Meta-analysis of the efficacy of invisible orthodontic appliances for maxillary molar distalization in adult patients / 口腔疾病防治

Objective@#To evaluate the clinical efficacy of invisible orthodontic appliances without brackets for the distal movement of maxillary molars to improve the ability of orthodontists to predict treatment outcomes.@*Methods@#Web of Science, Cochrane Library, Embase, PubMed, Wanfang Database, CNKI Database, and VIP Database were searched for studies investigating the efficacy of invisible orthodontic appliances for distal movement of maxillary molars in adult patients and published from database inception to August 1, 2023. A total of three researchers screened the studies and evaluated their quality and conducted a meta-analysis of those that met quality standards.@*Results@#This study included 13 pre- and postcontrol trials with a total sample size of 281 patients. The meta-analysis revealed no significant differences in the sagittal or vertical parameters of the jawbone after treatment when compared with those before treatment (P>0.05). The displacement of the first molar was MD=-2.34, 95% CI (-2.83, -1.85); the displacement was MD=-0.95, 95% CI (-1.34, -0.56); and the inclination was MD=-2.51, 95% CI (-3.56, -1.46). There was a statistically significant difference in the change in sagittal, vertical, and axial tilt of the first molar before and after treatment. After treatment, the average adduction distance of the incisors was MD=-0.82, 95% CI (-1.54, -0.09), and the decrease in lip inclination was MD=-1.61, 95% CI (-2.86, -0.36); these values were significantly different from those before treatment (P<0.05).@*Conclusion@#Invisible orthodontic appliances can effectively move the upper molars in a distal direction and control the vertical position of the molars. When the molars move further away, there is some degree of compression and distal tilt movement, which is beneficial for patients with high angles. The sagittal movement of incisors is beneficial for improving the patient's profile.

Evolution of chemistry and selection technology for DNA-encoded library

DNA-encoded chemical library (DEL) links the power of amplifiable genetics and the non-self-replicating chemical phenotypes, generating a diverse chemical world. In analogy with the biological world, the DEL world can evolve by using a chemical central dogma, wherein DNA replicates using the PCR reactions to amplify the genetic codes, DNA sequencing transcripts the genetic information, and DNA-compatible synthesis translates into chemical phenotypes. Importantly, DNA-compatible synthesis is the key to expanding the DEL chemical space. Besides, the evolution-driven selection system pushes the chemicals to evolve under the selective pressure, i.e., desired selection strategies. In this perspective, we summarized recent advances in expanding DEL synthetic toolbox and panning strategies, which will shed light on the drug discovery harnessing in vitro evolution of chemicals via DEL.

Let ′Rare Disease′ Been Seen: Delving into the Building up of Resource and Information Service in Medical Libraries for Rare Diseases / 罕见病研究

With the development of the diagnosis and treatment for rare diseases and the promotion of the construction of ′Double First-Class′ Universities in China, the libraries of medical schools have to make full use of their strengths to better face new challenges in discipline construction proactively. This article refers to resource and information service practices related to the rare disease carried out by medical libraries in China and in other countries; explores the possibilities of building up the resource and information in the future, aiming at improving the awareness of rare diseases among medical students, researchers, and the general public. The article also focuses on the need for strengthening the support for teaching and research into rare diseases, hoping to contribute to the overall improvement of the diagnosis, treatment, and educational research in rare diseases in China.

Promoting Innovative Development of Traditional Chinese Medicine Case Report Based on China Clinical Cases Library of Traditional Chinese Medicine / 中国实验方剂学杂志

China Clinical Cases Library of Traditional Chinese Medicine is built to promote the establishment of a scientific and technological talent evaluation system oriented on innovative value， ability and contribution in the backgroud of breaking the four only and setting new standards required by the document jointly issued by several national administrations and commissions. In the process of the construction， in order to further consolidate the foundation and ensure the quality and authority of case reports， we need to fully understand the origin and development of Chinese medical cases. Therefore， we clarified the development situation of Chinese medical cases by combing the characteristics of ancient and modern case reports， comparing the differences between Chinese and western medical case reports in terms of content and writing requirements， finally formed the main points of systematic case report norms and quality evaluation system， aiming to fully explore the unique advantages of Chinese medical cases in the fields of discipline development， scientific research innovation， clinical practice and guidance， talent evaluation and training， so as to promote its innovative development in a broader direction.

Diseño e implementación de la biblioteca virtual de la Facultad de Ciencias Médicas de Bayamo

Las páginas web constituyen un medio facilitador del conocimiento. El trabajo se realizó con el objetivo de diseñar e implementar una biblioteca virtual para favorecer el proceso de gestión de la información del Departamento de Información Científica-Técnica y Biblioteca de la Facultad de Ciencias Médicas de Bayamo. Para el desarrollo del contenido del sitio se emplearon: observación, encuestas y entrevistas. Para desarrollar el producto se llevaron a cabo cinco procesos: planificación inicial del sitio, definición, diseño y estándares, puesta en marcha y plan de mantenimiento. Para la confección de la página se empleó el gestor de contenidos WordPress, así como PHP, MySQL, Apache, XAMPP y Windows como lenguaje de programación, motor de bases de datos, servidor Web, paquete de software libre y sistema operativo respectivamente. Se concluye que la implementación de la biblioteca virtual, facilita el proceso de gestión de la información, despierta el interés por la investigación y contribuye a la alfabetización informacional de los usuarios de salud que ingresen a la web. Facilitará la visibilidad, la gestión técnica bibliotecaria; la divulgación, difusión, y uso de los servicios y recursos de información disponibles.

Web pages constitute a means of facilitating knowledge. The work was carried out with the objective of designing and implementing a virtual library to favor the information management process of the Department of Scientific and Technical Information and the Library of the Faculty of Medical Sciences of Bayamo. Observation, surveys and interviews were used in the development of the content of the site. Five processes were carried out to develop the product: initial planning of the site, definition, design and standards, commissioning, and maintenance plan. To create the page, the content manager WordPress was used; PHP, MySQL, Apache, XAMPP and Windows were used as the programming language, database engine, Web server, free software package and operating system, respectively. It is concluded that the implementation of the virtual library facilitates the information management process, awakens the interest in research, and contributes to the information literacy of health users who enter the web. It will facilitate visibility, library technical management, disclosure, dissemination, and use of available information services and resources.

Genomic constellations of RVA detected in Brazil from 1986 to 2016: a temporal and geographical distribution and occurrence of reassortments / Constelações genômicas de RVA detectadas no Brasil de 1986 a 2016: uma distribuição temporal e geográfica e ocorrência de rearranjos

INTRODUCTION: Species A rotavirus (RVA) infections are a major cause of severe gastroenteritis in children of <5 years worldwide. In Brazil, before vaccination, RVA was associated with 3.5 million episodes of acute diarrheal disease per year. Due to the segmented nature of their genomes, rotaviruses can exchange genes during co-infections, and generate new virus strains and new reinfections. OBJECTIVE: To evaluate the genomic diversity of RVA isolated in Brazil in 30 years, between 1986 to 2016, to investigate possible changes in the frequency of genotype constellations before and after the implementation of the vaccine. METHODS: In total, 4,474 nucleotide sequences were obtained from the Virus Variation Database. Genomic constellation was compared, and the proportion of rotavirus genotypes was analyzed by time and geographic region. RESULTS: Our results showed that major known genotypes were circulating in the country during the period under analysis, with a prevalence of the G1P[8] Wa-like genotype, decreasing only in the period immediately after the introduction of the vaccine. Regarding the geographical distribution, most of our constellations, 62 (39.2%), and 50 (31.6%) were concentrated in the North and Northeast regions. Our analysis also showed the circulation of multiple strains during the periods when the DS-1-like and AU-1-like genotypes were co-circulating with the Wa-like genotype. CONCLUSION: Therefore, it is likely that inter-genogroup reassortments are still occurring in Brazil and so it is important to establish an efficient surveillance system to follow the emergence of novel reassorted strains that might not be targeted by the vaccine.

INTRODUÇÃO: As infecções por rotavírus A (RVA) são uma das principais causas de gastroenterite grave em crianças <5 anos em todo o mundo. No Brasil, antes da vacinação, o RVA estava associado a 3,5 milhões de episódios de diarreia aguda por ano. Devido à natureza segmentada de seus genomas, os rotavírus podem trocar genes durante as coinfecções, gerar novas cepas de vírus e novas reinfecções. OBJETIVO: Avaliar a diversidade genômica de RVA isolados no Brasil entre 1986 a 2016 para investigar possíveis alterações na frequência das constelações de genótipos antes e após a implantação da vacina. MÉTODOS: No total, 4.474 sequências de nucleotídeos foram obtidas do Banco de Dados de Variação de Vírus. A constelação genômica foi comparada e a proporção dos genótipos de rotavírus foi analisada por tempo e região geográfica. RESULTADOS: Nossos resultados mostraram que os principais genótipos conhecidos circulavam no país no período em análise, com prevalência do genótipo G1P[8] Wa-like, diminuindo apenas no período imediatamente após a introdução da vacina. Em relação à distribuição geográfica, a maioria das nossas constelações, 62 (39,2%) e 50 (31,6%), concentrava-se nas regiões Norte e Nordeste. Nossa análise também mostrou a circulação de cepas múltiplas durante os períodos em que os genótipos DS-1-like e AU-1-like estavam co-circulando com o genótipo Wa-like. CONCLUSÃO: Portanto, é provável que rearranjos inter-genogrupos ainda estejam ocorrendo no Brasil e por isso é importante estabelecer um sistema de vigilância eficiente para acompanhar o surgimento de novas cepas rearranjadas que podem não ser protegidas pela vacina.

Screening and identification of single-chain fragment variable against the receptor-binding domain of spike protein of SARS-CoV-2 / 中国生物制品学杂志

@#Objective To construct a single-chain fragment variable(scFv)phage display library against receptor-binding domain(RBD)of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)spike protein(S)to screen specific scFv and identify the function.Methods m RNA was extracted from spleen cells of mice immunized with RBD protein and reversely transcribed into c DNA,with which as template,genes of the hight chain fragment of variable(VH)and light chain fragment of variable(VL)of scFv were amplified and then assembled into scFv gene fragment through splicing overlap extension PCR(SOE-PCR).The scFv gene fragment was inserted to phage vector to construct scFv phage display library.After four rounds of biopanning,the scFv gene with strong binding ability to RBD was screened and expressed recombinantly,purified and identified for biological activity.Results The constructed scFv phage library showed a titer of 6.0×10(11)pfu/m L.After four rounds of biopanning,four scFv strains with strong binding to RBD were selected,namely scFv11,scFv12,scFv25and scFv28.scFv was mainly expressed in the form of inclusion body with a relative molecular mass of about 27 000,a concentration of 2.4 mg/m L and a purity of about 90%,which bound specifically to mouse monoclonal antibody against His labeled by HRP after purification.All four scFv strains bound specifically to RBD recombinant protein,among which the other 3 scFv strains bound to the S protein of wild type and multiple mutant strains except scFv28.All four strains showed dose-dependent interaction with RBD,with affinity dynamic fitting dissociation constants(K_Ds)8.9,5.92,10.67and 2.36 nmol/L,and steady-state fitting dissociation constants(K_Ds)of 5.3,6.5,8.7 and 5.8 nmol/L,respectively.scFv11,scFv12 and scFv25 simultaneously identified three independent RBD polypeptides,including RBD2(S(11)pfu/m L.After four rounds of biopanning,four scFv strains with strong binding to RBD were selected,namely scFv11,scFv12,scFv25and scFv28.scFv was mainly expressed in the form of inclusion body with a relative molecular mass of about 27 000,a concentration of 2.4 mg/m L and a purity of about 90%,which bound specifically to mouse monoclonal antibody against His labeled by HRP after purification.All four scFv strains bound specifically to RBD recombinant protein,among which the other 3 scFv strains bound to the S protein of wild type and multiple mutant strains except scFv28.All four strains showed dose-dependent interaction with RBD,with affinity dynamic fitting dissociation constants(K_Ds)8.9,5.92,10.67and 2.36 nmol/L,and steady-state fitting dissociation constants(K_Ds)of 5.3,6.5,8.7 and 5.8 nmol/L,respectively.scFv11,scFv12 and scFv25 simultaneously identified three independent RBD polypeptides,including RBD2(S(334～353)),RBD9(S(334～353)),RBD9(S(439～458))and RBD13(S(439～458))and RBD13(S(499～518)).Homologous model of scFv constructed by online server SWISS-MODEL showed a good quality and was used for molecular docking.The interface at which scFv11 interacted with RBD only partially coincided with the interaction interface of human angiotensin converting enzyme 2(ACE2)and RBD,and the interaction interfaces of scFv12 and scFv25 with RBD were quite different from that of ACE2.Conclusion In this study,scFv specifically bound to SARS-Co V-2 RBD was screened and prepared through constructing scFv phage library against SARS-CoV-2 RBD,which provided experimental basis for further development of anti-SARS-CoV-2 drugs and detection reagents.

Virtual screening of potential ATR kinase inhibitors based on machine learning and molecular docking / 中国药科大学学报

@#Screening potential active compounds from molecular libraries is a common method for drug discovery.However, with the continuous exploration of chemical space, there are already compound libraries with more than billions of molecules, so molecular docking is no longer enough to quickly screen specific target inhibitors from the ultra-large compound libraries.This study proposes a method for screening potential active compounds, which involves filtering and selecting compounds from a candidate compound library containing over 5.5 billion molecules through a series of steps, including calculating physical and chemical property similarities, constructing machine learning prediction models, and molecular docking.In the end, 51 compounds with potential ataxia telangiectasia-mutated and rad3-related (ATR) inhibitory activity were obtained.This method is effective for rapidly screening novel potential active compounds from large compound libraries.

Dock-able linear and homodetic di,tri,tetra and pentapeptide library from canonical amino acids:SARS-CoV-2 Mpro as a case study / 药物分析学报

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide com-binations of the canonical residues has been previously reported.However,with increasing computa-tional power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the com-plete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify po-tential small peptide inhibitors.

Advances in the application of yeast surface display technology / 生物工程学报

Yeast surface display (YSD) is a technology that fuses the exogenous target protein gene sequence with a specific vector gene sequence, followed by introduction into yeast cells. Subsequently, the target protein is expressed and localized on the yeast cell surface by using the intracellular protein transport mechanism of yeast cells, whereas the most widely used YSD system is the α-agglutinin expression system. Yeast cells possess the eukaryotic post-translational modification mechanism, which helps the target protein fold correctly. This mechanism could be used to display various eukaryotic proteins, including antibodies, receptors, enzymes, and antigenic peptides. YSD has become a powerful protein engineering tool in biotechnology and biomedicine, and has been used to improve a broad range of protein properties including affinity, specificity, enzymatic function, and stability. This review summarized recent advances in the application of YSD technology from the aspects of library construction and screening, antibody engineering, protein engineering, enzyme engineering and vaccine development.

Application of deep mutational scanning technology in protein research / 生物工程学报

As central players in cellular structure and function, proteins have long been central themes in life science research. Analyzing the impact of protein sequence variation on its structure and function is one of the important means to study proteins. In recent years, a technology called deep mutational scanning (DMS) has been widely used in the field of protein research. It introduces thousands of mutations in parallel in specific regions of proteins through high-abundance DNA libraries. After screening, high-throughput sequencing is employed to score each mutation, revealing sequence-function correlations. Due to its high-throughput, fast and easy, and labor-saving features, DMS has become an important method for protein function research and protein engineering. This review briefly summarizes the principle of DMS technology, highlighting its applications in mammalian cells. Moreover, this review analyzes the current technical bottlenecks, aiming to facilitate relevant research.

Phage antibody library technology in tumor therapy: a review / 生物工程学报

Tumor is a serious threat to human health. At present, surgical resection, chemoradiotherapy, targeted therapy and immunotherapy are the main therapeutic strategies. Monoclonal antibody has gradually become an indispensable drug type in the clinical treatment of cancer due to its high efficiency and low toxicity. Phage antibody library technology (PALT) is a novel monoclonal antibody preparation technique. The recombinant immunoglobulin variable region of heavy chain (VH)/variable region of light chain (VL) gene is integrated into the phage vector, and the antibody is expressed on the phage surface in the form of fusion protein to obtain a diverse antibody library. Through the process of adsorption-elution-amplification, the antibody library can be screened to obtain the antibody molecule with specific binding antigen as well as its gene sequence. PALT has the advantages of short antibody production cycle, strong plasticity of antibody structure, large antibody yield, high diversity and direct production of humanized antibodies. It has been used in screening tumor markers and preparation of antibody drugs for breast cancer, gastric cancer, lung cancer and liver cancer. This article reviews the recent progress and the application of PALT in tumor therapy.

Construction of a High-Throughput Mutation Library of Mycobacterium Rifampin Resistance Gene rpoB / 中山大学学报(医学科学版)

ObjectiveTo establish a mutation library of rifampicin resistance gene rpoB. MethodsThe ΔrpoB attB：：rpoB strain of Mycobacterium smegmatis （M. smegmatis） be constructed by homologous recombination and L5 attB phage integration site exchange. Based on the L5 attB plasmid exchange system and resistance selection medium， 48 clones are selected to verify plasmid replacement efficiency. Degenerate primers are designed every 3 bases in the rifampicin resistance determining region （RRDR）， and a full-coverage mutation library of 81 bases in RRDR region is obtained by PCR amplification. The library fragments are seamlessly cloned into the vector and transformed into Escherichia coli （E. coli）to form an E. coli mutation library. Based on the principle of plasmid exchange， the mutant plasmid library is transformed into the M. smegmatis strain ΔrpoB attB：：rpoB， and the original L5 attB site plasmid is replaced to form the M. smegmatis mutant library. The genotype of the library are determined by genome extraction， library construction and high-throughput sequencing. ResultsCompared with the wild-type rpoB gene （5 600 bp）， the amplified fragment of the rpoB knockout strain is 2 200 bp， which proved that the ΔrpoB attB：：rpoB conditional knockout strain of M. smegmatis is successfully constructed. The success rate of plasmid replacement is 100%. There were 540 kinds of single amino acid mutations in both E. coli library and M. smegmatis library， 5 301 kinds of multi-point mutations in E. coli library， and 853 kinds of multi-point mutations in M. smegmatis library. The correlation coefficient between E. coli library and M. smegmatis library is 0.84. ConclusionsWe have developed a strategy to construct a library of mutants targeting the essential mycobacterial gene rpoB， and successfully established a mutant library of rifampicin resistance gene rpoB.

Application and management of human genetic resources in China / 上海预防医学

Human genetic resources include specimen samples and related information. The application and regulation of human genetic resources in China started at the end of the 20th century and have progressed rapidly. However， many challenges remain. In this paper， we reviewed the current status of sample conservation and management and provided recommendations for further development of human genetic resources in China. The aim is to effectively protect and rationally utilize China's human genetic resources， safeguard national security and people's health， and promote the building of a community of common health for mankind.

Investigating information literacy skills perception and practices among medical and non-medical first-year students at a Nigerian university

Background: The study appraisedthe perceived information literacy proficiency of first-year students enrolled in the faculties of Basic Medical Sciences, Clinical Sciences, and pure Sciences at the University of Medical Sciences(UNIMED)in Ondo City, Nigeria. Method:Employing a correlational descriptive survey methodology, 120 students were proportionately selectedfrom the first-year students'population in the three faculties surveyed. The response rate was84%. Data for the study was collected using a questionnaire sectioned into four or five-point Likert scales. For the data analysis, the responses were rated 4, 3, 2,and 1 points or 5, 4, 3, 2 and 1,respectively, depending on the questionnaire section.Results:Based on our rubric, the students reported average-level information literacy skills and high-level internet navigation skills. The ability to utilise information effectively had the highest rating (x̄= 2.9/4.0),while the ability to access information was the lowest(x̄=2.7/4.0). The students also reported Google(x̄= 4.1/5.0), subject textbooks, and peers as the most frequentlyutilisedinformation sources, while academicsources such as journal databases(x̄=2.3/5.0), library catalogues, and librarians were the least used. No statistically significant distinctions were observed in the information literacy capabilities of first-year students from the three faculties or secondary school backgrounds. Conclusion:To promote acquiringinformation literacy skills for academic success and lifelong learning, this study emphasises the necessity for increased awareness and training on the effective usage of scholarly sources among first-year students in Nigerian universities.

Crowdfunding como alternativa para el financiamiento de proyectos en bibliotecas: Una oportunidad frente a los recortes presupuestarios

Esta investigación nace debido a los recortes presupuestarios que sufre el sector cultural en Costa Rica, en particular como una alternativa de financiamiento a los proyectos que ejecutan las bibliotecas. Su objetivo principal es describir las oportunidades que ofrece el crowdfunding como método alternativo de financiamiento en las bibliotecas públicas y académicas para el desarrollo de proyectos sociales. Desde un enfoque cualitativo, se realiza una revisión bibliográfica con alcance descriptivo. Por tanto, se recopilan artículos y tesis sobre crowdfunding en bibliotecas públicas y académicas, asimismo es mediante el cuadro de categorías de análisis que se interpretan los principales puntos de interés para la investigación. Los resultados reflejan la efectividad y adaptabilidad de la implementación de campañas de crowdfunding de donación para la recaudación de fondos en bibliotecas de acuerdo a sus necesidades. Se concluye que en una campaña de este tipo se debe considerar el tiempo estimado para la recaudación de fondos, la adecuada gestión de las redes sociales, una excelente selección del tipo y plataforma de crowdfunding, así como de las habilidades y competencias de las personas a cargo. Los profesionales en bibliotecología deben utilizar el potencial de las TIC en tiempos de austeridad para aprovechar el crowdfunding como una alternativa de financiamiento que permite ejecutar más y mejores proyectos.

This research was born due to budget cuts suffered by the cultural sector in Costa Rica, as a financing alternative to the projects carried out by libraries. Its main objective is to describe the opportunities offered by crowdfunding as an alternative method of financing in public and academic libraries for the development of social projects. From a qualitative approach, a bibliographic review with a descriptive scope is carried out. Therefore, articles and theses on crowdfunding in public and academic libraries are compiled, through the table of analysis categories; the main points of interest for the investigation are interpreted. The results reflect the effectiveness and adaptability of the implementation of donation crowdfunding for fundraising in libraries according to their needs. It is concluded that in a campaign of this type, the estimated time for fundraising, the proper management of social networks, an excellent selection of the type and platform of crowdfunding, as well as the skills and competencies of the people involved should be considered. Library professionals must use the potential of ICT in times of austerity to take advantage of crowdfunding to execute more and better projects.

El bibliotecario en el Instituto Mexicano del Seguro Social / The librarian at the Instituto Mexicano del Seguro Social

En las unidades de información que integran el Sistema Bibliotecario del Instituto Mexicano del Seguro Social (IMSS), la tarea de orientar y formar a los usuarios sobre el uso de información es un proceso complejo, debido a la especificidad de las necesidades de información de los usuarios. Los sistemas de información que son utilizados en el Instituto exigen al personal bibliotecario contar con competencias informativas específicas para el acceso, evaluación, organización y uso de la información por medio de las tecnologías de la información. Sin embargo, existen grandes retos, como la carencia de la definición del perfil profesional del bibliotecario médico, ya que es indispensable para que el personal logre satisfacer de forma eficiente las demandas y necesidades de los usuarios de acuerdo con sus diversos perfiles.

In the information units that make up the Instituto Mexicano del Seguro Social (IMSS) Library System, the task of guiding and training users on the use of information is a complex process, due to the specificity of the users' information needs. The information systems that are used in the Institute require the personal librarian to have specific information skills for access, evaluation, organization and use of information through information technologies. However, there are important challenges, such as the lack of definition of the professional profile of the medical librarian, because it is essential for the staff to efficiently satisfy the demands and needs of users according to their various profiles.

Construction and application of a synthetic promoter library for Corynebacterium glutamicum / 生物工程学报

Promoter is an important genetic tool for fine-tuning of gene expression and has been widely used for metabolic engineering. Corynebacterium glutamicum is an important chassis for industrial biotechnology. However, promoter libraries that are applicable to C. glutamicum have been rarely reported, except for a few developed based on synthetic sequences containing random mutations. In this study, we constructed a promoter library based on the native promoter of odhA gene by mutating the -10 region and the bystanders. Using a red fluorescent protein (RFP) as the reporter, 57 promoter mutants were screened by fluorescence imaging technology in a high-throughput manner. These mutants spanned a strength range between 2.4-fold and 19.6-fold improvements of the wild-type promoter. The strongest mutant exhibited a 2.3-fold higher strength than the widely used strong inducible promoter Ptrc. Sequencing of all 57 mutants revealed that 55 mutants share a 1-4 bases shift (4 bases shift for 68% mutants) of the conserved -10 motif "TANNNT" to the 3' end of the promoter, compared to the wild-type promoter. Conserved T or G bases at different positions were observed for strong, moderate, and weak promoter mutants. Finally, five promoter mutants with different strength were employed to fine-tune the expression of γ-glutamyl kinase (ProB) for L-proline biosynthesis. Increased promoter strength led to enhanced L-proline production and the highest L-proline titer of 6.4 g/L was obtained when a promoter mutant with a 9.8-fold higher strength compared to the wild-type promoter was used for ProB expression. The use of stronger promoter variants did not further improve L-proline production. In conclusion, a promoter library was constructed based on a native C. glutamicum promoter PodhA. The new promoter library should be useful for systems metabolic engineering of C. glutamicum. The strategy of mutating native promoter may also guide the construction of promoter libraries for other microorganisms.

Discussion on the development of hospital library and its function of hospital's scientific research management based on texts analysis / 中华医学科研管理杂志

Objective:To analyze the situation of recent ten-year publications in Chinese hospital libraries, providing advice for the development and innovation of hospital libraries and the help to improvement of scientific research management.Methods:Publications in databases including CNKI, Wanfang, VIP were retrieved when " hospital library" is included as a key topic. The general information of the enrolled publications was statistically described. With respect to the key words with high frequency, co-word analysis and cluster analysis were performed to explore the research hotspots in hospital libraries.Results:The number of publications in Chinese hospital libraries shows an overall downward trend. By contrast, the total numbers of publications in hospital libraries from Shandong and Guangzhou rank top. In terms of the ratio of total number of publications to total number of hospitals, Liaoning and Chongqing rank top. The periodicals of interest are mainly grouped into three categories including intelligence information, library and hospital management; however, the cooperation with clinical or other departments should be strengthened. Discipline and personalized service, digital library and library innovation are the dominating research hotspots in hospital libraries from China. Studies of hospital library mainly focused on clinical and scientific research services, but paid less attention to the support to hospital scientific research management.Conclusions:The service of hospital library is involved in the whole process of scientific research management. To improve the role of hospital library in scientific management, embedded service is recommended to be applied into the whole process of hospital scientific research management; construction of institutional repository for scientific research management and transformation of the role of hospital library are also highly recommended.

Tailoring combinatorial lipid nanoparticles for intracellular delivery of nucleic acids, proteins, and drugs

Lipid nanoparticle (LNP)-based drug delivery systems have become the most clinically advanced non-viral delivery technology. LNPs can encapsulate and deliver a wide variety of bioactive agents, including the small molecule drugs, proteins and peptides, and nucleic acids. However, as the physicochemical properties of small- and macromolecular cargos can vary drastically, every LNP carrier system needs to be carefully tailored in order to deliver the cargo molecules in a safe and efficient manner. Our group applied the combinatorial library synthesis approach and in vitro and in vivo screening strategy for the development of LNP delivery systems for drug delivery. In this Review, we highlight our recent progress in the design, synthesis, characterization, evaluation, and optimization of combinatorial LNPs with novel structures and properties for the delivery of small- and macromolecular therapeutics both in vitro and in vivo. These delivery systems have enormous potentials for cancer therapy, antimicrobial applications, gene silencing, genome editing, and more. We also discuss the key challenges to the mechanistic study and clinical translation of new LNP-enabled therapeutics.