Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Variou...Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the “point of no return” and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.展开更多
The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregul...The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1–Nrf2PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1's cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1–Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1–Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.展开更多
Background:An e-nose or an e-tongue is a group of gas sensors or chemical sensors that simulate human nose or human tongue.Both e-nose and e-tongue have showngreat promise and utility in improving assessments of food ...Background:An e-nose or an e-tongue is a group of gas sensors or chemical sensors that simulate human nose or human tongue.Both e-nose and e-tongue have showngreat promise and utility in improving assessments of food quality characteristics compared with traditional detection methods.Scope and approach:This review summarizes the application of e-nose and e-tongue in determining the quality-related properties of foods.The working principles,applications,and limitations of the sensors employed by electronic noses and electronic tongueswere introduced and compared.Widelyemployed pattern recognition algorithms,including artificial neural network(ANN),convolutional neural network(CNN),principal component analysis(PCA),partial least square regression(PLS),and support vector machine(SVM),were introduced and compared in this review.Key findings and conclusions:Overall,e-nose or e-tongue combining pattern recognition algorithms are very powerful analytical tools,which are relatively low-cost,rapid,and accurate.E-nose and e-tongue are also suitable for both in-line and off-line measurements,which are very useful in monitoring food processing and detecting the end product quality.The user of e-nose and e-tongue need to strictly control sample preparation,sampling,and data processing.展开更多
p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human ca...p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.展开更多
Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expe...Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study. Methods A total of 30 patients with ＂complete＂ spinal cord injury or classified as American Spinal Injury Association （ASIA）-A were studied. Orthopedic treatment of the injured vertebra（e）, internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis. Results All the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint （12 cases, 40%）. Thirteen patients （43%） were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4-14 days after injury. Conclusions Early neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful.展开更多
Grazing exclusion using fences is a key policy being applied by the Chinese government to rehabilitate degraded grasslands on the Tibetan Plateau(TP)and elsewhere.However,there is a limited understanding of the effect...Grazing exclusion using fences is a key policy being applied by the Chinese government to rehabilitate degraded grasslands on the Tibetan Plateau(TP)and elsewhere.However,there is a limited understanding of the effects of grazing exclusion on alpine ecosystem functions and services and its impacts on herders’livelihoods.Our meta-analyses and questionnaire-based surveys revealed that grazing exclusion with fences was effective in promoting aboveground vegetation growth for up to four years in degraded alpine meadows and for up to eight years in the alpine steppes of the TP.Longer-term fencing did not bring any ecological and economic benefits.We also found that fencing hindered wildlife movement,increased grazing pressure in unfenced areas,lowered the satisfaction of herders,and rendered substantial financial costs to both regional and national governments.We recommend that traditional free grazing should be encouraged if applicable,short-term fencing(for 4-8 years)should be adopted in severely degraded grasslands,and fencing should be avoided in key wildlife habitat areas,especially the protected large mammal species.展开更多
Hepatocellular carcinoma(HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and he...Hepatocellular carcinoma(HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals withchronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.展开更多
Oxidation of aniline by persulfate in aqueous solutions was investigated and the reaction kinetic rates under different temperature, persulfate concentration and pH conditions were examined in batch experiments. The r...Oxidation of aniline by persulfate in aqueous solutions was investigated and the reaction kinetic rates under different temperature, persulfate concentration and pH conditions were examined in batch experiments. The results showed that, the aniline degradation followed pseudo first-order reaction model. Aniline degradation rate increased with increasing temperature or persulfate concentration. In the pH range of 3 to 11, a low aniline degradation rate was obtained at strong acid system （pH 3）, while a high degradation rate was achieved at strong alkalinity （pH 11）. Maximum aniline degradation occurred at pH 7 when the solution was in a weak level of acid and alkalinity （pH 5, 7 and 9）. Produced intermediates during the oxidation process were identified using liquid chromatography-mass spectrometry technology. And nitrobenzene, 4-4’-diaminodiphenyl and 1-hydroxy-1,2-diphenylhydrazine have been identified as the major intermediates of aniline oxidation by persulfate and the degradation mechanism of aniline was also tentatively proposed.展开更多
β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less of...β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes.展开更多
基金Supported by Grant,NIDDK,RO1DK63618 to KMD from the National Institutes of Health,Bethesda,MD
文摘Helicobacter pylori (H. pylori) infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis (AG), or gastric intestinal metaplasia (GIM), and cancer. Various molecular alterations are identified not only in gastric cancer (GC) but also in precancerous lesions. H. pylori treatment seems to improve AG and GIM, but still remains controversial. In contrast, many studies, including meta-analysis, show that H. pylori eradication reduces GC. Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H. pylori eradication. This indicates that these changes may be an important factor in the identification of high risk patients for cancer development. Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC. A randomized controlled trial from Japan concluded that prophylactic eradication of H. pylori after endoscopic resection should be used to prevent the development of metachronous GC, but recent retrospective studies did not show the tendency. Patients with precancerous lesions (molecular alterations) that do not reverse after H. pylori treatment, represent the “point of no return” and may be at high risk for the development of GC. Therefore, earlier H. pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.
基金the financial support of Grants CA133791, CA125868, and MH093197 from the National Institutes of Health, United States
文摘The Keap1–Nrf2–ARE pathway is an important antioxidant defense mechanism that protects cells from oxidative stress and the Keap1–Nrf2 protein–protein interaction(PPI) has become an important drug target to upregulate the expression of ARE-controlled cytoprotective oxidative stress response enzymes in the development of therapeutic and preventive agents for a number of diseases and conditions. However, most known Nrf2 activators/ARE inducers are indirect inhibitors of Keap1–Nrf2PPI and they are electrophilic species that act by modifying the sulfhydryl groups of Keap1's cysteine residues. The electrophilicity of these indirect inhibitors may cause "off-target" side effects by reacting with cysteine residues of other important cellular proteins. Efforts have recently been focused on the development of direct inhibitors of Keap1–Nrf2 PPI. This article reviews these recent research efforts including the development of high throughput screening assays, the discovery of peptide and small molecule direct inhibitors, and the biophysical characterization of the binding of these inhibitors to the target Keap1 Kelch domain protein. These non-covalent direct inhibitors of Keap1–Nrf2 PPI could potentially be developed into effective therapeutic or preventive agents for a variety of diseases and conditions.
文摘Background:An e-nose or an e-tongue is a group of gas sensors or chemical sensors that simulate human nose or human tongue.Both e-nose and e-tongue have showngreat promise and utility in improving assessments of food quality characteristics compared with traditional detection methods.Scope and approach:This review summarizes the application of e-nose and e-tongue in determining the quality-related properties of foods.The working principles,applications,and limitations of the sensors employed by electronic noses and electronic tongueswere introduced and compared.Widelyemployed pattern recognition algorithms,including artificial neural network(ANN),convolutional neural network(CNN),principal component analysis(PCA),partial least square regression(PLS),and support vector machine(SVM),were introduced and compared in this review.Key findings and conclusions:Overall,e-nose or e-tongue combining pattern recognition algorithms are very powerful analytical tools,which are relatively low-cost,rapid,and accurate.E-nose and e-tongue are also suitable for both in-line and off-line measurements,which are very useful in monitoring food processing and detecting the end product quality.The user of e-nose and e-tongue need to strictly control sample preparation,sampling,and data processing.
基金This work was supported in part by grants from the National Institutes of Health(NIHR01CA227912 and R01CA214746)to Z.F.and grants from NIH(R01CA203965)+1 种基金Congressionally Directed Medical Research Programs(CDMRPW81XWH-16-1-0358 and W81XWH1810238)to W.H.
文摘p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.
文摘Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study. Methods A total of 30 patients with ＂complete＂ spinal cord injury or classified as American Spinal Injury Association （ASIA）-A were studied. Orthopedic treatment of the injured vertebra（e）, internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis. Results All the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint （12 cases, 40%）. Thirteen patients （43%） were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4-14 days after injury. Conclusions Early neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful.
基金the Second Tibetan Plateau Scientific Expedition and Research Program(2019QZKK0405)the Science and Technology Service Network Initiative(KFJ-STS-QYZD060)+3 种基金the State Key Research Development Program of China(2016YFC0501802,2016YFC0501803 and 2016YFC0502002)the National Natural Science Foundation of China(41871040 and 41501057)the Innovative Research Team of the Ministry of Education of China(IRT_17R59)the Fundamental Research Funds for the Central Universities。
文摘Grazing exclusion using fences is a key policy being applied by the Chinese government to rehabilitate degraded grasslands on the Tibetan Plateau(TP)and elsewhere.However,there is a limited understanding of the effects of grazing exclusion on alpine ecosystem functions and services and its impacts on herders’livelihoods.Our meta-analyses and questionnaire-based surveys revealed that grazing exclusion with fences was effective in promoting aboveground vegetation growth for up to four years in degraded alpine meadows and for up to eight years in the alpine steppes of the TP.Longer-term fencing did not bring any ecological and economic benefits.We also found that fencing hindered wildlife movement,increased grazing pressure in unfenced areas,lowered the satisfaction of herders,and rendered substantial financial costs to both regional and national governments.We recommend that traditional free grazing should be encouraged if applicable,short-term fencing(for 4-8 years)should be adopted in severely degraded grasslands,and fencing should be avoided in key wildlife habitat areas,especially the protected large mammal species.
文摘Hepatocellular carcinoma(HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals withchronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.
基金supported by the Foundation of Science and Technology Planning Project of Guangdong Province(No. 2010B050200007)the Fundamental Research Funds for the Central Universities (No. 2011ZM0054)the Research Fund Program of Guangdong Provincial Key Laboratory of Environmental Pollution Control and Remediation Technology (China) (No. 2011K0013)
文摘Oxidation of aniline by persulfate in aqueous solutions was investigated and the reaction kinetic rates under different temperature, persulfate concentration and pH conditions were examined in batch experiments. The results showed that, the aniline degradation followed pseudo first-order reaction model. Aniline degradation rate increased with increasing temperature or persulfate concentration. In the pH range of 3 to 11, a low aniline degradation rate was obtained at strong acid system （pH 3）, while a high degradation rate was achieved at strong alkalinity （pH 11）. Maximum aniline degradation occurred at pH 7 when the solution was in a weak level of acid and alkalinity （pH 5, 7 and 9）. Produced intermediates during the oxidation process were identified using liquid chromatography-mass spectrometry technology. And nitrobenzene, 4-4’-diaminodiphenyl and 1-hydroxy-1,2-diphenylhydrazine have been identified as the major intermediates of aniline oxidation by persulfate and the degradation mechanism of aniline was also tentatively proposed.
基金supported by the National Natural Science Foundation of China (Grant No. 30870578)the National Basic Research Program of China (Grant No. 2006CB500700)funded by the US National Institutes of Health for providing nematode strains used in this work
文摘β-amyloid (Aβ) and copper play important roles in the pathogenesis of Alzheimer’s disease (AD).However,the behavioral correlativity and molecular mechanisms of Aβ and copper toxicity have been investigated less often.In the present study,we investigated the interaction and toxicity of Aβ1-42 and copper in the Aβ1-42 transgenic Caenorhabditis elegans worm model CL2006.Our data show that the paralysis behavior of CL2006 worms significantly deteriorated after exposure to 10-3 mol L-1 copper ions.However,the paralysis behavior was dramatically attenuated with exposure to 10-4 mol L-1 copper ions.The exogenous copper treatment also partially changed the homeostatic balance of zinc,manganese,and iron.Our data suggest that the accumulation of reactive oxygen species (ROS) was responsible for the paralysis induced by Aβ and copper in CL2006.The ROS generation induced by Aβ and copper appear to be through sod-1,prdx-2,skn-1,hsp-60 and hsp-16.2 genes.
