Breeding Report on Maize Jinxiu 206

Jinxiu 206 is a mid-early maize variety bred in the Maize Research Insti- tute, Shanxi Academy of Agricultural Sciences, derived from CC15-2 and Chang 7-2 Lv as male and female parents. The variety test in 2007-2012 showed that Jinxiu 206 has strong resistance to disease and stress, excellent quality and high stable yield, and is suitable for early spring maize producing areas.

Metal coordination-driven assembly of stimulator of interferon genes-activating nanoparticles for tumor chemo-immunotherapy

Activating the stimulator of interferon genes(STING)signaling pathway is critical for enhancing antitumor immunity and remodeling the immunosuppressive tumor microenvironment(TME).Herein,we report the preparation of STING-activating nanoparticles via metal coordination-driven assembly of a synthetic STING agonist(i.e.,SR717)and a chemotherapeutic drug(i.e.,curcumin).After intravenous administration,the assembled nanoparticles could efficiently accumulate in tumors to improve the bioavailability of SR717 and trigger potent STING pathway activation for effective immune responses.Meanwhile,the released curcumin evokes immunogenic cell death in tumors and regulates amino acid metabolism by inhibiting the activation of indoleamine 2,3-dioxygenase 1,leading to the reversal of the immunosuppressive TME.The antitumor immunity induced by nanoparticles significantly inhibits the growth of primary,recurrent,and metastatic tumors.The assembled nanoparticles are promising for the co-delivery of STING agonists and drugs in improved tumor chemo-immunotherapy.

The Role of MicroRNAs in Neural Stem Cells and Neurogenesis

Neural stem cells give rise to neurons through the process of neurogenesis, which includes neural stem cell proliferation, fate deter- mination of new neurons, as well as the new neuron＇s migration, maturation and integration. Currently, neurogenesis is divided into two phases： embryonic and adult phases. Embryonic neurogenesis occurs at high levels to form the central nervous system. Adult neurogenesis has been consistently identified only in restricted regions and occurs at low levels. As the basic process for embryonic neurodevelopment and adult brain maintenance, neurogenesis is tightly regulated by many factors and pathways. MicroRNA, short non-coding RNA that regulates gene expression at the post-transcriptional level, appears to be involved in multiple steps of neurogenesis. This review summarizes the emerging role of microRNAs in regulating embryonic and adult neurogenesis, with a particular emphasis on the proliferation and differentiation of neural stem cells.

Treatment of multiple sclerosis by transplantation of neural stem cells derived from induced pluripotent stem cells

Multiple sclerosis(MS) is an autoimmune disease of the central nervous system(CNS), with focal T lymphocytic infiltration and damage of myelin and axons. The underlying mechanism of pathogenesis remains unclear and there are currently no effective treatments. The development of neural stem cell(NSC) transplantation provides a promising strategy to treat neurodegenerative disease. However, the limited availability of NSCs prevents their application in neural disease therapy. In this study, we generated NSCs from induced pluripotent stem cells(iPSCs) and transplanted these cells into mice with experimental autoimmune encephalomyelitis(EAE), a model of MS. The results showed that transplantation of iPSC-derived NSCs dramatically reduced T cell infiltration and ameliorated white matter damage in the treated EAE mice. Correspondingly, the disease symptom score was greatly decreased, and motor ability was dramatically rescued in the iPSC-NSC-treated EAE mice, indicating the effectiveness of using iPSC-NSCs to treat MS. Our study provides pre-clinical evidence to support the feasibility of treating MS by transplantation of iPSC-derived NSCs.

Epigenetics: major regulators of embryonic neurogenesis

Mammalian cortical development is a dynamically and strictly regulated process orchestrated by extracellular signals and intracellular mechanisms. Recent studies show that epigenetic regulation serves as, at least in part, interfaces between genes and the environment, and also provides insight into the molecular and cellular bases of early embryonic cortical development. It is becoming increasingly clear that epigenetic regulation of cortical development occurs at multiple levels and that comprehensive knowledge of this complex regulatory landscape is essential to delineating embryonic neurogenesis.

Direct lineage conversion:induced neuronal cells and induced neural stem cells

Cellular reprogramming to neural cells is an area of ongoing study in developmental neuroscience,and recent research has generated remarkable achieve-ments.Several studies have shown that the ectopic expression of specific neural transcription factors can convert terminally differentiated cells into neural cells.Here,we review the most recent progress in the field of induced neuronal(iN)cells and induced neural stem(iNS)cells and their potential clinical applications.

Acquisition of functional neurons by direct conversion:Switching the developmental clock directly

Identifying approaches for treating neurodegeneration is a thorny task but is important for a growing number of patients.Researchers have focused on discovering the underlying molecular mechanisms of reprogramming and optimizing the technologies for acquiring neurons.Direct conversion is one of the most important processes for treating neurological disorders.Induced neurons derived from direct conversion,which bypass the pluripotency stage,are more effective,more quickly obtained,and are safer than those produced via induced pluripotent stem cells(iPSCs).Based on iPSC strategies,scientists have derived methods to obtain functional neurons by direct conversion,such as neuron-related transcriptional factors,small molecules.microRNAs,and epigenetic modifiers.In this review,we discuss the present strategies for direct conversion of somatic cells into functional neurons and the potentials of direct conversion for producing functional neurons and treating neurodeeeneration.

Fc effector of anti-Aβ antibody induces synapse loss and cognitive deficits in Alzheimer’s disease-like mouse model

Passive immunotherapy is one of the most promising interventions for Alzheimer’s disease(AD).However,almost all immune-modulating strategies fail in clinical trials with unclear causes although they attenuate neuropathology and cognitive deficits in AD animal models.Here,we showed that Aβ-targeting antibodies including their lgG1 and lgG4 subtypes induced microglial engulfment of neuronal synapses by activating CR3 or FcγRIIb via the complex of Aβ,antibody,and complement.Notably,anti-Aβantibodies without Fc fragment,or with blockage of CR3 or FcγRIIb,did not exert these adverse effects.Consistently,Aβ-targeting antibodies,but not their Fab fragments,significantly induced acute microglial synapse removal and rapidly exacerbated cognitive deficits and neuroinflammation in APP/PS1 mice post-treatment,whereas the memory impairments in mice were gradually rescued thereafter.Since the recovery rate of synapses in humans is much lower than that in mice,our findings may clarify the variances in the preclinical and clinical studies assessing AD immunotherapies.Therefore,Aβ-targeting antibodies lack of Fc fragment,or with reduced Fc effector function,may not induce microglial synaptic pruning,providing a safer and more efficient therapeutic alternative for passive immunotherapy for AD.

Cancer cell employs a microenvironmental neural signal transactivating nucleus-mitochondria coordination to acquire stemness

Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive.Here,a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element(CRE)transcription factors are convergent activators for cancer stemness.Deconvolution of transcriptomic profiles,specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity.Specifically,neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis,where ATF1 serves as a conserved hub.Upon activation by norepinephrine,ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM,thereby orchestrating nuclear reprograming and mitochondrial rejuvenating.Accordingly,single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells.These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program,suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals.