Single-nucleus analysis reveals microenvironment-specific neuron and glial cell enrichment in Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) is a complicated neurodegenerative disease. Neuron-glial cell interactions are an important but not fully understood process in the progression of AD. We used bioinformatic methods to analyze single-nucleus RNA sequencing (snRNA-seq) data to investigate the cellular and molecular biological processes of AD. METHOD: snRNA-seq data were downloaded from Gene Expression Omnibus (GEO) datasets and reprocessed to identify 240,804 single nuclei from healthy controls and patients with AD. The cellular composition of AD was further explored using Uniform Manifold Approximation and Projection (UMAP). Enrichment analysis for the functions of the DEGs was conducted and cell development trajectory analyses were used to reveal underlying cell fate decisions. iTALK was performed to identify ligand-receptor pairs among various cell types in the pathological ecological microenvironment of AD. RESULTS: Six cell types and multiple subclusters were identified based on the snRNA-seq data. A subcluster of neuron and glial cells co-expressing lncRNA-SNHG14, myocardin-related transcription factor A (MRTFA), and MRTFB was found to be more abundant in the AD group. This subcluster was enriched in mitogen-activated protein kinase (MAPK)-, immune-, and apoptosis-related pathways. Through molecular docking, we found that lncRNA-SNHG14 may bind MRTFA and MRTFB, resulting in an interaction between neurons and glial cells. CONCLUSIONS: The findings of this study describe a regulatory relationship between lncRNA-SNHG14, MRTFA, and MRTFB in the six main cell types of AD. This relationship may contribute to microenvironment remodeling in AD and provide a theoretical basis for a more in-depth analysis of AD.

Surface Treatment with Tailored π-Conjugated Fluorene Derivatives Significantly Enhances the Performance of Perovskite Light-Emitting Diodes.

Surface defect passivation and carrier injection regulation have emerged as effective strategies for enhancing the performance of perovskite light-emitting diodes (Pero-LEDs). It usually requires two functional molecules to realize defect passivation and carrier injection regulation separately. In other words, developing one single molecule possessing these capabilities remains challenging. Herein, we utilized π-conjugated fluorene derivatives as surface treatment materials, 9,9-Spirobi[fluorene] (SBF), 9,9-Spirobifluoren-2-yl-diphenylphosphine oxide (SPPO1), and 2,7-bis(diphenylphosphoryl)-9,9'-spirobifluorene (SPPO13), to investigate the influence of their chemical structure on device optoelectronic performance, especially for defect passivation and carrier injection regulation. Consequently, the passivation capability of double-bonded SPPO13 surpassed single-bonded SPPO1 and nonbonded SBF, which all showed excellent electron transport properties, enhancing electron injection. The maximum external quantum efficiencies (EQE) for Pero-LEDs treated with SBF, SPPO1, and SPPO13 were 8.13, 17.48, and 22.10%, respectively, exceeding that of the derivative-free device (6.55%). Notably, SPPO13-treated devices exhibited exceptional reproducibility, yielding an average EQE of 20.00 ± 1.10% based on 30 devices. This result emphasizes the potential of tailored fluorene derivatives for enhancing the device performance of Pero-LEDs.

Cross-Linkable Fullerene Enables Elastic and Conductive Grain Boundaries for Efficient and Wearable Tin-Based Perovskite Solar Cells.

Tin-based perovskite solar cells (TPSCs) have received increasing attention due to their low toxicity, high theoretical efficiency, and potential applications as wearable devices. However, the inherent fast and uncontrollable crystallization process of tin-based perovskites results in high defect density in the film. Meanwhile, when fabricated into flexible devices, the prepared perovskite film exhibits inevitable brittleness and high Young's modulus, seriously weakening the mechanical stability. In this work, we design and synthesize a cross-linkable fullerene, thioctic acid functionalized C60 fulleropyrrolidinium iodide (FTAI), which has multiple interactions with perovskite components and can finely regulate the crystallization quality of perovskite film. The obtained perovskite film shows an increased grain size and a more matched energy level with the electron transport material, effectively improving the carrier extraction efficiency. The FTAI-based rigid device achieves a champion efficiency of 14.91 % with enhanced stability. More importantly, the FTAI located at the perovskite grain boundaries could spontaneously cross-link during the perovskite annealing process, which effectively improves the conductivity and elasticity of grain boundaries, thereby giving the film excellent bending resistance. Finally, the FTAI-based wearable device yields a record efficiency of 12.35 % and displays robust bending durability, retaining about 90 % of the initial efficiency after 10,000 bending times.

Single-cell and spatial transcriptomics reveals that PTPRG activates the m6A methyltransferase VIRMA to block mitophagy-mediated neuronal death in Alzheimer's disease.

Neuronal death is one of the key pathologies in Alzheimer's disease (AD). How neuronal death begins in AD is far from clear, so clarifying this process may help develop effective therapies. This study collected single-cell RNA sequencing data of 85 AD samples and 83 control samples, covering the prefrontal cortex, internal olfactory cortex, superior parietal lobe, superior frontal gyrus, caudal internal olfactory cortex, somatosensory cortex, hippocampus, superior frontal cortex and peripheral blood mononuclear cells. Additionally, spatial transcriptomic data of coronal sections from 6 AppNL-G-F AD mice and 6 control C57Bl/6 J mice were acquired. The main single-cell and spatial transcriptomics results were experimentally validated in wild type and 5 × FAD mice. We found that the microglia subpopulation Mic_PTPRG can communicate with specific types of neurons (especially excitatory ExNeu_PRKN_VIRMA and inhibitory InNeu_PRKN_VIRMA neuronal subpopulations) and cause them to express PTPRG during AD progression. Within neurons, PTPRG binds and upregulates the m6A methyltransferase VIRMA, thus inhibiting translation of PRKN mRNA to prevent the clearance of damaged mitochondria in neurons through suppressing mitophagy. As the disease progresses, the energy and nutrient metabolic pathways in neurons are reprogrammed, leading to their death. Consistently, we determined that PTPTRG can physically interact with VIRMA in mouse brains and PRKN is significantly upregulated in 5 × FAD mouse brain. Altogether, our findings demonstrate that PTPRG activates the m6A methyltransferase VIRMA to block mitophagy-mediated neuronal death in AD, which is a potential pathway, through which microglia and neuronal PTPRG modify neuronal connections in the brain during AD progression.

Efficient Perovskite Light-Emitting Diodes with Chemically Bonded Contact and Regulated Charge Behavior.

Efficient charge injection and radiative recombination are essential to achieving high-performance perovskite light-emitting diodes (Pero-LEDs). However, the perovskite emission layer (EML) and the electron transport layer (ETL) form a poor physically interfacial contact and non-negligible charge injection barrier, limiting the device performance. Herein, we utilize a phosphine oxide, 2,4,6-tris[3-(diphenylphosphinyl)phenyl]-1,3,5-triazine (PO-T2T), to treat the perovskite/ETL interface and form a chemically bonded contact. Specifically, PO-T2T firmly bonds on the perovskite's surface and grain boundaries through a dative bond, effectively passivating the uncoordinated lead defects. Additionally, PO-T2T has high electron mobility and establishes an electron transport highway to bridge the ETL and EML. As a result, a maximum external quantum efficiency (EQEmax) of 22.06% (average EQEmax of 20.02 ± 1.00%) and maximum luminance (Lmax) of 103286 cd m-2 have been achieved for the champion device. Our results indicate that EML/ETL interface modifications are crucial for the fabrication of highly efficient Pero-LEDs.

Comparative transcriptome findings reveal the neuroinflammatory network and potential biomarkers to early detection of ischemic stroke.

INTRODUCTION: Ischemic stroke accounts for 70-80% of all stroke cases, leading to over two million people dying every year. Poor diagnosis and late detection are the major causes of the high death and disability rate. METHODS: In the present study, we used the middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomic analysis, followed by a systematic advanced bioinformatic analysis, including gene ontology enrichment analysis and Ingenuity Pathway Analysis (IPA). We aimed to identify novel biomarkers for the early detection of ischemic stroke. In addition, we aimed to delineate the molecular mechanisms underlying the development of ischemic stroke, in which we hoped to identify novel therapeutic targets for treating ischemic stroke. RESULTS: In the comparative transcriptomic analysis, we identified 2657 differentially expressed genes (DEGs) in the brain tissue of the MCAO model. The gene enrichment analysis highlighted the importance of these DEGs in oxygen regulation, neural functions, and inflammatory and immune responses. We identified the elevation of angiopoietin-2 and leptin receptor as potential novel biomarkers for early detection of ischemic stroke. Furthermore, the result of IPA suggested targeting the inflammasome pathway, integrin-linked kinase signaling pathway, and Th1 signaling pathway for treating ischemic stroke. CONCLUSION: The results of the present study provide novel insight into the biomarkers and therapeutic targets as potential treatments of ischemic stroke.

Methodological quality and reporting quality of COVID-19 living systematic review: a cross-sectional study.

OBJECTIVES: The main objective of this study is to evaluate the methodological quality and reporting quality of living systematic reviews (LSRs) on Coronavirus disease 2019 (COVID-19), while the secondary objective is to investigate potential factors that may influence the overall quality of COVID-19 LSRs. METHODS: Six representative databases, including Medline, Excerpta Medica Database (Embase), Cochrane Library, China national knowledge infrastructure (CNKI), Wanfang Database, and China Science, Technology Journal Database (VIP) were systematically searched for COVID-19 LSRs. Two authors independently screened articles, extracted data, and then assessed the methodological and reporting quality of COVID-19 LSRs using the "A Measurement Tool to Assess systematic Reviews-2" (AMSTAR-2) tool and "Preferred Reporting Items for Systematic reviews and Meta-Analyses" (PRISMA) 2020 statement, respectively. Univariate linear regression and multivariate linear regression were used to explore eight potential factors that might affect the methodological quality and reporting quality of COVID-19 LSRs. RESULTS: A total of 64 COVID-19 LSRs were included. The AMSTAR-2 evaluation results revealed that the number of "yes" responses for each COVID-19 LSR was 13 ± 2.68 (mean ± standard deviation). Among them, 21.9% COVID-19 LSRs were rated as "high", 4.7% as "moderate", 23.4% as "low", and 50% as "critically low". The evaluation results of the PRISMA 2020 statement showed that the sections with poor adherence were methods, results and other information. The number of "yes" responses for each COVID-19 LSR was 21 ± 4.18 (mean ± standard deviation). The number of included studies and registration are associated with better methodological quality; the number of included studies and funding are associated with better reporting quality. CONCLUSIONS: Improvement is needed in the methodological and reporting quality of COVID-19 LSRs. Researchers conducting COVID-19 LSRs should take note of the quality-related factors identified in this study to generate evidence-based evidence of higher quality.

Emerging role of artificial intelligence in diagnosis, classification and clinical management of glioma.

Glioma represents a dominant primary intracranial malignancy in the central nervous system. Artificial intelligence that mainly includes machine learning, and deep learning computational approaches, presents a unique opportunity to enhance clinical management of glioma through improving tumor segmentation, diagnosis, differentiation, grading, treatment, prediction of clinical outcomes (prognosis, and recurrence), molecular features, clinical classification, characterization of the tumor microenvironment, and drug discovery. A growing body of recent studies apply artificial intelligence-based models to disparate data sources of glioma, covering imaging modalities, digital pathology, high-throughput multi-omics data (especially emerging single-cell RNA sequencing and spatial transcriptome), etc. While these early findings are promising, future studies are required to normalize artificial intelligence-based models to improve the generalizability and interpretability of the results. Despite prominent issues, targeted clinical application of artificial intelligence approaches in glioma will facilitate the development of precision medicine of this field. If these challenges can be overcome, artificial intelligence has the potential to profoundly change the way patients with or at risk of glioma are provided with more rational care.

Importance of comprehensive genetic testing for patients with suspected vascular Ehlers-Danlos syndrome: a family case report and literature review.

Vascular Ehlers-Danlos syndrome (vEDS), the most severe type of Ehlers-Danlos syndrome, is caused by an autosomal-dominant defect in the COL3A1 gene. In this report, we describe the clinical history, specific phenotype, and genetic diagnosis of a man who died of vEDS. The precise diagnosis of this case using whole-exome sequencing provided solid evidence for the cause of death, demonstrating the practical value of genetic counseling and analysis. Early diagnosis for the proband's son, who was also affected by vEDS, revealed initial complications of vEDS in early childhood, which have rarely been reported. We also reviewed the literature on COL3A1 missense mutations and related phenotypes. We identified an association between digestion tract events and non-glycine missense variants, which disproves a previous hypothesis regarding the genotype-phenotype correlation of vEDS. Our results demonstrate the necessity of offering comprehensive genetic testing for every patient suspected of having vEDS.

Which is the most effective rescue treatment after the failure of mechanical thrombectomy for acute basilar artery occlusion?

Objective: The aim of this study was to evaluate the effectiveness and safety of rescue therapy, a therapy in which rescue devices such as balloon angioplasty, Apollo stent, Wingspan stent, Solitaire stent, or other self-expanding stents are used after the failure of mechanical thrombectomy (MT) and to determine the most effective rescue measure for acute basilar artery occlusion (BAO) after the failure of MT. Methods: For this study, we recruited patients from the BASILAR registry. All participants were divided into three groups: the recanalized with rescue therapy group, the recanalized without rescue therapy group, and the non-recanalized group. Clinical outcomes at 90 days and 1 year were compared. The association of rescue measures with favorable outcomes (modified Rankin Scale [mRS] score of 0-3) in patients achieving successful recanalization via rescue therapy was estimated using multivariate logistic regression analyses. Results: Among the participants, recanalization failure was found in 112 patients and successful recanalization in 473 patients, with 218 patients receiving rescue therapy and 255 patients without rescue therapy. Of these, 111 (43.5%) patients in the recanalized without rescue therapy group, 65 (29.8%) patients in the recanalized with rescue therapy group, and nine (8.0%) patients in the non-recanalized group achieved favorable outcomes at 90 days. Both the recanalization with rescue therapy and the recanalization without rescue therapy groups were associated with favorable outcomes at 90 days and 1 year compared with the non-recanalized group. Moreover, in patients receiving rescue therapy, Wingspan stents, Apollo stents, and balloon angioplasty were associated with higher rates of favorable outcomes at 90 days and 1 year than Solitaire stents. Conclusion: Whether rescue therapy is administered or not, recanalization leads to favorable outcomes in patients with acute BAO. For acute BAO after MT failure, balloon angioplasty, Wingspan stenting, and Apollo stenting could be considered effective and safe rescue options but not Solitaire stenting.

Potential biomarkers of Alzheimer's disease and cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) is associated with the pathogenesis of Alzheimer's disease (AD). Effective treatments to alleviate AD are still not currently available. Hence, we explored markers and underlying molecular mechanisms associated with AD by utilizing gene expression profiles of AD and CSVD patients from public databases, providing more options for early diagnosis and its treatment. Methods: Gene expression profiles were collected from GSE63060 (for AD) and GSE162790 (for CSVD). Differential analysis was performed between AD and mild cognitive impairment (MCI) or CSVD progression and CSVD no-progression. In both datasets, differentially expressed genes (DEGs) with the same expression direction were identified as common DEGs. Then protein-protein interaction (PPI) network was constructed for common DEGs. Differential immune cells and checkpoints were calculated between AD and MCI. Results: A total of 146 common DEGs were identified. Common DEGs were mainly enriched in endocytosis and oxytocin signaling pathways. Interestingly, endocytosis and metabolic pathways were shown both from MCI to AD and from CSVD no-progression to CSVD progression. Moreover, SIRT1 was identified as a key gene by ranking degree of connectivity in the PPI network. SIRT1 was associated with obesity-related genes and metabolic disorders. Additionally, SIRT1 showed correlations with CD8 T cells, NK CD56 bright cells, and checkpoints in AD. Conclusion: The study revealed that the progression of AD is associated with abnormalities in gene expression and metabolism and that the SIRT1 gene may serve as a promising therapeutic target for the treatment of AD.

Molecular mechanisms for the prevention and promoting the recovery from ischemic stroke by nutraceutical laminarin: A comparative transcriptomic approach.

Stroke is the second leading cause of death and a major cause of disability worldwide. Ischemic stroke caused by atherosclerosis accounts for approximately 87% of all stroke cases. Ischemic stroke is a preventable disease; therefore, a better understanding of the molecular mechanisms underlying its pathogenesis and recovery processes could provide therapeutic targets for drug development and reduce the associated mortality rate. Laminarin, a polysaccharide, is a nutraceutical that can be found in brown algae. Accumulating evidence suggests that laminarin could reduce the detrimental effects of neuroinflammation on brain damage after stroke. However, the molecular mechanism underlying its beneficial effects remains largely unknown. In the present study, we used a middle cerebral artery occlusion (MCAO) rat model and applied comparative transcriptomics to investigate the molecular targets and pathways involved in the beneficial effects of laminarin on ischemic stroke. Our results show the involvement of laminarin targets in biological processes related to blood circulation, oxygen supply, and anti-inflammatory responses in the normal brain. More importantly, laminarin treatment attenuated brain damage and neurodeficits caused by ischemic stroke. These beneficial effects are controlled by biological processes related to blood vessel development and brain cell death through the regulation of canonical pathways. Our study, for the first time, delineated the molecular mechanisms underlying the beneficial effects of laminarin on ischemic stroke prevention and recovery and provides novel therapeutic targets for drug development against ischemic stroke.

Characteristics of Living Systematic Review for COVID-19.

Purpose: The systematic review aims to analyze and summarize the characteristics of living systematic review (LSR) for coronavirus disease 2019 (COVID-19). Methods: Six databases including Medline, Excerpta Medica (Embase), Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Database and China Science, and Technology Journal Database (VIP), were searched as the source of basic information and methodology of LSR. Descriptive analytical methods were used to analyze the included COVID-19 LSRs, and the study characteristics of COVID-19 LSRs were further assessed. Results: Sixty-four COVID-19 LSRs were included. Eighty-nine point one percent of LSRs were published on Science Citation Index (SCI) journals, and 64.1% publication with an impact factor (IF) >5 and 17.2% with an IF >15 among SCI journals. The first unit of the published LSRs for COVID-19 came from 19 countries, with the largest contribution from the UK (17.2%, 11/64). Forty point six percent of LSRs for COVID-19 were related to therapeutics topic which was considered the most concerned perspective for LSRs for COVID-19. Seventy-six point six percent of LSRs focused on the general population, with less attention to children, pregnant women and the elderly. However, the LSR for COVID-19 was reported incomplete on "living" process, including 40.6% of studies without search frequency, 79.7% of studies without screening frequency, 20.3% of studies without update frequency, and 65.6% of studies without the timing or criteria of transitioning LSR out of living mode. Conclusion: Although researchers in many countries have applied LSRs to COVID-19, most of the LSRs for COVID-19 were incomplete in reporting on the "living" process and less focused on special populations. This could reduce the confidence of health-care providers and policy makers in the results of COVID-19 LSR, thereby hindering the translation of evidence on COVID-19 LSR into clinical practice. It was necessary to explicitly enact preferred reporting items for systematic reviews and meta-analyses (PRISMA) to improve the reporting quality of LSR and support ongoing efforts of therapeutics research for special patients with COVID-19.

Developing a Core Outcome Set for the Evaluation of Antibiotic Use in Prelabor Rupture of Membranes: A Systematic Review and Semi-Structured Interview.

Background: Prelabor rupture of membranes (PROM) is associated with maternal and neonatal infections. Although guidelines suggest prophylactic antibiotics for pregnant women with PROM, the optimal antibiotic regimen remains controversial. Synthesizing the data from different studies is challenging due to variations in reported outcomes. Objective: This study aimed to form the initial list of outcomes for the core outcome set (COS) that evaluates antibiotic use in PROM by identifying all existing outcomes and patients' views. Methods: Relevant studies were identified by searching PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, and VIP databases. We also screened the references of the included studies as a supplementary search. We extracted basic information from the articles and the outcomes. Two reviewers independently selected the studies, extracted the data, extracted the outcomes, and grouped them into domains. Then, semi-structured interviews based on the potential factors collected by the systematic review were conducted at West China Second Hospital of Sichuan University. Pregnant women who met the diagnostic criteria for PROM were enrolled. Participants reported their concerns about the outcomes. Two researchers identified the pregnant women's concerns. Results: A total of 90 studies were enrolled in this systematic review. The median outcomes in the included studies was 7 (1-31), and 109 different unique outcomes were identified. Pre-term PROM (PPROM) had 97 outcomes, and term PROM (TPROM) had 70 outcomes. The classification and order of the core outcome domains of PPROM and TPROM were consistent. The physiological domain was the most common for PPROM and TPROM outcomes. Furthermore, 35.1 and 57.1% outcomes were only reported once in PPROM and TPROM studies, respectively. Thirty pregnant women participated in the semi-structured interviews; 10 outcomes were extracted after normalized, and the outcomes were reported in the systematic review. However, studies rarely reported pregnant women's concerns. Conclusion: There was considerable inconsistency in outcomes selection and reporting in studies about antibiotics in PROM. An initial core outcomes set for antibiotics in PROM was formed.

REPS1 as a Potential Biomarker in Alzheimer's Disease and Vascular Dementia.

Vascular dementia (VD) and Alzheimer's disease (AD) are common types of dementia for which no curative therapies are known. In this study, we identified hub genes associated with AD and VD in order to explore new potential therapeutic targets. Genes differentially expressed in VD and AD in all three datasets (GSE122063, GSE132903, and GSE5281) were identified and used to construct a protein-protein interaction network. We identified 10 modules containing 427 module genes in AD and VD. Module genes showing an area under the diagnostic curve > 0.60 for AD or VD were used to construct a least absolute shrinkage and selection operator model and were entered into a support vector machine-recursive feature elimination algorithm, which identified REPS1 as a hub gene in AD and VD. Furthermore, REPS1 was associated with activation of pyruvate metabolism and inhibition of Ras signaling pathway. Module genes, together with differentially expressed microRNAs from the dataset GSE46579, were used to construct a regulatory network. REPS1 was predicted to bind to the microRNA hsa_miR_5701. Single-sample gene set enrichment analysis was used to explore immune cell infiltration, which suggested a negative correlation between REPS1 expression and infiltration by plasmacytoid dendritic cells in AD and VD. In conclusion, our results suggest core pathways involved in both AD and VD, and they identify REPS1 as a potential biomarker of both diseases. This protein may aid in early diagnosis, monitoring of treatment response, and even efforts to prevent these debilitating disorders.

Identification of Candidate Genes Associated With Prognosis in Glioblastoma.

Background: Glioblastoma (GBM) is the most common malignant primary brain tumor, which associated with extremely poor prognosis. Methods: Data from datasets GSE16011, GSE7696, GSE50161, GSE90598 and The Cancer Genome Atlas (TCGA) were analyzed to identify differentially expressed genes (DEGs) between patients and controls. DEGs common to all five datasets were analyzed for functional enrichment and for association with overall survival using Cox regression. Candidate genes were further screened using least absolute shrinkage and selection operator (LASSO) and random forest algorithms, and the effects of candidate genes on prognosis were explored using a Gaussian mixed model, a risk model, and concordance cluster analysis. We also characterized the GBM landscape of immune cell infiltration, methylation, and somatic mutations. Results: We identified 3,139 common DEGs, which were associated mainly with PI3K-Akt signaling, focal adhesion, and Hippo signaling. Cox regression identified 106 common DEGs that were significantly associated with overall survival. LASSO and random forest algorithms identified six candidate genes (AEBP1, ANXA2R, MAP1LC3A, TMEM60, PRRG3 and RPS4X) that predicted overall survival and GBM recurrence. AEBP1 showed the best prognostic performance. We found that GBM tissues were heavily infiltrated by T helper cells and macrophages, which correlated with higher AEBP1 expression. Stratifying patients based on the six candidate genes led to two groups with significantly different overall survival. Somatic mutations in AEBP1 and modified methylation of MAP1LC3A were associated with GBM. Conclusion: We have identified candidate genes, particularly AEBP1, strongly associated with GBM prognosis, which may help in efforts to understand and treat the disease.

Ocrelizumab for multiple sclerosis.

BACKGROUND: Ocrelizumab is a humanised anti-CD20 monoclonal antibody developed for the treatment of multiple sclerosis (MS). It was approved by the Food and Drug Administration (FDA) in March 2017 for using in adults with relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). Ocrelizumab is the only disease-modifying therapy (DMT) approved for PPMS. In November 2017, the European Medicines Agency (EMA) also approved ocrelizumab as the first drug for people with early PPMS. Therefore, it is important to evaluate the benefits, harms, and tolerability of ocrelizumab in people with MS. OBJECTIVES: To assess the benefits, harms, and tolerability of ocrelizumab in people with RRMS and PPMS. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, and two trials registers on 8 October 2021. We screened reference lists, contacted experts, and contacted the main authors of studies. SELECTION CRITERIA: All randomised controlled trials (RCTs) involving adults diagnosed with RRMS or PPMS according to the McDonald criteria, comparing ocrelizumab alone or associated with other medications, at the approved dose of 600 mg every 24 weeks for any duration, versus placebo or any other active drug therapy. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: Four RCTs met our selection criteria. The overall population included 2551 participants; 1370 treated with ocrelizumab 600 mg and 1181 controls. Among the controls, 298 participants received placebo and 883 received interferon beta-1a. The treatment duration was 24 weeks in one study, 96 weeks in two studies, and at least 120 weeks in one study. One study was at high risk of allocation concealment and blinding of participants and personnel; all four studies were at high risk of bias for incomplete outcome data. For RRMS, compared with interferon beta-1a, ocrelizumab was associated with: 1. lower relapse rate (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.52 to 0.73; 2 studies, 1656 participants; moderate-certainty evidence); 2. a lower number of participants with disability progression (hazard ratio (HR) 0.60, 95% CI 0.43 to 0.84; 2 studies, 1656 participants; low-certainty evidence); 3. little to no difference in the number of participants with any adverse event (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 1651 participants; moderate-certainty evidence); 4. little to no difference in the number of participants with any serious adverse event (RR 0.79, 95% CI 0.57 to 1.11; 2 studies, 1651 participants; low-certainty evidence); 5. a lower number of participants experiencing treatment discontinuation caused by adverse events (RR 0.58, 95% CI 0.37 to 0.91; 2 studies, 1651 participants; low-certainty evidence); 6. a lower number of participants with gadolinium-enhancing T1 lesions on magnetic resonance imaging (MRI) (RR 0.27, 95% CI 0.22 to 0.35; 2 studies, 1656 participants; low-certainty evidence); 7. a lower number of participants with new or enlarging T2-hyperintense lesions on MRI (RR 0.63, 95% CI 0.57 to 0.69; 2 studies, 1656 participants; low-certainty evidence) at 96 weeks. For PPMS, compared with placebo, ocrelizumab was associated with: 1. a lower number of participants with disability progression (HR 0.75, 95% CI 0.58 to 0.98; 1 study, 731 participants; low-certainty evidence); 2. a higher number of participants with any adverse events (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 725 participants; moderate-certainty evidence); 3. little to no difference in the number of participants with any serious adverse event (RR 0.92, 95% CI 0.68 to 1.23; 1 study, 725 participants; low-certainty evidence); 4. little to no difference in the number of participants experiencing treatment discontinuation caused by adverse events (RR 1.23, 95% CI 0.55 to 2.75; 1 study, 725 participants; low-certainty evidence) for at least 120 weeks. There were no data for number of participants with gadolinium-enhancing T1 lesions on MRI and number of participants with new or enlarging T2-hyperintense lesions on MRI. AUTHORS' CONCLUSIONS: For people with RRMS, ocrelizumab probably results in a large reduction in relapse rate and little to no difference in adverse events when compared with interferon beta-1a at 96 weeks (moderate-certainty evidence). Ocrelizumab may result in a large reduction in disability progression, treatment discontinuation caused by adverse events, number of participants with gadolinium-enhancing T1 lesions on MRI, and number of participants with new or enlarging T2-hyperintense lesions on MRI, and may result in little to no difference in serious adverse events (low-certainty evidence). For people with PPMS, ocrelizumab probably results in a higher rate of adverse events when compared with placebo for at least 120 weeks (moderate-certainty evidence). Ocrelizumab may result in a reduction in disability progression and little to no difference in serious adverse events and treatment discontinuation caused by adverse events (low-certainty evidence). Ocrelizumab was well tolerated clinically; the most common adverse events were infusion-related reactions and nasopharyngitis, and urinary tract and upper respiratory tract infections.

Safety and Effectiveness of Inhaling Different Dosage Recombinant Human Interferon α1B for Bronchiolitis in Children: a Systematic Review and Meta-Analysis.

Purpose: To systematically evaluate the safety and effectiveness of different dosages of recombinant human interferon α1b (IFNα1b) inhaled for bronchiolitis in children. Methods: 7 databases, including PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang Database, and VIP, were searched. The search time was from their inception dates to March 28, 2022. A randomized controlled trial (RCT) of 2 µg/kg IFNα1b (low dosage group) monotherapy or in combination with other drugs vs. 4 µg/kg IFNα1b (high dosage group) monotherapy or in combination with the other drugs was included. The risk of bias 2.0 evaluated the RCT's quality, and the grading of recommendations assessment, development and evaluation (GRADE) tool was used for evaluating the overall quality of the evidence. Then, a meta-analysis was performed by RevMan 5.4. Results: A total of 13 RCTs with 1719 children were included. The meta-analysis results showed that the high dosage group was significantly shorter than the low dosage group of the duration of hospital stays (MD = -0.40, 95%CI (-0.73, -0.07), P = 0.02) (low quality), three depressions sign disappearing time (MD = -0.60, 95%CI (-1.05, -0.14), P = 0.010) (low quality), and wheeze disappearing time (MD = -0.62, 95%CI (-1.17, -0.06), = 0.03) (low quality). There was no significant difference between the two groups in coughing disappearing time, pulmonary rales disappearing time, wheezing sound disappearing time, or adverse event rates. Conclusions: Compared with low dosage IFNα1b, high dosage IFNα1b reduces the duration of hospital stays, the disappearance time of the three depression signs, and the disappearance time of wheeze in the treatment of bronchiolitis in children. Limited by the low quality of the evidence, the conclusions still need to be supported by high-quality studies.

Melanin nanoparticles enhance the neuroprotection of mesenchymal stem cells against hypoxic-ischemic injury by inhibiting apoptosis and upregulating antioxidant defense.

Polydopamine nanoparticles are artificial melanin nanoparticles (MNPs) that show strong antioxidant activity. The effects of MNPs on the neuroprotection of mesenchymal stem cells (MSCs) against hypoxic-ischemic injury and the underlying mechanism have not yet been revealed. In this study, an oxygen-glucose deprivation (OGD)-injured neuron model was used to mimic neuronal hypoxic-ischemic injury in vitro. MSCs pretreated with MNPs and then cocultured with OGD-injured neurons were used to investigate the potential effects of MNPs on the neuroprotection of MSCs and to elucidate the underlying mechanism. After coculturing with MNPs-pretreated MSCs, MSCs, and MNPs in a transwell coculture system, the OGD-injured neurons were rescued by 91.24%, 79.32%, and 59.97%, respectively. Further data demonstrated that MNPs enhanced the neuroprotection against hypoxic-ischemic injury of MSCs by scavenging reactive oxygen species and superoxide and attenuating neuronal apoptosis by deactivating caspase-3, downregulating the expression of proapoptotic Bax proteins, and upregulating the expression of antiapoptotic Bcl-2 proteins. These findings suggest that MNPs enhance the neuroprotective effect of MSCs against hypoxic-ischemic injury by inhibiting apoptosis and upregulating antioxidant defense, which could provide some evidence for the potential application of combined MNPs and MSCs in the therapy for ischemic stroke.

Fullerene Derivative with Flexible Alkyl Chain for Efficient Tin-Based Perovskite Solar Cells.

Fullerene derivatives are considered excellent materials for the extraction and transportation of electrons in the production of efficient tin-based perovskite solar cells (TPSCs). However, it is not clear how the molecular structure of fullerene derivatives affects the efficiency and stability of TPSCs. In this study, the effects of fullerene derivatives, (6,6)-phenyl-C61-butyric acid hexyl ester (PCBH) and (6,6)-phenyl-C61-butyric acid methyl ester (PCBM), with different functional groups, on photovoltaic performance were investigated. The flexible alkyl chain of PCBH effectively improved the film morphology and stability, the electron extraction and transport capabilities, and the interface contact of fullerene and perovskite. As a result, the PCBH-based TPSC yielded a higher efficiency, of 9.21%, than the PCBM-based devices (7.54%). More importantly, the PCBH-based films exhibited higher stability and effectively suppressed the oxidation of Sn2+ by inhibiting oxygen permeation. Therefore, the PCBH-based devices exhibited significantly enhanced stability. This result indicates that optimizing the functional group of fullerene derivatives is crucial for improving the efficiency and stability of TPSCs.