Proteome-Wide Multicenter Mendelian Randomization Analysis to Identify Novel Therapeutic Targets for Lung Cancer.

INTRODUCTION: Lung cancer (LC) remains a leading cause of cancer mortality worldwide, underscoring the urgent need for novel therapeutic targets. The integration of Mendelian randomization (MR) with proteomic data presents a novel approach to identifying potential targets for LC treatment. METHODS: This study utilized a proteome-wide MR analysis, leveraging publicly available data from genome-wide association studies (GWAS) and protein quantitative trait loci (pQTL) studies. We analyzed genetic association data for LC from the TRICL-ILCCO Consortium and proteomic data from the Decode cohort. The MR framework was employed to estimate the causal effects of specific proteins on LC risk, supplemented by external validation, co-localization analyses, and exploration of protein-protein interaction (PPI) networks. RESULTS: Our analysis identified five proteins (TFPI, ICAM5, SFTPB, COL6A3, EPHB1) with significant associations to LC risk. External validation confirmed the potential therapeutic relevance of ICAM5 and SFTPB. Co-localization analyses and PPI network exploration provided further insights into the biological pathways involved and their potential mechanistic roles in LC pathogenesis. CONCLUSION: The study highlights the power of integrating genomic and proteomic data through MR analysis to uncover novel therapeutic targets for lung cancer. The identified proteins, particularly ICAM5 and SFTPB, offer promising directions for future research and development of targeted therapies, demonstrating the potential to advance personalized medicine in lung cancer treatment.

Association Between Social Determinants of Health and Receiving Timely Dental Treatment With General Anesthesia.

Purpose: To describe social determinants of health (SDOH) in a group of children with special health care needs (CSHCN) planned for dental procedures with general anesthesia (GA) at a pediatric hospital and explore associations between SDOH and completing this treatment in the recommended timeframe. Methods: SDOH were recorded for all patients planned for dental treatment with GA in 2019. Outcomes were treatment completed in the recommended timeframe or treatment not completed within two years of planning. Results: Dental surgery plans were made for 390 CSHCN: 190 were completed in the recommended timeframe, and 119 were not completed within two years. The SDOH associated with completing/not completing surgery were parents (guardian/caregiver)/household, and documentation of social work involvement with the family. Patients receiving optimally timed surgery more frequently had two parents/one household and/or an active social work plan on the record. Those not receiving surgery frequently had two parents/two households, single parents, and/or had no social work plan. Ethnicity, payer, and the need for an interpreter were not associated with receiving timely surgery. Conclusions: Multiple studies have found that social determinants of health contribute to disparate health outcomes. In this study, children with two parents in one household appear to be advantaged in receiving care in the recommended timeframe. Families with SDOH challenges who had a social work plan were frequently able to overcome SDOH barriers and receive dental treatment with general anesthesia in the timeframe recommended.

A Sustainable and Cost-Effective Nitrogen-Doped Three-Dimensional Porous Carbon for High-Performance Lithium-Sulfur Batteries.

Affordable clean energy is one of the major sustainable development goals that can transform our world. At present, researchers are working to develop cheap electrode materials to develop energy storage devices, the Lithium-sulfur (Li-S) battery is considered a promising energy storage device owing to its excellent theoretical specific capacity and energy density. Herein, utilizing the ramie degumming waste liquid as raw materials, after freeze-drying and high-temperature calcination, a sustainable and cost-effective three-dimensional (3D) porous nitrogen-doped ramie carbon (N-RC) was synthesized. The N-RC calcined at 800 °C (N-RC-800) shows a superior high specific surface area of 1491.85 m2·g-1 and a notable high pore volume of 0.90 cm3·g-1. When employed as a sulfur host, the S@N-RC-800 cathode illustrates excellent initial discharge capacity (1120.6 mAh·g-1) and maintains a reversible capacity of 625.4 mAh·g-1 after 500 cycles at 1 C. Simultaneously, the S@N-RC-800 cathode also shows excellent coulombic efficiency and ideal rate performance. Such exceptional electrochemical performance of S@N-RC-800 can be primarily attributable to N-RC's high specific surface area, high porosity, and abundant polar functional groups. This green and low-cost synthesis strategy offers a new avenue for harnessing the potential of waste biomass in the context of clean energy storage.

Qizhu Anticancer Prescription enhances immunosurveillance of liver cancer cells by regulating p21-dependent secretory phenotypes.

ETHNOPHARMACOLOGICAL RELEVANCE: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide, and this is largely attributed to the limitations of available therapeutic strategies. The traditional Chinese medicine Qizhu Anticancer Prescription (QZACP) can improve the quality of life and prolong the survival time of patients with HCC. However, the precise mechanisms underlying the anti-cancer properties of QZACP remain unclear. PURPOSE: This study examined the anti-hepatocarcinogenic properties of QZACP, with a specific focus on its influence on p21-activated secretory phenotype (PASP)-mediated immune surveillance, to elucidate the underlying molecular pathways involved in HCC. MATERIALS AND METHODS: Cell proliferation was measured using the Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and clonogenic assays. The cell cycle was evaluated using flow cytometry, and senescence was identified by staining with senescence-associated beta-galactosidase (SA-ß-gal). A primary liver cancer model produced by diethylnitrosamine was established in C57B/L6 mice to assess the tumor-inhibitory effect of QZACP. The liver's pathological characteristics were examined using hematoxylin and eosin staining. PASP screening was performed using GeneCards, DisGeNet, Online Mendelian Inheritance in Man, and The Cancer Genome Atlas databases. Western blot analysis, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and Transwell migration assays were performed. RESULTS: QZACP-containing serum enhanced p21 expression, triggered cell cycle arrest, accelerated cell senescence, and suppressed cell proliferation in Huh7 and MHCC-97H liver cancer cells. QZACP reduced the quantity and dimensions of liver tumor nodules and enhanced p21 protein expression, SA-ß-Gal staining in tumor lesions, and cytotoxic CD8+ T cell infiltration. Bioinformatic analyses showed that PASP factors, including hepatocyte growth factor, decorin (DCN), dermatopontin, C-X-C motif chemokine ligand 14 (CXCL14), and Wnt family member 2 (WNT2), play an important role in the development of HCC. In addition, these factors are associated with the presence of natural killer cells and CD8+ T cells within tumors. Western blotting and ELISA confirmed that QZACP increased DCN, CXCL14, and WNT2 levels in tumor tissues and peripheral blood. CONCLUSIONS: QZACP suppression of HCC progression may involve cell senescence mediated by P21 upregulation, DCN, CXCL14, and WNT2 secretion, and reversal of the immunosuppressive microenvironment. This study provides insights that can be used in the development of new treatment strategies for HCC.

Insights into dynamic evolution of glucuronofucogalactoglucan from water extract of Agrocybe cylindracea during maturation.

This study explored the physicochemical properties and structural characteristics of Agrocybe cylindracea polysaccharides at four developmental stages, as well as their dynamic evolution during maturation. Results showed that the polysaccharides from A. cylindracea water extract exhibited similar structural characteristics across all four maturity stages, despite a significant reduction in yields. Four water-soluble heteroglycans, including one high molecular weight (ACPM-Et50-I) and three low molecular weight (ACPM-Et50-II, ACPM-Et60, ACPM-Et80), were isolated from A. cylindracea at each maturity stage. ACPM-Et50-I was identified as branched heterogalactans, while ACPM-Et60 and ACPM-Et80 were branched heteroglucans. However, ACPM-Et50-II was characterized as a branched glucuronofucogalactoglucan at the tide-turning stage but a glucuronofucoglucogalactan at the pileus expansion stage due to the increase of its α-(1 â†’ 6)-D-Galp. In general, although the structural skeletons of most A. cylindracea heteroglycans were similar during maturation as shown by their highly consistent glycosyl linkages, there were still differences in the distribution of some heteroglucans. This work has for the first time reported a glucuronofucogalactoglucan in A. cylindracea and its dynamic evolution during maturation, which may facilitate the potential application of A. cylindracea in food and biomedicine industries.

The impact of hyperkalemia on ICU admission and mortality: a retrospective study of Chinese emergency department data.

OBJECTIVE: This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room. METHODS: This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated. RESULTS: 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline. CONCLUSION: Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.

Effects of cold acclimation on serum biochemical parameters and metabolite profiles in Schizothorax prenanti.

BACKGROUND: Environmental temperature is critical in regulating biological functions in fish. S. prenanti is a kind of cold-water fish, but of which we have little knowledge about the metabolic adaptation and physiological responses to long-term cold acclimation. RESULTS: In this study, we determined the physiological responses of S. prenanti serum after 30 days of exposure to 6℃. Compared with the control group, the levels of TC, TG, and LDL-C in the serum were significantly (P < 0.05) increased, and the level of glucose was significantly (P < 0.05) decreased under cold acclimation. Cold acclimation had no effect on the gene expression of pro-inflammatory factors and anti-inflammatory factors of S. prenanti. Metabolomics analysis by LC-MS showed that a total of 60 differential expressed metabolites were identified after cold acclimation, which involved in biosynthesis of amino acids, biosynthesis of unsaturated fatty acids, steroid degradation, purine metabolism, and citrate cycle pathways. CONCLUSION: The results indicate that cold acclimation can alter serum metabolites and metabolic pathways to alter energy metabolism and provide insights for the physiological regulation of cold-water fish in response to cold acclimation.

Deep learning in the diagnosis for cystic lesions of the jaws: a review of recent progress.

Cystic lesions of the gnathic bones present challenges in differential diagnosis. In recent years, artificial intelligence (AI) represented by deep learning (DL) has rapidly developed and emerged in the field of dental and maxillofacial radiology (DMFR) Dental radiography provides a rich resource for the study of diagnostic analysis methods for cystic lesions of the jaws and has attracted many researchers. The aim of the current study was to investigate the diagnostic performance of DL for cystic lesions of the jaws. Online searches on Google Scholar, PubMed, and IEEE Xplore databases, up to September 2023, with subsequent manual screening for confirmation. The initial search yielded 1862 titles, and 44 studies were ultimately included. All studies used DL methods or tools for the identification of a variable number of maxillofacial cysts. The performance of algorithms with different models varies. Although most of the reviewed stu dies demonstrated that DL methods have better discriminative performance than clinicians, further development is still needed before routine clinical implementation due to several challenges and limitations such as lack of model interpretability, multicenter data validation, etc Considering the current limitations and challenges, future studies for the differential diagnosis of cystic lesions of the jaws should follow actual clinical diagnostic scenarios to coordinate study design and enhance the impact of artificial intelligence in the diagnosis of oral and maxillofacial diseases.

Efficacy and Safety of Semaglutide in Weight Loss of Non-diabetic People.

OBJECTIVE: The study aimed to investigate the efficacy and safety of semaglutide in weight loss in non-diabetic people. METHODS: In this study, 84 non-diabetic people who used semaglutide to lose weight in the outpatient department of our hospital from January 1, 2022, to June 30, 2022, were enrolled and compared for changes in body weight, waist circumference, Body Mass Index (BMI), fasting blood glucose, blood pressure, pulse, and body composition (body fat ratio, visceral fat area, and skeletal muscle) before treatment and 12 weeks after the treatment to analyze the weight loss efficacy and safety. RESULTS: After administering semaglutide 0.25 mg, 0.5 mg, 0.75 mg, or 1 mg subcutaneously once a week for 12 weeks, 84 participants in this study obtained an average weight loss of 5.91 ± 3.37 kg, equivalent to 6.15 ± 4.28% of baseline body weight, and there was also a significant reduction in visceral fat area and a slight reduction in blood pressure. The most common adverse reactions included gastrointestinal reactions (nausea, vomiting, and diarrhea), which were mild and subsided within 1-2 days. No severe adverse reaction, such as hypoglycemia and hypotension, was observed. CONCLUSION: Low-dose semaglutide has been found to be effective and safe for short-term weight loss in non-diabetic people.

Analysis of risk factors, pathogenic bacteria characteristics, and drug resistance of postoperative surgical site infection in adults with limb fractures.

PURPOSE: We carried out the study aiming to explore and analyze the risk factors, the distribution of pathogenic bacteria, and their antibiotic-resistance characteristics influencing the occurrence of surgical site infection (SSI), to provide valuable assistance for reducing the incidence of SSI after traumatic fracture surgery. METHODS: A retrospective case-control study enrolling 3978 participants from January 2015 to December 2019 receiving surgical treatment for traumatic fractures was conducted at Tangdu Hospital of Air Force Medical University. Baseline data, demographic characteristics, lifestyles, variables related to surgical treatment, and pathogen culture were harvested and analyzed. Univariate analyses and multivariate logistic regression analyses were used to reveal the independent risk factors of SSI. A bacterial distribution histogram and drug-sensitive heat map were drawn to describe the pathogenic characteristics. RESULTS: Included 3978 patients 138 of them developed SSI with an incidence rate of 3.47% postoperatively. By logistic regression analysis, we found that variables such as gender (males) (odds ratio (OR) = 2.012, 95% confidence interval (CI): 1.235 - 3.278, p = 0.005), diabetes mellitus (OR = 5.848, 95% CI: 3.513 - 9.736, p < 0.001), hypoproteinemia (OR = 3.400, 95% CI: 1.280 - 9.031, p = 0.014), underlying disease (OR = 5.398, 95% CI: 2.343 - 12.438, p < 0.001), hormonotherapy (OR = 11.718, 95% CI: 6.269 - 21.903, p < 0.001), open fracture (OR = 29.377, 95% CI: 9.944 - 86.784, p < 0.001), and intraoperative transfusion (OR = 2.664, 95% CI: 1.572 - 4.515, p < 0.001) were independent risk factors for SSI, while, aged over 59 years (OR = 0.132, 95% CI: 0.059 - 0.296, p < 0.001), prophylactic antibiotics use (OR = 0.082, 95% CI: 0.042 - 0.164, p < 0.001) and vacuum sealing drainage use (OR = 0.036, 95% CI: 0.010 - 0.129, p < 0.001) were protective factors. Pathogens results showed that 301 strains of 38 species of bacteria were harvested, among which 178 (59.1%) strains were Gram-positive bacteria, and 123 (40.9%) strains were Gram-negative bacteria. Staphylococcus aureus (108, 60.7%) and Enterobacter cloacae (38, 30.9%) accounted for the largest proportion. The susceptibility of Gram-positive bacteria to Vancomycin and Linezolid was almost 100%. The susceptibility of Gram-negative bacteria to Imipenem, Amikacin, and Meropenem exceeded 73%. CONCLUSION: Orthopedic surgeons need to develop appropriate surgical plans based on the risk factors and protective factors associated with postoperative SSI to reduce its occurrence. Meanwhile, it is recommended to strengthen blood glucose control in the early stage of admission and for surgeons to be cautious and scientific when choosing antibiotic therapy in clinical practice.

Complete telomere-to-telomere genomes uncover virulence evolution conferred by chromosome fusion in oomycete plant pathogens.

Variations in chromosome number are occasionally observed among oomycetes, a group that includes many plant pathogens, but the emergence of such variations and their effects on genome and virulence evolution remain ambiguous. We generated complete telomere-to-telomere genome assemblies for Phytophthora sojae, Globisporangium ultimum, Pythium oligandrum, and G. spinosum. Reconstructing the karyotype of the most recent common ancestor in Peronosporales revealed that frequent chromosome fusion and fission drove changes in chromosome number. Centromeres enriched with Copia-like transposons may contribute to chromosome fusion and fission events. Chromosome fusion facilitated the emergence of pathogenicity genes and their adaptive evolution. Effectors tended to duplicate in the sub-telomere regions of fused chromosomes, which exhibited evolutionary features distinct to the non-fused chromosomes. By integrating ancestral genomic dynamics and structural predictions, we have identified secreted Ankyrin repeat-containing proteins (ANKs) as a novel class of effectors in P. sojae. Phylogenetic analysis and experiments further revealed that ANK is a specifically expanded effector family in oomycetes. These results revealed chromosome dynamics in oomycete plant pathogens, and provided novel insights into karyotype and effector evolution.

Hispidin Increases Cell Apoptosis and Ferroptosis in Prostate Cancer Cells Through Phosphatidylinositol-3-Kinase and Mitogen-activated Protein Kinase Signaling Pathway.

BACKGROUND/AIM: Chemotherapy is mainly used in the clinical treatment of prostate cancer. Different anticancer mechanisms can induce cell death in various cancers. Reactive oxygen species (ROS) play crucial roles in cell proliferation, differentiation, apoptosis, and signal transduction. It is widely accepted that ROS accumulation is closely related to chemical drug-induced cancer cell death. MATERIALS AND METHODS: We utilized the MTT assay to detect changes in cell proliferation. Additionally, colony formation and wound healing assay were conducted to investigate the effect of hispidin on cell colony formation and migration ability. Fluorescence microscopy was used to detect intracellular and mitochondrial ROS levels, while western blot was used for detection of cell apoptosis. RESULTS: Hispidin treatment significantly decreased viability of PC3 and DU145 cancer cells but exhibited no cytotoxicity in WPMY-1 cells. Furthermore, hispidin treatment inhibited cell migration and colony formation and triggered cellular and mitochondrial ROS accumulation, leading to mitochondrial dysfunction and mitochondrion-dependent apoptosis. Moreover, hispidin treatment induced ferroptosis in PC3 cells. Scavenging of ROS with N-acetyl cysteine significantly inhibited hispidin-induced apoptosis by altering the expression of apoptosis-related proteins, such as cleaved caspase-3, 9, Bax, and Bcl2. Furthermore, hispidin treatment dramatically up-regulated MAPK (involving p38, ERK, and JNK proteins) and NF-kB signaling pathways while down-regulating AKT phosphorylation. Hispidin treatment also inhibited ferroptosis signaling pathways (involving P53, Nrf-2, and HO-1 proteins) in PC3 cells. In addition, inhibiting these signaling pathways via treatment with specific inhibitors significantly reversed hispidin-induced apoptosis, cellular ROS levels, mitochondrial dysfunction, and ferroptosis. CONCLUSION: Hispidin may represent a potential candidate for treating prostate cancer.

The association among thriving in life, quality of life, and suicidal ideation in Chinese urban older adults: the moderating effects of attitude toward own aging.

BACKGROUND: As the global trend of population aging intensifies, the health and well-being of the older population has gradually become a focus of attention for the global community. This study assessed the status of thriving in life among Chinese urban older adults and identified its relationship with attitude toward own aging and quality of life (QoL). It also tested whether attitude toward own aging moderates the association between thriving in life and Qol or between thriving in life and suicidal ideation. METHODS: Primary data were collected through a cross-sectional survey among urban older adults from three provinces in China. They were invited to complete an anonymous survey using face-to-face interviews from December 2019 to January 2020. Data from 764 older adults were analyzed. RESULTS: Approximately 44.39% of participants reported positive responses toward the four domains of thriving in life. Thriving in life and attitude toward own aging had a significant association with QoL. Thriving in life was a protective factor for suicidal ideation for older adults. Moreover, attitude toward own aging moderated the association between thriving in life and QoL and that between thriving in life and suicidal ideation. CONCLUSIONS: Chinese urban older adults were reportedly thriving in life, which contributed to increased QoL and reduced suicidal ideation. Notably, the study revealed that more positive attitudes towards own aging were associated with higher levels of thriving in life, better QoL, and reduced suicidal ideation. Targeted interventions for older adults should be devised to promote thriving in life and prevent negative attitudes of older people towards their own aging, further raising QoL and reducing suicidal ideation.

Identification and validation of a novel apoptosis-related prognostic risk score model for lung adenocarcinoma.

The prognostic roles of apoptosis-related genes (ARGs) in lung adenocarcinoma (LUAD) have not been fully elucidated. In this study, differentially expressed genes (DEGs) associated with apoptosis and the hub genes were further identified. The prognostic values of the ARGs were evaluated using the LASSO Cox regression method. Prognostic values were determined using Kaplan-Meier (K-M) curves and receiver operating characteristic (ROC) curves in the TCGA and GEO datasets. The correlations, mutation data, and protein expression of the 10 ARGs predictive models were also analyzed. We identified 130 differentially expressed ARGs. DEGs were used to split LUAD cases into two subtypes whose overall survival (OS) were significantly different (P = 0.025). We developed a novel 10-gene signature using LASSO Cox regression. In both TCGA and GEO datasets, the results of the K-M curve and log-rank test showed significant difference in the survival rate of patients in the high-risk group and low-risk group (P < 0.0001). According to the GO and KEGG analyses, ARGs were enriched in cancer-related terms. In both cohorts, the immune status of the high-risk group was significantly lower than that of the low-risk group. Based on the differential expression of the ARGs, we established a new risk model to predict the prognosis of patients with LUAD.

Trends and disparities in the prevalence of physical activity among US adults with epilepsy, 2010-2022.

BACKGROUND: Physical activity may be associated with health benefits for people with epilepsy. It remains unclear how the prevalence of physical activity has changed at a national level over the years and whether this prevalence varies between subgroups. METHODS: The National Health and Interview Survey, which was conducted from 2010 to 2017 and again in 2022, was used for our nationally representative study. This study explored the trends and disparities in meeting physical activity guidelines among US individuals with epilepsy and non-epilepsy adults. RESULTS: The prevalence of adults with epilepsy meeting physical activity guidelines was consistently lower and remained unchanged compared to those without epilepsy. Among the population with epilepsy, the prevalence of aerobic physical activity was 38.1 % (95 % CI, 32.6 %-43.5 %) in 2010 and 39.0 % (95 % CI, 33.4 %-44.7 %) in 2017 (P for trend = 0.84), and remained unchanged in 2022 (39.1 %). For muscle-strength training, the prevalence was 17.5 % (95 % CI, 13.3 %-21.7 %) in 2010 and 18.8 % (95 % CI, 14.8 %-22.8 %) in 2017 (P for trend = 0.82). The prevalence for both activities combined was 12.4 % (95 % CI, 8.7 %-16.2 %) in 2010 and 16.6 % (95 % CI, 12.8 %-20.5 %) in 2017 (P for trend = 0.26). The prevalence of aerobic physical activity varied by educational attainment, body mass index, comorbid conditions, alcohol-drinking status, and epilepsy status. CONCLUSION: This study suggests that the adherence rate to meeting physical activity guidelines among US adults with epilepsy was at a low level and had not improved over time. This finding highlights the need for additional nationwide efforts to promote physical activity in the US population with epilepsy.

DUSP8-attenuated ERK1/2 signaling mediates lipogenesis and steroidogenesis in chicken granulosa cells.

The lipogenesis and steroidogenesis of granulosa cells are crucial during follicular development, yet it remains unclear whether dual-specificity phosphatase 8 (DUSP8) is involved. In this study, the specific role of DUSP8 in lipogenesis and steroidogenesis was investigated through culturing chicken granulosa cells in vitro. The results revealed that the expression levels of adipogenic genes were elevated after DUSP8 overexpression and reduced after knockdown. The same was observed for lipid deposition in granulosa cells. Meanwhile, the steroidogenic gene expression and progesterone synthesis were promoted after DUSP8 overexpression and inhibited after knockdown. In addition, we also found that DUSP8 blocked the phosphorylation of extracellular regulatory kinase 1/2 (ERK1/2). Based on the previous results that activated ERK1/2 signaling inhibited lipid deposition and progesterone synthesis in chicken granulosa cells, we demonstrated that DUSP8 promoted lipid deposition and progesterone synthesis through mediating the ERK1/2 signaling pathway. The results will improve our understanding of the molecular regulatory mechanisms regarding lipid metabolism and progesterone synthesis in chicken granulosa cells.

Elucidation of the anti-gastric cancer mechanism of Guiqi Baizhu Formula by integrative approach of chemical bioinformatics.

Gastric cancer (GC) has posed a great threat to the lives of people around the world. To date, safer and more cost-effective therapy for GC is lacking. Traditional Chinese medicine (TCM) may provide some new options for this. Guiqi Baizhu Formula (GQBZF), a classic TCM formula, has been extensively used to treat GC, while its bioactive components and therapeutic mechanisms remain unclear. In this study, we evaluated the underlying mechanisms of GQBZF in treating GC by integrative approach of chemical bioinformatics. GQBZF lyophilized powder (0.0625 mg/mL, 0.125 mg/mL) significantly attenuated the expression of p-IGF1R, PI3K, p-PDK1, p-VEGFR2 to inhibit the proliferation, migration and induce apoptosis of gastric cancer cells, which was consistent with the network pharmacology. Additionally, atractylenolide Ⅰ, quercetin, glycyrol, physcione and aloe-emodin, emodin, kaempferol, licoflavone A were found to be the key compounds of GQBZF regulating IGF1R and VEGFR2, respectively. And among which, glycyrol and emodin were determined as key active compounds against GC by farther vitro experiments and LC/MS. Meanwhile, we also found that glycyrol inhibited MKN-45 cells proliferation and enhanced apoptosis, which might be related to the inhibition of IGF1R/PI3K/PDK1, and emodin could significantly attenuate the MKN-45 cells migration, which might be related to the inhibition of VEGFR2-related signaling pathway. These results were verified again by molecular dynamics simulation and binding interaction pattern. In summary, this study suggested that GQBZF and its key active components (glycyrol and emodin) can suppress IGF1R/PI3K/PDK1 and VEGFR2-related signaling pathway, thereby inhibiting tumor cell proliferation and migration and inducing apoptosis. These findings provided an important strategy for developing new agents and facilitated clinical use of GQBZF against GC.

Eco-friendly high-throughput screening of cephalosporins impurities: Utilizing 2D-carbon microfiber fractionation system combined with quadrupole time of flight high-resolution mass spectrometer.

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Moxifloxacin Promotes Two-photon Microscopic Imaging for Discriminating Different Stages of DSS-induced Colitis on Mice.

BACKGROUND: Accurate diagnosis of patients with ulcerative colitis (UC) can reduce their risk of developing colorectal cancer. This study intended to explore whether moxifloxacin, an agent with fluorescence potential, could promote two-photon microscopy (TPM) diagnosis for mice with dextran sodium sulfate (DSS)-induced colitis, which could imitate human UC. METHODS: 32 Balb/c mice were randomly divided into 4 groups: control, acute colitis, remission colitis and chronic colitis. Fluorescence parameters, imaging performance, and tissue features of different mouse models were compared under moxifloxacin-assisted TPM and label-free TPM. RESULTS: Excitation wavelength of 720 nm and moxifloxacin labeling time of 2 min was optimal for moxifloxacin-assisted TPM. With moxifloxacin labeling for colonic tissues, excitation power was decreased to 1/10 of that without labeling while fluorescence intensity was increased to 10-fold of that without labeling. Photobleaching was negligible after moxifloxacin labeling and moxifloxacin fluorescence kept stable within 2 hours. Compared with the control group, moxifloxacin fluorescence was reduced in the three colitis groups (P<0.05). Meanwhile, the proportion of enhanced moxifloxacin fluorescence regions was (22.4±1.6)%, (7.7±1.0)%, (13.5±1.7)% and (5.0±1.3)% in the control, acute, remission and chronic groups respectively, with significant reduction in the three colitis groups (P<0.05). Besides, variant tissue features of experimental colitis models were presented under moxifloxacin-assisted TPM, such as crypt opening, glandular structure, adjacent glandular space and moxifloxacin distribution. CONCLUSIONS: With unique biological interaction between moxifloxacin and colonic mucosa, moxifloxacin-assisted TPM imaging is feasible and effective for accurate diagnosis of different stages of experimental colitis.

Epstein-Barr virus causes vascular abnormalities in epithelial malignancies through upregulating ANXA3-HIF-1α-VEGF pathway.

Angiogenesis is one of the characteristics of malignant tumors, and persistent generation of abnormal tumor blood vessels is an important factor contributing to tumor treatment resistance. Epstein-Barr virus (EBV) is a highly prevalent DNA oncogenic virus that is associated with the development of various epithelial malignancies. However, the relationship between EBV infection and tumor vascular abnormalities as well as its underlying mechanisms is still unclear. In this study, we found that compared to EBV-uninfected tumors, EBV-infected tumors were more angiogenic, but the neovascularization was mostly immature vessels without pericyte attachment in both clinical patient tumor samples and mouse xenograft models; These immature vessels exhibited aberrant functionality, characterized by poor blood perfusion and increased vascular permeability. The vascular abnormalities caused by EBV infection exacerbated tumor hypoxia and was responsible for accelerated tumor growth. Mechanistically, EBV infection upregulated ANXA3-HIF-1α-VEGF pathway. Silencing the ANXA3 gene or neutralizing ANXA3 with an antibody can diminish vascular abnormalities, thereby increasing immune cell infiltration and alleviating treatment resistance. Finally, a new therapy combining ANXA3 blockade and NK cell + PD1 antibody significantly inhibited the growth of EBV-infected xenografts in mice. In conclusion, our study identified a previously unrecognized role for EBV infection in tumor vascular abnormalities and revealed its underlying mechanism that upregulated the ANXA3-HIF-1α-VEGF pathway. ANXA3 is a potential therapeutic target for EBV-infected tumors and ANXA3 blockade to improve vascular conditions, in combination with NK cell + PD1 antibody therapy, holds promise as an effective treatment strategy for EBV-associated epithelial malignancies.