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.

Advances in Extraction Protocols, Degradation Methods, and Bioactivities of Proanthocyanidins.

Proanthocyanidins, natural polyphenolic compounds abundantly present in plants, exhibit diverse bioactivities, including antioxidative, anti-inflammatory, and antibacterial effects. These bioactivities are intricately linked to the degree of polymerization of these compounds. Through a comprehensive analysis of recent domestic and international research, this article synthesizes the latest advancements in the extraction process, degradation methods, as well as the biological activities and underlying mechanisms of proanthocyanidins. Furthermore, future research endeavors should prioritize the refinement of extraction techniques, the elucidation of bioactive mechanisms, and the development of formulations with enhanced potency. This will maximize the utilization of proanthocyanidins across diverse applications.

Investigating the Hepatoprotective Properties of Mulberry Leaf Flavonoids against Oxidative Stress in HepG2 Cells.

Oxidative stress significantly contributes to ageing and disease, with antioxidants holding promise in mitigating its effects. Functional foods rich in flavonoids offer a potential strategy to mitigate oxidative damage by free radicals. We investigated the protective effects of mulberry leaf flavonoids (MLF) against H2O2-induced oxidative damage in HepG2 cells. It assessed the inhibitory effect of MLF (62.5-500 µg/mL) on H2O2-induced oxidative damage by analyzing cellular morphology and oxidative stress markers, including ROS production, mitochondrial membrane potential, antioxidant enzyme levels, MDA, and apoptosis-related proteins. The results demonstrated that MLF prevented spiny cell formation triggered by 750 µM H2O2 and significantly reduced ROS levels, restored mitochondrial membrane potential, decreased lactate dehydrogenase and alanine transaminase leakage, and reduced MDA content induced by H2O2. MLF also modulated antioxidant enzymes and attenuated oxidative damage to HepG2 cell DNA, as confirmed by staining techniques. These findings indicate the potential of MLF as a hepatoprotective agent against oxidative damage in HepG2 cells.

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.

Knockdown of DDX46 suppresses the proliferation and invasion of gastric cancer through inactivating Akt/GSK-3ß/ß-catenin pathway.

DEAD-box RNA helicase 46 (DDX46) has recently been identified as a candidate oncogene in several types of human malignancies. To date, the role of DDX46 in gastric cancer has not been determined. The purpose of the current study was to explore the role of DDX46 in gastric cancer and the potential mechanism. DDX46-silecing or overexpressing gastric cancer cell lines were established to validate the role of DDX46. Our results showed that the expression of DDX46 was significantly increased in gastric cancer tissues and cell lines. Knockdown of DDX46 suppressed the proliferation and invasion of gastric cancer cells. Whereas, DDX46 overexpression enhanced the cell proliferation and invasion of gastric cancer cells. Furthermore, knockdown of DDX46 markedly suppressed the tumor growth of xenografts. Research into the mechanism revealed that DDX46 depletion inhibited the Akt/GSK-3ß/ß-catenin signaling pathway in gastric cancer cells. Notably, activation of Akt or ß-catenin overexpression reversed the DDX46 depletion-mediated anti-cancer effect. In conclusion, these findings indicated that DDX46 exerted an oncogenic role in gastric cancer via regulating the Akt/GSK-3ß/ß-catenin signaling pathway. Thus, DDX46 might be utilized as a therapeutic anti-cancer target.

Distinctions Between Fecal and Intestinal Mucosal Microbiota in Subgroups of Irritable Bowel Syndrome.

BACKGROUND AND AIMS: Recent studies have shown that changes in the intestinal microbiota contribute to the pathogenesis of irritable bowel syndrome (IBS). This study aimed to investigate the characteristics of the fecal and intestinal mucosal microbiota in IBS patients, and the correlation between microbiota and clinical manifestations. METHODS: Fecal and intestinal mucosal samples were collected from 14 constipation-predominant IBS (IBS-C) patients, 20 diarrhea-predominant IBS (IBS-D) patients, and 20 healthy controls (HCs). 16S rRNA gene sequencing and fluorescence in situ hybridization were used for the analysis of samples. RESULTS: Community richness and diversity of the fecal microbiota in IBS patients were significantly reduced compared with the HCs. The mucosal samples in IBS patients showed decreased Bifidobacterium and increased Bacteroides caccae compared with HCs; Eubacterium and Roseburia were decreased in IBS-C patients and increased in IBS-D patients. A comparison of the fecal and mucosal microbiota in IBS patients showed significantly increased Bifidobacterium in fecal samples and a decrease in mucosal samples in IBS-C patients; Bacteroides caccae and Roseburia were significantly reduced in fecal samples and increased in mucosal samples of IBS patients. A correlation between microbiota and clinical manifestations in IBS patients showed that Bacteroides caccae and Roseburia in fecal samples and Bifidobacterium and Eubacterium in mucosal samples were associated with abdominal pain and distention. CONCLUSIONS: Distinct differences exist between the fecal and intestinal mucosal microbiota in IBS patients, with the changes in the latter appearing more consistent with the pathophysiology of IBS. Changes in intestinal microbiota were associated with the clinical manifestations in IBS.

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.

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.

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.

Knockdown of TRIM47 inhibits glioma cell proliferation, migration and invasion through the inactivation of Wnt/ß-catenin pathway.

Tripartite motif 47 (TRIM47), a member of the TRIM protein family, plays a crucial role in tumor development and progression. However, the role of TRIM47 in glioma has not been investigated. In the present study, we investigated the expression of TRIM47 in glioma and explored the role of TRIM47 in glioma proliferation and migration both in vitro and in vivo. Our results showed that TRIM47 expression was significantly increased in glioma tissues compared to the normal brain tissues. Knockdown of TRIM47 in U87 and U251 cells inhibited cell proliferation, as well as cell migration and invasion. TRIM47 knockdown caused significant increase in E-cadherin expression and remarkable decrease in N-cadherin and vimentin expressions in both U87 and U251 cells. In vivo assay proved that knockdown of TRIM47 prevented tumor growth of glioma. Furthermore, TRIM47 silencing significantly inhibited the activation of Wnt/ß-catenin pathway. Additionally, treatment with LiCl reversed the inhibitory effects of TRIM47 knockdown on cell proliferation and migration in U87 cells. In conclusion, these findings indicated that knockdown of TRIM47 suppressed cell proliferation and metastasis of glioma both in vitro and in vivo. TRIM47 exerted an oncogenic role in glioma and might be a therapeutic target for the treatment of glioma.

Distinct Microbial Populations Exist in the Mucosa-associated Microbiota of Diarrhea Predominant Irritable Bowel Syndrome and Ulcerative Colitis.

GOALS: The goal of this study was to observe the bacterial colonization in the intestinal mucosa in the patients with diarrhea predominant irritable bowel syndrome (IBS-D) and ulcerative colitis (UC), and compare the mucosa-associated microbiota among the IBS-D patients, UC patients and the healthy control, and explore the correlation of the mucosa-associated microbiota with clinical manifestations. STUDY: A total of 20 IBS-D patients, 28 patients with UC (16 active, 12 inactive) and 16 healthy subjects were enrolled in the study. They all underwent colonoscopies in the Gastrointestinal Endoscopy Center in the Second Affiliated Hospital of Xi'an Jiaotong University from June 2016 to October 2016. The mucosa specimens were taken at the junction of rectum and sigmoid colon for fluorescent in situ hybridization (FISH). Then the observed mucosa-associated microbiota was counted and compared. RESULTS: (1) In the IBS-D patients, the mucosa-associated bacteria were found to colonize in the surface of mucosa and the adjacent mucin layer. And in active UC, Escherichia coli, and Bacteroides were found in the lamina propria, in addition to bacterial colonization in the above-mentioned areas. (2) The total count of mucosa-associated bacteria and the individual counts of E. coli, Clostridium, and Bacteroides were significantly increased, and Bifidobacteria significantly decreased (P<0.05) in the IBS-D patients and UC patients. Counts of Lactobacillus were decreased only in UC patients compared with the healthy control. And a significantly larger variation of the above-mentioned bacterial counts was found in the patients with UC, particularly in those with active UC, compared with those with IBS-D (P<0.05); the counts in the UC group were 1.3 to 5.3 times more or less than those in the IBS-D group. (3) Compared with healthy controls and IBS-D, the total count of bacteria and the individual counts of E. coli and Bacteroides in the lamina propria in active UC were significantly increased (P<0.05). (4) A significant negative correlation of the counts of Lactobacillus and Bifidobacteria with the defecation frequency and fecal characteristics (P<0.05) was found in the IBS-D patients; in those with UC, both the total count of bacteria and the individual counts of E. coli, Clostridium, Bacteroides, Lactobacillus, and Bifidobacteria were significantly correlated, positively or negatively, with the related clinical manifestations and the activity of the disease (P<0.05). CONCLUSIONS: Compared with the healthy control, intestinal microecology was changed most obviously in UC with much smaller differences though in the same direction in IBS-D. The translocation of some bacteria into the lamina propria was found in UC, particularly in active UC. The changes of mucosa-associated microbiota were related more or less to some clinical manifestations in IBS-D and UC.

White LED light source radar system for multi-wavelength remote sensing measurement of atmospheric aerosols.

A Mie scattering radar system with a white light-emitting diode (LED) light source is proposed for the multi-wavelength detection of atmospheric aerosols. By splitting the continuous spectrum, the multi-wavelength echo signals are extracted to achieve multi-wavelength real-time detection of atmospheric aerosols. The white LED spectrum characteristics are analyzed, and four detection wavelengths are set at 450, 525, 600, and 661 nm. The composition and detection principles of a white LED light source radar system are expounded, the design of each system part is described in detail, and the system parameters and data inversion algorithm are presented. We built a white LED light source radar system and conducted preliminary observation experiments. The results show that radar can achieve multi-wavelength real-time detection of atmospheric aerosols within a 300 m height, which can provide effective data for further study of aerosol particle distribution and lay a foundation for further studies of aerosol characteristics at special wavelengths.

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.

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.

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.

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.

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.

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.