Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-br...Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.展开更多
Hydroxyl-terminated polybutadiene/toluene diisocyanate(HTPB/TDI)system is widely used in composite solid propellants.The migrations of plasticizers and water molecules from solid propellants and surrounding environmen...Hydroxyl-terminated polybutadiene/toluene diisocyanate(HTPB/TDI)system is widely used in composite solid propellants.The migrations of plasticizers and water molecules from solid propellants and surrounding environment to the inhibitor have always been the important issues.This study focuses on the preparation,characterization and anti-migration behavior of graphene oxide(GO)/HTPB nanocomposite liner.The GO/HTPB(GH)composite liners affect the migration of small molecules through a tighter cross-linked structure and weakening function of small molecule adsorption.The anti-migration performance of the liner at different temperatures was analyzed,and the influence of the added amount of GO on the anti-migration performance and adhesion performance was also systematically studied.The overall performance of the liner is optimized when the amount of GO filler is 0.3 wt%.After adding 0.3 wt%GO,the concentration of dioctyl sebacate(DOS)migrated into the liner is decreased by 23.28%,and the concentration of water molecules is decreased by 51.89%,indicating that the introduction of GO can significantly improve the anti-migration performance of the liner.In addition,the bond strength is greatly increased from 0.25 MPa to 0.95 MPa,which meets the application requirements of the current propellant system.This research provides an important way for the preparation of structure-function synergistic anti-migration composite liners.展开更多
AIM: To investigate genetic diversity of Helicobacter pylori (H. pylorl) cell division-related gene A (cdrA) and its effect on the host response.METHODS: Inactivation of H. py/ori cdrA, which is involved in ceil...AIM: To investigate genetic diversity of Helicobacter pylori (H. pylorl) cell division-related gene A (cdrA) and its effect on the host response.METHODS: Inactivation of H. py/ori cdrA, which is involved in ceil division and morphological elonga- tion, has a role in chronic persistent infections. Ge- netic property of H. pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 (77 American and 51 Japanese) clinical isolates obtained from 48 and 51 patients, respectively. Enzyme-linked immunosorbent assay was performed to measure in- terleukin-8 (IL-8) secretion with gastric biopsy speci- mens obtained from American patients colonized with cdrA-positive or -negative strains and AGS cells co- cultured with wild-type HPK5 (cdrA-positive) or its de- rivative HPKT510 (cdrA-disruptant). Furthermore, the cytotoxin-associated gene A (cagA) status (transloca- tion and phosphorylation) and kinetics of transcription factors [nuclear factor-kappa B (NF-~:B) and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5, HPKT510 and its derivative HPKSCA (cagA- disruptant) by western blotting analysis with immuno- precipitation. RESULTS: Genetic diversity of the H. pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types, cdrA-positive (al- lele types, I and 11 ) and cdrA-negative (allele types; 111 and IV) categories, respectively. Almost all Japanese isolates were cdrA-positive ( 1 : 7.8% and 11 : 90.2%), whereas 16.9% of American isolates were cdrA-positive (11) and 83.1% were cdrA-negative (nl: 37.7% and IV: 45.5%), indicating extended diversity of cdrA in individual American isolates. Comparison of each isolate from different regions (antrum and corpus) in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases. However, 12 cases had a different cdrA al- lele and 6 of them exhibited a different cdrA category between two regions in the stomach. Furthermore, in 5 of the 6 cases possessing a different cdrA category, cdrA-negative isolate existed in the corpus, suggesting that cdrA-negative strain is more adaptable to coloni- zation in the corpus. IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower (P 〈 0.01) compared to wild- type HPK5: corresponding to 50%-60% of those of wild-type HPK5. These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL, respectively. Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation, however, nuclear accumulation of NF-κB was lower by HPKT510 com- pared to HPK5. CONCLUSION: Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB, and hence, atten- uate the host immunity leading to persistent infection.展开更多
Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. P...Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.展开更多
Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of diss...Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of disseminated murine cytomegalovirus(MCMV)infection in BALB/c and C57BL/6 mice,we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication,trying tofigure out whether AIM2 inflammasome is related to the chronic mechanism of MCMV.BALB/c and C57BL/6 mice were sacrificed on day 0,1,3,7,14 and 28 post infection.Expression levels of AIM2,pro-caspase-1,caspase-1 p20,pro-IL1β and mature IL1β in primary peritoneal macrophages(PMs)and spleens were detected by Western blotting.Contents of IL18 in the serum were detected by ELISA.Pathological examinations of livers were performed,and mRNA levels of MCMV glycoprotein B(gB)in salivary glands also assessed.Results showed that expression levels of AIM2 in PMs and spleens of C57BL/6 mice increased on day 3,even continued to day 28;caspase-1 p20 and mature IL1β increased on day 7,14 and 28;the persistently high expression of IL1β in the serum started on day 1,showing a double peak curve.As for BALB/c mice,expression of AIM2 in PMs increased on day 1 and day 7,while contents of AIM2 in spleens increased on day 1 and day 3;caspase-1 p20 and mature ILip merely increased 7 days fter infection.Thereafter,expression levels of AIM2,caspase-1 p20,mature IL1β and IL18 were limited;the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in C57BL/6 mice.The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to MCMV.In conclusion,the activation of AIM2 inflammasome in BALB/c mice was short-lived,which is quite possibly related to the chronicity of MCMV infection.展开更多
Objective: To discuss the ef ect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma(MFC). Methods: The constructed p CMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfect...Objective: To discuss the ef ect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma(MFC). Methods: The constructed p CMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-毷B signal pathway, downstream matrix metalloproteinase(MMP-2), MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. Results: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not af ected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell(P<0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-毷B p65 and I毷Bα was reduced in the BRMS1 transfection group, with the decreased expression of MMP 2, MMP 9 and osteopontin and the increased expression of E-cadherin(P<0.01). Results of animal experiment also showed that the expression of BRMS1 did not af ect the transplanted tumor. Conclusions: The expression of BRMS1 can signii cantly inhibit the adhesion, migration, invasion and metastasis of MCF gastric cancer cell, which is related to The NF-毷B signal pathway.展开更多
Increasing evidence has revealed that maternal cytomegalovirus (CMV) infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related...Increasing evidence has revealed that maternal cytomegalovirus (CMV) infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 (TLR2) and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV (MCMV) infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide (LPS)-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation (50 gg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.展开更多
Objective To investigate whether the presence of structured CagA proteins in Western- and Eastern-type Helicobacter pylori (H. pylori) induces different incidences of gastric diseases. Methods CagA and phosphorylatd...Objective To investigate whether the presence of structured CagA proteins in Western- and Eastern-type Helicobacter pylori (H. pylori) induces different incidences of gastric diseases. Methods CagA and phosphorylatd CagA were expressed in AGS gastric epithelial cells infected with wild type and mutant strains. The ability of individual CagA was determined by immunoprecipitation and Western blot assay. Morphological changes of these cells were observed under microscope to evaluate the appearance of elongation hummingbird phenotype. Results The sizes of CagA proteins in different strains were different, and no phosphorylated CagA proteins were detected in wild-type strains. Meanwhile, the kinetics of CagA status in AGS infected with H. pylori was detected. The molecular weight of phosphorylated CagA with the same size of CagA proteins in H. pylori was different in infections with different wild-type strains. CagA and phosphorylated CagA increased in a time-dependent manner after the infection. The hummingbird phenotype with H. pylori for time-course was observed under microscope. Instead of HPK5 strain, the wild-type 26695 strain induced hummingbird phenotype in a time-dependent manner. Conclusion Translocation and phosphorylation of CagA are necessary, but not sufficient, for the induction of hummingbird phenotype in AGS cells.展开更多
BACKGROUND In most cases of yellow nail syndrome(YNS),the classic triad of yellow nails,lymphedema and respiratory manifestations rarely manifest simultaneously.Therefore,diagnosis is delayed or frequently missed.CASE...BACKGROUND In most cases of yellow nail syndrome(YNS),the classic triad of yellow nails,lymphedema and respiratory manifestations rarely manifest simultaneously.Therefore,diagnosis is delayed or frequently missed.CASE SUMMARY We report a 62-year-old YNS patient presenting with bilateral pleural,pericardial and peritoneal effusions who,2 mo later,developed minimal-change nephrotic syndrome.After treatment with vitamin E,clarithromycin and prednisone for 3 mo,effusions in the chest,pericardium and abdominal cavity decreased while urine protein levels returned to within normal ranges.CONCLUSION Clinicians should consider the possibility of YNS for patients presenting with multiple serous effusions and nephrotic syndromes.展开更多
Background:Outbreaks of coronavirus disease 2019(COVID-19)have been recorded in different countries across the globe.The virus is highly contagious,hence early detection,isolation,and quarantine of infected patients w...Background:Outbreaks of coronavirus disease 2019(COVID-19)have been recorded in different countries across the globe.The virus is highly contagious,hence early detection,isolation,and quarantine of infected patients will play an important role in containing the viral spread.Diagnosis in a mobile lab can aid to find infected patients in time.Methods:Here,we develop a field-deployable diagnostic workflow that can reliably detect COVID-19.Instruments used in this workflow can easily fit in a mobile cabin hospital and also be installed in the community.Different steps from sample inactivation to detection were optimized to find the fastest steps and portable instruments in the detection of COVID-19.Each step was compared to that of the normal laboratory diagnosis setup.Results:From the results,our proposed workflow(80 min)was two times faster compared to that of the normal laboratory workflow(183 min)and a maximum of 32 samples could be detected at each run.Additionally,we showed that using 1%Rewocid WK-30 could inactivate the novel coronavirus directly without affecting the overall detection results.Comparison of our workflow using an in-house assay to that of a commercially acquired assay produced highly reliable results.From the 250 hospital samples tested,there was a high concordance 247/250(98.8%)between the two assays.The in-house assay sensitivity and specificity were 116/116(100%)and 131/134(97.8%)compared to that of the commercial assay.Conclusion:Based on these results,we believe that our workflow is fast,reliable,adaptable and most importantly,field-deployable.展开更多
Objective:This study aimed to assess the effects of electroacupuncture(EA)at the contralateral,ipsilateral,or bilateral"Zusanli(ST36)"and"Yanglingquan(GB34)"on neuropathic pain caused by chronic co...Objective:This study aimed to assess the effects of electroacupuncture(EA)at the contralateral,ipsilateral,or bilateral"Zusanli(ST36)"and"Yanglingquan(GB34)"on neuropathic pain caused by chronic contractile injury(CCI)and to explore the role of the nuclear factor erythroid 2-related factor 2(Nrf2)pathway in the effects of EA.Methods:Male Sprague-Dawley rats were subjected to the CCI model to induce neuropathic pain.A total of 45 rats were randomly divided into five groups(n=9):sham,CCI,EA-Co(CCI+EA at contralateral acupoints),EA-Ip(CCI+EA at ipsilateral acupoints),and EA-Bi(CCI+EA at bilateral acupoints).The rats received EA treatment on day 8 after CCI,once every alternate day,for a total of eight times.The time courses of mechanical pain threshold(MWT),hind paw withdrawal latency(HWL),and sciatic functional index(SFI)were determined.The expression levels of 8-hydroxydeoxyguanosine(8-OHdG),glutathione(GSH),superoxide dismutase(SOD)activity,interleukin-6(IL-6),interleukin-1 beta(IL-1β),and tumor necrosis factor factor-alpha(TNF-α)in the spinal cord were measured.The distribution of Nrf2,its expression of Nrf2 in both the cytosol and nucleus,and the protein levels of its downstream target genes,NQO1 and HO-1,were detected via double immunofluorescence staining and western blotting,respectively.Results:Following CCI,both MWT and HWL in the CCI group significantly decreased from day 14 after surgery(P<0.001).EA treatment exhibited significant antinociceptive effects induced by CCI by increasing the MWT and HWL values,especially bilateral EA(P<0.05).The SFI of the CCI group was significantly lower than that of the sham group(P<0.001).Only bilateral EA improved the SFI scores compared to the CCI group(P<0.05).8-OHdG levels in the spinal cord of the CCI group were significantly higher than those in the sham group(P<0.05),whereas GSH levels and SOD activity in the spinal cord of the CCI group were significantly lower than those in the sham group(P<0.001 and P<0.01,respectively).Bilateral EA administration significantly downregulated 8-OHdG levels(P<0.01)and upregulated GSH levels and SOD activity in the spinal cord(P<0.01).CCI significantly enhanced the production of IL-1β,IL-6,and TNF-αin the spinal cord compared with that in the sham group(all P<0.001).Meanwhile,the effects of EA were also accompanied by markedly decreased expression of IL-1βand IL-6 in the spinal cord(P<0.05).TNF-αlevels were only decreased in the EA-Ip and EA-Bi groups compared with those in the CCI group(P<0.001).Confocal microscopy revealed that Nrf2 was mainly localized in the neurons of the spinal cord.Notably,EA treatment enhanced nuclear translocation of Nrf2 in neurons.CCI significantly decreased the production of Nrf2,HO-1,and NQO1 in the spinal cord compared to the sham group(P<0.001),and bilateral EA up-regulated the protein levels of Nrf2 and its target genes HO-1 and NQO1(all P<0.001).Conclusion:Our results suggest that bilateral EA is an optimal therapeutic strategy for neuropathic pain.The effects of EA on neuropathic pain may be mediated by the restoration of the Nrf2 pathway in the spinal cord.展开更多
The micro robot based on screw motion wheels, which features high payload/mass ratio, fast and continuous motion, adaptation to pipe diameter or roundness variations, is suitable for locomotion and inspection inside s...The micro robot based on screw motion wheels, which features high payload/mass ratio, fast and continuous motion, adaptation to pipe diameter or roundness variations, is suitable for locomotion and inspection inside small diameter pipelines. The robot inspection system, Tubot I, developed at Shanghai University is composed of locomotion mechanism with an inner motor, a micro CCD camera and a monitor outside the pipeline. In the paper, the kinematics and statics analyses are presented for the screw locomotion system of Tubot I. The moving characteristics are obtained from experiments on the robot prototype.展开更多
Objective:To evaluate the effect of acupuncture on myelosuppression after chemotherapy and summarize its acupoint selection strategy.Methods:After a systematic search,an acupoint database on myelosuppression after che...Objective:To evaluate the effect of acupuncture on myelosuppression after chemotherapy and summarize its acupoint selection strategy.Methods:After a systematic search,an acupoint database on myelosuppression after chemotherapy was constructed.A meta-analysis was conducted to assess the efficacy of acupuncture.On this basis,association analysis and cluster analysis were performed to explore the distribution of acupoints in SPSS Modeler18.0 and SPSS 22.0.Results:40 studies with 2988 patients were included.The white blood cell count,platelet count,red blood cell count,and hemoglobin were significantly higher in patients receiving acupuncture versus convention therapy exclusively.The two groups,however,did not differ in neutrophils count.Most acupoints,mainly distributed in the limbs and the back,were from the bladder meridian,the stomach meridian,and the spleen meridian.The lower sea and transport points were the most preferred specific points,in which ST36 and SP6 ranked highest in use.ST36-RN6,SP6-SP10,and ST36-SP10 turned out to be the most significant correlations in association rule mining.In cluster analysis,LI4-RN12,ST36-RN4-RN6 were grouped for their high similarity.Conclusion:For patients with myelosuppression after chemotherapy,acupuncture significantly inhibited the decline in blood cell components(white blood cell count,platelet count,red blood cell count,and hemoglobin)except for neutrophils.As the central combination of acupuncture prescriptions for this population,ST36-SP6-RN6-SP10-RN4 presented promising prospects and deserved more exploration for clinical use.展开更多
For zinc air batteries,a non-noble metal-based electrocatalyst with a high performance and stability in oxygen evolution reaction(OER)and oxygen reduction reaction(ORR)is imperative in application.Herein,a catalyst ba...For zinc air batteries,a non-noble metal-based electrocatalyst with a high performance and stability in oxygen evolution reaction(OER)and oxygen reduction reaction(ORR)is imperative in application.Herein,a catalyst based on FeCo-N encapsuled in nitrogen-doped carbon nanotubes has been prepared,which provides an implementable method to design controlled structures with excellent bifunction al electrocatalytic activities.By adjusting the molar ratio of two metals,the synthesized FeCo-N-C catalyst delivers a competitive ORR and OER performance compared with commercial Pt/C and IrO_(2),performing a low overvoltage gap between ORR(E_(1/2))and OER(E_(j=10))of 0.8 V.Moreover,as a promising cathode in zinc air battery,the FeCo-N-C catalyst possesses an affirmative stability of over 100 h and large power density(129 mW·cm^(-2)).This work demonstrates that FeCo-N-C is one of the most promising catalysts for zinc air batteries and provides a possibility for exploration of batteries with high stability by adjusting the molar ratio of metals in the catalysts.展开更多
Supercapacitors(SCs)have been considered as the most promising energy storage device due to high power density,long cycle life,and fast energy storage and efficient delivery.The excellent electrode materials of SCs ge...Supercapacitors(SCs)have been considered as the most promising energy storage device due to high power density,long cycle life,and fast energy storage and efficient delivery.The excellent electrode materials of SCs generally have based on large porous structure,excellent conductivity,and heteroatom doping for charge transfer.Among various electrode materials,biomass-derived carbon materials have received widespread attention owing to excellent performances,environmental friendliness,lowcost and renewability.Additionally,composites materials based on biomass-derived carbon and transition metalbased material can obtain more advantages of structural and performance than single component,which opens up a new way for the fabrication of high-performance SC electrode materials.Therefore,this review aims to the recent progress on the design and fabrication of biomassderived carbons/transition metal-based composites in supercapacitor application.Finally,the development trends and challenges of biomass-derived electrode materials have been discussed and prospected.展开更多
Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides...Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.展开更多
Dear Editor,The prolonged outbreak and spread of coronavirus disease 2019(COVID-19),caused by SARS-CoV-2 poses a great threat to global economic and public health.The protective efficacy of the vaccines based on the s...Dear Editor,The prolonged outbreak and spread of coronavirus disease 2019(COVID-19),caused by SARS-CoV-2 poses a great threat to global economic and public health.The protective efficacy of the vaccines based on the spike protein(S)of SARS-CoV-2 has been compromised by the emergence of variants of concern(VOC).展开更多
基金supported by the National Key Research and Development Program of China,Nos.2016YFC1306300(to XMW),2016YFC1306000the National Key R&D Program of China-European Commission Horizon 2020,No.2017YFE0118800-779238(to YXW)+15 种基金the Notional Natural Science Foundation of Chino,Nos.81970992(to WZ),81571229(to WZ),81071015(to WZ),30770745(to WZ)Capital's Funds for Health Improvement and Research(CFH),No.2022-2-2048(to WZ)the Key Technology R&D Program of Beijing Municipal Education Commission,No.kz201610025030(to WZ)the Natural Science Foundation of Beijing,No.7082032(to WZ)the Key Project of the Natural Science Foundation of Beijing,No.4161004(to WZ)Capitol Clinical Characteristic Applicotion Research,No.Z121107001012161(to WZ)Project of Scientific and Technological Development of Traditional Chinese Medicine in Beijing,No.JJ2018-48(to WZ)High Level Technical Personnel Training Project of Beijing Health System of China,No.2009-3-26(to WZ)Excellent Personnel Training Project of Beijing,No.20071D0300400076(to WZ)Important National Science&Technology Specific Project,No.2011ZX09102-003-01(to WZ)Beijing Healthcare Research Project,No.JING-15-2(to WZ)Basic-Clinicol Research Cooperation Funding of Capitol Medical University of China,Nos.2015-JL-PT-X04(to WZ),10JL49(to WZ),14JL15(to WZ)the Natural Science Foundation of Capital Medical UniversityBeijingChina,No.PYZ2018077(to PG)Youth Research Fund of Beijing Tianton Hospital of Capital Medical University of China,Nos.2015-YQN-14(to PG),2015-YQN-15,2015-YQN-17。
文摘Previous studies have shown that reduced sleep duration,sleep fragmentation,and decreased sleep quality in patients with Alzheimer's disease are related to dysfunction in orexin signaling.At the same time,blood-brain barrier disruption is considered an early biomarker of Alzheimer's disease.However,currently no report has examined how changes in orexin signaling relate to changes in the blood-brain barrier of patients who have Alzheimer's disease with sleep insufficiency.This cross-sectional study included 50 patients with Alzheimer's disease who received treatment in 2019 at Beijing Tiantan Hospital.Patients were divided into two groups:those with insufficient sleep(sleep duration≤6 hours,n=19,age 61.58±8.54 years,10 men)and those with normal sleep durations(sleep duration>6 hours,n=31,age 63.19±10.09 years,18 men).Demographic variables were collected to evaluate cognitive function,neuropsychiatric symptoms,and activities of daily living.The levels of orexin,its receptor proteins,and several blood-brain barrier factors were measured in cerebrospinal fluid.Sleep insufficiency was associated with impaired overall cognitive function that spanned multiple cognitive domains.Furthermore,levels of orexin and its receptors were upregulated in the cerebrospinal fluid,and the blood–brain barrier was destroyed.Both these events precipitated each other and accelerated the progression of Alzheimer's disease.These findings describe the clinical characteristics and potential mechanism underlying Alzheimer's disease accompanied by sleep deprivation.Inhibiting the upregulation of elements within the orexin system or preventing the breakdown of the blood-brain barrier could thus be targets for treating Alzheimer's disease.
基金the financial support of the National Natural Science Foundation of China(grant number 22005145)the Natural Science Foundation of Jiangsu Province(grant number BK20180495,BK20180698)+1 种基金the Opening Project of Key Laboratory of Special Energy Materials(Nanjing University of Science and Technology)the Fundamental Research Funds for the Priority Academic Program Development of Jiangsu Higher Education Institutions(grant number 30919011404)。
文摘Hydroxyl-terminated polybutadiene/toluene diisocyanate(HTPB/TDI)system is widely used in composite solid propellants.The migrations of plasticizers and water molecules from solid propellants and surrounding environment to the inhibitor have always been the important issues.This study focuses on the preparation,characterization and anti-migration behavior of graphene oxide(GO)/HTPB nanocomposite liner.The GO/HTPB(GH)composite liners affect the migration of small molecules through a tighter cross-linked structure and weakening function of small molecule adsorption.The anti-migration performance of the liner at different temperatures was analyzed,and the influence of the added amount of GO on the anti-migration performance and adhesion performance was also systematically studied.The overall performance of the liner is optimized when the amount of GO filler is 0.3 wt%.After adding 0.3 wt%GO,the concentration of dioctyl sebacate(DOS)migrated into the liner is decreased by 23.28%,and the concentration of water molecules is decreased by 51.89%,indicating that the introduction of GO can significantly improve the anti-migration performance of the liner.In addition,the bond strength is greatly increased from 0.25 MPa to 0.95 MPa,which meets the application requirements of the current propellant system.This research provides an important way for the preparation of structure-function synergistic anti-migration composite liners.
基金Supported by The Project Research Fund from Kochi University,to Takeuchi Ha Grant-in-Aid for Scientific Research from the Ministry of Education,Science and Culture of Japan,No. 21590631 and 21590629,in part
文摘AIM: To investigate genetic diversity of Helicobacter pylori (H. pylorl) cell division-related gene A (cdrA) and its effect on the host response.METHODS: Inactivation of H. py/ori cdrA, which is involved in ceil division and morphological elonga- tion, has a role in chronic persistent infections. Ge- netic property of H. pylori cdrA was evaluated using polymerase chain reaction and sequencing in 128 (77 American and 51 Japanese) clinical isolates obtained from 48 and 51 patients, respectively. Enzyme-linked immunosorbent assay was performed to measure in- terleukin-8 (IL-8) secretion with gastric biopsy speci- mens obtained from American patients colonized with cdrA-positive or -negative strains and AGS cells co- cultured with wild-type HPK5 (cdrA-positive) or its de- rivative HPKT510 (cdrA-disruptant). Furthermore, the cytotoxin-associated gene A (cagA) status (transloca- tion and phosphorylation) and kinetics of transcription factors [nuclear factor-kappa B (NF-~:B) and inhibition kappa B] were investigated in AGS cells co-cultured with HPK5, HPKT510 and its derivative HPKSCA (cagA- disruptant) by western blotting analysis with immuno- precipitation. RESULTS: Genetic diversity of the H. pylori cdrA gene demonstrated that the cdrA status segregated into two categories including four allele types, cdrA-positive (al- lele types, I and 11 ) and cdrA-negative (allele types; 111 and IV) categories, respectively. Almost all Japanese isolates were cdrA-positive ( 1 : 7.8% and 11 : 90.2%), whereas 16.9% of American isolates were cdrA-positive (11) and 83.1% were cdrA-negative (nl: 37.7% and IV: 45.5%), indicating extended diversity of cdrA in individual American isolates. Comparison of each isolate from different regions (antrum and corpus) in the stomach of 29 Americans revealed that cdrA status was identical in both isolates from different regions in 17 cases. However, 12 cases had a different cdrA al- lele and 6 of them exhibited a different cdrA category between two regions in the stomach. Furthermore, in 5 of the 6 cases possessing a different cdrA category, cdrA-negative isolate existed in the corpus, suggesting that cdrA-negative strain is more adaptable to coloni- zation in the corpus. IL-8 secretions from AGS revealed that IL-8 levels induced by a cdrA-disrupted HPKT510 was significantly lower (P 〈 0.01) compared to wild- type HPK5: corresponding to 50%-60% of those of wild-type HPK5. These data coincided with in vivo data that an average value of IL-8 in biopsy specimens from cdrA-positive and cdrA-negative groups was 215.6 and 135.9 pg/mL, respectively. Western blotting analysis documented that HPKT510 had no effect on CagA translocation and phosphorylation, however, nuclear accumulation of NF-κB was lower by HPKT510 com- pared to HPK5. CONCLUSION: Colonization by a cdrA-negative or cdrA-dysfunctional strain resulted in decreased IL-8 production and repression of NF-κB, and hence, atten- uate the host immunity leading to persistent infection.
基金Supported by the National Natural Science Foundation of China,No.81470838the Science Foundation of Health Bureau of Zhejiang Province,No.2015KYB030
文摘Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.
基金the National Natural Science Foundation of China(No.81271807).
文摘Absent in melanoma 2(AIM2)inflammasome is a crucial link bridging the innate host defense and the subsequent adaptive immunity when activated by exogenous double stranded DNA(dsDNA).Through establishing models of disseminated murine cytomegalovirus(MCMV)infection in BALB/c and C57BL/6 mice,we evaluated dynamic expression of AIM2 inflammasome components and its relationship with pathological damage and viral replication,trying tofigure out whether AIM2 inflammasome is related to the chronic mechanism of MCMV.BALB/c and C57BL/6 mice were sacrificed on day 0,1,3,7,14 and 28 post infection.Expression levels of AIM2,pro-caspase-1,caspase-1 p20,pro-IL1β and mature IL1β in primary peritoneal macrophages(PMs)and spleens were detected by Western blotting.Contents of IL18 in the serum were detected by ELISA.Pathological examinations of livers were performed,and mRNA levels of MCMV glycoprotein B(gB)in salivary glands also assessed.Results showed that expression levels of AIM2 in PMs and spleens of C57BL/6 mice increased on day 3,even continued to day 28;caspase-1 p20 and mature IL1β increased on day 7,14 and 28;the persistently high expression of IL1β in the serum started on day 1,showing a double peak curve.As for BALB/c mice,expression of AIM2 in PMs increased on day 1 and day 7,while contents of AIM2 in spleens increased on day 1 and day 3;caspase-1 p20 and mature ILip merely increased 7 days fter infection.Thereafter,expression levels of AIM2,caspase-1 p20,mature IL1β and IL18 were limited;the duration of AIM2 inflammasome activation in BALB/c mice was much shorter than that in C57BL/6 mice.The severer pathological damage and more viral replications in BALB/c mice further proved the deficient antiviral immunity to MCMV.In conclusion,the activation of AIM2 inflammasome in BALB/c mice was short-lived,which is quite possibly related to the chronicity of MCMV infection.
基金supported by The National Science Fund for Distinguished Young Scholars(No.:0602150028)
文摘Objective: To discuss the ef ect of BRMS1 on the proliferation, migration and adhesion of mouse forestomach carcinoma(MFC). Methods: The constructed p CMV-myc-BRMS1 recombinant plasmid and blank plasmid were transfected into mouse forestomach carcinoma. MTT method was employed to measure the activity of gastric cancer cell; the scratch assay and Transwell assay to measure the migration and invasion of gastric cancer cell; the adhesion assay to measure the adhesion of gastric cancer cell; while the Western blot assay to measure the expression of The NF-毷B signal pathway, downstream matrix metalloproteinase(MMP-2), MMP-9 and osteopontin and E-cadherin in the gastric cancer cell. Besides, the transplanted animal model of gastric cancer in mice was constructed to measure the size of tumor xenograft. Results: Results of MTT assay showed that, compared with the empty vector control group, the activity of gastric cancer cell was not af ected in the BRMS1 transfection group. The improved expression of BRMS1 could inhibit the adhesion, migration and invasion of gastric cancer cell(P<0.01). Besides, compared with the empty vector control group, the phosphorylation of NF-毷B p65 and I毷Bα was reduced in the BRMS1 transfection group, with the decreased expression of MMP 2, MMP 9 and osteopontin and the increased expression of E-cadherin(P<0.01). Results of animal experiment also showed that the expression of BRMS1 did not af ect the transplanted tumor. Conclusions: The expression of BRMS1 can signii cantly inhibit the adhesion, migration, invasion and metastasis of MCF gastric cancer cell, which is related to The NF-毷B signal pathway.
文摘Increasing evidence has revealed that maternal cytomegalovirus (CMV) infection may be associated with neurodevelopmental disorders in offspring. Potential relevance between the placental inflammation and CMV-related autism has been reported by clinical observation. Meanwhile, abnormal expression of Toll-like receptor 2 (TLR2) and TLR4 in placenta of patients with chorioamnionitis was observed in multiple studies. IL-6 and IL- 10 are two important maternal inflammatory mediators involved in neurodevelopmental disorders. To investigate whether murine CMV (MCMV) infection causes alterations in placental IL-6/10 and TLR2/4 levels, we analyzed the dynamic changes in gene expression of TLR2/4 and IL-6/10 in placentas following acute MCMV infection. Mouse model of acute MCMV infection during pregnancy was created, and pre-pregnant MCMV infected, lipopolysaccharide (LPS)-treated and uninfected mice were used as controls. At E13.5, E 14.5 and E 18.5, placentas and fetal brains were harvested and mRNA expression levels of placental TLR2/4 and IL-6/10 were analyzed. The results showed that after acute MCMV infection, the expression levels of placental TLR2/4 and IL-6 were elevated at E13.5, accompanied by obvious placental inflammation and reduction of placenta and fetal brain weights. However, LPS 50 ktg/kg could decrease the IL-6 expression at E13.5 and E14.5. This suggests that acute MCMV infection during pregnancy could up-regulate the gene expression of TLR2/4 in placental trophoblasts and activate them to produce more pro- inflammatory cytokine IL-6. High dose of LPS stimulation (50 gg/kg) during pregnancy can lead to down-regulation of IL-6 levels in the late stage. Imbalance of IL-6 expression in placenta might be associated with the neurodevelopmental disorders in progeny.
基金supported by China Postdoctoral Science Foundation (Grant No. 20070420277)
文摘Objective To investigate whether the presence of structured CagA proteins in Western- and Eastern-type Helicobacter pylori (H. pylori) induces different incidences of gastric diseases. Methods CagA and phosphorylatd CagA were expressed in AGS gastric epithelial cells infected with wild type and mutant strains. The ability of individual CagA was determined by immunoprecipitation and Western blot assay. Morphological changes of these cells were observed under microscope to evaluate the appearance of elongation hummingbird phenotype. Results The sizes of CagA proteins in different strains were different, and no phosphorylated CagA proteins were detected in wild-type strains. Meanwhile, the kinetics of CagA status in AGS infected with H. pylori was detected. The molecular weight of phosphorylated CagA with the same size of CagA proteins in H. pylori was different in infections with different wild-type strains. CagA and phosphorylated CagA increased in a time-dependent manner after the infection. The hummingbird phenotype with H. pylori for time-course was observed under microscope. Instead of HPK5 strain, the wild-type 26695 strain induced hummingbird phenotype in a time-dependent manner. Conclusion Translocation and phosphorylation of CagA are necessary, but not sufficient, for the induction of hummingbird phenotype in AGS cells.
文摘BACKGROUND In most cases of yellow nail syndrome(YNS),the classic triad of yellow nails,lymphedema and respiratory manifestations rarely manifest simultaneously.Therefore,diagnosis is delayed or frequently missed.CASE SUMMARY We report a 62-year-old YNS patient presenting with bilateral pleural,pericardial and peritoneal effusions who,2 mo later,developed minimal-change nephrotic syndrome.After treatment with vitamin E,clarithromycin and prednisone for 3 mo,effusions in the chest,pericardium and abdominal cavity decreased while urine protein levels returned to within normal ranges.CONCLUSION Clinicians should consider the possibility of YNS for patients presenting with multiple serous effusions and nephrotic syndromes.
文摘Background:Outbreaks of coronavirus disease 2019(COVID-19)have been recorded in different countries across the globe.The virus is highly contagious,hence early detection,isolation,and quarantine of infected patients will play an important role in containing the viral spread.Diagnosis in a mobile lab can aid to find infected patients in time.Methods:Here,we develop a field-deployable diagnostic workflow that can reliably detect COVID-19.Instruments used in this workflow can easily fit in a mobile cabin hospital and also be installed in the community.Different steps from sample inactivation to detection were optimized to find the fastest steps and portable instruments in the detection of COVID-19.Each step was compared to that of the normal laboratory diagnosis setup.Results:From the results,our proposed workflow(80 min)was two times faster compared to that of the normal laboratory workflow(183 min)and a maximum of 32 samples could be detected at each run.Additionally,we showed that using 1%Rewocid WK-30 could inactivate the novel coronavirus directly without affecting the overall detection results.Comparison of our workflow using an in-house assay to that of a commercially acquired assay produced highly reliable results.From the 250 hospital samples tested,there was a high concordance 247/250(98.8%)between the two assays.The in-house assay sensitivity and specificity were 116/116(100%)and 131/134(97.8%)compared to that of the commercial assay.Conclusion:Based on these results,we believe that our workflow is fast,reliable,adaptable and most importantly,field-deployable.
基金Supported by National Natural Science Foundation of China:81973940Shanghai Clinical Research Center for Acupuncture and Moxibustion:20MC1920500Clinical Key Specialty Construction Foundation of Shanghai:shslczdzk04701。
文摘Objective:This study aimed to assess the effects of electroacupuncture(EA)at the contralateral,ipsilateral,or bilateral"Zusanli(ST36)"and"Yanglingquan(GB34)"on neuropathic pain caused by chronic contractile injury(CCI)and to explore the role of the nuclear factor erythroid 2-related factor 2(Nrf2)pathway in the effects of EA.Methods:Male Sprague-Dawley rats were subjected to the CCI model to induce neuropathic pain.A total of 45 rats were randomly divided into five groups(n=9):sham,CCI,EA-Co(CCI+EA at contralateral acupoints),EA-Ip(CCI+EA at ipsilateral acupoints),and EA-Bi(CCI+EA at bilateral acupoints).The rats received EA treatment on day 8 after CCI,once every alternate day,for a total of eight times.The time courses of mechanical pain threshold(MWT),hind paw withdrawal latency(HWL),and sciatic functional index(SFI)were determined.The expression levels of 8-hydroxydeoxyguanosine(8-OHdG),glutathione(GSH),superoxide dismutase(SOD)activity,interleukin-6(IL-6),interleukin-1 beta(IL-1β),and tumor necrosis factor factor-alpha(TNF-α)in the spinal cord were measured.The distribution of Nrf2,its expression of Nrf2 in both the cytosol and nucleus,and the protein levels of its downstream target genes,NQO1 and HO-1,were detected via double immunofluorescence staining and western blotting,respectively.Results:Following CCI,both MWT and HWL in the CCI group significantly decreased from day 14 after surgery(P<0.001).EA treatment exhibited significant antinociceptive effects induced by CCI by increasing the MWT and HWL values,especially bilateral EA(P<0.05).The SFI of the CCI group was significantly lower than that of the sham group(P<0.001).Only bilateral EA improved the SFI scores compared to the CCI group(P<0.05).8-OHdG levels in the spinal cord of the CCI group were significantly higher than those in the sham group(P<0.05),whereas GSH levels and SOD activity in the spinal cord of the CCI group were significantly lower than those in the sham group(P<0.001 and P<0.01,respectively).Bilateral EA administration significantly downregulated 8-OHdG levels(P<0.01)and upregulated GSH levels and SOD activity in the spinal cord(P<0.01).CCI significantly enhanced the production of IL-1β,IL-6,and TNF-αin the spinal cord compared with that in the sham group(all P<0.001).Meanwhile,the effects of EA were also accompanied by markedly decreased expression of IL-1βand IL-6 in the spinal cord(P<0.05).TNF-αlevels were only decreased in the EA-Ip and EA-Bi groups compared with those in the CCI group(P<0.001).Confocal microscopy revealed that Nrf2 was mainly localized in the neurons of the spinal cord.Notably,EA treatment enhanced nuclear translocation of Nrf2 in neurons.CCI significantly decreased the production of Nrf2,HO-1,and NQO1 in the spinal cord compared to the sham group(P<0.001),and bilateral EA up-regulated the protein levels of Nrf2 and its target genes HO-1 and NQO1(all P<0.001).Conclusion:Our results suggest that bilateral EA is an optimal therapeutic strategy for neuropathic pain.The effects of EA on neuropathic pain may be mediated by the restoration of the Nrf2 pathway in the spinal cord.
基金Supported by National High TechR&DProgramin China!( 86 3 5 1 2 970 4 2 6 86 3 5 1 2 980 4 1 8)
文摘The micro robot based on screw motion wheels, which features high payload/mass ratio, fast and continuous motion, adaptation to pipe diameter or roundness variations, is suitable for locomotion and inspection inside small diameter pipelines. The robot inspection system, Tubot I, developed at Shanghai University is composed of locomotion mechanism with an inner motor, a micro CCD camera and a monitor outside the pipeline. In the paper, the kinematics and statics analyses are presented for the screw locomotion system of Tubot I. The moving characteristics are obtained from experiments on the robot prototype.
基金supported by the Natural Science Foundation of China(Grant Nos.81703839,81874411).
文摘Objective:To evaluate the effect of acupuncture on myelosuppression after chemotherapy and summarize its acupoint selection strategy.Methods:After a systematic search,an acupoint database on myelosuppression after chemotherapy was constructed.A meta-analysis was conducted to assess the efficacy of acupuncture.On this basis,association analysis and cluster analysis were performed to explore the distribution of acupoints in SPSS Modeler18.0 and SPSS 22.0.Results:40 studies with 2988 patients were included.The white blood cell count,platelet count,red blood cell count,and hemoglobin were significantly higher in patients receiving acupuncture versus convention therapy exclusively.The two groups,however,did not differ in neutrophils count.Most acupoints,mainly distributed in the limbs and the back,were from the bladder meridian,the stomach meridian,and the spleen meridian.The lower sea and transport points were the most preferred specific points,in which ST36 and SP6 ranked highest in use.ST36-RN6,SP6-SP10,and ST36-SP10 turned out to be the most significant correlations in association rule mining.In cluster analysis,LI4-RN12,ST36-RN4-RN6 were grouped for their high similarity.Conclusion:For patients with myelosuppression after chemotherapy,acupuncture significantly inhibited the decline in blood cell components(white blood cell count,platelet count,red blood cell count,and hemoglobin)except for neutrophils.As the central combination of acupuncture prescriptions for this population,ST36-SP6-RN6-SP10-RN4 presented promising prospects and deserved more exploration for clinical use.
基金financially supported by Gansu Provincial Natural Science Foundation of China(Nos.17JR5RA198,2020HZ-2)the Cooperation project of Gansu Academy of Sciences(No.2020HZ-2)+1 种基金the Fundamental Research Funds for the Central Universities(Nos.lzujbky-2018-119,lzujbky-2018-ct08,lzujbky-2019-it23)the Key Areas Scientific and Technological Research Projects in Xinjiang Production and Construction Corps(No.2018AB004)。
文摘For zinc air batteries,a non-noble metal-based electrocatalyst with a high performance and stability in oxygen evolution reaction(OER)and oxygen reduction reaction(ORR)is imperative in application.Herein,a catalyst based on FeCo-N encapsuled in nitrogen-doped carbon nanotubes has been prepared,which provides an implementable method to design controlled structures with excellent bifunction al electrocatalytic activities.By adjusting the molar ratio of two metals,the synthesized FeCo-N-C catalyst delivers a competitive ORR and OER performance compared with commercial Pt/C and IrO_(2),performing a low overvoltage gap between ORR(E_(1/2))and OER(E_(j=10))of 0.8 V.Moreover,as a promising cathode in zinc air battery,the FeCo-N-C catalyst possesses an affirmative stability of over 100 h and large power density(129 mW·cm^(-2)).This work demonstrates that FeCo-N-C is one of the most promising catalysts for zinc air batteries and provides a possibility for exploration of batteries with high stability by adjusting the molar ratio of metals in the catalysts.
基金financially supported by the National Natural Science of China(Nos.22001156 and 21401121)General Financial Grant from the China Postdoctoral Science Foundation(No.2017M623095)Returned Personnel Science Foundation of Shaanxi Province,China(No.2018044)。
文摘Supercapacitors(SCs)have been considered as the most promising energy storage device due to high power density,long cycle life,and fast energy storage and efficient delivery.The excellent electrode materials of SCs generally have based on large porous structure,excellent conductivity,and heteroatom doping for charge transfer.Among various electrode materials,biomass-derived carbon materials have received widespread attention owing to excellent performances,environmental friendliness,lowcost and renewability.Additionally,composites materials based on biomass-derived carbon and transition metalbased material can obtain more advantages of structural and performance than single component,which opens up a new way for the fabrication of high-performance SC electrode materials.Therefore,this review aims to the recent progress on the design and fabrication of biomassderived carbons/transition metal-based composites in supercapacitor application.Finally,the development trends and challenges of biomass-derived electrode materials have been discussed and prospected.
基金supported by the National Key R&D Program of China(nos.2019YFA0904200 and 2018YFA0507600)the Tsinghua University Spring Breeze Fund(no.2020Z99CFY042)+1 种基金the National Natural Science Foundation of China(nos.92053108 and 31961143004)NCC Fund(no.NCC2020FH04).
文摘Stimulator of interferon genes,namely STING,an adaptor protein located in the endoplasmic reticulum,has been recognized as a shining target for cancer and infection research.However,STING agonists cyclic dinucleotides(CDNs)have shown almost zero efficacy in phase I clinical trials as a monotherapy,likely due to poor cellular permeability and rapid diffusion despite intratumoral injection.These deficiencies further affect other applications of CDNs,such as pandemic SARS-CoV-2 prevention and therapy.Here,we rationally design a supramolecular cytosolic delivery system based on controllable recognition of calixarene,namely CASTING(CAlixarene-STING),to improve CDN druggability,including degradation stability,cellular permeability,and tissue retention.CASTING efficiently enhances the immunostimulatory potency of CDGSF[a chemically modified cyclic di-GMP(CDG)]to generate an immunogenic microenvironment for melanoma regression,anti-PD-1 response rate increase,and durable memory formation against tumor recurrence.More importantly,CASTING displays a superior adjuvant activity on SARSCoV-2 recombinant spike/receptor binding domain vaccines,inducing robust and coordinated T-cell and antibody responses against SARS-CoV-2 infection in vivo.Collectively,the CASTING design represents an innovative advancement to facilitate the clinical translational capability of STING agonists.
基金supported by the National Key Research and Development Program of China(2018YFA0507201).
文摘Dear Editor,The prolonged outbreak and spread of coronavirus disease 2019(COVID-19),caused by SARS-CoV-2 poses a great threat to global economic and public health.The protective efficacy of the vaccines based on the spike protein(S)of SARS-CoV-2 has been compromised by the emergence of variants of concern(VOC).