By combing 20 documents of the Central Committee on the historical evolution of rural development policies since 1982, we hold that historical evolution has undergone reforms, adjustments, modernization developments a...By combing 20 documents of the Central Committee on the historical evolution of rural development policies since 1982, we hold that historical evolution has undergone reforms, adjustments, modernization developments and new ideas, and the path of reform experienced economic recovery, industrial nurturing agriculture, agriculture modernization and rural revitalization. The study found that: farmers' income has always been the focus of attention; agricultural production has shifted from total demand to green ecology; urban and rural resource elements are not well-organized, resulting in internal contradictions. The implementation of the rural revitalization strategy is an important measure to fundamentally solve the rural development problems in the new era.展开更多
Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play p...Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.展开更多
AIM: To investigate the association of serum glucocorticoid kinase gene-1(SGK-1) DNA variants with chronic central serous chorioretinopathy(CSC).METHODS: We enrolled 32 eyes of 32 patients who were diagnosed with chro...AIM: To investigate the association of serum glucocorticoid kinase gene-1(SGK-1) DNA variants with chronic central serous chorioretinopathy(CSC).METHODS: We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction amplification. SGK1 gene was sequenced by using Big Dye Terminator v3.1 cycle sequencing Kit(Applied Biosystems, Foster City, CA, USA). The SGK-1 gene and its variants were investigated in CSC patient group and control group.RESULTS: We identified a new polymorphism M32 V in two person in the patient group [Minor allele frequency(MAF) =0.009] on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK- 1 gene but not associated with CSC(P =0.68). An intrinsic rs1743966 is also not associated(P =0.28).CONCLUSION: The new polymorphism M32 V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.展开更多
High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the ex...High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.展开更多
Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with suba...Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with subacute CSC in Shenyang the 4th hospital from January 2014 to December 2015 were treated with 1/3-dose verteporfin PDT and followed up for at least 1 year. The symptoms and the diagnosed history were more than 3 months but shorter than 6 months. The central foveal thickness (CFT), neuroretinal thickness (NRT), height of subfoveal retinal fluid (SRF), and subfoveal choroidal thickness (SCT) were observed at baseline and after treated at 1, 2, 3, 6 and 12 months with EDI-OCT, Best-corrected visual acuity ( BCVA) was also studied at the same time. Results: After 1, 2, 3 and 6 months of 1/3-dose verteporfin PDT treatment, the BCVA improved significantly (P 0.05). The height of SRF changed significantly. There was no retinal pigment epithelium atrophy and choroidal neovascularization (CNV) in all cases after more than 12 months follow-up. Conclusion: Treatment of 1/3 dose verteporfin PDT could safely and effectively reduce expansion of choroidal vessel and choroidal choriocapillary, promoting absorbance of subretinal fluid for subacute CSC. 1/3-dose verteporfin PDT may be an alternative method to treat the subacute CSC.展开更多
DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early...DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early-onset Parkinson’s disease by regulating neuroinflammation,but its specific mechanism remains unclear.The study investigated the role of DJ-1 in mediating microglia-neuron communication to identify potential therapeutic targets for neuroinflammation in Parkinson’s disease.In this study,we observed a significant decrease in the levels of C-X3-C motif chemokine ligand 1(CX3CL1)in Park7 knockout mice and SH-SY5Y cells with Park7 knockdown.Protein microarray analysis and validation using GEO datasets confirmed that knockout of the Park7 gene led to downregulation of CX3CL1 and two other chemokines,namely monocyte chemoattractant protein-1 and interleukin-8.Further investigation revealed that Park7 deficiency reduced the processing of a disintegrin and metalloproteinase domain-containing protein 10(ADAM10)in the neuronal endoplasmic reticulum of both mice and SH-SY5Y cells,thereby decreasing CX3CL1 secretion.This subsequently led to abnormal microglial activation,with a shift toward the proinflammatory M1 phenotype,exacerbating neuroinflammatory responses.These effects were mitigated by exogenous CX3CL1 administration.Concurrently,exogenous CX3CL1 improved motor function in Parkinson’s disease model mice with the Park7 knockout,promoting survival of tyrosine hydroxylase-positive neurons in the substantia nigra and reducing Iba-1-positive microglial activation.These findings demonstrate that DJ-1 exerts neuroprotective effects on dopaminergic neurons by suppressing microglial activation through CX3CL1 regulation,suggesting that targeting the DJ-1/CX3CL1 axis may represent a novel therapeutic strategy for modulating neuroinflammation and protecting dopaminergic neurons.展开更多
NOD样受体蛋白1(NOD-like receptor protein 1,NLRP1)炎性小体在人体固有免疫反应中发挥着重要作用,可促进半胱氨酸蛋白水解酶(cysteinyl aspartate specific proteinases,Caspases)的活化,进一步激活白介素-18和白介素-1β,同时介导细...NOD样受体蛋白1(NOD-like receptor protein 1,NLRP1)炎性小体在人体固有免疫反应中发挥着重要作用,可促进半胱氨酸蛋白水解酶(cysteinyl aspartate specific proteinases,Caspases)的活化,进一步激活白介素-18和白介素-1β,同时介导细胞焦亡,NLRP1炎性小体在创伤性中枢神经损伤中发挥着作用,本文就NLRP1炎性小体的结构、NLRP1炎性小体在创伤性中枢神经损伤中的激活以及以NLRP1炎性小体为靶点的治疗等方面进行了综述。展开更多
文摘By combing 20 documents of the Central Committee on the historical evolution of rural development policies since 1982, we hold that historical evolution has undergone reforms, adjustments, modernization developments and new ideas, and the path of reform experienced economic recovery, industrial nurturing agriculture, agriculture modernization and rural revitalization. The study found that: farmers' income has always been the focus of attention; agricultural production has shifted from total demand to green ecology; urban and rural resource elements are not well-organized, resulting in internal contradictions. The implementation of the rural revitalization strategy is an important measure to fundamentally solve the rural development problems in the new era.
基金supported by the National Natural Science Foundation of China(No.82171599 and No.32270901)the National Key Research and Developmental Program of China(2022YFC2702601 and 2022YFA0806303)the Global Select Project(DJKLX-2022010)of the Institute of Health and Medicine,Hefei Comprehensive National Science Center.
文摘Male infertility can result from impaired sperm motility caused by multiple morphological abnormalities of the flagella(MMAF).Distinct projections encircling the central microtubules of the spermatozoal axoneme play pivotal roles in flagellar bending and spermatozoal movement.Mammalian sperm-associated antigen 17(SPAG17)encodes a conserved axonemal protein of cilia and flagella,forming part of the C1a projection of the central apparatus,with functions related to ciliary/flagellar motility,skeletal growth,and male fertility.This study investigated two novel homozygous SPAG17 mutations(M1:NM_206996.2,c.829+1G>T,p.Asp212_Glu276del;and M2:c.2120del,p.Leu707*)identified in four infertile patients from two consanguineous Pakistani families.These patients displayed the MMAF phenotype confirmed by Papanicolaou staining and scanning electron microscopy assays of spermatozoa.Quantitative real-time polymerase chain reaction(PCR)of patients’spermatozoa also revealed a significant decrease in SPAG17 mRNA expression,and immunofluorescence staining showed the absence of SPAG17 protein signals along the flagella.However,no apparent ciliary-related symptoms or skeletal malformations were observed in the chest X-rays of any of the patients.Transmission electron microscopy of axoneme cross-sections from the patients showed incomplete C1a projection and a higher frequency of missing microtubule doublets 1 and 9 compared with those from fertile controls.Immunofluorescence staining and Western blot analyses of spermatogenesis-associated protein 17(SPATA17),a component of the C1a projection,and sperm-associated antigen 6(SPAG6),a marker of the spring layer,revealed disrupted expression of both proteins in the patients’spermatozoa.Altogether,these findings demonstrated that SPAG17 maintains the integrity of spermatozoal flagellar axoneme,expanding the phenotypic spectrum of SPAG17 mutations in humans.
文摘AIM: To investigate the association of serum glucocorticoid kinase gene-1(SGK-1) DNA variants with chronic central serous chorioretinopathy(CSC).METHODS: We enrolled 32 eyes of 32 patients who were diagnosed with chronic CSC and composed 32 normal eyes as a control group. Peripheral blood was used for DNA extraction and polymerase chain reaction amplification. SGK1 gene was sequenced by using Big Dye Terminator v3.1 cycle sequencing Kit(Applied Biosystems, Foster City, CA, USA). The SGK-1 gene and its variants were investigated in CSC patient group and control group.RESULTS: We identified a new polymorphism M32 V in two person in the patient group [Minor allele frequency(MAF) =0.009] on the region of 1-60 amino acids. The rs1057293 was located in the encoder region of the SGK- 1 gene but not associated with CSC(P =0.68). An intrinsic rs1743966 is also not associated(P =0.28).CONCLUSION: The new polymorphism M32 V is located on the region of 1-60 amino acids which is necessary for localization to the mitochondria in CSC patient. This mutation is probably important for the energy metabolism and plays an important role in the cellular response to hyperosmotic stress and other stress stimuli. Both rs1057293 and rs1743966 are not associated with CSC.
基金supported by a grant of the M.D.-Ph.D./Medical Scientist Training Program through the Korea Health Industry Development Institute(KHIDI)funded by the Ministry of Health&Welfare,Republic of Korea(to HK)+3 种基金supported by National Research Foundation of Korea(NRF)grants funded by the Korean government(MSITMinistry of Science and ICT)(NRF2019R1A5A2026045 and NRF-2021R1F1A1061819)a grant from the Korean Health Technology R&D Project through the Korea Health Industry Development Institute(KHIDI),funded by the Ministry of Health&Welfare,Republic of Korea(HR21C1003)New Faculty Research Fund of Ajou University School of Medicine(to JYC)。
文摘High-mobility group box 1 was first discovered in the calf thymus as a DNA-binding nuclear protein and has been widely studied in diverse fields,including neurology and neuroscience.High-mobility group box 1 in the extracellular space functions as a pro-inflammatory damage-associated molecular pattern,which has been proven to play an important role in a wide variety of central nervous system disorders such as ischemic stroke,Alzheimer’s disease,frontotemporal dementia,Parkinson’s disease,multiple sclerosis,epilepsy,and traumatic brain injury.Several drugs that inhibit high-mobility group box 1 as a damage-associated molecular pattern,such as glycyrrhizin,ethyl pyruvate,and neutralizing anti-high-mobility group box 1 antibodies,are commonly used to target high-mobility group box 1 activity in central nervous system disorders.Although it is commonly known for its detrimental inflammatory effect,high-mobility group box 1 has also been shown to have beneficial pro-regenerative roles in central nervous system disorders.In this narrative review,we provide a brief summary of the history of high-mobility group box 1 research and its characterization as a damage-associated molecular pattern,its downstream receptors,and intracellular signaling pathways,how high-mobility group box 1 exerts the repair-favoring roles in general and in the central nervous system,and clues on how to differentiate the pro-regenerative from the pro-inflammatory role.Research targeting high-mobility group box 1 in the central nervous system may benefit from differentiating between the two functions rather than overall suppression of high-mobility group box 1.
文摘Purpose: To study the safety and efficacy of 1/3-dose verteporfin photodynamic therapy (PDT) for subacute central serous chorioretinopathy (CSC). Methods: In this case series, 59 eyes (59 patients) diagnosed with subacute CSC in Shenyang the 4th hospital from January 2014 to December 2015 were treated with 1/3-dose verteporfin PDT and followed up for at least 1 year. The symptoms and the diagnosed history were more than 3 months but shorter than 6 months. The central foveal thickness (CFT), neuroretinal thickness (NRT), height of subfoveal retinal fluid (SRF), and subfoveal choroidal thickness (SCT) were observed at baseline and after treated at 1, 2, 3, 6 and 12 months with EDI-OCT, Best-corrected visual acuity ( BCVA) was also studied at the same time. Results: After 1, 2, 3 and 6 months of 1/3-dose verteporfin PDT treatment, the BCVA improved significantly (P 0.05). The height of SRF changed significantly. There was no retinal pigment epithelium atrophy and choroidal neovascularization (CNV) in all cases after more than 12 months follow-up. Conclusion: Treatment of 1/3 dose verteporfin PDT could safely and effectively reduce expansion of choroidal vessel and choroidal choriocapillary, promoting absorbance of subretinal fluid for subacute CSC. 1/3-dose verteporfin PDT may be an alternative method to treat the subacute CSC.
基金National Natural Science Foundation of China,Nos.82471264(to YL),82201392(to AZ),82071415(to JL)Shanghai Rising Stars of Medical Talents Youth Development Program,No.2023-62(to YL)+2 种基金the Shanghai Municipal Health Commission Clinical Research Special Fund for the Health Industry,No.20234Y0026(to YL)the Shanghai Sailing Program,No.22YF1425100(to AZ)Chinese Postdoctoral Science Foundation,No.2021M702169(to YJ).
文摘DJ-1,also known as Parkinson’s disease protein 7(PARK7),is a multifunctional protein that plays an important role in oxidative stress regulation and neuroprotection.Previous studies have shown that DJ-1 affects early-onset Parkinson’s disease by regulating neuroinflammation,but its specific mechanism remains unclear.The study investigated the role of DJ-1 in mediating microglia-neuron communication to identify potential therapeutic targets for neuroinflammation in Parkinson’s disease.In this study,we observed a significant decrease in the levels of C-X3-C motif chemokine ligand 1(CX3CL1)in Park7 knockout mice and SH-SY5Y cells with Park7 knockdown.Protein microarray analysis and validation using GEO datasets confirmed that knockout of the Park7 gene led to downregulation of CX3CL1 and two other chemokines,namely monocyte chemoattractant protein-1 and interleukin-8.Further investigation revealed that Park7 deficiency reduced the processing of a disintegrin and metalloproteinase domain-containing protein 10(ADAM10)in the neuronal endoplasmic reticulum of both mice and SH-SY5Y cells,thereby decreasing CX3CL1 secretion.This subsequently led to abnormal microglial activation,with a shift toward the proinflammatory M1 phenotype,exacerbating neuroinflammatory responses.These effects were mitigated by exogenous CX3CL1 administration.Concurrently,exogenous CX3CL1 improved motor function in Parkinson’s disease model mice with the Park7 knockout,promoting survival of tyrosine hydroxylase-positive neurons in the substantia nigra and reducing Iba-1-positive microglial activation.These findings demonstrate that DJ-1 exerts neuroprotective effects on dopaminergic neurons by suppressing microglial activation through CX3CL1 regulation,suggesting that targeting the DJ-1/CX3CL1 axis may represent a novel therapeutic strategy for modulating neuroinflammation and protecting dopaminergic neurons.
文摘NOD样受体蛋白1(NOD-like receptor protein 1,NLRP1)炎性小体在人体固有免疫反应中发挥着重要作用,可促进半胱氨酸蛋白水解酶(cysteinyl aspartate specific proteinases,Caspases)的活化,进一步激活白介素-18和白介素-1β,同时介导细胞焦亡,NLRP1炎性小体在创伤性中枢神经损伤中发挥着作用,本文就NLRP1炎性小体的结构、NLRP1炎性小体在创伤性中枢神经损伤中的激活以及以NLRP1炎性小体为靶点的治疗等方面进行了综述。
