Association between egg consumption and mortality risk in United States adults with established coronary heart disease or stroke: A cohort study using data from NHANES 1999-2018.

BACKGROUND: To investigate the relationship between egg consumption and mortality in individuals with pre-existing coronary heart disease or stroke. METHODS: This study utilized data from the National Health and Nutrition Examination Survey conducted between 1999 and 2018. Egg consumption was evaluated through 24 h dietary recalls at baseline. Mortality status was tracked until December 31, 2019. Survey-weighted Cox proportional hazards models were utilized. RESULTS: The study involved 3,975 participants aged 20 years or older with a median follow-up of 89.00 months. A total of 1,675 individuals died during follow-up. Compared to individuals who did not consume eggs, the consumption of 0-50 g/day (hazard ratio [HR] = 1.033, 95% confidence interval [CI] =0.878-1.214) was not found to have a significant association with all-cause mortality. However, consuming 50-100 g/day (HR = 1.281, 95% CI = 1.004-1.635) and >100 g/day (HR = 1.312, 95% CI =1.036-1.661) exhibited a significant association with an increased risk of all-cause mortality. We identified a non-liner relationship between egg consumption and cardiovascular mortality, where the risk was found to be lowest at an intake of about 50 g/day. For individuals consuming more than 50 g/day, each additional 50 g increment in egg consumption was significantly linked to an elevated risk of cardiovascular mortality (HR = 1.276, 95% CI = 1.009-1.614). CONCLUSION: In U.S. adults with pre-existing cardiovascular disease, a significant positive association was found between consuming over 50 g of eggs per day and the risk of mortality, highlighting the importance of moderate intake.

Celastrol mediates CAV1 to attenuate pro-tumorigenic effects of senescent cells.

BACKGROUND: Cellular senescence is an emerging hallmark of cancers, primarily fuels cancer progression by expressing senescence-associated secretory phenotype (SASP). Caveolin-1 (CAV1) is a key mediator of cell senescence. Previous studies from our group have evidenced that the expression of CAV1 is downregulated by Celastrol (CeT). PURPOSE: To investigate the impact of CeT on cellular senescence and its subsequent influence on post-senescence-driven invasion, migration, and stemness of clear cell renal cell carcinoma (ccRCC). STUDY DESIGN AND METHODS: The expression levels of CAV1, canonical senescence markers, and markers associated with epithelial-mesenchymal transition (EMT) and stemness in clinical samples were assessed through Pearson correlation analysis. Senescent cell models were induced using DOX, and their impact on migration, invasion, and stemness was evaluated. The effects of CeT treatment on senescent cells and their pro-tumorigenic effects were examined. Subsequently, the underlying mechanism of CeT were explored using lentivirus transfection and CRISPR/Cas9 technology to silence CAV1. RESULTS: In human ccRCC clinical samples, the expression of the canonical senescence markers p53, p21, and p16 are associated with ccRCC progression. Senescent cells facilitated migration, invasion, and enhanced stemness in both ccRCC cells and ccRCC tumor-bearing mice. As expected, CeT treatment reduced senescence markers (p16, p53, p21, SA-ß-gal) and SASP factors (IL6, IL8, CXCL12), alleviating cell cycle arrest. However, it did not restore the proliferation of senescent cells. Additionally, CeT suppressed senescence-driven migration, invasion, and stemness. Further investigations into the underlying mechanism demonstrated that CAV1 is a critical mediator of cell senescence and represents a potential target for CeT to attenuate cellular senescence. CONCLUSIONS: This study presents a pioneering investigation into the intricate interplay between cellular senescence and ccRCC progression. We unveil a novel mechanism of CeT to mitigate cellular senescence by downregulating CAV1, thereby inhibiting the migration, invasion and stemness of ccRCC driven by senescent cells. These findings provide valuable insights into the underlying mechanisms of CeT and its potential as a targeted therapeutic approach for alleviating the aggressive phenotypes associated with senescent cells in ccRCC.

Occurrence, Risk Implications, Prevention and Control of CIT in Monascus Cheese: A Review.

Monascus is a filamentous fungus that has been used in the food and pharmaceutical industries. When used as an auxiliary fermenting agent in the manufacturing of cheese, Monascus cheese is obtained. Citrinin (CIT) is a well-known hepatorenal toxin produced by Monascus that can harm the kidneys structurally and functionally and is frequently found in foods. However, CIT contamination in Monascus cheese is exacerbated by the metabolic ability of Monascus to product CIT, which is not lost during fermentation, and by the threat of contamination by Penicillium spp. that may be introduced during production and processing. Considering the safety of consumption and subsequent industrial development, the CIT contamination of Monascus cheese products needs to be addressed. This review aimed to examine its occurrence in Monascus cheese, risk implications, traditional control strategies, and new research advances in prevention and control to guide the application of biotechnology in the control of CIT contamination, providing more possibilities for the application of Monascus in the cheese industry.

Association between irritable bowel syndrome and Parkinson's disease by Cohort study and Mendelian randomization analysis.

This study aimed to investigate the association between irritable bowel syndrome (IBS) and Parkinson's disease (PD) utilizing prospective cohort study and Mendelian randomization. The dataset contained a substantial cohort of 426,911 participants from the UK Biobank, discussing the association between IBS and PD with Cox proportional hazards models and case-control analysis while adjusting for covariates such as age, gender, ethnicity and education level. In univariate Cox regression model, the risk of PD was reduced in IBS patients (HR: 0.774, 95%CI: 0.625-0.956, P = 0.017), but the statistical significance diminished in the three models after adjusting for other variables. In a few subgroup analyses, IBS patients are less likely to develop into PD, and patients diagnosed with IBS after 2000 also had a lower risk (HR: 0.633, 95%CI: 0.403-0.994, P = 0.047) of subsequently developing PD. In addition, we matched five healthy control participants based on gender and age at the end of the study for each IBS patient diagnosed during the follow-up period, and logistic regression results (OR:1.239, 95%CI: 0.896-1.680, P = 0.181) showed that IBS was not associated with the risk of PD. Mendelian randomization did not find significant evidence of the causal relationship between IBS and Parkinson's disease (OR: 0.801, 95%CI: 0.570-1.278, P = 0.204). Overall, we suggest that IBS status is not associated with the risk of developing PD, and that these findings provide valuable insights into the clinical management and resource allocation of patients with IBS.

Melatonin enhanced the cardioprotective effects of HTK solution on Langendorff-perfused mouse hearts subjected to ischemia/reperfusion.

Objectives: Cardiac arrest is a crucial procedure in various cardiac surgeries, during which the heart is subjected to an ischemic state. The occurrence of ischemia/reperfusion (I/R) injury is inevitable due to aortic blockage and opening. The Histidine-tryptophan-ketoglutarate (HTK) solution is commonly used as an organ protection liquid to mitigate cardiac injury during cardiac surgery. Despite its widespread use, there is significant potential for improving its protective efficacy. Materials and Methods: The cardioprotective effect of HTK solution with and without melatonin was evaluated using the isolated Langendorff-perfused mouse heart model. The isolated C57bL/6 mouse hearts were randomly divided into four groups: control, I/R, HTK solution treatment before reperfusion (HTK+I/R), and HTK solution combined with melatonin before reperfusion (HTK+M+I/R). Cardiac function and myocardial injury markers were then measured. AMP-activated protein kinase α2 (AMPKα2) KO mice were used to investigate the underlying mechanism. Results: In our study, we found that melatonin significantly improved the protective effects of HTK solution in an isolated Langendorff-perfused mouse model, mechanistically by reducing mitochondrial damage, improving energy metabolism, inhibiting cardiomyocyte apoptosis, and reducing myocardial infarction size. We also observed that the HTK solution alone was ineffective in inhibiting ER stress, but when melatonin was added, there was a significant reduction in ER stress. Furthermore, melatonin was found to alleviate carbonyl stress during cardiac I/R. Interestingly, our results showed that the cardioprotective properties of melatonin were dependent on AMPKα2. Conclusion: The findings presented in this study offer a valuable empirical foundation for the development of perioperative cardioprotective strategies.

LncRNA CHROMR/miR-27b-3p/MET axis promotes the proliferation, invasion, and contributes to rituximab resistance in diffuse large B-cell lymphoma.

Long non-coding RNAs (LncRNAs) could regulate chemoresistance through sponging microRNAs (miRNAs) and sequestering RNA binding proteins. However, the mechanism of lncRNAs in rituximab resistance in diffuse large B-cell lymphoma (DLBCL) is largely unknown. Here, we investigated the functions and molecular mechanisms of lncRNA CHROMR in DLBCL tumorigenesis and chemoresistance. LncRNA CHROMR is highly expressed in DLBCL tissues and cells. We examined the oncogenic functions of lncRNA CHROMR in DLBCL by a panel of gain-or-loss-of-function assays and in vitro experiments. LncRNA CHROMR suppression promotes CD20 transcription in DLBCL cells and inhibits rituximab resistance. RNA immunoprecipitation, RNA pull-down, and dual luciferase reporter assay reveal that lncRNA CHROMR sponges with miR-27b-3p to regulate mesenchymal-epithelial transition factor (MET) levels and Akt signaling in DLBCL cells. Targeting the lncRNA CHROMR/miR-27b-3p/MET axis reduces DLBCL tumorigenesis. Altogether, these findings provide a new regulatory model, lncRNA CHROMR/miR-27b-3p/MET, which can serve as a potential therapeutic target for DLBCL.

Impact of lifestyle and clinical factors on the prognosis of tennis elbow.

Tennis elbow (lateral epicondylitis) typically responds well to conservative treatment, and few patients require surgical intervention. This study aimed to investigate the influence of lifestyle and clinical factors on the prognosis of tennis elbow. This prospective, multicenter, nested case-control study included patients diagnosed with lateral epicondylitis after excluding other conditions. Patients who required surgery because of inadequate improvement after 6 months of conservative treatment were defined as the case group; the remaining patients constituted the control group. Propensity score matching was performed to eliminate baseline differences. Univariate and multivariate analyses were performed using logistic regression. This study included 265 patients (53 in the case group, 212 in the control group). Multivariate analysis revealed that smoking, alcohol consumption, and frequent physical exercise were independent risk factors for surgical intervention, whereas combined treatment with oral nonsteroidal anti-inflammatory drugs (NSAIDs) and local corticosteroid injections was a protective factor against surgery. Subgroup analysis showed that heavy drinkers had a 3.74-fold higher risk of requiring surgical treatment within 1 year than occasional drinkers. Smoking and alcohol consumption were associated with non-operative treatment failure in patients with lateral epicondylitis. Combining oral NSAIDs and corticosteroid injections is a favorable conservative treatment option.

The varied restorative values of campus landscapes to students' well-being: evidence from a Chinese University.

BACKGROUND: The literature on therapeutic landscapes highlights that the university campus landscape has restorative effects on students. This deserves more scholarly attention since mental health has become an important issue among university students. However, existing empirical studies have revealed mixed evidence with little attention to the heterogeneity across the design and, therefore, the potential therapeutic effects across different landscapes. METHOD: This research examined how 13 landscape sites on a university campus might be differentially related to student well-being. These sites were identified from a variety of sources (campus design documents, photos used in the university's social media posts, and interviews with a small group of students) to represent a comprehensive list of places that students might visit. The data was collected in a large online survey of a Chinese university (n = 2,528). We asked about students' use of individual landscape sites and the associated motivations for visits, and measured well-being using a perceived stress scale and overall evaluation of the happiness level. Bivariate analysis was used to explore the zero-order associations between landscape use and well-being. OLS (for stress) and logistic regressions (for happiness) were conducted to further evaluate the associations after controlling the student background variables and potential correlations of uses across different landscapes. RESULTS: Among 13 landscape sites, four sites had significant positive associations with either or both measures of well-being after controlling for the student characteristics and use of the other landscape sites. There was also an additive benefit of visiting more landscapes. Compared to those who did not frequently visit any of the sites, well-being had a significant stepwise increase among those who frequently visited one or two and more sites. One site that was significantly related to both measures of well-being only offered distant views of landscapes, but it was right next to the study areas. CONCLUSIONS: This study demonstrates the heterogeneity of restorative effects across different landscapes on campus. The findings suggest that effective landscape design that aims to promote student well-being should be placed close to stressors (i.e., where they study), and between where they study and live to offer students opportunities to break from the common routines and to relax. The findings hold greater relevance for universities in China and institutions with similar student campus lifestyles, occupancies, and behavior patterns worldwide.

Multiple machine-learning tools identifying prognostic biomarkers for acute Myeloid Leukemia.

BACKGROUND: Acute Myeloid Leukemia (AML) generally has a relatively low survival rate after treatment. There is an urgent need to find new biomarkers that may improve the survival prognosis of patients. Machine-learning tools are more and more widely used in the screening of biomarkers. METHODS: Least Absolute Shrinkage and Selection Operator (LASSO), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), Random Forest (RF), eXtreme Gradient Boosting (XGBoost), lrFuncs, IdaProfile, caretFuncs, and nbFuncs models were used to screen key genes closely associated with AML. Then, based on the Cancer Genome Atlas (TCGA), pan-cancer analysis was performed to determine the correlation between important genes and AML or other cancers. Finally, the diagnostic value of important genes for AML was verified in different data sets. RESULTS: The survival analysis results of the training set showed 26 genes with survival differences. After the intersection of the results of each machine learning method, DNM1, MEIS1, and SUSD3 were selected as key genes for subsequent analysis. The results of the pan-cancer analysis showed that MEIS1 and DNM1 were significantly highly expressed in AML; MEIS1 and SUSD3 are potential risk factors for the prognosis of AML, and DNM1 is a potential protective factor. Three key genes were significantly associated with AML immune subtypes and multiple immune checkpoints in AML. The results of the verification analysis show that DNM1, MEIS1, and SUSD3 have potential diagnostic value for AML. CONCLUSION: Multiple machine learning methods identified DNM1, MEIS1, and SUSD3 can be regarded as prognostic biomarkers for AML.

Effects of UV-B radiation on pollen germination and tube growth: A global meta-analysis.

Despite widespread recognition of pollen's potential sensitivity to ultraviolet-B (UV-B) radiation (280-315 nm), there remains ongoing debate surrounding the extent and mechanisms of this effect. In this study, using published data on pollen germination and tube growth including 377 pair-wise comparisons from 77 species in 30 families, we present the first global quantification of the effects of UV-B radiation on pollen germination and tube growth, along with its underlying mechanisms. Our results showed a substantial reduction in both pollen germination and tube growth in response to UV-B radiation, affecting 90.9 % and 84.2 % of species, respectively. Notably, these reductions exhibited phylogenetic constraints, highlighting the role of evolutionary history in shaping the sensitivity of pollen germination and tube growth to UV-B radiation. A negative correlation between elevation and the sensitivity of pollen tube growth was detected, suggesting that pollens from plants at higher elevations exhibit greater resistance to UV-B radiation. Our investigation also revealed that the effects of UV-B radiation on pollen germination and tube growth were influenced by a range of abiotic and biotic factors. Nevertheless, the intensity and duration of UV-B radiation exposure exhibited the highest explanatory power for the effects on both pollen germination and tube growth. This suggests that the responses of pollens to UV-B radiation are profoundly influenced by its dose, a critical consideration within the context of global change. In conclusion, our study provides valuable insights into the diverse responses of pollen germination and tube growth to UV-B radiation, highlighting the environment and species-dependent nature of pollen's susceptibility to UV-B radiation, with substantial implications for our understanding of the ecological and agricultural consequences of ongoing changes in UV-B radiation.

Myocardial Metabolic Reprogramming in HFpEF.

Heart failure (HF) caused by structural or functional cardiac abnormalities is a significant cause of morbidity and mortality worldwide. While HF with reduced ejection fraction (HErEF) is well understood, more than half of patients have HF with preserved ejection fraction (HFpEF). Currently, the treatment for HFpEF primarily focuses on symptom alleviation, lacking specific drugs. The stressed heart undergoes metabolic switches in substrate preference, which is a compensatory process involved in cardiac pathological remodeling. Although metabolic reprogramming in HF has gained attention in recent years, its role in HFpEF still requires further elucidation. In this review, we present a summary of cardiac mitochondrial dysfunction and cardiac metabolic reprogramming in HFpEF. Additionally, we emphasize potential therapeutic approaches that target metabolic reprogramming for the treatment of HFpEF.

Influence of myoglobin on the antibacterial activity of carvacrol and the binding mechanism between the two compounds.

BACKGROUND: Myoglobin (MB), a pigmentation protein, can adversely affect the antibacterial activity of carvacrol (CAR) and weaken its bacteriostasis effect. This study aimed to clarify the influence of MB on the antibacterial activity of CAR and ascertain the mechanism involved in the observed influence, especially the interaction between the two compounds. RESULTS: Microbiological analysis indicated that the presence of MB significantly suppressed the antibacterial activity of CAR against Listeria monocytogenes. Ultraviolet-visible spectrometry and fluorescence spectroscopic analysis confirmed the interaction between CAR and MB. The stoichiometric number was determined as ~0.7 via double logarithmic Stern-Volmer equation analysis, while thermodynamic analysis showed that the conjugation of the two compounds occurred as an exothermal reaction (ΔH° = -32.3 ± 11.4 kJ mol-1 and ΔS° = -75 J mol-1 K-1 ). Circular dichroism, Fourier transform infrared spectroscopy and nuclear magnetic resonance spectroscopy showed hydrogen bonding in the carvacrol-myoglobin complex (CAR-MB). Molecular docking analysis confirmed that amino acid residues, including GLY80 and HIS82, were most likely to form hydrogen bonds with CAR, while hydrogen bonds represented the main driving force for CAR-MB formation. CONCLUSION: CAR antibacterial activity was significantly inhibited by the presence of MB in the environment due to the notable reduction in the effective concentration of CAR caused by CAR-MB formation. © 2023 Society of Chemical Industry.

ULK1 confers neuroprotection by regulating microglial/macrophages activation after ischemic stroke.

Microglial activation and autophagy play a critical role in the progression of ischemic stroke and contribute to the regulation of neuroinflammation. Unc-51-like kinase 1 (ULK1) is the primary autophagy kinase involved in autophagosome formation. However, the impact of ULK1 on neuroprotection and microglial activation after ischemic stroke remains unclear. In this study, we established a photothrombotic stroke model, and administered SBI-0206965 (SBI), an ULK1 inhibitor, and LYN-1604 hydrochloride (LYN), an ULK1 agonist, to modulate ULK1 activity in vivo. We assessed sensorimotor deficits, neuronal apoptosis, and microglial/macrophage activation to evaluate the neurofunctional outcome. Immunofluorescence results revealed ULK1 was primarily localized in the microglia of the infarct area following ischemia. Upregulating ULK1 through LYN treatment significantly reduced infarct volume, improved motor function, promoted the increase of anti-inflammatory microglia. In conclusion, ULK1 facilitated neuronal repair and promoted the formation of anti-inflammatory microglia pathway after ischemic injury.

EEG Power Spectral Density in NREM Sleep is Associated with the Degree of Hypoxia in Patients with Obstructive Sleep Apnea.

Purpose: Obstructive sleep apnea (OSA) is a prevalent sleep-related breathing disorder. Research conducted on patients with OSA using electroencephalography (EEG) has revealed a noticeable shift in the overnight polysomnography (PSG) power spectrum. To better quantify the effects of OSA on brain function and to identify the most reliable predictors of pathological cortical activation, this study quantified the PSG power and its association with the degree of hypoxia in OSA patients. Patients and Methods: This retrospective study recruited 93 patients with OSA. OSA patients were divided into three groups based on their apnea-hypopnea index (AHI) scores. The clinical characteristics and sleep macrostructure of these patients were examined, followed by an analysis of PSG signals. Power spectral density (PSD) in five frequency bands was analyzed during nonrapid eye movement (NREM) sleep, rapid eye movement (REM) sleep, and wakefulness. Finally, correlation analysis was conducted to assess the relationships among PSD, PSG parameters, and serum levels of S100ß and uric acid. Results: Obstructive sleep apnea occurred during both the NREM and REM sleep phases. Except for a decrease in the duration of N2 sleep and an increase in the microarousal index, there were no significant differences in sleep architecture based on disease severity. Compared to the mild OSA group, the theta and alpha band PSD in the frontal and occipital regions during NREM sleep and wakefulness were significantly decreased in the moderate and severe OSA groups. Correlation analysis revealed that theta PSD in N1 and N3 stages were negatively correlated the AHI, oxygen desaturation index, SaO2<90% and microarousal index. Conclusion: These findings imply that patients with more severe OSA exhibited considerable NREM hypoxia and abnormal brain activity in the frontal and occipital regions. Therefore, sleep EEG oscillation may be a useful neurophysiological indicator for assessing brain function and disease severity in patients with OSA.

Integrative Analysis of PAIP2B to Identify a Novel Biomarker for Pancreatic Ductal Adenocarcinoma.

The aim of the study was to evaluate the potential diagnostic and prognostic value of gene, Poly A-Binding Protein Interacting Protein 2B ( PAIP2B ) in pancreatic cancer. We used the gene expression data and clinical information of pancreatic adenocarcinoma patients from The Cancer Genome Atlas database and Gene Expression Omnibus database to analyze the expression of PAIP2B in pancreatic cancer samples, and validated the expression of PAIP2B in tumor tissue, using bioinformatics technology to explore the prognostic value of PAIP2B and its possible biological function. A significantly lower level of PAIP2B was observed in pancreatic cancer patients than in controls, and validated by immunohistochemistry. PAIP2B reduced the proliferation and invasion of cancer cells and had a significantly high expression in early stage. Patients with lower levels of PAIP2B had a significantly shorter median survival time than those with higher levels. DNA demethylation played an important role in PAIP2B expression. In addition, PAIP2B expression was significantly associated with the tumor-infiltrating immune cells, especially T cells CD8, T cells CD4 memory resting, macrophages M0, and dendritic cells resting. Our study also found that PAIP2B regulated miRNA function leading to disease progression in pancreatic cancer patients. Our study explored the potential value of PAIP2B as a biological link between prognosis and pancreatic cancer, and provided reference for the follow-up study on the role of PAIP2B in pancreatic cancer.

Shared Genetic Architecture between Parkinson's Disease and Brain Structural Phenotypes.

BACKGROUND: Patients with Parkinson's disease (PD) have consistently demonstrated brain structure abnormalities, indicating the presence of shared etiological and pathological processes between PD and brain structures; however, the genetic relationship remains poorly understood. OBJECTIVE: The aim of this study was to investigate the extent of shared genetic architecture between PD and brain structural phenotypes (BSPs) and to identify shared genomic loci. METHODS: We used the summary statistics from genome-wide association studies to conduct MiXeR and conditional/conjunctional false discovery rate analyses to investigate the shared genetic signatures between PD and BSPs. Subsequent expression quantitative trait loci mapping in the human brain and enrichment analyses were also performed. RESULTS: MiXeR analysis identified genetic overlap between PD and various BSPs, including total cortical surface area, average cortical thickness, and specific brain volumetric structures. Further analysis using conditional false discovery rate (FDR) identified 21 novel PD risk loci on associations with BSPs at conditional FDR < 0.01, and the conjunctional FDR analysis demonstrated that PD shared several genomic loci with certain BSPs at conjunctional FDR < 0.05. Among the shared loci, 16 credible mapped genes showed high expression in the brain tissues and were primarily associated with immune function-related biological processes. CONCLUSIONS: We confirmed the polygenic overlap with mixed directions of allelic effects between PD and BSPs and identified multiple shared genomic loci and risk genes, which are likely related to immune-related biological processes. These findings provide insight into the complex genetic architecture associated with PD. © 2023 International Parkinson and Movement Disorder Society.

Targeting B4GALT7 suppresses the proliferation, migration and invasion of hepatocellular carcinoma through the Cdc2/CyclinB1 and miR-338-3p/MMP2 pathway.

Background: As a three-dimensional network involving glycosaminoglycans (GAGs), proteoglycans (PGs) and other glycoproteins, the role of extracellular matrix (ECM) in tumorigenesis is well revealed. Abnormal glycosylation in liver cancer is correlated with tumorigenesis and chemoresistance. However, the role of galactosyltransferase in HCC (hepatocellular carcinoma) is largely unknown. Methods: Here, the oncogenic functions of B4GALT7 (beta-1,4-galactosyltransferase 7) were identified in HCC by a panel of in vitro experiments, including MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide), colony formation, transwell and flow cytometry assay. The expression of B4GALT7 in HCC cell lines and tissues were examined by qPCR (real-time quantitative polymerase chain reaction) and western blot assay. The binding between B4GALT7 and miR-338-3p was examined by dual-luciferase reporter assay. Results: B4GALT7 encodes galactosyltransferase I and it is highly expressed in HCC cells and human HCC tissues compared with para-tumor specimens. MiR-338-3p was identified to bind the 3' UTR (untranslated region) of B4GALT7. Highly expressed miR-338-3p suppressed HCC cell invasive abilities and rescued the tumor-promoting effect of B4GALT7 in HCC. ShRNA (short hairpin RNA) mediated B4GALT7 suppression reduced HCC cell invasive abilities, and inhibited the expression of MMP-2 and Erk signaling. Conclusion: These findings identified B4GALT7 as a potential prognostic biomarker and therapeutic target for HCC.

Expression of EGFR-mutant proteins and genomic evolution in EGFR-mutant transformed small cell lung cancer.

Background: The transformation of epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma (LUAD) into small cell lung cancer (SCLC) accounts for 3-14% of the resistance mechanism to EGFR tyrosine kinase inhibitors (TKIs). At present, there is no relevant research to explore the dynamic expression of EGFR-mutant proteins and genomic evolution in EGFR-mutant transformed SCLC/neuroendocrine carcinoma (NEC). Methods: Genetic analysis and protein level analysis by next-generation sequencing (NGS), Whole-exome sequencing (WES) and immunohistochemistry were performed to explore expression of EGFR-mutant proteins and genomic evolution in EGFR-mutant transformed SCLC. The research used three patient-derived organoids (PDOs) to explore the efficacy of combo [chemotherapy (chemo) plus TKI or bevacizumab] treatment. According to the subsequent treatment regimens after SCLC/NEC transformation, 35 patients were divided into chemo (n=21) and combo (n=14) groups. Results: EGFR L858R and EGFR E746-750 del protein expression by immunohistochemistry was 80.0% (4/5) and 100% (6/6), respectively (P=0.455) in initially-transformed tissues. Meanwhile, EGFR-mutant proteins were expressed in 85.7% (6/7) of dynamic rebiopsy tissues or effusion samples after the first transformation. Then, by the pathway enrichment analysis of tissue and plasma NGS, the EGFR-related pathways were still activated after SCLC/NEC transformation. Moreover, WES analysis revealed that transformed SCLC shared a common clonal origin from the baseline LUAD. The drug sensitivity of three PDOs demonstrated potent anti-cancer activity of EGFR-TKIs plus chemo, compared with chemo or TKI alone. There were significant differences in objective response rate (ORR) between the combo and chemo groups [42.9 % vs. 4.8%, P=0.010, 95% confidence interval (CI): 1.5-145.2]. Furthermore, the median post-transformation progression-free survival (pPFS) was significantly prolonged in the combo group, with 5.4 (95% CI: 3.4-7.4) versus 3.5 (95% CI: 2.7-4.3, P=0.012) months. Conclusions: EGFR 19del or L858R-mutant proteins could be constantly expressed, and EGFR pathway still existed in EGFR-mutant transformed SCLC/NEC with a common clonal origin from the baseline LUAD. Taking together, these molecular characteristics potentially favored clinical efficacy in transformed SCLC/NEC treated with the combo regimen.

The role of the Gas6/TAM signal pathway in the LPS-induced pulmonary epithelial cells injury.

BACKGROUND: Acute lung injury (ALI) is an acute inflammatory respiratory disease. The interaction between growth arrest-specific 6 (Gas6) and tyrosine kinases of the Tyro3, Axl, Mer (TAM) family plays an important role in a variety of physiological and pathological processes, including inflammation. In this study, we mainly clarified the mechanism of the Gas6/TAM signal pathway in lipopolysaccharide (LPS)-induced pulmonary epithelial cells (BEAS-2B cells) injury. METHODS: We cultured BEAS-2B cells in vitro and established a LPS-induced BEAS-2B cells injury model. Then, the siRNA sequence (siGas6-2) was transfected into cells. The expression of Gas6/TAM was measured based on quantitative reverse transcription polymerase chain reaction (qRT-RCR) and western blot (WB). Cell proliferation and apoptosis were measured by cell counting Kit-8 (CCK-8) and flow cytometry. The expression of pro-inflammatory factors was measured by qRT-RCR and WB. RESULTS: Our study showed that when the 40 µg/mL LPS-induced BEAS-2B cells injury model was established, cell viability was significantly reduced, but the Gas6/TAM signal pathway was activated. When transfection with siGas6-2, low expression of Gas6 directly reduced the expression of downstream TAM receptors. Furthermore, the inhibition of the Gas6/TAM signal pathway significantly reduced the occurrence of cell apoptosis and the expression of inflammatory factors, and promoted cell proliferation. CONCLUSION: Our research indicated that Gas6/TAM played an important role in cell proliferation, apoptosis, and inflammatory response in the LPS-induced BEAS-2B cells injury, and Gas6/TAM may be a new target in the treatment of ALI in the future.

Parasedimentitalea psychrophila sp. nov., a psychrophilic bacterium isolated from deep-sea sediment.

A novel bacterium, strain QS115T, was isolated from deep-sea sediment collected from the South China Sea at a depth of 1151 m. Phylogenetic analyses based on 16S rRNA gene sequences indicated that QS115T was most closely related to Parasedimentitalea marina W43T, with similarity of 98.21 %. Strain QS115T shared 82.39 % average nucleotide identity, 26.3 % digital DNA-DNA hybridization and 85.32 % average amino acid identity with P. marina W43T. Cells of strain QS115T were Gram-stain-negative, rod-shaped and grew optimally at 10 °C, pH 7.5 and 2 % (w/v) NaCl. The principal fatty acids were summed feature 8 (C18 : 1 ω7c/ω6c), the major respiratory quinone was ubiquinone-10 and predominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, glycophospholipid, phosphatidylglycerol and phosphatidylcholine. Polyphasic analyses of physiological and phenotypic characteristics and genomic studies suggested that strain QS115T represents a novel species of the genus Parasedimentitalea, for which the name Parasedimentitalea psychrophila sp. nov. is proposed (type strain QS115T=MCCC 1K04395T=JCM 34219T).