The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At...The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.展开更多
Herein,a simple synthetic approach is employed for the atomic dispersion of Rh atoms(Rh SAs)over the surface of interconnected Mo_(2)C nanosheets intimately embedded in a three-dimensional Ni_(x)MoO_(y)nanorod arrays(...Herein,a simple synthetic approach is employed for the atomic dispersion of Rh atoms(Rh SAs)over the surface of interconnected Mo_(2)C nanosheets intimately embedded in a three-dimensional Ni_(x)MoO_(y)nanorod arrays(Ni_(x)MoO_(y)NRs)framework;we found that the introduction of both isolated Rh SAs and Ni_(x)MoO_(y)NRs adjusts the electrocatalytic function of the host Mo_(2)C toward the direction of being an advanced and highly stable electrocatalyst for efficient hydrogen evolution at pH-universal conditions.As a result,the proposed catalyst outperforms most recently reported transition metal-based catalysts,and its performance even rivals that of commercial Pt/C,as demonstrated by its ultralow overpotentials of 31.7,109.7,and 95.4 mV at a current density of 10 mA cm^(-2),along with its small Tafel slopes of 42.4,51.2,and 46.8 mV dec^(-1)in acidic,neutral,and alkaline conditions,respectively.In addition,the catalyst shows remarkable long-term stability over all pH values with good maintenance of its catalytic activity and structural characteristics after continuous operation.展开更多
Introduction: According to WHO estimates, 57% of cases of liver cirrhosis and 78% of primary liver carcinoma are caused by a hepatitis B or C virus. This study aimed to assess the prevalence of these diseases and HIV ...Introduction: According to WHO estimates, 57% of cases of liver cirrhosis and 78% of primary liver carcinoma are caused by a hepatitis B or C virus. This study aimed to assess the prevalence of these diseases and HIV among a young male population, according to region. Methods: This was a descriptive cross-sectional study conducted from 17 February to 31 March 2014 in the ten administrative regions of Cameroon. The study included male subjects of Cameroonian nationality aged at least 18 and at most 23, and living in the regions concerned. It excluded subjects that did not match the age, gender, and nationality criteria. For each subject, 10 ml of blood was collected in a dry tube. After centrifugation at 3000 RPM for 5 minutes, the serum was collected for the detection of viral infections. For subjects that tested positive, a confirmatory test was conducted. Results: In total, 4367 subjects were selected, with an average age of 20.46 (+/- 1.17) years. The prevalence of hepatitis B virus stood at 13.01% (with 95% CI: 12.03% - 14.05%). That of viral hepatitis C was 0.30% (95% CI: 0.17% - 0.52%). Co-infection with hepatitis B and C viruses was 0.05% (95% CI: 0.01% - 0.18%). The prevalence of HIV infection was 1.01% (95% CI: 0.74% - 1.36%). Conclusion: The overall prevalence of HBsAg in the population of young males is high. It tallies with the early vertical and horizontal modes of transmission that prevail in our environment.展开更多
基金funded by the Ministry of Science and Higher Education of the Russian Federation(Grant No.075-15-2020-795 of 29.09.2020,unique project ID:RF-190220X0027).
文摘The tumor suppressor p53 is a transcription factor with a powerful antitumor activity that is controlled by its negative regulator murine double minute 2(MDM2,also termed HDM2 in humans)through a feedback mechanism.At the same time,TP53 is the most frequently mutated gene in human cancers.Mutant p53 proteins lose wild-type p53 tumor suppression functions but acquire new oncogenic properties,among which are deregulating cell proliferation,increasing chemoresistance,disrupting tissue architecture,and promoting migration,invasion and metastasis as well as several other pro-oncogenic activities.The oncogenic p53 mutation Y220C creates an extended surface crevice in the DNA-binding domain destabilizing p53 and causing its denaturation and aggregation.This cavity accommodates stabilizing small molecules that have therapeutic values.The development of suitable small-molecule stabilizers is one of the therapeutic strategies for reactivating the Y220C mutant protein.In this review,we summarize approaches that target p53-Y220C,including reactivating this mutation with small molecules that bind Y220C to the hydrophobic pocket and developing immunotherapies as the goal for the near future,which target tumor cells that express the p53-Y220C neoantigen.
基金Supported from the Regional Leading Research Center Program(2019R1A5A8080326)through the National Research Foundation funded by the Ministry of Science and ICT of Republic of Korea.
文摘Herein,a simple synthetic approach is employed for the atomic dispersion of Rh atoms(Rh SAs)over the surface of interconnected Mo_(2)C nanosheets intimately embedded in a three-dimensional Ni_(x)MoO_(y)nanorod arrays(Ni_(x)MoO_(y)NRs)framework;we found that the introduction of both isolated Rh SAs and Ni_(x)MoO_(y)NRs adjusts the electrocatalytic function of the host Mo_(2)C toward the direction of being an advanced and highly stable electrocatalyst for efficient hydrogen evolution at pH-universal conditions.As a result,the proposed catalyst outperforms most recently reported transition metal-based catalysts,and its performance even rivals that of commercial Pt/C,as demonstrated by its ultralow overpotentials of 31.7,109.7,and 95.4 mV at a current density of 10 mA cm^(-2),along with its small Tafel slopes of 42.4,51.2,and 46.8 mV dec^(-1)in acidic,neutral,and alkaline conditions,respectively.In addition,the catalyst shows remarkable long-term stability over all pH values with good maintenance of its catalytic activity and structural characteristics after continuous operation.
文摘Introduction: According to WHO estimates, 57% of cases of liver cirrhosis and 78% of primary liver carcinoma are caused by a hepatitis B or C virus. This study aimed to assess the prevalence of these diseases and HIV among a young male population, according to region. Methods: This was a descriptive cross-sectional study conducted from 17 February to 31 March 2014 in the ten administrative regions of Cameroon. The study included male subjects of Cameroonian nationality aged at least 18 and at most 23, and living in the regions concerned. It excluded subjects that did not match the age, gender, and nationality criteria. For each subject, 10 ml of blood was collected in a dry tube. After centrifugation at 3000 RPM for 5 minutes, the serum was collected for the detection of viral infections. For subjects that tested positive, a confirmatory test was conducted. Results: In total, 4367 subjects were selected, with an average age of 20.46 (+/- 1.17) years. The prevalence of hepatitis B virus stood at 13.01% (with 95% CI: 12.03% - 14.05%). That of viral hepatitis C was 0.30% (95% CI: 0.17% - 0.52%). Co-infection with hepatitis B and C viruses was 0.05% (95% CI: 0.01% - 0.18%). The prevalence of HIV infection was 1.01% (95% CI: 0.74% - 1.36%). Conclusion: The overall prevalence of HBsAg in the population of young males is high. It tallies with the early vertical and horizontal modes of transmission that prevail in our environment.
