Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro...Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.展开更多
Improving the capacitance and energy density is a significant challenge while developing practical and flexible energy storage system(ESS).Redox mediators(RMs),as redox-active electrolyte additives,can provide additio...Improving the capacitance and energy density is a significant challenge while developing practical and flexible energy storage system(ESS).Redox mediators(RMs),as redox-active electrolyte additives,can provide additional energy storing capability via electrochemical faradaic contribution on electrodes for high-performance flexible ESSs.Particularly,determining effective material combinations between electrodes and RMs is essential for maximizing surface faradaic redox reactions for energy-storage performance.In this study,an electrode-RM system comprising heterostructured hybrid(carbon fiber(CF)/MnO_(2)) faradaic electrodes and iodine RMs(I-RMs) in a redox-active electrolyte is investigated.The CF/MnO_(2)with the 1-RMs(CF/MnO_(2)-I) induces dominant catalytic faradaic interaction with the I-RMs,significantly enhancing the surface faradaic kinetics and increasing the overall energy-storage performance.The CF/MnO_(2)-I ESSs show a 12.6-fold(or higher) increased volumetric energy density of 793.81 mWh L^(-1)at a current of 10 μA relative to ESSs using CF/MnO_(2)without I-RMs(CF/MnO_(2)).Moreover,the CF/MnO_(2)-I retains 93.1% of its initial capacitance after 10,000 cycles,validating the excellent cyclability.Finally,the flexibility of the ESSs is tested at different bending angles(180° to 0°),demonstrating its feasibility for flexible and high-wear environments.Therefore,CF/MnO_(2)electrodes present a practical material combination for high-performance flexible energy-storage devices owing to the catalytic faradaic interaction with I-RMs.展开更多
Non-aqueous absorbents(NAAs)have attracted increasing attention for CO_(2)capture because of their great energy-saving potential.Primary diamines which can provide high CO_(2)absorption loading are promising candidate...Non-aqueous absorbents(NAAs)have attracted increasing attention for CO_(2)capture because of their great energy-saving potential.Primary diamines which can provide high CO_(2)absorption loading are promising candidates for formulating NAAs but suffer disadvantages in regenerability.In this study,a promising strategy that using tertiary amines(TAs)as proton-transfer mediators was proposed to enhance the regenerability of an aminoethylethanolamine(AEEA,diamine)/dimethyl sulfoxide(DMSO)(A/D)NAA.Surprisingly,some employed TAs such as N,N-diethylaminoethanol(DEEA),N,N,N’,N’’,N’’-pentamethyldiethylenetriamine(PMDETA),3-dimethylamino-1-propanol(3DMA1P),and N,N-dimethylethanolamine(DMEA)enhanced not only the regenerability of the A/D NAA but also the CO_(2)absorption performance.Specifically,the CO_(2)absorption loading and cyclic loading were increased by about 12.7%and 15.5%-22.7%,respectively.The TA-enhanced CO_(2)capture mechanism was comprehensively explored via nuclear magnetic resonance technique and quantum chemical calculations.During CO_(2)absorption,the TA acted as an ultimate proton acceptor for AEEA-zwitterion and enabled more AEEA to form carbamate species(AEEACOO-)to store CO_(2),thus enhancing CO_(2)absorption.For CO_(2)desorption,the TA first provided protons directly to AEEACOO-as a proton donor;moreover,it functioned as a proton carrier and facilitated the low-energy step-wise proton transfer from protonated AEEA to AEEACOO-.Consequently,the presence of TA made it easier for AEEACOO-to obtain protons to decompose,resulting in enhanced CO_(2)desorption.In a word,introducing the TA as a proton-transfer mediator into the A/D NAA enhanced both the CO_(2)absorption performance and the regenerability,which was an efficient way to“kill two birds with one stone”.展开更多
Although insulin-like growth factor-I （IGF-I） and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling...Although insulin-like growth factor-I （IGF-I） and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading. To test this, at 5 weeks of age, partial ovariectomy （pOVX） or a sham operation was performed on heterozygous IGF-I conditional knockout （H IGF-I KO） and control mice generated using a Cre-loxP approach. At 10 weeks of age, a 10 N axial load was applied on the right tibia of these mice for a period of 2 weeks and the left tibia was used as an internal non-non-loaded control. At the cortical site, partial estrogen loss reduced total volumetric bone mineral density （BMD） by 5% in control pOVX mice （P=0.05, one-way ANOVA）, but not in the H IGF-I KO pOVX mice. At the trabecular site, bone volume/total volume （BV/TV） was reduced by 5%-6% in both control pOVX （P〈0.05） and H IGF-I KO pOVX （P=0.05） mice. Two weeks of mechanical loading caused a 7 %-8% and an 11%-13% （P〈0.05 vs. non-loaded bones） increase in cortical BMD and cortical thickness （Ct.Th）, respectively, in the control sham, control pOVX and H IGF-I KO sham groups. By contrast, the magnitude of cortical BMD （4%, P=0.13） and Ct.Th （6%, P〈0.05） responses were reduced by 50% in the H IGF-I KO pOVX mice compared to the other three groups. The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant （P〈0.05） by two-way ANOVA. Two weeks of axial loading caused similar increases in trabecular BV/TV （13%-17%） and thickness （17%-23%） in all four groups of mice. In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.展开更多
Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain...Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in- terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no- ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery （n = 32） and sham surgery （n = 8） groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re- ceived anesthesia, but not an incision. Yon Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord （L3-5） showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons （diameter 〈 20 pm and 20-40 pm） and satellite cells in the dorsal root ganglia of the spinal cord （L3-5） in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons （diameter 〉 40 pm） at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci- sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me- chanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by in- cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.展开更多
In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclo...In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclopropyl)ethyl diazoacetoacetate 8a and methyl 2-diazo-3oxo-6-(2-phenylcyclopropyl) hexanoate 8b have been synthesized. Preliminary investigation of the intramolecular C-H insertion with Rh2(OAc)4 as catalyst supports a concerted insertion process.展开更多
Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung d...Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81971870,82172173(both to MCL)。
文摘Subarachnoid hemorrhage(SAH)is a dominant cause of death and disability wo rldwide.A sharp increase in intracranial pressure after SAH leads to a reduction in cerebral perfusion and insufficient blood supply for neuro ns,which subsequently promotes a series of pathophysiological responses leading to neuronal death.Many previous experimental studies have reported that excitotoxicity,mitochondrial death pathways,the release of free radicals,protein misfolding,apoptosis,nec rosis,autophagy,and inflammation are involved solely or in combination in this disorder.Among them,irreversible neuronal apoptosis plays a key role in both short-and long-term prognoses after SAH.Neuronal apoptosis occurs through multiple pathways including extrinsic,mitochondrial,endoplasmic reticulum,p53 and oxidative stress.Meanwhile,a large number of blood contents enter the subarachnoid space after SAH,and the secondary metabolites,including oxygenated hemoglo bin and heme,further aggravate the destruction of the blood-brain barrier and vasogenic and cytotoxic brain edema,causing early brain injury and delayed cerebral ischemia,and ultimately increasing neuronal apoptosis.Even there is no clear and effective therapeutic strategy for SAH thus far,but by understanding apoptosis,we might excavate new ideas and approaches,as targeting the upstream and downstream molecules of apoptosis-related pathways shows promise in the treatment of SAH.In this review,we summarize the existing evidence on molecules and related drugs or molecules involved in the apoptotic pathway after SAH,which provides a possible target or new strategy for the treatment of SAH.
基金supported by the National Research Foundation of Korea grant funded by the Korean government (MSIT)(2020R1A2C1101039)the Commercializations Promotion Agency for R&D Outcomes (COMPA) grant funded by the Korea government(MSIT)(2021E200)+1 种基金supported by“Regional Innovation Strategy (RIS)” through the National Research Foundation of Korea (NRF) funded by the Ministry of Education(MOE)(2021RIS-004)supported by the Soonchunhyang University Research Fund。
文摘Improving the capacitance and energy density is a significant challenge while developing practical and flexible energy storage system(ESS).Redox mediators(RMs),as redox-active electrolyte additives,can provide additional energy storing capability via electrochemical faradaic contribution on electrodes for high-performance flexible ESSs.Particularly,determining effective material combinations between electrodes and RMs is essential for maximizing surface faradaic redox reactions for energy-storage performance.In this study,an electrode-RM system comprising heterostructured hybrid(carbon fiber(CF)/MnO_(2)) faradaic electrodes and iodine RMs(I-RMs) in a redox-active electrolyte is investigated.The CF/MnO_(2)with the 1-RMs(CF/MnO_(2)-I) induces dominant catalytic faradaic interaction with the I-RMs,significantly enhancing the surface faradaic kinetics and increasing the overall energy-storage performance.The CF/MnO_(2)-I ESSs show a 12.6-fold(or higher) increased volumetric energy density of 793.81 mWh L^(-1)at a current of 10 μA relative to ESSs using CF/MnO_(2)without I-RMs(CF/MnO_(2)).Moreover,the CF/MnO_(2)-I retains 93.1% of its initial capacitance after 10,000 cycles,validating the excellent cyclability.Finally,the flexibility of the ESSs is tested at different bending angles(180° to 0°),demonstrating its feasibility for flexible and high-wear environments.Therefore,CF/MnO_(2)electrodes present a practical material combination for high-performance flexible energy-storage devices owing to the catalytic faradaic interaction with I-RMs.
基金supported by the Natural Science Foundation of Guangxi Province(Nos.2023GXNSFAA026381 and 2020GXNSFBA297071)the National Natural Science Foundation of China(Nos.22006027 and 52260023)。
文摘Non-aqueous absorbents(NAAs)have attracted increasing attention for CO_(2)capture because of their great energy-saving potential.Primary diamines which can provide high CO_(2)absorption loading are promising candidates for formulating NAAs but suffer disadvantages in regenerability.In this study,a promising strategy that using tertiary amines(TAs)as proton-transfer mediators was proposed to enhance the regenerability of an aminoethylethanolamine(AEEA,diamine)/dimethyl sulfoxide(DMSO)(A/D)NAA.Surprisingly,some employed TAs such as N,N-diethylaminoethanol(DEEA),N,N,N’,N’’,N’’-pentamethyldiethylenetriamine(PMDETA),3-dimethylamino-1-propanol(3DMA1P),and N,N-dimethylethanolamine(DMEA)enhanced not only the regenerability of the A/D NAA but also the CO_(2)absorption performance.Specifically,the CO_(2)absorption loading and cyclic loading were increased by about 12.7%and 15.5%-22.7%,respectively.The TA-enhanced CO_(2)capture mechanism was comprehensively explored via nuclear magnetic resonance technique and quantum chemical calculations.During CO_(2)absorption,the TA acted as an ultimate proton acceptor for AEEA-zwitterion and enabled more AEEA to form carbamate species(AEEACOO-)to store CO_(2),thus enhancing CO_(2)absorption.For CO_(2)desorption,the TA first provided protons directly to AEEACOO-as a proton donor;moreover,it functioned as a proton carrier and facilitated the low-energy step-wise proton transfer from protonated AEEA to AEEACOO-.Consequently,the presence of TA made it easier for AEEACOO-to obtain protons to decompose,resulting in enhanced CO_(2)desorption.In a word,introducing the TA as a proton-transfer mediator into the A/D NAA enhanced both the CO_(2)absorption performance and the regenerability,which was an efficient way to“kill two birds with one stone”.
基金supported by the National Institutes of Health grant R01 AR48139 (to SM)National Institute of Arthritis and Musculoskeletal Skin Diseases R03 grant AR056827 (to CK)
文摘Although insulin-like growth factor-I （IGF-I） and estrogen signaling pathways have been shown to be involved in mediating the bone anabolic response to mechanical loading, it is not known whether these two signaling pathways crosstalk with each other in producing a skeletal response to mechanical loading. To test this, at 5 weeks of age, partial ovariectomy （pOVX） or a sham operation was performed on heterozygous IGF-I conditional knockout （H IGF-I KO） and control mice generated using a Cre-loxP approach. At 10 weeks of age, a 10 N axial load was applied on the right tibia of these mice for a period of 2 weeks and the left tibia was used as an internal non-non-loaded control. At the cortical site, partial estrogen loss reduced total volumetric bone mineral density （BMD） by 5% in control pOVX mice （P=0.05, one-way ANOVA）, but not in the H IGF-I KO pOVX mice. At the trabecular site, bone volume/total volume （BV/TV） was reduced by 5%-6% in both control pOVX （P〈0.05） and H IGF-I KO pOVX （P=0.05） mice. Two weeks of mechanical loading caused a 7 %-8% and an 11%-13% （P〈0.05 vs. non-loaded bones） increase in cortical BMD and cortical thickness （Ct.Th）, respectively, in the control sham, control pOVX and H IGF-I KO sham groups. By contrast, the magnitude of cortical BMD （4%, P=0.13） and Ct.Th （6%, P〈0.05） responses were reduced by 50% in the H IGF-I KO pOVX mice compared to the other three groups. The interaction between genotype and estrogen deficiency on the mechanical loading-induced cortical bone response was significant （P〈0.05） by two-way ANOVA. Two weeks of axial loading caused similar increases in trabecular BV/TV （13%-17%） and thickness （17%-23%） in all four groups of mice. In conclusion, partial loss of both estrogen and IGF-I significantly reduced cortical but not the trabecular bone response to mechanical loading, providing in vivo evidence of the above crosstalk in mediating the bone response to loading.
基金supported by the Science and Technology Project of Hunan Province,No.2010SK3119125 Talents Project of 3~(rd) Xiangya Hospital,Central South University in China
文摘Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in- terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no- ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery （n = 32） and sham surgery （n = 8） groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re- ceived anesthesia, but not an incision. Yon Frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord （L3-5） showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons （diameter 〈 20 pm and 20-40 pm） and satellite cells in the dorsal root ganglia of the spinal cord （L3-5） in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons （diameter 〉 40 pm） at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci- sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me- chanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by in- cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.
文摘In order to investigate the reaction mechanism of intramolecular C-H insertion by Rh(II)-mediated carbenoids with trans-(2-phenylcyclopropyl) carbinal radical as the mechanistic probe, diazo compounds 2-(2-phenylcyclopropyl)ethyl diazoacetoacetate 8a and methyl 2-diazo-3oxo-6-(2-phenylcyclopropyl) hexanoate 8b have been synthesized. Preliminary investigation of the intramolecular C-H insertion with Rh2(OAc)4 as catalyst supports a concerted insertion process.
文摘Differentiated embryonic stem cells (ESC) can ameliorate lung inflammation and fibrosis in animal lung injury models;therefore, ESC, or their products, could be candidates for regenerative therapy for incurable lung diseases, such as idiopathic pulmonary fibrosis (IPF). In this study, we have investigated the paracrine effect of differentiated and undifferentiated human ESC on alveolar epithelial cell (AEC) wound repair. hESC line, SHEF-2 cells were differentiated with Activin treatment for 22 days in an embryoid body (EB) suspension culture. Conditioned media (CM) which contain cell secretory factors were collected at different time points of differentiation. CM were then tested onin vitro?wound repair model with human type II AEC line, A549 cells (AEC). Our study demonstrated that CM originated from undifferentiated hESC significantly inhibited AEC wound repair when compared to the control. Whereas, CM originated from Activin-directed hESC differentiated cell population demonstrated a differential reparative effect on AEC wound repair model. CM obtained from Day-11 of differentiation significantly enhanced AEC wound repair in comparison to CM collected from pre- and post-Day-11 of differentiation. Day-11 CM enhanced AEC wound repair through significant stimulation of cell migration and cell proliferation. RT-PCR and immunocytochemistry confirmed that Day-11 CM was originated form a mixed population of endodermal/mesodermal differentiated hESC. This report suggests a putative paracrine-mediated epithelial injury healing mechanism by hESC secreted products, which is valuable in the development of novel stem cell-based therapeutic strategies.
