Objective: This study aimed to explore the effects of Chinese patent medicine(CPM) in reducing the incidence of major adverse cardiovascular events(MACE) in patients with coronary heart disease(CHD) angina pectoris an...Objective: This study aimed to explore the effects of Chinese patent medicine(CPM) in reducing the incidence of major adverse cardiovascular events(MACE) in patients with coronary heart disease(CHD) angina pectoris and improving clinical effectiveness and provide evidence for its use as clinical adjuvant therapy.Methods: Twenty-eight thousand five hundred and seventeen patients hospitalized with CHD angina pectoris from 6 hospitals were divided into CPM group(n = 11,374) and non-CPM group(n = 17,143) to evaluate the incidence of MACE, including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting.Results: The incidence of MACE in the CPM group was lower than that in the non-CPM group. CPM therapy was an independent protective factor that reduced the overall risk of MACE [adjusted hazard ratio = 0.40, 95% confidence interval(0.33;0.49)]. Patients in the CPM group who received one, two, or three types of CPM could benefit from adjuvant treatment with CPM, and taking more types of CPM was associated with a lower risk of MACE. In addition, the male population was better than the female population at taking CPM, and middle-aged people aged 55 to 64 were more suited to take CPM based on Western medicine.Conclusions: The use of CPM as adjuvant therapy can decrease the occurrence of MACE in patients with CHD angina pectoris,especially in men and middle-aged people, and the drug treatment plan should be optimized accordingly. However, this conclusion needs further verification by prospective cohort studies in the future.展开更多
Trastuzumab has improved survival rates in human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC),but drug resistance leads to treatment failure.Natural killer(NK)cell-mediated antibody-dependent ce...Trastuzumab has improved survival rates in human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC),but drug resistance leads to treatment failure.Natural killer(NK)cell-mediated antibody-dependent cell cytotoxicity(ADCC)represents an essential antitumor immune mechanism of trastuzumab.Traditional Chinese medicine(TCM)has been used for centuries to treat diseases because of its capacity to improve immune responses.Xianling Lianxia formula(XLLXF),based on the principle of“strengthening body and eliminating toxin”,exhibits a synergistic effect in the trastuzumab treatment of patients with HER2-positive BC.Notably,this synergistic effect of XLLXF was executed by enhancing NK cells and ADCC,as demonstrated through in vitro co-culture of NK cells and BC cells and in vivo intervention experiments.Mechanistically,the augmented impact of XLLXF on NK cells is linked to a decrease in cytokine inducible Src homology 2(SH2)containing protein(CISH)expression,which in turn activates the Janus kinase 1(JAK1)/signal transducer and activator of transcription 5(STAT5)pathway.Collectively,these findings suggested that XLLXF holds promise for enhancing NK cell function and sensitizing patients with HER2-positive BC to trastuzumab.展开更多
Symbiotic stars are interacting binary systems, making them valuable for studying various astronomical phenomena, such as stellar evolution, mass transfer, and accretion processes. Despite recent progress in the disco...Symbiotic stars are interacting binary systems, making them valuable for studying various astronomical phenomena, such as stellar evolution, mass transfer, and accretion processes. Despite recent progress in the discovery of symbiotic stars, a significant discrepancy between the observed population of symbiotic stars and the number predicted by theoretical models. To bridge this gap, this study utilized machine learning techniques to efficiently identify new symbiotic star candidates. Three algorithms(XGBoost, LightGBM, and Decision Tree)were applied to a data set of 198 confirmed symbiotic stars and the resulting model was then used to analyze data from the LAMOST survey, leading to the identification of 11,709 potential symbiotic star candidates. Out of these potential symbiotic star candidates listed in the catalog, 15 have spectra available in the Sloan Digital Sky Survey(SDSS) survey. Among these 15 candidates, two candidates, namely V^(*)V603 Ori and V^(*)GN Tau, have been confirmed as symbiotic stars. The remaining 11 candidates have been classified as accreting-only symbiotic star candidates. The other two candidates, one of which has been identified as a galaxy by both SDSS and LAMOST surveys, and the other identified as a quasar by SDSS survey and as a galaxy by LAMOST survey.展开更多
Detection of estrogenic disrupting compounds（EDCs） in drinking waters around China has led to rising concerns about health risks associated with these compounds.There is,however,a paucity of studies on the occurrenc...Detection of estrogenic disrupting compounds（EDCs） in drinking waters around China has led to rising concerns about health risks associated with these compounds.There is,however,a paucity of studies on the occurrence and identification of the main compounds responsible for this pollution in the source waters.To fill this void,we screened estrogenic activities of 23 source water samples from six main river systems in China,using a recombinant two-hybrid yeast assay.All sample extracts induced significant estrogenic activity,with E2 equivalents（EEQ） of raw water ranging from 0.08 to 2.40 ng/L.Additionally,16 samples were selected for chemical analysis by gas chromatography-mass spectrometry.The EDCs of most concern,including estrone（E1）,17β-estradiol（E2）,17α-ethinylestradiol（EE2）,estriol（E3）,diethylstilbestrol（DES）,estradiol valerate（EV）,4-t-octylphenol（4-t-OP）,4-nonylphenols（4-NP） and bisphenol A（BPA）,were determined at concentrations of up to 2.98,1.07,2.67,4.37,2.52,1.96,89.52,280.19 and 710.65 ng/L,respectively.Causality analysis,involving comparison of EEQ values from yeast assay and chemical analysis identified E2,EE2 and 4-NP as the main responsible compounds,accounting for the whole estrogenic activities（39.74% to 96.68%）.The proposed approach using both chemical analysis and yeast assay could be used for the identification and evaluation of EDCs in source waters of China.展开更多
Studies on estrogenic disrupting compounds （EDCs） occurrence and identification of main responsible compounds in river water discharged into the sea are of significance. In the present research, we screened estrogen...Studies on estrogenic disrupting compounds （EDCs） occurrence and identification of main responsible compounds in river water discharged into the sea are of significance. In the present research, we screened estrogenic activities of 10 river water samples from 3 main rivers discharged into Bohai Sea in Tianjin using a recombinant two-hybrid yeast assay and chemical analysis by gas chromatography-mass spectrometry. All sample extracts induced significant estrogenic activity, with 17^-estradiol equivalents （EEQ） of raw water ranging from 5.72 to 59.06 ng/L. Six most concerned EDCs in the fiver water samples including estrone, 17（5-estradiol, 17ct-ethinylestradiol, estriol, diethylstilbestrol and estradiol valerate were determined, with their concentrations up to 50.70, 31.40, 24.40, 37.20, 2.56, and 8.47 ng/L, respectively. Through causality analysis by comparing the EEQ values of yeast assay and chemical analysis, 17ct-ethinylestradiol and 17[3-estradiol were identified as the main contributors to the estrogenic effects of the river samples, accounting for the whole estrogenic activities （62.99% to 185.66%）, and estrogen antagonistic compounds might presented in the heavy polluted water samples. The proposed approach using both chemical analysis and bioassay could be used for identification and evaluation of the estrogenic activity of EDCs in river water.展开更多
Surfactants such as alkylphenol polyethoxylates(APEOs) and nonylphenol ethoxylates(NPEOs) are commonly used worldwide, but the majority of these compounds, together with their metabolites, have been reported to induce...Surfactants such as alkylphenol polyethoxylates(APEOs) and nonylphenol ethoxylates(NPEOs) are commonly used worldwide, but the majority of these compounds, together with their metabolites, have been reported to induce severe biological toxicity. Here, we evaluated for the first time the cytotoxicity,genotoxicity and mitochondrial damage in Chinese hamster ovary(CHO-K1) cells caused by a novel non-ionic surfactant, vanillin ethoxylates(VAEOs), an alternative to APEOs. In parallel, the same in vitro bioassays were conducted on NPEOs along with their metabolic byproducts 4-nonylphenol(4-NP) and vanillin. The results showed that the cytotoxic potency order was NPEOs > 4-NP > VAEOs>vanillin using CCK-8 assays. Also, 4-NP showed potential direct DNA damage in SOS/umu tests, whereas NPEOs, VAEOs and vanillin showed no positive result with and without S9 addition. In addition, none of the test compounds showed obvious genotoxic effects with low olive tail moment value using comet assays. However, all test compounds were shown to cause mitochondrial impairment by increasing mitochondrial mass and decreasing mitochondrial membrane potential in a concentration-dependent manner. And further analysis of reactive oxygen species(ROS) and mitochondrial superoxide(MNSOD)measurement showed that mitochondrial impairment was induced by oxidative stress with intracellular ROS and MNSOD overproduction. It's worth noting that VAEOs and vanillin cause relative lower cytotoxic, genotoxic and mitochondrial damage effects than NPEOs and 4-NP, indicating that VAEOs have the potential to substitute NPEOs as suitable surfactants. Take together, this study elucidates the toxicity profiles of VAEOs and NPEOs relatively comprehensively, and further toxicity analyses are suggested in the population, community and ecosystem.展开更多
Environmental impact of pollutants can be analyzed effectively by acquiring fish behavioral signals in water with biological behavior sensors. However, a variety of factors, such as the complexity of biological organi...Environmental impact of pollutants can be analyzed effectively by acquiring fish behavioral signals in water with biological behavior sensors. However, a variety of factors, such as the complexity of biological organisms themselves, the device error and the environmental noise, may compromise the accuracy and timeliness of model predictions. The current methods lack prior knowledge about the fish behavioral signals corresponding to characteristic pollutants, and in the event of a pollutant invasion, the fish behavioral signals are poorly discriminated. Therefore, we propose a novel method based on Bayesian sequential,which utilizes multi-channel prior knowledge to calculate the outlier sequence based on wavelet feature followed by calculating the anomaly probability of observed values. Furthermore, the relationship between the anomaly probability and toxicity is analyzed in order to achieve forewarning effectively. At last, our algorithm for fish toxicity detection is verified by integrating the data on laboratory acceptance of characteristic pollutants. The results show that only one false positive occurred in the six experiments, the present algorithm is effective in suppressing false positives and negatives, which increases the reliability of toxicity detections, and thereby has certain applicability and universality in engineering applications.展开更多
Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disr...Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disruption of drinking water potency has not been reported. We used ERRy two-hybrid yeast assay to screen ERRy disrupting activities in a drinking water treatment plant （DWTP） located in north China and in source water from a reservoir, focusing on agonistic, antagonistic, and inverse agonistie activity to 4-hydroxytamoxifen （4-OHT）. Water treatment processes in the DWTP consisted of pre-chlorination, coagulation, coal and sand filtration, activated carbon filtration, and secondary chlorination processes. Samples were extracted by solid phase extraction. Results showed that ERRγ antagonistic activities were found in all sample extracts, but agonistic and inverse agonistic activity to 4-OHT was not found. When calibrated with the toxic equivalent of 4-OHT, antagonistic effluent effects ranged from 3.4 to 33.1 μg/L. In the treatment processes, secondary chlorination was effective in removing ERRy antagonists, but the coagulation process led to significantly increased ERRy antagonistic activity. The drinking water treatment processes removed 73.5 % of ERRy antagonists. To our knowledge, the occurrence of ERRy disruption activities on source and drinking water in vitro had not been reported previously. It is vital, therefore, to increase our understanding of ERRγ disrupting activities in drinking water.展开更多
INDETERMINATE-DOMAIN proteins(IDDs)are a plant-specific transcription factor family characterized by a conserved ID domain with four zinc finger motifs.Previous studies have demonstrated that IDDs coordinate a diversi...INDETERMINATE-DOMAIN proteins(IDDs)are a plant-specific transcription factor family characterized by a conserved ID domain with four zinc finger motifs.Previous studies have demonstrated that IDDs coordinate a diversity of physiological processes and functions in plant growth and development,including floral transition,plant architecture,seed and root development,and hormone signaling.In this review,we especially summarized the latest knowledge on the functions and working models of IDD members in Arabidopsis,rice,and maize,particularly focusing on their role in the regulatory network of biotic and abiotic environmental responses,such as gravity,temperature,water,and pathogens.Understanding these mechanisms underlying the function of IDD proteins in these processes is important for improving crop yields by manipulating their activity.Overall,the review offers valuable insights into the functions and mechanisms of IDD proteins in plants,providing a foundation for further research and potential applications in agriculture.展开更多
Dear Editor,Psychiatric disorders are a group of mental disorders characterized by psychological or behavioral disabilities.Losing of the ability to work and assuming the extensive cost of long-term treatment,patients...Dear Editor,Psychiatric disorders are a group of mental disorders characterized by psychological or behavioral disabilities.Losing of the ability to work and assuming the extensive cost of long-term treatment,patients with psychiatric disorders are forced to support a heavy financial and medical burden.The growth and development of brain structures are dynamic,and different brain structures have major and specific functions to control behavior and performance.展开更多
Dissolved organic matter(DOM)participates in and affects many biological processes in aquatic ecosystems,altering nutrient cycling,bioavailability and toxicity of pollutants.Lake water contains thousands of DOM molecu...Dissolved organic matter(DOM)participates in and affects many biological processes in aquatic ecosystems,altering nutrient cycling,bioavailability and toxicity of pollutants.Lake water contains thousands of DOM molecules,which largely originate from natural sources and are greatly influenced by external inputs through anthropogenic activities.To elucidate the shaping mechanism of the DOM composition under complex habitat conditions and anthropogenic disturbances,the characteristic molecular fingerprint of DOM was determined based on chemodiversity information obtained via ultrahigh-resolution mass spectrometry for the Baiyangdian wetland(a typical large macrophytic shallow lake in North China).In the Baiyangdian wetland,the DOM composition exhibited high complexity and spatial heterogeneity,and more recalcitrant DOM molecules were identified in summer than in spring.Although multiple natural factors(nutrient concentration,depth of water and quality of submerged macrophytes)and anthropogenic factors(different land uses and discharge of pollutants)were associated with the relative abundance of various DOM molecules,only the influences from the anthropogenic factors were statistically significant.The alpha diversity index of DOM could reflect variations in both the natural factors(total dissolved phosphorus)and the anthropogenic factors(discharge of nitrogen and phosphorus).Furthermore,the DOM composition in each group were clustered according to the ecological functions(natural reserves,tourism,breeding,and domestic supply functions),and exhibited molecular fingerprint features.This study provides an effective approach to characterize the molecular fingerprint features of DOM and critical information to better understand the shaping mechanism of the DOM composition under complex habitat conditions and anthropogenic disturbances.展开更多
Accurately predicting the synthesizability of inorganic crystal materials serves as a pivotal tool for the efficient screening of viable candidates,substantially reducing the costs associated with extensive experiment...Accurately predicting the synthesizability of inorganic crystal materials serves as a pivotal tool for the efficient screening of viable candidates,substantially reducing the costs associated with extensive experimental trial-and-error processes.However,existing methods,limited by static structural descriptors such as chemical composition and lattice parameters,fail to account for atomic vibrations,which may introduce spurious correlations and undermine predictive reliability.Here,we propose a deep learning model termed integrating graph and dynamical stability(IGDS)for predicting the synthesizability of inorganic crystals.IGDS employs graph representation learning to construct crystal graphs that precisely capture the static structures of crystals and integrates phonon spectral features extracted from pre-trained machine learning interatomic potentials to represent their dynamic properties.Our model exhibits outstanding performance in predicting the synthesizability of low-energy unsynthesizable crystals across 41 material systems,achieving precision and recall values of 0.916/0.863 for ternary compounds.By capturing both static structural descriptors and dynamic features,IGDS provides a physics-informed method for predicting the synthesizability of inorganic crystals.This approach bridges the gap between theoretical design concepts and their practical implementation,thereby streamlining the development cycle of new materials and enhancing overall research efficiency.展开更多
Muscle regeneration after damage or during myopathies requires a fine cooperation between myoblast proliferation and myogenic differentiation.A growing body of evidence suggests that microRNAs play critical roles in m...Muscle regeneration after damage or during myopathies requires a fine cooperation between myoblast proliferation and myogenic differentiation.A growing body of evidence suggests that microRNAs play critical roles in myocyte proliferation and differentiation transcriptionally.However,the molecular mechanisms underlying the orchestration are not fully understood.Here,we showed that miR-130b is able to repress myoblast proliferation and promote myogenic differentiation via targeting Sp1 transcription factor.Importantly,overexpression of miR-130b is capable of improving the recovery of damaged muscle in a freeze injury model.Moreover,miR-130b expression is declined in the muscle of muscular dystrophy patients.Thus,these results indicated that miR-130b may play a role in skeletal muscle regeneration and myopathy progression.Together,our findings suggest that the miR-130b/Sp1 axis may serve as a potential therapeutic target for the treatment of patients with muscle damage or severe myopathies.展开更多
Study on effective disposal and utilization of sewage sludge has recently been the target of growing interest in China. However, potential risks are associated with the use of sludge due to its contamination with toxi...Study on effective disposal and utilization of sewage sludge has recently been the target of growing interest in China. However, potential risks are associated with the use of sludge due to its contamination with toxic organics, heavy metals and pathogenic microorganisms. In this study, a screening assessment was conducted on sewage sludge samples collected from 17 different sewage treatment plants in Beijing, based on a batch of in vitro bioassays, including a set of recombinant gene yeast assays for endocrine disruption, and an ethoxy resorufin-O- deethylase （EROD） assay using H4IIE cells for aryl hydrocarbon receptor （Ah-R） agonistic activities. Our results suggested that moderate levels of estrogen receptor agonistic activities （0.9 ng E2. g-1 to 6.8 ng E2. gl, dw）, but relative higher androgen receptor antagonistic activ- ities （nd to 45%）, progestin receptor antagonistic activities （nd to 80%） and Ah-R agonistic activities （1390 to 6740 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）·g-1, dw） were found in sewage sludge samples. However, there were no significant correlations between the toxic effects of sewage sludge and the sewage treatment processes. In addition, the 17β-estradiol （E2） equivalent quantity （EEQ） level of the sewage sludge was increased after the composting treatment, whereas the 2,3,7,8-tetrachlorodi- benzo-p-dioxin toxic equivalent quantity （TEQ） level of sewagesludge composted was much lower than that of sewage sludge.展开更多
Generating novel molecules to satisfy specific properties is a challenging task in modern drug discovery,which requires the optimization of a specific objective based on satisfying chemical rules.Herein,we aim to opti...Generating novel molecules to satisfy specific properties is a challenging task in modern drug discovery,which requires the optimization of a specific objective based on satisfying chemical rules.Herein,we aim to optimize the properties of a specific molecule to satisfy the specific properties of the generated molecule.The Matched Molecular Pairs(MMPs),which contain the source and target molecules,are used herein,and logD and solubility are selected as the optimization properties.The main innovative work lies in the calculation related to a specific transformer from the perspective of a matrix dimension.Threshold intervals and state changes are then used to encode logD and solubility for subsequent tests.During the experiments,we screen the data based on the proportion of heavy atoms to all atoms in the groups and select 12365,1503,and 1570 MMPs as the training,validation,and test sets,respectively.Transformer models are compared with the baseline models with respect to their abilities to generate molecules with specific properties.Results show that the transformer model can accurately optimize the source molecules to satisfy specific properties.展开更多
Effluents from wastewater treatment plant （WWTP） have been reported to have a broad spectrum of endocrine disrupting compounds （EDCs）. The majority of studies have focused on the occurrence of estrogenic activity,...Effluents from wastewater treatment plant （WWTP） have been reported to have a broad spectrum of endocrine disrupting compounds （EDCs）. The majority of studies have focused on the occurrence of estrogenic activity, while ignoring nuclear hormone receptors （NRs） pathways. In the present study, a battery of in vitro yeast bioassays and a cell bioassay, including antagonistic and agonistic effects on estrogen receptor （ER）, androgen receptor （AR）, progesterone receptor （PR）, estrogen- related receptor （ERR） and aryl hydrocarbon receptor （AHR）, were conducted to evaluate the removal efficien- cies of EDCs by different treatment processes of a WWTP located in Beijing. Estrogenic, anti-estrogenic, anti- androgenic, anti-progesteronic, anti-ERR and the activa- tion of AHR activities were detected in samples from all treatment processes and the receiving water. The concen- tration of estrogenic contaminants with estradiol （E2） equivalent concentrations ranged from 0.82 x 10-9 to 3.54 x 10 9g Ee_EQ.L-1. The concentration of anti-estrogenic contaminants with 4-hydroxytamoxifen （4-OHT） equiva- lent concentrations ranged from 1.24 × 10-6 to 2.36 x 10-6 g 4-OHT-EQ.L-1. The concentration of anti-androgenic contaminants ranged from 2.21 x 10-s to 3.52 × 10-6g flutamide-EQ. L-1. The concentration of anti-progesteronic contaminants ranged from 3.15 x 10^-5 to 2.71 x 10^-4g RU486-EQ. L-1. The concentration of anti-ERR contami- nants ranged from 7.09 x 10-5 to 6.50 x 104 g 4-OHT-EQ × L^-10. The concentration of AHR activators ranged from 1.7 × 10-10 to 3.4 × 10^-10g TCDD-EQ-L-1. These processes including secondary clarifier, coagulation, as well as coal and sand filtration could eliminated 67.2% of estrogenic contaminants, 47.0% of anti-estrogenic contaminants, 98.3% of anti-androgenic contaminants, 88.4% of anti- progesteronic contaminants, 65.4% of anti-ERR contami- nants and 46.9% of AHR activators. WWTP effluents contain multiple receptor disruptors may have very complex adverse effects on exposed organisms.展开更多
基金supported by the National Basic Research Program of China(973 project,grant number:2014CB542902)Tianjin Hongrentang Pharmaceutical Co.,Ltd.,Tianjin,China(grant number:HX202016)。
文摘Objective: This study aimed to explore the effects of Chinese patent medicine(CPM) in reducing the incidence of major adverse cardiovascular events(MACE) in patients with coronary heart disease(CHD) angina pectoris and improving clinical effectiveness and provide evidence for its use as clinical adjuvant therapy.Methods: Twenty-eight thousand five hundred and seventeen patients hospitalized with CHD angina pectoris from 6 hospitals were divided into CPM group(n = 11,374) and non-CPM group(n = 17,143) to evaluate the incidence of MACE, including myocardial infarction, percutaneous coronary intervention, and coronary artery bypass grafting.Results: The incidence of MACE in the CPM group was lower than that in the non-CPM group. CPM therapy was an independent protective factor that reduced the overall risk of MACE [adjusted hazard ratio = 0.40, 95% confidence interval(0.33;0.49)]. Patients in the CPM group who received one, two, or three types of CPM could benefit from adjuvant treatment with CPM, and taking more types of CPM was associated with a lower risk of MACE. In addition, the male population was better than the female population at taking CPM, and middle-aged people aged 55 to 64 were more suited to take CPM based on Western medicine.Conclusions: The use of CPM as adjuvant therapy can decrease the occurrence of MACE in patients with CHD angina pectoris,especially in men and middle-aged people, and the drug treatment plan should be optimized accordingly. However, this conclusion needs further verification by prospective cohort studies in the future.
基金This work was supported by the National Natural Science Foundation of China(Grant No.:81774308)the Multi-center Clinical Research Project for Major Diseases of Shanghai Shenkang Hospital Development Center,China(Grant No.:SHDC2020CR1050B)the High-level University Building Innovation Team,China(Grant No.:601521D).
文摘Trastuzumab has improved survival rates in human epidermal growth factor receptor 2(HER2)-positive breast cancer(BC),but drug resistance leads to treatment failure.Natural killer(NK)cell-mediated antibody-dependent cell cytotoxicity(ADCC)represents an essential antitumor immune mechanism of trastuzumab.Traditional Chinese medicine(TCM)has been used for centuries to treat diseases because of its capacity to improve immune responses.Xianling Lianxia formula(XLLXF),based on the principle of“strengthening body and eliminating toxin”,exhibits a synergistic effect in the trastuzumab treatment of patients with HER2-positive BC.Notably,this synergistic effect of XLLXF was executed by enhancing NK cells and ADCC,as demonstrated through in vitro co-culture of NK cells and BC cells and in vivo intervention experiments.Mechanistically,the augmented impact of XLLXF on NK cells is linked to a decrease in cytokine inducible Src homology 2(SH2)containing protein(CISH)expression,which in turn activates the Janus kinase 1(JAK1)/signal transducer and activator of transcription 5(STAT5)pathway.Collectively,these findings suggested that XLLXF holds promise for enhancing NK cell function and sensitizing patients with HER2-positive BC to trastuzumab.
基金the generous support of the Natural Science Foundation of Xinjiang No. 2021D01C075the National Natural Science Foundation of China, project Nos. 12163005, 12003025, U2031204, 11863005, and 12288102+12 种基金the science research grants from the China Manned Space Project with No. CMS-CSST-2021-A10the Scientific Research Program of the Higher Education Institution of Xinjiang (No. XJEDU2022P003)supported by China National Astronomical Data Center (NADC) and Chinese Virtual Observatory (China-VO)supported by Astronomical Big Data Joint Research Center, co-founded by National Astronomical Observatories, Chinese Academy of Sciences and Alibaba CloudThis publication makes use of data products from the Wide-field Infrared Survey Explorer, which is a joint project of the University of California, Los Angeles, and the Jet Propulsion Laboratory/ California Institute of TechnologyNEOWISE, which is a project of the Jet Propulsion Laboratory/California Institute of TechnologyWISE and NEOWISE are funded by the National Aeronautics and Space AdministrationThis publication makes use of data products from the Two Micron All Sky Survey, which is a joint project of the University of Massachusetts and the Infrared Processing and Analysis Center/California Institute of Technologyfunded by the National Aeronautics and Space Administration and the National Science FoundationGuo Shou Jing Telescope (the Large Sky Area MultiObject Fiber Spectroscopic Telescope LAMOST) is a National Major Scientific Project built by the Chinese Academy of SciencesFunding for the project has been provided by the National Development and Reform CommissionFunding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutionssupport and resources from the Center for High Performance Computing at the University of Utah。
文摘Symbiotic stars are interacting binary systems, making them valuable for studying various astronomical phenomena, such as stellar evolution, mass transfer, and accretion processes. Despite recent progress in the discovery of symbiotic stars, a significant discrepancy between the observed population of symbiotic stars and the number predicted by theoretical models. To bridge this gap, this study utilized machine learning techniques to efficiently identify new symbiotic star candidates. Three algorithms(XGBoost, LightGBM, and Decision Tree)were applied to a data set of 198 confirmed symbiotic stars and the resulting model was then used to analyze data from the LAMOST survey, leading to the identification of 11,709 potential symbiotic star candidates. Out of these potential symbiotic star candidates listed in the catalog, 15 have spectra available in the Sloan Digital Sky Survey(SDSS) survey. Among these 15 candidates, two candidates, namely V^(*)V603 Ori and V^(*)GN Tau, have been confirmed as symbiotic stars. The remaining 11 candidates have been classified as accreting-only symbiotic star candidates. The other two candidates, one of which has been identified as a galaxy by both SDSS and LAMOST surveys, and the other identified as a quasar by SDSS survey and as a galaxy by LAMOST survey.
基金supported by the Chinese Academy of Sciences (No. KZCX1-YW-06-02)the National Basic Research Program of China (No. 2007CB407304)the Ministry of Environmental Protection of the People’sRepublic of China (No. 200909040)
文摘Detection of estrogenic disrupting compounds（EDCs） in drinking waters around China has led to rising concerns about health risks associated with these compounds.There is,however,a paucity of studies on the occurrence and identification of the main compounds responsible for this pollution in the source waters.To fill this void,we screened estrogenic activities of 23 source water samples from six main river systems in China,using a recombinant two-hybrid yeast assay.All sample extracts induced significant estrogenic activity,with E2 equivalents（EEQ） of raw water ranging from 0.08 to 2.40 ng/L.Additionally,16 samples were selected for chemical analysis by gas chromatography-mass spectrometry.The EDCs of most concern,including estrone（E1）,17β-estradiol（E2）,17α-ethinylestradiol（EE2）,estriol（E3）,diethylstilbestrol（DES）,estradiol valerate（EV）,4-t-octylphenol（4-t-OP）,4-nonylphenols（4-NP） and bisphenol A（BPA）,were determined at concentrations of up to 2.98,1.07,2.67,4.37,2.52,1.96,89.52,280.19 and 710.65 ng/L,respectively.Causality analysis,involving comparison of EEQ values from yeast assay and chemical analysis identified E2,EE2 and 4-NP as the main responsible compounds,accounting for the whole estrogenic activities（39.74% to 96.68%）.The proposed approach using both chemical analysis and yeast assay could be used for the identification and evaluation of EDCs in source waters of China.
基金supported by the National High Technology Research and Development Program (863) of China (No.2009AA06Z402)the National Science and Technology Major Project of China (No. 2008ZX07209-010)the National Natural Science Foundation of China (No.20921063)
文摘Studies on estrogenic disrupting compounds （EDCs） occurrence and identification of main responsible compounds in river water discharged into the sea are of significance. In the present research, we screened estrogenic activities of 10 river water samples from 3 main rivers discharged into Bohai Sea in Tianjin using a recombinant two-hybrid yeast assay and chemical analysis by gas chromatography-mass spectrometry. All sample extracts induced significant estrogenic activity, with 17^-estradiol equivalents （EEQ） of raw water ranging from 5.72 to 59.06 ng/L. Six most concerned EDCs in the fiver water samples including estrone, 17（5-estradiol, 17ct-ethinylestradiol, estriol, diethylstilbestrol and estradiol valerate were determined, with their concentrations up to 50.70, 31.40, 24.40, 37.20, 2.56, and 8.47 ng/L, respectively. Through causality analysis by comparing the EEQ values of yeast assay and chemical analysis, 17ct-ethinylestradiol and 17[3-estradiol were identified as the main contributors to the estrogenic effects of the river samples, accounting for the whole estrogenic activities （62.99% to 185.66%）, and estrogen antagonistic compounds might presented in the heavy polluted water samples. The proposed approach using both chemical analysis and bioassay could be used for identification and evaluation of the estrogenic activity of EDCs in river water.
基金supported by the Frontier Science Key Program of the Chinese Academy of Sciences(No.QYZDY-SSWDQC004)Beijing Municipal Science and Technology Project(No.Z171100004417025)the Open Project Program of SKLEAC of Research Center for Eco-Environmental Sciences(No.18K01KLDWST)
文摘Surfactants such as alkylphenol polyethoxylates(APEOs) and nonylphenol ethoxylates(NPEOs) are commonly used worldwide, but the majority of these compounds, together with their metabolites, have been reported to induce severe biological toxicity. Here, we evaluated for the first time the cytotoxicity,genotoxicity and mitochondrial damage in Chinese hamster ovary(CHO-K1) cells caused by a novel non-ionic surfactant, vanillin ethoxylates(VAEOs), an alternative to APEOs. In parallel, the same in vitro bioassays were conducted on NPEOs along with their metabolic byproducts 4-nonylphenol(4-NP) and vanillin. The results showed that the cytotoxic potency order was NPEOs > 4-NP > VAEOs>vanillin using CCK-8 assays. Also, 4-NP showed potential direct DNA damage in SOS/umu tests, whereas NPEOs, VAEOs and vanillin showed no positive result with and without S9 addition. In addition, none of the test compounds showed obvious genotoxic effects with low olive tail moment value using comet assays. However, all test compounds were shown to cause mitochondrial impairment by increasing mitochondrial mass and decreasing mitochondrial membrane potential in a concentration-dependent manner. And further analysis of reactive oxygen species(ROS) and mitochondrial superoxide(MNSOD)measurement showed that mitochondrial impairment was induced by oxidative stress with intracellular ROS and MNSOD overproduction. It's worth noting that VAEOs and vanillin cause relative lower cytotoxic, genotoxic and mitochondrial damage effects than NPEOs and 4-NP, indicating that VAEOs have the potential to substitute NPEOs as suitable surfactants. Take together, this study elucidates the toxicity profiles of VAEOs and NPEOs relatively comprehensively, and further toxicity analyses are suggested in the population, community and ecosystem.
基金supported by the National Key R & D Program of China (No. 2019YFD0901100)the Frontier Science Key Program of the Chinese Academy of Sciences (No. QYZDY-SSWDQC004)。
文摘Environmental impact of pollutants can be analyzed effectively by acquiring fish behavioral signals in water with biological behavior sensors. However, a variety of factors, such as the complexity of biological organisms themselves, the device error and the environmental noise, may compromise the accuracy and timeliness of model predictions. The current methods lack prior knowledge about the fish behavioral signals corresponding to characteristic pollutants, and in the event of a pollutant invasion, the fish behavioral signals are poorly discriminated. Therefore, we propose a novel method based on Bayesian sequential,which utilizes multi-channel prior knowledge to calculate the outlier sequence based on wavelet feature followed by calculating the anomaly probability of observed values. Furthermore, the relationship between the anomaly probability and toxicity is analyzed in order to achieve forewarning effectively. At last, our algorithm for fish toxicity detection is verified by integrating the data on laboratory acceptance of characteristic pollutants. The results show that only one false positive occurred in the six experiments, the present algorithm is effective in suppressing false positives and negatives, which increases the reliability of toxicity detections, and thereby has certain applicability and universality in engineering applications.
基金supported by the National High Technology Research and Development Program (863) of China(No. 2007AA06Z414)the National Natural Science Foundation of China(No. 50778170)
文摘Environmental chemicals in drinking water can impact human health through nuclear receptors. Additionally, estrogen-related receptors （ERRs） are vulnerable to endocrine-disrupting effects. To date, however, ERR disruption of drinking water potency has not been reported. We used ERRy two-hybrid yeast assay to screen ERRy disrupting activities in a drinking water treatment plant （DWTP） located in north China and in source water from a reservoir, focusing on agonistic, antagonistic, and inverse agonistie activity to 4-hydroxytamoxifen （4-OHT）. Water treatment processes in the DWTP consisted of pre-chlorination, coagulation, coal and sand filtration, activated carbon filtration, and secondary chlorination processes. Samples were extracted by solid phase extraction. Results showed that ERRγ antagonistic activities were found in all sample extracts, but agonistic and inverse agonistic activity to 4-OHT was not found. When calibrated with the toxic equivalent of 4-OHT, antagonistic effluent effects ranged from 3.4 to 33.1 μg/L. In the treatment processes, secondary chlorination was effective in removing ERRy antagonists, but the coagulation process led to significantly increased ERRy antagonistic activity. The drinking water treatment processes removed 73.5 % of ERRy antagonists. To our knowledge, the occurrence of ERRy disruption activities on source and drinking water in vitro had not been reported previously. It is vital, therefore, to increase our understanding of ERRγ disrupting activities in drinking water.
基金the National Natural Science Foundation of China(31800225 and 32370363)the Natural Science Foundation of Shandong Province(ZR2020MC027 and ZR2021QC213).
文摘INDETERMINATE-DOMAIN proteins(IDDs)are a plant-specific transcription factor family characterized by a conserved ID domain with four zinc finger motifs.Previous studies have demonstrated that IDDs coordinate a diversity of physiological processes and functions in plant growth and development,including floral transition,plant architecture,seed and root development,and hormone signaling.In this review,we especially summarized the latest knowledge on the functions and working models of IDD members in Arabidopsis,rice,and maize,particularly focusing on their role in the regulatory network of biotic and abiotic environmental responses,such as gravity,temperature,water,and pathogens.Understanding these mechanisms underlying the function of IDD proteins in these processes is important for improving crop yields by manipulating their activity.Overall,the review offers valuable insights into the functions and mechanisms of IDD proteins in plants,providing a foundation for further research and potential applications in agriculture.
基金supported by the National Natural Scientific Foundation of China (81673112)the Key Projects of International Cooperation among Governments in Scientific and Technological Innovation (2016YFE0119100)+1 种基金the Natural Science Basic Research Plan in Shaanxi Province of China (2017JZ024)the Fundamental Research Funds for the Central Universities。
文摘Dear Editor,Psychiatric disorders are a group of mental disorders characterized by psychological or behavioral disabilities.Losing of the ability to work and assuming the extensive cost of long-term treatment,patients with psychiatric disorders are forced to support a heavy financial and medical burden.The growth and development of brain structures are dynamic,and different brain structures have major and specific functions to control behavior and performance.
基金financial supported by the Open Research Fund of Key Laboratory of Drinking Water Source Protection of the Ministry of Ecology and Environment Chinese Research Academy of Environmental Sciences(No.2024YYSYKFZD08)the Fundamental Research Funds for the Central Public-interest Scientific Institution(China)(No.2024YSKY-02)+1 种基金the National Natural Science Foundation of China(No.52209039)the National Key Research and Development Program of China(Nos.2022YFC3204000 and 2022YFC3204004).
文摘Dissolved organic matter(DOM)participates in and affects many biological processes in aquatic ecosystems,altering nutrient cycling,bioavailability and toxicity of pollutants.Lake water contains thousands of DOM molecules,which largely originate from natural sources and are greatly influenced by external inputs through anthropogenic activities.To elucidate the shaping mechanism of the DOM composition under complex habitat conditions and anthropogenic disturbances,the characteristic molecular fingerprint of DOM was determined based on chemodiversity information obtained via ultrahigh-resolution mass spectrometry for the Baiyangdian wetland(a typical large macrophytic shallow lake in North China).In the Baiyangdian wetland,the DOM composition exhibited high complexity and spatial heterogeneity,and more recalcitrant DOM molecules were identified in summer than in spring.Although multiple natural factors(nutrient concentration,depth of water and quality of submerged macrophytes)and anthropogenic factors(different land uses and discharge of pollutants)were associated with the relative abundance of various DOM molecules,only the influences from the anthropogenic factors were statistically significant.The alpha diversity index of DOM could reflect variations in both the natural factors(total dissolved phosphorus)and the anthropogenic factors(discharge of nitrogen and phosphorus).Furthermore,the DOM composition in each group were clustered according to the ecological functions(natural reserves,tourism,breeding,and domestic supply functions),and exhibited molecular fingerprint features.This study provides an effective approach to characterize the molecular fingerprint features of DOM and critical information to better understand the shaping mechanism of the DOM composition under complex habitat conditions and anthropogenic disturbances.
文摘Accurately predicting the synthesizability of inorganic crystal materials serves as a pivotal tool for the efficient screening of viable candidates,substantially reducing the costs associated with extensive experimental trial-and-error processes.However,existing methods,limited by static structural descriptors such as chemical composition and lattice parameters,fail to account for atomic vibrations,which may introduce spurious correlations and undermine predictive reliability.Here,we propose a deep learning model termed integrating graph and dynamical stability(IGDS)for predicting the synthesizability of inorganic crystals.IGDS employs graph representation learning to construct crystal graphs that precisely capture the static structures of crystals and integrates phonon spectral features extracted from pre-trained machine learning interatomic potentials to represent their dynamic properties.Our model exhibits outstanding performance in predicting the synthesizability of low-energy unsynthesizable crystals across 41 material systems,achieving precision and recall values of 0.916/0.863 for ternary compounds.By capturing both static structural descriptors and dynamic features,IGDS provides a physics-informed method for predicting the synthesizability of inorganic crystals.This approach bridges the gap between theoretical design concepts and their practical implementation,thereby streamlining the development cycle of new materials and enhancing overall research efficiency.
基金This work was supported by grants from the National Natural Science Foundation of China(81570768 to Y.-C.W.,31900841 to Yan Li,91957205 and 31525012 to H.Y.,and 81471016 to J.J.)the Ministry of Science and Technology of China(2016YFA0500102 and 2016YFC1304905)CAS Key Laboratory of Nutrition,Metabolism and Food Safety(KLNMFS2019-01),and Chinese Academy of Sciences Interdisciplinary Innovation Team.
文摘Muscle regeneration after damage or during myopathies requires a fine cooperation between myoblast proliferation and myogenic differentiation.A growing body of evidence suggests that microRNAs play critical roles in myocyte proliferation and differentiation transcriptionally.However,the molecular mechanisms underlying the orchestration are not fully understood.Here,we showed that miR-130b is able to repress myoblast proliferation and promote myogenic differentiation via targeting Sp1 transcription factor.Importantly,overexpression of miR-130b is capable of improving the recovery of damaged muscle in a freeze injury model.Moreover,miR-130b expression is declined in the muscle of muscular dystrophy patients.Thus,these results indicated that miR-130b may play a role in skeletal muscle regeneration and myopathy progression.Together,our findings suggest that the miR-130b/Sp1 axis may serve as a potential therapeutic target for the treatment of patients with muscle damage or severe myopathies.
文摘Study on effective disposal and utilization of sewage sludge has recently been the target of growing interest in China. However, potential risks are associated with the use of sludge due to its contamination with toxic organics, heavy metals and pathogenic microorganisms. In this study, a screening assessment was conducted on sewage sludge samples collected from 17 different sewage treatment plants in Beijing, based on a batch of in vitro bioassays, including a set of recombinant gene yeast assays for endocrine disruption, and an ethoxy resorufin-O- deethylase （EROD） assay using H4IIE cells for aryl hydrocarbon receptor （Ah-R） agonistic activities. Our results suggested that moderate levels of estrogen receptor agonistic activities （0.9 ng E2. g-1 to 6.8 ng E2. gl, dw）, but relative higher androgen receptor antagonistic activ- ities （nd to 45%）, progestin receptor antagonistic activities （nd to 80%） and Ah-R agonistic activities （1390 to 6740 pg 2,3,7,8-tetrachlorodibenzo-p-dioxin （TCDD）·g-1, dw） were found in sewage sludge samples. However, there were no significant correlations between the toxic effects of sewage sludge and the sewage treatment processes. In addition, the 17β-estradiol （E2） equivalent quantity （EEQ） level of the sewage sludge was increased after the composting treatment, whereas the 2,3,7,8-tetrachlorodi- benzo-p-dioxin toxic equivalent quantity （TEQ） level of sewagesludge composted was much lower than that of sewage sludge.
基金This work was supported by the National Natural Science Foundation of China(Nos.62272288,61972451,and U22A2041)the Shenzhen Key Laboratory of Intelligent Bioinformatics(No.ZDSYS20220422103800001).
文摘Generating novel molecules to satisfy specific properties is a challenging task in modern drug discovery,which requires the optimization of a specific objective based on satisfying chemical rules.Herein,we aim to optimize the properties of a specific molecule to satisfy the specific properties of the generated molecule.The Matched Molecular Pairs(MMPs),which contain the source and target molecules,are used herein,and logD and solubility are selected as the optimization properties.The main innovative work lies in the calculation related to a specific transformer from the perspective of a matrix dimension.Threshold intervals and state changes are then used to encode logD and solubility for subsequent tests.During the experiments,we screen the data based on the proportion of heavy atoms to all atoms in the groups and select 12365,1503,and 1570 MMPs as the training,validation,and test sets,respectively.Transformer models are compared with the baseline models with respect to their abilities to generate molecules with specific properties.Results show that the transformer model can accurately optimize the source molecules to satisfy specific properties.
文摘Effluents from wastewater treatment plant （WWTP） have been reported to have a broad spectrum of endocrine disrupting compounds （EDCs）. The majority of studies have focused on the occurrence of estrogenic activity, while ignoring nuclear hormone receptors （NRs） pathways. In the present study, a battery of in vitro yeast bioassays and a cell bioassay, including antagonistic and agonistic effects on estrogen receptor （ER）, androgen receptor （AR）, progesterone receptor （PR）, estrogen- related receptor （ERR） and aryl hydrocarbon receptor （AHR）, were conducted to evaluate the removal efficien- cies of EDCs by different treatment processes of a WWTP located in Beijing. Estrogenic, anti-estrogenic, anti- androgenic, anti-progesteronic, anti-ERR and the activa- tion of AHR activities were detected in samples from all treatment processes and the receiving water. The concen- tration of estrogenic contaminants with estradiol （E2） equivalent concentrations ranged from 0.82 x 10-9 to 3.54 x 10 9g Ee_EQ.L-1. The concentration of anti-estrogenic contaminants with 4-hydroxytamoxifen （4-OHT） equiva- lent concentrations ranged from 1.24 × 10-6 to 2.36 x 10-6 g 4-OHT-EQ.L-1. The concentration of anti-androgenic contaminants ranged from 2.21 x 10-s to 3.52 × 10-6g flutamide-EQ. L-1. The concentration of anti-progesteronic contaminants ranged from 3.15 x 10^-5 to 2.71 x 10^-4g RU486-EQ. L-1. The concentration of anti-ERR contami- nants ranged from 7.09 x 10-5 to 6.50 x 104 g 4-OHT-EQ × L^-10. The concentration of AHR activators ranged from 1.7 × 10-10 to 3.4 × 10^-10g TCDD-EQ-L-1. These processes including secondary clarifier, coagulation, as well as coal and sand filtration could eliminated 67.2% of estrogenic contaminants, 47.0% of anti-estrogenic contaminants, 98.3% of anti-androgenic contaminants, 88.4% of anti- progesteronic contaminants, 65.4% of anti-ERR contami- nants and 46.9% of AHR activators. WWTP effluents contain multiple receptor disruptors may have very complex adverse effects on exposed organisms.
