Porcine epidemic diarrhea virus(PEDV),an enteric coronavirus,is widely spread worldwide and causes huge economic losses.The effective measure to control the viral infection is to develop ideal vaccines.Here,the collag...Porcine epidemic diarrhea virus(PEDV),an enteric coronavirus,is widely spread worldwide and causes huge economic losses.The effective measure to control the viral infection is to develop ideal vaccines.Here,the collagenase equivalent domain(COE)of PEDV was displayed on the surface of nanoparticles(NPs)in order to develop a newer,safer and more effective subunit vaccine against PEDV.The monomeric COE was displayed on the mi3 protein,which self-assembles into nanoparticles composed of 60 subunits,using the SpyTag/SpyCatcher system.The size,zeta potential,microstructure of the COE-mi3 virus-like particles(VLPs)were investigated.The COE-mi3 VLPs that possessed good security,stability and better retention can be more efficiently taken up by antigen-presenting cells(APCs)and help promote dendritic cells(DCs)maturation.Moreover,COE-mi3 VLPs could prominently improve specifc antibody levels including neutralizing antibodies(NAbs),and serum IgG,mucosal IgA.Moreover,COE-mi3 VLPs elicited more activation of CD4^(+)and CD8^(+)T cells and production of IFN-γand IL-4 cytokines.In particular,COE-mi3 VLPs is an effectual antigen-delivery platform to enhance germinal center(GC)B cell responses.This structure-based self-assembly of NP gives great potential to be developed as a new subunit vaccines attractive platform,and may also provide new ideas for the development of other enteric coronavirus vaccines.展开更多
Dengue fever remains a significant public health challenge in Malaysia,with its incidence continuing to rise despite existing control measures.Dengue,a disease caused by the dengue virus and transmitted by Aedes mosqu...Dengue fever remains a significant public health challenge in Malaysia,with its incidence continuing to rise despite existing control measures.Dengue,a disease caused by the dengue virus and transmitted by Aedes mosquitoes,places a substantial burden on healthcare systems and economic productivity.Despite efforts by the Malaysian government,including the release of Wolbachia-carrying Aedes aegypti mosquitoes in dengue hotspot areas since 2017,the problem persists.In 2023,Malaysia reported 123133 dengue cases,an 86.3%increase compared to 2022[1].This highlights the urgent need for more effective interventions,including the potential integration of dengue vaccines into routine immunization programs.Currently,two dengue vaccines have been licensed:Dengvaxia(CYD-TDV)by Sanofi Pasteur and Qdenga(TAK-003)by Takeda.Dengvaxia,the first licensed dengue vaccine,has significant limitations,as it increases the risk of hospitalization in dengue-naïve individuals due to antibody-dependent enhancement[2,3].As a result,it is only licensed for individuals with prior dengue infections,necessitating pre-vaccination screening.These constraints make it unsuitable for inclusion in Malaysia’s routine immunization programs.展开更多
Three plasmid expression vectors containing modified hepatitis B surface antigen (HBsAg) carrying pres epitopes were constructed. Transient expression after in vitro transfection in COS-M6 cells showed that under the ...Three plasmid expression vectors containing modified hepatitis B surface antigen (HBsAg) carrying pres epitopes were constructed. Transient expression after in vitro transfection in COS-M6 cells showed that under the transcriptional control of the human cytomegalovirus (CMV) immediate early promoter, fusion genes expressed the modified HBV envelope proteins which were efficiently secreted into culture medium and presented HBsAg, preS1 and preS2 antigenicity. DNA-based immunization with these plasmids carrying pres sequences induced anti-HBs antibody in BALB/c mice. The titers of anti-HBs antibody were higher than those appeared in mice immunized with plasmid carrying S gene only. DNA injection with plasmids containing preS1 sequences elicited also high titers of anti-preS1 antibody. Moreover, the antipreS1 antibodies were found to appear earlier than anti-HBs antibodies.展开更多
AIM To develop a safe and effective DNAvaccine for inducing humoral and cellularimmunological responses against hepatitis Bvirus surface antigen(HBsAg).METHODS BALB/c mice were inoculated withNV-HB/s,a recombinant pla...AIM To develop a safe and effective DNAvaccine for inducing humoral and cellularimmunological responses against hepatitis Bvirus surface antigen(HBsAg).METHODS BALB/c mice were inoculated withNV-HB/s,a recombinant plasmid that had beeninserted S gene of hepatitis B virus genome andcould express HBsAg in eukaryotes.HBsAgexpression was measured by ABC immunohis-tochemical assay,generation of anti-HBs byELISA and cytotoxic T lymphocyte(CTL),byMTT method,existence of vaccine DNA bySouthern blot hybridization and activation ofoncogene C-myc by in situ hybridization,RESULTS With NV-HB/s vaccination byintramuscular injection,anti-HBs was initiallypositive 2 weeks after inoculation while all micetested were HBsAg positive in the muscles.Thetiters and seroconversion rate of anti-HBs weresteadily increasing as time went on and weredose-dependent.All the mice inoculated with100 μg NV-HB/s were anti-HBs positive onemonth after inoculation,the titer was 1:1024 ormore.The humoral immune response was similarinduced by either intramuscular or intradermalinjection.CTL activities were much stronger(45.26%)in NV-HB/s DNA immunized mice as compared with those(only 6%)in plasma-derived HBsAg vaccine immunized mice.Twomonths after inoculation,all muscle sampleswere positive by Southern-blot hybridization forNV.HB/s DNA detection,but decreased to 25%and all were undetectable by in situhybridization after 6 months.No oncogene C-myc activation was found in the muscle ofinoculation site.CONCLUSION NV-HB/s could generatehumoral and cellular immunological responsesagainst HBsAg that had been safely expressed insitu by NV-HB/s vaccination.展开更多
DNA-based hydrogels are exceptional materials for biological applications because of their numerous advantages such as biodegradability,biocompatibility,hydrophilicity,super absorbency,porosity,and swelling.Among thes...DNA-based hydrogels are exceptional materials for biological applications because of their numerous advantages such as biodegradability,biocompatibility,hydrophilicity,super absorbency,porosity,and swelling.Among these advantages,the ability of DNA-based hydrogels to respond to specific physical and chemical triggers and undergo reversible phase transitions has garnered significant attention in the fields of disease diagnosis(biosensors)and treatment(drug delivery).This article focuses on the recent advancements in the research of DNA-based hydrogels and discusses the different types of these hydrogels,the synthetic methods,their unique properties,and their applications in biosensors and drug delivery.The types of DNA hydrogels are categorized based on their building blocks,and the process of synthesis as well as the unique characteristics of DNA-based hydrogels are described.Then,DNA-based responsive hydrogels utilized as intelligent materials for the development of biosensors are reviewed.Furthermore,this article also presents the current status of DNA-based responsive hydrogels in drug delivery for cancer treatment,wound healing,and other therapeutic applications.Ultimately,this paper discusses the current challenges in expanding the practical application of DNA-based hydrogels.展开更多
The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first i...The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.展开更多
Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain met...Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.展开更多
Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. ...Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. This study was conducted to identify key factors that need to be considered when deciding to introduce a new vaccine and current challenges faced by low and middle income countries using Malawi as an example. Methodology: The study employed a desk review approach, examining published literature from various sources such as PubMed, Medline, and Google Scholar. Policy documents from organizations like the World Health Organization, GAVI the Alliance, and the Ministry of Health for Malawi were also included. A total of 99 articles and documents on new vaccine introduction, challenges of immunization, policy documents in immunization and health systems strengthening were included. The review focused on addressing five key areas critical to new vaccine introduction namely: the need for a vaccine, availability of the vaccine, safety and effectiveness of the vaccine, demand for the vaccine, and the prudent use of public or private funds. Results: Malawi considered the burden of cervical cancer and the significance of malaria in the country when introducing the HPV and malaria vaccines. The country opted for vaccines that can be handled by the cold chain capacity and available human resources. Despite that malaria vaccine and Typhoid Conjugate Vaccine trials were done in country, there are limited vaccine safety and efficacy trials conducted in Malawi, leading to a reliance on WHO-prequalified vaccines. Demand for newly introduced vaccines varied, with high demand for Oral Cholera Vaccine during a cholera outbreak, while demand for COVID-19 vaccines decreased over time. Although cost-effectiveness studies were limited in the country, 2 studies indicated that Typhoid Conjugate Vaccine and malaria vaccine would be cost effective. All these have been implemented despite having challenges like lack of accurate surveillance data, inadequate cold chain capacity, limited safety and efficacy vaccine clinical trials, political influence, and limited funding. Conclusion: Despite several challenges Malawi set a good example of the careful considerations required before introducing a new vaccine. The process involves data review, priority setting, precise planning, and consultation with stakeholders. Low-income countries should invest in vaccine safety, efficacy, and cost-effectiveness trials.展开更多
BACKGROUND Immunization is a key component of primary health care and an indisputable human right.Vaccines are critical to the prevention and control of infectious disease outbreaks.The coronavirus disease 2019(COVID-...BACKGROUND Immunization is a key component of primary health care and an indisputable human right.Vaccines are critical to the prevention and control of infectious disease outbreaks.The coronavirus disease 2019(COVID-19)pandemic and associated disruptions over the past two years have strained the health systems,with many children missing out on essential childhood vaccines.AIM To evaluate the immunization coverage among 12-23-month-old children in the rural areas of Community Health Centre(CHC)Dighal and to determine the factors influencing the existing immunization coverage.METHODS A coverage evaluation survey was conducted according to the 30-cluster sampling technique,which is the standard methodology for such surveys devised by World Health Organization.A total of 300 children aged 12-23 months were included,whose immunization details were noted from their immunization cards.RESULTS Full immunization rate was noted in 86.7%of the children,with partial and non-immunized children accounting for 9%and 4.3%respectively.The full immunization dropout rate was 4.2%.The common reasons for partial or non-immunization were family problem including illness of mother,vaccine not being available and child being ill.Place of birth(P=0.014)and availability of immunization card(P<0.001)were significant predictors of the immunization status.Since the study was conducted in 2020/2021,health services were disrupted due to the COVID-19 lockdown.CONCLUSION Due to the coverage being higher than the national average,it was concluded that the immunization coverage was optimal and not affected by the COVID-19 pandemic.展开更多
BACKGROUND Patients with diabetes mellitus(DM)are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications.The Centers for Disease ...BACKGROUND Patients with diabetes mellitus(DM)are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications.The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices(CDC/ACIP)issued immunization recommendations to protect this patient population.AIM To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate.METHODS An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey.RESULTS Among participants,10.01%(n=71)had never received any vaccine,while 85.89%(n=609)received at least one dose of the coronavirus disease 2019(COVID-19)vaccine,and 34.83%(n=247)had received the annual influenza vaccine.Only 2.96%(n=21),2.11%(n=15),and 1.12%(n=8)received herpes zoster,tetanus,diphtheria,and pertussis(Tdap),and human papillomavirus(HPV)vaccines,respectively.For patients with DM in Saudi Arabia,the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,site of care,income level,DM-related hospitalization history,residency site,hemoglobin A1c(HbA1c)level,and health sector type can significantly influence the vaccination rate in patients with DM.Among non-vaccinated patients with DM,the most reported barriers were lack of knowledge and fear of side effects.This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM.CONCLUSION In Saudi Arabia,patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,the site of care,income level,DM-related hospitalization history,residency site,HbA1c level,and health sector type can significantly influence the vaccination rate in patients with DM.展开更多
Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic dat...Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.展开更多
Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)re...Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.展开更多
The immune system is involved in many age-related pathological changes,also plays an important role in tissue regeneration after injury.But no immune involvement has been discussed regarding cataract since it is presu...The immune system is involved in many age-related pathological changes,also plays an important role in tissue regeneration after injury.But no immune involvement has been discussed regarding cataract since it is presumed that lens has no source of immune cells as an avascular zone.Latest research has challenged the longstanding view of the lens as an immune-privileged tissue,revealing the presence of resident immune cells and active immune responses within the lens.Thus,we summarized the immune involvement in maintaining lens homeostasis,which may be a deleterious role in the induction of lens opacification if inappropriately activated.Furthermore,bioengineer-based immunomodulatory therapies to fine-tune the micro immune environment within lens may be future strategies for in situ lens regeneration,as a novel treatment for cataract.展开更多
BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact mo...BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.展开更多
The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation fa...The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation factor OseIF5A4,in rice immunity.OsBBI1 interacts with OseIF5A4 and other four members of the OseIF5A family.The RING domain in OsBBI1 and the eIF-5a domain in OseIF5A4 are critical for the OsBBI1-OseIF5A4 interaction.OsBBI1 ubiquitinates OseIF5A4 and mediates its degradation in vitro and in vivo.Moreover,the expression of OseIF5A4 was upregulated during early stage of compatible interaction but downregulated in incompatible interaction between rice and M.oryzae.Knockout of OseIF5A4 enhances rice immunity against M.oryzae and Xanthomonas oryzae pv.oryzae,boosts pattern-triggered immune responses,and strengthens pathogen-induced defense responses(e.g.,expression of defense genes,accumulation of reactive oxygen species and reinforcement of cell wall).However,overexpression of OseIF5A4 attenuates rice immunity and immune responses.These results demonstrate that OseIF5A4,a substrate of the immunity-associated E3 ligase OsBBI1,negatively regulates rice immunity against M.oryzae and X.oryzae pv.oryzae through modulating pathogen-induced defense responses,highlighting the importance of the protein translational machinery in rice immunity.展开更多
Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in th...Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.展开更多
Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal canc...Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.展开更多
The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple c...The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.展开更多
BACKGROUND Patients with early-stage hepatocellular carcinoma(HCC)generally have good survival rates following surgical resection.However,a subset of these patients experience recurrence within five years post-surgery...BACKGROUND Patients with early-stage hepatocellular carcinoma(HCC)generally have good survival rates following surgical resection.However,a subset of these patients experience recurrence within five years post-surgery.AIM To develop predictive models utilizing machine learning(ML)methods to detect early-stage patients at a high risk of mortality.METHODS Eight hundred and eight patients with HCC at Beijing Ditan Hospital were randomly allocated to training and validation cohorts in a 2:1 ratio.Prognostic models were generated using random survival forests and artificial neural networks(ANNs).These ML models were compared with other classic HCC scoring systems.A decision-tree model was established to validate the contri-bution of immune-inflammatory indicators to the long-term outlook of patients with early-stage HCC.RESULTS Immune-inflammatory markers,albumin-bilirubin scores,alpha-fetoprotein,tumor size,and International Normalized Ratio were closely associated with the 5-year survival rates.Among various predictive models,the ANN model gene-rated using these indicators through ML algorithms exhibited superior perfor-mance,with a 5-year area under the curve(AUC)of 0.85(95%CI:0.82-0.88).In the validation cohort,the 5-year AUC was 0.82(95%CI:0.74-0.85).According to the ANN model,patients were classified into high-risk and low-risk groups,with an overall survival hazard ratio of 7.98(95%CI:5.85-10.93,P<0.0001)between the two cohorts.INTRODUCTION Hepatocellular carcinoma(HCC)is one of the six most prevalent cancers[1]and the third leading cause of cancer-related mortality[2].China has some of the highest incidence and mortality rates for liver cancer,accounting for half of global cases[3,4].The Barcelona Clinic Liver Cancer(BCLC)Staging System is the most widely used framework for diagnosing and treating HCC[5].The optimal candidates for surgical treatment are those with early-stage HCC,classified as BCLC stage 0 or A.Patients with early-stage liver cancer typically have a better prognosis after surgical resection,achieving a 5-year survival rate of 60%-70%[6].However,the high postoperative recurrence rates of HCC remain a major obstacle to long-term efficacy.To improve the prognosis of patients with early-stage HCC,it is necessary to develop models that can identify those with poor prognoses,enabling stratified and personalized treatment and follow-up strategies.Chronic inflammation is linked to the development and advancement of tumors[7].Recently,peripheral blood immune indicators,such as neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and lymphocyte-to-monocyte ratio(LMR),have garnered extensive attention and have been used to predict survival in various tumors and inflammation-related diseases[8-10].However,the relationship between these combinations of immune markers and the outcomes in patients with early-stage HCC require further investigation.Machine learning(ML)algorithms are capable of handling large and complex datasets,generating more accurate and personalized predictions through unique training algorithms that better manage nonlinear statistical relationships than traditional analytical methods.Commonly used ML models include artificial neural networks(ANNs)and random survival forests(RSFs),which have shown satisfactory accuracy in prognostic predictions across various cancers and other diseases[11-13].ANNs have performed well in identifying the progression from liver cirrhosis to HCC and predicting overall survival(OS)in patients with HCC[14,15].However,no studies have confirmed the ability of ML models to predict post-surgical survival in patients with early-stage HCC.Through ML,a better understanding of the risk factors for early-stage HCC prognosis can be achieved.This aids in surgical decision-making,identifying patients at a high risk of mortality,and selecting subsequent treatment strategies.In this study,we aimed to establish a 5-year prognostic model for patients with early-stage HCC after surgical resection,based on ML and systemic immune-inflammatory indicators.This model seeks to improve the early monitoring of high-risk patients and provide personalized treatment plans.展开更多
Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to pro...Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.展开更多
基金supported by the Major Scientific and Technological Project of the Henan Province,China(221100110600)the Beijing Life Science Academy,China(2024500CA0010)+1 种基金the Major Program of National Natural Science Foundation of China(32192452)the Chinese Postdoctoral Science Foundation(2023M743209)。
文摘Porcine epidemic diarrhea virus(PEDV),an enteric coronavirus,is widely spread worldwide and causes huge economic losses.The effective measure to control the viral infection is to develop ideal vaccines.Here,the collagenase equivalent domain(COE)of PEDV was displayed on the surface of nanoparticles(NPs)in order to develop a newer,safer and more effective subunit vaccine against PEDV.The monomeric COE was displayed on the mi3 protein,which self-assembles into nanoparticles composed of 60 subunits,using the SpyTag/SpyCatcher system.The size,zeta potential,microstructure of the COE-mi3 virus-like particles(VLPs)were investigated.The COE-mi3 VLPs that possessed good security,stability and better retention can be more efficiently taken up by antigen-presenting cells(APCs)and help promote dendritic cells(DCs)maturation.Moreover,COE-mi3 VLPs could prominently improve specifc antibody levels including neutralizing antibodies(NAbs),and serum IgG,mucosal IgA.Moreover,COE-mi3 VLPs elicited more activation of CD4^(+)and CD8^(+)T cells and production of IFN-γand IL-4 cytokines.In particular,COE-mi3 VLPs is an effectual antigen-delivery platform to enhance germinal center(GC)B cell responses.This structure-based self-assembly of NP gives great potential to be developed as a new subunit vaccines attractive platform,and may also provide new ideas for the development of other enteric coronavirus vaccines.
文摘Dengue fever remains a significant public health challenge in Malaysia,with its incidence continuing to rise despite existing control measures.Dengue,a disease caused by the dengue virus and transmitted by Aedes mosquitoes,places a substantial burden on healthcare systems and economic productivity.Despite efforts by the Malaysian government,including the release of Wolbachia-carrying Aedes aegypti mosquitoes in dengue hotspot areas since 2017,the problem persists.In 2023,Malaysia reported 123133 dengue cases,an 86.3%increase compared to 2022[1].This highlights the urgent need for more effective interventions,including the potential integration of dengue vaccines into routine immunization programs.Currently,two dengue vaccines have been licensed:Dengvaxia(CYD-TDV)by Sanofi Pasteur and Qdenga(TAK-003)by Takeda.Dengvaxia,the first licensed dengue vaccine,has significant limitations,as it increases the risk of hospitalization in dengue-naïve individuals due to antibody-dependent enhancement[2,3].As a result,it is only licensed for individuals with prior dengue infections,necessitating pre-vaccination screening.These constraints make it unsuitable for inclusion in Malaysia’s routine immunization programs.
文摘Three plasmid expression vectors containing modified hepatitis B surface antigen (HBsAg) carrying pres epitopes were constructed. Transient expression after in vitro transfection in COS-M6 cells showed that under the transcriptional control of the human cytomegalovirus (CMV) immediate early promoter, fusion genes expressed the modified HBV envelope proteins which were efficiently secreted into culture medium and presented HBsAg, preS1 and preS2 antigenicity. DNA-based immunization with these plasmids carrying pres sequences induced anti-HBs antibody in BALB/c mice. The titers of anti-HBs antibody were higher than those appeared in mice immunized with plasmid carrying S gene only. DNA injection with plasmids containing preS1 sequences elicited also high titers of anti-preS1 antibody. Moreover, the antipreS1 antibodies were found to appear earlier than anti-HBs antibodies.
基金the National Natural Science Foundation of China,No.39670670
文摘AIM To develop a safe and effective DNAvaccine for inducing humoral and cellularimmunological responses against hepatitis Bvirus surface antigen(HBsAg).METHODS BALB/c mice were inoculated withNV-HB/s,a recombinant plasmid that had beeninserted S gene of hepatitis B virus genome andcould express HBsAg in eukaryotes.HBsAgexpression was measured by ABC immunohis-tochemical assay,generation of anti-HBs byELISA and cytotoxic T lymphocyte(CTL),byMTT method,existence of vaccine DNA bySouthern blot hybridization and activation ofoncogene C-myc by in situ hybridization,RESULTS With NV-HB/s vaccination byintramuscular injection,anti-HBs was initiallypositive 2 weeks after inoculation while all micetested were HBsAg positive in the muscles.Thetiters and seroconversion rate of anti-HBs weresteadily increasing as time went on and weredose-dependent.All the mice inoculated with100 μg NV-HB/s were anti-HBs positive onemonth after inoculation,the titer was 1:1024 ormore.The humoral immune response was similarinduced by either intramuscular or intradermalinjection.CTL activities were much stronger(45.26%)in NV-HB/s DNA immunized mice as compared with those(only 6%)in plasma-derived HBsAg vaccine immunized mice.Twomonths after inoculation,all muscle sampleswere positive by Southern-blot hybridization forNV.HB/s DNA detection,but decreased to 25%and all were undetectable by in situhybridization after 6 months.No oncogene C-myc activation was found in the muscle ofinoculation site.CONCLUSION NV-HB/s could generatehumoral and cellular immunological responsesagainst HBsAg that had been safely expressed insitu by NV-HB/s vaccination.
基金financially supported by the National Natural Science Foundation of China(No.21804014)the Natural Science Foundation of Chongqing Science&Technology Commission(No.2023jcyjA3529)+1 种基金the Science and Technology Research Program of Chongqing Municipal Education Commission(No.KJQN202200832)Construction of Graduate Joint Training Base of Chongqing Municipal Education Commission(No.yjd223005)。
文摘DNA-based hydrogels are exceptional materials for biological applications because of their numerous advantages such as biodegradability,biocompatibility,hydrophilicity,super absorbency,porosity,and swelling.Among these advantages,the ability of DNA-based hydrogels to respond to specific physical and chemical triggers and undergo reversible phase transitions has garnered significant attention in the fields of disease diagnosis(biosensors)and treatment(drug delivery).This article focuses on the recent advancements in the research of DNA-based hydrogels and discusses the different types of these hydrogels,the synthetic methods,their unique properties,and their applications in biosensors and drug delivery.The types of DNA hydrogels are categorized based on their building blocks,and the process of synthesis as well as the unique characteristics of DNA-based hydrogels are described.Then,DNA-based responsive hydrogels utilized as intelligent materials for the development of biosensors are reviewed.Furthermore,this article also presents the current status of DNA-based responsive hydrogels in drug delivery for cancer treatment,wound healing,and other therapeutic applications.Ultimately,this paper discusses the current challenges in expanding the practical application of DNA-based hydrogels.
基金supported by the National Natural Science Foundation of China,Nos.82104560(to CL),U21A20400(to QW)the Natural Science Foundation of Beijing,No.7232279(to XW)the Project of Beijing University of Chinese Medicine,No.2022-JYB-JBZR-004(to XW)。
文摘The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue regeneration.As the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the condition.After an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune response.This review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic stroke.We found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic effect.Th1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain injury.Th2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain injury.Immune interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke patients.Clinical trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic stroke.However,such studies have been relatively infrequent,and clinical experience is still insufficient.In summary,in ischemic stroke,T cell subsets and activated microglia act synergistically to regulate inflammatory progression,mainly by secreting inflammatory factors.In the future,a key research direction for ischemic stroke treatment could be rooted in the enhancement of anti-inflammatory factor secretion by promoting the generation of Th2 and Treg cells,along with the activation of M2-type microglia.These approaches may alleviate neuroinflammation and facilitate the repair of neural tissues.
基金supported by the National Natural Science Foundation of China, No.82274616the Key Laboratory Project for General Universities in Guangdong Province, No.2019KSYS005Guangdong Province Science and Technology Plan International Cooperation Project, No.2020A0505100052 (all to QW)。
文摘Meningeal lymphatic vessels form a relationship between the nervous system and periphery, which is relevant in both health and disease. Meningeal lymphatic vessels not only play a key role in the drainage of brain metabolites but also contribute to antigen delivery and immune cell activation. The advent of novel genomic technologies has enabled rapid progress in the characterization of myeloid and lymphoid cells and their interactions with meningeal lymphatic vessels within the central nervous system. In this review, we provide an overview of the multifaceted roles of meningeal lymphatic vessels within the context of the central nervous system immune network, highlighting recent discoveries on the immunological niche provided by meningeal lymphatic vessels. Furthermore, we delve into the mechanisms of crosstalk between meningeal lymphatic vessels and immune cells in the central nervous system under both homeostatic conditions and neurodegenerative diseases, discussing how these interactions shape the pathological outcomes. Regulation of meningeal lymphatic vessel function and structure can influence lymphatic drainage, cerebrospinal fluid-borne immune modulators, and immune cell populations in aging and neurodegenerative disorders, thereby playing a key role in shaping meningeal and brain parenchyma immunity.
文摘Introduction: As new vaccines become available, countries must assess the relevance to introduce them into their vaccination schedules. Malawi has recently introduced several new vaccines and plans to introduce more. This study was conducted to identify key factors that need to be considered when deciding to introduce a new vaccine and current challenges faced by low and middle income countries using Malawi as an example. Methodology: The study employed a desk review approach, examining published literature from various sources such as PubMed, Medline, and Google Scholar. Policy documents from organizations like the World Health Organization, GAVI the Alliance, and the Ministry of Health for Malawi were also included. A total of 99 articles and documents on new vaccine introduction, challenges of immunization, policy documents in immunization and health systems strengthening were included. The review focused on addressing five key areas critical to new vaccine introduction namely: the need for a vaccine, availability of the vaccine, safety and effectiveness of the vaccine, demand for the vaccine, and the prudent use of public or private funds. Results: Malawi considered the burden of cervical cancer and the significance of malaria in the country when introducing the HPV and malaria vaccines. The country opted for vaccines that can be handled by the cold chain capacity and available human resources. Despite that malaria vaccine and Typhoid Conjugate Vaccine trials were done in country, there are limited vaccine safety and efficacy trials conducted in Malawi, leading to a reliance on WHO-prequalified vaccines. Demand for newly introduced vaccines varied, with high demand for Oral Cholera Vaccine during a cholera outbreak, while demand for COVID-19 vaccines decreased over time. Although cost-effectiveness studies were limited in the country, 2 studies indicated that Typhoid Conjugate Vaccine and malaria vaccine would be cost effective. All these have been implemented despite having challenges like lack of accurate surveillance data, inadequate cold chain capacity, limited safety and efficacy vaccine clinical trials, political influence, and limited funding. Conclusion: Despite several challenges Malawi set a good example of the careful considerations required before introducing a new vaccine. The process involves data review, priority setting, precise planning, and consultation with stakeholders. Low-income countries should invest in vaccine safety, efficacy, and cost-effectiveness trials.
文摘BACKGROUND Immunization is a key component of primary health care and an indisputable human right.Vaccines are critical to the prevention and control of infectious disease outbreaks.The coronavirus disease 2019(COVID-19)pandemic and associated disruptions over the past two years have strained the health systems,with many children missing out on essential childhood vaccines.AIM To evaluate the immunization coverage among 12-23-month-old children in the rural areas of Community Health Centre(CHC)Dighal and to determine the factors influencing the existing immunization coverage.METHODS A coverage evaluation survey was conducted according to the 30-cluster sampling technique,which is the standard methodology for such surveys devised by World Health Organization.A total of 300 children aged 12-23 months were included,whose immunization details were noted from their immunization cards.RESULTS Full immunization rate was noted in 86.7%of the children,with partial and non-immunized children accounting for 9%and 4.3%respectively.The full immunization dropout rate was 4.2%.The common reasons for partial or non-immunization were family problem including illness of mother,vaccine not being available and child being ill.Place of birth(P=0.014)and availability of immunization card(P<0.001)were significant predictors of the immunization status.Since the study was conducted in 2020/2021,health services were disrupted due to the COVID-19 lockdown.CONCLUSION Due to the coverage being higher than the national average,it was concluded that the immunization coverage was optimal and not affected by the COVID-19 pandemic.
文摘BACKGROUND Patients with diabetes mellitus(DM)are predisposed to an increased risk of infection signifying the importance of vaccination to protect against its potentially severe complications.The Centers for Disease Control and Prevention/Advisory Committee on Immunization Practices(CDC/ACIP)issued immunization recommendations to protect this patient population.AIM To assess the adherence of patients with DM to the CDC/ACIP immunization recommendations in Saudi Arabia and to identify the factors associated with the vaccine adherence rate.METHODS An observational retrospective study conducted in 2023 was used to collect data on the vaccination records from 13 diabetes care centers in Saudi Arabia with 1000 eligible patients in phase I with data collected through chart review and 709 patients in phase II through online survey.RESULTS Among participants,10.01%(n=71)had never received any vaccine,while 85.89%(n=609)received at least one dose of the coronavirus disease 2019(COVID-19)vaccine,and 34.83%(n=247)had received the annual influenza vaccine.Only 2.96%(n=21),2.11%(n=15),and 1.12%(n=8)received herpes zoster,tetanus,diphtheria,and pertussis(Tdap),and human papillomavirus(HPV)vaccines,respectively.For patients with DM in Saudi Arabia,the rate of vaccination for annual influenza and COVID-19 vaccines was higher compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,site of care,income level,DM-related hospitalization history,residency site,hemoglobin A1c(HbA1c)level,and health sector type can significantly influence the vaccination rate in patients with DM.Among non-vaccinated patients with DM,the most reported barriers were lack of knowledge and fear of side effects.This signifies the need for large-scale research in this area to identify additional factors that might facilitate adherence to CDC/ACIP vaccine recommendations in patients with DM.CONCLUSION In Saudi Arabia,patients with DM showed higher vaccination rates for annual influenza and COVID-19 vaccines compared to other vaccinations such as herpes zoster,Tdap,pneumococcal,and HPV.Factors such as vaccine recommendations provided by family physicians or specialists,the site of care,income level,DM-related hospitalization history,residency site,HbA1c level,and health sector type can significantly influence the vaccination rate in patients with DM.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82272008)The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2021KJ194)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.
基金supported by the National Natural Science Foundation of China(82204634,82174047,81622051)the Zhejiang Provincial Natural Science Foundation of China(LQ22H280010)the Foundation of Zhejiang Chinese Medical University(2021ZR03).
文摘Drug delivery systems(DDS)have recently emerged as a promising approach for the unique advantages of drug protection and targeted delivery.However,the access of nanoparticles/drugs to the central nervous system(CNS)remains a challenge mainly due to the obstruction from brain barriers.Immune cells infiltrating the CNS in the pathological state have inspired the development of strategies for CNS foundation drug delivery.Herein,we outline the three major brain barriers in the CNS and the mechanisms by which immune cells migrate across the blood–brain barrier.We subsequently review biomimetic strategies utilizing immune cell-based nanoparticles for the delivery of nanoparticles/drugs to the CNS,as well as recent progress in rationally engineering immune cell-based DDS for CNS diseases.Finally,we discuss the challenges and opportunities of immune cell-based DDS in CNS diseases to promote their clinical development.
基金Supported by the National Natural Science Foundation of China(No.82271063No.82471054)Central Guidance for Local Scientific and Technological Development Funding Projects(No.2024ZY01057).
文摘The immune system is involved in many age-related pathological changes,also plays an important role in tissue regeneration after injury.But no immune involvement has been discussed regarding cataract since it is presumed that lens has no source of immune cells as an avascular zone.Latest research has challenged the longstanding view of the lens as an immune-privileged tissue,revealing the presence of resident immune cells and active immune responses within the lens.Thus,we summarized the immune involvement in maintaining lens homeostasis,which may be a deleterious role in the induction of lens opacification if inappropriately activated.Furthermore,bioengineer-based immunomodulatory therapies to fine-tune the micro immune environment within lens may be future strategies for in situ lens regeneration,as a novel treatment for cataract.
基金Supported by the Haihe Laboratory of Cell Ecosystem Innovation Fund,No.22HHXBJC00001the Key Discipline Special Project of Tianjin Municipal Health Commission,No.TJWJ2022XK016.
文摘BACKGROUND Hepatocellular carcinoma(HCC)has been a pervasive malignancy throughout the world with elevated mortality.Efficient therapeutic targets are beneficial to treat and predict the disease.Currently,the exact molecular mechanisms leading to the progression of HCC are still unclear.Research has shown that the microRNA-142-3p level decreases in HCC,whereas bioinformatics analysis of the cancer genome atlas database shows the ASH1L expression increased among liver tumor tissues.In this paper,we will explore the effects and mechanisms of microRNA-142-3p and ASH1L affect the prognosis of HCC patients and HCC cell bioactivity,and the association between them.AIM To investigate the effects and mechanisms of microRNA-142-3p and ASH1L on the HCC cell bioactivity and prognosis of HCC patients.METHODS In this study,we grouped HCC patients according to their immunohistochemistry results of ASH1L with pathological tissues,and retrospectively analyzed the prognosis of HCC patients.Furthermore,explored the roles and mechanisms of microRNA-142-3p and ASH1L by cellular and animal experiments,which involved the following experimental methods:Immunohistochemical staining,western blot,quantitative real-time-polymerase chain reaction,flow cytometric analysis,tumor xenografts in nude mice,etc.The statistical methods involved in this study contained t-test,one-way analysis of variance,theχ^(2)test,the Kaplan-Meier approach and the log-rank test.RESULTS In this study,we found that HCC patients with high expression of ASH1L possess a more recurrence rate as well as a decreased overall survival rate.ASH1L promotes the tumorigenicity of HCC and microRNA-142-3p exhibits reduced expression in HCC tissues and interacts with ASH1L through targeting the ASH1L 3′untranslated region.Furthermore,microRNA-142-3p promotes apoptosis and inhibits proliferation,invasion,and migration of HCC cell lines in vitro via ASH1L.For the exploration mechanism,we found ASH1L may promote an immunosuppressive microenvironment in HCC and ASH1L affects the expression of the cell junction protein zonula occludens-1,which is potentially relevant to the immune system.CONCLUSION Loss function of microRNA-142-3p induces cancer progression and immune evasion through upregulation of ASH1L in HCC.Both microRNA-142-3p and ASH1L can feature as new biomarker for HCC in the future.
基金supported by grants from the National Natural Science Foundation of China(32072403 and 31871945)the National Key Research and Development Program of China(2016YFD0100600).
文摘The RING-type E3 ligase OsBBI1 regulates rice resistance against Magnaporthe oryzae through modifying cell wall defenses.In this study,we report the function of an OsBBI1 substrate,eukaryotic translation initiation factor OseIF5A4,in rice immunity.OsBBI1 interacts with OseIF5A4 and other four members of the OseIF5A family.The RING domain in OsBBI1 and the eIF-5a domain in OseIF5A4 are critical for the OsBBI1-OseIF5A4 interaction.OsBBI1 ubiquitinates OseIF5A4 and mediates its degradation in vitro and in vivo.Moreover,the expression of OseIF5A4 was upregulated during early stage of compatible interaction but downregulated in incompatible interaction between rice and M.oryzae.Knockout of OseIF5A4 enhances rice immunity against M.oryzae and Xanthomonas oryzae pv.oryzae,boosts pattern-triggered immune responses,and strengthens pathogen-induced defense responses(e.g.,expression of defense genes,accumulation of reactive oxygen species and reinforcement of cell wall).However,overexpression of OseIF5A4 attenuates rice immunity and immune responses.These results demonstrate that OseIF5A4,a substrate of the immunity-associated E3 ligase OsBBI1,negatively regulates rice immunity against M.oryzae and X.oryzae pv.oryzae through modulating pathogen-induced defense responses,highlighting the importance of the protein translational machinery in rice immunity.
基金supported by the National Natural Science Foundation of China(Grant No.:82272749)the Natural Science Foundation of Liaoning Province,China(Grant No.:2022-MS-190).
文摘Mitochondria play a crucial role as organelles,managing several physiological processes such as redox balance,cell metabolism,and energy synthesis.Initially,the assumption was that mitochondria primarily resided in the host cells and could exclusively transmit from oocytes to offspring by a mechanism known as vertical inheritance of mitochondria.Recent scholarly works,however,suggest that certain cell types transmit their mitochondria to other developmental cell types via a mechanism referred to as intercellular or horizontal mitochondrial transfer.This review details the process of which mitochondria are transferred across cells and explains the impact of mitochondrial transfer between cells on the efficacy and functionality of cancer cells in various cancer forms.Specifically,we review the role of mitochondria transfer in regulating cellular metabolism restoration,excess reactive oxygen species(ROS)generation,proliferation,invasion,metastasis,mitophagy activation,mitochondrial DNA(mtDNA)inheritance,immune system modulation and therapeutic resistance in cancer.Additionally,we highlight the possibility of using intercellular mitochondria transfer as a therapeutic approach to treat cancer and enhance the efficacy of cancer treatments.
基金supported by the NationalNatural Science Foundation of China(no.32360888)the Jiangxi Students’Platform for Innovation and Entrepreneurship Training Program(no.202411843023).
文摘Background:Heat shock protein B8(HSPB8)is implicated in autophagy,and its aberrant expression has been linked to both the ini-tiation and progression of tumors.However,the role and function of HSPB8 in colorectal cancer(CRC)and across multiple cancer types remain unclear.This study aimed to map the transcriptome of autophagy-related genes in CRC and to conduct a pan-cancer analysis of HSPB8 as both a prognostic and immunological biomarker.Methods:We performed bioinformatics analyses on GSE113513 and GSE74602 to identify differentially expressed genes(DEGs)in CRC.These DEGs were then compared with autophagy-related genes to identify critical overlapping genes.The Kaplan-Meier plotter was used to verify the ex-pression of autophagy-linked DEGs and evaluate its prognostic value.The protein expression of Hub gene in CRC was analyzed using the Human Protein Atlas database.The cBioPortal was used to analyze the type and frequency of Hub gene mutations.The TIMER(Tumor Immune Estimation Resource)database was used to study the correlation between HSPB8 and immune infiltration in CRC.Results:In total,825 DEGs were identified,including 8 autophagy-linked DEGs:ATIC,MYC,HSPB8,TNFSF10,BCL2,TP53INP2,ITPR1,and NKX2-3.Survival analysis showed that increased HSPB8 expression significantly correlates with poor prognosis in patients with CRC(p<0.05).HSPB8 was also found to be differentially expressed in various cancer types,correlating with both prognosis and immune infiltration.Further,changes in HSPB8 methylation and phosphorylation status were observed across several cancers,suggesting potential regulatory mechanisms.Therefore,HSPB8 may serve as a crucial prognostic and immunological biomarker in CRC and other cancers.Conclusions:This study provides new insights into the role of autophagy-related genes in cancer progression and highlights HSPB8 as a potential target for cancer diagnostics and therapy.
基金supported by Research Program for Agricultural Science and Technology Development,Republic of Korea(PJ01570601)the Fellowship Program(PJ01661001)of the National Institute of Agricultural Sciences,Republic of KoreaRural Development Administration,Republic of Korea.
文摘The emergence of novel phytopathogens and the accelerated spread of plant diseases to new regions,driven by global climate change,constitute significant threats to agricultural resources.Rice,a major tropical staple crucial for global food security,possesses six transcription factor superfamilies-AP2/ERF,bHLH,bZIP,MYB,NAC,and WRKY-that function in innate immunity against pathogens.We review their biological functions and regulatory mechanisms in rice immunity.
基金Supported by High-Level Chinese Medicine Key Discipline Construction Project,No.zyyzdxk-2023005Capital Health Development Research Project,No.2024-1-2173the National Natural Science Foundation of China,No.82474426 and No.82474419。
文摘BACKGROUND Patients with early-stage hepatocellular carcinoma(HCC)generally have good survival rates following surgical resection.However,a subset of these patients experience recurrence within five years post-surgery.AIM To develop predictive models utilizing machine learning(ML)methods to detect early-stage patients at a high risk of mortality.METHODS Eight hundred and eight patients with HCC at Beijing Ditan Hospital were randomly allocated to training and validation cohorts in a 2:1 ratio.Prognostic models were generated using random survival forests and artificial neural networks(ANNs).These ML models were compared with other classic HCC scoring systems.A decision-tree model was established to validate the contri-bution of immune-inflammatory indicators to the long-term outlook of patients with early-stage HCC.RESULTS Immune-inflammatory markers,albumin-bilirubin scores,alpha-fetoprotein,tumor size,and International Normalized Ratio were closely associated with the 5-year survival rates.Among various predictive models,the ANN model gene-rated using these indicators through ML algorithms exhibited superior perfor-mance,with a 5-year area under the curve(AUC)of 0.85(95%CI:0.82-0.88).In the validation cohort,the 5-year AUC was 0.82(95%CI:0.74-0.85).According to the ANN model,patients were classified into high-risk and low-risk groups,with an overall survival hazard ratio of 7.98(95%CI:5.85-10.93,P<0.0001)between the two cohorts.INTRODUCTION Hepatocellular carcinoma(HCC)is one of the six most prevalent cancers[1]and the third leading cause of cancer-related mortality[2].China has some of the highest incidence and mortality rates for liver cancer,accounting for half of global cases[3,4].The Barcelona Clinic Liver Cancer(BCLC)Staging System is the most widely used framework for diagnosing and treating HCC[5].The optimal candidates for surgical treatment are those with early-stage HCC,classified as BCLC stage 0 or A.Patients with early-stage liver cancer typically have a better prognosis after surgical resection,achieving a 5-year survival rate of 60%-70%[6].However,the high postoperative recurrence rates of HCC remain a major obstacle to long-term efficacy.To improve the prognosis of patients with early-stage HCC,it is necessary to develop models that can identify those with poor prognoses,enabling stratified and personalized treatment and follow-up strategies.Chronic inflammation is linked to the development and advancement of tumors[7].Recently,peripheral blood immune indicators,such as neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and lymphocyte-to-monocyte ratio(LMR),have garnered extensive attention and have been used to predict survival in various tumors and inflammation-related diseases[8-10].However,the relationship between these combinations of immune markers and the outcomes in patients with early-stage HCC require further investigation.Machine learning(ML)algorithms are capable of handling large and complex datasets,generating more accurate and personalized predictions through unique training algorithms that better manage nonlinear statistical relationships than traditional analytical methods.Commonly used ML models include artificial neural networks(ANNs)and random survival forests(RSFs),which have shown satisfactory accuracy in prognostic predictions across various cancers and other diseases[11-13].ANNs have performed well in identifying the progression from liver cirrhosis to HCC and predicting overall survival(OS)in patients with HCC[14,15].However,no studies have confirmed the ability of ML models to predict post-surgical survival in patients with early-stage HCC.Through ML,a better understanding of the risk factors for early-stage HCC prognosis can be achieved.This aids in surgical decision-making,identifying patients at a high risk of mortality,and selecting subsequent treatment strategies.In this study,we aimed to establish a 5-year prognostic model for patients with early-stage HCC after surgical resection,based on ML and systemic immune-inflammatory indicators.This model seeks to improve the early monitoring of high-risk patients and provide personalized treatment plans.
文摘Objective:To explore the changes in the epidemiological characteristics of varicella before and after implementing the two-dose varicella vaccine(VarV)immunization program in the Banan District of Chongqing and to provide a reference for future epidemic prevention and control.Methods:The data of reported varicella cases in Banan District from 2014 to 2023 were collected and analyzed using the China Disease Prevention and Control Information System.Descriptive epidemiological methods were employed to assess the changes in the reported incidence of varicella before(2014-2018)and after(2019-2023)the implementation of the two-dose VarV immunization program.Results:The average annual reported incidence rate of varicella in Banan District from 2014 to 2023 was 81.53 per 100,000.From 2014 to 2018,the reported incidence rate showed an upward trend year by year(trend x2=223.96,P<0.05).However,the reported incidence rate decreased from 2019 to 2023(trend x?=189.51,P<0.05).Before and after the adjustment of the immunization program,the reported incidence rate for the 5-9 years old group was 774.62 per 100,000 and 476.98 per 100,000,respectively,with a statistically significant difference(x2=161.26,P<0.05).The onset of varicella showed a bimodal distribution,with peak incidence periods in May-June and October-December.From 2014 to 2023,a total of 155,181 doses of VarV were administered in Banan District.The estimated annual vaccination rate for the first varicella vaccine(VarV1)from 2019 to 2023 was 86.28%,and for the second dose(VarV2)was 59.18%.The primary vaccination targets were the 5-9-year-old group,accounting for 64.21%.Conclusion:After implementing the two-dose VarV immunization program in Banan District,the vaccination rate increased yearly,and the reported incidence of varicella showed a downward trend.The incidence rate of varicella in children aged 5-9 years reduced significantly,but the overall downward trend for the entire population was not as pronounced.Therefore,it is necessary to increase the vaccination rate of VarV2.
