Chronic nonbacterial prostatitis(CNP),also the typeⅢprostatitis account for more than 90%of all patients with prostatitis.It has a long course of disease,easy to repeat,unknown pathogenesis and poor clinical efficacy...Chronic nonbacterial prostatitis(CNP),also the typeⅢprostatitis account for more than 90%of all patients with prostatitis.It has a long course of disease,easy to repeat,unknown pathogenesis and poor clinical efficacy.At present,some scholars at home and abroad have found that there is differential expression of microRNA(miRNA)in prostatic fluid of CNP patients or prostate tissue of CNP rat model.Intervention of miRNA expression can alleviate the symptoms and pharmacodynamics of CNP to a certain extent,which opens up a new way and direction for the pathogenesis and diagnosis and treatment of CNP.Therefore,this paper reviews the research progress of miRNA and CNP in recent years.展开更多
The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategie...The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.展开更多
Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disabi...Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.展开更多
Current rates of mental illness are worrisome.Mental illness mainly affects females and younger age groups.The use of the internet to deliver mental health care has been growing since 2020 and includes the implementat...Current rates of mental illness are worrisome.Mental illness mainly affects females and younger age groups.The use of the internet to deliver mental health care has been growing since 2020 and includes the implementation of novel mental health treatments using virtual reality,augmented reality,and artificial intelligence.A new three dimensional digital environment,known as the metaverse,has emerged as the next version of the Internet.Artificial intelligence,augmented reality,and virtual reality will create fully immersive,experiential,and interactive online environments in the metaverse.People will use a unique avatar to do anything they do in their“real”lives,including seeking and receiving mental health care.In this opinion review,we reflect on how the metaverse could reshape how we deliver mental health treatment,its opportunities,and its challenges.展开更多
Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regu...Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.展开更多
Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples receiv...Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,2023.The results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and socio-demographics.Data was analyzed using descriptive statistics.Results:A total of 2141 stool samples from 1644 cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)surveillance.Both polioviruses(19/1644,1.15%)and non-polio enteroviruses(73/1644,4.44%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus isolated.Wild polioviruses or circulating VDPVs were not detected among the cases.During all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14 days of receipt,ensuring timely reporting as per global guidelines.Conclusions:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance indicators.Non-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.展开更多
N^(1)-methyladenosine(m^(1)A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remain...N^(1)-methyladenosine(m^(1)A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m^(1)A modification levels.Analysis of m^(1)A-associated genes identified TRMT61A as a key m^(1)A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m^(1)A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m^(1)A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m^(1)A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m^(1)A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.展开更多
Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poo...Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.展开更多
Objective:To establish Nipah virus diagnostic capabilities at the National Reference Laboratory in Sri Lanka using the NIV Pune real-time PCR kit.Methods:Strict safety precautions were adhered during testing due to th...Objective:To establish Nipah virus diagnostic capabilities at the National Reference Laboratory in Sri Lanka using the NIV Pune real-time PCR kit.Methods:Strict safety precautions were adhered during testing due to the high pathogenicity of the Nipah virus,with all diagnostics conducted in a BSL2+laboratory at the Medical Research Institute in Sri Lanka.RNA extraction was performed using the QIAamp Viral RNA Mini kit.The NIV Pune in-house real-time PCR kit was employed,following established primer/probe sequences and controls.The assay was validated using the Rotor-Gene Q Series Real-time PCR platform.Results:The validation run of the Nipah virus real-time PCR test demonstrated robust performance,with positive controls consistently detecting Nipah RNA at a Ct value of 21.50±0.01.Negative controls confirmed assay specificity with an external negative control which was also used as an extraction control and showed no interference.The internal control exhibited stable behavior,enhancing confidence in PCR results.The qPCR analysis graph illustrated the successful detection of internal and positive controls,validating the reliability of the assay.Conclusions:Establishing Nipah virus diagnostic capabilities in Sri Lanka signifies a proactive and collaborative response to the persistent global health threat.展开更多
Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the out...Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the outbreak.Methods:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri Lanka.According to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,respectively.Selected RNA positive samples were sequenced at reference laboratory,India.Analysis of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella Laboratory.Data was analyzed using descriptive statistics.Results:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or both.Males(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive patients.All provinces reported measles positive cases.All samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing Victoria.Australia origin.Conclusions:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating globally.Further,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.展开更多
Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to disc...Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.展开更多
BACKGROUND Various surgical techniques have been developed to enhance the nose shapes of Asian patients.Silicone implant augmentation rhinoplasty is widely used because it is relatively easy to perform and often yield...BACKGROUND Various surgical techniques have been developed to enhance the nose shapes of Asian patients.Silicone implant augmentation rhinoplasty is widely used because it is relatively easy to perform and often yields satisfactory outcomes.However,this technique may lead to complications,including ischemia,necrosis,and over-augmentation.The most appropriate management of these complications,including infection,is immediate implant removal and revision surgery once the accompanying inflammation has healed.Occasionally,the patient may experience distress from nasal deformities during the intervention period.CASE SUMMARY Herein,we describe the case of a patient who underwent a secondary dorsal augmentation,with a folded dermofat graft harvested from the inguinal area and simultaneous implant removal,successfully preventing dimpling of the nasal deformity.CONCLUSION This surgical method can effectively manage implant-related complications following augmentation rhinoplasty using a silicone implant and provide satis-factory patient outcomes.展开更多
BACKGROUND Musculoskeletal nontuberculous Mycobacterium(NTM)infections are rare,partic-ularly post-acupuncture therapy,and present diagnostic challenges due to their infrequency and potential severity.Prompt recogniti...BACKGROUND Musculoskeletal nontuberculous Mycobacterium(NTM)infections are rare,partic-ularly post-acupuncture therapy,and present diagnostic challenges due to their infrequency and potential severity.Prompt recognition and appropriate manage-ment are crucial for optimal outcomes.NTM-infected wounds involving the joints are difficult to treat,and only a few cases have been reported.CASE SUMMARY We present a case of a chronic intractable NTM-infected wound on the elbow joint that completely healed with conservative wound care and antibiotic treatment.An 81-year-old woman presented with a chronic,ulcerative wound on the right elbow joint where she had undergone repeated acupuncture therapy for chronic intolerable pain.Magnetic resonance imaging revealed synovial thickening,effusion,and subcutaneous cystic lesions.An orthopedic surgeon performed open synovectomy and serial debridement.However,1 month postoperatively,the wound had not healed and became chronic.A wound culture revealed NTM(Mycobacterium abscessus),and the patient was referred to the Department of Plastic and Reconstructive Surgery.Instead of surgical intervention,conservative wound care with intravenous antibiotics was provided,considering the wound status and the patient’s poor general condition.Complete wound healing was achieved in 12 months,with no impact on the range of motion of the elbow joint.CONCLUSION With clinical awareness,musculoskeletal NTM infection can be treated with conservative wound care and appropriate antimicrobial agents.展开更多
Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulati...Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).展开更多
Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monoge...Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.展开更多
Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk...Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.展开更多
The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected i...The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected individuals across the world, evolving into the COVID-19 pandemic. Notably, early signs of the virus’s existence were observed in various countries before the initial outbreak in Wuhan. As of 12<sup>th</sup> of April, the respiratory disease had infected over 762 million people worldwide, with over 6.8 million deaths recorded. This has led scientists to focus their efforts on understanding the virus to develop effective means to diagnose, treat, prevent, and control this pandemic. One of the areas of focus is the isolation of this virus, which plays a crucial role in understanding the viral dynamics in the laboratory. In this study, we report the isolation and detection of locally circulating SARS-CoV-2 in Kenya. The isolates were cultured on Vero Cercopithecus cell line (CCL-81) cells, RNA extraction was conducted from the supernatants, and reverse transcriptase-polymerase chain reaction (RT-PCR). Genome sequencing was done to profile the strains phylogenetically and identify novel and previously reported mutations. Vero CCL-81 cells were able to support the growth of SARS-CoV-2 in vitro, and mutations were detected from the two isolates sequenced (001 and 002). Genome sequencing revealed the circulation of two isolates that share a close relationship with the Benin isolate with the D614G common mutation identified along the S protein. These virus isolates will be expanded and made available to the Kenya Ministry of Health and other research institutions to advance SARS-CoV-2 research in Kenya and the region.展开更多
Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking it...Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.展开更多
Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment ...Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment method.Methods:An ecological study design was employed.We collected data about global uniform practices using an online survey.We searched for country/region-level estimates of school-aged youth meeting physical activity guidelines from international surveillance studies.Study selection was conducted in duplicate using a systematic process,and a random sample of all data was checked to ensure extraction and pooling processes were accurate.We calculated absolute and relative gender inequalities in physical activity for each country.Linear regression examined associations between country/region-level uniform practices(binary yes/no exposure variable) and country/region-level gender inequalities in physical activity guideline compliance(absolute and relative inequalities).We investigated moderation by school level,stratified analyses by income group,and repeated primary analyses using device-measured data.Results:Pooling data from 135 countries/regions(n=1,089,852),we found no association between population-level uniform practices and gender inequalities in physical activity across all ages(absolute:β=-0.2;95% confidence interval(95%CI):-1.7 to 1.3,p=0.74;relative:β=0.1;95%CI:-0.1 to 0.2,p=0.51).Subgroup analysis suggested a positive association in primary school settings(absolute:β=4.3;95%CI:-0.0 to 8.6,p=0.05).Among high-income countries,absolute inequalities were significantly greater in countries/regions with uniform practices(N=37) compared to those without(N=48)(9.1(SD=3.6) vs.7.8 percentage points(SD=4.3)).Repeating analyses using device-measured data(n=32,130;N=24) did not alter our primary finding.From initial descriptive statistics,we found that in countries/regions where a maj ority of schools(>50%) reportedly use uniforms,there was lower compliance with physical activity guidelines among all genders(median:16.0%,interquartile range:13.2%-19.9%,N=103) compared to generally non-uniform countries/regions(median:19.5%,interquartile range:16.4%-23.5 %,N=32)(z=3.04,p=0.002).(N=countries,regions and studies repre sented;n=sample size or participants included).Conclusion:School uniforms are associated with greater gender inequalities in physical activity in primary school settings and in high-income countries.Our population-level findings warrant testing using individual-level data across contexts.展开更多
Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study desi...Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.展开更多
基金supported by Key R&D Program of Hainan Province(ZDYF2018125)Natural Science Foundation of Hainan Province(818MS062)。
文摘Chronic nonbacterial prostatitis(CNP),also the typeⅢprostatitis account for more than 90%of all patients with prostatitis.It has a long course of disease,easy to repeat,unknown pathogenesis and poor clinical efficacy.At present,some scholars at home and abroad have found that there is differential expression of microRNA(miRNA)in prostatic fluid of CNP patients or prostate tissue of CNP rat model.Intervention of miRNA expression can alleviate the symptoms and pharmacodynamics of CNP to a certain extent,which opens up a new way and direction for the pathogenesis and diagnosis and treatment of CNP.Therefore,this paper reviews the research progress of miRNA and CNP in recent years.
基金suppor ted by the National Key Research and Development Program of China (2022YFC2702502)the National Natural Science Foundation of China (32170742, 31970646, and 32060152)+7 种基金the Start Fund for Specially Appointed Professor of Jiangsu ProvinceHainan Province Science and Technology Special Fund (ZDYF2021SHFZ051)the Natural Science Foundation of Hainan Province (820MS053)the Start Fund for High-level Talents of Nanjing Medical University (NMUR2020009)the Marshal Initiative Funding of Hainan Medical University (JBGS202103)the Hainan Province Clinical Medical Center (QWYH202175)the Bioinformatics for Major Diseases Science Innovation Group of Hainan Medical Universitythe Shenzhen Science and Technology Program (JCYJ20210324140407021)
文摘The application of single-cell RNA sequencing(scRNA-seq)in biomedical research has advanced our understanding of the pathogenesis of disease and provided valuable insights into new diagnostic and therapeutic strategies.With the expansion of capacity for high-throughput scRNA-seq,including clinical samples,the analysis of these huge volumes of data has become a daunting prospect for researchers entering this field.Here,we review the workflow for typical scRNA-seq data analysis,covering raw data processing and quality control,basic data analysis applicable for almost all scRNA-seq data sets,and advanced data analysis that should be tailored to specific scientific questions.While summarizing the current methods for each analysis step,we also provide an online repository of software and wrapped-up scripts to support the implementation.Recommendations and caveats are pointed out for some specific analysis tasks and approaches.We hope this resource will be helpful to researchers engaging with scRNA-seq,in particular for emerging clinical applications.
基金supported by a grant from the National Research Foundation(NRF)of Korea funded by the Korean Government,No.NRF-2022R1A2C1004022(to CM)。
文摘Multiple sclerosis is a chronic autoimmune disease of the central nervous system and is generally considered to be a non-traumatic,physically debilitating neurological disorder.In addition to experiencing motor disability,patients with multiple sclerosis also experience a variety of nonmotor symptoms,including cognitive deficits,anxiety,depression,sensory impairments,and pain.However,the pathogenesis and treatment of such non-motor symptoms in multiple scle rosis are still under research.Preclinical studies for multiple sclerosis benefit from the use of disease-appropriate animal models,including experimental autoimmune encephalomyelitis.Prior to understanding the pathophysiology and developing treatments for non-motor symptoms,it is critical to chara cterize the animal model in terms of its ability to replicate certain non-motor features of multiple sclerosis.As such,no single animal model can mimic the entire spectrum of symptoms.This review focuses on the non-motor symptoms that have been investigated in animal models of multiple sclerosis as well as possible underlying mechanisms.Further,we highlighted gaps in the literature to explain the nonmotor aspects of multiple sclerosis in expe rimental animal models,which will serve as the basis for future studies.
基金Supported by Instituto de Salud CarlosⅢ(ISCⅢ),with group funds the Research Network on Chronicity,Primary Care and Health Promotion(RICAPPS,RD21/0016/0005)that is part of the Results-Oriented Cooperative Research Networks in Health(RICORS)(CarlosⅢHealth Institute),co-funded by the European Union“NextGeneration EU/PRTR”funds and with group funds Mental health research group in Primary Care(B17_23R),which is part of the Department of Innovation,Research,and University in the Government of Aragón(Spain).
文摘Current rates of mental illness are worrisome.Mental illness mainly affects females and younger age groups.The use of the internet to deliver mental health care has been growing since 2020 and includes the implementation of novel mental health treatments using virtual reality,augmented reality,and artificial intelligence.A new three dimensional digital environment,known as the metaverse,has emerged as the next version of the Internet.Artificial intelligence,augmented reality,and virtual reality will create fully immersive,experiential,and interactive online environments in the metaverse.People will use a unique avatar to do anything they do in their“real”lives,including seeking and receiving mental health care.In this opinion review,we reflect on how the metaverse could reshape how we deliver mental health treatment,its opportunities,and its challenges.
基金supported by the National Key Research and Development Project of Stem Cell and Transformation Research,No.2019YFA0112100(to SF)the National Natural Science Foundation of China No.81930070(to SF)+1 种基金Multi-fund Investment Key Projects,No.21JCZDJC01100(to ZW)the Tianjin Science and Technology Planning Project,No.22JRRCRC00010(to SF)。
文摘Complete transverse injury of peripheral nerves is challenging to treat.Exosomes secreted by human umbilical cord mesenchymal stem cells are considered to play an important role in intercellular communication and regulate tissue regeneration.In previous studies,a collagen/hyaluronic acid sponge was shown to provide a suitable regeneration environment for Schwann cell proliferation and to promote axonal regeneration.This three-dimensional(3D)composite conduit contains a collagen/hyaluronic acid inner sponge enclosed in an electrospun hollow poly(lactic-co-glycolic acid)tube.However,whether there is a synergy between the 3D composite conduit and exosomes in the repair of peripheral nerve injury remains unknown.In this study,we tested a comprehensive strategy for repairing long-gap(10 mm)peripheral nerve injury that combined the 3D composite conduit with human umbilical cord mesenchymal stem cell-derived exosomes.Repair effectiveness was evaluated by sciatic functional index,sciatic nerve compound muscle action potential recording,recovery of muscle mass,measuring the cross-sectional area of the muscle fiber,Masson trichrome staining,and transmission electron microscopy of the regenerated nerve in rats.The results showed that transplantation of the 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes promoted peripheral nerve regeneration and restoration of motor function,similar to autograft transplantation.More CD31-positive endothelial cells were observed in the regenerated nerve after transplantation of the loaded conduit than after transplantation of the conduit without exosomes,which may have contributed to the observed increase in axon regeneration and distal nerve reconnection.Therefore,the use of a 3D composite conduit loaded with human umbilical cord mesenchymal stem cell-derived exosomes represents a promising cell-free therapeutic option for the treatment of peripheral nerve injury.
文摘Objective:To evaluate the polio laboratory surveillance carried out from January,2019 to May,2023 by the Polio Regional Reference Laboratory,Sri Lanka.Methods:This retrospective study analyzed all stool samples received under the acute flaccid paralysis(AFP)and immunodeficient vaccine-derived poliovirus(VDPV)surveillance at Polio Regional Reference Laboratory,Sri Lanka from January,2019 to May,2023.The results of the testing methodologies were extracted from the laboratory data system,i.e.,poliovirus virus isolation,intra-typic differentiation/VDPV real time reverse transcriptase polymerase chain reaction(ITD/VDPV rRTPCR)and sequencing,along with the data on timing of reporting results,stool adequacy and socio-demographics.Data was analyzed using descriptive statistics.Results:A total of 2141 stool samples from 1644 cases were received for AFP surveillance from Sri Lanka(93.61%),Maldives(1.52%),and immunodeficient VDPV(4.86%)surveillance.Both polioviruses(19/1644,1.15%)and non-polio enteroviruses(73/1644,4.44%)were isolated,while Sabin-like 3 virus was detected in majority(12/19,63.15%)among the poliovirus isolated.Wild polioviruses or circulating VDPVs were not detected among the cases.During all years of the study,the non-polio AFP detection rate was>1/100000 in children aged less than 15 years,whereas stool adequacy rate was>80%.All results were reported within 14 days of receipt,ensuring timely reporting as per global guidelines.Conclusions:The Polio Regional Reference Laboratory,Sri Lanka plays a vital role in maintaining the polio-free status in the country through its robust laboratory surveillance,while adhering to the surveillance indicators.Non-detection of wild polioviruses and circulating VDPV during the study period reinforces the polio-free status in the country.
基金supported by National Natural Science Foundation of China 82273202(Z.J.S.)82072996(Z.J.S.)+2 种基金National Key Research and Development Program 2022YFC2504200(Z.J.S.)Interdisciplinary innovative foundation of Wuhan University XNJC202303the Fundamental Research Funds for the Central Universities(2042022dx0003,2042024kf0021).
文摘N^(1)-methyladenosine(m^(1)A)RNA methylation is critical for regulating mRNA translation;however,its role in the development,progression,and immunotherapy response of head and neck squamous cell carcinoma(HNSCC)remains largely unknown.Using Tgfbr1 and Pten conditional knockout(2cKO)mice,we found the neoplastic transformation of oral mucosa was accompanied by increased m^(1)A modification levels.Analysis of m^(1)A-associated genes identified TRMT61A as a key m^(1)A writer linked to cancer progression and poor prognosis.Mechanistically,TRMT61A-mediated tRNA-m^(1)A modification promotes MYC protein synthesis,upregulating programmed death-ligand 1(PD-L1)expression.Moreover,m^(1)A modification levels were also elevated in tumors treated with oncolytic herpes simplex virus(oHSV),contributing to reactive PD-L1 upregulation.Therapeutic m^(1)A inhibition sustained oHSV-induced antitumor immunity and reduced tumor growth,representing a promising strategy to alleviate resistance.These findings indicate that m^(1)A inhibition can prevent immune escape after oHSV therapy by reducing PD-L1 expression,providing a mutually reinforcing combination immunotherapy approach.
基金supported by the Cutting Edge Development Fund of Advanced Medical Research Institute(GYY2023QY01)the China Postdoctoral Science Foundation(certificate number:2023M732093)。
文摘Background:Knee osteoarthritis(KOA)characterized by degeneration of knee cartilage and subsequent bone hyperplasia is a prevalent joint condition primarily affecting aging adults.The pathophysiology of KOA remains poorly understood,as it involves complex mechanisms that result in the same outcome.Consequently,researchers are interested in studying KOA and require appropriate animal models for basic research.Chinese herbal compounds,which consist of multiple herbs with diverse pharmacological properties,possess characteristics such as multicomponent,multipathway,and multitarget effects.The potential benefits in the treatment of KOA continue to attract attention.Purpose:This study aims to provide a comprehensive overview of the advantages,limitations,and specific considerations in selecting different species and methods for KOA animal models.This will help researchers make informed decisions when choosing an animal model.Methods:Online academic databases(e.g.,PubMed,Google Scholar,Web of Science,and CNKI)were searched using the search terms“knee osteoarthritis,”“animal models,”“traditional Chinese medicine,”and their combinations,primarily including KOA studies published from 2010 to 2023.Results:Based on literature retrieval,this review provides a comprehensive overview of the methods of establishing KOA animal models;introduces the current status of advantages and disadvantages of various animal models,including mice,rats,rabbits,dogs,and sheep/goats;and presents the current status of methods used to establish KOA animal models.Conclusion:This study provides a review of the animal models used in recent KOA research,discusses the common modeling methods,and emphasizes the role of traditional Chinese medicine compounds in the treatment of KOA.
文摘Objective:To establish Nipah virus diagnostic capabilities at the National Reference Laboratory in Sri Lanka using the NIV Pune real-time PCR kit.Methods:Strict safety precautions were adhered during testing due to the high pathogenicity of the Nipah virus,with all diagnostics conducted in a BSL2+laboratory at the Medical Research Institute in Sri Lanka.RNA extraction was performed using the QIAamp Viral RNA Mini kit.The NIV Pune in-house real-time PCR kit was employed,following established primer/probe sequences and controls.The assay was validated using the Rotor-Gene Q Series Real-time PCR platform.Results:The validation run of the Nipah virus real-time PCR test demonstrated robust performance,with positive controls consistently detecting Nipah RNA at a Ct value of 21.50±0.01.Negative controls confirmed assay specificity with an external negative control which was also used as an extraction control and showed no interference.The internal control exhibited stable behavior,enhancing confidence in PCR results.The qPCR analysis graph illustrated the successful detection of internal and positive controls,validating the reliability of the assay.Conclusions:Establishing Nipah virus diagnostic capabilities in Sri Lanka signifies a proactive and collaborative response to the persistent global health threat.
文摘Objective:To describe the situation of measles in Sri Lanka from May to November,2023 and to define the role of virology laboratory towards case confirmation and epidemiological and genetic characterization of the outbreak.Methods:This retrospective study analyzed all samples tested for measles from 1st of May to 30th of November,2023 at National Measles Rubella Laboratory,Sri Lanka.According to the World Health Organization(WHO)algorithm,serum and oropharyngeal/nasopharyngeal swabs were tested with WHO recommended kits for anti-measles IgM and measles virus specific RNA,respectively.Selected RNA positive samples were sequenced at reference laboratory,India.Analysis of sequencing data and construction of phylogenetic tree were carried out at National Measles Rubella Laboratory.Data was analyzed using descriptive statistics.Results:Of the total 1132 serum samples and 497 oropharyngeal/nasopharyngeal swabs from 1326 patients,657(49.5%)patients were confirmed as measles by anti-measles IgM,measles virus specific RNA or both.Males(55.6%,n=365)and the age group from>20 to≤30 years(33.0%,n=217)predominated positive patients.All provinces reported measles positive cases.All samples sequenced(100%,n=42)were genotype D8 with 95.2%(n=40)bearing Victoria.Australia origin.Conclusions:We described resurgence of measles in an eliminated country,confirming the genotype to be D8,one of the two genotypes currently circulating globally.Further,the study strongly convinced the importance of a strengthened virological surveillance system in an eliminated country,despite its eliminated status.
基金supported by a joint GUIPRS/AHEAD Scholarship and GU Postgraduate Research Scholarshipcurrently receiving funds from Cancer Australia (APP1145657)+2 种基金the National Health and Medical Research Council (APP 2002576 and APP 2012560)the Garnett Passe and Rodney Williams FoundationNIH R21 and the RBWH Foundation。
文摘Oral cancer (OC) is the most common form of head and neck cancer. Despite the high incidence and unfavourable patient outcomes, currently, there are no biomarkers for the early detection of OC. This study aims to discover, develop, and validate a novel saliva-based microRNA signature for early diagnosis and prediction of OC risk in oral potentially malignant disorders (OPMD).The Cancer Genome Atlas (TCGA) miRNA sequencing data and small RNA sequencing data of saliva samples were used to discover differentially expressed miRNAs. Identified miRNAs were validated in saliva samples of OC (n=50), OPMD (n=52), and controls(n=60) using quantitative real-time PCR. Eight differentially expressed miRNAs (miR-7-5p, miR-10b-5p, miR-182-5p, miR-215-5p,miR-431-5p, miR-486-3p, miR-3614-5p, and miR-4707-3p) were identified in the discovery phase and were validated. The efficiency of our eight-miRNA signature to discriminate OC and controls was:area under curve (AUC):0.954, sensitivity:86%, specificity:90%,positive predictive value (PPV):87.8%and negative predictive value (NPV):88.5%whereas between OC and OPMD was:AUC:0.911,sensitivity:90%, specificity:82.7%, PPV:74.2%and NPV:89.6%. We have developed a risk probability score to predict the presence or risk of OC in OPMD patients. We established a salivary miRNA signature that can aid in diagnosing and predicting OC,revolutionising the management of patients with OPMD. Together, our results shed new light on the management of OC by salivary miRNAs to the clinical utility of using miRNAs derived from saliva samples.
文摘BACKGROUND Various surgical techniques have been developed to enhance the nose shapes of Asian patients.Silicone implant augmentation rhinoplasty is widely used because it is relatively easy to perform and often yields satisfactory outcomes.However,this technique may lead to complications,including ischemia,necrosis,and over-augmentation.The most appropriate management of these complications,including infection,is immediate implant removal and revision surgery once the accompanying inflammation has healed.Occasionally,the patient may experience distress from nasal deformities during the intervention period.CASE SUMMARY Herein,we describe the case of a patient who underwent a secondary dorsal augmentation,with a folded dermofat graft harvested from the inguinal area and simultaneous implant removal,successfully preventing dimpling of the nasal deformity.CONCLUSION This surgical method can effectively manage implant-related complications following augmentation rhinoplasty using a silicone implant and provide satis-factory patient outcomes.
文摘BACKGROUND Musculoskeletal nontuberculous Mycobacterium(NTM)infections are rare,partic-ularly post-acupuncture therapy,and present diagnostic challenges due to their infrequency and potential severity.Prompt recognition and appropriate manage-ment are crucial for optimal outcomes.NTM-infected wounds involving the joints are difficult to treat,and only a few cases have been reported.CASE SUMMARY We present a case of a chronic intractable NTM-infected wound on the elbow joint that completely healed with conservative wound care and antibiotic treatment.An 81-year-old woman presented with a chronic,ulcerative wound on the right elbow joint where she had undergone repeated acupuncture therapy for chronic intolerable pain.Magnetic resonance imaging revealed synovial thickening,effusion,and subcutaneous cystic lesions.An orthopedic surgeon performed open synovectomy and serial debridement.However,1 month postoperatively,the wound had not healed and became chronic.A wound culture revealed NTM(Mycobacterium abscessus),and the patient was referred to the Department of Plastic and Reconstructive Surgery.Instead of surgical intervention,conservative wound care with intravenous antibiotics was provided,considering the wound status and the patient’s poor general condition.Complete wound healing was achieved in 12 months,with no impact on the range of motion of the elbow joint.CONCLUSION With clinical awareness,musculoskeletal NTM infection can be treated with conservative wound care and appropriate antimicrobial agents.
基金supported by the Merkin PNNR Center(23-DF/C2/261)(to HS).
文摘Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell body.For this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains.Although some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal compartment.For example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).
文摘Pregnancy in women with monogenic diabetes is potentially complex,with significant implications for both maternal and fetal health.Among these,maturity-onset diabetes of the young(MODY)stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice.Each subtype of MODY requires a distinct approach tailored to the pregnancy,diverging from management strategies in non-pregnant individuals.Glucokinase MODY(GCK-MODY)typically does not require treatment outside of pregnancy,but special considerations arise when a woman with GCK-MODY becomes pregnant.The glycemic targets in GCK-MODY pregnancies are not exclusively dictated by the maternal/paternal MODY genotype but are also influenced by the genotype of the developing fetus.During pregnancy,the choice between sulfonylurea or insulin for treating hepatocyte nuclear factor 1-alpha(HNF1A)-MODY and HNF4A-MODY depends on the mother’s specific circumstances and the available expertise.Management of other rarer MODY subtypes is individu-alized,with decisions made on a case-by-case basis.Therefore,a collaborative approach involving expert diabetes and obstetric teams is crucial for the compre-hensive management of MODY pregnancies.
基金supported by the National Natural Science Foundation of China(82373808)Chongqing Natural Science Foundation(cstc2021jcyj-bshX0125)+1 种基金Fundamental Research Funds for the Central Universities(SWURC2020001)the project for Chongqing University Innovation Research Group,Chongqing Education Committee(CXQT20006).
文摘Objective:In this study,we aim to enhance the anti-prostate cancer efficacy of cabazitaxel(CTX)and reduce its immunosuppression and systemic toxicity by developing CTX-loaded liposomes modified with ginsenoside Rk1(Rk1/CTX-Lip).Methods:Physical and chemical properties of Rk1/CTX-Lip were investigated.We evaluated the biological functions of Rk1/CTXLip,both in vitro and in vivo.A subcutaneous prostate cancer(RM-1)-bearing mouse model was established to study the efficacy of Rk1/CTX-Lip inhibition in tumors.Simultaneously,a Candida albicans infection model was established in tumor-bearing mice to study the infection-relieving efficacy of Rk1/CTX-Lip.Finally,biocompatibility and in vivo safety of Rk1/CTX-Lip were evaluated.Results:We successfully prepared Rk1/CTX-Lip,achieving high CTX encapsulation efficiency(97.24±0.75)%and physical stability.Rk1/CTX-Lip demonstrated evasion of macrophage phagocytosis,effective tumor tissue targeting,and a significant reduction(>50%)in average tumor volume compared with Chol/CTX-Lip.Moreover,it relieved the concurrent infection burden and effectively regulated immune organs and cells,demonstrating superior biocompatibility.Conclusion:Rk1/CTX-Lip presents a promising new therapy for prostate cancer and holds potential for relieving concurrent fungal infections in cancer patients with low immunity.
文摘The discovery of Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) in Wuhan, Hubei province, China, in December 2019 raised global health warnings. Quickly, in 2020, the virus crossed borders and infected individuals across the world, evolving into the COVID-19 pandemic. Notably, early signs of the virus’s existence were observed in various countries before the initial outbreak in Wuhan. As of 12<sup>th</sup> of April, the respiratory disease had infected over 762 million people worldwide, with over 6.8 million deaths recorded. This has led scientists to focus their efforts on understanding the virus to develop effective means to diagnose, treat, prevent, and control this pandemic. One of the areas of focus is the isolation of this virus, which plays a crucial role in understanding the viral dynamics in the laboratory. In this study, we report the isolation and detection of locally circulating SARS-CoV-2 in Kenya. The isolates were cultured on Vero Cercopithecus cell line (CCL-81) cells, RNA extraction was conducted from the supernatants, and reverse transcriptase-polymerase chain reaction (RT-PCR). Genome sequencing was done to profile the strains phylogenetically and identify novel and previously reported mutations. Vero CCL-81 cells were able to support the growth of SARS-CoV-2 in vitro, and mutations were detected from the two isolates sequenced (001 and 002). Genome sequencing revealed the circulation of two isolates that share a close relationship with the Benin isolate with the D614G common mutation identified along the S protein. These virus isolates will be expanded and made available to the Kenya Ministry of Health and other research institutions to advance SARS-CoV-2 research in Kenya and the region.
基金supported by the National Research Foundation (NRF)of Korea Grant funded by the Korean Government (NRF-2022R1A2C100402212RS-2023-00219517)。
文摘Structural plasticity is critical for the functional diversity of neurons in the brain.Experimental autoimmune encephalomyelitis(EAE)is the most commonly used model for multiple sclerosis(MS),successfully mimicking its key pathological features(inflammation,demyelination,axonal loss,and gliosis)and clinical symptoms(motor and non-motordysfunctions).Recentstudieshave demonstrated the importance of synaptic plasticity in EAE pathogenesis.In the present study,we investigated the features of behavioral alteration and hippocampal structural plasticity in EAE-affected mice in the early phase(11 days post-immunization,DPI)and chronic phase(28DPI).EAE-affected mice exhibited hippocampus-related behavioral dysfunction in the open field test during both early and chronic phases.Dendritic complexity was largely affected in the cornu ammonis 1(CA1)and CA3 apical and dentate gyrus(DG)subregions of the hippocampus during the chronic phase,while this effect was only noted in the CA1 apical subregion in the early phase.Moreover,dendritic spine density was reduced in the hippocampal CA1 and CA3 apical/basal and DG subregions in the early phase of EAE,but only reduced in the DG subregion during the chronic phase.Furthermore,mRNA levels of proinflammatory cytokines(Il1β,Tnfα,and Ifnγ)and glial cell markers(Gfap and Cd68)were significantly increased,whereas the expression of activity-regulated cytoskeletonassociated protein(ARC)was reduced during the chronic phase.Similarly,exposure to the aforementioned cytokines in primary cultures of hippocampal neurons reduced dendritic complexity and ARC expression.Primary cultures of hippocampal neurons also showed significantly reduced extracellular signal-regulated kinase(ERK)phosphorylation upon treatment with proinflammatory cytokines.Collectively,these results suggest that autoimmune neuroinflammation alters structural plasticity in the hippocampus,possibly through the ERK-ARC pathway,indicating that this alteration may be associated with hippocampal dysfunctions in EAE.
基金supported by the Economic and Social Research Council(ES/P000738/1)the Medical Research Council(MC_UU_00006/5)the University of Cambridge,and the National Health and Medical Research Council(GS2000053).
文摘Purpose:It is aimed to assess whether school uniforms are associated with population-level gender inequalities in physical activity,and whether associations differ by school level,country/region income,and assessment method.Methods:An ecological study design was employed.We collected data about global uniform practices using an online survey.We searched for country/region-level estimates of school-aged youth meeting physical activity guidelines from international surveillance studies.Study selection was conducted in duplicate using a systematic process,and a random sample of all data was checked to ensure extraction and pooling processes were accurate.We calculated absolute and relative gender inequalities in physical activity for each country.Linear regression examined associations between country/region-level uniform practices(binary yes/no exposure variable) and country/region-level gender inequalities in physical activity guideline compliance(absolute and relative inequalities).We investigated moderation by school level,stratified analyses by income group,and repeated primary analyses using device-measured data.Results:Pooling data from 135 countries/regions(n=1,089,852),we found no association between population-level uniform practices and gender inequalities in physical activity across all ages(absolute:β=-0.2;95% confidence interval(95%CI):-1.7 to 1.3,p=0.74;relative:β=0.1;95%CI:-0.1 to 0.2,p=0.51).Subgroup analysis suggested a positive association in primary school settings(absolute:β=4.3;95%CI:-0.0 to 8.6,p=0.05).Among high-income countries,absolute inequalities were significantly greater in countries/regions with uniform practices(N=37) compared to those without(N=48)(9.1(SD=3.6) vs.7.8 percentage points(SD=4.3)).Repeating analyses using device-measured data(n=32,130;N=24) did not alter our primary finding.From initial descriptive statistics,we found that in countries/regions where a maj ority of schools(>50%) reportedly use uniforms,there was lower compliance with physical activity guidelines among all genders(median:16.0%,interquartile range:13.2%-19.9%,N=103) compared to generally non-uniform countries/regions(median:19.5%,interquartile range:16.4%-23.5 %,N=32)(z=3.04,p=0.002).(N=countries,regions and studies repre sented;n=sample size or participants included).Conclusion:School uniforms are associated with greater gender inequalities in physical activity in primary school settings and in high-income countries.Our population-level findings warrant testing using individual-level data across contexts.
文摘Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.