Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ische...Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.展开更多
Objective: This case report aimed to demonstrate a possible neuromuscular effect of Latarjet nerves transection or truncal vagotomy, in association with sleeve gastrectomy plus antrojejunostomy, in order to reproduce ...Objective: This case report aimed to demonstrate a possible neuromuscular effect of Latarjet nerves transection or truncal vagotomy, in association with sleeve gastrectomy plus antrojejunostomy, in order to reproduce a Roux-en-Y gastric bypass (RYGB) mechanistic principles, in patients with previous Sleeve Gastrectomy (SG) who had had weight regain, with or without concomitant gastroesophageal reflux disease (GERD). Background: Sleeve gastrectomy (SG) is one of the most frequently performed bariatric operations worldwide. Nevertheless, weight regain and gastroesophageal reflux disease (GERD) have been consistently demonstrated, in association with this technique, which may require a revisional procedure. RYGB is an option in such a situation but, implies in gastrointestinal exclusions, which represents a shortcoming of this revision. Surpassing this inconvenient would be of great value for the patients. Methods: We describe herein two cases of SG revision for weight regain and GERD, with a follow-up of one year. Gastroesophageal reflux disease was evaluated by validated questionnaire, upper endoscopy, seriography, high resolution manometry (HRM) and impedance pHmetry (I-pHmetry), in the pre and postoperative periods. A re-Sleeve Gastrectomy with antrojejunal anastomosis was done in both cases, after informed consents. The Latarjet nerves were transected in one case, due to a bleeding in the left gastric vessels and a truncal vagotomy was required in the other, to appropriately treat an associated hiatal hernia. Results: In the postoperative evaluation it was observed a pyloric spasm in both cases, during seriography and endoscopy, kept until the one-year follow-up. There was unidirectional contrast flow to the gastrointestinal anastomosis, filling the jejunal limb, in radiologic contrast study. No contrast passed through the pylorus. Nonetheless, the duodenum was kept endoscopically accessible. In the one-year evaluation, weight loss was adequate and GERD resolution was obtained in both cases, confirmed by endoscopic and functional esophageal assessment, together with symptoms questionnaire. Conclusion: The association of Latarjet nerves sectioning or truncal vagotomy with re-sleeve gastrectomy plus gastrointestinal anastomosis (antrojejunal), in a revision for a failed sleeve, can represent a technical approach, to reproduce RYGB results, without exclusions and with duodenum endoscopic accessibility maintenance. It maybe could be applied for primary surgeries. Additional studies are necessary to confirm this hypothesis.展开更多
The development of active yet stable catalysts for oxygen reduction reaction(ORR)is still a major issue for the extensive permeation of fuel cells into everyday technology.While nanostructured Pt catalysts are to date...The development of active yet stable catalysts for oxygen reduction reaction(ORR)is still a major issue for the extensive permeation of fuel cells into everyday technology.While nanostructured Pt catalysts are to date the best available systems in terms of activity,the same is not true for stability,particularly under operating conditions.In this work,Pt_(Х)Y alloy nanoparticles are proposed as active and durable electrocatalysts for ORR.Pt_(Х)Y nanoalloys are synthesized and further optimized by laser ablation in liquid followed by laser fragmentation in liquid.The novel integrated laser-assisted methodology succeeded in producing Pt_(Х)Y nanoparticles with the ideal size(<10 nm)of commercial Pt catalysts,yet resulting remarkably more active with E_(1/2)=0.943 V vs.RHE,specific activity=1095μA cm^(-2) and mass activity>1000 A g^(-1).At the same time,the nanoalloys are embedded in a fine Pt oxide matrix,which allows a greater stability of the catalyst than the commercial Pt reference,as directly verified on a gas diffusion electrode.展开更多
Fritillaria taipaiensis P.Y.Li is a widely used medicinal herb in treating pulmonary diseases.In recent years,its wild resources have become scarce,and the demand for efficient artificial cultivation has significantly...Fritillaria taipaiensis P.Y.Li is a widely used medicinal herb in treating pulmonary diseases.In recent years,its wild resources have become scarce,and the demand for efficient artificial cultivation has significantly increased.This article is the first to apply phosphate solubilizing bacteria isolated from the rhizosphere soil of F.taipaiensis P.Y.Li to the cultivation process of F.taipaiensis P.Y.Li.The aim is to identify suitable reference strains for the artificial cultivation and industrial development of F.taipaiensis P.Y.Li by examining the effects of various phosphate solubilizing bacteria and their combinations on photosynthesis,physiological and biochemical properties,and gene expression related to the protective enzyme system in F.taipaiensis P.Y.Li.The experiment,conducted in pots at room temperature,included a control group(CK)and groups inoculated with inorganic phosphorussolubilizing bacteria:W1(Bacillus cereus),W2(Serratia plymuthica),W12(Bacillus cereus and Serratia plymuthica),and groups inoculated with organophosphorus-solubilizing bacteria:Y1(Bacillus cereus),Y2(Bacillus cereus),Y12(Bacillus cereus and Bacillus cereus),totaling seven groups.Compared to CK,most growth indices in the bacterial addition groups showed significant differences,with W12 achieving the highest values in all indices except the leaf area index.The content of photosynthetic pigments,photosynthetic parameters,and osmoregulatory substances increased variably in each bacterial treatment group.W12 exhibited the highest content of chlorophyll a and soluble protein,while W1 had the highest free proline content.The activities of peroxidase(POD),superoxide dismutase(SOD),and catalase(CAT)in all inoculated groups were higher than in CK,with significant changes in SOD and CAT activities.The malondialdehyde(MDA)content in all inoculated groups was lower than in CK,with Y12 being the lowest,at approximately 30%of CK.Gene expression corresponding to these three enzymes also increased variably,with POD expression in Y2 being the highest at 2.73 times that of CK.SOD and CAT expression in Y12 were the highest,at 1.84 and 4.39 times that of CK,respectively.These results indicate that inoculating phosphate solubilizing bacteria can enhance the growth of F.taipaiensis P.Y.Li,with the mixed inoculation groups W12 and Y12 demonstrating superior effects.This lays a theoretical foundation for selecting bacterial fertilizers in the cultivation process of F.taipaiensis P.Y.Li.展开更多
Objective: This case report aimed to demonstrate a possible neuromuscular effect of pyloric sympathectomy on the pylorus motility, leading to its permanent relaxation, observed in two bariatric surgical cases, one pri...Objective: This case report aimed to demonstrate a possible neuromuscular effect of pyloric sympathectomy on the pylorus motility, leading to its permanent relaxation, observed in two bariatric surgical cases, one primary and the other, revisional. Background: Pyloric sphincter is a physiological barrier to free gastric emptying. In sleeve gastrectomy and in Roux-en-Y gastric bypass revisions, that put the remnant stomach in transit, the pylorus can contribute to generate a high intragastric pressure, which could lead to acute gastric fistulas and/or chronic gastroesophageal reflux disease. The possibility of functionally relaxing the pylorus, promoting intragastric pressure reduction, could represent a protective maneuver against these complications. Methods: We describe herein a surgical maneuver applied in two cases of bariatric surgeries, with the intention of facilitating antrum-duodenal region exposure, in a sleeve gastrectomy and in a Roux-en-Y gastric bypass conversion to SADI-S. For this, a ligation of terminal peripyloric vessels was done, allowing a passage of a tape, which surrounded the pylorus, for its traction. In both cases, 30-day and 1-year endoscopic evaluations were done, to assess esophagitis signs, anastomosis healing and anatomical pouch aspect. A clinical evaluation was also done, to assess gastroesophageal symptoms (validated questionnaire). Results: In the postoperative endoscopic evaluations, no esophagitis were observed in any case and the gastric pouches had normal aspect, with the expected anatomical findings, compatible with the surgeries performed. The anastomosis healed without problems, in the revisional case. Interestingly, in both cases, it was observed a complete pyloric sphincter relaxation, which lasted until 1-year endoscopic evaluation. There were no fistulas, nor esophagitis in any of these cases. Clinically, there were no symptoms of gastroesophageal reflux disease (validated questionnaire). Conclusion: The observation of a pyloric durable atomy, that followed peripyloric dissection and vessels ligation (arterial branches), with its concomitant sympathectomy, can represent a new way of decompressing gastric chamber, either in primary or revisional bariatric surgeries. This maneuver can be protective against acute fistulas and gastroesophageal disease. Additional studies are necessary to confirm this hypothesis.展开更多
The effect of the Y spacer layer on the phase composition,coercivity,and magnetization reversal processes of La-Nd-Fe-B films has been investigated.The addition of a 10 nm Y spacer layer increases the coercivity of th...The effect of the Y spacer layer on the phase composition,coercivity,and magnetization reversal processes of La-Nd-Fe-B films has been investigated.The addition of a 10 nm Y spacer layer increases the coercivity of the film to 1.36 T at 300 K and remains 0.938 T at 380 K.As the thickness of the Y spacer layer increases,Y participates in the formation of the main phase in the film,and further regulates the formation of La-B phases.The results of the first-order reversal curve(FORC)and micromagnetic fitting show that the coercivity of all the films is dominated by nucleation mechanism.The c-axis preferred orientation,good magnetic microstructure parameters and the largest dipole interaction enhance the coercivity.Therefore,the introduction of the Y spacer layer can be an effective way to improve the coercivity of La-Nd-Fe-B film over a wide temperature range of 150 K-380 K.展开更多
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
Electrocatalysts with high activity and long-term durability are vital toward large-scale hydrogen pro-duction from electrocatalytic water splitting.Here,the self-supported electrode(FeO_(χ)H_(y)@Ni_(3)B/NF)with hier...Electrocatalysts with high activity and long-term durability are vital toward large-scale hydrogen pro-duction from electrocatalytic water splitting.Here,the self-supported electrode(FeO_(χ)H_(y)@Ni_(3)B/NF)with hierarchical heterostructure was simply prepared by using Ni_(3)B chunks grown on nickel foam as sub-strate to in situ form vertical FeO_(χ)H_(y)nanosheets.Such hybrid shows efficient oxygen evolution reaction activity with overpotentials as low as 267 and 249 mV at 100 mA cm^(-2)in 1 M KOH solution and 30 wt%KOH solution,respectively.Meanwhile,it also exhibits excellent catalytic stability,sustaining catalysis at 500 mA cm^(-2)in 1 M KOH solution for 200 h,and even for 200 h at 1000 mA cm^(-2)in 30 wt%KOH solution.Further experimental results reveal that the FeO_(χ)H_(y)@Ni_(3)B/NF is endowed with superhydrophilic and superaerophobic surface properties,which not only provide more mass transport channels,as well as facilitated the diffusion of reaction intermediates and gas bubbles.Also,it holds faster reaction kinetics,more accessible active sites and accelerated electron transfer rates due to strong synergistic interactions attheheterogeneous interface.展开更多
基金supported by the National Natural Science Foundation of China,No.82001604Guizhou Provincial Higher Education Science and Technology Innovation Team,No.[2023]072+1 种基金Guizhou Province Distinguished Young Scientific and Technological Talent Program,No.YQK[2023]040Guizhou Provincial Basic Research Program(Natural Science),No.ZK[2021]-368(all to LXiong),and Zunyi City Innovative Talent Team Training Plan,No.[2022]-2.
文摘Neonatal hypoxic-ischemic encephalopathy is often associated with permanent cerebral palsy,neurosensory impairments,and cognitive deficits,and there is no effective treatment for complications related to hypoxic-ischemic encephalopathy.The therapeutic potential of human placental chorionic plate-derived mesenchymal stem cells for various diseases has been explored.However,the potential use of human placental chorionic plate-derived mesenchymal stem cells for the treatment of neonatal hypoxic-ischemic encephalopathy has not yet been investigated.In this study,we injected human placental chorionic plate-derived mesenchymal stem cells into the lateral ventricle of a neonatal hypoxic-ischemic encephalopathy rat model and observed significant improvements in both cognitive and motor function.Protein chip analysis showed that interleukin-3 expression was significantly elevated in neonatal hypoxic-ischemic encephalopathy model rats.Following transplantation of human placental chorionic plate-derived mesenchymal stem cells,interleukin-3 expression was downregulated.To further investigate the role of interleukin-3 in neonatal hypoxic-ischemic encephalopathy,we established an in vitro SH-SY5Y cell model of hypoxic-ischemic injury through oxygen-glucose deprivation and silenced interleukin-3 expression using small interfering RNA.We found that the activity and proliferation of SH-SY5Y cells subjected to oxygen-glucose deprivation were further suppressed by interleukin-3 knockdown.Furthermore,interleukin-3 knockout exacerbated neuronal damage and cognitive and motor function impairment in rat models of hypoxic-ischemic encephalopathy.The findings suggest that transplantation of hpcMSCs ameliorated behavioral impairments in a rat model of hypoxic-ischemic encephalopathy,and this effect was mediated by interleukin-3-dependent neurological function.
文摘Objective: This case report aimed to demonstrate a possible neuromuscular effect of Latarjet nerves transection or truncal vagotomy, in association with sleeve gastrectomy plus antrojejunostomy, in order to reproduce a Roux-en-Y gastric bypass (RYGB) mechanistic principles, in patients with previous Sleeve Gastrectomy (SG) who had had weight regain, with or without concomitant gastroesophageal reflux disease (GERD). Background: Sleeve gastrectomy (SG) is one of the most frequently performed bariatric operations worldwide. Nevertheless, weight regain and gastroesophageal reflux disease (GERD) have been consistently demonstrated, in association with this technique, which may require a revisional procedure. RYGB is an option in such a situation but, implies in gastrointestinal exclusions, which represents a shortcoming of this revision. Surpassing this inconvenient would be of great value for the patients. Methods: We describe herein two cases of SG revision for weight regain and GERD, with a follow-up of one year. Gastroesophageal reflux disease was evaluated by validated questionnaire, upper endoscopy, seriography, high resolution manometry (HRM) and impedance pHmetry (I-pHmetry), in the pre and postoperative periods. A re-Sleeve Gastrectomy with antrojejunal anastomosis was done in both cases, after informed consents. The Latarjet nerves were transected in one case, due to a bleeding in the left gastric vessels and a truncal vagotomy was required in the other, to appropriately treat an associated hiatal hernia. Results: In the postoperative evaluation it was observed a pyloric spasm in both cases, during seriography and endoscopy, kept until the one-year follow-up. There was unidirectional contrast flow to the gastrointestinal anastomosis, filling the jejunal limb, in radiologic contrast study. No contrast passed through the pylorus. Nonetheless, the duodenum was kept endoscopically accessible. In the one-year evaluation, weight loss was adequate and GERD resolution was obtained in both cases, confirmed by endoscopic and functional esophageal assessment, together with symptoms questionnaire. Conclusion: The association of Latarjet nerves sectioning or truncal vagotomy with re-sleeve gastrectomy plus gastrointestinal anastomosis (antrojejunal), in a revision for a failed sleeve, can represent a technical approach, to reproduce RYGB results, without exclusions and with duodenum endoscopic accessibility maintenance. It maybe could be applied for primary surgeries. Additional studies are necessary to confirm this hypothesis.
基金the P-DISC Grant PROMETEO(project number:P-DiSC#03NExuS_BIRD2021-UNIPD)DYNAMO(project number:P-P-DiSC#01BIRD2020-UNIPD)the financial support of the Fellowship in Applied Electrochemistry 2020。
文摘The development of active yet stable catalysts for oxygen reduction reaction(ORR)is still a major issue for the extensive permeation of fuel cells into everyday technology.While nanostructured Pt catalysts are to date the best available systems in terms of activity,the same is not true for stability,particularly under operating conditions.In this work,Pt_(Х)Y alloy nanoparticles are proposed as active and durable electrocatalysts for ORR.Pt_(Х)Y nanoalloys are synthesized and further optimized by laser ablation in liquid followed by laser fragmentation in liquid.The novel integrated laser-assisted methodology succeeded in producing Pt_(Х)Y nanoparticles with the ideal size(<10 nm)of commercial Pt catalysts,yet resulting remarkably more active with E_(1/2)=0.943 V vs.RHE,specific activity=1095μA cm^(-2) and mass activity>1000 A g^(-1).At the same time,the nanoalloys are embedded in a fine Pt oxide matrix,which allows a greater stability of the catalyst than the commercial Pt reference,as directly verified on a gas diffusion electrode.
基金This work was funded by Chongqing Municipal Technology Innovation and Application Development Program(cstc2020jscx-gksb0001)Yunnan Academician(Expert)Workstation Project(202105AF150073).
文摘Fritillaria taipaiensis P.Y.Li is a widely used medicinal herb in treating pulmonary diseases.In recent years,its wild resources have become scarce,and the demand for efficient artificial cultivation has significantly increased.This article is the first to apply phosphate solubilizing bacteria isolated from the rhizosphere soil of F.taipaiensis P.Y.Li to the cultivation process of F.taipaiensis P.Y.Li.The aim is to identify suitable reference strains for the artificial cultivation and industrial development of F.taipaiensis P.Y.Li by examining the effects of various phosphate solubilizing bacteria and their combinations on photosynthesis,physiological and biochemical properties,and gene expression related to the protective enzyme system in F.taipaiensis P.Y.Li.The experiment,conducted in pots at room temperature,included a control group(CK)and groups inoculated with inorganic phosphorussolubilizing bacteria:W1(Bacillus cereus),W2(Serratia plymuthica),W12(Bacillus cereus and Serratia plymuthica),and groups inoculated with organophosphorus-solubilizing bacteria:Y1(Bacillus cereus),Y2(Bacillus cereus),Y12(Bacillus cereus and Bacillus cereus),totaling seven groups.Compared to CK,most growth indices in the bacterial addition groups showed significant differences,with W12 achieving the highest values in all indices except the leaf area index.The content of photosynthetic pigments,photosynthetic parameters,and osmoregulatory substances increased variably in each bacterial treatment group.W12 exhibited the highest content of chlorophyll a and soluble protein,while W1 had the highest free proline content.The activities of peroxidase(POD),superoxide dismutase(SOD),and catalase(CAT)in all inoculated groups were higher than in CK,with significant changes in SOD and CAT activities.The malondialdehyde(MDA)content in all inoculated groups was lower than in CK,with Y12 being the lowest,at approximately 30%of CK.Gene expression corresponding to these three enzymes also increased variably,with POD expression in Y2 being the highest at 2.73 times that of CK.SOD and CAT expression in Y12 were the highest,at 1.84 and 4.39 times that of CK,respectively.These results indicate that inoculating phosphate solubilizing bacteria can enhance the growth of F.taipaiensis P.Y.Li,with the mixed inoculation groups W12 and Y12 demonstrating superior effects.This lays a theoretical foundation for selecting bacterial fertilizers in the cultivation process of F.taipaiensis P.Y.Li.
文摘Objective: This case report aimed to demonstrate a possible neuromuscular effect of pyloric sympathectomy on the pylorus motility, leading to its permanent relaxation, observed in two bariatric surgical cases, one primary and the other, revisional. Background: Pyloric sphincter is a physiological barrier to free gastric emptying. In sleeve gastrectomy and in Roux-en-Y gastric bypass revisions, that put the remnant stomach in transit, the pylorus can contribute to generate a high intragastric pressure, which could lead to acute gastric fistulas and/or chronic gastroesophageal reflux disease. The possibility of functionally relaxing the pylorus, promoting intragastric pressure reduction, could represent a protective maneuver against these complications. Methods: We describe herein a surgical maneuver applied in two cases of bariatric surgeries, with the intention of facilitating antrum-duodenal region exposure, in a sleeve gastrectomy and in a Roux-en-Y gastric bypass conversion to SADI-S. For this, a ligation of terminal peripyloric vessels was done, allowing a passage of a tape, which surrounded the pylorus, for its traction. In both cases, 30-day and 1-year endoscopic evaluations were done, to assess esophagitis signs, anastomosis healing and anatomical pouch aspect. A clinical evaluation was also done, to assess gastroesophageal symptoms (validated questionnaire). Results: In the postoperative endoscopic evaluations, no esophagitis were observed in any case and the gastric pouches had normal aspect, with the expected anatomical findings, compatible with the surgeries performed. The anastomosis healed without problems, in the revisional case. Interestingly, in both cases, it was observed a complete pyloric sphincter relaxation, which lasted until 1-year endoscopic evaluation. There were no fistulas, nor esophagitis in any of these cases. Clinically, there were no symptoms of gastroesophageal reflux disease (validated questionnaire). Conclusion: The observation of a pyloric durable atomy, that followed peripyloric dissection and vessels ligation (arterial branches), with its concomitant sympathectomy, can represent a new way of decompressing gastric chamber, either in primary or revisional bariatric surgeries. This maneuver can be protective against acute fistulas and gastroesophageal disease. Additional studies are necessary to confirm this hypothesis.
基金Project supported by the National Key Research and Development Program of China(Grant No.2021YFB3500303)the National Natural Science Foundation of China(Grant Nos.52031014 and 51971219).
文摘The effect of the Y spacer layer on the phase composition,coercivity,and magnetization reversal processes of La-Nd-Fe-B films has been investigated.The addition of a 10 nm Y spacer layer increases the coercivity of the film to 1.36 T at 300 K and remains 0.938 T at 380 K.As the thickness of the Y spacer layer increases,Y participates in the formation of the main phase in the film,and further regulates the formation of La-B phases.The results of the first-order reversal curve(FORC)and micromagnetic fitting show that the coercivity of all the films is dominated by nucleation mechanism.The c-axis preferred orientation,good magnetic microstructure parameters and the largest dipole interaction enhance the coercivity.Therefore,the introduction of the Y spacer layer can be an effective way to improve the coercivity of La-Nd-Fe-B film over a wide temperature range of 150 K-380 K.
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 by the National Natural Science Foundation of China (12234018,52101256,51872115)
文摘Electrocatalysts with high activity and long-term durability are vital toward large-scale hydrogen pro-duction from electrocatalytic water splitting.Here,the self-supported electrode(FeO_(χ)H_(y)@Ni_(3)B/NF)with hierarchical heterostructure was simply prepared by using Ni_(3)B chunks grown on nickel foam as sub-strate to in situ form vertical FeO_(χ)H_(y)nanosheets.Such hybrid shows efficient oxygen evolution reaction activity with overpotentials as low as 267 and 249 mV at 100 mA cm^(-2)in 1 M KOH solution and 30 wt%KOH solution,respectively.Meanwhile,it also exhibits excellent catalytic stability,sustaining catalysis at 500 mA cm^(-2)in 1 M KOH solution for 200 h,and even for 200 h at 1000 mA cm^(-2)in 30 wt%KOH solution.Further experimental results reveal that the FeO_(χ)H_(y)@Ni_(3)B/NF is endowed with superhydrophilic and superaerophobic surface properties,which not only provide more mass transport channels,as well as facilitated the diffusion of reaction intermediates and gas bubbles.Also,it holds faster reaction kinetics,more accessible active sites and accelerated electron transfer rates due to strong synergistic interactions attheheterogeneous interface.