The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies reveal...The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.展开更多
Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers i...Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.展开更多
Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it:injecting fluid into the submucosa to elevate the lesion...Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it:injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en- bloc resection compared to endoscopic mucosal resection (EMR). Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects:(1) the possibility of nodal metastases of the lesion, (2) technical difficulty such as location, ulceration and operator’s skill, and (3) organ characteristics.展开更多
KaKs_Calculator is a software package that calculates nonsynonymous （Ka） and synonymous （Ks） substitution rates through model selection and model averaging. Since existing methods for this estimation adopt their s...KaKs_Calculator is a software package that calculates nonsynonymous （Ka） and synonymous （Ks） substitution rates through model selection and model averaging. Since existing methods for this estimation adopt their specific mutation （substitution） models that consider different evolutionary features, leading to diverse estimates, KaKs_Calculator implements a set of candidate models in a maximum likelihood framework and adopts the Akaike information criterion to measure fitness between models and data, aiming to include as many features as needed for accurately capturing evolutionary information in protein-coding sequences. In addition, several existing methods for calculating Ka and Ks are also incorporated into this software. KaKs_Calculator, including source codes, compiled executables, and documentation, is freely available for academic use at http：//evolution.genomics.org.cn/software.htm.展开更多
Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induce...Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induced pluripo- tent stem （iPS） cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDXl-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insuIin-producing ceils. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.展开更多
The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses.NF-κB induces the expression of various pro-inflammatory g...The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses.NF-κB induces the expression of various pro-inflammatory genes,including those encoding cytokines and chemokines,and also participates in inflammasome regulation.In addition,NF-κB plays a critical role in regulating the survival,activation and differentiation of innate immune cells and inflammatory T cells.Consequently,deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases.In this review,we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.展开更多
Cereal straw is one of the most abundant biomass burned in China but its contribution to fine particulates is not adequately understood. In this study, three main kinds of cereal straws were collected from five grain ...Cereal straw is one of the most abundant biomass burned in China but its contribution to fine particulates is not adequately understood. In this study, three main kinds of cereal straws were collected from five grain producing areas in China. Fine particulate matters （PMzs） from the cereal straws subjected to control burnings, both under smoldering and flaming status, were sampled by using a custom made dilution chamber and sampling system in the laboratory. Element carbon （EC） and organic carbon （OC） was analyzed. 141 compounds of organic matters were measured by gas chromatography-mass spectrum （GC-MS）. Source profiles of particulate organic matters emitted from cereal straw burnings were obtained. The results indicated that organic matters contribute a large fraction in fine particulate matters. Levoglucosan had the highest contributions with averagely 4.5% in mass of fine particulates and can be considered as the tracer of biomass burnings. Methyloxylated phenols from lignin degradation also had high concentrations in PM2.5, and contained approximately equal amounts of guaiacyl and syringyl compounds. 13-Sitostrol also made up relatively a large fraction of PMz5 compared with the other sterols （0.18%-0.63% of the total fine particle mass）. Normal alkanes, PAHs, fatty acids, as well as normal alkanols had relatively lower concentrations compared with the compounds mentioned above. Carbon preference index （CPI） of normal alkanes and alkanoic acids showed characteristics of biogenic fuel burnings. Burning status significantly influenced the formations of EC and PAHs. The differences between the emission profiles of straw and wood combustions were displayed by the fingerprint compounds, which may be used to identify the contributions between wood and straw burnings in source apportionment researches.展开更多
To identify the concentrations and sources of heavy metals, and to assess soil environmental quality, 63 soil samples were collected in Yibin City, Sichuan Province, China. Mean concentrations of As, Pb, Zn, and Cu we...To identify the concentrations and sources of heavy metals, and to assess soil environmental quality, 63 soil samples were collected in Yibin City, Sichuan Province, China. Mean concentrations of As, Pb, Zn, and Cu were 10.55, 61.23, 138.88 and 56.35 mg/kg, respectively. As concentrations were comparable to background values, while Pb, Zn, and Cu concentrations were higher than their corresponding background values. Industrial areas exhibited the highest concentrations of As, Pb, Zn, and Cu, while the lowest concentrations occurred in parks. Statistical analysis was performed and two cluster groups of metals were identified with Pb, Zn, and Cu in one group and As in the other. Spatial distribution maps indicated that Pb, Zn, and Cu were mainly controlled by anthropogenic activities, whereas As could be mainly accounted for by soil parent materials. Pollution index values of As, Pb, Zn, and Cu varied in the range of 0.24-1.93, 0.66-7.24, 0.42-4.19, and 0.62-5.25, with mean values of 0.86, 1.98, 1.61, and 1.78, respectively. The integrated pollution index （IPI） values of these metals varied from 0.82 to 3.54, with a mean of 1.6 and more than 90% of soil samples were moderately or highly contaminated with heavy metals. The spatial distribution of IPI showed that newer urban areas displayed relatively lower heavy metal contamination in comparison with older urban areas.展开更多
Plants of Artemisia annua produce artemisinin, a sesquiterpene lactone widely used in malaria treatment. Amorpha-4,11-diene synthase （ADS）, a sesquiterpene synthase, and CYP71AV1, a P450 monooxygenase, are two key e...Plants of Artemisia annua produce artemisinin, a sesquiterpene lactone widely used in malaria treatment. Amorpha-4,11-diene synthase （ADS）, a sesquiterpene synthase, and CYP71AV1, a P450 monooxygenase, are two key enzymes of the artemisinin biosynthesis pathway. Accumulation of artemisinin can be induced by the phytohormone jasmonate （JA）. Here, we report the characterization of two JA-responsive AP2 family transcription factors-AaERF1 and AaERF2-from A. annua L. Both genes were highly expressed in inflorescences and strongly induced by JA. Yeast one- hybrid and electrophoretic mobility shift assay （EMSA） showed that they were able to bind to the CRTDREHVCBF2 （CBF2） and RAVlAAT （RAA） motifs present in both ADS and CYP71AV1 promoters. Transient expression of either AaERF1 or AaERF2 in tobacco induced the promoter activities of ADS or CYP71AV1, and the transgenic A. annua plants overexpressing either transcription factor showed elevated transcript levels of both ADS and CYP71AV1, resulting in increased accumulation of artemisinin and artemisinic acid. By contrast, the contents of these two metabolites were reduced in the RNAi transgenic lines in which expression of AaERF1 or AaERF2 was suppressed. These results demonstrate that AaERF1 and AaERF2 are two positive regulators of artemisinin biosynthesis and are of great value in genetic engineering of arte- misinin production.展开更多
On the interannual timescale, the meridional displacement of the East Asian upper-tropospheric jet stream (EAJS) is significantly associated with the rainfall anomalies in East Asia in summer. In this study, using the...On the interannual timescale, the meridional displacement of the East Asian upper-tropospheric jet stream (EAJS) is significantly associated with the rainfall anomalies in East Asia in summer. In this study, using the data from the National Centers for Environmental Prediction-Department of Energy (NCEP/DOE) reanalysis-2 from 1979 to 2002, the authors investigate the interannual variations of the EAJS's meridional displacement in summer and their associations with the variations of the South Asian high (SAH) and the western North Pacific subtropical high (WNPSH), which are dominant circulation features in the upper and lower troposhere, respectively. The result from an EOF analysis shows that the meridional displacement is the most remarkable feature of the interannual variations of the EAJS in each month of summer and in summer as a whole. A composite analysis indicates that the summer (June-July-August, JJA) EAJS index, which is intended to depict the interannual meridional displacement of the EAJS, is not appropriate because the anomalies of the zonal wind at 200 hPa (U200) in July and August only, rather than in June, significantly contribute to the summer EAJS index. Thus, the index for each month in summer is defined according to the location of the EAJS core in each month. Composite analyses based on the monthly indexes show that corresponding to the monthly equatorward displacement of the EAJS, the South Asian high (SAH) extends southeastward clearly in July and August, and the western North Pacific subtropical high (WNPSH) withdraws southward in June and August.展开更多
Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is...Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.展开更多
This paper mainly summarizes the recent progresses for the cavitation study in the hydraulic machinery including turbo- pumps, hydro turbines, etc.. Especially, the newly developed numerical methods for simulating cav...This paper mainly summarizes the recent progresses for the cavitation study in the hydraulic machinery including turbo- pumps, hydro turbines, etc.. Especially, the newly developed numerical methods for simulating cavitating turbulent flows and the achievements with regard to the complicated flow features revealed by using advanced optical techniques as well as cavitation simulation are introduced so as to make a better understanding of the cavitating flow mechanism for hydraulic machinery. Since cavitation instabilities are also vital issue and rather harmful for the operation safety of hydro machines, we present the 1-D analysis method, which is identified to be very useful for engineering applications regarding the cavitating flows in inducers, turbine draft tubes, etc. Though both cavitation and hydraulic machinery are extensively discussed in literatures, one should be aware that a few problems still remains and are open for solution, such as the comprehensive understanding of cavitating turbulent flows especially inside hydro turbines, the unneglectable discrepancies between the numerical and experimental data, etc.. To further promote the study of cavitation in hydraulic machinery, some advanced tooics such as a Density-Based solver suitable for highly comoressible cavitating turbulent flows, a virtual cavitation tunnel, etc. are addressed for the future works.展开更多
Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is ...Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.展开更多
Neuroinflammation is associated with neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,ancamyotrophic lateral sclerosis.Microglia and astrocytes are key regulators of inflammatory resp...Neuroinflammation is associated with neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,ancamyotrophic lateral sclerosis.Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system.The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxi(M1-phenotype microglia and A1-phenotype astrocytes)or neuroprotective(M2-phenotype microglia and A2-phenotype astrocytes).However,this dichotomized classification may not reflect the various phenotypes of microgliaand astrocytes.The relationship between these activated glial cells is also very complicated,and the phenotypic distribution can change,based on the progression of neurodegenerative diseases.A better understanding of the rolesof microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies.In this review,we discuss the roles of inflammatory response in neurodegenerative diseases,focusing on the contributions of microglia and astrocytes and their relationship.In addition,we discuss biomarkers to measure neuroinflammation andstudies on therapeutic drugs that can modulate neuroinflammation.展开更多
Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption...Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment.展开更多
The Xianghualing Sn-polymetallic orefield in Hunan Province, southern China, is a largesize tin orefield. Although numerous studies have been undertaken on this orefield, its genesis, mineralization age, and tectonic ...The Xianghualing Sn-polymetallic orefield in Hunan Province, southern China, is a largesize tin orefield. Although numerous studies have been undertaken on this orefield, its genesis, mineralization age, and tectonic setting are still controversial, mainly because of the lack of reliable geochronological data on tin mineralization. The ^40Ar^39Ar stepwise heating dating method was first employed on muscovite from different deposits in this orefield. The muscovite sample from the Xianghualing Sn-polymetallic deposit defines a plateau age of 154.4±1.1 Ma and an isochron age of 151.9±3.0 Ma; muscovite from the Xianghuapu W-polymetallic deposit yields a plateau age of 161.3±1.1 Ma and an isochron age of 160.0±3.2 Ma; muscovite from the Jianfengling greisen-type Sn-polymetallic deposit gives a plateau age of 158.7±1.2 Ma and an isochron age of 160.3±3.2 Ma. The tungsten-tin mineralization ages in the Xianghualing area are therefore restricted within 150-160 Ma. The tungstentin mineralization in Xianghualing occurred at the same time as the regional tin-tungsten mineralization including the Furong tin orefield, Shizhuyuan tungsten-tin polymetallic deposit and Yaogangxian tungsten-polymetallic deposit. Thus, the large-scale tungsten-tin metallogenesis in South China occurring at 160-150 Ma, probably is closely related to asthenospheric upwelling and crustmantle interaction under a geodynamic setting of crustal extension and lithosphere thinning during the transformation of tectonic regimes during the Mid-Late Jurassic.展开更多
The prognosis of patients with hepatocellular cardnorna （HCC） accompanied by portal vein tumor thrombus （PVTT） is generally poor if leo untreated： a median survival time of 2.7-4.0 mo has been reported. Furthermo...The prognosis of patients with hepatocellular cardnorna （HCC） accompanied by portal vein tumor thrombus （PVTT） is generally poor if leo untreated： a median survival time of 2.7-4.0 mo has been reported. Furthermore, while transcatheter arterial chemoembolization （TACE） has been shown to be safe in selected patients, the median survival time with this treatment is still only 3.8-9.5 mo. Systemic single-agent chemotherapy for HCC with PVTT has failed to improve the prognosis, and the response rates have been less than 20%. While regional chemotherapy with low-dose cisplatin and 5-fluorouracil or interferon and 5-fluorouracil via hepatic arterial infusion has increased the response rate, the median survival time has not exceeded 12 （range 4.5-11.8） mo. Combined treatment consisting of radiation for PVTT and TACE for liver tumor has achieved a high response rate, but the median survival rates have still been only 3.8-10.7 mo. With hepatic resection as monotherapy, the 5-year survival rate and median survival time were reportedly 4%-28.5% and 6-14 mo. The most promising results were reported for combined treatments consisting of hepatectomy and TACE, chemotherapy, or internal radiation. The reported 5-year survival rates and median survival times were 42% and 31 mo for TACE followed by hepatectomy; 36.3% and 22.1 mo for hepatectomy followed by hepatic arterial infusion chemotherapy; and 56% for chemotherapy or internal radiation followed by hepatectomy.展开更多
Heavy metals in variable charge soil are highly bioavailable and easy to transfer into plants. Since it is impossible to completely eliminate rice planting on contaminated soils, some remediation and mitigation techni...Heavy metals in variable charge soil are highly bioavailable and easy to transfer into plants. Since it is impossible to completely eliminate rice planting on contaminated soils, some remediation and mitigation techniques are necessary to reduce metal bioavailability and uptake by rice. This pot experiment investigated the effects of seven amendments on the growth of rice and uptake of heavy metals from a paddy soil that was contaminated by copper and cadmium. The best results were from the application of limestone that increased grain yield by 12.5-16.5 fold, and decreased Cu and Cd concentrations in grain by 23.0%--50.4%. Application of calcium magnesium phosphate, calcium silicate, pig manure, and peat also increased the grain yield by 0.3-15.3 fold, and effectively decreased the Cu and Cd concentrations in grain. Cd concentration in grain was slightly reduced in the treatments of Chinese milk vetch and zinc sulfate. Concentrations of Cu and Cd in grain and straw were dependent on the available Cu and Cd in the soils, and soil available Cu and Cd were significantly affected by the soil pH.展开更多
Since extrahepatic bile duct cancer is difficult to diagnose and to cure, a safe and radical surgical strategy is needed. In this review, the modes of infiltration and spread of extrahepatic bile duct cancer and surgi...Since extrahepatic bile duct cancer is difficult to diagnose and to cure, a safe and radical surgical strategy is needed. In this review, the modes of infiltration and spread of extrahepatic bile duct cancer and surgical strategy are discussed. Extended hemihepatectomy, with or without pancreatoduodenectomy （PD）, plus extrahepatic bile duct resection and regional lyrnphadenectomy has recently been recognized as the standard curative treatment for hilar bile duct cancer. On the other hand, PD is the choice of treatment for middle and distal bile duct cancer. Major hepatectomy concomitant with PD （hepatopancreatoduodenectomy） has been applied to selected patients with widespread tumors. Preoperative biliary drainage （BD） followed by portal vein embolization （PVE） enables major hepatectomy in patients with hilar bile duct cancer without mortality. BD should be performed considering the surgical procedure, especially, in patients with separated intrahepatic bile ducts caused by hilar bile duct cancer. Right or left trisectoriectomy are indicated according to the tumor spread and biliary anatomy. As a result, extended radical resection offers a chance for cure of hilar bile duct cancer with improved resectability, curability, and a 5-year survival rate of 40%. A 5-year survival rate has ranged from 24% to 39% after PD for middle and distal bile duct cancer.展开更多
基金The research in authors'lab has been supported by The University of Texas MD Anderson Cancer Center,KC180131 from Department of Defense Kidney Cancer Research Program,R01CA181196,R01CA190370,R01CA244144 from the National Institutes of Health(to BG)CPRIT Research Training Grant(RP170067)Dr.John J.Kopchick Research Award from The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences(to PK).
文摘The cystine/glutamate antiporter SLC7A11(also commonly known as xCT)functions to import cystine for glutathione biosynthesis and antioxidant defense and is overexpressed in multiple human cancers.Recent studies revealed that SLC7A11 overexpression promotes tumor growth partly through suppressing ferroptosis,a form of regulated cell death induced by excessive lipid peroxidation.However,cancer cells with high expression of SLC7A11(SLC7A11^(high))also have to endure the significant cost associated with SLC7A11-mediated metabolic reprogramming,leading to glucose-and glutamine-dependency in SLC7A11^(high) cancer cells,which presents potential metabolic vulnerabilities for therapeutic targeting in SLC7A11^(high) cancer.In this review,we summarize diverse regulatory mechanisms of SLC7A11 in cancer,discuss ferroptosis-dependent and-independent functions of SLC7A11 in promoting tumor development,explore the mechanistic basis of SLC7A11-induced nutrient dependency in cancer cells,and conceptualize therapeutic strategies to target SLC7A11 in cancer treatment.This review will provide the foundation for further understanding SLC7A11 in ferroptosis,nutrient dependency,and tumor biology and for developing novel effective cancer therapies.
基金supported by the Andrew Sabin Family Fellow Award and Institutional Research Grant from the University of Texas MD Anderson Cancer Center,Grants from National Institutes of Health(CA181196 and CA190370)Anna Fuller Fund,and Ellison Medical Foundation(AG-NS-0973-13).
文摘Cancer cells often upregulate nutrient transporters to fulfill their increased biosynthetic and bioenergetic needs,and to maintain redox homeostasis.One nutrient transporter frequently overexpressed in human cancers is the cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT).SLC7A11 promotes cystine uptake and glutathione biosynthesis,resulting in protection from oxidative stress and ferroptotic cell death.Recent studies have unexpectedly revealed that SLC7A11 also plays critical roles in glutamine metabolism and regulates the glucose and glutamine dependency of cancer cells.This review discusses the roles of SLC7A11 in regulating the anti-oxidant response and nutrient dependency of cancer cells,explores our current understanding of SLC7A11 regulation in cancer metabolism,and highlights key open questions for future studies in this emerging research area.A deeper understanding of SLC7A11 in cancer metabolism may identify new therapeutic opportunities to target this important amino acid transporter for cancer treatment.
文摘Endoscopic submucosal dissection (ESD) is an advanced technique of therapeutic endoscopy for superficial gastrointestinal neoplasms. Three steps characterize it:injecting fluid into the submucosa to elevate the lesion, cutting the surrounding mucosa of the lesion, and dissecting the submucosa beneath the lesion. The ESD technique has rapidly permeated in Japan for treatment of early gastric cancer, due to its excellent results of en- bloc resection compared to endoscopic mucosal resection (EMR). Although there is still room for improvement to lessen its technical difficulty, ESD has recently been applied to esophageal and colorectal neoplasms. Favorable short-term results have been reported, but the application of ESD should be well considered by three aspects:(1) the possibility of nodal metastases of the lesion, (2) technical difficulty such as location, ulceration and operator’s skill, and (3) organ characteristics.
基金grants from the Ministry of Science and Technology of China （No. 2001AA231061） the National Natural Science Foundation of China （No. 30270748）
文摘KaKs_Calculator is a software package that calculates nonsynonymous （Ka） and synonymous （Ks） substitution rates through model selection and model averaging. Since existing methods for this estimation adopt their specific mutation （substitution） models that consider different evolutionary features, leading to diverse estimates, KaKs_Calculator implements a set of candidate models in a maximum likelihood framework and adopts the Akaike information criterion to measure fitness between models and data, aiming to include as many features as needed for accurately capturing evolutionary information in protein-coding sequences. In addition, several existing methods for calculating Ka and Ks are also incorporated into this software. KaKs_Calculator, including source codes, compiled executables, and documentation, is freely available for academic use at http：//evolution.genomics.org.cn/software.htm.
文摘Human pluripotent stem cells represent a potentially unlimited source of functional pancreatic endocrine lineage cells. Here we report a highly efficient approach to induce human embryonic stem （ES） cells and induced pluripo- tent stem （iPS） cells to differentiate into mature insulin-producing cells in a chemical-defined culture system. The differentiated human ES cells obtained by this approach comprised nearly 25% insulin-positive cells as assayed by flow cytometry analysis, which released insulin/C-peptide in response to glucose stimuli in a manner comparable to that of adult human islets. Most of these insulin-producing cells co-expressed mature β cell-specific markers such as NKX6-1 and PDX1, indicating a similar gene expression pattern to adult islet β cells in vivo. In this study, we also demonstrated that EGF facilitates the expansion of PDXl-positive pancreatic progenitors. Moreover, our protocol also succeeded in efficiently inducing human iPS cells to differentiate into insuIin-producing ceils. Therefore, this work not only provides a new model to study the mechanism of human pancreatic specialization and maturation in vitro, but also enhances the possibility of utilizing patient-specific iPS cells for the treatment of diabetes.
基金laboratory is supported by grants from the US National Institutes of Health(AI057555,AI064639,AI104519 and GM84459)Cancer Prevention and Research Institute of Texas(RP150235 and RP140244).
文摘The transcription factor NF-κB regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses.NF-κB induces the expression of various pro-inflammatory genes,including those encoding cytokines and chemokines,and also participates in inflammasome regulation.In addition,NF-κB plays a critical role in regulating the survival,activation and differentiation of innate immune cells and inflammatory T cells.Consequently,deregulated NF-κB activation contributes to the pathogenic processes of various inflammatory diseases.In this review,we will discuss the activation and function of NF-κB in association with inflammatory diseases and highlight the development of therapeutic strategies based on NF-κB inhibition.
基金Project supported by the Hi-Tech Research and Development Program (863) of China (No. 2001AA641060 2003AA641040)the National Basic Research Program (973) of China (No. 2002CB410801).
文摘Cereal straw is one of the most abundant biomass burned in China but its contribution to fine particulates is not adequately understood. In this study, three main kinds of cereal straws were collected from five grain producing areas in China. Fine particulate matters （PMzs） from the cereal straws subjected to control burnings, both under smoldering and flaming status, were sampled by using a custom made dilution chamber and sampling system in the laboratory. Element carbon （EC） and organic carbon （OC） was analyzed. 141 compounds of organic matters were measured by gas chromatography-mass spectrum （GC-MS）. Source profiles of particulate organic matters emitted from cereal straw burnings were obtained. The results indicated that organic matters contribute a large fraction in fine particulate matters. Levoglucosan had the highest contributions with averagely 4.5% in mass of fine particulates and can be considered as the tracer of biomass burnings. Methyloxylated phenols from lignin degradation also had high concentrations in PM2.5, and contained approximately equal amounts of guaiacyl and syringyl compounds. 13-Sitostrol also made up relatively a large fraction of PMz5 compared with the other sterols （0.18%-0.63% of the total fine particle mass）. Normal alkanes, PAHs, fatty acids, as well as normal alkanols had relatively lower concentrations compared with the compounds mentioned above. Carbon preference index （CPI） of normal alkanes and alkanoic acids showed characteristics of biogenic fuel burnings. Burning status significantly influenced the formations of EC and PAHs. The differences between the emission profiles of straw and wood combustions were displayed by the fingerprint compounds, which may be used to identify the contributions between wood and straw burnings in source apportionment researches.
基金supported by the National Basic Research Program (973) of China (No. 2008CB418200)the National Natural Science Foundation of China (No.40973087, U0833603)
文摘To identify the concentrations and sources of heavy metals, and to assess soil environmental quality, 63 soil samples were collected in Yibin City, Sichuan Province, China. Mean concentrations of As, Pb, Zn, and Cu were 10.55, 61.23, 138.88 and 56.35 mg/kg, respectively. As concentrations were comparable to background values, while Pb, Zn, and Cu concentrations were higher than their corresponding background values. Industrial areas exhibited the highest concentrations of As, Pb, Zn, and Cu, while the lowest concentrations occurred in parks. Statistical analysis was performed and two cluster groups of metals were identified with Pb, Zn, and Cu in one group and As in the other. Spatial distribution maps indicated that Pb, Zn, and Cu were mainly controlled by anthropogenic activities, whereas As could be mainly accounted for by soil parent materials. Pollution index values of As, Pb, Zn, and Cu varied in the range of 0.24-1.93, 0.66-7.24, 0.42-4.19, and 0.62-5.25, with mean values of 0.86, 1.98, 1.61, and 1.78, respectively. The integrated pollution index （IPI） values of these metals varied from 0.82 to 3.54, with a mean of 1.6 and more than 90% of soil samples were moderately or highly contaminated with heavy metals. The spatial distribution of IPI showed that newer urban areas displayed relatively lower heavy metal contamination in comparison with older urban areas.
基金This research was supported by State Key Basic Research Program of China （2007CB108800）, the National Natural Science Foundation of China （30630008）, and the National HighTech Program of China （2007AA021501 ）.ACKNO WLEDGMENTS We thank CYP71AV1. discussions Ke-Xuan Tang for supplying the promoter sequence of We thank Ji-Rong Huang and Gao-Jie Hong for he pfu No conflict of interest declared
文摘Plants of Artemisia annua produce artemisinin, a sesquiterpene lactone widely used in malaria treatment. Amorpha-4,11-diene synthase （ADS）, a sesquiterpene synthase, and CYP71AV1, a P450 monooxygenase, are two key enzymes of the artemisinin biosynthesis pathway. Accumulation of artemisinin can be induced by the phytohormone jasmonate （JA）. Here, we report the characterization of two JA-responsive AP2 family transcription factors-AaERF1 and AaERF2-from A. annua L. Both genes were highly expressed in inflorescences and strongly induced by JA. Yeast one- hybrid and electrophoretic mobility shift assay （EMSA） showed that they were able to bind to the CRTDREHVCBF2 （CBF2） and RAVlAAT （RAA） motifs present in both ADS and CYP71AV1 promoters. Transient expression of either AaERF1 or AaERF2 in tobacco induced the promoter activities of ADS or CYP71AV1, and the transgenic A. annua plants overexpressing either transcription factor showed elevated transcript levels of both ADS and CYP71AV1, resulting in increased accumulation of artemisinin and artemisinic acid. By contrast, the contents of these two metabolites were reduced in the RNAi transgenic lines in which expression of AaERF1 or AaERF2 was suppressed. These results demonstrate that AaERF1 and AaERF2 are two positive regulators of artemisinin biosynthesis and are of great value in genetic engineering of arte- misinin production.
基金This work was supported by the Chinese Academy of Sciences(Grant No.KZCX3 SW-221)the National Natural Science Foundation of China under Grant No.40221503.
文摘On the interannual timescale, the meridional displacement of the East Asian upper-tropospheric jet stream (EAJS) is significantly associated with the rainfall anomalies in East Asia in summer. In this study, using the data from the National Centers for Environmental Prediction-Department of Energy (NCEP/DOE) reanalysis-2 from 1979 to 2002, the authors investigate the interannual variations of the EAJS's meridional displacement in summer and their associations with the variations of the South Asian high (SAH) and the western North Pacific subtropical high (WNPSH), which are dominant circulation features in the upper and lower troposhere, respectively. The result from an EOF analysis shows that the meridional displacement is the most remarkable feature of the interannual variations of the EAJS in each month of summer and in summer as a whole. A composite analysis indicates that the summer (June-July-August, JJA) EAJS index, which is intended to depict the interannual meridional displacement of the EAJS, is not appropriate because the anomalies of the zonal wind at 200 hPa (U200) in July and August only, rather than in June, significantly contribute to the summer EAJS index. Thus, the index for each month in summer is defined according to the location of the EAJS core in each month. Composite analyses based on the monthly indexes show that corresponding to the monthly equatorward displacement of the EAJS, the South Asian high (SAH) extends southeastward clearly in July and August, and the western North Pacific subtropical high (WNPSH) withdraws southward in June and August.
文摘Diabetic retinopathy(DR)is a leading cause of vision-loss globally.Of an estimated 285 million people with diabetes mellitus worldwide,approximately one third have signs of DR and of these,a further one third of DR is vision-threatening DR,including diabetic macular edema(DME).The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR.Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME,especially those involved in inflammation and oxidative stress.Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility.In this review,major trends in the prevalence,incidence,progression and regression of DR and DME are explored,and gaps in literature identified.Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
基金Project supported by the National Natural Science Foun-dation of China(Grant No.51536008)the Beijing Key Laboratory Development Project(Grant No.Z151100001615006)
文摘This paper mainly summarizes the recent progresses for the cavitation study in the hydraulic machinery including turbo- pumps, hydro turbines, etc.. Especially, the newly developed numerical methods for simulating cavitating turbulent flows and the achievements with regard to the complicated flow features revealed by using advanced optical techniques as well as cavitation simulation are introduced so as to make a better understanding of the cavitating flow mechanism for hydraulic machinery. Since cavitation instabilities are also vital issue and rather harmful for the operation safety of hydro machines, we present the 1-D analysis method, which is identified to be very useful for engineering applications regarding the cavitating flows in inducers, turbine draft tubes, etc. Though both cavitation and hydraulic machinery are extensively discussed in literatures, one should be aware that a few problems still remains and are open for solution, such as the comprehensive understanding of cavitating turbulent flows especially inside hydro turbines, the unneglectable discrepancies between the numerical and experimental data, etc.. To further promote the study of cavitation in hydraulic machinery, some advanced tooics such as a Density-Based solver suitable for highly comoressible cavitating turbulent flows, a virtual cavitation tunnel, etc. are addressed for the future works.
文摘Hepatocellular carcinoma(HCC) is the fifth most common cancer and the second leading cause of cancer-related deaths worldwide. Although the prognosis of patients with HCC is generally poor, the5-year survival rate is > 70% if patients are diagnosed at an early stage. However, early diagnosis of HCC is complicated by the coexistence of inflammation and cirrhosis. Thus, novel biomarkers for the early diagnosis of HCC are required. Currently, the diagnosis of HCC without pathological correlation is achieved by analyzing serum α.fetoprotein levels combined with imaging techniques. Advances in genomics and proteomics platforms and biomarker assay techniques over the last decade have resulted in the identification of numerous novel biomarkers and have improved the diagnosis of HCC. The most promising biomarkers,such as glypican-3, osteopontin, Golgi protein-73 and nucleic acids including microRNAs, are most likely to become clinically validated in the near future. These biomarkers are not only useful for early diagnosis of HCC, but also provide insight into the mechanisms driving oncogenesis. In addition, such molecular insight creates the basis for the development of potentially more effective treatment strategies. In this article,we provide an overview of the biomarkers that are currently used for the early diagnosis of HCC.
基金supported by the Basic Science Research Program of the National Research Foundation of Korea,which was funded by the Ministry of Science,ICT,and Future Planning(2018R1A2A2A15023219)a grant of the Korea Health Technology R&D Projea through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(HI20C0253)the Medical Research Centre(2017R1A5A2015395).
文摘Neuroinflammation is associated with neurodegenerative diseases,such as Alzheimer's disease,Parkinson's disease,ancamyotrophic lateral sclerosis.Microglia and astrocytes are key regulators of inflammatory responses in the central nervous system.The activation of microglia and astrocytes is heterogeneous and traditionally categorized as neurotoxi(M1-phenotype microglia and A1-phenotype astrocytes)or neuroprotective(M2-phenotype microglia and A2-phenotype astrocytes).However,this dichotomized classification may not reflect the various phenotypes of microgliaand astrocytes.The relationship between these activated glial cells is also very complicated,and the phenotypic distribution can change,based on the progression of neurodegenerative diseases.A better understanding of the rolesof microglia and astrocytes in neurodegenerative diseases is essential for developing effective therapies.In this review,we discuss the roles of inflammatory response in neurodegenerative diseases,focusing on the contributions of microglia and astrocytes and their relationship.In addition,we discuss biomarkers to measure neuroinflammation andstudies on therapeutic drugs that can modulate neuroinflammation.
基金Supported by JSPS[Grant-in-Aid for Scientific Research(C)](to Miura K)
文摘Emerging data have shown a close association between compositional changes in gut microbiota and the development of nonalcoholic fatty liver disease(NAFLD).The change in gut microbiota may alter nutritional absorption and storage.In addition,gut microbiota are a source of Toll-like receptor(TLR)ligands,and their compositional change can also increase the amount of TLR ligands delivered to the liver.TLR ligands can stimulate liver cells to produce proinflammatory cytokines.Therefore,the gut-liver axis has attracted much interest,particularly regarding the pathogenesis of NAFLD.The abundance of the major gut microbiota,including Firmicutes and Bacteroidetes,has been considered a potential underlying mechanism of obesity and NAFLD,but the role of these microbiota in NAFLD remains unknown.Several reports have demonstrated that certain gut microbiota are associated with the development of obesity and NAFLD.For instance,a decrease in Akkermansia muciniphila causes a thinner intestinal mucus layer and promotes gut permeability,which allows the leakage of bacterial components.Interventions to increase Akkermansia muciniphila improve the metabolic parameters in obesity and NAFLD.In children,the levels of Escherichia were significantly increased in nonalcoholic steatohepatitis(NASH)compared with those in obese control.Escherichia can produce ethanol,which promotes gut permeability.Thus,normalization of gut microbiota using probiotics or prebiotics is a promising treatment option for NAFLD.In addition,TLR signaling in the liver is activated,and its downstream molecules,such as proinflammatory cytokines,are increased in NAFLD.To data,TLR2,TLR4,TLR5,and TLR9 have been shown to be associated with the pathogenesis of NAFLD.Therefore,gut microbiota and TLRs are targets for NAFLD treatment.
基金the Innovative Project of the Chinese Academy of Sciences （Grant No. KZCX3-SW-125） National Natural Science Foundation of China （Grant No. 40472053 , No. 40673021）.
文摘The Xianghualing Sn-polymetallic orefield in Hunan Province, southern China, is a largesize tin orefield. Although numerous studies have been undertaken on this orefield, its genesis, mineralization age, and tectonic setting are still controversial, mainly because of the lack of reliable geochronological data on tin mineralization. The ^40Ar^39Ar stepwise heating dating method was first employed on muscovite from different deposits in this orefield. The muscovite sample from the Xianghualing Sn-polymetallic deposit defines a plateau age of 154.4±1.1 Ma and an isochron age of 151.9±3.0 Ma; muscovite from the Xianghuapu W-polymetallic deposit yields a plateau age of 161.3±1.1 Ma and an isochron age of 160.0±3.2 Ma; muscovite from the Jianfengling greisen-type Sn-polymetallic deposit gives a plateau age of 158.7±1.2 Ma and an isochron age of 160.3±3.2 Ma. The tungsten-tin mineralization ages in the Xianghualing area are therefore restricted within 150-160 Ma. The tungstentin mineralization in Xianghualing occurred at the same time as the regional tin-tungsten mineralization including the Furong tin orefield, Shizhuyuan tungsten-tin polymetallic deposit and Yaogangxian tungsten-polymetallic deposit. Thus, the large-scale tungsten-tin metallogenesis in South China occurring at 160-150 Ma, probably is closely related to asthenospheric upwelling and crustmantle interaction under a geodynamic setting of crustal extension and lithosphere thinning during the transformation of tectonic regimes during the Mid-Late Jurassic.
文摘The prognosis of patients with hepatocellular cardnorna （HCC） accompanied by portal vein tumor thrombus （PVTT） is generally poor if leo untreated： a median survival time of 2.7-4.0 mo has been reported. Furthermore, while transcatheter arterial chemoembolization （TACE） has been shown to be safe in selected patients, the median survival time with this treatment is still only 3.8-9.5 mo. Systemic single-agent chemotherapy for HCC with PVTT has failed to improve the prognosis, and the response rates have been less than 20%. While regional chemotherapy with low-dose cisplatin and 5-fluorouracil or interferon and 5-fluorouracil via hepatic arterial infusion has increased the response rate, the median survival time has not exceeded 12 （range 4.5-11.8） mo. Combined treatment consisting of radiation for PVTT and TACE for liver tumor has achieved a high response rate, but the median survival rates have still been only 3.8-10.7 mo. With hepatic resection as monotherapy, the 5-year survival rate and median survival time were reportedly 4%-28.5% and 6-14 mo. The most promising results were reported for combined treatments consisting of hepatectomy and TACE, chemotherapy, or internal radiation. The reported 5-year survival rates and median survival times were 42% and 31 mo for TACE followed by hepatectomy; 36.3% and 22.1 mo for hepatectomy followed by hepatic arterial infusion chemotherapy; and 56% for chemotherapy or internal radiation followed by hepatectomy.
文摘Heavy metals in variable charge soil are highly bioavailable and easy to transfer into plants. Since it is impossible to completely eliminate rice planting on contaminated soils, some remediation and mitigation techniques are necessary to reduce metal bioavailability and uptake by rice. This pot experiment investigated the effects of seven amendments on the growth of rice and uptake of heavy metals from a paddy soil that was contaminated by copper and cadmium. The best results were from the application of limestone that increased grain yield by 12.5-16.5 fold, and decreased Cu and Cd concentrations in grain by 23.0%--50.4%. Application of calcium magnesium phosphate, calcium silicate, pig manure, and peat also increased the grain yield by 0.3-15.3 fold, and effectively decreased the Cu and Cd concentrations in grain. Cd concentration in grain was slightly reduced in the treatments of Chinese milk vetch and zinc sulfate. Concentrations of Cu and Cd in grain and straw were dependent on the available Cu and Cd in the soils, and soil available Cu and Cd were significantly affected by the soil pH.
文摘Since extrahepatic bile duct cancer is difficult to diagnose and to cure, a safe and radical surgical strategy is needed. In this review, the modes of infiltration and spread of extrahepatic bile duct cancer and surgical strategy are discussed. Extended hemihepatectomy, with or without pancreatoduodenectomy （PD）, plus extrahepatic bile duct resection and regional lyrnphadenectomy has recently been recognized as the standard curative treatment for hilar bile duct cancer. On the other hand, PD is the choice of treatment for middle and distal bile duct cancer. Major hepatectomy concomitant with PD （hepatopancreatoduodenectomy） has been applied to selected patients with widespread tumors. Preoperative biliary drainage （BD） followed by portal vein embolization （PVE） enables major hepatectomy in patients with hilar bile duct cancer without mortality. BD should be performed considering the surgical procedure, especially, in patients with separated intrahepatic bile ducts caused by hilar bile duct cancer. Right or left trisectoriectomy are indicated according to the tumor spread and biliary anatomy. As a result, extended radical resection offers a chance for cure of hilar bile duct cancer with improved resectability, curability, and a 5-year survival rate of 40%. A 5-year survival rate has ranged from 24% to 39% after PD for middle and distal bile duct cancer.
