Infiltration by monocytes of the central nervous system and its role in multiple sclerosis: reflections on therapeutic strategies

Mononuclear macrophage infiltration in the central nervous system is a prominent feature of neuroinflammation. Recent studies on the pathogenesis and progression of multiple sclerosis have highlighted the multiple roles of mononuclear macrophages in the neuroinflammatory process. Monocytes play a significant role in neuroinflammation, and managing neuroinflammation by manipulating peripheral monocytes stands out as an effective strategy for the treatment of multiple sclerosis, leading to improved patient outcomes. This review outlines the steps involved in the entry of myeloid monocytes into the central nervous system that are targets for effective intervention: the activation of bone marrow hematopoiesis, migration of monocytes in the blood, and penetration of the blood–brain barrier by monocytes. Finally, we summarize the different monocyte subpopulations and their effects on the central nervous system based on phenotypic differences. As activated microglia resemble monocyte-derived macrophages, it is important to accurately identify the role of monocyte-derived macrophages in disease. Depending on the roles played by monocyte-derived macrophages at different stages of the disease, several of these processes can be interrupted to limit neuroinflammation and improve patient prognosis. Here, we discuss possible strategies to target monocytes in neurological diseases, focusing on three key aspects of monocyte infiltration into the central nervous system, to provide new ideas for the treatment of neurodegenerative diseases.

Heteroatom substitution-induced asymmetric A–D–A type non-fullerene acceptor for efficient organic solar cells

Research on asymmetric A–D–A structured non-fullerene acceptors has lagged far behind the development of symmetric counterpart.In this contribution,by simply replacing one sulfur atom in indacenodithiophene unit with a selenium atom,an asymmetric building block Se PT and a corresponding asymmetric non-fullerene acceptor Se PT-IN have been developed.Asymmetric Se PT-IN achieved a high efficiency of 10.20% in organic solar cells when blended with PBT1-C,much higher than that of symmetric TPT-IN counterpart(8.91%).Our results demonstrated an effective heteroatom substitution strategy to develop asymmetric A–D–A structured non-fullerene acceptors.

Arabidopsis PRK6 interacts specifically with AtRopGEF8/12 and induces depolarized growth of pollen tubes when overexpressed

The pollen receptor kinases (PRK) are critical regulators of pollen tube growth. The Arabidopsis genome encodes eight PRK genes, of which six are highly expressed in pollen tubes. The potential functions of AtPRK1 through AtPRK5, but not of AtPRK6,in pollen growth were analyzed in tobacco. Herein, AtPRK6 was cloned, and its function was identified. AtPRK6 was expressed specifically in pollen tubes. A yeast two-hybrid screen of AtPRK6 against 14 Arabidopsis Rop guanine nucleotide exchange factors (RopGEFs) showed that AtPRK6 interacted with AtRopGEF8 and AtRopGEF12. These interactions were confirmed in Arabidopsis mesophyll protoplasts. The interactions between AtPRK6 and AtRopGEF8/12 were mediated by the C-termini of AtRopGEF8/12 and by the juxtamembrane and kinase domain of AtPRK6, but were not dependent on the kinase activity. In addition, transient overexpression of AtPRK6::GFP in Arabidopsis protoplasts revealed that AtPRK6 was localized to the plasma membrane. Tobacco pollen tubes overexpressing AtPRK6 exhibited shorter tubes with enlarged tips. This depolarized tube growth required the kinase domain of AtPRK6 and was not dependent on kinase activity. Taken together, the results show that AtPRK6,through its juxtamembrane and kinase domains (KD), interacts with AtRopGEF8/12 and plays crucial roles in polarized growth of pollen tubes.

A transceptor-channel complex couples nitrate sensing to calcium signaling in Ambidopsis

Nitrate-induced Ca^(2+) signaling is crucial for the primary nitrate response in plants.However,the molecular mechanism underlying the generation of the nitrate-specific calcium signature remains unknown.We report here that a cyclic nucleotide-gated channel(CNGC)protein,CNGC15,and the nitrate transceptor(NRT1.1)constitute a molecular switch that controls calcium influx depending on nitrate levels.The expression of CNGC15 is induced by nitrate,and its protein is localized at the plasma membrane after establishment of young seedlings.We found that disruption of CNGC15 results in the loss of the nitrate-induced Ca^(2+) signature(primary nitrate response)and retards root growth,reminiscent of the phenotype observed in the nrt1.1 mutant.We further showed that CNGC15 is an active Ca^(2+)-permeable channel that physically interacts with the NRT1.1 protein in the plasma membrane.Importantly,we discovered that CNGC15-NRT1.1 interaction silences the channel activity of the heterocomplex,which dissociates upon a rise in nitrate levels,leading to reactivation of the CNGC15 channel.The dynamic interactions between CNGC15 and NRT1.1 therefore control the channel activity and Ca^(2+) influx in a nitrate-dependent manner.Our study reveals a new nutrient-sensing mechanism that utilizes a nutrient transceptor-channel complex assembly to couple nutrient status to a specific Ca^(2+) signature.

A chloride efflux transporter,BIG RICE GRAIN 1,is involved in mediating grain size and salt tolerance in rice

Grain size is determined by the size and number of cells in the grain.The regulation of grain size is crucial for improving crop yield;however,the genes and molecular mechanisms that control grain size remain elusive.Here,we report that a member of the detoxification efflux carrier/Multidrug and Toxic Compound Extrusion(DTX/MATE)family transporters,BIG RICE GRAIN 1(BIRG1),negatively influences grain size in rice(Oryza sativa L.).BIRG1 is highly expressed in reproductive organs and roots.In birg1 grain,the outer parenchyma layer cells of spikelet hulls are larger than in wild-type(WT)grains,but the cell number is unaltered.When expressed in Xenopus laevis oocytes,BIRG1 exhibits chloride efflux activity.Consistent with this role of BIRG1,the birg1 mutant shows reduced tolerance to salt stress at a toxic chloride level.Moreover,grains from birg1 plants contain a higher level of chloride than those of WT plants when grown under normal paddy field conditions,and the roots of birg1 accumulate more chloride than those of WT under saline conditions.Collectively,the data suggest that BIRG1 in rice functions as a chloride efflux transporter that is involved in mediating grain size and salt tolerance by controlling chloride homeostasis.