Ethanol causes non-communicable disease through activation of NLRP3 inflammasome: a review on mechanism of action and potential interventions.

Background: Ethanol exposure has been suggested to be implicated in the initiation and progression of several non-communicable diseases (NCD), including neurological disorders, diabetes mellitus, alcoholic liver disease, gastric injury, pancreatitis, and atherosclerosis. Recent findings show that the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome is involved in the progression of ethanol-induced NCDs.Objective: The aim of this review was to summarize the research progress on NCDs associated with the action of the NLRP3 inflammasome by ethanol and potential interventions, with a specific focus on preclinical literature.Methods: A literature search was conducted on PubMed using the keywords "[ethanol] and [NLRP3]" up until January 2023. Articles describing cases of NCDs caused by ethanol and associated with the NLRP3 inflammasome were included.Results: After removing duplicates, 35 articles were included in this review. These studies, mostly conducted in animals or in vitro, provide evidence that ethanol can contribute to the development of NCDs, such as neurological disorders, alcoholic liver disease, gastric injury, pancreatitis, and atherosclerosis, by activating the NLRP3 inflammasome. Ethanol exposure primarily triggers NLRP3 inflammasome activation by influencing the TRL/NF-κB, ROS-TXNIP-NLRP3 and P2X7 receptor (P2X7R) signaling pathways. Several natural extracts and compounds have been found to alleviate NCDs caused by ethanol consumption by inhibiting the activation of the NLRP3 inflammasome.Conclusion: Preclinical research supports a role for ethanol-induced NLRP3 inflammasome in the development of NCDs. However, the clinical relevance remains uncertain in the relative absence of clinical studies.

Expression signature, prognosis value and immune characteristics of cathepsin F in non-small cell lung cancer identified by bioinformatics assessment.

BACKGROUND: In recent years, immunotherapies and targeted therapies contribute to population-level improvement in NSCLC cancer-specific survival, however, the two novel therapeutic options have mainly benefit patients containing mutated driven genes. Thus, to explore other potential genes related with immunity or targeted therapies may provide novel options to improve survival of lung cancer patients without mutated driven genes. CTSF is unique in human cysteine proteinases. Presently, CTSF has been detected in several cell lines of lung cancer, but its role in progression and prognosis of lung cancer remains unclear. METHODS: CTSF expression and clinical datasets of lung cancer patients were obtained from GTEx, TIMER, CCLE, THPA, and TCGA, respectively. Association of CTSF expression with clinicopathological parameters and prognosis of lung cancer patients was analyzed using UALCAN and Kaplan-Meier Plotter, respectively. LinkedOmics were used to analyze correlation between CTSF and CTSF co-expressed genes. Protein-protein interaction and gene-gene interaction were analyzed using STRING and GeneMANIA, respectively. Association of CTSF with molecular markers of immune cells and immunomodulators was analyzed with Immunedeconv and TISIDB, respectively. RESULTS: CTSF expression was currently only available for patients with NSCLC. Compared to normal tissues, CTSF was downregulated in NSCLC samples and high expressed CTSF was correlated with favorable prognosis of NSCLC. Additionally, CTSF expression was correlated with that of immune cell molecular markers and immunomodulators both in LUAD and LUSC. Noticeably, high expression of CTSF-related CTLA-4 was found to be associated with better OS of LUAD patients. Increased expression of CTSF-related LAG-3 was related with poor prognosis of LUAD patients while there was no association between CTSF-related PD-1/PD-L1 and prognosis of LUAD patients. Moreover, increased expression of CTSF-related CD27 was related with poor prognosis of LUAD patients while favorable prognosis of LUSC patients. CONCLUSIONS: CTSF might play an anti-tumor effect via regulating immune response of NSCLC.

Global research trends on the links between prostate cancer and erectile dysfunction between 2003 and 2023: A bibliometrics and visualized study.

Background: The incidence of prostate cancer (PC) has increased in recent years. Erectile dysfunction (ED) after prostate cancer treatment has aroused extensive attention. Bibliometric analysis was designed to investigate a systematic understanding of developments between PC and ED during the past 20 years. Methods: Literatures on PC and ED were retrieved from the Web of Science Core Collection database (WoSCC). By using the VOS viewer and CiteSpace software to analysis the metrics of bibliometric literature, such as number of articles, journals, countries, institutions, authors, keywords and associated information. The number of publications per year was statistically analysed and plotted thorough Microsoft Office. In addition, Pajek software was used to adjust the visual map. Results: A total of 2332 screened articles were included in the analysis. The Journal of Sexual Medicine, ranking first among the analysed journals, published 235 articles. The United States and Canada were leaders in PC and ED research. There is a need to strengthen inter-agency cooperation in this area of research on a global scale. Mulhall JP, as the most prolific author in this area of research, published 80 articles. And Rosen RC was the author with the most co-citated (693 co-citated). The main research focus on the prevention, treatment and management of ED after PC treatment in this field through the keyword analysis. Conclusions: Research on PC and ED is expected to expand further worldwide. We found ED, as new sustainable treatment modalities, scientific postoperative management and psychological interventions for patients, may become the research hotspots and should be closely concerned in this study.

The typical developmental trajectory and energy requirements of Shitou goose during the embryonic stage.

Low hatchability has been a persistent challenge in the goose industry. Establishing standard atlases and comprehending embryonic development patterns are essential to improving the hatching rates of goose eggs. However, comprehensive descriptions of normal atlases, embryonic development, and energy requirements in geese are lacking. In this study, a total of 120 fertile eggs from well-known large Shitou goose were incubated using 12 nesting purebred female geese. During hatching, both the temperature of the eggshells and the weight of eggs were recorded, and daily photographs of the embryos were captured to monitor their development closely. After hatching, counted the number of pores per unit area of eggshells by choosing eggs from without sperm, dead embryos, and normally hatched. Furthermore, 150 Shitou goose eggs were hatched by automatic incubator, with adjustments made based on observed normal developmental stages that incubated by female geese. The eggs were carefully opened to meticulously document embryonic morphology and create a detailed development map. Measurements were taken of the eye diameter, length of the lower beak, tarsometatarsus bone, and embryo length. Subsequently, an analysis was conducted to assess the calcium, phosphorus, crude protein, and crude fat content to study the energy requirements for embryo development. characteristics on the 7th, 15th, 23rd and 28th days of Shitou goose hatching corresponded to the 5th, 10th, 17th and 19th days of chicken egg incubation, respectively. These days were distinguished individually by "visible embryo's eye", "closure", "sealing the door", and "flashing hair". Besides, the hatch rate of the incubator reached 86.67%, and the cumulative water loss rate increased with embryo age. Notably, normally developing embryos displayed a significantly higher number of pores on the eggshell surface compared to dead embryos (P < 0.05). Additionally, embryonic body length, eyeball diameter, and lower beak length exhibited continuous growth until day 19 of incubation, while tarsometatarsus length increased steadily from days 12 to 31. Liver size measurement began on the 10th day of incubation, while both leg and chest muscles showed continuous growth from the 12th day. For energy demand, the embryo primarily relied on protein sourced from the egg yolk within the first 10 days of development. Afterward, the egg yolk provided both protein and fat for embryonic growth. In summary, this study has generated a comprehensive developmental map for Shitou goose embryos, offering valuable insights into their growth and morphological changes throughout the incubation period. This map can serve as a reference for optimizing machine incubation techniques to enhance goose egg hatching rates and provide fresh perspectives on the development of geese.

A personalized mRNA signature for predicting hypertrophic cardiomyopathy applying machine learning methods.

Hypertrophic cardiomyopathy (HCM) may lead to cardiac dysfunction and sudden death. This study was designed to develop a HCM signature applying bioinformatics and machine learning methods. Data of HCM and normal tissues were obtained from public databases to screen differentially expressed genes (DEGs) using the R software limma package. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed for enrichment analysis of HCM-associated DEGs. Hub genes for HCM were determined using weighted gene co-expression network analysis (WGCNA) together with two machine learning algorithms (SVM-RFE and LASSO). Finally, we introduced a zebrafish model to simulate changes in the hub genes in the HCM and to observe their effects on cardiac disease development. The mRNA expression data from a total of 106 HCM tissues and 39 normal samples were collected and we screened 157 DEGs. Enrichment analysis showed that immune pathways played an important role in the pathogenesis of HCM. Three hub genes (FCN3, MYH6 and RASD1) were identified using WGCNA, SVM-RFE, and LASSO analysis. In a zebrafish model, knockdown of MYH6 and RASD1 resulted in cardiac malformations with reduced ventricular capacity and heart rate, which validated the clinical significance of these genes in the diagnosis of HCM. Based on machine learning algorithms, our study created a signature with potential impact on cardiac function and cardiac quality index for HCM. The current findings had important implications for the early diagnosis and treatment of HCM.

Robust Field-Free Switching Using Large Unconventional Spin-Orbit Torque in an All-Van der Waals Heterostructure.

The emerging all-van der Waals (vdW) magnetic heterostructure provides a new platform to control the magnetization by the electric field beyond the traditional spintronics devices. One promising strategy is using unconventional spin-orbit torque (SOT) exerted by the out-of-plane polarized spin current to enable deterministic magnetization switching and enhance the switching efficiency. However, in all-vdW heterostructures, large unconventional SOT remains elusive and the robustness of the field-free switching against external magnetic field has not been examined, which hinders further applications. Here, the study demonstrates the field-free switching in an all-vdW heterostructure combining a type-II Weyl semimetal TaIrTe4 and above-room-temperature ferromagnet Fe3GaTe2. The fully field-free switching can be achieved at 2.56 × 1010 A m-2 at 300 K and a large SOT effective field efficiency of the out-of-plane polarized spin current generated by TaIrTe4 is determined to be 0.37. Moreover, it is found that the switching polarity cannot be changed until the external in-plane magnetic field reaches 252 mT, indicating a robust switching against the magnetic field. The numerical simulation suggests the large unconventional SOT reduces the switching current density and enhances the robustness of the switching. The work shows that all-vdW heterostructures are promising candidates for future highly efficient and stable SOT-based devices.

Field Emission of Multi-Walled Carbon Nanotubes from Pt-Assisted Chemical Vapor Deposition.

Multi-walled carbon nanotubes (MWNTs) were grown directly on a metal substrate with the assistance of Pt using a chemical vapor deposition method. In addition, the growth mechanism of Pt-assisted catalytic CNT was discussed. MWNTs were characterized by SEM, TEM, AFM, Raman, and EDS, and the field emission (FE) properties were investigated, comparing with the direct grown MWNTs. The results showed that CNTs could not been synthesized by Pt particles alone under the experimental condition, but Pt may accelerate the decomposition of the carbon source gas, i.e., assisting MWNT growth with other catalysts. The Pt-assisted MWNTs were longer with larger diameters of around 80 nm and possessed better structural qualities with very few catalyst particles inside. Improved field emission properties were demonstrated for the Pt-assisted MWNTs with lower turn-on fields (for 0.01 mA·cm-2 current density) of 2.0 V·µm-1 and threshold field (for 10 mA·cm-2 current density) of 3.5 V·µm-1, as well as better stability under a long-term test of 80 h (started at 3.0 mA for the Pt-assisted emitter and 3.25 mA for the direct grown emitter). This work demonstrated a promising approach to develop high performance CNT field emitters for device applications.

Integrating concept of pharmacophore with graph neural networks for chemical property prediction and interpretation.

Recently, graph neural networks (GNNs) have revolutionized the field of chemical property prediction and achieved state-of-the-art results on benchmark data sets. Compared with the traditional descriptor- and fingerprint-based QSAR models, GNNs can learn task related representations, which completely gets rid of the rules defined by experts. However, due to the lack of useful prior knowledge, the prediction performance and interpretability of the GNNs may be affected. In this study, we introduced a new GNN model called RG-MPNN for chemical property prediction that integrated pharmacophore information hierarchically into message-passing neural network (MPNN) architecture, specifically, in the way of pharmacophore-based reduced-graph (RG) pooling. RG-MPNN absorbed not only the information of atoms and bonds from the atom-level message-passing phase, but also the information of pharmacophores from the RG-level message-passing phase. Our experimental results on eleven benchmark and ten kinase data sets showed that our model consistently matched or outperformed other existing GNN models. Furthermore, we demonstrated that applying pharmacophore-based RG pooling to MPNN architecture can generally help GNN models improve the predictive power. The cluster analysis of RG-MPNN representations and the importance analysis of pharmacophore nodes will help chemists gain insights for hit discovery and lead optimization.

Differential expression of CXCR4 is associated with the metastatic potential of human non-small cell lung cancer cells.

PURPOSE: To evaluate the relation between CXCR4 expression and the presence of metastatic disease in human non-small cell lung cancer (NSCLC) patients and investigate whether modulation of CXCR4 expression could serve as a potential pathway in preventing metastasis of NSCLC. EXPERIMENTAL DESIGN: CXCR4 expression in 36 patients with NSCLC and 10 normal lung tissues was detected by real-time PCR and immunohistochemistry. CXCR4 expression in two human NSCLC clones (95C and 95D) with different metastatic potential was determined by real-time PCR and flow cytometry. 95C and 95D cells were transfected with the plasmid DNA containing CXCR4 coding gene or CXCR4 antisense nucleotide fragment, respectively, and the effects on in vitro cell migration, invasion, and adhesion and in vivo metastasis were measured. RESULTS: Up-regulated expression of CXCR4 was detected in 34 tumors, which were further divided into 17 high expression cancers and 17 low expression cancers by their staining intensities. High CXCR4 tumors (13 of 17) were more prone to clinical metastasis in comparison with low expression tumors. CXCR4 was differentially expressed in 95C and 95D cells with low or high metastatic potential, and the surface expression of CXCR4 were 50% up-regulated or down-regulated following the stable transfection. The metastatic potential of NSCLC in vitro, such as migration, invasion, and adhesion, were significantly enhanced or impaired. In addition, neutralizing the interactions of stromal cell-derived factor-1/CXCR4 in vitro with CXCR4-specific antibodies inhibited the CXCR4-dependent migration, invasion, and adhesion. Furthermore, s.c. inoculation of lung cancer cells with low expression of CXCR4 in nude mice showed 0- to 2-fold decrease in lung metastatic foci than that with high expression of CXCR4. CONCLUSIONS: Differential expression of CXCR4 is associated with the metastatic potential of human NSCLC, raising the possibility that blockade of CXCR4/stromal cell-derived factor-1 interaction may lead the way to design novel therapeutic tools for the treatment of metastatic NSCLC patients.

[The role of CXCL16 in immunological liver injury induced by BCG and LPS in mice].

OBJECTIVE: To investigate the pathophysiological role of CXCL16 in immunological liver injury induced by Bacille de Calmette et Guerin (BCG) and lipopolysaccharides (LPS). METHODS: Immunological liver injury was induced by BCG and LPS in mice, and the expression of CXCL16 was detected in the liver tissues by real-time quantitative PCR and immunohistochemical examination. The relationship of the expression of CXCL16 and the extent of hepatic necrosis was investigated histopathologically and immunohistochemically. Mononuclear cells were isolated from the liver tissues and their numbers were counted; T lymphocytes populations in the liver tissue were also analyzed with FACS. RESULTS: The immunological liver injury model was successfully created. Up-regulation of CXCL16 in injured livers correlated with the extent of liver injury and the amountmononuclear cell infiltrations. CONCLUSION: These findings suggest that up-regulation of CXCL16 was closely correlated with liver injury extent during the immunological liver injury induced by BCG-LPS in mice, and intrahepatic recruitment of specific lymphocytes might be an important mechanism of liver injury.

Classification of Aurora B kinase inhibitors using computational models.

Using Self-Organizing Map (SOM) and Support Vector Machine (SVM), four classification models were built to predict whether a compound is an active or weakly active inhibitor of Aurora B kinase. A dataset of 679 Aurora B kinase inhibitors was collected, and randomly split into a training set (278 active and 204 weakly active inhibitors) and a test set (109 active and 88 weakly active inhibitors). Based on 19 selected ADRIANA.Code descriptors and 135 MACCS fingerprints, all the four models showed a good prediction accuracy of over 87% on the test set. It benefited from the advantages of two different types of molecular descriptors in encoding structure information of compounds and characterizing the diversity of different inhibitors. Some molecular properties, such as hydrogen-bonding interactions and atom charge related descriptors were found to be important to the bioactivity of Aurora B kinase inhibitors.

Effects of estrogen replacement therapy on estrogen receptor expression and immunoregulatory cytokine secretion in surgically induced menopausal women.

To investigate the effect of oral and transdermal estrogen replacement therapy (ERT) on the expression of different estrogen receptor (ER) subtypes and the secretion of immunoregulatory cytokines, we performed a clinical investigation on previously healthy women who had undergone a total hysterectomy and bilateral salpingo-oopherectomy. These women were randomly distributed into two groups: an oral ERT group and transdermal ERT group. Before and after ERT, the serum levels of estradiol (E2) and follicle stimulating hormone (FSH) were measured, ERalpha and ERbeta expression of peripheral blood T lymphocytes was tested, and secretion of specific immunoregulatory cytokines (IFNgamma, IL-2 and IL-4) by T lymphocytes was examined. Our results confirm that for both groups, the serum E2 level was increased after ERT (P<0.01) and the serum FSH level was decreased after ERT (P<0.01), with no significant difference in hormone levels between the two groups. ERalpha expression by T lymphocytes was significantly higher after ERT than before (P<0.01) in both groups. Levels of type 1 cytokines (IL-2 and IFNgamma), which were secreted by T helper 1 (Th1), after ERT were substantially decreased. The level of type 2 cytokine (IL-4), which were secreted by T helper 2 (Th2), was significantly increased after ERT (P<0.01 for the oral group and P<0.05 for the transdermal group). In summary, both oral and transdermal ERT increased serum E2 levels, decreased serum FSH levels and relieved the effects of peri-menopausal symptoms. These data suggest that both oral and transdermal ERT act to improve the balance of Th1/Th2 cytokines by the effects of estrogen potentially acting in T lymphocytes mainly through ERalpha.