An Update on the Clinical Pipelines of New Antibacterial Drugs Developed in China

Antibacterial resistance is a global health threat that requires further concrete action on the part of all countries.In this context,one of the biggest concerns is whether enough new antibacterial drugs are being discovered and developed.Although several high-quality reviews on clinical antibacterial drug pipelines from a global perspective were published recently,none provides comprehensive information on original antibacterial drugs at clinical stages in China.In this review,we summarize the latest progress of novel antibacterial drugs approved for marketing and under clinical evaluation in China since 2019.Information was obtained by consulting official websites,searching commercial databases,retrieving literature,asking personnel from institutions or companies,and other means,and a considerable part of the data covered here has not been included in other reviews.As of June 30,2023,a total of 20 antibacterial projects from 17 Chinese pharmaceutical companies or developers were identified and updated.Among them,two new antibacterial drugs that belong to traditional antibiotic classes were approved by the National Medical Products Administration(NMPA)in China in 2019 and 2021,respectively,and 18 antibacterial agents are in clinical development,with one under regulatory evaluation,five in phase-3,six in phase-2,and six in phase-1.Most of the clinical candidates are new analogs or monocomponents of traditional antibacterial pharmacophore types,including two dual-acting hybrid antibiotics and a recombinant antibacterial protein.Overall,despite there being 17 antibacterial clinical candidates,our analysis indicates that there are still relatively few clinically differentiated antibacterial agents in stages of clinical development in China.Hopefully,Chinese pharmaceutical companies and institutions will develop more innovative and clinically differentiated candidates with good market potential in the future research and development(R&D)of original antibacterial drugs.

Mucosal-associated invariant T cells and oral microbiome in persistent apical periodontitis

Opportunistic bacteria in apical periodontitis (AP) may pose a risk for systemic dissemination.Mucosal-associated invariant T (MAIT) cells are innate-like T cells with a broad and potent antimicrobial activity important for gut mucosal integrity.It was recently shown that MAIT cells are present in the oral mucosal tissue,but the involvement of MAIT cells in AP is unknown.Here,comparison of surgically resected AP and gingival tissues demonstrated that AP tissues express significantly higher levels of Vα7.2-Jα33,Vα7.2- Jα20,Vα7.2-Jα12,Cα and tumour necrosis factor (TNF),interferon (IFN)-γ and interleukin (IL)-17A transcripts,resembling a MAIT cell signature.Moreover,in AP tissues the MR1-restricted MAIT cells positive for MR1–5-OP-RU tetramer staining appeared to be of similar levels as in peripheral blood but consisted mainly of CD4^+ subset.Unlike gingival tissues,the AP microbiome was quantitatively impacted by factors like fistula and high patient age and had a prominent riboflavin-expressing bacterial feature.When merged in an integrated view,the examined immune and microbiome data in the sparse partial least squares discriminant analysis could identify bacterial relative abundances that negatively correlated with Vα7.2-Jα33,Cα,and IL-17A transcript expressions in AP,implying that MAIT cells could play a role in the local defence at the oral tissue barrier.In conclusion,we describe the presence of MAIT cells at the oral site where translocation of oral microbiota could take place.These findings have implications for understanding the immune sensing of polymicrobial-related oral diseases.

Tumor angiogenesis and anti-angiogenic therapy

Anti-angiogenic drugs(AADs),which mainly target the vascular endothelial growth factor-A signaling pathway,have become a therapeutic option for cancer patients for two decades.During this period,tremendous clinical experience of anti-angiogenic therapy has been acquired,new AADs have been developed,and the clinical indications for AAD treatment of various cancers have been expanded using monotherapy and combination therapy.However,improvements in the therapeutic outcomes of clinically available AADs and the development of more effective next-generation AADs are still urgently required.This review aims to provide historical and perspective views on tumor angiogenesis to allow readers to gain mechanistic insights and learn new therapeutic development.We revisit the history of concept initiation and AAD discovery,and summarize the up-to-date clinical translation of anti-angiogenic cancer therapy in this field.

Cancer-associated fibroblasts express CD1d and activate invariant natural killer T cells under cellular stress

Invariant natural killer T(iNKT)cells are part of the family of unconventional T cells,and they recognize glycolipid antigens presented on the MHC class I like molecule CD1^([1]).In humans there are five CD1 molecules named CD1a to CD1e,whereas mice use only CD1d for lipid presentation.Functionally,iNKT cells can elicit both cytotoxicity similarly to conventional CD8 T cells and secrete cytokines that influence the adaptive immune response including providing direct T cell help to B cells^([2]).In the context of tumors,they can use both release of granzyme B and use Fas-mediated mechanisms for killing of tumor cells.As iNKT cells use a restricted TCR repertoire and CD1 molecules are non-heterogenous the risk of graft vs host disease is limited and thus these T cells have been an attractive option for off the shelf immunotherapy to treat cancer^([3]).

The role of corneal endothelium in macular corneal dystrophy development and recurrence

Macular corneal dystrophy(MCD)is a progressive,bilateral stromal dystrophic disease that arises from mutations in carbohydrate sulfotransferase 6(CHST6).Corneal transplantation is the ultimate therapeutic solution for MCD patients.Unfortunately,postoperative recurrence remains a significant challenge.We conducted a retrospective review of a clinical cohort comprising 102 MCD patients with 124 eyes that underwent either penetrating keratoplasty(PKP)or deep anterior lamellar keratoplasty(DALK).Our results revealed that the recurrence rate was nearly three times higher in the DALK group(39.13%,9/23 eyes)compared with the PKP group(10.89%,11/101 eyes),suggesting that surgical replacement of the corneal endothelium for treating MCD is advisable to prevent postoperative recurrence.Our experimental data confirmed the robust m RNA and protein expression of CHST6 in human corneal endothelium and the rodent homolog CHST5 in mouse endothelium.Selective knockdown of wild-type Chst5 in mouse corneal endothelium(AC^(siChst5)),but not in the corneal stroma,induced experimental MCD with similar extracellular matrix synthesis impairments and corneal thinning as observed in MCD patients.Mice carrying Chst5 point mutation also recapitulated clinical phenotypes of MCD,along with corneal endothelial abnormalities.Intracameral injection of wild-type Chst5 rescued the corneal impairments in AC^(siChst5)mice and retarded the disease progression in Chst5 mutant mice.Overall,our study provides new mechanistic insights and therapeutic approaches for MCD treatment by highlighting the role of corneal endothelium in MCD development.

Tumor-derived insulin-like growth factor-binding protein-1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

Background:Antiangiogenic tyrosine kinase inhibitors(TKIs)provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma(HCC).However,patients with HCC often develop resistance toward antiangiogenic TKIs,and the underlying mechanisms are not understood.The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC.Methods:We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients.We evaluated the prognosis,therapeutic response,and serum insulin-like growth factor-binding protein-1(IGFBP-1)levels of 31 lenvatinib-treated HCC patients.Based on the array of results,a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted.Additionally,in vivo genetic and pharmacological gain-and loss-of-function experiments were performed.Results:In the patient cohort,IGFBP-1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival.Mechanistically,antiangiogenic TKI treatment markedly elevated tumor IGFBP-1 levels via the hypoxia-hypoxia inducible factor signaling.IGFBP-1 stimulated angiogenesis through activation of the integrinα5β1-focal adhesion kinase pathway.Consequently,loss of IGFBP-1 and integrinα5β1 by genetic and pharmacological approaches re-sensitized HCC to lenvatinib treatment.Conclusions:Together,our data shed light onmechanisms underlying acquired resistance of HCC to antiangiogenic TKIs.Antiangiogenic TKIs induced an increase of tumor IGFBP-1,which promoted angiogenesis through activating the IGFBP-1-integrinα5β1 pathway.These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP-1 inhibitors.

Diabetes and cancer: Epidemiological and biological links

The incidence of diabetes and cancer has increased significantly in recent years.Furthermore,there are many common risk factors for both diabetes and cancer,such as obesity,sedentary lifestyle,smoking,and ageing.A large body of epidemiological evidence has indicated that diabetes is considered as an independent risk factor for increased rates of heterogeneous types of cancer occurrence and death.The incidence and mortality of various types of cancer,such as pancreas,liver,colorectal,breast,endometrial,and bladder cancers,have a modest growth in diabetics.However,diabetes may work as a protective factor for prostate cancer.Although the underlying biological mechanisms have not been totally understood,studies have validated that insulin/insulin-like growth factor(IGF)axis(including insulin resistance,hyperinsulinemia,and IGF),hyperglycemia,inflammatory cytokines,and sex hormones provide good circumstances for cancer cell proliferation and metastasis.Insulin/IGF axis activates several metabolic and mitogenic signaling pathways;hyperglycemia provides energy for cancer cell growth;inflammatory cytokines influence cancer cell apoptosis.Thus,these three factors affect all types of cancer,while sex hormones only play important roles in breast cancer,endometrial cancer,and prostate cancer.This minireview consolidates and discusses the epidemiological and biological links between diabetes and various types of cancer.

Gut microbiota and diabetic kidney diseases: Pathogenesis and therapeutic perspectives

Diabetic kidney disease(DKD)is one of the major chronic complications of diabetes mellitus(DM),as well as a main cause of end-stage renal disease.Over the last few years,substantial research studies have revealed a contributory role of gut microbiota in the process of DM and DKD.Metabolites of gut microbiota like lipopolysaccharide,short-chain fatty acids,and trimethylamine N-oxide are key mediators of microbial–host crosstalk.However,the underlying mechanisms of how gut microbiota influences the onset and progression of DKD are relatively unknown.Besides,strategies to remodel the composition of gut microbiota or to reduce the metabolites of microbiota have been found recently,representing a new potential remedial target for DKD.In this minireview,we will address the possible contribution of the gut microbiota in the pathogenesis of DKD and its role as a therapeutic target.

VEGFR2 inhibition hampers breast cancer cell proliferation via enhanced mitochondrial biogenesis

Objective:Vascular endothelial growth factor(VEGF),apart from its predominant roles in angiogenesis,can enhance cancer cell proliferation,but its mechanisms remain elusive.The purpose of the present study was therefore to identify how VEGF regulates cancer cell proliferation.Methods:VEGF effects on cancer cell proliferation were investigated with the VEGF receptor 2 inhibitor,Ki8751,and the breast cancer cell lines,MCF-7 and MDA-MB-231,using flow cytometry,mass spectrometry,immunoblotting,and confocal microscopy.Data were analyzed using one-way analysis of variance followed by Tukey’s multiple comparison test.Results:VEGF blockade by Ki8751 significantly reduced cancer cell proliferation,and enhanced breast cancer cell apoptosis.Mass spectrometric analyses revealed that Ki8751 treatment significantly upregulated the expression of mitochondrial proteins,suggesting the involvement of mitochondrial biogenesis.Confocal microscopy and flow cytometric analyses showed that Ki8751 treatment robustly increased the mitochondrial masses of both cancer cells,induced endomitosis,and arrested cancer cells in the high aneuploid phase.VEGFR2 knockdown by sh RNAs showed similar effects to those of Ki8751,confirming the specificity of Ki8751 treatment.Enhanced mitochondrial biogenesis increased mitochondrial oxidative phosphorylation and stimulated reactive oxygen species(ROS)production,which induced cancer cell apoptosis.Furthermore,Ki8751 treatment downregulated the phosphorylation of Akt and PGC1α,and translocated PGC1αinto the nucleus.The PGC1αalterations increased mitochondrial transcription factor A(TFAM)expression and subsequently increased mitochondrial biogenesis.Conclusions:VEGF enhances cancer cell proliferation by decreasing Akt-PGC1α-TFAM signaling-mediated mitochondrial biogenesis,ROS production,and cell apoptosis.These findings suggested the anticancer potential of Ki8751 via increased mitochondrial biogenesis and ROS production.

Future options of anti-angiogenic cancer therapy

In human patients,drugs that block tumor vessel growth are widely used to treat a variety of cancer types.Many rigorous phase 3 clinical trials have demonstrated significant survival benefits;however,the addition of an anti-angiogenic component to conventional therapeutic modalities has generally produced modest survival benefits for cancer patients.Currently,it is unclear why these clinically available drugs targeting the same angiogenic pathways produce dissimilar effects in preclinical models and human patients.In this article,we discuss possible mechanisms of various anti-angiogenic drugs and the future development of optimized treatment regimens.

Children with type 1 diabetes in COVID-19 pandemic:Difficulties and solutions

Children/adolescents with type 1 diabetes(T1D)require holistic approach and continuous care.However,the coronavirus disease 2019(COVID-19)pandemic has made challenges for the T1D children and their caregivers,professionals,and the healthcare system.This minireview aims to consolidate and discuss the difficulties and solutions of children with type 1 diabetes in the COVID-19 pandemic.T1D has been the most common type of diabetes in children and adolescents and the last decades has seen a rapid increase in the prevalence of T1D in youths worldwide,which deserves a public concern particularly in the COVID-19 pandemic.As reported in previous studies,T1D is a risk factor related to severe cases,while the virus may induce new-onset diabetes and serious complications.Moreover,restriction strategies influence medical availability and lifestyle,impact glycemic control and compilation management,and thus pose stress on families and health providers of youths with T1D,especially on those with certain fragile conditions.Therefore,special treatment plans are required for children provided by caregivers and the local health system.Latest health tools such as improved medical devices and telemedicine service,as well as a combined support may benefit in this period.This minireview emphasises that continued medical access and support are required to prevent deteriorated condition of children and adolescents with diabetes throughout this pandemic.Therefore,strategies are supposed to be formulated to mitigate the difficulties and stress among this group,particularly in the most at-risk population.Proposed solutions in this minireview may help individuals and the health system to overcome these problems and help youths with T1D in better diabetes management during such emergency situations.

Perivascular localized cells commit erythropoiesis in PDGF-B-expressing solid tumors

Background:Tumors possess incessant growth features,and expansion of their masses demands sufficient oxygen supply by red blood cells(RBCs).In adult mammals,the bone marrow(BM)is the main organ regulating hematopoiesis with dedicated manners.Other than BM,extramedullary hematopoiesis is discovered in various pathophysiological settings.However,whether tumors can contribute to hematopoiesis is completely unknown.Accumulating evidence shows that,in the tumor microenvironment(TME),perivascular localized cells retain progenitor cell properties and can differentiate into other cells.Here,we sought to better understand whether and how perivascular localized pericytes in tumors manipulate hematopoiesis.Methods:To test if vascular cells can differentiate into RBCs,genome-wide expression profiling was performed using mouse-derived pericytes.Genetic tracing of perivascular localized cells employing NG2-CreERT2:R26R-tdTomato mouse strain was used to validate the findings in vivo.Fluorescence-activated cell sorting(FACS),single-cell sequencing,and colony formation assays were applied for biological studies.The production of erythroid differentiationspecific cytokine,erythropoietin(EPO),in TME was checked using quantitative polymerase chain reaction(qPCR),enzyme-linked immunosorbent assay(ELISA,magnetic-activated cell sorting and immunohistochemistry.To investigate BM function in tumor erythropoiesis,BM transplantation mouse models were employed.Results:Genome-wide expression profiling showed that in response to plateletderived growth factor subunit B(PDGF-B),neural/glial antigen 2(NG2)+perivascular localized cells exhibited hematopoietic stem and progenitor-like features and underwent differentiation towards the erythroid lineage.PDGF-B simultaneously targeted cancer-associated fibroblasts to produce high levels of EPO,a crucial hormone that necessitates erythropoiesis.FACS analysis using genetic tracing of NG2+cells in tumors defined the perivascular localized cell-derived subpopulation of hematopoietic cells.Single-cell sequencing and colony formation assays validated the fact that,upon PDGF-B stimulation,NG2+cells isolated from tumors acted as erythroblast progenitor cells,which were distinctive from the canonical BM hematopoietic stem cells.Conclusions:Our data provide a new concept of hematopoiesis within tumor tissues and novel mechanistic insights into perivascular localized cell-derived erythroid cells within TME.Targeting tumor hematopoiesis is a novel therapeutic concept for treating various cancers that may have profound impacts on cancer therapy.

COVID-19 associated liver injury:An updated review on the mechanisms and management of risk groups

Coronavirus disease 2019(COVID-19)has been associated with various liver injury cases worldwide.To date,the prevalence,mechanism,clinical manifestations,diagnosis,and outcomes of COVID-19-induced liver injury in various at-risk groups are not well defined.Liver injury may arise in the prevention and treatment of COVID-19 from direct causes such as viral infection and indirect causes such as systemic inflammation,hypoxic changes,and drugs that exacerbate any pre-existing liver disease.Studies have found that patients with underlying liver disease are at higher risk of COVID-19-induced liver injury.Certain condition of cardiopulmonary and metabolic diseases and vulnerable stages in lifespan may also involve in the development of COVID-19-induced liver injury.This review summarized studies of COVID-19-induced liver injury in different at-risk groups regarding their clinical characteristics,parameters,and correlations of the severity with these indicators and signs as well as potential treatment suggestions,to increase attention to physiological and pathological conditions and continue liver function monitoring as they can help in strengthening early supportive treatment and reducing the incidence of adverse outcomes.

Ubiquitin-specific peptidase 18 regulates the differentiation and function of Treg cells

Ubiquitin-specific peptidase 18(USP18)plays an important role in the development of CD11b^(+)dendritic cells(DCs)and Th17 cells,however,its role in the differentiation of other T cell subsets,especially in regulatory T(Treg)cells,is unknown.In our study,we used Usp18 K0 mice to study the loss of USP18 on the impact of Treg cell differentiation and function.We found that USP18 deficiency upregulates the differentiation of Treg cells,which may lead to disrupted homeostasis of peripheral T cells,and downregulates INF-y,IL-2,IL-17A producing CD4^(+)T cells and INF-γproducing CD8^(+)T cells.Mechanistically,we also found that the upre-gulation of Tregs is due to elevated expression of CD25 in Usp18 KO mice.Finally,we found that the suppressive function of Usp18 KO Tregs is downregulated.Altogether,our study was the first to identify the role of USP18 in Tregs differentiation and its suppressive function,which may provide a new reference for the treatment of Treg function in many autoimmune diseases,and USP18 can be used as a new therapeutic target for precise medical treatment.

血管周细胞在表达PDGF-B的实体瘤中诱发造血

背景与目的肿瘤组织持续生长需要红细胞充分供氧。在各类病理生理情况下,成年哺乳动物可在主要造血器官骨髓之外发生髓外造血。然而,肿瘤组织能否造血是完全未知的。大量证据表明,在肿瘤微环境中,血管周细胞保留了祖细胞特性,可分化成其他细胞类型。在此,我们探究了肿瘤组织内周细胞是否能调节造血及其作用机制。方法使用鼠源周细胞进行全基因组表达谱分析以测试周细胞是否可向红细胞分化。使用NG2-CreERT2:R26R-tdTomato小鼠对血管周细胞进行在体遗传示踪。使用流式细胞术、单细胞测序和集落形成实验对分选细胞进行鉴定。使用定量聚合酶链反应(quantitative polymerase chain reactionq,PCR)、酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)、细胞磁珠分选和免疫染色检查红细胞生成素(erythropoietin,EPO)的表达。构建骨髓移植小鼠模型以研究骨髓对肿瘤红细胞生成的影响。结果表达谱显示,在PDGF-B处理后,NG2+周细胞表现出造血干祖样特征,并向红系谱系分化。同时,PDGF-B可靶向癌症相关成纤维细胞以产生促红细胞生成的关键激素EPO。通过遗传示踪及流式分析,我们定义了NG2+细胞衍生的造血亚群。进一步的单细胞测序和集落形成实验结果显示,在PDGF-B刺激下,肿瘤中的NG2+细胞形成了与典型的骨髓造血干细胞不同的红系祖细胞。结论本研究提出了肿瘤组织内造血的新概念,并阐明肿瘤周细胞分化为红细胞的分子机制。靶向肿瘤造血作为一种新的治疗理念,可能对肿瘤治疗产生深远影响。

Inhibition of p53 inhibitors:progress,challenges and perspectives

p53 is the major tumor suppressor and the most frequently inactivated gene in cancer.p53 could be disabled either by mutations or by upstream negative regulators,including,but not limited to MDM2 and MDMX.p53 activity is required for the prevention as well as for the eradication of cancers.Restoration of p53 activity in mouse models leads to the suppression of established tumors of different origin.These findings provide a strong support to the anti-cancer strategy aimed for p53 reactivation.In this review,we summarize recent progress in the development of small molecules,which restore the tumor suppressor function of wild-type p53 and discuss their clinical advance.We discuss different aspects of p53-mediated response,which contribute to suppression of tumors,including non-canonical p53 activities,such as regulation of immune response.While targeting p53 inhibitors is a very promising approach,there are certain limitations and concerns that the intensive research and clinical evaluation of compounds will hopefully help to overcome.

A facile and general method for synthesis of antibiotic-free protein-based hydrogel:Wound dressing for the eradication of drug-resistant bacteria and biofilms

Antibacterial protein hydrogels are receiving increasing attention in the aspect of bacteria-infected-wound healing. However, bacterial drug resistance and biofilm infections lead to hard healing of wounds, thus the construction of biological agents that can overcome these issues is essential. Here, a simple and universal method to construct antibiotic-free protein hydrogel with excellent biocompatibility and superior antibacterial activity against drug-resistant bacteria and biofilms was developed. The green industrial microbicide tetrakis (hydroxymethyl) phosphonium sulfate (THPS) as cross-linking agent can be quickly cross-linked with model protein bovine serum albumin (BSA) to form antibacterial hydrogel through simple mixing without any other initiators, subsequently promoting drug-resistance bacteria-infected wound healing. This simple gelatinization strategy allows at least ten different proteins to form hydrogels (e.g. BSA, human serum albumin (HSA), egg albumin, chymotrypsin, trypsin, lysozyme, transferrin, myohemoglobin, hemoglobin, and phycocyanin) under the same conditions, showing prominent universality. Furthermore, drug-resistance bacteria and biofilm could be efficiently destroyed by the representative BSA hydrogel (B-Hydrogel) with antibacterial activity, overcoming biofilm-induced bacterial resistance. The in vivo study demonstrated that the B-Hydrogel as wound dressing can promote reepithelization to accelerate the healing of methicillin-resistant staphylococcus aureus (MRSA)-infected skin wounds without inducing significant side-effect. This readily accessible antibiotic-free protein-based hydrogel not only opens an avenue to provide a facile, feasible and general gelation strategy, but also exhibits promising application in hospital and community MRSA disinfection and treatment.

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.

Helicobacter pylori in ancient human remains

The bacterium Helicobacter pylori(H.pylori)infects the stomachs of approximately 50%of all humans.With its universal occurrence,high infectivity and virulence properties it is considered as one of the most severe global burdens of modern humankind.It has accompanied humans for many thousands of years,and due to its high genetic variability and vertical transmission,its population genetics reflects the history of human migrations.However,especially complex demographic events such as the colonisation of Europe cannot be resolved with population genetic analysis of modern H.pylori strains alone.This is best exemplified with the reconstruction of the 5300-year-old H.pylori genome of the Iceman,a European Copper Age mummy.Our analysis provided precious insights into the ancestry and evolution of the pathogen and underlined the high complexity of ancient European population history.In this review we will provide an overview on the molecular analysis of H.pylori in mummified human remains that were done so far and we will outline methodological advancements in the field of ancient DNA research that support the reconstruction and authentication of ancient H.pylori genome sequences.

Combination of bacterial-targeted delivery of gold-based AIEgen radiosensitizer for fluorescence-image-guided enhanced radio-immunotherapy against advanced cancer

Aggregation-Induced Emission luminogen(AIEgen)possess great potential in enhancing bioimaging-guided radiotherapeutic effects and radioimmunotherapy to improve the therapeutic effects of the tumor with good biosafety.Bacteria as a natural carrier have demonstrated great advantages in tumor targeted delivery and penetration to tumor.Herein,we construct a delivery platform that Salmonella VNP20009 act as an activated bacteria vector loaded the as-prepared novel AIEgen(TBTP-Au,VNP@TBTP-Au),which showed excellent radioimmunotherapy.VNP@TBTP-Au could target and retain AIEgen at the tumor site and deliver it into tumor cells specially,upon X-ray irradiation,much ROS was generated to induce immunogenic cell death via cGAS-STING signaling pathway to evoke immune response,thus achieving efficient radioimmunotherapy of the primary tumor with good biosafety.More importantly,the radioimmunotherapy with VNP@TBTP-Au formatted good abscopal effect that was able to suppress the growth of distant tumor.Our strategy pioneer a novel and simple strategy for the organic combination of bacteria and imaging-guided radiotherapy,and also pave the foundation for the combination with immunotherapy for better therapeutic effects.