Construction and validation of a nomogram for predicting diabetes remission at 3 months after bariatric surgery in patients with obesity combined with type 2 diabetes mellitus.

AIM: Bariatric metabolic surgery (BMS) is a proven treatment option for patients with both obesity and type 2 diabetes mellitus (T2DM). However, there is a lack of comprehensive reporting on the short-term remission rates of diabetes, and the existing data are inadequate. Hence, this study aimed to investigate the factors that may contribute to diabetes remission (DR) in patients with obesity and T2DM, 3 months after undergoing BMS. Furthermore, our objective was to develop a risk-predicting model using a nomogram. METHODS: In total, 389 patients with obesity and T2DM, who had complete preoperative information and underwent either laparoscopic sleeve gastrectomy or laparoscopic gastric bypass surgery between January 2014 and May 2023, were screened in the Chinese Obesity and Metabolic Surgery Database. The patients were randomly divided into a training set (n = 272) and a validation set (n = 117) in a 7:3 ratio. Potential factors for DR were analysed through univariate and multivariate logistic regression analyses and then modelled using a nomogram. The model's performance was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Calibration plots were used to assess prediction accuracy and decision curve analyses were conducted to evaluate the clinical usefulness of the model. RESULTS: Glycated haemoglobin, triglycerides, duration of diabetes, insulin requirement and hypercholesterolaemia were identified as independent factors influencing DR. We have incorporated these five indicators into a nomogram, which has shown good efficacy in both the training cohort (AUC = 0.930) and validation cohort (AUC = 0.838). The calibration plots indicated that the model fits well in both the training and the validation cohorts, and decision curve analyses showed that the model had good clinical applicability. CONCLUSION: The prediction model developed in this study holds predictive value for short-term DR following BMS in patients with obesity and T2DM.

Do testosterone and sex hormone-binding globulin affect cancer risk? A Mendelian randomization and bioinformatics study.

Using Mendelian Randomization (MR) and large-scale Genome-Wide Association Study (GWAS) data, this study aimed to investigate the potential causative relationship between testosterone and sex hormone-binding globulin (SHBG) levels and the onset of several cancers, including pathway enrichment analyses of single nucleotide polymorphisms (SNPs) associated with cancer allowed for a comprehensive bioinformatics approach, which offered a deeper biological understanding of these relationships. The results indicated that increased testosterone levels in women were associated with a higher risk of breast and cervical cancers but a lower risk of ovarian cancer. Conversely, increased testosterone was linked to lower stomach cancer risk for men, whereas high SHBG levels were related to decreased risks of breast and prostate cancers. The corresponding genes of the identified SNPs, as revealed by pathway enrichment analysis, were involved in significant metabolic and proliferative pathways. These findings emphasize the need for further research into the biological mechanisms behind these associations, paving the way for potential targeted interventions in preventing and treating these cancers.

A Security Management and Control Solution of Smart Park Based on Sensor Networks.

As a typical application of sensor networks, there exist many information security problems in smart parks, such as confusion of personnel access, lack of security management, disorderly data flow, insufficient collection of audit evidence, and so on. Aiming at the scenario of personnel and equipment moving in different areas of smart parks, the paper proposes a joint authorization and dynamic access control mechanism, which can provide unified identity management services, access control services, and policy management services, and effectively solve the problem of multi-authorization in user identity and authority management. The license negotiation interaction protocol is designed to prevent common network attack threats in the process of identity authentication and authority management. In order to realize the tamper-proof storage of personnel and equipment movement trajectory, the paper also designs a movement trajectory traceability protocol based on a Merkle tree, which solves the problems of internal personnel malicious attack, trusted third-party dependency bottleneck, high overheads of tracking algorithms, and so on. The experimental results show that compared with the current security control mechanisms for sensor networks, the joint authorization, and dynamic access control mechanism can support multi-party authorization and traceability, while the overhead it generates in initialization, encryption, decryption, and key generation steps are basically the same as other mechanisms do.

Genetic insights into the role of cathepsins in cardiovascular diseases: a Mendelian randomization study.

AIMS: This study aimed to explore the causal relationships between cathepsins and cardiovascular diseases (CVDs) by Mendelian randomization (MR) analysis. METHODS AND RESULTS: Single nucleotide polymorphisms (SNPs) associated with nine cathepsin types (cathepsins B, E, F, G, H, O, S, L2, and Z) were obtained from the INTERVAL study (3301 individuals). CVDs data were acquired from the UK Biobank (coronary atherosclerosis: 14 334 cases, 346 860 controls) and a genome-wide association study (GWAS) (myocardial infarction: 20 917 cases, 440 906 controls; myocarditis: 633 cases, 427 278 controls; chronic heart failure: 14 262 cases, 471 898 controls; angina pectoris: 30 025 cases, 440 906 controls; stable angina pectoris: 17 894 cases, 325 132 controls; unstable angina pectoris: 9481 cases, 446 987 controls; pericarditis: 1795 cases, 453 370 controls). Inverse variance weighted (IVW), MR-Egger, weighted median methods were adopted to conduct univariable MR (UVMR), reverse MR, multivariable MR (MVMR) analyses to estimate causality. The UVMR analyses demonstrated significant causal relationships between higher cathepsin E levels and increased risk of coronary atherosclerosis [IVW: P = 0.0051, odds ratio (OR) = 1.0033, 95% confidence interval (CI) = 1.0010-1.0056] and myocardial infarction (IVW: P = 0.0097, OR = 1.0553, 95% CI = 1.0131-1.0993), while elevated cathepsin L2 levels were causally related to reduced risk of myocarditis (IVW: P = 0.0120, OR = 0.6895, 95% CI = 0.5158-0.9216) and chronic heart failure (IVW: P = 0.0134, OR = 0.9316, 95% CI = 0.8807-0.9854). Reverse MR analyses revealed that myocardial infarction increased cathepsin O levels (IVW: P = 0.0400, OR = 1.0708, 95% CI = 1.0031-1.1431). MVMR analyses treating nine cathepsins together revealed that the positive causality between cathepsin E levels and coronary atherosclerosis risk (IVW: P = 0.0390, OR = 1.0030, 95% CI = 1.0000-1.0060), and the protective effect of cathepsin L2 levels on myocarditis (IVW: P = 0.0030, OR = 0.6610, 95% CI = 0.5031-0.8676) and chronic heart failure (IVW: P = 0.0090, OR = 0.9259, 95% CI = 0.8737-0.9812) remained, as higher cathepsin O levels were found to be causally related to increased risks of myocarditis (IVW: P = 0.0030, OR = 1.6145, 95% CI = 1.1829-2.2034) and chronic heart failure (IVW: P = 0.0300, OR = 1.0779, 95% CI = 1.0070-1.1537). CONCLUSIONS: The study highlights the causalities of cathepsin E, L2, and O on CVDs, offering insights into their roles in cardiovascular biomarkers and therapeutic targets development. Further research is required to apply these genetic findings clinically.

Research trends between diabetes mellitus and bariatric surgery researches: Bibliometric analysis and visualization from 1998 to 2023.

This study conducted a bibliometric analysis using the Web of Science Core Collection (WOSCC) to explore the relationship between diabetes mellitus and bariatric surgery (BS) from January 1985 to August 2023. No publications were found between 1985 and 1998. However, from 1998 to 2023, a total of 9,496 English articles were identified, accumulating 291,289 citations (241,563 excluding self-citations) and achieving an H-Index of 197. Leading contributors to the field were the United States, China, and Italy. Noteworthy authors in this area of research included Philip R. Schauer, Wei-Jei Lee, and Carel W. le Roux. The major journals that featured this research were 'Obesity Surgery,' 'Diabetes Care,' and 'Surgery for Obesity and Related Diseases.' The most highly cited article focused on lifestyle, diabetes, and cardiovascular risks 10 years after BS, emphasizing the significant attention given to the nutritional, cardiac, and general internal medicine impacts of diabetes and BS. The increase in research output during the review period indicates a growing interest in the relationship between diabetes and BS, providing a valuable reference for future studies in this evolving field.

Novel diagnostic biomarkers of oxidative stress, ferroptosis, immune infiltration characteristics and experimental validation in ischemic stroke.

Ischemic stroke (IS) is a prominent type of cerebrovascular disease leading to death and disability in an aging society and is closely related to oxidative stress. Gene expression profiling (GSE222551) was derived from Gene Expression Omnibus (GEO), and 1934 oxidative stress (OS) genes were obtained from the GeneCards database. Subsequently, we identified 149 differentially expressed genes related to OS (DEOSGs). Finally, PTGS2, FOS, and RYR1 were identified as diagnostic markers of IS. Moreover, GSE16561 was used to validate the DEOSGs. Two diagnostic genes (PTGS2 and FOS) were significantly highly expressed, while RYR1 was significantly lowly expressed in the IS group. Remarkably, immune infiltration characteristics of these three genes were analyzed, and we found that PTGS2, FOS, and RYR1 were mainly correlated with Mast cells activated, Neutrophils, and Plasma cells, respectively. Next, we intersected three DEOSGs with the ferroptosis gene set, the findings revealed that only PTGS2 was a differentially expressed gene of ferroptosis. High PTGS2 expression levels in the infarcted cortex of middle cerebral artery occlusion (MCAO) rats were confirmed by immunofluorescence (IF), western blotting (WB), and Immunohistochemistry (IHC). Inhibition of PTGS2 clearly improved the neurological outcome of rats by decreasing infarct volume, neurological problems, and modified neurological severity scores following IS compared with the controls. The protective effect of silencing PTGS2 may be related to anti-oxidative stress and ferroptosis. In conclusion, this work may provide a new perspective for the research of IS, and further research based on PTGS2 may be a breakthrough.

Protective effect of cilostazol on vascular injury in rats with acute ischemic stroke complicated with chronic renal failure.

Chronic renal failure (CRF) resulting in vascular calcification, which does damage to blood vessels and endothelium, is an independent risk factor for stroke. It has been reported that cilostazol has a protective effect on the focal cerebral ischemic infarct. However, its impact on vascular injury in CRF combined stroke and its molecular protection mechanism have not been investigated. In this study, we carried out the effect of cilostazol on CRF combined stroke rats, and the results confirmed that it improved the neurobehavior, renal function as well as pathologic changes in both the kidney and brain. In addition, the inflammation and oxidative stress factors in the kidney and brain were suppressed. Moreover, the rates of brain edema and infarction were decreased. The injured brain-blood barrier (BBB) was recovered with less Evans blue extravasation and more expressions of zonula occludens-1(ZO-1) and occludin. More cerebral blood flow (CBF) in the ipsilateral hemisphere and more expression of CD31 and vascular endothelial growth factor (VEGF) in brain and kidney were found in the cilostazol group. Furthermore, cell apoptosis and cell autophagy became less, on the contrary, proteins of vascular endothelial growth factor receptor 2 (VEGFR2) after the cilostazol treatment were increased. More importantly, this protective effect is related to the pathway of Janus Kinase (JAK)/signal transducer and activator of transcription 3 (STAT3), mammalian target of rapamycin (mTOR), and the hypoxia inducible factor-1α (HIF-1α). In conclusion, our results confirmed that cilostazol exerted a protective effect on the brain and kidney function, specifically in vascular injury, oxidative stress, cell apoptosis, cell autophagy, and inflammation response in CRF combined with stroke rats which were related to the upregulation of JAK/STAT3/mTOR signal pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s43188-023-00217-w.

Association between Atopic Dermatitis and Colorectal Cancer: TET2 as a Shared Gene Signature and Prognostic Biomarker.

Background: Recent studies have linked atopic dermatitis (AD) to colorectal cancer (CRC) risk. Their causality and potential molecular mechanisms remain unclear. Methods: We performed Mendelian randomization (MR) analysis to evaluate the causality between AD and CRC. Summary statistic data-based Mendelian randomization (SMR) analysis was used to identify CRC-related causal genes. Transcriptome analyses and immunohistochemical methods were applied to investigate the shared gene signature and potential mechanisms that contribute to the pathogenesis of both AD and CRC. A predictive analysis was performed to examine the shared gene signature associated with immunotherapy response in CRC. Results: MR analysis indicated a causal association between AD and a decreased risk of CRC. SMR analysis uncovered TET2 as a CRC-related causal gene, showing an inverse relationship with the risk of CRC. Transcriptome analyses identified TET2 as a shared gene signature between AD and CRC. Decreased TET2 expression is associated with impaired demethylation and worse prognosis in CRC patients. We observed ten pathways related to the inflammatory response and immune regulation that may be shared mechanisms underlying both AD and CRC. These findings were validated through single-cell analysis. TET2 shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Conclusion: There is a causal association between AD and a decreased risk of CRC. AD may influence the occurrence of CRC by modulating immune and inflammatory responses. TET2 could serve as a potential biomarker for prognosis and may be considered a novel therapeutic target for methylation and immune-related interventions.

Uncovering the pathogenesis of obesity complicated with papillary thyroid carcinoma via bioinformatics and experimental validation.

This study aimed to investigate the common molecular mechanism between obesity and papillary thyroid cancer (PTC), the most common pathological type of thyroid cancer. In this study, we obtained gene expression datasets for obesity (GSE151839) and PTC (GSE33630) from the Gene Expression Omnibus (GEO). We used the Perl program and R software to identify differentially expressed genes (DEGs) and common genes, perform GO function and KEGG pathway enrichment analysis, construct a protein-protein interaction (PPI) network, identify hub genes, and perform transcription factors (TFs) analysis. After undergoing validation in external datasets and in vitro experiments, common targets for both diseases were ultimately identified. A total of 23 genes that were differentially expressed (DEGs) between obesity and papillary thyroid carcinoma (PTC) were identified in our study. Among these DEGs, 17 genes were up-regulated while 6 genes were down-regulated. Then the top ten key genes were identified from the PPI network using cytoHubba and MCODE plug-in. Further evidence from external datasets revealed that MMP9, MNDA, TNC, and CHIT1 were identified as hub genes for both diseases. The study utilized Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST) to perform an enrichment analysis of TFs. This analysis identified ELF4 and STAT3 as common TFs for both diseases. Additionally, in vitro experiments were conducted to further analyze the clinical significance and biological functions of these TFs. The identification and investigation of hub genes and their corresponding TFs that regulate abnormalities in obesity and PTC can enhance our comprehension of the underlying connection between these two diseases, thus leading to the development of novel diagnostic approaches.

Novel diagnostic biomarkers of oxidative stress, immune- infiltration characteristics and experimental validation of SERPINE1 in colon cancer.

BACKGROUND: Colon cancer (CC) is a prevalent malignant tumor that affects the colon in the gastrointestinal tract. Its aggressive nature, strong invasiveness, and rapid progression make it a significant health concern. In addition, oxidative stress can lead to the production of reactive oxygen species (ROS) that surpass the body's antioxidant defense capacity, causing damage to proteins, lipids, and DNA, potentially promoting tumor development. However, the relationship between CC and oxidative stress requires further investigation. METHODS: We collected gene expression data and clinical data from 473 CC patients from The Cancer Genome Atlas (TCGA) dataset. Additionally, we obtained 433 oxidative stress genes from Genecards ( https://www.genecards.org/ ). Using univariate, multivariate, and LASSO Cox regression analyses, we developed predictive models for oxidative stress-related genes in CC patients. To validate the models, we utilized data from the Gene Expression Omnibus (GEO) database. We assessed the accuracy of the models through various techniques, including the creation of a nomogram, receiver operating characteristic curve (ROC) analysis, and principal component analysis (PCA). The Cytoscape program was utilized to identify hub genes among differentially expressed genes (DEGs) in tumor patients using the TCGA dataset. Subsequently, we conducted survival analysis, clinical relevance analysis, and immune cell relevance analysis for the intersected genes obtained by combining the hub genes with the genes from the predictive models. Moreover, we investigated the mRNA expression and potential functions of these intersected genes using a range of experimental approaches. RESULTS: In both the TCGA and GSE17538 datasets, patients classified as high-risk had significantly shorter overall survival compared to those in the low-risk group (TCGA: p < 0.001; GSE17538: p = 0.010). As a result, we decided to further investigate the role of SERPINE1. Our survival analysis revealed that patients with high expression of SERPINE1 had a significantly lower probability of survival compared to those with low expression (p < 0.05). Additionally, our clinical correlation analysis showed a significant relationship between SERPINE1 expression and T, N, and M stages, as well as tumor grade. Furthermore, our immune infiltration correlation analysis demonstrated notable differences in multiple immune cells between the high- and low-expression groups of SERPINE1. To validate our findings, we conducted experimental tests and observed that knocking down SERPINE1 in colon cancer cells resulted in significant reductions in cell viability and proliferation. Interestingly, we also noticed an increase in oxidative stress parameters, such as ROS and MDA levels, while the levels of reduced GSH decreased upon SERPINE1 knockdown. These findings suggest that the antineoplastic effect of silencing SERPINE1 may be associated with the induction of oxidative stress. CONCLUSION: In conclusion, this study introduces a new approach for the early diagnosis and treatment of CC, and further exploration of SERPINE1 could potentially lead to a significant advancement.

Construction and Validation of a Prognostic Model Based on Novel Senescence-Related Genes in Non-Small Cell Lung Cancer Patients with Drug Sensitivity and Tumor Microenvironment.

Cellular senescence contributes to cancer pathogenesis and immune regulation. Using the LASSO Cox regression, we developed a 12-gene prognostic signature for lung adenocarcinoma (LUAD) from The Cancer Genome Atlas (TCGA) and a Gene Expression Omnibus (GEO) dataset. We assessed gene expression, drug sensitivity, immune infiltration, and conducted cell line experiments. High-risk LUAD patients showed increased mortality risk and shorter survival (P < 0.001). Senescence-related gene analysis indicated differences in protein phosphorylation and DNA methylation between normal individuals and LUAD patients. The high-risk group showed a positive association with PD-L1 expression (P = 0.003). Single-cell sequencing data suggested PEBP1 might significantly impact T cell infiltration. We predicted potential sensitive compounds for 12 senescence genes and found GAPDH promoted cell line proliferation. We established a novel prognostic system based on a newly identified senescence gene. High-risk patients had elevated immunosuppressive markers, and PEBP1 might influence T cell infiltration significantly. GAPDH, expressed at higher levels in tumors, could affect cancer progression. Our drug prediction model may guide treatment selection.

Designing Stacked Assembly of Type III Rubisco for CO2 Fixation with Higher Efficiency.

The slow catalytic rate of the carboxylation enzyme d-ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) is a major barrier to increasing the rate of carbon assimilation from the atmosphere into the biosphere. It is of great importance to establish a method to improve the carboxylation efficiency of Rubisco. Inspired by the assembly of Rubisco in carboxysomes, herein, we presented a rational protein engineering approach for the construction of one-dimensional (1D) protein arrays of type III Rubisco through designed π-π stacking interactions by using crystal structural information as a guide. In aqueous solutions, the dimensions of these 1D protein arrays collectively span nearly the entire nano- and micrometer scale (200 nm to 5.0 µm) by adjusting protein and NaCl concentrations. As a result, the stacked Rubisco assemblies increase by 40% in the carboxylase activity, while their turnover number (kcat) is around twofold larger than that of wild-type III Rubisco. Notably, upon heat treatment at temperature up to 75 °C for 30 min, most of the assembled nanostructures and the enzyme activity are retained. More importantly, the initial relative activity of stacked assemblies retained 91% after 10 cycles of reuse. This work provides a simple, effective solution for the improvement of the CO2 carboxylation efficiency of Rubisco.

Spatiotemporal control over 3D protein nanocage superlattices for the hierarchical encapsulation and release of different cargo molecules.

Taking inspiration from Nature, we have constructed a two-compartment system based on 3D ferritin nanocage superlattices, the self-assembly behavior of which can be spatiotemporally controlled using two designed switches. One pH switch regulates the assembly of the ferritin subunit into its shell-like structure, whereas the other metal switch is responsible for assembly of the 3D superlattices from ferritin nanocages as building blocks. Consequently, this system holds great promise for the hierarchical encapsulation and release of two different cargo molecules.

Identification and Verification of Immune-Related Genes Prognostic Signature Based on ssGSEA for Adrenocortical Carcinoma (ACC).

PURPOSE: Adrenocortical carcinoma (ACC) is an endocrine malignant tumor with poor prognosis. The study aimed to construct ACC immune-related gene prognostic signature and verify the efficacy of prognostic signature. METHODS: ACC RNA-seq data and clinical information are downloaded from TCGA databases and GEO databases. We used single sample gene set enrichment analysis (ssGSEA) to assess immune cell infiltration in ACC patients and ACC patients were divided into high- and low-immune cell infiltration clusters. The validity of ssGSEA grouping was verified using the ESTIMATE algorithm. A total of 275 differentially expressed immune-related genes (IRGs) were obtained from the intersection of IRGs and differentially expressed genes (DEGs) in high and low immune cell infiltration clusters. LASSO analysis was used to identify 13 IRGs that regulate the prognosis of ACC patients through immune infiltration. Kaplan-Meier analysis, ROC curve, univariate and multivariate Cox regression further confirmed that these 13 immune-related gene signatures were innovative and significant prognostic factors, which were independent of clinical features. Finally, ACC prognostic nomogram was constructed, ROC curve and calibration curve were drawn to evaluate the accuracy of the prognostic nomogram. RESULTS: LASSO regression analysis was used to screen out ACC survival-related genes. Univariate and multivariate Cox proportional risk regression models were used to analyze and construct the ACC prognosis nomogram. The AUC for predicting 1-, 3- and 5-year overall survival rate of ACC patients was 0.799, 0.966 and 0.969, suggesting good prediction accuracy. The calibration curve shows that the predicted results of the prognostic nomogram are in good agreement with the actual situation. CONCLUSION: ssGSEA technique plays an important role in the construction of ACC prognostic model. Based on IRGs associated with survival independently predicted ACC prognosis, we identified thirteen immune-related genes as prognostic signature for ACC.

Bionanomaterials based on protein self-assembly: Design and applications in biotechnology.

Elegant protein assembly to generate new biomaterials undergoes extremely rapid development for wide extension of biotechnology applications, which can be a powerful tool not only for creating nanomaterials but also for advancing understanding of the structure of life. Unique biological properties of proteins bestow these artificial biomaterials diverse functions that can permit them to be applied in encapsulation, bioimaging, biocatalysis, biosensors, photosynthetic apparatus, electron transport, magnetogenetic applications, vaccine development and antibodies design. This review gives a perspective view of the latest advances in the construction of protein-based nanomaterials. We initially start with distinguishable, specific interactions to construct sundry nanomaterials through protein self-assembly and concisely expound the assembly mechanism from the design strategy. And then, the design and construction of 0D, 1D, 2D, 3D protein assembled nanomaterials are especially highlighted. Furthermore, the potential applications have been discussed in detail. Overall, this review will illustrate how to fabricate highly sophisticated nanomaterials oriented toward applications in biotechnology based on the rules of supramolecular chemistry.