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Tropomyosin (TM) in shrimp is one of the predominant causes of food allergy around the world. In the present study, the effect of seabuckthorn juice against TM -induced shrimp allergy was investigated in BALB/c mice. Allergic symptoms, spleen index, intestinal section and diarrhea were measured in shrimp allergy mice. As the results, seabuckthorn juice suppressed the lesions in jejunum tissue, diarrhea and allergic symptoms in shrimp allergy mice. Seabuckthorn juice also reduced serum concentrations of tumor necrosis factor-α (TNF-α) as well as immunoglobulin E (IgE) and stimulated the secretion of interleukin-10 (IL-10) in mice with shrimp allergy. Taken together, our findings suggest that increased IL-10 by seabuckthorn juice inhibits Th2 cytokine production to suppress shrimp allergic symptoms. Furthermore, seabuckthorn juice also regulates shrimp allergy by reducing jejunum lesions, inhibiting levels of TNF-α and IgE.

BackgroundChina has long been with high Hepatitis B Virus(HBV) prevalence in the world. The HBV prevalence of people aged 1–59 decreased to less than 8% in 2006, and by 2020, HBsAg positive rate of children aged

Abstract The cGAS‐STING pathway, as a vital innate immune signaling pathway, has attracted considerable attention in tumor immunotherapy research. However, STING agonists are generally incapable of targeting tumors, thus limiting their clinical applications. Here, a photodynamic polymer (P1) is designed to electrostatically couple with 56MESS–a cationic platinum (II) agent–to form NPPDT‐56MESS. The accumulation of NPPDT‐56MESS in the tumors increases the efficacy and decreases the systemic toxicity of the drugs. Moreover, NPPDT‐56MESS generates reactive oxygen species (ROS) under the excitation with an 808 nm laser, which then results in the disintegration of NPPDT‐56MESS. Indeed, the ROS and 56MESS act synergistically to damage DNA and mitochondria, leading to a surge of cytoplasmic double‐stranded DNA (dsDNA). This way, the cGAS‐STING pathway is activated to induce anti‐tumor immune responses and ultimately enhance anti‐cancer activity. Additionally, the administration of NPPDT‐56MESS to mice induces an immune memory effect, thus improving the survival rate of mice. Collectively, these findings indicate that NPPDT‐56MESS functions as a chemotherapeutic agent and cGAS‐STING pathway agonist, representing a combination chemotherapy and immunotherapy strategy that provides novel modalities for the treatment of uveal melanoma.

Introduction: The acquisition of blood lactate concentration (BLC) during exercise is beneficial for endurance training, yet a convenient method to measure it remains unavailable. BLC and electrocardiogram (ECG) both exhibit variations with changes in exercise intensity and duration. In this study, we hypothesized that BLC during exercise can be predicted using ECG data.Methods: Thirty-one healthy participants underwent four cardiopulmonary exercise tests, including one incremental test and three constant work rate (CWR) tests at low, moderate, and high intensity. Venous blood samples were obtained immediately after each CWR test to measure BLC. A mathematical model was constructed using 31 trios of CWR tests, which utilized a residual network combined with long short-term memory to analyze every beat of lead II ECG waveform as 2D images. An artificial neural network was used to analyze variables such as the RR interval, age, sex, and body mass index.Results: The standard deviation of the fitting error was 0.12 mmol/L for low and moderate intensities, and 0.19 mmol/L for high intensity. Weighting analysis demonstrated that ECG data, including every beat of ECG waveform and RR interval, contribute predominantly.Conclusion: By employing 2D convolution and artificial neural network-based methods, BLC during exercise can be accurately estimated non-invasively using ECG data, which has potential applications in exercise training.

Trace elements play a crucial role in the growth and bioactive substance content of medicinal plants, but their utilization efficiency in soil is often low. In this study, soil and Aconitum carmichaelii samples were collected and measured from 22 different locations, followed by an analysis of the relationship between trace elements and the yield and alkaloid content of the plants. The results indicated a significant positive correlation between zinc, trace elements in the soil, and the yield and alkaloid content of A. carmichaelii. Subsequent treatment of A. carmichaelii with both bulk zinc oxide (ZnO) and zinc oxide nanoparticles (ZnO NPs) demonstrated that the use of ZnO NPs significantly enhanced plant growth and monoester-type alkaloid content. To elucidate the underlying mechanisms responsible for these effects, metabolomic analysis was performed, resulting in the identification of 38 differentially expressed metabolites in eight metabolic pathways between the two treatments. Additionally, significant differences were observed in the rhizosphere bacterial communities, with Bacteroidota and Actinobacteriota identified as valuable biomarkers for ZnO NP treatment. Covariation analysis further revealed significant correlations between specific microbial communities and metabolite expression levels. These findings provide compelling evidence that nanoscale zinc exhibits much higher utilization efficiency compared to traditional zinc fertilizer.

Background: Cancer is the most fatal disease in humans and the aberrant activity of various cell cycle proteins results in uncontrolled tumor cell proliferation, thus, regulating the cell cycle is an attractive target in cancer therapy. Objectives: Aurone is a naturally occurring active compound with a wide range of biological activities, of which 3, 4, 5-trimethoxyphenyl (TMP) is an important microtubule targeting pharmacophore. Based on the pharmacophore combination principle, we incorporate the TMP pharmacophore into the aurone structure and design a novel polymethoxy derivative that is expected to inhibit tumor cell proliferation through regulating the cell cycle. Methods: By introducing different substituents on C-4′ and C-3′, a series of new 4, 5, 6-trimethoxy aurone derivatives have been designed and synthesized. DU145, MCF-7 and H1299 cell lines were selected to evaluate their anticancer activity. The compound with the best cytotoxicity was then selected and the anticancer mechanisms were investigated by network pharmacology, flow cytometry, Western blot, and cell heat transfer assay. ADMET prediction evaluated the draggability of aurone derivatives. Results: Aurones 1b and 1c have selective anti-proliferative activity against DU145 cells. Among them, the compound 1c have better cytotoxicity against DU145. Compound 1c could bind the active cavity of CyclinB1/CDK1/CKS complex protein and induced G2/M phase arrest of DU145 cells by regulating the expression of CyclinB1 and p21. Compound 1c satisfies the Lipinski rule, is suitable for the absorption and metabolism index, and has a lower risk of cardiac toxicity. Conclusions: Polymethoxy aurones 1c might function as a CyclinB1/CDK1 inhibitor that deserved to be further developed for the treatment of prostate cancer.

Inactivated COVID-19 vaccines have been widely used to vaccinate the Chinese population. However, limited literature exists to explore the effect of obesity on the humoral and cellular immune response to these vaccines. In this study, 132 high BMI (Body mass index) (obesity and overweight, BMI ≥ 24 kg/m2) and 82 normal BMI (BMI < 24 kg/m2) participants were enrolled. Adverse events (AEs), Spike receptor-binding domain IgG antibody (anti-RBD-IgG), neutralizing antibodies (NAbs), and specific B-cell and T-cell responses were evaluated 21–105 days after full-course inactivated COVID-19 vaccination. The overall incidence of AEs was similar in individuals with and without obesity/overweight. No serious vaccine-related AEs occurred. Individuals with obesity/overweight had a reduced seropositivity rate of NAbs compared to those with normal BMI. Anti-RBD-IgG and NAbs titers in the high BMI group were significantly lower than those in the normal BMI group. The frequencies of RBD-specific memory B cells (MBCs) and the numbers of spike-specific TNF-α+ spot-forming cells (SFCs) in individuals with obesity/overweight were reduced compared with those noted in individuals without obesity/overweight. A similar trend of weakened humoral responses was also observed in individuals with central obesity. Our study results suggested that inactivated COVID-19 vaccines were safe and well tolerated but induced poor humoral and cellular immune responses in Chinese individuals with obesity/overweight.

Single cell transcriptomic sequencing (scRNA) can identify genes that are differentially expressed in cell populations in specific diseases. Here the authors perform scRNA sequencing in a high-altitude pulmonary hypertension (HAPH) cohort and show transcriptional differences in monocyte populations.

Abstract Background Nearly 90% children with cancer reside in low‐ and middle‐income countries, which face multiple challenges delivering high‐quality pediatric onco‐critical care (POCC). We recently identified POCC quality and capacity indicators for PROACTIVE (PediatRic Oncology cApaCity assessment Tool for IntensiVe carE), a tool that evaluates strengths and limitations in POCC services. This study describes pilot testing of PROACTIVE, development of center‐specific reports, and identification of common POCC challenges. Methods The original 119 consensus‐derived PROACTIVE indicators were converted into 182 questions divided between 2 electronic surveys for intensivists and oncologists managing critically ill pediatric cancer patients. Alpha‐testing was conducted to confirm face‐validity with four pediatric intensivists. Eleven centers representing diverse geographic regions, income levels, and POCC services conducted beta‐testing to evaluate usability, feasibility, and applicability of PROACTIVE. Centers' responses were scored and indicators with mean scores ≤75% in availability/performance were classified as common POCC challenges. Results Alpha‐testing ensured face‐validity and beta‐testing demonstrated feasibility and usability of PROACTIVE (October 2020–June 2021). Twenty‐two surveys (response rate 99.4%) were used to develop center‐specific reports. Adjustments to PROACTIVE were made based on focus group feedback and surveys, resulting in 200 questions. Aggregated data across centers identified common POCC challenges: (1) lack of pediatric intensivists, (2) absence of abstinence and withdrawal symptoms monitoring, (3) shortage of supportive care resources, and (4) limited POCC training for physicians and nurses. Conclusions PROACTIVE is a feasible and contextually appropriate tool to help clinicians and organizations identify challenges in POCC services across a wide range of resource‐levels. Widespread use of PROACTIVE can help prioritize and develop tailored interventions to strengthen POCC services and outcomes globally.

Objective: Discogenic low back pain (LBP) is associated with nociceptive nerve fibers that grow into degenerated intervertebral discs (IVD) but the etiopathogenesis of disease is not fully understood. The purpose of this study was to clarify the role of Netrin-1 in causing discogenic LBP. Methods: The level of nociceptive nerve innervation was examined in disc degenerative patients and rat needle-punctured models by immunohistochemistry. Nucleus pulposus (NP) cells were isolated from IVD tissues of rats and induced degeneration by interleukin-1β (IL-1β) or tumor necrosis factor α (TNFα). The candidate genes related to neuron outgrowth and migration were selected by Next-generation sequencing (NGS). CRISPR/Cas9 was used to knockdown Netrin-1 in NP cells. The impact of Netrin-1 on nerve innervation were evaluated with P2X2、NF200 staining and microfluidics assay. Meanwhile the CD31 staining and transwell assay were used to evaluate the impact of Netrin-1 in angiogenesis. The proteins and RNA extracted from NP cells related to catabolism and anabolism were examined by western blot assay and RT-qPCR experiment. ChIP and luciferase experiments were used to assess the intracellular transcriptional regulation of Netrin-1. Further, a needle-punctured rat model followed by histomorphometry and immunofluorescence histochemistry was used to explore the potential effect of Netrin-1 on LBP in vivo. Results: The level of nerve innervation was increased in severe disc degenerative patients while the expression of Netrin-1 was upregulated. The supernatants of NP cells stimulated with IL-1β or TNFα containing more Netrin-1 could promote axon growth and vascular endothelial cells migration. Knocking down Netrin-1 or overexpressing transcription factor TCF3 as a negative regulator of Netrin-1 attenuated this effect. The needle-punctured rat model brought significant spinal hypersensitivity, nerve innervation and angiogenesis, nevertheless knocking down Netrin-1 effectively prevented disc degeneration-induced adverse impacts. Conclusion: Discogenic LBP was induced by Netrin-1, which mediated nerve innervation and angiogenesis in disc degeneration. Knocking down Netrin-1 by CRISPR/Cas9 or negatively regulating Netrin1 by transcription factor TCF3 could alleviate spinal hypersensitivity. The translational potential of this article: This study on Netrin-1 could provide a new target and theoretical basis for the prevention and treatment for discogenic back pain.

Abstract Background Patients with type 2 diabetes mellitus (T2DM) have been reported to be more susceptible to 2019 novel coronavirus (2019-nCoV) and more likely to develop severe pneumonia. However, the safety and immunological responses of T2DM patients after receiving the inactivated vaccines are not quite definite. Therefore, we aimed to explore the safety, antibody responses, and B-cell immunity of T2DM patients who were vaccinated with inactivated coronavirus disease 2019 (COVID-19) vaccines. Methods Eighty-nine patients with T2DM and 100 healthy controls (HCs) were enrolled, all of whom had received two doses of full-course inactivated vaccines. At 21–105 days after full-course vaccines: first, the safety of the vaccines was assessed by questionnaires; second, the titers of anti-receptor binding domain IgG (anti-RBD-IgG) and neutralizing antibodies (NAbs) were measured; third, we detected the frequency of RBD-specific memory B cells (RBD-specific MBCs) to explore the cellular immunity of T2DM patients. Results The overall incidence of adverse events was similar between T2DM patients and HCs, and no serious adverse events were recorded in either group. Compared with HCs, significantly lower titers of anti-RBD-IgG (p = 0.004) and NAbs (p = 0.013) were observed in T2DM patients. Moreover, the frequency of RBD-specific MBCs was lower in T2DM patients than in HCs (p = 0.027). Among the 89 T2DM patients, individuals with lower body mass index (BMI) had higher antibody titers (anti-RBD-IgG: p = 0.009; NAbs: p = 0.084). Furthermore, we found that sex, BMI, and days after vaccination were correlated with antibody titers. Conclusions Inactivated COVID-19 vaccines were safe in patients with T2DM, but the antibody responses and memory B-cell responses were significantly decreased compared to HCs. Trial registration number and date NCT05043246. September 14, 2021. (Clinical Trials.gov)

Fluid overload is a common complication in patients who are on continuous ambulatory peritoneal dialysis (CAPD). Blood pressure is the traditional indicator of fluid status in these patients. However, it has poor sensitivity. Blood pressure variability (BPV) can detect fluctuations in blood pressure sooner and more accurately and be useful for the assessment of fluid volume in hemodialysis patient. However, there are limited relevant studies involving patients on CAPD. This retrospective study included 175 patients on CAPD who underwent regular assessment of the peritoneal dialysis adequacy at 2–3-month intervals at our center from January 2018 to December 2020. The overhydration (OH) value was measured using a body composition monitor. Blood pressure measurements obtained in each visit over one-year follow-up were used to determine each patient’s BPV under peritoneal dialysis. The patients were divided into the normal volume (OH ≤2 L), mild volume overload (OH 2–4 L), and severe volume overload groups (OH ≥4 L). There was no significant between-group difference in the mean blood pressure (p > 0.05). However, the systolic and diastolic BPV values were significantly higher in the severe volume overload group than in the other groups (p

It is important to know the safety and efficacy of vaccination in immunocompromised people living with HIV (PLWH), but currently, there is limited data on the inactivated SARS-CoV-2 vaccines’ safety and immune responses in PLWH. In this prospective observational study, 139 PLWH and 120 healthy controls were enrolled and monitored for 21–105 days after a two-dose vaccination. The safety, anti-receptor binding domain IgG (anti-RBD-IgG) and anti-spike-IgG responses, and RBD-specific memory B cell (MBC) responses were evaluated. The overall adverse events within seven days were reported in 12.9% (18/139) of PLWH and 13.3% (16/120) of healthy controls. No serious adverse events occurred in both groups. Overall, the seroprevalence of anti-RBD-IgG in PLWH was significantly decreased (87.1% vs. 99.2%; p