Tumor suppressor BAP1 suppresses disulfidptosis through the regulation of SLC7A11 and NADPH levels.

BAP1, BRCA1-Associated Protein 1, serves as a novel tumor suppressor through the deubiquitination of monoubiquitination of H2A and subsequent gene transcriptional regulation. Regulated cell death like apoptosis or ferroptosis is considered an essential mechanism mediating tumor suppression. Previous reports, including ours, have demonstrated that BAP1 could promote apoptosis and ferroptosis to inhibit tumor development. Whether BAP1 regulated additional types of cell death remains unclear. Disulfidptosis is a recently identified novel cell death mode characterized by aberrant accumulation of intracellular disulfide (e.g., cystine) and depletion of NADPH. In this study, we first demonstrated that BAP1 could significantly protect disulfidptosis induced by glucose starvation, which is validated by various cell death inhibitors and the accumulation of disulfide bonds in the cytoskeleton proteins. BAP1 is known to inhibit SLC7A11 expression. We found that the protective effect of BAP1 against disulfidptosis was counteracted when overexpressing SLC7A11 or adding additional cystine. Conversely, BAP1-mediated suppression of disulfidptosis was largely abrogated when SLC7A11-mediated cystine uptake was inhibited by the knockout of SLC7A11 or erastin treatment. Besides, high BAP1 expression showed lower NADP+/NADPH levels, which might confer resistance to disulfidptosis. Consistent with these observations, the expression level of BAP1 was also positively correlated with NADPH-related genes in KIRC patients, though the underlying mechanism mediating NADPH regulation remains further investigation. In summary, our results revealed the role of BAP1 in the regulation disulfidptosis and provided new insights into the understanding of disulfidptosis in tumor development.

Secreted protein TNA: a promising biomarker for understanding the adipose-bone axis and its impact on bone metabolism.

BACKGROUND: Osteoporosis (OP) is a systemic bone disease characterized by reduced bone mass and deterioration of bone microstructure, leading to increased bone fragility. Platelets can take up and release cytokines, and a high platelet count has been associated with low bone density. Obesity is strongly associated with OP, and adipose tissue can influence platelet function by secreting adipokines. However, the biological relationship between these factors remains unclear. METHODS: We conducted differential analysis to identify OP platelet-related plasma proteins. And, making comprehensive analysis, including functional enrichment, protein-protein interaction network analysis, and Friends analysis. The key protein, Tetranectin (TNA/CLEC3B), was identified through screening. Then, we analyzed TNA's potential roles in osteogenic and adipogenic differentiation using multiple RNA-seq data sets and validated its effect on osteoclast differentiation and bone resorption function through in vitro experiments. RESULTS: Six OP-platelet-related proteins were identified via differential analysis. Then, we screened the key protein TNA, which was found to be highly expressed in adipose tissue. RNA-seq data suggested that TNA may promote early osteoblast differentiation. In vitro experiments showed that knockdown of TNA expression significantly increased the expression of osteoclast markers, thereby promoting osteoclast differentiation and bone resorption. CONCLUSIONS: We identified TNA as a secreted protein that inhibits osteoclast differentiation and bone resorption. While, it potentially promoted early osteoblast differentiation from bioinformatic results. TNA may play a role in bone metabolism through the adipose-bone axis.

Glucose deprivation-induced disulfidptosis in human nucleus pulposus cells: a novel pathological mechanism of intervertebral disc degeneration.

BACKGROUND: Limited supply of certain nutrients and deregulation of nucleus pulposus (NP) plays a key role in the pathogenesis of intervertebral disc degeneration (IVDD). However, whether nutrient deprivation-induced cell death, particularly disulfidptosis, contributes to the depletion of NP cells and the development of IVDD, is unknown. METHODS: RNA-seq, single-cell RNA-seq, and Genome-wide DNA methylation datasets of nucleus pulposus tissue were collected for bioinformatic analysis. Predictive models of disulfidptosis related genes in IVDD were constructed by machine learning and their differential expression was analyzed. In addition, we performed cell subsets identification analysis, cell-cell communications analysis, and functional enrichment analysis of key genes in the core subset based on single-cell RNA-seq data of NP tissues isolated from one normal sample and one IVDD sample. Finally, glucose deprivation-induced disulfidptosis in human NP cells (HNPCs) was verified by various cell death inhibitors and disulfidptosis-related molecular markers. RESULTS: We found the disulfidptosis signal was significantly activated in the IVDD group. Using single-cell RNA-seq analysis, we focused on the chondrocytes and found that disulfidptosis-related genes significantly highly expressed in the IVDD C4 chondrocyte subset, which was identified as a new disulfidptosis-associated cell subset. Correlation analysis revealed the negative correlation between SLC7A11 (driving gene of disulfidptosis) and the glucose transporter GLUTs (SLC2A1-4) family genes (suppressing genes of disulfidptosis) in the IVDD group. We also found obvious cell death in HNPC upon glucose starvation, while employment of various cell death inhibitors could not inhibit glucose starvation-induced death in HNPCs. Moreover, the accumulation of disulfide bonds in cytoskeletal proteins was indicated by slowed migration in non-reducible protein blotting experiments. 2-DG, a key disulfidptosis inhibitor, significantly rescued cell death caused by glucose starvation through lowering the NADP+/NADPH ratio. CONCLUSIONS: We validated the occurrence of disulfidptosis in HPNCs and identified a novel disulfidptosis-associated cell subset, followed by experimental verification of disulfidptosis in a glucose-limited context to mimic a fall in nutrient supply during the development disc degeneration. These findings provided new insights into the pathological mechanisms of IVDD and encourage us to explore potential therapeutic targets involved in the regulation of disulfidptosis for the prevention of intervertebral disc degeneration.

Zinc finger BED-type containing 3 promotes hepatic steatosis by interacting with polypyrimidine tract-binding protein 1.

AIMS/HYPOTHESIS: The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and type 2 diabetes mellitus, insulin resistance and the metabolic syndrome is well established. While zinc finger BED-type containing 3 (ZBED3) has been linked to type 2 diabetes mellitus and the metabolic syndrome, its role in MASLD remains unclear. In this study, we aimed to investigate the function of ZBED3 in the context of MASLD. METHODS: Expression levels of ZBED3 were assessed in individuals with MASLD, as well as in cellular and animal models of MASLD. In vitro and in vivo analyses were conducted using a cellular model of MASLD induced by NEFA and an animal model of MASLD induced by a high-fat diet (HFD), respectively, to investigate the role of ZBED3 in MASLD. ZBED3 expression was increased by lentiviral infection or tail-vein injection of adeno-associated virus. RNA-seq and bioinformatics analysis were employed to examine the pathways through which ZBED3 modulates lipid accumulation. Findings from these next-generation transcriptome sequencing studies indicated that ZBED3 controls SREBP1c (also known as SREBF1; a gene involved in fatty acid de novo synthesis); thus, co-immunoprecipitation and LC-MS/MS were utilised to investigate the molecular mechanisms by which ZBED3 regulates the sterol regulatory element binding protein 1c (SREBP1c). RESULTS: In this study, we found that ZBED3 was significantly upregulated in the liver of individuals with MASLD and in MASLD animal models. ZBED3 overexpression promoted NEFA-induced triglyceride accumulation in hepatocytes in vitro. Furthermore, the hepatocyte-specific overexpression of Zbed3 promoted hepatic steatosis. Conversely, the hepatocyte-specific knockout of Zbed3 resulted in resistance of HFD-induced hepatic steatosis. Mechanistically, ZBED3 interacts directly with polypyrimidine tract-binding protein 1 (PTBP1) and affects its binding to the SREBP1c mRNA precursor to regulate SREBP1c mRNA stability and alternative splicing. CONCLUSIONS/INTERPRETATION: This study indicates that ZBED3 promotes hepatic steatosis and serves as a critical regulator of the progression of MASLD. DATA AVAILABILITY: RNA-seq data have been deposited in the NCBI Gene Expression Omnibus ( www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE231875 ). MS proteomics data have been deposited to the ProteomeXchange Consortium via the iProX partner repository ( https://proteomecentral.proteomexchange.org/cgi/GetDataset?ID=PXD041743 ).

Alpha tACS on Parieto-Occipital Cortex Mitigates Motion Sickness Based on Multiple Physiological Observation.

Approximately one third of the population is prone to motion sickness (MS), which is associated with the dysfunction in the integration of sensory inputs. Transcranial alternating current stimulation (tACS) has been widely used to modulate neurological functions by affecting neural oscillation. However, it has not been applied in the treatment of motion sickness. This study aims to investigate changes in brain oscillations during exposure to MS stimuli and to further explore the potential impact of tACS with the corresponding frequency and site on MS symptoms. A total of 19 subjects were recruited to be exposed to Coriolis stimuli to complete an inducing session. After that, they were randomly assigned to tACS stimulation group or sham stimulation group to complete a stimulation session. Electroencephalography (EEG), electrocardiogram, and galvanic skin response were recorded during the experiment. All the subjects suffering from obvious MS symptoms after inducing session were observed that alpha power of four channels of parieto-occipital lobe significantly decreased (P7: t =3.589, p <0.001; P8: t =2.667, p <0.05; O1: t =3.556, p <0.001; O2: t =2.667, p <0.05). Based on this, tACS group received the tACS stimulation at 10Hz from Oz to CPz. Compared to sham group, tACS stimulation significantly improved behavioral performance and entrained the alpha oscillation in individuals whose alpha power decrease during the inducing session. The findings show that parieto-occipital alpha oscillation plays a critical role in the integration of sensory inputs, and alpha tACS on parieto-occipital can become a potential method to mitigate MS symptoms.

Chronic PM2.5 exposure disrupts intestinal barrier integrity via microbial dysbiosis-triggered TLR2/5-MyD88-NLRP3 inflammasome activation.

BACKGROUND: PM2.5, a known public health risk, is increasingly linked to intestinal disorders, however, the mechanisms of its impact are not fully understood. PURPOSE: This study aimed to explore the impact of chronic PM2.5 exposure on intestinal barrier integrity and to uncover the underlying molecular mechanisms. METHODS: C57BL/6 J mice were exposed to either concentrated ambient PM2.5 (CPM) or filtered air (FA) for six months to simulate urban pollution conditions. We evaluated intestinal barrier damage, microbial shifts, and metabolic changes through histopathology, metagenomics, and metabolomics. Analysis of the TLR signaling pathway was also conducted. RESULTS: The mean concentration of PM2.5 in the CPM exposure chamber was consistently measured at 70.9 ± 26.8 µg/m³ throughout the study period. Our findings show that chronic CPM exposure significantly compromises intestinal barrier integrity, as indicated by reduced expression of the key tight junction proteins Occludin and Tjp1/Zo-1. Metagenomic sequencing revealed significant shifts in the microbial landscape, identifying 35 differentially abundant species. Notably, there was an increase in pro-inflammatory nongastric Helicobacter species and a decrease in beneficial bacteria, such as Lactobacillus intestinalis, Lactobacillus sp. ASF360, and Eubacterium rectale. Metabolomic analysis further identified 26 significantly altered metabolites commonly associated with intestinal diseases. A strong correlation between altered bacterial species and metabolites was also observed. For example, 4 Helicobacter species all showed positive correlations with 13 metabolites, including Lactate, Bile acids, Pyruvate and Glutamate. Additionally, increased expression levels of TLR2, TLR5, Myd88, and NLRP3 proteins were noted, and their expression patterns showed a strong correlation, suggesting a possible involvement of the TLR2/5-MyD88-NLRP3 signaling pathway. CONCLUSIONS: Chronic CPM exposure induces intestinal barrier dysfunction, microbial dysbiosis, metabolic imbalance, and activation of the TLR2/5-MyD88-NLRP3 inflammasome. These findings highlight the urgent need for intervention strategies to mitigate the detrimental effects of air pollution on intestinal health and identify potential therapeutic targets.

DNA damage response-related signatures characterize the immune landscape and predict the prognosis of HCC via integrating single-cell and bulk RNA-sequencing.

BACKGROUND: The occurrence and progression of hepatocellular carcinoma (HCC) are significantly affected by DNA damage response (DDR). Exploring DDR-related biomarkers can help predict the prognosis and immune characteristics of HCC. METHODS: First, the single-cell RNA sequencing (scRNA-seq) dataset GSE242889 was processed and performed manual annotation. Then we found the marker genes of DDR-active subgroups based on "AUCell" algorithm. The "Limma" R package was used to identify differentially expressed genes (DEGs) between tumor and normal samples of HCC. The risk prognostic model was constructed by filtering genes using univariate Cox and LASSO regression analyses. Finally, the signatures were analyzed for immune infiltration, gene mutation, and drug sensitivity. Last but not least, KPNA2, which had the largest coefficient in our model was validated by experiments including western blot, MTT, colony formation and γ-H2AX assays. RESULTS: We constructed a prognostic model based on 5 DDR marker genes including KIF2C, CDC20, KPNA2, UBE2S and ADH1B for HCC. We also proved that the model had an excellent performance in both training and validation cohorts. Patients in the high-risk group had a poorer prognosis, different immune features, gene mutation frequency, immunotherapy response and drug sensitivity compared with the low-risk group. Besides, our experimental results proved that KPNA2 was up-regulated in liver cancer cells than in hepatocytes. More importantly, the knockdown of KPNA2 significantly inhibited cell variability, proliferation and promoted DNA damage. CONCLUSIONS: We innovatively integrated scRNA-seq and bulk RNA sequencing to construct the DDR-related prognostic model. Our model could effectively predict the prognosis, immune landscape and therapy response of HCC.

Integrated bioinformatics combined with machine learning to analyze shared biomarkers and pathways in psoriasis and cervical squamous cell carcinoma.

Background: Psoriasis extends beyond its dermatological inflammatory manifestations, encompassing systemic inflammation. Existing studies have indicated a potential risk of cervical cancer among patients with psoriasis, suggesting a potential mechanism of co-morbidity. This study aims to explore the key genes, pathways, and immune cells that may link psoriasis and cervical squamous cell carcinoma (CESC). Methods: The cervical squamous cell carcinoma dataset (GSE63514) was downloaded from the Gene Expression Omnibus (GEO). Two psoriasis-related datasets (GSE13355 and GSE14905) were merged into one comprehensive dataset after removing batch effects. Differentially expressed genes were identified using Limma and co-expression network analysis (WGCNA), and machine learning random forest algorithm (RF) was used to screen the hub genes. We analyzed relevant gene enrichment pathways using GO and KEGG, and immune cell infiltration in psoriasis and CESC samples using CIBERSORT. The miRNA-mRNA and TFs-mRNA regulatory networks were then constructed using Cytoscape, and the biomarkers for psoriasis and CESC were determined. Potential drug targets were obtained from the cMAP database, and biomarker expression levels in hela and psoriatic cell models were quantified by RT-qPCR. Results: In this study, we identified 27 key genes associated with psoriasis and cervical squamous cell carcinoma. NCAPH, UHRF1, CDCA2, CENPN and MELK were identified as hub genes using the Random Forest machine learning algorithm. Chromosome mitotic region segregation, nucleotide binding and DNA methylation are the major enrichment pathways for common DEGs in the mitotic cell cycle. Then we analyzed immune cell infiltration in psoriasis and cervical squamous cell carcinoma samples using CIBERSORT. Meanwhile, we used the cMAP database to identify ten small molecule compounds that interact with the central gene as drug candidates for treatment. By analyzing miRNA-mRNA and TFs-mRNA regulatory networks, we identified three miRNAs and nine transcription factors closely associated with five key genes and validated their expression in external validation datasets and clinical samples. Finally, we examined the diagnostic effects with ROC curves, and performed experimental validation in hela and psoriatic cell models. Conclusions: We identified five biomarkers, NCAPH, UHRF1, CDCA2, CENPN, and MELK, which may play important roles in the common pathogenesis of psoriasis and cervical squamous cell carcinoma, furthermore predict potential therapeutic agents. These findings open up new perspectives for the diagnosis and treatment of psoriasis and squamous cell carcinoma of the cervix.

Machine Learning-based Development and Validation of a Cell Senescence Predictive and Prognostic Signature in Intrahepatic Cholangiocarcinoma.

Background: Previous studies have shown that cellular senescence is strongly associated with tumorigenesis and the tumor microenvironment. Accordingly, we developed a novel prognostic signature for intrahepatic cholangiocarcinoma (ICCA) based on senescence-associated long non-coding RNAs (SR-lncRNAs) and identified a lncRNA-miRNA-mRNA axis involving in ICCA. Methods: Based on the 197 senescence-associated genes (SRGs) from Genacards and their expression in Fu-ICCA cohort, we identified 20 lncRNAs as senescence-associated lncRNAs (SR-lncRNAs) through co-expression and cox-regression analysis. According to 20 SR-lncRNAs, patients with ICCA were classified into 2 molecular subtypes using unsupervised clustering machine learning approach and to explore the prognostic and functional heterogeneity between these two subtypes. Subsequently, we integrated 113 machine learning algorithms to develop senescence-related lncRNA signature, ultimately identifying 11 lncRNAs and constructing prognostic models and risk stratification. The correlation between the signature and the immune landscape, immunotherapy response as well as drug sensitivity are explored too. Results: We developed a novel senescence related signature. The predictive model and risk score calculated by the signature exhibited favorable prognostic predictive performance, which is a suitable independent risk factor for the prognosis of patients with ICCA based on Kaplan-Meier plotter, nomogram and receiving operating characteristic (ROC) curves. The results were validated using external datasets. Estimate, ssGSEA (single sample gene set enrichment analysis), IPS (immunophenotype score) and TIDE (tumor immune dysfunction and exclusion) algorithms revealed higher immune infiltration, higher immune scores, lower immune escape potential and better response to immunotherapy in the high-risk group. In addition, signature identifies eight chemotherapeutic agents, including cisplatin for patients with different risk levels, providing guidance for clinical treatment. Finally, we identified a set of lncRNA-miRNA-mRNA axes involved in ICCA through regulation of senescence. Conclusion: SR-lncRNAs signature can favorably predict the prognosis, risk stratification, immune landscape and immunotherapy response of patients with ICCA and consequently guide individualized treatment.

Association between visceral adipose tissue and asthma based on the NHANES and Mendelian randomization study.

BACKGROUND: Obesity is a crucial risk factor for asthma. Observational studies have examined the association between abdominal obesity and asthma symptoms. This study aimed to investigate the causal relationship between visceral adipose tissue (VAT) and asthma and its potential as an independent indicator. METHODS: This study utilized data from the National Health and Nutrition Examination Survey spanning 2011-8. Multivariable logistic regression and stratified variable selection were employed to identify associations between asthma and VAT. Moreover, a two-sample Mendelian randomization analysis, using 221 genetic variants as instrumental variables, was conducted to assess this relationship further. RESULTS: Our findings indicated that individuals with higher VAT levels were more likely to develop asthma. Visceral obesity remained a significant risk factor for asthma after adjusting for demographic characteristics. Genetic predictions suggest a positive association between VAT and an elevated risk of asthma (odds ratio [OR] = 1.393, 95% confidence interval [CI]: 1.266-1.534, and P = 1.43E-11). No significant polymorphisms were detected using the Mendelian randomization-Egger intercept test. CONCLUSIONS: This study presents potential evidence supporting the causal role of VAT in asthma development. Furthermore, the findings from the Mendelian randomization analysis further reinforce the relationship between VAT and asthma risk.

The significance of m6A RNA methylation regulators in diagnosis and subtype classification of HBV-related hepatocellular carcinoma.

In recent years, abnormal m6A alteration in hepatocellular carcinoma (HCC) has been a focus on investigating the biological implications. In this study, our objective is to determine whether m6A modification contributes to the progression of HBV-related HCC. To achieve this, we employed a random forest model to screen top 8 characteristic m6A regulators from 19 candidate genes. Subsequently, we developed a nomogram model that utilizes these 8 characteristic m6A regulators to predict the prevalence of HBV-related HCC. According to decision curve analysis, patients may benefit from the nomogram model. The clinical impact curves exhibited a robust predictive capability of the nomogram models. Additionally, consensus molecular subtyping was employed to identify m6A modification patterns and m6A-related gene signature. The quantification of immune cell subsets was accomplished through the implementation of ssGSEA algorithms. PCA algorithms were developed to compute the m6A score for individual tumors. Two distinct m6A modification patterns, namely cluster A and cluster B, exhibited significant correlations with distinct immune infiltration patterns and biological pathways. Notably, patients belonging to cluster B demonstrated higher m6A scores compared to those in cluster A, as determined by the m6A score metric. Furthermore, the expression of IGFBP3 proteins was validated through immunofluorescence, revealing their pronounced lower expression in tumor tissues. In summary, our study underscores the importance of m6A modification in the advancement of HBV-related HCC. This research has the potential to yield novel prognostic biomarkers and therapeutic targets for the identification of HBV-related HCC.

PCDH8 is a novel prognostic biomarker in thyroid cancer and promotes cell proliferation and viability.

Protocadherin 8 (PCDH8), a calcium-dependent transmembrane protein in the protocadherin family, regulates cell adhesion and signal transduction. While some studies have provided indirect evidence that PCDH8 has cancer-promoting properties, this association is controversial. In particular, its involvement in thyroid cancer (THCA) remains unclear. We aimed to elucidate the role of PCDH8 in THCA using bioinformatic analysis. Subsequently, the results were experimentally validated. The analysis conducted using the R programming language and online web tools explored PCDH8 expression levels, prognostic, and clinical implications, and its relationship with the tumor immune microenvironment in THCA. Furthermore, we examined the association between PCDH8 and co-expressed genes, highlighting their involvement in several biological processes relevant to THCA. The potential of PCDH8 as a therapeutic target for this pathology was also explored. Immunohistochemical (IHC) staining was performed on samples from 98 patients with THCA, and experimental validation was carried out. PCDH8 was significantly elevated in cancer tissues and associated with poor prognosis, several clinical factors, and immune cell and checkpoint abundance. Cox regression and survival analyses, together with Receiver Operating Curves (ROC) indicated that PCDH8 was an independent prognostic factor for THCA. Furthermore, PCDH8 impacts cell viability and proliferation, promoting tumorigenesis. Also, it influences tumor cell sensitivity to various drugs. Thus, PCDH8 might be a potential therapeutic target for THCA. IHC, cell culture, MTT, and colony formation experiments further confirmed our findings. This analysis provided insights into the potential carcinogenic role of PCDH8 in THCA, as it impacts cell viability and proliferation. Thus, PCDH8 might play an important role in its prognosis, immune infiltration, and diagnosis.

Colonic microflora and plasma metabolite-based comparative analysis of unilateral ureteral obstruction-induced chronic kidney disease after treatment with the Chinese medicine FuZhengHuaYuJiangZhuTongLuo and AST-120.

Background: Many researchers have investigated the use of Chinese herbs to delay the progression of chronic kidney disease (CKD) through their effects on colonic microflora and microbiota-derived metabolites. However, whether FuZhengHuaYuJiangZhuTongLuo (FZHY) has effects that are similar to those of AST-120 on CKD needs to be elucidated. Methods: In this study, we compared the effects of FZHY and AST-120 on the colonic microbiota and plasma metabolites in the CKD rat model. We developed a unilateral ureteral obstruction (UUO)-induced CKD rat model and then administered FZHY and AST-120 to these model rats. Non-targeted metabolomic LC-MS analysis, 16S rRNA sequencing, and histopathological staining were performed on plasma, stool, and kidney tissues, respectively, and the joint correlation between biomarkers and metabolites of candidate bacteria was analyzed. Results: Our results showed that administering FZHY and AST-120 effectively ameliorated UUO-induced abnormal renal function and renal fibrosis and regulated the composition of microbiota and metabolites. Compared to the UUO model group, the p_Firmicutes and o_Peptostreptococcales_Tissierellales were increased, while 14 negative ion metabolites were upregulated and 21 were downregulated after FZHY treatment. Additionally, 40 positive ion metabolites were upregulated and 63 were downregulated. On the other hand, AST-120 treatment resulted in an increase in the levels of g_Prevotellaceae_NK3B31_group and f_Prevotellaceae, as well as 12 upregulated and 23 downregulated negative ion metabolites and 56 upregulated and 63 downregulated positive ion metabolites. Besides, FZHY increased the levels of candidate bacterial biomarkers that were found to be negatively correlated with some poisonous metabolites, such as 4-hydroxyretinoic acid, and positively correlated with beneficial metabolites, such as l-arginine. AST-120 increased the levels of candidate bacterial biomarkers that were negatively correlated with some toxic metabolites, such as glycoursodeoxycholic acid, 4-ethylphenol, and indole-3-acetic acid. Conclusion: FZHY and AST-120 effectively reduced kidney damage, in which, the recovery of some dysregulated bacteria and metabolites are probably involved. As their mechanisms of regulation were different, FZHY might play a complementary role to AST-120 in treating CKD.

Is Kidney Stone Associated with Thyroid Disease? The United States National Health and Nutrition Examination Survey 2007-2018.

BACKGROUND: Kidney stones and thyroid disease are two common diseases in the general population, with multiple common risk factors. The associations between kidney stones and thyroid disease are unclear. AIM: This study aims to assess the association between 'once had a thyroid disease' and the odds of kidney stones. METHODS: Adult participants from the National Health and Nutrition Examination Survey (NHANES) 2007-2018 with reliable kidney stone and thyroid disease data were included. Adjusting for age, gender, race, education level, and marital status, diabetes, hypertension, gout, angina pectoris, stroke, and asthma, logistic regression was used to examine the relationship between kidney stones and thyroid illness. RESULTS: Using stratified analysis, the association between thyroid illness and kidney stones was investigated further. Among the participants, 4.9% had kidney stones, and 10.1% had thyroid disease. Kidney stone was associated with thyroid disease (OR=1.441, (95% CI:1.294-1.604), p <0.01), which remained significant (OR=1.166, (95% CI:1.041-1.305), p <0.01) after adjustments with age, gender, race, education level and marital status, diabetes, hypertension, gout, angina pectoris, stroke, and asthma. Stratified by blood lead, blood cadmium, and blood urea nitrogen levels in the human body, the odds of kidney stones still increased with once having a previous thyroid disease. CONCLUSIONS: In this large nationally representative survey over 10 years, kidney stone was strongly associated with thyroid disease. In this cross-sectional study, we explored the association between thyroid disease and kidney stones, which may help clinicians intervene in them early.

Changes in Blood Pressure is Associated with Bone Loss in US Adults: A Cross-Sectional Study from NHANES 2005-2018.

Hypertension and osteoporosis are common geriatric diseases, sharing similar risk factors. This study aims to investigate this association and explore relatively mixed variables. Our study included 12,787 eligible participants from the National Health and Nutrition Examination Survey (NHANES) 2005-2018. Included participants had valid data on hypertension and osteoporosis, without tumors, liver diseases, gout or thyroid diseases. We explored the association between hypertension and osteoporosis by logistic regression and examined blood pressure and BMD/BMC by linear and non-linear regression. Moreover, we used machine learning models to predict the importance of various factors in the occurrence of osteoporosis and evaluated causality by mendelian randomization. Our study found that osteoporosis is significantly associated with hypertension [OR 2.072 (95% CI 2.067-2.077), p < 0.001]. After adjusting for co-variances, the association remained significant [OR 1.223 (95% CI 1.220-1.227), p < 0.001]. Our study showed that osteoporosis is positively associated with hypertension in the US population. A variety of factors influence this relationship. Specific regulatory mechanisms and confounding factors need to be further investigated.

Integrated Multi-omics Analyses Identify CDCA5 as a Novel Biomarker Associated with Alternative Splicing, Tumor Microenvironment, and Cell Proliferation in Colon Cancer Via Pan-cancer Analysis.

Background: CDCA5 has been reported as a gene involved in the cell cycle, however current research provides little details. Our goal was to figure out its functions and probable mechanisms in pan-cancer. Methods: Pan-cancer bulk sequencing data and web-based analysis tools were applied to analyze CDCA5's correlations with the gene expression, clinical prognosis, genetic alterations, promoter methylation, alternative splicing, immune checkpoints, tumor microenvironment and enrichment. Real­time PCR, cell clone formation assay, CCK-8 assay, cell proliferation assay, migration assay, invasion assay and apoptosis assay were used to evaluate the effect of CDCA5 silencing on colon cancer cell lines. Results: CDCA5 is highly expressed in most tumors, which has been linked to a poor prognosis. Immune checkpoints analysis revealed that CDCA5 was associated with the immune gene CD276 in various tumors. Single-cell analysis showed that CDCA5 correlated with proliferating T cell infiltration in COAD. Enrichment analysis demonstrated that CDCA5 may modify cell cycle genes to influence p53 signaling. The examination of DLD1 cells revealed that CDCA5 increased the proliferation and blocked cell apoptosis. Conclusion: This study contributes to the knowledge of the role of CDCA5 in carcinogenesis, highlighting the prognostic potential and carcinogenic involvement of CDCA5 in pan-cancer.

Enhanced catalytic performance of penicillin G acylase by covalent immobilization onto functionally-modified magnetic Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles.

With the emergence of penicillin resistance, the development of novel antibiotics has become an urgent necessity. Semi-synthetic penicillin has emerged as a promising alternative to traditional penicillin. The demand for the crucial intermediate, 6-aminopicillanic acid (6-APA), is on the rise. Enzyme catalysis is the primary method employed for its production. However, due to certain limitations, the strategy of enzyme immobilization has also gained prominence. The magnetic Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles were successfully prepared by a rapid-combustion method. Sodium silicate was used to modify the surface of the Ni0.4Cu0.5Zn0.1Fe2O4 nanoparticles to obtain silica-coated nanoparticles (Ni0.4Cu0.5Zn0.1Fe2O4-SiO2). Subsequently, in order to better crosslink PGA, the nanoparticles were modified again with glutaraldehyde to obtain glutaraldehyde crosslinked Ni0.4Cu0.5Zn0.1Fe2O4-SiO2-GA nanoparticles which could immobilize the PGA. The structure of the PGA protein was analyzed by the PyMol program and the immobilization strategy was determined. The conditions of PGA immobilization were investigated, including immobilization time and PGA concentration. Finally, the enzymological properties of the immobilized and free PGA were compared. The optimum catalytic pH of immobilized and free PGA was 8.0, and the optimum catalytic temperature of immobilized PGA was 50°C, 5°C higher than that of free PGA. Immobilized PGA in a certain pH and temperature range showed better catalytic stability. Vmax and Km of immobilized PGA were 0.3727 µmol·min-1 and 0.0436 mol·L-1, and the corresponding free PGA were 0.7325 µmol·min-1 and 0.0227 mol·L-1. After five cycles, the immobilized enzyme activity was still higher than 25%.

Investigation of GPR143 as a promising novel marker for the progression of skin cutaneous melanoma through bioinformatic analyses and cell experiments.

BACKGROUND: Skin cutaneous melanoma (SKCM) is an aggressive and life-threatening skin cancer. G-protein coupled receptor 143 (GPR143) belongs to the superfamily of G protein-coupled receptors. METHODS: We used the TCGA, GTEx, CCLE, and the Human Protein Atlas databases to examine the mRNA and protein expression of GPR143. In addition, we performed a survival analysis and evaluated the diagnostic efficacy using the Receiver-Operating Characteristic (ROC) curve. Through CIBERSORT, R programming, TIMER, Gene Expression Profiling Interactive Analysis, Sangerbox, and Kaplan-Meier plotter database analyses, we explored the relationships between GPR143, immune infiltration, and gene marker expression of immune infiltrated cells. Furthermore, we investigated the proteins that potentially interact with GPR143 and their functions using R programming and databases including STRING, GeneMANIA, and GSEA. Meanwhile, the cBioPortal, UALCNA, and the MethSurv databases were used to examine the genomic alteration and methylation of GPR143 in SKCM. The Connectivity Map database was used to discover potentially effective therapeutic molecules against SKCM. Finally, we conducted cell experiments to investigate the potential role of GPR143 in SKCM. RESULTS: We demonstrated a significantly high expression level of GPR143 in SKCM compared with normal tissues. High GPR143 expression and hypomethylation status of GPR143 were associated with a poorer prognosis. ROC analysis showed that the diagnostic efficacy of the GPR143 was 0.900. Furthermore, GPR143 expression was significantly correlated with immune infiltration in SKCM. We identified 20 neighbor genes and the pathways they enriched were anabolic process of pigmentation, immune regulation, and so on. Genomic alteration analysis revealed significantly different copy number variations related to GPR143 expression in SKCM, and shallow deletion could lead to high expression of GPR143. Ten potential therapeutic drugs against SKCM were identified. GPR143 knockdown inhibited melanoma cell proliferation, migration, and colony formation while promoting apoptosis. CONCLUSIONS: Our findings suggest that GPR143 serves as a novel diagnostic and prognostic biomarker and is associated with the progression of SKCM.

Surpassing the limitation of a coherence length in lidar by digital coherence.

In this manuscript, we propose a digital coherent detection method to surpass the limitation of a coherent length on the detection range of a coherent lidar. This method rapidly reconstructs the laser phase noise utilizing the multi-channel delay self-homodyne and the generalized inverse of the system observation matrix. Subsequently, the reconstructed phase noise is utilized to expunge its perturbation onto the target information in the digital domain, thereby effectively surmounting the coherence length limitation. Through experimentation, the proposed method is verified to produce stable and high-quality interference even when the optical path difference between two beams exceeds 1000 times the coherence length. Additionally, the equivalent laser linewidth is compressed by 105 times.