Transcriptomic analysis of Andrias davidianus meat and experimental validation for exploring its bioactive components as functional foods

Andrias davidianus(Chinese giant salamander,CGS)is the largest and oldest extant amphibian species in the world and is a source of prospective functional food in China.However,the progress of functional peptides mining was slow due to lack of reference genome and protein sequence data.In this study,we illustrated full-length transcriptome sequencing to interpret the proteome of CGS meat and obtain 10703 coding DNA sequences.By functional annotation and amino acid composition analysis,we have discovered various genes related to signal transduction,and 16 genes related to longevity.We have also found vast variety of functional peptides through protein coding sequence(CDS)analysis by comparing the data obtained with the functional peptide database.Val-Pro-Ile predicted by the CDS analysis was released from the CGS meat through enzymatic hydrolysis,suggesting that our approach is reliable.This study suggested that transcriptomic analysis can be used as a reference to guide polypeptide mining in CGS meat,thereby providing a powerful mining strategy for the bioresources with unknown genomic and proteomic sequences.

Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Quantitative evaluation of DNA damage caused by atmospheric and room-temperature plasma (ARTP) and other mutagenesis methods using a rapid umu-microplate test protocol for microbial mutation breeding

Mutagenesis is an important technique for microbial mutation breeding.As the source of mutations,DNA damage extent is a key indicator for the effectiveness of mutagenesis.Therefore,a rapid and easy DNA damage quantification method is required for the comparison of mutagenesis effects and development of mutagenesis tools.Here,we used the umu-microplate test system to quantitatively compare the DNA damage strength caused by atmospheric and room-temperature plasma(ARTP)and other traditional mutagenesis methods including:ultraviolet radiation(UV),diethyl sulfate(DES)and 4-nitroquinoline-1-oxide(4-NQO).The test strain of Salmonella typhimurium TA1535/pSK1002 was used to monitor the time-course profile of b-galactosidase activity induced by DNA damage caused by different mutagenesis methods using a microplate reader.The umu-microplate test results showed that ARTP caused higher extent of DNA damage than UV and chemical mutagens,which agrees well with the result obtained by SOS-FACS-based quantification method as reported previously.This umu-microplate test is accessible for broad researchers who are lack of the expensive FACS instruments and allows the quick quantitative evaluation of DNA damage among living cells for different mutagenesis methods in the study of the microbial mutation breeding.

Isolation and characterization of novel peptides from fermented products of Lactobacillus for ulcerative colitis prevention and treatment

Ulcerative colitis(UC)is an incurable and highly complex digestive disease affecting millions of people worldwide.Compared to the current therapeutic drugs,bioactive peptides are more promising and safe substances as functional foods or drugs for the prevention and treatment of UC.The alcohol-soluble components from fermentation broth by fresh wheat germ and apple(AC-WGAF)were found to be effective in UC prevention in dextran sulfate sodium-induced mice in vivo.Herein,4 novel peptides are identifi ed from AC-WGAF by membrane ultrafi ltration,recycling preparative high-performance liquid chromatography,and matrix-assisted laser desorption–ionization time-of-fl ight/time-of-fl ight mass spectrometry,possessing anticolitis activity via using an in vitro model.One of those peptides named T24(PVLGPVRGPFPLL)exhibited the most remarkable anti-colitis activity by preventing tight junction protein loss,maintaining epithelial barrier integrity,and promoting cell proliferation during in vitro and in vivo studies by regulating mitogen-activated protein kinase signaling pathways.Thus,T24 is a promising peptide as a functional food or novel drug for UC prevention and treatment.

Emerging natural hemp seed proteins and their functions for nutraceutical applications

With changing dietary habits and increasing awareness of the nutraceutical role of dietary foods,the demand for natural plant proteins and interest in non-traditional protein sources in the food industry are increasing.Industrial hemp,belonging to the plant family Cannabaceae,is cultivated for its fibre and edible seeds.Due to its nutritional value,it has also been used in the food industry and medicine.In particular,hemp seed proteins have drawn considerable attention in both scientific and industrial fields because of their excellent nutraceutical values,superior digestibility,low allergenicity and diverse techno-functional properties.In this review,we provide a summary of the current research progress on the extraction and purification processes,physiochemical properties,nutraceutical functions,and applications of hemp seed proteins.Perspectives in the application of advanced technologies for hemp seed bioactive peptide mining are also discussed.This review provides up-to-date insights into the nutraceutical values,health benefits,and future applications of this emerging plant source protein.

Genome-scale metabolic models applied for human health and biopharmaceutical engineering

Over the last 15 years,genome-scale metabolic models(GEMs)have been reconstructed for human and model animals,such as mouse and rat,to systematically understand metabolism,simulate multicellular or multi-tissue interplay,understand human diseases,and guide cell factory design for biopharmaceutical protein production.Here,we describe how metabolic networks can be represented using stoichiometric matrices and well-defined constraints for flux simulation.Then,we review the history of GEM development for quantitative understanding of Homo sapiens and other relevant animals,together with their applications.We describe how model develops from H.sapiens to other animals and from generic purpose to precise context-specific simulation.The progress of GEMs for animals greatly expand our systematic understanding of metabolism in human and related animals.We discuss the difficulties and present perspectives on the GEM development and the quest to integrate more biological processes and omics data for future research and translation.We truly hope that this review can inspire new models developed for other mammalian organisms and generate new algorithms for integrating big data to conduct more in-depth analysis to further make progress on human health and biopharmaceutical engineering.

Biomimetic manganese-based theranostic nanoplatform for cancer multimodal imaging and twofold immunotherapy

The limited clinical response and serious side effect have been challenging in cancer immunotherapy resulting from immunosuppressive tumor microenvironment(TME)and inferior drug targeting.Herein,an active targeting TME nanoplatform capable of revising the immunosuppressive TME microenvironment is designed.Briefly,gold nanorods(GNRs)are covered with silica dioxide(SiO_(2))and then coated manganese dioxide(MnO_(2))to obtain GNRs@SiO_(2)@MnO_(2)(GSM).Myeloid-derived suppressor cells(MDSCs)membrane is further camouflaged on the surface of GSM to obtain GNRs@SiO_(2)@MnO_(2)@MDSCs(GSMM).In this system,GSMM inherits active targeting TME capacity of MDSCs.The localized surface plasmon resonance of GNRs is developed in near-infraredⅡwindow by MnO_(2)layer coating,realizing NIR-Ⅱwindow photothermal imaging and photoacoustic imaging of GSMM.Based on the release of Mn^(2+)in acidic TME,GSMM can be also used for magnetic resonance imaging.In cancer cells,Mn^(2+)catalyzes H_(2)O_(2)into·OH for(chemodynamic therapy)CDT leading to activate cGAS-STING,but also directly acts on STING inducing secretion of typeⅠinterferons,pro-inflammatory cytokines and chemokines.Additionally,photothermal therapy and CDT-mediated immunogenic cell death of tumor cells can further enhance anti-tumor immunity via exposure of CRT,HMGB1 and ATP.In summary,our nanoplatform realizes multimodal cancer imaging and dual immunotherapy.

Research progress on classification, sources and functions of dietary polyphenols for prevention and treatment of chronic diseases

Dietary polyphenols are the most abundant antioxidants in daily diet and widely distributed in plants and plant-based foods,including vegetables,fruits,cereals,nuts,and beverages(e.g.,tea,coffee,red wine).Over the past decades,there has been rising scientific interest in their diverse benefits to human health,since dietary polyphenols display various bioactivities,such as antioxidant activity,anti-inflammatory activity,anticancer,anti-microbial activity,neuro-protective activity,among others.Various studies have demonstrated that diet with polyphenols is strongly related to decrease the risk of chronic diseases.In this review,firstly,we systematically summarize classification and sources of dietary polyphenols,and focus on the current evidences defining their function and mechanism on improving chronic diseases,including diabetes,obesity,hypertension,hyperuricemia.Then,future directions of dietary polyphenols are discussed.Noteworthy,despite the physiological effects of dietary polyphenols have been widely convinced in vitro and in vivo,human trials show inconsistent evidence with their beneficial effects in chronic diseases administration,so as to their unclear molecular mechanism.More clinical studies are needed to provide clear evidence on dietary polyphenols against chronic diseases.In general,this paper provides comprehensive review of the sources and compositions of dietary polyphenols from plant materials,and presents an overview of the evidence on dietary polyphenols against chronic diseases,which may offer some constructive inspirations for further research on dietary polyphenols and industrial application in the food and medicine industry.

Base editor-mediated large-scale screening of functional mutations in bacteria for industrial phenotypes

Base editing,the targeted introduction of point mutations into cellular DNA,holds promise for improving genome-scale functional genome screening to single-nucleotide resolution.Current efforts in prokaryotes,however,remain confined to loss-of-function screens using the premature stop codons-mediated gene inactivation library,which falls far short of fully releasing the potential of base editors.Here,we developed a base editor-mediated functional single nucleotide variant screening pipeline in Escherichia coli.We constructed a library with 31,123 sgRNAs targeting 462 stress response-related genes in E.coli,and screened for adaptive mutations under isobutanol and furfural selective conditions.Guided by the screening results,we successfully identified several known and novel functional mutations.Our pipeline might be expanded to the optimization of other phenotypes or the strain engineering in other microorganisms.

Macrophages in immunoregulation and therapeutics

Macrophages exist in various tissues,several body cavities,and around mucosal surfaces and are a vital part of the innate immune system for host defense against many pathogens and cancers.Macrophages possess binary M1/M2 macrophage polarization settings,which perform a central role in an array of immune tasks via intrinsic signal cascades and,therefore,must be precisely regulated.Many crucial questions about macrophage signaling and immune modulation are yet to be uncovered.In addition,the clinical importance of tumor-associated macrophages is becoming more widely recognized as significant progress has been made in understanding their biology.Moreover,they are an integral part of the tumor microenvironment,playing a part in the regulation of a wide variety of processes including angiogenesis,extracellular matrix transformation,cancer cell proliferation,metastasis,immunosuppression,and resistance to chemotherapeutic and checkpoint blockade immunotherapies.Herein,we discuss immune regulation in macrophage polarization and signaling,mechanical stresses and modulation,metabolic signaling pathways,mitochondrial and transcriptional,and epigenetic regulation.Furthermore,we have broadly extended the understanding of macrophages in extracellular traps and the essential roles of autophagy and aging in regulating macrophage functions.Moreover,we discussed recent advances in macrophages-mediated immune regulation of autoimmune diseases and tumorigenesis.Lastly,we discussed targeted macrophage therapy to portray prospective targets for therapeutic strategies in health and diseases.

Design, synthesis and antitumor evaluations of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors

DNA methyl transferase(DNMT) and histone deacetylase(HDAC) are well recognized epigenetic targets for discovery of antitumor agents.In this study,we designed and synthesized a series of nucleoside base hydroxamic acid derivatives as DNMT and HDAC dual inhibitors.MTT assays and enzymatic inhibitory activity tests indicated that compound 204 exhibited potent DNMT1 and HDAC1/6 inhibitory potency simultaneously in enzymatic levels and at cellular levels,inducing hypomethylation of p16 and hyperacetylation of histones H_(3) K9 and H4 K8.Besides,204 remarkably inhibited proliferation against cancer cells U937 by prompting G0/G1 cell cycle arrest.Molecular docking models explained the functional mechanism of 204 inhibiting DNMT1 and HDAC.Preliminary studies on metabolic profiles revealed that 204 showed desirable stability in liver microsomes.Our study suggested that 204 inhibiting DNMT and HDAC concurrently can be a potential lead compound for epigenetic cancer therapy.

Cross-species binding spectrum of ACE2 to SARS-CoV-2 RBD

Dear Editor,Severe acute respiratory syndrome coronavirus 2(SARSCo V-2)is the cause of COVID-19,which has posed a massive threat to human health,economy,and security worldwide(Bai et al.,2022).Genomic analysis of SARS-Co V-2 and related coronaviruses revealed that SARS-Co V and SARS-Co V-2likely had ancestors(Xu et al.,2020),which might originate in bats,followed by subsequent spread within intermediate hosts(spillover hosts)and then transmission to humans(Wang et al.,2021).

Multi-functional engineered polypeptide-based drug delivery systems for improved cancer therapy

With the rapid development of chemical engineering and biotechnology,polypeptide,as a promising candidate in the biomedical field,has been thoroughly investigated and extensively used as the drug delivery vehicle for diseases treatment,especially cancer,owing to the high biocompatibility,good biodegradability,versatile con-structions,and diverse functions.Engineered polypeptide-based drug delivery system(so-called EPP-DDS)can deliver the cargos to the target site via a specific recognition effect,followed by overcoming the barriers like blood brain barrier(BBB)and releasing them by responding to the microenvironment cues,to improve the therapeutic efficacy and reduce the side-effect.Herein,it's of great importance to conclude and summarize the updates on EPP-DDS developed by chemical engineering methods.In this review,we first summarized the recent updates in the manufacturing of polypeptide and preparation of EPP-DDS based on green biochemical engineering and/or synthetic processes for cancer therapy,including chemotherapy,immunotherapy,photodynamic therapy(PDT),gene therapy,and combination therapy.Then,we surveyed the research progress of inflammation-mediated cancer treatment strategies based on EPP-DDS with high anti-inflammation activity.Finally,we concluded the discovery and green production process of engineered polypeptide,challenges,and perspectives of EPP-DDS.Overall,the EPP-DDS has great potential for cancer therapy in the clinic with improved therapeutic efficacy and reduced adverse effect,which needs the innovation of green biochemical engineering for customized design and production of polypeptides.

Enzymes immobilized in wood-derived cellulose scaffold for constructing a novel modular bioreactor

Modular bioreactors can provide a flexible platform for constructing complex multi-step pathways,which may be a solution for maximizing reactions and overcoming the complexity of multi-enzyme systems.Here,we selected wood-derived cellulose scaffold as a support for enzyme immobilization and constructed the modular bioreactor.Cellulose scaffold was prepared after removing lignin from wood,followed by citric acid functionalization and the addition of glutaraldehyde finally allowed the cross-linking of enzymes.Three enzymes,horseradish peroxidase(HRP),glucose oxidase(GOD),and catalase(CAT),were separately immobilized,resulting in the immobilized enzyme amount to over 40 mg/g.The introduction of carboxyl groups from citric acid facilitated the rapid enzyme adsorption on the support surface and immobilized enzymes possess~65%expressed activity.Modular bioreactors were constructed by using the immobilized enzymes.With the immobilized HRP module,reactor showed desired catalytic performance with the phenol degradation rate of>90%.Also,a pH regulation can occur in the bioreactors for preserving enzyme activities and neutralizing acid products.In the GOD/CAT modular bioreactor,the cascade reaction with adjusting pH values can achieve a 95%yield of sodium gluconate and exhibit a favorable reusability of 5 operation cycles.

Nanobody-based bispecific T-cell engager (Nb-BiTE): a new platform for enhanced T-cell immunotherapy

A novel bispecific T-cell engager(BiTE)has been developed as an efficient immunotherapeutic molecule specifically bringing the T-cell and the tumor target together for enhanced immunotherapy.The general BiTE construct consists of two single-chain variable antibody fragments(scFvs)targeting a tumor-associated antigen(TAA)and a T-cell marker in tandem.The binding of BiTEs to tumor antigens induces immediate T-cells’cytotoxicity against tumor cells without involving any typical costimulatory signals,specific TCR and MHC recognition.

超分子工程化细胞膜囊泡用于肿瘤免疫治疗

缺乏高效的递送系统已经成为纳米药物临床转化道路上的巨大障碍,寻找一种新的纳米载体材料来克服上述困境也就成为了科学家的主攻方向.尽管细胞膜递送系统已经成功引起了科研工作者的关注,但仍需要进一步的功能化修饰以增强其诊疗功能.为了克服化学修饰和基因修饰所带来的问题,本文提出利用环糊精的主客体分子识别这一细胞友好的超分子修饰策略对细胞膜进行工程化修饰.得益于肿瘤的"归巢"特性以及肿瘤的"增强渗透滞留效应",超分子细胞膜囊泡(SCMVs)实现了在肿瘤组织内高富集.SCMVs能够协同递送吲哚菁绿和吲哚胺2,3-双加氧酶抑制剂,实现了光动力疗法和免疫疗法的联合治疗,显著抑制了肿瘤的生长.在主客体识别作用力的驱动下,成功负载了雷西莫特的SCMVs可以将肿瘤相关巨噬细胞重新极化为M1表型,在增强肿瘤固有杀伤的同时能够与免疫检查点阻断疗法协同治疗肿瘤.这种基于非共价相互作用的超分子工程化方法为开发用于肿瘤精确治疗的活细胞来源的纳米材料提供了一种通用且生物友好的策略.

Gut lumen-targeted oral delivery system for bioactive agents to regulate gut microbiome

Gut microbiome(GM)is closely related to the overall health status for the human being.The dysfunction of microbiome can lead to many diseases such as inflammation,cancer and neurodegenerative disease.Therefore,it's of great importance to develop effective strategy to regulate GM.Gut lumen-targeted oral delivery system(GLT-ODS)has been extensively investigated and widely used in food science and engineering in these years,due to the targeted delivery property,controlled release profile,high biocompatibility and enhanced bioavailability of cargos.Herein,we comprehensively summarized the current advances in GLT-ODS for bioactive agent.Specifically,we systematically summarize the GLT-ODS for pre-agents(prebiotics and probiotics)and anti-agents(antibiotics and bacteriophages)according to the type of cargos.Through in-depth discussion of representative researches,we refined the limitations of existing research in carrier material and target selection,and drew a blueprint for the future technological research and development.We believe that GLT-ODS will become a safe,efficient,simple and precise GM management strategy for improvement of health and shine in the development of precision food and pharmaceutical engineering in future.