1.Engineered Bacteriophages for The Treatment of Multidrug-resistant Bacterial Infections
Yu-Ying CHEN ; Chun-Mei HUANG ; Jin-Zhi PAN ; De-Liang LIU ; Yang ZHOU ; Gui-Qin DAI ; Peng-Fei ZHAO ; Hong-Zhou LU ; Ming-Bin ZHENG
Progress in Biochemistry and Biophysics 2026;53(6):1581-1596
Multidrug-resistant (MDR) bacterial infections have emerged as a serious challenge of global public health crisis. The overuse and misuse of conventional antibiotics have dramatically accelerated the emergence, evolution and worldwide spread of drug-resistant bacterial strains, necessitating urgent exploration of novel antibacterial strategies. Bacteriophages serve as natural bacterial predators offering distinct advantages including high host specificity, autonomous self-replication capabilities and cost-effective large-scale production. However, wild-type phages present significant clinical limitations due to their narrow host ranges, susceptibility to rapid immune clearance and poor penetration of bacterial biofilms, which severely restrict their therapeutic applications. The convergence of synthetic biology, nanotechnology and advanced gene editing technologies has accelerated the development of engineered bacteriophage platforms, providing programmable, scalable and clinically translatable pathways to overcome these inherent biological constraints. Here, we systematically delineate four fundamental strategies for engineered bacteriophage development. Chemical modification utilizes reactive functional groups such as amino, carboxyl and thiol moieties on capsid proteins through esterification, amidation or click chemistry reactions to achieve precise drug conjugation and surface functionalization. In vivo editing encompasses ultraviolet or chemical mutagenesis for random mutation induction, homologous recombination for targeted genetic alterations, recombineering methodologies including electroporation-mediated bacteriophage recombination engineering, and CRISPR-Cas systems for precise genome editing to enable exact genetic reconstruction and host range reprogramming. In vitro synthesis leverages genome engineering platforms where intact phage genomes are transferred into yeast or host bacteria to facilitate highly efficient homologous recombination, enabling large DNA fragment assembly and cross-gene host range expansion without bacterial toxicity constraints. Directed evolution combines artificial selection through mutation library screening with rational design approaches involving chimeric receptor binding protein construction or site-specific mutagenesis, effectively balancing the discovery of unknown adaptive pathways with targeted host specificity modification. Moreover, we comprehensively discuss therapeutic applications across diverse clinical scenarios. Engineered bacteriophage effectively disrupt bacterial biofilms through sophisticated functionalized delivery platforms including nanozyme-conjugated phages, phage-liposome nanoconjugates and bio-responsive hydrogels, demonstrating significantly enhanced bactericidal efficiency compared to unmodified free phages. These bioengineered vectors attenuate bacterial virulence and resensitize pathogens to antibiotics by delivering CRISPR-Cas systems or base editors to disrupt critical virulence factors such as pili, capsule synthesis machineries and quorum sensing systems, or by inactivating antibiotic resistance determinants including beta-lactamase genes. As an intelligent nanomedicine delivery platform, engineered bacteriophage enable precise pathogen elimination an through photocatalytic reactive oxygen species generation, immunomodulatory interventions, or controlled release of antibacterial drugs. Furthermore, oral administration of engineered bacteriophage facilitates microbiota modulation, which selectively eliminate intestinal pathogens while preserve beneficial commensal microbiota, thereby restoring microbial community balance and preventing complications associated with dysbiosis. Finally, we critically analyze persistent challenges including host strain matching complexity, evolution of bacterial resistance mechanisms, pharmacokinetic optimization requirements, optimal administration route selection, large-scale production quality control standards and clinical dosing determination protocols. Through multidisciplinary integration of synthetic biology, infectious disease medicine and immunology, future translational medicine studies of bacteriophage should establish comprehensive technical platforms encompassing rapid phage screening, intelligent rational design, rigorous in vivo evaluation and standardized clinical validation processes, ultimately advancing engineered bacteriophage from laboratory innovations to clinically approved therapeutics for effectively combating MDR bacterial infections.
2.Clinical effects of Huoxue Qingre Formula combined with radiofrequency ablation on patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis
Jin-hui GAO ; Zhi-qiao WANG ; Hui-bin LI ; Ya-zhou LI
Chinese Traditional Patent Medicine 2025;47(5):1509-1513
AIM To investigate the clinical effects of Huoxue Qingre Formula combined with radiofrequency ablation on patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis.METHODS Ninety patients were randomly assigned into control group(45 cases)for 3-month intervention of both Huoxue Qingre Formula placebo and radiofrequency ablation,and observation group(45 cases)for 3-month intervention of both Huoxue Qingre Formula and radiofrequency ablation.The changes in clinical effects,VRR,TCM syndrome score,cytokines(TNF-α,IFN-γ,IL-23,IL-1β),biochemical indices[Ca2+,25(OH)D,CRP],thyroid function indices(TSH,FT3,FT4)and safety indices were detected.RESULTS At postoperative 12 months,the observation group demonstrated higher total effective rate than the control group(P<0.05).At postoperative 3-12 months,the two groups displayed increased VRR(P<0.05),especially for the observation group(P<0.05,P<0.01).At the 7th,30th postoperative days,the two groups displayed decreased TCM syndrome score and cytokines(P<0.05,P<0.01),especially for the observation group(P<0.05,P<0.01).At the 30th postoperative day,the two groups displayed decreased Ca2+(P<0.01)and increased 25(OH)D(P<0.01),especially for the observation group(P<0.01).At the 7th postoperative day,the two groups displayed increased CRP(P<0.01),especially for the control group(P<0.05),which were decreased at the 30th postoperative day(P<0.05,P<0.01),especially for the observation group(P<0.01).No significant differences in thyroid function indices and safety indices were found between the two groups(P>0.05).CONCLUSION For the patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis,Huoxue Qingre Formula combined with radiofrequency ablation can safely and effectively enhance nodule VRR,alleviate discomfort symptoms,reduce TCM syndrome score,inflammatory factor levels,and accelerate recovery.
3.STUDY ON THE POPULATION STRUCTURE OF MOSQUITOES AND THE APPLICATION OF MOSQUITO-REPELLENT SILICONE-BASED OIL FILM IN THE DRAINAGE SYSTEM OF MINHANG DISTRICT,SHANGHAI
Min-Hui ZHU ; Li-Jun LIU ; Lu ZHANG ; Xiao-Sa WEN ; Zhi-Yin XU ; Zhao-Wen ZHANG ; Yi-Bin ZHOU
Acta Parasitologica et Medica Entomologica Sinica 2025;32(2):105-111
Objective Understanding the population structure of mosquitoes in the drainage system of Minhang District,Shanghai,and exploring the physical prevention and control technology of mosquito traps with a Vazor mosquito repellent film in the drainage system.Methods A 500 mL water spoon was used to assist in visual inspection to investigate the breeding status of mosquito larvae in the drainage system.A carbon dioxide mosquito trap method was used to monitor adult mosquitoes around the ground drainage system,and the artificial hour method was used to monitor adult mosquitoes around the underground drainage system.Mosquito-repellent film was applied at a rate of 1 mL/m2 to the drainage system where mosquito larvae or pupae are found,and the breeding situation was observed and recorded.Results The positivity rate of mosquitoes breeding in the ground drainage system was 50%.The mosquito larvae in the drainage channels were primarily Aedes albopictus,whereas Ae.albopictus were primarily noted in the sewage wells.The proportions of Ae.albopictus and Culex pipiens pallens in the rainwater wells were similar,and the dominant mosquito species around the surface drainage system was Ae.Albopictus.The positive rate of mosquito breeding in the underground drainage system was 47%,with the dominant mosquito species being Cx.pipiens pallens(58.39%)followed by Ae.albopictus(41.6%).The dominant adult mosquito species around the drainage system were Cx.pipiens pallens(83%)followed by Ae.albopictus(11%).In terms of the effectiveness of mosquito-repellent water film,the mosquito breeding rates of the ground and underground drainage systems using mosquito-repellent water film decreased to 2.78%and 5%after 1 week of use,respectively,and then rebounded after the 3rd week.After a supplementary dose during the 5th week,the breeding rates returned to normal.No statistically significant differences were observed in the effect compared with the standard control group using 1%bisulfite granules;however,a statistically significant difference was noted compared with the blank control group without special treatment.Conclusions In the drainage system of Minhang District,Shanghai,mosquito breeding is severe,and variations exist in the dominant mosquito species in different environmental drainage facilities.The simultaneous use of mosquito-repellent films can effectively control mosquito breeding in drainage systems.
4.Harnessing Artificial Intelligence for Advances in Gene Editing
Zi-Yue ZHANG ; Xin-Zhi ZHOU ; Bin LU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(4):522-532
Gene editing technology has become an important tool for biomedical research because of its high efficiency and precision in target gene localization and cleavage.The technology not only facilitates basic research on gene function,but also provides new strategies for gene therapy of hereditary diseases and genetic improvement of crops.With the integration of artificial intelligence(AI)technology,espe-cially the application of machine learning algorithms,the design and execution of gene editing have be-come more intelligent.AI technology optimizes the design of sgRNAs through predictive analysis and pat-tern recognition,improving the specificity and efficiency of editing while reducing the risk of off-target effects.In addition,AI plays a key role in the parsing of large-scale genomic data,providing new per-spectives for understanding complex biological processes and disease mechanisms.This paper reviews the research progress of data-driven gene editing technology in target precision,safety enhancement and per-sonalized therapy,aiming to provide reference and inspiration for researchers in the field of gene editing technology and to promote the application and development of AI in gene editing technology.
5.OBE-based Design of Biochemistry Teaching:Taking the Teaching of"Classification and Specificity of Enzymes"as an Example
Hua HAI ; Li-Yan NA ; Ming-Lei HE ; Hong-Ze YANG ; Li-Ming JIN ; Chun-Bin LI ; Hua JIN ; Quan ZHOU ; De-Fu ZHI
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):903-913
Biochemistry,as a fundamental course for science and engineering majors related to biology and chemistry,holds a significant position in the curriculum.The course team at Dalian Minzu University is committed to teaching innovation,adopting the outcome-based education(OBE)concept for teaching de-sign and incorporating ideological and political elements,in order to achieve the dual goals of knowledge transmission and value guidance.The team has established a three-dimensional teaching goal of"knowl-edge,morality,and ability",covering"consolidating core knowledge,cultivating moral sentiment,and enhancing innovation ability".Through a multi-dimensional integrated teaching method of"three integra-tions and five combinations",multiple rounds of teaching practice have been carried out in the applied chemistry major using"classification and specificity of enzyme"as an example.The output of teaching re-sults and survey questionnaires show that students highly recognize the teaching design and its"process-based learning"evaluation method,fully reflecting the student-centered teaching idea.Research has shown that OBE design combined with ideological and political elements can effectively promote students' knowl-edge acquisition,moral growth,and innovation ability improvement in the course of Biochemistry.This teaching design not only helps students construct correct worldviews,outlooks on life,and values,but also significantly enhances their innovative thinking and practical abilities.This teaching design can not only ef-fectively improve the teaching quality of the course,but also provide new perspectives and ideas for the teaching design of Biochemistry,realizing the organic integration of professional knowledge imparting and i-deological and political education,and has certain innovation and practical significance.
6.A potentially imported zoonosis:transmission routes and global spreading pattern of Chagas disease(American trypanosomiasis)
Xiao-nen WU ; Bin-bin XIE ; Zhi-ying HOU ; Jun-hu CHEN ; Xiao-nong ZHOU
Chinese Journal of Zoonoses 2025;41(5):494-500
Chagas disease(American trypanosomiasis)is a zoonosis caused by Trypanosoma cruzi,which severely affects public health.Recently,with changes in economic globalization and increased population mobility,this disease has gradually spread from the original Latin American epidemic areas to non-epidemic areas,such as Europe,thus showing a trend of globalization.The main trans-mission routes have changed from transmission via the Triatomine vector to blood transfusion transmission,mother-to-child transmis-sion,oral transmission,and other routes.Consequently,Chagas disease is spreading globally,and more people are increasingly vul-nerable to infection.This article retrospectively reviews research on the transmission routes of Chagas disease,analyzes the changing trends in transmission routes,and provides a scientific basis for the formulation and optimization of Chagas disease prevention and con-trol strategies from a One Health perspective.
7.Harnessing Artificial Intelligence for Advances in Gene Editing
Zi-Yue ZHANG ; Xin-Zhi ZHOU ; Bin LU
Chinese Journal of Biochemistry and Molecular Biology 2025;41(4):522-532
Gene editing technology has become an important tool for biomedical research because of its high efficiency and precision in target gene localization and cleavage.The technology not only facilitates basic research on gene function,but also provides new strategies for gene therapy of hereditary diseases and genetic improvement of crops.With the integration of artificial intelligence(AI)technology,espe-cially the application of machine learning algorithms,the design and execution of gene editing have be-come more intelligent.AI technology optimizes the design of sgRNAs through predictive analysis and pat-tern recognition,improving the specificity and efficiency of editing while reducing the risk of off-target effects.In addition,AI plays a key role in the parsing of large-scale genomic data,providing new per-spectives for understanding complex biological processes and disease mechanisms.This paper reviews the research progress of data-driven gene editing technology in target precision,safety enhancement and per-sonalized therapy,aiming to provide reference and inspiration for researchers in the field of gene editing technology and to promote the application and development of AI in gene editing technology.
8.OBE-based Design of Biochemistry Teaching:Taking the Teaching of"Classification and Specificity of Enzymes"as an Example
Hua HAI ; Li-Yan NA ; Ming-Lei HE ; Hong-Ze YANG ; Li-Ming JIN ; Chun-Bin LI ; Hua JIN ; Quan ZHOU ; De-Fu ZHI
Chinese Journal of Biochemistry and Molecular Biology 2025;41(6):903-913
Biochemistry,as a fundamental course for science and engineering majors related to biology and chemistry,holds a significant position in the curriculum.The course team at Dalian Minzu University is committed to teaching innovation,adopting the outcome-based education(OBE)concept for teaching de-sign and incorporating ideological and political elements,in order to achieve the dual goals of knowledge transmission and value guidance.The team has established a three-dimensional teaching goal of"knowl-edge,morality,and ability",covering"consolidating core knowledge,cultivating moral sentiment,and enhancing innovation ability".Through a multi-dimensional integrated teaching method of"three integra-tions and five combinations",multiple rounds of teaching practice have been carried out in the applied chemistry major using"classification and specificity of enzyme"as an example.The output of teaching re-sults and survey questionnaires show that students highly recognize the teaching design and its"process-based learning"evaluation method,fully reflecting the student-centered teaching idea.Research has shown that OBE design combined with ideological and political elements can effectively promote students' knowl-edge acquisition,moral growth,and innovation ability improvement in the course of Biochemistry.This teaching design not only helps students construct correct worldviews,outlooks on life,and values,but also significantly enhances their innovative thinking and practical abilities.This teaching design can not only ef-fectively improve the teaching quality of the course,but also provide new perspectives and ideas for the teaching design of Biochemistry,realizing the organic integration of professional knowledge imparting and i-deological and political education,and has certain innovation and practical significance.
9.A potentially imported zoonosis:transmission routes and global spreading pattern of Chagas disease(American trypanosomiasis)
Xiao-nen WU ; Bin-bin XIE ; Zhi-ying HOU ; Jun-hu CHEN ; Xiao-nong ZHOU
Chinese Journal of Zoonoses 2025;41(5):494-500
Chagas disease(American trypanosomiasis)is a zoonosis caused by Trypanosoma cruzi,which severely affects public health.Recently,with changes in economic globalization and increased population mobility,this disease has gradually spread from the original Latin American epidemic areas to non-epidemic areas,such as Europe,thus showing a trend of globalization.The main trans-mission routes have changed from transmission via the Triatomine vector to blood transfusion transmission,mother-to-child transmis-sion,oral transmission,and other routes.Consequently,Chagas disease is spreading globally,and more people are increasingly vul-nerable to infection.This article retrospectively reviews research on the transmission routes of Chagas disease,analyzes the changing trends in transmission routes,and provides a scientific basis for the formulation and optimization of Chagas disease prevention and con-trol strategies from a One Health perspective.
10.Clinical effects of Huoxue Qingre Formula combined with radiofrequency ablation on patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis
Jin-hui GAO ; Zhi-qiao WANG ; Hui-bin LI ; Ya-zhou LI
Chinese Traditional Patent Medicine 2025;47(5):1509-1513
AIM To investigate the clinical effects of Huoxue Qingre Formula combined with radiofrequency ablation on patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis.METHODS Ninety patients were randomly assigned into control group(45 cases)for 3-month intervention of both Huoxue Qingre Formula placebo and radiofrequency ablation,and observation group(45 cases)for 3-month intervention of both Huoxue Qingre Formula and radiofrequency ablation.The changes in clinical effects,VRR,TCM syndrome score,cytokines(TNF-α,IFN-γ,IL-23,IL-1β),biochemical indices[Ca2+,25(OH)D,CRP],thyroid function indices(TSH,FT3,FT4)and safety indices were detected.RESULTS At postoperative 12 months,the observation group demonstrated higher total effective rate than the control group(P<0.05).At postoperative 3-12 months,the two groups displayed increased VRR(P<0.05),especially for the observation group(P<0.05,P<0.01).At the 7th,30th postoperative days,the two groups displayed decreased TCM syndrome score and cytokines(P<0.05,P<0.01),especially for the observation group(P<0.05,P<0.01).At the 30th postoperative day,the two groups displayed decreased Ca2+(P<0.01)and increased 25(OH)D(P<0.01),especially for the observation group(P<0.01).At the 7th postoperative day,the two groups displayed increased CRP(P<0.01),especially for the control group(P<0.05),which were decreased at the 30th postoperative day(P<0.05,P<0.01),especially for the observation group(P<0.01).No significant differences in thyroid function indices and safety indices were found between the two groups(P>0.05).CONCLUSION For the patients with thyroid nodules due to Phlegm Stagnation and Blood Stasis,Huoxue Qingre Formula combined with radiofrequency ablation can safely and effectively enhance nodule VRR,alleviate discomfort symptoms,reduce TCM syndrome score,inflammatory factor levels,and accelerate recovery.

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