In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the prolifer...In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.展开更多
BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and inflammation.Previous studies have shown that duodenal je...BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and inflammation.Previous studies have shown that duodenal jejunal bypass(DJB)surgery significantly improves brain glucose metabolism in T2DM rats,the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear.AIM To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.METHODS A T2DM rat model was induced via a high-glucose and high-fat diet,combined with a low-dose streptozotocin injection.T2DM rats were divided into DJB operation and Sham operation groups.DJB surgical intervention was carried out on T2DM rats.The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis.Proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry,quantitative real-time PCR,Western blotting,and immunofluorescence.RESULTS Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery,compared to the T2DM-Sham groups of rats.Oxidative stress-related proteins(glucagon-like peptide 1 receptor,Nrf2,and HO-1)were significantly increased(P<0.05)in the hypothalamus of rats with T2DM after DJB surgery.DJB surgery significantly reduced(P<0.05)hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin(IL)-1βand IL-6.DJB surgery significantly reduced(P<0.05)the expression of factors related to neuronal injury(glial fibrillary acidic protein and Caspase-3)in the hypothalamus of T2DM rats and upregulated(P<0.05)the expression of neuroprotective factors(C-fos,Ki67,Bcl-2,and BDNF),thereby reducing hypothalamic injury in T2DM rats.CONCLUSION DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.展开更多
Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistanc...Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer.However,the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer(CRC)cells is unclear.This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells.Methods The expression of TOPK was detected in CRC tissues by immunohistochemistry,and the effect of TOPK knockdown was detected in CRC cells by Western blotting.CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells.Furthermore,proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy.DNA damage was detected by the comet assay.Changes in the DNA damage response signaling pathway were analyzed by Western blotting,and apoptosis was detected by flow cytometry.Results The expression of TOPK was significantly greater in CRC tissues at grades 2–4 than in those at grade 1.After irradiation,CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins,including phospho-cyclin-dependent kinase 1(p-CDK1),phospho-ataxia telangiectasia-mutated(p-ATM),poly ADP-ribose polymerase(PARP),and meiotic recombination 11 homolog 1(MRE11).Conclusions TOPK was overexpressed in patients with moderately to poorly differentiated CRC.Moreover,TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.展开更多
BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE S...BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.展开更多
Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vit...Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.展开更多
A heterojunction structure design is a very good method for improving the properties of semiconductors in many research fields.This method is employed in the present study to promote the gas-sensing performance of Ag_...A heterojunction structure design is a very good method for improving the properties of semiconductors in many research fields.This method is employed in the present study to promote the gas-sensing performance of Ag_(3)PO_(4)nanocomposites at room temperature(25℃).A nanocomposite of Ag_(3)PO_(4)nanoparticles and three-dimensional peony-like WO_(3)(WO_(3)/Ag_(3)PO_(4))was successfully prepared by the precipitation method.The crystalline phases were analyzed by xray diffraction and the microstructure was characterized by scanning electron microscopy and transmission electron microscopy.The chemical bonding states were analyzed by x-ray photoelectron spectroscopy.The gas-sensing performance of WO_(3)/Ag_(3)PO_(4)sensors was systematically explored at room temperature.The composite sensors possessed a higher response and lower detection limit(1 ppm)to NH_(3)than those made of a single type of material;this is ascribed to the synergistic effect achieved by the heterojunction structure.Among the different composite sensors tested,gas sensor A5W5(Ag_(3)PO_(4):WO3mass ratio of 5:5)displayed the highest response to NH_(3)at room temperature.Interestingly,the A5W5 gas sensor exhibited relatively good stability and excellent selectivity to NH_(3).The A5W5 sensor also displayed a relatively good response under high humidity.The gas-sensing mechanism of the WO_(3)/Ag_(3)PO_(4)sensors is explained in detail.Taken together,the as-prepared sensor is highly efficient at detecting NH_(3)and could be suitable for practical applications.In addition,this study also provides a new method for developing Ag_(3)PO_(4)-based sensors in the gas-sensing field.展开更多
AIM:To analyze changes in amplitude of low-frequency fluctuations(ALFFs)and default mode network(DMN)connectivity in the brain,using resting-state functional magnetic resonance imaging(rs-fMRI),in high myopia(HM)patie...AIM:To analyze changes in amplitude of low-frequency fluctuations(ALFFs)and default mode network(DMN)connectivity in the brain,using resting-state functional magnetic resonance imaging(rs-fMRI),in high myopia(HM)patients.METHODS:Eleven patients with HM(HM group)and 15 age-and sex-matched non-HM controls(non-HM group)were recruited.ALFFs were calculated and compared between HM group and non-HM group.Independent component analysis(ICA)was conducted to identify DMN,and comparisons between DMNs of two groups were performed.Region-of-interest(ROI)-based analysis was performed to explore functional connectivity(FC)between DMN regions.RESULTS:Significantly increased ALFFs in left inferior temporal gyrus(ITG),bilateral rectus gyrus(REC),bilateral middle temporal gyrus(MTG),left superior temporal gyrus(STG),and left angular gyrus(ANG)were detected in HM group compared with non-HM group(all P<0.01).HM group showed increased FC in the posterior cingulate gyrus(PCC)/precuneus(preCUN)and decreased FC in the left medial prefrontal cortex(mPFG)within DMN compared with nonHM group(all P<0.01).Compared with non-HM group,HM group showed higher FC between mPFG and bilateral middle frontal gyrus(MFG),ANG,and MTG(all P<0.01).In addition,HM patients showed higher FC between PCC/(preCUN)and the right cerebellum,superior frontal gyrus(SFG),left pre CUN,superior frontal gyrus(SFG),and medial orbital of the superior frontal gyrus(ORB supmed;all P<0.01).CONCLUSION:HM patients show different ALFFs and DMNs compared with non-HM subjects,which may imply the cognitive alterations related to HM.展开更多
BACKGROUND Intradural cement leakage following percutaneous vertebroplasty is a rare but acute and devastating complication that usually requires emergent treatment.Here,we report a delayed complication of intradural ...BACKGROUND Intradural cement leakage following percutaneous vertebroplasty is a rare but acute and devastating complication that usually requires emergent treatment.Here,we report a delayed complication of intradural leakage after percutaneous vertebroplasty.CASE SUMMARY A 71-year-old female patient with an L1 osteoporotic compression fracture underwent percutaneous vertebroplasty in 2014.She was referred to our hospital 5 years later due to complaints of progressive weakness and numbness in both legs combined with urinary incontinence and constipation.Initially,she was suspected to have a spinal meningioma at the level of L1 according to imaging examinations.Postoperative pathological tests confirmed that cement had leaked into the dura during the first percutaneous vertebroplasty.CONCLUSION Guideline adherence is essential to prevent cement from leaking into the spinal canal or even the dura.Once leakage occurs,urgent evaluation and decompression surgery are necessary to prevent further neurological damage.展开更多
The 2009 annual special issue of Time Magazine on March 23rd summarized the ＇10 Ideas Changing the World Right Now＇, in which ＇Biobank＇ had been listed as the eighth. Biobank or biorepository has been developed si...The 2009 annual special issue of Time Magazine on March 23rd summarized the ＇10 Ideas Changing the World Right Now＇, in which ＇Biobank＇ had been listed as the eighth. Biobank or biorepository has been developed since last century. Tissue banks represented the early type of clinical biobanks and mainly concentrated on clinical usage such as transplantation at the beginning. The first tissue bank in the United States started in 1949 is the United States Navy Tissue Bank. In 1976, the foundation of American Association of Tissue Banks （AATB） claimed the official show of biobanks on social stage （www.aatb.org）. From the end of 20th Century to the beginning of 21st Century, diverse biobanks of clinical samples, seed banks, gene banks, germplasm banks of non-human species and other various types have sprung up.展开更多
Dear Editor,Type 2 diabetes is a chronic disease characterized by high glucose levels in the blood.Recently,it has been found that type 2 diabetic patients suffer from glucose and ribose dysmetabolism[1-3].The GotoKak...Dear Editor,Type 2 diabetes is a chronic disease characterized by high glucose levels in the blood.Recently,it has been found that type 2 diabetic patients suffer from glucose and ribose dysmetabolism[1-3].The GotoKakizaki(GK)rat is a nonobese,nonhypertensive model of type 2 diabetes,which,like humans,shares a susceptibility locus on chromosome 10[4-5].展开更多
Traumatic brain injury(TBI)is closely related to neuro-inflammatory response and causes a complex pathological process and serious consequence.In this study,we explored whether the formatted citrus peel extract gold l...Traumatic brain injury(TBI)is closely related to neuro-inflammatory response and causes a complex pathological process and serious consequence.In this study,we explored whether the formatted citrus peel extract gold lotion(GL)could have a therapeutic effect on rats suffered TBI.TBI rat model was prepared by the electric Cortical Contusion Impactor(eCCI)device.Prevention against TBI by GL was assessed by the behavioral,organizational of rats and the molecular markers in the brain injury area.The results showed that GL could reduce nerve damage and neurological dysfunction.The mechanisms probably due to that GL could not only reduce the associated damage markers including GFAP,OX-42,TNF-α,COX-2,NF-κB and TLR4 but also promote the expression of VEGF which is responsible for protecting neuronal cells in the injury area.These findings revealed that GL could be a promising preparation for TBI prevention.展开更多
BACKGROUND The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2,the causative agent of coronavirus disease 2019(COVID-19),by Sept...BACKGROUND The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2,the causative agent of coronavirus disease 2019(COVID-19),by September 13.AIM The aim was to investigate whether long-term use of renin-angiotensin-aldosterone system(RAAS)inhibitors for the treatment of hypertension aggravates the performance of COVID-19 patients with hypertension.METHODS This was a retrospective analysis of lung computed tomography(CT)data and laboratory values of COVID-19 patients with hypertension who were admitted to Huoshenshan Hospital,Wuhan,Hubei Province,between February 18 and March 31,2020.Patients were divided into two groups.Group A included 19 people who were long-term users of RAAS inhibitors for hypertension;and group B included 28 people who were randomly selected from the database and matched with group A by age,sex,basic diseases,and long-term use of other antihypertensive drugs.All patients underwent a series of CT and laboratory tests.We compared the most severe CT images of the two groups and the laboratory examination results within 2 d of the corresponding CT images.RESULTS The time until the most severe CT images from the onset of COVID-19 was 30.37±14.25 d group A and 26.50±11.97 d in group B.The difference between the two groups was not significant(t=1.01,P=0.32).There were no significant differences in blood laboratory values,C-reactive protein,markers of cardiac injury,liver function,or kidney function between the two groups.There was no significant difference in the appearance of the CT images between the two groups.The semiquantitative scores of each involved lobe were 11.84±5.88 in group A and 10.36±6.04 group B.The difference was not significantly different(t=0.84,P=0.41).CONCLUSION Chest CT is an important imaging tool to monitor the characteristics of COVID-19 and the degree of lung injury.Chronic use of RAAS inhibitors is not related to the severity of COVID-19,and it does not worsen the clinical process.展开更多
BACKGROUND We explored the genotype-phenotype correlation of the novel deletion 16p13.2p12.3 in an 8-year-old child with progressive total ophthalmoplegia,cervical dyskinesia,and lower limb weakness by comparing the p...BACKGROUND We explored the genotype-phenotype correlation of the novel deletion 16p13.2p12.3 in an 8-year-old child with progressive total ophthalmoplegia,cervical dyskinesia,and lower limb weakness by comparing the patient’s clinical features with previously reported data on adjacent copy number variation(CNV)regions.CASE SUMMARY Specifically,we first performed whole-exome sequencing,CNV-sequencing,and mitochondrial genome sequencing on the patient and his parents,then applied“MitoExome”(the entire mitochondrial genome and exons of nuclear genes encoding the mitochondrial proteome)analysis to screen for genetic mitochondrial diseases.We identified a de novo 7.23 Mb deletion,covering 16p13.2p12.3,by both whole-exome sequencing and CNV sequencing.We also detected 16p13.11 in the deleted region,which is the recurrent distinct region associated with neurodevelopmental disorder.However,the patient only displayed features of progressive total ophthalmoplegia,cervical dyskinesia,and weakness in his lower limbs without neurodevelopmental disorder.The“MitoExome”sequencing was negative.Brain magnetic resonance imaging revealed non-specific sporadic changes in the occipital parietal lobe and basal ganglia.CONCLUSION Taken together,these results indicated that 16p13.2p12.3 deletion causes a syndrome with the phenotype of early-onset total ophthalmoplegia.The“MitoExome”analysis is powerful for the differential diagnosis of mitochondrial diseases.We report a novel copy number variant in this case,but further confirmation is required.展开更多
BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also re...BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.展开更多
<strong>Background: </strong>Walking speed is a reliable barometer of adverse health outcomes, particularly among older people. Few studies evaluated factors associated with daily actual walking speed, rat...<strong>Background: </strong>Walking speed is a reliable barometer of adverse health outcomes, particularly among older people. Few studies evaluated factors associated with daily actual walking speed, rather than that measured in a laboratory setting or self-reported data.<strong> Methods: </strong>In a joint effort with The Pokémon Company, we recruited study participants through a women’s magazine and analyzed data from 63 Pokémon GO players. We measured the true walking speed in daily life among older women using a data-gathering mobile application. Then, using questionnaire survey data collected on these participants in 2019, we estimated the relationship between walking speed and their lifestyle and physiological factors. In the analysis, we employed a bi-directional stepwise linear regression approach, with the Akaike information criterion (AIC) for variable selection. <strong>Results: </strong>The mean age of the 63 participants was 63.03 years (standard deviation, SD 7.46);the average walking speed was 4.56 km per hour (SD 1.54);and 52 (82.5%) and 55 (87.3%) participants answered that they had excellent/good health physically and mentally, respectively. After adjusted for covariates in a stepwise regression approach, we identified a significant association between <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>1.33 (95% confidence intervals <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>2.52 to <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>0.15) km/hour lower walking speed and the experience of outdoor falls within a year. We also demonstrated that the walking speed was 1.07 (0.33 to 1.81) km/hour faster for those who had played Pokémon GO before the study started. <strong>Conclusions:</strong> The true walking speed in daily life among older women was measured by a data-gathering mobile application. Although all participants were women recruited on a voluntary basis with an understanding of the purpose of the study, and the surveys were conducted at a cross-sectional setting, a significant relationship with the experience of outdoor falls was demonstrated. We also present evidence suggesting a possible relationship between Pokémon GO play and faster walking speed.展开更多
Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the imm...Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.展开更多
Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatmen...Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.展开更多
Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of aging.Preventing and delaying skin aging has become one of the prominent ...Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of aging.Preventing and delaying skin aging has become one of the prominent research subjects in recent years.Mesenchymal stem celis(MsCs)are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential.MSC-derived extracellular vesicles(MSC-EVs)are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior.Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory,anti-oxidative stress,and wound healing promoting abilities.This review presents the latest progress of MSC-EVs in delaying skin aging.It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts,reducing the expression of matrix metalloproteinases,resisting oxidative stress,and regulating inflammation.We then briefly discuss the recently discovered treatment methods of MSc-EVs in the field of skin anti-aging.Moreover,the advantages and limitations of EV-based treatments are also presented.展开更多
Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts;however, their efficacy needs to be enhanced. Here we tested th...Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts;however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.展开更多
Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent s...Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.展开更多
基金financially supported by the National Natural Science Foundation of China(U2004104)the Natural Science Foundation of Henan Province(202300410080)+2 种基金the Key Project of Henan Education Committee(21A310005)the Internal Fund of Hebei University of Economics and Business(2020ZD10)the Postgraduate“Talent Program”of Henan University(SYL20060187 and SYL20060189)。
文摘In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.
基金Supported by the Natural Science Foundation of China,No.82070856the Science and Technology Development Plan of Shandong Medical and Health Science,No.202102040075+1 种基金Scientific Research Plan of Weifang Health Commission,No.WFWSJK-2022-010 and No.WFWSJK-2022-008Weifang Science and Technology Development Plan,No.2021YX071 and No.2021YX070.
文摘BACKGROUND Type 2 diabetes mellitus(T2DM)is often accompanied by impaired glucose utilization in the brain,leading to oxidative stress,neuronal cell injury and inflammation.Previous studies have shown that duodenal jejunal bypass(DJB)surgery significantly improves brain glucose metabolism in T2DM rats,the role and the metabolism of DJB in improving brain oxidative stress and inflammation condition in T2DM rats remain unclear.AIM To investigate the role and metabolism of DJB in improving hypothalamic oxidative stress and inflammation condition in T2DM rats.METHODS A T2DM rat model was induced via a high-glucose and high-fat diet,combined with a low-dose streptozotocin injection.T2DM rats were divided into DJB operation and Sham operation groups.DJB surgical intervention was carried out on T2DM rats.The differential expression of hypothalamic proteins was analyzed using quantitative proteomics analysis.Proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of T2DM rats were analyzed by flow cytometry,quantitative real-time PCR,Western blotting,and immunofluorescence.RESULTS Quantitative proteomics analysis showed significant differences in proteins related to oxidative stress,inflammation,and neuronal injury in the hypothalamus of rats with T2DM-DJB after DJB surgery,compared to the T2DM-Sham groups of rats.Oxidative stress-related proteins(glucagon-like peptide 1 receptor,Nrf2,and HO-1)were significantly increased(P<0.05)in the hypothalamus of rats with T2DM after DJB surgery.DJB surgery significantly reduced(P<0.05)hypothalamic inflammation in T2DM rats by inhibiting the activation of NF-κB and decreasing the expression of interleukin(IL)-1βand IL-6.DJB surgery significantly reduced(P<0.05)the expression of factors related to neuronal injury(glial fibrillary acidic protein and Caspase-3)in the hypothalamus of T2DM rats and upregulated(P<0.05)the expression of neuroprotective factors(C-fos,Ki67,Bcl-2,and BDNF),thereby reducing hypothalamic injury in T2DM rats.CONCLUSION DJB surgery improve oxidative stress and inflammation in the hypothalamus of T2DM rats and reduce neuronal cell injury by activating the glucagon-like peptide 1 receptor-mediated Nrf2/HO-1 signaling pathway.
基金supported by the Guangxi Zhuang Autonomous Region Program of China(No.Z-C20220797)Guangxi Science and Technology Planning Project of China(No.Guike AD20297047)National Natural Science Foundation of China(No.81902849).
文摘Objective Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase(TOPK)was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer.However,the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer(CRC)cells is unclear.This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells.Methods The expression of TOPK was detected in CRC tissues by immunohistochemistry,and the effect of TOPK knockdown was detected in CRC cells by Western blotting.CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells.Furthermore,proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy.DNA damage was detected by the comet assay.Changes in the DNA damage response signaling pathway were analyzed by Western blotting,and apoptosis was detected by flow cytometry.Results The expression of TOPK was significantly greater in CRC tissues at grades 2–4 than in those at grade 1.After irradiation,CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins,including phospho-cyclin-dependent kinase 1(p-CDK1),phospho-ataxia telangiectasia-mutated(p-ATM),poly ADP-ribose polymerase(PARP),and meiotic recombination 11 homolog 1(MRE11).Conclusions TOPK was overexpressed in patients with moderately to poorly differentiated CRC.Moreover,TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.
基金Key Health Science and Technology Development Project of Nanjing City,Jiangsu Province,No.ZKX19038.
文摘BACKGROUND The SETD1B gene is instrumental in human intelligence and nerve development.Mutations in the SETD1B gene have been linked in recent studies to neurodevelopmental disorders,seizures,and language delay.CASE SUMMARY This study aimed to analyze the clinical manifestations and treatment of three patients suffering from mental retardation,epilepsy,and language delay resulting from a new mutation in the SETD1B gene.Three individuals with these symptoms were selected,and their clinical symptoms,gene test results,and treatment were analyzed.This article discusses the impact of the SETD1B gene mutation on patients and outlines the treatment approach.Among the three patients(two females and one male,aged 8,4,and 1,respectively),all exhibited psychomotor retardation,attention deficit,and hyperactivity disorder,and two had epilepsy.Antiepileptic treatment with sodium tripolyvalproate halted the seizures in the affected child,although mental development remained somewhat delayed.Whole exome sequencing revealed new mutations in the SETD1B gene for all patients,specifically with c.5473C>T(p.Arg1825trp),c.4120C>T(p.Gln1374*,593),c.14_15insC(p.His5Hisfs*33).CONCLUSION Possessing the SETD1B gene mutation may cause mental retardation accompanied by seizures and language delay.Although the exact mechanism is not fully understood,interventions such as drug therapy,rehabilitation training,and family support can assist patients in managing their symptoms and enhancing their quality of life.Furthermore,genetic testing supplies healthcare providers with more precise diagnostic and therapeutic guidance,informs families about genetic disease risks,and contributes to understanding disease pathogenesis and drug research and development.
基金Fundings supported by grants from the National Key Research and Development Program of China(Grant No.2017YFA0103902,2018YFA0800300,2019YFA0801900,2019YFA0111400)National Natural Science Foundation of China(Grant No.31771283,91749104,31971074)+3 种基金the Fundamental Research Funds for the Central Universities of Tongji University(No.22120190210)Innovative Research Team of High-Level Local Universities in Shanghai(No.SSMUZDCX20180700)Key Laboratory Program of the Education Commission of Shanghai Municipality(No.DSYS14005)the Science and Technology Innovation Action Plan of Shanghai Science and Technology Committee(No.18140901300).
文摘Melanocortin 4 receptor(MC4R),the most important monogenetic cause of human metabolic disorders,has been of great interest to many researchers in the field of energy homeostasis and public health.Because MC4R is a vital pharmaceutical target for maintaining controllable appetite and body weight for professional athletes,previous studies have mainly focused on the central,rather than the peripheral,roles of MC4R.Thus,the local expression of MC4R and its behavioral regulation remain unclear.In an attempt to shed light on different directions for future studies of MC4R signaling,we review a series of recent and important studies exploring the peripheral functions of MC4R and the direct physiological interaction between peripheral organs and central MC4R neurons in this article.
基金financial support from the Collaborative Education Project of IndustryUniversity Cooperation of the Ministry of Education of China(Grant No.202101256024)the National Natural Science Foundation of China(Grant Nos.11904209 and 61802144)。
文摘A heterojunction structure design is a very good method for improving the properties of semiconductors in many research fields.This method is employed in the present study to promote the gas-sensing performance of Ag_(3)PO_(4)nanocomposites at room temperature(25℃).A nanocomposite of Ag_(3)PO_(4)nanoparticles and three-dimensional peony-like WO_(3)(WO_(3)/Ag_(3)PO_(4))was successfully prepared by the precipitation method.The crystalline phases were analyzed by xray diffraction and the microstructure was characterized by scanning electron microscopy and transmission electron microscopy.The chemical bonding states were analyzed by x-ray photoelectron spectroscopy.The gas-sensing performance of WO_(3)/Ag_(3)PO_(4)sensors was systematically explored at room temperature.The composite sensors possessed a higher response and lower detection limit(1 ppm)to NH_(3)than those made of a single type of material;this is ascribed to the synergistic effect achieved by the heterojunction structure.Among the different composite sensors tested,gas sensor A5W5(Ag_(3)PO_(4):WO3mass ratio of 5:5)displayed the highest response to NH_(3)at room temperature.Interestingly,the A5W5 gas sensor exhibited relatively good stability and excellent selectivity to NH_(3).The A5W5 sensor also displayed a relatively good response under high humidity.The gas-sensing mechanism of the WO_(3)/Ag_(3)PO_(4)sensors is explained in detail.Taken together,the as-prepared sensor is highly efficient at detecting NH_(3)and could be suitable for practical applications.In addition,this study also provides a new method for developing Ag_(3)PO_(4)-based sensors in the gas-sensing field.
基金Supported by the National Natural Science Foundation of China(No.81870685)Beijing Natural Science Foundation(No.7172173)Key Laboratory of Myopia,Ministry of Health(Fudan University)(No.EENTM-15-01)。
文摘AIM:To analyze changes in amplitude of low-frequency fluctuations(ALFFs)and default mode network(DMN)connectivity in the brain,using resting-state functional magnetic resonance imaging(rs-fMRI),in high myopia(HM)patients.METHODS:Eleven patients with HM(HM group)and 15 age-and sex-matched non-HM controls(non-HM group)were recruited.ALFFs were calculated and compared between HM group and non-HM group.Independent component analysis(ICA)was conducted to identify DMN,and comparisons between DMNs of two groups were performed.Region-of-interest(ROI)-based analysis was performed to explore functional connectivity(FC)between DMN regions.RESULTS:Significantly increased ALFFs in left inferior temporal gyrus(ITG),bilateral rectus gyrus(REC),bilateral middle temporal gyrus(MTG),left superior temporal gyrus(STG),and left angular gyrus(ANG)were detected in HM group compared with non-HM group(all P<0.01).HM group showed increased FC in the posterior cingulate gyrus(PCC)/precuneus(preCUN)and decreased FC in the left medial prefrontal cortex(mPFG)within DMN compared with nonHM group(all P<0.01).Compared with non-HM group,HM group showed higher FC between mPFG and bilateral middle frontal gyrus(MFG),ANG,and MTG(all P<0.01).In addition,HM patients showed higher FC between PCC/(preCUN)and the right cerebellum,superior frontal gyrus(SFG),left pre CUN,superior frontal gyrus(SFG),and medial orbital of the superior frontal gyrus(ORB supmed;all P<0.01).CONCLUSION:HM patients show different ALFFs and DMNs compared with non-HM subjects,which may imply the cognitive alterations related to HM.
文摘BACKGROUND Intradural cement leakage following percutaneous vertebroplasty is a rare but acute and devastating complication that usually requires emergent treatment.Here,we report a delayed complication of intradural leakage after percutaneous vertebroplasty.CASE SUMMARY A 71-year-old female patient with an L1 osteoporotic compression fracture underwent percutaneous vertebroplasty in 2014.She was referred to our hospital 5 years later due to complaints of progressive weakness and numbness in both legs combined with urinary incontinence and constipation.Initially,she was suspected to have a spinal meningioma at the level of L1 according to imaging examinations.Postoperative pathological tests confirmed that cement had leaked into the dura during the first percutaneous vertebroplasty.CONCLUSION Guideline adherence is essential to prevent cement from leaking into the spinal canal or even the dura.Once leakage occurs,urgent evaluation and decompression surgery are necessary to prevent further neurological damage.
文摘The 2009 annual special issue of Time Magazine on March 23rd summarized the ＇10 Ideas Changing the World Right Now＇, in which ＇Biobank＇ had been listed as the eighth. Biobank or biorepository has been developed since last century. Tissue banks represented the early type of clinical biobanks and mainly concentrated on clinical usage such as transplantation at the beginning. The first tissue bank in the United States started in 1949 is the United States Navy Tissue Bank. In 1976, the foundation of American Association of Tissue Banks （AATB） claimed the official show of biobanks on social stage （www.aatb.org）. From the end of 20th Century to the beginning of 21st Century, diverse biobanks of clinical samples, seed banks, gene banks, germplasm banks of non-human species and other various types have sprung up.
基金supported by a grant from Beijing Brain Project(Z161100000217141)。
文摘Dear Editor,Type 2 diabetes is a chronic disease characterized by high glucose levels in the blood.Recently,it has been found that type 2 diabetic patients suffer from glucose and ribose dysmetabolism[1-3].The GotoKakizaki(GK)rat is a nonobese,nonhypertensive model of type 2 diabetes,which,like humans,shares a susceptibility locus on chromosome 10[4-5].
文摘Traumatic brain injury(TBI)is closely related to neuro-inflammatory response and causes a complex pathological process and serious consequence.In this study,we explored whether the formatted citrus peel extract gold lotion(GL)could have a therapeutic effect on rats suffered TBI.TBI rat model was prepared by the electric Cortical Contusion Impactor(eCCI)device.Prevention against TBI by GL was assessed by the behavioral,organizational of rats and the molecular markers in the brain injury area.The results showed that GL could reduce nerve damage and neurological dysfunction.The mechanisms probably due to that GL could not only reduce the associated damage markers including GFAP,OX-42,TNF-α,COX-2,NF-κB and TLR4 but also promote the expression of VEGF which is responsible for protecting neuronal cells in the injury area.These findings revealed that GL could be a promising preparation for TBI prevention.
文摘BACKGROUND The World Health Organization reported that 28637952 people worldwide had been infected with severe acute respiratory syndrome coronavirus 2,the causative agent of coronavirus disease 2019(COVID-19),by September 13.AIM The aim was to investigate whether long-term use of renin-angiotensin-aldosterone system(RAAS)inhibitors for the treatment of hypertension aggravates the performance of COVID-19 patients with hypertension.METHODS This was a retrospective analysis of lung computed tomography(CT)data and laboratory values of COVID-19 patients with hypertension who were admitted to Huoshenshan Hospital,Wuhan,Hubei Province,between February 18 and March 31,2020.Patients were divided into two groups.Group A included 19 people who were long-term users of RAAS inhibitors for hypertension;and group B included 28 people who were randomly selected from the database and matched with group A by age,sex,basic diseases,and long-term use of other antihypertensive drugs.All patients underwent a series of CT and laboratory tests.We compared the most severe CT images of the two groups and the laboratory examination results within 2 d of the corresponding CT images.RESULTS The time until the most severe CT images from the onset of COVID-19 was 30.37±14.25 d group A and 26.50±11.97 d in group B.The difference between the two groups was not significant(t=1.01,P=0.32).There were no significant differences in blood laboratory values,C-reactive protein,markers of cardiac injury,liver function,or kidney function between the two groups.There was no significant difference in the appearance of the CT images between the two groups.The semiquantitative scores of each involved lobe were 11.84±5.88 in group A and 10.36±6.04 group B.The difference was not significantly different(t=0.84,P=0.41).CONCLUSION Chest CT is an important imaging tool to monitor the characteristics of COVID-19 and the degree of lung injury.Chronic use of RAAS inhibitors is not related to the severity of COVID-19,and it does not worsen the clinical process.
文摘BACKGROUND We explored the genotype-phenotype correlation of the novel deletion 16p13.2p12.3 in an 8-year-old child with progressive total ophthalmoplegia,cervical dyskinesia,and lower limb weakness by comparing the patient’s clinical features with previously reported data on adjacent copy number variation(CNV)regions.CASE SUMMARY Specifically,we first performed whole-exome sequencing,CNV-sequencing,and mitochondrial genome sequencing on the patient and his parents,then applied“MitoExome”(the entire mitochondrial genome and exons of nuclear genes encoding the mitochondrial proteome)analysis to screen for genetic mitochondrial diseases.We identified a de novo 7.23 Mb deletion,covering 16p13.2p12.3,by both whole-exome sequencing and CNV sequencing.We also detected 16p13.11 in the deleted region,which is the recurrent distinct region associated with neurodevelopmental disorder.However,the patient only displayed features of progressive total ophthalmoplegia,cervical dyskinesia,and weakness in his lower limbs without neurodevelopmental disorder.The“MitoExome”sequencing was negative.Brain magnetic resonance imaging revealed non-specific sporadic changes in the occipital parietal lobe and basal ganglia.CONCLUSION Taken together,these results indicated that 16p13.2p12.3 deletion causes a syndrome with the phenotype of early-onset total ophthalmoplegia.The“MitoExome”analysis is powerful for the differential diagnosis of mitochondrial diseases.We report a novel copy number variant in this case,but further confirmation is required.
基金Supported by the Special Fund of the Pediatric Medical Coordinated Development Center of Beijing Hospitals Authority,No.XTZD20180204。
文摘BACKGROUND The aberrant expression of the anaplastic lymphoma kinase(ALK)gene in ALKpositive(ALK+)anaplastic large cell lymphoma(ALCL)is usually due to t(2;5)/NPM-ALK.However,rarely,aberrant ALK expression can also result from a rearrangement of the ALK gene with various partner genes.Central nervous system(CNS)metastasis is very rare in ALK+ALCL.Patients with CNS involvement show an inferior prognosis.CASE SUMMARY Here,we present the case of an 8-year-old girl diagnosed with ALK+ALCL.She presented with fever,skin nodules,leg swelling,and abdominal pain over the preceding 6 mo.She had extensive involvement and showed an extraordinary rare translocation,t(2;17)/CLTC-ALK,as demonstrated by RNA-seq.She underwent chemotherapy as per ALCL99,followed by vinblastine(VBL)maintenance treatment,and achieved complete remission.However,she developed CNS relapse during VBL monotherapy.The patient achieved a durable second remission with high-dose chemotherapy(including methotrexate 8 g/m2)and continuous treatment with alectinib and VBL.CONCLUSION Alectinib showed significant and durable CNS effects in this patient.However,more cases are needed to prove the efficacy and safety of alectinib for pediatric ALK+ALCL patients.
文摘<strong>Background: </strong>Walking speed is a reliable barometer of adverse health outcomes, particularly among older people. Few studies evaluated factors associated with daily actual walking speed, rather than that measured in a laboratory setting or self-reported data.<strong> Methods: </strong>In a joint effort with The Pokémon Company, we recruited study participants through a women’s magazine and analyzed data from 63 Pokémon GO players. We measured the true walking speed in daily life among older women using a data-gathering mobile application. Then, using questionnaire survey data collected on these participants in 2019, we estimated the relationship between walking speed and their lifestyle and physiological factors. In the analysis, we employed a bi-directional stepwise linear regression approach, with the Akaike information criterion (AIC) for variable selection. <strong>Results: </strong>The mean age of the 63 participants was 63.03 years (standard deviation, SD 7.46);the average walking speed was 4.56 km per hour (SD 1.54);and 52 (82.5%) and 55 (87.3%) participants answered that they had excellent/good health physically and mentally, respectively. After adjusted for covariates in a stepwise regression approach, we identified a significant association between <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>1.33 (95% confidence intervals <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>2.52 to <span style="white-space:nowrap;"><span style="white-space:nowrap;">−</span></span>0.15) km/hour lower walking speed and the experience of outdoor falls within a year. We also demonstrated that the walking speed was 1.07 (0.33 to 1.81) km/hour faster for those who had played Pokémon GO before the study started. <strong>Conclusions:</strong> The true walking speed in daily life among older women was measured by a data-gathering mobile application. Although all participants were women recruited on a voluntary basis with an understanding of the purpose of the study, and the surveys were conducted at a cross-sectional setting, a significant relationship with the experience of outdoor falls was demonstrated. We also present evidence suggesting a possible relationship between Pokémon GO play and faster walking speed.
基金supported by the National Key Research and Development Program of China(No.2021YFA1201102)Henan Medical Science and Technology Joint Building Program(No.SBGJ202102132)+2 种基金Henan Province Youth Talent Promoting Project(No.2022HYTP047)the National Natural Science Foundation of China(Nos.82003255,82101385 and 82073231)Key Research and Development Project of Henan Province(No.232102311224)and First-Class Clinical Medicine Discipline Construction Talents Cultivation Project of Zhengzhou University.
文摘Rationally tailored lipid nanoparticles(LNPs)with efficient and tunable delivery of mRNA in vivo are crucial for mRNA vaccines.Selective expression of antigenic protein in lymphoid tissues/organs could improve the immunostimulatory efficacy and safety of LNPs-based mRNA vaccines.Inspired by the metabolic behavior that long-chain saturated fatty acids tending to enter lymphoid tissue rather than the liver,we developed fatty acid-doped LNPs capable of mediating differential protein expressions in the liver and spleen when administered intravenously.When the molar ratio of saturated fatty acid located 60%–70%,the doped LNPs achieved the spleen selective mRNA translation.The mechanism could be attributed to the different cellular uptake behaviors of saturated fatty acids in hepatocytes.Immunization with a model antigen(ovalbumin)mRNA-loaded spleen selective LNPs,we observed enhanced antigen-specific T cell immune responses,and potent immunotherapeutic and immunoprophylactic efficacy in the mouse lymphoma model.Our natural long-chain saturated fatty acids metabolic characteristics-inspired design of LNPs for spleen-selective mRNA vaccines delivery will provide references for designing mRNA vaccines with high efficacy and safety for tumor immunotherapy.
基金financially supported by the National Natural Science Foundation of China(No.82001189)The Project Tackling of Key Scientific and Technical Problems of Henan Provine(No.232102311163).
文摘Bone metastasis,a life-threatening complication of advanced breast cancer,is often accompanied by debilitating pain(cancer-induced bone pain,CIBP)that severely impairs life quality and survival.The concurrent treatment of bone metastases and CIBP remains a clinical challenge because the therapeutic options are limited.In this study,we construct a near-infrared light-activated nano-therapeutic system to meet this conundrum.In detail,sorafenib(SRF)and photosensitizer(chlorin e6,Ce6)are encapsulated into mesoporous hydroxyapatite nanoparticles(HANPs),which are further functionalized with hyaluronic acid(HA)to obtain HA-SRF/Ce6@HANPs system.The designed nanoplatform destroys tumor cells in vitro and in vivo via the synergism of SRF(interrupting the exchange of cystine/glutamate by inhibiting SLC7A11)and photodynamic therapy(PDT,inducing reactive oxygen species generation).The decrease in tumor burden and reduction of extracellular glutamate significantly attenuate CIBP in mice model with developing bone cancer.Moreover,the combination of HA-SRF/Ce6@HANPs and PDT inhibit osteoclasts activation,promote osteoblast differentiation and accelerate bone repair.Overall,the nanoagent with good biocompatibility may provide an effective therapy method for the concurrent treatment of breast cancer bone metastasis and CIBP.
基金the National Natural Science Foundation of China(Grant No.31971109)Shanghai Key Laboratory of Cell Engineering(Grant No.14DZ2272300)Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai.The figures were created with BioRender.com.
文摘Owing to its constant exposure to the external environment and various stimuli,skin ranks among the organs most vulnerable to manifestations of aging.Preventing and delaying skin aging has become one of the prominent research subjects in recent years.Mesenchymal stem celis(MsCs)are multipotent stem cells derived from mesoderm with high self-renewal ability and multilineage differentiation potential.MSC-derived extracellular vesicles(MSC-EVs)are nanoscale biological vesicles that facilitate intercellular communication and regulate biological behavior.Recent studies have shown that MSC-EVs have potential applications in anti-aging therapy due to their anti-inflammatory,anti-oxidative stress,and wound healing promoting abilities.This review presents the latest progress of MSC-EVs in delaying skin aging.It mainly includes the MSC-EVs promoting the proliferation and migration of keratinocytes and fibroblasts,reducing the expression of matrix metalloproteinases,resisting oxidative stress,and regulating inflammation.We then briefly discuss the recently discovered treatment methods of MSc-EVs in the field of skin anti-aging.Moreover,the advantages and limitations of EV-based treatments are also presented.
文摘Human pluripotent stem cell-derived cardiovascular progenitor cells (hCVPCs) and cardiomyocytes (hCMs) possess therapeutic potential for infarcted hearts;however, their efficacy needs to be enhanced. Here we tested the hypotheses that the combination of decellularized porcine small intestinal submucosal extracellular matrix (SIS-ECM) with hCVPCs, hCMs, or dual of them (Mix, 1:1) could provide better therapeutic effects than the SIS alone, and dual hCVPCs with hCMs would exert synergic effects in cardiac repair. The data showed that the SIS patch well supported the growth of hCVPCs and hCMs. Epicardially implanted SIS-hCVPC, SIS-hCM, or SIS-Mix patches at 7-day post-myocardial infarction significantly ameliorated functional worsening, ventricular dilation and scar formation at 28- and 90-day post-implantation in C57/B6 mice, whereas the SIS only mildly improved function at 90-day post-implantation. Moreover, the SIS and SIS-cell patches improved vascularization and suppressed MI-induced cardiomyocyte hypertrophy and expression of Col1 and Col3, but only the SIS-hCM and the SIS-Mix patches increased the ratio of collagen III/I fibers in the infarcted hearts. Further, the SIS-cell patches stimulated cardiomyocyte proliferation via paracrine action. Notably, the SIS-Mix had better improvements in cardiac function and structure, engraftments, and cardiomyocyte proliferation. Proteomic analysis showed distinct biological functions of exclusive proteins secreted from hCVPCs and hCMs, and more exclusive proteins secreted from co-cultivated hCVPCs and hCMs than mono-cells involving in various functional processes essential for infarct repair. These findings are the first to demonstrate the efficacy and mechanisms of mono- and dual-hCVPC- and hCM-seeding SIS-ECM for repair of infarcted hearts based on the side-by-side comparison.
基金the Ministry of Science and Technology of China(Nos.2021YFA1102000,2021YFC2700300,2019YFA0110000,and 2018YFA0108900)the National Natural Science Foundation of China(NSFC)(Nos.31721003,32022024,32270850,32100633,31871486,32070652,and 81630035)the Science and Technology Commission of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500).
文摘Human pluripotent stem cells provide an inexhaustible model to study human embryogenesis in vitro.Recent studies have provided diverse models to generate human blastoids by self-organization of different pluripotent stem cells or somatic reprogramming intermediates.However,whether blastoids can be generated from other cell types or whether they can recapitulate postimplantation development in vitro is unknown.Here,we develop a strategy to generate human blastoids from heterogeneous intermediates with epiblast,trophectoderm,and primitive endoderm signatures of the primed-to-naïve conversion process,which resemble natural blastocysts in morphological architecture,composition of cell lineages,transcriptome,and lineage differentiation potential.In addition,these blastoids reflect many features of human peri-implantation and pregastrulation development when further cultured in an in vitro 3D culture system.In summary,our study provides an alternative strategy to generate human blastoids and offers insights into human early embryogenesis by modeling peri-and postimplantation development in vitro.
