From the standpoint of chemical structures,the organic backbones of energetic materials can be classified into aromatic rings,nonaromatic rings,and open chains.Although the category of aromatic energetic compounds exh...From the standpoint of chemical structures,the organic backbones of energetic materials can be classified into aromatic rings,nonaromatic rings,and open chains.Although the category of aromatic energetic compounds exhibits several advantages in the regulation of energetic properties,the nonaromatic heterocycles,assembling nitramino explosophores with simple alkyl bridges,still have prevailed in benchmark materials.The methylene bridge plays a pivotal role in the constructions of the classic nonaromatic heterocycle-based energetic compounds,e.g.,hexahydro-1,3,5-trinitro-1,3,5-triazine(RDX)and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine(HMX),whereas ethylene bridge is the core moiety of state-of-the-art explosive 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane(CL-20).In this context,it is of great interest to employ simple and practical bridges to assemble aromatic and nonaromatic nitrogen-rich heterocycles,thereby expanding the structural diversity of energetic materials,e.g.,bridged and fused nitrogen-rich poly-heterocycles.Furthermore,alkyl-bridged poly-heterocycles highlight the potential for the open chain type of energetic materials.In this review,the development of alkyl bridges in linking nitrogen-rich heterocycles is presented,and the perspective of the newly constructed energetic backbones is summarized for the future design of advanced energetic materials.展开更多
Neurological disorders,including headaches(tension-type headaches,medication-overuse headaches,and migraines)and dementias that include Alzheimer’s disease,are among the most prevalent and debilitating global conditi...Neurological disorders,including headaches(tension-type headaches,medication-overuse headaches,and migraines)and dementias that include Alzheimer’s disease,are among the most prevalent and debilitating global conditions.In 2016,these disorders affected 276 million people worldwide and were the second leading cause of death that year[1].This highlights the urgent need for effective prevention,treatment,and support strategies.The etiology of neurological disorders is multifaceted and involves genetic,environmental,physiological,and social factors[2].展开更多
BACKGROUND Acute lower extremity deep venous thrombosis(LEDVT)is a common vascular emergency with significant morbidity risks,including post-thrombotic syndrome(PTS)and pulmonary embolism.Traditional treatments like c...BACKGROUND Acute lower extremity deep venous thrombosis(LEDVT)is a common vascular emergency with significant morbidity risks,including post-thrombotic syndrome(PTS)and pulmonary embolism.Traditional treatments like catheter-directed thrombolysis(CDT)often result in variable success rates and complications.AIM To investigate the therapeutic efficacy of percutaneous mechanical thrombus removal in acute LEDVT.METHODS A retrospective analysis was performed to examine 58 hospitalised patients with acute LEDVT between August 2019 and August 2022.The patients were categorised into the percutaneous mechanical thrombectomy(PMT)group(n=24)and CDT group(n=32).The follow-up,safety and treatment outcomes were compared between the two groups.The main observational indexes were venous patency score,thrombus removal effect,complications,hospitalisation duration and PTS.RESULTS The venous patency score was 9.04±1.40 in the PMT group and 8.81±1.60 in the CDT group,and the thrombus clearance rate was 100%in both groups.The complication rate was 8.33%in the PMT group and 34.84%in the CDT group,and the difference was statistically significant(P<0.05).The average hospitalisation duration was 6.54±2.48 days in the PMT group and 8.14±3.56 days in the CDT group.The incidence of PTS was lower in the PMT group than in the CDT group;however,the difference was not statistically significant(P<0.05).CONCLUSION Compared with CDT,treatment of LEDVT via PMT was associated with a better thrombus clearance rate,clinical therapeutic effect and PTS prevention function,but the difference was not statistically significant.Moreover,PMT was associated with a reduced urokinase dosage,shortened hospitalisation duration and reduced incidence of complications,such as infections and small haemorrhages.These results indicate that PMT has substantial beneficial effects in the treatment of LEDVT.展开更多
Geological Hazards Investigation and Evaluation is the core course of Environmental Geological Engineering,aiming to cultivate skilled talents with solid theoretical knowledge and excellent practical skills.At present...Geological Hazards Investigation and Evaluation is the core course of Environmental Geological Engineering,aiming to cultivate skilled talents with solid theoretical knowledge and excellent practical skills.At present,the course faces several issues,including a teaching environment disconnected from real-world work scenarios,course content that deviates from job-related tasks,a lack of digital teaching resources,and reliance on a single teaching method,leading to students’poor feedback from employers.Based on the concept of outcome-based education,the course team of Geological Hazards Investigation and Evaluation establishes a“five-step double-rotation”blended teaching model with the help of a Small Private Online Course platform.The program is designed to improve the teaching environment and expand the digitalized teaching resources in order to improve students’learning motivation,enhance learning effectiveness,and cultivate skillful talents who meet employers’satisfaction.展开更多
Scientific curriculum evaluation methods are critical for achieving talent training objectives.The Sydney Accord,one of the three major engineering education certification agreements,focuses on the training of“engine...Scientific curriculum evaluation methods are critical for achieving talent training objectives.The Sydney Accord,one of the three major engineering education certification agreements,focuses on the training of“engineering technologists.”Its logical system and three core principles align well with the connotation development of professional construction in China’s higher vocational colleges,offering significant insights for promoting reform and development in engineering education in Chinese colleges and universities.By incorporating the core principles,elements,and graduate quality defined in the Sydney Accord and focusing on the evaluation of curriculum achievement against“graduation requirements,”the quality of vocational education can be enhanced,making it an important direction for future teaching reforms in vocational education.展开更多
AIM:To rapidly detect molecular alterations in different malignancies and investigate the possible role of Tp53,C-myc,and CCND1 genes in development of tumors in human organs and their adjacent normal tissues,as well ...AIM:To rapidly detect molecular alterations in different malignancies and investigate the possible role of Tp53,C-myc,and CCND1 genes in development of tumors in human organs and their adjacent normal tissues,as well as the possible relation between well-and poorly-differentiated tumors.METHODS:A tissue array consisting of seven different tumors was generated.The tissue array included 120 points of esophagus,120 points of stomach,80 points of rectum,60 points of thyroid gland,100 points of mammary gland,80 points of liver,and 80 points of colon.Expressions of Tp53,C-myc,and CCND1 were determined by RNA in situ hybridization.3' terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe were used.RESULTS:The expression level of Tp53 gene was higher in six different carcinoma tissue samples than in paracancerous tissue samples with the exception in colon carcinoma tissue samples(P < 0.05).The expression level of CCND1 gene was significantly different in different carcinoma tissue samples with the exception in esophagus and colon carcinoma tissue samples.The expression level of C-myc gene was different in esophagus carcinoma tissue samples(c2 = 18.495,P = 0.000),stomach carcinoma tissue samples(c2 = 23.750,P = 0.000),and thyroid gland tissue samples(c2 = 10.999,P = 0.004).The intensity of signals was also different in different carcinoma tissue samples and paracancerous tissue samples.CONCLUSION:Over-expression of the Tp53,CCND1,and C-myc genes appears to play a role in development of human cancer by regulating the expression of mRNA.Tp53,CCND1 and C-myc genes are significantly correlated with the development of different carcinomas.展开更多
Body misperception plays an important role in the development of weight and dietary disorders among children and adolescents.A school-based health promotion program(2014-2015)was conducted to promote the school health...Body misperception plays an important role in the development of weight and dietary disorders among children and adolescents.A school-based health promotion program(2014-2015)was conducted to promote the school health education and improve the teenagers'physical health among Chinese children and adolescents.Based on this program,we intended to examine weight status and weight misperception among Chinese children and adolescents and to explore the relationship between weight misperception and lifestyle behaviors.A total of 10708 Chinese children and adolescents in 3rd and 7th grade from Shandong and Qinghai province participated in the program.The participants,dietary and activity patterns were clustered by latent class analysis(LCA).Logistic regression analysis was undertaken to explore the relationship between weight perception and demographic factors or dietary and activity patterns.Given the gender-specific difference of children and adolescents,analyses were separately conducted among boys and girls.The total prevalence of weight misperception was 44.50%.Boys,especially those in higher grade and living in wealthier district,were more likely to misperceive body weight.Girls were more likely to overestimate their weight(26.10%)while boys tended to underestimate the weight(28.32%).Three latent dietary and activity patterns including obesogenic pattern,malnourished pattern and healthy pattern were derived.The participants who had weight misperception were more likely to choose unhealthy dietary and exercise activities.The high prevalence of weight misperception was closely related to the unhealthy weight pattern and unhealthy dietary or exercise patterns.Our research found that most children and adolescents failed to perceive their weight correctly and boys tended to underestimate their weight while girls were subjected to overestimation.So,comprehensive intervention programs should focus on improving self-weight awareness,and appropriate guidance should be made to lead the adolescents to more healthy weight pattern.展开更多
Based on the 39 surface sediment samples collected in the flood season and the dry season in 2012 respectively and the measured hydrological data in October 2012, the sediment grain size characteristics has been analy...Based on the 39 surface sediment samples collected in the flood season and the dry season in 2012 respectively and the measured hydrological data in October 2012, the sediment grain size characteristics has been analyzed and the response mechanism of surface sediments to estuarine hydrodynamics was revealed by calculating the range of waves and tidal currents. The results show that:(1) The grain size of the surface sediment samples decreased gradually from land to sea in the flood season. The fine sediment was redistributed under marine hydrodynamics in the dry season and the sediments showed coarser tendency ingeneral;(2) tidal current stirring sediment was very obvious in Dagu River estuary area, and wave stirring sediments mainly occurred in the tidal flat area and estuary sand bar area;(3) in the flood season, surface sediment sat the estuary were transported towards south and southeast. In the dry season, surface sediments were transported towards southwest at the north area of Jiaozhou Bay Bridge, and sediments were transported towards northeast area at the south of Jiaozhou Bay Bridge.展开更多
Shandong has more than 70% of natural coasts are under erosion.Coastal erosion started from the 1970's and became a very serious problem at 1990 's.The dramatic decrease of sediment supplies from rivers caused...Shandong has more than 70% of natural coasts are under erosion.Coastal erosion started from the 1970's and became a very serious problem at 1990 's.The dramatic decrease of sediment supplies from rivers caused rapid erosion at the delta and estuary areas,especially in the abandoned Yellow River Delta.Most sandy coasts along the Peninsula were eroded due to lack of sand supply and interruption of alongshore sediment drift,sand dredging from the beach or the offshore area caused serious erosion during short time. Sea-level rise causes slow but constant shoreline retreats and became a more serious threat.Different types of hard solutions for coastal protection against erosion were used in Shandong.Seawalls are most widely used,especially at the Yellow River Delta and city center waterfront.Groynes,jetties and breakwater are used on the north and east sandy coast of the Peninsula.Hard approaches are effective to protect the coast erosion but not change the erosion causes and led secondary impact on the coast.Soft engineering solution or the combined solutions are taken into acts.Beach nourishment is mostly considered as the better soft solution,especially to those tourists attracting sandy beaches along the Shandong coast.Long term monitoring and continuous lessons learning from the coastal erosion management will be adaptive for better coast solution in the future.展开更多
The coastal cities are the most advanced regions in China.In the past few decades,the environment changed very significantly due to large scale human activities in the coastal regions.Polycyclic aromatic hydrocarbons ...The coastal cities are the most advanced regions in China.In the past few decades,the environment changed very significantly due to large scale human activities in the coastal regions.Polycyclic aromatic hydrocarbons (PAHs)in three dated sediment cores from the west coast of the Yellow Sea (core A01),the Yangtze River estuary (YRE;core A02)and the Oujiang River estuary (ORE;core A03)were analyzed to reconstruct the environmental evolutionary process of the east China coastal region over the past century. In the three cores,PAHs concentrations were increased rapidly.Lower concentrations of PAHs were measured in core A02 than in cores A01 and A03.The vertical variation of PAHs in the YRE Was dominated by the petrogenic sources.Historical records of PAHs in the ORE were controlled by pyrolytic sources.PAHs on the west coast of the Yellow Sea were contributed by the two sources.展开更多
Summary:Throughout the duration of the New Cooperative Medical Scheme(NCMS),it was found that an increasing number of rural patients were seeking out-of^county medical treatment,which posed a great burden on the NCMS ...Summary:Throughout the duration of the New Cooperative Medical Scheme(NCMS),it was found that an increasing number of rural patients were seeking out-of^county medical treatment,which posed a great burden on the NCMS fund.Our study was conducted to examine the prevalence of out-of^county hospitalizations and its related factors,and to provide a scientific basis for follow?up health insurance policies.A total of 215 counties in central and western China from 2008 to 2016 were selected.The total out-of-county hospitalization rate in nine years was 16.95%,which increased from 12.37%in 2008 to 19.21%in 2016 with an average annual growth rate of 5.66%.Its related expenses and compensations were shown to increase each year,with those in the central region being higher than those in the western region.Stepwise logistic regression reveals that the increase in out-of-county hospitalization rate was associated with region(XI),rural population(X2),per capita per year net income(X3),per capita gross domestic product(GDP)(X4),per capita funding amount of NCMS(X5),compensation ratio of out-of^county hospitalization cost(X6),per time average in-county(X7)and out-of-county hospitalization cost(X8).According to Bayesian network(BN),the marginal probability of high out-of^county hospitalization rate was as high as 81.7%.Out-of^county hospitalizations were directly related to X8,X3,X4 and X6.The probability of high out-of-county hospitalization obtained based on hospitalization expenses factors,economy factors,regional characteristics and NCMS policy factors was 95.7%,91.1%,93.0% and 88.8%,respectively.And how these factors affect out-of-county hospitalization and their interrelationships were found out.Our findings suggest that more attention should be paid to the influence mechanism of these factors on out-of-county hospitalizations,and the increase of hospitalizations outside the county should be reasonably supervised and controlled and our results will be used to help guide the formulation of proper intervention policies.展开更多
The plant UV-B photoreceptor UV RESISTANCE LOCUS 8(UVR8)exists as a homodimer in its inactive ground state.Upon UV-B exposure,UVR8monomerizes and interacts with a downstreamkey regulator,theCONSTITUTIVE PHOTOMORPHOGEN...The plant UV-B photoreceptor UV RESISTANCE LOCUS 8(UVR8)exists as a homodimer in its inactive ground state.Upon UV-B exposure,UVR8monomerizes and interacts with a downstreamkey regulator,theCONSTITUTIVE PHOTOMORPHOGENIC 1/SUPPRESSOR OF PHYA(COP1/SPA)E3 ubiquitin ligase complex,to initiate UV-B signaling.Two WD40 proteins,REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1(RUP1)and RUP2 directly interact with monomeric UVR8 and facilitate UVR8 ground state reversion,completing the UVR8 photocycle.Here,we reconstituted the RUP-mediated UVR8 redimerization process in vitro and reported the structure of the RUP2-UVR8^(W285A) complex(2.0A).RUP2 and UVR8^(W285A) formed a heterodimer via two distinct interfaces,designated Interface 1 and 2.The previously characterized Interface 1 is found between the RUP2 WD40 domain and the UVR8 C27 subregion.The newly identified Interface 2 is formed through interactions between the RUP2 WD40 domain and the UVR8 core domain.Disruption of Interface 2 impairedUV-B induced photomorphogenic development in Arabidopsis thaliana.Further biochemical analysis indicated that both interfaces are important for RUP2-UVR8 interactions and RUP2-mediated facilitation of UVR8 redimerization.Our findings suggest that the two-interface-interaction mode is adopted by both RUP2 and COP1 when they interact with UVR8,marking a step forward in understanding the molecular basis that underpins the interactions between UVR8 and its photocycle regulators.展开更多
Poly(ADP-ribose)polymerase(PARP)inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination(HR)deficiency.However,many patients without apparent HR defects also...Poly(ADP-ribose)polymerase(PARP)inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination(HR)deficiency.However,many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin.The biomarker responsible for this mechanism remains unclear.Here,we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients.PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage(ATM)signaling-induced pro-apoptotic ribosomal stress,which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage.Therefore,the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin.The gene panel as an independent biomarker was validated by multiple published clinical datasets,as well as by an ovarian cancer organoids library we established.More importantly,its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data.Furthermore,we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines.These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance.Together,our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.展开更多
As an important transportation infrastructure and transportation backbone in China,high-speed rail(HSR)plays a critical role in promoting the development of green and low-carbon transportation.Calculating the CO_(2) e...As an important transportation infrastructure and transportation backbone in China,high-speed rail(HSR)plays a critical role in promoting the development of green and low-carbon transportation.Calculating the CO_(2) emissions reduction performance of HSR will be conduci v e to pr omote the CO_(2) emissions r eduction w ork of the r ail w ay.Based on the Dalkic HSR CO_(2) emissions r eduction performance model,by adjusting the HSR CO_(2) emission factor(CEF HSR),the annual times of departures(T)and other parameters,this study develops a Chinese HSR CO_(2) emissions reduction performance model.Taking the Beijing-Shanghai HSR as the resear c h object,this study conducts a questionnaire survey to explore the substitution effect and demand effect of HSR on different transportation modes;collects data such as passenger v olume,av era ge electricity use and annual times of departures of the Beijing-Shanghai HSR in 2019;and calculates the CO_(2) emissions reduction performance of the Beijing-Shanghai HSR.This study has two main results:(1)It builds a Chinese HSR CO_(2) emissions reduction performance model based on substitution effect and demand effect.(2)In 2019,the CO_(2) emissions of the Beijing-Shanghai HSR are 2898233.62 t,the CO_(2) emissions reduction performance of the Beijing-Shanghai HSR is 17999482.8 t,the annual CO_(2) emissions of the Beijing-Shanghai line in‘No HSR’case are 7.2 times as in the’HSR’case and the PKT of the HSR is 10.2 g/pkm.Based on the research results,this study proposes three CO_(2) emissions reduction policy suggestions.This study would be helpful for further HSR CO_(2) emissions reduction resear c h and departments related to railway transportation management to make CO_(2) emissions reduction policies.展开更多
Heshouwu is a traditional non-toxic Chinese medicine commonly used in the clinical setting;however,clinical cases of Heshouwu-induced hepatotoxicity have been frequently reported^([1]).Pharmacoepidemiological studies ...Heshouwu is a traditional non-toxic Chinese medicine commonly used in the clinical setting;however,clinical cases of Heshouwu-induced hepatotoxicity have been frequently reported^([1]).Pharmacoepidemiological studies have found that Heshouwu-induced liver injury occurs only in a small fraction of individuals taking the drug;these patients presented with the typ-展开更多
N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previo...N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previously determined.However,the MTDs alone possess no enzymatic activity.Here we present the solution structure for the zinc finger domain(ZFD)of METTL3,the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14.We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3'consensus sequence,but does not to one without.The ZFD thus serves as the target recognition domain,a structural feature previously shown for DNA methyltransferases,and cooperates with the MTDs of METTL3-METTL14 for catalysis.However,the interaction between the ZFD and the specific RNA is extremely weak,with the binding affinity at several hundred micromolar under physiological conditions.The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel P-sheet.Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface.As a division of labor,the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues fromβ-sheet and zinc finger 2.Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded,which may permit the cooperation between the two domains during catalysis.Together,the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification.展开更多
Mitogen-activated protein kinase(MAPK)cascades regulate a myriad of plant biological processes,including disease resistance.Plant genomes encode a large number of MAPK kinase kinases(MAPKKKs)that can be divided into t...Mitogen-activated protein kinase(MAPK)cascades regulate a myriad of plant biological processes,including disease resistance.Plant genomes encode a large number of MAPK kinase kinases(MAPKKKs)that can be divided into two subfamilies,namely MEKK-like kinases and Raf-like kinases.Thus far,the func-tions of MEKK-like MAPKKKs have been relatively well characterized,but the roles of Raf-like MAPKKKs in.plant MAPK cascades remain less understood.Here,we report the role of OsEDR1,a Raf-like MAPKKK,in the regulation of the MAPK cascade in rice response tp the bacterial pathogen Xanthomonas oryzae pv.oryzicola(Xoc).We found that OsEDR1 inhibits OsMPKK10.2(a MAPK kinase)activity through physical interaction.Upon Xoc infection,OsMPKK10.2 is phosphorylated at S304 to activate OsMPK6(a MAPK).Interestingly,activated OsMPK6 phosphorylates OsEDR1 at S861,which destabilizes OsEDR1 and thus releases the inhibition of OsMPKK10.2,leading to increased OsMPKK10.2 activity and enhanced resistance of rice plants to Xoc.Taken together,these results provide new insights into the functions of Raf-like ki-nases in the regulation of the MAPK cascade in plant immunity.展开更多
More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of ep...More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of epitranscriptomies. The m^6A modification is the most abundant modification in mRNA and non-coding RNA （ncRNA）. At the molecular level, m^6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA （miRNA） maturation, playing essential roles in a range of cellular processes. The m^6A modification is regulated by three classes of proteins generally referred to as the ＂writer＂ （adenosine methyltransferase）, ＂eraser＂ （m^6A demethylating enzyme）, and ＂reader＂ （m^6A-binding protein）. The m^6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology （YTH） family proteins, selectively bind to RNA and affect its fate in an m^6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m^6A modification, and provide our insights into the m^6A-mediated gene regulation.展开更多
基金National Natural Science Foundation of China(Grant Nos.22075023,22205022,and 22235003)to provide fund for conducting experiments。
文摘From the standpoint of chemical structures,the organic backbones of energetic materials can be classified into aromatic rings,nonaromatic rings,and open chains.Although the category of aromatic energetic compounds exhibits several advantages in the regulation of energetic properties,the nonaromatic heterocycles,assembling nitramino explosophores with simple alkyl bridges,still have prevailed in benchmark materials.The methylene bridge plays a pivotal role in the constructions of the classic nonaromatic heterocycle-based energetic compounds,e.g.,hexahydro-1,3,5-trinitro-1,3,5-triazine(RDX)and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine(HMX),whereas ethylene bridge is the core moiety of state-of-the-art explosive 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane(CL-20).In this context,it is of great interest to employ simple and practical bridges to assemble aromatic and nonaromatic nitrogen-rich heterocycles,thereby expanding the structural diversity of energetic materials,e.g.,bridged and fused nitrogen-rich poly-heterocycles.Furthermore,alkyl-bridged poly-heterocycles highlight the potential for the open chain type of energetic materials.In this review,the development of alkyl bridges in linking nitrogen-rich heterocycles is presented,and the perspective of the newly constructed energetic backbones is summarized for the future design of advanced energetic materials.
基金supported by the National Key Research and Development Program of China[2018YFE0206900].
文摘Neurological disorders,including headaches(tension-type headaches,medication-overuse headaches,and migraines)and dementias that include Alzheimer’s disease,are among the most prevalent and debilitating global conditions.In 2016,these disorders affected 276 million people worldwide and were the second leading cause of death that year[1].This highlights the urgent need for effective prevention,treatment,and support strategies.The etiology of neurological disorders is multifaceted and involves genetic,environmental,physiological,and social factors[2].
基金the Health and Wellness Commission of Hebei Province,No.20160344the Health Commission of Shijiazhuang City,Hebei Province,No.221200763.
文摘BACKGROUND Acute lower extremity deep venous thrombosis(LEDVT)is a common vascular emergency with significant morbidity risks,including post-thrombotic syndrome(PTS)and pulmonary embolism.Traditional treatments like catheter-directed thrombolysis(CDT)often result in variable success rates and complications.AIM To investigate the therapeutic efficacy of percutaneous mechanical thrombus removal in acute LEDVT.METHODS A retrospective analysis was performed to examine 58 hospitalised patients with acute LEDVT between August 2019 and August 2022.The patients were categorised into the percutaneous mechanical thrombectomy(PMT)group(n=24)and CDT group(n=32).The follow-up,safety and treatment outcomes were compared between the two groups.The main observational indexes were venous patency score,thrombus removal effect,complications,hospitalisation duration and PTS.RESULTS The venous patency score was 9.04±1.40 in the PMT group and 8.81±1.60 in the CDT group,and the thrombus clearance rate was 100%in both groups.The complication rate was 8.33%in the PMT group and 34.84%in the CDT group,and the difference was statistically significant(P<0.05).The average hospitalisation duration was 6.54±2.48 days in the PMT group and 8.14±3.56 days in the CDT group.The incidence of PTS was lower in the PMT group than in the CDT group;however,the difference was not statistically significant(P<0.05).CONCLUSION Compared with CDT,treatment of LEDVT via PMT was associated with a better thrombus clearance rate,clinical therapeutic effect and PTS prevention function,but the difference was not statistically significant.Moreover,PMT was associated with a reduced urokinase dosage,shortened hospitalisation duration and reduced incidence of complications,such as infections and small haemorrhages.These results indicate that PMT has substantial beneficial effects in the treatment of LEDVT.
基金Scientific Research Fund of Hunan Provincial Education Department Excellent Youth Project(23B0953)Hunan Province Vocational College Education and Teaching Reform Research Project(ZJGB2022427)。
文摘Geological Hazards Investigation and Evaluation is the core course of Environmental Geological Engineering,aiming to cultivate skilled talents with solid theoretical knowledge and excellent practical skills.At present,the course faces several issues,including a teaching environment disconnected from real-world work scenarios,course content that deviates from job-related tasks,a lack of digital teaching resources,and reliance on a single teaching method,leading to students’poor feedback from employers.Based on the concept of outcome-based education,the course team of Geological Hazards Investigation and Evaluation establishes a“five-step double-rotation”blended teaching model with the help of a Small Private Online Course platform.The program is designed to improve the teaching environment and expand the digitalized teaching resources in order to improve students’learning motivation,enhance learning effectiveness,and cultivate skillful talents who meet employers’satisfaction.
基金Hunan Province Vocational College Education and Teaching Reform Research Project(ZJGB2023323)Hunan Provincial Department of Education Scientific Research Funding Excellent Youth Project(23B0953)Natural Science Foundation of Hunan Province(2023JJ60189,2024JJ8105)。
文摘Scientific curriculum evaluation methods are critical for achieving talent training objectives.The Sydney Accord,one of the three major engineering education certification agreements,focuses on the training of“engineering technologists.”Its logical system and three core principles align well with the connotation development of professional construction in China’s higher vocational colleges,offering significant insights for promoting reform and development in engineering education in Chinese colleges and universities.By incorporating the core principles,elements,and graduate quality defined in the Sydney Accord and focusing on the evaluation of curriculum achievement against“graduation requirements,”the quality of vocational education can be enhanced,making it an important direction for future teaching reforms in vocational education.
基金Supported by Foundation of Xiamen Science and Technology Bureau,Fujian Province,China,No.3502Z20074023
文摘AIM:To rapidly detect molecular alterations in different malignancies and investigate the possible role of Tp53,C-myc,and CCND1 genes in development of tumors in human organs and their adjacent normal tissues,as well as the possible relation between well-and poorly-differentiated tumors.METHODS:A tissue array consisting of seven different tumors was generated.The tissue array included 120 points of esophagus,120 points of stomach,80 points of rectum,60 points of thyroid gland,100 points of mammary gland,80 points of liver,and 80 points of colon.Expressions of Tp53,C-myc,and CCND1 were determined by RNA in situ hybridization.3' terminal digoxin-labeled anti-sense single stranded oligonucleotide and locked nucleic acid modifying probe were used.RESULTS:The expression level of Tp53 gene was higher in six different carcinoma tissue samples than in paracancerous tissue samples with the exception in colon carcinoma tissue samples(P < 0.05).The expression level of CCND1 gene was significantly different in different carcinoma tissue samples with the exception in esophagus and colon carcinoma tissue samples.The expression level of C-myc gene was different in esophagus carcinoma tissue samples(c2 = 18.495,P = 0.000),stomach carcinoma tissue samples(c2 = 23.750,P = 0.000),and thyroid gland tissue samples(c2 = 10.999,P = 0.004).The intensity of signals was also different in different carcinoma tissue samples and paracancerous tissue samples.CONCLUSION:Over-expression of the Tp53,CCND1,and C-myc genes appears to play a role in development of human cancer by regulating the expression of mRNA.Tp53,CCND1 and C-myc genes are significantly correlated with the development of different carcinomas.
基金This study was supported by grants from the National Natural Science Foundation of China(No.81573262)the Fundamental Research Funds for the Central Universities,HUST(No.2016YXZD042).
文摘Body misperception plays an important role in the development of weight and dietary disorders among children and adolescents.A school-based health promotion program(2014-2015)was conducted to promote the school health education and improve the teenagers'physical health among Chinese children and adolescents.Based on this program,we intended to examine weight status and weight misperception among Chinese children and adolescents and to explore the relationship between weight misperception and lifestyle behaviors.A total of 10708 Chinese children and adolescents in 3rd and 7th grade from Shandong and Qinghai province participated in the program.The participants,dietary and activity patterns were clustered by latent class analysis(LCA).Logistic regression analysis was undertaken to explore the relationship between weight perception and demographic factors or dietary and activity patterns.Given the gender-specific difference of children and adolescents,analyses were separately conducted among boys and girls.The total prevalence of weight misperception was 44.50%.Boys,especially those in higher grade and living in wealthier district,were more likely to misperceive body weight.Girls were more likely to overestimate their weight(26.10%)while boys tended to underestimate the weight(28.32%).Three latent dietary and activity patterns including obesogenic pattern,malnourished pattern and healthy pattern were derived.The participants who had weight misperception were more likely to choose unhealthy dietary and exercise activities.The high prevalence of weight misperception was closely related to the unhealthy weight pattern and unhealthy dietary or exercise patterns.Our research found that most children and adolescents failed to perceive their weight correctly and boys tended to underestimate their weight while girls were subjected to overestimation.So,comprehensive intervention programs should focus on improving self-weight awareness,and appropriate guidance should be made to lead the adolescents to more healthy weight pattern.
基金The authors are grateful to Lei Guo ,Xiao-lei Liu ,Yonggang Jia,Lu-lu Qiao,Bin Chen and others for discussions and help in this study. The authors are grateful to the anonymous reviewers and Dr. Yan Yang for their comments and suggestions,which significantly improved the quality of the manuscript. This study is supported financially by National Natural Science Foundation of China (41506107)Special Program for Basic Research of the Ministry of Science and Technology,China (2013FY112200),"China- ASEAN Marine Geoscience Research and Disaster Reduction and Prevention initiatives Project" Ministry of Foreign Affairs of China.
文摘Based on the 39 surface sediment samples collected in the flood season and the dry season in 2012 respectively and the measured hydrological data in October 2012, the sediment grain size characteristics has been analyzed and the response mechanism of surface sediments to estuarine hydrodynamics was revealed by calculating the range of waves and tidal currents. The results show that:(1) The grain size of the surface sediment samples decreased gradually from land to sea in the flood season. The fine sediment was redistributed under marine hydrodynamics in the dry season and the sediments showed coarser tendency ingeneral;(2) tidal current stirring sediment was very obvious in Dagu River estuary area, and wave stirring sediments mainly occurred in the tidal flat area and estuary sand bar area;(3) in the flood season, surface sediment sat the estuary were transported towards south and southeast. In the dry season, surface sediments were transported towards southwest at the north area of Jiaozhou Bay Bridge, and sediments were transported towards northeast area at the south of Jiaozhou Bay Bridge.
文摘Shandong has more than 70% of natural coasts are under erosion.Coastal erosion started from the 1970's and became a very serious problem at 1990 's.The dramatic decrease of sediment supplies from rivers caused rapid erosion at the delta and estuary areas,especially in the abandoned Yellow River Delta.Most sandy coasts along the Peninsula were eroded due to lack of sand supply and interruption of alongshore sediment drift,sand dredging from the beach or the offshore area caused serious erosion during short time. Sea-level rise causes slow but constant shoreline retreats and became a more serious threat.Different types of hard solutions for coastal protection against erosion were used in Shandong.Seawalls are most widely used,especially at the Yellow River Delta and city center waterfront.Groynes,jetties and breakwater are used on the north and east sandy coast of the Peninsula.Hard approaches are effective to protect the coast erosion but not change the erosion causes and led secondary impact on the coast.Soft engineering solution or the combined solutions are taken into acts.Beach nourishment is mostly considered as the better soft solution,especially to those tourists attracting sandy beaches along the Shandong coast.Long term monitoring and continuous lessons learning from the coastal erosion management will be adaptive for better coast solution in the future.
文摘The coastal cities are the most advanced regions in China.In the past few decades,the environment changed very significantly due to large scale human activities in the coastal regions.Polycyclic aromatic hydrocarbons (PAHs)in three dated sediment cores from the west coast of the Yellow Sea (core A01),the Yangtze River estuary (YRE;core A02)and the Oujiang River estuary (ORE;core A03)were analyzed to reconstruct the environmental evolutionary process of the east China coastal region over the past century. In the three cores,PAHs concentrations were increased rapidly.Lower concentrations of PAHs were measured in core A02 than in cores A01 and A03.The vertical variation of PAHs in the YRE Was dominated by the petrogenic sources.Historical records of PAHs in the ORE were controlled by pyrolytic sources.PAHs on the west coast of the Yellow Sea were contributed by the two sources.
基金This work was supported by the National Natural Science Foundation of China(No.71573192 and No.81573262)the Fundamental Research Funds for the Central Universities,HUST(No.2016YXZD042).
文摘Summary:Throughout the duration of the New Cooperative Medical Scheme(NCMS),it was found that an increasing number of rural patients were seeking out-of^county medical treatment,which posed a great burden on the NCMS fund.Our study was conducted to examine the prevalence of out-of^county hospitalizations and its related factors,and to provide a scientific basis for follow?up health insurance policies.A total of 215 counties in central and western China from 2008 to 2016 were selected.The total out-of-county hospitalization rate in nine years was 16.95%,which increased from 12.37%in 2008 to 19.21%in 2016 with an average annual growth rate of 5.66%.Its related expenses and compensations were shown to increase each year,with those in the central region being higher than those in the western region.Stepwise logistic regression reveals that the increase in out-of-county hospitalization rate was associated with region(XI),rural population(X2),per capita per year net income(X3),per capita gross domestic product(GDP)(X4),per capita funding amount of NCMS(X5),compensation ratio of out-of^county hospitalization cost(X6),per time average in-county(X7)and out-of-county hospitalization cost(X8).According to Bayesian network(BN),the marginal probability of high out-of^county hospitalization rate was as high as 81.7%.Out-of^county hospitalizations were directly related to X8,X3,X4 and X6.The probability of high out-of-county hospitalization obtained based on hospitalization expenses factors,economy factors,regional characteristics and NCMS policy factors was 95.7%,91.1%,93.0% and 88.8%,respectively.And how these factors affect out-of-county hospitalization and their interrelationships were found out.Our findings suggest that more attention should be paid to the influence mechanism of these factors on out-of-county hospitalizations,and the increase of hospitalizations outside the county should be reasonably supervised and controlled and our results will be used to help guide the formulation of proper intervention policies.
基金supported by funds from the National Key R&D Program of China(2018YFA0507700 and 2017YFA0506100)the National Natural Science Foundation of China(31722017,31870753,and 32122011)+1 种基金the Foundation of Hubei Hongshan Laboratory(2021hszd010)the China Postdoctoral Science Foundation(2020M682437 for Ling Ma).
文摘The plant UV-B photoreceptor UV RESISTANCE LOCUS 8(UVR8)exists as a homodimer in its inactive ground state.Upon UV-B exposure,UVR8monomerizes and interacts with a downstreamkey regulator,theCONSTITUTIVE PHOTOMORPHOGENIC 1/SUPPRESSOR OF PHYA(COP1/SPA)E3 ubiquitin ligase complex,to initiate UV-B signaling.Two WD40 proteins,REPRESSOR OF UV-B PHOTOMORPHOGENESIS 1(RUP1)and RUP2 directly interact with monomeric UVR8 and facilitate UVR8 ground state reversion,completing the UVR8 photocycle.Here,we reconstituted the RUP-mediated UVR8 redimerization process in vitro and reported the structure of the RUP2-UVR8^(W285A) complex(2.0A).RUP2 and UVR8^(W285A) formed a heterodimer via two distinct interfaces,designated Interface 1 and 2.The previously characterized Interface 1 is found between the RUP2 WD40 domain and the UVR8 C27 subregion.The newly identified Interface 2 is formed through interactions between the RUP2 WD40 domain and the UVR8 core domain.Disruption of Interface 2 impairedUV-B induced photomorphogenic development in Arabidopsis thaliana.Further biochemical analysis indicated that both interfaces are important for RUP2-UVR8 interactions and RUP2-mediated facilitation of UVR8 redimerization.Our findings suggest that the two-interface-interaction mode is adopted by both RUP2 and COP1 when they interact with UVR8,marking a step forward in understanding the molecular basis that underpins the interactions between UVR8 and its photocycle regulators.
基金supported by funds from the National Key Technology Research and Development Program of China(2022YFC2704200,2022YFC2704205)key research and development program of Zhejiang province(2019C03010)+1 种基金the National Natural Science Foundation of China(82072889,81772787)key project of CScO pilot oncology research funding(Y-2019AZZD-0359).
文摘Poly(ADP-ribose)polymerase(PARP)inhibitors are one of the most exciting classes of targeted therapy agents for cancers with homologous recombination(HR)deficiency.However,many patients without apparent HR defects also respond well to PARP inhibitors/cisplatin.The biomarker responsible for this mechanism remains unclear.Here,we identified a set of ribosomal genes that predict response to PARP inhibitors/cisplatin in HR-proficient patients.PARP inhibitor/cisplatin selectively eliminates cells with high expression of the eight genes in the identified panel via DNA damage(ATM)signaling-induced pro-apoptotic ribosomal stress,which along with ATM signaling-induced pro-survival HR repair constitutes a new model to balance the cell fate in response to DNA damage.Therefore,the combined examination of the gene panel along with HR status would allow for more precise predictions of clinical response to PARP inhibitor/cisplatin.The gene panel as an independent biomarker was validated by multiple published clinical datasets,as well as by an ovarian cancer organoids library we established.More importantly,its predictive value was further verified in a cohort of PARP inhibitor-treated ovarian cancer patients with both RNA-seq and WGS data.Furthermore,we identified several marketed drugs capable of upregulating the expression of the genes in the panel without causing HR deficiency in PARP inhibitor/cisplatin-resistant cell lines.These drugs enhance PARP inhibitor/cisplatin sensitivity in both intrinsically resistant organoids and cell lines with acquired resistance.Together,our study identifies a marker gene panel for HR-proficient patients and reveals a broader application of PARP inhibitor/cisplatin in cancer therapy.
基金This study was supported by the Fundamental Research Funds for the Central Universities(Grant No.2022YJS053).
文摘As an important transportation infrastructure and transportation backbone in China,high-speed rail(HSR)plays a critical role in promoting the development of green and low-carbon transportation.Calculating the CO_(2) emissions reduction performance of HSR will be conduci v e to pr omote the CO_(2) emissions r eduction w ork of the r ail w ay.Based on the Dalkic HSR CO_(2) emissions r eduction performance model,by adjusting the HSR CO_(2) emission factor(CEF HSR),the annual times of departures(T)and other parameters,this study develops a Chinese HSR CO_(2) emissions reduction performance model.Taking the Beijing-Shanghai HSR as the resear c h object,this study conducts a questionnaire survey to explore the substitution effect and demand effect of HSR on different transportation modes;collects data such as passenger v olume,av era ge electricity use and annual times of departures of the Beijing-Shanghai HSR in 2019;and calculates the CO_(2) emissions reduction performance of the Beijing-Shanghai HSR.This study has two main results:(1)It builds a Chinese HSR CO_(2) emissions reduction performance model based on substitution effect and demand effect.(2)In 2019,the CO_(2) emissions of the Beijing-Shanghai HSR are 2898233.62 t,the CO_(2) emissions reduction performance of the Beijing-Shanghai HSR is 17999482.8 t,the annual CO_(2) emissions of the Beijing-Shanghai line in‘No HSR’case are 7.2 times as in the’HSR’case and the PKT of the HSR is 10.2 g/pkm.Based on the research results,this study proposes three CO_(2) emissions reduction policy suggestions.This study would be helpful for further HSR CO_(2) emissions reduction resear c h and departments related to railway transportation management to make CO_(2) emissions reduction policies.
基金supported by the National Natural Science Foundation of China(81503350)the National Key Technology R&D Program(2015ZX09501-004-001-008)+1 种基金the National TCM Industry Science and Technology Program(201507004-04)the Open Research Fund of State Key Laboratory Breeding Base of Systematic research,Development and Utilization of Chinese Medicine Resources and China Postdoctoral Science Foundation(2016M590065)
文摘Heshouwu is a traditional non-toxic Chinese medicine commonly used in the clinical setting;however,clinical cases of Heshouwu-induced hepatotoxicity have been frequently reported^([1]).Pharmacoepidemiological studies have found that Heshouwu-induced liver injury occurs only in a small fraction of individuals taking the drug;these patients presented with the typ-
文摘N^6-methyladenosine(m6A),a ubiquitous RNA modification,is installed by METTL3-METTL14 complex.The structure of the heterodimeric complex between the methyltransferase domains(MTDs)of METTL3 and METTL14 has been previously determined.However,the MTDs alone possess no enzymatic activity.Here we present the solution structure for the zinc finger domain(ZFD)of METTL3,the inclusion of which fulfills the methyltransferase activity of METTL3-METTL14.We show that the ZFD specifically binds to an RNA containing 5'-GGACU-3'consensus sequence,but does not to one without.The ZFD thus serves as the target recognition domain,a structural feature previously shown for DNA methyltransferases,and cooperates with the MTDs of METTL3-METTL14 for catalysis.However,the interaction between the ZFD and the specific RNA is extremely weak,with the binding affinity at several hundred micromolar under physiological conditions.The ZFD contains two CCCH-type zinc fingers connected by an anti-parallel P-sheet.Mutational analysis and NMR titrations have mapped the functional interface to a contiguous surface.As a division of labor,the RNA-binding interface comprises basic residues from zinc finger 1 and hydrophobic residues fromβ-sheet and zinc finger 2.Further we show that the linker between the ZFD and MTD of METTL3 is flexible but partially folded,which may permit the cooperation between the two domains during catalysis.Together,the structural characterization of METTL3 ZFD paves the way to elucidate the atomic details of the entire process of RNA m6A modification.
基金This work was supported by grants from the National Natural Science Foundation of China(31772145 and 31901865)Huazhong Agricultural University Scientific&Technological Self-innovation Foundation(2012YB02).
文摘Mitogen-activated protein kinase(MAPK)cascades regulate a myriad of plant biological processes,including disease resistance.Plant genomes encode a large number of MAPK kinase kinases(MAPKKKs)that can be divided into two subfamilies,namely MEKK-like kinases and Raf-like kinases.Thus far,the func-tions of MEKK-like MAPKKKs have been relatively well characterized,but the roles of Raf-like MAPKKKs in.plant MAPK cascades remain less understood.Here,we report the role of OsEDR1,a Raf-like MAPKKK,in the regulation of the MAPK cascade in rice response tp the bacterial pathogen Xanthomonas oryzae pv.oryzicola(Xoc).We found that OsEDR1 inhibits OsMPKK10.2(a MAPK kinase)activity through physical interaction.Upon Xoc infection,OsMPKK10.2 is phosphorylated at S304 to activate OsMPK6(a MAPK).Interestingly,activated OsMPK6 phosphorylates OsEDR1 at S861,which destabilizes OsEDR1 and thus releases the inhibition of OsMPKK10.2,leading to increased OsMPKK10.2 activity and enhanced resistance of rice plants to Xoc.Taken together,these results provide new insights into the functions of Raf-like ki-nases in the regulation of the MAPK cascade in plant immunity.
基金supported by the National Natural Science Foundation of China(Grant No.31722017)
文摘More than 100 types of chemical modifications in RNA have been well documented. Recently, several modifications, such as N6-methyladenosine （m^6A）, have been detected in mRNA, opening the window into the realm of epitranscriptomies. The m^6A modification is the most abundant modification in mRNA and non-coding RNA （ncRNA）. At the molecular level, m^6A affects almost all aspects of mRNA metabolism, including splicing, translation, and stability, as well as microRNA （miRNA） maturation, playing essential roles in a range of cellular processes. The m^6A modification is regulated by three classes of proteins generally referred to as the ＂writer＂ （adenosine methyltransferase）, ＂eraser＂ （m^6A demethylating enzyme）, and ＂reader＂ （m^6A-binding protein）. The m^6A modification is reversibly installed and removed by writers and erasers, respectively. Readers, which are members of the YT521-B homology （YTH） family proteins, selectively bind to RNA and affect its fate in an m^6A-dependent manner. In this review, we summarize the structures of the functional proteins that modulate the m^6A modification, and provide our insights into the m^6A-mediated gene regulation.
