The fabrication of heterojunction catalysts is an effective strategy to enhance charge separation efficiency,thereby boosting the performance of photocatalysts.In this study,BiO_(2-x)nanosheets were synthesized throug...The fabrication of heterojunction catalysts is an effective strategy to enhance charge separation efficiency,thereby boosting the performance of photocatalysts.In this study,BiO_(2-x)nanosheets were synthesized through a hydrothermal process and loaded onto NaNbO_(3) microcube to construct a series of BiO_(2-x)/NaNbO_(3) heterojunctions for photocatalytic N_(2) fixation.Results indicated that 2.5%BiO_(2-x)/NaNbO_(3) had the highest photocatalytic performance.The NH_(3) production rate under simulated solar light reached 406.4μmol·L^(-1)·g^(-1)·h^(-1),which reaches 2.6 and 3.8 times that of NaNbO_(3) and BiO_(2-x),respectively.BiO_(2-x)nanosheets primarily act as electron trappers to enhance the separation efficiency of charge carriers.The strong interaction between BiO_(2-x)and NaNbO_(3) facilitates the electron migration between them.Meanwhile,the abundant oxygen vacancies in BiO_(2-x)nanosheets may facilitate the adsorption and activation of N_(2),which may be another possible reason of the high photocatalytic activity of the BiO_(2-x)/NaNbO_(3).This study may offer new insights for the development of semiconductor materials in photocatalytic nitrogen fixation.展开更多
With continually increasing urbanization,the land cover in urban areas continues to change,resulting in the loss of biodiversity.Birds are highly sensitive to changes in habitat.Most forest birds perch on plants that ...With continually increasing urbanization,the land cover in urban areas continues to change,resulting in the loss of biodiversity.Birds are highly sensitive to changes in habitat.Most forest birds perch on plants that provide increased safety to reduce the risk of predation,and small birds may also consider insulation when using roosting plants in winter because of cold weather.Landscaping plants thus shape the nocturnal roosting environment of urban birds,and proper planting is essential for the survival of birds at night.The use of roosting plants by urban birds should therefore be studied to provide a reference for landscaping.In the current study,we observed 1865 nocturnal roosting birds in Beijing from 2021 to 2022,with 23 species of birds from 12 families and 45 species of plants from 22 families recorded.Juniperus chinensis exhibited the highest bird rarity-weighted richness,followed by Fraxinus pennsylvanica,Phyllostachys propinqua,Pinus tabuliformis,and Ulmus pumila.The diameter at breast height,tree height,and crown width of plants used by birds was largest in summer and smallest in winter,and the perch height of birds was the highest in spring and summer and the lowest in winter.Birds used the highest proportion of deciduous plants in summer and the highest proportion of evergreen plants in winter.A significant seasonal difference in the use of evergreen and deciduous plants by small birds was noted,with a preference for deciduous plants in summer and evergreen plants in winter,while this preference was not found in large birds.These findings indicate that evergreen plants provide a vital nocturnal roosting environment for small birds in winter.To provide a better nocturnal roosting habitat for urban birds,we recommend paying attention to the combination of evergreen and deciduous plants when carrying out landscape construction.展开更多
In this work, a novel heterojunction composite Ag_(2)S/KTa_(x)Nb_(1-x)O_(3)was designed and synthesized through a combination of hydrothermal and precipitation procedures. The Ta/Nb ratio of the KTa_(x)Nb_(1-x)O_(3)an...In this work, a novel heterojunction composite Ag_(2)S/KTa_(x)Nb_(1-x)O_(3)was designed and synthesized through a combination of hydrothermal and precipitation procedures. The Ta/Nb ratio of the KTa_(x)Nb_(1-x)O_(3)and the Ag_(2)S content were optimized. The best 0.5% Ag_(2)S/KTa_(0.5)Nb_(0.5)O_(3)(KTN) sample presents an enhanced photocatalytic performance in ammonia synthesis than KTN and Ag_(2)S. Under simulated sunlight, the NH_(3)generation rate of 0.5% Ag_(2)S/KTN reaches 2.0 times that of pure KTN. Under visible light, the reaction rate ratio of the two catalysts is 6.0.XRD, XPS, and TEM analysis revealed that Ag2S was intimately decorated on the KTN nanocubes surface, which promoted the electron transfer between the two semiconductors. The band structure investigation indicated that the Ag_(2)S/KTN heterojunction established a type-Ⅱ band alignment with intimate contact, thus realizing the effective transfer and separation of photogenerated carriers. The change in charge separation was considered as the main reason for the enhanced photocatalytic performance. Interestingly, the Ag_(2)S/KTN composite exhibited higher NH3generation performance under the combined action of ultrasonic vibration and simulated sunlight. The enhanced piezo-photocatalytic performance can be ascribed that the piezoelectric effect of KTN improved the bulk separation of charge carriers in KTN. This study not only provides a potential catalyst for photocatalytic nitrogen fixation but also shows new ideas for the design of highly efficient catalysts via semiconductor modification and external field coupling.展开更多
As a widespread emerging contaminant,chloramphenicol(CAP)adversely impacts ecological communities in the water environment.Biological treatment is widely used for aquatic pollutant removal,and the performance of funct...As a widespread emerging contaminant,chloramphenicol(CAP)adversely impacts ecological communities in the water environment.Biological treatment is widely used for aquatic pollutant removal,and the performance of functional microbes determines its outcome.Herein,a consortium with a powerful CAPdegrading capacity was domesticated from activated sludge.As the common degradation products of CAP,4-nitrobenzoic acid(PNB)and 2,2-dichloroacetic acid(DCA)were also used as the sole substrates for long-term domestication.The successional pattern of the microbial community and critical functional genes through the 2.5-year domestication was revealed by metagenomic analysis.Sphingomonas,Caballeronia,and Cupriavidus became the most dominant populations in the CAP-,PNB-,and DCAdegrading consortia,respectively,and they were crucial degraders of PNB and DCA.Their collaboration contributed to the high mineralization rate of CAP.PNB was transformed into protocatechuic acid(PCA)and then mineralized through meta-cleavage and ortho-cleavage pathways.Crucial functional genes involved in CAP,PNB,and DCA metabolism,including CAP acetyltransferase,CAP oxidoreductase,haloacid dehalogenases,and protocatechuate dioxygenases,were significantly enriched in consortia.p H and carbon source had significant impacts on CAP biodegradation efficiency.The domesticated consortia and isolated strains are necessary microbial resources to enhance the bioremediation of CAP-,PNB-,or DCA-polluted environments.展开更多
Geopolymer is a new alternative cement binder to produce concrete.In the present study,a novel geopolymer composites containing bamboo shaving(0–2 wt.%)were fabricated and exposed to the temperatures of 200℃,400℃,...Geopolymer is a new alternative cement binder to produce concrete.In the present study,a novel geopolymer composites containing bamboo shaving(0–2 wt.%)were fabricated and exposed to the temperatures of 200℃,400℃,600℃and 800℃.Physical properties,micro-structure,and mechanical strengths of the geopolymer composites were evaluated before and after heating in order to understand their thermal properties,which are essential for the use as building materials.As the temperature rises,the drying shrinkage and apparent porosity of the composites increase,while the compressive and bending strengths decrease.At the temperature range of 200℃–800℃,the residual compressive strength rates of the geopolymer composite containning 2 wt.%bamboo shaving were respective 73.8%,61.47%,56.16%,and 29.56%,meanwhile,the residual flexural strength rates were respective 46.69%,8.68%,2.52%,and 2.33%.Correspondingly,the residual compressive strength rates of pure geopolymer were respective 72.81%,61.99%,54.55%,and 14.64%;the residual flexural strength rates were 48.87%,5.69%,3.22%,and 2.47%,respectively.Scanning electron microscope(SEM),optical microscope,and X-ray diffractometry(XRD)were applied to find the microscopic changes.The strength loss in the geopolymer composites was mainly because of the thermal degradation of bamboo shaving and shrinkage of geopolymer matrix.Bamboo shaving has great potential as reinforcer in developing low-cost geopolymer composites and may be used for applications up to 400℃.展开更多
The communication system of high-speed trains in railway tunnels needs to be built with leaky cables fixed on the tunnel wall with special fixtures.To ensure safety,checking the regular leaky cable fixture is necessar...The communication system of high-speed trains in railway tunnels needs to be built with leaky cables fixed on the tunnel wall with special fixtures.To ensure safety,checking the regular leaky cable fixture is necessary to elimi-nate the potential danger.At present,the existing fixture detection algorithms are difficult to take into account detection accuracy and speed at the same time.The faulty fixture is also insufficient and difficult to obtain,seriously affecting the model detection effect.To solve these problems,an innovative detection method is proposed in this paper.Firstly,we presented the Res-Net and Wasserstein-Deep Convolution GAN(RW-DCGAN)to implement data augmentation,which can enable the faulty fixture to export more high-quality and irregular images.Secondly,we proposed the Ghost SENet-YOLOv5(GS-YOLOv5)to enhance the expression of fixture feature,and further improve the detection accuracy and speed.Finally,we adopted the model compression strategy to prune redundant channels,and visualized training details with Grad-CAM to verify the reliability of our model.Experimental results show that the algorithm model is 69.06%smaller than the original YOLOv5 model,with 70.07%fewer parameters,2.1%higher accuracy and 14.82 fps faster speed,meeting the needs of tunnel fixture detection.展开更多
With the vigorous development of national infrastructure construction and public information construction,video surveillance systems have gradually penetrated various fields.The current key frame extraction technology...With the vigorous development of national infrastructure construction and public information construction,video surveillance systems have gradually penetrated various fields.The current key frame extraction technology has inadequate target details and inaccurate judgment of local actions.Addressing this problem,a key frame extraction method based on fractional Fourier transform is proposed.This method obtained the phase spectra information of different orders by performing fractional Fourier transform on the surveillance video frames.Next,the method designed an adaptive algorithm based on the golden section point to select the transformation order.Then,the phase spectrum information of two adjacent frames was used to characterize the changes in the global and local motion states of the target.The final step was to extract key frames based on this.Experimental results show that,compared with the previous methods,the key frames extracted by the method proposed in this paper can correctly capture the changes in the global and local motion states of the target.展开更多
Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture of southwestern Guizhou have a long well-conserved history.These markets,which are a feature of Buyi and Miao traditional medici...Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture of southwestern Guizhou have a long well-conserved history.These markets,which are a feature of Buyi and Miao traditional medicines,contain a rich diversity of medicinal plants and traditional medical knowledge.Today,people in southwestern Guizhou still believe that using herbs during the Dragon Boat Festival prevents and can treat disease.In this study,we identified the fresh herbal plants sold at the herbal markets of Xingren City and Zhenfeng County in Qianxinan Buyi and Miao Autonomous Prefecture and quantified their importance.We identified 141 plant species(belonging to 114 genera and 61 families).The plant family with the most species was Asteraceae(14 species).Informants reported that most medicinal plants are herbaceous,with 95.7%of plants used for decoction and 30.5%used for medicinal baths.Medicinal plants are most commonly used to treat rheumatism,injury,and abdominal diseases.The utilization frequency index and relative importance values indicated that Artemisia argyi and Acorus calamus are the most important plants sold at herbal markets during the Dragon Boat Festival.The price of medicinal materials sold in the market may serve as an indicator of the conservation status of species in the region.These findings indicate that the Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture fully embodies the characteristics of indigenous ethnomedicine and culture,and also exhibits the diversity of plant resources.We recommend that rare and endangered plants in this region be domesticated and protected.展开更多
The multidrug and toxic compound extrusion(MATE) family plays pivotal roles in the detoxification process in plants, while no information has been provided for this gene family in melon(Cucumis melo L.) thus far, limi...The multidrug and toxic compound extrusion(MATE) family plays pivotal roles in the detoxification process in plants, while no information has been provided for this gene family in melon(Cucumis melo L.) thus far, limiting our understanding of its functions in melon acclimation to stressful environments. In this study, a total of 39 MATEs(CmMATE1–CmMATE39) were observed in the melon genome;these were unevenly distributed in all chromosomes, with the most on Chromosome 1. Based on their orthologous relationship with those from Arabidopsis, rice, and sorghum, melon MATEs were clustered into three subfamilies of Clades Ⅰ, Ⅱ, and Ⅲ, wherein 23, 9, and 7 members were included, respectively.Variable exon number was observed in CmMATEs, and the most were harbored by CmMATE8. Gene ontology(GO) term and cis-regulatory element(CRE) analyses pointed to the potential roles of CmMATEs in both the regulation of melon development and acclimation to various abiotic and biotic stressors. The RNA-seq and qRT-PCR(quantitative real-time PCR) results demonstrated that under normal growth conditions, CmMATEs were expressed in a tissue-and development-specific manner, while their abundance apparently varied in a stress-dependent manner when melon plants were exposed to unfavorable environmental conditions. Altogether, these observations could expand our knowledge about the plant MATE family and benefit functional genomics analysis for CmMATEs in the future.展开更多
Geopolymers are inorganic aluminosilicate materials,which have been a great research interest as a material for sustainable development.However,they possess relatively low toughness properties similar to brittle solid...Geopolymers are inorganic aluminosilicate materials,which have been a great research interest as a material for sustainable development.However,they possess relatively low toughness properties similar to brittle solids.The limitation may be altered by fiber reinforcement to improve their strength and toughness.This research describes the synthesis of bamboo shaving(BS)reinforced geopolymer composites and the characterization of their mechanical properties.The effect of BS content(0–2 wt.%)on the physical and mechanical properties and microstructure of metakaolin based geopolymer paste were investigated.The workability,setting time,bulk density,apparent porosity,thermal conductivity,compressive strength,flexural strength,scanning electron microscopy(SEM),and X-ray diffraction(XRD)of geopolymer paste were determined.The results showed that the workability,setting time,density,and thermal conductivity decreased with the increasing of BS content.The BS content was proportional to the apparent porosity and a good linear relation was found between apparent porosity and BS content.The highest mechanical properties were achieved at an optimum BS content of 1.0 wt.%.The results of microstructural analysis revealed that BS act as inforcing phase in matrix,reducing cracks and making a dense geopolymer,which leads to favorable adhesion of the composites and produces a geopolymer composite with better mechanical properties than that of pure geopolymer.However,when the BS content exceeded 1.0 wt.%,interfacial bonding between BS and geopolymer matrix became less.XRD analysis showed that BS has little effect on the mineral composition of metakaolin-based geopolymer and no new phase is formed.展开更多
Objective:The aim of the study was to investigate the diagnostic value of fine needle aspiration cytology (FNAC) and its clinical application.Methods:From April 2009 to February 2011,thyroid FNAC were performed in a t...Objective:The aim of the study was to investigate the diagnostic value of fine needle aspiration cytology (FNAC) and its clinical application.Methods:From April 2009 to February 2011,thyroid FNAC were performed in a total of 186 patients with thyroid nodule or mass in our hospital and 78 of those 186 patients subsequently underwent thyroidectomy.The FNAC findings were compared with the results of the corresponding histological diagnosis.Results:The results of thyroid FNAC for 186 patients showed that,(1) 166 cases of benign lesions,the detection rate was 89.24% (166/186),including 96 cases of nodular colloid goiter (51.61%),28 cases of simple colloid goiter (15.05%),38 cases of Hashimoto's thyroiditis (HT) (20.43%) and 4 cases of thyroid adenoma (2.15%);(2) 4 cases of suspicious malignant lesion,the detection rate was 2.15% (4/186);(3) 16 cases of malignant tumor,the detection rate was 8.60% (16/186).Seventy eight patients including malignant (16),suspicious malignant (4),HT (20) and nodular colloid goiters (38) cases diagnosed by FNAC were performed operation with thyroidectomy and the postoperative histopathologic results showed that there were 2 cases HT combined thyroid papillary carcinoma in HT 20 cases by FNAC,15 cases of thyroid papillary carcinoma and 1 case of follicular carcinoma in 16 cases of malignant tumor by FNAC and 4 case of thyroid papillary carcinoma in 4 cases of suspicious malignant by FNAC.Conclusion:Thyroid FNAC is a valuable and reliable method for the diagnosis of the thyroid nodules or mass or even most diffuse thyroid diseases.Diagnosis of HT and thyroid papillary carcinoma can be made by thyroid FNAC.There was larger hint value for nodular colloid goiter and simple colloid goiter according to thyroid FNAC.展开更多
In recent years,pedestrian detection is a hot research topic in the field of computer vision and artificial intelligence,it is widely used in the field of security and pedestrian analysis.However,due to a large amount...In recent years,pedestrian detection is a hot research topic in the field of computer vision and artificial intelligence,it is widely used in the field of security and pedestrian analysis.However,due to a large amount of calculation in the traditional pedestrian detection technology,the speed of many systems for pedestrian recognition is very limited.But in some restricted areas,such as construction hazardous areas,real-time detection of pedestrians and cross-border behaviors is required.To more conveniently and efficiently detect whether there are pedestrians in the restricted area and cross-border behavior,this paper proposes a pedestrian cross-border detection method based on HOG(Histogram of Oriented Gradient)and SVM(Support Vector Machine).This method extracts the moving target through the GMM(Gaussian Mixture Model)background modeling and then extracts the characteristics of the moving target through gradient HOG.Finally,it uses SVM training to distinguish pedestrians from non-pedestrians,completes the detection of pedestrians,and labels the targets.The test results show that only the HOG feature extraction of the candidate area can greatly reduce the amount of calculation and reduce the time of feature extraction,eliminate background interference,thereby improving the efficiency of detection,and can be applied to occasions with real-time requirements.展开更多
The patient is a 37-year-old male with a right anterior tibial mass for more than one year and a left anterior tibial mass for more than one month.There was a history of hyperthyroidism.Histopathology of the lesions s...The patient is a 37-year-old male with a right anterior tibial mass for more than one year and a left anterior tibial mass for more than one month.There was a history of hyperthyroidism.Histopathology of the lesions showed epidermal hyperkeratosis of the skin tissue,thickening of the spinous layer,extensive collagen fibrillation in the superficial dermis and reticular layer,and numerous linear and granular mucoprotein deposits in the lower and middle dermis.Blastocystis hominis was routinely detected in the stool.Diagnosis:1.Pretibial myxedema 2.intestinal parasitosis(Blastocystis hominis infection).展开更多
Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma(HNSCC).The integrative analysis of all the metabolismrelated gene...Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma(HNSCC).The integrative analysis of all the metabolismrelated genes(MRGs)in HNSCC is lacking and the interaction between the metabolism and the immune characteristics also requires more exploration to uncover the potential mechanisms.Therefore,this study was designed to establish a prognostic signature based on all the MRGs in HNSCC.Genes of HNSCC samples were available from the TCGA and GEO databases while the MRGs were retrieved from a previous study.Ultimately 4 prognostic MRGs were selected to construct a model possessing robust prognostic value and accuracy in TCGA cohorts.The favorable reproducibility of this model was confirmed in validation cohorts from GEO databases.The risk score calculated by this model was an independent prognostic factor that further classified these HNSCC patients into high-/low-risk groups.GSEA analyses and somatic mutations indicated the low-risk group could activate several anti-tumor pathways and possessed lower TP53 mutation.The results of ESTIMATE,single-sample GSEA,CIBERSORT,and some immune-related molecules analyses suggested the low-risk group exhibited lower metabolic activities and higher immune characteristics.The Spearman correlation test implied most metabolic pathways with tumor-promoting function were negatively correlated with the immune activity,indicating a plausible approach of combining the anti-metabolism and the immunotherapy drugs in the high-risk group to enhance therapeutic effects than applied separately.In conclusion,this prognostic signature linking MRGs with the immune landscape could promote the individualized treatment for HNSCC patients.展开更多
With the explosive growth of surveillance video data,browsing videos quickly and effectively has become an urgent problem.Video key frame extraction has received widespread attention as an effective solution.However,a...With the explosive growth of surveillance video data,browsing videos quickly and effectively has become an urgent problem.Video key frame extraction has received widespread attention as an effective solution.However,accurately capturing the local motion state changes of moving objects in the video is still challenging in key frame extraction.The target center offset can reflect the change of its motion state.This observation proposed a novel key frame extraction method based on moving objects center offset in this paper.The proposed method utilizes the center offset to obtain the global and local motion state information of moving objects,and meanwhile,selects the video frame where the center offset curve changes suddenly as the key frame.Such processing effectively overcomes the inaccuracy of traditional key frame extraction methods.Initially,extracting the center point of each frame.Subsequently,calculating the center point offset of each frame and forming the center offset curve by connecting the center offset of each frame.Finally,extracting candidate key frames and optimizing them to generate final key frames.The experimental results demonstrate that the proposed method outperforms contrast methods to capturing the local motion state changes of moving objects.展开更多
In the field of educational examination,automatic marking technology plays an essential role in improving the efficiency of marking and liberating the labor force.At present,the implementation of the policy of expandi...In the field of educational examination,automatic marking technology plays an essential role in improving the efficiency of marking and liberating the labor force.At present,the implementation of the policy of expanding erolments has caused a serious decline in the teacher-student ratio in colleges and universities.The traditional marking system based on Optical Mark Reader technology can no longer meet the requirements of liberating the labor force of teachers in small and medium-sized examinations.With the development of image processing and artificial neural network technology,the recognition of handwritten character in the field of pattern recognition has attracted the attention of many researchers.In this paper,filtering and de-noise processing and binary processing are used as preprocessing methods for handwriting recognition.Extract the pixel feature of handwritten characters through digital image processing of handwritten character pictures,and then,get the feature vector from these feature fragments and use it as the description of the character.The extracted feature values are used to train the neural network to realize the recognition of handwritten English letters and numerical characters.Experimental results on Chars74K and MNIST data sets show that the recognition accuracy of some handwritten English letters and numerical characters can reach 90%and 99%,respectively.展开更多
Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer.Herein,a series of adenosine-containing derivatives were identified with DOT1LR231Q i...Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer.Herein,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell.The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar concentrations.The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays.In the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in rats.Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway.Moreover,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.展开更多
Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is ...Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.展开更多
Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer agents.Unlike traditiona...Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer agents.Unlike traditional drugs composed of non-replicating compounds or biomolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further studies.Despite some pharmacokinetics studies of OVs,mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague.Here,we characterized the pharmacokinetic profile of oncolytic virus M1(OVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of OVM pharmacokinetics.By suppressing the JAK-STAT pathway,early OVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor efficacy.Rather than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade,such as anti-PD-L1.Taken together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.展开更多
基金financially supported by the National Natural Science Foundation of China(22172144)Key Research and Development Program of Zhejiang Province(2023C03148)。
文摘The fabrication of heterojunction catalysts is an effective strategy to enhance charge separation efficiency,thereby boosting the performance of photocatalysts.In this study,BiO_(2-x)nanosheets were synthesized through a hydrothermal process and loaded onto NaNbO_(3) microcube to construct a series of BiO_(2-x)/NaNbO_(3) heterojunctions for photocatalytic N_(2) fixation.Results indicated that 2.5%BiO_(2-x)/NaNbO_(3) had the highest photocatalytic performance.The NH_(3) production rate under simulated solar light reached 406.4μmol·L^(-1)·g^(-1)·h^(-1),which reaches 2.6 and 3.8 times that of NaNbO_(3) and BiO_(2-x),respectively.BiO_(2-x)nanosheets primarily act as electron trappers to enhance the separation efficiency of charge carriers.The strong interaction between BiO_(2-x)and NaNbO_(3) facilitates the electron migration between them.Meanwhile,the abundant oxygen vacancies in BiO_(2-x)nanosheets may facilitate the adsorption and activation of N_(2),which may be another possible reason of the high photocatalytic activity of the BiO_(2-x)/NaNbO_(3).This study may offer new insights for the development of semiconductor materials in photocatalytic nitrogen fixation.
基金supported by the Beijing Municipal Commission of Science and Technology(No.D171100007217002).
文摘With continually increasing urbanization,the land cover in urban areas continues to change,resulting in the loss of biodiversity.Birds are highly sensitive to changes in habitat.Most forest birds perch on plants that provide increased safety to reduce the risk of predation,and small birds may also consider insulation when using roosting plants in winter because of cold weather.Landscaping plants thus shape the nocturnal roosting environment of urban birds,and proper planting is essential for the survival of birds at night.The use of roosting plants by urban birds should therefore be studied to provide a reference for landscaping.In the current study,we observed 1865 nocturnal roosting birds in Beijing from 2021 to 2022,with 23 species of birds from 12 families and 45 species of plants from 22 families recorded.Juniperus chinensis exhibited the highest bird rarity-weighted richness,followed by Fraxinus pennsylvanica,Phyllostachys propinqua,Pinus tabuliformis,and Ulmus pumila.The diameter at breast height,tree height,and crown width of plants used by birds was largest in summer and smallest in winter,and the perch height of birds was the highest in spring and summer and the lowest in winter.Birds used the highest proportion of deciduous plants in summer and the highest proportion of evergreen plants in winter.A significant seasonal difference in the use of evergreen and deciduous plants by small birds was noted,with a preference for deciduous plants in summer and evergreen plants in winter,while this preference was not found in large birds.These findings indicate that evergreen plants provide a vital nocturnal roosting environment for small birds in winter.To provide a better nocturnal roosting habitat for urban birds,we recommend paying attention to the combination of evergreen and deciduous plants when carrying out landscape construction.
基金financially supported by National Natural Science Foundation of China (Grant No. 22172144)Nature Science Foundation of Zhejiang Province (Grant No. LY20B030004)。
文摘In this work, a novel heterojunction composite Ag_(2)S/KTa_(x)Nb_(1-x)O_(3)was designed and synthesized through a combination of hydrothermal and precipitation procedures. The Ta/Nb ratio of the KTa_(x)Nb_(1-x)O_(3)and the Ag_(2)S content were optimized. The best 0.5% Ag_(2)S/KTa_(0.5)Nb_(0.5)O_(3)(KTN) sample presents an enhanced photocatalytic performance in ammonia synthesis than KTN and Ag_(2)S. Under simulated sunlight, the NH_(3)generation rate of 0.5% Ag_(2)S/KTN reaches 2.0 times that of pure KTN. Under visible light, the reaction rate ratio of the two catalysts is 6.0.XRD, XPS, and TEM analysis revealed that Ag2S was intimately decorated on the KTN nanocubes surface, which promoted the electron transfer between the two semiconductors. The band structure investigation indicated that the Ag_(2)S/KTN heterojunction established a type-Ⅱ band alignment with intimate contact, thus realizing the effective transfer and separation of photogenerated carriers. The change in charge separation was considered as the main reason for the enhanced photocatalytic performance. Interestingly, the Ag_(2)S/KTN composite exhibited higher NH3generation performance under the combined action of ultrasonic vibration and simulated sunlight. The enhanced piezo-photocatalytic performance can be ascribed that the piezoelectric effect of KTN improved the bulk separation of charge carriers in KTN. This study not only provides a potential catalyst for photocatalytic nitrogen fixation but also shows new ideas for the design of highly efficient catalysts via semiconductor modification and external field coupling.
基金funded by National Key Research and Development Program of China(2022YFE0103200)National Natural Science Foundation of China(22176107 and 22206107)+1 种基金Guangdong Basic and Applied Basic Research Foundation(2019B151502034 and 2021A1515110772)China Postdoctoral Science Foundation(2021M691772)。
文摘As a widespread emerging contaminant,chloramphenicol(CAP)adversely impacts ecological communities in the water environment.Biological treatment is widely used for aquatic pollutant removal,and the performance of functional microbes determines its outcome.Herein,a consortium with a powerful CAPdegrading capacity was domesticated from activated sludge.As the common degradation products of CAP,4-nitrobenzoic acid(PNB)and 2,2-dichloroacetic acid(DCA)were also used as the sole substrates for long-term domestication.The successional pattern of the microbial community and critical functional genes through the 2.5-year domestication was revealed by metagenomic analysis.Sphingomonas,Caballeronia,and Cupriavidus became the most dominant populations in the CAP-,PNB-,and DCAdegrading consortia,respectively,and they were crucial degraders of PNB and DCA.Their collaboration contributed to the high mineralization rate of CAP.PNB was transformed into protocatechuic acid(PCA)and then mineralized through meta-cleavage and ortho-cleavage pathways.Crucial functional genes involved in CAP,PNB,and DCA metabolism,including CAP acetyltransferase,CAP oxidoreductase,haloacid dehalogenases,and protocatechuate dioxygenases,were significantly enriched in consortia.p H and carbon source had significant impacts on CAP biodegradation efficiency.The domesticated consortia and isolated strains are necessary microbial resources to enhance the bioremediation of CAP-,PNB-,or DCA-polluted environments.
基金supported by the Excellent Youth Foundation of Education Department of Hunan Province,China(20B612)Changsha Natural Science Foundation of China(kq2014158).
文摘Geopolymer is a new alternative cement binder to produce concrete.In the present study,a novel geopolymer composites containing bamboo shaving(0–2 wt.%)were fabricated and exposed to the temperatures of 200℃,400℃,600℃and 800℃.Physical properties,micro-structure,and mechanical strengths of the geopolymer composites were evaluated before and after heating in order to understand their thermal properties,which are essential for the use as building materials.As the temperature rises,the drying shrinkage and apparent porosity of the composites increase,while the compressive and bending strengths decrease.At the temperature range of 200℃–800℃,the residual compressive strength rates of the geopolymer composite containning 2 wt.%bamboo shaving were respective 73.8%,61.47%,56.16%,and 29.56%,meanwhile,the residual flexural strength rates were respective 46.69%,8.68%,2.52%,and 2.33%.Correspondingly,the residual compressive strength rates of pure geopolymer were respective 72.81%,61.99%,54.55%,and 14.64%;the residual flexural strength rates were 48.87%,5.69%,3.22%,and 2.47%,respectively.Scanning electron microscope(SEM),optical microscope,and X-ray diffractometry(XRD)were applied to find the microscopic changes.The strength loss in the geopolymer composites was mainly because of the thermal degradation of bamboo shaving and shrinkage of geopolymer matrix.Bamboo shaving has great potential as reinforcer in developing low-cost geopolymer composites and may be used for applications up to 400℃.
基金supported by the National Natural Science Foundation of China(No.61702347,No.62027801)Natural Science Foundation of Hebei Province(No.F2022210007,No.F2017210161)+2 种基金Science and Technology Project of Hebei Education Department(No.ZD2022100,No.QN2017132)Central Guidance on Local Science and Technology Development Fund(No.226Z0501G)National innovation and Entrepreneurship training program for college students(No.202110107024).
文摘The communication system of high-speed trains in railway tunnels needs to be built with leaky cables fixed on the tunnel wall with special fixtures.To ensure safety,checking the regular leaky cable fixture is necessary to elimi-nate the potential danger.At present,the existing fixture detection algorithms are difficult to take into account detection accuracy and speed at the same time.The faulty fixture is also insufficient and difficult to obtain,seriously affecting the model detection effect.To solve these problems,an innovative detection method is proposed in this paper.Firstly,we presented the Res-Net and Wasserstein-Deep Convolution GAN(RW-DCGAN)to implement data augmentation,which can enable the faulty fixture to export more high-quality and irregular images.Secondly,we proposed the Ghost SENet-YOLOv5(GS-YOLOv5)to enhance the expression of fixture feature,and further improve the detection accuracy and speed.Finally,we adopted the model compression strategy to prune redundant channels,and visualized training details with Grad-CAM to verify the reliability of our model.Experimental results show that the algorithm model is 69.06%smaller than the original YOLOv5 model,with 70.07%fewer parameters,2.1%higher accuracy and 14.82 fps faster speed,meeting the needs of tunnel fixture detection.
基金supported by the National Natural Science Foundation of China(Nos.61702347,62027801 and 61972267)Natural Science Fund of Hebei Province(No.F2017210161),and Hebei Province Graduate Student Innovation Ability Training Funding Project.
文摘With the vigorous development of national infrastructure construction and public information construction,video surveillance systems have gradually penetrated various fields.The current key frame extraction technology has inadequate target details and inaccurate judgment of local actions.Addressing this problem,a key frame extraction method based on fractional Fourier transform is proposed.This method obtained the phase spectra information of different orders by performing fractional Fourier transform on the surveillance video frames.Next,the method designed an adaptive algorithm based on the golden section point to select the transformation order.Then,the phase spectrum information of two adjacent frames was used to characterize the changes in the global and local motion states of the target.The final step was to extract key frames based on this.Experimental results show that,compared with the previous methods,the key frames extracted by the method proposed in this paper can correctly capture the changes in the global and local motion states of the target.
基金This work was supported by the grants from the National Natural Science Foundation of China(31860074,U1812403)the Science and Technology project of Guizhou Province(QKHZC[2018]2799)and Guizhou Province Engineering Research Center for Natural Drugs.
文摘Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture of southwestern Guizhou have a long well-conserved history.These markets,which are a feature of Buyi and Miao traditional medicines,contain a rich diversity of medicinal plants and traditional medical knowledge.Today,people in southwestern Guizhou still believe that using herbs during the Dragon Boat Festival prevents and can treat disease.In this study,we identified the fresh herbal plants sold at the herbal markets of Xingren City and Zhenfeng County in Qianxinan Buyi and Miao Autonomous Prefecture and quantified their importance.We identified 141 plant species(belonging to 114 genera and 61 families).The plant family with the most species was Asteraceae(14 species).Informants reported that most medicinal plants are herbaceous,with 95.7%of plants used for decoction and 30.5%used for medicinal baths.Medicinal plants are most commonly used to treat rheumatism,injury,and abdominal diseases.The utilization frequency index and relative importance values indicated that Artemisia argyi and Acorus calamus are the most important plants sold at herbal markets during the Dragon Boat Festival.The price of medicinal materials sold in the market may serve as an indicator of the conservation status of species in the region.These findings indicate that the Dragon Boat Festival herbal markets in the Qianxinan Buyi and Miao Autonomous Prefecture fully embodies the characteristics of indigenous ethnomedicine and culture,and also exhibits the diversity of plant resources.We recommend that rare and endangered plants in this region be domesticated and protected.
基金supported by National Key Research and Development Program of China (Grant No. 2018YFD1000)Shandong Vegetable Research System (Grant No. SDAIT-05–05)+1 种基金Major Agricultural Application Technology Innovation Project of Shandong Province (2018)The Key Research and Development Program of Shandong and Chongqing Cooperation (Grant No. 2020LYXZ001)
文摘The multidrug and toxic compound extrusion(MATE) family plays pivotal roles in the detoxification process in plants, while no information has been provided for this gene family in melon(Cucumis melo L.) thus far, limiting our understanding of its functions in melon acclimation to stressful environments. In this study, a total of 39 MATEs(CmMATE1–CmMATE39) were observed in the melon genome;these were unevenly distributed in all chromosomes, with the most on Chromosome 1. Based on their orthologous relationship with those from Arabidopsis, rice, and sorghum, melon MATEs were clustered into three subfamilies of Clades Ⅰ, Ⅱ, and Ⅲ, wherein 23, 9, and 7 members were included, respectively.Variable exon number was observed in CmMATEs, and the most were harbored by CmMATE8. Gene ontology(GO) term and cis-regulatory element(CRE) analyses pointed to the potential roles of CmMATEs in both the regulation of melon development and acclimation to various abiotic and biotic stressors. The RNA-seq and qRT-PCR(quantitative real-time PCR) results demonstrated that under normal growth conditions, CmMATEs were expressed in a tissue-and development-specific manner, while their abundance apparently varied in a stress-dependent manner when melon plants were exposed to unfavorable environmental conditions. Altogether, these observations could expand our knowledge about the plant MATE family and benefit functional genomics analysis for CmMATEs in the future.
基金the Excellent Youth Foundation of Education Department of Hunan Province,China(20B612)Changsha Natural Science Foundation of China(kq2014158).
文摘Geopolymers are inorganic aluminosilicate materials,which have been a great research interest as a material for sustainable development.However,they possess relatively low toughness properties similar to brittle solids.The limitation may be altered by fiber reinforcement to improve their strength and toughness.This research describes the synthesis of bamboo shaving(BS)reinforced geopolymer composites and the characterization of their mechanical properties.The effect of BS content(0–2 wt.%)on the physical and mechanical properties and microstructure of metakaolin based geopolymer paste were investigated.The workability,setting time,bulk density,apparent porosity,thermal conductivity,compressive strength,flexural strength,scanning electron microscopy(SEM),and X-ray diffraction(XRD)of geopolymer paste were determined.The results showed that the workability,setting time,density,and thermal conductivity decreased with the increasing of BS content.The BS content was proportional to the apparent porosity and a good linear relation was found between apparent porosity and BS content.The highest mechanical properties were achieved at an optimum BS content of 1.0 wt.%.The results of microstructural analysis revealed that BS act as inforcing phase in matrix,reducing cracks and making a dense geopolymer,which leads to favorable adhesion of the composites and produces a geopolymer composite with better mechanical properties than that of pure geopolymer.However,when the BS content exceeded 1.0 wt.%,interfacial bonding between BS and geopolymer matrix became less.XRD analysis showed that BS has little effect on the mineral composition of metakaolin-based geopolymer and no new phase is formed.
文摘Objective:The aim of the study was to investigate the diagnostic value of fine needle aspiration cytology (FNAC) and its clinical application.Methods:From April 2009 to February 2011,thyroid FNAC were performed in a total of 186 patients with thyroid nodule or mass in our hospital and 78 of those 186 patients subsequently underwent thyroidectomy.The FNAC findings were compared with the results of the corresponding histological diagnosis.Results:The results of thyroid FNAC for 186 patients showed that,(1) 166 cases of benign lesions,the detection rate was 89.24% (166/186),including 96 cases of nodular colloid goiter (51.61%),28 cases of simple colloid goiter (15.05%),38 cases of Hashimoto's thyroiditis (HT) (20.43%) and 4 cases of thyroid adenoma (2.15%);(2) 4 cases of suspicious malignant lesion,the detection rate was 2.15% (4/186);(3) 16 cases of malignant tumor,the detection rate was 8.60% (16/186).Seventy eight patients including malignant (16),suspicious malignant (4),HT (20) and nodular colloid goiters (38) cases diagnosed by FNAC were performed operation with thyroidectomy and the postoperative histopathologic results showed that there were 2 cases HT combined thyroid papillary carcinoma in HT 20 cases by FNAC,15 cases of thyroid papillary carcinoma and 1 case of follicular carcinoma in 16 cases of malignant tumor by FNAC and 4 case of thyroid papillary carcinoma in 4 cases of suspicious malignant by FNAC.Conclusion:Thyroid FNAC is a valuable and reliable method for the diagnosis of the thyroid nodules or mass or even most diffuse thyroid diseases.Diagnosis of HT and thyroid papillary carcinoma can be made by thyroid FNAC.There was larger hint value for nodular colloid goiter and simple colloid goiter according to thyroid FNAC.
基金This work was supported by the National Nature Science Foundation of China(Grant Nos.61702347,61972267,61772225)Natural Science Foundation of Hebei Province(Grant Nos.F2017210161,F2018210148)。
文摘In recent years,pedestrian detection is a hot research topic in the field of computer vision and artificial intelligence,it is widely used in the field of security and pedestrian analysis.However,due to a large amount of calculation in the traditional pedestrian detection technology,the speed of many systems for pedestrian recognition is very limited.But in some restricted areas,such as construction hazardous areas,real-time detection of pedestrians and cross-border behaviors is required.To more conveniently and efficiently detect whether there are pedestrians in the restricted area and cross-border behavior,this paper proposes a pedestrian cross-border detection method based on HOG(Histogram of Oriented Gradient)and SVM(Support Vector Machine).This method extracts the moving target through the GMM(Gaussian Mixture Model)background modeling and then extracts the characteristics of the moving target through gradient HOG.Finally,it uses SVM training to distinguish pedestrians from non-pedestrians,completes the detection of pedestrians,and labels the targets.The test results show that only the HOG feature extraction of the candidate area can greatly reduce the amount of calculation and reduce the time of feature extraction,eliminate background interference,thereby improving the efficiency of detection,and can be applied to occasions with real-time requirements.
文摘The patient is a 37-year-old male with a right anterior tibial mass for more than one year and a left anterior tibial mass for more than one month.There was a history of hyperthyroidism.Histopathology of the lesions showed epidermal hyperkeratosis of the skin tissue,thickening of the spinous layer,extensive collagen fibrillation in the superficial dermis and reticular layer,and numerous linear and granular mucoprotein deposits in the lower and middle dermis.Blastocystis hominis was routinely detected in the stool.Diagnosis:1.Pretibial myxedema 2.intestinal parasitosis(Blastocystis hominis infection).
基金supported by the National Natural Science Foundation of China(No.81630025)The collection,analysis and interpretation of the data were supported by the National Natural Science Foundation of China(No.82001044)+1 种基金The composition of the manuscript was supported by the China Postdoctoral Science Foundation(2020M673019)the Guangdong Basic and Applied Basic Research Foundation(2019A1515110071).
文摘Metabolic reprogramming and immunologic suppression are two critical characteristics promoting the progression of head and neck squamous cell carcinoma(HNSCC).The integrative analysis of all the metabolismrelated genes(MRGs)in HNSCC is lacking and the interaction between the metabolism and the immune characteristics also requires more exploration to uncover the potential mechanisms.Therefore,this study was designed to establish a prognostic signature based on all the MRGs in HNSCC.Genes of HNSCC samples were available from the TCGA and GEO databases while the MRGs were retrieved from a previous study.Ultimately 4 prognostic MRGs were selected to construct a model possessing robust prognostic value and accuracy in TCGA cohorts.The favorable reproducibility of this model was confirmed in validation cohorts from GEO databases.The risk score calculated by this model was an independent prognostic factor that further classified these HNSCC patients into high-/low-risk groups.GSEA analyses and somatic mutations indicated the low-risk group could activate several anti-tumor pathways and possessed lower TP53 mutation.The results of ESTIMATE,single-sample GSEA,CIBERSORT,and some immune-related molecules analyses suggested the low-risk group exhibited lower metabolic activities and higher immune characteristics.The Spearman correlation test implied most metabolic pathways with tumor-promoting function were negatively correlated with the immune activity,indicating a plausible approach of combining the anti-metabolism and the immunotherapy drugs in the high-risk group to enhance therapeutic effects than applied separately.In conclusion,this prognostic signature linking MRGs with the immune landscape could promote the individualized treatment for HNSCC patients.
基金This work was supported by the National Nature Science Foundation of China(Grant No.61702347,61772225)Natural Science Foundation of Hebei Province(Grant No.F2017210161).
文摘With the explosive growth of surveillance video data,browsing videos quickly and effectively has become an urgent problem.Video key frame extraction has received widespread attention as an effective solution.However,accurately capturing the local motion state changes of moving objects in the video is still challenging in key frame extraction.The target center offset can reflect the change of its motion state.This observation proposed a novel key frame extraction method based on moving objects center offset in this paper.The proposed method utilizes the center offset to obtain the global and local motion state information of moving objects,and meanwhile,selects the video frame where the center offset curve changes suddenly as the key frame.Such processing effectively overcomes the inaccuracy of traditional key frame extraction methods.Initially,extracting the center point of each frame.Subsequently,calculating the center point offset of each frame and forming the center offset curve by connecting the center offset of each frame.Finally,extracting candidate key frames and optimizing them to generate final key frames.The experimental results demonstrate that the proposed method outperforms contrast methods to capturing the local motion state changes of moving objects.
基金This work was supported by the National Nature Science Foundation of China(Grant No.61702347).
文摘In the field of educational examination,automatic marking technology plays an essential role in improving the efficiency of marking and liberating the labor force.At present,the implementation of the policy of expanding erolments has caused a serious decline in the teacher-student ratio in colleges and universities.The traditional marking system based on Optical Mark Reader technology can no longer meet the requirements of liberating the labor force of teachers in small and medium-sized examinations.With the development of image processing and artificial neural network technology,the recognition of handwritten character in the field of pattern recognition has attracted the attention of many researchers.In this paper,filtering and de-noise processing and binary processing are used as preprocessing methods for handwriting recognition.Extract the pixel feature of handwritten characters through digital image processing of handwritten character pictures,and then,get the feature vector from these feature fragments and use it as the description of the character.The extracted feature values are used to train the neural network to realize the recognition of handwritten English letters and numerical characters.Experimental results on Chars74K and MNIST data sets show that the recognition accuracy of some handwritten English letters and numerical characters can reach 90%and 99%,respectively.
基金supported by the National Natural Science Foundation of China(No.82173685 and No.82073320)Chinese Pharma-ceutical Association-Yi ling Biomedical Innovation Fund(No.CPAYLJ202001,China)+3 种基金Liao Ning Revitalization Talents Program(No.XLYC2002115,China)Key R&D Plan of Liaoning Province in 2020(No.2020020215-JH2/103,China)Development Project of Ministry of Education Innovation Team(No.IRT1073,China)Natural Science Foundation of Shenyang(22-315-6-11,China).
文摘Recent research certified that DOT1L and its mutations represented by R231Q were potential targets for the treatment of lung cancer.Herein,a series of adenosine-containing derivatives were identified with DOT1LR231Q inhibition through antiproliferation assay and Western blot analysis in the H460R231Q cell.The most promising compound 37 significantly reduced DOT1LR231Q mediated H3K79 methylation and effectively inhibited the proliferation,self-renewal,migration,and invasion of lung cancer cell lines at low micromolar concentrations.The cell permeability and cellular target engagement of 37 were verified by both CETSA and DARTS assays.In the H460R231Q OE cell-derived xenograft(CDX)model,37 displayed pronounced tumor growth inhibition after intraperitoneal administration at 20 mg/kg dose for 3 weeks(TGI=54.38%),without obvious toxicities.A pharmacokinetic study revealed that 37 possessed tolerable properties(t_(1/2)=1.93±0.91 h,F=97.2%)after intraperitoneal administration in rats.Mechanism study confirmed that 37 suppressed malignant phenotypes of lung cancer carrying R231Q gain-of-function mutation via the MAPK/ERK signaling pathway.Moreover,analysis of the binding modes between molecules and DOT1LWT/R231Q proteins put forward the“Induced-fit”allosteric model in favor to the discovery of potent DOT1L candidates.
基金This work was financially supported by the National Natural Science Foundation of China(92249302,32370592)the National Key Research and Development Program of China(2023YFC3603300,2021YFA0909300).
文摘Intronic polyadenylation(IPA)is an RNA 3'end processing event which has been reported to play important roles in cancer development.However,the comprehensive landscape of IPA events across various cancer types is lacking.Here,we apply IPAFinder to identify and quantify IPA events in 10,383 samples covering all 33 cancer types from The Cancer Genome Atlas(TCGA)project.We identify a total of 21,835 IPA events,almost half of which are ubiquitously expressed.We identify 2761 unique dynamically changed IPA events across cancer types.Furthermore,we observe 8855 non-redundant clinically relevant IPA events,which could potentially be used as prognostic indicators.Our analysis also reveals that dynamic IPA usage within cancer signaling pathways may affect drug response.Finally,we develop a user-friendly data portal,IPACancer Atlas(http://www.tingni-lab.com/Pancan_IPA),to search and explore IPAs in cancer.
基金supported by National Key R&D Program of China(No.2021YFA0909800,China)Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515020056,2021A1515011881,2023A1515010737,China)+3 种基金Leading team for entrepreneurship in Guangzhou,Guangdong Province(No.201809020004,China)Fundamental Research Funds for the Central Universities(No.22ykqb12,China)Pioneering talents project of Guangzhou Development Zone,Guangdong Province(2020-L036,China)Natural Science Foundation of Guangdong Province(No.2022A1515011056,China).
文摘Oncolytic viruses(OVs),a group of replication-competent viruses that can selectively infect and kill cancer cells while leaving healthy cells intact,are emerging as promising living anticancer agents.Unlike traditional drugs composed of non-replicating compounds or biomolecules,the replicative nature of viruses confer unique pharmacokinetic properties that require further studies.Despite some pharmacokinetics studies of OVs,mechanistic insights into the connection between OV pharmacokinetics and antitumor efficacy remain vague.Here,we characterized the pharmacokinetic profile of oncolytic virus M1(OVM)in immunocompetent mouse tumor models and identified the JAK-STAT pathway as a key modulator of OVM pharmacokinetics.By suppressing the JAK-STAT pathway,early OVM pharmacokinetics are ameliorated,leading to enhanced tumor-specific viral accumulation,increased AUC and Cmax,and improved antitumor efficacy.Rather than compromising antitumor immunity after JAK-STAT inhibition,the improved pharmacokinetics of OVM promotes T cell recruitment and activation in the tumor microenvironment,providing an optimal opportunity for the therapeutic outcome of immune checkpoint blockade,such as anti-PD-L1.Taken together,this study advances our understanding of the pharmacokinetic-pharmacodynamic relationship in OV therapy.