Recombinant adeno-associated virus 8-mediated inhibition of microRNA let-7a ameliorates sclerosing cholangitis in a clinically relevant mouse model

BACKGROUND Primary sclerosing cholangitis(PSC)is characterized by chronic inflammation and it predisposes to cholangiocarcinoma due to lack of effective treatment options.Recombinant adeno-associated virus(rAAV)provides a promising platform for gene therapy on such kinds of diseases.A microRNA(miRNA)let-7a has been reported to be associated with the progress of PSC but the potential therapeutic implication of inhibition of let-7a on PSC has not been evaluated.AIM To investigate the therapeutic effects of inhibition of a miRNA let-7a transferred by recombinant adeno-associated virus 8(rAAV8)on a xenobiotic-induced mouse model of sclerosing cholangitis.METHODS A xenobiotic-induced mouse model of sclerosing cholangitis was induced by 0.1% 3,5-Diethoxycarbonyl-1,4-Dihydrocollidine(DDC)feeding for 2 wk or 6 wk.A single dose of rAAV8-mediated anti-let-7a-5p sponges or scramble control was injected in vivo into mice onset of DDC feeding.Upon sacrifice,the liver and the serum were collected from each mouse.The hepatobiliary injuries,hepatic inflammation and fibrosis were evaluated.The targets of let-7a-5p and downstream molecule NF-κB were detected using Western blot.RESULTS rAAV8-mediated anti-let-7a-5p sponges can depress the expression of let-7a-5p in mice after DDC feeding for 2 wk or 6 wk.The reduced expression of let-7a-5p can alleviate hepato-biliary injuries indicated by serum markers,and prevent the proliferation of cholangiocytes and biliary fibrosis.Furthermore,inhibition of let-7a mediated by rAAV8 can increase the expression of potential target molecules such as suppressor of cytokine signaling 1 and Dectin1,which consequently inhibit of NF-κB-mediated hepatic inflammation.CONCLUSION Our study demonstrates that a rAAV8 vector designed for liver-specific inhibition of let-7a-5p can potently ameliorate symptoms in a xenobiotic-induced mouse model of sclerosing cholangitis,which provides a possible clinical translation of PSC of human.

Study on the effect of Shixiang plaster on the expression of CD31,serum FN,and VEGF in a rat model with chronic wounds

Background:Chronic wounds pose a significant surgical challenge,often requiring traditional treatments with limited efficacy.This study explores the promising impact of Shixiang plaster,a classic Chinese ointment,on wound healing.We investigated the cluster of differentiation 31(CD31)expression,serum fibronectin(FN),and vascular endothelial growth factor(VEGF)levels in SPF rats with induced wounds to elucidate the mechanism behind Shixiang plaster’s effectiveness.We investigated the effect and explored the role of Shixiang plaster on the expression of CD31,serum FN,and VEGF in chronic wounds.Methods:The study involved 36 SPF rats divided into model,rb-bFGF,and Shixiang plaster groups.Penicillin was injected into the rats before modelling for 3 days to prevent infection.The skin was excised 2 cm below the horizontal line of the inferior border of the shoulder bone in the middle of the rat column up to the deep fascial layer and inoculated with a certain concentration of Staphylococcus aureus;the wound was covered aseptically for 3 days.The trauma area of the rats was observed at 3,7,and 14 days,respectively.Histopathology was observed using haematoxylin eosin and Masson staining.CD31 expression was detected using immunohistochemistry staining.FN and VEGF expression was detected using serum ELISA.Statistical analyses were carried out by the method of SPSS.Results:Regarding wound morphology,at 3 days,the recovery area of the Shixiang plaster group was larger than that of the other two groups,at 7 days,the wound healing rate of the Shixiang plaster group was significantly higher,and at 14 days,the wounds of the Shixiang plaster group had been mostly healed,with a healing rate of 98.3%.Haematoxylin eosin staining revealed a large amount of granulation tissue at 3 days in the Shixiang plaster group,and the epidermal scales disappeared at 14 days,with thinner epidermal thickness at 1 lesion and a large reduction in inflammatory cell infiltration.Masson staining showed that at 3,7,and 14 days,blue staining was the most abundant and deeper in the Shixiang plaster group,with richer collagen and a compact tissue matrix.Immunohistochemical testing showed strong positive expression of CD31 in the Shixiang plaster group,with abundant neovascularisation and large official lumens extending towards the surface of the wound.Statistically significant elevated expression of FN at 7 and 14 days was determined by ELISA in the Shixiang plaster group,and VEGF expression was significantly increased at 7 days,but expression had been expressed at a low level at 14 days.Conclusion:Shixiang plaster exhibits remarkable efficacy in healing chronic wounds.The proposed mechanism involves FN’s promotion of angiogenesis and cell proliferation,VEGF’s impact on angiogenesis and inflammation,and CD31’s regulatory role in inhibiting inflammation while promoting angiogenesis.

湖北省2008—2021年手足口病死亡病例特征分析

目的 分析湖北省手足口病死亡病例流行病学特点,为防治手足口病和减少死亡病例提供参考依据。方法 收集2008—2021年湖北省手足口病死亡病例个案信息,采用描述性方法分析病例三间分布、就诊机构、病程及病原学信息。结果 湖北省2008年—2021年共报告981 315例手足口病病例,其中死亡病例112例,病死率为0.0114%。发病高峰分布于4—6月,死亡病例主要集中在4—7月。死亡病例覆盖全省所有县区的38.83%(40/103),男女比为2.03∶1,年龄中位数1岁,5岁以下占98.21%(110/112),职业主要为散居儿童91.07%(102/112)。病原学检查结果以肠道病毒71型(EV71)为主(95.65%,88/92)。结论 手足口病死亡率总体呈现下降趋势,但仍应继续加强重症死亡病例的流行病学调查和病原学检测,以提高手足口病的诊断与救治及时性,避免死亡。

Research on the Path of Digital Transformation of Postgraduate Education in Chinese Universities under the Background of Digital Education Strategy

Digital transformation of education is an important strategic content of information construction in Chinese universities in recent years. Postgraduate education is characterized by many types of postgraduates, complex training links, long training process, and obvious individuation. Its information construction and digital transformation are the difficulties in the construction of smart campus in colleges and universities. This paper discusses the current situation and main problems of postgraduate education informatization in colleges and universities, and puts forward the key points and suggestions of digital transformation of postgraduate education in colleges and universities from the aspects of optimizing the information platform of postgraduate education management and service, driving the modernization and wisdom of postgraduate education with data, constructing the integrated platform of intelligent teaching, and continuously improving the digital literacy of teachers and students.

Exploration on the Construction of University Logistics Information Service Platform

Logistics information construction in colleges and universities is an important part of smart campus. This paper expounds the current situation and existing problems of the logistics information construction in colleges and universities. Taking China University of Geosciences (Beijing) as an example, this paper discusses the construction principles and Personnel organization structure of the logistics information construction, and provides the construction scheme of the logistics information service platform. It can be used for reference for the implementation of logistics information construction in other colleges and universities.

Research and Practice on High Availability Scheme of Unified Identity Authentication System Based on CAS in Colleges and Universities

Unified identity authentication has become the basic information service provided by colleges and universities for teachers and students. Security, stability, high concurrency and easy maintenance are our requirements for a unified identity authentication system. Based on the practical work experience of China University of Geosciences (Beijing), this paper proposes a high availability scheme of unified identity authentication system based on CAS, which is composed of multiple CAS Servers, Nginx for load balancing, and Redis as a cache database. The scheme has been practiced in China University of Geosciences (Beijing), and the application effect is good, which has practical reference significance for other universities.

Research and Development on the Visualization System for Official and Scientific Management in Enterprise

A visualization system for the official and scientific management has been designed on C++. By this system, the information of database has been shown to users intuitively, which makes it possible for users to be free from the data sea. The system can realize the information mining and the integrated display, at the same time, improve the information’s constructive level and integration degree.

Creation of a watermelon haploid inducer line via ClDMP3-mediated single fertilization of the central cell

The use of doubled haploids is one of the most efficient breeding methods in modern agriculture.Irradiation of pollen grains has been shown to induce haploids in cucurbit crops,possibly because it causes preferential fertilization of the central cell over the egg cell.Disruption of the DMP gene is known to induce single fertilization of the central cell,which can lead to the formation of haploids.In the present study,a detailed method of creating a watermelon haploid inducer line via ClDMP3 mutation is described.The cldmp3 mutant induced haploids in multiple watermelon genotypes at rates of up to 1.12%.These haploids were confirmed via fluorescent markers,flow cytometry,molecular markers,and immuno-staining.The haploid inducer created by this method has the potential to greatly advance watermelon breeding in the future.

Developing a highly efficient CGBE base editor in watermelon

Cytosine and adenosine base editors(CBEs and ABEs)are novel genome-editing tools that have been widely utilized in molecular breeding to precisely modify single-nucleotide polymorphisms(SNPs)critical for plant agronomic traits and species evolution.However,conventional BE editors are limited to achieve C-to-T and A-to-G substitutions,respectively.To enhance the applicability of base editing technology in watermelon,we developed an efficient CGBE editor(SCGBE2.0)by removing the uracil glycosylase inhibitor(UGI)unit from the commonly used hA3A-CBE and incorporating the uracil-DNA glycosylase(UNG)component.Seven specific guide RNAs(sgRNAs)targeting five watermelon genes were designed to assess the editing efficiency of SCGBE.The results obtained from stably transformed watermelon plants demonstrated that SCGBE2.0 could efficiently induce C-to-G mutations at positions C5–C9 in 43.2%transgenic plants(with a maximum base conversion efficiency of 46.1%)and C-to-A mutation at position C4 in 23.5%transgenic plants(with a maximum base conversion efficiency of 45.9%).These findings highlight the capability of our integrated SCGBE2.0 editor to achieve C-to-G/A mutations in a site-preferred manner,thus providing an efficient base editing tool for precise base modification and site-directed saturated mutagenesis in watermelon.

Genome-wide analysis of nuclear factor Y genes and functional investigation of watermelon ClNF-YB9 during seed development

The nuclear factor Y(NF-Y) gene family is a class of transcription factors that are widely distributed in eukaryotes and are involved in various biological processes. However, the NF-Y gene family members in watermelon, a valued and nutritious fruit, remain largely unknown and their functions have not been characterized. In the present study, 22 ClNF-Y genes in watermelon, 29 CsNF-Y genes in cucumber, and 24CmNF-Y genes in melon were identified based on the whole-genome investigation and their protein properties, gene location, gene structure, motif composition, conserved domain, and evolutionary relationship were investigated. ClNF-YB9 from watermelon and its homologs in cucumber and melon were expressed specifically in seeds. Its expression remained low in the early stages of watermelon seed development,increased at 20 days after pollination(DAP), and peaked at 45–50 DAP. Moreover, the knockout mutant Clnf-yb9 exhibited abnormal leafy cotyledon phenotype, implying its critical role during seed formation.Finally, protein interaction assays showed that ClNF-YB9 interacts with all ClNF-YCs and the ClNF-YB9-YC4 heterodimer was able to recruit a ClNF-YA7 subunit to assemble a complete NF-Y complex, which may function in seed development. This study revealed the structure and evolutionary relationships of the NF-Y gene family in Cucurbitaceae and the novel function of ClNF-YB9 in regulating seed development in watermelon.

Two-dimensional dumbbell silicene as a promising anode material for(Li/Na/K)-ion batteries

Rechargeable ion batteries require anode materials with excellent performance,presenting a key challenge for researchers.This paper explores the potential of using two-dimensional dumbbell silicene as an anode material for alkali metal ion batteries through density functional theory(DFT)calculations.Our findings demonstrate that alkali metal ions have negative adsorption energies on dumbbell silicene,and the energy barriers for Li/Na/K ion diffusion are as low as0.032 e V/0.055 e V/0.21 e V,indicating that metal ions can easily diffuse across the entire surface of dumbbell silicene.Additionally,the average open circuit voltages of dumbbell silicene as anode for Li-ion,Na-ion,and K-ion batteries are 0.42 V,0.41 V,and 0.60 V,respectively,with corresponding storage capacities of 716 m Ah/g,622 m Ah/g,and 716 m Ah/g.These results suggest that dumbbell silicene is an ideal anode material for Li-ion,Na-ion,and K-ion batteries,with high capacity,low open circuit voltage,and high ion diffusion kinetics.Moreover,our calculations show that the theoretical capacities obtained using DFT-D2 are higher than those obtained using DFT-D3,providing a valuable reference for subsequent theoretical calculations.

Research and Practice of Online Service Hall in Colleges and Universities

The needs of teachers and students, the requirements of educational modernization and informatization and the development of information technology promote the online service hall to become an important part of the smart campus. The online service hall is also a hot spot of information construction in universities in recent years. Taking China University of Geosciences (Beijing) for example, this paper probes into the problems and causes of the current difficulties of teachers and students in complicated school’s business process and puts forward the construction goal and ideas of the online service hall. A four-layer architecture which includes data layer, business service support layer, business service layer and presentation layer for service e-hall is designed and the organization and implementation steps of the online service hall are expounded. In addition, the extended applications such as integrated self-service printing terminal and electronic signature are considered. This paper can be used for reference for the construction and implementation of online service hall in other universities.

Research and Practice on Security Protection and Disaster Recovery Strategy of Oracle Database in Colleges and Universities

Database security protection, database backup and disaster recovery are important tasks for all colleges and universities to ensure the safe and stable operation of information systems. Based on the operating environment of the Oracle production database in China University of Geosciences (Beijing), combined with the practical operation and maintenance experience, this paper provides a design and implementation case of Oracle database security protection system and disaster recovery architecture. The network security protection architecture of the three-layer firewall and fortress machine, the detection and repair of security vulnerabilities, the management of system accounts and permissions, data encryption and database audit constitute the security protection system of the database. Oracle RAC (Real Application Clusters), Oracle DataGuard, redundant backup management and backup recovery constitute the disaster recovery architecture of the database. The case has practical significance for database operation and maintenance management in other colleges and universities.

Exploration of Digital Transformation Schema for Professional Degree Postgraduate Training

Professional degree postgraduate education is the strategic focus of the reform and development of postgraduate education in China, and the digital transformation of education is also the strategic theme of the reform and development of education in China. This paper analyzes the current situation of informatization of professional degree postgraduate training in China, and puts forward the construction scheme of digital comprehensive service platform for professional degree postgraduate education and teaching based on the actual situation of China University of Geosciences (Beijing). It focuses on three aspects: postgraduate education information management, intelligent online teaching and teachers’ digital literacy improvement. The article also discusses the significance of the digital ecology of the education industry and the entire country for the evaluation of the cultivation of professional degree postgraduates in colleges and universities.

The Practice of a Method of Self-Study Students Counting in Classrooms Based on Head Detection in Colleges and Universities

In order to solve the problem that it is difficult for students to find self-study classrooms because of the limited classroom resources, combined with the current situation of informatization in colleges and universities, a feasible method of students counting in classrooms based on head detection is proposed. This method first collects the scene images in the classroom at regular intervals based on the existing examination monitoring system, and then uses the offline trained AdaBoost cascade detector to detect the head candidate region in the images. Then, the trained CNN-SVM model is used to further identify the head, and finally the identification results are processed and the number of students in the classrooms is counted. The test and practice show that the query system for the idle situation of self-study classrooms constructed by coordinating the classroom seat capacity, classroom scheduling data and the students counting in the classroom based on the above method can easily query the current crowded degree of the students in the classrooms, which plays a good guiding role for students to find self-study classrooms. The method has strong reference and promotion significance for solving similar problems in other universities.

变频器在煤矿的应用

主要介绍了变频器在矿井主扇风机和矿井提升机上的应用,通过变频调速原理,介绍了变频器的选用,并对变频器在煤矿中的应用进行了展望。

Immune mechanisms of Concanavalin A model of autoimmune hepatitis

As a chronic inflammatory disease of the liver,the pathogenic mechanisms of autoimmune hepatitis (AIH) have not yet been elucidated,with prognosis and diagnosis remaining unsatisfied.Currently the only viable treatments of AIH are immunosuppressant application and liver transplantation.It is considered that lack of good animal AIH models is the main reason for the shortage of a simple and efficient cure.The Concanavalin A (Con A) model is a typical and well established model for investigating T-cell and macrophage dependent liver injury in mice,which closely mimics the pathogenesis mechanisms and pathological changes of patients,and is regarded as the best experimental model for AIH research so far.In this paper we eluci-dated the pathogenic mechanisms of AIH and the evolution of relative animal models.We go on to further focus on Con A-induced liver injury from the point of immunological mechanisms and the change of cytokine levels.Finally,we manifested the clinical significance of the AIH animal models and the challenges they would meet during their future development.

Comparison of the oncological,perioperative and functional outcomes of partial nephrectomy versus radical nephrectomy for clinical T1b renal cell carcinoma:A systematic review and metaanalysis of retrospective studies

Objective:To conduct a meta-analysis assessing the perioperative,functional and oncological outcomes of partial nephrectomy(PN)and radical nephrectomy(RN)for T1b tumours.The primary endpoints were the oncological outcomes.The secondary endpoints were the perioperative and functional outcomes.Methods:A systematic literature review was performed by searching multiple databases through February 2019 to identify eligible comparative studies according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement.Identified reports were assessed according to the Newcastle-Ottawa Scale for nonrandomized controlled trials.Results:Overall,13 retrospective cohort studies were included in the analysis.Patients undergoing PN were younger(weighted mean difference[WMD]3.49 years,95%confidence interval[CI]5.16 to1.82;p<0.0001)and had smaller masses(WMD0.45 cm,95%CI0.59 to0.31;p<0.0001).There were no differences in the oncological outcome,which was demonstrated by progression-free survival(hazard ratio[HR]0.70;pZ0.22),cancerspecific mortality(HR 0.91;pZ0.57)and all-cause mortality(HR 1.01;pZ0.96).The two procedures were similar in estimated blood loss(WMD16.47 mL;pZ0.53)and postoperative complications(risk ratio[RR]1.32;pZ0.10),and PN provided better renal function preservation and was related to a lower likelihood of chronic kidney disease onset(RR 0.38;pZ0.006).Conclusion:PN is an effective treatment for T1b tumours because it offers similar surgical morbidity,equivalent cancer control,and better renal preservation compared to RN.

Evaluation of right-to-left shunt on contrast-enhanced transcranial Doppler in patent foramen ovale-related cryptogenic stroke: Research based on imaging

BACKGROUND Cardiogenic embolism caused by patent foramen ovale(PFO)is a common etiology of cryptogenic stroke(CS),particularly in young and middle-aged patients.Studies about right-to-left shunt(RLS)detection using contrast-enhanced transcranial Doppler(c-TCD)are numerous.According to the time phase and number of microbubbles detected on c-TCD,RLS can be classified and graded.We hypothesized that the characteristics of an infarction lesion on diffusion-weighted imaging differs when combining the type and grade of RLS on c-TCD in patients with PFO-related CS.AIM To explore the characteristics of infarction lesions on diffusion-weighted imaging when combining the RLS type and grade determined by c-TCD.METHODS We retrospectively evaluated CS patients from August 2015 to December 2019 at a tertiary hospital.In total,111 PFO-related CS patients were divided according to whether RLS was permanent(microbubbles detected both at resting state and after the Valsalva maneuver)or latent(microbubbles detected only after the Valsalva maneuver)on c-TCD.Each group was subdivided into small,mild and large RLS according to the grade of shunt on c-TCD.A normal control group was composed of 33 patients who suffered from simple dizziness.Intragroup and intergroup differences were analyzed in terms of clinical,laboratory and diffusion-weighted imaging lesion characteristics.The correlation between RLS grade evaluated by c-TCD and size of PFO determined by transesophageal echocardiography were also analyzed.RESULTS In 111 patients with PFO-related CS,68 had permanent RLS and 43 had latent RLS.Clinical characteristics and laboratory tests were not significantly different among the permanent RLS,latent RLS and normal control groups.The proportion of patients with multiple territory lesions in the permanent RLS group(50%)was larger than that in the latent RLS group(27.91%;P=0.021).Posterior circulation was more likely to be affected in the latent RLS group than in the permanent RLS group(30.23%vs 8.82%,P=0.004).Permanent-large and latent-large RLS were both more likely to be related to multiple(P_(trend)=0.017 and 0.009,respectively),small(P_(trend)=0.035 and 0.006,respectively)and cortical(P_(trend)=0.031 and 0.033,respectively)lesions.The grade of RLS evaluated by c-TCD was correlated to the size of PFO determined by transesophageal echocardiography(r=0.758,P<0.001).CONCLUSION Distribution of the infarct suggested the possible type of RLS.Multiple,small and cortical infarcts suggest large RLS induced by a large PFO.

Effects of slope position and land use on the stability of aggregateassociated organic carbon in calcareous soils

Topography and land use affect soil organic carbon(SOC) storage, stabilization, and turnover, through several biogeochemical processes. This study investigated the aggregate composition and SOC content of bulk soils and aggregates at different slope positions under different land uses in a typical karst catchment of southwestern China. Our results show that the proportion of macro-aggregates and the SOC content of bulk soils and aggregates at different slope positions decreased from the upper to the lower slope. The SOC content generally increased with an increase in the mean weight diameter and proportion of macro-aggregates under different land uses. Our results indicate that macro-aggregates in forest and grassland soils make a greater contribution to both aggregate composition and SOC content than that in arable land soils. Therefore,converting farmland to forest or grassland can facilitate the accumulation of macro-aggregates as well as the storage of SOC.