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Background and Objectives: Chronic active Epstein-Barr virus disease (CAEBV) is a proliferative disease of EBV + T or natural killer (NK) cells with an unclear pathogenesis. This study aimed to examine the frequency and exhaustion levels of lymphocyte subsets in patients with CAEBV to further investigate the pathogenesis., Methods: Using flow cytometry, we detected the frequency, expression levels of programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1), and EBV infection status of peripheral T subsets and NK cells in patients with CAEBV and healthy individuals., Results: 24 patients and 15 healthy individuals were enrolled in this study. Patients showed notably higher expression levels of PD-1 and PD-L1 in peripheral T subsets and NK cells compared to healthy individuals (P < 0.05). EBV + lymphocytes exhibited significantly higher PD-L1 expression levels than EBV - lymphocytes. Additionally, the frequency of effector memory T (Tem) cells was significantly increased in patients, and the PD-L1 expression level was positively correlated with the EBV load. Besides, helper T cell 2 (Th2) immune bias, also favoring EBV amplification, was found in patients, including increased Th2 cell frequency, enhanced response capacity, and elevated serum levels of associated cytokines. The distribution and PD-1 expression levels of peripheral T subsets returned to normal in patients who responded to PD-1 blockade therapy., Conclusions: The up-regulation of the PD-1/PD-L1 pathway of peripheral T and NK cells and Th2 immune predominance jointly promoted EBV replication and the development of CAEBV. PD-1 blockade therapy reduced the PD-1 expression level of lymphocytes and helped normalize the distribution of the T subsets., Competing Interests: Competing interests: The authors declare no conflict of Interest.

Hepatic ischemia/reperfusion injury (HIRI) is a common and inevitable factor leading to poor prognosis in various liver diseases, making the outcomes of current treatments in clinic unsatisfactory. Metformin has been demonstrated to be beneficial to alleviate HIRI in recent studies, however, the underpinning mechanism remains unclear. In this study, we found metformin mitigates HIRI-induced ferroptosis through reshaped gut microbiota in mice, which was confirmed by the results of fecal microbiota transplantation treatment but showed the elimination of the beneficial effects when gut bacteria were depleted using antibiotics. Detailedly, through 16S rRNA and metagenomic sequencing, we identified that the metformin-reshaped microbiota was characterized by the increase of gamma-aminobutyric acid (GABA) producing bacteria. This increase was further confirmed by the elevation of GABA synthesis key enzymes, glutamic acid decarboxylase and putrescine aminotransferase, in gut microbes of metformin-treated mice and healthy volunteers. Furthermore, the benefit of GABA against HIRI-induced ferroptosis was demonstrated in GABA-treated mice. Collectively, our data indicate that metformin can mitigate HIRI-induced ferroptosis by reshaped gut microbiota, with GABA identified as a key metabolite., Competing Interests: FW, FH, YZ, XW, ZS, SW, XW, DS, GR, XJ, EZ, ZT, CW, WW No competing interests declared, XL, YY, JZ Employee of Suzhou Inhal Pharma Co, Ltd, (© 2023, Wang, Liu, Huang et al.)

Objectives: Baduanjin is a traditional Chinese exercise that combines respiration and movement. The study is designed to evaluate the effects of Baduanjin on physical function, daily living activities, and quality of life in stroke patients., Methods: Eleven databases were searched from inception through 16 September 2022. The methodological quality evaluation of the studies was evaluated with the Cochrane Handbook for Systematic Reviews of Interventions v5.1.0. The quality evaluation of the evidence was graded with the Guideline Development Tool ., Results: A total of 24 studies were included. Three indicators with moderate quality evidence, six indicators with low quality evidence, and one indicator with very low quality evidence. Meta-analysis results suggest that Baduanjin group is better than the control group in increasing Berg balance scale [MD = 7.99, 95%CI (4.99, 10.99), P  < 0.00001], Fugl- Meyer balance scale [MD = 5.26, 95%CI (0.12, 10.40), P  = 0.04]; Total Fugl-Meyer assessment scale [MD = 7.17, 95%CI (3.13, 11.2), P  = 0.0005], Fugl-Meyer assessment lower extremity scale[MD = 3.05, 95%CI(0.95, 5.15), P  = 0.004], Fugl-Meyer assessment upper extremity scale[MD = 4.60, 95%CI (1.64,7.56), P  = 0.002]; walking function scale[SMD = 0.69, 95%CI (0.14, 1.23), P  = 0.01]; trunk function scale[MD = 2.46, 95%CI (1.75,3.17), P  < 0.00001]; Barthel index[MD = 9.43, 95%CI (6.20,12.65), P  < 0.00001] and quality of life score[SMD = 1.85, 95%CI (1.46, 2.23), P  < 0.00001]. Meanwhile, Baduanjin reduced Neurological deficit scores SMD = -1.41, 95%CI (-1.83, -0.98), P  < 0.00001])., Conclusions: Baduanjin is probably an effective rehabilitation method to improve balance, motor, trunk, neurological functions, daily living activities, and quality of life in stroke patients. However, the result of Baduanjin in improving walking function is unstable, and further high-quality randomized controlled trials are needed to confirm the results.

Ferroptosis was reported to be involved in cerebral ischemia-reperfusion injury (CIRI), on which the effects of berberine (BBR) remain unclear. Moreover, based on the critical role of gut microbiota in pleiotropic actions of BBR, we hypothesized that BBR can suppress CIRI-induced ferroptosis by modulating the gut microbiota. In this study, the results showed that BBR obviously attenuated the behavioral deficits of CIRI mice, accompanied with the improved survival rate and neuron damages, as phenocopied by dirty cage experiment. The typical morphological changes in ferroptotic cells and biomarkers of ferroptosis were attenuated in BBR- and its fecal microbiota-treated mice, accompanied by reduced malondialdehyde and reactive oxygen species, and the increased glutathione (GSH). BBR was found to alter the gut microbiota of CIRI mice with decreased abundance of Muribaculaceae, Erysipelotrichaceae, Helicobacteraceae, Streptococcaceae and Tannerellaceae, but elevated Bacteroidaceae and Enterobacteriaceae. KEGG analysis based on the 16S rRNA results indicated that multiple metabolic pathways including ferroptosis and GSH metabolism, were altered by BBR. Oppositely, the antibiotics administration counteracted the protective properties of BBR. Summarily, this study revealed the therapeutic potential of BBR on CIRI via inhibiting neuronal ferroptosis, in which upregulated glutathione peroxidase 1 (GPX1) was possibly involved. Moreover, the BBR-modulated gut microbiota was shown to play the critical role in the underlying mechanism., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Cervical cancer (CC) is a common gynecological malignancy with high morbidity worldwide. Butyrate, a short-chain fatty acid produced by intestinal flora, has been reported to inhibit cervical carcinogenesis. This study aimed to investigate the pro-apoptotic effects of butyrate on CC and the underlying mechanisms., Methods: Human HeLa and Ca Ski cells were used in this study. Cell proliferation, cell migration and invasion were detected by CCK-8 and EdU staining, transwell and wound healing assay, respectively. Cell cycle, mitochondrial membrane potential and apoptosis were evaluated by flow cytometry. Western blot and RT-qPCR were carried out to examine the related genes and proteins to the mitochondrial complex Ι and apoptosis. Metabolite changes were analyzed by energy metabolomics and assay kits. The association between G protein-coupled receptor 41, 43, 109a and CC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA)., Results: CCK-8 results showed significant inhibition of CC cell proliferation induced by butyrate treatment, which was confirmed by EdU staining and cell cycle detection. Data from the transwell and wound healing assay revealed that CC cell migration was dramatically reduced following butyrate treatment. Additionally, invasiveness was also decreased by butyrate. Western blot analysis showed that cleaved Caspase 3 and cleaved PARP, the enforcers of apoptosis, were increased by butyrate treatment. The results of Annexin V/PI staining and TUNEL also showed an increase in butyrate-induced apoptotic cells. Expression of Cytochrome C (Cytc), Caspase 9, Bax, but not Caspase 12 or 8, were up-regulated under butyrate exposure. Mechanistically, the decrease in mitochondrial NADH and NAD + levels after treatment with butyrate was observed by energy metabolomics and the NAD+/NADH Assay Kit, similar to the effects of the complex Ι inhibitor rotenone. Western blot results also demonstrated that the constituent proteins of mitochondrial complex Ι were reduced by butyrate. Furthermore, mitochondria-dependent apoptosis has been shown to be initiated by inhibition of the complex Ι., Conclusion: Collectively, our results revealed that butyrate inhibited the proliferation, migration and invasion of CC cells, and induced mitochondrial-dependent apoptosis by inhibiting mitochondrial complex Ι., (© 2023. The Author(s).)

Objective: Lung ischemia/reperfusion injury (LIRI) is a clinical syndrome of acute lung injury that occurs after lung transplantation or remote organ ischemia. Ferroptosis and inflammation are involved in the pathogenesis of LIRI according to the results of several studies on animal models. However, the interactive mechanisms between ferroptosis and inflammation contributing to LIRI remain unclear., Methods: HE staining and indicators of oxidative stress were used to evaluated the lung injury. The reactive oxygen species (ROS) level was examined by DHE staining. The quantitative Real-time PCR (qRT-PCR) and western blot analysis were employed to detect the level of inflammation and ferroptosis, and deferoxamine (DFO) was used to assess the importance of ferroptosis in LIRI and its effect on inflammation., Results: In the present study, the link of ferroptosis with inflammation was evaluated at reperfusion 30-, 60- and 180-minute time points, respectively. As the results at reperfusion 30-minute point shown, the pro-ferroptotic indicators, especially cyclooxygenase (COX)-2 and acyl-CoA synthetase long-chain family member 4 (ACSL4), were upregulated while the anti-ferroptotic factors glutathione peroxidase 4 (GPX4), cystine-glumate antiporter (XCT) and ferritin heavy chain (FTH1) were downregulated. Meanwhile, the increased level of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α) and IL-1β were observed beginning at reperfusion 60-minute point but mostly activated at reperfusion 180-minute point. Furthermore, deferoxamine (DFO) was employed to block ferroptosis, which can alleviate lung injury. Expectedly, the survival rate of rats was increased and the lung injury was mitigated containing the improvement of type II alveolar cells ultrastructure and ROS production. In addition, at the reperfusion 180-minute point, the inflammation was observed to be dramatically inhibited after DFO administration as verified by IL-6, TNF-α and IL-1β detection., Conclusion: These findings suggest that ischemia/reperfusion-activated ferroptosis plays an important role as the trigger for inflammation to further deteriorate lung damages. Inhibiting ferroptosis may have therapeutic potential for LIRI in clinical practice., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Pan, Wang, Xu, Wang, Song, Zhang, Wang and Wang.)

With the application of positive psychology in health management, many studies have confirmed the close relationship between post-traumatic growth, psychological capital and uncertainty in illness. However, there is still a lack of attention to the positive psychology of patients with Parkinson's disease, and previous studies have not clarify the specific relationship. Therefore, the present study sought to explore the multiple mediating roles of psychological capital between post-traumatic growth and uncertainty in illness among patients with Parkinson's disease. We conducted a cross-sectional survey, a total of 268 patients with Parkinson's disease were investigated by the Post-Traumatic Growth Inventory, the Positive Psychological Capital Questionnaire and the Mishel Uncertainty in Illness Scale - Adults from November 2021 to June 2022 in the Parkinson's specialist outpatient department of three 3a-grade hospitals in Tianjin, China. The results showed that the score of post-traumatic growth was (51.78±17.872), the score of uncertainty in illness was (68.08±17.555), and the score of self-efficacy, resilience, hope, and optimism dimensions of psychological capital were (28.93±10.511), (28.79±11.553), (27.57±8.558) and (25.35±9.768). Post-traumatic growth was negatively correlated with uncertainty in illness and positively correlated with all four dimensions of psychological capital (p < 0.01), and uncertainty in illness was negatively correlated with all four dimensions of psychological capital (p < 0.01). Bootstrap test showed that the direct effect of post-traumatic growth on uncertainty in illness of patients with Parkinson's disease was not significant; the total indirect effect of psychological capital between post-traumatic growth and uncertainty in illness was significant. The mediating effects of resilience and hope were significant, accounting for 53.07% and 19.41% of the total indirect effects, respectively. Based on the research results, psychological capital played a completely mediating role between post-traumatic growth and uncertainty in illness of patients with Parkinson's disease. Post-traumatic growth affected uncertainty in illness through two dimensions: resilience and hope. Healthcare professionals should pay attention to the level of psychological capital of patients with Parkinson's disease and implement targeted positive psychological interventions focusing on the two dimensions of resilience and hope, to enhance post-traumatic growth and reduce the level of uncertainty in illness., Competing Interests: Declaration of Competing Interest The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023. Published by Elsevier Inc.)

Background: Fibroblastic reticular cells (FRCs) are a type of stromal cells located in the T zone in secondary lymphoid organs. Previous studies showed that FRCs possess the potential to promote myeloid differentiation. We aim to investigate whether FRCs in lymph nodes (LNs) could induce tolerogenic macrophage generation and further influence T-cell immunity at an early stage of allogeneic hematopoietic stem cell transplantation (allo-HSCT)., Methods: LNs were assayed to confirm the existence of proliferating macrophages after allo-HSCT. Ex vivo-expanded FRCs and bone marrow cells were cocultured to verify the generation of macrophages. Real-time quantitative PCR and ELISA assays were performed to observe the cytokines expressed by FRC. Transcriptome sequencing was performed to compare the difference between FRC-induced macrophages (FMs) and conventional macrophages. Mixed lymphocyte reaction and the utilization of FMs in acute graft-versus-host disease (aGVHD) mice were used to test the inhibitory function of FMs in T-cell immunity in vitro and in vivo., Results: We found a large number of proliferating macrophages near FRCs in LNs with tolerogenic phenotype under allo-HSCT conditions. Neutralizing anti-macrophage colony-stimulating factor receptor antibody abolished FMs generation in vitro. Phenotypic analysis and transcriptome sequencing suggested FMs possessed immunoinhibitory function. Mixed lymphocyte reaction proved that FMs could inhibit T-cell activation and differentiation toward Th1/Tc1 cells. Injection of FMs in aGVHD mice effectively attenuated aGVHD severity and mortality., Conclusions: This study has revealed a novel mechanism of immune regulation through the generation of FRC-induced tolerogenic macrophages in LNs at an early stage of allo-HSCT., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Gastric cancer (GC) remains a common cause of cancer death in East Asia. Current treatment strategies for GC, including medical and surgical interventions, are suboptimal. Butyrate, a short-chain fatty acid produced by the intestinal flora, has been reported to be able to inhibit gastric carcinogenesis. This study aimed to investigate the effects of butyrate on human GC and its underlying mechanisms., Materials and Methods: Human GC cell lines BGC-823 and SGC-7901, human GC tissues and adjacent normal tissues were used for this study. Cell proliferation was assessed using CCK-8 and EdU staining. TUNEL fluorescence and Annexin V/PI staining were adopted for qualitative and quantitative evaluation of cell apoptosis, respectively. Reactive oxygen species (ROS) assay was performed to analyse mitochondrial function. Real-time q-PCR and western blot were carried out to examine the expression of apoptosis-related genes and the synthesis of apoptosis-related proteins. The association between G protein-coupled receptor 109a (GPR109a) and GC prognosis was analyzed using data from The Cancer Genome Atlas (TCGA)., Results: CCK-8 and EdU staining confirmed inhibitory activities of butyrate against human GC cells. Annexin V/PI staining and TUNEL fluorescence microscopy showed that butyrate promoted GC cell apoptosis. No difference in the expression of GPR109a was found between GC tissues and adjacent normal tissues, and no direct association between GPR109a and GC prognosis was discovered, suggesting that GPR109a may not be a key factor mediating the apoptosis of GC cells. Butyrate increased the synthesis of caspase 9 and decreased BCL-2, the well-known effector and regulator of mitochondria-mediated apoptosis, and significantly induced mitochondrial ROS., Conclusion: Collectively, our results suggest that butyrate is able to inhibit the proliferation of GC cells and induce GC apoptosis, possibly via a mitochondrial pathway., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A new method was developed for the identification and determination of L-ergothioneine in cosmetics based on ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The pretreatment method, chromatographic column, chromatographic conditions, and mass spectrometric conditions of cosmetic samples were optimized. Methanol was chosen as the extraction solvent, 85% acetonitrile with 0.1% FA was selected as the mobile phase, and the Waters CORTECS UPLC hydrophilic interaction liquid chromatography (HILIC) column was chosen for the separation. The sample was extracted with methanol and filtered, then separated by HILIC and detected by triple-quadrupole mass spectrometry. The quantitation was done under the matrix calibration curve using the external standard method. The results showed good linear relationships in the range of 5-200 ng/mL, and the correlation coefficient was greater than 0.999 in cosmetic samples. The limit of detection was in the range of 25-50  μ g/kg and the limit of quantitation was in the range of 50-100  μ g/kg. The recoveries of the method spiked ranged from 85.3% to 96.2% and the relative standard deviation (RSD) was in the range of 0.84%-2.08% ( n  = 6). The method is simple, quick, and accurate for the determination of L-ergothioneine in cosmetics, and has great practical value., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2022 Li Liu et al.)

Background: Patients with amyloid light-chain (AL) amyloidosis with a bone marrow plasma cell ratio > 10% (AL-PCMM) have a poorer prognosis than patients with AL amyloidosis with a bone marrow plasma cell ratio of <10% (AL-only), similar to that of patients with AL amyloidosis and multiple myeloma (AL-MM). However, the prognostic factors for AL-PCMM and AL-MM have not been studied. Methods: A total of 49 patients with AL-PCMM or AL-MM in the Peking University First Hospital registry in 2010-2018 were enrolled. Clinical and follow-up data were collected. The relationship between clinical parameters and survival time was also assessed. Results: Compared with patients with AL-PCMM, patients with AL-MM only had a higher incidence of bone marrow plasma cell ratio ≥ 20%. In AL-PCMM and AL-MM, the survival time was significantly shorter in patients with alkaline phosphatase (ALP) ≥ 187.5 IU/L, γ-glutamyl transpeptidase (GGT) ≥ 85 IU/L, total bilirubin (TBIL) ≥ 20 µmol/L, cardiac troponin I (CTNI) ≥ 0.1 ng/mL, ejection fraction (EF) < 50%, initial therapeutic effect (ITE) < very good partial response (VGPR), and Boston University (BU) staging system stage ≥ III. ALP at diagnosis was correlated with brain natriuretic peptide (BNP) level, CTNI level, and EF rather than TBIL level. Cox regression analyses revealed that BU staging system stage ≥ III ( P =0.001, hazard ratio [HR]=5.579), ALP ≥ 187.5 IU/L ( P =0.011, HR=3.563), and ITE < VGPR ( P =0.002, HR=7.462) were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM. Conclusion: ALP level, which is related to cardiac amyloidosis rather than liver involvement, can be a prognostic factor for this group of patients. A BU staging system stage ≥ III, ALP ≥ 187.5 IU/L, and ITE < VGPR were independent significant risk factors for a poor prognosis of AL-PCMM and AL-MM., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In order to explore the correlation between the production of propionic acid (PA) and the succession of bacterial community during the fermentation of gray sufu, high-throughput sequencing and HPLC (High Performance Liquid Chromatography) were used to monitor the changes of bacterial community and metabolite content. The abundance and metabolite concentration of Propionibacterium increased rapidly in the early stage of fermentation. In the middle stage, the abundance of Lactobacillus began to increase, while the pH decreased rapidly. In the late stage, the concentration of PA began to decrease, but it remained at a high level at the end of fermentation. Correlation analysis showed that Lactobacillus and Bacillus had a strong negative correlation with PA and its precursor. The results showed that Fusobacterium, Providencia, Lactobacillus and Bacillus could be the key factors to reduce the PA content. This study provides a new idea for the quality control of traditional fermented food., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Acute graft-versus-host disease (aGVHD) is a lethal complication after allogeneic hematopoietic stem cell transplantation. The mechanism involves the recognition of host antigens by donor-derived T cells which induces augmented response of alloreactive T cells. In this study, we characterized the role of a previously identified novel classical secretory protein with antitumor function-LYG1 (Lysozyme G-like 1), in aGVHD. LYG1 deficiency reduced the activation of CD4 + T cells and Th1 ratio, but increased Treg ratio in vitro by MLR assay. By using major MHC mismatched aGVHD model, LYG1 deficiency in donor T cells or CD4 + T cells attenuated aGVHD severity, inhibited CD4 + T cells activation and IFN-γ expression, promoted FoxP3 expression, suppressed CXCL9 and CXCL10 expression, restrained allogeneic CD4 + T cells infiltrating in target organs. The function of LYG1 in aGVHD was also confirmed using haploidentical transplant model. Furthermore, administration of recombinant human LYG1 protein intraperitoneally aggravated aGVHD by promoting IFN-γ production and inhibiting FoxP3 expression. The effect of rhLYG1 could partially be abrogated with the absence of IFN-γ. Furthermore, LYG1 deficiency in donor T cells preserved graft-versus-tumor response. In summary, our results indicate LYG1 regulates aGVHD by the alloreactivity of CD4 + T cells and the balance of Th1 and Treg differentiation of allogeneic CD4 + T cells, targeting LYG1 maybe a novel therapeutic strategy for preventing aGVHD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Yu, Tang, Miao, Qin, Li, Liang, Shi, Zhang, Wang, Yan, Song, Ren and Dong.)

Background: Male-specifically inherited Y-STRs have been widely used in population genetics and forensic investigations., Methods: We genotyped and analyzed Y chromosome haplotypes of 408 unrelated Tibeto-Burman-speaking Yi male individuals from Guizhou using Goldeneye ® Y-PLUS kit. Population comparisons between the Guizhou Yi and 67 reference groups were performed via the AMOVA, MDS, and phylogenetic relationship reconstruction., Results: A total of 389 alleles and 396 haplotypes could be detected, and the allelic frequencies ranged from 0.0025 to 0.9875. The haplotype diversity, random match probability, and discrimination capacity values were 0.9999, 0.0026, and 0.9900, respectively. The gene diversity (GD) of 36 Y-STR loci in the studied group ranged from 0.0248 (DYS645) to 0.9601 (DYS385a/b). Our newly genotyped Yi samples show a close affinity with other Tibeto-Burman speaking groups in China and Southeast Asia., Conclusions: The population stratification was almost consistent with the geographic distribution and language-family, both among Chinese and worldwide ethnic groups. Our data may provide useful information for paternal lineage in the forensic application and population genetics, as well as evidence for archaeological and historical research., (© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)