Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in large...Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level.Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate(SA) and sodium butyrate(SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC(9% starch), HC(18% starch), HCSA(18% starch;2 g/kg SA), HCSB(18% starch;2 g/kg SB), and HCSASB(18% starch;1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d.Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy(ATG101, LC3B and TFEB), promoting lipolysis(CPT1α, HSL and AMPKα), and inhibiting adipogenesis(FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver(CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors(IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate(Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition.Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition;and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.展开更多
Pancreatic cancer is a malignant disease characterized by low survival and high recurrence rate,whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed.Early diagnosis is ...Pancreatic cancer is a malignant disease characterized by low survival and high recurrence rate,whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed.Early diagnosis is particularly important because prognostic/predictive markers help guide optimal individualized treatment regimens.So far,CA19-9 is the only biomarker for pancreatic cancer approved by the FDA,but its effectiveness is limited by low sensitivity and specificity.With recent advances in genomics,proteomics,metabolomics,and other analytical and sequencing technologies,the rapid acquisition and screening of biomarkers is now possible.Liquid biopsy also occupies a significant place due to its unique advantages.In this review,we systematically describe and evaluate the available biomarkers that have the greatest potential as vital tools in diagnosing and treating pancreatic cancer.展开更多
Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacteria...Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella sp.have been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal models.These bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,B.fragilis toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from Salmonella.These bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 MAPK.Moreover,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy process.Treatments with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different degrees.In this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial therapies.Specific bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC.These bacteria may be useful as biomarkers or therapeutic targets for CRC.展开更多
Near-infrared (NIR) spectroscopy combined with chemometrics methods was applied to the rapid and reagent-free analysis of serum urea nitrogen (SUN). The mul-partitions modeling was performed to achieve parameter stabi...Near-infrared (NIR) spectroscopy combined with chemometrics methods was applied to the rapid and reagent-free analysis of serum urea nitrogen (SUN). The mul-partitions modeling was performed to achieve parameter stability. A large-scale parameter cyclic and global optimization platform for Norris derivative filter (NDF) of three parameters (the derivative order: d, the number of smoothing points: s and the number of differential gaps: g) was developed with PLS regression. Meantime, the parameters’ adaptive analysis of NDF algorithm was also given, and achieved a significantly better modeling effect than one without spectral pre-processing. After eliminating the interference wavebands of saturated absorption, the modeling performance was further improved. In validation, the root mean square error (SEP), correlation coefficient (RP) for prediction and the ratio of performance to deviation (RPD) were 1.66 mmol?L-1, 0.966 and 4.7, respectively. The results showed that the high-precision analysis of SUN was feasibility based on NIR spectroscopy and Norris-PLS. The global optimization method of NDF is also expected to be applied to other analysis objects.展开更多
High-carbohydrate(HC)diets decrease the intestinal levels of sodium acetate(SA)and sodium butyrate(SB)and impair the gut health of largemouth bass;however,SA and SB have been shown to enhance immunity and improve inte...High-carbohydrate(HC)diets decrease the intestinal levels of sodium acetate(SA)and sodium butyrate(SB)and impair the gut health of largemouth bass;however,SA and SB have been shown to enhance immunity and improve intestinal health in farmed animals.Thus,the present study was to investigate the effects of dietary SA and SB on HC diet-induced intestinal injury and the potential mechanisms in juvenile largemouth bass.The experiment set five isonitrogenous and isolipidic diets,including a lowcarbohydrate diet(9%starch)(LC),a high carbohydrate diet(18%starch)(HC),and the HC diet supplemented with 2 g/kg SA(HCSA),2 g/kg SB(HCSB)or a combination of 1 g/kg SA and 1 g/kg SB(HCSASB).The feeding experiment was conducted for 8 weeks.A total of 525 juvenile largemouth bass with an initial body weight of 7.00±0.20 g were used.The results showed that dietary SA and SB improved the weight gain rate and specific growth rate(P<0.05)and ameliorated serum parameters(alkaline phosphatase,acid phosphatase,glutamate transaminase,and glutamic oxaloacetic transaminase)(P<0.05).And,importantly,dietary SA and SB repaired the intestinal barrier by increasing the expression levels of zonula occludens-1,occludin,and claudin-7(P<0.05),reduced HC-induced intestinal damage,and alleviated intestinal inflammation and cell apoptosis by attenuating HC-induced intestinal endoplasmic reticulum stress(P<0.05).Further results revealed that dietary SA and SB reduced HC-induced intestinal fat deposition by inhibiting adipogenesis and promoting lipolysis(P<0.05).In summary,this study demonstrated that dietary SA and SB attenuated HC-induced intestinal damage and reduced excessive intestinal fat deposition in largemouth bass.展开更多
Objective: To isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities.Methods: The chemical constituents w...Objective: To isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities.Methods: The chemical constituents were isolated and purified by combining with ODS column chromatography, silica gel column chromatography and by performing semipreparative HPLC. Their structures were established on the basis of 1D NMR(1H-NMR and13C-NMR) and 2D NMR(1H–1H COSY,HSQC, HMBC and NOESY), as well as HRESIMS and comparison with literature data. In addition, the absolute configuration of compound 1 was determined by calculated ECD data.Results: One previously undescribed tetracyclic triterpenoid derivative, named as integracide L(1), 12aacetoxy-4,4-dimethyl-24-methylene-5a-cholesta-8,14-diene-2a,3β,11β-triol(2), 12a-acetoxy-4,4-dime thyl-24-methylene-5a-cholesta-8-momoene-2a,3β,11β-triol(3), 12a-acetoxy-4,4-dimethyl-24-methy lene-5a-cholesta-8,14-diene-3β,11β-triol(4), and 12a-acetoxy-4,4-dimethyl-24-methylene-5acholesta-8-momoene-3β,11β-triol(5) were isolated from F. sporotrichioide. Moreover, compound 1 was rare tetracyclic triterpenoid with single methyl replacement at C-4 position.Conclusion: Compound 1 was a new tetracyclic triterpenoid isolated from the endophytic fungus F.sporotrichioides. In addition, compound 2 could inhibit the growth of three different human cancer cells significantly. Compounds 3 and 5 were found to possess better cytotoxic activities on Hep G-2 cells than the other compounds, with IC50values of(2.8 ± 0.1) and(6.3 ± 0.3) μmol/L respectively.展开更多
Non-invasive characterization of powders may take one of two approaches:imaging and counting individual particles;or relying on scattered light to estimate the particle size distribution(PSD)of the ensemble.The former...Non-invasive characterization of powders may take one of two approaches:imaging and counting individual particles;or relying on scattered light to estimate the particle size distribution(PSD)of the ensemble.The former approach runs into practical difficulties,as the system must conform to the working distance and other restrictions of the imaging optics.The latter approach requires an inverse map from the speckle autocorrelation to the particle sizes.The principle relies on the pupil function determining the basic sidelobe shape,whereas the particle size spread modulates the sidelobe intensity.We recently showed that it is feasible to invert the speckle autocorrelation and obtain the PSD using a neural network,trained efficiently through a physics-informed semi-generative approach.In this work,we eliminate one of the most time-consuming steps of our previous method by engineering the pupil function.By judiciously blocking portions of the pupil,we sacrifice some photons but in return we achieve much enhanced sidelobes and,hence,higher sensitivity to the change of the size distribution.The result is a 60×reduction in total acquisition and processing time,or 0.25 seconds per frame in our implementation.Almost real-time operation in our system is not only more appealing toward rapid industrial adoption,it also paves the way for quantitative characterization of complex spatial or temporal dynamics in drying,blending,and other chemical and pharmaceutical manufacturing processes.展开更多
Due to a higher operating temperature(≥800 ℃),Solar Particle Receiver(SPR)which uses particles as the working medium is considered as one of best candidates to improve the thermoelectric conversion efficiency of con...Due to a higher operating temperature(≥800 ℃),Solar Particle Receiver(SPR)which uses particles as the working medium is considered as one of best candidates to improve the thermoelectric conversion efficiency of concentrating solar power plants.In this paper,a quartz tube solid particle receiver model is fully developed by using the discretized lumped parameter method,in which the calculation process of particle temperature and thermal loss is clearly given.In order to improve the manipulation level of particle receiver during the operation,the dynamic characteristics of the quartz tube particle receiver are comprehensively studied by the disturbance test of selected input parameters.Besides,in order to grasp the influence rule of key parameters on the thermal performance of particle receiver,the key parameters'sensitivity analysis is also deeply studied.The results show that the particle outlet temperature can reach as high as 810 ℃ under a relatively small value of solar flux 600 kW/m^(2),but the receiver efficiency is only about 75%;Besides,the receiver efficiency shows a variation tendency that it rises first falls afterwards with the increase of incident solar flux.The validity of proposed model is verified by a heating experi-mental system with a single quartz tube,and the relative error is not more than 7.9%.The research results are beneficial for understanding the dynamic characteristics and designing the particle receiver.展开更多
Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell surface.They can transport nucleic acids,proteins,and lipids for intercellular comm...Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell surface.They can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target cells.In cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting angiogenesis.They are also involved in the development of resistance to chemotherapeutic drugs.Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers.Because of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.展开更多
Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sino...Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of cancer.Here,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activity on GBM and explored the underlying mechanism.SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells.It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis.Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3 K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body.SW33 also induced autophagy through the PI3 K/AKT/mTOR and AMPK/mTOR pathways.Thus,SW33 appears to be a promising drug for treating GBM effectively and safely.展开更多
Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effectiv...Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effective drug for GBM in the clinic.Therefore,it is urgent to identify new drug targets and corresponding drugs for GBM.In this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall survival.Overexpression of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite effect.SPHK1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of PTX3.SPHK1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM growth.Inhibition of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse models.In summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy.展开更多
BACKGROUND Liangshan,officially the Liangshan Yi Autonomous Prefecture,is an autonomous prefecture occupying much of the southern portion of Sichuan Province.It has been a remote and deeply impoverished area and also ...BACKGROUND Liangshan,officially the Liangshan Yi Autonomous Prefecture,is an autonomous prefecture occupying much of the southern portion of Sichuan Province.It has been a remote and deeply impoverished area and also has the largest population of ethnic Yi people in China(1).For many years,due to geographical environment conditions,traffic conditions,and other historic restrictions,the human immunodeficiency virus(HIV)epidemic in Liangshan Prefecture has become the focus of HIV prevention and control in China since the first acquired immunodeficiency syndrome(AIDS)case was reported in this area in 1995(2-3).展开更多
基金supported by the Double Support Project (035–2221993229)。
文摘Background Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate(HC) diet disrupt the homeostasis of the gut–liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level.Method Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate(SA) and sodium butyrate(SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC(9% starch), HC(18% starch), HCSA(18% starch;2 g/kg SA), HCSB(18% starch;2 g/kg SB), and HCSASB(18% starch;1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d.Results We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy(ATG101, LC3B and TFEB), promoting lipolysis(CPT1α, HSL and AMPKα), and inhibiting adipogenesis(FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver(CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors(IL-1β, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate(Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition.Conclusions In conclusion, dietary SA and SB can reduce hepatic lipid deposition;and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.
基金This work was supported by Beijing Natural Science Foundation(7212157,China)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-029 and 2022-12M-JB-011,China)National Natural Science Foundation of China(81703536,China).
文摘Pancreatic cancer is a malignant disease characterized by low survival and high recurrence rate,whose patients are mostly at the stage of locally advanced or metastatic disease when first diagnosed.Early diagnosis is particularly important because prognostic/predictive markers help guide optimal individualized treatment regimens.So far,CA19-9 is the only biomarker for pancreatic cancer approved by the FDA,but its effectiveness is limited by low sensitivity and specificity.With recent advances in genomics,proteomics,metabolomics,and other analytical and sequencing technologies,the rapid acquisition and screening of biomarkers is now possible.Liquid biopsy also occupies a significant place due to its unique advantages.In this review,we systematically describe and evaluate the available biomarkers that have the greatest potential as vital tools in diagnosing and treating pancreatic cancer.
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-3-007)the National Natural Science Foundation of China(Grant No.81803584)+1 种基金the Technology Major Projects for“Major New Drugs Innovation and Development”(Grant Nos.2018ZX09711001-005-025 and 2018ZX09711001-012)the Inner Mongolian Natural Science Foundation(Grant No.2018LH08032)。
文摘Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella sp.have been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal models.These bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,B.fragilis toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from Salmonella.These bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 MAPK.Moreover,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy process.Treatments with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different degrees.In this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial therapies.Specific bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC.These bacteria may be useful as biomarkers or therapeutic targets for CRC.
文摘Near-infrared (NIR) spectroscopy combined with chemometrics methods was applied to the rapid and reagent-free analysis of serum urea nitrogen (SUN). The mul-partitions modeling was performed to achieve parameter stability. A large-scale parameter cyclic and global optimization platform for Norris derivative filter (NDF) of three parameters (the derivative order: d, the number of smoothing points: s and the number of differential gaps: g) was developed with PLS regression. Meantime, the parameters’ adaptive analysis of NDF algorithm was also given, and achieved a significantly better modeling effect than one without spectral pre-processing. After eliminating the interference wavebands of saturated absorption, the modeling performance was further improved. In validation, the root mean square error (SEP), correlation coefficient (RP) for prediction and the ratio of performance to deviation (RPD) were 1.66 mmol?L-1, 0.966 and 4.7, respectively. The results showed that the high-precision analysis of SUN was feasibility based on NIR spectroscopy and Norris-PLS. The global optimization method of NDF is also expected to be applied to other analysis objects.
基金sponsored by Natural Science Foundation of Sichuan Province(2023NSFSC1220)
文摘High-carbohydrate(HC)diets decrease the intestinal levels of sodium acetate(SA)and sodium butyrate(SB)and impair the gut health of largemouth bass;however,SA and SB have been shown to enhance immunity and improve intestinal health in farmed animals.Thus,the present study was to investigate the effects of dietary SA and SB on HC diet-induced intestinal injury and the potential mechanisms in juvenile largemouth bass.The experiment set five isonitrogenous and isolipidic diets,including a lowcarbohydrate diet(9%starch)(LC),a high carbohydrate diet(18%starch)(HC),and the HC diet supplemented with 2 g/kg SA(HCSA),2 g/kg SB(HCSB)or a combination of 1 g/kg SA and 1 g/kg SB(HCSASB).The feeding experiment was conducted for 8 weeks.A total of 525 juvenile largemouth bass with an initial body weight of 7.00±0.20 g were used.The results showed that dietary SA and SB improved the weight gain rate and specific growth rate(P<0.05)and ameliorated serum parameters(alkaline phosphatase,acid phosphatase,glutamate transaminase,and glutamic oxaloacetic transaminase)(P<0.05).And,importantly,dietary SA and SB repaired the intestinal barrier by increasing the expression levels of zonula occludens-1,occludin,and claudin-7(P<0.05),reduced HC-induced intestinal damage,and alleviated intestinal inflammation and cell apoptosis by attenuating HC-induced intestinal endoplasmic reticulum stress(P<0.05).Further results revealed that dietary SA and SB reduced HC-induced intestinal fat deposition by inhibiting adipogenesis and promoting lipolysis(P<0.05).In summary,this study demonstrated that dietary SA and SB attenuated HC-induced intestinal damage and reduced excessive intestinal fat deposition in largemouth bass.
基金funded by Outstanding Youth Foundation of Heilongjiang province(NO.YQ2021H009).
文摘Objective: To isolate bioactive compounds from the endophytic fungus Fusarium sporotrichioides isolated from Rauwolfia yunnanensis, and investigate their pharmacological activities.Methods: The chemical constituents were isolated and purified by combining with ODS column chromatography, silica gel column chromatography and by performing semipreparative HPLC. Their structures were established on the basis of 1D NMR(1H-NMR and13C-NMR) and 2D NMR(1H–1H COSY,HSQC, HMBC and NOESY), as well as HRESIMS and comparison with literature data. In addition, the absolute configuration of compound 1 was determined by calculated ECD data.Results: One previously undescribed tetracyclic triterpenoid derivative, named as integracide L(1), 12aacetoxy-4,4-dimethyl-24-methylene-5a-cholesta-8,14-diene-2a,3β,11β-triol(2), 12a-acetoxy-4,4-dime thyl-24-methylene-5a-cholesta-8-momoene-2a,3β,11β-triol(3), 12a-acetoxy-4,4-dimethyl-24-methy lene-5a-cholesta-8,14-diene-3β,11β-triol(4), and 12a-acetoxy-4,4-dimethyl-24-methylene-5acholesta-8-momoene-3β,11β-triol(5) were isolated from F. sporotrichioide. Moreover, compound 1 was rare tetracyclic triterpenoid with single methyl replacement at C-4 position.Conclusion: Compound 1 was a new tetracyclic triterpenoid isolated from the endophytic fungus F.sporotrichioides. In addition, compound 2 could inhibit the growth of three different human cancer cells significantly. Compounds 3 and 5 were found to possess better cytotoxic activities on Hep G-2 cells than the other compounds, with IC50values of(2.8 ± 0.1) and(6.3 ± 0.3) μmol/L respectively.
基金the following funding support:Millennium Pharmaceuticals,Inc.(a subsidiary of Takeda Pharmaceuticals)D824-MT15National Research Foundation,Singapore,Intra-Create thematic grant NRF2019-THE002-0006.
文摘Non-invasive characterization of powders may take one of two approaches:imaging and counting individual particles;or relying on scattered light to estimate the particle size distribution(PSD)of the ensemble.The former approach runs into practical difficulties,as the system must conform to the working distance and other restrictions of the imaging optics.The latter approach requires an inverse map from the speckle autocorrelation to the particle sizes.The principle relies on the pupil function determining the basic sidelobe shape,whereas the particle size spread modulates the sidelobe intensity.We recently showed that it is feasible to invert the speckle autocorrelation and obtain the PSD using a neural network,trained efficiently through a physics-informed semi-generative approach.In this work,we eliminate one of the most time-consuming steps of our previous method by engineering the pupil function.By judiciously blocking portions of the pupil,we sacrifice some photons but in return we achieve much enhanced sidelobes and,hence,higher sensitivity to the change of the size distribution.The result is a 60×reduction in total acquisition and processing time,or 0.25 seconds per frame in our implementation.Almost real-time operation in our system is not only more appealing toward rapid industrial adoption,it also paves the way for quantitative characterization of complex spatial or temporal dynamics in drying,blending,and other chemical and pharmaceutical manufacturing processes.
基金financial support provided by Beijing Municipal Natural Science Foundation“Study on the gas-solid heat transfer characteristics and enhancement mechanism of fluidized bed solid particle/sCO_(2) heat exchanger in solar thermal power plant”(No.3222033)by Chinese Universities Scientific Fund(No.15052003).
文摘Due to a higher operating temperature(≥800 ℃),Solar Particle Receiver(SPR)which uses particles as the working medium is considered as one of best candidates to improve the thermoelectric conversion efficiency of concentrating solar power plants.In this paper,a quartz tube solid particle receiver model is fully developed by using the discretized lumped parameter method,in which the calculation process of particle temperature and thermal loss is clearly given.In order to improve the manipulation level of particle receiver during the operation,the dynamic characteristics of the quartz tube particle receiver are comprehensively studied by the disturbance test of selected input parameters.Besides,in order to grasp the influence rule of key parameters on the thermal performance of particle receiver,the key parameters'sensitivity analysis is also deeply studied.The results show that the particle outlet temperature can reach as high as 810 ℃ under a relatively small value of solar flux 600 kW/m^(2),but the receiver efficiency is only about 75%;Besides,the receiver efficiency shows a variation tendency that it rises first falls afterwards with the increase of incident solar flux.The validity of proposed model is verified by a heating experi-mental system with a single quartz tube,and the relative error is not more than 7.9%.The research results are beneficial for understanding the dynamic characteristics and designing the particle receiver.
基金supported by CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007,China)Technology Major Projects for‘Major New Drugs Innovation and Development’(2018ZX09711001-005-025 and 2018ZX09711001-012,China)supported by National Natural Science Foundation of China(No.81703536 and 81803584)
文摘Exosomes are cell-derived nano vesicles with diameters from 30 to 150 nm,released upon fusion of multi vesicular bodies with the cell surface.They can transport nucleic acids,proteins,and lipids for intercellular communication and activate signaling pathways in target cells.In cancers,exosomes may participate in growth and metastasis of tumors by regulating the immune response,blocking the epithelial-mesenchymal transition,and promoting angiogenesis.They are also involved in the development of resistance to chemotherapeutic drugs.Exosomes in liquid biopsies can be used as non-invasive biomarkers for early detection and diagnosis of cancers.Because of their amphipathic structure,exosomes are natural drug delivery vehicles for cancer therapy.
基金funded by Beijing Natural Science Foundation(7212157,China)CAMS Innovation Fund for Medical Sciences(2016-I2M-3-007,China)+1 种基金National Natural Science Foundation of China(81703536,81803584,81703565,China)Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09711001-005-025,2018ZX09711001012,China)。
文摘Glioblastoma multiforme(GBM)in the central nervous system is the most lethal advanced glioma and currently there is no effective treatment for it.Studies of sinomenine,an alkaloid from the Chinese medicinal plant,Sinomenium acutum,showed that it had inhibitory effects on several kinds of cancer.Here,we synthesized a sinomenine derivative,sino-wcj-33(SW33),tested it for antitumor activity on GBM and explored the underlying mechanism.SW33 significantly inhibited proliferation and colony formation of GBM and reduced migration and invasion of U87 and U251 cells.It also arrested the cell cycle at G2/M phase and induced mitochondria-dependent apoptosis.Differential gene enrichment analysis and pathway validation showed that SW33 exerted anti-GBM effects by regulating PI3 K/AKT and AMPK signaling pathways and significantly suppressed tumorigenicity with no obvious adverse effects on the body.SW33 also induced autophagy through the PI3 K/AKT/mTOR and AMPK/mTOR pathways.Thus,SW33 appears to be a promising drug for treating GBM effectively and safely.
基金This work was supported by Beijing Natural Science Foundation(7212157,China)This work was also supported by CAMS Innovation Fund for Medical Sciences(2021-I2M-1-029 and 2022-12M-JB-011,China)National Natural Science Foundation of China(81703536,China).
文摘Glioblastoma(GBM)is the most challenging malignant tumor of the central nervous system because of its high morbidity,mortality,and recurrence rate.Currently,mechanisms of GBM are still unclear and there is no effective drug for GBM in the clinic.Therefore,it is urgent to identify new drug targets and corresponding drugs for GBM.In this study,in silico analyses and experimental data show that sphingosine kinase 1(SPHK1)is up-regulated in GBM patients,and is strongly correlated with poor prognosis and reduced overall survival.Overexpression of SPHK1 promoted the proliferation,invasion,metastasis,and clonogenicity of GBM cells,while silencing SPHK1 had the opposite effect.SPHK1 promoted inflammation through the NF-κB/IL-6/STAT3 signaling pathway and led to the phosphorylation of JNK,activating the JNK-JUN and JNK-ATF3 pathways and promoting inflammation and proliferation of GBM cells by transcriptional activation of PTX3.SPHK1 interacted with PTX3 and formed a positive feedback loop to reciprocally increase expression,promote inflammation and GBM growth.Inhibition of SPHK1 by the inhibitor,PF543,also decreased tumorigenesis in the U87-MG and U251-MG SPHK1 orthotopic mouse models.In summary,we have characterized the role and molecular mechanisms by which SPHK1 promotes GBM,which may provide opportunities for SPHK1-targeted therapy.
文摘BACKGROUND Liangshan,officially the Liangshan Yi Autonomous Prefecture,is an autonomous prefecture occupying much of the southern portion of Sichuan Province.It has been a remote and deeply impoverished area and also has the largest population of ethnic Yi people in China(1).For many years,due to geographical environment conditions,traffic conditions,and other historic restrictions,the human immunodeficiency virus(HIV)epidemic in Liangshan Prefecture has become the focus of HIV prevention and control in China since the first acquired immunodeficiency syndrome(AIDS)case was reported in this area in 1995(2-3).
