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Phenylacetylglycine (PAGly) is a small molecule derived from phenylalanine in the gut via glycine degradation and conjugation. It has been associated with both the progression of atherosclerosis and protective effects on the myocardium. This study evaluated the function and the underlying mechanisms of PAGly in a rat cerebral ischemia/reperfusion (I/R) injury model. The results indicated that PAGly markedly alleviated cerebral infarct volume (P = 0.0024) and improved the neurobehavioral outcomes (P = 0.0149) after I/R injury. PAGly is structurally analogous to catecholamines and binds to β2-adrenergic receptors (β2AR) on microglia without altering the expression of these receptors (P = 0.9137), but instead inhibiting their activity. It was also observed that when β2AR was engaged in microglia, PAGly suppressed the release of TNF-α (P = 0.0018), IL-1β (P = 0.0310), and IL-6 (P = 0.0017), thereby reducing neuronal apoptosis (P = 0.000003). Furthermore, the protective effect of PAGly diminished after the administration of β2AR-specific agonist fenoterol (P = 0.0055). These data indicate that PAGly mitigates cerebral I/R injury by inhibiting microglial inflammation via β2AR, highlighting its potential as a therapeutic agent. These findings position PAGly as a promising candidate for therapeutic intervention in cerebrovascular injuries, warranting further exploration in clinical settings.

Background and objective Brivudine has been used in herpes zoster (HZ) treatment for years, but the safety and efficacy of brivudine are inconclusive. Here we perform a meta-analysis to assess the efficacy, safety, incidence of postherpetic neuralgia of brivudine.Methods Data of randomized controlled Trials (RCTS) were obtained from the databases of both English (PubMed, Embase, and Cochrane Library) and Chinese (China National Knowledge Infrastructure, China Science Journal Database, and WanFang Database) literatures from inception to 12 September 2022. Meta-analyses of efficacy and safety of Brivudine for the treatment of herpes zoster for RCTS were conducted.Results The analyses included seven RCTS (2095 patients in experimental group and 2076 patients in control group) in the treatment of HZ with brivudine. It suggested that the brivudine group was superior to the control group in terms of efficacy (p = .0002) and incidence of postherpetic neuralgia (p = .04). But the incidence of adverse reactions has no significant difference between the brivudine and the control groups (p = .22). In addition, subgroup analysis of adverse events also showed that brivudine was about the same safety as other modalities in the treatment of HZ (p > .05).Conclusions Brivudine is effective for HZ. However, the evidence on the safety of brivudine is insufficient.

Artesunate (ATS) is considered the most widely employed artemisnin derivative in the treatment of Plasmodium falciparum malaria. However, poor solubility and low bioavailability of ATS limit its further clinical application. Herein, we developed a new strategy based on the exosome (exo) - drug conjugation (EDC) using the milk-derived exosomes for ATS delivery. The Exo-ATS conjugates (EACs) which formed via a facile bio-conjugation of ATS to the exosomal surface, have been demonstrated to be able to not only boost the solubility and bioavailability of ATS but also enable a sustained-release of ATS from exosomes. Maximal improvement of 71.4-fold in the solubility of ATS was attained by EACs. The corresponding entrapment efficiency and drug loading capacities were found to be 90.3% and 73.9% for EACs, respectively. Further, in vivo pharmacokinetics study manifested that maximum 2.6-fold improved bioavailability of ATS was achieved by oral delivery of EACs. Moreover, EACs displayed a distinct sustained-release profile of maximum 36.2-fold prolonged half-life of ATS via intravenous delivery. We reported that for the first time the administration of EACs could be a potential drug delivery strategy aimed at ameliorating the pharmacokinetic profile of ATS based on our encouraging results and hoped that our work opened up a new avenue for the development of EDC delivery system.

Abstract. Background:. Atopic dermatitis (AD) affects approximately 10% of adults worldwide. CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling. This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD. Methods:. This multicenter, randomized, double-blind, placebo-controlled, phase 2b trial was conducted in 21 medical institutions in China from February to November 2021. Totally 120 eligible patients were enrolled and randomized (1:1:1) to receive subcutaneous injections of 300 mg CM310, 150 mg CM310, or placebo every 2 weeks for 16 weeks, followed by an 8-week follow-up period. The primary endpoint was the proportion of patients achieving ≥75% improvement in the Eczema Area and Severity Index (EASI-75) score from baseline at week 16. Safety and pharmacodynamics were also studied. Results:. At week 16, the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups (70% [28/40] for high-dose and 65% [26/40] for low-dose) than that in the placebo group (20%[8/40]). The differences in EASI-75 response rate were 50% (high vs. placebo, 95% CI 31%-69%) and 45% (low vs. placebo, 95% CI 26%-64%), with both P values

Introduction: Pycnogenol (PYC), a standardized extract from French maritime pine, has traditionally been used to treat inflammation. However, its primary active components and their mechanisms of action have not yet been determined.Methods: This study employed UPLC-MS/MS (Ultra-high performance liquid chromatography-tandem mass spectrometry) and network pharmacology to identify the potential active components of PYC and elucidate their anti-inflammatory mechanisms by cell experiments.Results: 768 PYC compounds were identified and 19 anti-inflammatory compounds were screened with 85 target proteins directly involved in the inflammation. PPI (protein-protein interaction) analysis identified IL6, TNF, MMP9, IL1B, AKT1, IFNG, CXCL8, NFKB1, CCL2, IL10, and PTGS2 as core targets. KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis suggested that the compound in PYC might exert anti-inflammatory effects through the IL17 and TNF signal pathways. Cell experiments determined that PYC treatment can reduce the expression of IL6 and IL1β to relieve inflammation in LPS (lipopolysaccharide)-induced BV2 cells.Conclusion: PYC could affect inflammation via multi-components, -targets, and -mechanisms.

ObjectiveTo systematically understand the research frontiers, hotspots and development trends of exercise therapy in the intervention of tumor-related sleep-wake disorders, and to provide scientific basis for follow-up research.MethodsDownloaded the original research papers on February 26, 2024, from the Web of Science core collection database, on tumor-associated sleep-wake disorders. The data that met the inclusion criteria were imported into the Bibliometric Analysis Platform (http://biblimetric.com), CiteSpace 6.3.R1 and VOSviwer1.6.20 software for visual analysis, and imported into Excel2021. Scientometric analysis was performed with Oringin2021 and PyCharm Community Edition 2022.1.3.ResultsA total of 512 original research papers on tumor-related sleep-wake disorders were obtained. The most influential countries in the subject area are the United States, Spain and German, the institutions are the University of California System, Sun Yat Sen University and Northwestern University, et al., the authors are Berger AM, Aaronson NK, Bower JE, et al., and the journals are Cancer, Brit J Cancer and Cancer Nurs. The co-cited references suggest that the current research frontier in the field mainly involves the level, place and program of exercise therapy, including the relationship between physical activity, sedentary behavior and cancer prevention and control. The results of co-occurrence keyword network analysis showed that quality of life, physical activity, breast cancer, exercise, fatigue, and survivors may be the research hotspots in this field, with breast cancer, health, aerobic exercise, adults, and chemotherapy being the most popular.ConclusionsThe number of papers published and the research enthusiasm in this field show a steady upward trend. However, there is a lack of influential institutions and scholars, and there is relatively little research collaboration across countries/regions/institutions. The scientific research influence of institutions and scholars in most European and American countries/regions is significantly ahead of that of institutions and scholars in Asian and African countries/regions. But Sun Yat Sen University in China is a relatively active and influential scientific research institution in recent years, which is worthy of attention. In addition, the research frontier of this discipline is the level, place and program of exercise therapy auxiliary intervention, and the research hotspots involve breast cancer, health, aerobic exercise, adults, chemotherapy, et al. Their clinical efficacy needs to be further demonstrated in multi-center, large-sample and high-quality prospective studies.

Abstract Background Chronic cholecystitis, characterized by persistent inflammation of the gallbladder, predominantly stems from the prolonged presence of gallstones. Calculous cholecystitis has demonstrated a consistent escalation in its incidence over time.Gallbladder stones have been recognized as a predisposing factor for the development of biliary tract infections.Concomitantly, there have been substantial shifts in the distribution and resistance profiles of pathogenic microorganisms responsible for biliary tract infections. The timely acquisition of bile samples for pathogen analysis is of paramount importance, given its critical role in guiding judicious clinical pharmacotherapy and enhancing patient prognosis. Case Presentation We present a case involving a 66-year-old female patient who had previously undergone subtotal gastrectomy due to diffuse large B-cell lymphoma. The patient was admitted to our institution with complaints of abdominal pain. Subsequent diagnostic evaluation revealed concurrent choledocholithiasis and cholecystolithiasis. The patient underwent surgical cholecystectomy as the therapeutic approach. Histopathological examination of the excised gallbladder disclosed characteristic features indicative of chronic cholecystitis. Subsequent laboratory analysis of the patient’s bile specimen yielded Gram-positive cocci, subsequently identified through biochemical assays, mass spectrometry, and 16 S rRNA analysis as Vagococcus fluvialis. Further in vitro antimicrobial susceptibility testing using disk diffusion and microfluidic dilution showed that this strain exhibited inhibition zone diameters ranging from 12.0 to 32.0 mm in response to 26 antibiotics, including ampicillin, cefazolin, cefuroxime, cefotaxime, ceftriaxone, cefepime, ampicillin/sulbactam, piperacillin, ciprofloxacin, cefoperazone/sulbactam, imipenem, meropenem, piperacillin/tazobarb, penicillin, erythromycin, chloramphenicol, vancomycin, methotrexate/sulfamethoxazole, teicoplanin, linezolid, tigecycline, cefoxitin, ceftazidime, levofloxacin, minocycline and tobramycin. However, the inhibition zone diameters were 6.0 mm for amikacin, oxacillin, clindamycin, and tetracycline. The patient received ceftazidime anti-infective therapy both preoperatively and within 24 h postoperatively and was discharged successfully one week after surgery. Conclusion In this study, we present the inaugural isolation and identification of Vagococcus fluvialis from bile specimens of patients afflicted with calculous cholecystitis. This novel finding lays a substantial experimental groundwork for guiding clinically rational antimicrobial therapy and advancing the exploration of relevant pathogenic mechanisms pertaining to Vagococcus fluvialis infections.

Because of the crucial role of epidermal permeability barrier in regulation of cutaneous and extracutaneous functions, great efforts have been made to identify and develop the regimens that can improve epidermal permeability barrier function. Studies have demonstrated that oral administration of natural ingredients can improve epidermal permeability barrier in various skin conditions, including inflammatory dermatoses and UV-irradiation. Moreover, topical applications of some natural ingredients can also accelerate the repair of epidermal permeability barrier after acute barrier disruption and lower transepidermal water loss in the intact skin. Natural ingredient-induced improvements in epidermal permeability barrier function can be attributable to upregulation of keratinocyte differentiation, lipid production, antioxidant, hyaluronic acid production, expression of aquaporin 3 and sodium-hydrogen exchanger 1. In this review, we summarize the benefits of topical natural ingredients in epidermal permeability barrier in normal skin with or without acute barrier disruption and the underlying mechanisms.

Objectives: This review aimed to harmoniously summarize and compare outlier rates for various cardiac troponin (cTn) assays, including high-sensitivity-cTn (hs-cTn) assays and contemporary cTn (generation of assays prior to hs-cTn ones) assays, from the published studies. Methods: The PRISMA guidelines were utilized to perform this systematic review. Five databases, including PubMed, Scopus, Embase, Cochrane Library, and Web of Science, were searched using specific keywords up to June 30th, 2023. Studies reporting specifically calculated outlier rates for cTn assays when conducting in-vitro diagnosis in human samples were included. Selected studies were then further assessed using the GRADE tool. Results: Thirteen studies were included. The data from the studies were summarized statistically in this review. The results showed substantial evidence of improved analytical robustness or reduced respective mean rates of outliers, critical outliers, and analytical outliers for hs-cTn assays (0.14 %, 0.18 %, and 0.18 %) compared to contemporary cTn assays (0.63 %, 0.71 %, and 0.50 %). Conclusion: The findings offer promisingly provide a comprehensive reference for laboratory scientists and clinical staff in choosing the most suitable cTn assay for patient care regrading outlier rates. Besides, this review reveals the advancements of hs-cTn assays with lower outlier rates than contemporary cTn assays. The emerging challenges for continuously improving analytical robustness of cTn assays are also elaborated.

Abstract Background Psoriasis is a common, chronic and relapsing immune-related inflammatory dermal disease. Patients with psoriasis suffering from the recurrences is mainly caused by immune response disorder. Thus, our study is aimed to identify novel immune subtypes and select targeted drugs for the precision therapy in different subtypes of psoriasis. Methods Differentially expressed genes of psoriasis were identified from the Gene Expression Omnibus database. Functional and disease enrichment were performed by Gene Set Enrichment Analysis and Disease Ontology Semantic and Enrichment analysis. Hub genes of psoriasis were selected from protein–protein interaction networks using Metascape database. The expression of hub genes was validated in human psoriasis samples by RT-qPCR and immunohistochemistry. Further, novel immune subtypes of psoriasis were identified by ConsensusClusterPlus package and its association with hub genes were calculated. Immune infiltration analysis was performed, and its candidate drugs were evaluated by Connectivity Map analysis. Results 182 differentially expressed genes of psoriasis were identified from GSE14905 cohort, in which 99 genes were significantly up-regulated and 83 genes were down-regulated. We then conducted functional and disease enrichment in up-regulated genes of psoriasis. Five potential hub genes of psoriasis were obtained, including SOD2, PGD, PPIF, GYS1 and AHCY. The high expression of hub genes was validated in human psoriasis samples. Notably, two novel immune subtypes of psoriasis were determined and defined as C1 and C2. Bioinformatic analysis showed C1 and C2 had different enrichment in immune cells. Further, candidate drugs and mechanism of action that applicable to different subtypes were evaluated. Conclusions Our study identified two novel immune subtypes and five potential hub genes of psoriasis. These findings might give insight into the pathogenesis of psoriasis and provide effective immunotherapy regimens for the precise treatment of psoriasis.

Congenital anomalous origin of coronary artery is a rare cardiovascular malformation and the most common anomaly is the left circumflex (LCX) arising from the right sinus of Valsalva (RSV). Other forms include both coronary arteries from RSV, the left anterior descending coronary artery from RSV, and a single coronary artery from the left sinus of Valsalva. Despite being rare, anomalous origin of left main coronary artery (LMCA) from RSV carries a high risk of sudden cardiac death. Here, we report a case of 13-year-old boy with chest pain and acute extensive anterior ST-segment elevation myocardial infarction (STEMI) who was initially diagnosed as acute myocarditis in the emergency department. A bedside echocardiogram showed severe global hypokinesia of left ventricle (LV) and normal right ventricle (RV) function. Coronary computed tomography angiography (CCTA) examination showed LMCA originated from the RSV. The patient underwent coronary artery bypass grafting surgery and was discharged without complications. A timely correct diagnosis of an anomalous coronary artery is critical in symptomatic patients, CCTA plays an important role in clinical decision making.

Objective To investigate the effect of optimized preoperative hemoglobin (Hb) level on clinical outcome in patients undergoing coronary artery bypass grafting (CABG). Methods Retrospective analysis was performed on patients who were selected to receive CABG from April 2020 to August 2021 in our hospital. Preoperative basic data, perioperative blood transfusion volume, blood transfusion rate, acute liver function impairment, renal function impairment (AKI), ICU stay, length of hospital stay, and in-hospital mortality of patients, meeting the inclusion criteria, were collected. According to the perioperative red blood cell transfusion, the optimal preoperative Hb threshold was calculated by receiver operating characteristic curve (ROC). According to the threshold, all patients were divided into two groups, and the blood transfusion volume and clinical outcomes of the two groups were compared to evaluate the predictive value of the optimal threshold of Hb. Results A total of 915 patients who met the inclusion criteria were enrolled in the study. The optimal threshold for predicting red blood cell transfusion rate by calculating preoperative Hb value by ROC curve was 118 g/L for males and 116g/L for females. Group A: Hb≤ threshold (n=293) was divided into the red blood cell transfusion group A1 and the red blood cell non-transfusion group A2. Group B: Hb>threshold (n=622) was divided into the red blood cell non-transfusion group B1 and no red blood cell non-transfusion group B2. The risk factors for perioperative red blood cell transfusion were age (OR=1.033 874, 95%CI 1.000 4-1.068 3, P

PurposeResistance training (RT) can intervene in aging, which can effectively improve trainees’ life. However, unhealthy living habits such as irregular life, obesity and hyperlipidemia, and chronic diseases lead to a significant decline in the energy level of the population, seriously affecting the health of the population. Our research identifies the research hotspots of RT to intervene in aging from the perspective of bibliometrics, predicts research frontiers and development trends, and provides more perspectives for research on aging populations.MethodsIn this study, we used CiteSpace and VOSviewer visualization software to draw the scientific knowledge map of countries/regions, institutions, authors, co-occurrence keywords, and co-cited references of published articles, and explore the Web of Science core collection database all about the RT intervention aging research status, hotspots, frontiers, and development trends of articles on aging.ResultsAmong the 760 articles that meet the inclusion criteria, the number of articles published and the frequency of citations have increased steadily in the past 5 years. Judging from the countries/regions, institutions, scholars, and journals that published articles, the ones with the largest numbers are the USA, Univ Estadual Londrina, Cyrino ES, and Exp Gerontol. The ones with the highest influence are England, Univ Arkansas Med Sci, Frontera WR, and Biochem Biophys Rep Co. The top five co-occurrence keywords of include exercise, strength, resistance training, skeletal muscle, and muscle strength. The research frontier is physical function.ConclusionIn the field of RT intervention aging research, relevant scholars deserve further in-depth research and exploration. The United States, Brazil, Canada, and other economically developed countries/regions, institutions, and authors have greater influence and productivity. These quantitative research results can provide references for relevant scholars’ follow-up research and government departments to formulate and modify health policies or measures.

Background. Poor anticoagulation quality was a major problem among warfarin-treated patients, which called for innovative and effective methods to improve it. Objective. To investigate whether social app could be used to reduce warfarin-associated adverse events among post-MHVR Chinese patients. Method. 735 warfarin-treated patients (aged 50.8±9.6 years, 59.9% female) were enrolled and randomized to a social app care group (warfarin therapy was guided by experienced clinicians via a social app) or a routine care group (warfarin therapy was managed through traditional in-office visits) at a 1 : 1 ratio. Ending points (bleeding and thrombotic events) were recorded during an 18-month follow-up period. Results. A total of 718 patients were included in analysis. 57 of them suffered warfarin-associated adverse events, including 30 major bleedings and 27 thrombotic events. The time in the therapeutic range (TTR, Rosendaal method) in the social app group was 71.5%, which was significantly better than 52.6% in the routine care group (difference: 18.8%, 95% CI: 16.8-20.8). Compared with the patients from the social app group, patients under routine care experienced more bleeding (hazard ratio (HR): 2.31, 95% CI: 1.13-4.72). The social app care group had lower variation (0.55 vs. 0.70) in the international normalized ratio (INR) values and fewer incidents of extremely high INR (e.g., INR>5.0, 0.87% vs. 3.42%) than the routine care group. Conclusions. Social app management could significantly improve warfarin control and was associated with a reduction in bleeding risk. This trial was registered with NCT03264937.

BackgroundConventional treatment techniques have limited efficacy and more side effects in the treatment of prurigo nodularis. The better alternative treatment option for better outcomes of the disease is dupilumab.ObjectiveThe objective of this study was to systematically review dupilumab-related treatment outcomes in prurigo nodularis.MethodsSeveral databases like Embase, PubMed, Web of Science, and Cochrane library were searched for data acquisition on October 8, 2022. Based on Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, 24 publications were included in this study.ResultsAfter 4,12,16 and more than 16 weeks of dupilumab treatment, 8.3% (n=5/60), 34.4% (n=11/32), 3.6% (n=2/56), and 45.3% (n=29/64) of patients had complete remission, respectively. In addition, 85.0% (n=51/60), 59.4% (n=19/32), 83.9% (n=47/56), and 43.8% (n=28/64) had partial remission, respectively. Moreover, 6.7% (n=4/60), 6.3% (n=2/32), 12.5% (n=7/56), and 10.9% (n=7/64) showed no remission, respectively, and significant reduction of numeric rating scale itch intensity (from 9.0 to 4.9, 2.1, 2.8, 0.9) was attained. There were no serious adverse events observed during treatment, but the most common event observed was conjunctivitis (12.6%, n=15/119).ConclusionsDupilumab has definite effectiveness and safety in prurigo nodularis treatment.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier (CRD42022365802).

A unique starch encapsulated Cu2O nanoparticles were synthesized through a simple and ‘green’ route using ultrasonic irradiation. The polar functional groups on the starch (OH) facilitate the NP capping and stabilization. Structural features of the material were assessed over several advanced techniques like fourier transformed infra-red (FT-IR), UV–vis spectroscopy, scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), energy dispersive X-ray analysis (EDX) elemental mapping, transmission electron microscopy (TEM), X-ray diffraction analysis (XRD), and inductively coupled plasma-atomic emission spectrometry (ICP-AES) analysis. It was catalytically explored in reducing an organic dye (Methylene blue - MB) in the presence of NaBH4 at ambient conditions, being monitored in a UV–vis spectrophotometer. The nanocatalyst was recycled 11 times keeping consistency in its reactivity. Biologically, the nanocomposite exhibited excellent cytotoxicity against lung adenocarcinoma (PC-14, LC-2/ad and HLC-1) cell lines without affecting the normal (HUVEC) cell line. IC50values of the nanocomposite were found at 618, 56 and 379 against HLC-1, LC-2/ad, and PC-14 cell lines respectively and accordingly, PC-14 afforded the best adenocarcinoma activity.

Objective Myocardial infarction is a severe disease with high in-hospital mortality without aggressive clinical treatment. The study aims to evaluate prognostic worth of D-dimer-to-fibrinogen (FIB) ratio (DFR) for patients with acute myocardial infarction (AMI). Methods 133 patients (65 (37, 93) years old) from our hospital (China) with AMI were enlisted from January 2017 to December 2019. Patients were assigned into the survivor and nonsurvivor group based on in-hospital outcomes. Receiver operating characteristics (ROC) and multivariate analysis were fulfilled to analyze the prognostic value of DFR. Results The degree of DFR in the nonsurvivor group was significantly higher than that in the survivor group ( p < 0.05). Logistic regression analysis presented that DFR (hazard ratio (HR), 2.207; 95% confidence interval (CI), 1.050–4.640; p = 0.037) was independently related with in-hospital death. ROC demonstrated that the area under the curve (AUC) of DFR was = 0.808 (0.725–0.892) (sensitivity, 85.3%; specificity, 69.7%). Conclusion DFR might be a new independent predictor of in-hospital death for AMI patients. Further studies are needed to validate this preliminary finding.

Abstract A prey–predator model with constant-effort harvesting on the prey and predators is investigated in this paper. First, we discuss the number and type of the equilibria by analyzing the equations of equilibria and the distribution of eigenvalues. Second, with the rescaled harvesting efforts as bifurcation parameters, a subcritical Hopf bifurcation is exhibited near the multiple focus and a Bogdanov–Takens bifurcation is also displayed near the BT singularity by analyzing the versal unfolding of the model. With the variation of bifurcation parameters, the system shows multi-stable structure, and the attractive domains for different attractors are constituted by the stable and unstable manifolds of saddles and the limit cycles bifurcated from Hopf and Bogdanov–Takens bifurcations. Finally, a cusp point and two generalized Hopf points are found on the saddle-node bifurcation curve and the Hopf bifurcation curves, respectively. Several phase diagrams for parameters near one of the generalized Hopf points are exhibited through the generalized Hopf bifurcation.

In this paper, we study the existence of square-mean asymptotically almost periodic mild solutions for a class of second order nonautonomous stochastic evolution equations in Hilbert spaces. By using the principle of Banach contractive mapping principle, the existence and uniqueness of square-mean asymptotically almost periodic mild solutions of the equation are obtained. To illustrate the abstract result, a concrete example is given.

Cloudy fruit and vegetable mixed juice (MJ) pasteurized by high pressure processing (HPP) showed an increasing market demand. However, browning, sedimentation, and flavor changes of HPP juice during storage have been a great challenge for the beverage industry. The aim of this work was to investigate quality changes of HPP MJs during storage and to explore the potential to create the shelf-stable MJs with fresh-like organoleptic quality through HPP. In the work, commercial MJ1 (orange, mango, and kiwifruit) and MJ2 (carrot and pineapple) were formulated and their quality changes during storage were investigated. The results indicated no visible color changes and sedimentation were observed in MJ1 and MJ2 during refrigerated storage (90 days). However, sucrose decreased as glucose and fructose increased; a large number of aldehydes and alcohols decreased but some terpenoids increased during storage. In general, blending proper fruit and vegetable to produce MJs combing with HPP could maintain high cloud and color stability, but sugars and volatiles clearly changed during storage.

BackgroundBullous pemphigoid (BP) is the most common autoimmune subepidermal bullous disease of the skin. First-line treatment of systemic corticosteroids may cause serious adverse events. Rituximab, omalizumab, and dupilumab should be explored as alternative treatment options to improve outcomes.ObjectiveTo systematically review the rituximab, omalizumab, and dupilumab treatment outcomes in bullous pemphigoid.MethodsA PubMed, Embase, Web of Science, and Cochrane library search were conducted on March 10, 2022. A total of 75 studies were included using Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.ResultsUse of rituximab (n=122), omalizumab (n=53) and dupilumab (n=36) were reported in 211 patients with BP. Rituximab led to complete remission in 70.5% (n=86/122) and partial remission in 23.8% (n=29/122) of patients within 5.7 months, with a recurrence rate of 20.5% (n=25/122). 9.0% (n=11/122) of patients died and infection (6.6%, n=8/122) was the most common adverse event. Omalizumab led to complete remission in 67.9% (n=36/53) and partial remission in 20.8% (n=11/53) of patients within 6.6 months, with a recurrence rate of 5.7% (n=3/53). 1.9% (n=1/53) of patients died and thrombocytopenia (1.9%, n=1/53) was observed as the most common adverse event. Dupilumab led to complete remission in 66.7% (n=24/36) and partial remission in 19.4% (n=7/36) of patients within 4.5 months of treatment without any reported adverse events, with a recurrence rate of 5.6% (n=2/36).ConclusionsRituximab, omalizumab, and dupilumab have similar clinical benefits for BP patients. However, rituximab resulted in higher recurrence rates, adverse events, and mortality rates.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022316454.

Abstract In this paper, we provide the connectedness of the sets of weak efficient solutions, Henig efficient solutions and Benson proper efficient solutions for set-valued vector equilibrium problems under improvement sets.

Background: Skin cutaneous melanoma (SKCM) is an aggressive malignant skin tumor. Ferroptosis is an iron-dependent cell death that may mobilize tumor-infiltrating immunity against cancer. The potential mechanism of long non-coding RNAs (lncRNAs) in ferroptosis in SKCM is not clear. In this study, the prognostic and treatment value of ferroptosis-related lncRNAs was explored in SKCM, and a prognostic model was established.Methods: We first explored the mutation state of ferroptosis-related genes in SKCM samples from The Cancer Genome Atlas database. Then, we utilized consensus clustering analysis to divide the samples into three clusters based on gene expression and evaluated their immune infiltration using gene-set enrichment analysis (GSEA) ESTIMATE and single-sample gene-set enrichment analysis (ssGSEA) algorithms. In addition, we applied univariate Cox analysis to screen prognostic lncRNAs and then validated their prognostic value by Kaplan–Meier (K-M) and transcripts per kilobase million (TPM) value analyses. Finally, we constructed an 18-ferroptosis-related lncRNA prognostic model by multivariate Cox analysis, and SKCM patients were allocated into different risk groups based on the median risk score. The prognostic value of the model was evaluated by K-M and time-dependent receiver operating characteristic (ROC) analyses. Additionally, the immunophenoscore (IPS) in different risk groups was detected.Results: The top three mutated ferroptosis genes were TP53, ACSL5, and TF. The SKCM patients in the cluster C had the highest ferroptosis-related gene expression with the richest immune infiltration. Based on the 18 prognosis-related lncRNAs, we constructed a prognostic model of SKCM patients. Patients at low risk had a better prognosis and higher IPS.Conclusion: Our findings revealed that ferroptosis-related lncRNAs were expected to become potential biomarkers and indicators of prognosis and immunotherapy treatment targets of SKCM.

Tartary buckwheat is an alternative cereal crop. This study sought to establish the mechanisms whereby tartary buckwheat root polysaccharide (TBRP-1) treatment can alleviate diabetes mellitus. TBRP-1 was extracted and purified by hot water and gel permeation column chromatography. Its structure was determined by Fourier transform-infrared spectroscopy (FT-IR), monosaccharide analysis, and nuclear magnetic resonance (NMR) spectroscopy. TBRP-1 was composed of fucose, arabinose, rhamnose, galactose, glucose, xylose, mannose, galacturonic acid, and glucuronic acid. The molecular weight was 2.731 × 104 Da. In addition, for in vitro, HepG2 cells were treated with high insulin concentrations to establish a model of insulin resistance. For in vivo modeling, diabetic mice were established by injecting with streptozotocin (STZ). Body weight, blood glucose levels, glycosylated hemoglobin (HbA1c) levels, and changes in hepatic lipids were analyzed. The expression of suppressor of cytokine signaling 3 (SOCS3), insulin receptor substrate 1 (IRS1), and glucose transporter type 4 (GLUT4) was assessed via qPCR and western blotting. TBRP-1 treatment was sufficient to enhance the ability of insulin resistant HepG2 cells to take up glucose. TBRP-1 also lowered levels of blood glucose, HbA1c, and hepatic lipids in diabetic mice. The underlying molecular mechanisms suggested that TBRP-1 was able to suppress SOCS3 expression to thereby enhance IRS1 expression, thus alleviating insulin resistance.

To solve the problem of the low secret space and security of some image schemes, a novel 4D chaotic system is derived in this paper. Compared with other similar chaotic systems, the new system only has one equilibrium point and can exhibit hyperchaotic characteristics, under some parameter space. The system has better dynamic characters represented by calculation of the Lyapunov exponents, phase planes, and visual 0–1 test diagram. In this study, a novel image encryption algorithm is employed based on the new dynamic system, Zigzag transform, and DNA operation. Based on the improved Zigzag transformation, the plain image is block-scrambled, and DNA encoded with the treated chaotic sequences. The transformation efficiency is improved by combining multiple images at the same time. Numerical analysis has been carried out; the results show that our algorithm achieves much better performance in security, i.e., with enhanced pseudo-randomness, higher key sensitivity, weak correlation, fairly large key space, higher security, and a stronger ability to resist various attacks. Through visual analysis, the algorithm is deemed safe and effective for digital images.

Chronic urticaria (CU) is a debilitating skin disease that lasts for more than 6 weeks with wheals and/or angioedema, including chronic spontaneous urticaria (CSU) and chronic inducible urticaria (CIndU). In China, the prevalence of this disease is high, more than 1%, and on the rise. CU has a major impact on the quality of life (QoL) of patients who frequently experience sleep disturbance, depression, and anxiety. Nearly one-third of patients with CSU, in China, are resistant to second-generation H1-antihistamines (sgAHs), even at a fourfold dose (second line; off-label). Omalizumab is approved for the treatment of CSU treatment in Europe and shows remarkable efficacy and safety. In China, regulatory approval for the use of omalizumab is pending, and its use in clinical practice varies widely. Consensus on omalizumab CU treatment in China is urgently needed. The aim of this article is to propose a practical omalizumab treatment algorithm for the management of antihistamine-resistant CSU and CIndU in adults and special population including children and adolescents, and pregnant or breast feeding women, to guide daily clinical practice in China. In the development of this consensus, an expert group including mainly dermatologists, allergists, but also pulmonologists, ENTs, immunologists, and pediatricians in Allergic Disease Prevention and Control Committee, Chinese Preventive Medicine Association, reviewed the existing evidence and developed consensus on the use of omalizumab in CU patients from China. The goal of this consensus is to assist clinicians in making rational decisions in the management of refractory CU with omalizumab. The key clinical questions covered by the treatment algorithm are: 1) Omalizumab treatment routine strategy in both CSU and CIndU patients; 2) Recommended dose and treatment duration for different age stratification; 3) Treatment duration for CU patients with other allergic comorbidities; 4) Recommendation on omalizumab stopping strategy.

Background: Deep learning has the potential to improve diagnostic accuracy and efficiency in medical image recognition. In the current study, we developed a deep learning algorithm and assessed its performance in discriminating melanoma from nevus using whole-slide pathological images (WSIs). Methods: The deep learning algorithm was trained and validated using a set of 781 WSIs (86 melanomas, 695 nevi) from PLA General Hospital. The diagnostic performance of the algorithm was tested on an independent test set of 104 WSIs (29 melanomas, 75 nevi) from Tianjin Chang Zheng Hospital. The same test set was also diagnostically classified by 7 expert dermatopathologists. Results: The deep learning algorithm receiver operating characteristic (ROC) curve achieved a sensitivity 100% at the specificity of 94.7% in the classification of melanoma and nevus on the test set. The area under ROC curve was 0.99. Dermatopathologists achieved a mean sensitivity and specificity of 95.1% (95% confidence interval [CI]: 92.0%-98.2%) and 96.0% (95% CI: 94.2%-97.8%), respectively. At the operating point of sensitivity of 95.1%, the algorithm revealed a comparable specificity with 7 dermatopathologists (97.3% vs. 96.0%, P = 0.11). At the operating point of specificity of 96.0%, the algorithm also achieved a comparable sensitivity with 7 dermatopathologists (96.5% vs. 95.1%, P = 0.30). A more transparent and interpretable diagnosis could be generated by highlighting the regions of interest recognized by the algorithm in WSIs. Conclusion: The performance of the deep learning algorithm was on par with that of 7 expert dermatopathologists in interpreting WSIs with melanocytic lesions. By pre-screening the suspicious melanoma regions, it might serve as a supplemental diagnostic tool to improve working efficiency of pathologists.

Photosynthetic hydrogen (H2 ) production by green algae has fascinated biologists and energy experts, due to the potential application of this process for renewable energy. In this study, H2 photoproduction and PSII photochemical activities were investigated in Chlorella sorokiniana exposed to simultaneous nitrogen limitation and sulfur (S-) and/ or phosphorus (P-) deprivation. Under S-deprivation, C. sorokiniana produced about 48.2 mL L-1 of H2 . Moreover, simultaneous nitrogen limitation (0.7 mM NH4 Cl) and sulfur- and/or phosphorus-deprivation significantly increased H2 production of C. sorokiniana over that of S-deprivation alone. Maximum H2 outputs of 77.3, 98.1 and 125.1 mL L-1 were obtained in the N-limited cultures exposed to P-deprivation (TAP-P), S-deprivation (TAP-S) and simultaneous S- and P-deprivation (TAP-S-P), respectively. The average rate of H2 production for the N-limited culture exposed to TAP-P, TAP-S and TAP-S-P was 1.07, 1.36 and 1.50 mL L-1 h-1, respectively. Interestingly, the H2 inducement time in the culture subjected to simultaneous N-limitation and S- and/or P-deprivation was much shorter than that of traditional S-deprivation. The photosynthetic inhibitors, 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) and 2,5-dibromo-3-methyl-6-isopropylp-benzoquinone (DBMIB) repressed H2 production in TAP-S-P (0.7 mM NH4 Cl) medium by 68.04% and 98.65%, respectively. The conditions of simultaneous N-limitation, S- and P-deprivation provided another efficient method for inducing H2 production in C. sorokiniana. In addition, we also found that two-thirds of the required electrons were generated from the splitting of H2 O in PSII and that the remaining onethird possibly came from some other substrate catabolism.

Background In some sedimentary environments, such as coastal intertidal and subtidal mudflats, sulfide levels can reach millimolar concentrations (2–5 mM) and can be toxic to marine species. Interestingly, some organisms have evolved biochemical strategies to overcome and tolerate high sulfide conditions, such as the echiuran worm, Urechis unicinctus. Mitochondrial sulfide oxidation is important for detoxification, in which sulfur dioxygenase (SDO) plays an indispensable role. Meanwhile, the body wall of the surface of the worm is in direct contact with sulfide. In our study, we chose the body wall to explore the SDO response to sulfide. Methods Two sulfide treatment groups (50 µM and 150 µM) and a control group (natural seawater) were used. The worms, U. unicinctus, were collected from the intertidal flat of Yantai, China, and temporarily reared in aerated seawater for three days without feeding. Finally, sixty worms with similar length and mass were evenly assigned to the three groups. The worms were sampled at 0, 6, 24, 48 and 72 h after initiation of sulfide exposure. The body walls were excised, frozen in liquid nitrogen and stored at −80 °C for RNA and protein extraction. Real-time quantitative RT-PCR, enzyme-linked immunosorbent assay and specific activity detection were used to explore the SDO response to sulfide in the body wall. Results The body wall of U. unicinctus consists of a rugal epidermis, connective tissue, outer circular muscle and middle longitudinal muscle. SDO protein is mainly located in the epidermis. When exposed to 50 µM sulfide, SDO mRNA and protein contents almost remained stable, but SDO activity increased significantly after 6 h (P

β-catenin is a key signaling molecule in the canonical Wnt pathway, which is involved in animal development. However, little information has been reported for β-catenin in bivalves. In the present study, we cloned a homolog of β-catenin from the scallop Chlamys farreri and determined its expression characteristics. The full-length cDNA of β-catenin was 3,353 bp, including a 2,511 bp open reading frame that encoded a predicted 836 amino acid protein. Level of the β-catenin mRNA increased significantly (P

Algae in the order Trentepohliales have a broad geographic distribution and are generally characterized by the presence of abundant β-carotene. The many monographs published to date have mainly focused on their morphology, taxonomy, phylogeny, distribution and reproduction; molecular studies of this order are still rare. High-throughput RNA sequencing (RNA-Seq) technology provides a powerful and efficient method for transcript analysis and gene discovery in Trentepohlia jolithus.Illumina HiSeq 2000 sequencing generated 55,007,830 Illumina PE raw reads, which were assembled into 41,328 assembled unigenes. Based on NR annotation, 53.28% of the unigenes (22,018) could be assigned to gene ontology classes with 54 subcategories and 161,451 functional terms. A total of 26,217 (63.44%) assembled unigenes were mapped to 128 KEGG pathways. Furthermore, a set of 5,798 SSRs in 5,206 unigenes and 131,478 putative SNPs were identified. Moreover, the fact that all of the C4 photosynthesis genes exist in T. jolithus suggests a complex carbon acquisition and fixation system. Similarities and differences between T. jolithus and other algae in carotenoid biosynthesis are also described in depth.This is the first broad transcriptome survey for T. jolithus, increasing the amount of molecular data available for the class Ulvophyceae. As well as providing resources for functional genomics studies, the functional genes and putative pathways identified here will contribute to a better understanding of carbon fixation and fatty acid and carotenoid biosynthesis in T. jolithus.

BACKGROUND: Sulfide is a common toxin to animals and is abundant in coastal and aquatic sediments. Sulfur dioxygenase (SDO) is thought to be the key enzyme involved in sulfide oxidation in some organisms. The echiuran worm, Urechis unicinctus, inhabits coastal sediment and tolerates high concentrations of sulfide. The SDO is presumably important for sulfide tolerance in U. unicinctus. RESULTS: The full-length cDNA of SDO from the echiuran worm U. unicinctus, proven to be located in the mitochondria, was cloned and the analysis of its sequence suggests that it belongs to the metallo-β-lactamase superfamily. The enzyme was produced using an E. coli expression system and the measured activity is approximately 0.80 U mg protein(-1). Furthermore, the expression of four sub-segments of the U. unicinctus SDO was accomplished leading to preliminary identification of functional domains of the enzyme. The identification of the conserved metal I (H113, H115, H169 and D188), metal II (D117, H118, H169 and H229) as well as the potential glutathione (GSH) (R197, Y231, M279 and I283) binding sites was determined by enzyme activity and GSH affinity measurements. The key residues responsible for SDO activity were identified by analysis of simultaneous mutations of residues D117 and H118 located close to the metal II binding site. CONCLUSION: The recombinant SDO from U. unicinctus was produced, purified and characterized. The metal binding sites in the SDO were identified and Y231 recognized as the mostly important amino acid residue for GSH binding. Our results show that SDO is located in the mitochondria where it plays an important role in sulfide detoxification of U. unicinctus.

The net photosynthetic rate, chlorophyll content, chlorophyll fluorescence and 820 nm transmission were investigated to explore the behavior of the photosynthetic apparatus, including light absorption, energy transformation and the photoactivities of photosystem II (PSII) and photosystem I (PSI) during senescence in the stay-green inbred line of maize (Zea mays) Q319 and the quick-leaf-senescence inbred line of maize HZ4. The relationship between the photosynthetic performance and the decrease in chlorophyll content in the two inbred lines was also studied. Both the field and laboratory data indicated that the chlorophyll content, net photosynthetic rate, and the photoactivities of PSII and PSI decreased later and slower in Q319 than in HZ4, indicating that Q319 is a functional stay-green inbred line. In order to avoid the influence of different development stages and environmental factors on senescence, age-matched detached leaf segments from the two inbred lines were treated with ethephon under controlled conditions to induce senescence. The net photosynthetic rate, light absorption, energy transformation, the activities of PSII acceptor side and donor side and the PSI activities decreased much slower in Q319 than in HZ4 during the ethephon-induced senescence. These results suggest that the retention of light absorption, energy transformation and activity of electron transfer contribute to the extended duration of active photosynthesis in Q319. Although the chlorophyll content decreased faster in HZ4, with decrease of chlorophyll content induced by ethephon, photosynthetic performance of Q319 deteriorated much more severely than that of HZ4, indicating that, compared with Q319, HZ4 has an advantage at maintaining higher photosynthetic activity with decrease of chlorophyll although HZ4 is a quick-leaf-senescence inbred line. We conclude that attention should be paid to two favorable characteristics in breeding long duration of active photosynthesis hybrids: 1) maintaining more chlorophyll content during senescence and 2) maintaining higher photosynthetic activity during the loss of chlorophyll.