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Pharmacodynamic evaluation and network pharmacology analysis of a novel anti-heat stress Chinese herbal formula

Frequent extreme heat events around the world not only pose a major threat to human health but also cause significant economic losses to the livestock industry. The existing management practices are insufficient to fully prevent heat stress with an urgent need to develop preventive medicines. The aim of this study was to develop an anti-heat stress Chinese herbal formula (CHF) via big data analysis techniques and to evaluate its anti-heat stress effect and mechanism of action via pharmacodynamic evaluation and network pharmacology analysis. Many anti-heat stress CHFs were collected from the Chinese National Knowledge Infrastructure (CNKI) database. Three alternative CHFs were obtained via unsupervised entropy hierarchical clustering analysis, and the most effective CHF against heat stress, Shidi Jieshu decoction (SJD), was obtained by screening in a mouse heat stress model. In dry and hot environments, SJD significantly improved the heat tolerance of AA broilers by 4–6°C. In a humid and hot environment, pretreatment with 2% SJD resulted in 100% survival of Wenchang chickens at high temperatures. The main active ingredients of SJD were identified as muntjacoside E, timosaponin C, macrostemonoside H and mangiferin via ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) and database comparison. The active ingredients of SJD were found to target tumor necrosis factor-α (TNF-α), signal transducer activator of transcription 3 (STAT3) and epidermal growth factor receptor (EGFR). Finally, the safety of the new formulation was assessed in an acute oral toxicity study in rats. The SJDs developed in this study provide a new option for the prevention of heat stress in animal husbandry and offer new insights for further research on anti-heat stress.

Striate palmoplantar keratoderma: a novel DSG1 mutation, combined with an LDLR mutation.

Palmoplantar keratoderma (PPK) is a heterogeneous group of disorders characterized by abnormal thickening of the skin on the palms and soles. Striate palmoplantar keratoderma (SPPK) is commonly caused by heterozygous mutations in the desmoglein-1 (DSG1) gene. This study aimed to report a case of a 36-year-old Chinese female patient with SPPK caused by a novel DSG1 gene mutation, along with her family history, and explore its potential relationship with other genetic variants. Whole-exome sequencing was performed on the patient and their family members to identify the pathogenic mutation, which was validated by Sanger sequencing. Histological and electron microscopy analyses were conducted to examine the pathological characteristics of skin tissue.of skin tissue. A frameshift mutation, c.1285del, in exon 10 of the DSG1 gene was identified, leading to a loss of protein function and resulting in SPPK. This mutation was also detected in two other family members with similar phenotypes. Additionally, a classical splicing variant, c.313+2dup, in the low-density lipoprotein receptor (LDLR) gene associated with hypercholesterolemia was identified in the patient; however, no direct association with SPPK was observed. This study was the first to report a novel mutation in the DSG1 gene associated with SPPK and suggested a potential role of the LDLR gene variant in SPPK patients, providing new insights for further research into the genetic mechanisms underlying SPPK.

Causal relationship between cortical structural changes and onset of anxiety disorder: evidence from Mendelian randomization.

Previous studies have reported a correlation between anxiety disorders and changes in brain structure, yet the specific alterations in brain region volumes remain unclear. This study aimed to infer the causal relationship between anxiety disorders and changes in brain structure volume through Mendelian Randomization analysis. We selected 63 cortical structure volumes from the GWAS database as exposure data and anxiety disorder data from the FinnGen and UK Biobank databases as outcomes. We found a significant correlation between atrophy in the Left precentral volume area (Odds Ratio [OR] = 0.935, 95% Confidence intervals [CI]: 0.891-0.981, P value, P = 0.007) and an increased risk of anxiety disorders. Additionally, changes identified in specific brain regions, such as atrophy in the Right rostral anterior cingulate area (OR = 0.993, 95% CI: 0.987-0.999, P = 0.025) and increased volume in the Left superior parietal area (OR = 1.001, 95% CI: 1.000-1.001, P = 0.028), may correlate with an increased risk of anxiety disorders. Furthermore, both phenotypes demonstrated directional consistency in their respective and overall meta-analyzed OR values pre- and post-merger, enhancing the reliability of the results. This study elucidates the causal relationship between anxiety disorders and specific brain structures, providing new insights for further research into psychiatric disorders.

Pan-Genome-Wide Investigation and Co-Expression Network Analysis of HSP20 Gene Family in Maize

Heat shock protein 20 (HSP20) is a diverse and functionally important protein family that plays a crucial role in plants’ tolerance to various abiotic stresses. In this study, we systematically analyzed the structural and functional characteristics of the HSP20 gene family within the Zea pan-genome. By identifying 56 HSP20 pan-genes, we revealed the variation in the number of these genes across different maize inbreds or relatives. Among those 56 genes, only 31 are present in more than 52 inbreds or relatives. Further phylogenetic analysis classified these genes into four major groups (Class A, B, C, D) and explored their diversity in subcellular localization, physicochemical properties, and the terminal structures of those HSP20s. Through collinearity analysis and Ka/Ks ratio calculations, we found that most HSP20 genes underwent purifying selection during maize domestication, although a few genes showed signs of positive selection pressure. Additionally, expression analysis showed that several HSP20 genes were significantly upregulated under high temperatures, particularly in tassels and leaves. Co-expression network analysis revealed that HSP20 genes were significantly enriched in GO terms related to environmental stress responses, suggesting that HSP20 genes not only play key roles in heat stress but may also be involved in regulating various other biological processes, such as secondary metabolism and developmental processes. These findings expand our understanding of the functions of the maize HSP20 family and provide new insights for further research into maize’s response mechanisms to environmental stresses.

Identification and Characterization of the DOF Gene Family in Phoebe bournei and Its Role in Abiotic Stress-Drought, Heat and Light Stress.

Phoebe bournei is a second-class endangered and protected species unique to China, and it holds significant ecological and economic value. DNA binding one zinc finger (Dof) transcription factors are plant-specific regulators. Numerous studies have demonstrated that Dof genes are involved in plant growth, development and responses to abiotic stress. In this study, we identified and analyzed 34 PbDof gene members at the whole-genome level. The results indicated that the 34 PbDof genes were unevenly distributed across 12 chromosomes. We utilized the Dof genes from Arabidopsis thaliana and P. bournei to construct a phylogenetic tree and categorized these genes into eight subgroups. In the collinearity analysis, there were 16 homologous gene pairs between AtDof and PbDof and nine homologous gene pairs between ZmDof and PbDof. We conducted a cis-acting element analysis and found that cis-acting elements involved in light response were the most abundant in PbDof genes. Through SSR site prediction, we analyzed that the evolution level of Dof genes is low. Additionally, we assessed the expression profiles of eight PbDof genes under high temperature, drought, and light stress using qRT-PCR. In particular, PbDof08 and PbDof16 are significantly upregulated under the three stresses. This study provides foundational information for PbDof genes and offers new insights for further research on the mechanism of Dof transcription factors responding to stress, as well as the adaptation of P. bournei to environmental changes.

Identification of significant biomarkers for predicting the risk of bipolar disorder with arteriosclerosis based on integrative bioinformatics and machine learning.

Increasing evidence has indicated a connection between bipolar disorder (BD) and arteriosclerosis (AS), yet the specific molecular mechanisms remain unclear. This study aims to investigate the hub genes and molecular pathways for BD with AS. BD-related dataset GSE12649 were downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) and key module genes derived from Limma and weighted gene co-expression network analyses (WGCNA) were identified. AS-related genes were sourced from the DisGeNET database, and the overlapping genes between DEGs and AS-related genes were characterized as differentially expressed arteriosclerosis-related genes (DE-ASRGs). The functional enrichment analysis, protein-protein interaction (PPI) network and three machine learning algorithms were performed to explore the hub genes, which were validated with two external validation sets. Additionally, immune infiltration was performed in BD. Overall, 67 DE-ASRGs were found to be overlapping between the DEGs and AS-related genes. Functional enrichment analysis highlighted the cancer pathways between BD and AS. We identified seven candidate hub genes (CTSD, IRF3, NPEPPS, ST6GAL1, HIF1A, SOX9 and CX3CR1). Eventually, two hub genes (CX3CR1 and ST6GAL1) were identified as BD and AS co-biomarkers by using machine learning algorithms. Immune infiltration had revealed the disorder of immunocytes. This study identified the hub genes CX3CR1 and ST6GAL1 in BD and AS, providing new insights for further research on the bioinformatic mechanisms of BD with AS and contributing to the diagnosis and prevention of AS in psychiatric clinical practice.

Comprehensive macro and micro views on immune cells in ischemic heart disease.

Ischemic heart disease (IHD) is a prevalent cardiovascular condition that remains the primary cause of death due to its adverse ventricular remodelling and pathological changes in end-stage heart failure. As a complex pathologic condition, it involves intricate regulatory processes at the cellular and molecular levels. The immune system and cardiovascular system are closely interconnected, with immune cells playing a crucial role in maintaining cardiac health and influencing disease progression. Consequently, alterations in the cardiac microenvironment are influenced and controlled by various immune cells, such as macrophages, neutrophils, dendritic cells, eosinophils, and T-lymphocytes, along with the cytokines they produce. Furthermore, studies have revealed that Gata6+ pericardial cavity macrophages play a key role in regulating immune cell migration and subsequent myocardial tissue repair post IHD onset. This review outlines the role of immune cells in orchestrating inflammatory responses and facilitating myocardial repair following IHD, considering both macro and micro views. It also discusses innovative immune cell-based therapeutic strategies, offering new insights for further research on the pathophysiology of ischemic heart disease and immune cell-targeted therapy for IHD.

Exploring the Mechanism of Zhishi-Xiebai-Guizhi Decoction for the Treatment of Hypoxic Pulmonary Hypertension Based on Network Pharmacology and Experimental Analyses.

Hypoxic Pulmonary Hypertension (HPH), a prevalent disease in highland areas, is a crucial factor in various complex highland diseases with high mortality rates. Zhishi-Xiebai-Guizhi Decoction (ZXGD), traditional Chinese medicine with a long history of use in treating heart and lung diseases, lacks a clear understanding of its pharmacological mechanism. This study aimed to investigate the pharmacological effects and mechanisms of ZXGD on HPH. We conducted a network pharmacological prediction analysis and molecular docking to predict the effects, which were verified through in vivo experiments. Network pharmacological analysis revealed 51 active compounds of ZXGD and 701 corresponding target genes. Additionally, there are 2,116 target genes for HPH, 311 drug-disease co-target genes, and 17 core target genes. GO functional annotation analysis revealed that the core target genes primarily participate in biological processes such as apoptosis and cellular response to hypoxia. Furthermore, KEGG pathway enrichment analysis demonstrated that the core targets are involved in several pathways, including the phosphatidylinositol- 3 kinase/protein kinase B (PI3K/Akt) signaling pathway and Hypoxia Inducible Factor 1 (HIF1) signaling pathway. In vivo experiments, the continuous administration of ZXGD demonstrated a significant improvement in pulmonary artery pressure, right heart function, pulmonary vascular remodeling, and pulmonary vascular fibrosis in HPH rats. Furthermore, ZXGD was found to inhibit the expression of PI3K, Akt, and HIF1α proteins in rat lung tissue. In summary, this study confirmed the beneficial effects and mechanism of ZXGD on HPH through a combination of network pharmacology and in vivo experiments. These findings provided a new insight for further research on HPH in the field of traditional Chinese medicine.

Identification of Cuproptosis-related Gene Lipoyltransferase 1 as a Promising Biomarker in Oral Squamous Cell Carcinoma.

To find efficient cuproptosis-related biomarkers to explore the oncogenesis and progression of oral squamous cell carcinoma (OSCC). All the original data were downloaded from the Cancer Genome Atlas (TCGA) database. Univariate Cox analysis and Kaplan-Meier survival analysis were used to identify the gene related to survival. Tumor Immune Estimation Resource 2.0 (TIMER 2.0) was used to reveal the different expression of cuproptosis-related gene lipoyltransferase 1 (LIPT1) in various kinds of tumours. LIPT1, as a cuproptosis-related gene, was found to be differentially expressed in the OSCC group and the control group. It was also found to be related to the prognosis of OSCC. Pan cancer analysis showed LIPT1 was also involved in various kinds of tumours. All the results demonstrate that the cuproptosis-related gene LIPT1 is highly involved in the oncogenesis and progression of OSCC. These findings give new insight for further research into the cuproptosis-related biomarkers in OSCC.

Effect of regionalized structures on rock fracture process

The structure of rocks plays a crucial role in their failure process. However, it is ignored that the interactions between rock internal structure and the effect of its own evolution on the rock fracture process. To investigate the effect between the evolution law of rock regionalized structures and their interaction relationships during failure. We conducted an experiment using visual acoustic imaging monitoring to study rock failure, introducing a new concept of characteristics of rock structure—regionalized structures. The findings reveal three main types of regionalized structures in rocks: skeleton regions, variable regions, and damage regions. These structures combine to form four categories of complex rock structures: block-type support skeletons, point column-type support skeletons, suspension-type weak support skeletons, and no skeletons. During the failure process, we found that these regionalized structures worked together synergistically to control rock failure. Although the evolutionary relationships among the structures show some similarities, the final fracture states vary significantly. Stress and strain distribution patterns clearly demonstrate that variations in the force capacities and roles of the regionalized structures influence the synergistic evolutionary relationships, ultimately impacting the mode of rock failure. This work provides new insights for further research on rock failure mechanisms and can significantly contribute to preventing rock engineering disasters related to regionalized structures.

Overexpression of SYNGAP1 suppresses the proliferation of rectal adenocarcinoma via Wnt/β-Catenin signaling pathway

Rectal adenocarcinoma (READ) is a common malignant tumor of the digestive tract. Growing studies have confirmed Ras GTPase-activating proteins are involved in the progression of several tumors. This study aimed to explore the expression and function of Ras GTPase-activating proteins in READ. In this study, we analyzed RNA sequencing data from 165 patients with READ and 789 normal tissue samples, identifying 5603 differentially expressed genes (DEGs), including 2937 upregulated genes and 2666 downregulated genes. Moreover, we also identified two dysregulated genes, RASA4 and SYNGAP1, among six Ras GTPase-activating proteins. High NF1 expression was associated with longer overall survival, while high SYNGAP1 expression showed a trend towards extended overall survival. Further analysis revealed the mutation frequency and copy number variations of Ras GTPase-activating proteins in various cancer samples. Additionally, DNA methylation analysis demonstrated a negative correlation between DNA methylation of Ras GTPase-activating proteins and their expression. Moreover, among Ras GTPase-activating proteins, we focused on SYNGAP1, and experimental validation confirmed that the overexpression of SYNGAP1 in READ significantly suppressed READ cell proliferation and increased apoptosis via regulating the Wnt/β-Catenin signaling pathway. These findings underscored the potential significance of SYNGAP1 in READ and provide new insights for further research and treatment.

PagPXYs improve drought tolerance by regulating reactive oxygen species homeostasis in the cambium of Populus alba × P. glandulosa

PXY (Phloem intercalated with xylem) is a receptor kinase required for directional cell division during the development of plant vascular tissue. Drought stress usually affects plant stem cell division and differentiation thereby limiting plant growth. However, the role of PXY in cambial activities of woody plants under drought stress is unclear. In this study, we analyzed the biological functions of two PXY genes (PagPXYa and PagPXYb) in poplar growth and development and in response to drought stress in a hybrid poplar (Populus alba × P. glandulosa, ‘84K’). Expression analysis indicated that PagPXYs, similar to their orthologs PtrPXYs in Populus trichocarpa, are mainly expressed in the stem vascular system, and related to drought. Interestingly, overexpression of PagPXYa and PagPXYb in poplar did not have a significant impact on the growth status of transgenic plants under normal condition. However, when treated with 8 % PEG6000 or 100 mM H2O2, PagPXYa and PagPXYb overexpressing lines consistently exhibited more cambium cell layers, fewer xylem cell layers, and enhanced drought tolerance compared to the non-transgenic control ‘84K’. In addition, PagPXYs can alleviate the damage caused by H2O2 to the cambium under drought stress, thereby maintaining the cambial division activity of poplar under drought stress, indicating that PagPXYs play an important role in plant resistance to drought stress. This study provides a new insight for further research on the balance of growth and drought tolerance in forest trees.

IL-33 regulates adipogenesis via Wnt/β-catenin/PPAR-γ signaling pathway in preadipocytes

Interleukin-33 (IL-33), an emerging cytokine within the IL-1 family, assumes a pivotal function in the control of obesity. However, the specific mechanism of its regulation of obesity formation remains unclear. In this study, we found that the expression level of IL-33 increased in visceral adipose tissue in mice fed with a high-fat diet (HFD) compared with that in mice fed with a normal diet (ND). In vitro, we also found the expression level of IL-33 was upregulated during the adipogenesis of 3T3-L1 cells. Functional test results showed that knockdown of IL-33 in 3T3-L1 cells differentiation could promote the accumulation of lipid droplets, the content of triglyceride and the expression of adipogenic–related genes (i.e. PPAR-γ, C/EBPα, FABP4, LPL, Adipoq and CD36). In contrast, overexpression of IL-33 inhibits adipogenic differentiation. Meanwhile, the above tests were repeated after over-differentiation of 3T3-L1 cells induced by oleic acid, and the results showed that IL-33 played a more significant role in the regulation of adipogenesis. To explore the mechanism, transcriptome sequencing was performed and results showed that IL-33 regulated the PPAR signaling pathway in 3T3-L1 cells. Further, Western blot and confocal microscopy showed that the inhibition of IL-33 could promote PPAR-γ expression by inhibiting the Wnt/β-catenin signal in 3T3-L1 cells. This study demonstrated that IL-33 was an important regulator of preadipocyte differentiation and inhibited adipogenesis by regulating the Wnt/β-catenin/PPAR-γ signaling pathway, which provided a new insight for further research on IL-33 as a new intervention target for metabolic disorders.

Comprehensive bioinformatics analysis and systems biology approaches to identify the interplay between COVID-19 and pericarditis.

Increasing evidence indicating that coronavirus disease 2019 (COVID-19) increased the incidence and related risks of pericarditis and whether COVID-19 vaccine is related to pericarditis has triggered research and discussion. However, mechanisms behind the link between COVID-19 and pericarditis are still unknown. The objective of this study was to further elucidate the molecular mechanisms of COVID-19 with pericarditis at the gene level using bioinformatics analysis. Genes associated with COVID-19 and pericarditis were collected from databases using limited screening criteria and intersected to identify the common genes of COVID-19 and pericarditis. Subsequently, gene ontology, pathway enrichment, protein-protein interaction, and immune infiltration analyses were conducted. Finally, TF-gene, gene-miRNA, gene-disease, protein-chemical, and protein-drug interaction networks were constructed based on hub gene identification. A total of 313 common genes were selected, and enrichment analyses were performed to determine their biological functions and signaling pathways. Eight hub genes (IL-1β, CD8A, IL-10, CD4, IL-6, TLR4, CCL2, and PTPRC) were identified using the protein-protein interaction network, and immune infiltration analysis was then carried out to examine the functional relationship between the eight hub genes and immune cells as well as changes in immune cells in disease. Transcription factors, miRNAs, diseases, chemicals, and drugs with high correlation with hub genes were predicted using bioinformatics analysis. This study revealed a common gene interaction network between COVID-19 and pericarditis. The screened functional pathways, hub genes, potential compounds, and drugs provided new insights for further research on COVID-19 associated with pericarditis.

Circulating micronutrient levels and respiratory infection susceptibility and severity: a bidirectional Mendelian randomization analysis.

Limited and inconclusive data from observational studies and randomized controlled trials exist on the levels of circulating micronutrients in the blood and their association with respiratory infections. A Mendelian randomization (MR) analysis was conducted to assess the impact of 12 micronutrients on the risk of three types of infections [upper respiratory tract infections (URTI), lower respiratory tract infections (LRTI), and pneumonia] and their 14 subtypes. This study utilized a bidirectional MR approach to evaluate causal relationships and included a range of sensitivity analyses and multivariable MR to address potential heterogeneity and pleiotropy. The threshold for statistical significance was set at p < 1.39 × 10-3. Meta-analysis revealed that higher levels of circulating copper were significantly associated with a reduced risk of URTI (odds ratio (OR) = 0.926, 95% CI: 0.890 to 0.964, p = 0.000195). Additionally, copper demonstrated a suggestive association with a reduced risk of LRTI (p = 0.0196), and Vitamin B6 was nominally associated with a reduced risk of pneumonia (p = 0.048). Subtype analyses further indicated several suggestive associations: copper reduces the risk of acute pharyngitis (p = 0.029), vitamin C increases the risk of critical care admissions for pneumonia (p = 0.032) and LRTI (p = 0.021), and folate reduces the risk of viral pneumonia (p = 0.042). No significant connections were observed for other micronutrients. We observed a genetically predicted potential protective effect of copper in susceptibility to upper respiratory infections. This provides new insights for further research into the role of micronutrients in the prevention and treatment of infection.

Copper metabolism in osteoarthritis and its relation to oxidative stress and ferroptosis in chondrocytes.

Ferroptosis, an iron-ion-dependent process of lipid peroxidation, damages the plasma membrane, leading to non-programmed cell death. Osteoarthritis (OA), a prevalent chronic degenerative joint disease among middle-aged and older adults, is characterized by chondrocyte damage or loss. Emerging evidence indicates that chondrocyte ferroptosis plays a role in OA development. However, most research has concentrated on ferroptosis regulation involving typical iron ions, potentially neglecting the significance of elevated copper ions in both serum and joint fluid of patients with OA. This review aims to fill this gap by systematically examining the interplay between copper metabolism, oxidative stress, ferroptosis, and copper-associated cell death in OA. It will provide a comprehensive overview of copper ions' role in regulating ferroptosis and their dual role in OA. This approach seeks to offer new insights for further research, prevention, and treatment of OA.

Insights into myopic choroidal neovascularization based on quantitative proteomics analysis of the aqueous humor

BackgroundPrevious studies on the biomarkers of pathologic myopia choroidal neovascularization (pmCNV) development merely detected limited types of proteins and provide a meagre illustration of the underlying pathways. Hence, a landscape of protein changes in the aqueous humor (AH) of pmCNV patients is lacking. Here, to explore the potential mechanisms and biomarkers of pmCNV, we analyzed the clinical data and protein profile among atrophic (A) lesions, tractional lesions (T) and neovascular (N) lesions in myopic patients based on the ATN grading system for myopic maculopathy (MM).ResultsAfter investigating demographic data of our patients, a correlation was found between A and N lesions (R = 0.5753, P < 0.0001). Accordingly, groups were divided into patients without MM, patients with myopic atrophic maculopathy (MAM), and patients with pmCNV (N2a lesion). In proteomics analysis, the increased protein level of GFAP and complement-associated molecules in AH samples of the 3 groups also indicated that MAM and pmCNV shared similar characteristics. The GO enrichment and KEGG pathway analysis were performed, which mapped that differential expressed proteins mainly engaged in JAK-STAT pathway between the pmCNV group and two controls. Furthermore, we identified several potential biomarkers for pmCNV, including FCN3, GFAP, EGFR, SFRP3, PPP2R1A, SLIT2, and CD248.ConclusionsAtrophic lesions under pathologic myopic conditions demonstrated similarities to neovascularization development. Potential biomarkers including GFAP were associated with the pathogenesis of pmCNV. In summary, our study provides new insights for further research on pmCNV development.

How to leverage flexibility-oriented HRM systems to build organizational resilience in the digital era: the mediating role of intellectual capital

PurposeThe main purpose of this study is to investigate the effects of flexibility-oriented human resource management (FHRM) systems on intellectual capital and organizational resilience. This study also examines the moderating effect of digital capability on the relationship between intellectual capital and organizational resilience.Design/methodology/approachData were collected from 219 Chinese businesses in the Yangtze River Delta region of China during the COVID-19 pandemic. Confirmatory factor analysis was used to verify the validity and reliability of the measurements, and hypotheses were tested using hierarchical regression.FindingsThe empirical results show that FHRM systems are positively correlated with intellectual capital and organizational resilience. Intellectual capital mediates the link between FHRM systems and organizational resilience. Moreover, digital capability serves as a positive moderator between intellectual capital and organizational resilience.Originality/valueFrom the perspectives of resilience theory, the resource-based view and the theory of dynamic capabilities, this study is among the first to identify the process mechanism by which FHRM systems affect organizational resilience through intellectual capital. Digital capability is introduced as a situational factor for understanding the effect of intellectual capital on organizational resilience, which provides new insights for further research.

A novel strategy for key gene identification in hypertrophic cardiomyopathy based on cuproptosis and multiple WGCNA analyses

Abstract Background Hypertrophic cardiomyopathy (HCM) is a potentially fatal disease, and early diagnosis is crucial for effective treatment. Microarray analysis and the discovery of cuproptosis, a new form of cell death, offer new possibilities for identifying potential biomarkers for early diagnosis. Purpose This study aimed to identify cuproptosis-related genes associated with HCM and potential biomarkers for early diagnosis using machine learning. Methods Expression data of cuproptosis-related genes were extracted from the GSE36961 dataset, and differential expression analysis was conducted. Immune infiltration analyses were also performed. Samples were categorized into two clusters, and cluster weighted gene coexpression network analysis (WGCNA) was performed based on HCM and cluster clinical data. The results were combined to develop the best machine learning model, which was verified through calibration and external validation (GSE1145 and GSE32453). Results Cuproptosis-related genes (NLRP3, ATP7B, ATP7A, SLC31A1, LIAS, LIPT1, DLD, DLAT, PDHB, and DBT) were differentially expressed between HCM and control samples. Five key genes (TSPAN12, ANP32C, C4ORF18, COL21A1, and HMGB2) were identified, which showed great efficiency in the diagnosis of HCM in external validation, with an AUC of 0.948. These genes may play critical roles in megakaryocyte differentiation, RAGE receptor binding, and protein digestion and absorption. Conclusions Cuproptosis-related genes may play significant roles in HCM, and TSPAN12, ANP32C, C4ORF18, COL21A1, and HMGB2 may be potential biomarkers for the early diagnosis of HCM. This study provides new insights for further research on HCM diagnosis and treatment.Flow chart of research designEvaluation and verification results

Land Subsidence Prediction Model Based on the Long Short-Term Memory Neural Network Optimized Using the Sparrow Search Algorithm

Land subsidence is a prevalent geological issue that poses significant challenges to construction projects. Consequently, the accurate prediction of land subsidence has emerged as a focal point of research among scholars and experts. Traditional mathematical models exhibited certain limitations in forecasting the extent of land subsidence. To address this issue, the sparrow search algorithm (SSA) was introduced to optimize the efficacy of the long short-term memory (LSTM) neural network in land subsidence prediction. This prediction model has been successfully applied to the Huanglong Commercial City project in the Guanghua unit of Wenzhou city, Zhejiang province, China, and has been compared with the predictions of other models. Using monitoring location 1 as a reference, the MAE, MSE, and RMSE of the test samples for the LSTM neural network optimized using the SSA are 0.0184, 0.0004, and 0.0207, respectively, demonstrating a commendable predictive performance. This new model provides a fresh strategy for the land subsidence prediction of the project and offers new insights for further research on combined models.