Association of HBeAg decline rate from mid-pregnancy to delivery with HBeAg seroconversion after delivery in hepatitis B virus-infected mothers.

There is still controversy about whether to continue antiviral therapy (AVT) after delivery, especially for pregnant women in the immune tolerance (IT) phase. In this study, a retrospective cohort study was conducted to explore the relationship between hepatitis B e antigen (HBeAg) decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum among patients using nucleos(t)ide analogs (NAs) to prevent mother-to-child transmission (MTCT), with the goal of identifying the ideal candidates for postpartum AVT continuation. This retrospective cohort study included 151 postpartum women. Univariate and multivariable logistic regression analyses were conducted to assess the association between the HBeAg decline rate (%) from mid-pregnancy to delivery and HBeAg seroconversion postpartum. Receiver operating characteristic (ROC) analysis was utilized to evaluate the predictive capacity of the HBeAg decline rate (%) and determine the optimal cut-off point. The univariate analysis revealed a significant association between the HBeAg decline rate (%) and HBeAg seroconversion postpartum (OR 1.068, 95% CI: 1.034-1.103, p < .001). In the multivariate regression analysis, adjusting for age, hepatitis B surface antigen (HBsAg) titre (log10 IU/mL) at mid-pregnancy, HBeAg titre (log10 S/CO) at mid-pregnancy, and hepatitis B virus (HBV) DNA load decline rate (%) from mid-pregnancy to delivery, the HBeAg decline rate(%) remained significantly associated with HBeAg seroconversion postpartum (OR 1.050, 95% CI: 1.015-1.093, p = .009). Then HBeAg decline rate (%) was treated as a categorical variable (tertiles) for sensitivity analysis. In the three distinct models, taking Tertile1 as a reference, women in Tertile3 still had a 4.201-fold (OR 4.201, 95% CI: 1.382-12.773, p = .011) higher risk of developing HBeAg seroconversion (p for trend <.05) after adjusting above covariates. The area under the curve (AUC) was 0.723 (95% CI: 0.627-0.819). The optimal cut-off value was 5.43%, with a sensitivity of 0.561, specificity of 0.791, and Youden's index of 0.352.A higher HBeAg decline rate (%) from mid-pregnancy to delivery independently correlated with an increased risk of HBeAg seroconversion postpartum. This decline rate can serve as a valuable clinical indicator for predicting HBeAg seroconversion.

Preliminary efficacy and safety of YSCH-01 in patients with advanced solid tumors: an investigator-initiated trial.

OBJECTIVE: To evaluate the safety and preliminary efficacy of YSCH-01 (Recombinant L-IFN adenovirus) in subjects with advanced solid tumors. METHODS: In this single-center, open-label, investigator-initiated trial of YSCH-01, 14 patients with advanced solid tumors were enrolled. The study consisted of two distinct phases: (1) the dose escalation phase and (2) the dose expansion phase; with three dose groups in the dose escalation phase based on dose levels (5.0×109 viral particles (VP)/subject, 5.0×1010 VP/subject, and 5.0×1011 VP/subject). Subjects were administered YSCH-01 injection via intratumoral injections. The safety was assessed using National Cancer Institute Common Terminology Criteria for Adverse Events V.5.0, and the efficacy evaluation was performed using Response Evaluation Criteria in Solid Tumor V.1.1. RESULTS: 14 subjects were enrolled in the study, including 9 subjects in the dose escalation phase and 5 subjects in the dose expansion phase. Of the 13 subjects included in the full analysis set, 4 (30.8%) were men and 9 (69.2%) were women. The most common tumor type was lung cancer (38.5%, 5 subjects), followed by breast cancer (23.1%, 3 subjects) and melanoma (23.1%, 3 subjects). During the dose escalation phase, no subject experienced dose-limiting toxicities. The content of recombinant L-IFN adenovirus genome and recombinant L-IFN protein in blood showed no trend of significant intergroup changes. No significant change was observed in interleukin-6 and interferon-gamma. For 11 subjects evaluated for efficacy, the overall response rate with its 95% CI was 27.3% (6.02% to 60.97%) and the disease control rate with its 95% CI was 81.8% (48.22% to 97.72%). The median progression-free survival was 4.97 months, and the median overall survival was 8.62 months. In addition, a tendency of decrease in the sum of the diameters of target lesions was observed. For 13 subjects evaluated for safety, the overall incidence of adverse events (AEs) was 92.3%, the overall incidence of adverse drug reactions (ADRs) was 84.6%, and the overall incidence of >Grade 3 AEs was 7.7%, while no AEs/ADRs leading to death occurred. The most common AEs were fever (69.2%), nausea (30.8%), vomiting (30.8%), and hypophagia (23.1%). CONCLUSIONS: The study shows that YSCH-01 injections were safe and well tolerated and exhibited preliminary efficacy in patients with advanced solid tumors, supporting further investigation to evaluate its efficacy and safety. TRIAL REGISTRATION NUMBER: NCT05180851.

Exploring the potential of ume-derived proanthocyanidins: novel applications for blueberry preservation.

Proanthocyanidins (PCs) extracted from ume have many well-known functional properties. The aim of this study was to explore a novel natural food preservative using ume plum pulp proanthocyanidins (UPPP). The crude product of PCs from ume plum was obtained by using ethanol as extraction solvent and ultrasonic-assisted extraction, and then the pure product of UPPP was obtained by purification with AB-8 resin. The bacteriostatic ability of UPPP and the freshness preservation effect on blueberry were analyzed. The results showed that UPPP had a high inhibitory effect on Staphylococcus aureus (MIC of 1.563 mg/mL) and Escherichia coli (MIC of 3.125 mg/mL). Findings revealed that, in comparison to 0.02% potassium sorbate, blueberries treated with a high concentration of UPPP in a dipping treatment displayed superior quality maintenance after 7 days of storage at 4°C. Importantly, analysis of the various metrics showed that treatment with UPPP was significantly better compared to blueberries treated with 0.02% potassium sorbate. For example, the decay rate, weight loss, and total number of colonies of blueberries treated with 0.02% potassium sorbate were 55.56, 3.48%, and 4.24 ± 0.07 log CFU/mL, whereas the values of the above indexes for blueberries treated with 25 mg/mL of UPPP were 22.22, 3.09%, and 3.10 ± 0.17 log CFU/mL, respectively. Conversely, blueberries that were not dipped in any preservative displayed signs of deterioration as early as the 3rd day of the storage period, highlighting the potential of UPPP as a valuable method for preserving fruits and vegetables. Therefore, UPPP holds great promise as an innovative natural food preservative, effectively enhancing food safety, quality, and extending shelf-life.

Development and evaluation of a Chinese herbal gel for analgesic and anti-inflammatory effects.

This study aimed to develop a film-forming gel containing three Chinese herbal extracts, an extracted mixture of Corydalis yanhusuo, Cynanchum paniculatum and Armadillidium vulgare (Latreille) (MCCA) and evaluate its analgesic and anti-inflammatory activities. Using the Box Behnken Design, the optimal prescription for the MCCA gel was determined. The analgesic effects were tested through acid writhing and formalin pain models. while the rheumatoid arthritis model assessed the pain and anti-inflammatory effects. For the evaluation of the effect of MCCA gels on pro-inflammatory cytokines, as well, Elisa was used. Results showed that the MCCA Gel with 2% mint oil had the highest transdermal volume of 32.57±0.92µg/cm2. High doses of MCCA gel were effective in suppressing pain, with a pain inhibition rate of 54.37% during the acetic acid peristaltic test that showed pronounced inhibition in the second phase of the formalin-induced analgesia test. In the rheumatoid arthritis model, the MCCA gel reduced inflammation scores in rat feet and decreased the expressions of four inflammatory factors in serum. Generally, The MCCA gel exhibits noticeable pain-relieving and anti-inflammatory properties with high penetration with the skin.

SFPQ promotes the proliferation, migration and invasion of hepatocellular carcinoma cells and is associated with poor prognosis.

Liver cancer is a prevalent type of tumor worldwide. CRISPR-Cas9 technology can be utilized to identify therapeutic targets for novel therapeutic approaches. In this study, our goal was to identify key genes related to the survival of hepatocellular carcinoma (HCC) cells by analyzing the DepMap database based on CRISPR-Cas9. We screened candidate genes associated with HCC cell survival and proliferation from DepMap and identified their expression levels in HCC from the TCGA database. To develop a prognostic risk model based on these candidate genes, we performed WGCNA, functional pathway enrichment analysis, protein interaction network construction, and LASSO analysis. Our findings show that 692 genes were critical for HCC cell proliferation and survival, and among them, 571 DEGs were identified in HCC tissues. WGCNA categorized these 584 genes into three modules, and the blue module consisting of 135 genes was positively linked to the tumor stage. Using the MCODE approach in Cytoscape, we identified ten hub genes in the PPI network, and through Cox univariate analysis and Lasso analysis, we developed a prognostic model consisting of three genes (SFPQ, SSRP1, and KPNB1). Furthermore, knocking down SFPQ inhibited HCC cell proliferation, migration, and invasion. In conclusion, we identified three core genes (SFPQ, SSRP1, and KPNB1) that are essential for the proliferation and survival of HCC cells. These genes were used to develop a prognostic risk model, and knockdown of SFPQ was found to inhibit the proliferation, migration, and invasion of HCC cells.

Valproic acid increases CAR T cell cytotoxicity against acute myeloid leukemia.

The treatment of B cell malignancies has dramatically changed with the introduction of immunotherapy, especially chimeric antigen receptor T (CAR-T) cell therapy. However, only limited efficacy is observed in acute myeloid leukaemia (AML). In the study, We detected CD123 and CLL-1 expression on leukaemia cells from Relapsed/Refractory AML (R/R AML) patients. Then, we constructed anti-CD123 CAR and CLL-1 CAR with different co-stimulation domains (CD28 or 4-1BB) and detected their anti-AML effects. To increase the efficacy of CAR-T cell therapy, we tested different strategies, including application of combined checkpoint inhibitors and histone deacetylase inhibitors (HDACi) in vivo and in vitro We found CD123 and CLL-1 were highly expressed on AML cells. The proportions of T cell subsets and NK cells involved in anti-tumour or anti-inflammation processes in AML patients significantly decreased when compared with healthy donors. Both CD123 CAR and CLL-1 CAR displayed specific anti-AML effects in vitro To improve the lysis effects of CAR-T cells, we combined CAR-T cell therapy with different agents. PD-1/PD-L1 antibodies only slightly improved the potency of CAR-T cell therapy (CD123 CAR-T 60.92% ± 2.9087% vs. 65.43% ± 2.1893%, 60.92% ± 2.9087% vs. 67.43% ± 3.4973%; 37.37% ± 3.908% vs. 41.89% ± 5.1568%, 37.37% ± 3.908% vs. 42.84% ± 4.2635%). However, one HDACi (valproic acid [VPA]) significantly improved CAR-T cell potency against AML cells (CLL-1 CAR-T 34.97% ± 0.3051% vs. 88.167% ± 1.5327%, p < 0.0001; CD123 CAR-T 26.87% ± 2.7010% vs. 82.56% ± 3.086%, p < 0.0001 in MV411; CLL-1 CAR-T 78.77% ± 1.2061% vs. 93.743% ± 1.2333%, p < 0.0001; CD123 CAR-T 64.10% ± 1.5130% vs. 94.427% ± 0.142%, p = 0.0001 in THP-1). Combination therapy prolonged the overall survival of mice when compared with single CD123 CAR-T cell therapy (median survival: 180 days vs. unfollowed). A possible mechanism is that activated CD8+T cells upregulate natural-killer group 2 member D (NKG2D), and VPA upregulates NKG2D ligand expression in AML cells, contributing to NKG2D-mediated cytotoxicity of CAR-T cells against tumour cells. In conclusion, CD123 and CLL-1 are promising targets for AML CAR-T cell therapy. A combination of VPA pre-treatment and CAR-T against AML exhibits synergic effects.

Cardiovascular involvement in Epstein-Barr virus infection.

Cardiovascular involvement is an uncommon but severe complication of Epstein-Barr virus (EBV) infection caused by direct damage and immune injury. Recently, it has drawn increasing attention due to its dismal prognosis. It can manifest in various ways, including coronary artery dilation (CAD), coronary artery aneurysm (CAA), myocarditis, arrhythmias, and heart failure, among others. If not treated promptly, cardiovascular damage can progress over time and even lead to death, which poses a challenge to clinicians. Early diagnosis and treatment can improve the prognosis and reduce mortality. However, there is a lack of reliable large-scale data and evidence-based guidance for the management of cardiovascular damage. Consequently, in this review, we attempt to synthesize the present knowledge of cardiovascular damage associated with EBV and to provide an overview of the pathogenesis, classification, treatment, and prognosis, which may enhance the recognition of cardiovascular complications related to EBV and may be valuable to their clinical management.

Development of a food preservative from sea buckthorn together with chitosan: Application in and characterization of fresh-cut lettuce storage.

The purpose was to create a novel composite food preservative for fresh-cut lettuce using flavonoids and chitosan from sea buckthorn leaves (SBL). Sea buckthorn leaves were extracted with ethanol as the extraction solvent and ultrasonic-assisted extraction to obtain flavonoid from sea buckthorn leaf crude (FSL), and then the FSL was secondarily purified with AB-8 resin and polyamide resin to obtain flavonoid from sea buckthorn leaf purified (FSL-1). Different concentrations of FSL-1 and chitosan were made into a composite preservative (FCCP) by magnetic stirring and other methods, containing 1% chitosan preservative (CP) alone, 0.5-2 mg/ml of FSL-1 and 1% chitosan composite preservative (FCCP-1, FCCP-2, FCCP-3, and FCCP-4), and the FSL-1 concentrations were analyzed the effect of FSL-1 concentration on the physicochemical properties of the composite preservatives, including their film-forming ability, antioxidant capacity and ability to prevent bacterial growth, was analyzed. To further investigate the effect of the combined preservatives on fresh-cut lettuce, different FCCPs were applied to the surface was stored at 4°C for 7 days. Then the changes in weight loss, hardness, browning index, total chlorophyll content, SOD and MDA were analyzed. It was used to assess the physicochemical indicators of fresh-cut lettuce throughout storage. According to the results of Fourier transform infrared spectroscopy, FSL-1 and chitosan interacted to form hydrogen bonds, and the contact angle and viscosity of FCCP increased on both horizontal glass and polystyrene plates, indicating the good film-forming properties of the composite preservation solution. With the diameter of the antibacterial zone of Staphylococcus aureus, Escherichia coli, Salmonella typhimurium, and Listeria monocytogenes being (21.39 ± 0.22), (17.43 ± 0.24), (15.30 ± 0.12), and (14.43 ± 0.24) mm, respectively. It was proved that the antibacterial activity of FCCP became stronger with the increase of FSL-1 concentration and had the best antibacterial effect on S. aureus. The complex preservative showed the best scavenging effect on ferric reducing antioxidant capacity, DPPH radicals (96.64%) and 2,2'-Azinobis- (3-ethylbenzthiazoline-6-sulphonate) (ABTS) radicals (99.42%) when FSL-1 was added at 2 mg/ml. When fresh-cut lettuce was coated with FCCP for the same storage time, various indicators of lettuce such as weight loss, hardness, browning index, SOD activity and MDA content were better than the control group showing good potential in fresh-cut vegetables and fruits preservation. FCCP holds great promise for food safety quality and shelf-life extension as a new natural food preservative. The waste utilization of sea buckthorn leaves can greatly improve his utilization and economic benefits.

Preparation and characterization of geraniol nanoemulsions and its antibacterial activity.

Geraniol nanoemulsions (G-NE) based on Tween 80 and medium chain triglyceride (MCT) as surfactant and co-surfactant, respectively, has been prepared by the spontaneous emulsification method. Its physical and chemical properties such as mean particle size, zeta potential, PDI, pH, viscosity, contact angle, appearance morphology, and stability (storage stability, thermal stability, centrifugal properties, acid-base stability, and freeze-thaw properties) of the droplet were analyzed. The results showed that the mean particle size of G-NE was 90.33 ± 5.23 nm, the PDI was 0.058 ± 0.0007, the zeta potential was -17.95 ± 5.85 mV and the encapsulation efficiency was >90%. The produced G-NE has been demonstrated to be fairly stable in long-term storage at 4°C, pH = 5 and high-speed centrifuges. Moreover, G-NE had a significant inhibition effect on Staphylococcus aureus, Escherichia coli, Salmonella typhimurium and Listeria monocytogenes (p < 0.05). The bacterial inhibition rates of G-NE at a concentration of 1 MIC were 48, 99, 71.73, and 99% after 12 h of action against these four foodborne pathogenic bacteria, respectively. Therefore, the results obtained indicated that nanoemulsification enhanced the stability and antibacterial activity of geraniol to some extent, which will promote the utilization of geraniol in food preservation.

Cellular Antioxidant Properties of Ischnoderma Resinosum Polysaccharide.

A predominant polysaccharide isolated from Ischnoderma resinosum underwent evaluation for its capacity to scavenge free radicals and its potential antioxidant properties at a cellular-oriented level. This proved that Ischnoderma resinosum polysaccharide (IRP) remarkably curtailed AAPH-induced erythrocyte hemolysis through the inhibition of the generation of ROS (p < 0.05). Rather, it caused the restoration of intracellular antioxidant enzyme (SOD, GSH-Px, and CAT) activities at an acceptable pace and the silencing of intracellular MDA formation, as well as the rescaling of LDH leakage. Furthermore, a model of oxidative stress in HepG2 cells was established by adopting 400 µM of hydrogen peroxide, which suggested that IRP manifests promising antioxidant activity. Notably, after the intervention of IRP in the H2O2-induced HepG2 cells, there was a statistical elevation in cell survivability (p < 0.05). IRP diminished the morphological alterations in the nucleus and decreased the secretion of ROS (p < 0.05), with a dose-dependent abrogation of apoptosis (p < 0.05). Consequently, IRP, which was isolated and purified, was able to scavenge free radicals and possessed favorable antioxidant activity that could dampen the occurrence of oxidative stimulation and effectively alleviate the AAPH-induced erythrocyte hemolysis and H2O2-induced oxidative damage in HepG2 cells. This provides a basis and theoretical reference for the development and utilization of IRP as a natural antioxidant, with emphasis on the exploitation of environmentally friendly and cost-effective antioxidants.

Low FNDC5/Irisin expression is associated with aggressive phenotypes in gastric cancer.

Background: FNDC5 belongs to the family of proteins called fibronectin type III domain-containing which carry out a variety of functions. The expression of FNDC5 is associated with the occurrence and development of tumors. However, the role of FNDC5 in gastric cancer remains relatively unknown. Methods: In the research, the expression of FNDC5 and its value for the prognosis of gastric cancer patients were observed with the TCGA database and GEO datasets of gastric cancer patients. The role of FNDC5 in the regulation of gastric cancer cells proliferation, invasion, and migration was determined. WGCNA and Enrichment analysis was performed on genes co-expressed with FNDC5 to identify potential FNDC5-related signaling pathways. Meanwhile, the LASSO Cox regression analysis based on FNDC5-related genes develops a risk score to predict the survival of gastric cancer patients. Results: The expression of FNDC5 was decreased in gastric cancer tissues compared to normal gastric tissues. However, survival analysis indicated that lower FNDC5 mRNA levels were associated with better overall survival and disease-free survival in gastric cancer patients. Meanwhile, a significant negative correlation was found between FNDC5 and the abundance of CD4+ memory T cells in gastric cancer. In vitro overexpression of FNDC5 inhibits the migration and invasion of gastric cancer cells, without affecting proliferation. Finally, A two-gene risk score module based on FNDC5 co-expressed gene was built to predict the overall clinical ending of patients. Conclusion: FNDC5 is low expressed in gastric cancer and low FNDC5 predicts a better prognosis. The better prognosis of low FNDC5 expression may be attributed to the increased number of CD4+ memory activated T-cell infiltration in tumors, but the exact mechanism of the effect needs to be further explored. Overexpressing FNDC5 inhibits the invasion and migration of gastric cancer but does not affect proliferation. At last, we constructed a clinical risk score model composed of two FNDC5-related genes, and this model may help lay the foundation for further in-depth research on the individualized treatment of gastric cancer patients.

Neuroprotection of Gastrodia elata polyphenols against H2O2-induced PC12 cell cytotoxicity by reducing oxidative stress.

It has been suggested that oxidative stress (OS) has a role in the development of aging and neurodegenerative disorders. Biological molecules are easily damaged by reactive oxygen species, which can ultimately result in necrotic or apoptotic cell death. Foods containing phytochemicals, such as phenolic compounds, may have potential preventive effects against several diseases, including alzheimer's disease (AD), according to epidemiological and in vitro research. Gastrodia elata is a well-known homology of medicine and food plant that has been used for centuries in China and other East Asian countries to treat central nervous system disorders. In this study, we focused on the potential of the extract, Gastrodia elata polyphenols (GPP), for the prevention and treatment of AD. H2O2 induced PC12 cell damage was used to simulate the oxidative stress of AD. The effects of GPP on the injury model were evaluated by cell survival rate, lactate dehydrogenase (LDH), lipid peroxidation (MDA), production of intracellular antioxidant enzymes, reactive oxygen species (ROS), mitochondrial membrane potential (MMP), cellular inflammation level and apoptosis level. The results showed that GPP pretreatment had a protective effect by increasing cell viability, reducing lactate dehydrogenase infiltration, decreasing MDA and increasing intracellular antioxidant enzymes, diminishing reactive oxygen species production and decreasing mitochondrial membrane potential, reducing cell inflammation and decreasing apoptosis. Accordingly, it is suggested that GPP possessed promising neuroprotective benefits which enabled the prevention or therapeutic implementation of AD along with serving as a reference towards the exploitation of functional foods or drugs derived from Gastrodia elata.

The prebiotic properties of polysaccharides obtained by differentiated deproteinization methods from Flos Sophorae Immaturus on Lactobacillus fermentum.

The polysaccharides derived from various deproteinization methods were prepared from Flos Sophorae Immaturus (FSI) to investigate the prebiotic efficacy of Lactobacillus fermentum (L.f ). The implications of polysaccharides from FSI (PFSI) gained after purification performed by non-deproteinization and different deproteinization processes (Savage method, papain method, and TCA method) via one-factor optimization were firstly investigated for the influences on the growth of L.f. The utilization of carbohydrate sources and the synthesis of protein and lactate during its growth were analyzed, as well as the variations of LDH, SOD, and GSH- Px enzyme dynamics. The results showed that the one-factor optimization of the deproteinization process with the protein removal rate and polysaccharide retention rate as the indexes led to the optimal methods of the Sevage method with 5 elution times, papain method with 80 U/mL concentration, and TCA method with 2.5 ratio, respectively. In addition, the PFSI obtained with or without deproteinization purification had a certain effect on promoting L.f proliferation. Moreover, the PFSI gained by the third deproteinization purification, at a concentration of 10 g/L, significantly elevated L.f biomass and growth rate compared with the blank control, and the utilization of reducing sugars and the synthesis of protein and lactic acid were higher than the control (P < 0.05); improved LDH, SOD, and GSH-Px activity in L.f (P < 0.05), and the TCA method could be effectively applied to eliminate the proteins affecting FSI in probiotics, and PFSI may be a potentially beneficial prebiotic and intestinal reinforcer.

Protective Effect of Flavonoids from Mulberry Leaf on AAPH-Induced Oxidative Damage in Sheep Erythrocytes.

To evaluate the antioxidant activity of flavonoids extracted from Chinese herb mulberry leaves (ML), flavonoids from mulberry leaves (FML) were extracted and purified by using ultrasonic-assisted enzymatic extraction and D101 macroporous resin. Using LC-MS/MS-Liquid Chromatography with tandem mass spectrometry analysis, hesperidin, rutoside, hyperoside, cyanidin-3-o-glucoside, myricitrin, cyanidin, and quercetin were identified, and NMR and UV were consistent with the verification of IR flavonoid characteristics. The antioxidant activity of FML has also been evaluated as well as the protective effect on 2,2 0-azobis (2-amidinopropane) dihydrochloride (AAPH)-induced oxidative stress. The results showed that FML exhibited powerful antioxidant activity. Moreover, FML showed dose-dependent protection against AAPH-induced sheep erythrocytes' oxidative hemolysis. In the enzymatic antioxidant system, pretreatment with high FML maintained the balance of SOD, CAT, and GSH-Px; in the non-enzymatic antioxidant system, the content of MDA can be effectively reduced after FML treatment. This study provides a research basis for the development of natural products from mulberry leaves.

High DAPK1 Expression Promotes Tumor Metastasis of Gastric Cancer.

Gastric cancer (GC) is a common upper gastrointestinal tumor. Death-associated protein kinase (DAPK1) was found to participate in the development of various malignant tumors. However, there are few reports on DAPK1 in gastric cancer. In this study, the TCGA and GEO datasets were used to explore the expression and role of DAPK1 in gastric cancer. The functions of DAPK1 in gastric cancer were determined by proliferation, migration and invasion assays. In addition, genes co-expressed with DAPK1 in gastric cancer were estimated through the WGCNA and correlation analysis. A DAPK1-related gene prognostic model was constructed using the Cox regression and lasso analyses. The expression of DAPK1 was significantly up-regulated in gastric cancer tissues. Kaplan-Meier analysis showed that low expression of DAPK1 was a favorable prognostic factor of overall survival and disease-free survival for gastric cancer patients. Functional experiments demonstrated that DAPK1 can promote the migration and invasion of gastric cancer cells. WGCNA, correlation analysis, Cox regression, and lasso analyses were applied to construct the DAPK1-related prognostic model. The prognostic value of this prognostic model of DAPK1-related genes was further successfully validated in an independent database. Our results indicated that DAPK1 can promote gastric cancer cell migration and invasion and established four DAPK1-related signature genes for gastric cancer that could independently predict the survival of GC patients.

The Chemical Profiling and Anticancer Potential of Functional Polysaccharides from Flos Sophorae Immaturus.

Polysaccharides from Flos Sophorae Immaturus (FSI) are one of its pharmacological compounds that can perform effective activities. Aiming to extract the most effective polysaccharides against hepatocellular carcinoma (HCC), the polysaccharides were separated from FSI through ultrasonic microwave extraction, and the first comparison was carried out on the characterization of the structure and its cytotoxic properties on HCC SMMC 7721 cells of undeproteinized purified polysaccharides (PFSI-1) and papain-deproteinized polysaccharides (PFSI-2) from FSI. The findings indicated that PFSI-1 and PFSI-2 had characteristic absorption peaks of polysaccharides; PFSI-1 contained three monosaccharides and PFSI-2 contained ten; and SEM, AFM, and NMR were consistent with the verification of IR polysaccharide characteristics, suggesting probable additional latent activities. The pharmacotoxic effects of both PFSI-1 and PFSI-2 on SMMC 7721 cells (p < 0.05), attenuated the migration ability of SMMC 7721 cells (p < 0.05) and promoted apoptosis (p < 0.05), with an increase in G0/G1-phase cells and decrease in S-phase cells in the PFSI-1 as well as a decrease in G0/G1-phase cells, increase in S-phase cells, and decrease in apoptosis in the PFSI-2 (p < 0.05). The significant cytotoxic effect of PFSI-2 on SMMC 7721 cells (p < 0.05) and its protective effect on human hepatic L02 cells (HL-7702) at low concentrations (p > 0.05) could indicate its potential as a new drug for the treatment of HCC.

Antibacterial effect and mechanism of anthocyanin from Lycium ruthenicum Murr.

The inhibitory effects of the anthocyanin obtained from Lycium ruthenicum Murr were tested against several food-borne pathogens were evaluated, such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Aspergillus niger and Penicillium sp. In general, anthocyanin had different antibacterial effect on different bacteria, and the best antibacterial effect on S. aureus, with minimal inhibitory concentration (MIC) of 3.125 mg/mL. Anthocyanin increased the surface hydrophobicity of S. aureus, discharged the intracellular K+, and reduced the total soluble protein, affecting protein synthesis. Fluorescent inverted microscope and flow cytometry (FCM) found a significant increase in fluorescence intensity and lethality relative to the control group, and the dead P3 region to 77.21%. The above suggested a correlation between the antibacterial mechanism of anthocyanin and cell membrane permeability integrity. Biofilm formation was evaluated by the crystal violet assay (CV), silver staining method and methyl thiazolyl tetrazolium (MTT). Scanning electron microscopy (SEM) showed that anthocyanins could change the structure of biofilm.

Emerging trends in sacubitril/valsartan research: A bibliometric analysis of the years 1995-2021.

BACKGROUND: Sacubitril/valsartan has been approved for the treatment of heart failure (HF) patients with reduced ejection fraction; since then, it gradually became a new star drug in the therapy of HF. Nevertheless, the effectiveness of sacubitril/valsartan remains under investigation. Thus far, only a few bibliometric studies have systematically analyzed the application of sacubitril/valsartan. METHODS: Publications on sacubitril/valsartan were retrieved from the Web of Science Core Collection on April 29, 2021. Data were analyzed using Microsoft Excel 2019 (Redmond, WA), VOS viewer (Redmond, WA), and Cite Space V (Drexel University, Philadelphia, PA). RESULTS: A total of 1309 publications on sacubitril/valsartan published from 1995 to 2021 were retrieved. The number of publications regarding sacubitril/valsartan increased sharply in the last 6 years (2015-2021), and American scholars authored >40% of those publications. Most were published in the European Journal of Heart Failure, the United States was the bellwether with a solid academic reputation in this area. Solomon published the highest number of related articles and was the most frequently cited author. "Heart failure" was the leading research hotspot. The keywords, "inflammation," "fibrosis," and "oxidative stress" appeared most recently as research fronts. CONCLUSIONS: Research attention should be focused on clinical trial outcomes. Considering its effectiveness in HF, the mechanisms and further applications of sacubitril/valsartan may become research hotspots in the future and should be closely examined.

Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma.

Background: Renal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC. Methods: The expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database. Results: The mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients' prognosis in different subgroups of ccRCC. Conclusion: Our study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.

Divergent Reassortment and Transmission Dynamics of Highly Pathogenic Avian Influenza A(H5N8) Virus in Birds of China During 2021.

Highly pathogenic influenza A(H5N8) viruses had caused several outbreaks among wild bird and poultry populations across the globe, and strikingly, caused human infection, posing serious public health concerns. In this study, we conducted influenza surveillance in China during 2021 to monitor the evolution of influenza viruses in poultry. A total of 35 influenza viruses were obtained in chickens, ducks, and geese, of which 30 H5N8 viruses, 3 H5N1 viruses, and 2 H5N6 viruses. Phylogenetic analysis suggested all of H5N1, H5N6, and H5N8 isolates were derived from clade 2.3.4.4b H5N8 viruses during 2020/21 season, and notably, the internal genes of H5N1 and H5N6 viruses shared different genetic heterogeneity with H5N8 viruses and had been reassorted with wild bird-origin H5N1 viruses from Europe. By contrast, almost all H5N8 viruses exhibited only one phylogenic cluster with wild bird-origin H5N8 viruses in China and Korea, indicating that H5N8 viruses in China were more stable. Besides, we found that Korea is the main output geographic location in the spread of these H5N8 viruses to northern and eastern China, and especially, the co-circulation of H5N8 viruses occurred within China, with central China acted as a seeding population during the H5N8 epidemic. The statistical support was strong for viral migration from wild birds to chickens and ducks, indicating that 2.3.4.4b poultry-origin H5N8 viruses during 2020-2021 were originated from wild birds. Our findings provide novel insights into evolution and transmission dynamics of H5 subtype influenza viruses among poultry after novel H5N8 viruses invaded China for nearly one year.