R-loop-dependent promoter-proximal termination ensures genome stability.

The proper regulation of transcription is essential for maintaining genome integrity and executing other downstream cellular functions1,2. Here we identify a stable association between the genome-stability regulator sensor of single-stranded DNA (SOSS)3 and the transcription regulator Integrator-PP2A (INTAC)4-6. Through SSB1-mediated recognition of single-stranded DNA, SOSS-INTAC stimulates promoter-proximal termination of transcription and attenuates R-loops associated with paused RNA polymerase II to prevent R-loop-induced genome instability. SOSS-INTAC-dependent attenuation of R-loops is enhanced by the ability of SSB1 to form liquid-like condensates. Deletion of NABP2 (encoding SSB1) or introduction of cancer-associated mutations into its intrinsically disordered region leads to a pervasive accumulation of R-loops, highlighting a genome surveillance function of SOSS-INTAC that enables timely termination of transcription at promoters to constrain R-loop accumulation and ensure genome stability.

G-quadruplex in hepatitis B virus pregenomic RNA promotes its translation.

Hepatitis B virus (HBV) is a hepatotropic DNA virus that has a very compact genome. Due to this genomic density, several distinct mechanisms are used to facilitate the viral life cycle. Recently, accumulating evidence show that G-quadruplex (G4) in different viruses play essential regulatory roles in key steps of the viral life cycle. Although G4 structures in the HBV genome have been reported, their function in HBV replication remains elusive. In this study, we treated an HBV replication-competent cell line and HBV-infected cells with the G4 structure stabilizer pyridostatin (PDS) and evaluated different HBV replication markers to better understand the role played by the G4. In both models, we found PDS had no effect on viral precore RNA (pcRNA) or pre-genomic RNA (pgRNA), but treatment did increase HBeAg/HBc ELISA reads and intracellular levels of viral core/capsid protein (HBc) in a dose-dependent manner, suggesting post-transcriptional regulation. To further dissect the mechanism of G4 involvement, we used in vitro-synthesized HBV pcRNA and pgRNA. Interestingly, we found PDS treatment only enhanced HBc expression from pgRNA but not HBeAg expression from pcRNA. Our bioinformatic analysis and CD spectroscopy revealed that pgRNA harbors a conserved G4 structure. Finally, we introduced point mutations in pgRNA to disrupt its G4 structure and observed the resulting mutant failed to respond to PDS treatment and decreased HBc level in in vitro translation assay. Taken together, our data demonstrate that HBV pgRNA contains a G4 structure that plays a vital role in the regulation of viral mRNA translation.

Ligand-induced native G-quadruplex stabilization impairs transcription initiation.

G-quadruplexes (G4s) are noncanonical DNA secondary structures formed through the self-association of guanines, and G4s are distributed widely across the genome. G4 participates in multiple biological processes including gene transcription, and G4-targeted ligands serve as potential therapeutic agents for DNA-targeted therapies. However, genome-wide studies of the exact roles of G4s in transcriptional regulation are still lacking. Here, we establish a sensitive G4-CUT&Tag method for genome-wide profiling of native G4s with high resolution and specificity. We find that native G4 signals are cell type-specific and are associated with transcriptional regulatory elements carrying active epigenetic modifications. Drug-induced promoter-proximal RNA polymerase II pausing promotes nearby G4 formation. In contrast, G4 stabilization by G4-targeted ligands globally reduces RNA polymerase II occupancy at gene promoters as well as nascent RNA synthesis. Moreover, ligand-induced G4 stabilization modulates chromatin states and impedes transcription initiation via inhibition of general transcription factors loading to promoters. Together, our study reveals a reciprocal genome-wide regulation between native G4 dynamics and gene transcription, which will deepen our understanding of G4 biology toward therapeutically targeting G4s in human diseases.

Concurrent spinal meningioma and giant invasive schwannoma without neurofibromatosis in children: A case report and literature review.

BACKGROUND: Spinal meningiomas coexisting with schwannomas in patients without neurofibromatosis are extremely rare lesions. There were only 15 cases reported to date, which were concurrent intradural tumors of different pathological types. CASE PRESENTATION: Herein, we present a rare case of a 15-year-old child with concurrent spinal dorsal meningioma and ventral giant invasive schwannoma at C7-T3 and T10-S5 spinal levels. Preoperative magnetic resonance imaging and computed tomography indicated the schwannoma across the thoracic and lumbosacral transitional vertebra, with extensive bony erosion of the sacrum. The results of surgical resection were mostly satisfactory. CONCLUSIONS: The present case is the youngest patient diagnosed with concurrent intradural tumors at different spinal levels. The pathogenetic mechanism remains unclear. The clinical presentations are always atypical. Surgical resection of the tumors is the first choice. We use the non-fusion surgery to preserve the function of the lumbar spine.

Effects of Enteral Nutrition Support with Ultrasound-guided Three-lumen Gastrojejunal Tube Insertion on Success Rate of Catheterization, Nutritional Status and Aspiration Rate in Patients with Severe Neurological Diseases.

Objective: The primary aim of this study is to explore the effects of enteral nutrition support with ultrasound-guided three-lumen gastrojejunal tube insertion on nutritional status in patients with severe neurological diseases. Additionally, we aim to assess the impact of this intervention on the success rate of catheterization and the aspiration rate, to comprehensively evaluate its benefits and optimize patient care. Methods: Between March 2022 and March 2023, 60 patients were recruited and randomly divided into ultrasound-guided and control groups of 30 patients each using the Simple Randomisation method. In the control group, a triple-lumen feeding tube was blindly inserted at the bedside for enteral nutritional therapy, and in the ultrasound-guided group, ultrasound-guided identification of gastric structures for placement of a triple-lumen feeding tube for enteral nutritional support, and both treatments were continued for 2 weeks. The success rate of catheterization, nutritional status, aspiration rate, patient satisfaction, and incidence of complications were compared between the two groups before and after treatment. Results: The difference in the success rate of catheterization between the ultrasound guidance group and control group was not statistically significant (93.33% vs 96.67%, P>0.05). After treatment, TP (70.84±3.54 vs 67.15±4.23), ALB (41.23±3.65 vs 38.22±3.47), and Hb (11.54±0.62 vs 9.35±0.28) levels in the ultrasound guidance group were higher than in the control group (P < .05). The difference in aspiration rate between the ultrasound guidance group and control group was not statistically significant [0.00% (0/30) vs 3.33% (1/30), P > .05]. The patient satisfaction in the ultrasound guidance group was higher than that in the control group (P < .05). The difference in the incidence of complications (stomachache, headache, nausea, and vomiting) between the ultrasound guidance group and control group was not statistically significant (6.67% vs 20.00%, P > .05). Conclusion: Enteral nutrition support with ultrasound-guided three-lumen gastrojejunal tube insertion can improve the success rate of catheterization and nutritional status, reduce aspiration rate, and improve satisfaction in patients with severe neurological diseases. In the future, we need to further investigate the incorporation of ultrasound guidance into standard care protocols for patients with severe neurological disorders requiring enteral nutrition. The indications for ultrasound guidance in nursing should also be expanded. In conclusion, ultrasound-guided insertion should be considered the technique of choice for improving nutritional status in the population of patients with severe neurological disease.

Thrombectomy alone vs thrombectomy with over 2/3-dose intravenous thrombolysis pretreatment in the DIRECT-MT trial.

BACKGROUND: The DIRECT-MT trial showed that endovascular thrombectomy (EVT) alone was noninferior to EVT preceded by intravenous alteplase. However, the infusion of intravenous alteplase was uncompleted before the initiation of EVT in most cases of this trial. Therefore, the additional benefit and risk of over 2/3-dose intravenous alteplase pretreatment remain to be assessed. METHODS: We assessed patients with acute anterior circulation ischemic stroke who received EVT alone or with over 2/3-dose intravenous alteplase pretreatment from the DIRECT-MT trial. Patients were assigned to the thrombectomy-alone group and the alteplase pretreatment group. The primary outcome was the distribution of modified Rankin Scale (mRS) at 90 days. The interaction of treatment allocation and collateral capacity was assessed. RESULTS: A total of 393 patients (thrombectomy alone: 315; alteplase pretreatment: 78) were identified. The thrombectomy alone was comparable with alteplase pretreatment prior to the thrombectomy on the distribution of mRS at 90 days without significant effect modification by collateral capacity (adjusted common odds ratio (acOR), 1.12; 95% CI, 0.72-1.74; adjusted P for interaction = 0.83). Successful reperfusion before thrombectomy and the number of passes in the thrombectomy alone group differed significantly from the alteplase pretreatment group (2.6% vs. 11.5%; corrected P = 0.02 and 2 vs. 1; corrected P = 0.003). There was no interaction between treatment allocation and collateral capacity on all outcomes. CONCLUSIONS: EVT alone and EVT preceded by over 2/3-dose intravenous alteplase might have equal efficacy and safety for patients with acute anterior circulation large vessel occlusion, except for successful perfusion before thrombectomy and the number of passes.

Characteristics of oral mucosal pressure injuries in children with orotracheal intubation in intensive care units: An observational study.

BACKGROUND: Tracheal intubation can be used for ventilation to ensure an unobstructed respiratory tract, and it is the most common respiratory support technique used in paediatric intensive care unit (PICU) patients. Orotracheal intubation is usually the preferred method of tracheal intubation. However, it can cause stress-related damage to the oral mucosa. Identifying the factors that cause oral mucosal pressure injury (OMPI) can prevent its occurrence in children with oral endotracheal intubation. AIMS: To examine the characteristics of OMPI in children who underwent orotracheal intubation in the PICU and to assess their influencing factors. STUDY DESIGN: An observational, prospective study. Data were gathered from the PICU of a tertiary hospital in China between January 2023 and October 2023. The patient data were obtained from the 'General Information Questionnaire', 'Paediatric Critical Illness Score', 'STRONGkids Scale' and 'OMPI Staging and Assessment Tools'. Data analysis was subsequently performed using univariate and logistic regression analyses. RESULTS: A total of 187 children who underwent orotracheal intubation were analysed. During the observation period, 44.92% (n = 84) of the children developed OMPI. It comprised 63.10% (n = 53) of stage I injuries, 33.33% (n = 28) of stage II injuries and 3.57% (n = 3) of stage III injuries. The common injury sites were the lower jaw (48.81%), upper jaw (29.76%), tongue (20.24%) and joints (10.71%). The logistic regression analysis results revealed that high critical illness (OR = 0.835, 95% CI: 0.726-0.961), long intubation time (OR = 1.043, 95% CI: 1.021-1.067), prone ventilation (OR = 6.708, 95% CI: 1.421-31.670), hypothermia (OR = 5.831, 95% CI: 1.208-28.149), use of dental pads (OR = 5.520, 95% CI: 1.150-26.487) and low albumin levels (OR = 6.238, 95% CI: 1.285-30.281) were the main contributing factors for OMPI in children with orotracheal intubation (p < .05). CONCLUSIONS: The occurrence of OMPI in children who underwent orotracheal intubation in the PICU was notable and was predominantly observed in stages I and II. Consequently, clinical nursing personnel should proactively recognize risk factors and administer timely interventions to mitigate the occurrence of OMPI in such children. RELEVANCE TO CLINICAL PRACTICE: The incidence of OMPI in children who underwent orotracheal intubation was relatively high. Nurses and doctors should closely monitor the risk factors for orotracheal intubation in children to prevent the occurrence of OMPI.

Solution Versus On-Surface Synthesis of Peripherally Oxygen-Annulated Porphyrins through C-O Bond Formation.

This study investigates the synthesis of tetra- and octa-O-fused porphyrinoids employing an oxidative O-annulation approach through C-H activation. Despite encountering challenges such as overoxidation and instability in conventional solution protocols, successful synthesis was achieved on Au(111) surfaces under ultra-high vacuum (UHV) conditions. X-ray photoelectron spectroscopy, scanning tunneling microscopy, and non-contact atomic force microscopy elucidated the preferential formation of pyran moieties via C-O bond formation and subsequent self-assembly driven by C-H⋅⋅⋅O interactions. Furthermore, the O-annulation process was found to reduce the HOMO-LUMO gap by lifting the HOMO energy level, with the effect rising upon increasing the number of embedded O-atoms.

Endovascular Thrombectomy with or without Intravenous Alteplase in Acute Stroke.

BACKGROUND: In acute ischemic stroke, there is uncertainty regarding the benefit and risk of administering intravenous alteplase before endovascular thrombectomy. METHODS: We conducted a trial at 41 academic tertiary care centers in China to evaluate endovascular thrombectomy with or without intravenous alteplase in patients with acute ischemic stroke. Patients with acute ischemic stroke from large-vessel occlusion in the anterior circulation were randomly assigned in a 1:1 ratio to undergo endovascular thrombectomy alone (thrombectomy-alone group) or endovascular thrombectomy preceded by intravenous alteplase, at a dose of 0.9 mg per kilogram of body weight, administered within 4.5 hours after symptom onset (combination-therapy group). The primary analysis for noninferiority assessed the between-group difference in the distribution of the modified Rankin scale scores (range, 0 [no symptoms] to 6 [death]) at 90 days on the basis of a lower boundary of the 95% confidence interval of the adjusted common odds ratio equal to or larger than 0.8. We assessed various secondary outcomes, including death and reperfusion of the ischemic area. RESULTS: Of 1586 patients screened, 656 were enrolled, with 327 patients assigned to the thrombectomy-alone group and 329 assigned to the combination-therapy group. Endovascular thrombectomy alone was noninferior to combined intravenous alteplase and endovascular thrombectomy with regard to the primary outcome (adjusted common odds ratio, 1.07; 95% confidence interval, 0.81 to 1.40; P = 0.04 for noninferiority) but was associated with lower percentages of patients with successful reperfusion before thrombectomy (2.4% vs. 7.0%) and overall successful reperfusion (79.4% vs. 84.5%). Mortality at 90 days was 17.7% in the thrombectomy-alone group and 18.8% in the combination-therapy group. CONCLUSIONS: In Chinese patients with acute ischemic stroke from large-vessel occlusion, endovascular thrombectomy alone was noninferior with regard to functional outcome, within a 20% margin of confidence, to endovascular thrombectomy preceded by intravenous alteplase administered within 4.5 hours after symptom onset. (Funded by the Stroke Prevention Project of the National Health Commission of the People's Republic of China and the Wu Jieping Medical Foundation; DIRECT-MT ClinicalTrials.gov number, NCT03469206.).

What information can we gain from the quality appraisal of guidelines with physical activity recommendations for cancer patients?A systematic review using the AGREE II and AGREE-REX tools.

PURPOSE: There has been growing amount of evidence supporting the benefits of physical activity (PA) on oncological patients' cancer-related health outcomes. Although guidelines on cancer rehabilitation are widely available, the varying quality and practical applicability limited the clinical application of PA recommendations. To assist the future development of guidelines, in this systematic review, we evaluated the quality and applicability of current cancer rehabilitation guidelines with PA recommendations and synthesized PA recommendations for the oncological population. METHODS: A systematic search was conducted in PubMed, CINAHL, PEDro, EMBASE, and guideline repositories to identify guidelines with PA recommendations for cancer patients from 1 May 2016 to 1 June 2022. The quality of included guidelines was appraised using the tools "Appraisal of Guidelines for Research and Evaluation II" (AGREE II) and AGREE-REX (Recommendation Excellence). PA recommendations were synthesized from the guidelines. RESULTS: Sixteen guidelines were extracted. The AGREE II domain "clarity of presentation" obtained the highest score, while "applicability" received the lowest, ranging from 33.33% to 98.58%. The AGREE-REX domains "values and preferences" and "implementability" generally scored lower and ranged from 45.83% to 74.17% and 55% to 88.33%, respectively. Eight high-quality guidelines were identified, and the included PA recommendations were extracted. CONCLUSION: There were some disparities in the quality of the included guidelines. Methodological weaknesses were commonly observed in domains "applicability," "values and preferences," and "implementability"; particular attention should be given to these domains when developing future guidelines. Furthermore, this analysis indicated that more rigorous, high-quality studies are needed to generate evidence for supporting PA recommendations and provide guidance on research gaps in the field of cancer rehabilitation.

Is physical activity effective against cancer-related fatigue in lung cancer patients? An umbrella review of systematic reviews and meta-analyses.

OBJECTIVES: To discuss the effects of physical activity on cancer-related fatigue (CRF) in lung cancer patients, summarize the types of physical activity in the published reviews, assess the quality of the evidence, and provide suggestions for the clinical selection of exercise intervention. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Database of Systematic Reviews were searched through 8 November 2021 to identify relevant systematic reviews and meta-analyses. We also performed a manual search of the reference lists of included articles as supplements. Two researchers independently performed literature screening, data extraction, and quality assessment. The umbrella review has been registered in the International Prospective Register of Systematic Review (PROSPERO) registry (CRD42021292548). RESULTS: From the 13 systematic reviews or meta-analyses identified, 10 physical activity interventions were included. The most mentioned intervention was aerobic combined with resistance exercise; however, no reduction of the symptoms of CRF was observed in lung cancer patients by this exercise intervention. Most of the patients who performed aerobic exercises alone showed improvement in CRF after the intervention. In addition, Tai Chi and breathing exercises have been shown to improve fatigue, but more high-quality research is still needed to support its effectiveness. CONCLUSIONS: Aerobic exercise, respiratory muscle training, aerobic combined with balance training, and other exercise interventions have been shown to improve CRF in lung cancer patients. But it should be noted that according to the different treatment methods and disease stages of patients, individualized rehabilitation programs should be developed for patients. Due to the low methodological quality and evidence quality of some systematic reviews and meta-analyses included in this study, more high-quality clinical studies and systematic reviews are still needed for validation in the future. This umbrella review helps to identify effective ways of exercise to improve fatigue in lung cancer patients before dedicated evidence-based medical guidelines are established.

The Role of Gut Microbiota in Various Neurological and Psychiatric Disorders-An Evidence Mapping Based on Quantified Evidence.

Methods: We searched PubMed, Cochrane Library, and Epistemonikos to identify systematic reviews and meta-analysis (SRs). We searched for neurological diseases and psychiatric disorders, including Alzheimer's disease (AD), attention deficit hyperactivity disorder (ADHD), amyotrophic lateral sclerosis (ALS), autism spectrum disorder (ASD), anorexia nervosa (AN), bipolar disorder (BD), eating disorder (ED), generalized anxiety disorder (GAD), major depressive disorder (MDD), multiple sclerosis (MS), obsessive compulsive disorder (OCD), Parkinson's disease (PD), posttraumatic stress disorder (PTSD), spinal cord injury (SCI), schizophrenia, and stroke. We used A Measurement Tool to Assess Systematic Reviews (AMSTAR-2) to evaluate the quality of included SRs. We also created an evidence map showing the role of gut microbiota in neurological diseases and the certainty of the evidence. Results: In total, 42 studies were included in this evidence mapping. Most findings were obtained from observational studies. According to the AMSTAR-2 assessment, 21 SRs scored "critically low" in terms of methodological quality, 16 SR scored "low," and 5 SR scored "moderate." A total of 15 diseases have been investigated for the potential association between gut microbiome alpha diversity and disease, with the Shannon index and Simpson index being the most widely studied. A total of 12 diseases were investigated for potential link between beta diversity and disease. At the phylum level, Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, and Verrucomicrobia were more researched. At the genus level, Prevotella, Coprococcus, Parabacteroides, Phascolarctobacterium, Escherichia Shigella, Alistipes, Sutteralla, Veillonella, Odoribacter, Faecalibacterium, Bacteroides, Bifidobacterium, Dialister, and Blautia were more researched. Some diseases have been found to have specific flora changes, and some diseases have been found to have common intestinal microbiological changes. Conclusion: We found varied levels of evidence for the associations between gut microbiota and neurological diseases; some gut microbiota increased the risk of neurological diseases, whereas others showed evidence of benefit that gut microbiota might be promising therapeutic targets for such diseases.

Focus on the impact of social factors and lifestyle on the disease burden of low back pain: findings from the global burden of disease study 2019.

BACKGROUND: Low back pain (LBP) is one of the leading causes of disability worldwide. Differences in social backgrounds and lifestyles in various regions and countries may contribute to the discrepancies in the disease burden of LBP. METHODS: Based on the GBD 2019, we collected and analyzed numbers and age-standardized rates (ASR) of LBP disability-adjusted life years (DALYs). Temporal trends in ASR were also analyzed using estimated annual percentage change (EAPC). The Age-period-cohort (APC) model was used to estimate age, period and cohort trends in DALYs of LBP. An autoregressive integrated moving average (ARIMA) model was used to forecast DALYs of LBP trends from 2020 to 2035. RESULTS: The DALYs due to LBP increased from 1990 to 2019. The APC model showed that the risk of DALYs for global LBP increased with age and year and that the risk of DALYs was lower in the later-born cohort than in the earlier-born cohort. The main risk factors which GBD estimates were available for DALYs of LBP include smoking, occupational ergonomic factors and high BMI. It is expected that DALYs of LBP will continue to rise until 2035. CONCLUSION: From 1990 to 2019, the global disease burden of LBP remained high. It is necessary to pay attention to the influence of social factors and lifestyle on LBP. Focusing on the impact of social factors as well as lifestyle on the prognosis of LBP and targeting interventions may further reduce the disease burden of LBP.

Evidence Mapping Based on Systematic Reviews of Cognitive Behavioral Therapy for Neuropathic Pain.

Objective: This evidence mapping is aimed at identifying, summarizing, and analyzing the available evidence on cognitive behavioral therapy (CBT) for neuropathic pain (NP). Methods: This study was conducted following the methodology of Global Evidence Mapping (GEM). Searches were conducted in PubMed, Embase, the Cochrane Library, and PsycINFO to identify systematic reviews (SRs) with or without meta-analysis published before February 15, 2022. The authors independently assessed eligibility, extracted data, and evaluated the methodological quality of the included SRs using AMSTAR-2. The results were presented in the tables and a bubble plot based on the identified population-intervention-comparison-outcome (PICO) questions. Results: A total of 34 SRs met the eligibility criteria. According to the AMSTAR-2, 2 SRs were rated "high," 2 SRs were rated "moderate," 6 SRs were rated "low," and 24 SRs were rated "critically low." The most common study design utilized to evaluate the efficacy of CBT for NP was the randomized controlled trial. In total, 24 PICOs were identified. Migraine was the most studied population. CBT for NP usually reaches the "potentially better" result at follow-up. Conclusions: Evidence mapping is a useful way to present existing evidence. Currently, the existing evidence on CBT for NP is limited. Overall, the methodological quality of the included SRs was low. Further improvements in the methodological quality of SRs and more research on the most efficient CBT formats for NP are recommended in the future.

Protection roles of serum vitamin D levels in the cardiovascular system.

Protection roles of serum vitamin D levels in the cardiovascular system. This observational study enrolled 286 young ACI patients with type 2 diabetes mellitus in our Hospital from October 2016 to April 2020 as the study group. 127 healthy individuals as the control group. Serum levels of vitamin D and blood pressure indexes of the two groups were measured and the correlation between vitamin D levels and the clinical phenotype of young cerebral infarction was explored. Significantly higher 25-hydroxyvitamin D was observed in the study group vs. control group. During the day, The values of systolic and diastolic blood pressure and mean blood pressure was well-balanced between the two groups. However, at night and within 24 hours, significant differences in systolic and diastolic blood pressure and mean value were observed between the two groups. The higher the vitamin D level, the greater the decrease in blood pressure at night. Serum 25-hydroxyvitamin D was positively correlated with the reduction of night systolic and diastolic blood pressure. Low levels of 25-hydroxyvitamin D led to a small decrease in blood pressure at night, resulting in a vulnerable cardiovascular system and an increased incidence of cerebral infarction in the young population.

EGF signaling promotes the lineage conversion of astrocytes into oligodendrocytes.

BACKGROUND: The conversion of astrocytes activated by nerve injuries to oligodendrocytes is not only beneficial to axonal remyelination, but also helpful for reversal of glial scar. Recent studies have shown that pathological niche promoted the Sox10-mediated astrocytic transdifferentiation to oligodendrocytes. The extracellular factors underlying the cell fate switching are not known. METHODS: Astrocytes were obtained from mouse spinal cord dissociation culture and purified by differential adherent properties. The lineage conversion of astrocytes into oligodendrocyte lineage cells was carried out by Sox10-expressing virus infection both in vitro and in vivo, meanwhile, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) inhibitor Gefitinib were adopted to investigate the function of EGF signaling in this fate transition process. Pharmacological inhibition analyses were performed to examine the pathway connecting the EGF with the expression of oligodendrogenic genes and cell fate transdifferentiation. RESULTS: EGF treatment facilitated the Sox10-induced transformation of astrocytes to O4+ induced oligodendrocyte precursor cells (iOPCs) in vitro. The transdifferentiation of astrocytes to iOPCs went through two distinct but interconnected processes: (1) dedifferentiation of astrocytes to astrocyte precursor cells (APCs); (2) transformation of APCs to iOPCs, EGF signaling was involved in both processes. And EGF triggered astrocytes to express oligodendrogenic genes Olig1 and Olig2 by activating extracellular signal-regulated kinase 1 and 2 (Erk1/2) pathway. In addition, we discovered that EGF can enhance astrocyte transdifferentiation in injured spinal cord tissues. CONCLUSIONS: These findings provide strong evidence that EGF facilitates the transdifferentiation of astrocytes to oligodendrocytes, and suggest that targeting the EGF-EGFR-Erk1/2 signaling axis may represent a novel therapeutic strategy for myelin repair in injured central nervous system (CNS) tissues.

Subthalamic nucleus-deep brain stimulation improves autonomic dysfunctions in Parkinson's disease.

BACKGROUND: To study the effects of subthalamic nucleus-deep brain stimulation (STN-DBS) on autonomic dysfunctions in Parkinson's disease (PD) patients. METHODS: A total of 57 PD patients who underwent bilateral STN-DBS from March to December 2018, were retrospectively analyzed. Preplanned assessments at baseline and postoperatively at 1, 3, and 6 months also included the Scales for Outcomes in Parkinson's Disease-Autonomic questionnaire (SCOPA-Aut), the Unified Parkinson's Disease Rating Scale (UPDRS) III score, levodopa equivalent day dose (LEDD), Parkinson's Disease Quality of Life Scale (PDQ-39), the Hamilton Anxiety Rating Scale (HAMA), and the Hamilton Depression Rating Scale (HAMD). RESULTS: The SCOPA-Aut scores improved significantly [14.59% (18.32%), 24.00% (27.05%), 22.16% (27.07%), all P < 0.001] at 1 month, 3 months, and 6 months of STN-DBS, respectively. Analysis of the SCOPA-Aut sub-items showed significant improvements only in urine and thermoregulation sub-items at 6 months after surgery (P < 0.001). There was no significant correlation between improvements of SCOPA-Aut scores and improvements of PDQ-39 scores (P > 0.05) at 6 months after surgery. SCOPA-Aut scores were positively correlated with age (r = 0.428, P = 0.001); the improvements of SCCOPA-Aut scores were positively correlated with improvements of HAMA and HAMD scores (HAMA: r = 0.325, P = 0.015; HAMD: r = 0.265, P = 0.049) at 6 months after surgery. CONCLUSION: STN-DBS improved autonomic dysfunction symptoms of PD patients, and urinary and thermoregulatory sub-items of autonomic dysfunction were improved in the short-term after surgery. There was a close relationship between improved autonomic symptoms and improved anxiety and depression 6 months after surgery. We should therefore direct more attention to autonomic dysfunctions in PD involving detailed preoperative evaluations and postoperative follow-ups, to improve the quality of life of patients.

Dermoscopy, reflectance confocal microscopy, and fluorescence staining for the noninvasive diagnosis of crusted scabies.

A 91-year-old woman presented with a 3-month history of [extensive](javascript:;) cutaneous lesions with intense pruritus. She lived in a nursing home for a long time. Physical examination revealed a generalized erythematous and scaly rash with intense hyperkeratotic lesions on the neck, trunk, and limbs. Dermoscopy showed a sinuous burrow filled with white dot eggs and feces on the hand with a mite at the end of the burrow. Reflectance confocal microscopy (RCM) manifested a sinuous burrow and a mite. The presence of mites was confirmed with fluorescence staining. The patient was diagnosed with crusted scabies and started treatment with 10% sulfur ointment. Her lesions and pruritus were resolved after 2 weeks.

Phellinus baumii Polyphenol: A Potential Therapeutic Candidate against Lung Cancer Cells.

Phellinus baumii, a fungus that grows on mulberry trees and is used in traditional Chinese medicine, exerts therapeutic effects against various diseases, including cancer. Polyphenols, generally considered to be antioxidants, have antitumor and proapoptotic effects. In this study, we identified the composition of Phellinus baumii polyphenol (PBP) and characterized its 17 chemical components by UPLC-ESI-QTOF-MS. Furthermore, to clarify the potential mechanism of PBP against Lung Cancer Cells, network pharmacology and experimental verification were combined. Molecular docking elucidated the binding conformation and mechanism of the primary active components (Osmundacetone and hispidin) to the core targets CASP3, PARP1 and TP53. In addition, potential molecular mechanisms of PBP predicted by network pharmacology analysis were validated in vitro. PBP significantly inhibited the human lung cancer A549 cells and showed typical apoptotic characteristics, without significant cytotoxicity to normal human embryonic kidney (HEK293) cells. Analysis using flow cytometry and western blot indicated that PBP caused apoptosis, cell cycle arrest, reactive oxygen species (ROS) accumulation, and mitochondrial membrane potential (MMP) depression in A549 cells to exercise its antitumor effects. These results reveal that PBP has great potential for use as an active ingredient for antitumor therapy.

Chloroplast Thylakoidal Ascorbate Peroxidase, PtotAPX, Has Enhanced Resistance to Oxidative Stress in Populus tomentosa.

Chloroplasts are the most major producers of reactive oxygen species (ROS) during photosynthesis. However, the function of thylakoid ascorbate peroxidase (tAPX) in response to oxidative stress in wood trees is largely unknown. Our results showed that PtotAPX of Populus tomentosa could effectively utilize ascorbic acid (AsA) to hydrolyze hydrogen peroxide (H2O2) in vitro. The overexpression or antisense of PtotAPX (OX-PtotAPX or anti-PtotAPX, respectively) in Populus tomentosa plants did not significantly affect plant morphology during plant growth. When treated with methyl viologen (MV), the OX-PtotAPX plants exhibited less morphological damage under stress conditions compared to WT plants. OX-PtotAPX plants maintained lower H2O2 levels and malondialdehyde (MDA) contents, but more reduced AsA levels, a higher photosynthetic rate (Pn), and the maximal photochemical efficiency of PSII (Fv/Fm), whereas anti-PtotAPX plants showed the opposite phenotype. Furthermore, the activity of APX was slightly higher in OX-PtotAPX under normal growth conditions, and this activity significantly decreased after stress treatment, which was the lowest in anti-P. Based on these results, we propose that PtotAPX is important for protecting the photosynthetic machinery under severe oxidative stress conditions in P. tomentosa, and is a potential genetic resource for regulating the stress tolerance of woody plants.