Computational fluid dynamics(CFD)and the finite element method(FEM)are used to investigate the wind-driven dynamic response of cantilever traffic signal support structures as a whole.By building a finite element model...Computational fluid dynamics(CFD)and the finite element method(FEM)are used to investigate the wind-driven dynamic response of cantilever traffic signal support structures as a whole.By building a finite element model with the same scale as the actual structure and performing modal analysis,a preliminary understanding of the dynamic properties of the structure is obtained.Based on the two-way fluid-structure coupling calculation method,the wind vibration response of the structure under different incoming flow conditions is calculated,and the vibration characteristics of the structure are analyzed through the displacement time course data of the structure in the crosswind direction and along-wind direction.The results show that the maximum response of the structure increases gradually with the increase of wind speed under 90°wind direction angle,showing a vibration dispersion state,and the vibration response characteristics are following the vibration phenomenon of galloping;under 270°wind direction angle,the maximum displacement response of the structure occurs at the lower wind speed of 5 and 6m/s,and the vibration generated by the structure is vortex vibration at this time;the displacement response of the structure in along-wind direction increaseswith the increase of wind speed.The along-wind displacement response of the structure will increase with increasing wind speed,and the effective wind area and shape characteristics of the structurewill also affect the vibration response of the structure.展开更多
A series of N-doped carbon materials(NCs)were synthesized by using biomass citric acid and dicyandiamide as renewable raw materials via a facile onestep pyrolysis method. The characterization of microstructural featur...A series of N-doped carbon materials(NCs)were synthesized by using biomass citric acid and dicyandiamide as renewable raw materials via a facile onestep pyrolysis method. The characterization of microstructural features shows that the NCs samples are composed of few-layered graphene-like nanoflakes with controlled in situ N doping, which is attributed to the confined pyrolysis of citric acid within the interlayers of the dicyandiamide-derived g-C_3N_4 with high nitrogen contents. Evidently, the pore volumes of the NCs increased with the increasing content of dicyandiamide in the precursor. Among these samples, the NCs nanoflakes prepared with the citric acid/dicyandiamide mass ratio of 1:6, NC-6,show the highest N content of ~6.2 at%, in which pyridinic and graphitic N groups are predominant. Compared to the commercial Pt/C catalyst, the as-prepared NC-6 exhibits a small negative shift of ~66 mV at the half-wave potential, demonstrating excellent electrocatalytic activity in the oxygen reduction reaction. Moreover, NC-6 also shows better long-term stability and resistance to methanol crossover compared to Pt/C. The efficient and stable performance are attributed to the graphene-like microstructure and high content of pyridinic and graphitic doped nitrogen in the sample, which creates more active sites as well as facilitating charge transfer due to the close four-electron reaction pathway. The superior electrocatalytic activity coupled with the facile synthetic method presents a new pathway to cost-effective electrocatalysts for practical fuel cells or metal–air batteries.展开更多
Pears with red skin are attractive to consumers and provide additional health benefits.Identification of the gene(s)responsible for skin coloration can benefit cultivar selection and breeding.The use of QTL-seq,a bulk...Pears with red skin are attractive to consumers and provide additional health benefits.Identification of the gene(s)responsible for skin coloration can benefit cultivar selection and breeding.The use of QTL-seq,a bulked segregant analysis method,can be problematic when heterozygous parents are involved.The present study modified the QTL-seq method by introducing a|Δ(SNP-index)|parameter to improve the accuracy of mapping the red skin trait in a group of highly heterozygous Asian pears.The analyses were based on mixed DNA pools composed of 28 red-skinned and 27 green-skinned pear lines derived from a cross between the‘Mantianhong’and‘Hongxiangsu’red-skinned cultivars.The‘Dangshansuli’cultivar genome was used as reference for sequence alignment.An average single-nucleotide polymorphism(SNP)index was calculated using a sliding window approach(200-kb windows,20-kb increments).Nine scaffolds within the candidate QTL interval were in the fifth linkage group from 111.9 to 177.1 cM.There was a significant linkage between the insertions/deletions and simple sequence repeat markers designed from the candidate intervals and the red/green skin(R/G)locus,which was in a 582.5-kb candidate interval that contained 81 predicted protein-coding gene models and was composed of two subintervals at the bottom of the fifth chromosome.The ZFRI 130-16,In2130-12 and In2130-16 markers located near the R/G locus could potentially be used to identify the red skin trait in Asian pear populations.This study provides new insights into the genetics controlling the red skin phenotype in this fruit.展开更多
We studied the influence of doctor-patient communication skills training on brain functional architecture using resting-state functional MRI(rs-fMRI) with a regional homogeneity(ReHo) method. Ten medical students ...We studied the influence of doctor-patient communication skills training on brain functional architecture using resting-state functional MRI(rs-fMRI) with a regional homogeneity(ReHo) method. Ten medical students participated in the study. A 1-year long doctor-patient communication skills training program was conducted. RsfMRI data were collected at baseline, one month and one year after training. There was a significant increase in the communication skills test average scores between baseline and 1-month duration of training(P〈0.001). After one month of communication skills training, medical students had decreased ReHo in the right superior temporal gyrus compared with the baseline. After one year of communication skills training, students had increased ReHo in multiple regions and decreased ReHo in several regions(P 〈0.05, Alphasim corrected). The change of ReHo values in the superior temporal gyrus negatively correlated with the change of communication skills scale score between one month after communication skills training and baseline(r=-0.734, P= 0.036). The training program we used can be an effective approach of improving doctor-patient communication skills, and the training resulted in functional plasticity of the brain’s architecture toward optimizing locally functional organization.展开更多
Development of high performance electrocatalysts for oxygen evolution reaction (OER) in acidic media remains a challenge for direct water splitting using an electrolyzer.Recently,Ruddlesden-Popper phase Sr_(2)IrO_(4)w...Development of high performance electrocatalysts for oxygen evolution reaction (OER) in acidic media remains a challenge for direct water splitting using an electrolyzer.Recently,Ruddlesden-Popper phase Sr_(2)IrO_(4)was discovered to be an efficient OER catalyst because of its unique structure,which consists of layers of both rock salt and perovskite phases simultaneously.In this study,we prepared a series of B-site mixed,Ruddlesden-Popper phase of Sr_(2)(Ru_(x)Ir_(1-x))O_(4) and examined their electrocatalytic properties for OER in acidic media.Through partial substitution of Ru in the B-site of Ruddlesden-Popper phase materials,we achieved much enhanced OER performance for this series of Sr_(2)(Ru_(x)Ir_(1-x))O_(4)electrocatalysts,among which Sr_(2)(Ru_(0.5)Ir_(0.5))O_(4)exhibited the best catalytic activity with a current density of 8.06 m A/cm^(2) at 1.55 V and a Tafel slope of 47 m V/dec.This current density is three times higher than that of Sr_(2)Ir O_(4).The B-site mixed Sr_(2)(Ru_(0.5)Ir_(0.5))O_(4)retained good stability in acidic conditions for>24 h at 10 m A/cm^(2).A range of techniques were used to characterize the crystal and electronic structures of the Sr_(2)(Ru_(x)Ir_(1-x))O_(4)samples.Our data indicate that the improved OER performance can be correlated to the formation of high level of hydroxyl groups and the enhanced overlap between Ir/Ru 4d and O_(2)p orbitals,revealing a new way for the design of efficient OER electrocatalysts by regulating their composition and electronic structures.展开更多
Results Sixty-one cancer survivors and 183 matched non-cancer patients were screened from 2,828 COVID-19 infected patients admitted to 4 hospitals in Wuhan,China.The median ages of the cancer survivor cohort and non-c...Results Sixty-one cancer survivors and 183 matched non-cancer patients were screened from 2,828 COVID-19 infected patients admitted to 4 hospitals in Wuhan,China.The median ages of the cancer survivor cohort and non-cancer patient cohort were 64.0(55.0–73.0)and 64.0(54.0–73.5),respectively(P=0.909).Cancer survivors reported a higher incidence of symptom onset than non-cancer patients.Fever(80.3%vs.65.0%;P=0.026)was the most prevalent symptom,followed by cough(65.6%vs.37.7%;P<0.001),myalgia,and fatigue(45.9%vs.13.6%;P<0.001).The risks of the development of severe events(adjusted hazard ratio[AHR]=1.25;95%confidence interval[CI]:0.76–2.06;P=0.378)and mortality(relative risk[RR]=0.90,95%CI:0.79–1.04;P=0.416)in the cancer survivor cohort were comparable to those of the matched non-cancer patient cohort.However,the cancer survivor cohort showed a higher incidence of secondary infection(52.5%vs.30.1%;RR=1.47,95%CI:1.11–1.95;P=0.002)and a prolonged viral RNA shedding duration(32 days[IQR 26.0–46.0]vs.24.0 days[IQR 18.0–33.0];AHR=0.54;95%CI:0.38–0.80;P<0.05).Conclusion Compared to non-cancer patients,cancer survivors with COVID-19 exhibited a higher incidence of secondary infection,a prolonged period of viral shedding,but comparable risks of the development of severe events and mortality.It is helpful for clinicians to take tailored measures to treat cancer survivors with COVID-19.展开更多
BACKGROUND: Water decoction of the Chinese traditional medicine mixture of pinellia ternate and scorpion is an effective treatment for epilepsy. OBJECTIVE: To compare nanometer particles and effects of water decocti...BACKGROUND: Water decoction of the Chinese traditional medicine mixture of pinellia ternate and scorpion is an effective treatment for epilepsy. OBJECTIVE: To compare nanometer particles and effects of water decoction of Chinese traditional medicine mixture on P53 protein levels and apoptosis in the cerebral cortex and hippocampus of epileptic rats. DESIGN, TIME AND SETTING: This randomized, controlled molecular biology study was performed at the Key Laboratory of Child Neural Rehabilitation of Jiamusi University from October to December 2007. MATERIALS: Forty healthy male Wistar rats were used in this study. Convulsion rat models were established by intraperitoneal infusion of 35 mg/kg pentylenetetrazol, once a day, for 28 successive days. The Chinese traditional medicine mixture, comprising pinellia ternate, scorpion, centipede, bupleurum, peach pit and glycyrrhiza, was purchased from Beijing Tongrentang, China. The mixture was made into nanometer particles and water decoction. The apoptosis determination kit and P53 immunohistochemistry kit were bought from Boster, China. METHODS: Forty Wistar rats were randomly divided into four groups of ten rats per group, control, nanometer particle, water decoction and epileptic model groups. Rats in the nanometer particle and water decoction groups were respectively treated with 300 mg/kg Chinese herb nanometer particle suspension and water decoction by gavage, once a day, for 28 days. Rats in the epileptic model group were fed an equal volume of saline by gavage. Rats in the control group were only administered with the same volume of saline by gavage. MAIN OUTCOME MEASURES: Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) and immunohistochemistry were used to respectively detect neuronal apoptosis and P53 protein expression in the rat brain cortex and hippocampus at 28 days following administration. RESULTS: The number of apoptotic neurons was lower in the nanometer particle and water decoction groups compared with the epileptic model group. The number of apoptotic cells and P53 protein expression in the rat cerebral cortex and hippocampus was greater in the epileptic model group compared with the control group (P 〈 0.05), but lower in the nanometer particle and water decoction groups compared with the epileptic model group (P 〈 0.05), and lower in the nanometer particle group compared with the water decoction group (P 〈 0.05). CONCLUSION: Chinese traditional medicine mixture decreases neuronal apoptosis and P53 protein expression in epileptic rats. The effect of nanometer particles is significant compared with water decoction.展开更多
Improving the emission performance of colloidal quantum dots(QDs)is of paramount importance for their applications on light-emitting diodes(LEDs),displays and lasers.A highly promising approach is to tune the carrier ...Improving the emission performance of colloidal quantum dots(QDs)is of paramount importance for their applications on light-emitting diodes(LEDs),displays and lasers.A highly promising approach is to tune the carrier recombination channels and lifetime by exploiting the energy transfer process.However,to achieve this precise emission optimization,quantitative modulation on energy transfer efficiency is highly desirable but still challenging.Here,we demonstrate a convenient approach to realize tunable energy transfer efficiency by forming QDs mixture with controllable donor/acceptor(D/A)ratio.With the mixing ratio ranging from 16/1 to 1/16,the energy transfer efficiency could be effectively tuned from near zero to~70%.For the high mixing ratio of 16/1,acceptors obtain adequate energy supplied by closely surrounding donors,leading to~2.4-fold PL enhancement.While for the low mixing ratio,the ultrafast and efficient energy extraction process directly suppresses the multi-exciton and Auger recombination in the donor,bringing about a higher threshold.The facile modulation of emission performance by controllably designed mixing ratio and quantitatively tunable energy transfer efficiency will facilitate QD-based optoelectronic and photovoltaic applications.展开更多
This paper attempts to establish a framework of upgrading mechanism in China's foreign economic opening strate莒y in order to conclude the new connotation of upgrade for China's foreign economic opening,with t...This paper attempts to establish a framework of upgrading mechanism in China's foreign economic opening strate莒y in order to conclude the new connotation of upgrade for China's foreign economic opening,with the basic starting point of ternary marginal extension on extensive growth,in the perspective of corporate heterogeneity theory.It also involves the new path of the transformation from"quantity1'to"quality"regarding the amounts,models and locations of China's foreign trade and investment.At last,this theoretical frame is complemented upon a case study of free trade zone and regional cooperation of Guangdong,Hong Kong and Macao.展开更多
After nearly 40 years of development, privateeducation in China has become an important growthpoint for the development of education and an importantforce for promoting education reform. Private educationinstitutions ...After nearly 40 years of development, privateeducation in China has become an important growthpoint for the development of education and an importantforce for promoting education reform. Private educationinstitutions can be divided into two categories: privateschools engaged in academic education and privateeducation training institutions engaged in non-academiceducation. Private non-academic education institutionshave played an important role in expanding domesticdemand, adjusting the structure, increasing employmentand promoting social development, and thus haveflourished. For example, Yu Minhong founded newOriental school in 1993, and Yin Xiong founded gianteducation in 1994. In September 2006, new Orientaleducation group was listed in the United States. Sincethen, a number of private education enterprises, suchas Bowen net, China net education, Xuesi and Xuedaeducation, have been listed in the United States, whichhas pushed the private non-academic education in Chinato a new height. However, with the rapid developmentof private non-academic education enterprises, they arealso facing great challenges.展开更多
Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality worldwide.Post-translational modifications(PTMs)of proteins have a great impact on protein function.Almost all proteins...Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality worldwide.Post-translational modifications(PTMs)of proteins have a great impact on protein function.Almost all proteins can undergo PTMs,including phosphorylation,acetylation,methylation,glycosylation,ubiquitination,and so on.Many studies have shown that PTMs are related to the occurrence and development of cancers.The findings provide novel therapeutic targets for cancers,such as glypican-3 and mucin-1.Other clinical implications are also found in the studies of PTMs.Diagnostic or prognostic value,and response to therapy have been identified.In HCC,it has been shown that glycosylated alpha-fetoprotein(AFP)has a higher detection rate for early liver cancer than conventional AFP.In this review,we mainly focused on the diagnostic and prognostic value of PTM,in order to provide new insights into the clinical implication of PTM in HCC.展开更多
Plants secrete defense molecules into the extracellular space (the apoplast) to combat attacking microbes. However, the mechanisms by which successful pathogens subvert plant apoplastic immunity remain poorly understo...Plants secrete defense molecules into the extracellular space (the apoplast) to combat attacking microbes. However, the mechanisms by which successful pathogens subvert plant apoplastic immunity remain poorly understood. In this study, we show that PsAvh240, a membrane-localized effector of the soybean pathogen Phytophthora sojae, promotes P. sojae infection in soybean hairy roots. We found that PsAvh240 interacts with the soybean-resistant aspartic protease GmAP1 in planta and suppresses the secretion of GmAP1 into the apoplast. By solving its crystal structure we revealed that PsAvh240 contain six a helices and two WY motifs. The first two a helices of PsAvh240 are responsible for its plasma membrane-localization and are required for PsAvh240's interaction with GmAP1. The second WY motifs of two PsAvh240 molecules form a handshake arrangement resulting in a handshake-like dimer. This dimerization is required for the effector's repression of GmAP1 secretion. Taken together, these data reveal that PsAvh240 localizes at the plasma membrane to interfere with GmAP1 secretion, which represents an effective mechanism by which effector proteins suppress plant apoplastic immunity.展开更多
As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear tra...As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.展开更多
Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure.It is very promising to find the strategies ...Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure.It is very promising to find the strategies to slow or even prevent the progression of fibrosis.This study focused on whether renal fibrosis decellularized scaffolds has the potential to be a model of cellular mechanisms of tissue fibrosis or donors for tissue engineering.In order to evaluate the feasibility of decellularized scaffolds derived from pathological kidneys,histology,proteomics and ELISA will be used to analysis the changes in the structure and main components of fibrotic tissue.The fibrosis model in this paper was induced by adenine-fed and the results showed that the structure of fibrotic scaffold was changed and some protein were up-regulated or down-regulated,but the cytokines associated with renal regeneration after injury were remained.In cell experiments,endothelial progenitor cells proliferated well,which proved that the fibrotic scaffolds have non-cytotoxic.All these conclusions indicate that the renal fibrosis decellularized scaffolds model has the ability to study fibrosis mechanism and the potential to be engineering donors as well as normal scaffolds.展开更多
For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stim...For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass (MBG)/upconversion nanoparticle (UCNP) nanocomposite [UCNPs@SiO2@mSiO2-XCa (X = 0, 5, 10, 15, and 20)] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells (BMSCs) was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core--sheU structure composed of UCNPs and a mesoporous SiO2/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine (ZnPc), red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200-500 ~g/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.展开更多
Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audit...Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audition over a wide dynamic range,but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear.By means of three-dimensional electron microscopy and artificial intelligence-based algorithms,we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice.We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization.Moreover,our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.展开更多
DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs.Hence,small molecules that inhibit DDR are expected to enhance the an...DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs.Hence,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy.Through a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins.Mechanistically,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(ATR),two master upstream regulators of the DDR signal,through inducing degradation of ATM and ATR-interacting protein(ATRIP),an obligate associating protein of ATR,respectively.As a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models.While degradation of ATRIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not proteasome.Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs.These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin.Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.展开更多
The global outbreak of the coronavirus disease 2019(COVID-19) led to the suspension of most treatments with assisted reproductive technique(ART). However, with the recent successful control of the pandemic in China, t...The global outbreak of the coronavirus disease 2019(COVID-19) led to the suspension of most treatments with assisted reproductive technique(ART). However, with the recent successful control of the pandemic in China, there is an urgent public need to resume full reproductive care. To determine whether the COVID-19 pandemic had any adverse effects on female fertility and the pregnancy outcomes of women undergoing ART, a systematic review and meta-analysis was conducted using the electronic Chinese and English databases. Dichotomous outcomes were summarized as prevalence, and odds ratios(ORs)and continuous outcomes as standardized mean difference(SMD) with 95% confidence interval(CI). The risk of bias and subgroup analyses were assessed using Stata/SE 15.1 and R 4.1.2. The results showed that compared with women treated by ART in the pre-COVID-19 time frame, women undergoing ART after the COVID-19 pandemic exhibited no significant difference in the clinical pregnancy rate(OR 1.07, 95% CI 0.97 to 1.19;I^(2)=0.0%), miscarriage rate(OR 0.95, 95% CI 0.79 to1.14;I^(2)=38.4%), embryo cryopreservation rate(OR 2.90, 95% CI 0.17 to 48.13;I^(2)=85.4%), and oocyte cryopreservation rate(OR 0.30, 95% CI 0.03 to 3.65;I^(2)=81.6%). This review provided additional evidence for gynecologists to guide the management of women undergoing ART treatment during the COVID-19 pandemic timeframe.展开更多
A high-vanadium alloy composite layer was prepared on the surface of a carbon steel using cast composite technology,and the wear properties of the composite layer were investigated.The results showed that the microstr...A high-vanadium alloy composite layer was prepared on the surface of a carbon steel using cast composite technology,and the wear properties of the composite layer were investigated.The results showed that the microstructure of the composite layer was composed of primary vanadium carbides(VC),flake martensite,residual austenite,and fine VC.The hardness of the cast alloy layer was 63 HRC.The abrasive wear resistance and impact wear resistance were increased by 60%and 26%,respectively,compared with those of high-chromium cast iron.The excellent wear resistance of the cast alloy layer is attributed to the high-hardness primary vanadium carbide and the large number of fine secondary vanadium carbides precipitated out of the cast alloy layer.展开更多
基金funded by the National Natural Science Foundation of China(Grant No.51578512)the Cultivating Fund Project for Young Teachers of Zhengzhou University(Grant No.JC21539028).
文摘Computational fluid dynamics(CFD)and the finite element method(FEM)are used to investigate the wind-driven dynamic response of cantilever traffic signal support structures as a whole.By building a finite element model with the same scale as the actual structure and performing modal analysis,a preliminary understanding of the dynamic properties of the structure is obtained.Based on the two-way fluid-structure coupling calculation method,the wind vibration response of the structure under different incoming flow conditions is calculated,and the vibration characteristics of the structure are analyzed through the displacement time course data of the structure in the crosswind direction and along-wind direction.The results show that the maximum response of the structure increases gradually with the increase of wind speed under 90°wind direction angle,showing a vibration dispersion state,and the vibration response characteristics are following the vibration phenomenon of galloping;under 270°wind direction angle,the maximum displacement response of the structure occurs at the lower wind speed of 5 and 6m/s,and the vibration generated by the structure is vortex vibration at this time;the displacement response of the structure in along-wind direction increaseswith the increase of wind speed.The along-wind displacement response of the structure will increase with increasing wind speed,and the effective wind area and shape characteristics of the structurewill also affect the vibration response of the structure.
基金the financial support from the National Key Research and Development Program of China (2016YFB0700204)Natural Science Foundation of Jiangsu Province (No. BK20140472)+2 种基金NSFC (51602332, 51502327)Science and Technology Commission of Shanghai Municipality (15520720400, 15YF1413800, 14DZ2261203, 16DZ2260603)One Hundred Talent Plan of Chinese Academy of Sciences
文摘A series of N-doped carbon materials(NCs)were synthesized by using biomass citric acid and dicyandiamide as renewable raw materials via a facile onestep pyrolysis method. The characterization of microstructural features shows that the NCs samples are composed of few-layered graphene-like nanoflakes with controlled in situ N doping, which is attributed to the confined pyrolysis of citric acid within the interlayers of the dicyandiamide-derived g-C_3N_4 with high nitrogen contents. Evidently, the pore volumes of the NCs increased with the increasing content of dicyandiamide in the precursor. Among these samples, the NCs nanoflakes prepared with the citric acid/dicyandiamide mass ratio of 1:6, NC-6,show the highest N content of ~6.2 at%, in which pyridinic and graphitic N groups are predominant. Compared to the commercial Pt/C catalyst, the as-prepared NC-6 exhibits a small negative shift of ~66 mV at the half-wave potential, demonstrating excellent electrocatalytic activity in the oxygen reduction reaction. Moreover, NC-6 also shows better long-term stability and resistance to methanol crossover compared to Pt/C. The efficient and stable performance are attributed to the graphene-like microstructure and high content of pyridinic and graphitic doped nitrogen in the sample, which creates more active sites as well as facilitating charge transfer due to the close four-electron reaction pathway. The superior electrocatalytic activity coupled with the facile synthetic method presents a new pathway to cost-effective electrocatalysts for practical fuel cells or metal–air batteries.
基金This work was funded by the National Natural Science Foundation of China(31272140)the Agricultural Science and Technology Innovation Program(ASTIP)(CAAS-ASTIP).
文摘Pears with red skin are attractive to consumers and provide additional health benefits.Identification of the gene(s)responsible for skin coloration can benefit cultivar selection and breeding.The use of QTL-seq,a bulked segregant analysis method,can be problematic when heterozygous parents are involved.The present study modified the QTL-seq method by introducing a|Δ(SNP-index)|parameter to improve the accuracy of mapping the red skin trait in a group of highly heterozygous Asian pears.The analyses were based on mixed DNA pools composed of 28 red-skinned and 27 green-skinned pear lines derived from a cross between the‘Mantianhong’and‘Hongxiangsu’red-skinned cultivars.The‘Dangshansuli’cultivar genome was used as reference for sequence alignment.An average single-nucleotide polymorphism(SNP)index was calculated using a sliding window approach(200-kb windows,20-kb increments).Nine scaffolds within the candidate QTL interval were in the fifth linkage group from 111.9 to 177.1 cM.There was a significant linkage between the insertions/deletions and simple sequence repeat markers designed from the candidate intervals and the red/green skin(R/G)locus,which was in a 582.5-kb candidate interval that contained 81 predicted protein-coding gene models and was composed of two subintervals at the bottom of the fifth chromosome.The ZFRI 130-16,In2130-12 and In2130-16 markers located near the R/G locus could potentially be used to identify the red skin trait in Asian pear populations.This study provides new insights into the genetics controlling the red skin phenotype in this fruit.
文摘We studied the influence of doctor-patient communication skills training on brain functional architecture using resting-state functional MRI(rs-fMRI) with a regional homogeneity(ReHo) method. Ten medical students participated in the study. A 1-year long doctor-patient communication skills training program was conducted. RsfMRI data were collected at baseline, one month and one year after training. There was a significant increase in the communication skills test average scores between baseline and 1-month duration of training(P〈0.001). After one month of communication skills training, medical students had decreased ReHo in the right superior temporal gyrus compared with the baseline. After one year of communication skills training, students had increased ReHo in multiple regions and decreased ReHo in several regions(P 〈0.05, Alphasim corrected). The change of ReHo values in the superior temporal gyrus negatively correlated with the change of communication skills scale score between one month after communication skills training and baseline(r=-0.734, P= 0.036). The training program we used can be an effective approach of improving doctor-patient communication skills, and the training resulted in functional plasticity of the brain’s architecture toward optimizing locally functional organization.
基金supported in part by the US National Science Foundation(NSF-2055734)a start-up fund from University of Illinois at Urbana-Champaignthe support of a scholarship from the China Scholarship Council(CSC)。
文摘Development of high performance electrocatalysts for oxygen evolution reaction (OER) in acidic media remains a challenge for direct water splitting using an electrolyzer.Recently,Ruddlesden-Popper phase Sr_(2)IrO_(4)was discovered to be an efficient OER catalyst because of its unique structure,which consists of layers of both rock salt and perovskite phases simultaneously.In this study,we prepared a series of B-site mixed,Ruddlesden-Popper phase of Sr_(2)(Ru_(x)Ir_(1-x))O_(4) and examined their electrocatalytic properties for OER in acidic media.Through partial substitution of Ru in the B-site of Ruddlesden-Popper phase materials,we achieved much enhanced OER performance for this series of Sr_(2)(Ru_(x)Ir_(1-x))O_(4)electrocatalysts,among which Sr_(2)(Ru_(0.5)Ir_(0.5))O_(4)exhibited the best catalytic activity with a current density of 8.06 m A/cm^(2) at 1.55 V and a Tafel slope of 47 m V/dec.This current density is three times higher than that of Sr_(2)Ir O_(4).The B-site mixed Sr_(2)(Ru_(0.5)Ir_(0.5))O_(4)retained good stability in acidic conditions for>24 h at 10 m A/cm^(2).A range of techniques were used to characterize the crystal and electronic structures of the Sr_(2)(Ru_(x)Ir_(1-x))O_(4)samples.Our data indicate that the improved OER performance can be correlated to the formation of high level of hydroxyl groups and the enhanced overlap between Ir/Ru 4d and O_(2)p orbitals,revealing a new way for the design of efficient OER electrocatalysts by regulating their composition and electronic structures.
基金Supported by grants from the SGC’s Rapid Response Funding for Bilgateral Collaborative Emergence COVID-19 Project between China and Germany(No.C-0065)COVID-19 Emergency Project of Huazhong University of Science and Technology(No.2020kfyXGYJ062)Hepatobiliary and Pancreatic Cancer Grant,Hubei Chen Xiaoping Science and Technology Development Foundation(No.CXPJJH12000001-2020344).
文摘Results Sixty-one cancer survivors and 183 matched non-cancer patients were screened from 2,828 COVID-19 infected patients admitted to 4 hospitals in Wuhan,China.The median ages of the cancer survivor cohort and non-cancer patient cohort were 64.0(55.0–73.0)and 64.0(54.0–73.5),respectively(P=0.909).Cancer survivors reported a higher incidence of symptom onset than non-cancer patients.Fever(80.3%vs.65.0%;P=0.026)was the most prevalent symptom,followed by cough(65.6%vs.37.7%;P<0.001),myalgia,and fatigue(45.9%vs.13.6%;P<0.001).The risks of the development of severe events(adjusted hazard ratio[AHR]=1.25;95%confidence interval[CI]:0.76–2.06;P=0.378)and mortality(relative risk[RR]=0.90,95%CI:0.79–1.04;P=0.416)in the cancer survivor cohort were comparable to those of the matched non-cancer patient cohort.However,the cancer survivor cohort showed a higher incidence of secondary infection(52.5%vs.30.1%;RR=1.47,95%CI:1.11–1.95;P=0.002)and a prolonged viral RNA shedding duration(32 days[IQR 26.0–46.0]vs.24.0 days[IQR 18.0–33.0];AHR=0.54;95%CI:0.38–0.80;P<0.05).Conclusion Compared to non-cancer patients,cancer survivors with COVID-19 exhibited a higher incidence of secondary infection,a prolonged period of viral shedding,but comparable risks of the development of severe events and mortality.It is helpful for clinicians to take tailored measures to treat cancer survivors with COVID-19.
文摘BACKGROUND: Water decoction of the Chinese traditional medicine mixture of pinellia ternate and scorpion is an effective treatment for epilepsy. OBJECTIVE: To compare nanometer particles and effects of water decoction of Chinese traditional medicine mixture on P53 protein levels and apoptosis in the cerebral cortex and hippocampus of epileptic rats. DESIGN, TIME AND SETTING: This randomized, controlled molecular biology study was performed at the Key Laboratory of Child Neural Rehabilitation of Jiamusi University from October to December 2007. MATERIALS: Forty healthy male Wistar rats were used in this study. Convulsion rat models were established by intraperitoneal infusion of 35 mg/kg pentylenetetrazol, once a day, for 28 successive days. The Chinese traditional medicine mixture, comprising pinellia ternate, scorpion, centipede, bupleurum, peach pit and glycyrrhiza, was purchased from Beijing Tongrentang, China. The mixture was made into nanometer particles and water decoction. The apoptosis determination kit and P53 immunohistochemistry kit were bought from Boster, China. METHODS: Forty Wistar rats were randomly divided into four groups of ten rats per group, control, nanometer particle, water decoction and epileptic model groups. Rats in the nanometer particle and water decoction groups were respectively treated with 300 mg/kg Chinese herb nanometer particle suspension and water decoction by gavage, once a day, for 28 days. Rats in the epileptic model group were fed an equal volume of saline by gavage. Rats in the control group were only administered with the same volume of saline by gavage. MAIN OUTCOME MEASURES: Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling (TUNEL) and immunohistochemistry were used to respectively detect neuronal apoptosis and P53 protein expression in the rat brain cortex and hippocampus at 28 days following administration. RESULTS: The number of apoptotic neurons was lower in the nanometer particle and water decoction groups compared with the epileptic model group. The number of apoptotic cells and P53 protein expression in the rat cerebral cortex and hippocampus was greater in the epileptic model group compared with the control group (P 〈 0.05), but lower in the nanometer particle and water decoction groups compared with the epileptic model group (P 〈 0.05), and lower in the nanometer particle group compared with the water decoction group (P 〈 0.05). CONCLUSION: Chinese traditional medicine mixture decreases neuronal apoptosis and P53 protein expression in epileptic rats. The effect of nanometer particles is significant compared with water decoction.
基金Project supported by the National Natural Science Foundation of China(Grant Nos.52025023,51991342,52021006,11888101,and 61922028)the Key R&D Program of Guangdong Province,China(Grant Nos.2020B010189001,2019B010931001,and 2018B030327001)+3 种基金the Strategic Priority Research Program of Chinese Academy of Sciences(Grant No.XDB33000000)Beijing Natural Science Foundation,China(Grant No.JQ19004)the Pearl River Talent Recruitment Program of Guangdong Province,China(Grant No.2019ZT08C321)China Postdoctoral Science Foundation(Grant No.2021T140022)。
文摘Improving the emission performance of colloidal quantum dots(QDs)is of paramount importance for their applications on light-emitting diodes(LEDs),displays and lasers.A highly promising approach is to tune the carrier recombination channels and lifetime by exploiting the energy transfer process.However,to achieve this precise emission optimization,quantitative modulation on energy transfer efficiency is highly desirable but still challenging.Here,we demonstrate a convenient approach to realize tunable energy transfer efficiency by forming QDs mixture with controllable donor/acceptor(D/A)ratio.With the mixing ratio ranging from 16/1 to 1/16,the energy transfer efficiency could be effectively tuned from near zero to~70%.For the high mixing ratio of 16/1,acceptors obtain adequate energy supplied by closely surrounding donors,leading to~2.4-fold PL enhancement.While for the low mixing ratio,the ultrafast and efficient energy extraction process directly suppresses the multi-exciton and Auger recombination in the donor,bringing about a higher threshold.The facile modulation of emission performance by controllably designed mixing ratio and quantitatively tunable energy transfer efficiency will facilitate QD-based optoelectronic and photovoltaic applications.
文摘This paper attempts to establish a framework of upgrading mechanism in China's foreign economic opening strate莒y in order to conclude the new connotation of upgrade for China's foreign economic opening,with the basic starting point of ternary marginal extension on extensive growth,in the perspective of corporate heterogeneity theory.It also involves the new path of the transformation from"quantity1'to"quality"regarding the amounts,models and locations of China's foreign trade and investment.At last,this theoretical frame is complemented upon a case study of free trade zone and regional cooperation of Guangdong,Hong Kong and Macao.
文摘After nearly 40 years of development, privateeducation in China has become an important growthpoint for the development of education and an importantforce for promoting education reform. Private educationinstitutions can be divided into two categories: privateschools engaged in academic education and privateeducation training institutions engaged in non-academiceducation. Private non-academic education institutionshave played an important role in expanding domesticdemand, adjusting the structure, increasing employmentand promoting social development, and thus haveflourished. For example, Yu Minhong founded newOriental school in 1993, and Yin Xiong founded gianteducation in 1994. In September 2006, new Orientaleducation group was listed in the United States. Sincethen, a number of private education enterprises, suchas Bowen net, China net education, Xuesi and Xuedaeducation, have been listed in the United States, whichhas pushed the private non-academic education in Chinato a new height. However, with the rapid developmentof private non-academic education enterprises, they arealso facing great challenges.
基金funded by National Natural Science Foundation of China(81772982)the Special Innovation Fund of Department of Education of Guangdong Province(2019KTSCX049)+1 种基金Discipline Construction Project of Guang-dong Medical University(4SG23034G)Talent Development Foundation of The First Dongguan Affiliated Hospital of Guangdong Medical University(PF100-2-03).
文摘Hepatocellular carcinoma(HCC)is a common malignant tumor with high incidence and cancer mortality worldwide.Post-translational modifications(PTMs)of proteins have a great impact on protein function.Almost all proteins can undergo PTMs,including phosphorylation,acetylation,methylation,glycosylation,ubiquitination,and so on.Many studies have shown that PTMs are related to the occurrence and development of cancers.The findings provide novel therapeutic targets for cancers,such as glypican-3 and mucin-1.Other clinical implications are also found in the studies of PTMs.Diagnostic or prognostic value,and response to therapy have been identified.In HCC,it has been shown that glycosylated alpha-fetoprotein(AFP)has a higher detection rate for early liver cancer than conventional AFP.In this review,we mainly focused on the diagnostic and prognostic value of PTM,in order to provide new insights into the clinical implication of PTM in HCC.
基金supported by grants to Yuanchao Wang from the China National Funds for Innovative Research Groups(31721004)the key program of the National Natural Science Foundation of China(31430073)+2 种基金the Chinese Modern Agricultural Industry Technology System(CARS-004-PS14)the National Key R&D Program of China(SQ2018YFD020042)Research in the W.X.laboratory is supported by the Chinese Thousand Talents Plan and the Chinese Academy of Sciences.B.G.is supported by the Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX18.0662).
文摘Plants secrete defense molecules into the extracellular space (the apoplast) to combat attacking microbes. However, the mechanisms by which successful pathogens subvert plant apoplastic immunity remain poorly understood. In this study, we show that PsAvh240, a membrane-localized effector of the soybean pathogen Phytophthora sojae, promotes P. sojae infection in soybean hairy roots. We found that PsAvh240 interacts with the soybean-resistant aspartic protease GmAP1 in planta and suppresses the secretion of GmAP1 into the apoplast. By solving its crystal structure we revealed that PsAvh240 contain six a helices and two WY motifs. The first two a helices of PsAvh240 are responsible for its plasma membrane-localization and are required for PsAvh240's interaction with GmAP1. The second WY motifs of two PsAvh240 molecules form a handshake arrangement resulting in a handshake-like dimer. This dimerization is required for the effector's repression of GmAP1 secretion. Taken together, these data reveal that PsAvh240 localizes at the plasma membrane to interfere with GmAP1 secretion, which represents an effective mechanism by which effector proteins suppress plant apoplastic immunity.
基金supported by the National Key Research and Development Program of China (2017YFC1001303)International Cooperation Project of China and Canada NSFC (81661128010)+2 种基金National Natural Science Foundation of China (31471405, 81671456, 81671412)the National Key Basic Research Program (2013CB967404) the Doctoral Innovation Fund of School of Medicine, Shanghai Jiao Tong University (BXJ201640)
文摘As shown in our previous study, two alternatively spliced androgen receptor(AR) variants, which are exclusively expressed in the granulosa cells of patients with polycystic ovary syndrome, exhibit retarded nuclear translocation compared with wild-type AR. However, researchers have not yet determined whether these abnormalities correlate with heat shock protein 90(HSP90)and importin α(the former is a generally accepted co-chaperone of AR, and the latter is a component of classical nuclear import complexes). Here, these two variants were mainly retained in cytoplasm with HSP90 and importin α in the presence of dihydrotestosterone(DHT), and their levels in nucleus were significantly reduced, according to the immunofluorescence staining. The binding affinity of two AR variants for importin α was consistently decreased, while it was increased in WT-AR following DHT stimulation, leading to reduced nuclear import, particularly for the insertion-AR(Ins-AR). However, the binding affinities of two AR variants for HSP90 were increased in the absence of DHT compared with WT-AR, which functioned to maintain spatial structural stability, particularly for the deletion-AR(Del-AR). Therefore, the retarded nuclear translocation of two AR variants is associated with HSP90 and importin α, and the abnormal binding affinities for them play critical roles in this process.
基金The authors would like to acknowledge the Institute of Bioscaffold Transplantation and Immunology whose research was funded by the National Natural Science Foundation of China(grant NO.81970653)And the Medical Research Center of Ningbo City First Hospital whose research was funded by Zhejiang Medical and Health Technology Project(grant No.2018248656)Zhejiang pharmacy Top Key Project(grant No.YKFJ2-008).
文摘Chronic kidney disease has been recognized as a major public health problem worldwide and renal fibrosis is a common pathological process occurring in chronic renal failure.It is very promising to find the strategies to slow or even prevent the progression of fibrosis.This study focused on whether renal fibrosis decellularized scaffolds has the potential to be a model of cellular mechanisms of tissue fibrosis or donors for tissue engineering.In order to evaluate the feasibility of decellularized scaffolds derived from pathological kidneys,histology,proteomics and ELISA will be used to analysis the changes in the structure and main components of fibrotic tissue.The fibrosis model in this paper was induced by adenine-fed and the results showed that the structure of fibrotic scaffold was changed and some protein were up-regulated or down-regulated,but the cytokines associated with renal regeneration after injury were remained.In cell experiments,endothelial progenitor cells proliferated well,which proved that the fibrotic scaffolds have non-cytotoxic.All these conclusions indicate that the renal fibrosis decellularized scaffolds model has the ability to study fibrosis mechanism and the potential to be engineering donors as well as normal scaffolds.
基金supported by the National Natural Science Foundation of China(31930063,81771533,81901531,31971137,and 81871163)the National Key Research and Development Program of China(2018YFC2000102,2018YFA0107004,and 2018YFC1003000)+2 种基金the Shanghai Municipal Health Commission and Collaborative Innovation Cluster Project(2019CXJQ01)SHIPM-pi Fund(JY201801)SHIPM-mu Fund(JC201802)。
基金Funding for this study was provided by the China Postdoctroal Science Foundation funded project (No. 2014M561526), the Recruitment Program of Global Young Talent, China (Dr. Wu), the National High-tech R&D Program of China (No. SS2015AA020302), the National Natural Science Foundation of China (No. 81190132), Program of Shanghai Outstanding Academic Leaders (No. 15XD1503900), and the Key Research Program of Chinese Academy of Sciences (No. KGZD- EW-T06).
文摘For the therapy and regeneration of bone defects resulting from malignant bone tumors, it is necessary to develop multifunctional biomaterials that are able to deliver therapeutic drugs, monitor drug release, and stimulate bone formation. Herein, a multifunctional mesoporous bioactive glass (MBG)/upconversion nanoparticle (UCNP) nanocomposite [UCNPs@SiO2@mSiO2-XCa (X = 0, 5, 10, 15, and 20)] with the ability to deliver anti-cancer drugs, monitor drug release, and stimulate osteogenic differentiation of bone marrow stromal cells (BMSCs) was successfully prepared using a layer-by-layer strategy. The nanocomposite spheres possess a core--sheU structure composed of UCNPs and a mesoporous SiO2/Ca layer with a uniform size distribution of 100 nm. The incorporation of Ca into the nanocomposites induced phase transformation from a pure hexagonal phase to a cubic phase, and facilitated the occurrence of red emission, which significantly improved fluorescence penetration for deep tissue imaging. In addition, since the red emission strongly overlaps with the maximum absorbance of the anti-cancer drug zinc phthalocyanine (ZnPc), red luminescence could be strongly quenched by ZnPc. Consequently, drug release could be quantified by monitoring changes in fluorescence intensity. Furthermore, the incorporation of Ca into MBG/UCNP nanocomposites remarkably improved bioactivity, i.e., it stimulated apatite mineralization in simulated body fluids and enhanced cell proliferation and bone-related gene expression in BMSCs for the concentration range of 200-500 ~g/mL. Our results suggest that the prepared MBG/UCNP nanocomposites are useful for the therapy and regeneration of bone defects resulting from malignant bone tumors owing to their distinct multifunctionality, including strong red emission and functions in drug-delivery monitoring and osteostimulation.
基金the National Natural Science Foundation of China(81800901)the Program for Professor of Special Appointment(Eastern Scholar)at Shanghai Institutions of Higher Learning(QD2018015)+2 种基金the Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases(14DZ2260300)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB32030200)the Bureau of International Cooperation,Chinese Academy of Sciences(153D31KYSB20170059).
文摘Recent studies have revealed great functional and structural heterogeneity in the ribbon-type synapses at the basolateral pole of the isopotential inner hair cell(IHC).This feature is believed to be critical for audition over a wide dynamic range,but whether the spatial gradient of ribbon morphology is fine-tuned in each IHC and how the mitochondrial network is organized to meet local energy demands of synaptic transmission remain unclear.By means of three-dimensional electron microscopy and artificial intelligence-based algorithms,we demonstrated the cell-wide structural quantification of ribbons and mitochondria in mature mid-cochlear IHCs of mice.We found that adjacent IHCs in staggered pairs differ substantially in cell body shape and ribbon morphology gradient as well as mitochondrial organization.Moreover,our analysis argues for a location-specific arrangement of correlated ribbon and mitochondrial function at the basolateral IHC pole.
基金supported by Guangdong Basic and Applied Basic Research Foundation(2021A1515011244,China)to Jinshan Tangthe National 111 Project of China(No.B13038,China)to Xinsheng Yao。
文摘DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic drugs.Hence,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of chemotherapy.Through a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different origins.Mechanistically,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(ATR),two master upstream regulators of the DDR signal,through inducing degradation of ATM and ATR-interacting protein(ATRIP),an obligate associating protein of ATR,respectively.As a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse models.While degradation of ATRIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not proteasome.Overexpression of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic drugs.These novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of shikonin.Our data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.
基金supported by the Health High-Level Talent Training Project (Innovative Talents)the Health Commission of Zhejiang Province (File [2021] 40)+1 种基金the 151 Talent Project (Second Level)Zhejiang Province Human Resources and Social Security Department (File [2018] 126), China。
文摘The global outbreak of the coronavirus disease 2019(COVID-19) led to the suspension of most treatments with assisted reproductive technique(ART). However, with the recent successful control of the pandemic in China, there is an urgent public need to resume full reproductive care. To determine whether the COVID-19 pandemic had any adverse effects on female fertility and the pregnancy outcomes of women undergoing ART, a systematic review and meta-analysis was conducted using the electronic Chinese and English databases. Dichotomous outcomes were summarized as prevalence, and odds ratios(ORs)and continuous outcomes as standardized mean difference(SMD) with 95% confidence interval(CI). The risk of bias and subgroup analyses were assessed using Stata/SE 15.1 and R 4.1.2. The results showed that compared with women treated by ART in the pre-COVID-19 time frame, women undergoing ART after the COVID-19 pandemic exhibited no significant difference in the clinical pregnancy rate(OR 1.07, 95% CI 0.97 to 1.19;I^(2)=0.0%), miscarriage rate(OR 0.95, 95% CI 0.79 to1.14;I^(2)=38.4%), embryo cryopreservation rate(OR 2.90, 95% CI 0.17 to 48.13;I^(2)=85.4%), and oocyte cryopreservation rate(OR 0.30, 95% CI 0.03 to 3.65;I^(2)=81.6%). This review provided additional evidence for gynecologists to guide the management of women undergoing ART treatment during the COVID-19 pandemic timeframe.
基金The authors greatly acknowledge the National Natural Science Foundation of China(No.51171060)Program for Changjiang Scholars and Innovative Research Team in University(No.IRT1234).
文摘A high-vanadium alloy composite layer was prepared on the surface of a carbon steel using cast composite technology,and the wear properties of the composite layer were investigated.The results showed that the microstructure of the composite layer was composed of primary vanadium carbides(VC),flake martensite,residual austenite,and fine VC.The hardness of the cast alloy layer was 63 HRC.The abrasive wear resistance and impact wear resistance were increased by 60%and 26%,respectively,compared with those of high-chromium cast iron.The excellent wear resistance of the cast alloy layer is attributed to the high-hardness primary vanadium carbide and the large number of fine secondary vanadium carbides precipitated out of the cast alloy layer.