a key regulator of lipoprotein metabolism. In vitro and in vivo analyses demonstrate SmarcAL1’s vital role in maintaining cellular lipid homeostasis. The observed translocation of SmarcAL1 to cytoplasmic peroxisomes suggests a potential regulatory role in lipid metabolism through gene expression. SmarcAL1 gene inactivation reduces the expression of key genes in cellular lipid catabolism. Population genetics investigations highlight significant associations between SMARCAL1 genetic variations and body mass index, along with lipid-related traits. This study underscores SMARCAL1’s pivotal role in cellular lipid metabolism, likely contributing to the observed lipid phenotypes in SIOD patients.