The Notch1/Hes1 pathway regulates Neuregulin 1/ErbB4 and participates in microglial activation in rats with VPA-induced autism.

The core clinical characteristics of autism, which is a neurodevelopmental disease, involve repetitive behavior and impaired social interactions. Studies have shown that the Notch and Neuregulin1 (NRG1) signaling pathways are abnormally activated in autism, but the mechanism by which these two signaling pathways interact to contribute to the progression of autism has not been determined. Our results suggest that the levels of Notch1, Hes1, NRG1, and phosphorylated ErbB4 in the cerebellum (CB), hippocampus (HC), and prefrontal cortex (PFC) were increased in rats with valproic acid (VPA)-induced autism compared to those in the Con group. However, 3, 5-difluorophenyl-L-alanyl-L-2-phenylglycine tert-butyl (DAPT), which is a Notch pathway inhibitor, ameliorated autism-like behavioral abnormalities and decreased the protein levels of NRG1 and phosphorylated ErbB4 in rats with VPA-induced autism; these results demonstrated that the Notch1/Hes1 pathway could participate in the pathogenesis of autism by regulating the NRG1/ErbB4 signaling pathway. Studies have shown that the Notch pathway regulates microglial differentiation and activation during the onset of neurological disorders and that microglia affect autism-like behavior via synaptic pruning. Therefore, we hypothesized that the Notch1/Hes1 pathway could regulate the NRG1/ErbB4 pathway and thus participate in the development of autism by regulating microglial functions. The present study showed that AG1478, which is an ErbB4 inhibitor, ameliorated the autism-like behaviors in a VPA-induced autism rat model, reduced abnormal microglial activation, and decreased NRG1 and Iba-1 colocalization; however, AG1478 did not alter Notch1/Hes1 activity. These results demonstrated that Notch1/Hes1 may participate in the microglial activation in autism by regulating NRG1/ErbB4, revealing a new mechanism underlying the pathogenesis of autism.

Predicting sequenced dental treatment plans from electronic dental records using deep learning.

BACKGROUND: Designing appropriate clinical dental treatment plans is an urgent need because a growing number of dental patients are suffering from partial edentulism with the population getting older. OBJECTIVES: The aim of this study is to predict sequential treatment plans from electronic dental records. METHODS: We construct a clinical decision support model, MultiTP, explores the unique topology of teeth information and the variation of complicated treatments, integrates deep learning models (convolutional neural network and recurrent neural network) adaptively, and embeds the attention mechanism to produce optimal treatment plans. RESULTS: MultiTP shows its promising performance with an AUC of 0.9079 and an F score of 0.8472 over five treatment plans. The interpretability analysis also indicates its capability in mining clinical knowledge from the textual data. CONCLUSIONS: MultiTP's novel problem formulation, neural network framework, and interpretability analysis techniques allow for broad applications of deep learning in dental healthcare, providing valuable support for predicting dental treatment plans in the clinic and benefiting dental patients. CLINICAL IMPLICATIONS: The MultiTP is an efficient tool that can be implemented in clinical practice and integrated into the existing EDR system. By predicting treatment plans for partial edentulism, the model will help dentists improve their clinical decisions.

Novel Transcription Factor CXRD Regulates Cellulase and Xylanase Biosynthesis in Penicillium oxalicum under Solid-State Fermentation.

Penicillium oxalicum produces an integrated, extracellular cellulase and xylanase system, strictly regulated by several transcription factors. However, the understanding of the regulatory mechanism of cellulase and xylanase biosynthesis in P. oxalicum is limited, particularly under solid-state fermentation (SSF) conditions. In our study, deletion of a novel gene, cxrD (cellulolytic and xylanolytic regulator D), resulted in 49.3 to 2,230% enhanced production of cellulase and xylanase, except for 75.0% less xylanase at 2 days, compared with the P. oxalicum parental strain, when cultured on solid medium containing wheat bran plus rice straw for 2 to 4 days after transfer from glucose. In addition, the deletion of cxrD delayed conidiospore formation, leading to 45.1 to 81.8% reduced asexual spore production and altered mycelial accumulation to various extents. Comparative transcriptomics and real-time quantitative reverse transcription-PCR found that CXRD dynamically regulated the expression of major cellulase and xylanase genes and conidiation-regulatory gene brlA under SSF. In vitro electrophoretic mobility shift assays demonstrated that CXRD bound to the promoter regions of these genes. The core DNA sequence 5'-CYGTSW-3' was identified to be specifically bound by CXRD. These findings will contribute to understanding the molecular mechanism of negative regulation of fungal cellulase and xylanase biosynthesis under SSF. IMPORTANCE Application of plant cell wall-degrading enzymes (CWDEs) as catalysts in biorefining of lignocellulosic biomass into bioproducts and biofuels reduces both chemical waste production and carbon footprint. The filamentous fungus Penicillium oxalicum can secrete integrated CWDEs, with potential for industrial application. Solid-state fermentation (SSF), simulating the natural habitat of soil fungi, such as P. oxalicum, is used for CWDE production, but a limited understanding of CWDE biosynthesis hampers the improvement of CWDE yields through synthetic biology. Here, we identified a novel transcription factor CXRD, which negatively regulates the biosynthesis of cellulase and xylanase in P. oxalicum under SSF, providing a potential target for genetic engineering to improve CWDE production.

Organophotoredox and Hydrogen Atom Transfer Cocatalyzed C-H Alkylation of Quinoxalin-2(1H)-ones with Aldehydes, Amides, Alcohols, Ethers, or Cycloalkanes.

Described is a mild method that merges organophotoredox catalysis with hydrogen atom transfer to enable C-H alkylation of quinoxalin-2(1H)-ones with feedstock aldehydes, amides, alcohols, ethers, or cycloalkanes. This reaction occurred under environmentally benign and external oxidant-free reaction conditions, providing a general and sustainable access to various C3-alkylated quinoxalinone derivatives with broad substituent diversity and good functional group compatibility.

Function and transcriptional regulation of CsKCS20 in the elongation of very-long-chain fatty acids and wax biosynthesis in Citrus sinensis flavedo.

Cuticular wax on plant aerial surfaces plays a vital role in the defense against various stresses, and the genes related to wax metabolism have been well documented in several model plants. However, there is very limited research on the key enzymes and transcription factors (TFs) associated with carbon chain distribution and wax biosynthesis in citrus fruit. In this study, an analysis of wax metabolites indicated that even carbon-chain (C24-C28) metabolites are the dominant wax components in citrus fruit, and a 3-ketoacyl-CoA synthase (KCS) family gene (CsKCS20) plays an important role in the carbon chain distribution during wax biosynthesis in a wax-deficient mutant (MT). Expression of CsKCS20 in yeast indicated that CsKCS20 can catalyze the biosynthesis of C22 and C24 very-long-chain fatty acids (VLCFAs). In addition, transcriptome and sequence analysis indicated that the differential expression of CsKCS20 between the wild-type (WT) and MT fruit can be partly attributed to the regulation of CsMYB96, which was further confirmed by yeast one-hybrid (Y1H) assays, electrophoretic mobility shift assays (EMSAs) and dual luciferase assays. The functions of CsMYB96 and CsKCS20 in wax biosynthesis were further validated by heterologous expression in Arabidopsis. In summary, this study elucidates the important roles of CsKCS20 and CsMYB96 in regulating VLCFA elongation and cuticular wax biosynthesis, which provides new directions for the improvement of citrus fruit wax quality in genetic breeding programs.

Traditional Chinese medicine for Helicobacter pylori infection: A protocol for a systematic review and meta-analysis.

BACKGROUND: Helicobacter pylori (Hp) is the only bacterium in the stomach. It is characterized by its ability to adhere to gastric mucosa and cause a series of pathological changes in the gastric mucosa. Modern research shows that Hp is an important pathogenic factor for chronic gastritis, gastroduodenal ulcer, and gastric cancer. Triple, quadruple, and triple combinations of antibacterial drugs, proton pump inhibitors, and bismuth aluminate preparations have been developed in modern medical research. Sequential therapy is used to treat Hp, but antibiotic resistance and repeated infections still exist. A large number of clinical trials have proved that traditional Chinese medicine has a good therapeutic effect on Hp. In this systematic review, we aim to evaluate the efficacy and safety of traditional Chinese medicine in the treatment of Hp. METHODS AND ANALYSIS: We will search for publications from Web of Science, PubMed, Science Direct, Wan Fang Data Knowledge Service Platform, Chinese Biomedical Literature Database (CBM), Chinese Scientific Journal Database (VIP database), China National Knowledge Infrastructure (CNKI) and EMBASE, which should be published from inception to December 2020. Two researchers will independently perform the selection of the studies, data extraction, and synthesis. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias in the randomized controlled trials. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software. The I2 test will be used to identify the extent of heterogeneity. We will use the Egger funnel chart to evaluate possible publication biases, in addition, when possible we will perform a subgroup/meta-regression analysis. The strength of the evidence will be assessed according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE). RESULTS AND CONCLUSIONS: This study will systematically evaluate the efficacy of traditional Chinese medicine in the treatment of Hp infection, and provide evidence for the clinical application of this treatment. The results of the research will be published in a peer-reviewed journal. ETHICS: This systematic review will evaluate the efficacy of traditional Chinese medicine for Hp infection. Because all data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. TRIAL REGISTRATION NUMBER: INPLASY2020120057.

Traditional Chinese medicine on treating splenomegaly due to portal hypertension in cirrhosis: A protocol for systematic review and meta-analysis.

BACKGROUND: Liver cirrhosis is a common clinical chronic progressive disease. Due to the obstruction of blood flow after cirrhosis, it leads to long-term congestion of splenic sinus, hyperplasia of fibrous tissue and proliferation of splenic myeloid cells, resulting in hepatocirrhosis and splenomegaly. At present, western medicine still uses splenectomy and interventional therapy are the main treatment, but the adverse reactions are more and the curative effect is not good. Many clinical trials have proved that Traditional Chinese medicine has a great therapeutic effect on Hepatocirrhosis with splenomegaly, which can effectively delay the development of the disease and improve the survival rate of patients. This systematic review aims to evaluate the efficacy and safety of Traditional Chinese medicine in the treatment of hepatocirrhosis with splenomegaly. METHODS: The databases of Pubmed, CENTRAL (The Cochrane Central Register of Controlled Trials), China National Knowledge Infrastructure (CNKI), Wanfang Data Knowledge Service Platform (WANFANG Data), Weipu Information Chinese Periodical Service Platform (VIP), and China Biomedical Literature Service System (SinoMed) will be searched online to collect randomized controlled trials related to the treatment of hepatocirrhosis with splenomegaly with Traditional Chinese medicine The time is limited from the construction of the library to November 2020. We will use the criteria provided by Cochrane 5.1.0 for quality assessment and risk assessment of the included studies, and use the Revman 5.3 and Stata 13.0 software so as to systematically review the effectiveness of Traditional Chinese medicine for hepatocirrhosis with splenomegaly. ETHICS AND DISSEMINATION: This systematic review will evaluate the efficacy and safety of Traditional Chinese medicine for hepatocirrhosis with splenomegaly. Because all data used in this systematic review and meta-analysis have been published, this review does not require ethical approval. In addition, all data will be analyzed anonymously during the review process. RESULTS: In this study, we will evaluate the efficacy of Traditional Chinese medicine in the treatment of cirrhosis with splenomegaly. CONCLUSION: The conclusion of this study will be evidence to ensure the efficacy of Traditional Chinese medicine© in the treatment of cirrhosis with splenomegaly and provide guidance for its treatment. TRIAL REGISTRATION NUMBER: INPLASY2020110121.

Efficacy and safety evaluation of acupuncture therapy for patients with salpingitis in IVF-ET: A protocol of systematic review and meta-analysis.

BACKGROUND: As an alternative for salpingitis in IVF-ET, acupuncture has gradually attracted the attention of clinicians based on the theory of syndrome differentiation and treatment of Chinese traditional medicine. However, due to the lack of evidence-based medical evidence, the author designed the program to evaluate the effectiveness and safety of acupuncture. METHODS: From the beginning to August 2020, 7 electronic databases will be searched. Two of our researchers will independently conduct research selection, data extraction, and risk assessment of bias. We will use Review Manager 5.3 software for meta-analysis and heterogeneity assessment. In addition, we will use the grading of recommendations assessment, development, and evaluation to evaluate the evidence quality. RESULTS: This study will demonstrate an evidence-based review of acupuncture for salpingitis in IVF-ET. CONCLUSION: The study will provide clear evidence to assess the effectiveness and side effects of acupuncture for salpingitis in IVF-ET. TRIAL REGISTRATION NUMBER: INPLASY2020110125.

The efficacy of Tuina for asthma: A protocol for a systematic review and meta-analysis.

BACKGROUND: Asthma is one of the most common chronic diseases in the world, with ∼100 million asthma patients worldwide. China has become one of the countries with the highest asthma death rate in the world. Asthma is a chronic airway inflammatory disease. Patients with this disease may have symptoms such as cough, wheezing, and difficulty breathing. For many years, Western medicine has mainly used anti-inflammatory, anti-bronchial spasm, asthma, cough, and oxygen to treat this disease, but the effect is not good. Tuina is a common treatment for asthma in China. But at present, there is no systematic evaluation report on its therapeutic effectiveness and safety. This protocol aims to reveal the efficacy and safety of Tuina for treating asthma. METHODS: The following databases will be searched by electronic methods: PubMed, EBASE, WHO International Clinical Trials Registry Platform, Embase, the Chinese Biomedical Literature Database (CBM), Wan-fang Data (WANFANG), the China National Knowledge Infrastructure (CNKI), and other sources from inception to November 2020. Bias risk, subgroup analysis, data synthesis, and meta-analyses will be assessed with RevMan V.5.3 software if the data is met inclusion conditions. RESULTS: This study will present a quality evidence of Tuina for the treatment of astma patients. CONCLUSION: The systematic review will present reliable evidence to judge whether or not Tuina is a safe and effective intervention for asthma patients. International Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) registration number: INPLASY2020110100.

Chinese herbal medicine for previous cesarean scar defect: A protocol for systematic review and meta-analysis.

BACKGROUND: Previous cesarean scar defect (PCSD) is a gynecological disease that can cause bleeding after intercourse, prolonging menstrual period, intermenstrual bleeding, dysmenorrhea, and even lead to infertility. Chinese herbal medicine plays an important role in the treatment of gynecological diseases in China and East Asia. This study aims to assess the efficacy and safety of Chinese herbal medicine for PCSD. METHODS: We search the following databases: PubMed, the Cochrane Library, Chinese Biomedical Literature Database (CB), Chinese Science and Technique Journals Database (VIP), EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and the Wanfang Database. Other sources will also be searched like Google Scholar and gray literature. All databases mentioned above are searched from the start date to the latest version. Randomized controlled trials will be included which recruiting PCSD participants to assess the efficacy and safety of Chinese herbal medicines against controls (placebo or other therapeutic agents). Primary outcomes will include the size of PCSD, menstrual cycle, menstrual phase, menstrual volume, duration of disease, security index. Two authors will independently scan the searched articles, extract the data from attached articles, and import them into Endnote X8 and use Microsoft Excel 2013 to manage data and information. We will assess the risk of bias by Cochrane tool of risk of bias. Disagreements will be resolved by consensus or the participation of a third party. All analysis will be performed based on the Cochrane Handbook for Systematic Reviews of Interventions. The meta-analysis in this review will use RevMan 5.3 software. RESULTS: The study aims to evaluate the efficacy and safety of the treatment that Chinese herbal medicine for PCSD. CONCLUSION: This study of the meta-analysis could provide evidence for clinicians and help patients to make a better choice. INPLASY REGISTRATION NUMBER: INPLASY202090080.

Integrated transcriptomic and metabolomic analyses of a wax deficient citrus mutant exhibiting jasmonic acid-mediated defense against fungal pathogens.

Naturally, resistant crop germplasms are important resources for managing the issues of agricultural product safety and environment deterioration. We found a spontaneous mutant of 'Newhall' navel orange (Citrus sinensis Osbeck) (MT) with broad-spectrum protections against fungal pathogens in the orchard, postharvest-storage, and artificial inoculation conditions. To understand the defense mechanism of MT fruit, we constructed a genome-scale metabolic network that integrated metabolome and transcriptome datasets. The coordinated transcriptomic and metabolic data were enriched in two sub-networks, showing the decrease in very long chain fatty acid (by 41.53%) and cuticular wax synthesis (by 81.34%), and increase in the synthesis of jasmonic acid (JA) (by 95.23%) and JA-induced metabolites such as 5-dimethylnobietin (by 28.37%) in MT. Furthermore, cytological and biochemical analyses confirmed that the response to fungal infection in MT was independent of wax deficiency and was correlated with the levels of jasmonates, and the expression of plant defensin gene PDF1.2. Results of exogenous application of MeJA and JA inhibitors such as propyl gallate proved that JA-mediated defense contributes to the strong tolerance against pathogens in MT. Our results indicated that jasmonate biosynthesis and signaling are stimulated by the fatty acid redirection of MT, and participate in the tolerance of pathogenic fungi.

[Clinical characteristics and antimicrobial resistance of invasive group A ß-hemolytic streptococcus infection in children].

OBJECTIVE: Group A ß-hemolytic streptococcus (GAS) or Streptococcus pyogenes may be encountered in diverse clinical situations in children. A rising incidence of invasive group A streptococcus (IGAS) infections has been noted in children in the past three decades. The aim of this study was to summarize the clinical characteristics and antimicrobial resistance of IGAS in children, and to raise the level of diagnosis and treatment of this infection. METHOD: The clinical data from 19 cases of IGAS younger than 14 years old seen from January 2004 to December 2011 treated in the authors' hospital were analyzed. IGAS infections are defined as the isolation of GAS from a normally sterile site in patients. RESULT: The 19 cases were identified as IGAS infections, among whom 15 were male and 4 were female, and the ratio of them was 3.75. The age ranged from 1 day to 14 years, with a median age of 4 years. The course of disease was 4 h-10 days. The average length of stay was 12.2 days. In 13 cases the episodes of the infection occurred in winter and spring. In 18 cases the infection was community-acquired. Overall, 10 cases had neck or foot dorsum abscess, four cases had purulent peritonitis, and 3 cases were diagnosed as streptococcal toxic shock syndrome (STSS) complicated with empyema, pyopneumothorax occurred in 1 case and neonatal septicemia in another. Three cases had an underlying disease, including 2 cases wounded in a car accident and 1 case of congenital esophageal atresia and tracheoesophageal fistula. Before the isolation of GAS, 5 cases had stayed in ICUs, the length of ICU stay was 1-32 days, 4 cases had received intubation and mechanical ventilation, the ventilation time was 8 h-24 days, 2 cases had received major surgery; 5 cases had other pathogen coinfection, including 4 cases of abdominal pus at the same time and Escherichia coli was isolated, and 1 case had parainfluenza virus type I coinfection. Peripheral blood leucocyte increased in 18 cases, one case dropped off. The C-reactive protein (CRP) levels increased in all patients, including 16 cases who had 14-160 mg/L, 3 cases had levels higher than 160 mg/L. Twenty strains of GAS were isolated from 19 cases' sterile sites, of them 10 strains were isolated from abscess, 4 strains were isolated from blood and another 4 from ascites. Two strains were from the same patient at different times of pleural effusion. All 20 strains displayed a full susceptibility to cefazolin, levofloxacin and vancomycin, and the rates of resistance to both cefotaxime and penicillin were 10.0%. The rates of resistance to erythromycin and clindamycin were 55.0% and 70.0% respectively. Among the patients 3 cases were cured, 14 cases improved, and 2 cases died, of whom 1 case died of STSS secondary to multiple organ dysfunction, 1 case died of basic disease secondary to multiple organ dysfunction. CONCLUSION: Skin and soft tissues were the most common IGAS infection sites in children, and IGAS infection also can lead to serious STSS and even can be life threatening. Penicillin and cephalosporin are still sensitive for children IGAS infections.

[Clinical characteristics and antibiotic resistance in children with invasive Acinetobacter baumannii infection].

OBJECTIVE: To analyze the clinical characteristics and antibiotic resistance in children with invasive Acinetobacter baumannii infection (IABI). METHODS: A retrospective analysis was performed on the clinical and drug sensitivity data of 52 children with IABI between January 2004 and December 2011. RESULTS: Of the 52 children with IABI, 35 (67%) were less than one year old and 35 (67%) had IABI in the summer and autumn, 19 (37%) of these children were clinically diagnosed with septicemia, 16 (31%) with urinary tract infection, and 12 (23%) with skin and soft tissue infection, and 38 (73%) of them suffered from underlying diseases. The incidence rates of hospital-acquired and community-acquired IABIs were 90% and 10% respectively; 44 cases (85%) were cured or showed improvement in symptoms, and 8 cases (15%) died. All the IAB strains isolated from these children were sensitive to amikacin, 82% of them were sensitive to imipenem, more than 70% were sensitive to fluoroquinolone and to cefoperazone/sulbactam, 13% were sensitive to cefoperazone, 8% were sensitive to aztreonam, 21% developed multidrug resistance, and 17% developed pan-drug resistance. CONCLUSIONS: IABI occurs more frequently in children under one year of age, and most children with IABI have underlying diseases. IABI mainly results in septicemia, urinary tract infection and skin and soft tissue infection and is mostly hospital-acquired. Multi-drug resistance and pan-drug resistance are severe in IAB strains.

[Rising attention to the market to ratio meet demand of improving efficiency of pharmaceutical circulation--based on complicated variety and specification of drugs].

Analyzing the complicated variety and specification of drugs and the objective demand of pharmaceutical circulation, to seek out the key factors in improving the efficiency of pharmaceutical circulation, for putting forward suggestions to promote the development of pharmaceutical circulation in China. The conclusion is drawed from industrial organization theory and successful experience of foreign countries, high market attention met with the demand of complicated variety and specification of drugs in pharmaceutical circulation.

[Experimental studies on the extract technology of tea polysaccharide from green tea by orthogonal test].

The effect factor of extraction of tea polysaccharide was investigated with orthogonal test. The effects of extraction conditions on yield, purity of tea polysaccharide and cost of extraction were discussed. The results show that the optimum conditions for extracting tea polysaccharide from green tea are as follows: extraction time is 30 minutes with water at 95 degrees C, extraction times with chloroform is 3, extraction times with CH3COOC2H5 is 1 and concentration of alcohol is 60%.