Background:The traditional Sox10 ^(Dom/+)mouse breeding strategy is costly and timeconsuming,so this study aims to optimize the breeding method and improve the scientific research efficiency.Methods:We select the offs...Background:The traditional Sox10 ^(Dom/+)mouse breeding strategy is costly and timeconsuming,so this study aims to optimize the breeding method and improve the scientific research efficiency.Methods:We select the offspring from mating B6C3Fe Sox10 ^(Dom/+)male mice with C57BL/6J female mice,and name the progeny B6C3Fe-g.Further,conduct separate self-breeding for both the B6C3Fe and B6C3Fe-g strains,adhering to the principle of pairing mutants with non-mutants.By comparing the number of offspring,survival rates,and the phenotype of aganglionosis in the colon,a comprehensive evaluation of their breeding capacity and phenotypic stability is conducted.Results:Sanger sequencing results show that the mutation sites of B6C3Fe and B6C3Fe-g mice are consistent.After fluorescent staining of intestinal nerves,it was found that the heterozygous mice of the two strains had neuronal deletion in the distal colon,and this pathological phenotype was consistent with the pathological features of the diseased colon of Hirschsprung disease(HSCR).However,compared with the B6C3Fe strain,the B6C3Fe-g strain has a higher number of offspring and greater survival rates.Conclusions:The breeding strategy of the B6C3Fe-g strain ensures genetic and phenotypic stability,while improving reproductive efficiency,and is an ideal scheme for breeding Sox10 ^(Dom/+)mice.展开更多
Considering the effect of crack gap, the bending deformation of the Timoshenko beam with switching cracks is studied. To represent a crack with gap as a nonlinear unidirectional rotational spring, the equivalent flexu...Considering the effect of crack gap, the bending deformation of the Timoshenko beam with switching cracks is studied. To represent a crack with gap as a nonlinear unidirectional rotational spring, the equivalent flexural rigidity of the cracked beam is derived with the generalized Dirac delta function. A closed-form general solution is obtained for bending of a Timoshenko beam with an arbitrary number of switching cracks. Three examples of bending of the Timoshenko beam are presented. The influence of the beam＇s slenderness ratio, the crack＇s depth, and the external load on the crack state and bending performances of the cracked beam is analyzed. It is revealed that a cusp exists on the deflection curve, and a jump on the rotation angle curve occurs at a crack location. The relation between the beam＇s deflection and load is bilinear, each part corresponding to an open or closed state of crack, respectively. When the crack is open, flexibility of the cracked beam decreases with the increase of the beam＇s slenderness ratio and the decrease of the crack depth. The results are useful in identifying non-destructive cracks on a beam.展开更多
BACKGROUND:It is controversial whether prophylactic endotracheal intubation(PEI)protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding(UGIB).The study aimed to explore the...BACKGROUND:It is controversial whether prophylactic endotracheal intubation(PEI)protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding(UGIB).The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy.METHODS:Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database(eICU-CRD).The composite cardiopulmonary outcomes included aspiration,pneumonia,pulmonary edema,shock or hypotension,cardiac arrest,myocardial infarction,and arrhythmia.The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups.Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes.Moreover,restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes(yes/no)in the PEI group.RESULTS:A total of 946 patients were divided into the PEI group(108/946,11.4%)and the non-PEI group(838/946,88.6%).After propensity score matching,the PEI group(n=50)had a higher incidence of cardiopulmonary outcomes(58.0%vs.30.3%,P=0.001).PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders(odds ratio[OR]3.176,95%confidence interval[95%CI]1.567-6.438,P=0.001).The subgroup analysis indicated the similar results.A shock index>0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI(P=0.015).The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index(OR 1.465,95%CI 1.079-1.989,P=0.014)and shock index>0.77(compared with shock index≤0.77[OR 2.981,95%CI 1.186-7.492,P=0.020,AUC=0.764]).CONCLUSION:PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy.Furthermore,a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.展开更多
Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanis...Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanisms.Using single-cell RNA sequencing,we analyzed the molecular profile of individual cells within control and AAA abdominal aortas.We found cellular heterogeneity,with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells(VSMCs)in AAA.Up-regulated genes in AAA were associated with muscle tissue development and apoptosis.Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA.Additionally,VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation.Similar observations were made in a mouse model of AAA induced by Angiotensin II,further affirming the relevance of our findings to human AAA.The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention.Nicotinamide phosphoribosyltransferase(NAMPT,also named VISFATIN)signaling emerged as a signature event in AAA.NAMPT was significantly downregulated in AAA.NAMPT-extracellular vesicles(EVs)derived from mesenchymal stem cells restored NAMPT levels,and offered protection against AAA.Furthermore,NAMPT-EVs not only repressed injuries,such as cell senescence and DNA damage,but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models,suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment.These findings shed light on the cellular heterogeneity and injuries in AAA,and offered promising therapeutic intervention for AAA treatment.展开更多
Enzyme-free autocatalytic nucleic acidmachinery has been widely used to engineer various self-assembled nanostructures as well as high-performance bioanalysis,yet has rarely been realized in live cells for complicated...Enzyme-free autocatalytic nucleic acidmachinery has been widely used to engineer various self-assembled nanostructures as well as high-performance bioanalysis,yet has rarely been realized in live cells for complicated design,low robustness,and limited reliability.Herein,we constructed simple yet versatile enthalpy-driven autocatalytic hybridization chain reaction(AHCR)machinery with high reliability and robustness for in situ microRNA analysis in live cells.The homogeneous AHCR machine was composed of two differently designed HCR modules,the lead-in HCR-1 amplification module,and the reverse HCR-2 feedback module.After the AHCR amplification system was delivered into live cells,target microRNA stimulated the autonomous cross-invasion of the HCR-1 module and the HCR-2 module for assembling hyperbranched dsDNA nanostructures with synergistically amplified Förster resonance energy transfer readout,thus enabling accurate intracellular micro-RNA imaging.The synergistic AHCR execution was systematically investigated by a series of experimental studies and computer-aided theoretical simulations.The multiple recognition capacity of HCR constituents and the successive signal amplification of the AHCR machine enabled the accurate intracellular microRNA imaging with precise signal localization inside living cells.Based on its intriguing and modular design,the AHCR machinery can be extended for analyzing diverse biomarkers,thus supplementing a powerful toolbox for clinical diagnosis and therapeutic assessment.展开更多
基金Basic and Applied Basic Research Foundation of Guangxi Province of China,Grant/Award Number:2025GXNSFBA069072National Natural Science Foundation of China,Grant/Award Number:81970450,82070528,82170528,82200561,82201893,82301955,82370526 and 82560108+2 种基金Medical Scientific Research Foundation of Guangdong Province of China,Grant/Award Number:A2024374The Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2024A03J1171,2024A03J1238 and 2024A1515013190Science and Technology Projects in Guangzhou,Grant/Award Number:202201020006。
文摘Background:The traditional Sox10 ^(Dom/+)mouse breeding strategy is costly and timeconsuming,so this study aims to optimize the breeding method and improve the scientific research efficiency.Methods:We select the offspring from mating B6C3Fe Sox10 ^(Dom/+)male mice with C57BL/6J female mice,and name the progeny B6C3Fe-g.Further,conduct separate self-breeding for both the B6C3Fe and B6C3Fe-g strains,adhering to the principle of pairing mutants with non-mutants.By comparing the number of offspring,survival rates,and the phenotype of aganglionosis in the colon,a comprehensive evaluation of their breeding capacity and phenotypic stability is conducted.Results:Sanger sequencing results show that the mutation sites of B6C3Fe and B6C3Fe-g mice are consistent.After fluorescent staining of intestinal nerves,it was found that the heterozygous mice of the two strains had neuronal deletion in the distal colon,and this pathological phenotype was consistent with the pathological features of the diseased colon of Hirschsprung disease(HSCR).However,compared with the B6C3Fe strain,the B6C3Fe-g strain has a higher number of offspring and greater survival rates.Conclusions:The breeding strategy of the B6C3Fe-g strain ensures genetic and phenotypic stability,while improving reproductive efficiency,and is an ideal scheme for breeding Sox10 ^(Dom/+)mice.
文摘Considering the effect of crack gap, the bending deformation of the Timoshenko beam with switching cracks is studied. To represent a crack with gap as a nonlinear unidirectional rotational spring, the equivalent flexural rigidity of the cracked beam is derived with the generalized Dirac delta function. A closed-form general solution is obtained for bending of a Timoshenko beam with an arbitrary number of switching cracks. Three examples of bending of the Timoshenko beam are presented. The influence of the beam＇s slenderness ratio, the crack＇s depth, and the external load on the crack state and bending performances of the cracked beam is analyzed. It is revealed that a cusp exists on the deflection curve, and a jump on the rotation angle curve occurs at a crack location. The relation between the beam＇s deflection and load is bilinear, each part corresponding to an open or closed state of crack, respectively. When the crack is open, flexibility of the cracked beam decreases with the increase of the beam＇s slenderness ratio and the decrease of the crack depth. The results are useful in identifying non-destructive cracks on a beam.
基金supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2020AAA0109605)the National Natural Science Grant of China(82072225,82272246)+2 种基金High-level Hospital Construction Project of Guangdong Provincial People’s Hospital(DFJHBF202104)Science and Technology Program of Guangzhou(202206010044)Leading Medical Talents in Guangdong Province of Guangdong Provincial People’s Hospital(KJ012019425)。
文摘BACKGROUND:It is controversial whether prophylactic endotracheal intubation(PEI)protects the airway before endoscopy in critically ill patients with upper gastrointestinal bleeding(UGIB).The study aimed to explore the predictive value of PEI for cardiopulmonary outcomes and identify high-risk patients with UGIB undergoing endoscopy.METHODS:Patients undergoing endoscopy for UGIB were retrospectively enrolled in the eICU Collaborative Research Database(eICU-CRD).The composite cardiopulmonary outcomes included aspiration,pneumonia,pulmonary edema,shock or hypotension,cardiac arrest,myocardial infarction,and arrhythmia.The incidence of cardiopulmonary outcomes within 48 h after endoscopy was compared between the PEI and non-PEI groups.Logistic regression analyses and propensity score matching analyses were performed to estimate effects of PEI on cardiopulmonary outcomes.Moreover,restricted cubic spline plots were used to assess for any threshold effects in the association between baseline variables and risk of cardiopulmonary outcomes(yes/no)in the PEI group.RESULTS:A total of 946 patients were divided into the PEI group(108/946,11.4%)and the non-PEI group(838/946,88.6%).After propensity score matching,the PEI group(n=50)had a higher incidence of cardiopulmonary outcomes(58.0%vs.30.3%,P=0.001).PEI was a risk factor for cardiopulmonary outcomes after adjusting for confounders(odds ratio[OR]3.176,95%confidence interval[95%CI]1.567-6.438,P=0.001).The subgroup analysis indicated the similar results.A shock index>0.77 was a predictor for cardiopulmonary outcomes in patients undergoing PEI(P=0.015).The probability of cardiopulmonary outcomes in the PEI group depended on the Charlson Comorbidity Index(OR 1.465,95%CI 1.079-1.989,P=0.014)and shock index>0.77(compared with shock index≤0.77[OR 2.981,95%CI 1.186-7.492,P=0.020,AUC=0.764]).CONCLUSION:PEI may be associated with cardiopulmonary outcomes in elderly and critically ill patients with UGIB undergoing endoscopy.Furthermore,a shock index greater than 0.77 could be used as a predictor of a worse prognosis in patients undergoing PEI.
基金funded by the National Natural Science Grant of China(No.82072225,82272246)High-level Hospital Construction Project of Guangdong Provincial People’s Hospital(No.DFJHBF202104,No.DFJH201918)+1 种基金Science and Technology Program of Guangzhou,China(No.202206010044)Guangdong Basic and Applied Basic Research Foundation(2021B1515120062).
文摘Abdominal Aortic Aneurysm(AAA)is a life-threatening vascular disease characterized by the weakening and ballooning of the abdominal aorta,which has no effective therapeutic approaches due to unclear molecular mechanisms.Using single-cell RNA sequencing,we analyzed the molecular profile of individual cells within control and AAA abdominal aortas.We found cellular heterogeneity,with increased plasmacytoid dendritic cells and reduced endothelial cells and vascular smooth muscle cells(VSMCs)in AAA.Up-regulated genes in AAA were associated with muscle tissue development and apoptosis.Genes controlling VSMCs aberrant switch from contractile to synthetic phenotype were significantly enriched in AAA.Additionally,VSMCs in AAA exhibited cell senescence and impaired oxidative phosphorylation.Similar observations were made in a mouse model of AAA induced by Angiotensin II,further affirming the relevance of our findings to human AAA.The concurrence of gene expression changes between human and mouse highlighted the impairment of oxidative phosphorylation as a potential target for intervention.Nicotinamide phosphoribosyltransferase(NAMPT,also named VISFATIN)signaling emerged as a signature event in AAA.NAMPT was significantly downregulated in AAA.NAMPT-extracellular vesicles(EVs)derived from mesenchymal stem cells restored NAMPT levels,and offered protection against AAA.Furthermore,NAMPT-EVs not only repressed injuries,such as cell senescence and DNA damage,but also rescued impairments of oxidative phosphorylation in both mouse and human AAA models,suggesting NAMPT supplementation as a potential therapeutic approach for AAA treatment.These findings shed light on the cellular heterogeneity and injuries in AAA,and offered promising therapeutic intervention for AAA treatment.
基金This work is supported by the National Natural Science Foundation of China(nos.21874103 and 22074112).
文摘Enzyme-free autocatalytic nucleic acidmachinery has been widely used to engineer various self-assembled nanostructures as well as high-performance bioanalysis,yet has rarely been realized in live cells for complicated design,low robustness,and limited reliability.Herein,we constructed simple yet versatile enthalpy-driven autocatalytic hybridization chain reaction(AHCR)machinery with high reliability and robustness for in situ microRNA analysis in live cells.The homogeneous AHCR machine was composed of two differently designed HCR modules,the lead-in HCR-1 amplification module,and the reverse HCR-2 feedback module.After the AHCR amplification system was delivered into live cells,target microRNA stimulated the autonomous cross-invasion of the HCR-1 module and the HCR-2 module for assembling hyperbranched dsDNA nanostructures with synergistically amplified Förster resonance energy transfer readout,thus enabling accurate intracellular micro-RNA imaging.The synergistic AHCR execution was systematically investigated by a series of experimental studies and computer-aided theoretical simulations.The multiple recognition capacity of HCR constituents and the successive signal amplification of the AHCR machine enabled the accurate intracellular microRNA imaging with precise signal localization inside living cells.Based on its intriguing and modular design,the AHCR machinery can be extended for analyzing diverse biomarkers,thus supplementing a powerful toolbox for clinical diagnosis and therapeutic assessment.
