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The gut microbiota, a pivotal component of the intestinal mucosal barrier, is critical for host resistance to enteric pathogen infection. Here, we report a novel function of the potentially probiotic Lactococcus garvieae strain LG1 ( L. garvieae strain LG1) in maintaining intestinal mucosal barrier integrity and protecting against foodborne Clostridium perfringens ( C. perfringens ) infection. L. garvieae was isolated from the intestinal contents of Chinese Mongolian sheep (MS) and exhibited potential probiotic properties. In a C. perfringens enterocolitis model, L. garvieae- pretreated mice were less susceptible to C. perfringens infection compared with Phosphate buffered solution (PBS) - pretreated mice, which manifested as higher survival rates, lower pathogen loads, less weight loss, mild clinical symptoms and intestinal damage, and minor inflammation. Further mechanistic analysis showed that L. garvieae could ameliorate the disruption of intestinal permeability and maintain the integrity of the intestinal mucosal barrier by promoting the expression of tight junction proteins and mucoproteins. Moreover, L. garvieae was also able to facilitate antimicrobial peptide expression and ameliorate dysbiosis of the gut microbiota caused by C. perfringens . Together, these findings highlight the prospect of immunomodulatory potentially probiotic L. garvieae and might offer valuable strategies for prophylaxis and/or treatment of pathogenic C. perfringens mucosal infection., Importance: C. perfringens necrotic enteritis leads to losses of about US $2 billion to the poultry industry worldwide every year. Worse, US Centers for Disease Control and Prevention (CDC) has estimated that C. perfringens causes nearly 1 million foodborne illnesses in the United States annually. Nowadays, the treatment recommendation is a combination of a broad-spectrum synergistic penicillin with clindamycin or a carbapenem, despite growing scientific concern over antibiotic resistance. The global understanding of the gut microbiome for C. perfringens infection may provide important insights into the intervention. L. garvieae originated from Mongolian sheep intestine, exhibited potentially probiotic properties, and was able to limit C. perfringens enterocolitis and pathogenic colonization. Importantly, we found that L. garvieae limits C. perfringens invasion via improving intestinal mucosal barrier function. Also, L. garvieae alleviates C. perfringens -induced gut microbiota dysbiosis. It allowed us to convince that utilization of probiotics to promote protective immunity against pathogens infection is of pivotal importance., Competing Interests: The authors declare no conflict of interest.

Wild giant pandas are inherently solitary creatures, however, the ex-situ conservation efforts significantly alter the living circumstances of their captive counterparts. Following the breeding period, giant pandas in captivity may be maintained in social groups. Currently, there is a lack of research on the effects of group housing on the physiology, behavior, and gut microbiota of captive giant pandas. This study divided six captive giant pandas into two groups following the breeding period. By comparing the behavior, physiology, and microorganisms of the two groups, we aim to investigate the behavioral responses and physiological adaptation mechanisms exhibited by captive giant pandas in a "group living" state. Our findings indicate that sub-adult giant pandas housed in group settings exhibit a significantly longer duration of playing behavior (including interactive and non-interactive play) compared to their counterparts housed separately ( p < 0.001) while also demonstrating a significantly lower duration of stereotyped behavior than their separately housed counterparts. Additionally, an analysis of urine cortisol and heart rate variability between the two groups revealed no significant differences. Simultaneously, the group housing strategy markedly elevated the β diversity of gut microbiota in sub-adult giant pandas. In conclusion, the group-rearing model during the sub-adult stage has been shown to significantly alter the behavioral patterns of captive giant pandas. In conclusion, within the present captive setting, the group-rearing approach during the sub-adult stage proved to be less distressing for adult captive giant pandas.

Background: This study aims to explore the efficacy of Relaxation Response Meditation Training (RRMT) on elderly individuals with different levels of vividness of visual imagery., Methods: In this randomized controlled, double-blind, multi-center clinical trial, we recruited a total of 136 elderly individuals who were over 60 years with nonorganic sleep disorders to participate in a 4-week RRMT intervention from October 2020 to October 2022. The intervention occurred twice a week, totaling eight times. These individuals were divided into high and low groups based on the vividness of visual imagery, and then randomly assigned to either the control or intervention groups, as follows: low-visualizers intervention group (LI group); low-visualizers control group (LC group); high-visualizers intervention group (HI group); high-visualizers control group (HC group). Their social and psychological parameters were assessed before and after the intervention by the Pittsburgh Sleep Quality Index (PSQI), the Revised Piper's fatigue scale (RPFS), General well-being scale (GWB), and Satisfaction rating. The alpha waves of patients were also collected through electroencephalogram to assess their level of relaxation., Results: Compared to the LI group, the HI group had a greater reduction rate in the PSQI score [25.2 % (18.8 % to 31.7 %), P < 0∙001], shorter sleep latency (P = 0.001), lower frequency of sleep medication (P < 0.001), lower PSQI scores (P < 0.001), and higher GWB scores (P < 0.001). There were significant differences in all indicators in the HI group vs. HC group and in the LI group vs. LC group. In the first five relaxation training sessions, there was no statistically significant difference in the proportion of α waves between the LI group and the LC group; however, from the sixth session onward, we observed a statistically significant difference (t = 2.86, P = 0.019)，while The HI group and HC group showing significant differences in the first relaxation training session (t = 4.464, P < 0.001). There was a statistically significant difference in subjective satisfaction between the intervention group and the control group (x 2  = 49.605, P < 0.001)., Conclusion: In this study, we found that most elderly people benefitted from RRMT regardless of their vividness of visual imagery. However, low-visualizers experienced slower and less effective results, so these patients may benefit more from alternative approaches., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the role of autophagy, ferroptosis, and pyroptosis in the antitumour mechanism of harmine (Har) and its crosstalk in ovarian cancer. By transmission electron microscopy, we found that compared with those in the control group, the cytoplasm of human ovarian cancer cells (SKOV3) treated with Har showed increased numbers of autophagic vesicles, decreased intracellular mitochondrial volume, increased bilayer membrane density, and decreased cristae. Western blot, immunofluorescence, and monodasylcadaverine (MDC) staining all suggested that Har promoted autophagy in SKOV3 cells. LY294002 and siFOXO3 rescued the inhibition of the PI3K/AKT/mTOR/FOXO3 signalling pathway and the promotion of autophagy by Har. Additionally, the levels of ferroptosis- and pyroptosis-related proteins and the levels of Fe 2+  , glutathione (GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) suggested that Har promoted ferroptosis and pyroptosis in SKOV3 cells. Interestingly, pretreatment with chloroquine (CQ), erastin, rapamycin (Rap), or ferrostatin-1 (Fer-1) increased or reversed the ferroptosis and pyroptosis promoted by Har, respectively. In vivo, the volume of tumours in the Har group was decreased, and immunohistochemistry revealed decreased levels of Ki-67 and GPX4 and increased levels of ATG5 and NARL3. In conclusion, Har exerts its anti-ovarian cancer effect not only by promoting autophagy by regulating the PI3K/AKT/mTOR/FOXO3 signalling pathway but also by promoting ferroptosis and pyroptosis. Additionally, there is complex crosstalk between autophagy, ferroptosis, and pyroptosis in ovarian cancer., (© 2024. The Author(s).)

Toxoplasma gondii (T. gondii)-derived heat shock protein 70 (T.g.HSP70) is a toxic protein that downregulates host defense responses against T. gondii infection. T.g.HSP70 was proven to induce fatal anaphylaxis in T. gondii infected mice through cytosolic phospholipase A 2 (cPLA 2 ) activated-platelet-activating factor (PAF) production via Toll-like receptor 4 (TLR4)-mediated signaling. In this study, we investigated the effect of arctiin (ARC; a major lignan compound of Fructus arctii) on allergic liver injury using T.g.HSP70-stimulated murine liver cell line (NCTC 1469) and a mouse model of T. gondii infection. Localized surface plasmon resonance, ELISA, western blotting, co-immunoprecipitation, and immunofluorescence were used to investigate the underlying mechanisms of action of ARC on T. gondii-induced allergic acute liver injury. The results showed that ARC suppressed the T.g.HSP70-induced allergic liver injury in a dose-dependent manner. ARC could directly bind to T.g.HSP70 or TLR4, interfering with the interaction between these two factors, and inhibiting activation of the TLR4/mitogen-activated protein kinase/nuclear factor-kappa B signaling, thereby inhibiting the overproduction of cPLA 2 , PAF, and interferon-γ. This result suggested that ARC ameliorates T.g.HSP70-induced allergic acute liver injury by disrupting the TLR4-mediated activation of inflammatory mediators, providing a theoretical basis for ARC therapy to improve T.g.HSP70-induced allergic liver injury., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Conservation of genetic resources is an important way to protect endangered species. At present, mesenchymal stem cells (MSCs) have been isolated from the bone marrow and umbilical cords of giant pandas. However, the types and quantities of preserved cell resources were rare and limited, and none of MSCs was derived from female reproductive organs. Here, we first isolated MSCs from the endometrium of giant panda. These cells showed fibroblast morphology and expressed Sox2, Klf4, Thy1, CD73, CD105, CD44, CD49f, and CD105. Endometrium mesenchymal stem cells (eMSCs) of giant panda could induce differentiation into three germ layers in vitro. RNA-seq analysis showed that 833 genes were upregulated and 716 genes were downregulated in eMSCs compared with skin fibroblast cells. The results of GO and the KEGG analysis of differentially expressed genes (DEGs) were mainly focused on transporter activity, signal transducer activity, pathways regulating pluripotency of stem cells, MAPK signaling pathway, and PI3K-Akt signaling pathway. The genes PLCG2, FRK, JAK3, LYN, PIK3CB, JAK2, CBLB, and MET were identified as hub genes by PPI network analysis. In addition, the exosomes of eMSCs were also isolated and identified. The average diameter of exosomes was 74.26 ± 13.75 nm and highly expressed TSG101 and CD9 but did not express CALNEXIN. A total of 277 miRNAs were detected in the exosomes; the highest expression of miRNA was the has-miR-21-5p. A total of 14461 target genes of the whole miRNAs were predicted and proceeded with functional analysis. In conclusion, we successfully isolated and characterized the giant panda eMSCs and their exosomes, and analyzed their functions through bioinformatics techniques. It not only enriched the conservation types of giant panda cell resources and promoted the protection of genetic diversity, but also laid a foundation for the application of eMSCs and exosomes in the disease treatment of giant pandas., (© 2023. The Society for In Vitro Biology.)

Ammonium (NH 4 + ) ion as charge carrier is attracting attention in aqueous batteries. Yet, most NH 4 + host materials are still limited by the relatively low capacities. Here, we fabricated a manganese phosphate (MP-20) for NH 4 + ion storage. MP-20 displays a high capacity of 299.6 mAh g -1 at 1 A g -1 in ammonium acetate (NH 4 Ac) electrolyte, outperforming other reported NH 4 + host materials. Spectroscopy studies suggest a new NH 4 + /H + co-insertion mechanism. We surprisingly discover that the NH 4 Ac electrolyte plays an important role in improving the charge storage capability of the materials. Experimental and computational results indicate acetate ions can form coordination bonds with the Mn atoms, tailoring the electronic structure of the Mn atoms and the surrounding O atoms, and therefore facilitating the NH 4 + storage process. Our findings provide a new NH 4 + host material and propose the important role of the electrolyte-electrode coordination effect in aqueous ammonium batteries., (© 2022 Wiley-VCH GmbH.)

Mate choice was an important factor affecting the success rate of natural mating of captive giant pandas. The influencing factors and mechanisms of the mate preference of captive giant pandas were still unclear, and it was speculated that they might be related to the psychological stress caused by the long-term confined environment restricting their free choice of physiological needs. In order to test this hypothesis, this work explored the urinary metabolites of 6 adult captive male giant pandas during breeding period. Differences in metabolite levels in giant panda urine samples were analyzed via Ultra High Performance LC-MS (UHPLC/-MS) comparing preservation to loss of natural reproductive capacity and success to failure of mating choice, trying to understand the psychological feelings of captive giant pandas in the process of mate choice from the perspective of all metabolites and related biochemical pathways, and fully revealed the mechanism of decline of their natural reproductive ability. The analysis results indicated that the loss of natural mating behavior of adult captive male giant pandas might be related to the disorder of tryptophan metabolism pathway and inhibition of arginine synthesis; the reason for the failure of mating choice caused by decreased libido might be related to the temporary decrease of androgen contents caused by the down-regulated of TCA cycle function and galactose metabolic pathway. These findings not only provide that adult male giant pandas in captivity do have psychological frustration caused by the inability to freely choose their favorite mate or failure of mating preference, but also showed that the changes in stress-related metabolic pathways caused by psychological frustration were an important reason for the decline of natural mating behavior of adult captive male giant pandas., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Aqueous rechargeable Zn-manganese dioxide (Zn-MnO 2 ) hybrid batteries based on dissolution-deposition mechanisms exhibit ultrahigh capacities and energy densities due to the two-electron transformation between MnO 2 /Mn 2+ . However, the reported Zn-MnO 2 hybrid batteries usually use strongly acidic and/or alkaline electrolytes, which may lead to environmental hazards and corrosion issues of the Zn anodes. Herein, we propose a new Zn-MnO 2 hybrid battery by adding Al 3+ into the sulfate-based electrolyte. The hybrid battery undergoes reversible MnO 2 /Mn 2+ transformation and exhibits good electrochemical performances, such as a high discharge capacity of 564.7 mAh g -1 with a discharge plateau of 1.65 V, an energy density of 520.8 Wh kg -1 , and good cycle life without capacity decay upon 2000 cycles. Experimental results and theoretical calculation suggest that the aquo Al 3+ with Brønsted weak acid nature can act as the proton-donor reservoir to maintain the electrolyte acidity near the electrode surface and prevent the formation of Zn 4 (OH) 6 (SO 4 )·0.5H 2 O during discharging. In addition, Al 3+ doping during charging introduces oxygen vacancies in the oxide structure and weakens the Mn-O bond, which facilitates the dissolution reaction during discharge. The mechanistic investigation discloses the important role of Al 3+ in the electrolyte, providing a new fundamental understanding of the promising aqueous Zn-MnO 2 batteries.

Objective: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model., Methods: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17β-estradiol (E2, 50 μg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17β-estrogen (17β-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis., Results: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17β-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01)., Conclusion: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

Xanthine oxidase (XOD) and paraoxonase 1 (PON1) are important enzymes in redox reactions in vivo, and are predominantly synthesized by the liver. The aim of the present study was to investigate the redox state in nonalcoholic fatty liver disease, and determine the association between the activities of XOD and PON1 and the severity of NAFLD. Sprague‑Dawley rats were randomly divided into control, model and α‑lipoic acid (high and low dose) groups. The rats in the NAFLD model were induced by feeding a high fat diet for 12 weeks and the in vitro cell model of hepatocyte steatosis was induced by treating L‑02 cells with oleic acid for 24 h. The body weight, liver function, lipid and oxidative stress indices, and histological features of the liver were examined in the rats. Compared with the control group, the rats in the NAFLD model group showed impaired liver function, lipid disorders and damage from oxidative stress. The serum activity of XOD increased significantly from the 4th week and was markedly higher, compared with that in the control group, reaching a peak in the 12th week. The activity of PON1 was negatively correlated with that of XOD. Compared with the control cells, the activity of XOD and levels of free‑fatty acids were significantly higher, and the activity of PON1 was significantly lower in the NAFLD L‑02 cell model. All the above indicators were significantly improved by treatment with the antioxidant, α‑lipoic acid. The activities of XOD and PON1 may be promising as markers in a noninvasive approach for detecting the severity of NAFLD clinically. α‑lipoic acid had protective effects on the NAFLD rats, and the potential mechanism may be associated with the inhibition of oxidative stress and lipid peroxidation.

Objective: To investigate the local control of radiotherapy following Ivor-Lewis esophagectomy in the patients with stage IIA middle-third thoracic esophageal cancer., Methods: From June 1999 to June 2002, 125 patients with stage IIA squamous cell carcinoma of the middle-third thoracic esophagus were treated with Ivor-Lewis esophagectomy with two-fields lymphadenectomy. The survival rate was calculated by Kaplan-meier method and the difference of recurrence rate compared by chi(2) test., Results: The 3-year and 5-year survival rates were 58.4% and 43.2% in this group, respectively. Tumor recurrence occurred in 61 of the 125 patients (48.8%) within 3 years after operation. Of all cases of recurrence, 38 patients (30.4%) developed locoregional recurrence (including 5 patients with locoregional and hematogenous recurrence simultaneously). The locoregional recurrence rate of patients who received postoperative radiotherapy (20.3%) was significantly lower than that of both the group who received adjunctive chemotherapy (40.6%) and the group without adjunctive therapy (41.4%) (P < 0.05)., Conclusions: About half of the patients would develop recurrence disease within 3 years after Ivor-Lewis esophagectomy with two-fields lymph-adenectomy. Radiotherapy following Ivor-Lewis esophagectomy is an effective strategy to control local recurrence of the stage II A middle-third thoracic esophageal cancer.

Objective: To study the genotoxicity of components of diesel engine exhausts with ethanol-diesel blending fuel. To provide scientific arguments to find more economical and less polluted fuels., Methods: Ames test, comet assay and GC-MS technique were used to test the genotoxicity and 16 kinds of PAHs on diesel engine exhausts with different proportions of ethanol (E0, E5, E10, E20)., Results: Both Ames test and comet assay were positive. It shows that diesel engine exhausts can lead to mutation and DNA damage, especially in pure diesel oil. But the content of 16 kinds of PAHs and DNA damage level decreased in exhausts of E5. With the increase of ethanol proportion in diesel oil, the content of 16 kinds of PAHs and DNA damage level increased., Conclusion: Compared with pure diesel oil and high proportion of ethanol fuel, E5 can reduce the genotoxicity and the brake specific exhausts of PAHs.