Three-pressure prediction method of jointing well-seismic data in JT1 well area of Sichuan Basin in China.

With the high yield of many wells represented by Well JT1 in the Maokou Formation, has catalyzed a surge in exploration activities along the platform margin facies of the Maokou Formation in central Sichuan and further showed the significant exploration potential of the Maokou Formation in the northern slope. However, the fracture cave body of the Maokou Formation exhibits a high degree of development, strong longitudinal and horizontal heterogeneity, large formation pressure differences, and drilling events such as gas kicks and lost circulation occur frequently, which seriously affects the efficient implementation of drilling. Understanding the spatial distribution of the three-pressure in the formation can help better deal with and solve the above problems. Therefore, in order to help the safe, high-quality and rapid drilling of the Maokou Formation in the study area, and enhance the efficiency of oil and gas development, this paper explores the research on the prediction method of the three-pressure of jointing well-seismic data based on the geomechanical experimental data and the actual drilling data. In the process of prediction of pore pressure, this study found that the pore pressure and formation velocity in the study area have an exponential relationship. In order to enhance the applicability of the Filippone's method in the study area and improve the prediction accuracy of pore pressure, the linear relationship between pore pressure and formation velocity in the Filippone's method is modified to an exponential relationship, and a pore pressure prediction model suitable for the work area was established. Based on the Mohr-Coulomb criterion and Huang's model, the prediction models of collapse pressure and fracture pressure applicable to the study area were established, respectively. Then, the elastic parameters were obtained through pre-stack inversion, and the three-pressure bodies were calculated based on the elastic parameter bodies. The results indicate that: (1) The three-pressure prediction method of the jointing well-seismic data in this paper can predict the formation's longitudinal and transverse pressure anomaly zones in advance. (2) The Maokou Formation in the study area is characterized by abnormally high pressure, to balance the pressure of the high-ground formation, high-density drilling fluid is necessary. (3) The prediction results of three-pressure in this paper are highly consistent with the actual drilling engineering events, which verifies the reliability of the three-pressure prediction results presented in this study. The results of the study can provide a basis for decision-making in drilling geological design, such as the determination of drilling fluid density, the evaluation of borehole stability and other engineering problems that require support from three-pressure data.

Transcriptional regulation of transcription factor genes WRI1 and LAFL during Brassica napus seed development.

The WRINKLED1 (WRI1) and LAFL [LEAFY COTYLEDON1 (LEC1), ABSCISIC ACID INSENSITIVE3 (ABI3), FUSCA3 (FUS3), and LEC2] transcription factors play essential roles in governing seed development and oil biosynthesis. To gain a comprehensive understanding of the transcriptional regulation of WRI1 and LAFL, we conducted genome-wide association studies for the expression profiles of WRI1 and LAFL in developing seeds at 20 and 40 days after flowering (DAF) using 302 rapeseed (Brassica napus) accessions. We identified a total of 237 expression quantitative trait nucleotides (eQTNs) and 51 expression QTN-by-environment interactions (eQEIs) associated with WRI1 and LAFL. Around these eQTNs and eQEIs, we pinpointed 41 and 8 candidate genes with known transcriptional regulations or protein interactions with their expression traits, respectively. Based on RNA-seq and ATAC-seq data, we employed the XGBoost and Basenji models which predicted 15 candidate genes potentially regulating the expression of WRI1 and LAFL. We further validated the predictions via tissue expression profile, haplotype analysis, and expression correlation analysis, and verified the transcriptional activation activity of BnaC03.MYB56 (R2R3-MYB transcription factor 56) on the expression of BnaA09.LEC1 by dual-luciferase reporter and yeast one-hybrid assays. BnaA10.AGL15 (AGAMOUS-LIKE 15), BnaC04.VAL1 (VIVIPAROUS1/ABSCISIC ACID INSENSITIVE3-LIKE 1), BnaC03.MYB56, and BnaA10.MYB56 were co-expressed with WRI1 and LAFL at 20 DAF in M35, a key module for seed development and oil biosynthesis. We further validated the positive regulation of MYB56 on seed oil accumulation using Arabidopsis (Arabidopsis thaliana) mutants. This study not only delivers a framework for future eQEI identification but also offers insights into the developmental regulation of seed oil accumulation.

N-P covalent bond regulation of mesoporous carbon-based catalyst for lowered oxygen reduction overpotential and enhanced zinc-air battery performance.

Developing sustainable metal-free carbon-based electrocatalysts is essential for the deployment of metal-air batteries such as zinc-air batteries (ZABs), among which doping of heteroatoms has attracted tremendous interest over the past decade. However, the effect of the heteroatom covalent bonds in carbon matrix on catalysis was neglected in most studies. Here, an efficient metal-free oxygen reduction reaction (ORR) catalyst is demonstrated by the N-P bonds anchored carbon (termed N,P-C-1000). The N,P-C-1000 catalyst exhibits superior specific surface area of 1362 m2 g-1 and ORR activity with a half-wave potential of 0.83 V, close to that of 20 wt% Pt/C. Theoretical computations reveal that the p-band center for C-2p orbit in N,P-C-1000 has higher interaction strength with the intermediates, thus reducing the overall reaction energy barrier. The N,P-C-1000 assembled primary ZAB can attain a large peak power density of 121.9 mW cm-2 and a steady discharge platform of ∼1.20 V throughout 120 h. Besides, when served as the cathodic catalyst in a solid-state ZAB, the battery shows flexibility, conspicuous open circuit potential (1.423 V), and high peak power density (85.8 mW cm-2). Our findings offer a strategy to tune the intrinsic structure of carbon-based catalysts for improved electrocatalytic performance and shed light on future catalysts design for energy storage technologies beyond batteries.

Research on spatial carving method of glutenite reservoir based on opacity voxel imaging.

The glutenite reservoir in an exploration area in eastern China is well-developed and holds significant exploration potential as an important oil and gas alternative layer. However, due to the influence of sedimentary characteristics, the glutenite reservoir exhibits strong lateral heterogeneity, significant vertical thickness variations, and low accuracy in reservoir space characterization, which affects the reasonable and effective deployment of development wells. Seismic data contains the three-dimensional spatial characteristics of geological bodies, but how to design a suitable transfer function to extract the nonlinear relationship between seismic data and reservoirs is crucial. At present, the transfer functions are concentrated in low-dimensional or high-dimensional fixed mathematical models, which cannot accurately describe the nonlinear relationship between seismic data and complex reservoirs, resulting in low spatial description accuracy of complex reservoirs. In this regard, this paper first utilizes a fusion method based on probability kernel to fuse seismic attributes such as wave impedance, effective bandwidth, and composite envelope difference. This provide a more intuitive reflection of the distribution characteristics of glutenite reservoirs. Moreover, a hybrid nonlinear transfer function is established to transform the fused attribute cube into an opaque attribute cube. Finally, the illumination model and ray casting method are used to perform voxel imaging of the glutenite reservoirs, brighten the detailed characteristics of reservoir space, and then form a set of methods for ' brightening reservoirs and darkening non-reservoirs ', which improves the spatial engraving accuracy of glutenite reservoirs.

Comparison of three colloidal gold immunoassays and GeneXpert Carba-R for the detection of Klebsiella pneumoniae blaKPC-2 variants.

The increasing use of ceftazidime-avibactam has led to the emergence of a wide range of ceftazidime-avibactam-resistant blaKPC-2 variants. Particularly, the conventional carbapenemase phenotypic assay exhibited a high false-negative rate for KPC-2 variants. In this study, three colloidal gold immunoassays, including the Gold Mountainriver CGI test, Dynamiker CGI test and NG-Test CARBA5, and GeneXpert Carba-R, were used to detect the presence of KPC-2 carbapenemase and its various variants in 42 Klebsiella pneumoniae strains. These strains covered blaKPC-2 (13/42) and 16 other blaKPC-2 variants including blaKPC-12 (1/42), blaKPC-23 (1/42), blaKPC-25 (1/42), blaKPC-33 (6/42), blaKPC-35 (1/42), blaKPC-44 (1/42), blaKPC-71 (1/42), blaKPC-76 (8/42), blaKPC-78 (1/42), blaKPC-79 (1/42), blaKPC-100 (1/42), blaKPC-127 (1/42), blaKPC-128 (1/42), blaKPC-144 (1/42), blaKPC-157 (2/42), and blaKPC-180 (1/42). For KPC-2 strains, all four assays showed 100% negative percentage agreement (NPA) and 100% positive percentage agreement (PPA) with sequencing results. For all 16 KPC-2 variants, GeneXpert Carba-R showed 100% NPA and 100% PPA, and the three colloidal gold immunoassays showed 100% NPA, while the PPAs of the Gold Mountainriver CGI test, Dynamiker CGI test, and NG-Test CARBA5 were 87.5%, 87.5%, and 68.8%, respectively. We also found a correlation between the mutation site in the amino acid of the variants and false-negative results by colloidal gold immunoassays. In conclusion, the GeneXpert Carba-R has been proven to be a reliable method in detecting KPC-2 and its variants, and the colloidal gold immunoassay tests offer a practical and cost-effective approach for their detection. For the sample with a negative result by a colloidal gold immunoassay test but not matching the drug-resistant phenotype, it is recommended to retest using another type of kit or the GeneXpert Carba-R assay, which can significantly improve the accuracy of detection.

Immunolabeling-compatible PEGASOS tissue clearing for high-resolution whole mouse brain imaging.

Novel brain clearing methods revolutionize imaging by increasing visualization throughout the brain at high resolution. However, combining the standard tool of immunostaining targets of interest with clearing methods has lagged behind. We integrate whole-mount immunostaining with PEGASOS tissue clearing, referred to as iPEGASOS (immunostaining-compatible PEGASOS), to address the challenge of signal quenching during clearing processes. iPEGASOS effectively enhances molecular-genetically targeted fluorescent signals that are otherwise compromised during conventional clearing procedures. Additionally, we demonstrate the utility of iPEGASOS for visualizing neurochemical markers or viral labels to augment visualization that transgenic mouse lines cannot provide. Our study encompasses three distinct applications, each showcasing the versatility and efficacy of this approach. We employ whole-mount immunostaining to enhance molecular signals in transgenic reporter mouse lines to visualize the whole-brain spatial distribution of specific cellular populations. We also significantly improve the visualization of neural circuit connections by enhancing signals from viral tracers injected into the brain. Last, we show immunostaining without genetic markers to selectively label beta-amyloid deposits in a mouse model of Alzheimer's disease, facilitating the comprehensive whole-brain study of pathological features.

Anoikis-related gene signatures in colorectal cancer: implications for cell differentiation, immune infiltration, and prognostic prediction.

Colorectal cancer (CRC) is a malignant tumor originating from epithelial cells of the colon or rectum, and its invasion and metastasis could be regulated by anoikis. However, the key genes and pathways regulating anoikis in CRC are still unclear and require further research. The single cell transcriptome dataset GSE221575 of GEO database was downloaded and applied to cell subpopulation type identification, intercellular communication, pseudo time cell trajectory analysis, and receptor ligand expression analysis of CRC. Meanwhile, the RNA transcriptome dataset of TCGA, the GSE39582, GSE17536, and GSE17537 datasets of GEO were downloaded and merged into one bulk transcriptome dataset. The differentially expressed genes (DEGs) related to anoikis were extracted from these data sets, and key marker genes were obtained after feature selection. A clinical prognosis prediction model was constructed based on the marker genes and the predictive effect was analyzed. Subsequently, gene pathway analysis, immune infiltration analysis, immunosuppressive point analysis, drug sensitivity analysis, and immunotherapy efficacy based on the key marker genes were conducted for the model. In this study, we used single cell datasets to determine the anoikis activity of cells and analyzed the DEGs of cells based on the score to identify the genes involved in anoikis and extracted DEGs related to the disease from the transcriptome dataset. After dimensionality reduction selection, 7 marker genes were obtained, including TIMP1, VEGFA, MYC, MSLN, EPHA2, ABHD2, and CD24. The prognostic risk model scoring system built by these 7 genes, along with patient clinical data (age, tumor stage, grade), were incorporated to create a nomogram, which predicted the 1-, 3-, and 5-years survival of CRC with accuracy of 0.818, 0.821, and 0.824. By using the scoring system, the CRC samples were divided into high/low anoikis-related prognosis risk groups, there are significant differences in immune infiltration, distribution of immune checkpoints, sensitivity to chemotherapy drugs, and efficacy of immunotherapy between these two risk groups. Anoikis genes participate in the differentiation of colorectal cancer tumor cells, promote tumor development, and could predict the prognosis of colorectal cancer.

Bacterial community analysis of the skin microbiota of cultured Chinese giant salamander infected with Ranavirus.

Skin microorganisms are an important component of host innate immunity and serve as the first line of defense against pathogenic infections. The relative abundance of bacterial species, microbial community assembly, and secretion of specific bacterial metabolites are closely associated with host health. In this study, we investigated the association between the skin microbiome and Ranavirus, and compared the bacterial community assemblage, alpha and beta diversity, and functional predictions of the skin bacterial assemblage in cultured healthy Chinese giant salamanders (Andrias davidianus) and individuals infected with Chinese giant salamander iridovirus (GSIV or ADRV). To achieve this, we employed 16S rRNA amplicon sequencing. The results identified Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota as the dominant phyla in the diseased and healthy groups. Alpha diversity analysis indicated that the skin bacterial community in the diseased group exhibited no significant differences in bacterial species diversity and lower species richness compared to the healthy group. Beta diversity suggested that the two group bacterial community was quite different. Kyoto encyclopedia of genes and genomes (KEGG) pathway analyze and clusters of orthologous groups of proteins (COG) function predictions revealed that changes and variations occurred in the metabolic pathways and function distribution of skin bacterial communities in two groups.

Distinct roles of excitatory and inhibitory neurons in the medial prefrontal cortex in the expression and reconsolidation of methamphetamine-associated memory in male mice.

Methamphetamine, a commonly abused drug, is known for its high relapse rate. The persistence of addictive memories associated with methamphetamine poses a significant challenge in preventing relapse. Memory retrieval and subsequent reconsolidation provide an opportunity to disrupt addictive memories. However, the key node in the brain network involved in methamphetamine-associated memory retrieval has not been clearly defined. In this study, using the conditioned place preference in male mice, whole brain c-FOS mapping and functional connectivity analysis, together with chemogenetic manipulations of neural circuits, we identified the medial prefrontal cortex (mPFC) as a critical hub that integrates inputs from the retrosplenial cortex and the ventral tegmental area to support both the expression and reconsolidation of methamphetamine-associated memory during its retrieval. Surprisingly, with further cell-type specific analysis and manipulation, we also observed that methamphetamine-associated memory retrieval activated inhibitory neurons in the mPFC to facilitate memory reconsolidation, while suppressing excitatory neurons to aid memory expression. These findings provide novel insights into the neural circuits and cellular mechanisms involved in the retrieval process of addictive memories. They suggest that targeting the balance between excitation and inhibition in the mPFC during memory retrieval could be a promising treatment strategy to prevent relapse in methamphetamine addiction.

Arrhythmia onsets triggered by acute myocardial ischemia are not mediated by lysophosphoglycerides accumulation in ventricular myocardium.

Lysophosphoglycerides (LPLs) have been reported to accumulate in myocardium and serve as a cause of arrhythmias in acute myocardial ischemia. However, in this study we found that LPLs level in the ventricular myocardium was decreased by the onset of acute myocardial ischemia in vivo in rats. Decreasing of LPLs level in left ventricular myocardium, but not right, was observed within 26 min of left myocardial ischemia, regardless of whether arrhythmias were triggered. Lower LPLs level in the ventricular myocardium was also observed in aconitine-simulated ventricular fibrillation (P < 0.0001) and ouabain-simulated III° atrioventricular block (P < 0.0001). Shot-lasting electric shock, e.g., ≤ 40 s, decreased LPLs level, while long-lasting, e.g., 5 min, increased it (fold change = 2.27, P = 0.0008). LPLs accumulation was observed in long-lasting myocardial ischemia, e.g., 4 h (fold change = 1.20, P = 0.0012), when caspase3 activity was elevated (P = 0.0012), indicating increased cell death, but not coincided with higher frequent arrhythmias. In postmortem human ventricular myocardium, differences of LPLs level in left ventricular myocardium was not observed among coronary artery disease- and other heart diseases-caused sudden death and non-heart disease caused death. LPLs level manifested a remarkable increasing from postmortem 12 h on in rats, thus abolishing the potential for serving as biomarkers of sudden cardiac death. Token together, in this study we found that LPLs in ventricular myocardium were initially decreased by the onset of ischemia, LPLs accumulation do not confer arrhythmogenesis during acute myocardial ischemia. It is necessary to reassess the roles of LPLs in myocardial infarction.

Analyzing the spatiotemporal pattern of the decoupling degree between carbon metabolism and economic development in village and town units.

In the context of green and sustainable development and rural revitalization, analysis of the relationship between economic development and the evolution of carbon metabolism is of great significance for China's future transformation of development models. This study analyzed the spatial characteristics and spatiotemporal evolution pattern of the decoupling status between carbon metabolism and economic development of Laiwu during two periods from 2001 to 2018 at the village and town unit scales by using the Tapio decoupling model. The results showed that the growth rate of carbon metabolism from 2001 to 2009 was significantly higher than that from 2009 to 2018. The spatial heterogeneity of the decoupling states between economic development and carbon metabolism from 2009 to 2018 was significantly stronger than that from 2001 to 2009 in two units. From 2001 to 2018, the development trend gradually trended towards spatial imbalance. The decoupling status between villages and towns had a high degree of consistency from 2001 to 2009 and inconsistency from 2009 to 2018. From 2001 to 2009, the decoupling status of about 78% of villages was consistent with that of towns. Moreover, from 2009 to 2018, the consistency reduced to 32.2%, and the decoupling status of about 48% of villages was weaker than that of towns. According to the reclassification results of different decoupling state change types, from 2001 to 2018, about 52.2% of the villages had a decoupling state evolution type of eco-deteriorated economic development, which is an unsatisfactory development trend in a short time. Moreover, about 12.1% of the villages had a decoupling state evolution type of eco-improved economic development, which is a satisfactory development trend.

CBX2 Deletion Suppresses Growth and Metastasis of Colorectal Cancer by Mettl3-p38/ERK MAPK Signalling Pathway.

Colorectal cancer (CRC) seriously endangers human health owing to its high morbidity and mortality. Previous studies have suggested that high expression of CBX2 may be associated with poor prognosis in CRC patients. However, its functional role in CRC remains to be elucidated. Herein, we found that CBX2 overexpression in colorectal cancer tissue compared with adjacent tissues. Additionally, forest maps and the nomogram model indicated that elevated CBX2 expression was an independent prognostic factor in CRC. Moreover, we confirmed that the deletion of CBX2 markedly suppressed the proliferation and migration of CRC cells in vitro and in vivo. Furthermore, downregulation of CBX2 promotes CRC cell apoptosis and hinders the cell cycle. Mechanistically, our data demonstrated that deletion of CBX2 inhibited the MAPK signaling pathway by regulating the protein levels of Mettl3. In conclusion, our study demonstrated that CBX2 is a vital tumor suppressor in CRC and could be a promising anti-cancer therapeutic target.

Functional genomics of Brassica napus: Progresses, challenges, and perspectives.

Brassica napus, commonly known as rapeseed or canola, is a major oil crop contributing over 13% to the stable supply of edible vegetable oil worldwide. Identification and understanding the gene functions in the B. napus genome is crucial for genomic breeding. A group of genes controlling agronomic traits have been successfully cloned through functional genomics studies in B. napus. In this review, we present an overview of the progress made in the functional genomics of B. napus, including the availability of germplasm resources, omics databases and cloned functional genes. Based on the current progress, we also highlight the main challenges and perspectives in this field. The advances in the functional genomics of B. napus contribute to a better understanding of the genetic basis underlying the complex agronomic traits in B. napus and will expedite the breeding of high quality, high resistance and high yield in B. napus varieties.

Preoperative ultrasound-guided dual localization with titanium clips and carbon nanoparticles for predicting the surgical approach and guiding the resection of Siewert type II esophagogastric junction adenocarcinoma.

OBJECTIVE: To investigate the superiority of preoperative ultrasound-guided titanium clip and nanocarbon dual localization over traditional methods for determining the surgical approach and guiding resection of Siewert type II adenocarcinoma of the esophagogastric junction (AEG). METHOD: This study included 66 patients with Siewert type II AEG who were treated at the PLA Joint Logistics Support Force 900th Hospital between September 1, 2021, and September 1, 2023. They were randomly divided into an experimental group (n = 33), in which resection was guided by the dual localization technique, and the routine group (n = 33), in which the localization technique was not used. Surgical approach predictions, proximal esophageal resection lengths, pathological features, and the occurrence of complications were compared between the groups. RESULT: The use of the dual localization technique resulted in higher accuracy in predicting the surgical approach (96.8% vs. 75.9%, P = 0.02) and shorter proximal esophageal resection lengths (2.39 ± 0.28 cm vs. 2.86 ± 0.39 cm, P < 0.001) in the experimental group as compared to the routine group, while there was no significant difference in the incidence of postoperative complications (22.59% vs. 24.14%, P = 0.88). CONCLUSION: Preoperative dual localization with titanium clips and carbon nanoparticles is significantly superior to traditional methods and can reliably delineate the actual infiltration boundaries of Siewert type II AEG, guide the surgical approach, and avoid excessive esophageal resection.

A Wnt10a-Notch signaling axis controls Hertwig's epithelial root sheath cell behaviors during root furcation patterning.

Human with bi-allelic WNT10A mutations and epithelial Wnt10a knockout mice present enlarged pulp chamber and apical displacement of the root furcation of multi-rooted teeth, known as taurodontism; thus, indicating the critical role of Wnt10a in tooth root morphogenesis. However, the endogenous mechanism by which epithelial Wnt10a regulates Hertwig's epithelial root sheath (HERS) cellular behaviors and contributes to root furcation patterning remains unclear. In this study, we found that HERS in the presumptive root furcating region failed to elongate at an appropriate horizontal level in K14-Cre;Wnt10afl/fl mice from post-natal day 0.5 (PN0.5) to PN4.5. EdU assays and immunofluorescent staining of cyclin D1 revealed significantly decreased proliferation activity of inner enamel epithelial (IEE) cells of HERS in K14-Cre;Wnt10afl/fl mice at PN2.5 and PN3.5. Immunofluorescent staining of E-Cadherin and acetyl-α-Tubulin demonstrated that the IEE cells of HERS tended to divide perpendicularly to the horizontal plane, which impaired the horizontal extension of HERS in the presumptive root furcating region of K14-Cre;Wnt10afl/fl mice. RNA-seq and immunofluorescence showed that the expressions of Jag1 and Notch2 were downregulated in IEE cells of HERS in K14-Cre;Wnt10afl/fl mice. Furthermore, after activation of Notch signaling in K14-Cre;Wnt10afl/fl molars by Notch2 adenovirus and kidney capsule grafts, the root furcation defect was partially rescued. Taken together, our study demonstrates that an epithelial Wnt10a-Notch signaling axis is crucial for modulating HERS cell proper proliferation and horizontal-oriented division during tooth root furcation morphogenesis.

Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin.

The function of mitochondria as a regulator of myocyte calcium homeostasis has been extensively discussed. The aim of the present work was further clarification of the details of modulation of the functional activity of rat cardiac mitochondria by exogenous Ca2+ ions either in the absence or in the presence of the plant flavonoid naringin. Low free Ca2+ concentrations (40-250 nM) effectively inhibited the respiratory activity of heart mitochondria, remaining unaffected the efficacy of oxygen consumption. In the presence of high exogenous Ca2+ ion concentrations (Ca2+ free was 550 µM), we observed a dramatic increase in mitochondrial heterogeneity in size and electron density, which was related to calcium-induced opening of the mitochondrial permeability transition pores (MPTP) and membrane depolarization (Ca2+free ions were from 150 to 750 µM). Naringin partially prevented Ca2+-induced cardiac mitochondrial morphological transformations (200 µM) and dose-dependently inhibited the respiratory activity of mitochondria (10-75 µM) in the absence or in the presence of calcium ions. Our data suggest that naringin (75 µM) promoted membrane potential dissipation, diminishing the potential-dependent accumulation of calcium ions by mitochondria and inhibiting calcium-induced MPTP formation. The modulating effect of the flavonoid on Ca2+-induced mitochondria alterations may be attributed to the weak-acidic nature of the flavonoid and its protonophoric/ionophoric properties. Our results show that the sensitivity of rat heart mitochondria to Ca2+ ions was much lower in the case of MPTP opening and much higher in the case of respiration inhibition as compared to liver mitochondria.

Identification of novel T cell proliferation patterns, potential biomarkers and therapeutic drugs in colorectal cancer.

Background: T cells are crucial components of antitumor immunity. A list of genes associated with T cell proliferation was recently identified; however, the impact of T cell proliferation-related genes (TRGs) on the prognosis and therapeutic responses of patients with colorectal cancer (CRC) remains unclear. Methods: 33 TRG expression information and clinical information of patients with CRC gathered from multiple datasets were subjected to bioinformatic analysis. Consensus clustering was used to determine the molecular subtypes associated with T cell proliferation. Utilizing the Lasso-Cox regression, a predictive signature was created and verified in external cohorts. A tumor immune environment analysis was conducted, and potential biomarkers and therapeutic drugs were identified and confirmed via in vitro and in vivo studies. Results: CRC patients were separated into two TRG clusters, and differentially expressed genes (DEGs) were identified. Patient information was divided into three different gene clusters, and the determined molecular subtypes were linked to patient survival, immune cells, and immune functions. Prognosis-associated DEGs in the three gene clusters were used to evaluate the risk score, and a predictive signature was developed. The ability of the risk score to predict patient survival and treatment response has been successfully validated using multiple datasets. To discover more possible biomarkers for CRC, the weighted gene co-expression network analysis algorithm was utilized to screen key TRG variations between groups with high- and low-risk. CDK1, BATF, IL1RN, and ITM2A were screened out as key TRGs, and the expression of key TRGs was confirmed using real-time reverse transcription polymerase chain reaction. According to the key TRGs, 7,8-benzoflavone was identified as the most significant drug molecule, and MTT, colony formation, wound healing, transwell assays, and in vivo experiments indicated that 7,8-benzoflavone significantly suppressed the proliferation and migration of CRC cells. Conclusion: T cell proliferation-based molecular subtypes and predictive signatures can be utilized to anticipate patient results, immunological landscape, and treatment response in CRC. Novel biomarker candidates and potential therapeutic drugs for CRC were identified and verified using in vitro and in vivo tests.

S100A6 drives lymphatic metastasis of liver cancer via activation of the RAGE/NF-kB/VEGF-D pathway.

Patients diagnosed with lymph node (LN) metastatic liver cancer face an exceedingly grim prognosis. In-depth analysis of LN metastatic patients' characteristics and tumor cells' interactions with human lymphatic endothelial cells (HLECs), can provide important biological and therapeutic insights. Here we identify at the single-cell level that S100A6 expression differs between primary tumor and their LN metastasis. Of particular significance, we uncovered the disparity in S100A6 expression between tumors and normal tissues is greater in intrahepatic cholangiocarcinoma (ICC) patients, frequently accompanied by LN metastases, than that in hepatocellular carcinoma (HCC), with rare occurrence of LN metastasis. Furthermore, in the infrequent instances of LN metastasis in HCC, heightened S100A6 expression was observed, suggesting a critical role of S100A6 in the process of LN metastasis. Subsequent experiments further uncovered that S100A6 secreted from tumor cells promotes lymphangiogenesis by upregulating the expression and secretion of vascular endothelial growth factor-D (VEGF-D) in HLECs through the RAGE/NF-kB/VEGF-D pathway while overexpression of S100A6 in tumor cells also augmented their migration and invasion. Taken together, these data reveal the dual effects of S100A6 in promoting LN metastasis in liver cancer, thus highlighting its potential as a promising therapeutic target.

Robust machine-learning based prognostic index using cytotoxic T lymphocyte evasion genes highlights potential therapeutic targets in colorectal cancer.

BACKGROUND: A minute fraction of patients stands to derive substantial benefits from immunotherapy, primarily attributable to immune evasion. Our objective was to formulate a predictive signature rooted in genes associated with cytotoxic T lymphocyte evasion (CERGs), with the aim of predicting outcomes and discerning immunotherapeutic response in colorectal cancer (CRC). METHODS: 101 machine learning algorithm combinations were applied to calculate the CERGs prognostic index (CERPI) under the cross-validation framework, and patients with CRC were separated into high- and low-CERPI groups. Relationship between immune cell infiltration levels, immune-related scores, malignant phenotypes and CERPI were further analyzed. Various machine learning methods were used to identify key genes related to both patient survival and immunotherapy benefits. Expression of HOXC6, G0S2, and MX2 was evaluated and the effects of HOXC6 and G0S2 on the viability and migration of a CRC cell line were in-vitro verified. RESULTS: The CERPI demonstrated robust prognostic efficacy in predicting the overall survival of CRC patients, establishing itself as an independent predictor of patient outcomes. The low-CERPI group exhibited elevated levels of immune cell infiltration and lower scores for tumor immune dysfunction and exclusion, indicative of a greater potential benefit from immunotherapy. Moreover, there was a positive correlation between CERPI levels and malignant tumor phenotypes, suggesting that heightened CERPI expression contributes to both the occurrence and progression of tumors. Thirteen key genes were identified, and their expression patterns were scrutinized through the analysis of single-cell datasets. Notably, HOXC6, G0S2, and MX2 exhibited upregulation in both CRC cell lines and tissues. Subsequent knockdown experiments targeting G0S2 and HOXC6 resulted in a significant suppression of CRC cell viability and migration. CONCLUSION: We developed the CERPI for effectively predicting survival and response to immunotherapy in patients, and these results may provide guidance for CRC diagnosis and precise treatment.

LncRNA HCP5 is Highly Expressed in Gestational Diabetes Mellitus to Suppress Insulin Secretion.

Purpose: LncRNA HCP5 has been reported to participate in high glucose-induced pathological processes, whereas its role in gestational diabetes mellitus (GDM) is unclear. This study aimed to explore the role of HCP5 in GDM. Methods: This study enrolled a total of 220 pregnant women (gestational age = 1 month). A follow-up study was performed until delivery. The occurrence of GDM was checked every month during follow-up. Plasma samples were collected from all participants and expression of HCP5 was determined with RT-qPCR. The 220 patients were divided into high and low GDM groups, and GDM-free curves were plotted for both groups and compared. The ROC curve was plotted to explore the predictive value of plasma HCP5 on the day of admission for GDM. INS-1 cells were transfected with HCP5 expression vector or siRNA, and cell viability under high glucose was determined by the MTT assay. An ELISA was applied to determine insulin levels in the cell culture medium. Results: During follow-up, the level of HCP5 was increased during pregnancy and the high HCP5 level group showed a significantly higher incidence of GDM. Plasma levels of HCP5 on the day of admission effectively separated GDM patients from healthy controls. HCP5 negatively regulated cell viability and insulin secretion under high glucose treatment. Conclusion: HCP5 may act as a predictor for GDM, and it negatively regulated INS-1 cell viability and insulin secretion under high glucose conditions.