miR-107 reverses the multidrug resistance of gastric cancer by targeting the CGA/EGFR/GATA2 positive feedback circuit.

Chemotherapy is still the main therapeutic strategy for gastric cancer (GC). However, most patients eventually acquire multidrug resistance (MDR). Hyperactivation of the EGFR signaling pathway contributes to MDR by promoting cancer cell proliferation and inhibiting apoptosis. We previously identified the secreted protein CGA as a novel ligand of EGFR and revealed a CGA/EGFR/GATA2 positive feedback circuit that confers MDR in GC. Herein, we outline a microRNA-based treatment approach for MDR reversal that targets both CGA and GATA2. We observed increased expression of CGA and GATA2 and increased activation of EGFR in GC samples. Bioinformatic analysis revealed that miR-107 could simultaneously target CGA and GATA2, and the low expression of miR-107 was correlated with poor prognosis in GC patients. The direct interactions between miR-107 and CGA or GATA2 were validated by luciferase reporter assays and western blot analysis. Overexpression of miR-107 in MDR GC cells increased their susceptibility to chemotherapeutic agents, including fluorouracil, adriamycin and vincristine, in vitro. Notably, intratumor injection of the miR-107 prodrug enhanced MDR xenograft sensitivity to chemotherapies in vivo. Molecularly, targeting CGA and GATA2 with miR-107 inhibited EGFR downstream signaling, as evidenced by the reduced phosphorylation of ERK and AKT. These results suggest that miR-107 may contribute to the development of a promising therapeutic approach for the treatment of MDR in GC.

The Concentration of Benzo[a]pyrene in Food Cooked by Air Fryer and Oven: A Comparison Study.

The air fryer utilizes heated air rather than hot oil to achieve frying, eliminating the need for cooking oil, rendering it a healthier cooking method than traditional frying and baking. However, there is limited evidence supporting that the air fryer could effectively reduce the level of food-derived carcinogen. In this study, we compared the concentration of Benzo[a]pyrene (BaP), a typical carcinogen, in beef patties cooked using an air fryer and an oven, under different cooking conditions, including temperatures (140 °C, 160 °C, 180 °C, and 200 °C), times (9, 14, and 19 min), and oil added or not. The adjusted linear regression analysis revealed that the BaP concentration in beef cooked in the air fryer was 22.667 (95% CI: 15.984, 29.349) ng/kg lower than that in beef cooked in the oven. Regarding the air fryer, the BaP concentration in beef cooked without oil brushing was below the detection limit, and it was significantly lower than in beef cooked with oil brushing (p < 0.001). Therefore, cooking beef in the air fryer can effectively reduce BaP concentration, particularly due to the advantage of oil-free cooking, suggesting that the air fryer represents a superior option for individuals preparing meat at high temperatures.

Plant regeneration in the new era: from molecular mechanisms to biotechnology applications.

Plants or tissues can be regenerated through various pathways. Like animal regeneration, cell totipotency and pluripotency are the molecular basis of plant regeneration. Detailed systematic studies on Arabidopsis thaliana gradually unravel the fundamental mechanisms and principles underlying plant regeneration. Specifically, plant hormones, cell division, epigenetic remodeling, and transcription factors play crucial roles in reprogramming somatic cells and reestablishing meristematic cells. Recent research on basal non-vascular plants and monocot crops has revealed that plant regeneration differs among species, with various plant species using distinct mechanisms and displaying significant differences in regenerative capacity. Conducting multi-omics studies at the single-cell level, tracking plant regeneration processes in real-time, and deciphering the natural variation in regenerative capacity will ultimately help understand the essence of plant regeneration, improve crop regeneration efficiency, and contribute to future crop design.

Network Pharmacology and Bioinformatics Analysis to Identify the Molecular Targets and its Biological Mechanisms of Sciadopitysin against Glioblastoma.

Glioblastoma multiform (GBM) is categorized as the most malignant subtype of gliomas, which comprise nearly 75% of malignant brain tumors in adults. Increasing evidence suggests that network pharmacology will be a novel method for identifying the systemic mechanism of therapeutic compounds in diseases like cancer. The present study aimed to use a network pharmacology approach to establish the predictive targets of sciadopitysin against GBM and elucidate its biological mechanisms. Firstly, targets of sciadopitysin were obtained from the SwissTargetPrediction database, and genes associated with the pathogenesis of GBM were identified from the DiGeNET database. Sixty-four correlative hits were identified as anti-glioblastoma targets of sciadopitysin. Functional enrichment and pathway analysis revealed significant biological mechanisms of the targets. Interaction of protein network and cluster analysis using STRING resulted in two crucial interacting hub genes, namely, HSP90 and AKT1. Additionally, the in vitro cytotoxic potential of sciadopitysin was assessed on GBM U87 cells. The findings indicate that the pharmacological action of sciadopitysin against GBM might be associated with the regulation of two core targets: HSP90 and AKT1. Thus, the network pharmacology undertaken in the current study established the core active targets of sciadopitysin, which may be extensively applied with further validations for treatment in GBM.

Microalgal extracellular polymeric substances (EPS) and their roles in cultivation, biomass harvesting, and bioproducts extraction.

Microalgae extracellular polymeric substances (EPS) are complex high-molecular-weight polymers and the physicochemical properties of EPS strongly affect the core features of microalgae cultivation and resource utilization. Revealing the key roles of EPS in microalgae life-cycle processes in an interesting and novelty topic to achieve energy-efficient practical application of microalgae. This review found that EPS showed positive effect in non-gas uptake, extracellular electron transfer, toxicity resistance and heterotrophic symbiosis, but negative impact in gas transfer and light utilization during microalgae cultivation. For biomass harvesting, EPS favored biomass flocculation and large-size cell self-flocculation, but unfavored small size microalgae self-flocculation, membrane filtration, charge neutralization and biomass dewatering. During bioproducts extraction, EPS exhibited positive impact in extractant uptake, but the opposite effect in cellular membrane permeability and cell rupture. Future research on microalgal EPS were also identified, which offer suggestions for comprehensive understanding of microalgal EPS roles in various scenarios.

Cardiovascular mortality among patients with diffuse large B-cell lymphoma: a population-based study.

We aim to investigate cardiovascular mortality risk among diffuse large B-cell lymphoma (DLBCL) patients and explore cardiovascular mortality trends in the past decades in United States. We extracted data from the Surveillance, Epidemiology, and End Results database for adult patients diagnosed with DLBCL between 1975 and 2019. Standardized mortality ratio, joinpoint regression analysis, and competing risk model were analyzed. Overall, 49,918 patients were enrolled, of whom 4167 (8.3%) cardiovascular deaths were observed, which was 1.22 times the number expected (95%CI, 1.19-1.26). During 1985-2019, the incidence-based cardiovascular mortality rate increased by 0.98% per year (95%CI, 0.58-1.39%), with statistically significant increases in age groups younger than 75 years. The cumulative mortality from cardiovascular disease increased by age but never exceeded that from DLBCL. Older age, male sex, earlier year of diagnosis, lower tumor stage at diagnosis, chemotherapy, radiotherapy, and surgery were all poor prognostic factors for cardiovascular mortality.

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The alteration of stand age instigates modifications in soil properties and microbial communities. Understanding the impacts of stand age on soil enzyme stoichiometry and microbial nutrient limitations in Camellia oleifera plantation is crucial for nutrient management. Taking C. oleifera plantation across four age groups (<10 a, 15-25 a, 30-50 a, >60 a) in a subtropical red soil region as test objects, we examined the response of soil enzyme stoichiometry and microbial nutrient limitations to change in stand age and analyzed the pathways for such responses. The results showed that, compared to that of stand age <10 a, enzyme C:N in the 15-25 a was increased and enzyme N:P was significantly reduced. Microbial biomass carbon (MBC), microbial biomass nitrogen (MBN), and microbial biomass phosphorus (MBP) exhibited a trend of initially decreasing and then increasing with stand age. MBN and MBN:MBP were significantly higher in the <10 a compared to that in the 30-50 a. MBC:MBN was significantly higher in the 30-50 a and >60 a compared to the <10 a and 15-25 a. Results of redundancy analysis revealed that soil nutrients, microbial biomass and their stoichiometry explained 92.4% of the variations in enzyme stoichiometry. Partial least squares path modeling (PLS-PM) results demonstrated that soil organic carbon (SOC) had a positive effect on microbial C limitation; MBN, MBN:MBP, MBC:MBP, SOC, and total nitrogen had a nega-tive overall effect on microbial P limitation, whereas soil C:N had a positive overall effect on microbial P limitation. There was a significant positive correlation between microbial C and P limitations. With increasing stand age, microbial nutrient limitation shifted from N and P limitation (<10 a) to C and P limitation (15-25 a, 30-50 a, >60 a).

D-dimer levels predict the treatment efficacy and prognosis of esophageal squamous cell carcinoma treated with PD-1/PD-L1 inhibitors.

OBJECTIVES: This study aimed to explore the value of D-dimer levels in predicting the treatment efficacy and prognosis of advanced esophageal squamous cell carcinoma (ESCC) treated with programmed cell death protein-1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors. METHODS: The study retrospectively analyzed 233 ESCC patients who received PD-1/PD-L1 inhibitors. The optimal cut-off values for platelets, fibrinogen, and D-dimer were calculated based on maximally selected rank statistics for patients' overall survival. Univariate and multivariate analyses of progression-free survival and overall survival were conducted by Cox proportional hazards regression model. Subgroup analyses of D-dimer levels in different fibrinogen levels were performed by log-rank test. RESULTS: The multivariate Cox regression analyses demonstrated that ESCC patients with D-dimer levels > 236 ng/mL exhibited both poorer progression-free survival (P = 0.004) and overall survival (P < 0.0001) compared to those with low D-dimer levels. The subgroup analyses further indicated that in the group of low fibrinogen levels, the higher D-dimer levels of ESCC patients exhibited significantly shorter progression-free survival (P = 0.0021) and overall survival (P < 0.0001). CONCLUSIONS: The study revealed that the D-dimer levels possess predictive value for the treatment efficacy and prognosis of ESCC patients treated with PD-1/PD-L1 inhibitors.

Global distribution of zoonotic digenetic trematodes: a scoping review.

BACKGROUND: Digenetic trematodes, including blood flukes, intestinal flukes, liver flukes, lung flukes, and pancreatic flukes, are highly diverse and distributed widely. They affect at least 200 million people worldwide, so better understanding of their global distribution and prevalence are crucial for controlling and preventing human trematodiosis. Hence, this scoping review aims to conduct a comprehensive investigation on the spatio-temporal distribution and epidemiology of some important zoonotic digenetic trematodes. METHODS: We conducted a scoping review by searching PubMed, Web of Science, Google Scholar, China National Knowledge Infrastructure, and Wanfang databases for articles, reviews, and case reports of zoonotic digenetic trematodes, without any restrictions on the year of publication. We followed the inclusion and exclusion criteria to identify relevant studies. And relevant information of the identified studies were collected and summarized. RESULTS: We identified a total of 470 articles that met the inclusion criteria and were included in the review finally. Our analysis revealed the prevalence and global distribution of species in Schistosoma, Echinostoma, Isthmiophora, Echinochasmus, Paragonimus, Opisthorchiidae, Fasciolidae, Heterophyidae, and Eurytrema. Although some flukes are distributed worldwide, developing countries in Asia and Africa are still the most prevalent areas. Furthermore, there were some overlaps between the distribution of zoonotic digenetic trematodes from the same genus, and the prevalence of some zoonotic digenetic trematodes was not entirely consistent with their global distribution. The temporal disparities in zoonotic digenetic trematodes may attribute to the environmental changes. The gaps in our knowledge of the epidemiology and control of zoonotic digenetic trematodes indicate the need for large cohort studies in most countries. CONCLUSIONS: This review provides important insights into the prevalence and global distribution of some zoonotic digenetic trematodes, firstly reveals spatio-temporal disparities in these digenetic trematodes. Countries with higher prevalence rate could be potential sources of transmitting diseases to other areas and are threat for possible outbreaks in the future. Therefore, continued global efforts to control and prevent human trematodiosis, and more international collaborations are necessary in the future.

IDEAL-IQ measurement can distinguish dysplastic nodule from early hepatocellular carcinoma: a case-control study.

Background: Previous studies have confirmed that malignant transformation of dysplastic nodule (DN) into hepatocellular carcinoma (HCC) is accompanied by reduction of iron content in nodules. This pathological abnormality can serve as the basis for magnetic resonance imaging (MRI). This study was designed to identify the feasibility of iterative decomposition of water and fat with echo asymmetry and least squares estimation-iron quantitative (IDEAL-IQ) measurement to distinguish early hepatocellular carcinoma (eHCC) from DN. Methods: We reviewed MRI studies of 35 eHCC and 23 DN lesions (46 participants with 58 lesions total, 37 males, 9 females, 31-80 years old). The exams include IDEAL-IQ sequence and 3.0T MR conventional scan [including T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), diffusion-weighted imaging (DWI), and Gadopentic acid (Gd-GDPA)-enhanced]. Then, 3 readers independently diagnosed eHCC, DN, or were unable to distinguish eHCC from DN using conventional MRI (CMRI), and then assessed R2* value of nodules [R2* value represents the nodule iron content (NIC)] and R2* value of liver background [R2* value represents the liver background iron content (LBIC)] with IDEAL-IQ. Statistical analysis was conducted using the t-test for comparison of means, the Mann-Whitney test for comparison of medians, the chi-square test for comparison of frequencies, and diagnostic efficacy was evaluated by using receiver operating characteristic (ROC) curve. Results: This study evaluated 35 eHCC participants (17 males, 6 females, 34-81 years old, nodule size: 10.5-27.6 mm, median 18.0 mm) and 23 DN participants (20 males, 3 females, 31-76 years old, nodule size: 16.30±4.095 mm). The NIC and ratio of NIC to LIBC (NIC/LBIC) of the eHCC group (35.926±12.806 sec-1, 0.327±0.107) was lower than that of the DN group (176.635±87.686 sec-1, 1.799±0.629) (P<0.001). Using NIC and NIC/LBIC to distinguish eHCC from DN, the true positive/false positive rates were 91.3%/94.3% and 87.0%/97.1%, respectively. The rates of CMRI, NIC and NIC/LBIC in diagnosis of eHCC were 77.1%, and 94.3%, 97.1%, respectively, and those of DN were 65.2%, 91.3%, and 87.0%, respectively. The diagnosis rate of eHCC and DN by CMRI was lower than that of NIC and NIC/LBIC (eHCC: P=0.03, 0.04, DN: P=0.02, 0.04). Conclusions: Using IDEAL-IQ measurement can distinguish DN from eHCC.

Cerium oxide nanoparticles in wound care: a review of mechanisms and therapeutic applications.

Skin wound healing is a complex and tightly regulated process. The frequent occurrence and reoccurrence of acute and chronic wounds cause significant skin damage to patients and impose socioeconomic burdens. Therefore, there is an urgent requirement to promote interdisciplinary development in the fields of material science and medicine to investigate novel mechanisms for wound healing. Cerium oxide nanoparticles (CeO2 NPs) are a type of nanomaterials that possess distinct properties and have broad application prospects. They are recognized for their capabilities in enhancing wound closure, minimizing scarring, mitigating inflammation, and exerting antibacterial effects, which has led to their prominence in wound care research. In this paper, the distinctive physicochemical properties of CeO2 NPs and their most recent synthesis approaches are discussed. It further investigates the therapeutic mechanisms of CeO2 NPs in the process of wound healing. Following that, this review critically examines previous studies focusing on the effects of CeO2 NPs on wound healing. Finally, it suggests the potential application of cerium oxide as an innovative nanomaterial in diverse fields and discusses its prospects for future advancements.

Inflammation, nutrition, and biological aging: The prognostic role of Naples prognostic score in nonalcoholic fatty liver disease outcomes.

AIM: This study aimed to evaluate the prognostic value of the Naples Prognostic Score (NPS) for predicting mortality in patients with nonalcoholic fatty liver disease (NAFLD) and compare its performance with established non-invasive fibrosis scores, including the fibrosis-4 index (FIB-4) and NAFLD fibrosis score (NFS). METHODS: Data from 10,035 NAFLD patients identified within the 1999-2018 National Health and Nutrition Examination Survey (NHANES) were analyzed. Cox regression models assessed the association between NPS and all-cause mortality, while time-dependent ROC analysis compared its predictive accuracy with FIB-4 and NFS. Mediation analysis explored the role of phenotypic age acceleration (PhenoAgeAccel). RESULTS: NPS was significantly associated with all-cause mortality, with each point increase corresponding to a 26 % increased risk (HR = 1.26, 95 % CI: 1.19-1.34). NPS demonstrated comparable predictive performance to FIB-4 and NFS, with further improvement when combined with either score (HRs of 2.03 and 2.11 for NPS + FIB-4 and NPS + NFS, respectively). PhenoAgeAccel mediated 31.5 % of the effect of NPS on mortality. CONCLUSIONS: This study found that NPS has the potential to be an independent, cost-effective, and reliable novel prognostic indicator for NAFLD that may complement existing tools and help improve risk stratification and management strategies for NAFLD, thereby preventing adverse outcomes.

The petroleum ether extracts of Chloranthus fortunei(A. Gray) Solms-Laub.with bioactivities: A rising source in HCC drug treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular Carcinoma (HCC) is an aggressive killer worldwide with high incidence and mortality. The herb Chloranthus fortunei (A. Gray) Solms-Laub is known as "Si Ji Feng" and is classified as a Feng-type medicine in classic Yao medicines. According to Yao's medical beliefs, Chloranthus fortunei has the functions of dispelling Feng, regulating qi, detoxifying, promoting blood circulation, etc. Folk uses its decoctions to treat stagnant liver conditions, such as liver abscesses, cirrhosis, hepatitis, and liver cancer. However, the bioactivity and mechanisms of Chloranthus fortunei extract against HCC have not been reported. AIM OF THE STUDY: To investigate the anti-HCC bioactivity and potential mechanism of the extract of Chloranthus fortunei (CFS). MATERIALS AND METHODS: Using 70% ethanol for reflux extraction of CFS resulted in the CFS ethanol extract, followed by sequential extractions with petroleum ether, chloroform, ethyl acetate, and n-butanol, yielding four fractions. The CCK-8 assay was utilized to examine the cytotoxic effects of 4 fractions on MHCC97-H and HepG2 cells, exploring the most effective component, namely petroleum ether extracts of CFS (PECFS). The major active ingredients of PECFS were identified using LC/MS technology, and the impact on cell proliferation and apoptosis in HCC cells was studied. The key genes and proteins in the pathway were validated using RT-PCR and Western blotting. BALB/c nude mice were chosen for tumor xenotransplantation and PECFS therapy. hinders the proliferation of HCC cells and promotes apoptosis. RESULTS: Among the four fractions, it was found that PECFS have the highest antiproliferative activity against MHCC97-H and HepG2 cells (IC50 = 13.86, 10.55 µg/mL), with sesquiterpene compounds being the primary active constituents. The antiproliferative activity of PECFS on HCC cells was linked to the inhibition of cell cloning, invasion, and metastasis abilities, as well as the arrest of the cell cycle at the G2/M phase. Additionally, exerts pro-apoptotic effects on HCC cells by upregulating the pro-apoptotic protein Bax, downregulating the anti-apoptotic protein Bcl-2, and activating the expression of the Caspase family. Moreover, protein and m-RNA expression data showed that PECFS inhibits HCC cell proliferation and promotes apoptosis by regulating the PI3K/AKT/mTOR pathway. Besides, after PECFS treatment, tumor growth in nude mice was suppressed. CONCLUSION: PECFS can inhibit the viability of HCC cells by acting on the PI3K/AKT/mTOR pathway, demonstrating anti-tumor potential. This study's findings suggest that PECFS may represent a promising source of novel agents for liver cancer treatment, providing scientific evidence for the traditional application of CFS in treating HCC.

PANI/GO and Sm co-modified Ti/PbO2 dimensionally stable anode for highly efficient amoxicillin degradation: Performance assessment, impact parameters and degradation mechanism.

The abuse and uncontrolled discharge of antibiotics present a severe threat to environment and human health, necessitating the development of efficient and sustainable treatment technology. In this work, we employ a facile one-step electrodeposition method to prepare polyaniline/graphite oxide (PANI/GO) and samarium (Sm) co-modified Ti/PbO2 (Ti/PbO2-PANI/GO-Sm) electrode for the degradation of amoxicillin (AMX). Compared with traditional Ti/PbO2 electrode, Ti/PbO2-PANI/GO-Sm electrode exhibits more excellent oxygen evolution potential (2.63 V) and longer service life (56 h). In degradation experiment, under optimized conditions (50 mg L-1 AMX, 20 mA cm-2, pH 3, 0.050 M Na2SO4, 25 °C), Ti/PbO2-PANI/GO-Sm electrode achieves remarkable removal efficiencies of 88.76% for AMX and 79.92% for chemical oxygen demand at 90 min. In addition, trapping experiment confirms that ·OH plays a major role in the degradation process. Based on theoretical calculation and liquid chromatography-mass spectrometer results, the heterocyclic portion of AMX molecule is more susceptible to ·OH attacks. Thus, this novel electrode offers a sustainable and efficient solution to address environmental challenges posed by antibiotic-contaminated wastewater.

FAP positive cancer-associated fibroblasts promote tumor progression and radioresistance in esophageal squamous cell carcinoma by transferring exosomal lncRNA AFAP1-AS1.

Cancer-associated fibroblasts (CAFs) are abundant and heterogeneous stromal cells in the tumor microenvironment, which play important roles in regulating tumor progression and therapy resistance by transferring exosomes to cancer cells. However, how CAFs modulate esophageal squamous cell carcinoma (ESCC) progression and radioresistance remains incompletely understood. The expression of fibroblast activation protein (FAP) in CAFs was evaluated by immunohistochemistry in 174 ESCC patients who underwent surgery and 78 pretreatment biopsy specimens of ESCC patients who underwent definitive chemoradiotherapy. We sorted CAFs according to FAP expression, and the conditioned medium (CM) was collected to culture ESCC cells. The expression levels of several lncRNAs that were considered to regulate ESCC progression and/or radioresistance were measured in exosomes derived from FAP+ CAFs and FAP- CAFs. Subsequently, cell counting kit-8, 5-ethynyl-2'-deoxyuridine, transwell, colony formation, and xenograft assays were performed to investigate the functional differences between FAP+ CAFs and FAP- CAFs. Finally, a series of in vitro and in vivo assays were used to evaluate the effect of AFAP1-AS1 on radiosensitivity of ESCC cells. FAP expression in stromal CAFs was positively correlated with nerve invasion, vascular invasion, depth of invasion, lymph node metastasis, lack of clinical complete response and poor survival. Culture of ESCC cells with CM/FAP+ CAFs significantly increased cancer proliferation, migration, invasion and radioresistance, compared with culture with CM/FAP- CAFs. Importantly, FAP+ CAFs exert their roles by directly transferring the functional lncRNA AFAP1-AS1 to ESCC cells via exosomes. Functional studies showed that AFAP1-AS1 promoted radioresistance by enhancing DNA damage repair in ESCC cells. Clinically, high levels of plasma AFAP1-AS1 correlated with poor responses to dCRT in ESCC patients. Our findings demonstrated that FAP+ CAFs promoted radioresistance in ESCC cells through transferring exosomal lncRNA AFAP1-AS1; and may be a potential therapeutic target for ESCC treatment.

Enantioselective Synthesis of the Active Sex Pheromone Components of the Female Lichen Moth, Lyclene dharma dharma, and Their Enantiomers.

The Lichen moth, Lyclene dharma dharma (Arctiidae, Lithosiinae), plays a significant role in forest ecosystem dynamics. A concise and novel method to synthesize the active sex pheromone components, (S)-14-methyloctadecan-2-one ((S)-1), (S)-6-methyloctadecan-2-one ((S)-2), and their enantiomers has been developed. Key steps in the synthesis include the use of Evans' chiral auxiliaries, Grignard cross-coupling reactions, hydroboration-oxidation, and Wacker oxidation. The synthesized sex pheromone components hold potential value for studies on communication mechanisms, species identification, and ecological management.

Potential marker genes for chronic obstructive pulmonary disease revealed based on single-cell sequencing and Mendelian randomization analysis.

BACKGROUND: Progress is being made in the prevention and treatment of chronic obstructive pulmonary disease (COPD), but it is still unsatisfactory. With the development of genetic technology, validated genetic information can better explain COPD. OBJECTIVE: The study utilized scRNA-seq and Mendelian randomization analysis of eQTLs to identify crucial genes and potential mechanistic pathways underlying COPD pathogenesis. MEHODS: Single-cell sequencing data were used to identify marker genes for immune cells in the COPD process. Data on eQTLs for immune cell marker genes were obtained from the eQTLGen consortium. To estimate the causal effect of marker genes on COPD, we selected an independent cohort (ukb-b-16751) derived from the UK Biobank database for two-sample Mendelian randomization analysis. Subsequently, we performed immune infiltration analysis, gene set enrichment analysis (GSEA), and co-expression network analysis on the key genes. RESULTS: The 154 immune cell-associated marker genes identified were mainly involved in pathways such as vacuolar cleavage, positive regulation of immune response and regulation of cell activation. Mendelian randomization analysis screened four pairs of marker genes (GZMH, COTL1, CSTA and CD14) were causally associated with COPD. These four key genes were significantly associated with immune cells. In addition, we have identified potential transcription factors associated with these key genes using the Cistrome database, thus contributing to a deeper understanding of the regulatory network of these gene expressions. CONCLUSIONS: This eQTLs Mendelian randomization study identified four key genes (GZMH, COTL1, CSTA, and CD14) causally associated with COPD, providing new insights for prevention and treatment of COPD.

The role of THBS1 and PDGFD in the immune microenvironment of Helicobacter pylori-associated gastric cancer.

BACKGROUND AND STUDY AIMS: Immunotherapy has emerged as a hot topic in cancer treatment in recent years and has also shown potential in the treatment of Helicobacter pylori-associated gastric cancer. However, there is still a need to identify potential immunotherapy targets. MATERIAL AND METHODS: We used the GSE116312 dataset of Helicobacter pylori-associated gastric cancer to identify differentially expressed genes, which were then overlapped with immune genes from the ImmPort database. The identified immune genes were used to classify gastric cancer samples and evaluate the relationship between classification and tumor mutations, as well as immune infiltration. An immune gene-based prognostic model was constructed, and the expression levels of the genes involved in constructing the model were explored in the tumor immune microenvironment. RESULTS: We successfully identified 60 immune genes and classified gastric cancer samples into two subtypes, which showed differences in prognosis, tumor mutations, immune checkpoint expression, and immune cell infiltration. Subsequently, we constructed an immune prognostic model consisting of THBS1 and PDGFD, which showed significant associations with macrophages and fibroblasts. CONCLUSION: We identified abnormal expression of THBS1 and PDGFD in cancer-associated fibroblasts (CAFs) within the tumor immune microenvironment, suggesting their potential as therapeutic targets.

A novel lncRNA associated with the prognosis of patients with colorectal cancer resists apoptosis through the LYN/BCL-2 pathway.

PURPOSE: We found a novel lncRNA named lncAC138150.2 related to the overall survival and staging of patients with colorectal cancer (CRC) by bioinformatic analysis using data from the Cancer Genome Atlas (TCGA), and the study aimed to elucidate the function of lncAC138150.2 and underlying mechanisms. METHODS: Target molecules were knocked down by transfection with antisense oligonucleotides (ASOs), siRNAs, or lentiviruses and overexpressed by transfection with plasmids. The function of lncAC138150.2 was determined using histological, cytological, and molecular biology methods. The underlying mechanism of lncAC138150.2 function was investigated using RNA-seq, bioinformatics analysis, and molecular biology methods. RESULTS: The expression of lncAC138150.2 was increased in colorectal tissues compared with paired normal tissues. The lncAC138150.2 knockdown increased apoptosis but did not change the cell proliferation, cell cycle distribution, or cell migration ability of CRC cells, while lncAC138150.2 overexpression decreased CRC apoptosis. lncAC138150.2 was mainly located in the cell nucleus, and each lncAC138150.2 transcript knockdown increased CRC apoptosis. BCL-2 pathway was significantly altered in apoptosis induced by lncAC138150.2 knockdown, which was alleviated by BAX knockdown. The expression of LYN was significantly decreased with lncAC138150.2 knockdown, LYN knockdown increased CRC apoptosis, and its overexpression completely alleviated CRC apoptosis induced by lncAC138150.2 knockdown. CONCLUSION: lncAC138150.2 significantly inhibited CRC apoptosis and affected the prognosis of patients with CRC, through the LYN/BCL-2 pathway.

Sucrose and Ca2+ synergistically regulate the rheological properties of apple high-methoxyl pectin.

The thickening and gelling mechanism of high-methoxyl pectins (HMPs) with different degree of esterification (DE) values (60.6 %, 66.1 %, and 72.4 %) synergistically affected by calcium ion (Ca2+) and sucrose was investigated using several technical methods. Rheological measurements, including steady-shear flow, thixotropy and dynamic viscoelasticity tests, texture analysis, water-holding capacity (WHC), thermal analyses (TG), and microstructure observation (TEM), were all systemically conducted. The results showed that the main thickening and gelling mechanism of Ca2+ on different HMPs was complex and the presence of sucrose had a synergistic effect on structure formation in HMP systems. Ca2+ was not always conducive to structure formation, and excessive Ca2+ addition may hinder structure formation. HMP systems with lower DE values had higher gel strengths due to the presence of more binding domains. The results of the texture properties, WHC, and thermal characteristics coincided with those obtained from the rheological measurements, which reflect the variations in HMPs affected by Ca2+ and DE. All of these results showed that Ca2+ addition at an appropriate concentration in the presence of sucrose favors HMP gelation even in the absence of acid. The results obtained here are expected to broaden the application of HMPs in acid-free gel food products.