Background. Migraine is a common neurological disease, which burdens individuals and society all over the world. Acupuncture, an important method in Traditional Chinese Medicine, is widely used in ...clinical practice as a treatment for migraine. Several systematic reviews (SRs) have investigated the effectiveness and safety of acupuncture for migraine. Objective. To summarize and critically assess the quality of relevant SRs and present an objective and comprehensive evidence on the effectiveness and safety of acupuncture for migraine. Data Sources. MEDLINE, Embase, Cochrane Library, PROSPERO database, Chinese National Knowledge Infrastructure (CNKI), Chinese Biological Medicine (CBM), China Science and Technology Journal (SCTJ), and WanFang database (WF) were searched from inception to December 2019 and grey literatures were manually searched. Selection Criteria. SRs which meet the criteria were independently selected by 2 reviewers according to a predetermined protocol. Data Extraction. Characteristics of included SRs were independently extracted by 2 reviewers following a predefined data extraction form. Review Appraisal. The methodological quality, risk of bias, and reporting quality of included SRs were assessed, respectively, by a Measurement Tool to Assess Systematic Reviews (AMSTAR) 2, the Risk of Bias in Systematic reviews (ROBIS) tool, and the Preferred Reporting Item for Systematic Review and Meta-analysis-Acupuncture (PRISMA-A) statement. The quality of outcomes was evaluated by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). Results. A total of 15 SRs were included. All the SRs were published between 2011–2019. Based on AMSTAR 2, 14 out of 15 SRs were rated critically low quality and 1 was rated low quality. According to ROBIS tool, 9 SRs (60%) were low risk of bias. With the PRISMA-A checklist, we found 11 out of 15 SRs were found adequately reported over 70%. With the GRADE tool, we found high quality of evidence indicated that the effective rate of acupuncture was superior to western medicine in treatment of migraine. Besides, acupuncture reduced more headache days and the times of using painkiller and was more effective in reducing the frequency and degree of headache than western medicine and sham acupuncture. Limitations. There might be some missing information. The accuracy of the conclusions may be decreased reduced since we were unable to synthesis all the evidence. Conclusions. Based on high quality of evidence, we concluded that acupuncture may be an effective and safe therapy for migraine. However, the quality of SRs in acupuncture for migraine still needs more improvement.
Mutations in the proline-rich transmembrane protein 2 （PRRT2） are associated with paroxysmal kinesigenic dys- kinesia （PKD） and several other paroxysmal neurological diseases, but the PRRT2 function ...and pathogenic mecha- nisms remain largely obscure. Here we show that PRRT2 is a presynaptic protein that interacts with components of the SNARE complex and downregulates its formation. Loss-of-function mutant mice showed PKD-like phenotypes triggered by generalized seizures, hyperthermia, or optogenetic stimulation of the cerebellum. Mutant mice with spe- cific PRRT2 deletion in cerebellar granule cells （GCs） recapitulate the behavioral phenotypes seen in Prrt2-null mice. Furthermore, recording made in cerebellar slices showed that optogenetic stimulation of GCs results in transient elevation followed by suppression of Purkinje cell firing. The anticonvulsant drug carbamazepine used in PKD treat- ment also relieved PKD-like behaviors in mutant mice. Together, our findings identify PRRT2 as a novel regulator of the SNARE complex and provide a circuit mechanism underlying the PRRT2-related behaviors.
Chemical doping is often used to enhance electric conductivity of the conjugated molecule as hole‐transporting material (HTM) for the application in optoelectronics. However, chemical dopants can ...promote ion migration at the electrical field, which deteriorates the device efficiency as well as increases the fabrication cost. Here, two star HTMs, namely 2,2′,7,7′‐tetrakis(N,N‐di‐p‐methoxyphenyl‐amine) 9,9′‐spirobifluorene (Spiro‐OMeTAD) and poly(triarylamine) are subjeted to chemical combination to yield dopant‐free N2,N2,N2′,N2′,N7,N7,N7′,N7′‐octakis(4‐methoxyphenyl)‐10‐phenyl‐10H‐spiroacridine‐9,9′‐fluorene‐2,2′,7,7′‐tetraamine (SAF‐OMe). The power conversion efficiencies (PCEs) of 12.39% achieved by solar cells based on pristine, dopant‐free SAF‐OMe are among the highest reported for perovskite solar cells and are even comparable to devices based on chemically doped Spiro‐OMeTAD (14.84%). Moreover, using a HTM comprised of SAF‐OMe with an additional dopant results in a record PCE of 16.73%. Compared to Spiro‐OMeTAD‐based devices, SAF‐OMe significantly improves stability.
A dopant‐free hole‐transporting material (HTM), N2,N2,N2′,N2′,N7,N7,N7′,N7′‐octakis(4‐methoxyphenyl)‐10‐phenyl‐10H‐spiroacridine‐9,9′‐fluorene‐2,2′,7,7′‐tetraamine (SAF‐OMe), is developed and implemented for use in perovskite solar cells. The power conversion efficiency (PCE) achieved by using SAF‐OMe as HTM is 12.39%, more than two times the reference 2,2′,7,7′‐tetrakis(N,N‐di‐p‐methoxyphenyl‐amine)9,9′‐spirobifluorene (Spiro‐OMeTAD).
To elucidate potential molecular mechanisms differentiating osteoarthritis (OA) and rheumatoid arthritis (RA) through a bioinformatics analysis of differentially expressed genes (DEGs) in patient ...synovial cells, aiming to provide new insights for clinical treatment strategies.
Gene expression datasets GSE1919, GSE82107, and GSE77298 were downloaded from the Gene Expression Omnibus (GEO) database to serve as the training groups, with GSE55235 being used as the validation dataset. The OA and RA data from the GSE1919 dataset were merged with the standardized data from GSE82107 and GSE77298, followed by batch effect removal to obtain the merged datasets of differential expressed genes (DEGs) for OA and RA. Intersection analysis was conducted on the DEGs between the two conditions to identify commonly upregulated and downregulated DEGs. Enrichment analysis was then performed on these common co-expressed DEGs, and a protein-protein interaction (PPI) network was constructed to identify hub genes. These hub genes were further analyzed using the GENEMANIA online platform and subjected to enrichment analysis. Subsequent validation analysis was conducted using the GSE55235 dataset.
The analysis of differentially expressed genes in the synovial cells from patients with Osteoarthritis (OA) and Rheumatoid Arthritis (RA), compared to a control group (individuals without OA or RA), revealed significant changes in gene expression patterns. Specifically, the genes APOD, FASN, and SCD were observed to have lower expression levels in the synovial cells of both OA and RA patients, indicating downregulation within the pathological context of these diseases. In contrast, the SDC1 gene was found to be upregulated, displaying higher expression levels in the synovial cells of OA and RA patients compared to normal controls.Additionally, a noteworthy observation was the downregulation of the transcription factor PPARG in the synovial cells of patients with OA and RA. The decrease in expression levels of PPARG further validates the alteration in lipid metabolism and inflammatory processes associated with the pathogenesis of OA and RA. These findings underscore the significance of these genes and the transcription factor not only as biomarkers for differential diagnosis between OA and RA but also as potential targets for therapeutic interventions aimed at modulating their expression to counteract disease progression.
The outcomes of this investigation reveal the existence of potentially shared molecular mechanisms within Osteoarthritis (OA) and Rheumatoid Arthritis (RA). The identification of APOD, FASN, SDC1, TNFSF11 as key target genes, along with their downstream transcription factor PPARG, highlights common potential factors implicated in both diseases. A deeper examination and exploration of these findings could pave the way for new candidate targets and directions in therapeutic research aimed at treating both OA and RA. This study underscores the significance of leveraging bioinformatics approaches to unravel complex disease mechanisms, offering a promising avenue for the development of more effective and targeted treatments.
Inosine monophosphate dehydrogenase (IMPDH) of human is an attractive target for immunosuppressive agents. Currently, small-molecule inhibitors do not show good selectivity for different IMPDH ...isoforms (IMPDH1 and IMPDH2), resulting in some adverse effects, which limit their use. Herein, we used a small-molecule probe specifically targeting IMPDH2 and identified Cysteine residue 140 (Cys140) as a selective druggable site. On covalently binding to Cys140, the probe exerts an allosteric regulation to block the catalytic pocket of IMPDH2 and further induces IMPDH2 inactivation, leading to an effective suppression of neuroinflammatory responses. However, the probe does not covalently bind to IMPDH1. Taken together, our study shows Cys140 as a druggable site for selectively inhibiting IMPDH2, which provides great potential for development of therapy agents for autoimmune and neuroinflammatory diseases with less unfavorable tolerability profile.
The genetic mechanisms underlying the poor prognosis of esophageal squamous cell carcinoma (ESCC) are not well understood. Here, we report somatic mutations found in ESCC from sequencing 10 ...whole-genome and 57 whole-exome matched tumor-normal sample pairs. Among the identified genes, we characterized mutations in VANGL1 and showed that they accelerated cell growth in vitro. We also found that five other genes, including three coding genes (SHANK2, MYBL2, FADD) and two non-coding genes (miR-4707-5p, PCAT1), were involved in somatic copy-number alterations (SCNAs) or structural variants (SVs). A survival analysis based on the expression profiles of 321 individuals with ESCC indicated that these genes were significantly associated with poorer survival. Subsequently, we performed functional studies, which showed that miR-4707-5p and MYBL2 promoted proliferation and metastasis. Together, our results shed light on somatic mutations and genomic events that contribute to ESCC tumorigenesis and prognosis and might suggest therapeutic targets.
Mitochondrial fusion/fission dynamics plays a fundamental role in neuroprotection; however, there is still a severe lack of therapeutic targets for this biological process. Here, we found that the ...naturally derived small molecule echinacoside (ECH) significantly promotes mitochondrial fusion progression. ECH selectively binds to the previously uncharacterized casein kinase 2 (CK2) α' subunit (CK2α') as a direct cellular target, and genetic knockdown of CK2α' abolishes ECH-mediated mitochondrial fusion. Mechanistically, ECH allosterically regulates CK2α' conformation to recruit basic transcription factor 3 (BTF3) to form a binary protein complex. Then, the CK2α'/BTF3 complex facilitates β-catenin nuclear translocation to activate TCF/LEF transcription factors and stimulate transcription of the mitochondrial fusion gene Mfn2. Strikingly, in a mouse middle cerebral artery occlusion (MCAO) model, ECH administration was found to significantly improve cerebral injuries and behavioral deficits by enhancing Mfn2 expression in wild-type but not CK2α'
mice. Taken together, our findings reveal, for the first time, that CK2 is essential for promoting mitochondrial fusion in a Wnt/β-catenin-dependent manner and suggest that pharmacologically targeting CK2 is a promising therapeutic strategy for ischemic stroke.
Since December 2019, COVID-19 has occurred unexpectedly and emerged as a health problem worldwide. Despite the rapidly increasing number of cases in subsequent weeks, the clinical characteristics of ...pediatric cases are rarely described. A cross-sectional multicenter study was carried out in 10 hospitals across Hubei province. A total of 25 confirmed pediatric cases of COVID-19 were collected. The demographic data, epidemiological history, underlying diseases, clinical manifestations, laboratory and radiological data, treatments, and outcomes were analyzed. Of 25 hospitalized patients with COVID-19, the boy to girl ratio was 1.27:1. The median age was 3 years. COVID-19 cases in children aged <3 years, 3.6 years, and ≥6-years patients were 10 (40%), 6 (24%), and 9 (36%), respectively. The most common symptoms at onset of illness were fever (13 52%), and dry cough (11 44%). Chest CT images showed essential normal in 8 cases (33.3%), unilateral involvement of lungs in 5 cases (20.8%), and bilateral involvement in 11 cases (45.8%). Clinical diagnoses included upper respiratory tract infection (n=8), mild pneumonia (n=15), and critical cases (n=2). Two critical cases (8%) were given invasive mechanical ventilation, corticosteroids, and immunoglobulin. The symptoms in 24 (96%) of 25 patients were alleviated and one patient had been discharged. It was concluded that children were susceptible to COVID-19 like adults, while the clinical presentations and outcomes were more favorable in children. However, children less than 3 years old accounted for majority cases and critical cases lied in this age group, which demanded extra attentions during home caring and hospitalization treatment.
The essential transcription factor PoxCxrA is required for cellulase and xylanase gene expression in the filamentous fungus Penicillium oxalicum that is potentially applied in biotechnological ...industry as a result of the existence of the integrated cellulolytic and xylolytic system. However, the regulatory mechanism of cellulase and xylanase gene expression specifically associated with PoxCxrA regulation in fungi is poorly understood. In this study, the novel regulator PoxCbh (POX06865), containing a centromere protein B‐type helix‐turn‐helix domain, was identified through screening for the PoxCxrA regulon under Avicel induction and genetic analysis. The mutant ∆PoxCbh showed significant reduction in cellulase and xylanase production, ranging from 28.4% to 59.8%. Furthermore, PoxCbh was found to directly regulate the expression of important cellulase and xylanase genes, as well as the known regulatory genes PoxNsdD and POX02484, and its expression was directly controlled by PoxCxrA. The PoxCbh‐binding DNA sequence in the promoter region of the cellobiohydrolase 1 gene cbh1 was identified. These results expand our understanding of the diverse roles of centromere protein B‐like protein, the regulatory network of cellulase and xylanase gene expression, and regulatory mechanisms in fungi.
This work identified the novel regulator PoxCbh, which controls the expression of major cellulase and xylanase genes, and the known regulatory genes POX02484 and PoxNsdD in P. oxalicum. PoxCbh acts downstream of the key TF PoxCxrA. PoxCbh is a CENPB‐homologous protein.
Relevant evidence suggests that angiogenic factors contribute significantly to fibril matrix reconstruction following physical injuries to tendon ligaments. Vascular endothelial growth factor A ...(VEGFA), with its potent angiogenic effect, has been studied extensively, and its functional polymorphisms, including rs699947, rs1570360, and rs2010963, have been the focus of numerous investigations. Some scholars have explored the association between gene polymorphisms in the VEGFA and the risk of tendon ligament injury, but the findings are not entirely consistent.
The purpose of this study was to investigate the association between rs699947, rs1570360, and rs2010963 gene polymorphisms in VEGFA and the risk of tendon and ligament injuries.
After including articles about the association of VEGFA rs699947, rs1570360, and rs2010963 polymorphisms with tendon and ligament injuries according to the search strategy, we assessed their quality and conducted meta-analyses to examine the link between these polymorphisms and the risk of tendon and ligament injuries using odds ratios and 95% confidence intervals.
Of 86 related articles, six were included in the meta-analysis. Some of these suggest an association between VEGFA rs2010963 and the risk of tendon and ligament injury in the population, with the specific C allele being one of the adverse factors for knee injury. Some studies suggest that VEGFA rs699947 and VEGFA rs1570360 single-nucleotide polymorphisms are associated with anterior cruciate ligament rupture. The risk of non-contact anterior cruciate ligament rupture is nearly doubled in individuals with the rs699947 CC genotype compared to the control group. Our analysis did not find any significant relationship between VEGFA gene polymorphisms (rs699947, rs1570360, and rs2010963) and the chance of tendon and ligament injury without consideration of race. However, the European population reveals that the CC genotype of VEGFA rs699947 can result in a greater risk of tendon and ligament injury, whereas the AG genotype for rs1570360 provides some protection. Additionally, rs2010963 was significantly associated with tendon and ligament injury; individuals with the C allele and the CC genotype had higher risk. False-positive report probability confirmed the high credibility of our results.
Overall, this study found no significant association between VEGFA rs699947, rs1570360, and rs2010963 polymorphisms and the risk of tendon ligament injury. However, in subgroup analysis, some genotypes of VEGFA rs699947, rs1570360, and rs2010963 were found to increase the risk of tendon ligament injury in European populations.
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