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
Small cell lung cancer(SCLC)constitutes approximately 15%of all lung cancer cases,characterized by rapid tumor growth,a high pro-liferation rate,and a propensity for early metastasis.1 Approximately one-third of SCLC ...Small cell lung cancer(SCLC)constitutes approximately 15%of all lung cancer cases,characterized by rapid tumor growth,a high pro-liferation rate,and a propensity for early metastasis.1 Approximately one-third of SCLC patients are diagnosed at the limited-stage.Histor-ically,the standard of care for these patients has been 4-6 cycles of concurrent chemoradiotherapy(cCRT),with the exception of a minor-ity of early-stage T1-2N0 patients who may undergo radical surgery.2 Despite an initial high sensitivity to treatment,over 50%of patients experience disease recurrence within two years,with a median overall survival(OS)ranging from 16 to 24 months.For the past three decades,while there have been novel explorations in radiotherapy dosing and fractionation,the treatment paradigm for limited-stage SCLC(LS-SCLC)has remained largely unchanged,with no significant improvement in patient survival outcomes.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
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
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
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
The development of semiconductors is always accompanied by the progress in controllable doping techniques.Taking AlGaN-based ultraviolet(UV)emitters as an example,despite a peak wall-plug efficiency of 15.3%at the wav...The development of semiconductors is always accompanied by the progress in controllable doping techniques.Taking AlGaN-based ultraviolet(UV)emitters as an example,despite a peak wall-plug efficiency of 15.3%at the wavelength of 275 nm,there is still a huge gap in comparison with GaN-based visible light-emitting diodes(LEDs),mainly attributed to the inefficient doping of AlGaN with increase of the Al composition.First,p-doping of Al-rich AlGaN is a long-standing challenge and the low hole concentration seriously restricts the carrier injection efficiency.Although p-GaN cladding layers are widely adopted as a compromise,the high injection barrier of holes as well as the inevitable loss of light extraction cannot be neglected.While in terms of n-doping the main issue is the degradation of the electrical property when the Al composition exceeds 80%,resulting in a low electrical efficiency in sub-250 nm UV-LEDs.This review summarizes the recent advances and outlines the major challenges in the efficient doping of Al-rich AlGaN,meanwhile the corresponding approaches pursued to overcome the doping issues are discussed in detail.展开更多
This paper investigates the anomaly-resistant decentralized state estimation(SE) problem for a class of wide-area power systems which are divided into several non-overlapping areas connected through transmission lines...This paper investigates the anomaly-resistant decentralized state estimation(SE) problem for a class of wide-area power systems which are divided into several non-overlapping areas connected through transmission lines. Two classes of measurements(i.e., local measurements and edge measurements) are obtained, respectively, from the individual area and the transmission lines. A decentralized state estimator, whose performance is resistant against measurement with anomalies, is designed based on the minimum error entropy with fiducial points(MEEF) criterion. Specifically, 1) An augmented model, which incorporates the local prediction and local measurement, is developed by resorting to the unscented transformation approach and the statistical linearization approach;2) Using the augmented model, an MEEF-based cost function is designed that reflects the local prediction errors of the state and the measurement;and 3) The local estimate is first obtained by minimizing the MEEF-based cost function through a fixed-point iteration and then updated by using the edge measuring information. Finally, simulation experiments with three scenarios are carried out on the IEEE 14-bus system to illustrate the validity of the proposed anomaly-resistant decentralized SE scheme.展开更多
This article mainly investigates the fuzzy optimization robust control issue for nonlinear networked systems characterized by the interval type-2(IT2)fuzzy technique under a differential evolution algorithm.To provide...This article mainly investigates the fuzzy optimization robust control issue for nonlinear networked systems characterized by the interval type-2(IT2)fuzzy technique under a differential evolution algorithm.To provide a more reasonable utilization of the constrained communication channel,a novel adaptive memory event-triggered(AMET)mechanism is developed,where two event-triggered thresholds can be dynamically adjusted in the light of the current system information and the transmitted historical data.Sufficient conditions with less conservative design of the fuzzy imperfect premise matching(IPM)controller are presented by introducing the Wirtinger-based integral inequality,the information of membership functions(MFs)and slack matrices.Subsequently,under the IPM policy,a new MFs intelligent optimization technique that takes advantage of the differential evolution algorithm is first provided for IT2 TakagiSugeno(T-S)fuzzy systems to update the fuzzy controller MFs in real-time and achieve a better system control effect.Finally,simulation results demonstrate that the proposed control scheme can obtain better system performance in the case of using fewer communication resources.展开更多
In this paper,the recursive filtering problem is considered for stochastic systems over filter-and-forward successive relay(FFSR)networks.An FFSR is located between the sensor and the remote filter to forward the meas...In this paper,the recursive filtering problem is considered for stochastic systems over filter-and-forward successive relay(FFSR)networks.An FFSR is located between the sensor and the remote filter to forward the measurement.In the successive relay,two cooperative relay nodes are adopted to forward the signals alternatively,thereby existing switching characteristics and inter-relay interferences(IRI).Since the filter-and-forward scheme is employed,the signal received by the relay is retransmitted after it passes through a linear filter.The objective of the paper is to concurrently design optimal recursive filters for FFSR and stochastic systems against switching characteristics and IRI of relays.First,a uniform measurement model is proposed by analyzing the transmission mechanism of FFSR.Then,novel filter structures with switching parameters are constructed for both FFSR and stochastic systems.With the help of the inductive method,filtering error covariances are presented in the form of coupled difference equations.Next,the desired filter gain matrices are further obtained by minimizing the trace of filtering error covariances.Moreover,the stability performance of the filtering algorithm is analyzed where the uniform bound is guaranteed on the filtering error covariance.Finally,the effectiveness of the proposed filtering method over FFSR is verified by a three-order resistance-inductance-capacitance circuit system.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
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.
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(grant number:QL201813).
文摘Small cell lung cancer(SCLC)constitutes approximately 15%of all lung cancer cases,characterized by rapid tumor growth,a high pro-liferation rate,and a propensity for early metastasis.1 Approximately one-third of SCLC patients are diagnosed at the limited-stage.Histor-ically,the standard of care for these patients has been 4-6 cycles of concurrent chemoradiotherapy(cCRT),with the exception of a minor-ity of early-stage T1-2N0 patients who may undergo radical surgery.2 Despite an initial high sensitivity to treatment,over 50%of patients experience disease recurrence within two years,with a median overall survival(OS)ranging from 16 to 24 months.For the past three decades,while there have been novel explorations in radiotherapy dosing and fractionation,the treatment paradigm for limited-stage SCLC(LS-SCLC)has remained largely unchanged,with no significant improvement in patient survival outcomes.
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.
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This work was supported by the National Key Research and Development Program of China(No.2022YFB3605100)the National Natural Science Foundation of China(Nos.62234001,61927806,61974002,62135013,and 62075081)+1 种基金the Key-Area Research and Development Program of Guangdong Province(No.2020B010172001)the Major Scientific and Technological Innovation Project(MSTIP)of Shandong Province(No.2019JZZY010209).
文摘The development of semiconductors is always accompanied by the progress in controllable doping techniques.Taking AlGaN-based ultraviolet(UV)emitters as an example,despite a peak wall-plug efficiency of 15.3%at the wavelength of 275 nm,there is still a huge gap in comparison with GaN-based visible light-emitting diodes(LEDs),mainly attributed to the inefficient doping of AlGaN with increase of the Al composition.First,p-doping of Al-rich AlGaN is a long-standing challenge and the low hole concentration seriously restricts the carrier injection efficiency.Although p-GaN cladding layers are widely adopted as a compromise,the high injection barrier of holes as well as the inevitable loss of light extraction cannot be neglected.While in terms of n-doping the main issue is the degradation of the electrical property when the Al composition exceeds 80%,resulting in a low electrical efficiency in sub-250 nm UV-LEDs.This review summarizes the recent advances and outlines the major challenges in the efficient doping of Al-rich AlGaN,meanwhile the corresponding approaches pursued to overcome the doping issues are discussed in detail.
基金supported in part by the National Natural Science Foundation of China(61933007, U21A2019, 62273005, 62273088, 62303301)the Program of Shanghai Academic/Technology Research Leader of China (20XD1420100)+2 种基金the Hainan Province Science and Technology Special Fund of China(ZDYF2022SHFZ105)the Natural Science Foundation of Anhui Province of China (2108085MA07)the Alexander von Humboldt Foundation of Germany。
文摘This paper investigates the anomaly-resistant decentralized state estimation(SE) problem for a class of wide-area power systems which are divided into several non-overlapping areas connected through transmission lines. Two classes of measurements(i.e., local measurements and edge measurements) are obtained, respectively, from the individual area and the transmission lines. A decentralized state estimator, whose performance is resistant against measurement with anomalies, is designed based on the minimum error entropy with fiducial points(MEEF) criterion. Specifically, 1) An augmented model, which incorporates the local prediction and local measurement, is developed by resorting to the unscented transformation approach and the statistical linearization approach;2) Using the augmented model, an MEEF-based cost function is designed that reflects the local prediction errors of the state and the measurement;and 3) The local estimate is first obtained by minimizing the MEEF-based cost function through a fixed-point iteration and then updated by using the edge measuring information. Finally, simulation experiments with three scenarios are carried out on the IEEE 14-bus system to illustrate the validity of the proposed anomaly-resistant decentralized SE scheme.
基金supported by the National Natural Science Foundation of China(61973105,62373137)。
文摘This article mainly investigates the fuzzy optimization robust control issue for nonlinear networked systems characterized by the interval type-2(IT2)fuzzy technique under a differential evolution algorithm.To provide a more reasonable utilization of the constrained communication channel,a novel adaptive memory event-triggered(AMET)mechanism is developed,where two event-triggered thresholds can be dynamically adjusted in the light of the current system information and the transmitted historical data.Sufficient conditions with less conservative design of the fuzzy imperfect premise matching(IPM)controller are presented by introducing the Wirtinger-based integral inequality,the information of membership functions(MFs)and slack matrices.Subsequently,under the IPM policy,a new MFs intelligent optimization technique that takes advantage of the differential evolution algorithm is first provided for IT2 TakagiSugeno(T-S)fuzzy systems to update the fuzzy controller MFs in real-time and achieve a better system control effect.Finally,simulation results demonstrate that the proposed control scheme can obtain better system performance in the case of using fewer communication resources.
基金supported in part by the National Natural Science Foundation of China(62103004,62273088,62273005,62003121)Anhui Provincial Natural Science Foundation of China(2108085QA13)+4 种基金the Natural Science Foundation of Zhejiang Province(LY24F030006)the Science and Technology Plan of Wuhu City(2022jc24)Anhui Polytechnic University Youth Top-Notch Talent Support Program(2018BJRC009)Anhui Polytechnic University High-End Equipment Intelligent Control Innovation Team(2021CXTD005)Anhui Future Technology Research Institute Foundation(2023qyhz08,2023qyhz09)。
文摘In this paper,the recursive filtering problem is considered for stochastic systems over filter-and-forward successive relay(FFSR)networks.An FFSR is located between the sensor and the remote filter to forward the measurement.In the successive relay,two cooperative relay nodes are adopted to forward the signals alternatively,thereby existing switching characteristics and inter-relay interferences(IRI).Since the filter-and-forward scheme is employed,the signal received by the relay is retransmitted after it passes through a linear filter.The objective of the paper is to concurrently design optimal recursive filters for FFSR and stochastic systems against switching characteristics and IRI of relays.First,a uniform measurement model is proposed by analyzing the transmission mechanism of FFSR.Then,novel filter structures with switching parameters are constructed for both FFSR and stochastic systems.With the help of the inductive method,filtering error covariances are presented in the form of coupled difference equations.Next,the desired filter gain matrices are further obtained by minimizing the trace of filtering error covariances.Moreover,the stability performance of the filtering algorithm is analyzed where the uniform bound is guaranteed on the filtering error covariance.Finally,the effectiveness of the proposed filtering method over FFSR is verified by a three-order resistance-inductance-capacitance circuit system.
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.
