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The green fluorescent reporter gene was inserted into the gene interval of polymyxin resistant mcr-1-carrying plasmid (pSH13G841) by homologous recombination of suicide plasmid. At the same time, E. coli J53 with red fluorescent reporter gene was constructed. Using the ability of spontaneous conjugation of drug resistant plasmid (pSH13G841), pSH13G841-GFP plasmid was transferred into J53 RFP bacteria to construct a double fluorescent labeled donor bacterium. The two light-emitting systems could stably and spontaneously express fluorescence without mutual interference. The dual fluorescence report system constructed can be used for visual tracing horizontal transfer of mcr-1-carrying plasmid, the subsequent model can study the colonization, transfer and prognosis of drug-resistant bacteria/drug-resistant genes mcr-1 by using mouse in vivo imaging technology.
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Sclerostin, a protein secreted from osteocytes, negatively regulates the WNT signaling pathway by binding to the LRP5/6 co-receptors and further inhibits bone formation and promotes bone resorption. Sclerostin contributes to musculoskeletal system-related diseases, making it a promising therapeutic target for the treatment of WNT-related bone diseases. Additionally, emerging evidence indicates that sclerostin contributes to the development of cancers, obesity, and diabetes, suggesting that it may be a promising therapeutic target for these diseases. Notably, cardiovascular diseases are related to the protective role of sclerostin. In this review, we summarize three distinct types of inhibitors targeting sclerostin, monoclonal antibodies, aptamers, and small-molecule inhibitors, from which monoclonal antibodies have been developed. As the first-in-class sclerostin inhibitor approved by the U.S. FDA, the monoclonal antibody romosozumab has demonstrated excellent effectiveness in the treatment of postmenopausal osteoporosis; however, it conferred high cardiovascular risk in clinical trials. Furthermore, romosozumab could only be administered by injection, which may cause compliance issues for patients who prefer oral therapy. Considering these above safety and compliance concerns, we therefore present relevant discussion and offer perspectives on the development of next-generation sclerostin inhibitors by following several ways, such as concomitant medication, artificial intelligence-based strategy, druggable modification, and bispecific inhibitors strategy.
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Since its founding 100 years ago, the Communist Party of China (CPC) has attached great importance to the occupational health of workers, and closely linked the safeguard of occupational safety and health of workers with the missions of leading the people to stand up, get rich, and become strong. Based on this, the achievements of occupational health work made under the leadership of the CPC since the new democratic revolution, socialist revolution and construction, the new period of reform and opening up and socialist modernization, and socialism with Chinese characteristics for a new era were summarized, so as to provide reference for understanding the legacy of China's occupational health undertaking, and innovating to create the future.
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Biological complexity and the need for personalized medicine means that biomarker development has become increasingly challenging. Thus, new paradigms for research need to be created that bring together a different classifier of individuals. One potential solution is collaboration between biomarker development and Chinese medicine pattern classification. In this article, two examples of rheumatoid arthritis are discussed, including a new biomarker candidate casein kinase 2 interacting protein 1 (CKIP-1) and a micro RNA 214. The authors obtained a "snapshot" of pattern classification with disease in biomarker identification. Bioinformatics analyses revealed underlying biological functions of two biomarker candidates, in varying degrees, are correlated with Chinese medicine pattern of rheumatoid arthritis. The authors' initial attempt can provide a new window for studying the win-win potential correlation between the biomarkers and pattern classification in Chinese medicine.
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Over the past 30 years, Yarrowia lipolytica, Kluyveromyces, Pichia, Candida, Hansenula and other non-conventional yeasts have attracted wide attention because of their desirable phenotypes, such as rapid growth, capability of utilizing multiple substrates, and stress tolerance. A variety of synthetic biology tools are being developed for exploitation of their unique phenotypes, making them potential cell factories for the production of recombinant proteins and renewable bio-based chemicals. This review summarizes the gene editing tools and the metabolic engineering strategies recently developed for non-conventional yeasts. Moreover, the challenges and future perspectives for developing non-conventional yeasts into efficient cell factories for the production of useful products through metabolic engineering are discussed.
Subject(s)
Gene Editing , Metabolic Engineering , Pichia/genetics , Synthetic Biology , Yarrowia/genetics , YeastsABSTRACT
Objective: To study the therapeutic effect of Huoxue Tongluo Decoction (HXTLD) on erectile dysfunction caused by ischemic stroke and identify the mechanisms involved. Methods: Network pharmacology was used to predict the key active ingredients and targets of HXTLD. Surgical methods were used to create a rat model of ischemic stroke. The rats were then given a suspension of HXTLD by ig administration. Erectile function was evaluated by Apomorphine (APO) induction. Real-time fluorescence quantitative reverse transcription-polymerase chain reaction (Real-time PCR) and Western blotting were used to detect the expression of related mRNAs and proteins in rat penile corpus cavernous tissue and brain tissue. Hematoxylin & Eosin (HE) staining was used to investigate structural changes in the penile cavernous tissue. Results: Network pharmacology showed that tumor necrosis factor (TNF), nitric oxide synthase 3 (eNOS), and vascular endothelial growth factor (VEGF) were the key targets of HXTLD in the treatment of erectile dysfunction caused by ischemic stroke. Experimental studies showed that HXTLD improved erectile dysfunction caused by ischemic stroke. HE results showed that HXTLD improved the structure of the corpus cavernosa. HXTLD also inhibited the expression of TNF and VEGF proteins in penile tissue (P < 0.05) and enhanced the expression of eNOS protein in penile tissue (P < 0.05). Conclusion: HXTLD improved the erectile function of rats with erectile dysfunction caused by ischemic stroke by regulating the mRNA and protein levels of TNF, eNOS and VEGF.
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To evaluate whether midlife consumption of sugar-sweetened beverages (SSBs), including juices and soft drinks, were associated with late-life cognitive impairment in Chinese adults. Follow up was conducted for participants from Singapore Chinese Health Study, a population-based prospective cohort, for 16-23 (mean 20) years. The information about their SSBs consumption were collected at baseline survey from 1993 to 1998 by using a validated food frequency questionnaire and their cognition status were evaluated by using a Singapore-modified Mini-Mental State Examination Scale in the 3(rd) follow-up visit during 2014- 2016. Multivariable logistic regression models were used to estimate the and 95s. A total of 16 948 participants were included in the analysis and 2 443 of them were identified as cognitive impairment using education-specific cutoffs. Sex, age, ancestral home, education level, physical activity level, total diet fiber intake level, BMI, alcohol drinking were significantly associated with cognitive impairment (0.05). Compared with those who never or hardly ever drank soft drinks, no significant differences in cognitive impairment risk were observed for those who drank soft drinks 2 or more times a week (=0.91, 95: 0.77-1.08), those who drank 1 time a week (=1.00, 95:0.82-1.23) and those who drank 1-3 times a month (=0.94, 95: 0.80-1.09) (trend =0.306). Compared with those who never or hardly ever drank juices, no significant differences in cognitive impairment risk were observed for those who drank juices 2 or more times a week (=1.03, 95:0.88-1.20), those who drank 1 time a week (=0.96, 95: 0.82-1.12) and those who drank 1-3 times a month (=0.94, 95: 0.82-1.08) (trend =0.930). No significant interactions were found with age, sex, and BMI status. SSBs consumption in midlife was not significantly associated with risk of late-life cognitive impairment in Singaporean Chinese adults with relatively low consumption levels. Further researches are needed to verify the results.
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Objective:To observe the effect of melodic intonation therapy combined with speech training on nonfluent aphasia after stroke, and the changes of brain function. Methods:From March, 2017 to August, 2019, 40 patients with nonfluent aphasia after stroke were randomly divided into control group (n = 20) and intensive group (n = 20). Both groups accepted routine speech training, and the intensive group accepted melodic intonation therapy in addition. They were assessed with China Rehabilitation Research Center Chinese Standard Aphasia Examination before and four weeks after treatment. Three patients from each group were examined with resting-state functional magnetic resonance imaging to observe the changes of regional homogeneity (ReHo) of cerebral hemisphere. Results:The scores of comprehension (noun, verb and sentence), repetition (noun and verb), read (noun) and naming (verb) increased in the control group (t > 2.221, P < 0.05), while it increased in comprehension (noun, verb and sentence), repetition (noun, verb and sentence), reading (noun and verb) and naming (noun and verb) in the intensive group (t > 2.179, P < 0.05). The scores of repetition (noun and verb) increased more in the intensive group than in the control group (t > 2.299, P < 0.05)， and the scores of reading (sentence) increased somehow. The ReHo in left cerebellum and temporal occipital area increased and the ReHo in bilateral frontal and temporal cortex decreased after treatment. Conclusion:Melodic intonation therapy based on speech therapy can promote the recovery of speech function for patients with nonfluent aphasia after stroke, especially in sentence reading and words repetition. The changes of the ReHo in resting state may associate with the neurological repairment after brain injury.
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Objective To understand the distribution characteristics of death causes and potential life loss of residents in Pudong New Area from 2009 to 2018, assess the disease burden caused by different diseases, and provide a basis for formulating regional prevention and control strategies. Methods The mortality data of residents in Pudong New Area of Shanghai from 2009 to 2018 were collected. The death causes were classified by International Classification of Diseases (ICD-10). The crude mortality rate, standardized mortality rate, potential years of life lost (PYLL), potential years of life lost rate (PYLLR), and average years of life lost (AYLL) were calculated. Results The crude mortality and standardized mortality of residents in Pudong New Area between 2009 and 2018 were 7.55‰ and 3.65‰, respectively. The top five causes of death in Pudong New Area residents were circulatory system diseases, tumors, respiratory diseases, endocrine nutrition and metabolic diseases, and injury and poisoning, accounting for 87.85% of the total deaths. The PYLL was 687 729 person-years, the PYLLR was 24.11‰ and the AYLL was 3.19 years per person. The top 5 causes of life loss of residents in Pudong New Area was tumor, circulatory system disease, injury and poisoning, endocrine nutrition and metabolism illness, and congenital anomalies, accounting for 82.08% of total life loss of residents. Conclusion Chronic non-infectious diseases, including circulatory diseases, tumors, and endocrine nutritional metabolism diseases, were the main causes of death of residents in Pudong New Area, and caused a heavy disease burden, which should be the focus of prevention and control in the future. Comprehensive preventive and control measures should be taken to protect the residents from the harm due to chronic non-communicable diseases and improve the health condition of the residents in Pudong New Area.
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OBJECTIVE: To prepare siRNA/HDL modified Dox/micelle multimeric polymer(siRNA/HDL-Dox/micelle) by using HDL as a siRNA carrier and a targeting ligand and to realize the effective co-delivery of siRNA and antitumor drug. METHODS: HDL was incubated with chol-siRNA to prepare siRNA/LDL complex, then coupled with Dox/micelle to form siRNA/HDL modified Dox/micelle multimeric polymer (siRNA/HDL-Dox/micelle). The particle size and stability were investigated in different medium. HepG2/ADM with P-glycoprotein(P-gp) over-expressed were used to study the cell uptake, sub-cellular localization and anti-tumor efficacy in vitro. The ability of siRNA to silence target genes at mRNA and protein level was examined by RT-PCR and Western blot. RESULTS: HDL exhibited an efficient binding ability for siRNA and protected siRNA from RNase. The size and surface morphology of siRNA/HDL-Dox/micelle confirmed by TEM showed that most of the micelles were compact and spherical, exhibited a narrow size distribution and good dispersion. The particle size and Zeta potential increased with increasing incubation time in pH 5.3 PBS. The siRNA was efficiently delivered into the cells by encapsulation into HDL, and the expression of P-gp is effectively down-regulated at the mRNA level and the protein level, thereby increasing the accumulation of intracellular Dox and enhancing the antitumor activity. CONCLUSION: siRNA/HDL-Dox/micelle could effectively deliver siRNA and Dox into tumor cells, thereby exerting gene silencing, reversing tumor drug resistance and enhancing anti-tumor effect.
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@#Retinal degenerative disease can lead to decreased vision, which is a blinding ophthalmopathy caused by irreversible damage or apoptosis of retinal pigment epithelium(RPE)cells or photoreceptor cells, often resulting in visual impairment or even blindness. Human embryonic stem cells(hESCs)are a kind of multi-directional differentiation cells. By appropriate methods, hESCs can be differentiated into various retinal cells. Since human PRE cells cannot be regenerated, studies have shown that the clinical treatment of retinopathy with stem cell derived RPE cell transplantation has practical prospects and has made a breakthrough in recent years. Due to the limitations of multiple factors, the selection of methods and the complexity of induction conditions, the efficiency of induced differentiation of RPE and the survival rate after transplantation vary greatly and are unstable. Therefore, the current researches should focus on how to integrate different culture methods, take advantages and eliminate disadvantages, so as to improve the directed differentiation efficiency of hESCs, as well as the number and quality of induced cells, thus reducing culture pollution and immune rejection and so on. Here, we will summarize the current examples of various culture methods and give a review from different perspectives.
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OBJECTIVE@#To explore the molecular-level mechanism on the hematopoiesis effect of Angelicae sinensis Radix (ASR) with systems-based interactome analysis.@*METHODS@#This systems-based interactome analysis was designed to enforce the workflow of "ASR (herb)→compound→target protein→internal protein actions→ending regulated protein for hematopoiesis". This workflow was deployed with restrictions on regulated proteins expresses in bone marrow and anemia disease and futher validated with experiments.@*RESULTS@#The hematopoiesis mechanism of ASR might be accomplished through regulating pathways of cell proliferation towards hemopoiesis with cross-talking agents of spleen tyrosine kinase (SYK), Janus kinase 2 (JAK2), and interleukin-2-inducible T-cell kinase (ITK). The hematopoietic function of ASR was also validated by colony-forming assay performed on mice bone marrow cells. As a result, SYK, JAK2 and ITK were activated.@*CONCLUSION@#This study provides a new approach to systematically study and predict the therapeutic mechanism for ASR based on interactome analysis towards biological process with experimental validations.
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As part of systematic research of Corydalis hendersonii,a typical traditional Tibetan herbal medicine with clearing heat,relieving pain,and lowering blood pressure effects,a novel isoquinoline alkaloid,named hendersine G was isolated from the ethanol extract of the whole plant by various chromatographic techniques,including silica gel column,reverse phase column (ODS),Sephadex LH-20,and semi-preparative HPLC.Its structure was elucidated by MS,NMR and other spectroscopic data analysis.Hendersine G can be regarded as a condensation product of a tetrahydroberberine and a succinic acid,however,its absolute configuration has not been determined due to its structural complexity and less obtained amount.This present study provides an inspiration for further exploration of novel molecules from C.hendersonii.
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Comprehensive interventions have been widely used in health system, public health, education and communities and have become increasingly focus of systematic reviews. There have been many reporting guidelines about systematic reviews, but they do not take the features of comprehensive interventions in medical area into consideration. As a result, PRISMA-CI has been developed as an extension of PRISMA, which adds or modifies the essential items of PRISMA. This paper introduces the items of PRISMA-CI and explains the items with an example to help authors, publishers, and readers understand PRISMA-CI and use it in systematic reviews on comprehensive interventions. As it become more and more popular with comprehensive interventions, PRISMA-CI will provide important structure and guidance for its systematic review and Meta-analysis.
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Purpose:@#To investigate the characteristics of the onset and treatment of radial head subluxation (RHS) in pediatric clinics and emergency departments.@*Methods:@#A retrospective study was performed on 11, 404 RHS cases in 9827 children who visited pediatric clinics and emergency departments from January 2015 to December 2018. The patients who with history of trauma and fracture of the affected limb were excluded. The following factors were examined: the mechanisms of RHS, the type of manual reduction, the attending physician's clinical background (emergency surgeon, junior pediatric orthopedic surgeon or senior pediatric orthopedic surgeon), and the epidemiological features (gender, age, climate and location) of the injury.@*Results:@#The mean age of the patients was 27.93 ± 17.94 months (range 0.93-214.53 months), with a peak incidence of 10.73-44.53 months. Approximately two-thirds of RHS cases occurred in cold weather from January to March and from September to December. Females accounted for 53.81% (n = 6137) of the cases, and left injuries were predominant (56.87%, n = 6485) in all cases. Mechanisms of injury were classified as "pull" (90.57%, n =10, 339), "fall" (1.56%, n = 178), "hit" (0.75%, n = 86) and "unknown" (7.02%, n = 801). The overall success rate of manual reduction was 99.47%, and the success rate of reduction was higher for senior pediatric orthopedic surgeons than for emergency surgeons and junior pediatric orthopedic surgeons (p < 0.05). However, there was still a recurrence rate of 12.16% in the 9827 patients.@*Conclusion:@#Younger children are predisposed to RHS, and there is a possibility of recurrence. Trained emergency doctors can handle it well, but it is essential to refer patients to specialists when manual reduction failed.
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Objective@#To investigate the effects of interferon inducible protein 16 (IFI16), a cytosolic DNA sensor, on the expression of human T-cell leukemia virus type 1 (HTLV-1) proteins and pro-inflammatory cytokines in adult HTLV-1-positive T cells.@*Methods@#IFI16 expression in different HTLV-1-positive T cell lines was detected by immunoblot assay. Specific siRNA targeting the IFI16 gene was constructed and the gene silencing efficiency was detected by immunoblot assay. Expression of HTLV-1 Tax protein at mRNA and protein levels was respectively detected by real-time PCR and immunoblot assay after knocking down the expression of IFI16 in HTLV-1-positive T cells with siRNA. Expression of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, Tax and Env were detected by real-time PCR.@*Results@#Compared with the HTLV-1-negative T cell line Jurkat, IFI16 expression was enhanced in the HTLV-1-positive T cell lines MT2, MT4 and C8166. Tax expression was increased, while that of IFN-α, IFN-γ and TNF-α was decreased in MT2 and MT4 cells after silencing the expression of IFI16 with siRNA.@*Conclusions@#IFI16 expression was increased in HTLV-1-positive MT2 and MT4 cells. Meanwhile, IFI16 promoted the production of interferon and pro-inflammatory cytokines and inhibited the expression of HTLV-1 proteins.
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Objective@#To detect the expression of NRAGE protein in esophageal squamous cell carcinoma and investigate the relationship between NRAGE and therapeutic effect of radiotherapy.@*Methods@#The expression level of NRAGE in 44 patients with esophageal squamous cell carcinoma was evaluated by immunohistochemistry and statistically analyzed along with clinical data by using multivariate analysis using Cox regression model.@*Results@#The overall expression level of NRAGE protein in esophageal squamous cell carcinoma (P=0.025) and the expression level of NRAGE nuclear protein (P=0.008) were negatively correlated with short-term efficacy. In terms of the overall expression level of NRAGE protein, the 3-year survival rates in the strongly positive group and the positive weakly positive group were 16% and 36%(P=0.198). As for the expression of NRAGE nuclear protein, the 3-year survival rates in the strongly positive group and the positive+ weakly positive group were 0% and 41%(P<0.001). Multivariate analysis using Cox regression model demonstrated that as for the expression of NRAGE nuclear protein, the risk of death in the strongly positive group was significantly higher than those in the positive+ weakly positive group (P=0.002).@*Conclusion@#The overall expression level of NRAGE protein in the esophageal cancer is negatively correlated with the short-term efficacy of radiotherapy, whereas it is not correlated with long-term survival rate. The strongly positive expression level of NRAGE nuclear protein is negatively correlated with the short-term efficacy of radiotherapy and the long-term survival rate, prompting that NRAGE may be a molecular indicator for predicting radiation resistance and even the efficacy of radiotherapy for esophageal squamous cell carcinoma
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Objective To investigate the effects of interferon inducible protein 16 (IFI16), a cy-tosolic DNA sensor, on the expression of human T-cell leukemia virus type 1 (HTLV-1) proteins and pro-in-flammatory cytokines in adult HTLV-1-positive T cells. Methods IFI16 expression in different HTLV-1-positive T cell lines was detected by immunoblot assay. Specific siRNA targeting the IFI16 gene was con-structed and the gene silencing efficiency was detected by immunoblot assay. Expression of HTLV-1 Tax pro-tein at mRNA and protein levels was respectively detected by real-time PCR and immunoblot assay after knocking down the expression of IFI16 in HTLV-1-positive T cells with siRNA. Expression of interferon ( IFN)-α, IFN-γ, tumor necrosis factor ( TNF )-α, Tax and Env were detected by real-time PCR. Re-sults Compared with the HTLV-1-negative T cell line Jurkat, IFI16 expression was enhanced in the HTLV-1-positive T cell lines MT2, MT4 and C8166. Tax expression was increased, while that of IFN-α, IFN-γand TNF-α was decreased in MT2 and MT4 cells after silencing the expression of IFI16 with siRNA. Con-clusions IFI16 expression was increased in HTLV-1-positive MT2 and MT4 cells. Meanwhile, IFI16 pro-moted the production of interferon and pro-inflammatory cytokines and inhibited the expression of HTLV-1 proteins.
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Objective To detect the expression of NRAGE protein in esophageal squamous cell carcinoma and investigate the relationship between NRAGE and therapeutic effect of radiotherapy.Methods The expression level of NRAGE in 44 patients with esophageal squamous cell carcinoma was evaluated by immunohistochemistry and statistically analyzed along with clinical data by using multivariate analysis using Cox regression model.Results The overall expression level of NRAGE protein in esophageal squamous cell carcinoma (P=0.025) and the expression level of NRAGE nuclear protein (P=0.008) were negatively correlated with short-term efficacy.In terms of the overall expression level of NRAGE protein,the 3-year survival rates in the strongly positive group and the positive weakly positive group were 16％ and 36％(P=0.198).As for the expression of NRAGE nuclear protein,the 3-year survival rates in the strongly positive group and the positive+ weakly positive group were 0％ and 41％(P＜0.001).Multivariate analysis using Cox regression model demonstrated that as for the expression of NRAGE nuclear protein,the risk of death in the strongly positive group was significantly higher than those in the positive+ weakly positive group (P=0.002).Conclusion The overall expression level of NRAGE protein in the esophageal cancer is negatively correlated with the short-term efficacy of radiotherapy,whereas it is not correlated with long-term survival rate.The strongly positive expression level of NRAGE nuclear protein is negatively correlated with the shortterm efficacy of radiotherapy and the long-term survival rate,prompting that NRAGE may be a molecular indicator for predicting radiation resistance and even the efficacy of radiotherapy for esophageal squamous cell carcinoma
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OBJECTIVE: To investigate the related factors effecting the teicoplanin concentration..METHODS: The patients′ information who accepted teicoplanin therapy and their plasma on the fourth day treatment were collected. The plasma was processed and detected by HPLC method. A multiple linear regression method was used to explore the relationship between the teicoplanin concentration and other factors. RESULTS: The result of multiple linear regression shows that the teicoplanin concentration relates with the creatine clearance and hypersensitive C-reactive protein. CONCLUSION: The teicoplanin treatment regimen could be altered by the level of patients′ creatine clearance and hypersensitive C-reactive protein in order to deliver a better individual treatment.