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Fibrotic skin disease represents a major global healthcare burden, characterized by fibroblast hyperproliferation and excessive accumulation of extracellular matrix. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. In this study, we explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases, by using single-cell RNA-seq. Our results indicate that keloid fibroblasts can be divided into 4 subpopulations: secretory-papillary, secretory-reticular, mesenchymal and pro-inflammatory. Interestingly, the percentage of mesenchymal fibroblast subpopulation is significantly increased in keloid compared to normal scar. Functional studies indicate that mesenchymal fibroblasts are crucial for collagen overexpression in keloid. Increased mesenchymal fibroblast subpopulation is also found in another fibrotic skin disease, scleroderma, suggesting this is a broad mechanism for skin fibrosis. These findings will help us better understand skin fibrotic pathogenesis, and provide potential targets for fibrotic disease therapies. Fibroblasts are found to be heterogeneous in multiple fibrotic diseases, but fibroblast heterogeneity in fibrotic skin diseases is not well characterized. Here the authors employ scRNA-seq to explore fibroblast heterogeneity in keloid, a paradigm of fibrotic skin diseases.

Aim： Our preliminary study shows that a bibenzyl compound isolated from Gastrodia elata, 2-[4-hydroxy-3-（4-hydroxybenzyl）benzyl]-4-（4-hydroxybenzyl）phenol （designated 20C）, protects PC12 cells against H202-induced injury. In this study we investigated whether 20C exerted neuroprotective action in a cell model of Parkinson＇s disease. Methods： A cell model of Parkinson＇s disease was established in PC12 cells by exposure to rotenone （4 pmol/L） for 48 h. Cell viability and apoptosis were assessed, and intracellular ROS level and the mitochondrial membrane potential （MMP） were detected. The expression of apoptosis-related proteins Bax, Bcl-2, cytochrome c, cleaved caspase-3, and oxidative stress-related proteins Nrf2, HO-1 and NQ01 were examined using Western blotting. The mRNA levels of HO-1 and NQ01 were determined with RT-PCR. The nuclear translocation of Nrf2 was observed with immunofluorescence staining. Results： Treatment with rotenone significantly increased the number of apoptotic cells, accompanied by marked increases in the Bax/ Bcl-2 ratio, cytochrome c release and caspase-3 activation. Rotenone also increased ROS accumulation, reduced MMP, and increased the nuclear translocation of Nrf2 as well as the mRNA and protein levels of the Nrf2 downstream target genes HO-1 and NQ01 in PC12 cells. Co-treatment with 20C （0.01-1 pmol/L） dose-dependently attenuated rotenone-induced apoptosis and oxidative stress in PC12 cells. Nrf2 knockdown by siRNA partially reversed the protective effects of 20C in rotenone-treated PC12 cells. Conclusion： The bibenzyl compound 20C protects PC12 cells from rotenone-induced apoptosis, at least in part, via activation of the Nrf2/ARE/HO-1 signaling pathway.

In this study, Schwann cells, at a density of 1 x 105 cells/well, were cultured on regenerated silk fibroin nanofibers （305 ＋ 84 nm） prepared using the electrospinning method. Schwann cells cultured on the silk fibroin nanofibers appeared more ordered, their processes extended further, and they formed more extensive and complex interconnections. In addition, the silk fibroin nanofibers had no impact on the proliferation of Schwann cells or on the secretion of ciliary neurotrophic factor, brain-derived neurotrophic factor or nerve growth factor. These findings indicate that regenerated electrospun silk fibroin nanofibers can promote Schwann cell adhesion, growth and proliferation, and have excellent biocompatibility.

Objective： To observe the effect of needle-retaining time in scalp acupuncture on therapeutic efficacy for post-stroke hemiplegia. Methods： A total of 82 cases who met the inclusion criteria were randomly allocated into a control group （22 cases）, a short-time needle- retaining group （30 cases） and a long-time needle-retaining group （30 cases）. Conventional Bobath therapy was employed in the control group while the scalp acupuncture was combined in the short-time （0.5 h） needle-retaining group and long-time （24 h） needle-retaining group. Then functional assessments were made 1 month and 3 months after treatment using FugI-Meyer motor scale {FMMS）, FugI-Meyer assessment of balance （FMA-B） and modified Barthel index （MBI） score. Results： Cases in the long-time needle-retaining group obtained better effects in motor function of the limbs and activities of daily living （ADL） than the other two groups （P〈0.05）. In addition, there was no statistical significance between the short-time needle-retaining group and the control group （P〉0.05）. Conclusion： The needle-retaining time in scalp acupuncture is substantially associated with the effect for post-stroke hemiplegia and long-time needle-retaining is more advisable.

Research on human glioma stem cells began early in the 21st century and since then has become a rapidly growing research field with the number of publications increasing year by year. The research conducted by our diverse group of investigators focused primarily on cell culture techniques, molecular regulation, signaling pathways, cancer treatment, the stem cell microenvironment and the cellular origin and function of glioma stem cells. In particular, we put forward our view that there are inverse or forward transformations among neural stem cells, glial cells and glioma stem cells in glioma tissues under certain conditions. Based on the background of the progress of international research on human glioma stem cells, we aim to share our progress and current findings of human glioma stem cell research in China with colleagues around the world.

Background： As medication does not normalize outcomes of children with attention deficit hyperactivity disorder （ADHD）, especially in real-life functioning, nonpharmacological methods are important to target this field. This randomized controlled clinical trial was designed to evaluate the effects of a comprehensive executive skill training program for school-aged children with ADHD in a relatively large sample. Methods： The children （aged 6-12 years） with ADHD were randomized to the intervention or waitlist groups. A healthy control group was composed of gender- and age-matched healthy children. The intervention group received a 12-session training program lbr multiple executive skills. Executive function （EF）, ADHD symptoms, and social functioning in the intervention and waitlist groups were evaluated at baseline and the end of the final training session. The healthy controls （HCs） were only assessed once at baseline. Repeated measures analyses of variance were used to compare EF, ADHD symptoms, and social function between intervention and waitlist groups. Results： Thirty-eight children with ADH D in intervention group, 30 in waitlist group, and 23 healthy children in healthy control group were included in final analysis. At posttreatment, intervention group showed significantly lower Behavior Rating Inventory of Executive Function （BRIEF） total score （135.89 ±16.80 vs. 146.09 ± 23.92, P = 0.04） and monitoring score （18.05 ± 2.67 vs. 19.77 ± 3.10, P = 0.02）, ADHD-IV overall score （41.11 ± 7.48 vs. 47.20 ± 8.47, P 〈 0.01 ）, hyperactivity-impulsivity （HI） subscale score （ 18.92 ± 5.09 vs. 21.93 ± 4.93, P = 0.02）, and inattentive subscale score （22.18 ±3.56 vs. 25.27± 5.06, P 〈 0.01 ）, compared with the waitlist group. Repeated measures analyses of variance revealed significant interactions between time and group on the BRIEF inhibition subscale （F = 5.06, P 0.03）, working memory （F- 4.48, P = 0.04）, A DH D-IV overall score （F = 21.72, P 〈 0.01）, HI subscale score （F = 19.08, P 〈 0.01）, and inattentive subscale score （F- 12,40, P 〈 0.01 ）. Multiple-way analysis of variance showed significant differences on all variables of BRIEF, ADHD-rating scale-IV, and WEISS Functional Impairment Scale-Parent form （WFIRS-P） among the intervention and waitlist groups at posttreatment and HCs at baseline. Conclusions： This randomized controlled study on executive skill training in a relatively large sample provided some evidences that the training could improve EF deficits, reduce problematic symptoms, and potentially enhance the social thnctioning in school-aged children with ADHD.

To date, the missed diagnosis rate of pulmonary hypertension (PH) was high, and there has been limited development of a rapid, simple, and effective way to screen the disease. The purpose of this study is to develop a deep learning approach to achieve rapid detection of possible abnormalities in chest radiographs suggesting PH for screening patients suspected of PH. We retrospectively collected frontal chest radiographs and the pulmonary artery systolic pressure (PASP) value measured by Doppler transthoracic echocardiography from 762 patients (357 healthy controls and 405 with PH) from three institutes in China from January 2013 to May 2019. The wohle sample comprised 762 images (641 for training, 80 for internal test, and 41 for external test). We firstly performed a 8-fold cross-validation on the 641 images selected for training (561 for pre-training, 80 for validation), then decided to tune learning rate to 0.0008 according to the best score on validation data. Finally, we used all the pre-training and validation data (561+80 = 641) to train our models (Resnet50, Xception, and Inception V3), evaluated them on internal and external test dataset to classify the images as having manifestations of PH or healthy according to the area under the receiver operating characteristic curve (AUC/ROC). After that, the three deep learning models were further used for prediction of PASP using regression algorithm. Moreover, we invited an experienced chest radiologist to classify the images in the test dataset as having PH or not, and compared the prediction accuracy performed by deep learing models with that of manual classification. The AUC performed by the best model (Inception V3) achieved 0.970 in the internal test, and slightly declined in the external test (0.967) when using deep learning algorithms to classify PH from normal based on chest X-rays. The mean absolute error (MAE) of the best model for prediction of PASP value was smaller in the internal test (7.45) compared to 9.95 in the external test. Manual classification of PH based on chest X-rays showed much lower AUCs compared to that performed by deep learning models both in the internal and external test. The present study used deep learning algorithms to classify abnormalities suggesting PH in chest radiographs with high accuracy and good generalizability. Once tested prospectively in clinical settings, the technology could provide a non-invasive and easy-to-use method to screen patients suspected of having PH.

Oxidative stress results from an imbalance between the production and neutralization of reactive oxygen species. It induces oxidative damage to cellular components including proteins, lipids, nucleic acids, and membranes, therefore intrinsically linking to aging‐related diseases such as cancer, cardiovascular disease, and neurological disorders. Emerging evidence suggests that oxidative stress may promote tumor development by influencing various aspects of cellular senescence, such as its onset, pro‐inflammatory secretion, and alteration of cellular function and structure. Modulating oxidative stress to target cellular senescence offers a novel strategy for cancer prevention and treatment. However, a thorough grasp of the specific mechanisms at play is lacking. This review will present the association between oxidative stress and cellular senescence and their regulatory role in tumor progression and treatment, with emphasis on senescence‐associated secretory phenotype, immunosenescence and therapy‐induced senescence. Current agents and strategies that remove side effects of cellular senescence via killing senescent cancer cells or modulating oxidative stress to improve antitumor efficacy will be summarized. This review will help readers better understand the complex relationship between oxidative stress and senescence in cancer, and will also provide a basis for further research in this area. Cellular senescence is intrinsically related to multiple aspects of tumor development. Oxidative stress contributes to tumor development by regulating cellular senescence. Targeting cellular senescence by modulating oxidative stress can benefit tumor management.

Depression is one of the most important mental illnesses and is closely related to inflammation. Betaine is a natural product with an anti-inflammatory and antioxidant activities. However, the mechanism by which betaine ameliorates depression-like behaviors induced by lipopolysaccharide (LPS) is poorly understood. The purpose of this study was to investigate the neuroprotective effect of betaine on LPS-induced depression-like behavior in mice and its mechanism of action. ICR mice were randomly divided into four groups: the control group, the LPS model group (0.83 mg/kg), the positive drug group (MIDO, 50 mg/kg), and the betaine group (5% and 1% in drinking water). The betaine group was administered for 21 days, and on the 22nd day, except for the blank group, LPS (0.83 mg/kg) was intraperitoneally injected to establish a lipopolysaccharide-induced mice depression-like model. Twenty-four hours after LPS injection, the tail suspension test (TST), open field test (OFT), and sucrose preference test (SPT) were performed to evaluate the effect of betaine on LPS-induced depressive behavior in mice. After the behavioral study, the mouse brain, hippocampus, and serum were taken for detection. The expressions of cytokines and inflammatory mediators were detected by ELISA, HE staining, immunofluorescence, immunohistochemistry, and western blotting. Western blotting was used to detect the protein expression levels of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), caspase-1, and ASC, the protein expression levels of the microglial polarization markers COX-2, inducible nitric oxide synthase (iNOS), and CD206. The results showed that betaine significantly ameliorated the depression-like behavior in LPS-induced mice, significantly attenuated the production of proinflammatory cytokines and increased the release of an anti-inflammatory cytokines. Betaine decreased the expression of the NLRP3 inflammasome, decreased the expression of M1 polarization markers, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-2, and iNOS and promoted the expression of M2 polarization marker CD206. Our study suggests that betaine may promote the transition of microglia from the M1 to the M2 phenotype by inhibiting NLRP3 inflammasome activation, thereby attenuating lipopolysaccharide-induced depression-like behavior.