Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiologic...Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions.Deciphering the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue.In this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone hemisections.Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae.The protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow cavity.Completed within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals.The bone hemisections are compatible with diverse antibody labeling strategies.Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of parameters.With proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months.This protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.展开更多
Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and...Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.展开更多
Inflammatory bowel diseases(IBD),conventionally consist of Crohn’s disease(CD)and ulcerative colitis.They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental facto...Inflammatory bowel diseases(IBD),conventionally consist of Crohn’s disease(CD)and ulcerative colitis.They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors.The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis,which in turn is triggered due to exposure to various inciting environmental factors.But there is no clearly defined etiology of IBD and this type of disease is termed as“idiopathic IBD”,“classic IBD”,or“primary IBD”.We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions,and we consider this form of de novo IBD as“secondary IBD”.Currently known factors that are potentially responsible for giving rise to secondary IBD are medications;bowel altering surgeries and transplantation of organs,stem cells or fecal microbiome.Medications associated with the development of secondary IBD include;immunomodulators,anti-tumor necrosis factor alpha agents,anti-interleukin agents,interferons,immune stimulating agents and checkpoint inhibitors.Colectomy can in some cases give rise to de novo CD,pouchitis of the ileal pouch,or postcolectomy enteritis syndrome.After solid organ transplantation or hematopoietic stem cell transplantation,the recipient may develop de novo IBD or IBD flare.Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.展开更多
Integrated satellite-terrestrial network(ISTN)has been considered a novel network architecture to achieve global three-dimensional coverage and ultra-wide area broadband access anytime and anywhere.Being a promising p...Integrated satellite-terrestrial network(ISTN)has been considered a novel network architecture to achieve global three-dimensional coverage and ultra-wide area broadband access anytime and anywhere.Being a promising paradigm,cloud computing and mobile edge computing(MEC)have been identified as key technology enablers for ISTN to further improve quality of service and business continuity.However,most of the existing ISTN studies based on cloud computing and MEC regard satellite networks as relay networks,ignoring the feasibility of directly deploying cloud computing nodes and edge computing nodes on satellites.In addition,most computing tasks are transferred to cloud servers or offloaded to nearby edge servers,the layered design of integrated satellite-air-terrestrial architecture and the cloud-edge-device cooperative processing problems have not been fully considered.Therefore,different from previous works,this paper proposed a novel satellite-air-terrestrial layered architecture for cloud-edge-device collaboration,named SATCECN.Then this paper analyzes the appropriate deployment locations of cloud servers and edge servers in ISTN,and describes the processing flow of typical satellite computing tasks.For computing resource allocation problems,this paper proposed a device-edge-cloud Multi-node Cross-layer Collaboration Computing(MCCC)method to find the optimal task allo-cation strategy that minimizes the task completion delay and the weighted system energy consumption.Furthermore,the approximate optimal solutions of the optimization model are obtained by using successive convex approxi-mation algorithm,and the outstanding advantages of the proposed method in reducing system energy consumption and task execution delay are verified through experiments.Finally,some potential issues and directions for future research are highlighted.展开更多
Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8...Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.展开更多
Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for ...Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for patients with advanced NSCLC bearing sensitive EGFR mutations,significantly prolongs the progression-free survival(PFS)to 25.5 months1.Despite great breakthroughs in survival data,patients inevitably experience disease progression.A large meta-analysis has indicated that,compared with chemother-apy,immuno-based therapies achieve longer PFS in patients with EGFR mutation who progressed on third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)2.Therefore,immunotherapies are often used after EGFR-TKI resistance is observed.展开更多
In this paper, the attack detection problem is investigated for a class of closed-loop systems subjected to unknownbutbounded noises in the presence of stealthy attacks. The measurement outputs from the sensors are qu...In this paper, the attack detection problem is investigated for a class of closed-loop systems subjected to unknownbutbounded noises in the presence of stealthy attacks. The measurement outputs from the sensors are quantized before transmission.A specific type of perfect stealthy attack, which meets certain rather stringent conditions, is taken into account. Such attacks could be injected by adversaries into both the sensor-toestimator and controller-to-actuator channels, with the aim of disrupting the normal data flow. For the purpose of defending against these perfect stealthy attacks, a novel scheme based on watermarks is developed. This scheme includes the injection of watermarks(applied to data prior to quantization) and the recovery of data(implemented before the data reaches the estimator).The watermark-based scheme is designed to be both timevarying and hidden from adversaries through incorporating a time-varying and bounded watermark signal. Subsequently, a watermark-based attack detection strategy is proposed which thoroughly considers the characteristics of perfect stealthy attacks,thereby ensuring that an alarm is activated upon the occurrence of such attacks. An example is provided to demonstrate the efficacy of the proposed mechanism for detecting attacks.展开更多
Despite compelling preclinical and epidemiological evidence(e.g.,reduced lung cancer incidence in the CANTOS trial),IL-1βinhibition with canakinumab failed to achieve the expected therapeutic effect in the Phase III ...Despite compelling preclinical and epidemiological evidence(e.g.,reduced lung cancer incidence in the CANTOS trial),IL-1βinhibition with canakinumab failed to achieve the expected therapeutic effect in the Phase III clinical trials(CANOPY series)of non-small cell lung cancer(NSCLC).This perspective analyzes the disconnect between mechanistic promise and clinical outcomes.IL-1βdrives NSCLC progression by promoting immunosuppression,angiogenesis,and metastasis.However,CANOPY-2 showed no overall survival(OS)benefit,though a trend emerged in patients with an elevated baseline of high-sensitivity C-reactive protein(hs-CRP).Similarly,CANOPY-1 and adjuvant CANOPY-A missed primary endpoints for progression-free survival(PFS)and disease-free survival(DFS),respectively.These failures highlight limitations of IL-1 monotherapy in advanced,immunosuppressive microenvironments and underscore inadequate patient selection.We propose that IL-1 antagonism retains therapeutic potential but requires refined strategies:biomarker-driven enrichment(e.g.,inflammation signatures like hs-CRP),rational combinatorial regimens informed by successful multi-target agents(e.g.,cadonilimab),and early-stage intervention.Repositioning IL-1 blockers through precision approaches could unlock their value in immuno-oncology.展开更多
AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth in...AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS： Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization （ISH） and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-（4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium （MTT） bromide colorimetric assay. Celecoxib- induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry （FCM）. The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS： Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 μmol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01±3.08%, 26.40±3.05%,and 30.60±2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt （Thr^308）. Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt （Thr^308） after treatment with celecoxib. CONCLUSION： COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.展开更多
Dendrobium plants are used commonly as tonic herbs and health food in many Asian countries, especially in China. Here we report the genetic map construction of two Dendrobium species with a double pseudo-testcross str...Dendrobium plants are used commonly as tonic herbs and health food in many Asian countries, especially in China. Here we report the genetic map construction of two Dendrobium species with a double pseudo-testcross strategy using random amplified polymorphic DNA （RAPD） and sequence-related amplified polymorphism （SRAP） markers. A F1 mapping population of 90 individuals was developed from a cross between D. officinale and D. hercoglossum. A total of 307 markers, including 209 RAPD and 98 SRAP, were identified and used for genetic linkage group （LG） analysis. The D. officinale linkage map consisted of 11 major linkage groups and 3 doublets, which covered 629.4 cM by a total of 62 markers with an average locus distance of 11.2 cM between two adjacent markers. The D. hercoglos- sum linkage map contained 112 markers mapped on 15 major and 4 minor linkage groups, spanning a total length of 1,304.6 cM with an average distance of I 1.6 cM between two adjacent markers. The maps constructed in this study covered 92.7% and 82.7% of the D. hercoglossum and D. officinale genomes respectively, providing an important basis for the mapping of horticultural and medicinal traits and for the application of marker-assisted selection in Dendrobium breeding program.展开更多
AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal ti...AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2<sup>-ΔCT</sup> was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25<sup>th</sup> 3, 75<sup>th</sup> 10 vs 2, 25<sup>th</sup> 1, 75<sup>th</sup> 5) (P < 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.展开更多
Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associ...Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.展开更多
Monoclinic gallium oxide(Ga_2O_3) has been grown on(0001) sapphire(Al_2O_3) substrate by plasma-assisted molecular beam epitaxy(PA-MBE). The epitaxial relationship has been confirmed to be [010]( 2ˉ01) β-Ga_2O_3||[ ...Monoclinic gallium oxide(Ga_2O_3) has been grown on(0001) sapphire(Al_2O_3) substrate by plasma-assisted molecular beam epitaxy(PA-MBE). The epitaxial relationship has been confirmed to be [010]( 2ˉ01) β-Ga_2O_3||[ 011ˉ0](0001)Al_2O_3 via in-situ reflection high energy electron diffraction(RHEED) monitoring and ex-situ X-ray diffraction(XRD) measurement. Crystalline quality is improved and surface becomes flatter with increasing growth temperature, with a best full width at half maximum(FWHM) of XRD ω-rocking curve of( 2ˉ01) plane and root mean square(RMS) roughness of 0.68° and 2.04 nm for the sample grown at 730 °C,respectively. Room temperature cathodoluminescence measurement shows an emission at ～417 nm, which is most likely originated from recombination of donor–acceptor pair(DAP).展开更多
基金National Natural Science Foundation of China(grant number 82272563 to B.S.)National Science and Technology Major Project of the Ministry of Science and Technology of China(grant number 2023ZD0501202 to B.S.)+4 种基金institutional grants allocated to the National Institute of Biological Sciences,Beijing(NIBS)from the Chinese Ministry of Science and Technology,Beijing Municipal Commission of Science and Technology,and Tsinghua Universitythe support from China Pharmaceutical University(grant number 3150140001 to S.F.)National Natural Science Foundation of China(grant numbers 82203653 to S.F.,82371957 to L.W.,and 82371956 to X.C.)Beijing Municipal Public Welfare Development and Reform Pilot Project for Medical Research Institutes(grant number JYY2023-8 to X.C.)Research Grants Council of University Grants Committee Hong Kong(grant numbers 14113723,14108720,14121721,14202920,N_CUHK472/22,C7030-18G,T13-402/17-N,and AoE/M-402/20)。
文摘Tissue clearing combined with high-resolution confocal imaging is a cutting-edge approach for dissecting the three-dimensional(3D)architecture of tissues and deciphering cellular spatial interactions under physiological and pathological conditions.Deciphering the spatial interaction of leptin receptor-expressing(LepR^(+))stromal cells with other compartments in the bone marrow is crucial for a deeper understanding of the stem cell niche and the skeletal tissue.In this study,we introduce an optimized protocol for the 3D analysis of skeletal tissues,enabling the visualization of hematopoietic and stromal cells,especially LepR+stromal cells,within optically cleared bone hemisections.Our method preserves the 3D tissue architecture and is extendable to other hematopoietic sites such as calvaria and vertebrae.The protocol entails tissue fixation,decalcification,and cryosectioning to reveal the marrow cavity.Completed within approximately 12 days,this process yields highly transparent tissues that maintain genetically encoded or antibody-stained fluorescent signals.The bone hemisections are compatible with diverse antibody labeling strategies.Confocal microscopy of these transparent samples allows for qualitative and quantitative image analysis using Aivia or Bitplane Imaris software,assessing a spectrum of parameters.With proper storage,the fluorescent signal in the stained and cleared bone hemisections remains intact for at least 2–3 months.This protocol is robust,straightforward to implement,and highly reproducible,offering a valuable tool for tissue architecture and cellular interaction studies.
文摘Clostridium difficile(C.difficile)infection(CDI)is the leading identifiable cause of antibiotic-associated diarrhea.While there is an alarming trend of increasing incidence and severity of CDI in the United States and Europe,superimposed CDI in patients with inflammatory bowel disease(IBD)has drawn considerable attention in the gastrointestinal community.The majority of IBD patients appear to contract CDI as outpatients.C.difficile affects disease course of IBD in several ways,including triggering disease flares,sustaining activity,and in some cases,acting as an"innocent"bystander.Despite its wide spectrum of presentations,CDI has been reported to be associated with a longer duration of hospitalization and a higher mortality in IBD patients.IBD patients with restorative proctocolectomy or with diverting ileostomy are not immune to CDI of the small bowel or ileal pouch.Whether immunomodulator or corticosteroid therapy for IBD should be continued in patients with superimposed CDI is controversial.It appears that more adverse outcomes was observed among patients treated by a combination of immunomodulators and antibiotics than those treated by antibiotics alone.The use of biologic agents does not appear to increase the risk of acquisition of CDI.For CDI in the setting of underlying IBD,vancomycin appears to be more efficacious than metronidazole.Randomized controlled trials are required to clearly define the appropriate management for CDI in patients with IBD.
文摘Inflammatory bowel diseases(IBD),conventionally consist of Crohn’s disease(CD)and ulcerative colitis.They occur in individuals with high risk genotype for the disease in the setting of appropriate environmental factors.The pathogenesis of IBD involves a dysregulated autoimmune response to gut dysbiosis,which in turn is triggered due to exposure to various inciting environmental factors.But there is no clearly defined etiology of IBD and this type of disease is termed as“idiopathic IBD”,“classic IBD”,or“primary IBD”.We reviewed the current medical literature and found that certain etiological factors may be responsible for the development of IBD or IBD-like conditions,and we consider this form of de novo IBD as“secondary IBD”.Currently known factors that are potentially responsible for giving rise to secondary IBD are medications;bowel altering surgeries and transplantation of organs,stem cells or fecal microbiome.Medications associated with the development of secondary IBD include;immunomodulators,anti-tumor necrosis factor alpha agents,anti-interleukin agents,interferons,immune stimulating agents and checkpoint inhibitors.Colectomy can in some cases give rise to de novo CD,pouchitis of the ileal pouch,or postcolectomy enteritis syndrome.After solid organ transplantation or hematopoietic stem cell transplantation,the recipient may develop de novo IBD or IBD flare.Fecal microbiota transplantation has been widely used to treat patients suffering from recurrent Clostridium difficile infection but can also causes IBD flares.
基金supported by the Academic Discipline,Post-Graduate Education Project of the Beijing Municipal Commission of Education,and Fundamental Research Funds for the Central Universities under Grant 2022YJS015the National Natural Science Foundation of China under Grant 62173026.
文摘Integrated satellite-terrestrial network(ISTN)has been considered a novel network architecture to achieve global three-dimensional coverage and ultra-wide area broadband access anytime and anywhere.Being a promising paradigm,cloud computing and mobile edge computing(MEC)have been identified as key technology enablers for ISTN to further improve quality of service and business continuity.However,most of the existing ISTN studies based on cloud computing and MEC regard satellite networks as relay networks,ignoring the feasibility of directly deploying cloud computing nodes and edge computing nodes on satellites.In addition,most computing tasks are transferred to cloud servers or offloaded to nearby edge servers,the layered design of integrated satellite-air-terrestrial architecture and the cloud-edge-device cooperative processing problems have not been fully considered.Therefore,different from previous works,this paper proposed a novel satellite-air-terrestrial layered architecture for cloud-edge-device collaboration,named SATCECN.Then this paper analyzes the appropriate deployment locations of cloud servers and edge servers in ISTN,and describes the processing flow of typical satellite computing tasks.For computing resource allocation problems,this paper proposed a device-edge-cloud Multi-node Cross-layer Collaboration Computing(MCCC)method to find the optimal task allo-cation strategy that minimizes the task completion delay and the weighted system energy consumption.Furthermore,the approximate optimal solutions of the optimization model are obtained by using successive convex approxi-mation algorithm,and the outstanding advantages of the proposed method in reducing system energy consumption and task execution delay are verified through experiments.Finally,some potential issues and directions for future research are highlighted.
基金Scientific and Technical Development Project of Jiangsu Province (No. BS2006005)
文摘Objective: To compare the efficacy and toxicity between gemcitabine plus cisplatin and plus carboplatin in first-line treatment of advanced non-small cell lung cancer (NSCLC). Methods: Gemcitabine 1000 mg/m2 iv, d1, 8; cisplatin 75 mg/m2 iv, d1, or 25 mg/m2 iv, d1-3; carboplatin AUC = 5 iv, d1; repeated every 21 days. Results: All 76 cases were available for objective response. Gemcitabine + cisplatin (GCis) group: among 33 cases, CR 1 case, PR 13 cases, MR 3 cases, SD 7 cases, PD 9 cases, response rate, disease control rate, time to progress (TTP), median survival time (MST) and 1-, 2-year survival rates were 42.42% (14/33), 72.73% (24/33), 5 months, 14 months and 66.67% (22/33), 12.12% (4/33), respectively; Gemcitabine + carboplatin (GCarb) group: among 43 cases, PR 13 cases, MR 11 cases, SD 7 cases, PD 12 cases, the results while comparing with those of GCis group were 30.23% (13/43), 72.09% (31/43), 4 months, 11 months and 48.84% (21/43), 2.33% (1/43), respectively. Among them, only MST between the two groups had significant statistic difference (χ2 = 2.45, P = 0.017). Mild to modest myelo-suppression as well as nausea and vomiting were observed. Conclusion: Both GCis and GCarb regimens had active and well-tolerated toxicity for advanced NSCLC. Cisplatin-based chemotherapy yields a substantial effective advantage over carboplatin-based regimens. Therefore, carboplatin and cisplatin are not equal-active and that cisplatin-based doublet regimens should remain the standard first-line therapy for patients with advanced NSCLC with good performance status.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82273162)Jiangsu Cancer Hospital Science and Technology Development Fund Project(Grant No.YSZD202409).
文摘Epidermal growth factor receptor(EGFR)mutations are among the most prevalent driver gene alterations in non-small cell lung cancer(NSCLC).Osimertinib,with or without chemotherapy,the first-line standard treatment for patients with advanced NSCLC bearing sensitive EGFR mutations,significantly prolongs the progression-free survival(PFS)to 25.5 months1.Despite great breakthroughs in survival data,patients inevitably experience disease progression.A large meta-analysis has indicated that,compared with chemother-apy,immuno-based therapies achieve longer PFS in patients with EGFR mutation who progressed on third-generation epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)2.Therefore,immunotherapies are often used after EGFR-TKI resistance is observed.
基金supported in part by the National Natural Science Foundation of China(61933007,62273087,62273088,U21A2019)the Shanghai Pujiang Program of China(22PJ1400400)+2 种基金the Hainan Province Science and Technology Special Fund of China(ZDYF2022SHFZ105)the Royal Society of U.K.the Alexander von Humboldt Foundation of Germany
文摘In this paper, the attack detection problem is investigated for a class of closed-loop systems subjected to unknownbutbounded noises in the presence of stealthy attacks. The measurement outputs from the sensors are quantized before transmission.A specific type of perfect stealthy attack, which meets certain rather stringent conditions, is taken into account. Such attacks could be injected by adversaries into both the sensor-toestimator and controller-to-actuator channels, with the aim of disrupting the normal data flow. For the purpose of defending against these perfect stealthy attacks, a novel scheme based on watermarks is developed. This scheme includes the injection of watermarks(applied to data prior to quantization) and the recovery of data(implemented before the data reaches the estimator).The watermark-based scheme is designed to be both timevarying and hidden from adversaries through incorporating a time-varying and bounded watermark signal. Subsequently, a watermark-based attack detection strategy is proposed which thoroughly considers the characteristics of perfect stealthy attacks,thereby ensuring that an alarm is activated upon the occurrence of such attacks. An example is provided to demonstrate the efficacy of the proposed mechanism for detecting attacks.
文摘Despite compelling preclinical and epidemiological evidence(e.g.,reduced lung cancer incidence in the CANTOS trial),IL-1βinhibition with canakinumab failed to achieve the expected therapeutic effect in the Phase III clinical trials(CANOPY series)of non-small cell lung cancer(NSCLC).This perspective analyzes the disconnect between mechanistic promise and clinical outcomes.IL-1βdrives NSCLC progression by promoting immunosuppression,angiogenesis,and metastasis.However,CANOPY-2 showed no overall survival(OS)benefit,though a trend emerged in patients with an elevated baseline of high-sensitivity C-reactive protein(hs-CRP).Similarly,CANOPY-1 and adjuvant CANOPY-A missed primary endpoints for progression-free survival(PFS)and disease-free survival(DFS),respectively.These failures highlight limitations of IL-1 monotherapy in advanced,immunosuppressive microenvironments and underscore inadequate patient selection.We propose that IL-1 antagonism retains therapeutic potential but requires refined strategies:biomarker-driven enrichment(e.g.,inflammation signatures like hs-CRP),rational combinatorial regimens informed by successful multi-target agents(e.g.,cadonilimab),and early-stage intervention.Repositioning IL-1 blockers through precision approaches could unlock their value in immuno-oncology.
基金Supported by Medical Science Research Foundation of Jiangsu Health Bureau Grant Z200314 (to JL)Medical Science Research Foundation of Nanjing Medical University Grant NY1999023 (to NBL) and CX2003012 (to JL)
文摘AIM： To investigate the cyclooxygenase-2 （COX-2） expression level in human HepG2, Bel-7402 and SMMC-7721 hepatoma cell lines and the molecular mechanism of COX-2 selective inhibitor celecoxib-induced cell growth inhibition and cell apoptosis. METHODS： Hepatoma cells were cultured and treated with celecoxib. Cell in situ hybridization （ISH） and immunocytochemistry were used to detect COX-2 mRNA and protein expression. Proliferating cell nuclear antigen and phosphorylated Akt were also detected by immunocytochemistry assay. Cell growth rates were assessed by 3-（4, 5-dimethylthiazol-2-yl-2, 5-diphenyltetrazolium （MTT） bromide colorimetric assay. Celecoxib- induced cell apoptosis was measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） and flow cytometry （FCM）. The phosphorylated Akt and activated fragments of caspase-9, caspase-3 were examined by Western blotting analysis. RESULTS： Increased COX-2 mRNA and protein expression were detected in all three hepatoma cell lines. Celecoxib could significantly inhibit cell growth and the inhibitory effect was in a dose- and time-dependent manner evidenced by MTT assays and morphological changes. The apoptotic index measured by TUNEL increased correspondingly with the increased concentration of celecoxib and the reaction time. With 50 μmol/L celecoxib treatment for 24 h, the apoptotic index of HepG2, BEL-7402 and SMMC-7721 cells was 25.01±3.08%, 26.40±3.05%,and 30.60±2.89%, respectively. Western blotting analysis showed remarkable activation of caspase-9, caspase-3 and dephosphorylation of Akt （Thr^308）. Immunocytochemistry also showed the reduction of PCNA expression and phosphorylation Akt （Thr^308） after treatment with celecoxib. CONCLUSION： COX-2 mRNA and protein overexpression in HepG2, Bel-7402 and SMMC-7721 cell lines correlate with the increased cell growth rate. Celecoxib can inhibit proliferation and induce apoptosis of hepatoma cell strains in a dose- and time-dependent manner.
基金funded in part by the National Natural Science Foundation (No.30670199,30870180 and 30770185)the Zhejiang Scientific and Technological Program (No.2008C12081)+1 种基金the Hangzhou Scientific and Technological Program (No.20080432T06)Qianjiang Scholar Program
文摘Dendrobium plants are used commonly as tonic herbs and health food in many Asian countries, especially in China. Here we report the genetic map construction of two Dendrobium species with a double pseudo-testcross strategy using random amplified polymorphic DNA （RAPD） and sequence-related amplified polymorphism （SRAP） markers. A F1 mapping population of 90 individuals was developed from a cross between D. officinale and D. hercoglossum. A total of 307 markers, including 209 RAPD and 98 SRAP, were identified and used for genetic linkage group （LG） analysis. The D. officinale linkage map consisted of 11 major linkage groups and 3 doublets, which covered 629.4 cM by a total of 62 markers with an average locus distance of 11.2 cM between two adjacent markers. The D. hercoglos- sum linkage map contained 112 markers mapped on 15 major and 4 minor linkage groups, spanning a total length of 1,304.6 cM with an average distance of I 1.6 cM between two adjacent markers. The maps constructed in this study covered 92.7% and 82.7% of the D. hercoglossum and D. officinale genomes respectively, providing an important basis for the mapping of horticultural and medicinal traits and for the application of marker-assisted selection in Dendrobium breeding program.
基金Supported by The National Clinical Key Institute Foundation of Chinese Health and Family Planning MinistryNo.2013-544
文摘AIM: To investigate Fusobacterium nucleatum (F. nucleatum) abundance in colorectal cancer (CRC) tissues and its association with CRC invasiveness in Chinese patients.METHODS: The resected cancer and adjacent normal tissues (10 cm beyond cancer margins) from 101 consecutive patients with CRC were collected. Fluorescent quantitative polymerase chain reaction (FQ-PCR) was applied to detect F. nucleatum in CRC and normal tissues. The difference of F. nucleatum abundance between cancer and normal tissues and the relationship of F. nucleatum abundance with clinical variables were evaluated. Fluorescence in situ hybridization (FISH) analysis was performed on 22 CRC tissues with the highest F. nucleatum abundance by FQ-PCR testing to confirm FQ-PCR results.RESULTS: The median abundance of F. nucleatum in CRC tissues [0.242 (0.178-0.276)] was significantly higher than that in normal controls [0.050 (0.023-0.067)] (P < 0.001). F. nucleatum was over-represented in 88/101 (87.1%) CRC samples. The abundance of F. nucleatum determined by 2<sup>-ΔCT</sup> was significantly greater in tumor samples [0.242 (0.178, 0.276)] than in normal controls [0.050 (0.023, 0.067)] (P < 0.001). The frequency of patients with lymph node metastases was higher in the over-abundance group [52/88 (59.1%)] than in the under-abundance group [0/13 (0%)] (P < 0.005). No significant association of F. nucleatum with other clinico-pathological variables was observed (P > 0.05). FISH analysis also found more F. nucleatum in CRC than in normal tissues (median number 6, 25<sup>th</sup> 3, 75<sup>th</sup> 10 vs 2, 25<sup>th</sup> 1, 75<sup>th</sup> 5) (P < 0.01).CONCLUSION: F. nucleatum was enriched in CRC tissues and associated with CRC development and metastasis.
基金supported by grants from the Demonstrative Research Platform of Clinical Evaluation Technology for New Anticancer Drugs(Grant Nos.18ZX09201-015 and 2017ZX09304015)the Innovation Fund for Medical Sciences of the Chinese Academy of Medical Sciences(Grant No.CIFMS,2016-I2M-1-001)。
文摘Chemotherapy-induced neutropenia(CIN)is a potentially fatal and common complication in myelosuppressive chemotherapy.The timing and grade of CIN may play prognostic and predictive roles in cancer therapy.CIN is associated with older age,poor functional and nutritional status,the presence of significant comorbidities,the type of cancer,previous chemotherapy cycles,the stage of the disease,specific chemotherapy regimens,and combined therapies.There are many key points and new challenges in the management of CIN in adults including:(1)Genetic risk factors to evaluate the patient’s risk for CIN remain unclear.However,these risk factors urgently need to be identified.(2)Febrile neutropenia(FN)remains one of the most common reasons for oncological emergency.No consensus nomogram for FN risk assessment has been established.(3)Different assessment tools[e.g.,Multinational Association for Supportive Care in Cancer(MASCC),the Clinical Index of Stable Febrile Neutropenia(CISNE)score model,and other tools]have been suggested to help stratify the risk of complications in patients with FN.However,current tools have limitations.The CISNE score model is useful to support decision-making,especially for patients with stable FN.(4)There are still some challenges,including the benefits of granulocyte colony stimulating factor treatment and the optimal antibiotic regimen in emergency management of FN.In view of the current reports,our group discusses the key points,new challenges,and management of CIN.
基金supported by the National Key R&D Program of China(No.2018YFB0406502)the National Natural Science Foundation of China(Nos.61734001,61521004)
文摘Monoclinic gallium oxide(Ga_2O_3) has been grown on(0001) sapphire(Al_2O_3) substrate by plasma-assisted molecular beam epitaxy(PA-MBE). The epitaxial relationship has been confirmed to be [010]( 2ˉ01) β-Ga_2O_3||[ 011ˉ0](0001)Al_2O_3 via in-situ reflection high energy electron diffraction(RHEED) monitoring and ex-situ X-ray diffraction(XRD) measurement. Crystalline quality is improved and surface becomes flatter with increasing growth temperature, with a best full width at half maximum(FWHM) of XRD ω-rocking curve of( 2ˉ01) plane and root mean square(RMS) roughness of 0.68° and 2.04 nm for the sample grown at 730 °C,respectively. Room temperature cathodoluminescence measurement shows an emission at ～417 nm, which is most likely originated from recombination of donor–acceptor pair(DAP).
