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Alzheimer's disease (AD) is a progressive neurodegenerative disease for which there is a lack of effective therapeutic drugs. There is great potential for natural products to be used in the development of anti-AD drugs. P-coumaric acid (PCA), a small molecule phenolic acid widely distributed in the plant kingdom, has pharmacological effects such as neuroprotection, but its anti-AD mechanism has not been fully elucidated. In the current study, we investigated the mechanism of PCA intervention in the Aβ25–35-induced AD model using gut microbiomics and serum metabolomics combined with in vitro and in vivo pharmacological experiments. PCA was found to ameliorate cognitive dysfunction and neuronal cell damage in Aβ25–35-injected mice as measured by behavioral, pathological and biochemical indicators. 16S rDNA sequencing and serum metabolomics showed that PCA reduced the abundance of pro-inflammatory-associated microbiota (morganella, holdemanella, fusicatenibacter and serratia) in the gut, which were closely associated with metabolites of the glucose metabolism, arachidonic acid metabolism, tyrosine metabolism and phospholipid metabolism pathways in serum. Next, in vivo and in vitro pharmacological investigations revealed that PCA regulated Aβ25–35-induced disruption of glucose metabolism through activation of PI3K/AKT/Glut1 signaling. Additionally, PCA ameliorated Aβ25–35-induced neuroinflammation by inhibiting nuclear translocation of NF-κB and by modulating upstream MAPK signaling. In conclusion, PCA ameliorated cognitive deficits in Aβ25–35-induced AD mice by regulating glucose metabolism and neuroinflammation, and the mechanism is related not only to restoring homeostasis of gut microbiota and serum metabolites, but also to PI3K/AKT/Glut1 and MAPK/NF-κB signaling.

Abstract Rheumatoid arthritis (RA) is a chronic autoimmune disease of unexplained causes. Its pathological features include synovial tissue hyperplasia, inflammatory cell infiltration in joint cavity fluid, cartilage bone destruction, and joint deformation. C–C motif chemokine ligand 3 (CCL3) belongs to inflammatory cell chemokine. It is highly expressed in inflammatory immune cells. Increasingly, studies have shown that CCL3 can promote the migration of inflammatory factors to synovial tissue, the destruction of bone and joint, angiogenesis, and participate in the pathogenesis of RA. These symptoms indicate that the expression of CCL3 is highly correlated with RA disease. Therefore, this paper reviews the possible mechanism of CCL3 in the pathogenesis of RA, which may provide some new insights for the diagnosis and treatment of RA.

ObjectiveTo examine the resumption of purchase behavior and its influencing factors after food safety incidents among the residents in Shanxi province for providing evidence to the improvement of food safety risk management. MethodsA self-administered questionnaire survey was conducted among 2 275 adult residents ( ≥ 18 years) recruited in 70 districts/counties of 11 municipalities of Shanxi province using stratified random sampling from December 2020 through March 2021. ResultsOf the 1 991 participants with valid responses, 1 045 (52.5%) reported the unwillingness to resume purchase behavior after a food safety crisis in comparison to 946 (47.5%) reporting the willingness to resume purchase behavior. The results of unconditional multivariate logistic regression analysis results showed that the participants with following characteristics are more likely to resume purchase behavior after a food safety incident: male gender, with a family annual income of more than 5 000 yuan (RMB) per capita per month, suffering from chronic disease, being generally concerned about food safety, and having confidence in enterprises′ capability on food safety management; in contrast, the participants being female, with a food safety knowledge score of equal to or higher than the average score, considering a generally higher domestic food safety risk, and believing in government management on food safety were less likely to resume purchase behavior after a food safety accidents. ConclusionSlightly more than a half of adult residents in Shanxi province would resume purchase behavior after a food safety incident and the residents′ willingness to resume purchase behavior after food safety incident is mainly influenced by the consideration on domestic overall risk of unsafe food, concerns about food safety, household annual income per capita, and the confidence in government management on food safety.

Abstract Background Phospholipase C-like 1 (PLCL1), a protein that lacks catalytic activity, has similar structures to the PLC family. The aim of this research was to find the function and underlying mechanisms of PLCL1 in fibroblast-like synoviocyte (FLS) of rheumatoid arthritis (RA). Methods In this study, we first analyzed the expression of PLCL1 in the synovial tissue of RA patients and K/BxN mice by immunohistochemical staining. Then silencing or overexpressing PLCL1 in FLS before stimulating by TNF-α. The levels of IL-6, IL-1β and CXCL8 in FLS and supernatants were detected by Western Blot (WB), Real-Time Quantitative PCR and Enzyme Linked Immunosorbent Assay. We used INF39 to specifically inhibit the activation of NLRP3 inflammasomes, and detected the expression of NLRP3, Cleaved Caspase-1, IL-6 and IL-1β in FLS by WB. Result When PLCL1 was silenced, the level of IL-6, IL-1β and CXCL8 were down-regulated. When PLCL1 was overexpressed, the level of IL-6, IL-1β and CXCL8 were unregulated. The previous results demonstrated that the mechanism of PLCL1 regulating inflammation in FLS was related to NLRP3 inflammasomes. INF39 could counteract the release of inflammatory cytokines caused by overexpression of PLCL1. Conclusion Result showed that the function of PLCL1 in RA FLS might be related to the NLRP3 inflammasomes. We finally confirmed our hypothesis with the NLRP3 inhibitor INF39. Our results suggested that PLCL1 might promote the inflammatory response of RA FLS by regulating the NLRP3 inflammasomes.

Abstract Rheumatoid arthritis is a chronic systemic autoimmune disease characterized by synovial hyperplasia, inflammatory cell infiltration, and proliferation of inflammatory tissue (angiogranuloma). The destruction of joints and surrounding tissues eventually causes joint deformities and dysfunction or even loss. The S100 protein family is one of the biggest subtribes in the calcium-binding protein family and has more than 20 members. The overexpression of most S100 proteins in rheumatoid arthritis is closely related to its pathogenesis. This paper reviews the relationship between S100 proteins and the occurrence and development of rheumatoid arthritis. It will provide insights into the development of new clinical diagnostic markers and therapeutic targets for rheumatoid arthritis.

Abstract Atopic dermatitis (AD) is a common and complex skin disorder, and the 5q22.1 region had been reported to be associated with AD. To confirm the susceptibility gene for AD in the 5q22.1 region by haplotype and targeted capture sequencing. The haplotypes were reconstructed with the genotyping data of four SNPs and six deletions from 3624 Chinese Hans AD patients and 5076 controls. The targeted capture sequencing spanning 5q22.1 region was performed in the selected samples. The gene level enrichment analysis was done using loss of function variants. A total of 62 haplotypes were found, and the H15 haplotype had the strongest association with AD (P = 3.92 × 10−10, OR 0.17, 95% CI 0.09–0.32). However, no co-segregation mutation sites were found in the sequencing analysis within the 16 selected samples, while the enrichment analysis indicated that TMEM232 was significantly associated with AD (P = 7.33 × 10–5, OR 0.33, 95% CI 0.19–0.58). This study confirms previous findings that the TMEM232 gene is associated with AD by haplotype analysis and targeted capture sequencing.

Background and Objective: Opioid medications used to be the key method for the pain management after spine surgery; most of the opioids may cause many adverse reactions. The purpose of this research was to observe the role of dexmedetomidine combined with butorphanol in the pain management of patients after posterior spinal surgery.Methods: This research was conducted in the First Hospital Affiliated to Jinzhou Medical University, China from May 2018 to January 2019. Sixty patients who underwent posterior spinal surgery were equally divided into two groups randomly: Group B who received butorphanol 0.125 mg/kg and Group DB who received dexmedetomidine (DEX) 0.1 μg/kg/hour plus butorphanol 0.125 mg/kg. The patient-controlled analgesia was conducted to deliver a bolus dose of 0.5 ml. followed by an infusion of 2 ml/hour and a lockout time of 15 minutes. Heart rate, mean arterial pressure, respiration rate, pulse oxygen saturation, visual analog scale score (VAS), and Ramsay sedation score were recorded as follows: 1 hour (T1), 2 hours (T2), 6 hours (T3), 12 hours (T4), and 24 hours (T5) post‑surgery. The total number of buttons pressing of patient controlled intravenous analgesia (PCIA) and supplementary analgesic agents was observed and adverse drug reactions and total rate of patient satisfaction were evaluated statistically.Results: VAS scores at different intervals in DB group were significantly lower compared with the B group after surgery; while the score of Ramsay sedation was remarkably higher in DB group. The total number of buttons pressing of PCIA was less than that of the B group and the frequency of nausea was notably lower in DB group (p < 0.05). The total rate of satisfaction with analgesia in DB group was higher after surgery.Conclusion: DEX could enhance the analgesic effect of butorphanol after posterior spinal surgery with lesser adverse reactions

Two new ethyl maltolato coordinated mononuclear oxidovanadium(V) complexes [VOLa(emt)]·DMF (1) and [VOLb(emt)] (2), where H2La = N’-(4-bromo-2-hydroxybenzylidene)-3-hydroxybenzohydrazide, H2Lb = N’-(4-bromo-2-hydroxybenzylidene)benzohydrazide, Hemt = ethyl maltol, have been synthesized and characterized on the basis of CHN elemental analysis, FT-IR and UV-Vis spectroscopy and powder XRD analysis. Structures of the complexes were further characterized by single crystal X-ray diffraction, which indicated that the V atoms in the complexes adopt octahedral coordination. The hydrazones behave as NOO tridentate ligands. The catalytic epoxidation properties on cyclooctene of the complexes were investigated.

A variety of therapeutic methods can be used to treat keratoconus. This article provides practical information for clinicians to make the most appropriate choices by reviewing the treatment of keratoconus. Search for keywords such as “keratoconus” “contact lenses” “corneal collagen cross-linking” “Intacs(corneal ring)” “keratoplasty” “gene therapy” “irregular astigmatism” through a database. According to the related literature, the treatment methods of keratoconus are reviewed. Glasses and contact lenses can be used for early keratoconus, while bowman layer transplantation, penetrating keratoplasty(PK), deep anterior lamellar keratoplasty(DALK), conductive keratoplasty and gene therapy can be used in advanced disease. In addition, cross-linking can prevent keratoconus progression, and intrastromal corneal ring segments(ICRS)reduce refractive error for therapeutic purposes by flattening the deformed cornea. In general, the development of ophthalmic diagnostic techniques and treatments can slow the progression of keratoconus, thereby reducing the need for corneal transplantation in patients with advanced keratoconus. Choosing the right keratoconus treatment can help patients with vision recover and prevent blindness.

AIM: To investigate the correlation between retinal microstructural changes and visual function after scleral buckling and vitrectomy with rhegmatogenous retinal detachment.METHODS: Prospective clinical study was conducted. With PVR grade B-C1, 75 patients with 75 eyes of aged 15-30 years who were macular-off retinal detachment were selected. PPV was performed for posterior equatorial retinal hiatus(35 eyes, PPV group), and SB was performed for anterior equatorial retinal hiatus(40 eyes, SB group).The patients in the two groups were followed up for 6mo to observe the changes in the best corrected visual acuity(BCVA)and retinal microstructures.RESULTS: Compared with SB group, the probability of inner sensory layer/outer sensory layer and inner boundary membrane fracture after operation in PPV group was 2.812 times, with a statistically significant difference(P=0.020), and the probability of subretinal effusion was 0.115 times, with a statistically significant difference(PP=0.700)between the two groups. And with the extension of observation time, the possibility of inner sensory layer/outer sensory layer and inner boundary membrane, persistent subretinal fluid and interlayer effusion in the two groups of patients gradually decreased. After the operation, the thickness of the neurosensory retinal and outer nuclear layer in the two groups gradually increased, and BCVA gradually improved. With the prolonging of observation time, the thickness of the neurosensory retinal in SB group increased greatly, and BCVA recovered better.CONCLUSION: The integrity of the inner sensory layer/outer sensory layer and inner boundary membrane, subretinal effusion, interlaminar effusion, and the thickness of the neurosensory retinal are the key factors affecting the recovery of visual function after SB or PPV.

Gut microbial β-glucuronidase (GUS) is a potential therapeutic target to reduce gastrointestinal toxicity caused by irinotecan. In this study, the inhibitory effects of 17 natural cinnamic acid derivatives on Escherichia coli GUS (EcGUS) were characterised. Seven compounds, including caffeic acid ethyl ester (CAEE), had a stronger inhibitory effect (IC50 = 3.2–22.2 µM) on EcGUS than the positive control, D-glucaric acid-1,4-lactone. Inhibition kinetic analysis revealed that CAEE acted as a competitive inhibitor. The results of molecular docking analysis suggested that CAEE bound to the active site of EcGUS through interactions with Asp163, Tyr468, and Glu504. In addition, structure–activity relationship analysis revealed that the presence of a hydrogen atom at R1 and bulky groups at R9 in cinnamic acid derivatives was essential for EcGUS inhibition. These data are useful to design more potent cinnamic acid-type inhibitors of EcGUS.

Plant microbial diseases caused global production constraints have become one of the most challenging events, thus urgently needing to be addressed nowadays. To efficiently promote the discovery of promising antimicrobial surrogates, a type of 1,3,4-oxadiazole thioethers owning naturally bioactive thiazolium patterns was designed and fabricated. Antibacterial screening results revealed that title compounds could significantly inhibit the growth of pathogens Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri. And the related antibacterial efficacy was elevated by approximately 386-, 16-, and 24-folds comparing those of mainly used commercial agents bismerthiazol and thiodiazole copper. In vivo experiment suggested that A9 could manage rice bacterial blight with the corresponding curative and protection efficiencies of 48.01% and 50.55% at 200 μg/mL. Moreover, SEM patterns and fluorescence spectra were performed to explore the possible antibacterial mechanism. Preliminary antifungal bioassays revealed that these molecules paraded broad-spectrum inhibition effects against three tested fungal strains. Considering the simple molecular skeleton and significant biological actions, title compounds can be further explored as potential antimicrobial surrogates for managing plant bacterial and fungal diseases. Keywords: Thiazolium, 1,3,4-Oxadiazole, In vitro and in vivo bioassays, Antimicrobial

Selenoprotein V (SELENOV) is a new and the least conserved member of the selenoprotein family. Herein we generated Selenov knockout (KO) mice to determine its in vivo function. The KO led to 16–19% increases (P

Rheumatoid arthritis (RA), one of the most common autoimmune diseases, is characterized by immune cell infiltration, fibroblast-like synovial cell hyperproliferation, and cartilage and bone destruction. To date, numerous studies have demonstrated that immune cells are one of the key targets for the treatment of RA. N6-methyladenosine (m6A) is the most common internal modification to eukaryotic mRNA, which is involved in the splicing, stability, export, and degradation of RNA metabolism. m6A methylated-related genes are divided into writers, erasers, and readers, and they are critical for the regulation of cell life. They play a significant role in various biological processes, such as virus replication and cell differentiation by controlling gene expression. Furthermore, a growing number of studies have indicated that m6A is associated with the occurrence of numerous diseases, such as lung cancer, bladder cancer, gastric cancer, acute myeloid leukemia, and hepatocellular carcinoma. In this review, we summarize the history of m6A research and recent progress on RA research concerning m6A enzymes. The relationship between m6A enzymes, immune cells, and RA suggests that m6A modification offers evidence for the pathogenesis of RA, which will help in the development of new therapies for RA.

Rheumatoid arthritis (RA) is characterized by a tumor-like expansion of the synovium and subsequent destruction of adjacent articular cartilage and bone. In our previous work we showed that phosphatase and tension homolog deleted on chromosome 10 (PTEN) contributes to the activation of fibroblast-like synoviocytes (FLS) in adjuvant-induced arthritis (AIA), but the underlying mechanism is not unknown. In this study, we show that PTEN is downregulated while DNA methyltransferase (DNMT)1 is upregulated in FLS from RA patients and a rat model of AIA. DNA methylation of PTEN was increased by administration of tumor necrosis factor (TNF)-α in FLS of RA patients, as determined by chromatin immunoprecipitation and methylation-specific PCR. Treatment with the methylation inhibitor 5-azacytidine suppressed cytokine and chemokine release and FLS activation in vitro and alleviated paw swelling in vivo. PTEN overexpression reduced inflammation and activation of FLS via protein kinase B (AKT) signaling in RA, and intra-articular injection of PTEN-expressing adenovirus into the knee of AIA rats markedly reduced inflammation and paw swelling. Thus, PTEN methylation promotes the inflammation and activation of FLS in the pathogenesis of RA. These findings provide insight into the molecular basis of articular cartilage destruction in RA, and indicate that therapeutic strategies that prevent PTEN methylation may an effective treatment.

This study aims to evaluate the association between free triiodothyronine (FT3) and outcomes of coronary artery disease (CAD) patients, as well as to assess the predictive power of FT3 and related functional markers from the perspective of potential mechanism. A total of 5104 CAD patients with an average follow-up of three years were enrolled into our study. Multivariate Cox regression was used to evaluate the associations between FT3, FT4 (free thyroxin), FT3/FT4 and death, MACE. We developed and validated an age, biomarker, and clinical history (ABC) model based on FT3 indicators to predict the prognosis of patients with CAD. In the multivariable Cox proportional hazards model, FT3 and FT3/FT4 were independent predictors of mortality (Adjusted HR = 0.624, 95% CI = 0.486–0.801; adjusted HR = 0.011, 95% CI = 0.002–0.07, respectively). Meanwhile, emerging markers pre-brain natriuretic peptide, fibrinogen, and albumin levels are significantly associated with low FT3 (p < 0.001). The new risk death score based on biomarkers can be used to well predict the outcomes of CAD patients (C index of 0.764, 95% CI = 0.731–0.797). Overall, our findings suggest that low levels of FT3 and FT3/FT4 are independent predictors of death and MACE risk in CAD patients. Besides, the prognostic model based on FT3 provides a useful tool for the death risk stratification of CAD patients.

Dried ginger-aconite decoction (DAD) is a traditional Chinese medicine (TCM) formula that has been extensively used in the treatment of myocardial ischemia reperfusion injury (MI/RI). However, its specific mechanism against MI/RI has not been reported yet. Therefore, this paper studies the potential active components and mechanism of DAD against MI/RI based on network pharmacology and experimental verification. Sixteen active components of DAD were screened according to oral bioavailability and drug similarity indices. Through Cytoscape 3.7.0, a component-target network diagram was drawn, and potential active components of DAD against MI/RI were determined. Protein-protein interaction (PPI) and compound-target-pathway (C-T-P) networks were established through the software to discover the biological processes, core targets and core pathways of DAD against MI/RI. High Performance Liquid Chromatography (HPLC) analysis identified the presence of potentially active core components for network pharmacological prediction in DAD. It was found that DAD might have played a therapeutic role in anti-MI/RI by activating the PI3K/Akt/GSK-3β signaling pathway in order to reduce mitochondrial hypoxia injury and myocardial cell apoptosis. The network pharmacological prediction was validated by Hypoxia/reoxygenation(H/R) model in vitro and ligation model of the ligation of the left anterior descending branch in vivo. It was verified that DAD had activated PI3K/AKT/GSK-3β to reduce myocardial apoptosis and play a therapeutic function in MI/RI.

Neurofibromatosis (NF) is an autosomal genetic disorder for which early and definite clinical diagnoses are difficult. To identify the diagnosis, five affected probands with suspected NF from unrelated families were included in this study. Molecular analysis was performed using multigene panel testing and Sanger sequencing. Ultradeep sequencing was used to analyze the mutation rate in the tissues from the proband with mosaic mutations. Three different pathogenic variants of the NF1 gene were found in three probands who mainly complained of café-au-lait macules (CALMs), including one frameshift variant c.5072_5073insTATAACTGTAACTCCTGGGTCAGGGAGTACACCAA:p.Tyr1692Ilefs in exon 37, one missense variant c.3826C > T:p.Arg1276Ter in exon 28, and one splicing variant c.4110 + 1G > T at the first base downstream of the 3′-end of exon 30. One NF1 gene mosaic variant was found in a proband who complained of cutaneous neurofibroma with the frameshift variant c.495_498del:p.Thr165fs in exon 5, and ultradeep sequencing showed the highest mutation rate of 10.81% in cutaneous neurofibromas. A frameshift variant, c.36_39del:p.Ser12fs in exon 1 of the NF2 gene, was found in a proband who presented with skin plaques and intracranial neurogenic tumors. All of these pathogenic variants were heterozygous, one was not reported, and one not in Chinese before. This study expands the pathogenic variant spectrum of NF and demonstrates the clinical diagnosis.

The present study aimed to investigate the effects of organic acids (OA) as alternatives for antibiotic growth promoters (AGP) on growth performance, intestinal structure, as well as intestinal microbial composition and short-chain fatty acids (SCFAs) profiles in broilers. A total of 336 newly hatched male Arbor Acres broiler chicks were randomly allocated into 3 dietary treatments including the basal diet [negative control (NC)], the basal diet supplemented with 5 mg/kg flavomycin, and the basal diet supplemented with OA feed additives. Each treatment had eight replicates with 14 birds each. The results showed that AGP and OA promoted growth during day 22–42 compared with the NC group (P < 0.05). OA significantly increased the jejunal goblet cell density and ileal villus height on day 42 compared with the NC group (P < 0.05). Meanwhile, OA up-regulated the mRNA expression of jejunal barrier genes (Claudin-3 and ZO-1) relative to the NC group (P < 0.05). Significant changes of microbiota induced by the OA were also found on day 42 (P < 0.05). Several SCFAs-producing bacteria like Ruminococcaceae, Christensenellaceae, and Peptococcaceae affiliated to the order Clostridiales were identified as biomarkers of the OA group. Higher concentrations of SCFAs including formic acid and butyric acid were observed in the cecum of OA group (P < 0.05). Simultaneously, the abundance of family Ruminococcaceae showed highly positive correlations with the body weight and mRNA level of ZO-1 on day 42 (P < 0.05). However, AGP supplementation had the higher mRNA expression of Claudin-2, lower goblet cell density of jejunum, and decreased Firmicutes to Bacteroidetes ratio, suggesting that AGP might have a negative impact on intestinal immune and microbiota homeostasis. In conclusion, the OA improved growth performance, intestinal morphology and barrier function in broilers, which might be attributed to the changes of intestinal microbiota, particularly the enrichment of SCFAs-producing bacteria, providing a more homeostatic and healthy intestinal microecology.

Abstract Background In avian species, liver is the main site of de novo lipogenesis, and hepatic lipid metabolism relates closely to adipose fat deposition. Using our fat and lean chicken lines of striking differences in abdominal fat content, post-hatch lipid metabolism in both liver and adipose tissues has been studied extensively. However, whether molecular discrepancy for hepatic lipid metabolism exists in chicken embryos remains obscure. Results We performed transcriptome and proteome profiling on chicken livers at five embryonic stages (E7, E12, E14, E17 and E21) between the fat and lean chicken lines. At each stage, 521, 141, 882, 979 and 169 differentially expressed genes were found by the digital gene expression, respectively, which were significantly enriched in the metabolic, PPAR signaling and fatty acid metabolism pathways. Quantitative proteomics analysis found 20 differentially expressed proteins related to lipid metabolism, PPAR signaling, fat digestion and absorption, and oxidative phosphorylation pathways. Combined analysis showed that genes and proteins related to lipid transport (intestinal fatty acid-binding protein, nucleoside diphosphate kinase, and apolipoprotein A-I), lipid clearance (heat shock protein beta-1) and energy metabolism (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and succinate dehydrogenase flavoprotein subunit) were significantly differentially expressed between the two lines. Conclusions For hepatic lipid metabolism at embryonic stages, molecular differences related to lipid transport, lipid clearance and energy metabolism exist between the fat and lean chicken lines, which might contribute to the striking differences of abdominal fat deposition at post-hatch stages.

The objective of this study is to evaluate the effects of organic acids on piglet growth performance and health status. A total of 360 weanling pigs (5.3 ± 0.6 kg) were randomly allotted to 3 treatment groups with 12 replicates of 10 pigs/pen. Piglets were fed the same basal diet and given either water (control) or water plus 2.0 L/Ton organic acid (OA) blends, such as OA1 or OA2, respectively, for 7 weeks. Compared to the control, OA1 and OA2 improved growth performance and/or reduced the piglets’ diarrhea rate during the various periods and improved small intestinal morphology at days 14 and/or 49. OA1 and OA2 also increased serum CAT and SOD activities and/or T-AOC and, as expected, decreased MDA concentration. Moreover, at day 14 and/or day 49, OA1 and OA2 increased the jejunal mRNA levels of host defense peptides (PBD1, PBD2, NPG1, and NPG3) and tight junction genes (claudin-1) and decreased that of cytokines (IL-1β and IL-2). Additionally, the two acidifiers regulated the abundance of several cecum bacterial genera, including Blautia, Bulleidia, Coprococcus, Dorea, Eubacterium, Subdoligranulum, and YRC2. In conclusion, both of the organic acid blends improved piglet growth performance and health status, potentially by regulating intestinal redox homeostasis, immunity, and microflora.

The objectives of this study were to determine the protective effects of organic acids (OA) in broilers exposed to Salmonella Pullorum challenge at early stage and to explore the potential benefits of OA by metabolomics analysis. The treatment groups included non-challenged, S. Pullorum-challenged, challenged group supplemented with virginiamycin, challenged group supplemented with OA in drinking water, challenged group supplemented with OA in feed, and challenged group supplemented with OA in combination in drinking water and feed. Results showed that early Salmonella challenge induced an acute systemic infection of broilers in the starter phase, followed by the grower phase without triggering clinical signs. OA supplementation promoted growth during the grower phase, and while OA in water contributed more, the positive effects of OA in combination were comparable to those of virginiamycin supplementation in challenged birds. Furthermore, OA could modulate the systemic metabolic perturbation caused by challenge as it alleviated stress responses mediated by steroid hormone, potentially attenuated antioxidant or immune defense, and modified intestinal microbiota metabolism. These results show a metabolic mechanism that may partly explain the potential benefits of OA in Salmonella challenged birds, and may contribute to the use of OA to control or reduce S. Pullorum infection in farm animals.

Atopic dermatitis (AD) is a common inflammatory skin disease with high heritability. Two susceptibility loci have been confirmed in our previous AD genome-wide association study (GWAS). To look for additional genetic factors in Chinese Han ethnicity, we performed a large-scale GWAS follow-up study. Forty-nine top single nucleotide polymorphisms (SNPs) that had never been reported previously were genotyped using Sequenom Massarray system in an independent cohort, which consist of northern Chinese (1634 cases and 1263 controls) and southern Chinese (2985 cases and 9526 controls). Association analyses were performed using PLINK 2 software. Three SNPs in northern and ten SNPs in southern were found exhibiting association evidence with AD (P < 0.05). Finally, SNP rs224108 on 10q21.2 showed high significance for AD in joint analysis of GWAS and replication study (Pmeta = 4.55 × 10−9, OR = 1.21), and was confirmed as an independent genetic marker by Linkage disequilibrium calculation and conditional logistic regression analysis. Bioinformatics analysis strongly suggested that rs224108 may have the potential to alter the target gene expression through non-coding epigenetic regulation effects. Meanwhile, SNP rs11150780 on 17q25.3 was also found suggestive association with AD (Pmeta = 7.64 × 10−7, OR = 1.18). Our findings confirmed a novel susceptibility signal on 10q21.2 for AD in Chinese Han population and advanced the understanding of the genetic contribution to AD.

The objective of this study was to evaluate the efficacy of mycotoxin binders in reducing the adverse effects of co-occurring dietary aflatoxin B1 (AFB1), deoxynivalenol (DON) and ochratoxin A (OTA) on laying hens. Three hundred and sixty 26-week-old Roman laying hens were randomly allocated into four experimental groups with 10 replicates of nine birds each. The four groups received either a basal diet (BD; Control), a BD supplemented with 0.15 mg/kg AFB1 + 1.5 mg/kg DON + 0.12 mg/kg OTA (Toxins), a BD + Toxins with Toxo-HP binder (Toxins + HP), or a BD + Toxins with TOXO XL binder (Toxins + XL) for 12 weeks. Compared to the control, dietary supplementation of mycotoxins decreased (P < 0.10) total feed intake, total egg weight, and egg-laying rate, but increased feed/egg ratio by 2.5–6.1% and mortality during various experimental periods. These alterations induced by mycotoxins were alleviated by supplementation with both TOXO HP and XL binders (P < 0.10). Furthermore, dietary mycotoxins reduced (P < 0.05) eggshell strength by 12.3% and caused an accumulation of 249 μg/kg of DON in eggs at week 12, while dietary supplementation with TOXO HP or XL mitigated DON-induced changes on eggshell strength and prevented accumulation of DON in eggs (P < 0.05). Moreover, dietary mycotoxins increased relative liver weight, but decreased spleen and proventriculus relative weights by 11.6–22.4% (P < 0.05). Mycotoxin exposure also increased alanine aminotransferase activity and reduced immunoglobulin (Ig) A, IgM, and IgG concentrations in serum by 9.2–26.1% (P < 0.05). Additionally, mycotoxin exposure induced histopathological damage and reduced villus height, villus height/crypt depth, and crypt depth in duodenum, jejunum and (or) ileum (P < 0.05). Notably, most of these histological changes were mitigated by supplementation with both TOXO HP and XL (P < 0.05). In conclusion, the present study demonstrated that the mycotoxin binders TOXO HP and XL can help to mitigate the combined effects of AFB1, DON, and OTA on laying hen performance, egg quality, and health.

Purpose: To develop a multicultural nursing competence instrument for use in assessing undergraduate student nurses (SNs). Methods: This study enrolled 322 student nurses (SNs) employed at five hospitals in Hunan Province. The nurses were identified by the cluster sampling method. The items on the competence instrument were retained or deleted after analyzing their coefficient of variation, coefficient of correlation with the total score, t-test results. Reliability tests and correlation analysis were used to examine internal consistency, while exploratory factor analysis was used to determine construct validity. Results: After analyzing items, the final multicultural nursing competence instrument comprised a total of 49 items that evaluated five dimensions. The instrument showed good overall reliability (0.958), and the internal consistency of the five dimensions ranged from 0.884 to 0.952. Furthermore, the correlations among the five dimensions were statistically significant (P

In tumors associated with inflammation such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), high numbers of regulatory T cells (Tregs) are associated with both favorable and poor prognoses. The functions of Tregs in CRC remain elusive and have yet to be clearly defined. With new evidence supporting many subsets of Tregs, the research on the development and functions of these cells has begun to come to fruition. The sphingosine 1 phosphate (S1P) pathway was recently reported to regulate the development and function of regulatory T cells. This pathway may shine new light into the pleiotropic nature of these cells in cancer. In this review, we will examine current literature on the many functions of Tregs in CRC and highlight the significance of the S1P signaling pathway in Treg development/function with the implication of novel therapeutic strategies in treatment of CRC patients.

The objective of this study was to analyze the expression levels of IL-8 in serum and liver tissues from patients with chronic hepatitis B (CHB) infection and to investigate whether IL-8 may antagonize interferon-alpha (IFN-α) antiviral activity against HBV. IL-8 expression in serum was determined by enzyme linked immunosorbent assay (ELISA), and fluorescence-based quantitative real-time PCR (RT-qPCR) was used to measure IL-8 mRNA in peripheral blood mononuclear cells (PBMCs) in patients with CHB. IL-8 protein expression was detected in liver biopsy tissues by immunohistochemistry. In addition, the differences in serum IL-8 and PBMCs mRNA levels were also observed in patients with different anti-viral responses to IFN-α. Compared to normal controls, serum IL-8 protein and mRNA levels were increased in CHB patients, IL-8 levels were positively correlated with the severity of liver inflammation/fibrosis. Moreover, serum IL-8 protein and mRNA levels were positively correlated with serum alanine aminotransferase (ALT) level and negatively correlated with serum prealbumin (PA) level. IL-8 expression was mainly located in portal area of liver tissues and was increased with the severity of liver inflammation and fibrosis stage. The expression serum and mRNA levels of IL-8 in the CHB patients with a complete response to IFN-α are significantly lower than that of the patients with non-response to IFN-α treatment. It is suggested that IL-8 might play important roles in the pathogenesis of CHB. Moreover, interferon resistance may be related to the up-regulation of IL-8 expression in the patients did not respond to IFN-α treatment.

Chronic inflammation is an important risk factor for the development of colorectal cancer; however, the mechanism of tumorigenesis especially tumor progression to malignancy in the inflamed colon is still unclear. Our study shows that epithelial signal transducer and activator of transcription 3 (STAT3), persistently activated in inflamed colon, is not required for inflammation-induced epithelial overproliferation and the development of early-stage tumors; however, it is essential for tumor progression to advanced malignancy. We found that one of the mechanisms that epithelial STAT3 regulates in tumor progression might be to modify leukocytic infiltration in the large intestine. Activation of epithelial STAT3 promotes the infiltration of the CD8+ lymphocyte population but inhibits the recruitment of regulatory T (Treg) lymphocytes. The loss of Stat3 in epithelial cells promoted the expression of cytokines/chemokines including CCL19, CCL28, and RANTES, which are known to be able to recruit Treg lymphocytes. Linked to these changes was the pathway mediated by sphingosine 1-phosphate receptor 1 and sphingosine 1-phosphate kinases, which is activated in colonic epithelial cells in inflamed colon with functional STAT3 but not in epithelial cells deleted of STAT3. Our data suggest that epithelial STAT3 plays a critical role in inflammation-induced tumor progression through regulation of leukocytic recruitment especially the infiltration of Treg cells in the large intestine.

Pain memory is considered as endopathic factor underlying stubborn chronic pain. Our previous study demonstrated that electroacupuncture (EA) can alleviate retrieval of pain memory. This study was designed to observe the different effects between EA and indomethacin (a kind of nonsteroid anti-inflammatory drugs, NSAIDs) in a rat pain memory model. To explore the critical role of protein kinase A (PKA) in pain memory, a PKA inhibitor was microinjected into anterior cingulate cortex (ACC) in model rats. We further investigated the roles of the cyclic adenosine monophosphate (cAMP), PKA, cAMP response element-binding protein (CREB), and cAMP/PKA/CREB pathway in pain memory to explore the potential molecular mechanism. The results showed that EA alleviates the retrieval of pain memory while indomethacin failed. Intra-ACC microinjection of a PKA inhibitor blocked the occurrence of pain memory. EA reduced the activation of cAMP, PKA, and CREB and the coexpression levels of cAMP/PKA and PKA/CREB in the ACC of pain memory model rats, but indomethacin failed. The present findings identified a critical role of PKA in ACC in retrieval of pain memory. We propose that the proper mechanism of EA on pain memory is possibly due to the partial inhibition of cAMP/PKA/CREB signaling pathway by EA.