Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)...Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.展开更多
Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with ...Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.展开更多
Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem ce...Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.展开更多
AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured R...AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.展开更多
Low-temperature,ambient processing of high-quality CsPbBr_(3)films is demanded for scalable production of efficient,low-cost carbon-electrode perovskite solar cells(PSCs).Herein,we demonstrate a crystal orientation en...Low-temperature,ambient processing of high-quality CsPbBr_(3)films is demanded for scalable production of efficient,low-cost carbon-electrode perovskite solar cells(PSCs).Herein,we demonstrate a crystal orientation engineering strategy of PbBr_(2)precursor film to accelerate its reaction with CsBr precursor during two-step sequential deposition of CsPbBr_(3)films.Such a novel strategy is proceeded by adding CsBr species into PbBr_(2)precursor,which can tailor the preferred crystal orientation of PbBr_(2)film from[020]into[031],with CsBr additive staying in the film as CsPb_(2)Br_(5)phase.Theoretical calculations show that the reaction energy barrier of(031)planes of PbBr_(2)with CsBr is lower about 2.28 eV than that of(O2O)planes.Therefore,CsPbBr_(3)films with full coverage,high purity,high crystallinity,micro-sized grains can be obtained at a low temperature of 150℃.Carbon-electrode PSCs with these desired CsPbBr_(3)films yield the record-high efficiency of 10.27%coupled with excellent operation stability.Meanwhile,the 1 cm^(2)area one with the superior efficiency of 8.00%as well as the flexible one with the champion efficiency of 8.27%and excellent mechanical bending characteristics are also achieved.展开更多
Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of vario...Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.展开更多
Crystallization process determines the quality of perovskite films and the performances of resultant perovskite solar cells(PSCs).Dimethylamine oxalate has been proven as a multifunctional modulator,and is explored as...Crystallization process determines the quality of perovskite films and the performances of resultant perovskite solar cells(PSCs).Dimethylamine oxalate has been proven as a multifunctional modulator,and is explored as an efficient additive in manipulating the crystallization process of CsPbI_(3) perovskite films.On one hand,oxalate serves as the precipitator that facilitates the nucleation process of intermediate.The larger size of intermediate is conductive to the larger size and smaller grain boundaries of resultant perovskite.On the other hand,in subsequent annealing process,the phase conversion and growth process of transient perovskite can be decelerated due to the strong interactions of oxalate with both dimethylamine cation(DMA^(+))and Pb^(2+).Due to the optimized crystallization kinetics,the morphology and quality of CsPbI_(3) perovskite films are comprehensively improved with lower defect concentrations,and charge recombination loss is effectively suppressed.Benefiting from the optimized crystal quality of perovskite films,the carbon electrode-based CsPbI_(3) PSCs exhibit a champion efficiency of 18.48%.This represents one of the highest levels among all hole transport layer-free inorganic perovskite solar cells.展开更多
Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landra...Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows.However,the functions of miR-24-3p on GCs are unclear.In this study,using flow cytometry,5-ethynyl-2′-de-oxyuridine(EdU)staining,and cell count,we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes,moreover,miR-24-3p inhibited GC apoptosis.Mechanistically,on-line prediction,bioinformatics analysis,a luciferase reporter assay,RT-qPCR,and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B(P27/CDKN1B).Furthermore,the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression.These findings suggest that miR-24-3p regulates the physiological functions of GCs.展开更多
Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a promine...Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.展开更多
Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is...Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.展开更多
Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling path...Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling pathway and the impact of endoplasmic reticulum(ER)stress and autophagy.Methods: Necrostatin-1(Nec-1),lactate dehydrogenase release(LDH)assay,and Hoechst/propidium iodide(PI)double staining were employed to validate the mode of cell death.Western blot was used to detect the cleavage of GSDME and the expression of light chain 3(LC3)and BIP.Results: Celastrol induced cell swelling with large bubbles,which is consistent with the pyroptotic phenotype.Moreover,treatment with celastrol induced GSDME cleavage,indicating the activation of GSDME-mediated pyroptosis.GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells.In addition,cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells,suggesting that GSDME activation was induced by caspase-3.Mechanistically,celastrol induced endoplasmic reticulum(ER)stress and autophagy in HeLa cells,and other ER stress inducers produced effects consistent with those of celastrol.Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress,which may shed light on the potential antitumor clinical applications of celastrol.展开更多
Formamidine lead triiodide(FAPbI_(3))perovskites have become the most promising photovoltaic materials for perovskite solar cells with record power conversion efficiency(PCE).However,random nucleation,phase transition...Formamidine lead triiodide(FAPbI_(3))perovskites have become the most promising photovoltaic materials for perovskite solar cells with record power conversion efficiency(PCE).However,random nucleation,phase transition,and lattice defects are still the key challenges limiting the quality of FAPbI_(3) films.Previous studies show that the introduction or adding of seeds in the precursor is effective to promote the nucleation and crystallization of perovskite films.Nevertheless,the seed-assisted approach focuses on heterogeneous seeds or hetero-composites,which inevitably induce a lattice-mismatch,the genera-tion of strain or defects,and the phase segregation in the perovskite films.Herein,we first demonstrate that high-quality perovskite films are controllably prepared using α-and δ-phases mixed FAPbI_(3) micro-crystal as the homogeneous seeds with the one-step antisolvent method.The partially dissolved seeds with suitable sizes improve the crystallinity of the perovskite flm with preferable orientation,improved carrier lifetime,and increased carrier mobility.More importantly,the α-phase-containing seeds promote the formation of α-phase FAPbI_(3) films,leading to the reduction of residual lattice strain and the suppres-sion of I-ion migration.Besides,the adding of dimethyl 2,6-pyridine dicarboxylate(DPD)into the pre-cursor further suppresses the generation of defects,contributing to the PCE of devices prepared in air ambient being significantly improved to 23.75%,among the highest PCEs for fully air-processed FAPbI_(3) solar cells.The unpackaged target devices possess a high stability,maintaining 80%of the initial PCE under simulated solar illumination exceeding 800 h.展开更多
Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible...Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness.While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D,they often have limitations,such as being too harsh for fragile 3D cell cultures,requiring complex handling protocols,or inducing tissue deformation with shrinkage or expansion.To address this issue,we proposed a modified optical clearing method for 3D cell cultures,called MACS-W,which is simple,highly efficient,and morphology-preserving.In our evaluation of MACS-W,we found that it exhibits excellent clearing capability in just 10 min,with minimal deformation,and helps drug evaluation on tumor spheroids.In summary,MACS-W is a fast,minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.展开更多
Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:...Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.展开更多
Hole transport material free carbon-based all-inorganic CsPbBr_(3)perovskite solar cells(PSCs)are promising for commercialization due to its low-cost,high open-circuit voltage(V_(oc))and superior stability.Due to the ...Hole transport material free carbon-based all-inorganic CsPbBr_(3)perovskite solar cells(PSCs)are promising for commercialization due to its low-cost,high open-circuit voltage(V_(oc))and superior stability.Due to the different solubility of PbBr_(2)and CsBr in conventional solvents,CsPbBr_(3)films are mainly obtained by multi-step spin-coating through the phase evolution from PbBr_(2)to CsPb_(2)Br_(5)and then to CsPbBr_(3).The scalable fabrication of high-quality CsPbBr_(3)films has been rarely studied.Herein,an inkjet-printing method is developed to prepare high-quality CsPbBr_(3)films.The formation of long-range crystalline CsPb_(2)Br_(5)phase can effectively improve phase purity and promote regular crystal stacking of CsPbBr_(3).Consequently,the inkjet-printed CsPbBr_(3)C-PSCs realized PCEs up to 9.09%,8.59%and 7.81%with active areas of 0.09,0.25,and 1 cm^(2),respectively,demonstrating the upscaling potential of our fabrication method and devices.This high performance is mainly ascribed to the high purity,strong crystal orientation,reduced surface roughness and lower trap states density of the as-printed CsPbBr_(3)films.This work provides insights into the relationship between the phase evolution mechanisms and crystal growth dynamics of cesium lead bromide halide films.展开更多
Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomer...Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.展开更多
基金supported by the National Natural Science Foundation of China,No.8227050826(to PL)Tianjin Science and Technology Bureau Foundation,No.20201194(to PL)Tianjin Graduate Research and Innovation Project,No.2022BKY174(to CW).
文摘Cerebral edema caused by blood-brain barrier injury after intracerebral hemorrhage is an important factor leading to poor prognosis.Human-induced pluripotent stem cell-derived neural stem cell exosomes(hiPSC-NSC-Exos)have shown potential for brain injury repair in central nervous system diseases.In this study,we explored the impact of hiPSC-NSC-Exos on blood-brain barrier preservation and the underlying mechanism.Our results indicated that intranasal delivery of hiPSC-NSC-Exos mitigated neurological deficits,enhanced blood-brain barrier integrity,and reduced leukocyte infiltration in a mouse model of intracerebral hemorrhage.Additionally,hiPSC-NSC-Exos decreased immune cell infiltration,activated astrocytes,and decreased the secretion of inflammatory cytokines like monocyte chemoattractant protein-1,macrophage inflammatory protein-1α,and tumor necrosis factor-αpost-intracerebral hemorrhage,thereby improving the inflammatory microenvironment.RNA sequencing indicated that hiPSC-NSC-Exo activated the PI3K/AKT signaling pathway in astrocytes and decreased monocyte chemoattractant protein-1 secretion,thereby improving blood-brain barrier integrity.Treatment with the PI3K/AKT inhibitor LY294002 or the monocyte chemoattractant protein-1 neutralizing agent C1142 abolished these effects.In summary,our findings suggest that hiPSC-NSC-Exos maintains blood-brain barrier integrity,in part by downregulating monocyte chemoattractant protein-1 secretion through activation of the PI3K/AKT signaling pathway in astrocytes.
基金supported by grants from the Spanish Ministry of Health-PNSD(2019-I039 and 2023-I024)(to MP)FEDER/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación PID2021-1243590B-I100(to VMM)+2 种基金GVA(CIAICO/2021/203)(to MP)the Primary Addiction Care Research Network(RD21/0009/0005)(to MP)a predoctoral fellowship from the Generalitat Valenciana(ACIF/2021/338)(to CPC).
文摘Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.
基金supported by the National Nature Science Foundation of China,No.81471308(to JL)the Innovative Leading Talents of Liaoning Province,No.XLYC1902031(to JL)+2 种基金Science and Technology Projects in Liaoning Province,No.2022-BS-238(to CH)Young Top Talents of Liaoning Province,No.XLYC1907009(to LW)Dalian Science and Technology Innovation Fund,No.2018J11CY025(to JL)。
文摘Human neural stem cell-derived extracellular vesicles exhibit analogous functions to their parental cells,and can thus be used as substitutes for stem cells in stem cell therapy,thereby mitigating the risks of stem cell therapy and advancing the frontiers of stem cell-derived treatments.This lays a foundation for the development of potentially potent new treatment modalities for ischemic stroke.However,the precise mechanisms underlying the efficacy and safety of human neural stem cell-derived extracellular vesicles remain unclear,presenting challenges for clinical translation.To promote the translation of therapy based on human neural stem cell-derived extracellular vesicles from the bench to the bedside,we conducted a comprehensive preclinical study to evaluate the efficacy and safety of human neural stem cell-derived extracellular vesicles in the treatment of ischemic stroke.We found that administration of human neural stem cell-derived extracellular vesicles to an ischemic stroke rat model reduced the volume of cerebral infarction and promoted functional recovery by alleviating neuronal apoptosis.The human neural stem cell-derived extracellular vesicles reduced neuronal apoptosis by enhancing phosphorylation of phosphoinositide 3-kinase,mammalian target of rapamycin,and protein kinase B,and these effects were reversed by treatment with a phosphoinositide 3-kinase inhibitor.These findings suggest that human neural stem cell-derived extracellular vesicles play a neuroprotective role in ischemic stroke through activation of phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway.Finally,we showed that human neural stem cell-derived extracellular vesicles have a good in vivo safety profile.Therefore,human neural stem cell-derived extracellular vesicles are a promising potential agent for the treatment of ischemic stroke.
基金Supported by Science and Technology Research Project of Hubei Provincial Department of Education(No.B2021108).
文摘AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.
基金the financial support from the National Key R&D program of China(2021YFF0500501 and 2021YFF0500504)the Fundamental Research Funds for the Central Universities(YJS2213 and JB211408)+1 种基金the National Natural Science Foundation of China(61874083)the Joint Research Funds of Department of Science&Technology of Shaanxi Province and Northwestern Polytechnical University(No.2020GXLH-Z-014)
文摘Low-temperature,ambient processing of high-quality CsPbBr_(3)films is demanded for scalable production of efficient,low-cost carbon-electrode perovskite solar cells(PSCs).Herein,we demonstrate a crystal orientation engineering strategy of PbBr_(2)precursor film to accelerate its reaction with CsBr precursor during two-step sequential deposition of CsPbBr_(3)films.Such a novel strategy is proceeded by adding CsBr species into PbBr_(2)precursor,which can tailor the preferred crystal orientation of PbBr_(2)film from[020]into[031],with CsBr additive staying in the film as CsPb_(2)Br_(5)phase.Theoretical calculations show that the reaction energy barrier of(031)planes of PbBr_(2)with CsBr is lower about 2.28 eV than that of(O2O)planes.Therefore,CsPbBr_(3)films with full coverage,high purity,high crystallinity,micro-sized grains can be obtained at a low temperature of 150℃.Carbon-electrode PSCs with these desired CsPbBr_(3)films yield the record-high efficiency of 10.27%coupled with excellent operation stability.Meanwhile,the 1 cm^(2)area one with the superior efficiency of 8.00%as well as the flexible one with the champion efficiency of 8.27%and excellent mechanical bending characteristics are also achieved.
基金supported by the Chongqing Natural Science Foundation(No.2023NSCQ-MSX3161 and No.cstc2020jcyj-msxmX1058)the National Natural Science Foundation of China(No.81800172).
文摘Objective SUMO-specific protease 3(SENP3),a member of the SUMO-specific protease family,reverses the SUMOylation of SUMO-2/3 conjugates.Dysregulation of SENP3 has been proven to be involved in the development of various tumors.However,its role in mantle cell lymphoma(MCL),a highly aggressive lymphoma,remains unclear.This study was aimed to elucidate the effect of SENP3 in MCL.Methods The expression of SENP3 in MCL cells and tissue samples was detected by RT-qPCR,Western blotting or immunohistochemistry.MCL cells with stable SENP3 knockdown were constructed using short hairpin RNAs.Cell proliferation was assessed by CCK-8 assay,and cell apoptosis was determined by flow cytometry.mRNA sequencing(mRNA-seq)was used to investigate the underlying mechanism of SENP3 knockdown on MCL development.A xenograft nude mouse model was established to evaluate the effect of SENP3 on MCL growth in vivo.Results SENP3 was upregulated in MCL patient samples and cells.Knockdown of SENP3 in MCL cells inhibited cell proliferation and promoted cell apoptosis.Meanwhile,the canonical Wnt signaling pathway and the expression of Wnt10a were suppressed after SENP3 knockdown.Furthermore,the growth of MCL cells in vivo was significantly inhibited after SENP3 knockdown in a xenograft nude mouse model.Conclusion SENP3 participants in the development of MCL and may serve as a therapeutic target for MCL.
基金supported by the National Natural Science Foundation of China(Nos.U21A20310,22278164,22122805,22308112)the Science and Technology Program of Guangzhou,China(No.2023A04J0665)China Postdoctoral Science Foundation(No.2023M741214)。
文摘Crystallization process determines the quality of perovskite films and the performances of resultant perovskite solar cells(PSCs).Dimethylamine oxalate has been proven as a multifunctional modulator,and is explored as an efficient additive in manipulating the crystallization process of CsPbI_(3) perovskite films.On one hand,oxalate serves as the precipitator that facilitates the nucleation process of intermediate.The larger size of intermediate is conductive to the larger size and smaller grain boundaries of resultant perovskite.On the other hand,in subsequent annealing process,the phase conversion and growth process of transient perovskite can be decelerated due to the strong interactions of oxalate with both dimethylamine cation(DMA^(+))and Pb^(2+).Due to the optimized crystallization kinetics,the morphology and quality of CsPbI_(3) perovskite films are comprehensively improved with lower defect concentrations,and charge recombination loss is effectively suppressed.Benefiting from the optimized crystal quality of perovskite films,the carbon electrode-based CsPbI_(3) PSCs exhibit a champion efficiency of 18.48%.This represents one of the highest levels among all hole transport layer-free inorganic perovskite solar cells.
基金supported by the National Natural Science Foundation of China(32272849)the National Key R&D Program of China(2021YFF1000602)the earmarked fund for CARS-35-PIG。
文摘Ovarian follicle development is associated with the physiological functions of granulosa cells(GCs),including proliferation and apoptosis.The level of miR-24-3p in ovarian tissue of high-yielding Yorkshire×Landrace sows was significantly higher than that of low-yielding sows.However,the functions of miR-24-3p on GCs are unclear.In this study,using flow cytometry,5-ethynyl-2′-de-oxyuridine(EdU)staining,and cell count,we showed that miR-24-3p promoted the proliferation of GCs increasing the proportion of cells in the S phase and upregulating the expression of cell cycle genes,moreover,miR-24-3p inhibited GC apoptosis.Mechanistically,on-line prediction,bioinformatics analysis,a luciferase reporter assay,RT-qPCR,and Western blot results showed that the target gene of miR-24-3p in proliferation and apoptosis is cyclin-dependent kinase inhibitor 1B(P27/CDKN1B).Furthermore,the effect of miR-24-3p on GC proliferation and apoptosis was attenuated by P27 overexpression.These findings suggest that miR-24-3p regulates the physiological functions of GCs.
基金supported by the National Natural Science Foundation of China(Grant No.:82074092),Natural Science Foundation of Guangdong Province,China(Grant No.:2021A1515012219)Guangzhou University of Chinese Medicine“Double First-Class”and High-level University Discipline Collaborative Innovation Team Project,China(Grant No.:2021xk81) and Graduate Research Innovation Project of Guangzhou University of Chinese Medicine,China.
文摘Inhibiting the death receptor 3(DR3)signaling pathway in group 3 innate lymphoid cells(ILC3s)presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis(UC).Paeoniflorin,a prominent component of Paeonia lactiflora Pall.,has demonstrated the ability to restore barrier function in UC mice,but the precise mechanism remains unclear.In this study,we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s.C57BL/6 mice were subjected to random allocation into 7 distinct groups,namely the control group,the 2%dextran sodium sulfate(DSS)group,the paeoniflorin groups(25,50,and 100 mg/kg),the anti-tumor necrosis factor-like ligand 1A(anti-TL1A)antibody group,and the IgG group.We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry,respectively.Meanwhile,DR3-overexpressing MNK-3 cells and 2%DSS-induced Rag1^(-/-)mice were used for verification.The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier.Simultaneously,paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines(interleukin-17A,granulocyte-macrophage colony stimulating factor,and interleukin-22).Alternatively,paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system.We additionally confirmed that paeoniflorin-conditioned medium(CM)restored the expression of tight junctions in Caco-2 cells via coculture.In conclusion,paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner,and its mechanism is associated with the inhibition of the DR3 signaling pathway.
基金supported by the Science and Technology Innovation Program of Hunan Province(Grant Numbers:2021SK1014 and 2022WZ1027)the Colleges and Universities of Hunan Province(Grant Number:HNJG 20200440)+1 种基金the Scientific Research Fund of Hunan Provincial Education Department(Grant Number:21B0411)the Scientific Research Project of Changsha Central Hospital(Number:YNKY202201).
文摘Background:Nasopharyngeal carcinoma(NPC)exhibits a significant prevalence in the southern regions of China,and paclitaxel(PTX)is frequently employed as a medication for managing advanced NPC.However,drug resistance is typically accompanied by a poor prognosis.Exploring the synergistic potential of combining multiple chemotherapeutic agents may represent a promising avenue for optimizing treatment efficacy.Methods:This study investigated whether 3-Methyladenine(3-MA)could potentiated the effect of PTX and its potential molecular mechanism.Samples were divided into the following categories:Negative control(NC)with the solvent dimethyl sulfoxide(DMSO,0.5%v/v),PTX(400 nM),3-MA(4 mM),and PTX(400 nM)+3-MA(4 mM).The viability of NPC cells was assessed using both the cell counting kit-8(CCK-8)assay and the colony formation assay.Microscopic observation was performed to identify morphological cell changes.Flow cytometry was used to assess cell cycle status,mitochondrial membrane potential(MMP),and apoptotic cells.Western blotting was conducted to quantify the protein expression.Results:3-MA enhanced PTX-specific inhibition of NPC cell proliferation.PTX,either alone or in combination with 3-MA,caused cell cycle halt at the G2/M phase in the majority of NPC cells,and the combination treatment of PTX with 3-MA induced a higher rate of NPC cell death compared to PTX alone.Western blotting results revealed the combination of PTX with 3-MA heightened activation of cyclin-dependent kinase 1(CDK1),a key molecule in shifting cells from mitotic arrest to apoptosis,led to a reduction in Myeloid Cell Leukemia 1(MCL-1)expression and an increase in Poly(ADP-ribose)polymerase(PARP)cleavage.Conclusion:The concurrent administration of PTX with 3-MA effectively enhances PTX’s inhibitory impact on NPC and activates the apoptosis signal regulated by CDK1.
基金supported by grants from startup fund program at Beijing University of Chinese Medicine(90011451310011)key research fund for drug discovery in Chinese medicine at Beijing University of Chinese Medicine(1000061223476)startup fund program at Beijing University of Chinese Medicine(90020361220006).
文摘Objective:To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved,specifically focusing on the role of the caspase-3/gasdermin E(GSDME)signaling pathway and the impact of endoplasmic reticulum(ER)stress and autophagy.Methods: Necrostatin-1(Nec-1),lactate dehydrogenase release(LDH)assay,and Hoechst/propidium iodide(PI)double staining were employed to validate the mode of cell death.Western blot was used to detect the cleavage of GSDME and the expression of light chain 3(LC3)and BIP.Results: Celastrol induced cell swelling with large bubbles,which is consistent with the pyroptotic phenotype.Moreover,treatment with celastrol induced GSDME cleavage,indicating the activation of GSDME-mediated pyroptosis.GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells.In addition,cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells,suggesting that GSDME activation was induced by caspase-3.Mechanistically,celastrol induced endoplasmic reticulum(ER)stress and autophagy in HeLa cells,and other ER stress inducers produced effects consistent with those of celastrol.Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress,which may shed light on the potential antitumor clinical applications of celastrol.
基金supported by the National Natural Science Foundation of China (61604131,62025403)the Natural Science Foundation of Zhejiang Province (LY19F040009)+1 种基金the Fundamental Research Funds of Zhejiang SciTech University (23062120-Y)the Open Project of Key Laboratory of Solar Energy Utilization and Energy Saving Technology of Zhejiang Province (ZJS-OP-2020-07)
文摘Formamidine lead triiodide(FAPbI_(3))perovskites have become the most promising photovoltaic materials for perovskite solar cells with record power conversion efficiency(PCE).However,random nucleation,phase transition,and lattice defects are still the key challenges limiting the quality of FAPbI_(3) films.Previous studies show that the introduction or adding of seeds in the precursor is effective to promote the nucleation and crystallization of perovskite films.Nevertheless,the seed-assisted approach focuses on heterogeneous seeds or hetero-composites,which inevitably induce a lattice-mismatch,the genera-tion of strain or defects,and the phase segregation in the perovskite films.Herein,we first demonstrate that high-quality perovskite films are controllably prepared using α-and δ-phases mixed FAPbI_(3) micro-crystal as the homogeneous seeds with the one-step antisolvent method.The partially dissolved seeds with suitable sizes improve the crystallinity of the perovskite flm with preferable orientation,improved carrier lifetime,and increased carrier mobility.More importantly,the α-phase-containing seeds promote the formation of α-phase FAPbI_(3) films,leading to the reduction of residual lattice strain and the suppres-sion of I-ion migration.Besides,the adding of dimethyl 2,6-pyridine dicarboxylate(DPD)into the pre-cursor further suppresses the generation of defects,contributing to the PCE of devices prepared in air ambient being significantly improved to 23.75%,among the highest PCEs for fully air-processed FAPbI_(3) solar cells.The unpackaged target devices possess a high stability,maintaining 80%of the initial PCE under simulated solar illumination exceeding 800 h.
基金support from the National Key Research and Development Program of China(Grant No.2017YFA0700501),and the Innovation Fund of WNLO.
文摘Three-dimensional(3D)cell cultures have contributed to a variety of biological research fields by filling the gap between monolayers and animal models.The modern optical sectioning microscopic methods make it possible to probe the complexity of 3D cell cultures but are limited by the inherent opaqueness.While tissue optical clearing methods have emerged as powerful tools for investigating whole-mount tissues in 3D,they often have limitations,such as being too harsh for fragile 3D cell cultures,requiring complex handling protocols,or inducing tissue deformation with shrinkage or expansion.To address this issue,we proposed a modified optical clearing method for 3D cell cultures,called MACS-W,which is simple,highly efficient,and morphology-preserving.In our evaluation of MACS-W,we found that it exhibits excellent clearing capability in just 10 min,with minimal deformation,and helps drug evaluation on tumor spheroids.In summary,MACS-W is a fast,minimally-deformative and fluorescence compatible clearing method that has the potential to be widely used in the studies of 3D cell cultures.
基金The present study was supported by the National Science and Technology Council,Taiwan(MOST-107-2320-B-471-001 to YYL and MOST-110-2320-B-006-025-MY3 to BMH)by An Nan Hospital(ANHRF111-55 to TCC and BMH).
文摘Background:Paclitaxel is a compound derived from Pacific yew bark that induces various cancer cell apoptosis.However,whether it also has anticancer activities in KOSC3 cells,an oral cancer cell line,is unclear.Methods:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,flow cytometry,and western blotting assays were carried out to assess cell viability,subG1 phase of the cell cycle,and apoptosis-related protein expression,respectively.Results:Ourfindings indicate that paclitaxel could inhibit cell viability and increase the expression of apoptotic markers,including plasma membrane blebbing and the cleavage of poly ADP-ribose polymerase in KOSC3 cells.Also,the treatment with paclitaxel remarkably elevated the percentage of the subG1 phase in KOSC3 cells.In addition,treatment with a pan-caspase inhibitor could recover paclitaxel-inhibited cell viability.Moreover,caspase-8,caspase-9,caspase-7,and BH3 interacting domain death agonist(Bid)were activated in paclitaxel-treated KOSC3 cells.Conclusions:Paclitaxel induced apoptosis through caspase cascade in KOSC3 cells.
基金supported by the National Key Research and Development Program of China(Grant Nos.2021YFB3800100 and 2021YFB3800101)the National Natural Science Foundation of China(62004089,U2001217,and U19A2089)+6 种基金the Guangdong Basic and Applied Basic Research Foundation(2019A1515110439,2019B1515120083,and2022A1515011218)the Shenzhen Science and Technology Program(JCYJ20190809150811504 and KQTD2015033110182370)the HKRGC General Research Funds(16312216)the Shenzhen&Hong Kong Joint Research Program(SGLH20180622092406130)the Shenzhen Engineering Research and Development Center for Flexible Solar Cel s Project funding from Shenzhen Development and Reform Committee(2019-126)the Key Fundamental Research Project funding from the Shenzhen Science and Technology Innovation Committee(JCYJ20200109141014474)the Guangdong-Hong Kong-Macao Joint Laboratory(2019B121205001)
文摘Hole transport material free carbon-based all-inorganic CsPbBr_(3)perovskite solar cells(PSCs)are promising for commercialization due to its low-cost,high open-circuit voltage(V_(oc))and superior stability.Due to the different solubility of PbBr_(2)and CsBr in conventional solvents,CsPbBr_(3)films are mainly obtained by multi-step spin-coating through the phase evolution from PbBr_(2)to CsPb_(2)Br_(5)and then to CsPbBr_(3).The scalable fabrication of high-quality CsPbBr_(3)films has been rarely studied.Herein,an inkjet-printing method is developed to prepare high-quality CsPbBr_(3)films.The formation of long-range crystalline CsPb_(2)Br_(5)phase can effectively improve phase purity and promote regular crystal stacking of CsPbBr_(3).Consequently,the inkjet-printed CsPbBr_(3)C-PSCs realized PCEs up to 9.09%,8.59%and 7.81%with active areas of 0.09,0.25,and 1 cm^(2),respectively,demonstrating the upscaling potential of our fabrication method and devices.This high performance is mainly ascribed to the high purity,strong crystal orientation,reduced surface roughness and lower trap states density of the as-printed CsPbBr_(3)films.This work provides insights into the relationship between the phase evolution mechanisms and crystal growth dynamics of cesium lead bromide halide films.
基金Supported by the Project of Sichuan Medical Association (No.S22058)National Key R&D Project (No.2018YFC1106103).
文摘Retinal degenerative diseases were a large group of diseases characterized by the primary death of retinal ganglion cells(RGCs).Recent studies had shown an interaction between autophagy and nucleotide-binding oligomerization domain-like receptor 3(NLRP3)inflammasomes,which may affect RGCs in retinal degenerative diseases.The NLRP3 inflammasome was a protein complex that,upon activation,produces caspase-1,mediating the apoptosis of retinal cells and promoting the occurrence and development of retinal degenerative diseases.Upregulated autophagy could inhibit NLRP3 inflammasome activation,while inhibited autophagy can promote NLRP3 inflammasome activation,which leaded to the accelerated emergence of drusen and lipofuscin deposition under the neurosensory retina.The activated NLRP3 inflammasome could further inhibit autophagy,thus forming a vicious cycle that accelerated the damage and death of RGCs.This review discussed the relationship between NLRP3 inflammasome and autophagy and its effects on RGCs in age-related macular degeneration,providing a new perspective and direction for the treatment of retinal diseases.
