Electrostimulation suppresses allograft rejection via promoting lymphatic regulatory T cell migration mediated by lymphotoxin (LT)-LTß receptor signaling.

Conventional immunosuppressants that suppress allograft rejection cause various side-effects. Although regulatory T cells (Tregs) are essential for allograft survival, limited efficacy of Treg therapy demands improvement. Thus, it is imperative to seek new approaches to enhancing Treg suppression. Low-intensity electrostimulation (ES) has been shown to exert anti-inflammatory effects without causing major adverse reactions. However, it remains unknown whether and how ES regulates alloimmunity. Here we found that regional ES delayed murine skin allograft rejection and promoted long-term allograft survival induced by an mTOR inhibitor, rapamycin. ES also extended islet allograft survival. Mechanistically, ES enhanced expression of LTα on Tregs after transplantation. Blockade of lymphotoxin ß receptor (LTßR)-mediated non-classical NFκB signaling suppressed lymphatic Treg migration and largely reversed the effects of ES on allograft survival. Moreover, ES failed to extend allograft survival when recipients lacked LTα/lymph nodes or if transferred Tregs lacked LTα. Therefore, ES promoted the lymphatic migration of CD4+Foxp3+ Tregs by upregulating their surface expression of LTα. Finally, ES augmented expression of LTα on murine or human Tregs, but not conventional T cells, while promoting their calcium influx in vitro. This ES-mediated upregulation of LTα relied on calcium influx. Thus, our findings have unveiled novel mechanisms underlying ES-mediated immunoregulation.

Endoplasmic reticulum stress interferes with the development of type 1 regulating T cells.

BACKGROUND: A variety of stimuli can cause endoplasmic reticulum (ER) stress, which is a common cellular reaction. It is not yet clear how ER stress contributes to the pathogenesis of ulcerative colitis (UC). The deregulation of regulatory T cell (Treg) is associated with UC. The goal of this study is to shed light on how ER stress affects Treg's development. METHODS: CD4+ CD25- T cells were isolated from blood samples collected from UC patients and healthy control (HC) subjects. ER stress-associated molecule expression in CD4+ CD25- T cell was assessed by RNA sequencing and RT-qPCR. RESULTS: The presence of ER stress in peripheral CD4+ CD25- T cells was observed in patients with UC compared to HC subjects. The induction of ER stress in HC CD4+ CD25- T cells by polyclonal activation was made worse by the presence of 3-methyl-4-nitrophenol (MNP; a common environmental pollutant). Exposure to MNP in culture resulted in an increase in the expression of ring finger protein 20 (Rnf20) in CD4+ CD25- T cells. The synergistic effects of MNP and ER stress on the reduction of IL-10 levels in CD4+ CD25- T cells are mediated by Rnf20, which prevents the development of Tr1 cells. Inhibition of Rnf20 resulted in the development of Tr1 cells from CD4+ CD25- T cells in UC patients. CONCLUSIONS: The synergistic effects of ER stress and MNP interfere with the development of Tr1 cells. The development of Tr1 from CD4+ CD25- T cells in patients with UC is re-established by Rnf20 inhibition.

Comparison of patient-controlled epidural analgesia and epidural morphine for post-cesarean section analgesia: experience from a tertiary center in China.

PURPOSE: To compare patient-controlled epidural analgesia (PCEA) and epidural morphine (EM) for post-cesarean section analgesia in real-world experience from China. METHODS: Parturients receiving one dose of EM (1-2 mg), PCEA, or both EM and PCEA from Peking Union Medical College Hospital were retrospectively recruited. Logistic models were used to identify risk factors. RESULTS: Of 1079 parturients enrolled, 919 (85.2%) parturients received only EM, 105 (9.7%) parturients received PCEA, and 55 (5.1%) parturients received both EM and PCEA. Significantly more parturients from EM group requested supplementary analgesia than those from PCEA and PCEA + EM group (583, 63.4% vs 52, 49.5% vs 25, 45.5%, P = 0.001) with more times of supplementary analgesia (1, IQR: 0-2 vs 0, IQR: 0-1 vs 0, IQR: 0-1 times, P < 0.001) and larger amounts of nonsteroidal anti-inflammatory drugs (NSAIDs) (50, IQR: 0-100 mg vs 0, IQR: 0-50 mg vs 0, IQR: 0-50 mg, P < 0.001). In multivariable Logistic regression for the supplementary analgesia risk, the application of PCEA (OR: 0.557, 95%CI 0.396-0.783, P = 0.001) and the use of NSAIDs intraoperatively (OR: 2.996, 95%CI 1.811-4.957, P < 0.001) were identified as independent predictors. A total of 1040 (96.4%) patients received prophylactic antiemetic therapy during surgery. Only 13 (1.2%) and 7 (0.6%) patients in our cohort requested antiemetic and antipruritic drugs, respectively. CONCLUSION: The use of PCEA was an independent protective factor for supplementary analgesia during the post-cesarean section. Prophylactic antiemetic therapy may reduce the side effects of post-cesarean analgesia.

Cancer occurrence after SLE: effects of medication-related factors, disease-related factors and survival from an observational study.

OBJECTIVES: To explore the survival and risk factors for cancer occurrence after SLE (SLE-CA). METHODS: Patients with cancer diagnosed after SLE in Peking Union Medical College Hospital between January 2006 and September 2017 were recruited and followed. Data regarding medication-related and disease-related factors and survival were collected and compared with matched controls. Logistic regressions were applied to identify risk factors. The Kaplan-Meier method with a log-rank test was performed to evaluate survival. RESULTS: Forty-five SLE-CA patients and 128 controls were included, with the most common cancer site being the female genital system. SLE-CA patients were exposed to a higher cumulative dosage of CYC, with less mucocutaneous and haematologic involvement and higher anti-dsDNA positivity. At the time of cancer diagnosis, SLE-CA patients had lower SLEDAI 2000 (SLEDAI-2K), tended to achieve Definitions of Remission in SLE remission and minimal disease activity, but had higher SLICC/ACR Damage Index. Multivariable analysis identified high dosage of CYC [odds ratio (OR) 1.027, 95% CI 1.008, 1.046; P = 0.005] and low SLEDAI-2K at cancer diagnosis (OR 0.756, 95% CI 0.579, 0.986; P = 0.039) as risk factors. Mucocutaneous (OR 0.330, 95% CI 0.110, 0.991; P = 0.048) and haematologic involvement (OR 0.304, 95% CI 0.103, 0.902; P = 0.032) were negatively associated with cancer occurrence after SLE. The 5- and 10-year survival rates in SLE-CA patients were 95.2% and 92.1%, respectively. No significant difference of survival was observed between SLE-CA patients and controls (P = 0.177). CONCLUSION: High dosage of CYC and disease-related factors (low SLEDAI-2K, less mucocutaneous and haematologic involvement) were related factors for cancer occurrence after SLE, while no survival difference was observed.

High-frame-rate reconfigurable diffractive neural network based on superpixels.

The existing implementations of reconfigurable diffractive neural networks rely on both a liquid-crystal spatial light modulator and a digital micromirror device, which results in complexity in the alignment of the optical system and a constrained computational speed. Here, we propose a superpixel diffractive neural network that leverages solely a digital micromirror device to control the neuron bias and connection. This approach considerably simplifies the optical system and achieves a computational speed of 326 Hz per neural layer. We validate our method through experiments in digit classification, achieving an accuracy of 82.6%, and action recognition, attaining a perfect accuracy of 100%. Our findings demonstrate the effectiveness of the superpixel diffractive neural network in simplifying the optical system and enhancing computational speed, opening up new possibilities for real-time optical information processing applications.

Rnf20 inhibition enhances immunotherapy by improving regulatory T cell generation.

BACKGROUND: Allergic disorders are common all over the world. The pathogenesis of allergy is unclear. Therapies for allergic disorders require improvement. Endoplasmic reticulum (ER) stress is one of the factors influencing immune response. The purpose of this study is to improve the effectiveness of immunotherapy for experimental respiratory allergy by targeting the ER stress signal pathway. METHODS: Committed CD4+ T cells were isolated from blood samples collected from patients with allergic rhinitis (AR) and TCR ovalbumin transgenic mice. The effects of TCR engagement and 3-methyl-4-nitrophenol (MNP) on inducing ER stress in committed CD4+ T cells were evaluated. RESULTS: ER stress was detected in antigen-specific CD4+ T cells (sCD4+ T cells) of AR patients. The environmental pollutant MNP increased the expression of the X-binding protein-1 (XBP1) in the committed CD4+ T cells during the TCR engagement. XBP1 mediated the effects of MNP on inhibiting regulatory T cell (Treg) generation. The effects of MNP on induction of protein 20 (Rnf20) in CD4+ T cells were mediated by XBP1. Inhibition of Rnf20 rescued the Treg development from MNP-primed sCD4+ T cells. The ablation of Rnf20 improved the immunotherapy of AR through the restoration of the Treg generation. CONCLUSIONS: ER stress can be detected in CD4+ T cells in TCR engagement. Exposure to MNP exacerbates ER stress in committed CD4+ T cells. Regulation of the ER stress-related Rnf20 expression can restore the generation of Treg from CD4+ T cells of subjects with allergic diseases.

Characterization of the immune regulatory property of CD22+ CD9+ B cells.

Immunodisruptive homeostasis is recognized in allergic disorders. The mechanism of restoration of immunologic homeostasis in the body is not fully understood. Galectin-9 (Gal9) and CD22 have immune regulatory functions. The goal of this study is to test the role of CD22+ CD9+ B regulatory cells in immune homeostasis the body. A much smaller amount of IL-10 in B10 cells was detected in patients with allergic rhinitis (AR) in contrast to healthy subjects. The IL-10 expression levels in B10 cells were positively correlated with the CD22 expression. CD22 mediated the effects of Gal9 on the enhanced expression of IL-10 in AR B10 cells. Gal9 overcame the refractory induction of IL-10 in B-cells of AR subjects. The immune regulatory ability of AR B10 cells could be restored by Gal9. Combination of Gal9 and SIT induced and activated antigen-specific B10 cells. The B10 cells of Gal9/specific immunotherapy-treated AR mice showed immunosuppressive functions on T-cell activities and induction of type 1 regulatory T cells in an antigen-specific manner. Administration of Gal9 potentiated the effects of specific immunotherapy in mice with AR. In summary, a fraction of regulatory B cells, the CD19+ CD22+ CD9+ B cells, was characterized in the present study. CD22 mediates the effects of Gal9 to promote immunotherapy for allergic diseases by inducing B10 cells. In an antigen-specific manner, the B10 cells suppressed CD4+ T cell activities, and alleviated experimental AR.

Monoclonal gammopathy in autoimmune diseases: Analysis and follow-up of 160 cases in a tertiary center in China.

Monoclonal gammopathy (MG) is common in autoimmune diseases (AID), but its progression to hematological neoplasm (HN) and the predictors for the progression are unclear. Patients diagnosed with AID and MG in our hospital from January 2010 to June 2017 were reviewed and followed. Cox proportional hazard regression analysis was applied. Of 160 patients with AID and MG, the most common AID was primary SjÓ§gren's syndrome (37, 23.1%). Thirty-nine (24.4%) patients developed HN during follow-up (median: 3.7 years, IQR: 0.3-5.5 years). The cumulative probability of HN progression was 21.8% at one year and 29.3% at six years after the finding of MG. High levels of monoclonal protein (> 14.35% of total serum protein) (HR 11.71, 95%CI: 5.37-25.54), significant weight loss (HR 6.24, 95%CI: 2.87-13.59), and reduction of other types of immunoglobulins (HR 3.02, 95%CI: 1.40-6.48) are independent risk indicators for HN whose presence warrants vigorous follow-up and monitoring.

Characterization of allergic inflammation in chronic uterine cervicitis.

Female genital tract chronic inflammation is common in clinics; the pathogenesis is not fully understood yet. House dust mite (HDM) involves the pathogenesis of many chronic diseases in human. This study aims to identify HDM-specific allergic response in the cervix of patients with cervical inflammation. Patients (n = 80) with chronic cervicitis (CC) and non-CC control (NC) subjects (n = 80) were recruited into this study. Vaginal lavage fluids (VLF) were collected from CC patients and NC subjects. Cellular components and fluid part of VLF were separated by centrifugation, and analyzed by flow cytometry and enzyme-linked immunosorbent assay. We found that a portion (52 out of 80) of CC patients responded to HDM, manifesting positive skin prick test, and HDM-specific IgE and IgG was detected in the VLF (designated CCp patients). VLF of CCp patients showed a Th2-dominant profile. HDM-specific Th2 cells were detected in VLF in CCp patients. Exposure to HDM in the culture induced proinflammatory cytokine release from CCp VLF CD4+ T cells. Exposure to CCp VLF CD4+ T cell-conditioned medium induced de novo Th2 response. Direct exposure to HDM induced allergic response in the cervix of CCp patients. In summary, a portion of CC patients respond to HDM challenge in the cervix. Exposure to HDM induces an allergy-like response in the cervix of CCp patients.

Pathological mechanisms and crosstalk among different forms of cell death in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder characterized by a profound immune dysregulation and the presence of a variety of autoantibodies. Aberrant activation of programmed cell death (PCD) signaling and accelerated cell death is critical in the immunopathogenesis of SLE. Accumulating cellular components from the dead cells and ineffective clearance of the dead cell debris, in particular the nucleic acids and nucleic acids-protein complexes, provide a stable source of self-antigens, which potently activate auto-reactive B cells and promote IFN-I responses in SLE. Different cell types display distinct susceptibility and characteristics to a certain type of cell death, while different PCDs in various cells have mutual and intricate connections to promote immune dysregulation and contribute to the development of SLE. In this review, we discuss the role of various cell death pathways and their interactions in the pathogenesis of SLE. An in depth understanding of the interconnections among various forms cell death in SLE will lead to a better understanding of disease pathogenesis, shedding light on the development of novel therapeutic targets.

Flagellin maintains eosinophils in the intestine.

Eosinophils (Eos) are the major effector cells in allergic response. The regulation of Eo is not fully understood yet. Flagellin (FGN) has immune regulatory functions. This study aims to elucidate the role of FGN in maintaining Eo at the static status in the intestinal tissues. A mouse food allergy (FA) model was developed. Eo mediator levels in the serum or culture supernatant or intestinal lavage fluids were assessed and used as an indicator of Eo activation. The results showed that less FGN amounts were detected in the FA mouse intestinal tissues, that were negatively correlated with the Eo activation. Mast cell-derived chymase bound FGN to induce FGN degradation. FGN formed complexes with FcγRI on Eos to prevent specific antigens from binding FcγRI, and thus, to prevent Eo activation. Administration of FGN efficiently alleviated experimental FA. In conclusion, FGN plays a critical role in maintaining Eos at static status in the intestine. Administration of FGN can alleviate experimental FA. FGN may be a novel drug candidate to be used in the treatment of Eo-related diseases.

Amniotic epithelial cells accelerate diabetic wound healing by protecting keratinocytes and fibroblasts from high-glucose-induced senescence.

Human amniotic epithelial cells (hAECs), one of the stem cells identified from the human placenta, possess numerous advantages and have been considered as an attractive and available cell source for regenerative medicine. Accumulating evidence has showed that cellular senescence was one of the pathogenic hubs of diabetic wound chronicity. Keratinocytes and fibroblasts are the primary cells involved in wound healing. Therefore, in this study, we aimed to investigate the anti-senescence effects of hAECs on keratinocytes and fibroblasts in diabetic wounds. Sustained hyperglycemia impaired cell function and accelerated senescence in vitro. However, this phenotype was rescued by hAECs-conditioned medium (hAECs-CM), with increased migration and proliferation in keratinocytes and fibroblasts and enhanced collagen synthesis and α-smooth muscle actin (α-SMA) production in fibroblasts. In addition, hAECs-CM dramatically inhibited intracellular reactive oxygen species (ROS) and senescence-associated ß-galactosidase (SA-ß-gal) in keratinocytes and fibroblasts under high-glucose (HG) condition. Moreover, hAECs-CM could downregulate the increased RAGE and P21 induced by continuous HG stimulation. Intradermal injection of hAECs in diabetic wounds promoted re-epithelialization and granulation tissue formation, accompanied by decreased P21+ cells and increased PCNA+ cells in epidermis and dermis, as well as promoted collagen deposition and α-SMA expression. Furthermore, CM-Dil-labeled hAECs survived to Day 5 but disappeared by Day 10 in diabetic wounds. These findings indicated that hAECs could inhibit diabetes-induced premature senescence and enhance the function of keratinocytes and fibroblasts via paracrine effects, partly by inhibiting RAGE/P21 signaling pathway. Thus, hAECs targeting cellular senescence induced by a hyperglycemic environment may be a new strategy for the treatment of diabetic wounds.

Ablative fractional carbon dioxide laser improves quality of life in patients with extensive burn scars: A nested case-control study.

BACKGROUND AND OBJECTIVES: Ablative fractional carbon dioxide laser (CO2 -AFL) for small-area burn scar management shows encouraging outcomes. Few studies, however, focused on comprehensive outcomes following CO2 -AFL treatment for extensive burn scars. This study evaluated whether CO2 -AFL surgery improved the quality of life (QoL) for burn survivors with extensive hypertrophic scars. METHODS: A retrospective nested case-control study was initiated to analyze the efficacy of CO2 -AFL treatment for patients with large-area burn scars. Patients with extensive burn scars (≥30% total body surface area [TBSA]) were registered in our hospital from March 2016 to October 2018. Patients undergoing CO2 -AFL surgery were divided into CO2 -AFL group, and patients undergoing conventional surgery were matched in a 1:1 ratio as the conventional surgery group according to the burned area. The questionnaires were collected and followed up. The 36-Item Short Form Health Survey (SF-36) and Burns Specific Health Scale-Brief (BSHS-B) were the primary parameters. Secondary parameters included the Pittsburgh Sleep Quality Index (PSQI), University of North Carolina "4P" Scars Scale (UNC4P), Patient Scars Assessment Scale for Patient (POSAS-P), and Douleur Neuropathique 4 questions (DN4). RESULTS: 23 patients (55.96 ± 21.59% TBSA) were included in CO2 -AFL group and 23 patients (57.87 ± 18.21% TBSA) in conventional surgery group. Both the BSHS-B total score (CO2 -AFL vs. conventional surgery: 115.35 ± 29.24 vs. 85.43 ± 33.19, p = 0.002) and the SF-36 total score (CO2 -AFL vs. conventional surgery: 427.79 ± 118.27 vs. 265.65 ± 81.66, p < 0.001) for the CO2 -AFL group were higher than those for the conventional surgery group. Parameters for the CO2 -AFL group were lower than those for the conventional surgery group in all of the following comparisons: PSQI total score (CO2 -AFL vs. conventional surgery: 7.70 ± 3.74 vs. 12.26 ± 4.61, p = 0.001), POSAS-P total score (CO2 -AFL vs. conventional surgery: 26.48 ± 6.60 vs. 33.04 ± 4.56, p < 0.001), UNC4P total score (CO2 -AFL vs. conventional surgery: 5.57 ± 1.97 vs. 7.26 ± 1.81, p = 0.004), and DN4 score (CO2 -AFL vs. conventional surgery: 3 [2-5] vs. 5 [4-8], p = 0.004). CONCLUSIONS: Compared to conventional surgery, whole scar CO2 -AFL surgery dramatically improved physical and mental health as well as QoL for people with extensive burn scars. Additionally, CO2 -AFL enhanced the evaluation of scars including their appearance, pain, itching, and a host of other symptoms.

Ventricular arrhythmia predicts poor outcome in polymyositis/dermatomyositis with myocardial involvement.

OBJECTIVE: Myocardial involvement (MCI) is known to increase morbidity and mortality in polymyositis (PM) and dermatomyositis (DM). This study aims to investigate whether complicating with ventricular arrhythmia (VA) predicts poor outcomes in patients with PM/DM-related myocardial involvement (PM/DM-MCI). METHODS: We reviewed all PM/DM-MCI patients admitted to Peking Union Medical College Hospital from October 1997 to April 2019. VA and the other possible risk factors for the composite endpoint, including death from any cause and rehospitalization for cardiac causes, were analyzed. RESULTS: A total of 75 PM/DM-MCI patients (44 PM and 31 DM) were enrolled, of which 27 (36%) met the composite endpoint during a median follow-up of 24 months. Independent prognostic factors for the composite endpoint include VA [HR 4.215, 95% CI (1.737, 10.230)], NT-proBNP > 3415 pg/ml [HR 2.606, 95% CI (1.203, 5.646)], interstitial lung disease [HR 2.688, 95% CI (1.209, 5.978)], and anti-cardiac remodelling therapy [HR 0.302, 95% CI (0.115, 0.792)]. The 3-year event-free survival rate of patients without VA was significantly higher than that of patients with VA (63.3% vs 40.7%, P = 0.034). Skin lesions [OR 0.163, 95% CI (0.051, 0.523)] and positive antimitochondrial antibody [OR 3.484, 95% CI (1.192, 10.183)] were independent predictors of VA. CONCLUSION: VA provides prognostic insights for PM/DM-MCI patients and predicts poor outcome. Polymyositis and positive antimitochondrial antibody are closely associated with the presence of VA in PM/DM-MCI.

Sex differences in growth performance are related to cecal microbiota in chicken.

In poultry industry, male chickens have a better growth performance than female ones under the same genetic background and diet. Emerging evidences proposed an important role of intestinal microbiota in chicken's growth performance. This study aimed to determine gut microbiota related gender based differences in the growth performance of chickens. Therefore, male and female chickens (n = 20) at 7-week age were used to carry out histomorphological, molecular, gene expression analysis with their liver, chest and leg muscle, as well as 16S rRNA sequencing analysis for gut microbiota. The results revealed that Bacteroides and Megamonas genera were more prominently colonized in the cecum of male chickens. The male chicken's cecal microbiota indicated a closer relation with glycan metabolism, while in the female chickens it was more related with lipid metabolism. Gene expression levels associated with glycan and lipid metabolism were different between male and female chickens. Further, using Spearman correlation analysis, we found a positive correlation between glycan and lipid metabolism, and the relative abundance of Bacteroides, Megamona and Lactobacillus in male chickens. Similarly, we also found a positive correlation between the lipid metabolism and the relative abundance of Ruminococcaceae and Enterococcus in female chickens. These findings revealed the association of chicken growth performance with cecal microbiota that contributed to the metabolism of glycan and lipid in a sex-dependent manner.

Single cell RNA sequencing (scRNA-Seq) deciphering pathological alterations in streptozotocin-induced diabetic retinas.

Diabetic retinopathy (DR) is an irreversible and progressive diabetic complication leading to visual impairment, even blindness. Due to the delicate and complicated structure of the retina, the pathology of DR has not been completely elucidated yet. We constructed a transcriptome atlas of >14,000 single cells from healthy and streptozotocin (STZ)-induced diabetic murine retinas to decipher pathological alterations of DR. We found four stress-inducible genes Cirbp, Rmb3, Mt1 and Mt2 commonly induced in most types of retinal cells. Bipolar cells were little affected on both number and gene expression. Diabetes increased expression of inflammatory factor genes in retinal microglia, and stimulated expression of immediate early genes (IEGs) in retinal astrocytes. A large number of genes were deregulated in diabetic vascular endothelial cells (ECs), and the differentially expressed genes were paired to the pathways functioning in metabolism, shear stress and vascular permeability. These pathways were mapped by more deregulated genes in a subpopulation of ECs specifically presented in diabetic retinas (diabetic retinal ECs, DRECs). Moreover, several inflammation pathways were activated in DRECs, and the most significant one is the IL-17 signaling pathway. According to the EC markers, DRECs were mainly capillary ECs, confirmed by immunofluorescent staining of S100a9, a target gene of the IL-17 signaling pathway. This study deciphered pathological alterations of DR, and provided clues for potential targets for DR therapy.

A Novel Immunosuppressant, Luteolin, Modulates Alloimmunity and Suppresses Murine Allograft Rejection.

An allograft is rejected in the absence of any immunosuppressive treatment because of vigorous alloimmunity and thus requires extensive immunosuppression for its survival. Although there are many conventional immunosuppressants for clinical use, it is necessary to seek alternatives to existing drugs, especially in case of transplant patients with complicated conditions. Luteolin, a natural ingredient, exists in many plants. It exhibits multiple biological and pharmacological effects, including anti-inflammatory properties. In particular, luteolin has been shown to upregulate CD4+CD25+ regulatory T cells (Tregs) in the context of airway inflammation. However, it remains unknown whether luteolin regulates alloimmune responses. In this study, we demonstrated that luteolin significantly prolonged murine skin allograft survival, ameliorated cellular infiltration, and downregulated proinflammatory cytokine gene expression in skin allografts. Furthermore, luteolin increased the percentage of CD4+Foxp3+ Tregs while reducing frequency of mature dendritic cells and CD44highCD62Llow effector CD4+/CD8+ T cells posttransplantation. It also suppressed the proliferation of T cells and their production of cytokines IFN-γ and IL-17A in vitro while increasing IL-10 level in the supernatant. Moreover, luteolin promoted CD4+Foxp3+ Treg generation from CD4+CD25- T cells in vitro. Depleting Tregs largely, although not totally, reversed luteolin-mediated extension of allograft survival. More importantly, luteolin inhibited AKT/mTOR signaling in T cells. Thus, for the first time, to our knowledge, we found that luteolin is an emerging immunosuppressant as an mTOR inhibitor in allotransplantation. This finding could be important for the suppression of human allograft rejection, although it remains to be determined whether luteolin has an advantage over other conventional immunosuppressants in suppression of allograft rejection.

Before-after cohort study to assess the efficacy of fractional ablative carbon dioxide laser treatment of pediatric hand scars.

The purpose of this study is to investigate the efficacy of fractional ablative carbon dioxide laser (AFXL) surgery in patients with pediatric hand scars. This study enrolled hand scar patients who received treatment in our hospital between May 2018 and April 2019. Patients were assigned to undergo AFXL surgery based on their personal intents and condition, whereas the fractional laser was used for stiffness and abnormal texture. Outcomes were as follows: hand function was evaluated using the Michigan hand outcomes questionnaire; scar condition was evaluated using the Vancouver scar scale and UNC4P scar scale. Total 30 pediatric patients (mean age, 11.4 years) were eligible for the study and laser-treated scars were significantly improved in Michigan hand outcomes questionnaire from 52.30 ± 6.14 to 66.91 ± 6.43 (p < 0.001). Provider-rated Vancouver scar scale dropped from 8.80 ± 2.75 to 6.73 ± 2.52 (p < 0.001). Patient-reported UNC4P scar scale declined from7.07 ± 2.02 to 4.73 ± 1.31 (p < 0.001). AFXL surgery can significantly improve hand function and appearance of pediatric hand scars, suggesting its advantages over traditional methods of operative intervention.

Identification and Characterization of a Pear Chlorotic Leaf Spot-Associated Virus, a Novel Emaravirus Associated with a Severe Disease of Pear Trees in China.

Pear chlorotic leaf spot (PCLS) is a recently emerged disease of commercially cultivated sandy pear (Pyrus pyrifolia) trees in central and southern China. By integrating high-throughput sequencing and conventional Sanger sequencing of reverse-transcription (RT)-PCR products, a novel emaravirus infecting pear trees was identified and molecularly characterized. The virus was provisionally named pear chlorotic leaf spot-associated virus (PCLSaV). PCLSaV shows the typical molecular features of members of the genus Emaravirus in the family Fimoviridae. It has a genome composed of at least five negative-sense RNA segments, with each containing a single open reading frame and two complementary 13-nucleotide stretches at the 5' and 3' termini. PCLSaV shows a close phylogenetic relationship with recognized emaraviruses but forms a separate clade. Moreover, double-membrane-bound bodies were observed in PCLSaV-infected tissues and in extracts of PCLSaV-infected leaves. For the first time, our study revealed the profile distribution of viral RNA reads from the RNA-seq libraries of three samples along the RNA1 to RNA5 of an emaravirus. Field surveys combined with specific RT-PCR assays revealed the presence of PCLSaV in almost all PCLS-diseased pear samples, strongly supporting the association of the virus with the PCLS disease. This study revealed the first emaravirus infecting pear trees and its association with a severe pear chlorotic leaf disease.