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Abstract Background Under global warming, high temperature (HT) has become a major meteorological factor affecting soybean production. To explore the candidate genes and regulatory mechanism of the soybean bud response to HT stress, previously identified as HT-tolerant (‘Handou14’; HD14) and HT-sensitive (‘Jiadou36’; JD36) were treated for 5 days in an artificial climate incubator either with HT (43 °C (day)/ 33 °C (night), 16 h light/8 h darkness) or the non-stress growth condition (25 °C, 16 h light/8 h darkness) as the control at the bud stage were used as experimental materials in this study. After HT treatment, changes in physiological indicators including hypocotyl length, enzyme activity and hormone content were detected; at the same time, the cotyledons, hypocotyls, and main roots were collected for transcriptome sequencing analysis. Analyzing the mechanisms of HT stress response in the bud stage of HD14 and JD36 at physiological and transcription levels. Results Analysis of physiological indicator showed that the activities of superoxide dismutase (SOD) were significantly increased 47.4% and 41.2% in the cotyledon of HD14 and the main root of JD36, and the contents of peroxidase (POD) were significantly increased 61.5% and 125% in the hypocotyl of HD14 and JD36; the contents of malonaldehyde (MDA) were significantly increased 44.8% and 22.2% in the main root of HD14 and JD36 after HT treatment. The content of abscisic acid (ABA) were significantly increased 1.9 fold and 1.2 fold in the root of HD14 and JD36 in response to HT treatment, whereas the content of gibberellin (GA) were decreased 2.2 fold and 1.3 fold in the cotyledon and root, and increased 1.6 fold in the hypocotyl in HD14 (P

Objective: To provide theoretical basis and basic research data for the technological development of inoculated Chinese traditional fermented fish, Mei yu, the effects of inoculated fermentation with Lactobacillus sake JXNU1-3 on the quality of Mei yu were investigated. Methods: The sensory evaluation, color, texture and composition of volatile flavor compounds of Mei yu prepared by traditional fermentation and inoculated fermentation with Lactobacillus sakei JXNU1-3 with different salt concentration during fermentation were compared by sensory evaluation, electronic nose, texture analyzer and solid phase micro-extraction and gas chromatography-mass spectrometry (SPEM/GC-MS). Result: It was showed that inoculated fermented Mei yu with a salt concentration of 2% and fermentation time of 3 days had better color, texture, and higher sensory score. The inoculated fermented Mei yu had lower response values to sulfides and methylated compounds compared with the traditional fermented Mei yu. Further, the main flavor substances and key flavor components of these two fermented fish samples were similar. However, compared with inoculated fermented Mei yu, isoamyl alcohol (sour odor) and 2-acetylpyrrole (musty odor) compounds were only detected in traditional fermented Mei yu. Conclusions: Compared with traditional fermentation, inoculated fermentation could reduce the corruption degree and improve the sensory quality of Mei yu, which indicated that Lactobacillus sakei JXNU1-3 could be used as a good starter culture for the development of inoculated fermentation technology of Mei yu.

Abstract Patients with multiple myeloma (MM) experience relapse and drug resistance; therefore, novel treatments are essential. Clotrimazole (CTZ) is a wide-spectrum antifungal drug with antitumor activity. However, CTZ’s effects on MM are unclear. We investigated CTZ’s effect on MM cell proliferation and apoptosis induction mechanisms. CTZ’s effects on MM.1S, NCI- H929, KMS-11, and U266 cell growth were investigated using Cell Counting Kit-8 (CCK-8) assay. The apoptotic cell percentage was quantified with annexin V-fluorescein isothiocyanate/7-amino actinomycin D staining. Mitochondrial membrane potential (MMP) and cell cycle progression were evaluated. Reactive oxygen species (ROS) levels were measured via fluorescence microscopy. Expression of apoptosis-related and nuclear factor (NF)-κB signaling proteins was analyzed using western blotting. The CCK-8 assay indicated that CTZ inhibited cell proliferation based on both dose and exposure time. Flow cytometry revealed that CTZ decreased apoptosis and MMP and induced G0/G1 arrest. Immunofluorescence demonstrated that CTZ dose-dependently elevated in both total and mitochondrial ROS production. Western blotting showed that CTZ enhanced Bax and cleaved poly ADP-ribose polymerase and caspase-3 while decreasing Bcl-2, p-p65, and p-IκBα. Therefore, CTZ inhibits MM cell proliferation by promoting ROS-mediated mitochondrial apoptosis, inducing G0/G1 arrest, inhibiting the NF-κB pathway, and has the potential for treating MM.

Abstract The application of ChatGPTin the medical field has sparked debate regarding its accuracy. To address this issue, we present a Multi-Role ChatGPT Framework (MRCF), designed to improve ChatGPT's performance in medical data analysis by optimizing prompt words, integrating real-world data, and implementing quality control protocols. Compared to the singular ChatGPT model, MRCF significantly outperforms traditional manual analysis in interpreting medical data, exhibiting fewer random errors, higher accuracy, and better identification of incorrect information. Notably, MRCF is over 600 times more time-efficient than conventional manual annotation methods and costs only one-tenth as much. Leveraging MRCF, we have established two user-friendly databases for efficient and straightforward drug repositioning analysis. This research not only enhances the accuracy and efficiency of ChatGPT in medical data science applications but also offers valuable insights for data analysis models across various professional domains.

Abstract Background This study aimed to develop a higher performance nomogram based on explainable machine learning methods, and to predict the risk of death of stroke patients within 30 days based on clinical characteristics on the first day of intensive care units (ICU) admission. Methods Data relating to stroke patients were extracted from the Medical Information Marketplace of the Intensive Care (MIMIC) IV and III database. The LightGBM machine learning approach together with Shapely additive explanations (termed as explain machine learning, EML) was used to select clinical features and define cut-off points for the selected features. These selected features and cut-off points were then evaluated using the Cox proportional hazards regression model and Kaplan-Meier survival curves. Finally, logistic regression-based nomograms for predicting 30-day mortality of stroke patients were constructed using original variables and variables dichotomized by cut-off points, respectively. The performance of two nomograms were evaluated in overall and individual dimension. Results A total of 2982 stroke patients and 64 clinical features were included, and the 30-day mortality rate was 23.6% in the MIMIC-IV datasets. 10 variables (“sofa (sepsis-related organ failure assessment)”, “minimum glucose”, “maximum sodium”, “age”, “mean spo2 (blood oxygen saturation)”, “maximum temperature”, “maximum heart rate”, “minimum bun (blood urea nitrogen)”, “minimum wbc (white blood cells)” and “charlson comorbidity index”) and respective cut-off points were defined from the EML. In the Cox proportional hazards regression model (Cox regression) and Kaplan-Meier survival curves, after grouping stroke patients according to the cut-off point of each variable, patients belonging to the high-risk subgroup were associated with higher 30-day mortality than those in the low-risk subgroup. The evaluation of nomograms found that the EML-based nomogram not only outperformed the conventional nomogram in NIR (net reclassification index), brier score and clinical net benefits in overall dimension, but also significant improved in individual dimension especially for low “maximum temperature” patients. Conclusions The 10 selected first-day ICU admission clinical features require greater attention for stroke patients. And the nomogram based on explainable machine learning will have greater clinical application.

The skin is the largest organ in the human body and is made up of various cells and structures. Over time, the skin will age, which is not only influenced by internal factors, but also by external environmental factors, especially ultraviolet radiation. Aging causes immune system weakening in the elderly, which makes them more susceptible to dermatosis, such as type 2 inflammatory mediated pruritus. The immune response in this condition is marked by senescent cells consistently releasing low amounts of pro-inflammatory cytokines through a senescence-associated secretory phenotype (SASP). This continuous inflammation may accelerate immune system aging and establish a connection between immune aging and type 2 inflammatory skin diseases. In addition, two chronic pigmentation disorders, vitiligo and chloasma, are also associated with skin aging. Aged cells escape the immune system and accumulate in tissues, forming a microenvironment that promotes cancer. At the same time, “photoaging” caused by excessive exposure to ultraviolet radiation is also an important cause of skin cancer. This manuscript describes the possible links between skin aging and type 2 inflammation, chronic pigmentation disorders, and skin cancer and suggests some treatment options.

Abstract Metabolic dysregulation is a key driver of cellular senescence, contributing to the progression of systemic aging. The heterogeneity of senescent cells and their metabolic shifts are complex and unexplored. A microfluidic SlipChip integrated with surface‐enhanced Raman spectroscopy (SERS), termed SlipChip‐SERS, is developed for single‐cell metabolism analysis. This SlipChip‐SERS enables compartmentalization of single cells, parallel delivery of saponin and nanoparticles to release intracellular metabolites and to realize SERS detection with simple slipping operations. Analysis of different cancer cell lines using SlipChip‐SERS demonstrated its capability for sensitive and multiplexed metabolic profiling of individual cells. When applied to human primary fibroblasts of different ages, it identified 12 differential metabolites, with spermine validated as a potent inducer of cellular senescence. Prolonged exposure to spermine can induce a classic senescence phenotype, such as increased senescence‐associated β‐glactosidase activity, elevated expression of senescence‐related genes and reduced LMNB1 levels. Additionally, the senescence‐inducing capacity of spermine in HUVECs and WRL‐68 cells is confirmed, and exogenous spermine treatment increased the accumulation and release of H2O2. Overall, a novel SlipChip‐SERS system is developed for single‐cell metabolic analysis, revealing spermine as a potential inducer of senescence across multiple cell types, which may offer new strategies for addressing ageing and ageing‐related diseases.

Autophagy is a highly conserved cellular self-digestive process that underlies the maintenance of cellular homeostasis. Autophagy is classified into three types: macrophage, chaperone-mediated autophagy (CMA) and microphagy, which maintain cellular homeostasis through different mechanisms. Altered autophagy regulation affects the progression of various skin diseases, including psoriasis (PA), systemic lupus erythematosus (SLE), vitiligo, atopic dermatitis (AD), alopecia areata (AA) and systemic sclerosis (SSc). In this review, we review the existing literature focusing on three mechanisms of autophagy, namely macrophage, chaperone-mediated autophagy and microphagy, as well as the roles of autophagy in the above six dermatological disorders in order to aid in further studies in the future.

Lung disease development involves multiple cellular processes, including inflammation, cell death, and proliferation. Research increasingly indicates that autophagy and its regulatory proteins can influence inflammation, programmed cell death, cell proliferation, and innate immune responses. Autophagy plays a vital role in the maintenance of homeostasis and the adaptation of eukaryotic cells to stress by enabling the chelation, transport, and degradation of subcellular components, including proteins and organelles. This process is essential for sustaining cellular balance and ensuring the health of the mitochondrial population. Recent studies have begun to explore the connection between autophagy and the development of different lung diseases. This article reviews the latest findings on the molecular regulatory mechanisms of autophagy in lung diseases, with an emphasis on potential targeted therapies for autophagy.

Aiming at the problems of Flow Direction Algorithm (FDA), such as premature convergence and tendency to fall into local optimum, this paper proposes an efficient improved version named FDA_CPR. Firstly, the embedding of the topological structure of cellular automata to increase the population diversity of the algorithm. Then, Lévy flight is used to replace the D8 algorithm of FDA and a position update strategy based on Sine Cosine Algorithm to slow down the convergence of the algorithm. Furthermore, a new concept of “potential energy” is introduced to calculate the energy score of the flow and determine the new direction of movement to improve the search efficiency of the algorithm. Finally, a “rockfall strategy” based on dynamic opposite learning is designed to help the algorithm jump out of the local optimum. FDA_CPR is compared with eight well-known algorithms on CEC2017 and several feature selection problems to evaluate its performance. Qualitative analysis, Friedman's test and Wilcoxon signed rank test confirmed the effectiveness of the improvement in different ways. Various experimental results show that FDA_CPR has considerable advantages in solving both discrete and continuous problems, and its comprehensive performance is better than that of FDA and other comparison algorithms.

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation and lipid peroxidation, ferroptosis has been implicated in the progression of various skin conditions, including psoriasis, photosensitive dermatitis, and melanoma. This review provides an in-depth analysis of the molecular mechanisms underlying ferroptosis and compares its cellular effects with other forms of cell death in the context of skin health and disease. We systematically examine the role of ferroptosis in five specific skin diseases, including ichthyosis, psoriasis, polymorphous light eruption (PMLE), vitiligo, and melanoma, detailing its influence on disease pathogenesis and progression. Moreover, we explore the current clinical landscape of ferroptosis-targeted therapies, discussing their potential in managing and treating skin diseases. Our aim is to shed light on the therapeutic potential of modulating ferroptosis in skin disease research and practice.

Maternal obesity is a potential cause of non-alcoholic fatty liver disease (NAFLD) in the offspring. There is growing evidence that sea buckthorn plays an important role in protecting the liver. In this study, we established three dietary models of maternal to study the effects of different diets of maternal mice on the occurrence of NAFLD in their offspring and explored the underlying potential mechanisms. Studies have found that feeding sea buckthorn to maternal mice can improve liver steatosis and lipid deposition in the offspring. In addition, the expression of inflammation-related factors was reduced, the IκB/NF-κB pathway was inhibited, and inflammatory response was reduced in the offspring of maternal mice fed sea buckthorn. Furthermore, offspring exhibited increased antioxidant enzyme activity. Further, the results revealed that sea buckthorn inhibited glycolysis regulates AMPK/PKM2 activity, thereby reducing the occurrence of NAFLD. This study provides a novel strategy for treating NAFLD at the maternal level.

Abstract Background Root caries is preventable and can be arrested at any stage of disease development. The aim of this study was to investigate the potential mineral exchange and fluorapatite formation within artificial root carious lesions (ARCLs) using different toothpastes containing 5,000 ppm F, 1,450 ppm F or bioactive glass (BG) with 540 ppm F. Materials and methods The crowns of each extracted sound tooth were removed. The remaining roots were divided into four parts (n = 12). Each sample was randomly allocated into one of four groups: Group 1 (Deionised water); Group 2 (BG with 540 ppm F); Group 3 (1,450 ppm F) and Group 4 (5,000 ppm F). ARCLs were developed using demineralisation solution (pH 4.8). The samples were then pH-cycled in 13 days using demineralisation solution (6 h) and remineralisation solution (pH 7) (16 h). Standard tooth brushing was carried out twice a day with the assigned toothpaste. X-ray Microtomography (XMT) was performed for each sample at baseline, following ARCL formation and after 13-day pH-cycling. Scanning Electron Microscope (SEM) and 19F Magic angle spinning nuclear magnetic resonance (19F-MAS-NMR) were also performed. Results XMT results showed that the highest mineral content increase (mean ± SD) was Group 4 (0.09 ± 0.05), whilst the mineral content decreased in Group 1 (-0.08 ± 0.06) after 13-day pH-cycling, however there was evidence of mineral loss within the subsurface for Groups 1, 3 and 4 (p

Background: Ferroptosis, a newly recognized form of programmed cell death, is distinguished by its reliance on reactive oxygen species and iron-mediated lipid peroxidation, setting it apart from established types like apoptosis, cell necrosis, and autophagy. Recent studies suggest its role in exacerbating or mitigating diseases by influencing metabolic and signaling pathways in conditions such as tumors and ischemic organ damage. Evidence also links ferroptosis to various kidney diseases, prompting a review of its research status and potential breakthroughs in understanding and treating these conditions. Summary: In acute kidney disease (AKI), ferroptosis has been confirmed in animal kidneys after being induced by various factors such as renal ischemia-reperfusion and cisplatin, and glutathione peroxidase 4 (GPX4) is linked with AKI. Ferroptosis is associated with renal fibrosis in chronic kidney disease (CKD), TGF-β1 being crucial in this regard. In diabetic nephropathy (DN), high SLC7A11 and low nuclear receptor coactivator 4 (NCOA4) expressions are linked to disease progression. For polycystic kidney disease (PKD), ferroptosis promotes the disease by regulating ferroptosis in kidney tissue. Renal cell carcinoma (RCC) and lupus nephritis (LN) also have links to ferroptosis, with mtDNA and iron accumulation causing RCC and oxidative stress causing LN. Key Messages: Ferroptosis is a newly identified form of programmed cell death that is associated with various diseases. It targets metabolic and signaling pathways and has been linked to kidney diseases such as AKI, CKD, PKD, DN, LN, and clear cell RCC. Understanding its role in these diseases could lead to breakthroughs in their pathogenesis, etiology, and treatment.

Abstract Natural killer (NK) cells are unique from other immune cells in that they can rapidly kill multiple neighboring cells without the need for antigenic pre-sensitization once the cells display surface markers associated with oncogenic transformation. Given the dynamic role of NK cells in tumor surveillance, NK cell-based immunotherapy is rapidly becoming a "new force" in tumor immunotherapy. However, challenges remain in the use of NK cell immunotherapy in the treatment of solid tumors. Many metabolic features of the tumor microenvironment (TME) of solid tumors, including oxygen and nutrient (e.g., glucose, amino acids) deprivation, accumulation of specific metabolites (e.g., lactate, adenosine), and limited availability of signaling molecules that allow for metabolic reorganization, multifactorial shaping of the immune-suppressing TME impairs tumor-infiltrating NK cell function. This becomes a key barrier limiting the success of NK cell immunotherapy in solid tumors. Restoration of endogenous NK cells in the TME or overt transfer of functionally improved NK cells holds great promise in cancer therapy. In this paper, we summarize the metabolic biology of NK cells, discuss the effects of TME on NK cell metabolism and effector functions, and review emerging strategies for targeting metabolism-improved NK cell immunotherapy in the TME to circumvent these barriers to achieve superior efficacy of NK cell immunotherapy.

Abstract Currently three major problems seriously limit the practical application of cancer photodynamic therapy (PDT): (i) the hypoxic tumor microenvironment (TME); (ii) low generation efficiency of toxic reactive oxygen species (ROS) in aggregates and (iii) shallow tissue penetration depth of excitation light. Very limited approaches are available for addressing all the above three problems with a single design. Herein, a rational “three birds with one stone” molecular and nanoengineering strategy is demonstrated: a photodynamic nanoplatform U‐Ir@PAA‐ABS based on the covalent combination of lanthanide‐doped upconversion nanoparticles (UCNPs) and an AIE‐active dinuclear Ir(III) complex provides a low oxygen concentration‐dependent type‐I photochemical process upon 980 nm irradiation by Föster resonance energy transfer (FRET). U‐Ir@PAA‐ABS targets mitochondria and has excellent phototoxicity even in severe hypoxia environments upon 980 nm irradiation, inducing a dual‐mode cell death mechanism by apoptosis and ferroptosis. Taken together, the in vitro and in vivo results demonstrate a successful strategy for improving the efficacy of PDT against hypoxic tumors.

The functional heterogeneity and ecological niche of prostate cancer stem cells (PCSCs), which are major drivers of prostate cancer development and treatment resistance, have attracted considerable research attention. Cancer-associated fibroblasts (CAFs), which are crucial components of the tumor microenvironment (TME), substantially affect PCSC stemness. Additionally, CAFs promote PCSC growth and survival by releasing signaling molecules and modifying the surrounding environment. Conversely, PCSCs may affect the characteristics and behavior of CAFs by producing various molecules. This crosstalk mechanism is potentially crucial for prostate cancer progression and the development of treatment resistance. Using organoids to model the TME enables an in-depth study of CAF-PCSC interactions, providing a valuable preclinical tool to accurately evaluate potential target genes and design novel treatment strategies for prostate cancer. The objective of this review is to discuss the current research on the multilevel and multitarget regulatory mechanisms underlying CAF-PCSC interactions and crosstalk, aiming to inform therapeutic approaches that address challenges in prostate cancer treatment.

Studies have indicated cancer-associated fibroblasts (CAFs) could have a significant impact in gastric cancer (GC) progression and chemotherapy resistance. However, the gene related to cancer fibroblasts that can be used as biomarkers to judge the occurrence of gastric cancer has not been fully explored. Based on two Gene Expression Omnibus (GEO) datasets, we focus on differentially expressed genes which may act as CAFs markers related to GC. Through COX regression, LASSO regression and Kaplan-Meier survival analysis, we discovered three upregulated genes (GLT8D2, GNAS and EDA) associated with poor GC patients’ survival. By single-cell analysis and nomogram, we found that EDA may affect fibroblast production and disease prognosis in GC patients. EDA expression showed a positive correlation with 5-Fluorouracil IC50 values. Immunohistochemistry (IHC) and real time PCR indicated elevated EDA levels in GC tissues and cells. Enrichment analysis revealed that EDA was closely linked to immune system regulation. IHC and single-cell analysis indicated that EDA gene was associated with cancer fibroblasts marker FGF12 and influence cell interferon-gamma response, which may play a role in regulating immune-related characteristics. In summary, we concluded that EDA may be used as a new therapeutic CAFs marker for GC.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

The variation in precipitation in Motuo is closely associated with the transport of water vapor from the India Ocean and the Bay of Bengal to inland China， the Asia summer monsoon， and the progression of the rain band in eastern China.A rain band with an average annual precipitation of more than 2000 mm has been formed due to the interaction of the distinctive topography of Motuo and the southwest air flow.However， it has been challenging to observe precipitation in Motuo due to the peculiar topography， insufficient electricity， and inadequate traffic conditions.An X-band dual-polarization phased array radar （XPAR） is installed during the Second Qinghai-Xizang Plateau Scientific Expedition and Research Program.The advanced dual-polarization phased array radar is used to continuously observe the precipitation in Motuo and is of great significance to the research of the local ecological environment and cloud water resources， and the impact on downstream.Based on XPAR data collected for the period from June to August 2020， we selected the radial precipitation echoes using a statistical method， and after integrating the precipitation echoes， we created the hybrid elevation angle that tallied with the topography of Motuo.Using DSD data from Motuo in 2019， we calculated radar parameters and obtained the localized QPE （Quantitative Precipitation Estimation） formulas of X-band weather radar.We selected three processes of precipitation with different cumulative precipitation， duration， and average rain rate from July to August 2020， calculated ΦDP （Differential Propagation Phase Shift） using the linear programming method， KDP （Differential Propagation Phase Shift Rate） using the ordinary least square method， and corrected ZH （Reflectivity Factor） using the “ZPHI” rain profiling algorithm.Using ZH and KDP as thresholds， we estimated precipitation piecewise utilizing R（ZH） and R（KDP）， and contrasted results with the QPE results from the R（ZH） and R（KDP） methods， respectively.And explored the relationship between precipitation distribution and the topography of Motuo based on the QPE results.The quality of ZH and KDP had been significantly improved.The hybrid elevation angle constructed using a statistical method had a larger echo area than the hybrid elevation angle constructed using STRM1 v3.0 data.The PPI （Plane Position Indicator） diagrams of three precipitation （radar parameters at typical times， and average radar parameters） processes can show the relationship between the variation in precipitation and the topography of Motuo.The QPE formulas and Piecewise Estimation Method （PEM） used in the research functioned well， and each evaluation parameter performed well.The following conclusions are drawn： （1） The hybrid elevation angle constructed using the statistical method outperformed the hybrid elevation angle constructed using topography data in QPE， due to the drastic variation of the topography around the XPAR in Motuo； （2） The data quality control method， the QPE formulas， and the PEM utilized in the research all performed well at precipitation retrieval.The estimation error of the QPE results was significantly reduced， without causing significant changes in CC and RMSE； （3） Precipitation in Motuo may occur and grow as a result of the lifting of the southwest air flow by northern slopes of the valley.Clouds with higher rain rates and smaller drops are found near the level bottom of the valley.

An excellent Fe-3.3 wt% Si steel was fabricated by double cold rolling and final annealing. The evolution of the microstructure and texture was studied by optical microscope (OM), X-ray diffraction (XRD), ex situ, and quasi-in situ electron backscattered diffraction (EBSD) to investigate the recrystallization behavior. Double cold rolling significantly reduced the adverse γ texture in the final annealed sheets, and a stronger η texture was observed. With a reduction ratio of 50% and 65% during double cold rolling, the γ texture almost disappeared, whereas the η texture was obviously improved. Consequently, the texture factor reached its peak, leading to a reduction in iron loss and an enhancement of magnetic induction. By combining texture regulation with dislocation strengthening, the magnetic properties of Fe-3.3 wt% Si steel were improved, and the yield strength also increased. The final sheet exhibiting exceptional magnetic characteristics and enhanced strength attained a reduction in iron loss (P10/400 = 21.84 W/kg) of 6.43 W/kg, along with an enhancement of magnetic induction (B50 = 1.698 T) of 0.038 T and yield strength (Rp0.2 = 578 MPa) of 37 MPa compared to a single-stage cold rolling process.

Background: Ventricular tachycardia (VT) can broadly be categorised into ischemic heart disease, non-ischemic structural heart disease, and idiopathic VT. There are few studies related to the application of machine learning for the etiological diagnosis of VT, and the interpretable methods are still in the exploratory stage for clinical decision-making applications. Objectives: The aim is to propose a machine learning model for the etiological diagnosis of VT. Interpretable results based on models are compared with expert knowledge, and interpretable evaluation protocols for clinical decision-making applications are developed. Methods: A total of 1305 VT patient data from 1 January 2013 to 1 September 2023 at the Arrhythmia Centre of Fuwai Hospital were included in the study. Clinical data collected during hospitalisation included demographics, medical history, vital signs, echocardiographic results, and laboratory test outcomes. Results: The XGBoost model demonstrated the best performance in VT etiological diagnosis (precision, recall, and F1 were 88.4%, 88.5%, and 88.4%, respectively). A total of four interpretable machine learning methods applicable to clinical decision-making were evaluated in terms of visualisation, clinical usability, clinical applicability, and efficiency with expert knowledge interpretation. Conclusions: The XGBoost model demonstrated superior performance in the etiological diagnosis of VT, and SHAP and decision tree interpretable methods are more favoured by clinicians for decision-making.

Hepatocellular carcinoma is the most common form of primary liver cancer and poses a significant challenge to the medical community because of its high mortality rate. In recent years, ferroptosis, a unique form of cell death, has garnered widespread attention. Ferroptosis, which is characterized by iron-dependent lipid peroxidation and mitochondrial alterations, is closely associated with the pathological processes of various diseases, including hepatocellular carcinoma. Long non-coding RNAs (lncRNAs), are a type of functional RNA, and play crucial regulatory roles in a variety of biological processes. In this manuscript, we review the regulatory roles of lncRNAs in the key aspects of ferroptosis, and summarize the research progress on ferroptosis-related lncRNAs in hepatocellular carcinoma.

Corneal transplantation is a common treatment for corneal diseases. Secondary glaucoma after corneal transplantation is the second leading cause of failure of keratoplasty. This article reviews the mechanism and treatment of secondary glaucoma after corneal transplantation.

With the development of global social economy and the deepening of the aging population, diseases related to aging have received increasing attention. The pathogenesis of many respiratory diseases remains unclear, and lung aging is an independent risk factor for respiratory diseases. The aging mechanism of the lung may be involved in the occurrence and development of respiratory diseases. Aging-induced immune, oxidative stress, inflammation, and telomere changes can directly induce and promote the occurrence and development of lung aging. Meanwhile, the occurrence of lung aging also further aggravates the immune stress and inflammatory response of respiratory diseases; the two mutually affect each other and promote the development of respiratory diseases. Explaining the mechanism and treatment direction of these respiratory diseases from the perspective of lung aging will be a new idea and research field. This review summarizes the changes in pulmonary microenvironment, metabolic mechanisms, and the progression of respiratory diseases associated with aging.

Most early-stage fires originating in small confined spaces may not be effectively mitigated by automatic fire-extinguishing systems. Leveraging the unique controlled release capability and barrier properties of microcapsules presents a promising avenue for developing multifunctional and intelligent fire-extinguishing agents tailored for early-stage fire suppression. This paper introduces two types of microcapsules that integrate automatic detection and fire extinguishing functions, utilizing fluorinated liquids specifically perfluoro(2-methyl-3-pentanone) and 1,1,1,2,2,3,4,5,5,5 decafluoro-3-methoxy-4(trifluoromethyl)-pentane as core materials. The preparation process was optimized, and the thermal response of the microcapsules was evaluated by directly incorporating them into combustible materials. The results indicated a correlation between the preparation method, coating efficiency, and thermal stability of microcapsules with the core-wall materials. When the fluoride solution in the core material reaches the thermal response threshold temperature, the gas pressure generated during vaporization and phase change can break through the shell, enabling early active fire protection. Beyond a specific threshold of additive microcapsules in the material, the material exhibits self-extinguishing potential during combustion. In cases where the additive amount falls short of achieving self-extinguishing, the fire-resistant performance of materials can be enhanced through various measures. For instance, reducing the amount of fire-extinguishing agents, delaying the ignition time of fuel, and lowering the heat release rate during combustion are effective strategies. Moreover, the degree of improvement is related to the additional amount and the type of core-wall materials. The thermal-response mechanism of microcapsules constitutes a comprehensive mechanism with physical and chemical effects. The finding of this research offer a new technical approach for microencapsulating high-boiling-point gas extinguishing agents, facilitating intelligent and precise prevention of early fires resulting from combustible materials.

ABSTRACT: Pro-Glu-Trp (PEW) and Leu-Leu-Trp (LLW) are peptides derived from whey protein digestive products; both peptides exhibit xanthine oxidase inhibitory activity in vitro. However, it remains unclear whether these peptides can alleviate hyperuricemia (HUA) in vivo. In this study, we investigated the roles of PEW and LLW, both individually and in combination, in alleviating HUA induced by potassium oxonate and hypoxanthine. Together, PEW and LLW exhibited synergistic effects in reducing the serum levels of uric acid (UA), creatinine, and blood urea nitrogen, as well as increasing the fractional excretion of UA. The combined treatment with PEW and LLW inhibited UA synthesis, promoted UA excretion, and restored renal oxidative stress and mitochondrial damage. Moreover, the combined treatment alleviated dysbiosis of the gut microbiota, characterized by increased helpful microbial abundance, decreased harmful bacterial abundance, and increased production of short-chain fatty acids. Taken together, these results indicate that the combination of PEW and LLW mitigate HUA and kidney injury by rebalancing UA synthesis and excretion, modulating gut microbiota composition, and improving oxidative stress.

Research on the role of paraprobiotics in ameliorating the pathology of ulcerative colitis and its intestinal homeostatic imbalance is still limited. In this study, we investigated the effects of the anti-inflammatory probiotic HF05 and HF06 derived paraprobiotics 5-PA and 6-PA on mice with ulcerative colitis and their intestinal homeostasis. 5-PA and 6-PA alleviated inflammation, intestinal damage, and weight loss in mice, suppressed the activation of the NF-κB/NLRP3 signaling pathway, and upregulated the expression of intestinal tight junction proteins (ZO-1, occludin, and claudin-1). Notably, the two paraprobiotic regulated the gut microbiota and their metabolic interactions with the host. Specific taxa of gut microbes, including unclassified f_Muribaculaceae, Lactobacillus, Adlercreutzia, and Candidatus_Homeothermus, as well as bile acids and glycerophospholipid metabolites, were closely associated with gut homeostasis. In conclusion, this study confirms the beneficial effects of 5-PA and 6-PA in alleviating ulcerative colitis and promoting intestinal homeostasis.

With the increasing number of software projects, within-project defect prediction (WPDP) has already been unable to meet the demand, and cross-project defect prediction (CPDP) is playing an increasingly significant role in the area of software engineering. The classic CPDP methods mainly concentrated on applying metric features to predict defects. However, these approaches failed to consider the rich semantic information, which usually contains the relationship between software defects and context. Since traditional methods are unable to exploit this characteristic, their performance is often unsatisfactory. In this paper, a transfer long short-term memory (TLSTM) network model is first proposed. Transfer semantic features are extracted by adding a transfer learning algorithm to the long short-term memory (LSTM) network. Then, the traditional metric features and semantic features are combined for CPDP. First, the abstract syntax trees (AST) are generated based on the source codes. Second, the AST node contents are converted into integer vectors as inputs to the TLSTM model. Then, the semantic features of the program can be extracted by TLSTM. On the other hand, transferable metric features are extracted by transfer component analysis (TCA). Finally, the semantic features and metric features are combined and input into the logical regression (LR) classifier for training. The presented TLSTM model performs better on the f-measure indicator than other machine and deep learning models, according to the outcomes of several open-source projects of the PROMISE repository. The TLSTM model built with a single feature achieves 0.7% and 2.1% improvement on Log4j-1.2 and Xalan-2.7, respectively. When using combined features to train the prediction model, we call this model a transfer long short-term memory for defect prediction (DPTLSTM). DPTLSTM achieves a 2.9% and 5% improvement on Synapse-1.2 and Xerces-1.4.4, respectively. Both prove the superiority of the proposed model on the CPDP task. This is because LSTM capture long-term dependencies in sequence data and extract features that contain source code structure and context information. It can be concluded that: (1) the TLSTM model has the advantage of preserving information, which can better retain the semantic features related to software defects; (2) compared with the CPDP model trained with traditional metric features, the performance of the model can validly enhance by combining semantic features and metric features.

Background: Machine learning models have promising applications in capturing the complex relationship between mixtures of exposures and outcomes. Objective: Our study aimed at introducing an explainable machine learning (EML) model to assess the association between metal mixtures with potentially opposing renal effects and renal function in middle-aged and older adults. Methods: This study extracted data from two cycle years of the National Health and Nutrition Examination Survey (NHANES). Participants aged 45 years or older with complete data on six metals (lead, cadmium, manganese, mercury, and selenium) and related covariates were enrolled. The EML model was developed by the optimized machine learning model together with Shapley Additive exPlanations (SHAP) to assess the chronic kidney disease (CKD) risk with metal mixtures. The results from EML were further compared in detail with multiple logistic regression (MLR) and Bayesian kernel machine regression (BKMR). Results: After adjusting for included covariates, MLR pointed out the lead and arsenic were generally positively associated with CKD, but manganese had a negative association. In the BKMR analysis, each metal was found to have a non-linear association with the risk of CKD, and interactions can exist between metals, especially for arsenic and lead. The EML ranked the feature importance: lead, manganese, arsenic and selenium were close behind in importance after gender, age or BMI for participants with CKD. Strong interactions between mercury and lead, manganese and cadmium and arsenic and manganese were identified by partial dependence plot (PDP) of SHAP and bivariate exposure-response effect plots of BKMR. The EML model determined the “trigger point” at which the risk of CKD abruptly changed. Conclusion: Co-exposure to metals with different nephrotoxicity could have different joint association with renal function, and EML can be a powerful method for studying complex exposure mixtures.

Abstract Introduction This study conducted an ethnobotanical survey of wild medicinal plants in the multi-ethnic areas of Gansu–Ningxia–Inner Mongolia intersection zone. Traditional knowledge of medicinal plant use in the region was compiled to identify important medicinal plants currently used for treating relevant diseases and to determine species with potential for development. Methods Key informant interviews, semi-structured interviews, participatory rural appraisal methods, and ethnobotanical quantitative evaluation were used to investigate and study the traditional knowledge of local residents' use of wild medicinal plants in the region. The relative importance of the referenced plants was assessed, as well as the prominent species widely used in medicinal applications. Results The study found that the region has a total of 204 wild medicinal plant resources, belonging to 149 genera of 51 families. Among these resources, a total of 50 commonly used plants were identified (44 of which were herbs, some of which were multi-origin), belonging to 27 families, with the most species found in the Asteraceae family, with 11 species. These herbs are mainly used for preventing and treating colds and nourishing health, followed by treatment of fever, stomach problems, and bleeding. The most frequently used medicinal plant in the region is “Ai”, which includes Artemisia argyi Lévl. et Van. and Artemisia kanashiroi Kitam. All respondents provided information about the use of this medicinal plant to varying degrees, followed by Artemisia annua Linn., Ephedra sinica Stapf, Taraxacum mongolicum Hand.-Mazz., Sonchus arvensis Linn., Artemisia capillaris Thunb., among others. Conclusion Our investigation gained a wealth of traditional knowledge about the use of wild herbs, using wild herbs, which plays an important role in the lives of local residents. Especially, the herbs and application methods used for treating colds, bleeding, and stomach problems are worthy of further research and development.

Abstract Objectives The objective of this review is to assess the available literature systematically related to the effect of silver diamine fluoride (SDF) for the management of occlusal and root carious lesions in permanent teeth regardless of age. Materials and Methods This systematic review was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Review and Meta‐Analyses statement. A literature search was performed using PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, DOAJ, and Open Gray with no language restrictions up to December 2022. Three reviewers critically assessed the studies for eligibility. Any disputes between the reviewers were handled by a fourth independent reviewer. The quality assessment and data extraction of the studies were performed. Results A total of 2176 studies were screened. The titles and abstracts of the studies were then reviewed (n = 346), and 52 studies met the search criteria. Following the full‐text review, 11 studies investigated the effect of SDF against other treatments such as chlorhexidine, sodium fluoride, ammonium bifluoride, tricalcium silicate paste, casein phosphopeptide amorphous calcium phosphate, glass ionomer cement (GIC) combined with fluoride varnish, resin‐modified GIC, and atraumatic restorative treatment were assessed. Conclusions Within the limitations of this review, the use of SDF is promising with high preventative fractions in permanent teeth of children and older populations when compared to other topical applications such as dental varnish containing sodium fluoride.

ABSTRACT: The objective of this study was to investigate the mechanism by which the α-lactalbumin peptides Gly-Ile-Asn-Tyr (GINY) and Asp-Gln-Trp (DQW) ameliorate free fatty acid–induced lipid deposition in HepG2 cells. The results show that GINY and DQW reduced triglyceride, total cholesterol, and free fatty acid levels significantly in free fatty acid–treated HepG2 cells. Based on proteomic analysis, GINY and DQW alleviated lipid deposition and oxidative stress mainly through the peroxisome proliferator-activated receptor (PPAR) pathway, fatty acid metabolism, oxidative phosphorylation, and response to oxidative stress. In vitro experiments confirmed that GINY and DQW upregulated the mRNA and protein expression of fatty acid β-oxidation–related and oxidative stress–related genes, and downregulated the mRNA and protein expression of lipogenesis-related genes by activating peroxisome proliferator-activated receptor α (PPARα). Meanwhile, GINY and DQW reduced free fatty acid–induced lipid droplet accumulation and reactive oxygen species generation, and enhanced the mitochondrial membrane potential and ATP levels. Furthermore, GINY and DQW enhanced carnitine palmitoyl-transferase 1a (CPT-1a) and superoxide dismutase activities, and diminished acetyl-coenzyme A carboxylase 1 (ACC1) and fatty acid synthase (FASN) activities in a PPARα-dependent manner. Interestingly, GW6471 (a PPARα inhibitor) weakened the effects of GINY and DQW on the PPARα pathway. Hence, our findings suggest that GINY and DQW have the potential to alleviate nonalcoholic fatty liver disease by activating the PPARα pathway.

The shales of the Taiyuan Formation and Shanxi Formation in the North China Basin have good prospects for shale gas exploration and development. In this study, Well KP1 at the northern margin of the North China Basin was used as the research object for rock mineral, organic geochemical, and elemental geochemical analyses. The results show that brittle minerals in the shales of the Taiyuan Formation and Shanxi Formation are relatively rare (50%). The average TOC content is 3.68%. The organic matter is mainly mixed and sapropelic. The source rocks of the Taiyuan Formation and Shanxi Formation are mainly felsic, and the tectonic background lies in the continental island arc area. The primary variables that influenced the enrichment of organic materials during the sedimentary stage of the Taiyuan Formation were paleosalinity and paleoproductivity. Paleosalinity acted as the primary regulator of organic matter enrichment during the sedimentary stage of the Shanxi Formation.

As a traditional delicacy in China, preserved eggs inevitably experience instances of substandard quality during the production process. Chinese preserved egg production facilities can only rely on experienced workers to select the preserved eggs. However, the manual selection of preserved eggs presents challenges such as a low efficiency, subjective judgments, high costs, and hindered industrial production processes. In response to these challenges, this study procured the transmitted imagery of preserved eggs and refined the ConvNeXt network across four pivotal dimensions: the dimensionality reduction of model feature maps, the integration of multi-scale feature fusion (MSFF), the incorporation of a global attention mechanism (GAM) module, and the amalgamation of the cross-entropy loss function with focal loss. The resultant refined model, ConvNeXt_PEgg, attained proficiency in classifying and grading preserved eggs. Notably, the improved model achieved a classification accuracy of 92.6% across the five categories of preserved eggs, with a grading accuracy of 95.9% spanning three levels. Moreover, in contrast to its predecessor, the refined model witnessed a 24.5% reduction in the parameter volume, alongside a 3.2 percentage point augmentation in the classification accuracy and a 2.8 percentage point boost in the grading accuracy. Through meticulous comparative analysis, each enhancement exhibited varying degrees of performance elevation. Evidently, the refined model outshone a plethora of classical models, underscoring its efficacy in discerning the internal quality of preserved eggs. With its potential for real-world implementation, this technology portends to heighten the economic viability of manufacturing facilities.

Chemical modifications are a specific and efficient way to regulate the function of biological macromolecules. Among them, RNA molecules exhibit a variety of modifications that play important regulatory roles in various biological processes. More than 170 modifications have been identified in RNA molecules, among which the most common internal modifications include N6-methyladenine (m6A), n1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanine nucleotide (m7G). The most widely affected RNA modification is m6A, whose writers, readers, and erasers all have regulatory effects on RNA localization, splicing, translation, and degradation. These functions, in turn, affect RNA functionality and disease development. RNA modifications, especially m6A, play a unique role in renal cell carcinoma disease. In this manuscript, we will focus on the biological roles of m6A in renal diseases such as acute kidney injury, chronic kidney disease, lupus nephritis, diabetic kidney disease, and renal cancer.

Abstract Cancer has always been a worldwide problem, and the application of radiotherapy has greatly improved the survival rate of cancer patients. Radiotherapy can modulate multiple cell fate decisions to kill tumor cells and achieve its therapeutic effect. With the development of radiotherapy technology, how to increase the killing effect of tumor cells and reduce the side effects on normal cells has become a new problem. In this review, we summarize the mechanisms by which radiotherapy induces tumor cell apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis, autophagy, senescence, mitotic catastrophe, and cuproptosis. An in-depth understanding of these radiotherapy-related cell fate decisions can greatly improve the efficiency of radiotherapy for cancer.

Immune thrombocytopenia (ITP) is common in the elderly. Because of the coexistence of multiple diseases, there are many reservations regarding corticosteroid use in the elderly. Thrombopoietin (TPO) and its analogs can promote platelet production, but it is often difficult to correct TP in a short period. Recombinant human TPO (rh-TPO) acting on the cell membrane and the small-molecule TPO-receptor (MPL) agonist acting on the transmembrane receptor may have synergistic effects and accelerate platelet production because of different sites of action in the signaling pathway. In this study, two elderly patients with refractory ITP were successfully treated with two TPO-MPL signaling pathway agonists: recombinant human thrombopoietin (rh-TPO) and eltrombopag. This combination is safe with rapid and lasting effects. However, in elderly patients with refractory, recurrent, and glucocorticoid contraindications, the combination of different TPO agonists' clinical efficacy and adverse reactions needs to be further evaluated.

Abstract Background Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease. The role of surgical resection in PCNSL has always been the center of debate. Here we investigated the clinical and follow-up data of single lesion PCNSL operated in our center, focusing on the comparison between surgical resection and biopsy. Methods All consecutive cases of single lesion PCNSL between October 2004 and December 2019 were retrospectively collected from the database of the Second Affiliated Hospital of Zhejiang University, School of Medicine. Patients were divided into resection group and biopsy group. Clinical information including age, gender, Karnofsky performance status, imaging features and postoperative treatment was collected from the medical records. All the patients were followed for survival analysis. Results A total of 105 patients with PCNSL were finally involved in our analysis. Neither PFS nor OS were significantly different between the resection group and biopsy group. The univariate analysis revealed that age

Abstract Background The Pax transcription activation domain-interacting protein (PTIP) is a nuclear protein that is an essential component of H3K4 methylation for gene activation in vascular, kidney, B cell, and adipocyte development. Furthermore, it plays a key role in genomic stability in higher eukaryotic cells. It binds to 53BP1 and antagonizes inappropriate homologous recombination for a proper DNA damage response. Interestingly, an early study reported mitotic defects after PTIP inactivation, but it is not clear whether PTIP directly facilitates mitotic processes. Results Here, we showed that PTIP is essential for the mitotic integrity of HeLa cells. PTIP inactivation increases cell death during mitotic exit, which appears to result from direct mitotic defects. PTIP inactivation did not affect the G2M DNA damage checkpoint during interphase upon etoposide treatment. However, in mitosis, PTIP inactivation results in prolonged mitotic time, inefficient chromosome alignment, and increased cell death. Furthermore, PTIP localizes to the mitotic centrosome via BRCT domains at the C-terminus. Conclusion This study reveals a novel function of PTIP in maintaining the genomic stability of higher eukaryotes during mitosis. Therefore, its deregulation, which occurs in various tumors, may destabilize the genome by introducing an abnormal DNA damage response, as well as erroneous chromosome segregation.

Solid tumor cells live in a highly dynamic mechanical microenvironment. How the extracellular-matrix-generated mechanotransduction regulates tumor cell development and differentiation remains an enigma. Here, we show that a low mechanical force generated from the soft matrix induces dedifferentiation of moderately stiff tumor cells to soft stem-cell-like cells. Mechanistically, integrin β8 was identified to transduce mechano-signaling to trigger tumor cell dedifferentiation by recruiting RhoGDI1 to inactivate RhoA and subsequently Yes-associated protein (YAP). YAP inactivation relieved the inhibition of v-maf avian musculoaponeurotic fibrosarcoma oncogene homolog G (MAFG), allowing MAFG to transactivate the stemness genes NANOG, SOX2, and NESTIN. Inactivation also restored β8 expression, thereby forming a closed mechanical loop. Importantly, MAFG expression is correlated with worse prognosis. Our findings provide mechanical insights into the regulation of tumor cell dedifferentiation, which has therapeutic implications for exploring innovative strategies to attack malignancies.

Background: Alveolar epithelial cell injury is a key factor in the occurrence and development of pulmonary acute respiratory distress syndrome (ARDSp). Yet the gene expression profile of alveolar epithelial cells of patients with ARDSp remains unclear. Methods: We analyzed single nuclear RNA sequencing (snRNA-Seq) data from autopsy lung tissues of both ARDSp patients and healthy donors. Sequence data for type 2 alveolar epithelizal cells (AT2) were extracted by the Seurat package. Differentially expressed genes (DEGs) in AT2 were identified by the criteria |log2FC| ≥ 0.25 and P

Objective: Using bioinformatics analyses, this study aimed to identify lncRNAs related to the immune status of acute myeloid leukemia (AML) patients and ascertain the potential impact in immunity-related competing endogenous RNA (ceRNA) networks on AML prognosis.Methods: AML-related RNA-seq FPKM data, AML-related miRNA expression microarray data, and gene sets associated with immunity-related pathways were, respectively, obtained from the TCGA, GEO, and ImmReg databases. An immunity-related ceRNA network was then constructed according to the predicted interactions between AML-related mRNAs, lncRNAs, and miRNAs. After performing LASSO and multivariate Cox regression analyses, lncRNAs in the ceRNA network were used to establish an AML prognostic model. According to mutual regulatory relationships and consistent trends of expression among candidate ceRNAs, two ceRNA subnetworks related to the AML prognostic model were determined. Finally, the correlation between the expression levels of mRNAs, lncRNAs, and miRNAs in each ceRNA subnetwork and immune cell infiltration (assessed by combining the ESTIMATE and CIBERSORT methods and ssGSEA) was analyzed.Results: A total of 424 immunity-related differentially expressed (IR-DE) mRNAs (IR-DEmRNAs), 191 IR-DElncRNAs, and 69 IR-DEmiRNAs were obtained, and a ceRNA network of 20 IR-DElncRNAs, 6 IR-DEmRNAs, and 3 IR-DEmiRNAs was established. Univariate Cox regression analysis was conducted on 20 IR-DElncRNAs, and 7 of these were identified to be significantly correlated with the overall survival (OS) time in AML patients. Then, two IR-DElncRNAs (MEG3 and HCP5) were screened as independent OS-related factors by LASSO and multivariable Cox regression analyses, and a prognostic model was constructed to evaluate the survival risk in AML patients. Survival analyses indicated that the OS of patients was often poor in the high-risk group. Additionally, from this model, two ceRNA regulatory pathways, namely, MEG3/miR-125a-5p/SEMA4C and HCP5/miR-125b-5p/IL6R, which were potentially involved in the immune regulation of AML prognosis were identified.Conclusion: lncRNAs HCP5 and MEG3 may act as key ceRNAs in the pathogenesis in AML by regulating immune cell representation as part of the regulatory lncRNA-miRNA-mRNA axes. The candidate mRNAs, lncRNAs, and miRNAs included in the ceRNA network identified here may serve as useful prognostic biomarkers and immunotherapeutic targets for AML.

It is well documented that high temperature (HT) severely affects the development of soybean male reproductive organs. However, the molecular mechanism of thermo-tolerance in soybean remains unclear. To explore the candidate genes and regulatory mechanism of soybean response to HT stress and flower development, here, the anthers of two previously identified HT-tolerant (JD21) and HT-sensitive (HD14) varieties were analyzed by RNA-seq. In total, 219 (172 upregulated and 47 downregulated), 660 (405 upregulated and 255 downregulated), and 4,854 (2,662 upregulated and 2,192 downregulated) differentially expressed genes (DEGs) were identified between JD21 anthers treated with HT stress vs. JD21 anthers in the natural field conditions (TJA vs. CJA), HD14 anthers treated with HT stress vs. HD14 anthers in the natural field conditions (THA vs. CHA), and JD21 vs. HD14 anthers treated with HT stress (TJA vs. THA), respectively. The results showed that there were more DEGs upregulated in JD21; this might be the reason why JD21 was more HT-resistant than the HT-sensitive variety HD14. GO annotation and KEGG enriched analysis showed that many DEGs are mainly involved in defense response, response to biological stimuli, auxin-activated signaling pathway, plant hormone signal transduction, MAPK signaling pathway-plant, starch and sucrose metabolism, etc. The conjoint analysis of RNA-seq and previous iTRAQ results found that there were 1, 24, and 54 common DEGs/DAPs showing the same expression pattern and 1, 2, and 13 common DEGs/DAPs showing the opposite pattern between TJA vs. CJA, THA vs. CHA, and TJA vs. THA at the protein and gene level, respectively, among which HSPs, transcription factor, GSTU, and other DEGs/DAPs participated in the response to HT stress and flower development. Notably, the qRT-PCR analysis and physiological index change results coincided with the sequencing results of RNA-seq and iTRAQ. In conclusion, the HT-tolerant cultivar performed better under stress than the HT-sensitive cultivar through modulation of HSP family proteins and transcription factors, and by keeping key metabolic pathways such as plant hormone signal transduction normal. This study provided important data and some key candidate genes to better study the effect and molecular basis of HT on anther in soybean at a transcription and translation level.

Cardiovascular and cerebrovascular diseases are the number one killer threatening people's life and health, among which cardiovascular thrombotic events are the most common. As the cause of particularly serious cardiovascular events, thrombosis can trigger fatal crises such as acute coronary syndrome (myocardial infarction and unstable angina), cerebral infarction and so on. Circulating monocytes are an important part of innate immunity. Their main physiological functions are phagocytosis, removal of injured and senescent cells and their debris, and development into macrophages and dendritic cells. At the same time, they also participate in the pathophysiological processes of pro-coagulation and anticoagulation. According to recent studies, monocytes have been found to play a significant role in thrombosis and thrombotic diseases of the immune system. In this manuscript, we review the relationship between monocyte subsets and cardiovascular thrombotic events and analyze the role of monocytes in arterial thrombosis and their involvement in intravenous thrombolysis. Finally, we summarize the mechanism and therapeutic regimen of monocyte and thrombosis in hypertension, antiphospholipid syndrome, atherosclerosis, rheumatic heart disease, lower extremity deep venous thrombosis, and diabetic nephropathy.

Timely and accurate detection of oestrus in cows is an essential element of the good management of dairy farms. At present, the detection of cows in oestrus by acoustic means is impeded by the problems of filtering, incomplete feature selection, and poor recognition accuracy. To overcome these difficulties, this study proposes a sound detection method for cows in oestrus based on machine learning technology using an optimal feature combination and an optimal time window. Firstly, a dual-channel sound detection tag consisting of a unidirectional microphone and an omnidirectional microphone (OM) was developed. The Least Mean Squares adaptive algorithm based on wavelet thresholds was used to filter the signals from the OM, and the dual-channel endpoint detection algorithm was used to identify the lowing of individual cows. The Friedman analysis was then used to select the sound features with significant differences before and after oestrus in terms of time, frequency, and cepstrum, and these were used to determine the most acceptable feature combination. We then analysed the effects of Back Propagation Neural Network (BPNN), Cartesian Regression Tree, Support Vector Machine, and Random Forest classification on the accuracy, precision, sensitivity, specificity, and F1 score of oestrus discrimination. Different time windows were used, and the discrimination performance of these algorithms was evaluated using the Area under Receiver Operating Characteristic Curve to find the most satisfactory match between the time window and the recognition algorithm. The dual-channel acoustic tag’s accuracy, precision, sensitivity, and specificity results were 91.25, 98.83, 91.75, and 83.68%, respectively. BPNN with the 70 ms time window and the feature combination (spectral roll-off + spectral flatness + Mel-Frequency Cepstrum Coefficients) was confirmed as the most suitable oestrus recognition method. The average accuracy, precision, sensitivity, specificity, and F1 score of this method were 97.62, 98.07, 97.17, 97.19, and 97.63%, respectively. Based on these results, the approach was shown to be a feasible means of oestrus detection in dairy cows. Based on its ability to differentiate cows and its consistency, it was demonstrated that sound has the potential to replace accelerometers as an early indicator of oestrus in dairy cows.