Unsymmetrical bisacridines(UAs) are a novel potent class of antitumor-active therapeutics.A significant route of phase II drug metabolism is conjugation with glutathione(GSH),which can be non-enzymatic and/or catalyze...Unsymmetrical bisacridines(UAs) are a novel potent class of antitumor-active therapeutics.A significant route of phase II drug metabolism is conjugation with glutathione(GSH),which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes.The aim of this work was to investigate the GSHmediated metabolic pathway of a representative UA,C-2028.GSH-supplemented incubations of C-2028 with rat,but not with human,liver cytosol led to the formation of a single GSH-related metabolite.Interestingly,it was also revealed with rat liver microsomes.Its formation was NADPH-independent and was not inhibited by co-incubation with the cytochrome P450(CYP450) inhibitor 1-aminobenzotriazole.Therefore,the direct conjugation pathway occurred without the prior CYP450-catalyzed bioactivation of the substrate.In turn,incubations of C-2028 and GSH with human recombinant glutathione S-transferase(GST) P1-1 or with heat-/ethacrynic acid-inactivated liver cytosolic enzymes resulted in the presence or lack of GSH conjugated form,respectively.These findings proved the necessary participation of GST in the initial activation of the GSH thiol group to enable a nucleophilic attack on the substrate molecule.Another C-2028-GSH S-conjugate was also formed during non-enzymatic reaction.Both GSH S-conjugates were characterized by combined liquid chromatography/tandem mass spectrometry.Mechanisms for their formation were proposed.The ability of C-2028 to GST-mediated and/or direct GSH conjugation is suspected to be clinically important.This may affect the patient’s drug clearance due to GST activity,loss of GSH,or the interactions with GSH-conjugated drugs.Moreover,GST-mediated depletion of cellular GSH may increase tumor cell exposure to reactive products of UA metabolic transformations.展开更多
The mechanisms of action on monofunctional guanine adducts of analogues of transplatin with aliphatic amine ligands,such as trans-[Pt(Am)(isopropylamine)(G)(H2O)] where Am represents dimethylamine,propylamine ...The mechanisms of action on monofunctional guanine adducts of analogues of transplatin with aliphatic amine ligands,such as trans-[Pt(Am)(isopropylamine)(G)(H2O)] where Am represents dimethylamine,propylamine or isopropylamine and their cis isomers reacting with sulfur- and nitrogen-containing amino acid residues,were explored. Histidine and lysine residues are chosen as the model ligands of nitrogen-containing amino acid residues of proteins; meanwhile,methionine and cysteine residues are chosen as the model ligands of sulfur-containing amino acid residues of proteins. A dominating preference for sulfur-containing ligand over nitrogen-containing ligand is established. The calculated smallest activation barrier for sulfur-containing ligand is 9.9,and 21.1 kcal/mol for nitrogen-containing ligand in aqueous solution,and both of them have trans configurations. The difference in activation energy is 11.2 kcal/mol,indicating the platination of sulfur-containing amino acid residues is faster by seven to eight orders of magnitude than that of nitrogen-containing amino acid residues.展开更多
In recent years,skeleton-based action recognition has made great achievements in Computer Vision.A graph convolutional network(GCN)is effective for action recognition,modelling the human skeleton as a spatio-temporal ...In recent years,skeleton-based action recognition has made great achievements in Computer Vision.A graph convolutional network(GCN)is effective for action recognition,modelling the human skeleton as a spatio-temporal graph.Most GCNs define the graph topology by physical relations of the human joints.However,this predefined graph ignores the spatial relationship between non-adjacent joint pairs in special actions and the behavior dependence between joint pairs,resulting in a low recognition rate for specific actions with implicit correlation between joint pairs.In addition,existing methods ignore the trend correlation between adjacent frames within an action and context clues,leading to erroneous action recognition with similar poses.Therefore,this study proposes a learnable GCN based on behavior dependence,which considers implicit joint correlation by constructing a dynamic learnable graph with extraction of specific behavior dependence of joint pairs.By using the weight relationship between the joint pairs,an adaptive model is constructed.It also designs a self-attention module to obtain their inter-frame topological relationship for exploring the context of actions.Combining the shared topology and the multi-head self-attention map,the module obtains the context-based clue topology to update the dynamic graph convolution,achieving accurate recognition of different actions with similar poses.Detailed experiments on public datasets demonstrate that the proposed method achieves better results and realizes higher quality representation of actions under various evaluation protocols compared to state-of-the-art methods.展开更多
Regular exercise is a crucial aspect of daily life, as it enables individuals to stay physically active, lowers thelikelihood of developing illnesses, and enhances life expectancy. The recognition of workout actions i...Regular exercise is a crucial aspect of daily life, as it enables individuals to stay physically active, lowers thelikelihood of developing illnesses, and enhances life expectancy. The recognition of workout actions in videostreams holds significant importance in computer vision research, as it aims to enhance exercise adherence, enableinstant recognition, advance fitness tracking technologies, and optimize fitness routines. However, existing actiondatasets often lack diversity and specificity for workout actions, hindering the development of accurate recognitionmodels. To address this gap, the Workout Action Video dataset (WAVd) has been introduced as a significantcontribution. WAVd comprises a diverse collection of labeled workout action videos, meticulously curated toencompass various exercises performed by numerous individuals in different settings. This research proposes aninnovative framework based on the Attention driven Residual Deep Convolutional-Gated Recurrent Unit (ResDCGRU)network for workout action recognition in video streams. Unlike image-based action recognition, videoscontain spatio-temporal information, making the task more complex and challenging. While substantial progresshas been made in this area, challenges persist in detecting subtle and complex actions, handling occlusions,and managing the computational demands of deep learning approaches. The proposed ResDC-GRU Attentionmodel demonstrated exceptional classification performance with 95.81% accuracy in classifying workout actionvideos and also outperformed various state-of-the-art models. The method also yielded 81.6%, 97.2%, 95.6%, and93.2% accuracy on established benchmark datasets, namely HMDB51, Youtube Actions, UCF50, and UCF101,respectively, showcasing its superiority and robustness in action recognition. The findings suggest practicalimplications in real-world scenarios where precise video action recognition is paramount, addressing the persistingchallenges in the field. TheWAVd dataset serves as a catalyst for the development ofmore robust and effective fitnesstracking systems and ultimately promotes healthier lifestyles through improved exercise monitoring and analysis.展开更多
The reaction of cyanoacetylhydrazine 1 with furan-2-aldehyde 2 gives the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The ...The reaction of cyanoacetylhydrazine 1 with furan-2-aldehyde 2 gives the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were recorded. Some of the synthesized compounds show high inhibitory effects.展开更多
The reaction of cyanoacetylhydrazine with chloroacetone gave the N-(1-chloropropan-2-ylidene)-2-cyanoacetohy- drazide. This compound reacted with either hydrazine hydrate or phenylhydrazine to give the corresponding 1...The reaction of cyanoacetylhydrazine with chloroacetone gave the N-(1-chloropropan-2-ylidene)-2-cyanoacetohy- drazide. This compound reacted with either hydrazine hydrate or phenylhydrazine to give the corresponding 1,2,4-tri- azine derivatives. On the other hand, its reaction with either benzenediazonium chloride or benzaldehyde gave in each case the 1,3,4-oxadiazine derivatives. Moreover, the reaction of the cyanoacetylhydrazine with 2-boromocyclohexa- none gave the corresponding hydrazine-hydrozon derivative. The antitumor evaluation of the newly synthesized prod- ucts against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) was recorded. Some of the tested compounds showed activities which was higher than the reference doxorubicin.展开更多
The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with benzoylisothiocyanate (2) afforded the thiourea derivatives 3a,b. Cyclization of the latter products gave the annulated products 4a,b. Compounds 3a...The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with benzoylisothiocyanate (2) afforded the thiourea derivatives 3a,b. Cyclization of the latter products gave the annulated products 4a,b. Compounds 3a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 7a-d which underwent cyclization for compounds 7a,c afforded compound 9. On the other hand compounds 4a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 6a-d a second pathway was applied to synthesize compound 6c which underwent cyclization afforded compound 9. Also compounds 4a,b reacted with either phenacyl bromide (10) afforded compounds 11a,b or ethylchloroacetae (12) compounds 13a,b were produced. The latter products reacted with each hydrazine hydrate (5a) and phenyl hydrazine (5b) afforded compounds 14a-d. Their antitumor activities were tested using three different cell lines.展开更多
Electric power training is essential for ensuring the safety and reliability of the system.In this study,we introduce a novel Abnormal Action Recognition(AAR)system that utilizes a Lightweight Pose Estimation Network(...Electric power training is essential for ensuring the safety and reliability of the system.In this study,we introduce a novel Abnormal Action Recognition(AAR)system that utilizes a Lightweight Pose Estimation Network(LPEN)to efficiently and effectively detect abnormal fall-down and trespass incidents in electric power training scenarios.The LPEN network,comprising three stages—MobileNet,Initial Stage,and Refinement Stage—is employed to swiftly extract image features,detect human key points,and refine them for accurate analysis.Subsequently,a Pose-aware Action Analysis Module(PAAM)captures the positional coordinates of human skeletal points in each frame.Finally,an Abnormal Action Inference Module(AAIM)evaluates whether abnormal fall-down or unauthorized trespass behavior is occurring.For fall-down recognition,three criteria—falling speed,main angles of skeletal points,and the person’s bounding box—are considered.To identify unauthorized trespass,emphasis is placed on the position of the ankles.Extensive experiments validate the effectiveness and efficiency of the proposed system in ensuring the safety and reliability of electric power training.展开更多
We are writing in response to the article titled“Addressing the needs and rights of sex workers for HIV healthcare services in the Philippines”[1].The article calls for attention on the significant challenges faced ...We are writing in response to the article titled“Addressing the needs and rights of sex workers for HIV healthcare services in the Philippines”[1].The article calls for attention on the significant challenges faced by sex workers in the Philippines in accessing HIV healthcare.We appreciate the article’s effort to examine these issues in depth.We would like to present a constant flow of thoughts in this letter while highlighting the positive aspects,potential obstacles,and additional points that contribute to this ongoing discussion.展开更多
Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor imm...Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.展开更多
Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability an...Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.展开更多
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is...Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.展开更多
Laboratory safety is a critical area of broad societal concern,particularly in the detection of abnormal actions.To enhance the efficiency and accuracy of detecting such actions,this paper introduces a novel method ca...Laboratory safety is a critical area of broad societal concern,particularly in the detection of abnormal actions.To enhance the efficiency and accuracy of detecting such actions,this paper introduces a novel method called TubeRAPT(Tubelet Transformer based onAdapter and Prefix TrainingModule).Thismethod primarily comprises three key components:the TubeR network,an adaptive clustering attention mechanism,and a prefix training module.These components work in synergy to address the challenge of knowledge preservation in models pretrained on large datasets while maintaining training efficiency.The TubeR network serves as the backbone for spatio-temporal feature extraction,while the adaptive clustering attention mechanism refines the focus on relevant information.The prefix training module facilitates efficient fine-tuning and knowledge transfer.Experimental results demonstrate the effectiveness of TubeRAPT,achieving a 68.44%mean Average Precision(mAP)on the CLA(Crazy LabActivity)small-scale dataset,marking a significant improvement of 1.53%over the previous TubeR method.This research not only showcases the potential applications of TubeRAPT in the field of abnormal action detection but also offers innovative ideas and technical support for the future development of laboratory safety monitoring technologies.The proposed method has implications for improving safety management systems in various laboratory environments,potentially reducing accidents and enhancing overall workplace safety.展开更多
This study presents a general optimal trajectory planning(GOTP)framework for autonomous vehicles(AVs)that can effectively avoid obstacles and guide AVs to complete driving tasks safely and efficiently.Firstly,we emplo...This study presents a general optimal trajectory planning(GOTP)framework for autonomous vehicles(AVs)that can effectively avoid obstacles and guide AVs to complete driving tasks safely and efficiently.Firstly,we employ the fifth-order Bezier curve to generate and smooth the reference path along the road centerline.Cartesian coordinates are then transformed to achieve the curvature continuity of the generated curve.Considering the road constraints and vehicle dynamics,limited polynomial candidate trajectories are generated and smoothed in a curvilinear coordinate system.Furthermore,in selecting the optimal trajectory,we develop a unified and auto-tune objective function based on the principle of least action by employing AVs to simulate drivers’behavior and summarizing their manipulation characteristics of“seeking benefits and avoiding losses.”Finally,by integrating the idea of receding-horizon optimization,the proposed framework is achieved by considering dynamic multi-performance objectives and selecting trajectories that satisfy feasibility,optimality,and adaptability.Extensive simulations and experiments are performed,and the results demonstrate the framework’s feasibility and effectiveness,which avoids both dynamic and static obstacles and applies to various scenarios with multi-source interactive traffic participants.Moreover,we prove that the proposed method can guarantee real-time planning and safety requirements compared to drivers’manipulation.展开更多
Recognition of human gesture actions is a challenging issue due to the complex patterns in both visual andskeletal features. Existing gesture action recognition (GAR) methods typically analyze visual and skeletal data...Recognition of human gesture actions is a challenging issue due to the complex patterns in both visual andskeletal features. Existing gesture action recognition (GAR) methods typically analyze visual and skeletal data,failing to meet the demands of various scenarios. Furthermore, multi-modal approaches lack the versatility toefficiently process both uniformand disparate input patterns.Thus, in this paper, an attention-enhanced pseudo-3Dresidual model is proposed to address the GAR problem, called HgaNets. This model comprises two independentcomponents designed formodeling visual RGB (red, green and blue) images and 3Dskeletal heatmaps, respectively.More specifically, each component consists of two main parts: 1) a multi-dimensional attention module forcapturing important spatial, temporal and feature information in human gestures;2) a spatiotemporal convolutionmodule that utilizes pseudo-3D residual convolution to characterize spatiotemporal features of gestures. Then,the output weights of the two components are fused to generate the recognition results. Finally, we conductedexperiments on four datasets to assess the efficiency of the proposed model. The results show that the accuracy onfour datasets reaches 85.40%, 91.91%, 94.70%, and 95.30%, respectively, as well as the inference time is 0.54 s andthe parameters is 2.74M. These findings highlight that the proposed model outperforms other existing approachesin terms of recognition accuracy.展开更多
X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.Howev...X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.展开更多
Water decoupling charge blasting excels in rock breaking,relying on its uniform pressure transmission and low energy dissipation.The water decoupling coefficients can adjust the contributions of the stress wave and qu...Water decoupling charge blasting excels in rock breaking,relying on its uniform pressure transmission and low energy dissipation.The water decoupling coefficients can adjust the contributions of the stress wave and quasi-static pressure.However,the quantitative relationship between the two contributions is unclear,and it is difficult to provide reasonable theoretical support for the design of water decoupling blasting.In this study,a theoretical model of blasting fracturing partitioning is established.The mechanical mechanism and determination method of the optimal decoupling coefficient are obtained.The reliability is verified through model experiments and a field test.The results show that with the increasing of decoupling coefficient,the rock breaking ability of blasting dynamic action decreases,while quasi-static action increases and then decreases.The ability of quasi-static action to wedge into cracks changes due to the spatial adjustment of the blast hole and crushed zone.The quasi-static action plays a leading role in the fracturing range,determining an optimal decoupling coefficient.The optimal water decoupling coefficient is not a fixed value,which can be obtained by the proposed theoretical model.Compared with the theoretical results,the maximum error in the model experiment results is 8.03%,and the error in the field test result is 3.04%.展开更多
In traditional Chinese medicine(TCM),based on various pathogenic symptoms and the‘golden chamber’medical text,Huangdi Neijing,diabetes mellitus falls under the category‘collateral disease’.TCM,with its wealth of e...In traditional Chinese medicine(TCM),based on various pathogenic symptoms and the‘golden chamber’medical text,Huangdi Neijing,diabetes mellitus falls under the category‘collateral disease’.TCM,with its wealth of experience,has been treating diabetes for over two millennia.Different antidiabetic Chinese herbal medicines re-duce blood sugar,with their effective ingredients exerting unique advantages.As well as a glucose lowering effect,TCM also regulates bodily functions to prevent diabetes associated complications,with reduced side effects compared to western synthetic drugs.Chinese herbal medicine is usually composed of polysaccharides,saponins,al-kaloids,flavonoids,and terpenoids.These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion,enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals.These actions regulate glycolipid metabolism in the body,eventually achiev-ing the goal of normalizing blood glucose.Using different animal models,a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer.Nonetheless,there is a dearth of scientific data about the pharmacology,dose-effect relationship,and structure-activity relationship of TCM and its constituents.Further research into the efficacy,toxicity and mode of action of TCM,using different metabolic and molecular markers,is key to developing novel TCM antidiabetic formulations.展开更多
Oil leakages cause environmental pollution,economic losses,and even engineering safety accidents.In cold regions,researchers urgently investigate the movement of oil spill in soils exposed to freeze-thaw cycles.In thi...Oil leakages cause environmental pollution,economic losses,and even engineering safety accidents.In cold regions,researchers urgently investigate the movement of oil spill in soils exposed to freeze-thaw cycles.In this study,a series of laboratory model experiments were carried out on the migration of oil leakage under freeze-thaw action,and the distributions of the soil temperature,unfrozen water content,and displacement were analyzed.The results showed that under freeze-thaw action,liquid water in soils migrated to the freezing front and accumulated.After the pipe cracked,oil pollutants first gathered at one side of the leak hole,and then moved around.The pipe wall temperature affected the soil temperature field,and the thermal influence range below and transverse the pipe wall(35–40 cm)was larger than that above the pipe wall(8 cm)owing to the soil surface temperature.The leaked oil's temperature would make the temperature of the surrounding soil rise.Oil would inhibit the cooling of the soils.Besides,oil migration was significantly affected by the gravity and water flow patterns.The freeze-thaw action would affect the migration of the oil,which was mainly manifested as inhibiting the diffusion and movement of oil when soils were frozen.Unfrozen water transport caused by freeze-thaw cycles would also inhibit oil migration.The research results would provide a scientific reference for understanding the relationship between the movement of oil pollutants,water,and soil temperature,and for establishing a waterheat-mass transport model in frozen soils.展开更多
文摘Unsymmetrical bisacridines(UAs) are a novel potent class of antitumor-active therapeutics.A significant route of phase II drug metabolism is conjugation with glutathione(GSH),which can be non-enzymatic and/or catalyzed by GSH-dependent enzymes.The aim of this work was to investigate the GSHmediated metabolic pathway of a representative UA,C-2028.GSH-supplemented incubations of C-2028 with rat,but not with human,liver cytosol led to the formation of a single GSH-related metabolite.Interestingly,it was also revealed with rat liver microsomes.Its formation was NADPH-independent and was not inhibited by co-incubation with the cytochrome P450(CYP450) inhibitor 1-aminobenzotriazole.Therefore,the direct conjugation pathway occurred without the prior CYP450-catalyzed bioactivation of the substrate.In turn,incubations of C-2028 and GSH with human recombinant glutathione S-transferase(GST) P1-1 or with heat-/ethacrynic acid-inactivated liver cytosolic enzymes resulted in the presence or lack of GSH conjugated form,respectively.These findings proved the necessary participation of GST in the initial activation of the GSH thiol group to enable a nucleophilic attack on the substrate molecule.Another C-2028-GSH S-conjugate was also formed during non-enzymatic reaction.Both GSH S-conjugates were characterized by combined liquid chromatography/tandem mass spectrometry.Mechanisms for their formation were proposed.The ability of C-2028 to GST-mediated and/or direct GSH conjugation is suspected to be clinically important.This may affect the patient’s drug clearance due to GST activity,loss of GSH,or the interactions with GSH-conjugated drugs.Moreover,GST-mediated depletion of cellular GSH may increase tumor cell exposure to reactive products of UA metabolic transformations.
文摘The mechanisms of action on monofunctional guanine adducts of analogues of transplatin with aliphatic amine ligands,such as trans-[Pt(Am)(isopropylamine)(G)(H2O)] where Am represents dimethylamine,propylamine or isopropylamine and their cis isomers reacting with sulfur- and nitrogen-containing amino acid residues,were explored. Histidine and lysine residues are chosen as the model ligands of nitrogen-containing amino acid residues of proteins; meanwhile,methionine and cysteine residues are chosen as the model ligands of sulfur-containing amino acid residues of proteins. A dominating preference for sulfur-containing ligand over nitrogen-containing ligand is established. The calculated smallest activation barrier for sulfur-containing ligand is 9.9,and 21.1 kcal/mol for nitrogen-containing ligand in aqueous solution,and both of them have trans configurations. The difference in activation energy is 11.2 kcal/mol,indicating the platination of sulfur-containing amino acid residues is faster by seven to eight orders of magnitude than that of nitrogen-containing amino acid residues.
基金supported in part by the 2023 Key Supported Project of the 14th Five Year Plan for Education and Science in Hunan Province with No.ND230795.
文摘In recent years,skeleton-based action recognition has made great achievements in Computer Vision.A graph convolutional network(GCN)is effective for action recognition,modelling the human skeleton as a spatio-temporal graph.Most GCNs define the graph topology by physical relations of the human joints.However,this predefined graph ignores the spatial relationship between non-adjacent joint pairs in special actions and the behavior dependence between joint pairs,resulting in a low recognition rate for specific actions with implicit correlation between joint pairs.In addition,existing methods ignore the trend correlation between adjacent frames within an action and context clues,leading to erroneous action recognition with similar poses.Therefore,this study proposes a learnable GCN based on behavior dependence,which considers implicit joint correlation by constructing a dynamic learnable graph with extraction of specific behavior dependence of joint pairs.By using the weight relationship between the joint pairs,an adaptive model is constructed.It also designs a self-attention module to obtain their inter-frame topological relationship for exploring the context of actions.Combining the shared topology and the multi-head self-attention map,the module obtains the context-based clue topology to update the dynamic graph convolution,achieving accurate recognition of different actions with similar poses.Detailed experiments on public datasets demonstrate that the proposed method achieves better results and realizes higher quality representation of actions under various evaluation protocols compared to state-of-the-art methods.
文摘Regular exercise is a crucial aspect of daily life, as it enables individuals to stay physically active, lowers thelikelihood of developing illnesses, and enhances life expectancy. The recognition of workout actions in videostreams holds significant importance in computer vision research, as it aims to enhance exercise adherence, enableinstant recognition, advance fitness tracking technologies, and optimize fitness routines. However, existing actiondatasets often lack diversity and specificity for workout actions, hindering the development of accurate recognitionmodels. To address this gap, the Workout Action Video dataset (WAVd) has been introduced as a significantcontribution. WAVd comprises a diverse collection of labeled workout action videos, meticulously curated toencompass various exercises performed by numerous individuals in different settings. This research proposes aninnovative framework based on the Attention driven Residual Deep Convolutional-Gated Recurrent Unit (ResDCGRU)network for workout action recognition in video streams. Unlike image-based action recognition, videoscontain spatio-temporal information, making the task more complex and challenging. While substantial progresshas been made in this area, challenges persist in detecting subtle and complex actions, handling occlusions,and managing the computational demands of deep learning approaches. The proposed ResDC-GRU Attentionmodel demonstrated exceptional classification performance with 95.81% accuracy in classifying workout actionvideos and also outperformed various state-of-the-art models. The method also yielded 81.6%, 97.2%, 95.6%, and93.2% accuracy on established benchmark datasets, namely HMDB51, Youtube Actions, UCF50, and UCF101,respectively, showcasing its superiority and robustness in action recognition. The findings suggest practicalimplications in real-world scenarios where precise video action recognition is paramount, addressing the persistingchallenges in the field. TheWAVd dataset serves as a catalyst for the development ofmore robust and effective fitnesstracking systems and ultimately promotes healthier lifestyles through improved exercise monitoring and analysis.
文摘The reaction of cyanoacetylhydrazine 1 with furan-2-aldehyde 2 gives the hydrazide-hydrazone derivative 3. The latter compound undergoes a series of heterocyclization reactions to give new heterocyclic compounds. The antitumor evaluation of the newly synthesized products against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) were recorded. Some of the synthesized compounds show high inhibitory effects.
文摘The reaction of cyanoacetylhydrazine with chloroacetone gave the N-(1-chloropropan-2-ylidene)-2-cyanoacetohy- drazide. This compound reacted with either hydrazine hydrate or phenylhydrazine to give the corresponding 1,2,4-tri- azine derivatives. On the other hand, its reaction with either benzenediazonium chloride or benzaldehyde gave in each case the 1,3,4-oxadiazine derivatives. Moreover, the reaction of the cyanoacetylhydrazine with 2-boromocyclohexa- none gave the corresponding hydrazine-hydrozon derivative. The antitumor evaluation of the newly synthesized prod- ucts against three cancer cell lines, namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460) and CNS cancer (SF-268) was recorded. Some of the tested compounds showed activities which was higher than the reference doxorubicin.
文摘The reaction of the tetrahydrobenzo[b]thiophene derivatives 1a,b with benzoylisothiocyanate (2) afforded the thiourea derivatives 3a,b. Cyclization of the latter products gave the annulated products 4a,b. Compounds 3a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 7a-d which underwent cyclization for compounds 7a,c afforded compound 9. On the other hand compounds 4a,b reacted with either hydrazine hydrate (5a) or phenyl hydrazine (5b) afforded compounds 6a-d a second pathway was applied to synthesize compound 6c which underwent cyclization afforded compound 9. Also compounds 4a,b reacted with either phenacyl bromide (10) afforded compounds 11a,b or ethylchloroacetae (12) compounds 13a,b were produced. The latter products reacted with each hydrazine hydrate (5a) and phenyl hydrazine (5b) afforded compounds 14a-d. Their antitumor activities were tested using three different cell lines.
基金supportted by Natural Science Foundation of Jiangsu Province(No.BK20230696).
文摘Electric power training is essential for ensuring the safety and reliability of the system.In this study,we introduce a novel Abnormal Action Recognition(AAR)system that utilizes a Lightweight Pose Estimation Network(LPEN)to efficiently and effectively detect abnormal fall-down and trespass incidents in electric power training scenarios.The LPEN network,comprising three stages—MobileNet,Initial Stage,and Refinement Stage—is employed to swiftly extract image features,detect human key points,and refine them for accurate analysis.Subsequently,a Pose-aware Action Analysis Module(PAAM)captures the positional coordinates of human skeletal points in each frame.Finally,an Abnormal Action Inference Module(AAIM)evaluates whether abnormal fall-down or unauthorized trespass behavior is occurring.For fall-down recognition,three criteria—falling speed,main angles of skeletal points,and the person’s bounding box—are considered.To identify unauthorized trespass,emphasis is placed on the position of the ankles.Extensive experiments validate the effectiveness and efficiency of the proposed system in ensuring the safety and reliability of electric power training.
文摘We are writing in response to the article titled“Addressing the needs and rights of sex workers for HIV healthcare services in the Philippines”[1].The article calls for attention on the significant challenges faced by sex workers in the Philippines in accessing HIV healthcare.We appreciate the article’s effort to examine these issues in depth.We would like to present a constant flow of thoughts in this letter while highlighting the positive aspects,potential obstacles,and additional points that contribute to this ongoing discussion.
基金supported by the Startup Foundation for Junior Faculty,Nankai University(Grant No.:63191439)the National Natural Science Foundation of China(Grant Nos.:32100418,3210040345)+1 种基金The Health Commission Foundation of China(Grant No.:2018ZX10712001-017)the Chongqing Medical College Natural Fund(Grant Nos.:ygz2019302 and ygz2019305).
文摘Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.
基金supported by the National Natural Science Foundation of China(No.82272847,82202318,82304417,82303529)The Henan Province Fund for Cultivating Advantageous Disciplines(No.222301420012)+2 种基金Central Plains science and technology innovation leading talent project(No.234200510005)The project tackling of key scientific and technical problems of Henan Provine(No.232102311163)China Postdoctoral Science Foundation(2022TQ0310,2023TQ0307,2023M730971)。
文摘Bacterial-based antitumor immunity has become a promising strategy to activate the immune system for fighting cancer.However,the potential application of bacterial therapy is hindered by the presence of instability and susceptibility to infections within bacterial populations.Furthermore,monotherapy is ineffective in completely eliminating complex cancer with multiple contributing factors.In this study,based on our discovery that spore shell(SS)of Bacillus coagulans exhibits excellent tumor-targeting ability and adjuvant activity,we develop a biomimetic spore nanoplatform to boost bacteria-mediated antitumor therapy,chemodynamic therapy and antitumor immunity for synergistic cancer treatment.In detail,SS is separated from probiotic spores and then attached to the surface of liposome(Lipo)that was loaded with hemoglobin(Hb),glucose oxidase(GOx)and JQ1to construct SS@Lipo/Hb/GOx/JQ1.In tumor tissue,highly toxic hydroxyl radicals(·OH)are generated via sequential catalytic reactions:GOx catalyzing glucose into H_(2)O_(2)and Fe^(2+)in Hb decomposing H_(2)O_(2)into·OH.The combination of·OH and SS adjuvant can improve tumor immunogenicity and activate immune system.Meanwhile,JQ1-mediated down-regulation of PD-L1 and Hb-induced hypoxia alleviation synergistically reshape immunosuppressive tumor microenvironment and potentiate immune response.In this manner,SS@Lipo/Hb/GOx/JQ1 significantly suppresses tumor growth and metastasis.To summarize,the nanoplatform represents an optimum strategy to potentiate bacteria-based cancer immunotherapy.
文摘Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by cognitive impairments in the initial stage, which lead to severe cognitive dysfunction in the later stage. Action observation therapy (AOT) is a multisensory cognitive rehabilitation technique where the patient initially observes the actions and then tries to perform. The study aimed to examine the impact of AOT along with usual physiotherapy interventions to reduce depression, improve cognition and balance of a patient with AD. A 67 years old patient with AD was selected for this study because the patient has been suffering from depression, dementia, and physical dysfunction along with some other health conditions like diabetes and hypertension. Before starting intervention, a baseline assessment was done through the Beck Depression Inventory (BDI) tool, the Mini-Cog Scale, and the Berg Balance Scale (BBS). The patient received 12 sessions of AOT along with usual physiotherapy interventions thrice a week for four weeks, which included 45 minutes of each session. After four weeks of intervention, the patient demonstrated significant improvement in depression, cognition, and balance, whereas the BDI score declined from moderate 21/63 to mild 15/63 level of depression. The Mini-Cog score improved from 2/5 to 4/5, and the BBS score increased from 18/56 to 37/56. It is concluded that AOT along with usual physiotherapy intervention helps to reduce depression, improve cognition and balance of people with AD.
基金supported by the Philosophy and Social Sciences Planning Project of Guangdong Province of China(GD23XGL099)the Guangdong General Universities Young Innovative Talents Project(2023KQNCX247)the Research Project of Shanwei Institute of Technology(SWKT22-019).
文摘Laboratory safety is a critical area of broad societal concern,particularly in the detection of abnormal actions.To enhance the efficiency and accuracy of detecting such actions,this paper introduces a novel method called TubeRAPT(Tubelet Transformer based onAdapter and Prefix TrainingModule).Thismethod primarily comprises three key components:the TubeR network,an adaptive clustering attention mechanism,and a prefix training module.These components work in synergy to address the challenge of knowledge preservation in models pretrained on large datasets while maintaining training efficiency.The TubeR network serves as the backbone for spatio-temporal feature extraction,while the adaptive clustering attention mechanism refines the focus on relevant information.The prefix training module facilitates efficient fine-tuning and knowledge transfer.Experimental results demonstrate the effectiveness of TubeRAPT,achieving a 68.44%mean Average Precision(mAP)on the CLA(Crazy LabActivity)small-scale dataset,marking a significant improvement of 1.53%over the previous TubeR method.This research not only showcases the potential applications of TubeRAPT in the field of abnormal action detection but also offers innovative ideas and technical support for the future development of laboratory safety monitoring technologies.The proposed method has implications for improving safety management systems in various laboratory environments,potentially reducing accidents and enhancing overall workplace safety.
基金supported by the National Natural Science Foundation of China(the Key Project,52131201Science Fund for Creative Research Groups,52221005)+1 种基金the China Scholarship Councilthe Joint Laboratory for Internet of Vehicles,Ministry of Education–China MOBILE Communications Corporation。
文摘This study presents a general optimal trajectory planning(GOTP)framework for autonomous vehicles(AVs)that can effectively avoid obstacles and guide AVs to complete driving tasks safely and efficiently.Firstly,we employ the fifth-order Bezier curve to generate and smooth the reference path along the road centerline.Cartesian coordinates are then transformed to achieve the curvature continuity of the generated curve.Considering the road constraints and vehicle dynamics,limited polynomial candidate trajectories are generated and smoothed in a curvilinear coordinate system.Furthermore,in selecting the optimal trajectory,we develop a unified and auto-tune objective function based on the principle of least action by employing AVs to simulate drivers’behavior and summarizing their manipulation characteristics of“seeking benefits and avoiding losses.”Finally,by integrating the idea of receding-horizon optimization,the proposed framework is achieved by considering dynamic multi-performance objectives and selecting trajectories that satisfy feasibility,optimality,and adaptability.Extensive simulations and experiments are performed,and the results demonstrate the framework’s feasibility and effectiveness,which avoids both dynamic and static obstacles and applies to various scenarios with multi-source interactive traffic participants.Moreover,we prove that the proposed method can guarantee real-time planning and safety requirements compared to drivers’manipulation.
基金the National Natural Science Foundation of China under Grant No.62072255.
文摘Recognition of human gesture actions is a challenging issue due to the complex patterns in both visual andskeletal features. Existing gesture action recognition (GAR) methods typically analyze visual and skeletal data,failing to meet the demands of various scenarios. Furthermore, multi-modal approaches lack the versatility toefficiently process both uniformand disparate input patterns.Thus, in this paper, an attention-enhanced pseudo-3Dresidual model is proposed to address the GAR problem, called HgaNets. This model comprises two independentcomponents designed formodeling visual RGB (red, green and blue) images and 3Dskeletal heatmaps, respectively.More specifically, each component consists of two main parts: 1) a multi-dimensional attention module forcapturing important spatial, temporal and feature information in human gestures;2) a spatiotemporal convolutionmodule that utilizes pseudo-3D residual convolution to characterize spatiotemporal features of gestures. Then,the output weights of the two components are fused to generate the recognition results. Finally, we conductedexperiments on four datasets to assess the efficiency of the proposed model. The results show that the accuracy onfour datasets reaches 85.40%, 91.91%, 94.70%, and 95.30%, respectively, as well as the inference time is 0.54 s andthe parameters is 2.74M. These findings highlight that the proposed model outperforms other existing approachesin terms of recognition accuracy.
基金funded by the National Natural Science Foundation of China (Nos.81771972,52171243,and 52371256)the National Key Research and Development Program of China (No.2017YFC0107405).
文摘X-ray excited photodynamic therapy(X-PDT)is the bravo answer of photodynamic therapy(PDT)for deep-seated tumors,as it employs X-ray as the irradiation source to overcome the limitation of light penetration depth.However,high X-ray irradiation dose caused organ lesions and side effects became the major barrier to X-PDT application.To address this issue,this work employed a classic-al co-precipitation reaction to synthesize NaLuF_(4):15%Tb^(3+)(NLF)with an average particle size of(23.48±0.91)nm,which was then coupled with the photosensitizer merocyanine 540(MC540)to form the X-PDT system NLF-MC540 with high production of singlet oxygen.The system could induce antitumor efficacy to about 24%in relative low dose X-ray irradiation range(0.1-0.3 Gy).In vivo,when NLF-MC540 irradiated by 0.1 Gy X-ray,the tumor inhibition percentage reached 89.5%±5.7%.The therapeutic mechanism of low dose X-PDT was found.A significant increase of neutrophils in serum was found on the third day after X-PDT.By immunohistochemical staining of tumor sections,the Ly6G^(+),CD8^(+),and CD11c^(+)cells infiltrated in the tumor microenvironment were studied.Utilizing the bilat-eral tumor model,the NLF-MC540 with 0.1 Gy X-ray irradiation could inhibit both the primary tumor and the distant tumor growth.De-tected by enzyme linked immunosorbent assay(ELISA),two cytokines IFN-γand TNF-αin serum were upregulated 7 and 6 times than negative control,respectively.Detected by enzyme linked immune spot assay(ELISPOT),the number of immune cells attributable to the IFN-γand TNF-αlevels in the group of low dose X-PDT were 14 and 6 times greater than that in the negative control group,respectively.Thus,it conclude that low dose X-PDT system could successfully upregulate the levels of immune cells,stimulate the secretion of cy-tokines(especially IFN-γand TNF-α),activate antitumor immunity,and finally inhibit colon tumor growth.
基金funded by the National Natural Science Foundation of China(No.42372331)the Henan Excellent Youth Science Fund Project(No.242300421145)the Colleges and Universities Youth and Innovation Science and Technology Support Plan of Shandong Province(No.2021KJ024).
文摘Water decoupling charge blasting excels in rock breaking,relying on its uniform pressure transmission and low energy dissipation.The water decoupling coefficients can adjust the contributions of the stress wave and quasi-static pressure.However,the quantitative relationship between the two contributions is unclear,and it is difficult to provide reasonable theoretical support for the design of water decoupling blasting.In this study,a theoretical model of blasting fracturing partitioning is established.The mechanical mechanism and determination method of the optimal decoupling coefficient are obtained.The reliability is verified through model experiments and a field test.The results show that with the increasing of decoupling coefficient,the rock breaking ability of blasting dynamic action decreases,while quasi-static action increases and then decreases.The ability of quasi-static action to wedge into cracks changes due to the spatial adjustment of the blast hole and crushed zone.The quasi-static action plays a leading role in the fracturing range,determining an optimal decoupling coefficient.The optimal water decoupling coefficient is not a fixed value,which can be obtained by the proposed theoretical model.Compared with the theoretical results,the maximum error in the model experiment results is 8.03%,and the error in the field test result is 3.04%.
基金the National Key Research and Development Program of China,Grant/Award Number:2021YFD1600100 and 2022YFD1600303。
文摘In traditional Chinese medicine(TCM),based on various pathogenic symptoms and the‘golden chamber’medical text,Huangdi Neijing,diabetes mellitus falls under the category‘collateral disease’.TCM,with its wealth of experience,has been treating diabetes for over two millennia.Different antidiabetic Chinese herbal medicines re-duce blood sugar,with their effective ingredients exerting unique advantages.As well as a glucose lowering effect,TCM also regulates bodily functions to prevent diabetes associated complications,with reduced side effects compared to western synthetic drugs.Chinese herbal medicine is usually composed of polysaccharides,saponins,al-kaloids,flavonoids,and terpenoids.These active ingredients reduce blood sugar via various mechanism of actions that include boosting endogenous insulin secretion,enhancing insulin sensitivity and adjusting key enzyme activity and scavenging free radicals.These actions regulate glycolipid metabolism in the body,eventually achiev-ing the goal of normalizing blood glucose.Using different animal models,a number of molecular markers are available for the detection of diabetes induction and the molecular pathology of the disease is becoming clearer.Nonetheless,there is a dearth of scientific data about the pharmacology,dose-effect relationship,and structure-activity relationship of TCM and its constituents.Further research into the efficacy,toxicity and mode of action of TCM,using different metabolic and molecular markers,is key to developing novel TCM antidiabetic formulations.
基金the Science and Technology program of Gansu Province(Grant No.23ZDFA017)the National Natural Science Foundation of China(Grant Nos.U21A2012,42101136)the Program for Top Leading Talents of Gansu Province(Granted to Dr.MingYi Zhang).
文摘Oil leakages cause environmental pollution,economic losses,and even engineering safety accidents.In cold regions,researchers urgently investigate the movement of oil spill in soils exposed to freeze-thaw cycles.In this study,a series of laboratory model experiments were carried out on the migration of oil leakage under freeze-thaw action,and the distributions of the soil temperature,unfrozen water content,and displacement were analyzed.The results showed that under freeze-thaw action,liquid water in soils migrated to the freezing front and accumulated.After the pipe cracked,oil pollutants first gathered at one side of the leak hole,and then moved around.The pipe wall temperature affected the soil temperature field,and the thermal influence range below and transverse the pipe wall(35–40 cm)was larger than that above the pipe wall(8 cm)owing to the soil surface temperature.The leaked oil's temperature would make the temperature of the surrounding soil rise.Oil would inhibit the cooling of the soils.Besides,oil migration was significantly affected by the gravity and water flow patterns.The freeze-thaw action would affect the migration of the oil,which was mainly manifested as inhibiting the diffusion and movement of oil when soils were frozen.Unfrozen water transport caused by freeze-thaw cycles would also inhibit oil migration.The research results would provide a scientific reference for understanding the relationship between the movement of oil pollutants,water,and soil temperature,and for establishing a waterheat-mass transport model in frozen soils.