Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life ...Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.展开更多
Machine learning(ML)efficiently and accurately processes dense seismic array data,improving earthquake catalog creation,which is crucial for understanding earthquake sequences and fault systems;analyzing its reliabili...Machine learning(ML)efficiently and accurately processes dense seismic array data,improving earthquake catalog creation,which is crucial for understanding earthquake sequences and fault systems;analyzing its reliability is also essential.An M5.8 earthquake struck Alxa Left Banner,Inner Mongolia,China on April 15,2015,a region with limited CENC monitoring capabilities,making analysis challenging.However,abundant data from ChinArray provided valuable observations for assessing the event.This study leveraged ChinArray data from the 2015 Alxa Left Banner earthquake sequence,employing machine learning(specifically PhaseNet,a deep learning method,and GaMMA,a Bayesian approach)for automated seismic phase picking,association,and location analysis.Our generated catalog,comprising 10,432 phases from 708 events,is roughly ten times larger than the CENC catalog,encompassing all CENC events with strong consistency.A slight magnitude overestimation is observed only at lower magnitudes.Furthermore,the catalog adheres to the Gutenberg-Richter and Omori laws spatially,temporally,and in magnitude distribution,demonstrating its high reliability.Double-difference tomography refined locations for 366 events,yielding a more compact spatial distribution with horizontal errors within 100m,vertical errors within 300m,and travel-time residuals within 0.05s.Depths predominantly range from 10-30km.Aftershocks align primarily NEE,with the mainshock east of the aftershock zone.The near-vertical main fault plane dips northwestward,exhibiting a Y-shaped branching structure,converging at depth and expanding towards the surface.FOCMEC analysis,using first motion and amplitude ratios,yielded focal mechanism solutions for 10 events,including the mainshock.These solutions consistently indicate a strike-slip mechanism with a minor extensional component.Integrating the earthquake sequence's spatial distribution and focal mechanisms suggests the seismogenic structure is a negative flower structure,consistent with the Dengkou-Benjing fault.Comparing the CENC and ML-generated catalogs using the maximum curvature(MAXC)method reveals a 0.6 decrease in completeness magnitude(M_(C)).However,magnitude-frequency distribution discrepancies above the MAXC-estimated M_(C)suggest MAXC may underestimate both M_(C)and the b-value.This study analyzes the 2015 Alxa Left Banner M5.8 earthquake using a reliable,MLgenerated earthquake catalog,revealing detailed information about the sequence,faulting structure,aftershock distribution,and stress characteristics.展开更多
基金supported by the National Natural Science Foundation of China,Nos.81730033,82171193(to XG)the Key Talent Project for Strengthening Health during the 13^(th)Five-Year Plan Period,No.ZDRCA2016069(to XG)+1 种基金the National Key R&D Program of China,No.2018YFC2001901(to XG)Jiangsu Provincial Medical Key Discipline,No.ZDXK202232(to XG)。
文摘Postoperative cognitive dysfunction is a seve re complication of the central nervous system that occurs after anesthesia and surgery,and has received attention for its high incidence and effect on the quality of life of patients.To date,there are no viable treatment options for postoperative cognitive dysfunction.The identification of postoperative cognitive dysfunction hub genes could provide new research directions and therapeutic targets for future research.To identify the signaling mechanisms contributing to postoperative cognitive dysfunction,we first conducted Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of the Gene Expression Omnibus GSE95426 dataset,which consists of mRNAs and long non-coding RNAs differentially expressed in mouse hippocampus3 days after tibial fracture.The dataset was enriched in genes associated with the biological process"regulation of immune cells,"of which Chill was identified as a hub gene.Therefore,we investigated the contribution of chitinase-3-like protein 1 protein expression changes to postoperative cognitive dysfunction in the mouse model of tibial fractu re surgery.Mice were intraperitoneally injected with vehicle or recombinant chitinase-3-like protein 124 hours post-surgery,and the injection groups were compared with untreated control mice for learning and memory capacities using the Y-maze and fear conditioning tests.In addition,protein expression levels of proinflammatory factors(interleukin-1βand inducible nitric oxide synthase),M2-type macrophage markers(CD206 and arginase-1),and cognition-related proteins(brain-derived neurotropic factor and phosphorylated NMDA receptor subunit NR2B)were measured in hippocampus by western blotting.Treatment with recombinant chitinase-3-like protein 1 prevented surgery-induced cognitive impairment,downregulated interleukin-1βand nducible nitric oxide synthase expression,and upregulated CD206,arginase-1,pNR2B,and brain-derived neurotropic factor expression compared with vehicle treatment.Intraperitoneal administration of the specific ERK inhibitor PD98059 diminished the effects of recombinant chitinase-3-like protein 1.Collectively,our findings suggest that recombinant chitinase-3-like protein 1 ameliorates surgery-induced cognitive decline by attenuating neuroinflammation via M2 microglial polarization in the hippocampus.Therefore,recombinant chitinase-3-like protein1 may have therapeutic potential fo r postoperative cognitive dysfunction.
基金funded by the Inner Mongolia Natural Science Foundation(No.2024MS04021)the Science and Technology Plan of Inner Mongolia Autonomous Region(No.2023YFSH0004)the Director Fund of the Inner Mongolia Autonomous Region Seismological Bureau(No.2023GG01,No.2023GG02,No.2023MS05,No.2023QN13)。
文摘Machine learning(ML)efficiently and accurately processes dense seismic array data,improving earthquake catalog creation,which is crucial for understanding earthquake sequences and fault systems;analyzing its reliability is also essential.An M5.8 earthquake struck Alxa Left Banner,Inner Mongolia,China on April 15,2015,a region with limited CENC monitoring capabilities,making analysis challenging.However,abundant data from ChinArray provided valuable observations for assessing the event.This study leveraged ChinArray data from the 2015 Alxa Left Banner earthquake sequence,employing machine learning(specifically PhaseNet,a deep learning method,and GaMMA,a Bayesian approach)for automated seismic phase picking,association,and location analysis.Our generated catalog,comprising 10,432 phases from 708 events,is roughly ten times larger than the CENC catalog,encompassing all CENC events with strong consistency.A slight magnitude overestimation is observed only at lower magnitudes.Furthermore,the catalog adheres to the Gutenberg-Richter and Omori laws spatially,temporally,and in magnitude distribution,demonstrating its high reliability.Double-difference tomography refined locations for 366 events,yielding a more compact spatial distribution with horizontal errors within 100m,vertical errors within 300m,and travel-time residuals within 0.05s.Depths predominantly range from 10-30km.Aftershocks align primarily NEE,with the mainshock east of the aftershock zone.The near-vertical main fault plane dips northwestward,exhibiting a Y-shaped branching structure,converging at depth and expanding towards the surface.FOCMEC analysis,using first motion and amplitude ratios,yielded focal mechanism solutions for 10 events,including the mainshock.These solutions consistently indicate a strike-slip mechanism with a minor extensional component.Integrating the earthquake sequence's spatial distribution and focal mechanisms suggests the seismogenic structure is a negative flower structure,consistent with the Dengkou-Benjing fault.Comparing the CENC and ML-generated catalogs using the maximum curvature(MAXC)method reveals a 0.6 decrease in completeness magnitude(M_(C)).However,magnitude-frequency distribution discrepancies above the MAXC-estimated M_(C)suggest MAXC may underestimate both M_(C)and the b-value.This study analyzes the 2015 Alxa Left Banner M5.8 earthquake using a reliable,MLgenerated earthquake catalog,revealing detailed information about the sequence,faulting structure,aftershock distribution,and stress characteristics.
