Multifaceted roles of lymphatic and blood endothelial cells in the tumor microenvironment of hepatocellular carcinoma: A comprehensive review.

The tumor microenvironment is a complex network of cells, extracellular matrix, and signaling molecules that plays a critical role in tumor progression and metastasis. Lymphatic and blood vessels are major routes for solid tumor metastasis and essential parts of tumor drainage conduits. However, recent studies have shown that lymphatic endothelial cells (LECs) and blood endothelial cells (BECs) also play multifaceted roles in the tumor microenvironment beyond their structural functions, particularly in hepatocellular carcinoma (HCC). This comprehensive review summarizes the diverse roles played by LECs and BECs in HCC, including their involvement in angiogenesis, immune modulation, lymphangiogenesis, and metastasis. By providing a detailed account of the complex interplay between LECs, BECs, and tumor cells, this review aims to shed light on future research directions regarding the immune regulatory function of LECs and potential therapeutic targets for HCC.

Intelligent Cell Profiling and Precision Release: Multimolecular Marker-Activated Transmembrane DNA Computing Nanosystem.

Accurate classification of tumor cells is of importance for cancer diagnosis and further therapy. In this study, we develop multimolecular marker-activated transmembrane DNA computing systems (MTD). Employing the cell membrane as a native gate, the MTD system enables direct signal output following simple spatial events of "transmembrane" and "in-cell target encounter", bypassing the need of multistep signal conversion. The MTD system comprises two intelligent nanorobots capable of independently sensing three molecular markers (MUC1, EpCAM, and miR-21), resulting in comprehensive analysis. Our AND-AND logic-gated system (MTDAND-AND) demonstrates exceptional specificity, allowing targeted release of drug-DNA specifically in MCF-7 cells. Furthermore, the transformed OR-AND logic-gated system (MTDOR-AND) exhibits broader adaptability, facilitating the release of drug-DNA in three positive cancer cell lines (MCF-7, HeLa, and HepG2). Importantly, MTDAND-AND and MTDOR-AND, while possessing distinct personalized therapeutic potential, share the ability of outputting three imaging signals without any intermediate conversion steps. This feature ensures precise classification cross diverse cells (MCF-7, HeLa, HepG2, and MCF-10A), even in mixed populations. This study provides a straightforward yet effective solution to augment the versatility and precision of DNA computing systems, advancing their potential applications in biomedical diagnostic and therapeutic research.

Semantic partitioning facilitates memory for object location through category-partition cueing.

In our lived environments, objects are often semantically organised (e.g., cookware and cutlery are placed close together in the kitchen). Across four experiments, we examined how semantic partitions (that group same-category objects in space) influenced memory for object locations. Participants learned the locations of items in a semantically partitioned display (where each partition contained objects from a single category) as well as a purely visually partitioned display (where each partition contained a scrambled assortment of objects from different categories). Semantic partitions significantly improved location memory accuracy compared to the scrambled display. However, when the correct partition was cued (highlighted) to participants during recall, performance on the semantically partitioned display was similar to the scrambled display. These results suggest that semantic partitions largely benefit memory for location by enhancing the ability to use the given category as a cue for a visually partitioned area (e.g., toys - top left). Our results demonstrate that semantically structured spaces help location memory across partitions, but not items within a partition, providing new insights into the interaction between meaning and memory.

Variation of Young's modulus suggested the main active sites for four different aging plastics at an early age time.

Precisely determining which bonds are more sensitive when plastic aging occurs is critical to better understand the mechanisms of toxic release and microplastics formation. However, the relationship between chemical bonds with the active aging sites changes and the aging behavior of plastics at an early age is still unclear. Herein, the mechanical behavior of four polymers with different substituents was characterized by the high-resolution AFM. Young's modulus (YM) changes suggested that the cleavage of C-Cl bonds in PVC, C-H bonds in PE and PP, and C-F bonds in PTFE are the main active aging sites for plastic aging. The aging degree of the plastics followed the order of PVC > PP > PE > PTFE. Two aging periods exhibited different YM change behavior, the free radical and cross-linking resulted in a minor increase in YM during the initiation period. Numerous free radicals formed and cross-linking reaction happened, causing a significant increase in YM during the propagation period. Raman spectroscopy verified the formation of microplastics. This research develops promising strategies to quantitatively evaluate the aging degrees using AFM and establish the relationship between chemical bonds and mechanical behavior, which would provide new method to predict plastic pollution in actual environments.

The rat acute oral toxicity of trifluoromethyl compounds (TFMs): a computational toxicology study combining the 2D-QSTR, read-across and consensus modeling methods.

All areas of the modern society are affected by fluorine chemistry. In particular, fluorine plays an important role in medical, pharmaceutical and agrochemical sciences. Amongst various fluoro-organic compounds, trifluoromethyl (CF3) group is valuable in applications such as pharmaceuticals, agrochemicals and industrial chemicals. In the present study, following the strict OECD modelling principles, a quantitative structure-toxicity relationship (QSTR) modelling for the rat acute oral toxicity of trifluoromethyl compounds (TFMs) was established by genetic algorithm-multiple linear regression (GA-MLR) approach. All developed models were evaluated by various state-of-the-art validation metrics and the OECD principles. The best QSTR model included nine easily interpretable 2D molecular descriptors with clear physical and chemical significance. The mechanistic interpretation showed that the atom-type electro-topological state indices, molecular connectivity, ionization potential, lipophilicity and some autocorrelation coefficients are the main factors contributing to the acute oral toxicity of TFMs against rats. To validate that the selected 2D descriptors can effectively characterize the toxicity, we performed the chemical read-across analysis. We also compared the best QSTR model with public OPERA tool to demonstrate the reliability of the predictions. To further improve the prediction range of the QSTR model, we performed the consensus modelling. Finally, the optimum QSTR model was utilized to predict a true external set containing many untested/unknown TFMs for the first time. Overall, the developed model contributes to a more comprehensive safety assessment approach for novel CF3-containing pharmaceuticals or chemicals, reducing unnecessary chemical synthesis whilst saving the development cost of new drugs.

ATF3-CBS signaling axis coordinates ferroptosis and tumorigenesis in colorectal cancer.

The induction of ferroptosis is promising for cancer therapy. However, the mechanisms enabling cancer cells to evade ferroptosis, particularly in low-cystine environments, remain elusive. Our study delves into the intricate regulatory mechanisms of Activating transcription factor 3 (ATF3) on Cystathionine ß-synthase (CBS) under cystine deprivation stress, conferring resistance to ferroptosis in colorectal cancer (CRC) cells. Additionally, our findings establish a positively correlation between this signaling axis and CRC progression, suggesting its potential as a therapeutic target. Mechanistically, ATF3 positively regulates CBS to resist ferroptosis under cystine deprivation stress. In contrast, the suppression of CBS sensitizes CRC cells to ferroptosis through targeting the mitochondrial tricarboxylic acid (TCA) cycle. Notably, our study highlights that the ATF3-CBS signaling axis enhances ferroptosis-based CRC cancer therapy. Collectively, the findings reveal that the ATF3-CBS signaling axis is the primary feedback pathway in ferroptosis, and blocking this axis could be a potential therapeutic approach for colorectal cancer.

Productions Need Not Match Study Items to Confer a Production Advantage, But It Helps.

The production effect is the finding that, relative to silent reading, producing information at study (e.g., reading aloud) leads to a benefit in memory. In most studies of this effect, individuals are presented with a set of unique items, and they produce a subset of these items (e.g., they are presented with the to-be-remembered target item TABLE and produce table) such that the production is both unique and representative of the target. Across two preregistered experiments, we examined the influence of a production that is unique but that does not match the target (e.g., producing fence to the target TABLE, producing car to the target TREE, and so on). This kind of production also yielded a significant effect-the mismatching production effect-although it was smaller than the standard production effect (i.e., when productions are both unique and representative of their targets) and was detectable only when targets with standard productions were included in the same study phase (i.e., when the type of production was manipulated within participant). We suggest that target-production matching is an important precursor to the production effect and that the kind of production that brings about a benefit depends on the other productions that are present.

Exhaled breath and urinary volatile organic compounds (VOCs) for cancer diagnoses, and microbial-related VOC metabolic pathway analysis: a systematic review and meta-analysis.

BACKGROUND: The gradual evolution of the detection and quantification of volatile organic compounds (VOCs) has been instrumental in cancer diagnosis. The primary objective of this study was to assess the diagnostic potential of exhaled breath and urinary VOCs in cancer detection. As VOCs are indicative of tumor and human metabolism, our work also sought to investigate the metabolic pathways linked to the development of cancerous tumors. MATERIALS AND METHODS: An electronic search was performed in the PubMed database. Original studies on VOCs within exhaled breath and urine for cancer detection with a control group were included. A meta-analysis was conducted using a bivariate model to assess the sensitivity and specificity of the VOCs for cancer detection. Fagan's nomogram was designed to leverage the findings from our diagnostic analysis for the purpose of estimating the likelihood of cancer in patients. Ultimately, MetOrigin was employed to conduct an analysis of the metabolic pathways associated with VOCs in relation to both human and/or microbiota. RESULTS: The pooled sensitivity, specificity and the area under the curve for cancer screening utilizing exhaled breath and urinary VOCs were determined to be 0.89, 0.88, and 0.95, respectively. A pretest probability of 51% can be considered as the threshold for diagnosing cancers with VOCs. As the estimated pretest probability of cancer exceeds 51%, it becomes more appropriate to emphasize the 'ruling in' approach. Conversely, when the estimated pretest probability of cancer falls below 51%, it is more suitable to emphasize the 'ruling out' approach. A total of 14, 14, 6, and 7 microbiota-related VOCs were identified in relation to lung, colorectal, breast, and liver cancers, respectively. The enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in the aforementioned tumor types. CONCLUSIONS: The analysis of exhaled breath and urinary VOCs showed promise for cancer screening. In addition, the enrichment analysis of volatile metabolites revealed a significant enrichment of butanoate metabolism in four tumor types, namely lung, colorectum, breast and liver. These findings hold significant implications for the prospective clinical application of multiomics correlation in disease management and the exploration of potential therapeutic targets.

Semantic partitioning facilitates memory for object location through category-partition cueing.

In our lived environments, objects are often semantically organised (e.g., cookware and cutlery are placed close together in the kitchen). Across four experiments, we examined how semantic partitions (that group same-category objects in space) influenced memory for object locations. Participants learned the locations of items in a semantically partitioned display (where each partition contained objects from a single category) as well as a purely visually partitioned display (where each partition contained a scrambled assortment of objects from different categories). Semantic partitions significantly improved location memory accuracy compared to the scrambled display. However, when the correct partition was cued (highlighted) to participants during recall, performance on the semantically partitioned display was similar to the scrambled display. These results suggest that semantic partitions largely benefit memory for location by enhancing the ability to use the given category as a cue for a visually partitioned area (e.g., toys - top left). Our results demonstrate that semantically structured spaces help location memory across partitions, but not items within a partition, providing new insights into the interaction between meaning and memory.

The Microbiota Architecture of the Chinchilla Gastrointestinal Tract.

The gastrointestinal microbiota develop alongside the host and play a vital role in the health of cecal fermenters such as chinchillas. However, little is known about the microbiota architecture in healthy chinchillas. Illumine-based 16S rRNA gene amplicon sequencing was used to investigate the microbiota present in six different gastrointestinal tract regions of three healthy adult chinchillas. The findings revealed significantly more abundant microbiota in the large intestine compared with the proximal segments. In addition, the cecum exhibited better evenness compared to the colon. The core microbiota are Firmicutes, Bacteroidota, Actinobacteriota, and Proteobacteria at the phylum level. The signature microbiota of each segment were identified. The cecum had 10 signature microbiota, which had the widest coverage and overlapped with that of the cecum. The stomach had five signature microbiota, exhibiting the second widest coverage and overlapping with the duodenum. No signature microbiota were detected in the jejunum and ileum. While similarities exist with the microbiota of other cecal fermenters, chinchillas exhibit distinct microbiota closely related to their unique digestive mechanisms. This study is a preliminary study of the gastrointestinal microbiota architecture and distribution in healthy chinchillas. Further study is needed in order to better understand the effect of gastrointestinal microbiota on the health of the chinchilla.

Research on the village layout optimization in China's developed areas based on daily life circles.

Public service facilities are the basic material carrier of social services. It is of great significance for the operation of social justice and the improvement of residents' wellbeing. In the process of rapid urbanization, the demand for traffic convenience and diversity of public service facilities in rural areas has been further improved. Since the sudden outbreak of the COVID-19 epidemic, it is more necessary to meet the public service needs of human daily life within a certain space. The huge gap between urban and rural infrastructures, human living conditions, and supporting public services such as education, health, and culture has become a key bottleneck constraining the integration of urban and rural areas. It is appropriate to focus on the requirements for the construction of daily life circles and prioritize the satisfaction of villagers' increasing demand for public services in regions characterized by high levels of urban-rural integration. The behavior preference of public service facilities significantly affects the choice of residential areas. The existing research on village layout optimization focused on the spatial pattern, landscape morphology, influencing factors, and other contents. To some extent, the preference for equalization of public services in the context of urban-rural integration has been ignored. Uneven distribution and low utilization of public service facilities in villages resulted in an inability to adapt spatially and functionally in response to the renewal of urban-rural relations. Taking a highly developed urban and rural integration area named Wuxi City of Jiangsu Province in China as an example, this paper combines the current situation of public service facility allocation and the transport situation of residents in rural areas to build a life-circle system of different levels. On this basis, combined with the optimization goal of public service facilities and the constraints of agglomeration coverage, we try to determine the village layout optimization scheme under the construction of both the daily life circle and location-allocation model. The study can effectively adjust the allocation of public resources in rural areas and solve the problems of irrational village layout leading to long travel distances. It can also serve as a reference for improving the situation of lagging rural public service functions and promoting urban-rural equalization.

Development and validation of a diagnostic nomogram in pulmonary hypertension due to left heart disease.

BACKGROUND: Pulmonary hypertension (pH) due to left heart disease (pH-LHD) is the most common form of pH in clinical practice. OBJECTIVES: The purpose of the study is to develop a diagnostic nomogram predictive model combining conventional noninvasive examination and detection indicators. METHODS: Our study retrospectively included 361 patients with left heart disease (LHD) who underwent right heart catheterization between 2013 and 2020. All patients were randomly divided into a training cohort (253, 70 %) and a validation cohort (108, 30 %). pH was defined as resting mean pulmonary arterial pressure (mPAP) ≥25 mmHg measured by RHC examination. Data dimension reduction and feature selection were used by Lasso regression model. The nomogram was constructed based on multivariable logistic regression. RESULTS: A total of 175 patients with LHD were diagnosed with pH during their hospitalization, representing 48.5 % of the cohort. The mean age of the overall group was 55.6 years, with 76.7 % being male patients. Excessive resting heart rate, elevated New York Heart Association functional class, increased red blood cell distribution width, right ventricular end-diastolic diameter, and pulmonary artery systolic pressure measured by echocardiography were independently associated with the prevalence of pH-LHD. The inclusion of these 5 variables in the nomogram showed good discrimination (AUC = 0.866 [95 % CI, 0.820-0.911]) and optimal calibration (Hosmer-Lemeshow test, P = 0.791) for the validation cohort. CONCLUSIONS: The noninvasive nomogram of pH-LHD developed in this study has excellent diagnostic value and clinical applicability, and can more accurately evaluate the presence risk of pH in patients with LHD.

Conserved mechanisms of self-renewal and pluripotency in mouse and human ESCs regulated by simulated microgravity using a 3D clinostat.

Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

NAD metabolic therapy in metabolic dysfunction-associated steatotic liver disease: Possible roles of gut microbiota.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly named non-alcoholic fatty liver disease (NAFLD), is induced by alterations of hepatic metabolism. As a critical metabolites function regulator, nicotinamide adenine dinucleotide (NAD) nowadays has been validated to be effective in the treatment of diet-induced murine model of MASLD. Additionally, gut microbiota has been reported to have the potential to prevent MASLD by dietary NAD precursors metabolizing together with mammals. However, the underlying mechanism remains unclear. In this review, we hypothesized that NAD enhancing mitochondrial activity might reshape a specific microbiota signature, and improve MASLD progression demonstrated by fecal microbiota transplantation. Here, this review especially focused on the mechanism of Microbiota-Gut-Liver Axis together with NAD metabolism for the MASLD progress. Notably, we found significant changes in Prevotella associated with NAD in a gut microbiome signature of certain MASLD patients. With the recent researches, we also inferred that Prevotella can not only regulate the level of NAD pool by boosting the carbon metabolism, but also play a vital part in regulating the branched-chain amino acid (BCAA)-related fatty acid metabolism pathway. Altogether, our results support the notion that the gut microbiota contribute to the dietary NAD precursors metabolism in MASLD development and the dietary NAD precursors together with certain gut microbiota may be a preventive or therapeutic strategy in MASLD management.

A monomeric structure of human TMEM63A protein.

OSCA/TMEM63 is a newly identified family of mechanically activated (MA) ion channels in plants and animals, respectively, which convert physical forces into electrical signals or trigger intracellular cascades and are essential for eukaryotic physiology. OSCAs and related TMEM16s and transmembrane channel-like (TMC) proteins form homodimers with two pores. However, the molecular architecture of the mammalian TMEM63 proteins remains unclear. Here we elucidate the structure of human TMEM63A in the presence of calcium by single particle cryo-EM, revealing a distinct monomeric architecture containing eleven transmembrane helices. It has structural similarity to the single subunit of the Arabidopsis thaliana OSCA proteins. We locate the ion permeation pathway within the monomeric configuration and observe a nonprotein density resembling lipid. These results lay a foundation for understanding the structural organization of OSCA/TMEM63A family proteins.

Correlation of ventricle epicardial fat volume and triglyceride-glucose index in patients with chronic heart failure.

To explore the association of ventricle epicardial fat volume (EFV) calculated by cardiac magnetic resonance (CMR) and the insulin resistance indicator of triglyceride-glucose (TyG) index in patients with chronic HF (CHF), this retrospective cohort study included adult CHF patients with confirmed diagnosis of heart failure from January 2018 to December 2020. All patients underwent 3.0T CMR, and EFV were measured under short-axis cine. Spearman correlation, multivariate linear regression, and restricted cubic spline (RCS) regression were used to analyze their association. There were 516 patients with CHF, of whom 69.8% were male. Median EFV was 57.14mL and mean TyG index was 8.48. Spearman correlation analysis showed that TyG index was significantly correlated with the EFV in CHF patients (r = 0.247, P < 0.001). Further analysis showed that TyG index levels were significantly associated with EFV as both continuous variables (Unstandardized ß = 6.556, P < 0.001) and across the increasing quartiles (ß = 7.50, 95% CI [1.41, 13.59], P < 0.05). RCS demonstrated there were a positive trend and linear association between EFV and TyG index in CHF patients (P for nonliearity = 0.941). In patients with CHF, the TyG index was positively and linearly associated with the EFV, which supports the metabolic roles of epicardial adipose tissue regarding insulin resistance.

Omental coating attenuates implant-induced foreign body reaction in rats.

The objective of this study is to clarify whether the omental coating can effectively attenuate foreign body reaction (FBR) induced by implanted materials. Male Sprague-Dawley rats were injected with polydextran particle slurry intraperitoneally to activate the omentum. 7 days later, polyether polyurethane sponge discs were implanted subcutaneously on each side of the rat's back as the foreign implants to induce FBR. The next day, omental transposition were performed. The disc on the left side of each rat's back was wrapped with omental flap (omental group); the disc on the right side was untreated (control group). All discs were removed 21 days after implantation and assessed by determining the components of the fibrovascular tissue (angiogenesis, inflammation, foreign body giant cells (FBGCs) aggregation and fibrogenesis). In implants in omental group, micro vessel density (MVD), Hemoglobin (Hb) content and VEGF levels (pro-angiogenic cytokine) were increased when compared with implants from control group. Inflammatory parameters (IL-1ß; macrophage accumulation-NAG activity; neutrophil accumulation- MPO levels) were decreased in implants after omental coating. Also, collagen deposition, fibrous capsule thickness, and FBGCs decreased in implants from omental group. However, intra-implant levels of TNF-α and TGF-ß1 were not different after omental coating. Our findings showed for the first time that the omental coating around the implants attenuate the adverse FBR, it may be critical in developing new strategies to control FBR and improve the function and performance of the implanted materials.

Thiol-Ene Click Reaction in Constructing Liquid Separation Membranes for Water Treatment.

In the evolving landscape of water treatment, membrane technology has ascended to an instrumental role, underscored by its unmatched efficacy and ubiquity. Diverse synthesis and modification techniques are employed to fabricate state-of-the-art liquid separation membranes. Click reactions, distinguished by their rapid kinetics, minimal byproduct generation, and simple reaction condition, emerge as a potent paradigm for devising eco-functional materials. While the metal-free thiol-ene click reaction is acknowledged as a viable approach for membrane material innovation, a systematic elucidation of its applicability in liquid separation membrane development remains conspicuously absent. This review elucidates the pre-functionalization strategies of substrate materials tailored for thiol-ene reactions, notably highlighting thiolation and introducing unsaturated moieties. The consequential implications of thiol-ene reactions on membrane properties-including trade-off effect, surface wettability, and antifouling property-are discussed. The application of thiol-ene reaction in fabricating various liquid separation membranes for different water treatment processes, including wastewater treatment, oil/water separation, and ion separation, are reviewed. Finally, the prospects of thiol-ene reaction in designing novel liquid separation membrane, including pre-functionalization, products prediction, and solute-solute separation membrane, are proposed. This review endeavors to furnish invaluable insights, paving the way for expanding the horizons of thiol-ene reaction application in liquid separation membrane fabrication.