Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In ...Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.展开更多
<strong>Objective:</strong> This retrospective study aims to survey the clinical outcomes of 341 consecutive patients surgically treated for and diagnosed with craniopharyngioma (CP) treated in a 10-year p...<strong>Objective:</strong> This retrospective study aims to survey the clinical outcomes of 341 consecutive patients surgically treated for and diagnosed with craniopharyngioma (CP) treated in a 10-year period in a single institution. <strong>Methods:</strong> The clinical reports of three hundred forty-one patients CP patients treated surgically between January 2006 and December 2016 were reviewed and analyzed retrospectively. <strong>Results:</strong> Our cohort consisted of 341 patients (202 male, 139 female) with a mean age of 34.9 years (range 1 - 74 years);Tumor Features: 129 patients (37.8%) had cystic tumors, 88 (23.8%) had solid tumors whereas 126 (36.4%) had heterogeneous lesions with a solid and cystic portion;calcifications were present in 139 (40.8%);Tumor Topography: Suprasellar 198 (58.1%), Intrasellar 40 (11.7%), Intra-third ventricular 103 (30.2%);Surgical approaches used among the patients included: Pterional 262 (76.8%), Transsphenoidal (TS) 42 (12.3%) Transcallosal 20 (5.9%), Transcortical 16 (4.7%) suboccipital 1 and combined approach 1;Gross total removal (GTR) was achieved in 247 patients (72.4%), Subtotal removal (STR) in 94 patients (27.6%). Good postoperative outcome at discharge was achieved in 324 (95%) patients while 17 (5%) patients had poor outcome including 5 (1.5%) perioperative deaths. Mean hospital length of stay was 21.87 (8 - 129). There were 42 (12.9%) recurrences with a mean time to recurrence of 28.36 (3 - 84) months, among which 37 (88.1%) underwent surgery for recurrence treatment. Follow-up time ranged from 3 months to 10 years. There was a statistical significance between open transcranial surgery and suprasellar tumors (p < 0.0001), TS and intrasellar tumors (p < 0.0001);postoperative diabetes inspidus and gross total resection (p < 0.0001);GTR and cystic tumors (p = 0.034) calcification and GTR (p = 0.0008). <strong>Conclusion:</strong> Good surgical outcome and long-term tumor control can be achieved through individual-based selective resection, whether total or subtotal resection. Whereas surgical prehistory of CP was found to be a significant risk factor to recurrence (p < 0.0001), the clinical risk factors of CP of recurrence are still arguable, including the presence residual tumor due to subtotal resection. More future studies are necessary.展开更多
Optimized nitrogen(N)management can increase N-use efficiency in intercropping systems.Legume-nonlegume intercropping systems can reduce N input by exploiting biological N fixation by legumes.Measurement of N utilizat...Optimized nitrogen(N)management can increase N-use efficiency in intercropping systems.Legume-nonlegume intercropping systems can reduce N input by exploiting biological N fixation by legumes.Measurement of N utilization can help in dissecting the mechanisms underlying N uptake and utilization in legume-nonlegume intercropping systems.An experiment was performed with three planting patterns:monoculture maize(MM),monoculture soybean(SS),and maize-soybean relay intercropping(IMS),and three N application levels:zero N(NN),reduced N(RN),and conventional N(CN)to investigate crop N uptake and utilization characteristics.N recovery efficiency and 15N recovery rate of crops were higher under RN than under CN,and those under RN were higher under intercropping than under the corresponding monocultures.Compared with MM,IMS showed a lower soil N-dependent rate(SNDR)in 2012.However,the SNDR of MM rapidly declined from 86.8%in 2012 to 49.4%in 2014,whereas that of IMS declined slowly from 75.4%in 2012 to 69.4%in 2014.The interspecific N competition rate(NCRms)was higher under RN than under CN,and increased yearly.Soybean nodule dry weight and nitrogenase activities were respectively 34.2%and 12.5%higher under intercropping than in monoculture at the beginning seed stage.The amount(Ndfa)and ratio(%Ndfa)of soybean N2 fixation were significantly greater under IS than under SS.In conclusion,N fertilizer was more efficiently used under RN than under CN;in particular,the relay intercropping system promoted N fertilizer utilization in comparison with the corresponding monocultures.An intercropping system helps to maintain soil fertility because interspecific N competition promotes biological N fixation by soybean by reducing N input.Thus,a maize-soybean relay intercropping system with reduced N application is sustainable and environmentally friendly.展开更多
The latest edition of the WHO classification of the central nervous system was published in 2021.This review summarizes the major revisions to the classification of anterior pituitary tumors.The most important revisio...The latest edition of the WHO classification of the central nervous system was published in 2021.This review summarizes the major revisions to the classification of anterior pituitary tumors.The most important revision involves preferring the terminology of pituitary neuroendocrine tumor(PitNET),even though the terminology of pituitary adenoma(PA)still can be used according to this WHO classification compared to the previous one.Moreover,immunohistochemistry(IHC)examination of pituitary-specific transcription factors(TFs),including PIT1,TPIT,SF-1,GATA2/3,and ERα,is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups.However,TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages,which includes unclassified plurihormonal(PH)tumors and null cell(NC)tumors in this edition.The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors.However,due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA,the application of this new classification system in practice should be further evaluated and validated.Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery,this classification system offers no additional help for neurosurgeons in clinical practice,especially in determining the treatment strategies.Therefore,it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis,as well as pathological diagnosis,thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.展开更多
A growing number of children and adolescents are being diagnosed as Chiari malformation type I （CM- I ） for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this stu...A growing number of children and adolescents are being diagnosed as Chiari malformation type I （CM- I ） for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM- I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM- I underwent surgical treatment in our department. We divided the patients into two groups： pediatric group （n=l 1, age 〈18 years） and adult group （n=73, age 〉18 years）. Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis （36.4%） and developmental delay （36.4%） were more common in pediatric patients, whereas, sensory disturbance （58.9%） and motor weakness （41. 1%） were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group （P〈0.05）. Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments （P〈0.05）. The total Chicago Chiari Outcome Scale （CCOS） score in pediatric patients at the last follow- up was significantly higher than that in adult patients （P=0.002）. In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM- I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.展开更多
Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectiou...Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectious rate,a long incubation period and a variety of manifestations.In the absence of effective treatments for the virus,it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission.Hereby we focused on the surgical practice in Neurosurgery Department,Tongji Hospital,Wuhan,and drafted several recommendations based on the latest relevant guidelines and our experience.These recommendations have helped us until now to achieve'zero infection'of doctors and nurses in our department,we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.展开更多
Objective In this study,we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery(ETTS).Meth...Objective In this study,we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery(ETTS).Methods Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021.Based on the results of the endocrinological evaluation and MRI examinations before and after surgery,the fluctuation of pituitary function and the extent of resection were analyzed.Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual.Results Among the 144 patients with pituitary macroadenomas,72(50.0%)were female and 72(50.0%)were male,the median age was 50 years,26(18.1%)had invasiveness grade 0,46(31.9%)had grade I,57(39.6%)had grade II,and 15(10.4%)had grade III according to Lu’s classification method.Based on observation during surgery,37 cases(25.7%)had no pseudocapsule,54 cases(37.5%)had incomplete pseudocapsule,and 53 cases(36.8%)had intact pseudocapsule.In addition,91(63.2%)patients had total resection,39(27.1%)had subtotal resection,and 14(9.7%)had partial resection.As for anterior pituitary function,13 of 19 hypothyroid patients had recovery after surgery,with a remission rate of 68.4%.Eighteen of the 26 decreased cortisol patients got back to normal,with a remission rate of 69.2%.A total of 27 of 51 patients with hypogonadism improved,with a remission rate of 52.9%.Univariate and multivariate analyses indicated that gender,tumor size,and invasiveness were predictors of postoperative residual in patients(P<0.05).Conclusion The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas.Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.展开更多
Objective To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma.Methods The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal...Objective To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma.Methods The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery(ETTS)for different indications in our department since 2011 was retrospectively analyzed.Results The most common indication was the ineffectiveness of oral medication(41.1%),followed by the personal willingness of the patient(35.5%),and 20.6%of the patients were young women with clear tumor boundaries.The pseudocapsule was not observed in 63 cases(58.9%),incomplete pseudocapsule was observed in 26 cases(24.3%),and complete pseudocapsule in 18 cases(16.8%).A total of 97 patients(90.7%)obtained 1-year post-operation remission.According to the relative location of the adenoma and pituitary gland on the MRI scan,46 patients were classified into a central type,59 a lateral type,and 2 a supra-pituitary type.Two patients developed hypogonadism,one patient developed hypocortisolism,and one patient developed post-operative hypothyroidism.Two patients were administrated with hormone replacement treatment,and the treatment was stopped within one week.There was no permanent hypopituitarism.Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma.Conclusion ETTS was an effective treatment for pituitary microprolactinomas.This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation.Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.展开更多
Parenchymal neurocysticercosis is the most common form of neurocysticercosis in the central nervous system(CNS),which mainly causes epilepsy and usually responses well to routine medications.However,there are apprecia...Parenchymal neurocysticercosis is the most common form of neurocysticercosis in the central nervous system(CNS),which mainly causes epilepsy and usually responses well to routine medications.However,there are appreciable cases of relapses refractory to medical treatment.We investigated microsurgical treatment of epilepsy with parenchymal neurocysticercosis.Nine cases of epilepsy caused by parenchymal neurocysticercosis from 2002 to 2018 were analyzed retrospectively.Cysts in 7 cases were completely removed.No case died of operation and no new dysfunction of the nervous system was observed after surgery.Among the other 9 cases,8 cases became seizure-free or controlled by medicine according to the postoperative followup for 6 months to 9 years.One case was lost for followup.It was suggested that epilepsy with parenchymal neurocysticercosis can usually be controlled after routine medications.However,surgery is still indicated in some cases and careful microsurgery is associated with satisfactory clinical outcomes in appropriately selected cases.展开更多
The histopathological features of the middle cerebral artery（MCA） and superficial temporal artery（STA） from moyamoya disease（MMD） and their relationships with gender,age,angiography stage were explored.The cause...The histopathological features of the middle cerebral artery（MCA） and superficial temporal artery（STA） from moyamoya disease（MMD） and their relationships with gender,age,angiography stage were explored.The causes and the clinical significance of vasculopathy of STA were also discussed.The clinical data and specimens of MCA and STA from 30 MMD patients were collected.Twelve samples of MCA and STA from non-MMD patients served as control group.Histopathological examination was then performed by measuring the thickness of intima and media,and statistical analysis was conducted.The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group.There was no significant pathological difference between the hemorrhage group and non-hemorrhage group,and between the males and females in MMD patients.Neither the age nor the digital subtraction angiography（DSA） stage was correlated with the thickness of intima in MCA and STA.MMD is a systemic vascular disease involving both intracranial and extracranial vessels.Preoperative external carotid arteriography,especially super-selective arteriography of the STA,benefits the selection of donor vessel.展开更多
Objective Typically,the transcranial approach has been used for the treatment of craniopharyngiomas with suprasellar extension,whereas the transsphenoidal approach has been used mostly for infradiaphragmatic craniopha...Objective Typically,the transcranial approach has been used for the treatment of craniopharyngiomas with suprasellar extension,whereas the transsphenoidal approach has been used mostly for infradiaphragmatic craniopharyngioma.Total resection of craniopharyngioma can reduce the recurrence rate,especially in young children,but it may lead to severe complications.Therefore,any benefit of the degree of resection must be weighed against the risk of complications by the surgeons.The purpose of this study was to explore the therapeutic outcome after transsphenoidal microsurgical treatment of infradiaphragmatic craniopharyngioma and share our experiences.Methods Between January 2003 and June 2013,30 patients with infradiaphragmatic craniopharyngioma underwent transsphenoidal microsurgical resection in our hospital.The neurological,visual,and endocrine functions,and extent of resection were analyzed retrospectively.Recurrence or growth of residual tumor tissue during follow-up was assessed using magnetic resonance imaging(MRI).Results Total resection was achieved in 25 patients(83.3%),subtotal resection was achieved in 4 patients(13.3%),and partial resection was achieved in 1 patient(3.4%).There were no perioperative deaths.Cerebrospinal fluid(CSF) leakage occurred in 6 patients,and among them,2 required surgical repair of the sella.New-onset postoperative diabetes insipidus(DI) developed in 8 patients.Vision and visual fields were improved at different levels in 13 out of 16 patients who had sight impediments before treatment.Tumor recurrence and regrowth was observed in 2 patients;1 patient underwent transsphenoidal reoperation,the condition of the other patient who had undergone several craniotomies grew worse over the 6-month follow-up period.Conclusion Transsphenoidal surgery is an ideal choice in treating infradiaphragmatic craniopharyngioma.The transsphenoidal approach,which preserves pituitary function and avoids damage to the hypothalamic structures and optic nerve,is associated with fewer complications than the transcranial approach and a low mortality rate.展开更多
Objective： To investigate the role of tissue factor （TF） in chemotherapeutic reagent - induced apoptosis on human glioblastoma and explore its mechanism. Methods： The expression of TF was examined by Western blott...Objective： To investigate the role of tissue factor （TF） in chemotherapeutic reagent - induced apoptosis on human glioblastoma and explore its mechanism. Methods： The expression of TF was examined by Western blotting. The cytotoxicity of doxorubicin was determined by WST assay. The activation of Caspase-3 and PARP induced by adoxorubicin were tested by Western blotting. Results： Human glioblastoma cell line U373MG expressed high level of TF while LN-229 was with low-TF level. The chemotherapeutic reagent doxorubicin revealed stronger cytotoxic effect on high-TF U373MG cells than IowoTF LN-229 cells. Enforced strong expression of TF was achieved by transfection of TF-pcDNA3 combinant on LN-229 cells in a dose-dependent manner. Enforced TF expression in transfected LN-229 cells not only impaired the doxorubicin-induced cleavage of Caspase-3 and PARP, but also inhibited the cytotoxic effect of doxorubicin. Furthermore, activation of Akt was strong in high-TF U373MG cells but weak in IowoTF LN-229 cells. Incubation of factor VII （FVII） with enforced TF-expressing LN-229 cells increased the phosphorylaUon of Akt in a time-dependent manner. Conclusion： These results suggest that over-expression of TF on glioblastoma could inhibit doxorubicin-induced apoptosis. Interaction of FVII and TF activates the downstream PI3K/Akt pathway. Tumor-derived over-expression of TF might play a role in chemotherapy resistance in glioblastoma, at lest in part, by activating PI3K/Akt-mediated survival and anti-apoptotic mechanism through the interaction of TF/FVII signaling.展开更多
Objective This study aimed to improve the antitumor immunocompetence of a tumor lysate-pulsed dendritic cell(DC)vaccine through differential centrifugation and provide a theoretical basis for its clinical application ...Objective This study aimed to improve the antitumor immunocompetence of a tumor lysate-pulsed dendritic cell(DC)vaccine through differential centrifugation and provide a theoretical basis for its clinical application in glioblastoma.Methods Peripheral blood mononuclear cells were extracted using Ficoll-Paque PLUS and induced into mature DCs in vitro with a cytokine cocktail.The modified tumor lysate was generated by differential centrifugation.The maturity markers of DCs in each group,namely the modified tumor lysate,tumor lysate,and negative and positive control groups,were assessed using flow cytometry.Furthermore,their ability to stimulate lymphocyte proliferation and in vitro antitumor effects were assessed using Cell Trace TM CFSE.IFN-γsecretion levels were measured with ELISA.Intracellular reactive oxygen species were measured using 2’,7’-dichlorofluorescein diacetate(DCFDA)staining.The results were statistically analyzed using an unpaired Student’s t-test and were considered significant at P<0.05.Results Compared with tumor lysate-pulsed DCs,modified tumor lysate-pulsed DCs had a higher expression of maturity markers:CD1a(7.38±0.53%vs.4.47±0.75%)and CD83(19.81±4.09%vs.9.64±1.50%),were better capable of stimulating lymphocyte proliferation[proliferation index(PI):8.54±0.16 vs.7.35±0.05],secreting IFN-γ,and inducing stronger in-vitro cytotoxic T lymphocyte(CTL)cytotoxicity against glioblastoma cells.In addition,we found that the level of ROS in modified tumor lysate-pulsed DCs was lower than that in tumor lysate-pulsed DCs.Conclusion Differential centrifugation of tumor lysates can improve the antitumor immunocompetence of DC vaccines,and reactive oxygen species may be the key to affecting DC function in the whole tumor lysate.展开更多
Objective: This review article attempts to examine and provide an overview of the risk factors associated with craniopharyngioma recurrence. Methods: A literature review of articles relating to the recurrences of cran...Objective: This review article attempts to examine and provide an overview of the risk factors associated with craniopharyngioma recurrence. Methods: A literature review of articles relating to the recurrences of craniopharyngioma and the clinical, molecular prognostic indicators of recurrence and treatment outcomes was performed retrospectively. Results: A total of 107 studies which described specific risk factors related to craniopharyngioma recurrence were identified which included but not limited to 54 retrospective case series, 7 systematic reviews, 21 laboratory reports, 13 case reports and 12 literature reviews. Conclusion: Based on the evidence identified in this review, the risk factors for recurrence in craniopharyngioma management are interrelated in a complex way, and surgery with or without adjuvant radiotherapy is reported to be of long-term benefit, but a disparity in findings suggests no definitive consensus on the risk factors of craniopharyngioma recurrence. More high-quality research is needed.展开更多
Transcriptional regulation plays a key role in the control of seed dormancy,and many transcription factors(TFs)have been documented.However,the mechanisms underlying the interactions between different TFs within a tra...Transcriptional regulation plays a key role in the control of seed dormancy,and many transcription factors(TFs)have been documented.However,the mechanisms underlying the interactions between different TFs within a transcriptional complex regulating seed dormancy remain largely unknown.Here,we showed that TF PHYTOCHROME-INTERACTING FACTOR4(PIF4)physically interacted with the abscisic acid(ABA)signaling responsive TF ABSCISIC ACID INSENSITIVE4(ABI4)to act as a transcriptional complex to promote ABA biosynthesis and signaling,finally deepening primary seed dormancy.Both pif4 and abi4 single mutants exhibited a decreased primary seed dormancy phenotype,with a synergistic effect in the pif4/abi4 double mutant.PIF4 binds to ABI4 to form a heterodimer,and ABI4 stabilizes PIF4 at the protein level,whereas PIF4 does not affect the protein stabilization of ABI4.Subsequently,both TFs independently and synergistically promoted the expression of ABI4 and NCED6,a key gene for ABA anabolism.The genetic evidence is also consistent with the phenotypic,physiological and biochemical analysis results.Altogether,this study revealed a transcriptional regulatory cascade in which the PIF4–ABI4 transcriptional activator complex synergistically enhanced seed dormancy by facilitating ABA biosynthesis and signaling.展开更多
Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and...Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of dementia.However,the underlying mechanisms of social isolation in AD progression remain elusive.In the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice.We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related proteins.Interestingly,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious cycle.Finally,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its partners.Moreover,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice.Taken together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.展开更多
Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dorman...Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dormancy to germination is not only a critical developmental step in the life cycle of plants but is also impor- tant for agricultural production. These processes are precisely regulated by diverse endogenous hormones and environmental cues. Although ABA （abscisic acid） and GAs （gibberellins） are known to be the primary phytohormones that antagonistically regulate seed dormancy, recent findings demonstrate that another phytohormone, auxin, is also critical for inducing and maintaining seed dormancy, and therefore might act as a key protector of seed dormancy. In this review, we summarize our current understanding of the sophisticated molecular networks involving the critical roles of phytohormones in regulating seed dormancy and germination, in which AP2-domain-containing transcription factors play key roles. We also discuss the interactions （crosstalk） of diverse hormonal signals in seed dormancy and germination, focusing on the ABA/GA balance that constitutes the central node.展开更多
Although ABSCISIC ACID INSENSITIVE 4(ABI4)was initially demonstrated as a key positive regulator in the phytohormone abscisic acid(ABA)signaling cascade,multiple studies have now shown that it is actually involved in ...Although ABSCISIC ACID INSENSITIVE 4(ABI4)was initially demonstrated as a key positive regulator in the phytohormone abscisic acid(ABA)signaling cascade,multiple studies have now shown that it is actually involved in the regulation of several other cascades,including diverse phytohormone biogenesis and signaling pathways,various developmental processes(such as seed dormancy and germination,seedling establishment,and root development),disease resistance and lipid metabolism.Consistent with its versatile biological functions,ABI4 either activates or represses transcription of its target genes.The upstream regulators of ABI4 at both the transcription and post-transcription levels have also been documented in recent years.Consequently,a complicated network consisting of the direct target genes and upstreamregulators of ABI4,through which ABI4 participates in several phytohormone crosstalk networks,has been generated.In this review,we summarize current understanding of the sophisticated ABI4-mediated molecular networks,mainly focusing on diverse phytohormone(including ABA,gibberellin,cytokinin,ethylene,auxin,and jasmonic acid)crosstalks.We also discuss the potential mechanisms through which ABI4 receives the ABA signal,focusing on protein phosphorylation modification events.展开更多
Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavaila...Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavailable.Here,we established a mouse model of PSD through photothrombosis-induced focal ischemia.By using a combination of brain imaging,transcriptome sequencing,and bioinformatics analysis,we found that the hippocampus of PSD mice had a signifcantly lower metabolic level than other brain regions.RNA sequencing revealed a signifcant reduction of miR34b-3p,which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E(eIF4E).Furthermore,silencing eIF4E inactivated microglia,inhibited neuroinfammation,and abolished the depression-like behaviors in PSD mice.Together,our data demonstrated that insufcient miR34b-3p after stroke cannot inhibit eIF4E translation,which causes PSD by the activation of microglia in the hippocampus.Therefore,miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.展开更多
基金supported by the Fundamental Research Program of Shanxi Province of China,No.20210302124277the Science Foundation of Shanxi Bethune Hospital,No.2021YJ13(both to JW)。
文摘Repetitive traumatic brain injury impacts adult neurogenesis in the hippocampal dentate gyrus,leading to long-term cognitive impairment.However,the mechanism underlying this neurogenesis impairment remains unknown.In this study,we established a male mouse model of repetitive traumatic brain injury and performed long-term evaluation of neurogenesis of the hippocampal dentate gyrus after repetitive traumatic brain injury.Our results showed that repetitive traumatic brain injury inhibited neural stem cell proliferation and development,delayed neuronal maturation,and reduced the complexity of neuronal dendrites and spines.Mice with repetitive traumatic brain injuryalso showed deficits in spatial memory retrieval.Moreover,following repetitive traumatic brain injury,neuroinflammation was enhanced in the neurogenesis microenvironment where C1q levels were increased,C1q binding protein levels were decreased,and canonical Wnt/β-catenin signaling was downregulated.An inhibitor of C1 reversed the long-term impairment of neurogenesis induced by repetitive traumatic brain injury and improved neurological function.These findings suggest that repetitive traumatic brain injury–induced C1-related inflammation impairs long-term neurogenesis in the dentate gyrus and contributes to spatial memory retrieval dysfunction.
文摘<strong>Objective:</strong> This retrospective study aims to survey the clinical outcomes of 341 consecutive patients surgically treated for and diagnosed with craniopharyngioma (CP) treated in a 10-year period in a single institution. <strong>Methods:</strong> The clinical reports of three hundred forty-one patients CP patients treated surgically between January 2006 and December 2016 were reviewed and analyzed retrospectively. <strong>Results:</strong> Our cohort consisted of 341 patients (202 male, 139 female) with a mean age of 34.9 years (range 1 - 74 years);Tumor Features: 129 patients (37.8%) had cystic tumors, 88 (23.8%) had solid tumors whereas 126 (36.4%) had heterogeneous lesions with a solid and cystic portion;calcifications were present in 139 (40.8%);Tumor Topography: Suprasellar 198 (58.1%), Intrasellar 40 (11.7%), Intra-third ventricular 103 (30.2%);Surgical approaches used among the patients included: Pterional 262 (76.8%), Transsphenoidal (TS) 42 (12.3%) Transcallosal 20 (5.9%), Transcortical 16 (4.7%) suboccipital 1 and combined approach 1;Gross total removal (GTR) was achieved in 247 patients (72.4%), Subtotal removal (STR) in 94 patients (27.6%). Good postoperative outcome at discharge was achieved in 324 (95%) patients while 17 (5%) patients had poor outcome including 5 (1.5%) perioperative deaths. Mean hospital length of stay was 21.87 (8 - 129). There were 42 (12.9%) recurrences with a mean time to recurrence of 28.36 (3 - 84) months, among which 37 (88.1%) underwent surgery for recurrence treatment. Follow-up time ranged from 3 months to 10 years. There was a statistical significance between open transcranial surgery and suprasellar tumors (p < 0.0001), TS and intrasellar tumors (p < 0.0001);postoperative diabetes inspidus and gross total resection (p < 0.0001);GTR and cystic tumors (p = 0.034) calcification and GTR (p = 0.0008). <strong>Conclusion:</strong> Good surgical outcome and long-term tumor control can be achieved through individual-based selective resection, whether total or subtotal resection. Whereas surgical prehistory of CP was found to be a significant risk factor to recurrence (p < 0.0001), the clinical risk factors of CP of recurrence are still arguable, including the presence residual tumor due to subtotal resection. More future studies are necessary.
基金supported by the National Natural Science Foundation of China(31671625,31271669)the National Key Research and Development Program of China(2016YFD0300202)
文摘Optimized nitrogen(N)management can increase N-use efficiency in intercropping systems.Legume-nonlegume intercropping systems can reduce N input by exploiting biological N fixation by legumes.Measurement of N utilization can help in dissecting the mechanisms underlying N uptake and utilization in legume-nonlegume intercropping systems.An experiment was performed with three planting patterns:monoculture maize(MM),monoculture soybean(SS),and maize-soybean relay intercropping(IMS),and three N application levels:zero N(NN),reduced N(RN),and conventional N(CN)to investigate crop N uptake and utilization characteristics.N recovery efficiency and 15N recovery rate of crops were higher under RN than under CN,and those under RN were higher under intercropping than under the corresponding monocultures.Compared with MM,IMS showed a lower soil N-dependent rate(SNDR)in 2012.However,the SNDR of MM rapidly declined from 86.8%in 2012 to 49.4%in 2014,whereas that of IMS declined slowly from 75.4%in 2012 to 69.4%in 2014.The interspecific N competition rate(NCRms)was higher under RN than under CN,and increased yearly.Soybean nodule dry weight and nitrogenase activities were respectively 34.2%and 12.5%higher under intercropping than in monoculture at the beginning seed stage.The amount(Ndfa)and ratio(%Ndfa)of soybean N2 fixation were significantly greater under IS than under SS.In conclusion,N fertilizer was more efficiently used under RN than under CN;in particular,the relay intercropping system promoted N fertilizer utilization in comparison with the corresponding monocultures.An intercropping system helps to maintain soil fertility because interspecific N competition promotes biological N fixation by soybean by reducing N input.Thus,a maize-soybean relay intercropping system with reduced N application is sustainable and environmentally friendly.
文摘The latest edition of the WHO classification of the central nervous system was published in 2021.This review summarizes the major revisions to the classification of anterior pituitary tumors.The most important revision involves preferring the terminology of pituitary neuroendocrine tumor(PitNET),even though the terminology of pituitary adenoma(PA)still can be used according to this WHO classification compared to the previous one.Moreover,immunohistochemistry(IHC)examination of pituitary-specific transcription factors(TFs),including PIT1,TPIT,SF-1,GATA2/3,and ERα,is endorsed to determine the tumor cell lineage and to facilitate the classification of PitNET/PA subgroups.However,TF-negative IHC staining indicates PitNET/PA with no distinct cell lineages,which includes unclassified plurihormonal(PH)tumors and null cell(NC)tumors in this edition.The new WHO classification of PitNET/PA has incorporated tremendous advances in the understanding of the cytogenesis and pathogenesis of pituitary tumors.However,due to the shortcomings of the technology used in the diagnosis of PitNET/PA and the limited understanding of the tumorigenesis of PitNET/PA,the application of this new classification system in practice should be further evaluated and validated.Besides providing information for deciding the follow-up plans and adjunctive treatment after surgery,this classification system offers no additional help for neurosurgeons in clinical practice,especially in determining the treatment strategies.Therefore,it is necessary for neurosurgeons to establish a comprehensive pituitary classification system for PitNET/PA that incorporates neuroimaging grading data or direct observation of invasiveness during operation or the predictor of prognosis,as well as pathological diagnosis,thereby distinguishing the invasiveness of the tumor and facilitating neurosurgeons to decide on the treatment strategies and follow-up plans as well as adjunctive treatment after surgery.
基金This project was supported by grants from the National Natural Science Foundation of China （No. 81702478 and No. 81270865） and China Postdoctoral Science Foundation （No. 2016M600596）.
文摘A growing number of children and adolescents are being diagnosed as Chiari malformation type I （CM- I ） for behavioral disorders, developmental delay, seizures, or abnormal orpharyngeal function. The aim of this study was to compare the clinical characteristics, imaging findings and surgical outcomes of CM- I in pediatric and adult patients. Between January 2014 and June 2017, 84 patients with CM- I underwent surgical treatment in our department. We divided the patients into two groups： pediatric group （n=l 1, age 〈18 years） and adult group （n=73, age 〉18 years）. Data on clinical characteristics, imaging findings, surgical outcomes, and prognosis were retrospectively reviewed and compared between these two groups. For clinical presentation, scoliosis （36.4%） and developmental delay （36.4%） were more common in pediatric patients, whereas, sensory disturbance （58.9%） and motor weakness （41. 1%） were more common in adult patients. Imaging findings showed that the incidence of hydrocephalus and craniovertebral junctional abnormalities was significantly higher in pediatric group than in adult group （P〈0.05）. Compared to adult group, pediatric group showed a better improvement or resolution of syrinx and tonsillar herniation after surgical treatments （P〈0.05）. The total Chicago Chiari Outcome Scale （CCOS） score in pediatric patients at the last follow- up was significantly higher than that in adult patients （P=0.002）. In conclusion, the clinical characteristics and imaging findings appeared to be different in pediatric and adult patients with CM- I. The surgical outcomes of pediatric patients were shown to be significantly better than those of adult patients.
文摘Since December 2019,an outbreak of coronavirus disease 2019(COVID-19)has.posed significant threats to the public health and life in China.Unlike the other 6 identified coronaviruscs,the SARS-Cov-2 has a high infectious rate,a long incubation period and a variety of manifestations.In the absence of effective treatments for the virus,it becomes extremely urgent to develop scientific and standardized proposals for prevention and control of virus transmission.Hereby we focused on the surgical practice in Neurosurgery Department,Tongji Hospital,Wuhan,and drafted several recommendations based on the latest relevant guidelines and our experience.These recommendations have helped us until now to achieve'zero infection'of doctors and nurses in our department,we would like to share them with other medical staff of neurosurgery to fight 2019-nCoV infection.
文摘Objective In this study,we investigated the surgical technique and endocrine assessment of pituitary function of patients with macroadenoma treated by extra-pseudocapsular transnasal transsphenoidal surgery(ETTS).Methods Clinical data of 144 patients with pituitary macroadenomas in the same surgical group at the Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology were retrospectively analyzed from January 2019 to June 2021.Based on the results of the endocrinological evaluation and MRI examinations before and after surgery,the fluctuation of pituitary function and the extent of resection were analyzed.Multiple Logistic regression analysis was used to determine the predictors affecting postoperative tumor residual.Results Among the 144 patients with pituitary macroadenomas,72(50.0%)were female and 72(50.0%)were male,the median age was 50 years,26(18.1%)had invasiveness grade 0,46(31.9%)had grade I,57(39.6%)had grade II,and 15(10.4%)had grade III according to Lu’s classification method.Based on observation during surgery,37 cases(25.7%)had no pseudocapsule,54 cases(37.5%)had incomplete pseudocapsule,and 53 cases(36.8%)had intact pseudocapsule.In addition,91(63.2%)patients had total resection,39(27.1%)had subtotal resection,and 14(9.7%)had partial resection.As for anterior pituitary function,13 of 19 hypothyroid patients had recovery after surgery,with a remission rate of 68.4%.Eighteen of the 26 decreased cortisol patients got back to normal,with a remission rate of 69.2%.A total of 27 of 51 patients with hypogonadism improved,with a remission rate of 52.9%.Univariate and multivariate analyses indicated that gender,tumor size,and invasiveness were predictors of postoperative residual in patients(P<0.05).Conclusion The results showed that ETTS is an effective treatment modality for restoring the function of pituitary gland of the patients with macroadenomas.Tumor size and invasiveness are predictors of the extent of surgical resection and postoperative residual of macroadenomas.
文摘Objective To elucidate the role of transsphenoidal surgery in the treatment of pituitary microprolactinoma.Methods The clinical data of 107 prolactinoma cases treated by extra-pseudocapsular transnasal transsphenoidal surgery(ETTS)for different indications in our department since 2011 was retrospectively analyzed.Results The most common indication was the ineffectiveness of oral medication(41.1%),followed by the personal willingness of the patient(35.5%),and 20.6%of the patients were young women with clear tumor boundaries.The pseudocapsule was not observed in 63 cases(58.9%),incomplete pseudocapsule was observed in 26 cases(24.3%),and complete pseudocapsule in 18 cases(16.8%).A total of 97 patients(90.7%)obtained 1-year post-operation remission.According to the relative location of the adenoma and pituitary gland on the MRI scan,46 patients were classified into a central type,59 a lateral type,and 2 a supra-pituitary type.Two patients developed hypogonadism,one patient developed hypocortisolism,and one patient developed post-operative hypothyroidism.Two patients were administrated with hormone replacement treatment,and the treatment was stopped within one week.There was no permanent hypopituitarism.Further investigation demonstrated that the adenoma types could affect the remission rates of hyperprolactinemia and gross total resection rate in microprolactinoma.Conclusion ETTS was an effective treatment for pituitary microprolactinomas.This could be the first choice for patients who presented enclosed adenoma on the MRI and were potentially curable in a preoperative evaluation.Maximal safe removal of the adenoma by ETTS with the aim to increase the sensitivity of the drugs was also recommended for patients with invasive dopamine agonist resistant prolactinomas and patients with difficulty in childbirth.
基金Hubei Province Natural Science Foundation of China(No.2017CFB643).
文摘Parenchymal neurocysticercosis is the most common form of neurocysticercosis in the central nervous system(CNS),which mainly causes epilepsy and usually responses well to routine medications.However,there are appreciable cases of relapses refractory to medical treatment.We investigated microsurgical treatment of epilepsy with parenchymal neurocysticercosis.Nine cases of epilepsy caused by parenchymal neurocysticercosis from 2002 to 2018 were analyzed retrospectively.Cysts in 7 cases were completely removed.No case died of operation and no new dysfunction of the nervous system was observed after surgery.Among the other 9 cases,8 cases became seizure-free or controlled by medicine according to the postoperative followup for 6 months to 9 years.One case was lost for followup.It was suggested that epilepsy with parenchymal neurocysticercosis can usually be controlled after routine medications.However,surgery is still indicated in some cases and careful microsurgery is associated with satisfactory clinical outcomes in appropriately selected cases.
基金supported by the key project of the Natural Science Foundation of Hubei Province of China(No.ZRZ2014000254)the National Natural Science Foundation of China(No.81571146)
文摘The histopathological features of the middle cerebral artery（MCA） and superficial temporal artery（STA） from moyamoya disease（MMD） and their relationships with gender,age,angiography stage were explored.The causes and the clinical significance of vasculopathy of STA were also discussed.The clinical data and specimens of MCA and STA from 30 MMD patients were collected.Twelve samples of MCA and STA from non-MMD patients served as control group.Histopathological examination was then performed by measuring the thickness of intima and media,and statistical analysis was conducted.The MCA and STA specimens from MMD group had apparently thicker intima and thinner media than those from the control group.There was no significant pathological difference between the hemorrhage group and non-hemorrhage group,and between the males and females in MMD patients.Neither the age nor the digital subtraction angiography（DSA） stage was correlated with the thickness of intima in MCA and STA.MMD is a systemic vascular disease involving both intracranial and extracranial vessels.Preoperative external carotid arteriography,especially super-selective arteriography of the STA,benefits the selection of donor vessel.
基金Supported by the grants from the National Clinical Key Specialty Construction Project and National Natural Science Foundation of China(No.81270865)
文摘Objective Typically,the transcranial approach has been used for the treatment of craniopharyngiomas with suprasellar extension,whereas the transsphenoidal approach has been used mostly for infradiaphragmatic craniopharyngioma.Total resection of craniopharyngioma can reduce the recurrence rate,especially in young children,but it may lead to severe complications.Therefore,any benefit of the degree of resection must be weighed against the risk of complications by the surgeons.The purpose of this study was to explore the therapeutic outcome after transsphenoidal microsurgical treatment of infradiaphragmatic craniopharyngioma and share our experiences.Methods Between January 2003 and June 2013,30 patients with infradiaphragmatic craniopharyngioma underwent transsphenoidal microsurgical resection in our hospital.The neurological,visual,and endocrine functions,and extent of resection were analyzed retrospectively.Recurrence or growth of residual tumor tissue during follow-up was assessed using magnetic resonance imaging(MRI).Results Total resection was achieved in 25 patients(83.3%),subtotal resection was achieved in 4 patients(13.3%),and partial resection was achieved in 1 patient(3.4%).There were no perioperative deaths.Cerebrospinal fluid(CSF) leakage occurred in 6 patients,and among them,2 required surgical repair of the sella.New-onset postoperative diabetes insipidus(DI) developed in 8 patients.Vision and visual fields were improved at different levels in 13 out of 16 patients who had sight impediments before treatment.Tumor recurrence and regrowth was observed in 2 patients;1 patient underwent transsphenoidal reoperation,the condition of the other patient who had undergone several craniotomies grew worse over the 6-month follow-up period.Conclusion Transsphenoidal surgery is an ideal choice in treating infradiaphragmatic craniopharyngioma.The transsphenoidal approach,which preserves pituitary function and avoids damage to the hypothalamic structures and optic nerve,is associated with fewer complications than the transcranial approach and a low mortality rate.
文摘Objective： To investigate the role of tissue factor （TF） in chemotherapeutic reagent - induced apoptosis on human glioblastoma and explore its mechanism. Methods： The expression of TF was examined by Western blotting. The cytotoxicity of doxorubicin was determined by WST assay. The activation of Caspase-3 and PARP induced by adoxorubicin were tested by Western blotting. Results： Human glioblastoma cell line U373MG expressed high level of TF while LN-229 was with low-TF level. The chemotherapeutic reagent doxorubicin revealed stronger cytotoxic effect on high-TF U373MG cells than IowoTF LN-229 cells. Enforced strong expression of TF was achieved by transfection of TF-pcDNA3 combinant on LN-229 cells in a dose-dependent manner. Enforced TF expression in transfected LN-229 cells not only impaired the doxorubicin-induced cleavage of Caspase-3 and PARP, but also inhibited the cytotoxic effect of doxorubicin. Furthermore, activation of Akt was strong in high-TF U373MG cells but weak in IowoTF LN-229 cells. Incubation of factor VII （FVII） with enforced TF-expressing LN-229 cells increased the phosphorylaUon of Akt in a time-dependent manner. Conclusion： These results suggest that over-expression of TF on glioblastoma could inhibit doxorubicin-induced apoptosis. Interaction of FVII and TF activates the downstream PI3K/Akt pathway. Tumor-derived over-expression of TF might play a role in chemotherapy resistance in glioblastoma, at lest in part, by activating PI3K/Akt-mediated survival and anti-apoptotic mechanism through the interaction of TF/FVII signaling.
基金Supported by the National Natural Science Foundation of China(No.81602202 and 82173136).
文摘Objective This study aimed to improve the antitumor immunocompetence of a tumor lysate-pulsed dendritic cell(DC)vaccine through differential centrifugation and provide a theoretical basis for its clinical application in glioblastoma.Methods Peripheral blood mononuclear cells were extracted using Ficoll-Paque PLUS and induced into mature DCs in vitro with a cytokine cocktail.The modified tumor lysate was generated by differential centrifugation.The maturity markers of DCs in each group,namely the modified tumor lysate,tumor lysate,and negative and positive control groups,were assessed using flow cytometry.Furthermore,their ability to stimulate lymphocyte proliferation and in vitro antitumor effects were assessed using Cell Trace TM CFSE.IFN-γsecretion levels were measured with ELISA.Intracellular reactive oxygen species were measured using 2’,7’-dichlorofluorescein diacetate(DCFDA)staining.The results were statistically analyzed using an unpaired Student’s t-test and were considered significant at P<0.05.Results Compared with tumor lysate-pulsed DCs,modified tumor lysate-pulsed DCs had a higher expression of maturity markers:CD1a(7.38±0.53%vs.4.47±0.75%)and CD83(19.81±4.09%vs.9.64±1.50%),were better capable of stimulating lymphocyte proliferation[proliferation index(PI):8.54±0.16 vs.7.35±0.05],secreting IFN-γ,and inducing stronger in-vitro cytotoxic T lymphocyte(CTL)cytotoxicity against glioblastoma cells.In addition,we found that the level of ROS in modified tumor lysate-pulsed DCs was lower than that in tumor lysate-pulsed DCs.Conclusion Differential centrifugation of tumor lysates can improve the antitumor immunocompetence of DC vaccines,and reactive oxygen species may be the key to affecting DC function in the whole tumor lysate.
文摘Objective: This review article attempts to examine and provide an overview of the risk factors associated with craniopharyngioma recurrence. Methods: A literature review of articles relating to the recurrences of craniopharyngioma and the clinical, molecular prognostic indicators of recurrence and treatment outcomes was performed retrospectively. Results: A total of 107 studies which described specific risk factors related to craniopharyngioma recurrence were identified which included but not limited to 54 retrospective case series, 7 systematic reviews, 21 laboratory reports, 13 case reports and 12 literature reviews. Conclusion: Based on the evidence identified in this review, the risk factors for recurrence in craniopharyngioma management are interrelated in a complex way, and surgery with or without adjuvant radiotherapy is reported to be of long-term benefit, but a disparity in findings suggests no definitive consensus on the risk factors of craniopharyngioma recurrence. More high-quality research is needed.
基金supported by the National Natural Science Foundation of China(31872804 and 32101670)Natural Science Basic Research Program of Shaanxi(2024JC-YBMS-151)+3 种基金Shaanxi Fundamental Science Research Project for Chemistry&Biology(22JHQ054 and 22JHZ007)GuangDong Basic and Applied Basic Research Foundation(2021A1515110341)the Innovation Foundation for Doctoral Dissertations of Northwestern Polytechnical University(CX2021040,CX2022079 and CX2023096)Postdoctoral Research Foundation of China(2021M692644,2021M702674)。
文摘Transcriptional regulation plays a key role in the control of seed dormancy,and many transcription factors(TFs)have been documented.However,the mechanisms underlying the interactions between different TFs within a transcriptional complex regulating seed dormancy remain largely unknown.Here,we showed that TF PHYTOCHROME-INTERACTING FACTOR4(PIF4)physically interacted with the abscisic acid(ABA)signaling responsive TF ABSCISIC ACID INSENSITIVE4(ABI4)to act as a transcriptional complex to promote ABA biosynthesis and signaling,finally deepening primary seed dormancy.Both pif4 and abi4 single mutants exhibited a decreased primary seed dormancy phenotype,with a synergistic effect in the pif4/abi4 double mutant.PIF4 binds to ABI4 to form a heterodimer,and ABI4 stabilizes PIF4 at the protein level,whereas PIF4 does not affect the protein stabilization of ABI4.Subsequently,both TFs independently and synergistically promoted the expression of ABI4 and NCED6,a key gene for ABA anabolism.The genetic evidence is also consistent with the phenotypic,physiological and biochemical analysis results.Altogether,this study revealed a transcriptional regulatory cascade in which the PIF4–ABI4 transcriptional activator complex synergistically enhanced seed dormancy by facilitating ABA biosynthesis and signaling.
基金supported partially by the National Key Research and Development Program of China(Grant Nos.2019YFE0121200,2022YFC2403905)the National Natural Science Foundation of China(Grant Nos.82325017,82371403,82030032,82261138555,31721002,32070960,82001164,82001256)+5 种基金Top-Notch Young Talents Program of China of 2014,the China Postdoctoral Science Foundation(Grant No.2018M642855)the Hubei Provincial Natural Science Foundation(Grant No.2022CFA004 to Dr.Ling-Qiang Zhu,2023AFA068 to Dr.Dan Liu,2020CFB657 to Dr.Kai Shu)University of South China Clinical Research 4310 Program(Grant No.20224310NHYCG08)the Science and Technology Innovation Program of Hunan Province(Grant No.2022RC4044)The Key R&D and Promotion Program of Henan Science and Technology Department(Grant Nos.182102310512,202102310354,222102310084)the Henan Province Medical Science and Technology Research Project(Grant No.SBGJ202103052).
文摘Sporadic or late-onset Alzheimer’s disease(LOAD)accounts for more than 95%of Alzheimer’s disease(AD)cases without any family history.Although genome-wide association studies have identified associated risk genes and loci for LOAD,numerous studies suggest that many adverse environmental factors,such as social isolation,are associated with an increased risk of dementia.However,the underlying mechanisms of social isolation in AD progression remain elusive.In the current study,we found that 7 days of social isolation could trigger pattern separation impairments and presynaptic abnormalities of the mossy fibre-CA3 circuit in AD mice.We also revealed that social isolation disrupted histone acetylation and resulted in the downregulation of 2 dentate gyrus(DG)-enriched miRNAs,which simultaneously target reticulon 3(RTN3),an endoplasmic reticulum protein that aggregates in presynaptic regions to disturb the formation of functional mossy fibre boutons(MFBs)by recruiting multiple mitochondrial and vesicle-related proteins.Interestingly,the aggregation of RTN3 also recruits the PP2A B subunits to suppress PP2A activity and induce tau hyperphosphorylation,which,in turn,further elevates RTN3 and forms a vicious cycle.Finally,using an artificial intelligence-assisted molecular docking approach,we determined that senktide,a selective agonist of neurokinin3 receptors(NK3R),could reduce the binding of RTN3 with its partners.Moreover,application of senktide in vivo effectively restored DG circuit disorders in socially isolated AD mice.Taken together,our findings not only demonstrate the epigenetic regulatory mechanism underlying mossy fibre synaptic disorders orchestrated by social isolation and tau pathology but also reveal a novel potential therapeutic strategy for AD.
文摘Seed plants have evolved to maintain the dormancy of freshly matured seeds until the appropriate time for germination. Seed dormancy and germination are distinct physiological processes, and the transition from dormancy to germination is not only a critical developmental step in the life cycle of plants but is also impor- tant for agricultural production. These processes are precisely regulated by diverse endogenous hormones and environmental cues. Although ABA （abscisic acid） and GAs （gibberellins） are known to be the primary phytohormones that antagonistically regulate seed dormancy, recent findings demonstrate that another phytohormone, auxin, is also critical for inducing and maintaining seed dormancy, and therefore might act as a key protector of seed dormancy. In this review, we summarize our current understanding of the sophisticated molecular networks involving the critical roles of phytohormones in regulating seed dormancy and germination, in which AP2-domain-containing transcription factors play key roles. We also discuss the interactions （crosstalk） of diverse hormonal signals in seed dormancy and germination, focusing on the ABA/GA balance that constitutes the central node.
基金supported by funding from the National Natural Science Foundation of China(31872804,31701064)the Talents Team Construction Fund of Northwestern Polytechnical University(31020190QD007)the National Key Research and Development Program of China(2017YFD0201300)。
文摘Although ABSCISIC ACID INSENSITIVE 4(ABI4)was initially demonstrated as a key positive regulator in the phytohormone abscisic acid(ABA)signaling cascade,multiple studies have now shown that it is actually involved in the regulation of several other cascades,including diverse phytohormone biogenesis and signaling pathways,various developmental processes(such as seed dormancy and germination,seedling establishment,and root development),disease resistance and lipid metabolism.Consistent with its versatile biological functions,ABI4 either activates or represses transcription of its target genes.The upstream regulators of ABI4 at both the transcription and post-transcription levels have also been documented in recent years.Consequently,a complicated network consisting of the direct target genes and upstreamregulators of ABI4,through which ABI4 participates in several phytohormone crosstalk networks,has been generated.In this review,we summarize current understanding of the sophisticated ABI4-mediated molecular networks,mainly focusing on diverse phytohormone(including ABA,gibberellin,cytokinin,ethylene,auxin,and jasmonic acid)crosstalks.We also discuss the potential mechanisms through which ABI4 receives the ABA signal,focusing on protein phosphorylation modification events.
基金supported by the National Natural Science Foundation of China(81870932,81571078,51627807,31721002,81920208014,31930051)China Postdoctoral Science Foundation Funded Project(2020M672324,2020TQ0113).
文摘Post-stroke depression(PSD)is a serious and common complication of stroke,which seriously afects the rehabilitation of stroke patients.To date,the pathogenesis of PSD is unclear and efective treatments remain unavailable.Here,we established a mouse model of PSD through photothrombosis-induced focal ischemia.By using a combination of brain imaging,transcriptome sequencing,and bioinformatics analysis,we found that the hippocampus of PSD mice had a signifcantly lower metabolic level than other brain regions.RNA sequencing revealed a signifcant reduction of miR34b-3p,which was expressed in hippocampal neurons and inhibited the translation of eukaryotic translation initiation factor 4E(eIF4E).Furthermore,silencing eIF4E inactivated microglia,inhibited neuroinfammation,and abolished the depression-like behaviors in PSD mice.Together,our data demonstrated that insufcient miR34b-3p after stroke cannot inhibit eIF4E translation,which causes PSD by the activation of microglia in the hippocampus.Therefore,miR34b-3p and eIF4E may serve as potential therapeutic targets for the treatment of PSD.
