Self-Healable, Self-Adhesive and Degradable MXene-Based Multifunctional Hydrogel for Flexible Epidermal Sensors.

Conductive hydrogels have garnered significant interest in the realm of wearable flexible sensors due to their close resemblance to human tissue, wearability, and precise signal acquisition capabilities. However, the concurrent attainment of an epidermal hydrogel sensor incorporating reliable self-healing capabilities, biodegradability, robust adhesiveness, and the ability to precisely capture subtle electrophysiological signals poses a daunting and intricate challenge. Herein, an innovative MXene-based composite hydrogel (PBM hydrogel) with exceptional self-healing, self-adhesive, and versatile functionality is engineered through the integration of conductive MXene nanosheets into a well-structured poly(vinyl alcohol) (PVA) and bacterial cellulose (BC) hydrogel three-dimensional (3D) network, utilizing multiple dynamic cross-linking synergistic repeated freeze-thaw strategy. The hydrogel harnesses the presence of dynamically reversible borax ester bonds and multiple hydrogen bonds between its constituents, endowing it with rapid self-healing efficiency (97.8%) and formidable self-adhesive capability. The assembled PBM hydrogel epidermal sensor possesses a rapid response time (10 ms) and exhibits versatility in detecting diverse external stimuli and human movements such as vocalization, handwriting, joint motion, Morse code signals, and even monitoring infusion status. Additionally, the PBM hydrogel sensor offers the added advantage of swift degradation in phosphate-buffered saline solution (within a span of 56 days) and H2O2 solution (in just 53 min), maintaining an eco-friendly profile devoid of any environmental pollution. This work lays the groundwork for possible uses in electronic skins, interactions between humans and machines, and the monitoring of individualized healthcare.

Node-personalized multi-graph convolutional networks for recommendation.

Graph neural networks have revealed powerful potential in ranking recommendation. Existing methods based on bipartite graphs for ranking recommendation mainly focus on homogeneous graphs and usually treat user and item nodes as the same kind of nodes, however, the user-item bipartite graph is always heterogeneous. Additionally, various types of nodes have varying effects on recommendations, and a good node representation can be learned by successfully differentiating the same type of nodes. In this paper, we develop a node-personalized multi-graph convolutional network (NP-MGCN) for ranking recommendation. It consists of a node importance awareness block, a graph construction module, and a node information propagation and aggregation framework. Specifically, a node importance awareness block is proposed to encode nodes using node degree information to highlight the differences between nodes. Subsequently, the Jaccard similarity and co-occurrence matrix fusion graph construction module is devised to acquire user-user and item-item graphs, enriching correlation information between users and between items. Finally, a composite hop node information propagation and aggregation framework, including single-hop and double-hop branches, is designed. The high-order connectivity is used to aggregate heterogeneous information for the single-hop branch, while the multi-hop dependency is utilized to aggregate homogeneous information for the double-hop branch. It makes user and item node embedding more discriminative and integrates the different nodes' heterogeneity into the model. Experiments on several datasets manifest that NP-MGCN achieves outstanding recommendation performance than existing methods.

Ecological role of reed belts in lakeside zone: Impacts on nutrient retention and bacterial community assembly during Hydrilla verticillata decomposition.

Reed belts acting as basic nutrient filters are important parts of lake buffer riparian zones. However, little is known about their impacts on nutrient release and bacterial community during plant litter decomposition. In this study, a field experiment was conducted in west-lake Taihu to monitor the changes in nutrients, bacterial enzymatic activities, and bacterial community in plant debris during Hydrilla verticillata (H. verticillata) decomposition in open water (HvC) and reed belts (HvL) area for 126 days. We found that there was lower temperature but higher nutrient concentrations in overlying water in HvL than HvC. Partial least squares path modeling revealed that environmental parameters in overlying water had important impacts on bacterial activities and nutrient release (such as alkaline phosphatase, cellulase, and soluble sugar) and therefore affected dissolved organic matter components in plant debris. According to Illumina sequencing, 46,003 OTUs from 10 dominant phyla were obtained and Shannon index was higher in HvL than HvC at the same sampling time. Neutral community model explained 49% of bacterial community variance and immigration rate by the estimate of dispersal in HvC (Nm: 27,154) and HvL (Nm: 25,765), respectively. Null model showed stochastic factors governed the bacterial community assembly in HvC (66.67%) and HvL (87.28%). TP and pH were key factors affecting the bacterial community structure at the phylum level. More hubs and complex interactions among bacteria were observed in HvL than HvC. Function analysis showed bacterial community had important role in carbon, organic phosphorus, and nitrogen removal but phosphorus-starvation was detected in debris of H. verticillata. This study provides useful information for understanding the changes in nutrients and bacterial community in litter during H. verticillata decomposition and highlights the role of reed belts on retained plant litter to protect lake from pollution.

Corin deficiency alleviates mucosal lesions in a mouse model of colitis induced by dextran sulfate sodium.

AIMS: High dietary salt consumption is a risk factor for inflammatory bowel disease (IBD). Corin is a protease that activates atrial natriuretic peptide (ANP), thereby regulating sodium homeostasis. Corin acts in multiple tissues, including the intestine. In mice, corin deficiency impairs intestinal sodium excretion. This study aims to examine if reduced intestinal sodium excretion alters the pathophysiology of IBD. MAIN METHODS: Wild-type (WT), Corin knockout (KO), and Corin kidney conditional KO (kcKO) mice were tested in a colitis model induced by dextran sulfide sodium (DSS). Effects of ANP on DSS-induced colitis were tested in WT and Corin KO mice. Body weight changes in the mice were monitored. Necropsy, histological analysis, and immunostaining studies were conducted to examine colon length and mucosal lesions. Fecal sodium levels were measured. RT-PCR was done to analyze proinflammatory genes in colon samples. KEY FINDINGS: DSS-treated Corin KO mice had an ameliorated colitis phenotype with less body weight loss, longer colon lengths, smaller mucosal lesions, lower disease scores, more preserved goblet cells, and suppressed proinflammatory genes in the colon. In longitudinal studies, the DSS-treated Corin KO mice had delayed onset of colon mucosal lesions. ANP administration lessened the colitis in WT, but not Corin KO, mice. Analyses of WT, Corin KO, and Corin kcKO mice indicated that fecal sodium excretion, controlled by intestinal corin, may regulate inflammatory responses in DSS-induced colitis in mice. SIGNIFICANCE: Our findings indicate a role of corin in intestinal pathophysiology, suggesting that reduced intestinal sodium level may offer protective benefits against IBD.

Design, synthesis and biological evaluation of the positional isomers of the galactose conjugates able to target hepatocellular carcinoma cells via ASGPR-mediated cellular uptake and cytotoxicity.

Galactose as a recognizing motif for asialoglycoprotein receptor (ASGPR) is a widely accepted vector to deliver cytotoxic agents in the therapy of hepatocellular carcinoma (HCC), however, the individual hydroxyl group of galactose (Gal) contributed to recognizing ASGPR is obscure and remains largely unanswered in the design of glycoconjugates. Herein, we designed and synthesized five positional isomers of Gal-anthocyanin Cy5.0 conjugates and three Gal-doxorubicin (Dox) isomers, respectively. The fluorescence intensity of Gal-Cy5.0 conjugates accumulated in cancer cells hinted the optimal modification sites of positions C2 and C6. Comparing to the cytotoxicity of other conjugates, C2-Gal-Dox (11) was the most potent. Moreover, Gal-Dox conjugates significantly the toxicity of Dox. A progressively lower internalization capacity and siRNA technology implied the cellular uptake and cytotoxicity directly related to the ASGPR expression level. Accordingly, position C2 of galactose may be the best substitution site via ASGPR mediation in the design of anti-HCC glycoconjugates.

Cyclic di-GMP inhibits nitrate assimilation by impairing the antitermination function of NasT in Pseudomonas putida.

The ubiquitous bacterial second messenger cyclic diguanylate (c-di-GMP) coordinates diverse cellular processes through its downstream receptors. However, whether c-di-GMP participates in regulating nitrate assimilation is unclear. Here, we found that NasT, an antiterminator involved in nitrate assimilation in Pseudomonas putida, specifically bound c-di-GMP. NasT was essential for expressing the nirBD operon encoding nitrite reductase during nitrate assimilation. High-level c-di-GMP inhibited the binding of NasT to the leading RNA of nirBD operon (NalA), thus attenuating the antitermination function of NasT, resulting in decreased nirBD expression and nitrite reductase activity, which in turn led to increased nitrite accumulation in cells and its export. Molecular docking and point mutation assays revealed five residues in NasT (R70, Q72, D123, K127 and R140) involved in c-di-GMP-binding, of which R140 was essential for both c-di-GMP-binding and NalA-binding. Three diguanylate cyclases (c-di-GMP synthetases) were found to interact with NasT and inhibited nirBD expression, including WspR, PP_2557, and PP_4405. Besides, the c-di-GMP-binding ability of NasT was conserved in the other three representative Pseudomonas species, including P. aeruginosa, P. fluorescens and P. syringae. Our findings provide new insights into nitrate assimilation regulation by revealing the mechanism by which c-di-GMP inhibits nitrate assimilation via NasT.

The phosphodiesterase DibA interacts with the c-di-GMP receptor LapD and specifically regulates biofilm in Pseudomonas putida.

The ubiquitous bacterial second messenger c-di-GMP is synthesized by diguanylate cyclase and degraded by c-di-GMP-specific phosphodiesterase. The genome of Pseudomonas putida contains dozens of genes encoding diguanylate cyclase/phosphodiesterase, but the phenotypical-genotypical correlation and functional mechanism of these genes are largely unknown. Herein, we characterize the function and mechanism of a P. putida phosphodiesterase named DibA. DibA consists of a PAS domain, a GGDEF domain, and an EAL domain. The EAL domain is active and confers DibA phosphodiesterase activity. The GGDEF domain is inactive, but it promotes the phosphodiesterase activity of the EAL domain via binding GTP. Regarding phenotypic regulation, DibA modulates the cell surface adhesin LapA level in a c-di-GMP receptor LapD-dependent manner, thereby inhibiting biofilm formation. Moreover, DibA interacts and colocalizes with LapD in the cell membrane, and the interaction between DibA and LapD promotes the PDE activity of DibA. Besides, except for interacting with DibA and LapD itself, LapD is found to interact with 11 different potential diguanylate cyclases/phosphodiesterases in P. putida, including the conserved phosphodiesterase BifA. Overall, our findings demonstrate the functional mechanism by which DibA regulates biofilm formation and expand the understanding of the LapD-mediated c-di-GMP signaling network in P. putida.

IGF2BP3-mediated regulation of GLS and GLUD1 gene expression promotes treg-induced immune escape in human cervical cancer.

This study aimed to investigate the impact of IGF2BP3, a well-known m6A modification-related protein, on the metabolic and immune microenvironment of human cervical cancer. Bioinformatics analysis was performed to analyze the expression of IGF2BP3 in various databases, and its findings were validated using human cervical cancer tissue microarrays. We conducted a study to investigate the impact of IGF2BP3 on glutamine metabolism in cervical cancer cells through the application of metabolomics and metabolic flow analysis. Additionally, we explored how cervical cancer cells promote immune escape by secreting glutamine-derived lactate in a 3D culture setting. To identify the specific targets of IGF2BP3 that influence glutamine metabolism in cervical cancer, we employed RIP-seq analysis. IGF2BP3 exhibited high expression levels in multiple cervical cancer datasets, and its expression was significantly associated with the prognosis of cervical cancer patients. In mixed 3D cell cultures of cervical cancer and T cells, IGF2BP3 was found to enhance glutamate and glutamine metabolism in cervical cancer cells by up regulating the expression of GLS and GLUD1 genes. Moreover, it influenced the differentiation of Treg cells by promoting lactate production and secretion in cervical cancer, leading to immune escape. Mechanistic analysis revealed that IGF2BP3 stabilized the mRNA of GLS and GLUD1 genes through m6A modification, thereby facilitating glutamate and glutamine metabolism in cervical cancer cells and regulating lactate production. Additionally, we investigated the correlation between GLS, GLUD1 protein expression, and IGF2BP3 expression in human cervical cancer through multicolor immunofluorescence staining. The relevance of IGF2BP3 in the context of Treg cell-associated immune escape in cervical cancer was also confirmed. IGF2BP3 exhibits high expression in human cervical cancer and plays a crucial role in stabilizing the mRNA of GLS and GLUD1 genes, key metabolic enzymes in glutamate and glutamine metabolism, through m6A modification. This process leads to immune escape in cervical cancer by promoting lactate production and secretion.

First report of powdery mildew caused by Podosphaera fusca on Coreopsis tinctoria in China.

Coreopsis tinctoria is an annual herb and commonly cultivated in gardens due to its attractive flowers, its capitula also have been used as a traditional medicine in China, Asia, North America and Europe (Shen et al. 2021). In June 2023, severe powdery mildew infection was observed on C. tinctoria in a hillside near headwork of the middle route of the South to North Water Diversion Project (32°40'55''N, 111°41'59''E). Abundant irregular white spots were found on adaxial surface of the leaves and tender stems. Approximately 75% of the observed C. tinctoria plants showed these signs and symptoms. Generative hyphae were thin-walled, smooth or almost so, and 5 to 9 µm wide. Conidiophores were unbranched, straight, 80.5 to 162.5 × 9.3 to 12.9 µm (n=25), and produced one to three immature conidia. Foot-cells of conidiophores were cylindrical, 38.5 to 62.3 µm (n=20) long. Conidia were ellipsoid to ovoid, 25.1 to 31.9 × 15.2 to 19.5 µm (n=30). The morphological characteristics of asexual structures corresponded to Podosphaera sp. (Braun and Cook 2012). For further identification, genomic DNA was extracted directly from the mycelia and conidia using Chelex 100 (Sigma Aldrich, Shanghai, China). The internal transcribed spacer (ITS) regions and 28S large subunit (LSU) of ribosomal DNA from the specimen (CT2302) were amplified using the primers ITS1/ITS4 (expected amplicon size 566 bp) (White et al. 1990) and NL1/NL4 (expected amplicon size 618 bp) (Baten et al. 2014), respectively. The sequences of ITS (GenBank accession no. OR649304) and LSU (GenBank accession no. OR649305) showed 99.63% and 100% identity values to the Podosphaera fusca isolate HMNWAFU-CF2012074 in the NCBI database (KR048109 for ITS and KR048178 for LSU), respectively. Phylogenetic analyses based on the combined ITS and LSU sequences using MEGA 7.0 software indicated that CT2302 formed a monophyletic clade together with isolates of P. fusca. Therefore, this fungus was identified as P. fusca based on the morphological and molecular characteristics. Pathogenicity tests were performed by gently pressing the infected leaves onto 15 young leaves of five healthy plants and three noninoculated plants were used as controls. All plants were maintained in a greenhouse (25℃ and 70% relative humidity). Powdery mildew symptoms similar to those of originally diseased plants were observed on all inoculated leaves after 12 days, whereas no symptoms were observed on the control leaves. Powdery mildew caused by P. fusca (previously Sphaerotheca fusca) on C. tinctoria has been reported in Russia, Poland, Korea, Romania and Ukraine (Cho and Shin 2004; Rusanov and Bulgakow 2008). To our knowledge, this is the first report of P. fusca on C. tinctoria in China. The identification of P. fusca as the causal agent on C. tinctoria is critical to the prevention and control of this disease in the future.

Alterations of brain activity in patients with alcohol use disorder: a resting-state fMRI study.

BACKGROUND: Alcohol use disorder (AUD) has a negative impact on one's health and wastes a lot of societal resources since it damages one's brain tissue. Yet the knowledge of the neural mechanisms underlying alcohol addiction still remains limited. This study aims to investigate the neural mechanisms underlying alcohol addiction by using voxel-wise binarized degree centrality (DC), weighted DC and functional connectivity (FC) methods to analyze brain network activity in individuals with AUD. METHODS: Thirty-three AUD patients and 29 healthy controls (HC) participated in this study. Binarized and weighted DC approach coupled with a second seed-based FC algorithm was used to assess the abnormal intrinsic hub features in AUD. We also examined the correlation between changes in functional network nodes and the severity of alcohol dependence. RESULTS: Thirty AUD patients and 26 HC were retained after head motion correction. The spatial distribution maps of the binarized DC and weighted DC for the AUD and HC groups were roughly similar. In comparison to HC, the AUD group had decreased binarized DC and decreased weighted DC in the left precentral gyrus (PreCG) and the left inferior parietal lobule (IPL). Significantly different brain regions in the DC analysis were defined as seed points in the FC analysis. Compared with HC, changes in FC within the right inferior temporal gyrus (ITG), right middle temporal gyrus (MTG), left dorsolateral superior frontal gyrus (SFGdor), bilateral IPL, left precuneus (PCUN), left lingual gyrus (LING), right cerebellum_crus1/ITG/inferior occipital gyrus (IOG) and right superior parietal gyrus (SPG) were observed. The correlation analysis revealed that FC of right MTG-right PreCG was negatively correlated with MAST scores, and FC of right IPL-left IPL was positively correlated with ADS scores. CONCLUSIONS: Alcohol use disorder is associated with aberrant regional activities in multiple brain areas. Binarized DC, weighted DC and FC analyses may be useful biological indicators for the detection of regional brain activities in patients with AUD. Intergroup differences in FC have also been observed in AUD patients, and these variations were connected to the severity of the symptoms. The AUD patients with lower FC value of the right IPL - left IPL has a lighter dependence on alcohol. This difference in symptom severity may be a compensation for cognitive impairment, indicating a difference in pathological pathways. Future AUD research will now have a fresh path thanks to these discoveries.

Activity-based locomotor training: improving the movement in children with spinal cord injury.

OBJECTIVE: The objective of this study was to investigate the effects of activity-based locomotor training (ABLT) on motor function and walking ability in children with spinal cord injury (SCI). MATERIALS AND METHODS: The Chinese National Knowledge Infrastructure, WanFang, VIP, PubMed, and Web of Science databases were searched for related studies, with two reviewers subsequently evaluating the literature quality using the Cochrane Handbook. RESULTS: A total of 11 studies were eligible, while only one met the ABLT standard program criteria. Overall, ABLT significantly improved the lower limb motor function, increased walking speed and distance, and improved the daily living ability of children with SCI. CONCLUSIONS: The ABLT strategy is of great significance to the motor function and walking ability of children with SCI. At present, there exist few studies on the application of ABLT for pediatric SCI. Further control studies with a larger sample size are required to improve the ABLT program guidelines for children with SCI.

OBJETIVO: Discuta el impacto del entrenamiento ejercicio basado en la actividad en la lesión de la médula espinal en la función de movimiento de los niños y la capacidad de caminar. MATERIALS Y MÉTODOS: Según China Zhiwang, Wanfang, VIP, PubMed, Science Network y otros documentos relacionados como fuente de datos. Dos revisores usan calidad de evaluación manual de Cochrane. RESULTADOS: Un total de 11 estudios cumplen con las condiciones. Solo hay un estudio que cumple con los proyectos estándar de ABLT. General, ABLT mejora significativamente la función de los niños con lesiones de la médula espinal, aumenta la velocidad y la distancia de caminar y mejora la capacidad de la vida diaria. CONCLUSIÓN: La estrategia ABLT es de gran importancia para la función de movimiento de los niños de la médula espinal y la capacidad de caminar. En la actualidad, ABLT tiene menos investigación en lesión pediátrica de la médula espinal. Es necesario mostrar la cantidad de muestra y controlar la investigación para mejorar las pautas del plan ABLT para el daño de la médula espinal a los niños.

Paraventricular Mast Cell-Derived Histamine Activates CRH Neurons to Mediate Adult Visceral Hypersensitivity Induced by Neonatal Maternal Separation.

Neonatal maternal separation (NMS) is an early-life stress (ELS) that can result in adult visceral hypersensitivity, which is usually manifested as chronic visceral pain. Although mast cells and corticotropin-releasing hormone (CRH) neurons are involved in stress response, whether there is an interaction between mast cells and CRH neurons in hypothalamic paraventricular nucleus (PVN) during the ELS-induced visceral hypersensitivity remains elusive. Herein, we established an NMS model by separating neonatal mice from their mothers, and observed that these mice presented visceral hypersensitivity in adulthood, as indicated by elevated abdominal withdrawal reflex and lowered visceral pain threshold. The NMS-induced adult visceral hypersensitivity was accompanied by activation of mast cells and CRH neurons in PVN. Also, NMS increased the histamine content (an inflammatory mediator mainly released by mast cells) and histamine H2 receptor (H2R) expression of CRH neurons in PVN. Remarkably, intra-PVN administration with mast cell stabilizer attenuated the NMS-induced CRH neuronal activation and adult visceral pain, while histamine administration showed the opposite effects. Moreover, intra-PVN injection with H2R antagonist alleviated the NMS-induced CRH neuronal activation, PKA and CREB phosphorylation, and importantly, adult visceral pain. Together, our findings revealed a role of an interaction between paraventricular mast cells and CRH neurons in NMS-induced adult visceral hypersensitivity, thereby providing a perspective for the management of visceral pain.

Effect of adding hip exercises to general rehabilitation treatment of knee osteoarthritis on patients' physical functions: a randomized clinical trial.

BACKGROUND: Hip adductor and abductor strength were both reduced in KOA patients. But to date, most of the researches have only focused on quadriceps combined with hip abductor strengthening versus quadriceps strengthening. OBJECTIVE: The aim of the study is to evaluate the effect of adding hip abductor and adductor strengthening to quadriceps strengthening on lower limb strength, knee pain and physical function in patients with medial compartmental knee osteoarthritis. METHODS: In this study, 42 participants, were randomly divided into two groups: the general treatment group (GT group) and the added-hip-exercise group (AH group). All participants were given a general rehabilitation treatment. The AH group performed hip abductor and adductor strengthening in addition to the general rehabilitation treatment. Knee and hip muscle strength, Five Times Sit-to-Stand Test (FTSST), the Timed Up and Go Test (TUGT), Numerical Rating Scale (NRS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores were assessed at baseline and 6 weeks. A two-sided 2-sample unpaired t test was performed to compare the difference in mean change scores between AH and GT groups. RESULTS: Finally, 36 participants completed the study: both groups consist of 18 participants. In the per-protocol analysis, the AH group had a greater improvement in knee extension strength (mean changes, 7.84 versus 36.48; P < 0.001) and hip abduction strength (mean changes, 5.05 versus 26.62; P = 0.001) than the control group. Similarly, the AH group had a greater improvement in the FTSST time (mean changes, 0.40 s versus 3.57 s; P < 0.001) and the TUFT time (mean changes, 0.18 s versus 1.67 s; P = 0.002) than the GH group. No statistical difference was found in the change of WOMAC pain scores and NRS between the 2 groups. CONCLUSIONS: Older adults with knee OA in the AH group had superior muscle strength, symptoms and daily activity performance at the 6th week than those in the GT group. And adding hip exercises could expedite improvement of pain at the 2th week, but not at the 6th week. TRIAL REGISTRATION: Clinical trial registration numbers and date of registration: ChiCTR-IOR-16009124, Registered 30 August 2016.

Estimating the impact of vadose zone heterogeneity on agricultural managed aquifer recharge: A combined experimental and modeling study.

Agricultural managed aquifer recharge (Ag-MAR) is a promising approach to replenish groundwater resources using flood water and cropland as spreading grounds. However, site selection, particularly the layering of sediment deposits in the subsurface, can greatly influence Ag-MAR efficacy as it controls water flow and solute transport in the vadose zone. In this study, we use the HYDRUS-1D software to simulate water flow and solute transport from the land surface to the groundwater table in three vadose zone profiles (LS, MS, HS) characterized by differing fractions of sand (44 %, 47 %, and 64 %). For each profile, the single- and dual-porosity models (i.e., considering or not nonequilibrium water flow and solute transport) were calibrated using observed surface ponding, soil water content, and KBr breakthrough data. Water flow and bromide transport in the profile with the lowest sand fraction (LS) were best captured using the model that considered both preferential flow and nonequilibrium bromide transport. Water flow and bromide transport in the profile with the highest sand fraction (HS) was best simulated with the model that considered preferential flow and equilibrium bromide transport. Uniform water flow and nonequilibrium bromide transport provided the best fit for the third profile (MS). The degree of preferential flow was highest in the profile with the largest sand fraction (HS), which also showed the largest flow velocities compared to the profiles with lower sand amounts (LS and MS). Preferential flow did not significantly impact the overall water balance (within 3 %), but caused a significant decrease in vadose zone travel times (bromide) by up to 38 %, relative to a single-porosity model fit. Recharge efficiency varied between 88 % and 90 %, while the average travel times from the soil surface to groundwater varied up to 119 % (from 3.6 to 7.9 days) between the three sites. This study demonstrates that similar recharge efficiency can be achieved at sites with differing soil texture profiles, but subsurface heterogeneity can substantially affect contaminant transport processes and their travel times.

Safety analysis of a live attenuated mumps vaccine in healthy adolescents in China: A phase 4, observational, open-label trial.

Mumps is an acute infectious disease, which was well controlled in the past, but recently it has resurged in some areas. This study aimed to evaluate the safety profile of the live attenuated mumps vaccine after large-scale vaccination. We conducted an observational, open-label phase 4 trial in Shaanxi, China from October 2020 to March 2021. Eligible participants were freshmen of junior high school who were not above 14 years old. Adverse events following immunization (AEFI) monitoring was carried out by active and passive surveillance. Safety follow-ups were conducted during the study participation. Overall, 10057 subjects were enrolled in the active surveillance analysis. A total of 214 subjects reported adverse reactions with an incidence of 2.13% (214/10057). Most adverse reactions were grade 1, and the incidence of grade 1 adverse reactions was 1.44% (145/10057); 0.60% for grade 2 (60/10057); and 0.09% for grade 3 (9/10057). The majority of adverse reactions were solicited (1.73%, 174/10057). Injection-site pain was the most frequently reported local adverse reaction (0.71%, 71/10057), followed by redness (0.29%, 29/10057). The most common systemic adverse reactions were nausea (0.19%, 19/10057) and fever (0.16%, 16/10057). For passive AEFI surveillance, 57 AEFI cases were reported, with an incidence of 19.28/100000 (57/287608). And most AEFI cases were common adverse reactions (66.67%, 38/57). In total, the live attenuated mumps vaccine evaluated in this trial has a favorable safety profile and can be used for large-scale inoculation.

Corin deficiency impairs cardiac function in mouse models of heart failure.

Introduction: Corin is a protease in the natriuretic peptide system. Deleterious CORIN variants are associated with hypertension and heart disease. It remains unclear if and to what extent corin deficiency may contribute to heart failure (HF). Methods: Corin knockout (KO) mice were used as a model. Cardiac function was assessed by echocardiography and tissue analysis in Corin KO mice at different ages or subjected to transverse aortic constriction (TAC), which increased pressure overload. Heart and lung tissues were analyzed for cardiac hypertrophy and lung edema using wheat germ agglutinin, Sirius red, Masson's trichrome, and Prussian blue staining. Recombinant corin was tested for its effect on cardiac function in the TAC-operated Corin KO mice. Selected gene expression in the heart was examined by RT-PCR. ELISA was used to analyze factors in plasma. Results: Corin KO mice had progressive cardiac dysfunction with cardiac hypertrophy and fibrosis after 9 months of age, likely due to chronic hypertension. When Corin KO mice were subjected to TAC at 10-12 weeks of age, cardiac function decreased more rapidly than in similarly treated wild-type mice. When the TAC-operated Corin KO mice were treated with recombinant corin protein, cardiac dysfunction, hypertrophy, and fibrosis were ameliorated. The corin treatment also decreased the gene expression associated with cardiac hypertrophy and fibrosis, increased plasma cGMP levels, lowered plasma levels of N-terminal pro-atrial natriuretic peptide, angiotensin II, and aldosterone, and lessened lung edema in the Corin KO mice subjected to TAC. Conclusion: Corin deficiency impairs cardiac function and exacerbates HF development in mice. Corin protein may be used to reduce cardiac hypertrophy and fibrosis, suppress the renin-angiotensin-aldosterone system, and improve cardiac function in HF.

Antibacterial activities of anthraquinones: structure-activity relationships and action mechanisms.

With the increasing prevalence of untreatable infections caused by antibiotic-resistant bacteria, the discovery of new drugs from natural products has become a hot research topic. The antibacterial activity of anthraquinones widely distributed in traditional Chinese medicine has attracted much attention. Herein, the structure and activity relationships (SARs) of anthraquinones as bacteriostatic agents are reviewed and elucidated. The substituents of anthraquinone and its derivatives are closely related to their antibacterial activities. The stronger the polarity of anthraquinone substituents is, the more potent the antibacterial effects appear. The presence of hydroxyl groups is not necessary for the antibacterial activity of hydroxyanthraquinone derivatives. Substitution of di-isopentenyl groups can improve the antibacterial activity of anthraquinone derivatives. The rigid plane structure of anthraquinone lowers its water solubility and results in the reduced activity. Meanwhile, the antibacterial mechanisms of anthraquinone and its analogs are explored, mainly including biofilm formation inhibition, destruction of the cell wall, endotoxin inhibition, inhibition of nucleic acid and protein synthesis, and blockage of energy metabolism and other substances.

A Review on Edible Fungi-Derived Bioactive Peptides: Preparation, Purification and Bioactivities.

Edible fungi bioactive peptides (BAPs) are extracted from fruiting bodies and the mycelium of edible fungus. They have various physiological functions such as antioxidant activity, antihypertensive activity, and antibacterial activity. In this paper, the preparation and purification methods of edible fungus BAPs were reviewed, their common biological activities and structure-activity relationships were analyzed, and their application prospects were discussed.

Garlic essential oil supplementation modulates colonic microbiota compositions and regulates immune response in weaned piglets.

The objective of this study was to investigate the colonic microbiome compositions and immune response and reveal their correlations in weaned piglets fed with garlic essential oil (GEO). Twelve 21-day-old crossbred piglets with the same parity and similar weight (BW = 7.07 ± 0.37 Kg) were randomly divided into control and experimental groups based on BW and sex, which fed either a basal diet (CON group), or a basal diet supplemented with 1.5 g/kg GEO (GEO group). UHPLC-QE-MS showed the main component of GEO were belonged to carbohydrates, organic acid, flavonoids, phenylpropanoids and terpenoids. GEO decreased serum IL-1ß, IL-8 content and the down-regulated mRNA expression of IFN-γ, TLR2 in jejunal mucosa but increased serum IgG, IL-4 content and up-regulated the mRNA expression of IL-4, IL-1ß, TNF-α in ileal mucosa. What's more, the metagenomic analysis demonstrated that GEO increased the abundance of Bacteroidetes, Euryarchaeota and Spirochaetes, while decreased the abundance of Firmicutes and Actinobacteria at Phylum level and Selenomonas_boris, Selenomonadaceae_bacterium_DSM_108025, Clostridiales_bacterium and Phascolarctobacterium_succinatutens at species level. Notably, the main function pathway of virulence factor (VFDB) enriched in GEO group were Fibronection-binding protein, Zn++ metallophrotease and Capsular polysaccharide, while the main function pathway of VFDB enriched in CON group were heme biosynthesis, Lap and FeoAB. Spearman correlation analysis indicated the Spirochaetes had a positive association with IL-6 and IL-4. Acinobacteria was positively correlated with IL-1ß, while negative with the IL-6; In addition, Euryarchaeota had a positive correlation with IL-4, but a negative correlation with IL-1ß; Tenericutes was negative with IL-8; Phascolarcolarctobacterium_succinatutens and was negative with IL-6; Ruminococcaceae_bacterium was negative with TNF-α. While Selenomonadaceae_bacterium_DSM_108025 had a positive correlation with IL-8. In conclusion, our results uncovered that immune regulation effects of GEO may be associated with the microbiome compositions in response to GEO.

Effects of cold isostatic press pretreatment of rice straw on microstructure and efficiency of anaerobic digestion for methane production.

In this study, rice straw was pretreated using by cold isostatic pressure to disrupt its microstructure and improve the performance of anaerobic digestion, and the optimal process parameters were optimized using the response surface methodology. The results showed that cold isostatic pressure pretreatment under optimal conditions (pressure of 400 MPa and holding time of 9 min) was effective in disrupting the structure of rice straw and improving its biodegradability. The cumulative methane production of the cold isostatic pressure pretreatment group increased by 76% compared to the untreated group. In addition, microbial community analysis showed that the relative abundance of Firmicutes, Halobacterota, DMER64 and Methanosaeta was higher in groups pretreated with cold isostatic pressure than in untreated groups. This study demonstrated the potential of pretreatment of rice straw with cold isostatic pressure to increase methane production during anaerobic digestion.