BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically...BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically associated with hypertrophic cardiomyopathy(HCM).However,in this case,the patient exhibited atrial and ventricular septal defects(VSDs).CASE SUMMARY This case report describes an 11-year-old boy diagnosed with Noonan syndrome,in whom genetic testing revealed a c.770C>T(p.Ser257 Leu)mutation in RAF1.The patient presented with intermittent chest discomfort and shortness of breath,symptoms that significantly worsened after physical activity.Clinical evaluation revealed marked growth retardation and multiple physical abnormalities.Electrocardiographic and echocardiographic assessments revealed VSDs,atrial septal defects,and left ventricular outflow tract obstruction.Following multidisciplinary consultation,the patient underwent cardiac surgical intervention,which led to clinical improvement;however,they subsequently developed a third-degree atrioventricular block,necessitating the implantation of a permanent pacemaker.During follow-up,echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa,significant improvement in left ventricular outflow tract obstruction,and notable reduction in ventricular septal thickness.A genetic mutation at the c.770C>T(p.Ser257 Leu)locus of RAF1 is typically associated with HCM and pulmonary hypertension.However,this patient’s clinical phenotype manifested as HCM,atrial septal defect,and VSD,suggesting that this mutation may involve a different pathophysiological mechanism.CONCLUSION This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of RAF1 mutation-associated cardiac pathologies.Early surgical intervention can ameliorate structural defects,but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.展开更多
BACKGROUND Cases of esophageal,airway,and pericardial perforations caused by chicken bone ingestion are rare worldwide,but their incidence has shown an upward trend in recent years.Injuries caused by chicken bones are...BACKGROUND Cases of esophageal,airway,and pericardial perforations caused by chicken bone ingestion are rare worldwide,but their incidence has shown an upward trend in recent years.Injuries caused by chicken bones are often more severe,leading to infections and,in extreme cases,perforation of the common carotid artery,pericardium,trachea,or even the heart,posing life-threatening risks.CASE SUMMARY We present a case of a patient who sustained combined esophageal and pericardial injuries with subsequent pericardial effusion due to chicken bone ingestion.The clinical manifestations included chest pain and widespread ST-segment elevation on electrocardiography.CONCLUSION The patient’s symptoms and signs were not entirely consistent with myocardial infarction.Chest computed tomography played a crucial role in clarifying the etiology and provided critical evidence for devising an effective treatment strategy.展开更多
Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a na...Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.展开更多
AIM: To investigate the fundus manifestations and human immunodeficiency virus(HIV) viral loads of acquired immune deficiency syndrome(AIDS) patients before and after highly active antiretroviral therapy(HAART).METHOD...AIM: To investigate the fundus manifestations and human immunodeficiency virus(HIV) viral loads of acquired immune deficiency syndrome(AIDS) patients before and after highly active antiretroviral therapy(HAART).METHODS: This retrospective study included 21 AIDS patients(42 eyes) who presented to the Department of Ophthalmology, Peking Union Medical College Hospital, from 2007 to 2011. Among the patients, 16 showed a good response to HAART, 3 presented drug resistance and 2 were pre-HAART. All patients underwent comprehensive ophthalmic examinations. The HIV viral loads and the CD4+ T-cell counts were also determined.RESULTS: The best-corrected visual acuity(BCVA) of 38 eyes(19 patients) was improved, and cytomegalovirus retinitis(CMVR) in 5 eyes(3 patients) regressed after HAART. Furthermore, 16 patients treated with effective HAART had decreased plasma HIV viral loads(<78 copies/mL)and increased CD4+ T-cell counts(343±161 cells/μL, P<0.005), but the HIV viral load in tears was still detected at 2404 copies/mL. The CD4+ T-cell count was lower in the CMVR group than in the non-CMVR group(P=0.022), but the HIV viral load in the tears was not significantly different between the two groups(P=0.439).CONCLUSION: Most patients with AIDS show a good viral response with a decreased HIV viral load and an increased CD4+ T-cell count in plasma after HAART. However, the HIV viral load remain quite high in the tear samples. Based on our results, we suggest that AIDS patients undergo long-term HAART that should not be interrupted.展开更多
The characteristics of wintertime volatile organic compounds(VOCs)in the North China Plain(NCP)region are complicated and remain obscure.VOC measurements were conducted by a proton transfer reaction time-of-flight mas...The characteristics of wintertime volatile organic compounds(VOCs)in the North China Plain(NCP)region are complicated and remain obscure.VOC measurements were conducted by a proton transfer reaction time-of-flight mass spectrometer(PTR-ToF-MS)at a rural site in the NCP from November to December 2018.Uncalibrated ions measured by PTRToF-MS were quantified and the overall VOC compositions were investigated by combining the measurements of PTR-ToF-MS and gas chromatography-mass spectrometer/flame ionization detector(GC-MS/FID).The measurement showed that although atmospheric VOCs concentrations are often dominated by primary emissions,the secondary formation of oxygenated VOCs(OVOCs)is non-negligible in the wintertime,i.e.,OVOCs accounts for 42%±7%in the total VOCs(151.3±75.6 ppbV).We demonstrated that PTR-MS measurements for isoprene are substantially overestimated due to the interferences of cycloalkanes.The chemical changes of organic carbon in a pollution accumulation period were investigated,which suggests an essential role of fragmentation reactions for large,chemically reduced compounds during the heavy-polluted stage in wintertime pollution.The changes of emission ratios of VOCs between winter 2011 and winter 2018 in the NCP support the positive effect of“coal to gas”strategies in curbing air pollutants.The high abundances of some key species(e.g.oxygenated aromatics)indicate the strong emissions of coal combustion in wintertime of NCP.The ratio of naphthalene to C8 aromatics was proposed as a potential indicator of the influence of coal combustion on VOCs.展开更多
Daytime HONO photolysis is an important source of atmospheric hydroxyl radicals(OH).Knowledge of HONO formation chemistry under typical haze conditions,however,is still limited.In the Multiphase chemistry experiment i...Daytime HONO photolysis is an important source of atmospheric hydroxyl radicals(OH).Knowledge of HONO formation chemistry under typical haze conditions,however,is still limited.In the Multiphase chemistry experiment in Fogs and Aerosols in the North China Plain in 2018,we investigated the wintertime HONO formation and its atmospheric implications at a rural site Gucheng.Three different episodes based on atmospheric aerosol loading levels were classified:clean periods(CPs),moderately polluted periods(MPPs)and severely polluted periods(SPPs).Correlation analysis revealed that HONO formation via heteroge.neous conversion of NO_(2)was more efficient on aerosol surfaces than on ground,highlighting the important role of aerosols in promoting HONO formation.Daytime HONO budget analysis indicated a large missing source(with an average production rate of 0.66±0.26,0.97±0.47 and 1.45±0.55 ppbV/hr for CPs,MPPs and SPPs,respectively),which strongly correlated with photo-enhanced reactions(NO_(2)heterogeneous reaction and particulate nitrate photolysis).Average OH formation derived from HONO photolysis reached up to(0.92±0.71),(1.75±1.26)and(1.82±1.47)ppbV/hr in CPs,MPPs and SPPs respectively,much higher than that from O3 photolysis(i.e.,(0.004±0.004),(0.006±0.007)and(0.0035±0.0034)ppbV/hr).Such high OH production rates could markedly regulate the atmospheric oxidation capacity and hence promote the formation of secondary aerosols and pollutants.展开更多
Rose(Rosa hybrida)is widely used for cut flowers and as garden plants.Stable and efficient transformation system is required for functional genomics of rose.Here,we established an efficient transformation method for r...Rose(Rosa hybrida)is widely used for cut flowers and as garden plants.Stable and efficient transformation system is required for functional genomics of rose.Here,we established an efficient transformation method for rose using Agrobacterium tumefaciens-mediated transformation of embryogenic callus.Expanding rose leaves were used as explants to induce somatic embryos,which were subjected to transformation with A.tumefaciens strain GV3101 using Green Fluorescence Protein(GFP)as a marker gene.It took about 8 months to generate transgenic shoots from embryogenic callus.PCR,RT-PCR,Southern and Western blotting,as well as stereoscopic fluorescence microscopy analysis demonstrated that GFP transgenes integrated stably into the rose genome.According to our data,a transformation efficiency of up to 6%can be achieved by following this optimized protocol.展开更多
Low temperature usually results in the developmental deformity of flower organs,immensely affecting the quality of rose flowers.However,it's largely unknown about the regulatory mechanisms activated by low tempera...Low temperature usually results in the developmental deformity of flower organs,immensely affecting the quality of rose flowers.However,it's largely unknown about the regulatory mechanisms activated by low temperature.Here,we used a low temperature-sensitive Rosa hybrida cv.‘Peach Avalanche’to screen a MADS-box gene RhAGL6 via conjoint analysis between RNA sequencing(RNA-seq)and whole-genome bisulfite sequencing(WGBS).Furthermore,we found that low temperature induced the hypermethylation and elevated histone 3 lys-27 trimethylation(H3K27me3)level on the RhAGL6 promoter,leading to decreased RhAGL6 expression.In addition,RhAGL6 silencing resulted in the formation of abnormal receptacles.We also found that the levels of gibberellins(GA3)and abscisic acid(ABA)in the receptacle under low temperature were lower and higher,respectively,than under normal temperature.Promoter activity analysis revealed that GA3 significantly activated RhAGL6 promoter activity,whereas ABA inhibited it.Thus,we propose that RhAGL6 regulates rose receptacle development by integrating epigenetic regulation and phytohormones signaling at low temperature.展开更多
BACKGROUND Rheumatoid arthritis(RA)is a common autoimmune disease.Nursing education for family caregivers is considered a workable and effective intervention,but the validity of this intervention in RA has not been re...BACKGROUND Rheumatoid arthritis(RA)is a common autoimmune disease.Nursing education for family caregivers is considered a workable and effective intervention,but the validity of this intervention in RA has not been reported.AIM To explore whether family caregiver nursing education(FCNE)works on patients with RA and the factors that influence FCNE.METHODS In this randomized controlled study,a sample of 158 pairs was included in the study with 80 in the intervention group and 78 in the control group.Baseline data of patients and caregivers was collected.The FCNE intervention was admi-nistered to caregivers,and inflammation level indicators,disease activity indicators and mood disorder indicators of patients were followed up and analyzed.RESULTS Baseline characteristics of the intervention and the control groups had no significant difference.Indicators were significantly reduced in the intervention group compared to the control group.The intervention group showed significant differences in stratification of relationship,education duration and age.CONCLUSION The effect of FCNE on RA is multifaceted,weakening inflammation level,alleviating disease activity and relieving mood disorder.Relationship between caregiver and patient,caregiver’s education level and patient’s age may act as impact factors of FCNE.展开更多
OBJECTIVE A system was established to evaluate the metastasis and prognosis of oral squamous cell carcinoma by analyzing the tumor differentiation, the TNM stage, the mode of invasion, and the expression of E-cadherin...OBJECTIVE A system was established to evaluate the metastasis and prognosis of oral squamous cell carcinoma by analyzing the tumor differentiation, the TNM stage, the mode of invasion, and the expression of E-cadherin and S100A4. METHODS Squamous cell carcinoma of the oral cavity of 86 cases was the focus of our study. In this system, the histopathological grade and the histochemical patterns were estimated on a 0-3 point scale, the total points graded from 0 to 13. RESULTS The incidence of metastasis and prognosis in the cases with total points more than 8 was significantly higher than that with total points less than 7 （P 〈 0.05,χ^2= 22.0658 and P 〈 0.05, χ^2= 10.7047）. The system had a significant higher specificity than that of ＇DIAGS index＇ system （Differentiation, Invasion mode, Adhesion molecules, Glycosaminoglycan, and the Sugar chain） in the evaluation of metastasis （P 〈 0.05, u = 2.2339）. Moreover, the specificity for evaluation of metastasis in the system was significantly higher than that of E-cadherin （P 〈 0.05, u = 2.4996） or S100A4 （P 〈 0.05, u = 2.4289） only. Furthermore the specificity for evaluation of unfavorable prognosis in the system was also significantly higher than that of E-cadherin （P 〈 0.05, u = 2.1313） or S100A4 only （P 〈 0.05, u = 2.0301）. CONCLUSION This is a valuable evaluation system with high specificity to predict metastatic potential and prognosis of oral squamous cell carcinoma.展开更多
To improve the resilience of a distribution system against extreme weather,a fuel-based distributed generator(DG)allocation model is proposed in this study.In this model,the DGs are placed at the planning stage.When a...To improve the resilience of a distribution system against extreme weather,a fuel-based distributed generator(DG)allocation model is proposed in this study.In this model,the DGs are placed at the planning stage.When an extreme event occurs,the controllable generators form temporary microgrids(MGs)to restore the load maximally.Simultaneously,a demand response program(DRP)mitigates the imbalance between the power supply and demand during extreme events.To cope with the fault uncertainty,a robust optimization(RO)method is applied to reduce the long-term investment and short-term operation costs.The optimization is formulated as a tri-level defenderattacker-defender(DAD)framework.At the first level,decision-makers work out the DG allocation scheme;at the second level,the attacker finds the optimal attack strategy with maximum damage;and at the third level,restoration measures,namely distribution network reconfiguration(DNR)and demand response are performed.The problem is solved by the nested column and constraint generation(NC&CG)method and the model is validated using an IEEE 33-node system.Case studies validate the effectiveness and superiority of the proposed model according to the enhanced resilience and reduced cost.展开更多
Aiming at the problems of image super-resolution algorithm with many convolutional neural networks, such as large parameters, large computational complexity and blurred image texture, we propose a new algorithm model....Aiming at the problems of image super-resolution algorithm with many convolutional neural networks, such as large parameters, large computational complexity and blurred image texture, we propose a new algorithm model. The classical convolutional neural network is improved, the convolution kernel size is adjusted, and the parameters are reduced;the pooling layer is added to reduce the dimension. Reduced computational complexity, increased learning rate, and reduced training time. The iterative back-projection algorithm is combined with the convolutional neural network to create a new algorithm model. The experimental results show that compared with the traditional facial illusion method, the proposed method can obtain better performance.展开更多
[Objectives] To investigate the mechanism of DNA damage of cisplatin( DDP),a broad spectrum anticancer drug on breast cancer MCF-7 cells,and to study the mechanism of apoptosis induced by DDP.[Methods]MCF-7 cells were...[Objectives] To investigate the mechanism of DNA damage of cisplatin( DDP),a broad spectrum anticancer drug on breast cancer MCF-7 cells,and to study the mechanism of apoptosis induced by DDP.[Methods]MCF-7 cells were treated by DDP( 0 mg/L,2 mg/L,4 mg/L,6 mg/L,6 mg/L,and 10 mg/L) for 48 hours. MTT assay was used to detect the inhibitory effect of DDP on MCF-7 cells and IC50 value was calculated. Western blot was adopted to detect the expression of γ-H2 AX,which was the marker of DNA double stranded breaks( DSBs) and ATM( sensory molecules of DSBs),the apoptotic signal transduction molecule cleaved caspase-3,and the proteins associated with apoptosis calpain.[Results]DDP inhibited MCF-7 cell activity in a concentration-dependent manner and IC50 was 7. 57 mg/L. In contrast to the control group( without DDP treatment),MCF-7 cells with DDP treatment expressed more γ-H2 AX,ATM,cleaved caspase-3 and calpain.[Conclusions] DDP could inhibit the activity of breast cancer MCF-7 cells. Its mechanisms may be associated with inhibition of MCF-7 cell apoptosis,induction of DNA double strand breaking and the expression of pro-apoptotic protein up-regulation.展开更多
The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA P...The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE4(RhSPL4)positively regulates flowering time in rose.Transient silencing or overexpression transgenic rose plants of RhSPL4 exhibited delayed or early flowering,respectively.Analysis of transcriptome data from transgenic lines overexpressing RhSPL4 compared to the wild type indicated that differentially expressed genes were significantly enriched in the circadian rhythm pathway.Among the proteins encoded by these genes,RhSPL4 binds to the promoter of PSEUDO-RESPONSE REGULATOR 5-LIKE(RhPRR5L),as revealed in yeast one-hybrid,dual-Luciferase/Renilla luciferase reporter,chromatin immunoprecipitation-quantitative PCR and electrophoretic mobility shift assay.Furthermore,RhSPL4 specifically binds to the478 to441 bp region of the RhPRR5L promoter and activates its transcription.The silencing of RhPRR5L delayed flowering time in rose,resembling the phenotype of RhSPL4-silenced plants.Together,these results indicate that the RhSPL4-RhPRR5L module positively regulates flowering time in rose,laying the foundation for the genetic improvement of flowering time in this important horticultural crop.展开更多
This study tested a chain mediation model on whether hopelessness and nostalgia play a mediating role in psychache and suicidal ideation of firefighters.A total of 652 firefighters participated in the survey(male=94.9...This study tested a chain mediation model on whether hopelessness and nostalgia play a mediating role in psychache and suicidal ideation of firefighters.A total of 652 firefighters participated in the survey(male=94.94%;mean age=23.71 years,SD=4.18 years).The firefighters completed the Chinese Revised Psychache Scale(PAS),Beck Hopelessness Scale(BHS),Southampton Nostalgia Scale(SNS),and Columbia-Suicide Severity Rating Scale(CSSRS).The path analysis results indicated that psychache positively predicted suicidal ideation.Hopelessness plays a significant mediating role between psychache and suicidal ideation further strengthening this relationship.In contrast,nostalgia mediates and weakened the relationship between psychache and suicidal ideation.Hopelessness and nostalgia jointly constructed a chain mediating effect between psychache and suicidal ideation,for higher suicidal ideation with higher hopelessness and lower nostalgia.The findings align with the Three-Step Theory of Suicide,which proposes that suicidal ideation results from the combination of pain and hopelessness and that connectedness is a key protective factor against escalating ideation.Therefore,interventions to reduce suicidal ideation in firefighters should aim to enhance their nostalgia,while reducing sense of hopelessness.展开更多
Water-soluble organic aerosol(WSOA)plays a significant role in air quality and human health.Here we characterized the chemical properties and molecular compositions of WSOA at a rural site in North China Plain during ...Water-soluble organic aerosol(WSOA)plays a significant role in air quality and human health.Here we characterized the chemical properties and molecular compositions of WSOA at a rural site in North China Plain during winter using a high-resolution aerosol mass spectrometer and electrospray ionization high-resolution orbitrap mass spectrometer(ESI-HRMS).Our results show that the mass concentration of WSOA was significantly higher than that observed in Beijing in winter 2020,contributing about 56%of OA on average.CHO compounds(56%-74%)and CHN compounds(66%-80%)dominated in negative mode and positive mode,respectively,while CHON accounted for 15%-41%across both modes.The chemical characteristics of WSOA varied with polluted levels and between day and night.As pollution intensified,the abundance of CHO-compounds with condensed aromatics increased by 9%and the number of highly oxygenated molecules(HOMs)molecular formula detected in server haze was more than double that of clean days.CHO-compounds with ten carbon atoms(C_(10))were more abundant at night while those with nine carbon atoms(C_(9))were higher during the day.High levels of CHN+compounds were linked to nighttime biomass burning,whereas CHON compounds were more abundant during the day.Increased pollution also led to the formation of more complex CHON-compounds,indicating that organonitrates continue to play a significant role in rural pollution.展开更多
基金Supported by the Gansu Provincial Science and Technology Plan Project,No.24JRRA886 and No.23JRRA1287Gansu Provincial People’s Hospital:Excellent Doctoral Student Cultivation Program,No.22GSSYD-14.
文摘BACKGROUND Noonan syndrome is a relatively common autosomal dominant genetic disorder characterized by cardiovascular defects owing to functional abnormalities in key genes such as RAF1.Mutations in RAF1 are typically associated with hypertrophic cardiomyopathy(HCM).However,in this case,the patient exhibited atrial and ventricular septal defects(VSDs).CASE SUMMARY This case report describes an 11-year-old boy diagnosed with Noonan syndrome,in whom genetic testing revealed a c.770C>T(p.Ser257 Leu)mutation in RAF1.The patient presented with intermittent chest discomfort and shortness of breath,symptoms that significantly worsened after physical activity.Clinical evaluation revealed marked growth retardation and multiple physical abnormalities.Electrocardiographic and echocardiographic assessments revealed VSDs,atrial septal defects,and left ventricular outflow tract obstruction.Following multidisciplinary consultation,the patient underwent cardiac surgical intervention,which led to clinical improvement;however,they subsequently developed a third-degree atrioventricular block,necessitating the implantation of a permanent pacemaker.During follow-up,echocardiographic findings demonstrated near-complete resolution of the shunt across the atrial and ventricular septa,significant improvement in left ventricular outflow tract obstruction,and notable reduction in ventricular septal thickness.A genetic mutation at the c.770C>T(p.Ser257 Leu)locus of RAF1 is typically associated with HCM and pulmonary hypertension.However,this patient’s clinical phenotype manifested as HCM,atrial septal defect,and VSD,suggesting that this mutation may involve a different pathophysiological mechanism.CONCLUSION This case confirms the genotype-phenotype heterogeneity of Noonan syndrome and highlights the complex management requirements of RAF1 mutation-associated cardiac pathologies.Early surgical intervention can ameliorate structural defects,but it must be integrated with genetic counseling and lifelong monitoring to optimize patient outcomes.
文摘BACKGROUND Cases of esophageal,airway,and pericardial perforations caused by chicken bone ingestion are rare worldwide,but their incidence has shown an upward trend in recent years.Injuries caused by chicken bones are often more severe,leading to infections and,in extreme cases,perforation of the common carotid artery,pericardium,trachea,or even the heart,posing life-threatening risks.CASE SUMMARY We present a case of a patient who sustained combined esophageal and pericardial injuries with subsequent pericardial effusion due to chicken bone ingestion.The clinical manifestations included chest pain and widespread ST-segment elevation on electrocardiography.CONCLUSION The patient’s symptoms and signs were not entirely consistent with myocardial infarction.Chest computed tomography played a crucial role in clarifying the etiology and provided critical evidence for devising an effective treatment strategy.
基金supported in part by the National Key Research&Development Program of China,No.2022YFA1104900(to LS)the National Natural Science Foundation of China,Nos.82371175,82071535(both to LS),82101614(to YP)+5 种基金the International Science and Technology Cooperation Projects of Guangdong Province,No.2023A0505050121(to LS)Guangdong Basic and Applied Basic Research Foundation,Nos.2022B1515130007(to LS),2023A1515030012(to SZ),2022A1515010666(to WL)the Science and Technology Program of Guangzhou,Nos.202102070001(to LS),202201010041(to YP)Shenzhen Basic Research Grant,Nos.JCYJ20200109140414636,JCYJ20230807145103007(both to WL)awarded a Royal Society Newton Advanced Fellowship,No.AOMS-NAF0051003in collaboration with Zoltán Molnár,Department of Physiology,Anatomy and Genetics,University of Oxford(2017–2021)。
文摘Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.
基金Supported by the National Key Technologies R&D Program for the 11th Five-year Plan(No.2008ZX10001-006)
文摘AIM: To investigate the fundus manifestations and human immunodeficiency virus(HIV) viral loads of acquired immune deficiency syndrome(AIDS) patients before and after highly active antiretroviral therapy(HAART).METHODS: This retrospective study included 21 AIDS patients(42 eyes) who presented to the Department of Ophthalmology, Peking Union Medical College Hospital, from 2007 to 2011. Among the patients, 16 showed a good response to HAART, 3 presented drug resistance and 2 were pre-HAART. All patients underwent comprehensive ophthalmic examinations. The HIV viral loads and the CD4+ T-cell counts were also determined.RESULTS: The best-corrected visual acuity(BCVA) of 38 eyes(19 patients) was improved, and cytomegalovirus retinitis(CMVR) in 5 eyes(3 patients) regressed after HAART. Furthermore, 16 patients treated with effective HAART had decreased plasma HIV viral loads(<78 copies/mL)and increased CD4+ T-cell counts(343±161 cells/μL, P<0.005), but the HIV viral load in tears was still detected at 2404 copies/mL. The CD4+ T-cell count was lower in the CMVR group than in the non-CMVR group(P=0.022), but the HIV viral load in the tears was not significantly different between the two groups(P=0.439).CONCLUSION: Most patients with AIDS show a good viral response with a decreased HIV viral load and an increased CD4+ T-cell count in plasma after HAART. However, the HIV viral load remain quite high in the tear samples. Based on our results, we suggest that AIDS patients undergo long-term HAART that should not be interrupted.
基金supported by the National Key R&D Plan of China(No.2019YFE0106300)the National Natural Science Foundation of China(No.41877302)+3 种基金Guangdong Natural Science Funds for Distinguished Young Scholar(No.2018B030306037)Key-Area Research and Development Program of Guangdong Province(No.2019B110206001)Guangdong Innovative and Entrepreneurial Research Team Program(No.2016ZT06N263)supported by Special Fund Project for Science and Technology Innovation Strategy of Guangdong Province(No.2019B121205004)
文摘The characteristics of wintertime volatile organic compounds(VOCs)in the North China Plain(NCP)region are complicated and remain obscure.VOC measurements were conducted by a proton transfer reaction time-of-flight mass spectrometer(PTR-ToF-MS)at a rural site in the NCP from November to December 2018.Uncalibrated ions measured by PTRToF-MS were quantified and the overall VOC compositions were investigated by combining the measurements of PTR-ToF-MS and gas chromatography-mass spectrometer/flame ionization detector(GC-MS/FID).The measurement showed that although atmospheric VOCs concentrations are often dominated by primary emissions,the secondary formation of oxygenated VOCs(OVOCs)is non-negligible in the wintertime,i.e.,OVOCs accounts for 42%±7%in the total VOCs(151.3±75.6 ppbV).We demonstrated that PTR-MS measurements for isoprene are substantially overestimated due to the interferences of cycloalkanes.The chemical changes of organic carbon in a pollution accumulation period were investigated,which suggests an essential role of fragmentation reactions for large,chemically reduced compounds during the heavy-polluted stage in wintertime pollution.The changes of emission ratios of VOCs between winter 2011 and winter 2018 in the NCP support the positive effect of“coal to gas”strategies in curbing air pollutants.The high abundances of some key species(e.g.oxygenated aromatics)indicate the strong emissions of coal combustion in wintertime of NCP.The ratio of naphthalene to C8 aromatics was proposed as a potential indicator of the influence of coal combustion on VOCs.
基金supported by the National Key Research and Development Program of China (No. 2017YFC210104)the National Natural Science Foundation of China (No. 91644218)+2 种基金the Guangdong Innovative and Entrepreneurial Research Team Program (No. 2016ZT06N263)the Special Fund Project for Science and Technology Innovation Strategy ofGuangdong Province (No. 2019B121205004)the financial support from the China Scholarship Council (CSC)
文摘Daytime HONO photolysis is an important source of atmospheric hydroxyl radicals(OH).Knowledge of HONO formation chemistry under typical haze conditions,however,is still limited.In the Multiphase chemistry experiment in Fogs and Aerosols in the North China Plain in 2018,we investigated the wintertime HONO formation and its atmospheric implications at a rural site Gucheng.Three different episodes based on atmospheric aerosol loading levels were classified:clean periods(CPs),moderately polluted periods(MPPs)and severely polluted periods(SPPs).Correlation analysis revealed that HONO formation via heteroge.neous conversion of NO_(2)was more efficient on aerosol surfaces than on ground,highlighting the important role of aerosols in promoting HONO formation.Daytime HONO budget analysis indicated a large missing source(with an average production rate of 0.66±0.26,0.97±0.47 and 1.45±0.55 ppbV/hr for CPs,MPPs and SPPs,respectively),which strongly correlated with photo-enhanced reactions(NO_(2)heterogeneous reaction and particulate nitrate photolysis).Average OH formation derived from HONO photolysis reached up to(0.92±0.71),(1.75±1.26)and(1.82±1.47)ppbV/hr in CPs,MPPs and SPPs respectively,much higher than that from O3 photolysis(i.e.,(0.004±0.004),(0.006±0.007)and(0.0035±0.0034)ppbV/hr).Such high OH production rates could markedly regulate the atmospheric oxidation capacity and hence promote the formation of secondary aerosols and pollutants.
基金The authors thank Dr.Manzhu Bao(Huazhong Agricultural University,Wuhan,China),Dr.Hibrand-Saint Oyant L.(INRA,Agrocampus-Ouest,Universitéd’Angers,Beaucouzé,France)and Dr.Fabrice Foucher(INRA,78026 Versailles Cedex,France)for their excellent suggestions.We are also grateful to Dr.Wenxue Li and Dr.Hongqiu Wang(Chinese Academy of Agricultural Sci-ences,Beijing,China)for assistance with the experiments.This work was supported by grants from National Natural Science Foundation of China(Grant No.31522049)Construction of Beijing Science and Technology Innovation and Service Capacity in Top Subjects(Grant No.CEFF-PXM2019_014207_000032).
文摘Rose(Rosa hybrida)is widely used for cut flowers and as garden plants.Stable and efficient transformation system is required for functional genomics of rose.Here,we established an efficient transformation method for rose using Agrobacterium tumefaciens-mediated transformation of embryogenic callus.Expanding rose leaves were used as explants to induce somatic embryos,which were subjected to transformation with A.tumefaciens strain GV3101 using Green Fluorescence Protein(GFP)as a marker gene.It took about 8 months to generate transgenic shoots from embryogenic callus.PCR,RT-PCR,Southern and Western blotting,as well as stereoscopic fluorescence microscopy analysis demonstrated that GFP transgenes integrated stably into the rose genome.According to our data,a transformation efficiency of up to 6%can be achieved by following this optimized protocol.
基金the National Natural Science Foundation of China(Grant Nos.31972438,31902054,32202530)the Postdoctoral Initiation Project of Shenzhen Polytechnic(Grant Nos.6021330012K0,6020330006K0,and 6022312017K)+1 种基金Natural Science Foundation of Guangdong Province(Grant No.2021A1515110368)Major Agricultural Science and Technology Projects in Yunnan Province(Grant No.202102AE090052).
文摘Low temperature usually results in the developmental deformity of flower organs,immensely affecting the quality of rose flowers.However,it's largely unknown about the regulatory mechanisms activated by low temperature.Here,we used a low temperature-sensitive Rosa hybrida cv.‘Peach Avalanche’to screen a MADS-box gene RhAGL6 via conjoint analysis between RNA sequencing(RNA-seq)and whole-genome bisulfite sequencing(WGBS).Furthermore,we found that low temperature induced the hypermethylation and elevated histone 3 lys-27 trimethylation(H3K27me3)level on the RhAGL6 promoter,leading to decreased RhAGL6 expression.In addition,RhAGL6 silencing resulted in the formation of abnormal receptacles.We also found that the levels of gibberellins(GA3)and abscisic acid(ABA)in the receptacle under low temperature were lower and higher,respectively,than under normal temperature.Promoter activity analysis revealed that GA3 significantly activated RhAGL6 promoter activity,whereas ABA inhibited it.Thus,we propose that RhAGL6 regulates rose receptacle development by integrating epigenetic regulation and phytohormones signaling at low temperature.
基金Key Project of Medical-Science Research of Hebei Province,No.20180432.
文摘BACKGROUND Rheumatoid arthritis(RA)is a common autoimmune disease.Nursing education for family caregivers is considered a workable and effective intervention,but the validity of this intervention in RA has not been reported.AIM To explore whether family caregiver nursing education(FCNE)works on patients with RA and the factors that influence FCNE.METHODS In this randomized controlled study,a sample of 158 pairs was included in the study with 80 in the intervention group and 78 in the control group.Baseline data of patients and caregivers was collected.The FCNE intervention was admi-nistered to caregivers,and inflammation level indicators,disease activity indicators and mood disorder indicators of patients were followed up and analyzed.RESULTS Baseline characteristics of the intervention and the control groups had no significant difference.Indicators were significantly reduced in the intervention group compared to the control group.The intervention group showed significant differences in stratification of relationship,education duration and age.CONCLUSION The effect of FCNE on RA is multifaceted,weakening inflammation level,alleviating disease activity and relieving mood disorder.Relationship between caregiver and patient,caregiver’s education level and patient’s age may act as impact factors of FCNE.
基金supported by a grant from the Project Sponsored by the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry,China(No.2005383).
文摘OBJECTIVE A system was established to evaluate the metastasis and prognosis of oral squamous cell carcinoma by analyzing the tumor differentiation, the TNM stage, the mode of invasion, and the expression of E-cadherin and S100A4. METHODS Squamous cell carcinoma of the oral cavity of 86 cases was the focus of our study. In this system, the histopathological grade and the histochemical patterns were estimated on a 0-3 point scale, the total points graded from 0 to 13. RESULTS The incidence of metastasis and prognosis in the cases with total points more than 8 was significantly higher than that with total points less than 7 （P 〈 0.05,χ^2= 22.0658 and P 〈 0.05, χ^2= 10.7047）. The system had a significant higher specificity than that of ＇DIAGS index＇ system （Differentiation, Invasion mode, Adhesion molecules, Glycosaminoglycan, and the Sugar chain） in the evaluation of metastasis （P 〈 0.05, u = 2.2339）. Moreover, the specificity for evaluation of metastasis in the system was significantly higher than that of E-cadherin （P 〈 0.05, u = 2.4996） or S100A4 （P 〈 0.05, u = 2.4289） only. Furthermore the specificity for evaluation of unfavorable prognosis in the system was also significantly higher than that of E-cadherin （P 〈 0.05, u = 2.1313） or S100A4 only （P 〈 0.05, u = 2.0301）. CONCLUSION This is a valuable evaluation system with high specificity to predict metastatic potential and prognosis of oral squamous cell carcinoma.
基金supported by the Technology Project of State Grid Jiangsu Electric Power Co.,Ltd.,China (J2022160,Research on Key Technologies of Distributed Power Dispatching Control for Resilience Improvement of Distribution Networks).
文摘To improve the resilience of a distribution system against extreme weather,a fuel-based distributed generator(DG)allocation model is proposed in this study.In this model,the DGs are placed at the planning stage.When an extreme event occurs,the controllable generators form temporary microgrids(MGs)to restore the load maximally.Simultaneously,a demand response program(DRP)mitigates the imbalance between the power supply and demand during extreme events.To cope with the fault uncertainty,a robust optimization(RO)method is applied to reduce the long-term investment and short-term operation costs.The optimization is formulated as a tri-level defenderattacker-defender(DAD)framework.At the first level,decision-makers work out the DG allocation scheme;at the second level,the attacker finds the optimal attack strategy with maximum damage;and at the third level,restoration measures,namely distribution network reconfiguration(DNR)and demand response are performed.The problem is solved by the nested column and constraint generation(NC&CG)method and the model is validated using an IEEE 33-node system.Case studies validate the effectiveness and superiority of the proposed model according to the enhanced resilience and reduced cost.
文摘Aiming at the problems of image super-resolution algorithm with many convolutional neural networks, such as large parameters, large computational complexity and blurred image texture, we propose a new algorithm model. The classical convolutional neural network is improved, the convolution kernel size is adjusted, and the parameters are reduced;the pooling layer is added to reduce the dimension. Reduced computational complexity, increased learning rate, and reduced training time. The iterative back-projection algorithm is combined with the convolutional neural network to create a new algorithm model. The experimental results show that compared with the traditional facial illusion method, the proposed method can obtain better performance.
基金Supported by Project of National Natural Science Foundation(30600753&81172154)Hunan Provincial Natural Science Foundation of China(2016JJ2088)+1 种基金Project of Hunan Provincial Department of Education(13C541)Project of Hunan Administration of Traditional Chinese Medicine(2015123)
文摘[Objectives] To investigate the mechanism of DNA damage of cisplatin( DDP),a broad spectrum anticancer drug on breast cancer MCF-7 cells,and to study the mechanism of apoptosis induced by DDP.[Methods]MCF-7 cells were treated by DDP( 0 mg/L,2 mg/L,4 mg/L,6 mg/L,6 mg/L,and 10 mg/L) for 48 hours. MTT assay was used to detect the inhibitory effect of DDP on MCF-7 cells and IC50 value was calculated. Western blot was adopted to detect the expression of γ-H2 AX,which was the marker of DNA double stranded breaks( DSBs) and ATM( sensory molecules of DSBs),the apoptotic signal transduction molecule cleaved caspase-3,and the proteins associated with apoptosis calpain.[Results]DDP inhibited MCF-7 cell activity in a concentration-dependent manner and IC50 was 7. 57 mg/L. In contrast to the control group( without DDP treatment),MCF-7 cells with DDP treatment expressed more γ-H2 AX,ATM,cleaved caspase-3 and calpain.[Conclusions] DDP could inhibit the activity of breast cancer MCF-7 cells. Its mechanisms may be associated with inhibition of MCF-7 cell apoptosis,induction of DNA double strand breaking and the expression of pro-apoptotic protein up-regulation.
基金supported by Yunnan Province Agricultural Joint Key Project(Grant No.202401BD070001-016)the National Natural Science Foundation of China(Grant No.32202530)+3 种基金Talent Introduction and Training Project of Yunnan Academy of Agricultural Sciences(Grant No.2024RCYP-09)Fundamental Research Project(Grant No.202401CF070046)Xingdian Talent support program(XDYC-QNRC-2023-0457)Yunnan Technology Innovation Center of Flower Technique.
文摘The proper flowering time of rose(Rosa hybrida)is vital for the market value of this horticultural crop,but the mechanism regulating this trait is largely unclear.Here,we found that the transcription factor SQUAMOSA PROMOTER BINDING PROTEIN-LIKE4(RhSPL4)positively regulates flowering time in rose.Transient silencing or overexpression transgenic rose plants of RhSPL4 exhibited delayed or early flowering,respectively.Analysis of transcriptome data from transgenic lines overexpressing RhSPL4 compared to the wild type indicated that differentially expressed genes were significantly enriched in the circadian rhythm pathway.Among the proteins encoded by these genes,RhSPL4 binds to the promoter of PSEUDO-RESPONSE REGULATOR 5-LIKE(RhPRR5L),as revealed in yeast one-hybrid,dual-Luciferase/Renilla luciferase reporter,chromatin immunoprecipitation-quantitative PCR and electrophoretic mobility shift assay.Furthermore,RhSPL4 specifically binds to the478 to441 bp region of the RhPRR5L promoter and activates its transcription.The silencing of RhPRR5L delayed flowering time in rose,resembling the phenotype of RhSPL4-silenced plants.Together,these results indicate that the RhSPL4-RhPRR5L module positively regulates flowering time in rose,laying the foundation for the genetic improvement of flowering time in this important horticultural crop.
文摘This study tested a chain mediation model on whether hopelessness and nostalgia play a mediating role in psychache and suicidal ideation of firefighters.A total of 652 firefighters participated in the survey(male=94.94%;mean age=23.71 years,SD=4.18 years).The firefighters completed the Chinese Revised Psychache Scale(PAS),Beck Hopelessness Scale(BHS),Southampton Nostalgia Scale(SNS),and Columbia-Suicide Severity Rating Scale(CSSRS).The path analysis results indicated that psychache positively predicted suicidal ideation.Hopelessness plays a significant mediating role between psychache and suicidal ideation further strengthening this relationship.In contrast,nostalgia mediates and weakened the relationship between psychache and suicidal ideation.Hopelessness and nostalgia jointly constructed a chain mediating effect between psychache and suicidal ideation,for higher suicidal ideation with higher hopelessness and lower nostalgia.The findings align with the Three-Step Theory of Suicide,which proposes that suicidal ideation results from the combination of pain and hopelessness and that connectedness is a key protective factor against escalating ideation.Therefore,interventions to reduce suicidal ideation in firefighters should aim to enhance their nostalgia,while reducing sense of hopelessness.
基金supported by the National Natural Science Foundation of China(No.42307139)the Strategic Priority Research Program of the Chinese Academy of Sciences(No.XDB0760200)。
文摘Water-soluble organic aerosol(WSOA)plays a significant role in air quality and human health.Here we characterized the chemical properties and molecular compositions of WSOA at a rural site in North China Plain during winter using a high-resolution aerosol mass spectrometer and electrospray ionization high-resolution orbitrap mass spectrometer(ESI-HRMS).Our results show that the mass concentration of WSOA was significantly higher than that observed in Beijing in winter 2020,contributing about 56%of OA on average.CHO compounds(56%-74%)and CHN compounds(66%-80%)dominated in negative mode and positive mode,respectively,while CHON accounted for 15%-41%across both modes.The chemical characteristics of WSOA varied with polluted levels and between day and night.As pollution intensified,the abundance of CHO-compounds with condensed aromatics increased by 9%and the number of highly oxygenated molecules(HOMs)molecular formula detected in server haze was more than double that of clean days.CHO-compounds with ten carbon atoms(C_(10))were more abundant at night while those with nine carbon atoms(C_(9))were higher during the day.High levels of CHN+compounds were linked to nighttime biomass burning,whereas CHON compounds were more abundant during the day.Increased pollution also led to the formation of more complex CHON-compounds,indicating that organonitrates continue to play a significant role in rural pollution.
