A prognostic risk model based on lactate metabolism and transport-related lncRNAs for gastric adenocarcinoma.

BACKGROUND: Increased lactate levels and metastasis in tumours are strongly associated with dismal outcomes. But prognostic value of lactate metabolism and transport-related lncRNAs in gastric adenocarcinoma (GA) patients remains unaddressed. METHODS: Gene expression data of GA were provided by The Cancer Genome Atlas. Lactate metabolism and transport-related gene data were accessed from GSEA. LncRNAs related to lactate metabolism and transport were identified by correlation analysis. A prognostic model was built by regression analysis. Validity of prognostic model was confirmed through survival analysis and receiver operating characteristic (ROC) curve. Immunity of each risk group was evaluated by immune correlation analysis .LncRNA-mRNA network was built by correlation analysis using Cytoscape software. RESULTS: A 12-gene prognostic model based on lactate metabolism and transport-related lncRNAs was built in GA. Median riskscore was utilized to classify GA samples into high- and low-risk groups. Survival analysis and ROC curves demonstrated validity of prognostic model. Most immune checkpoint molecules and TIDE scores were lower in the low-risk group. LINC01303 and LINC01545 may be the key prognostic factors in patients with GA. CONCLUSION: This study successfully built a prognostic model of lactate metabolism and transport-related lncRNAs in GA. The findings guide prognostic management of GA patients.

Optimal Reactivity and Improved Self-Healing Capability of Structurally Dynamic Polymers Grafted on Janus Nanoparticles Governed by Chain Stiffness and Spatial Organization.

Structurally dynamic polymers are recognized as a key potential to revolutionize technologies ranging from design of self-healing materials to numerous biomedical applications. Despite intense research in this area, optimizing reactivity and thereby improving self-healing ability at the most fundamental level pose urgent issue for wider applications of such emerging materials. Here, the authors report the first mechanistic investigation of the fundamental principle for the dependence of reactivity and self-healing capabilities on the properties inherent to dynamic polymers by combining large-scale computer simulation, theoretical analysis, and experimental discussion. The results allow to reveal how chain stiffness and spatial organization regulate reactivity of dynamic polymers grafted on Janus nanoparticles and mechanically mediated reaction in their reverse chemistry, and, particularly, identify that semiflexible dynamic polymers possess the optimal reactivity and self-healing ability. The authors also develop an analytical model of blob theory of polymer chains to complement the simulation results and reveal essential scaling laws for optimal reactivity. The findings offer new insights into the physical mechanism in various systems involving reverse/dynamic chemistry. These studies highlight molecular engineering of polymer architecture and intrinsic property as a versatile strategy in control over the structural responses and functionalities of emerging materials with optimized self-healing capabilities.

Image method for electrostatic energy of polarizable dipolar spheres.

The multiple-scattering theory for the electrostatics of many-body systems of monopolar spherical particles, embedded in a dielectric medium, is generalized to describe the electrostatics of these particles with embedded dipoles and multipoles. The Neumann image line construction for the electrostatic polarization produced by one particle is generalized to compute the energy, forces, and torques for the many-body system as functions of the positions of the particles. The approach is validated by comparison with direct numerical calculation, and the convergence rate is analyzed and expressed in terms of the discontinuity in dielectric contrast and particle density. As an illustration of this formalism, the stability of small particle clusters is analyzed. The theory is developed in a form that can readily be adapted to Monte Carlo and molecular dynamics simulations for polarizable particles and, more generally, to study the interactions among polarizable molecules.

Entropy-mediated mechanical response of the interfacial nanoparticle patterning.

The precise organization of nano-objects into well-defined patterns at interfaces is an outstanding challenge in the field of nanocomposites toward technologically important materials and devices. Herein, by means of computer simulations we show novel mechanomutable nanocomposites designed by binary mixtures of tethered Janus nanoparticles at the interface of a binary fluid mixture under mechanical pressure. Our simulations demonstrate that the nanoparticle organization in the systems undergo reversible transition between random state and long-ranged intercalation state, controlled by various structural parameters of the tethered chains and the applied pressure. The dynamical mechanism during the transition is explored through examining the diffusion trajectories of the nanoparticles confined at the interfaces. We provide a theoretical analysis of the lateral pressure induced by the tethered chains, which is fully supported by simulation data and reveals that the compression-induced transition is fundamentally attributed to the entropic effect from the tethered chains. Our study leads to a class of interface-reactive nanomaterials in which the transfer and recovery of interfacial nanopatterning presents precise and tunable mechanical responses.

Galectin-1 Promotes Gastric Carcinoma Progression and Cisplatin Resistance Through the NRP-1/c-JUN/Wee1 Pathway.

PURPOSE: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. MATERIALS AND METHODS: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. RESULTS: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. CONCLUSIONS: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.

Meta-analysis of the correlation between high expression of lncRNA NEAT1 in rectal cancer and pathological features and prognosis.

Background: To systematically evaluate the relationship between the expression level of long noncoding RNA NEAT1 and the clinical characteristics and prognostic value of rectal cancer patients. Methods: PubMed, EMBASE, Cochrane library database and case-control studies on the correlation between abnormal expression of lncRNA NEAT1 and prognosis of rectal cancer patients published by the American clinical trials registry before May 1, 2023 were searched. The search time was from the establishment of the database to May 30, 2023. Results: A total of 7 case-control studies were included, including 1063 cancer patients. The results of meta-analysis showed that the high expression of lncRNA NEAT1 was significantly correlated with the degree of differentiation [or=0.45, 95%CI=0.32-0.63, P<0.01], tumor size [or=0.59, 95%CI=0.42-0.82, P<0.01], and overall survival [HR=1.34, 95%CI=1.21-1.48, P<0.001]; However, it was not associated with gender [or=1.23, 95%CI= 0.88-1.72, P=0.23] and lymph node metastasis [or=0.87, 95%CI=0.45-1.66, P=0.67]. Conclusions: The high expression of lncRNA NEAT1 may be a risk factor for poor prognosis in patients with malignant tumors, and lncRNA NEAT1 can be used as a potential biomarker to evaluate its prognosis.

Identification of a ceRNA Network Driven by Copy Number Variations in Esophageal Cancer.

BACKGROUND: Copy number variation (CNV) is associated with progression of esophageal cancer (EC), a common gastrointestinal neoplasm. METHODS: Using sequencing data, CNV data, and clinical data of EC transcriptome samples obtained from public databases, we performed differential expression analysis on sequencing data. Differentially expressed CNV-driven lncRNAs were screened using the chi-square test, and CNV-driven lncRNA-associated miRNAs and mRNAs were predicted. Cytoscape software was then used to construct ceRNA networks. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to investigate biological functions of mRNAs in the ceRNA network. Survival curves were plotted to explore correlations between lncRNAs in the ceRNA network and overall survival of CNV patients. Multiple databases were used to predict lncRNAs-related drugs. RESULTS: A dysregulated lncRNA-associated ceRNA network driven by CNV in EC, including 11 lncRNAs, 11 miRNAs and 159 mRNAs, was constructed. Downstream enrichment of mRNAs was related to biological processes such as extracellular matrix organization, indicating that these mRNAs mainly participate in intercellular exchange between tumor cells. Additionally, expression of all lncRNAs in the ceRNA network, except LINC00950, LINC01270 and MIR181A1HG, was correlated with patients' CNV. In addition, none of the 11 lncRNAs was significantly correlated with overall survival of CNV patients. CH5424802 and PD-033299CNV mainly affected the RTK signaling pathway and the cell cycle of tumor cells via RP11-180N14.1 and RP11-273 G15.2 in the ceRNA network. CONCLUSIONS: This study identified 11 CNV-driven lncRNAs that might affect EC development, 2 of which have promising effects if applied to drug treatment. These findings might assist in identifying novel treatments for EC.

PBRM1 presents a potential prognostic marker and therapeutic target in duodenal papillary carcinoma.

BACKGROUND: Due to its rarity, duodenal papillary carcinoma (DPC) is seldom studied as a unique disease and no specific molecular features or treatment guidelines are provided. METHODS: Whole-exome sequencing was performed to gain new insights into the DPC mutation landscape and to identify potential signalling pathways and therapeutic targets. Mechanistically, immunohistochemistry (IHC), immunofluorescence, RNA-seq, ATAC-seq and in vitro cell function experiments were performed to confirm the underlying mechanisms. RESULTS: We described the mutational landscape of DPC for the first time as a group of rare tumours with a high frequency of dysregulation in the chromatin remodelling pathway, particularly PBRM1-inactivating mutations that are significantly higher than duodenal adenocarcinomas and ampullary adenocarcinoma (27% vs. 0% vs. 7%, p < .01). In vitro cell experiments showed that downregulation of PBRM1 expression could significantly promote the cancer progression and epithelial-to-mesenchymal transition via the PBRM1-c-JUN-VIM axis. The IHC data indicated that PBRM1 deficiency (p = .047) and c-JUN expression (p < .001) were significantly associated with poor prognosis. Meanwhile, the downregulation of PBRM1 expression in HUTU-80 cells was sensitive to radiation, which may be due to the suppression of c-JUN by irradiation. CONCLUSIONS: Our findings define a novel molecular subgroup of PBRM1-inactivating mutations in DPC. PBRM1 play an important role in DPC progression and may serve as a potential therapeutic target and prognostic indicator.

Ergonomic risk exposure and work ability among young dental professionals in China: A cross-sectional study.

BACKGROUND: Exposure to high ergonomic risk resulted in an increasing prevalence of musculoskeletal disorders among dental professional. However, little is known about the high exposure risk impact on work ability among dental professionals. OBJECTIVE: We conducted a cross-sectional study to examine the association between ergonomic risk exposure and work ability among young dental professionals in their early careers. METHODS: A total of 230 dental professionals including dentists, dental assistants, and nurses were clustered sampled from three hospitals in Guangzhou, south of China. We used the Quick Ergonomic Check (QEC) to assess participants' ergonomic risk exposure and Work Ability Index (WAI) to evaluate their work ability. Demographics and other factors related with WAI were also included in the data collection. Multiple linear regression was applied to analyze the association between ergonomic exposure scores and WAI. RESULTS: A total of 218 participants (94.8%) had valid data and consent forms. The participants' average WAI was 39.6, of which the poor and moderate WAI composed 31%. High and very high ergonomic risk exposure level was 45.9% for the neck and 21.1% for the wrist/hand. In general, WAI decreased with higher ergonomic exposure level. With adjustment of other potential risk factors, the ergonomic scores for wrist/hand and total scores for the whole body were significantly associated with the decreased WAI. CONCLUSION: High ergonomic risk exposure might risk in reducing work ability among young dental professionals. Intervention measures toward ergonomic risk should be taken to prevent WAI from decreasing in their early careers.

Tea drinking and the risk of esophageal cancer: focus on tea type and drinking temperature.

The association between tea drinking and esophageal cancer is still contradictory. This study is to determine the association between tea drinking and esophageal squamous cell carcinoma focusing on drinking temperature and tea types. A population-based case-control study was conducted in a high esophageal squamous cell carcinoma risk area in China. A total of 942 incident esophageal squamous cell carcinoma cases with historical confirmation and 942 age- and sex- individually matched community controls were recruited from the study area. Trained interviewers using a structured questionnaire collected detailed information on tea drinking, diet, smoking and alcohol drinking habits. Habitual tea drinking temperature was measured with a thermometer during interviews. We analyzed the association between tea consumption, drinking temperature and esophageal squamous cell carcinoma, stratified by tea type, while adjusting for other potentially confounding factors. Drinking very hot tea (>65°C) was significantly associated with the increased risk of esophageal squamous cell carcinoma (odds ratio = 1.67, 95% confidential interval 1.25-2.24) relative to non-drinkers. Consumption of black tea, irrespective of the frequency, intensity and tea leaf amount, was significantly associated with a higher risk (P for trend <0.01). Compared to those who consumed <300 g/month tea leaves at ≤65°C, those who consumed more than 300 g/month tea leave at >65°C had a more than 1.8-fold higher risk of esophageal squamous cell carcinoma for both green tea and black tea. Our results provide more evidence that drinking very hot tea (above 65°C) are significantly associated with an increased risk of esophageal squamous cell carcinoma.

Fabrication of poly(methyl methacrylate) capillary electrophoresis microchips by in situ surface polymerization.

A novel method based on in situ surface polymerization of methyl methacrylate (MMA) has been developed for the rapid fabrication of poly(methyl methacrylate) (PMMA) capillary electrophoresis (CE) microchips. MMA containing both thermal and ultraviolet (UV) initiators was allowed to prepolymerize in a water bath to form a fast curing molding solution that was subsequently sandwiched between a nickel template and a PMMA plate. The images of the raised microchannels on the nickel template were precisely replicated into the synthesized PMMA substrates during the UV-initiated polymerization of the molding solution within 30 min under ambient temperature. The attractive performances of the novel PMMA microchips have been demonstrated in connection with amperometric detection for the separation and detection of several model analytes. The new approach significantly simplifies the process for fabricating PMMA devices and could be applied to other materials that undergo light-initiated polymerization.

Chain stiffness regulates entropy-templated perfect mixing at single-nanoparticle level.

The mixing on a single-particle level of chemically incompatible nanoparticles is an outstanding challenge for many applications. Burgeoning research activity suggests that entropic templating is a potential strategy to address this issue. Herein, using systematic computer simulations of model nanoparticle systems, we show that the entropy-templated interfacial organization of nanoparticles significantly depends on the stiffness of tethered chains. Unexpectedly, the optimal chain stiffness can be identified wherein a system exhibits the most perfect mixing for a certain compression ratio. Our simulations demonstrate that entropic templating regulated by chain stiffness precisely reflects various entropic repulsion states that arise from typical conformation regimes of semiflexible chains. The physical mechanism of the chain stiffness effect is revealed by analyzing the entropic repulsion states of tethered chains and quantitatively estimating the resulting entropy penalties, which provides direct evidence that supports the key role of entropic transition in the entropic templating strategy, as suggested in experiments. Moreover, the model nanoparticle systems are found to evolve into binary nanoparticle superlattices by remixing at extremely high stiffness. The findings facilitate the wide application of the entropic templating strategy in creating interfacially reactive nanomaterials with ordered structures on the single-nanoparticle level as well as mechanomutable responses.

Anodic coupling reactions and the synthesis of C-glycosides.

A convenient, two-step procedure has been developed for converting sugar derivatives into C-glycosides containing a masked aldehyde functional group. The chemistry takes advantage of an anodic coupling reaction between an electron-rich olefin and an alcohol. The sequence works for the formation of both furanose and pyranose derivatives if less polarized vinyl sulfide derived radical cation intermediates are used. With more polarized enol ether derived radical cations, the cyclizations work best for the formation of furanose derivatives where the rate of five-membered ring formation precludes elimination reactions triggered by the radical cation.