We study a novel replication mechanism to ensure service continuity against multiple simultaneous server failures.In this mechanism,each item represents a computing task and is replicated intoξ+1 servers for some int...We study a novel replication mechanism to ensure service continuity against multiple simultaneous server failures.In this mechanism,each item represents a computing task and is replicated intoξ+1 servers for some integerξ≥1,with workloads specified by the amount of required resources.If one or more servers fail,the affected workloads can be redirected to other servers that host replicas associated with the same item,such that the service is not interrupted by the failure of up toξservers.This requires that any feasible assignment algorithm must reserve some capacity in each server to accommodate the workload redirected from potential failed servers without overloading,and determining the optimal method for reserving capacity becomes a key issue.Unlike existing algorithms that assume that no two servers share replicas of more than one item,we first formulate capacity reservation for a general arbitrary scenario.Due to the combinatorial nature of this problem,finding the optimal solution is difficult.To this end,we propose a Generalized and Simple Calculating Reserved Capacity(GSCRC)algorithm,with a time complexity only related to the number of items packed in the server.In conjunction with GSCRC,we propose a robust replica packing algorithm with capacity optimization(RobustPack),which aims to minimize the number of servers hosting replicas and tolerate multiple server failures.Through theoretical analysis and experimental evaluations,we show that the RobustPack algorithm can achieve better performance.展开更多
Ultrasonic neuromodulation has gained recognition as a promising therapeutic approach.A miniature transducer capable of generating suitable-strength and broadband ultrasound is of great significance for achieving high...Ultrasonic neuromodulation has gained recognition as a promising therapeutic approach.A miniature transducer capable of generating suitable-strength and broadband ultrasound is of great significance for achieving high spatial precision ultrasonic neural stimulation.However,the ultrasound transducer with the above integrated is yet to be challenged.Here,we developed a fiber-optic photoacoustic emitter(FPE)with a diameter of 200μm,featuring controllable sound intensity and a broadband response(−6 dB bandwidth:162%).The device integrates MXene(Ti_(3)C_(2)Tx),known for its exceptional photothermal properties,and polydimethylsiloxane,which offers a high thermal expansion coefficient.This FPE,exhibiting high spatial precision(lateral:163.3μm,axial:207μm),is capable of selectively activating neurons in targeted regions.Using the TetTagging method to selectively express a cfos-promoter-inducible mCHERRY gene within the medial prefrontal cortex(mPFC),we found that photoacoustic stimulation significantly and temporarily activated the neurons.In vivo fiber photometry demonstrated that photoacoustic stimulation induced substantial calcium transients in mPFC neurons.Furthermore,we confirmed that photoacoustic stimulation of the mPFC using FPE markedly alleviates acute social defeat stress-induced emotional stress in mice.This work demonstrates the potential of FPEs for clinical applications,with a particular focus on modulating neural activity to regulate emotions.展开更多
Objective:Distinguishing immune-related adverse events(irAEs)caused by immune checkpoint inhibitors(ICIs)from the AEs caused by chemotherapy,targeted therapy,or infection is highly difficult.This study offers new insi...Objective:Distinguishing immune-related adverse events(irAEs)caused by immune checkpoint inhibitors(ICIs)from the AEs caused by chemotherapy,targeted therapy,or infection is highly difficult.This study offers new insights into evaluating the diagnosis,differential diagnostic,and prognostic value of ferritin for irAEs induced by ICIs.Methods:From December 1,2018,to April 1,2019,we examined 318 patients with malignant tumors who received serum ferritin monitoring.The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy,and 87 patients treated with chemotherapy.Of the 231 patients,90 had irAEs(irAE group),70 had non-irAEs(non-irAE group),67 had no AEs(no irAE-non irAE group),and 4 had unclassified AEs.In the 87 patients,60 had AEs(AE group),and 27 had no AEs(no AE group).Statistical analyses were conducted with nonparametric Mann-Whitney tests.Results:At the onset of AEs in the irAE group,ferritin(normal range,35–150μg/L)rose to a median of 927μg/L(range,117–17,825μg/L)from 86μg/L at baseline(range,29–421μg/L)(P<0.001).Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group(median,81μg/L;range,32–478μg/L)(P<0.001)and the AE group(median,103μg/L;range,23–712μg/L)(P<0.001).After treatment in the irAE group,ferritin continuously decreased to a normal range in recovered patients,showed no significant changes in stable patients,and continued to rise in patients who died.Conclusions:Ferritin can be used as a diagnostic,differential diagnostic,and prognostic marker for irAEs in patients treated with ICIs.展开更多
目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgt...目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgtC转录的影响。最后,通过评估细菌生长曲线和关键代谢基因的转录水平研究药物对细菌生长的影响。结果:所有27个候选中药成分均显示出与MgtC结合的潜力。阿魏酸、对羟基肉桂酸、牛蒡子苷和掌叶防己碱使mgtC的转录活性降低了15%以上。这四个成分对mgtC转录的最低抑制浓度分别为:阿魏酸16μM;对羟基肉桂酸40μM;牛蒡子苷80μM;掌叶防己碱160μM。此外,我们证实这四种成分均未抑制细菌生长。结论:在本研究中,我们建立了一种基于β-半乳糖苷酶测定法的鼠伤寒沙门氏菌毒力抑制剂筛选方法。以SPI-3为靶标,筛选了27种中药成分,发现有4种对鼠伤寒沙门氏菌毒力具有潜在的强效抑制作用。这为未来从草药中开发新型抗生素提供了先导化合物。这种方法也可用于筛选其他致病菌的毒力抑制剂。展开更多
In order to improve electrokinetic remediation efficiency of cadmium-contaminated soil,the effects of electric field intensity,remediation time and electrolyte on removal rate of total Cd in Cd-contaminated soil by el...In order to improve electrokinetic remediation efficiency of cadmium-contaminated soil,the effects of electric field intensity,remediation time and electrolyte on removal rate of total Cd in Cd-contaminated soil by electrokinetic remediation were studied through the preparation of Cd-contaminated soil and the construction of electrokinetic remediation equipment. The results showed that under the same condition,with the electric field intensity increasing from 2. 5 to 3 V/cm,the total Cd removal rate increased by 10. 62%,and with the increase of the electric field intensity from 3 to 3. 5 V/cm,the removal rate increased by 1. 87%;when the remediation time was prolonged from 72 to 96 h,the removal rate of total Cd increased by 6. 68%,and with the remediation time prolonged from 96 to120 h,the removal rate of total Cd increased by 8. 75%; and with the remediation time prolonged from 120 to 144 h,the removal rate of total Cd only increased by1. 07%. Compared with citric acid as the electrolyte,the acetic acid group improved the remediation efficiency by 12. 14% and the total energy consumption by62. 13%,while the hydrochloric acid group improved the remediation efficiency by 18. 04% and the total energy consumption by 187. 9%. Comprehensively from total Cd removal rate and energy consumption,the remediation effect was the best under the electric field intensity of 3 V/cm and the electrokinetic time of 120 h with acetic acid as the electrolyte,which achieved a total Cd removal rate of 41. 95%.展开更多
The Localized Weighted Ensemble Kalman Filter(LWEnKF)is a new nonlinear/non-Gaussian data assimilation(DA)method that can effectively alleviate the filter degradation problem faced by particle filtering,and it has gre...The Localized Weighted Ensemble Kalman Filter(LWEnKF)is a new nonlinear/non-Gaussian data assimilation(DA)method that can effectively alleviate the filter degradation problem faced by particle filtering,and it has great prospects for applications in geophysical models.In terms of operational applications,along-track sea surface height(AT-SSH),swath sea surface temperature(S-SST)and in-situ temperature and salinity(T/S)profiles are assimilated using the LWEnKF in the northern South China Sea(SCS).To adapt to the vertical S-coordinates of the Regional Ocean Modelling System(ROMS),a vertical localization radius function is designed for T/S profiles assimilation using the LWEnKF.The results show that the LWEnKF outperforms the local particle filter(LPF)due to the introduction of the Ensemble Kalman Filter(EnKF)as a proposal density;the RMSEs of SSH and SST from the LWEnKF are comparable to the EnKF,but the RMSEs of T/S profiles reduce significantly by approximately 55%for the T profile and 35%for the S profile(relative to the EnKF).As a result,the LWEnKF makes more reasonable predictions of the internal ocean temperature field.In addition,the three-dimensional structures of nonlinear mesoscale eddies are better characterized when using the LWEnKF.展开更多
In contrast with orthogonal multiple access(OMA)technologies,non-orthogonal multiple access(NOMA)technology can achieve higher spectral effi-ciency and support more users simultaneously.Multiple relays can be deployed...In contrast with orthogonal multiple access(OMA)technologies,non-orthogonal multiple access(NOMA)technology can achieve higher spectral effi-ciency and support more users simultaneously.Multiple relays can be deployed in NOMA networks,in order to combat fading and thus increase the transmission reliability.In the existing works on cooperative NOMA networks with multiple relays,the decoding error at the relays and the imperfect successive interference cancellation(SIC)are not taken into account simultaneously.In this work,we consider the bit error rate(BER)analysis of relay-aided NOMA networks,where max-min relay selection is employed.Particularly,closed-form BER expressions are derived for NOMA networks with Rayleigh fading,in the existence of the relay decoding error and imperfect SIC.The asymptotic BER performance is then obtained to provide some useful insights into the system design such as the diversity order.Finally,simulation results illustrate the correctness of the derived expressions.The presented results reveal the effects of imperfect SIC and relay decoding error on the performance of cooperative NOMA networks.展开更多
BACKGROUND Extracorporeal membrane oxygenation(ECMO)is a new type of extracorporeal respiratory and circulatory assistance device.It can drain venous blood out of the body and inject it into veins or arteries after be...BACKGROUND Extracorporeal membrane oxygenation(ECMO)is a new type of extracorporeal respiratory and circulatory assistance device.It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator(membrane lung)to replace lung and heart functions in a short time.ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function.CASE SUMMARY We report a case of an 81-year-old woman who underwent whole cerebral angiography,basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO.The patient was admitted to the hospital due to myocardial infarction.Considering that the cause of the patient’s disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO,the department of Radioactive Intervention performed cerebral angiography.And the result of the angiography indicated vascular occlusion.After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain,the patency of the occlusive vessel was achieved.CONCLUSION Although the patient eventually died of circulatory failure,the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.展开更多
In order to improve the catalytic ozonation effect of resorcinol, the spinel CuFe_2O_4 was modified by doped CeO_2, and X-ray diffraction(XRD) and scanning electron microscopy(SEM) were used for characterization analy...In order to improve the catalytic ozonation effect of resorcinol, the spinel CuFe_2O_4 was modified by doped CeO_2, and X-ray diffraction(XRD) and scanning electron microscopy(SEM) were used for characterization analysis. The effects of composite catalyst CeO_2/CuFe_2O_4 dosage, ozone dosage, initial pH and reaction temperature on degradation were studied, and the stability of the catalyst was tested. The results showed that the composite effect of CeO_2/CuFe_2O_4 prepared by combustion method was good, and the catalyst presented a laminated structure, in which 30 wt% CeO_2/CuFe_2O_4 degradation effect was significant. The removal rate of resorcinol using CeO_2/CuFe_2O_4 composite catalyst was higher than that using ozone or CuFe_2O_4 separately by 41.8% and 11.9%, respectively. In a reaction with resorcinol concentration of 100 mg/L, the catalyst dosage of 1.0 g/L, the ozone dosage of 2.5 mg/(L·min), at pH=9, temperature of 20 ℃, for reaction time of 40 min, the resorcinol removal rate was 88.5%. The catalyst CeO_2/CuFe_2O_4 still showed good degradation effect after repeatedly using for 10 times, and the dissolution rate of metal ions was lower than that of CuFe_2O_4.展开更多
Some heart diseases need long-term monitoring to diagnose. In this paper, we present a wearable single lead ECG monitoring device with low power consumption based on MSP430 and single-lead ECG front-end AD8232, which ...Some heart diseases need long-term monitoring to diagnose. In this paper, we present a wearable single lead ECG monitoring device with low power consumption based on MSP430 and single-lead ECG front-end AD8232, which could acquire and store patient’s ECG data for 7 days continuously. This device is available for long-term wearing with a small volume. Also, it could detect user’s motion status with an acceleration sensor and supports Bluetooth 4.0 protocol. So it could be expanded to be a dynamic heart rate monitor and/or sleep quality monitor combined with smart phone. The device has huge potential of application for health care of human daily life.展开更多
With global warming,heat stress is becoming a more frequent event and a major limiting factor for crop production.The evaluation of thermo-tolerance is essential for the cultivators to obtain the heat resistant genoty...With global warming,heat stress is becoming a more frequent event and a major limiting factor for crop production.The evaluation of thermo-tolerance is essential for the cultivators to obtain the heat resistant genotypes and breeders to improve the thermo-tolerance of plants.Therefore,it is very important to perfect the existing evaluation system for thermo-tolerance.In this study,30 tomato genotypes were treated with heat stress at germination,seedling and flowering stages.Each index was different and diverse in different tomato genotypes by doing variability analysis,difference analysis and Student's t test.Before principal component analysis(PCA),a positive treatment for the negative and moderation indexes was performed.After correlation analysis,the authors performed PCA(including dimensionality reduction(DR),no dimensionality reduction(NDR)and optimal index(OI)),combining with subordinate function(SF),weight and cluster analysis.No matter at germination or seedling stage,the members of the groups were basically identical for DR,NDR and OI.Then 10 tomato genotypes were chosen from 30 randomly for verification.Compared all the evaluation systems,OI was the simplest and also could get as credible results as other methods.Therefore,in this study,OI could be adopted and improve the efficiency during the evaluation.At germination stage,germination power(GP)can accurately evaluate the thermo-tolerance,and at seedling stage,it was fresh weight(FW),internode length(IL)and dry matter percentage of seedling(DMP).Finally,all the indexes in the three stages were applied correlation analysis.Seedling stage showed significant positive correlation with flowering stage.In conclusion,this work improves the current system and set up a new comprehensive evaluation method named OI,which also improves the efficiency,guarantees reliability in screening thermo-tolerance of tomato for cultivators and expedites the process of breeding for resistance.展开更多
Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma,accompanied by dynamic changes in the tumor microenvironment(TME).A randomized controlled trial has confirmed the efficacy and safety of She...Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma,accompanied by dynamic changes in the tumor microenvironment(TME).A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction(SBJDD)in preventing colorectal tumorigenesis.However,the mechanism remains unclear.In this study,we employed single-cell RNA sequencing(scRNA-seq)to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry.Bulk RNA sequencing was utilized to assess the underlying mechanisms.Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc^(Min/+)mice and clinical patients.There was a marked accumulation of CCL22^(+)dendritic cells(DCs)and an enhanced immunosuppressive action,which SBJDD and berberine reversed.Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22^(+)DCs,which may represent“exhausted DCs”.Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects.TMEM131 derived CCL22+DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis.These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer(CRC),suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.展开更多
BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous th...BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous thromboembolism,and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.AIM To explore whether ulinastatin(UTI)can prevent VTE after brain tumor resection.METHODS The present research included patients who underwent brain tumor resection.Patients received UTIs(400,000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were the incidence of VTE,coagulation function,pulmonary emboli,liver function,renal function,and drug-related adverse effects.RESULTS A total of 405 patients were evaluated between January 2019 and December 2021,and 361 of these were initially enrolled in the study to form intention-to-treat,which was given UTI(n=180)or placebo(n=181)treatment in a random manner.There were no statistically significant differences in baseline clinical data between the two groups.The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group.UTI can improve coagulation dysfunction,pulmonary emboli,liver function,and renal function.No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea,vomiting,hospital stays,or hospitalization costs.The incidence of allergies was higher in the UTI group than in the placebo group.CONCLUSION The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.展开更多
Objective:The combination of epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)and immune checkpoint inhibitors(ICIs)leads to an increased incidence of severe immune-related adverse events(irAEs)....Objective:The combination of epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)and immune checkpoint inhibitors(ICIs)leads to an increased incidence of severe immune-related adverse events(irAEs).However,the mechanisms underlying macrophages in irAEs have not been elucidated.Methods:An osimertinib and ICI-induced irAE mouse model was constructed.Lung micro-CT scans were used to assess the degree of inflammatory infiltration.Hematoxylin-eosin staining was used to analyze the histopathologic inflammatory infiltration in mouse liver and lung tissues.Flow cytometry was used to detect the percentages of T cells,NK cells,and macrophages and the expression of EGFR.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum interleukin(IL)-6,alanine transaminase(ALT),ferritin,and tumor necrosis factor(TNF)-αlevels.Total RNA extracted from mouse liver macrophages was analyzed by RNA-seq.Simple Western blot analysis was used to detect the IL-6/JAK/STAT3 pathway activation state.Results:Osimertinib combined with ICIs upregulated EGFR expression on macrophages with increased serum IL-6,ALT,and ferritin levels.RNA-seq and simple Western blot analysis of mouse liver macrophages confirmed that that the IL-6/JAK/STAT3 pathway was activated in the combination treatment group.Ruxolitinib blocked the IL-6/JAK/STAT3 pathway and significantly decreased the serum IL-6,ALT,and ferritin levels in the combination treatment group.Conclusions:An osimertinib and ICI-induced irAE mouse model was constructed that showed osimertinib combined with ICIs inhibited EGFR phosphorylation and activated the IL-6/JAK/STAT3 signaling pathway in mouse liver macrophages,which led to the release of relevant cytokines.展开更多
With the development of network technology and cloud computing, data sharing is becoming increasingly popular, and many scholars have conducted in-depth research to promote its flourish. As the scale of data sharing e...With the development of network technology and cloud computing, data sharing is becoming increasingly popular, and many scholars have conducted in-depth research to promote its flourish. As the scale of data sharing expands, its privacy protection has become a hot issue in research. Moreover, in data sharing, the data is usually maintained in multiple parties, which brings new challenges to protect the privacy of these multi-party data. In this paper, we propose a trusted data sharing scheme using blockchain. We use blockchain to prevent the shared data from being tampered, and use the Paillier cryptosystem to realize the confidentiality of the shared data. In the proposed scheme, the shared data can be traded, and the transaction information is protected by using the （p, t）-threshold Paillier cryptosystem. We conduct experiments in cloud storage scenarios and the experimental results demonstrate the efficiency and effectiveness of the proposed scheme.展开更多
基金supported in part by the National Key R&D Program of China under No.2023YFB2703800the National Science Foundation of China under Grants U22B2027,62172297,62102262,61902276 and 62272311+3 种基金Tianjin Intelligent Manufacturing Special Fund Project under Grants 20211097the China Guangxi Science and Technology Plan Project(Guangxi Science and Technology Base and Talent Special Project)under Grant AD23026096(Application Number 2022AC20001)Henan Provincial Natural Science Foundation of China under Grant 622RC616CCF-Nsfocus Kunpeng Fund Project under Grants CCF-NSFOCUS202207。
文摘We study a novel replication mechanism to ensure service continuity against multiple simultaneous server failures.In this mechanism,each item represents a computing task and is replicated intoξ+1 servers for some integerξ≥1,with workloads specified by the amount of required resources.If one or more servers fail,the affected workloads can be redirected to other servers that host replicas associated with the same item,such that the service is not interrupted by the failure of up toξservers.This requires that any feasible assignment algorithm must reserve some capacity in each server to accommodate the workload redirected from potential failed servers without overloading,and determining the optimal method for reserving capacity becomes a key issue.Unlike existing algorithms that assume that no two servers share replicas of more than one item,we first formulate capacity reservation for a general arbitrary scenario.Due to the combinatorial nature of this problem,finding the optimal solution is difficult.To this end,we propose a Generalized and Simple Calculating Reserved Capacity(GSCRC)algorithm,with a time complexity only related to the number of items packed in the server.In conjunction with GSCRC,we propose a robust replica packing algorithm with capacity optimization(RobustPack),which aims to minimize the number of servers hosting replicas and tolerate multiple server failures.Through theoretical analysis and experimental evaluations,we show that the RobustPack algorithm can achieve better performance.
基金supported by the National Nature Science Foundation of China(Grant Number:U24A20306,12102140,6227031087,62035006,and 6207030117).
文摘Ultrasonic neuromodulation has gained recognition as a promising therapeutic approach.A miniature transducer capable of generating suitable-strength and broadband ultrasound is of great significance for achieving high spatial precision ultrasonic neural stimulation.However,the ultrasound transducer with the above integrated is yet to be challenged.Here,we developed a fiber-optic photoacoustic emitter(FPE)with a diameter of 200μm,featuring controllable sound intensity and a broadband response(−6 dB bandwidth:162%).The device integrates MXene(Ti_(3)C_(2)Tx),known for its exceptional photothermal properties,and polydimethylsiloxane,which offers a high thermal expansion coefficient.This FPE,exhibiting high spatial precision(lateral:163.3μm,axial:207μm),is capable of selectively activating neurons in targeted regions.Using the TetTagging method to selectively express a cfos-promoter-inducible mCHERRY gene within the medial prefrontal cortex(mPFC),we found that photoacoustic stimulation significantly and temporarily activated the neurons.In vivo fiber photometry demonstrated that photoacoustic stimulation induced substantial calcium transients in mPFC neurons.Furthermore,we confirmed that photoacoustic stimulation of the mPFC using FPE markedly alleviates acute social defeat stress-induced emotional stress in mice.This work demonstrates the potential of FPEs for clinical applications,with a particular focus on modulating neural activity to regulate emotions.
基金This work was supported by grants from the National Key R&D Program of China(Grant No.2018YFC1313400)the National Major Scientific and Technological Special Project for“Significant New Drug Development”of China(Grant No.2018ZX09201-015)the National Natural Science Foundation of China(Grants Nos.81872487,81872166,U20A20375,and 81974416).
文摘Objective:Distinguishing immune-related adverse events(irAEs)caused by immune checkpoint inhibitors(ICIs)from the AEs caused by chemotherapy,targeted therapy,or infection is highly difficult.This study offers new insights into evaluating the diagnosis,differential diagnostic,and prognostic value of ferritin for irAEs induced by ICIs.Methods:From December 1,2018,to April 1,2019,we examined 318 patients with malignant tumors who received serum ferritin monitoring.The cohort comprised 231 patients treated with PD-1 inhibitor or combination with chemotherapy,and 87 patients treated with chemotherapy.Of the 231 patients,90 had irAEs(irAE group),70 had non-irAEs(non-irAE group),67 had no AEs(no irAE-non irAE group),and 4 had unclassified AEs.In the 87 patients,60 had AEs(AE group),and 27 had no AEs(no AE group).Statistical analyses were conducted with nonparametric Mann-Whitney tests.Results:At the onset of AEs in the irAE group,ferritin(normal range,35–150μg/L)rose to a median of 927μg/L(range,117–17,825μg/L)from 86μg/L at baseline(range,29–421μg/L)(P<0.001).Ferritin levels at the onset of AEs in the irAE group were significantly higher than those in the non-irAE group(median,81μg/L;range,32–478μg/L)(P<0.001)and the AE group(median,103μg/L;range,23–712μg/L)(P<0.001).After treatment in the irAE group,ferritin continuously decreased to a normal range in recovered patients,showed no significant changes in stable patients,and continued to rise in patients who died.Conclusions:Ferritin can be used as a diagnostic,differential diagnostic,and prognostic marker for irAEs in patients treated with ICIs.
基金supported by the National Natural Science Foundation of China(82072247 and 82374154)National Key Research and Development Project of China(2022YFC3502300)+2 种基金Natural Science Foundation of Beijing Municipality(L222150)Tianjin Chasesun Pharmaceutical(BUCM-2022-JS-FW-076)Zhuhai Yourun Co.,Ltd.(BUCM-2023-JS-KF-018)
文摘目的:筛选中药活性成分作为鼠伤寒沙门氏菌致病性岛III(Salmonella pathogenicity island III,SPI-3)潜在毒力抑制剂。方法:通过分子对接技术明确中药成分与SPI-3中的MgtC蛋白的潜在结合关系。使用β-半乳糖苷酶测定法评估中药成分对mgtC转录的影响。最后,通过评估细菌生长曲线和关键代谢基因的转录水平研究药物对细菌生长的影响。结果:所有27个候选中药成分均显示出与MgtC结合的潜力。阿魏酸、对羟基肉桂酸、牛蒡子苷和掌叶防己碱使mgtC的转录活性降低了15%以上。这四个成分对mgtC转录的最低抑制浓度分别为:阿魏酸16μM;对羟基肉桂酸40μM;牛蒡子苷80μM;掌叶防己碱160μM。此外,我们证实这四种成分均未抑制细菌生长。结论:在本研究中,我们建立了一种基于β-半乳糖苷酶测定法的鼠伤寒沙门氏菌毒力抑制剂筛选方法。以SPI-3为靶标,筛选了27种中药成分,发现有4种对鼠伤寒沙门氏菌毒力具有潜在的强效抑制作用。这为未来从草药中开发新型抗生素提供了先导化合物。这种方法也可用于筛选其他致病菌的毒力抑制剂。
基金Supported by National Science Foundation of China(41641032)
文摘In order to improve electrokinetic remediation efficiency of cadmium-contaminated soil,the effects of electric field intensity,remediation time and electrolyte on removal rate of total Cd in Cd-contaminated soil by electrokinetic remediation were studied through the preparation of Cd-contaminated soil and the construction of electrokinetic remediation equipment. The results showed that under the same condition,with the electric field intensity increasing from 2. 5 to 3 V/cm,the total Cd removal rate increased by 10. 62%,and with the increase of the electric field intensity from 3 to 3. 5 V/cm,the removal rate increased by 1. 87%;when the remediation time was prolonged from 72 to 96 h,the removal rate of total Cd increased by 6. 68%,and with the remediation time prolonged from 96 to120 h,the removal rate of total Cd increased by 8. 75%; and with the remediation time prolonged from 120 to 144 h,the removal rate of total Cd only increased by1. 07%. Compared with citric acid as the electrolyte,the acetic acid group improved the remediation efficiency by 12. 14% and the total energy consumption by62. 13%,while the hydrochloric acid group improved the remediation efficiency by 18. 04% and the total energy consumption by 187. 9%. Comprehensively from total Cd removal rate and energy consumption,the remediation effect was the best under the electric field intensity of 3 V/cm and the electrokinetic time of 120 h with acetic acid as the electrolyte,which achieved a total Cd removal rate of 41. 95%.
基金The National Key Research and Development Program of China under contract No.2018YFC1406202the National Natural Science Foundation of China under contract No.41830964.
文摘The Localized Weighted Ensemble Kalman Filter(LWEnKF)is a new nonlinear/non-Gaussian data assimilation(DA)method that can effectively alleviate the filter degradation problem faced by particle filtering,and it has great prospects for applications in geophysical models.In terms of operational applications,along-track sea surface height(AT-SSH),swath sea surface temperature(S-SST)and in-situ temperature and salinity(T/S)profiles are assimilated using the LWEnKF in the northern South China Sea(SCS).To adapt to the vertical S-coordinates of the Regional Ocean Modelling System(ROMS),a vertical localization radius function is designed for T/S profiles assimilation using the LWEnKF.The results show that the LWEnKF outperforms the local particle filter(LPF)due to the introduction of the Ensemble Kalman Filter(EnKF)as a proposal density;the RMSEs of SSH and SST from the LWEnKF are comparable to the EnKF,but the RMSEs of T/S profiles reduce significantly by approximately 55%for the T profile and 35%for the S profile(relative to the EnKF).As a result,the LWEnKF makes more reasonable predictions of the internal ocean temperature field.In addition,the three-dimensional structures of nonlinear mesoscale eddies are better characterized when using the LWEnKF.
基金This work was supported by the National Natural Science Foundation of China under Grants 61971360 and 61871139.
文摘In contrast with orthogonal multiple access(OMA)technologies,non-orthogonal multiple access(NOMA)technology can achieve higher spectral effi-ciency and support more users simultaneously.Multiple relays can be deployed in NOMA networks,in order to combat fading and thus increase the transmission reliability.In the existing works on cooperative NOMA networks with multiple relays,the decoding error at the relays and the imperfect successive interference cancellation(SIC)are not taken into account simultaneously.In this work,we consider the bit error rate(BER)analysis of relay-aided NOMA networks,where max-min relay selection is employed.Particularly,closed-form BER expressions are derived for NOMA networks with Rayleigh fading,in the existence of the relay decoding error and imperfect SIC.The asymptotic BER performance is then obtained to provide some useful insights into the system design such as the diversity order.Finally,simulation results illustrate the correctness of the derived expressions.The presented results reveal the effects of imperfect SIC and relay decoding error on the performance of cooperative NOMA networks.
基金Supported by Joint Projects of the Medical Science and Technology Research Program of Henan Province,No.LHGJ20210255.
文摘BACKGROUND Extracorporeal membrane oxygenation(ECMO)is a new type of extracorporeal respiratory and circulatory assistance device.It can drain venous blood out of the body and inject it into veins or arteries after being oxygenated by an oxygenator(membrane lung)to replace lung and heart functions in a short time.ECMO can provide tissue blood perfusion and gas exchange almost equivalent to cardiac output and extend the effective treatment time window for patients with acute circulatory failure to restore cardiopulmonary function.CASE SUMMARY We report a case of an 81-year-old woman who underwent whole cerebral angiography,basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain after implantation of ECMO.The patient was admitted to the hospital due to myocardial infarction.Considering that the cause of the patient’s disturbance of consciousness was unknown and cerebrovascular accident could not be ruled out after the implantation of ECMO,the department of Radioactive Intervention performed cerebral angiography.And the result of the angiography indicated vascular occlusion.After the basilar artery thrombectomy and stent thrombectomy in the posterior artery of the left brain,the patency of the occlusive vessel was achieved.CONCLUSION Although the patient eventually died of circulatory failure,the result of this case verifies the feasibility of cerebral angiography and thrombectomy in patients with implanted ECMO in the intubated state.
基金Supported by the National Natural Science Foundation of China(41772240)
文摘In order to improve the catalytic ozonation effect of resorcinol, the spinel CuFe_2O_4 was modified by doped CeO_2, and X-ray diffraction(XRD) and scanning electron microscopy(SEM) were used for characterization analysis. The effects of composite catalyst CeO_2/CuFe_2O_4 dosage, ozone dosage, initial pH and reaction temperature on degradation were studied, and the stability of the catalyst was tested. The results showed that the composite effect of CeO_2/CuFe_2O_4 prepared by combustion method was good, and the catalyst presented a laminated structure, in which 30 wt% CeO_2/CuFe_2O_4 degradation effect was significant. The removal rate of resorcinol using CeO_2/CuFe_2O_4 composite catalyst was higher than that using ozone or CuFe_2O_4 separately by 41.8% and 11.9%, respectively. In a reaction with resorcinol concentration of 100 mg/L, the catalyst dosage of 1.0 g/L, the ozone dosage of 2.5 mg/(L·min), at pH=9, temperature of 20 ℃, for reaction time of 40 min, the resorcinol removal rate was 88.5%. The catalyst CeO_2/CuFe_2O_4 still showed good degradation effect after repeatedly using for 10 times, and the dissolution rate of metal ions was lower than that of CuFe_2O_4.
文摘Some heart diseases need long-term monitoring to diagnose. In this paper, we present a wearable single lead ECG monitoring device with low power consumption based on MSP430 and single-lead ECG front-end AD8232, which could acquire and store patient’s ECG data for 7 days continuously. This device is available for long-term wearing with a small volume. Also, it could detect user’s motion status with an acceleration sensor and supports Bluetooth 4.0 protocol. So it could be expanded to be a dynamic heart rate monitor and/or sleep quality monitor combined with smart phone. The device has huge potential of application for health care of human daily life.
基金This work was supported by grants from the Natural Science Foundation of Youth Jiangsu Province(BIC20160579).
文摘With global warming,heat stress is becoming a more frequent event and a major limiting factor for crop production.The evaluation of thermo-tolerance is essential for the cultivators to obtain the heat resistant genotypes and breeders to improve the thermo-tolerance of plants.Therefore,it is very important to perfect the existing evaluation system for thermo-tolerance.In this study,30 tomato genotypes were treated with heat stress at germination,seedling and flowering stages.Each index was different and diverse in different tomato genotypes by doing variability analysis,difference analysis and Student's t test.Before principal component analysis(PCA),a positive treatment for the negative and moderation indexes was performed.After correlation analysis,the authors performed PCA(including dimensionality reduction(DR),no dimensionality reduction(NDR)and optimal index(OI)),combining with subordinate function(SF),weight and cluster analysis.No matter at germination or seedling stage,the members of the groups were basically identical for DR,NDR and OI.Then 10 tomato genotypes were chosen from 30 randomly for verification.Compared all the evaluation systems,OI was the simplest and also could get as credible results as other methods.Therefore,in this study,OI could be adopted and improve the efficiency during the evaluation.At germination stage,germination power(GP)can accurately evaluate the thermo-tolerance,and at seedling stage,it was fresh weight(FW),internode length(IL)and dry matter percentage of seedling(DMP).Finally,all the indexes in the three stages were applied correlation analysis.Seedling stage showed significant positive correlation with flowering stage.In conclusion,this work improves the current system and set up a new comprehensive evaluation method named OI,which also improves the efficiency,guarantees reliability in screening thermo-tolerance of tomato for cultivators and expedites the process of breeding for resistance.
基金supported by the National Key R&D Program of China(2022YFC3500200,2022YFC3500202)National Natural Science Foundation of China(U24A20794,82103197)+4 种基金Jiangsu Province Postgraduate Training Innovation Project Grant(KYCX23_2132,China)the Integrated Traditional Chinese and Western Medicine Clinical Medicine Innovation Center Fund for Colorectal Polyps from Jiangsu Province Hospital of Chinese Medicine(No.Y2023zx10)the project funding from Jiangsu Province Hospital of Chinese Medicine(No.kgr0253,China)Natural Science Foundation of Jiangsu Province(BK20210686,China)Nanjing University of Chinese Medicine’s Key Project:“Leading the Charge with Open Competition”(AD202405,China).
文摘Colorectal tumorigenesis generally progresses from adenoma to adenocarcinoma,accompanied by dynamic changes in the tumor microenvironment(TME).A randomized controlled trial has confirmed the efficacy and safety of Shen-Bai-Jie-Du decoction(SBJDD)in preventing colorectal tumorigenesis.However,the mechanism remains unclear.In this study,we employed single-cell RNA sequencing(scRNA-seq)to investigate the dynamic evolution of the TME and validated cell infiltration with multiplex immunohistochemistry and flow cytometry.Bulk RNA sequencing was utilized to assess the underlying mechanisms.Our results constructed the mutually verifiable single-cell transcriptomic atlases in Apc^(Min/+)mice and clinical patients.There was a marked accumulation of CCL22^(+)dendritic cells(DCs)and an enhanced immunosuppressive action,which SBJDD and berberine reversed.Combined treatment with cholesterol and lipopolysaccharide induced characteristic gene expression of CCL22^(+)DCs,which may represent“exhausted DCs”.Intraperitoneal injection of these DCs after SBJDD treatment eliminated its therapeutic effects.TMEM131 derived CCL22+DCs generation by TNF signaling pathway and may be a potential target of berberine in retarding colorectal tumorigenesis.These findings emphasize the role of exhausted DCs and the regulatory mechanisms of SBJDD and berberine in colorectal cancer(CRC),suggesting that the multi-component properties of SBJDD may help restore TME homeostasis and offer novel cancer therapy.
基金The registration number for the study was CWXH-IPR-2018004(date:January 11,2019).
文摘BACKGROUND Venous thromboembolism(VTE)is a common neurosurgical complication after brain tumor resection,and its prophylaxis has been widely studied.There are no effective drugs in the clinical management of venous thromboembolism,and there is an absence of evidence-based medicine concerning the treatment of severe multiple traumas.AIM To explore whether ulinastatin(UTI)can prevent VTE after brain tumor resection.METHODS The present research included patients who underwent brain tumor resection.Patients received UTIs(400,000 IU)or placebos utilizing computer-based random sequencing(in a 1:1 ratio).The primary outcome measures were the incidence of VTE,coagulation function,pulmonary emboli,liver function,renal function,and drug-related adverse effects.RESULTS A total of 405 patients were evaluated between January 2019 and December 2021,and 361 of these were initially enrolled in the study to form intention-to-treat,which was given UTI(n=180)or placebo(n=181)treatment in a random manner.There were no statistically significant differences in baseline clinical data between the two groups.The incidence of VTE in the UTI group was remarkably improved compared with that in the placebo group.UTI can improve coagulation dysfunction,pulmonary emboli,liver function,and renal function.No significant difference was identified between the two groups in the side effects of UTI-induced diarrhea,vomiting,hospital stays,or hospitalization costs.The incidence of allergies was higher in the UTI group than in the placebo group.CONCLUSION The findings from the present research indicated that UTI can decrease the incidence of VTE and clinical outcomes of patients after brain tumor resection and has fewer adverse reactions.
基金funded by grants from the National Natural Science Foundation of China(Grant Nos.82003288,U20A20375,82372779,and 82103001)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Objective:The combination of epithelial growth factor receptor tyrosine kinase inhibitors(EGFR-TKIs)and immune checkpoint inhibitors(ICIs)leads to an increased incidence of severe immune-related adverse events(irAEs).However,the mechanisms underlying macrophages in irAEs have not been elucidated.Methods:An osimertinib and ICI-induced irAE mouse model was constructed.Lung micro-CT scans were used to assess the degree of inflammatory infiltration.Hematoxylin-eosin staining was used to analyze the histopathologic inflammatory infiltration in mouse liver and lung tissues.Flow cytometry was used to detect the percentages of T cells,NK cells,and macrophages and the expression of EGFR.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum interleukin(IL)-6,alanine transaminase(ALT),ferritin,and tumor necrosis factor(TNF)-αlevels.Total RNA extracted from mouse liver macrophages was analyzed by RNA-seq.Simple Western blot analysis was used to detect the IL-6/JAK/STAT3 pathway activation state.Results:Osimertinib combined with ICIs upregulated EGFR expression on macrophages with increased serum IL-6,ALT,and ferritin levels.RNA-seq and simple Western blot analysis of mouse liver macrophages confirmed that that the IL-6/JAK/STAT3 pathway was activated in the combination treatment group.Ruxolitinib blocked the IL-6/JAK/STAT3 pathway and significantly decreased the serum IL-6,ALT,and ferritin levels in the combination treatment group.Conclusions:An osimertinib and ICI-induced irAE mouse model was constructed that showed osimertinib combined with ICIs inhibited EGFR phosphorylation and activated the IL-6/JAK/STAT3 signaling pathway in mouse liver macrophages,which led to the release of relevant cytokines.
文摘With the development of network technology and cloud computing, data sharing is becoming increasingly popular, and many scholars have conducted in-depth research to promote its flourish. As the scale of data sharing expands, its privacy protection has become a hot issue in research. Moreover, in data sharing, the data is usually maintained in multiple parties, which brings new challenges to protect the privacy of these multi-party data. In this paper, we propose a trusted data sharing scheme using blockchain. We use blockchain to prevent the shared data from being tampered, and use the Paillier cryptosystem to realize the confidentiality of the shared data. In the proposed scheme, the shared data can be traded, and the transaction information is protected by using the （p, t）-threshold Paillier cryptosystem. We conduct experiments in cloud storage scenarios and the experimental results demonstrate the efficiency and effectiveness of the proposed scheme.
