Effective emission control of cooking oil fumes(COFs),particularly for grease particles,has always been a cause of great concern for catering industry.The review and evaluation of combinations of purification technolo...Effective emission control of cooking oil fumes(COFs),particularly for grease particles,has always been a cause of great concern for catering industry.The review and evaluation of combinations of purification technology are urgently required.This work presents a literature review and combination strategy evaluation of purification technology of grease particles of commercial kitchens.A variety of mainstream purification technologies,such as mechanical separation(M),filtration(F),washing absorption(W)and electrostatic deposition(E)are discussed.In order to establish a complete and efficient fume purification system for commercial kitchen,this study proposes the four-point principles of combined purification technologies as:(1)from easy to difficult(for grease particle diameter);(2)fire prevention and noise reduction;(3)electrostatic deposition postposition;(4)Absorption and dissolution(by-product from electrostatic).Based on the above principles and separation characteristics,the recommended combinations of purification strategies are M-E,F-E,M-F-E and M-E-F.The combination strategy of M-F-E is adopted as an example to evaluate and optimize COFs purification system use life cycle assessment approach.The results indicate that the optimization of the M-F-E purification system using rotating mesh plate instead of baffle filter can reduce the environmental impact of global warming and eutrophication by about 35%which reduces the emissions of CO_(2)and SO_(2)from 92.533 kg and 0.110 kg to 60.214 kg and 0.072 kg,respectively.Besides the review of relevant purification technologies,the study also proposes the combination of principles of purification technologies and the evaluation and optimization of life cycle assessment for the optimal design of combined purification system.展开更多
Human immunodeficiency virus(HIV)-1 infection creates a persistent latent reservoir even after antiretroviral therapy,which is the main barrier to HIV cure.One of the most explored strategies is the use of latent reve...Human immunodeficiency virus(HIV)-1 infection creates a persistent latent reservoir even after antiretroviral therapy,which is the main barrier to HIV cure.One of the most explored strategies is the use of latent reversal agents(LRAs)to activate HIV latent reservoirs,followed by immunotherapy to remove infected cells.Immunomodulatory LRAs have the dual advantage of activating viral latency and promoting immune cell elimination of HIV-infected cells.The emergence of novel immunotherapies has also enhanced the possibility ofHIV clearance.Here we review the activity and potential mechanisms of immunomodulatory agonists and immunotherapies.The possible combinational strategies to achieve HIV functional cure and the problems encountered using this approach are discussed.展开更多
Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylbor...Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylboronic acid(PBA)were synthesized,of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA.The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges.The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract.After reaching the lesions,the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release,while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside.The drugmicelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation.The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable,safe and flexible anti-infectious drug delivery systems.展开更多
The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chem...The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.展开更多
Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of ...Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.展开更多
The flowering forecast provides recommendations for orchard cleaning, pest control, field management and fertilization, which can help increase tree vigor and resistance. Flowering forecast is not only an important pa...The flowering forecast provides recommendations for orchard cleaning, pest control, field management and fertilization, which can help increase tree vigor and resistance. Flowering forecast is not only an important part of the construction of agro-meteorological index system, but also an important part of the meteorological service system. In this paper, by analyzing local meteorological data and phenological data of “Red Fuji” apples in Fen County, Linfen City, Shanxi Province, with the help of machine learning and neural networks, we proposed a method based on the combination of time series forecasting and classification forecasting is proposed to complete the dynamic forecasting model of local flowering in Ji County. Then, we evaluated the effectiveness of the model based on the number of error days and the number of days in advance. The implementation shows that the proposed multivariable LSTM network has a good effect on the prediction of meteorological factors. The model loss is less than 0.2. In the two-category task of flowering judgment, the idea of combining strategies in ensemble learning improves the effect of flowering judgment, and its AUC value increases from 0.81 and 0.80 of single model RF and AdaBoost to 0.82. The proposed model has high applicability and accuracy for flowering forecast. At the same time, the model solves the problem of rounding decimals in the prediction of flowering dates by the regression method.展开更多
A novel algorithm for constructing support vector machine regression ensemble is proposed. As to regression prediction, support vector machine regression (SVMR) ensemble is proposed by resampling from given training...A novel algorithm for constructing support vector machine regression ensemble is proposed. As to regression prediction, support vector machine regression (SVMR) ensemble is proposed by resampling from given training data sets repeatedly and aggregating several independent SVMRs, each of which is trained to use a replicated training set. After training, several independently trained SVMRs need to be aggregated in an appropriate combination manner. Generally, the linear weighting is usually used like expert weighting score in Boosting Regression and it is without optimization capacity. Three combination techniques are proposed, including simple arithmetic mean, linear least square error weighting and nonlinear hierarchical combining that uses another upper-layer SVMR to combine several lower-layer SVMRs. Finally, simulation experiments demonstrate the accuracy and validity of the presented algorithm.展开更多
Background:Improving financial time series forecasting is one of the most challenging and vital issues facing numerous financial analysts and decision makers.Given its direct impact on related decisions,various attemp...Background:Improving financial time series forecasting is one of the most challenging and vital issues facing numerous financial analysts and decision makers.Given its direct impact on related decisions,various attempts have been made to achieve more accurate and reliable forecasting results,of which the combining of individual models remains a widely applied approach.In general,individual models are combined under two main strategies:series and parallel.While it has been proven that these strategies can improve overall forecasting accuracy,the literature on time series forecasting remains vague on the choice of an appropriate strategy to generate a more accurate hybrid model.Methods:Therefore,this study’s key aim is to evaluate the performance of series and parallel strategies to determine a more accurate one.Results:Accordingly,the predictive capabilities of five hybrid models are constructed on the basis of series and parallel strategies compared with each other and with their base models to forecast stock price.To do so,autoregressive integrated moving average(ARIMA)and multilayer perceptrons(MLPs)are used to construct two series hybrid models,ARIMA-MLP and MLP-ARIMA,and three parallel hybrid models,simple average,linear regression,and genetic algorithm models.Conclusion:The empirical forecasting results for two benchmark datasets,that is,the closing of the Shenzhen Integrated Index(SZII)and that of Standard and Poor’s 500(S&P 500),indicate that although all hybrid models perform better than at least one of their individual components,the series combination strategy produces more accurate hybrid models for financial time series forecasting.展开更多
As the science and technology develop,crime methods and scenes have become increasingly complex and diverse.Trace evidence analysis has become amore and more important criminal investigation technology and liquid is t...As the science and technology develop,crime methods and scenes have become increasingly complex and diverse.Trace evidence analysis has become amore and more important criminal investigation technology and liquid is the main form of trace evidence.Food can provide not only energy,but clues to solve crimes.In this study,we build a hyperspectral imaging system to detect liquid residue traces,including apple juice,coffee,cola,milk and tea,on denims with light,middle and dark colors.The obtained hyperspectral images are first subjected to spectral calibration and hyperspectral data pretreatment.Subsequently,Partial Least Squares(PLS)is applied to select the informative wavelengths from the preprocessed spectra.For modeling phase,the combination optimal strategy,support vector machine(SVM)combined with random forest(RF),is developed to establish classification models.The experimental results demonstrate that the combination optimal model can achieve TPR,FPR,Precision,Recall,F1,and AUC of 83.5%,2.30%,79.7%,83.5%,81.6%,and 94.7%for classifying fabrics contaminated by various food residuals.With respect to the classification of liquid and fabric types,the combination optimalmodel also yields satisfactory classification performance.In future work,wewill expand the types of liquid,and make appropriate adjustment to algorithms for improving the robustness of classification models.This research may play a positive role in the construction of a harmonious society.展开更多
Described as a“don't eat me”signal,CD47 becomes a vital immune checkpoint in cancer.Its interaction with signal regulatory protein alpha(SIRPa)prevents macrophage phagocytosis.In recent years,a growing body of e...Described as a“don't eat me”signal,CD47 becomes a vital immune checkpoint in cancer.Its interaction with signal regulatory protein alpha(SIRPa)prevents macrophage phagocytosis.In recent years,a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect.Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies,indicating the combination strategy as a general trend of the future.In this review,clinical and preclinical cases about the current combination strategies targeting CD47 are collected,their underlying mechanisms of action are discussed,and ideas from future perspectives are shared.展开更多
Understanding the structure-property relationships in polycyclic conjugated hydrocarbons(PCHs)is crucial in controlling their electronic properties and developing new optically functional materials.Aromaticity is a fu...Understanding the structure-property relationships in polycyclic conjugated hydrocarbons(PCHs)is crucial in controlling their electronic properties and developing new optically functional materials.Aromaticity is a fundamentally important and intriguing property of numerous organic chemical structures and has stimulated a myriad of experimental and theoretical investigations.Exploiting aromaticity rules for the rational design of optoelectronic materials with the desired photophysical characteristics is a challenging yet fascinating task.Herein we present an in-depth computational and spectroscopic study on the structure-property relationships of dinaphthopentalenes(DNPs).Results highlight that the different fusion patterns between 4nπand 4n+2πunits endow these PCHs with the tunable aromaticity in the ground state/excited state,which leads to the diverse electronic structures and consequently the distinctive excited state photophysics.Accordingly,we propose a combined aromaticity design strategy for rationally modulating and tailoring electronic and optical properties of PCH skeletons.These outcomes not only present a full picture of the excited state dynamics of the DNP system and afford a new class of efficient singlet fission-active materials but also provide some basic guidelines for exploiting aromaticity rules to design and develop new optical function materials.展开更多
The clinical efficacy of current cancer therapies falls short,and there is a pressing demand to integrate new targets with conventional therapies.Autophagy,a highly conserved self-degradation process,has received cons...The clinical efficacy of current cancer therapies falls short,and there is a pressing demand to integrate new targets with conventional therapies.Autophagy,a highly conserved self-degradation process,has received considerable attention as an emerging therapeutic target for cancer.With the rapid development of nanomedicine,nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance.Hence,considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy,we outline the latest advances in autophagy-based nanotherapeutics.Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression,the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated.Further,emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways,including modulation of the mammalian target of rapamycin(mTOR)pathway,autophagy-related(ATG)and its complex expression,reactive oxygen species(ROS)and mitophagy,interference with autophagosome-lysosome fusion,and inhibition of hypoxia-mediated autophagy.In addition,combination therapies in which nano-autophagy modulation is combined with chemotherapy,phototherapy,and immunotherapy are also described.Finally,the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.展开更多
The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity a...The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.展开更多
T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T...T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.展开更多
The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a r...The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of “eat me” signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.展开更多
Immunotherapies based on immune checkpoint blockade(ICB)have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade.To date,immune checkpoint inhibitors(ICIs)of CTLA-...Immunotherapies based on immune checkpoint blockade(ICB)have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade.To date,immune checkpoint inhibitors(ICIs)of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy.Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers,however,a large subset of refractory patients presents poor responsiveness to ICB therapy;and the underlying mechanism remains elusive.Recently,numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment(TME)with various products of metabolism,and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy.Nevertheless,a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance.Here,we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints(CTLA-4,PD-1,and PD-L1)to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.展开更多
T cell mediated adoptive immune response has been characterized as the key to anti-tumor immunity. Scientists around the world including in China, have been trying to harness the power of T cells against tumors for de...T cell mediated adoptive immune response has been characterized as the key to anti-tumor immunity. Scientists around the world including in China, have been trying to harness the power of T cells against tumors for decades. Recently, the biosynthetic chimeric antigen receptor engineered T cell(CAR-T) strategy was developed and exhibited encouraging clinical efficacy, especially in hematological malignancies. Chimeric antigen receptor research reports began in 2009 in China according to our Pub Med search results. Clinical trials have been ongoing in China since 2013 according to the trial registrations on clinicaltrials.gov.. After years of assiduous efforts, research and clinical scientists in China have made their own achievements in the CAR-T therapy field. In this review, we aim to highlight CAR-T research and clinical trials in China, to provide an informative reference for colleagues in the field.展开更多
Modular Solar-Powered Aircraft(M-SPA)is a kind of High-Altitude Long-Endurance(HALE)aircraft which exploits the mission advantage of swarm UAV and the HALE advantage of large aspect-ratio SPA.M-SPA’s separated mode a...Modular Solar-Powered Aircraft(M-SPA)is a kind of High-Altitude Long-Endurance(HALE)aircraft which exploits the mission advantage of swarm UAV and the HALE advantage of large aspect-ratio SPA.M-SPA’s separated mode and combined mode give it the potential to maximize the mission efficiency with limited solar energy.In this paper,firstly,oriented by the mission of maximizing the cruise area,the overall design of the M-SPA is modeled,including the energy model,the aerodynamic model and the flight environment settings.Secondly,by analyzing the energy consumption of the flight modes,we design a multi-phase flight mission strategy.Then,a 24-hour three-dimensional(3D)flight profile of the M-SPA is optimized,including the sub-SPA cooperative path planning in the separation mode.Finally,inspired by the Traveling Salesman Problem(TSP),an improved Ant Colony Algorithm(ACA)is exploited to find the optimal path for each sub-SPA,which is further developed into a dynamic separation and combination scheme for the M-SPA.The simulation results show that the mission performance of the M-SPA outperforms that of the conventional SPA,and explicitly,the mission coverage of the M-SPA is slightly less than a linear increase under comparable simulation conditions.展开更多
Bladder cancer is a complex disease of the urinary system with high morbidity and mortality.Recently,the introduction of immunother-apies such as immune checkpoint inhibitors(eg,programmed cell death protein 1/program...Bladder cancer is a complex disease of the urinary system with high morbidity and mortality.Recently,the introduction of immunother-apies such as immune checkpoint inhibitors(eg,programmed cell death protein 1/programmed death-ligand 1)has proven to be a re-liable means of improving survival outcomes,including patients with limited response to conventional treatment.Nevertheless,difficult questions remain in clinical practice,such as how to select appropriate patients for personalized treatment,how to predict and assess therapeutic efficacy in advance,and how to enhance the therapeutic benefits of immunotherapy treatment.These issues require urgent attention.Herein,we describe recent clinical applications of immune checkpoint inhibitors in bladder cancer therapy,examine underlying mechanisms for treatment failure in a subset of patients,and discuss potential approaches to improve their therapeutic effects.展开更多
基金This research was financially supported by the National Key R&D Program of China(No.2017YFC0211500).
文摘Effective emission control of cooking oil fumes(COFs),particularly for grease particles,has always been a cause of great concern for catering industry.The review and evaluation of combinations of purification technology are urgently required.This work presents a literature review and combination strategy evaluation of purification technology of grease particles of commercial kitchens.A variety of mainstream purification technologies,such as mechanical separation(M),filtration(F),washing absorption(W)and electrostatic deposition(E)are discussed.In order to establish a complete and efficient fume purification system for commercial kitchen,this study proposes the four-point principles of combined purification technologies as:(1)from easy to difficult(for grease particle diameter);(2)fire prevention and noise reduction;(3)electrostatic deposition postposition;(4)Absorption and dissolution(by-product from electrostatic).Based on the above principles and separation characteristics,the recommended combinations of purification strategies are M-E,F-E,M-F-E and M-E-F.The combination strategy of M-F-E is adopted as an example to evaluate and optimize COFs purification system use life cycle assessment approach.The results indicate that the optimization of the M-F-E purification system using rotating mesh plate instead of baffle filter can reduce the environmental impact of global warming and eutrophication by about 35%which reduces the emissions of CO_(2)and SO_(2)from 92.533 kg and 0.110 kg to 60.214 kg and 0.072 kg,respectively.Besides the review of relevant purification technologies,the study also proposes the combination of principles of purification technologies and the evaluation and optimization of life cycle assessment for the optimal design of combined purification system.
基金funded by the Beijing Municipal Science and Technology Commission(No.D17110700050000).
文摘Human immunodeficiency virus(HIV)-1 infection creates a persistent latent reservoir even after antiretroviral therapy,which is the main barrier to HIV cure.One of the most explored strategies is the use of latent reversal agents(LRAs)to activate HIV latent reservoirs,followed by immunotherapy to remove infected cells.Immunomodulatory LRAs have the dual advantage of activating viral latency and promoting immune cell elimination of HIV-infected cells.The emergence of novel immunotherapies has also enhanced the possibility ofHIV clearance.Here we review the activity and potential mechanisms of immunomodulatory agonists and immunotherapies.The possible combinational strategies to achieve HIV functional cure and the problems encountered using this approach are discussed.
基金financial support from National Key Research and Development Program(2017YFD0501403)National Natural Science Foundation of China(Nos.81872819)+4 种基金Natural Science Foundation of Jiangsu Province(No.BK20171390)supported by Double First-Rate construction plan of China Pharmaceutical University(CPU2018GY26)the Project of State Key Laboratory of Natural Medicines,China Pharmaceutical University(No.SKLNMZZCX201816)the National Science and Technology Major Project(2017ZX09101001)the financial support from Development Funds for Priority Academic Programs in Jiangsu Higher Education Institutions-Young Talent Program。
文摘Stimuli-triggered drug delivery systems hold vast promise in local infection treatment for the site-specific targeting and shuttling of drugs.Herein,chitosan conjugates(SPCS)installed with sialic acid(SA)and phenylboronic acid(PBA)were synthesized,of which SA served as targeting ligand for coccidium and reversible-binding bridge for PBA.The enhanced drug-loading capacity of SPCS micelles was attributed to a combination assembly from hydrophobicity-driving and reversible borate bridges.The drug-loaded SPCS micelles shared superior biostability in upper gastrointestinal tract.After reaching the lesions,the borate bridges were snipped by carbohydrates under a higher pH followed by accelerated drug release,while SA exposure on micellar surface facilitated drug cellular internalization to eliminate parasites inside.The drugmicelles revealed an enhanced anti-coccidial capacity with a higher index of 185.72 compared with commercial preparation.The dual-responsive combination of physicochemical assembly could provide an efficient strategy for the exploitation of stable,safe and flexible anti-infectious drug delivery systems.
基金the Science and Technology Commission of Shanghai,China(Grant Nos.:20DZ2270800 and 19JC1410200)Innovative Research Team of High-Level Local Universities in Shanghai,China(Grant No.:SHSMU-ZDCX20210900)the National Natural Science Foundation of China(Grant No.:82073889).
文摘The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and immune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.
基金This work was supported by the Science and Technology Development Fund,Macao SAR(No.0053-2021-AGJ)the Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao(No.SKL-QRCM-IRG2023-011)the Natural Science Foundation of Sichuan Province(No.2023NSFSC1783).
文摘Liver cancer stands as a significant global health concern,contributing substantially to cancer incidence and mortality,particularly in Asian countries[1].Hepatocellular carcinoma(HCC)accounts for approximately 90%of all liver cancer cases and is characterized by a high-risk profile and a generally poor prognosis[2].To address advanced HCC,systemic therapy has been recommended,leading to the approval of a range of treatment regimens in clinical practice.Traditionally,first-line therapy involved the use of multitargeted tyrosine kinase inhibitors(TKIs)such as sorafenib or lenvatinib,while cabozantinib,ramucirumab.
文摘The flowering forecast provides recommendations for orchard cleaning, pest control, field management and fertilization, which can help increase tree vigor and resistance. Flowering forecast is not only an important part of the construction of agro-meteorological index system, but also an important part of the meteorological service system. In this paper, by analyzing local meteorological data and phenological data of “Red Fuji” apples in Fen County, Linfen City, Shanxi Province, with the help of machine learning and neural networks, we proposed a method based on the combination of time series forecasting and classification forecasting is proposed to complete the dynamic forecasting model of local flowering in Ji County. Then, we evaluated the effectiveness of the model based on the number of error days and the number of days in advance. The implementation shows that the proposed multivariable LSTM network has a good effect on the prediction of meteorological factors. The model loss is less than 0.2. In the two-category task of flowering judgment, the idea of combining strategies in ensemble learning improves the effect of flowering judgment, and its AUC value increases from 0.81 and 0.80 of single model RF and AdaBoost to 0.82. The proposed model has high applicability and accuracy for flowering forecast. At the same time, the model solves the problem of rounding decimals in the prediction of flowering dates by the regression method.
基金The project was supported by the National Science Foundation of China (70572045)
文摘A novel algorithm for constructing support vector machine regression ensemble is proposed. As to regression prediction, support vector machine regression (SVMR) ensemble is proposed by resampling from given training data sets repeatedly and aggregating several independent SVMRs, each of which is trained to use a replicated training set. After training, several independently trained SVMRs need to be aggregated in an appropriate combination manner. Generally, the linear weighting is usually used like expert weighting score in Boosting Regression and it is without optimization capacity. Three combination techniques are proposed, including simple arithmetic mean, linear least square error weighting and nonlinear hierarchical combining that uses another upper-layer SVMR to combine several lower-layer SVMRs. Finally, simulation experiments demonstrate the accuracy and validity of the presented algorithm.
文摘Background:Improving financial time series forecasting is one of the most challenging and vital issues facing numerous financial analysts and decision makers.Given its direct impact on related decisions,various attempts have been made to achieve more accurate and reliable forecasting results,of which the combining of individual models remains a widely applied approach.In general,individual models are combined under two main strategies:series and parallel.While it has been proven that these strategies can improve overall forecasting accuracy,the literature on time series forecasting remains vague on the choice of an appropriate strategy to generate a more accurate hybrid model.Methods:Therefore,this study’s key aim is to evaluate the performance of series and parallel strategies to determine a more accurate one.Results:Accordingly,the predictive capabilities of five hybrid models are constructed on the basis of series and parallel strategies compared with each other and with their base models to forecast stock price.To do so,autoregressive integrated moving average(ARIMA)and multilayer perceptrons(MLPs)are used to construct two series hybrid models,ARIMA-MLP and MLP-ARIMA,and three parallel hybrid models,simple average,linear regression,and genetic algorithm models.Conclusion:The empirical forecasting results for two benchmark datasets,that is,the closing of the Shenzhen Integrated Index(SZII)and that of Standard and Poor’s 500(S&P 500),indicate that although all hybrid models perform better than at least one of their individual components,the series combination strategy produces more accurate hybrid models for financial time series forecasting.
基金sponsored by the National Natural Science Foundation of China(No.61901172,No.61831015,No.U1908210)the Shanghai Sailing Program(No.19YF1414100)+3 种基金the“Chenguang Program”supported by Shanghai Education Development Foundation and Shanghai Municipal Education Commission(No.19CG27)the Science and Technology Commission of Shanghai Municipality(No.19511120100,No.18DZ2270700,No.18DZ2270800)the foundation of Key Laboratory of Artificial Intelligence,Ministry of Education(No.AI2019002)and the Fundamental Research Funds for the Central Universities.
文摘As the science and technology develop,crime methods and scenes have become increasingly complex and diverse.Trace evidence analysis has become amore and more important criminal investigation technology and liquid is the main form of trace evidence.Food can provide not only energy,but clues to solve crimes.In this study,we build a hyperspectral imaging system to detect liquid residue traces,including apple juice,coffee,cola,milk and tea,on denims with light,middle and dark colors.The obtained hyperspectral images are first subjected to spectral calibration and hyperspectral data pretreatment.Subsequently,Partial Least Squares(PLS)is applied to select the informative wavelengths from the preprocessed spectra.For modeling phase,the combination optimal strategy,support vector machine(SVM)combined with random forest(RF),is developed to establish classification models.The experimental results demonstrate that the combination optimal model can achieve TPR,FPR,Precision,Recall,F1,and AUC of 83.5%,2.30%,79.7%,83.5%,81.6%,and 94.7%for classifying fabrics contaminated by various food residuals.With respect to the classification of liquid and fabric types,the combination optimalmodel also yields satisfactory classification performance.In future work,wewill expand the types of liquid,and make appropriate adjustment to algorithms for improving the robustness of classification models.This research may play a positive role in the construction of a harmonious society.
基金supported by The Science and Technology Development Fund,Macao SAR,China(File No.:0129/2019/A3)Internal Research Grant of the State Key Laboratory of Quality Research in Chinese Medicine,University of Macao(File No.:QRCM-IRG2022-016,China)+1 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,File No.:2020B1212030006,China)the National Natural Science Foundation of China(File No.:81973516)。
文摘Described as a“don't eat me”signal,CD47 becomes a vital immune checkpoint in cancer.Its interaction with signal regulatory protein alpha(SIRPa)prevents macrophage phagocytosis.In recent years,a growing body of evidences have unveiled that CD47-based combination therapy exhibits a superior anti-cancer effect.Latest clinical trials about CD47 have adopted the regimen of collaborating with other therapies or developing CD47-directed bispecific antibodies,indicating the combination strategy as a general trend of the future.In this review,clinical and preclinical cases about the current combination strategies targeting CD47 are collected,their underlying mechanisms of action are discussed,and ideas from future perspectives are shared.
基金supported by the National Natural Science Foundation of China(grant nos.22005210,21833005,and 22231009).
文摘Understanding the structure-property relationships in polycyclic conjugated hydrocarbons(PCHs)is crucial in controlling their electronic properties and developing new optically functional materials.Aromaticity is a fundamentally important and intriguing property of numerous organic chemical structures and has stimulated a myriad of experimental and theoretical investigations.Exploiting aromaticity rules for the rational design of optoelectronic materials with the desired photophysical characteristics is a challenging yet fascinating task.Herein we present an in-depth computational and spectroscopic study on the structure-property relationships of dinaphthopentalenes(DNPs).Results highlight that the different fusion patterns between 4nπand 4n+2πunits endow these PCHs with the tunable aromaticity in the ground state/excited state,which leads to the diverse electronic structures and consequently the distinctive excited state photophysics.Accordingly,we propose a combined aromaticity design strategy for rationally modulating and tailoring electronic and optical properties of PCH skeletons.These outcomes not only present a full picture of the excited state dynamics of the DNP system and afford a new class of efficient singlet fission-active materials but also provide some basic guidelines for exploiting aromaticity rules to design and develop new optical function materials.
基金the National Natural Science Foundation of China(No.81971729)for financial support.
文摘The clinical efficacy of current cancer therapies falls short,and there is a pressing demand to integrate new targets with conventional therapies.Autophagy,a highly conserved self-degradation process,has received considerable attention as an emerging therapeutic target for cancer.With the rapid development of nanomedicine,nanomaterials have been widely utilized in cancer therapy due to their unrivaled delivery performance.Hence,considering the potential benefits of integrating autophagy and nanotechnology in cancer therapy,we outline the latest advances in autophagy-based nanotherapeutics.Based on a brief background related to autophagy and nanotherapeutics and their impact on tumor progression,the feasibility of autophagy-based nanotherapeutics for cancer treatment is demonstrated.Further,emerging nanotherapeutics developed to modulate autophagy are reviewed from the perspective of cell signaling pathways,including modulation of the mammalian target of rapamycin(mTOR)pathway,autophagy-related(ATG)and its complex expression,reactive oxygen species(ROS)and mitophagy,interference with autophagosome-lysosome fusion,and inhibition of hypoxia-mediated autophagy.In addition,combination therapies in which nano-autophagy modulation is combined with chemotherapy,phototherapy,and immunotherapy are also described.Finally,the prospects and challenges of autophagy-based nanotherapeutics for efficient cancer treatment are envisioned.
基金This work was supported by the National Postdoctoral Foundation of China(No.2023M730375)Liaoning Province Department of Education Project(No.LJKMZ20221365,China)+3 种基金the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215,China)the National Natural Science Foundation of China(No.82173766)Liaoning Province Applied Basic Research Program(No.2022JH2/101300097,China)the Natural Science Foundation of Shandong Province(No.ZR2021QH084,China)。
文摘The non-selective cytotoxicity of toxins limits the clinical relevance of the toxins.In recent years,toxins have been widely used as warheads for antibody-drug conjugates(ADCs)due to their eff-cient killing activity against various cancer cells.Although ADCs confer certain targeting properties to the toxins,low drug loading capacity,possible immunogenicity,and other drawbacks also limit the po-tential application of ADCs.Recently,non-ADC delivery strategies for toxins have been extensively investigated.To further understand the application of toxins in anti-tumor,this paper provided an over-view of prodrugs,nanodrug delivery systems,and biomimetic drug delivery systems.In addition,toxins and their combination strategies with other therapies were discussed.Finally,the prospect and challenge of toxins in cancertreatmentwerealso summarized.
基金supported by the National Natural Science Foundation of China(Nos.32070940 and 81991491)the China Postdoctoral Science Foundation(No.2021M700115)+2 种基金the Postdoctoral Innovation Talents Support Program(No.BX20220189,China)the Science and Technology Planning Project of Fujian Province(No.2022L3080,China)the CAMS Innovation Fund for Medical Sciences(No.2019RU022,China).
文摘T cell-redirecting bispecific antibodies are specifically designed to bind to tumor-associated antigens,thereby engaging with CD3 on the T cell receptor.This linkage between tumor cells and T cells actively triggers T cell activation and initiates targeted killing of the identified tumor cells.These antibodies have emerged as one of the most promising avenues within tumor immunotherapy.However,despite success in treating hematological malignancies,significant advancements in solid tumors have yet to be explored.In this review,we aim to address the critical challenges associated with T cellredirecting bispecific antibodies and explore novel strategies to overcome these obstacles,with the ultimate goal of expanding the application of this therapy to include solid tumors.
基金the Science and Technology Development Fund,Macao SAR(File no.0129/2019/A3).
文摘The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of “eat me” signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.
基金supported by the National Natural Science Foundation of China (Nos.82130081 and 32270756)the National Key R&D Program of China (No.2022YFA1302803)the Beijing Natural Science Foundation (No.5212008).
文摘Immunotherapies based on immune checkpoint blockade(ICB)have significantly improved patient outcomes and offered new approaches to cancer therapy over the past decade.To date,immune checkpoint inhibitors(ICIs)of CTLA-4 and PD-1/PD-L1 represent the main class of immunotherapy.Blockade of CTLA-4 and PD-1/PD-L1 has shown remarkable efficacy in several specific types of cancers,however,a large subset of refractory patients presents poor responsiveness to ICB therapy;and the underlying mechanism remains elusive.Recently,numerous studies have revealed that metabolic reprogramming of tumor cells restrains immune responses by remodeling the tumor microenvironment(TME)with various products of metabolism,and combination therapies involving metabolic inhibitors and ICIs provide new approaches to cancer therapy.Nevertheless,a systematic summary is lacking regarding the manner by which different targetable metabolic pathways regulate immune checkpoints to overcome ICI resistance.Here,we demonstrate the generalized mechanism of targeting cancer metabolism at three crucial immune checkpoints(CTLA-4,PD-1,and PD-L1)to influence ICB therapy and propose potential combined immunotherapeutic strategies co-targeting tumor metabolic pathways and immune checkpoints.
基金supported by Science and Technology Planning Project of Beijing City (Z151100003915076 to Weidong Han)National Natural Science Foundation of China (31270820, 81230061 to Weidong Han, 81502679 to Can Luo)
文摘T cell mediated adoptive immune response has been characterized as the key to anti-tumor immunity. Scientists around the world including in China, have been trying to harness the power of T cells against tumors for decades. Recently, the biosynthetic chimeric antigen receptor engineered T cell(CAR-T) strategy was developed and exhibited encouraging clinical efficacy, especially in hematological malignancies. Chimeric antigen receptor research reports began in 2009 in China according to our Pub Med search results. Clinical trials have been ongoing in China since 2013 according to the trial registrations on clinicaltrials.gov.. After years of assiduous efforts, research and clinical scientists in China have made their own achievements in the CAR-T therapy field. In this review, we aim to highlight CAR-T research and clinical trials in China, to provide an informative reference for colleagues in the field.
基金supported by the National Natural Science Foundation of China(Nos.61901448,61871401,12002340).
文摘Modular Solar-Powered Aircraft(M-SPA)is a kind of High-Altitude Long-Endurance(HALE)aircraft which exploits the mission advantage of swarm UAV and the HALE advantage of large aspect-ratio SPA.M-SPA’s separated mode and combined mode give it the potential to maximize the mission efficiency with limited solar energy.In this paper,firstly,oriented by the mission of maximizing the cruise area,the overall design of the M-SPA is modeled,including the energy model,the aerodynamic model and the flight environment settings.Secondly,by analyzing the energy consumption of the flight modes,we design a multi-phase flight mission strategy.Then,a 24-hour three-dimensional(3D)flight profile of the M-SPA is optimized,including the sub-SPA cooperative path planning in the separation mode.Finally,inspired by the Traveling Salesman Problem(TSP),an improved Ant Colony Algorithm(ACA)is exploited to find the optimal path for each sub-SPA,which is further developed into a dynamic separation and combination scheme for the M-SPA.The simulation results show that the mission performance of the M-SPA outperforms that of the conventional SPA,and explicitly,the mission coverage of the M-SPA is slightly less than a linear increase under comparable simulation conditions.
基金supported by a grant from The National Natural Science Foundation of China(No.82072818).
文摘Bladder cancer is a complex disease of the urinary system with high morbidity and mortality.Recently,the introduction of immunother-apies such as immune checkpoint inhibitors(eg,programmed cell death protein 1/programmed death-ligand 1)has proven to be a re-liable means of improving survival outcomes,including patients with limited response to conventional treatment.Nevertheless,difficult questions remain in clinical practice,such as how to select appropriate patients for personalized treatment,how to predict and assess therapeutic efficacy in advance,and how to enhance the therapeutic benefits of immunotherapy treatment.These issues require urgent attention.Herein,we describe recent clinical applications of immune checkpoint inhibitors in bladder cancer therapy,examine underlying mechanisms for treatment failure in a subset of patients,and discuss potential approaches to improve their therapeutic effects.