Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke,...Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.展开更多
Designing high-performance and low-cost electrocatalysts for oxygen evolu-tion reaction(OER)is critical for the conversion and storage of sustainable energy technologies.Inspired by the biomineralization process,we ut...Designing high-performance and low-cost electrocatalysts for oxygen evolu-tion reaction(OER)is critical for the conversion and storage of sustainable energy technologies.Inspired by the biomineralization process,we utilized the phosphorylation sites of collagen molecules to combine with cobalt-based mononuclear precursors at the molecular level and built a three-dimensional(3D)porous hierarchical material through a bottom-up biomimetic self-assembly strategy to obtain single-atom catalysts confined on carbonized biomimetic self-assembled carriers(Co SACs/cBSC)after subsequent high-temperature annealing.In this strategy,the biomolecule improved the anchoring efficiency of the metal precursor through precise functional groups;meanwhile,the binding-then-assembling strategy also effectively suppressed the nonspecific adsorption of metal ions,ultimately preventing atomic agglomeration and achieving strong electronic metal-support interactions(EMSIs).Experimental characterizations confirm that binding forms between cobalt metal and carbonized self-assembled substrate(Co–O_(4)–P).Theoretical calculations disclose that the local environment changes significantly tailored the Co d-band center,and optimized the binding energy of oxygenated intermediates and the energy barrier of oxygen release.As a result,the obtained Co SACs/cBSC catalyst can achieve remarkable OER activity and 24 h durability in 1 M KOH(η10 at 288 mV;Tafel slope of 44 mV dec-1),better than other transition metal-based catalysts and commercial IrO_(2).Overall,we presented a self-assembly strategy to prepare transition metal SACs with strong EMSIs,providing a new avenue for the preparation of efficient catalysts with fine atomic structures.展开更多
Developing wide-temperature and high-safety lithium-ion batteries(LIBs)presents significant challenges attributed to the absence of suitable solvents possessing broad liquid range and non-flammability properties.γ-Bu...Developing wide-temperature and high-safety lithium-ion batteries(LIBs)presents significant challenges attributed to the absence of suitable solvents possessing broad liquid range and non-flammability properties.γ-Butyrolactone(GBL)has emerged as a promising solvent;however,its incompatibility with graphite anode has hindered its application.This limitation necessitates a comprehensive investigation into the underlying mechanisms and potential solutions.In this study,we achieve a molecular-level understanding of the perplexing interphase formation process by employing in-situ spectroelectrochemical techniques and density function calculations.Our findings reveal that,even at high salt concentrations,GBL consistently occupies the primary Li^(+)solvation sheath,leading to extensive GBL decomposition and the formation of a high-impedance and inorganic-poor solid-electrolyte interphase(SEI)layer.Contrary to manipulating solvation structures,our research demonstrates that the utilization of filmforming additives with higher reduction potential facilitates the pre-establishment of a robust SEI film on the graphite anode.This approach effectively inhibits GBL decomposition and significantly enhances the battery's lifespan.This study provides the first reported intrinsic understanding of the unique GBLgraphite incompatibility and offers valuable insights for the development of wide-temperature and high-safety LIBs.展开更多
●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:T...●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.展开更多
BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC...BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.展开更多
BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression...BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for patients.AIM To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022.According to the Miller-Payne grading system,the pathological response,i.e.efficacy,of the NAC in the initial breast lesion after NAC was evaluated.Of these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches.RESULTS In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(P<0.05).The area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,respectively.Also,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictive value for NAC efficacy,they are significantly associated with poor response to NAC in breast cancer patients.展开更多
This study investigated the current status of course satisfaction among 416 undergraduate students majoring in preschool education from four universities in China.And it explored the predictive effects of five influen...This study investigated the current status of course satisfaction among 416 undergraduate students majoring in preschool education from four universities in China.And it explored the predictive effects of five influencing factors(teacher instruction,course management,course setting,course environment,and course resources)on student satisfaction.Through SPSS data analysis,the findings revealed that:1.the mean value of course experience was M=3.861(out of 5);2.there were differences in the satisfaction of undergraduate students'course experience by different background variables;3.course,course resources,and loyalty had significant predictive power on undergraduate students'satisfaction with course experience;4.instructor instruction(TI)did not significantly predict students'satisfaction with course experience(SCES)(p>0.001);5.Faculty instruction(TI)in this study had the highest mean satisfaction score(M=4.191)and the mean satisfaction score was only(M=3.861).The results show that the current status of course satisfaction among Chinese preschool undergraduates is at an moderate level,and there is more space for improvement;although students'satisfaction with teacher instruction(TI)is high,effective teacher instruction does not have a substantial impact on the acquisition of SCES or general competencies,and this passive learning and teaching style leads to a lack of independent learning and active participation among Chinese preschool undergraduate students.展开更多
基金supported by the National Natural Science Foundation of China(numbers:81774416 and 81473764)。
文摘Background: Blocking the Rho A/ROCK Ⅱ/MLC 2(Ras homolog gene family member A/Rho kinase Ⅱ/myosin light chain 2) signaling pathway can initiate neuroprotective mechanisms against neurological diseases such as stroke, cerebral ischemia, and subarachnoid hemorrhage. Nevertheless, it is not clear whether and how disrupting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway changes the pathogenic processes of the blood–brain barrier(BBB) after intracerebral hemorrhage(ICH). The present investigation included the injection of rat caudal vein blood into the basal ganglia area to replicate the pathophysiological conditions caused by ICH. Methods: Scalp acupuncture(SA) therapy was performed on rats with ICH at the acupuncture point “Baihui”-penetrating “Qubin,” and the ROCK selective inhibitor fasudil was used as a positive control to evaluate the inhibitory effect of acupuncture on the Rho A/ROCK Ⅱ/MLC 2 signaling pathway. Post-assessments included neurological deficits, brain edema, Evans blue extravasation, Western blot, quantitative polymerase chain reaction, and transmission electron microscope imaging. Results: We found that ROCK Ⅱ acts as a promoter of the Rho A/ROCK Ⅱ/MLC 2 signaling pathway, and its expression increased at 6 h after ICH, peaked at 3 days, and then decreased at 7 days after ICH, but was still higher than the preintervention level. According to some experimental results, although 3 days is the peak, 7 days is the best time point for acupuncture treatment. Starting from 6 h after ICH, the neurovascular structure and endothelial cell morphology around the hematoma began to change. Based on the changes in the promoter ROCK Ⅱ, a 7-day time point was selected as the breakthrough point for treating ICH model rats in the main experiment. The results of this experiment showed that both SA at “Baihui”-penetrating “Qubin” and treatment with fasudil could improve the expression of endothelial-related proteins by inhibiting the Rho A/ROCK Ⅱ/MLC 2 signaling pathway and reduce neurological dysfunction, brain edema, and BBB permeability in rats. Conclusion: This study found that these experimental data indicated that SA at “Baihui”-penetrating “Qubin” could preserve BBB integrity and neurological function recovery after ICH by inhibiting Rho A/ROCK Ⅱ/MLC 2 signaling pathway activation and by regulating endothelial cell–related proteins.
基金The work was supported by the National Natural Science Foundation of China(52372174)Carbon Neutrality Research Institute Fund(CNIF20230204)Special Project of Strategic Cooperation between China National Petroleum Corporation and China University of Petroleum(Beijing)(ZLZX-2020-04).
文摘Designing high-performance and low-cost electrocatalysts for oxygen evolu-tion reaction(OER)is critical for the conversion and storage of sustainable energy technologies.Inspired by the biomineralization process,we utilized the phosphorylation sites of collagen molecules to combine with cobalt-based mononuclear precursors at the molecular level and built a three-dimensional(3D)porous hierarchical material through a bottom-up biomimetic self-assembly strategy to obtain single-atom catalysts confined on carbonized biomimetic self-assembled carriers(Co SACs/cBSC)after subsequent high-temperature annealing.In this strategy,the biomolecule improved the anchoring efficiency of the metal precursor through precise functional groups;meanwhile,the binding-then-assembling strategy also effectively suppressed the nonspecific adsorption of metal ions,ultimately preventing atomic agglomeration and achieving strong electronic metal-support interactions(EMSIs).Experimental characterizations confirm that binding forms between cobalt metal and carbonized self-assembled substrate(Co–O_(4)–P).Theoretical calculations disclose that the local environment changes significantly tailored the Co d-band center,and optimized the binding energy of oxygenated intermediates and the energy barrier of oxygen release.As a result,the obtained Co SACs/cBSC catalyst can achieve remarkable OER activity and 24 h durability in 1 M KOH(η10 at 288 mV;Tafel slope of 44 mV dec-1),better than other transition metal-based catalysts and commercial IrO_(2).Overall,we presented a self-assembly strategy to prepare transition metal SACs with strong EMSIs,providing a new avenue for the preparation of efficient catalysts with fine atomic structures.
基金financially supported by the National Natural Science Foundation of China(21972049,22272175)the National Key R&D Program of China(2022YFA1504002)+3 种基金the“Scientist Studio Funding”from Tianmu Lake Institute of Advanced Energy Storage Technologies Co.,Ltd.Dalian Supports High-Level Talent Innovation and Entrepreneurship Projects(2021RD14)the Dalian Institute of Chemical Physics(DICP I202213)the 21C Innovation Laboratory,Contemporary Ampere Technology Ltd.by project No.21C-OP-202208。
文摘Developing wide-temperature and high-safety lithium-ion batteries(LIBs)presents significant challenges attributed to the absence of suitable solvents possessing broad liquid range and non-flammability properties.γ-Butyrolactone(GBL)has emerged as a promising solvent;however,its incompatibility with graphite anode has hindered its application.This limitation necessitates a comprehensive investigation into the underlying mechanisms and potential solutions.In this study,we achieve a molecular-level understanding of the perplexing interphase formation process by employing in-situ spectroelectrochemical techniques and density function calculations.Our findings reveal that,even at high salt concentrations,GBL consistently occupies the primary Li^(+)solvation sheath,leading to extensive GBL decomposition and the formation of a high-impedance and inorganic-poor solid-electrolyte interphase(SEI)layer.Contrary to manipulating solvation structures,our research demonstrates that the utilization of filmforming additives with higher reduction potential facilitates the pre-establishment of a robust SEI film on the graphite anode.This approach effectively inhibits GBL decomposition and significantly enhances the battery's lifespan.This study provides the first reported intrinsic understanding of the unique GBLgraphite incompatibility and offers valuable insights for the development of wide-temperature and high-safety LIBs.
文摘●AIM:To evaluate the effectiveness and safety of early lens extraction during pars plana vitrectomy(PPV)for proliferative diabetic retinopathy(PDR)compared to those of PPV with subsequent cataract surgery.●METHODS:This multicenter randomized controlled trial was conducted in three Chinese hospitals on patients with PDR,aged>45y,with mild cataracts.The participants were randomly assigned to the combined(PPV combined with simultaneously cataract surgery,i.e.,phacovitrectomy)or subsequent(PPV with subsequent cataract surgery 6mo later)group and followed up for 12mo.The primary outcome was the change in best-corrected visual acuity(BCVA)from baseline to 6mo,and the secondary outcomes included complication rates and medical expenses.●RESULTS:In total,129 patients with PDR were recruited and equally randomized(66 and 63 in the combined and subsequent groups respectively).The change in BCVA in the combined group[mean,36.90 letters;95%confidence interval(CI),30.35–43.45]was significantly better(adjusted difference,16.43;95%CI,8.77–24.08;P<0.001)than in the subsequent group(mean,22.40 letters;95%CI,15.55–29.24)6mo after the PPV,with no significant difference between the two groups at 12mo.The overall surgical risk of two sequential surgeries was significantly higher than that of the combined surgery for neovascular glaucoma(17.65%vs 3.77%,P=0.005).No significant differences were found in the photocoagulation spots,surgical time,and economic expenses between two groups.In the subsequent group,the duration of work incapacity(22.54±9.11d)was significantly longer(P<0.001)than that of the combined group(12.44±6.48d).●CONCLUSION:PDR patients aged over 45y with mild cataract can also benefit from early lens extraction during PPV with gratifying effectiveness,safety and convenience,compared to sequential surgeries.
基金the Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2020KJ133Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009A.
文摘BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely studied.CDK9,a key regulator of transcription,may influence the occurrence and progression of CRC.The expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in CRC.Under normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor growth.Therefore,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this research.AIM To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and prognosis.METHODS We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of CDK9.We also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma tissues.RESULTS The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy resistance.Further analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal cancer.CONCLUSION This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.
文摘BACKGROUND Breast cancer ranks as one of the most prevalent malignant tumors among women,significantly endangering their health and lives.While radical surgery has been a pivotal method for halting disease progression,it alone is insufficient for enhancing the quality of life for patients.AIM To investigate the correlation between ultrasound characteristic parameters of breast cancer lesions and clinical efficacy in patients undergoing neoadjuvant chemotherapy(NAC).METHODS Employing a case-control study design,this research involved 178 breast cancer patients treated with NAC at our hospital from July 2019 to June 2022.According to the Miller-Payne grading system,the pathological response,i.e.efficacy,of the NAC in the initial breast lesion after NAC was evaluated.Of these,59 patients achieved a pathological complete response(PCR),while 119 did not(non-PCR group).Ultrasound characteristics prior to NAC were compared between these groups,and the association of various factors with NAC efficacy was analyzed using univariate and multivariate approaches.RESULTS In the PCR group,the incidence of posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II were significantly lower compared to the non-PCR group(P<0.05).The area under the curve values for predicting NAC efficacy using posterior echo attenuation,lesion diameter,and Alder grade were 0.604,0.603,and 0.583,respectively.Also,rates of pathological stage II,lymph node metastasis,vascular invasion,and positive Ki-67 expression were significantly lower in the PCR group(P<0.05).Logistic regression analysis identified posterior echo attenuation,lesion diameter≥2.0 cm,Alder blood flow grade≥II,pathological stage III,vascular invasion,and positive Ki-67 expression as independent predictors of poor response to NAC in breast cancer patients(P<0.05).CONCLUSION While ultrasound characteristics such as posterior echo attenuation,lesion diameter≥2.0 cm,and Alder blood flow grade≥II exhibit limited predictive value for NAC efficacy,they are significantly associated with poor response to NAC in breast cancer patients.
文摘This study investigated the current status of course satisfaction among 416 undergraduate students majoring in preschool education from four universities in China.And it explored the predictive effects of five influencing factors(teacher instruction,course management,course setting,course environment,and course resources)on student satisfaction.Through SPSS data analysis,the findings revealed that:1.the mean value of course experience was M=3.861(out of 5);2.there were differences in the satisfaction of undergraduate students'course experience by different background variables;3.course,course resources,and loyalty had significant predictive power on undergraduate students'satisfaction with course experience;4.instructor instruction(TI)did not significantly predict students'satisfaction with course experience(SCES)(p>0.001);5.Faculty instruction(TI)in this study had the highest mean satisfaction score(M=4.191)and the mean satisfaction score was only(M=3.861).The results show that the current status of course satisfaction among Chinese preschool undergraduates is at an moderate level,and there is more space for improvement;although students'satisfaction with teacher instruction(TI)is high,effective teacher instruction does not have a substantial impact on the acquisition of SCES or general competencies,and this passive learning and teaching style leads to a lack of independent learning and active participation among Chinese preschool undergraduate students.
