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Journal of Genetics and Genomics 2024年第8期51卷 836-843页

作者： Shibo Hou Jingheng Chen Ruobing Feng Xuejiao Xu Nan Liang Jackson Champer center for bioinformatics Center for Life SciencesSchool of Life SciencesPeking UniversityBeijing 100871China

CRISPR homing gene drives have considerable potential for managing populations of medically and agriculturally significant *** operate by Cas9 cleavage followed by homology-directed repair,copying the drive allele to the wild-type chromosome and thus increasing in frequency and spreading throughout a ***,resistance alleles formed by end-joining repair pose a significant *** address this,we create a homing drive targeting the essential hairy gene in Drosophila *** resistance alleles are recessive lethal,while drive carriers have a recoded“rescue”version of *** drive inheritance rate is moderate,and multigenerational cage studies show drive spread to 96%–97%of the ***,the drive does not reach 100%due to the formation of functional resistance alleles despite using four *** alleles have a large deletion but likely utilize an alternate start ***,revised designs targeting more essential regions of a gene may be necessary to avoid such functional *** of the rescue element’s native 3'UTR with a homolog from another species increases drive inheritance by 13%–24%.This was possibly because of reduced homology between the rescue element and surrounding genomic DNA,which could also be an important design consideration for rescue gene drives.

关键词： Genedrive Homing drive Rescueelement Population modification Multiplexed gRNAs Resistance alleles Cage study

DIProT:A deep learning based interactive toolkit for efficient and effective Protein design

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Synthetic and Systems biotechnology 2024年第2期9卷 217-222页

作者： Jieling He Wenxu Wu Xiaowo Wang Ministry of Education Key Laboratory of bioinformatics Center for Synthetic and Systems BiologyBioinformatics DivisionBeijing National Research Center for Information Science and TechnologyDepartment of AutomationTsinghua UniversityBeijingChina

The protein inverse folding problem,designing amino acid sequences that fold into desired protein structures,is a critical challenge in biological *** numerous data-driven and knowledge-driven methods,there remains a need for a user-friendly toolkit that effectively integrates these approaches for in-silico protein *** this paper,we present DIProT,an interactive protein design *** leverages a non-autoregressive deep generative model to solve the inverse folding problem,combined with a protein structure prediction *** integration allows users to incorporate prior knowledge into the design process,evaluate designs in silico,and form a virtual design loop with human *** inverse folding model demonstrates competitive performance in terms of effectiveness and efficiency on TS50 and CATH4.2 datasets,with promising sequence recovery and inference *** studies further illustrate how DIProT can facilitate user-guided protein design.

关键词： Computational Protein design Interactive design toolkit Protein inverse folding Non-autoregressive decoding

Gedunin attenuates streptozotocin-induced diabetic hepatopathy in rats

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Asian Pacific Journal of Tropical Biomedicine 2024年第7期14卷 288-297页

作者： Suchismita Mazumdar Thankamani M Marar Jyoti M Patki School of biotechnology and bioinformatics D.Y.Patil Deemed to be UniversityNavi Mumbai 400614India

Objective:To examine the hepatoprotective effects of gedunin in streptozotocin(STZ)-induced diabetic ***:Rats were divided into 4 groups:control,STZ,gedunin,and STZ+*** parameters for liver function and liver histology were *** molecular interaction of gedunin with the liver glucose transporters GLUT2 and SGLT1 was examined using AutoDock ***:Gedunin attenuated STZ-induced increase in the levels of aspartate transaminase,alanine transaminase,alkaline phosphatase,lactate dehydrogenase and gamma-glutamyl transferase in the serum and liver tissue,reduced lipid peroxidation,and enhanced antioxidant *** studies showed considerable restoration of liver architecture in gedunin-treated diabetic *** silico studies revealed stable binding of gedunin with GLUT2 and ***:Gedunin exerts hepatoprotective effects in STZ-induced diabetic rats by reducing liver enzymatic activities and oxidative *** studies are warranted to verify the mechanism of its hepatoprotective action.

关键词： Gedunin GLUT2 SGLT1 Diabetic hepatopathy Docking Histology Homology modelling

Allosteric modulation of G protein-coupled receptors as a novel therapeutic strategy in neuropathic pain

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Acta Pharmaceutica Sinica B 2024年第1期14卷 67-86页

作者： Chunhao Zhu Xiaobing Lan Zhiqiang Wei Jianqiang Yu Jian Zhang School of Pharmacy Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and bioinformatics center Shanghai Jiao Tong University School of MedicineShanghai 200025China School of Basic Medical Science Ningxia Medical UniversityYinchuan 750004China Medicinal Chemistry and bioinformatics center Ocean University of ChinaQingdao 266100China State Key Laboratory of Pharmaceutical biotechnology Nanjing UniversityNanjing 210023China

Neuropathic pain is a debilitating pathological condition that presents significant therapeutic challenges in clinical ***,current pharmacological treatments for neuropathic pain lack clinical efficacy and often lead to harmful adverse *** G protein-coupled receptors(GPCRs)are widely distributed throughout the body,including the pain transmission pathway and descending inhibition pathway,the development of novel neuropathic pain treatments based on GPCRs allosteric modulation theory is gaining *** research has shown that allosteric modulators targeting GPCRs on the pain pathway can effectively alleviate symptoms of neuropathic pain while reducing or eliminating adverse *** review aims to provide a comprehensive summary of the progress made in GPCRs allosteric modulators in the treatment of neuropathic pain,and discuss the potential benefits and adverse factors of this *** will also concentrate on the development of biased agonists of GPCRs,and based on important examples of biased agonist development in recent years,we will describe universal strategies for designing structure-based biased *** is foreseeable that,with the continuous improvement of GPCRs allosteric modulation and biased agonist theory,effective GPCRs allosteric drugs will eventually be available for the treatment of neuropathic pain with acceptable safety.

关键词： Neuropathic pain Allosteric modulators G protein-coupled receptors Analgesia

Facilitating stable gene integration expression and copy number amplification in Bacillus subtilis through a reversible homologous recombination switch

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Synthetic and Systems biotechnology 2024年第3期9卷 577-585页

作者： Haoyu Guo Rongzhen Tian Yaokang Wu Xueqin Lv Jianghua Li Long Liu a b Guocheng Du Jian Chen Yanfeng Liu Key Laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China Science center for Future Foods Jiangnan UniversityWuxi214122China Engineering Research center of Ministry of Education on Food Synthetic biotechnology Jiangnan UniversityWuxi214122China Jiangsu Province Engineering Research center of Food Synthetic biotechnology Jiangnan UniversityWuxi214122China

Strengthening the expression level of integrated genes on the genome is crucial for consistently expressing key enzymes in microbial cell factories for efficient bioproduction in synthetic *** comparison to plasmid-based multi-copy expression,the utilization of chromosomal multi-copy genes offers increased stability of expression level,diminishes the metabolic burden on host cells,and enhances overall genetic *** this study,we developed the“BacAmp”,a stabilized gene integration expression and copy number amplification system for high-level expression in Bacillus subtilis,which was achieved by employing a combination of repressor and non-natural amino acids(ncAA)-dependent expression system to create a reversible switch to control the key gene recA for homologous *** the reversible switch is turned on,genome editing and gene amplification can be ***,the reversible switch was turned off therefore stabilizing the gene copy *** stabilized gene amplification system marked by green fluorescent protein,achieved a 3-fold increase in gene expression by gene amplification and maintained the average gene copy number at 10 after 110 *** we implemented the gene amplification system for the regulation of N-acetylneuraminic acid(NeuAc)synthesis,the copy number of the critical gene increased to an average of 7.7,which yielded a 1.3-fold NeuAc *** research provides a new avenue for gene expression in synthetic biology and can be applied in metabolic engineering in ***.

关键词： Bacillus subtilis Stabilized gene amplification system Homologous recombination recA

EMT transcription factors activated circuits:A novel tool to study EMT dynamics and its therapeutic implications

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Synthetic and Systems biotechnology 2024年第1期9卷 1-10页

作者： Tianying Chen Wangyue Jia Bo Zhang Hanqi Xie Qiong Wu MOE Key Laboratory of bioinformatics Center for Synthetic and System BiologySchool of Life SciencesTsinghua UniversityBeijing100084China

The epithelial mesenchymal transition(EMT)plays significant roles in the progression of cancer and fibrotic ***,this process is reversible,resulting in mesenchymal epithelial transition(MET),which plays an important role in cancer *** is a lack of methods to trace and target EMT cells using synthetic biology circuits,which makes it difficult to study the cell fate or develop targeted *** this study,we introduced responsive EMT sensing circuits,which sense the EMT using specific promoters that respond to transcription factors typical of EMT activation(EMT-TFs).The transcriptional strength of EMT-sensing promoters decreased more than 13-fold in response to the overexpression of the ***,the NOT gate circuits were built by placing the tetR transcription repressor under the control of EMT sensing promoters and expressed an output signal using the constitutive CMV promoter modified with tetO sites This circuit is named EMT sensing and responding *** the EMT transcription factors was present,we observed a 5.8-fold signal increase in the ***,we successfully distinguished mesenchymal breast cancer cells from epithelial cancer cells and repressed the proliferation of EMT tumor cells using our *** EMT sensing and responding circuits are promising tools for the identification of EMT cells,which is crucial for EMT-related disease therapy and investigating the mechanisms underlying the reversible EMT process.

关键词： Epithelial mesenchymal transition Synthetic biology Tumor killing

Advancements and Challenges in Biomarkers for Colorectal Cancer Detection:A Comprehensive Review

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Proceedings of Anticancer Research 2024年第5期8卷 64-75页

作者： Yasir Hameed Department of biotechnology Institute of BiochemistryBiotechnologyand BioinformaticsThe Islamia University of BahawalpurPakistan

This study provides an overview of the current landscape of biomarkers for colorectal cancer(CRC)detection,focusing on genetic,proteomic,circulating microRNA(miRNA),and metabolomic *** remains a significant global health challenge,ranking among the most prevalent cancers worldwide and being a leading cause of cancer-related *** advancements in screening methods such as colonoscopy,sigmoidoscopy,and fecal occult blood tests(FOBT),the asymptomatic nature of early-stage CRC often results in late diagnoses,negatively impacting patient *** biomarkers like APC,KRAS,TP53,and microsatellite instability(MSI)play critical roles in CRC pathogenesis and *** biomarkers,detectable through polymerase chain reaction,next-generation sequencing,and other advanced techniques,guide early detection and personalized treatment *** biomarkers such as CEA,CA 19-9,and novel signatures offer insights into CRC’s physiological changes and disease status,aiding prognosis and treatment response assessments through enzyme-linked immunosorbent assay and mass *** miRNAs,including miR-21 and miR-92a,present promising non-invasive biomarkers that can be detected in blood and stool samples,reflecting CRC presence,progression,and therapeutic *** biomarkers,encompassing amino acids,lipids,and TCA cycle intermediates,provide further insights into CRC-associated metabolic alterations,which are crucial for early detection and treatment monitoring using mass spectrometry and nuclear magnetic *** these advancements,challenges such as biomarker validation,standardization,and clinical utility *** research directions include integrating multi-omics approaches and leveraging technologies like liquid biopsies and AI for enhanced biomarker discovery and clinical *** addressing these challenges and advancing research in biomarker development,CRC screening and management could pote

关键词： Colorectal cancer Biomarker Diagnosis Detection

Regulatory RNAs in Bacillus subtilis:A review on regulatory mechanism and applications in synthetic biology

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Synthetic and Systems biotechnology 2024年第2期9卷 223-233页

作者： Anqi Peng Guobin Yin Wenjie Zuo Luyao Zhang Guocheng Du Jian Chen Yang Wang Zhen Kang The Science center for Future Foods Jiangnan UniversityWuxi214122China The Key Laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China The Key Laboratory of Industrial biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China

Bacteria exhibit a rich repertoire of RNA molecules that intricately regulate gene expression at multiple hierarchical levels,including small RNAs(sRNAs),riboswitches,and antisense ***,the majority of these regulatory RNAs lack or have limited protein-coding capacity but play pivotal roles in orchestrating gene expression by modulating transcription,post-transcription or translation *** and redesigning these regulatory RNA elements have emerged as pivotal strategies in the domains of metabolic engineering and synthetic *** previous investigations predominantly focused on delineating the roles of regulatory RNA in Gram-negative bacterial models such as Escherichia coli and Salmonella enterica,this review aims to summarize the mechanisms and functionalities of endogenous regulatory RNAs inherent to typical Gram-positive bacteria,notably Bacillus ***,we explore the engineering and practical applications of these regulatory RNA elements in the arena of synthetic biology,employing *** as a foundational chassis.

关键词： Regulatory RNA devices Small RNAs Riboswitches Synthetic biology Bacillus subtilis

A Pan-Cancer Analysis of GAPDH as a Common Biomarker for Various Cancers

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Proceedings of Anticancer Research 2024年第5期8卷 105-120页

作者： Yasir Hameed Department of biotechnology Institute of BiochemistryBiotechnologyand BioinformaticsThe Islamia University of BahawalpurPakistan

Objective:To investigate the expression levels of glyceraldehyde-3-phosphate dehydrogenase(GAPDH)and explore its prognostic value across 24 different human *** investigation was conducted using comprehensive bioinformatics and in vitro approaches,incorporating multiple layers of ***:GAPDH expression and methylation levels were assessed using bioinformatics tools and validated in cell lines through RNA-seq and targeted bisulfite-seq *** potential prognostic significance of GAPDH was evaluated using the KM ***,cBioPortal was employed to investigate genetic alterations associated with this *** analysis was conducted using ***,a correlation analysis between GAPDH expression and CD8+T immune cells was performed using TIMER and ***,a gene-drug interaction network analysis was conducted using Cytoscape to examine the relationship between GAPDH and various ***:GAPDH was found to be commonly upregulated in 24 types of human cancers,with its upregulation significantly correlated with poor relapse-free survival(RFS)and overall survival(OS)in BLCA,CESC,HNSC,KIRP,LIHC,and *** suggests that GAPDH plays a significant role in the development of these *** upregulation was also associated with various clinicopathological features in patients with BLCA,CESC,HNSC,KIRP,LIHC,and *** analysis revealed GAPDH’s involvement in diverse ***,notable correlations were observed between GAPDH expression and its promoter methylation level,genetic alterations,and CD8+T immune cell ***,several regulatory drugs targeting GAPDH were identified,with the potential to modulate its expression and potentially prevent conditions such as BLCA,CESC,HNSC,KIRP,LIHC,and ***:Based on our findings,GAPDH emerges as a promising diagnostic and prognostic biomarker for BLCA,CESC,HNSC,KIRP,LIHC,and LUAD.

关键词： Cancer Expression GAPDH Biomarker

Minimizing endogenous cryptic plasmids to construct antibiotic-free expression systems for Escherichia coli Nissle 1917

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Synthetic and Systems biotechnology 2024年第1期9卷 165-175页

作者： Siyan Zhou Linlin Zhao Wenjie Zuo Yilin Zheng Ping Zhang Yanan Sun Yang Wang Guocheng Du Zhen Kang The Science center for Future Foods Jiangnan UniversityWuxi214122China The Key Laboratory of Carbohydrate Chemistry and biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China The Key Laboratory of Industrial biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi214122China

The probiotic bacterium Escherichia coli Nissle 1917(EcN)holds significant promise for use in clinical and biological ***,the reliance on antibiotics to maintain plasmid-borne genes has overshadowed its *** this study,we addressed this issue by engineering the endogenous cryptic plasmids pMUT1 and *** non-essential elements were removed to create more stable derivatives pMUT1NR△and pMUT2HBC△.Synthetic promoters by integrating binding motifs on sigma factors were further constructed and applied for expression of Bacteroides thetaiotaomicron heparinaseⅢand the biosynthesis of *** to traditional antibiotic-dependent expression systems,our newly constructed antibiotic-free expression systems offer considerable advantages for clinical and synthetic biology applications.

关键词： Cryptic plasmids Antibiotic-free Gene expression Plasmid stability E.coli Nissle 1917