High-quality haplotype-resolved genome assembly of cultivated octoploid strawberry.

Cultivated strawberry (Fragaria × ananassa), a perennial herb belonging to the family Rosaceae, is a complex octoploid with high heterozygosity at most loci. However, there is no research on the haplotype of the octoploid strawberry genome. Here we aimed to obtain a high-quality genome of the cultivated strawberry cultivar, "Yanli", using single molecule real-time sequencing and high-throughput chromosome conformation capture technology. The "Yanli" genome was 823 Mb in size, with a long terminal repeat assembly index of 14.99. The genome was phased into two haplotypes, Hap1 (825 Mb with contig N50 of 26.70 Mb) and Hap2 (808 Mb with contig N50 of 27.51 Mb). Using the combination of Hap1 and Hap2, we obtained for the first time a haplotype-resolved genome with 56 chromosomes for the cultivated octoploid strawberry. We identified a ~ 10 Mb inversion and translocation on chromosome 2-1. 104 957 and 102 356 protein-coding genes were annotated in Hap1 and Hap2, respectively. Analysis of the genes related to the anthocyanin biosynthesis pathway revealed the structural diversity and complexity in the expression of the alleles in the octoploid F. × ananassa genome. In summary, we obtained a high-quality haplotype-resolved genome assembly of F. × ananassa, which will provide the foundation for investigating gene function and evolution of the genome of cultivated octoploid strawberry.

Phosphorylation of KRT8 (keratin 8) by excessive mechanical load-activated PKN (protein kinase N) impairs autophagosome initiation and contributes to disc degeneration.

Excessive mechanical load (overloading) is a well-documented pathogenetic factor for many mechano stress-induced pathologies, i.e. intervertebral disc degeneration (IDD). Under overloading, the balance between anabolism and catabolism within nucleus pulposus (NP) cells are badly thrown off, and NP cells undergo apoptosis. However, little is known about how the overloading is transduced to the NP cells and contributes to disc degeneration. The current study shows that conditional knockout of Krt8 (keratin 8) within NP aggravates load-induced IDD in vivo, and overexpression of Krt8 endows NP cells greater resistance to overloading-induced apoptosis and degeneration in vitro. Discovery-driven experiments shows that phosphorylation of KRT8 on Ser43 by overloading activated RHOA-PKN (protein kinase N) impedes trafficking of Golgi resident small GTPase RAB33B, suppresses the autophagosome initiation and contributes to IDD. Overexpression of Krt8 and knockdown of Pkn1 and Pkn2, at an early stage of IDD, ameliorates disc degeneration; yet only knockdown of Pkn1 and Pkn2, when treated at late stage of IDD, shows a therapeutic effect. This study validates a protective role of Krt8 during overloading-induced IDD and demonstrates that targeting overloading activation of PKNs could be a novel and effective approach to mechano stress-induced pathologies with a wider window of therapeutic opportunity.Abbreviations: AAV: adeno-associated virus; AF: anulus fibrosus; ANOVA: analysis of variance; ATG: autophagy related; BSA: bovine serum albumin; cDNA: complementary deoxyribonucleic acid; CEP: cartilaginous endplates; CHX: cycloheximide; cKO: conditional knockout; Cor: coronal plane; CT: computed tomography; Cy: coccygeal vertebra; D: aspartic acid; DEG: differentially expressed gene; DHI: disc height index; DIBA: dot immunobinding assay; dUTP: 2'-deoxyuridine 5'-triphosphate; ECM: extracellular matrix; EDTA: ethylene diamine tetraacetic acid; ER: endoplasmic reticulum; FBS: fetal bovine serum; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GPS: group-based prediction system; GSEA: gene set enrichment analysis; GTP: guanosine triphosphate; HE: hematoxylin-eosin; HRP: horseradish peroxidase; IDD: intervertebral disc degeneration; IF: immunofluorescence staining; IL1: interleukin 1; IVD: intervertebral disc; KEGG: Kyoto encyclopedia of genes and genomes; KRT8: keratin 8; KD: knockdown; KO: knockout; L: lumbar vertebra; LBP: low back pain; LC/MS: liquid chromatograph mass spectrometer; LSI: mouse lumbar instability model; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MMP3: matrix metallopeptidase 3; MRI: nuclear magnetic resonance imaging; NC: negative control; NP: nucleus pulposus; PBS: phosphate-buffered saline; PE: p-phycoerythrin; PFA: paraformaldehyde; PI: propidium iodide; PKN: protein kinase N; OE: overexpression; PTM: post translational modification; PVDF: polyvinylidene fluoride; qPCR: quantitative reverse-transcriptase polymerase chain reaction; RHOA: ras homolog family member A; RIPA: radio immunoprecipitation assay; RNA: ribonucleic acid; ROS: reactive oxygen species; RT: room temperature; TCM: rat tail compression-induced IDD model; TCS: mouse tail suturing compressive model; S: serine; Sag: sagittal plane; SD rats: Sprague-Dawley rats; shRNA: short hairpin RNA; siRNA: small interfering RNA; SOFG: safranin O-fast green; SQSTM1: sequestosome 1; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VG/ml: viral genomes per milliliter; WCL: whole cell lysate.

Facet joint degeneration-An initial procedure of the cervical spine degeneration.

Objective: This study aims to emphasize the initiating role of facet joint (FJ) degeneration in the process of cervical spine degeneration induced by tangential load, and we further validate it in a novel cervical spine degeneration animal model. Methods: The characteristics of cervical degeneration in patients of different ages were summarized through case collection. In the rat models, Hematoxylin-Eosin, Safranin O staining, and micro-computed tomography were used to show the histopathological changes and bone fiber structure of FJ and the height of intervertebral disc (IVD) space. The ingrowth of nociceptive sensory nerve fibers was observed by immunofluorescence staining. Results: FJ degeneration without IVDs degeneration was more common in people with cervical spondylosis in young patients. The obvious degeneration phenotypes of the FJs preceded the IVDs at the same cervical segment in our animal model. The SP+ and CGRP+ sensory nerve fibers were observed in the articular subchondral bone of degenerated FJs and porous endplates of degenerated IVDs. Conclusion: The FJ degeneration may act as the major contributor to cervical spine degeneration in young people. The dysfunction of functional unit of spine, not a certain part of IVD tissue, results in the occurrence of cervical degeneration and neck pain.

Development of Line-Detected UV-Vis Absorption Microscope and Its Application to Quantitative Evaluation of Lithium Surface Reactivity.

Electrochemical reactions in practical batteries occur in confined environments where anode and cathode electrodes are separated only by a thin separator. Therefore, their electrochemical behaviors may differ from those obtained in the conventional experimental cells, where the two electrodes (working and counter electrodes) are largely separated compared to the batteries. The spatial and temporal distributions of the chemical species in the vicinity of each electrode are highly expected to be determined for quantitatively understanding the phenomena in confined environments. In the present study, we developed a line-detected UV-vis absorption microscope that simultaneously measures space-resolved UV-vis absorption spectra. This novel technique has been successfully applied to evaluate the reactivities of the highly reactive lithium (Li) surfaces in organic electrolyte solutions under in situ conditions. The quantitative evaluations of the dissolution rate of Li and the diffusion constant of the product were successfully realized by analyzing the space- and time-resolved absorption spectra based on Fick's law of diffusion. The microscopic technique is expected to open the door to understanding the fundamental electrochemistry in batteries.

SIRT5-related desuccinylation modification of AIFM1 protects against compression-induced intervertebral disc degeneration by regulating mitochondrial homeostasis.

Mitochondrial dysfunction plays a major role in the development of intervertebral disc degeneration (IDD). Sirtuin 5 (SIRT5) participates in the maintenance of mitochondrial homeostasis through its desuccinylase activity. However, it is still unclear whether succinylation or SIRT5 is involved in the impairment of mitochondria and development of IDD induced by excessive mechanical stress. Our 4D label-free quantitative proteomic results showed decreased expression of the desuccinylase SIRT5 in rat nucleus pulposus (NP) tissues under mechanical loading. Overexpression of Sirt5 effectively alleviated, whereas knockdown of Sirt5 aggravated, the apoptosis and dysfunction of NP cells under mechanical stress, consistent with the more severe IDD phenotype of Sirt5 KO mice than wild-type mice that underwent lumbar spine instability (LSI) surgery. Moreover, immunoprecipitation-coupled mass spectrometry (IP-MS) results suggested that AIFM1 was a downstream target of SIRT5, which was verified by a Co-IP assay. We further demonstrated that reduced SIRT5 expression resulted in the increased succinylation of AIFM1, which in turn abolished the interaction between AIFM1 and CHCHD4 and thus led to the reduced electron transfer chain (ETC) complex subunits in NP cells. Reduced ETC complex subunits resulted in mitochondrial dysfunction and the subsequent occurrence of IDD under mechanical stress. Finally, we validated the efficacy of treatments targeting disrupted mitochondrial protein importation by upregulating SIRT5 expression or methylene blue (MB) administration in the compression-induced rat IDD model. In conclusion, our study provides new insights into the occurrence and development of IDD and offers promising therapeutic approaches for IDD.

FveARF2 negatively regulates fruit ripening and quality in strawberry.

Auxin response factors (ARFs) are transcription factors that play important roles in plants. ARF2 is a member of the ARF family and participates in many plant growth and developmental processes. However, the role of ARF2 in strawberry fruit quality remains unclear. In this study, FveARF2 was isolated from the woodland strawberry 'Ruegen' using reverse transcription-polymerase chain reaction (RT-PCR), which showed that FveARF2 expression levels were higher in the stem than in other organs of the 'Ruegen' strawberry. Moreover, FaARF2 was higher in the white fruit stage of cultivated strawberry fruit than in other stage. Subcellular localization analysis showed that FveARF2 is located in the nucleus, while transcriptional activation assays showed that FveARF2 inhibited transcription in yeast. Silencing FveARF2 in cultivated strawberry fruit revealed earlier coloration and higher soluble solid, sugar, and anthocyanin content in the transgenic fruit than in the control fruit, overexpression of FveARF2 in strawberry fruit delayed ripening and lower soluble solid, sugar, and anthocyanin content compared to the control fruit. Gene expression analysis indicated that the transcription levels of the fruit ripening genes FaSUT1, FaOMT, and FaCHS increased in FveARF2-RNAi fruit and decreased in FveARF2-OE fruit, when compared with the control. Furthermore, yeast one-hybrid (Y1H) and GUS activity experiments showed that FveARF2 can directly bind to the AuxRE (TGTCTC) element in the FaSUT1, FaOMT, and FaCHS promoters in vitro and in vivo. Potassium ion supplementation improved the quality of strawberry fruit, while silencing FveARF2 increased potassium ion content in transgenic fruit. The Y1H and GUS activity experiments also confirmed that FveARF2 could directly bind to the promoter of FveKT12, a potassium transporter gene, and inhibited its expression. Taken together, we found that FveARF2 can negatively regulate strawberry fruit ripening and quality, which provides new insight for further study of the molecular mechanism of strawberry fruit ripening.

Targeting clock-controlled gene Nrf2 ameliorates inflammation-induced intervertebral disc degeneration.

BACKGROUND: Intervertebral disc (IVD) is a highly rhythmic tissue, which experiences a diurnal cycle of high/low mechanical loading via the changes of activity/rest phase. There are signs that disruption of the peripheral IVD clock is related to the process of intervertebral disc degeneration (IDD). However, it is still unclear whether inflammation could disturb the IVD clock and thus induce the process of IDD. METHODS AND RESULTS: In this study, we used IL-1ß, a commonly used inflammatory factor, to induce IDD and found that the IVD clock was dampened in degenerated human nucleus pulposus specimens, rat nucleus pulposus (NP) tissues, and cells. In this study, we found that the circadian clock of NP cells was totally disrupted by knockdown of the core clock gene brain and muscle arnt-like protein-1 (Bmal1), which thus induced the dysfunction of NP cells. Next, we explored the mechanism of dampened clock-induced IDD and found that knockdown of Bmal1 decreased the expression of nuclear factor erythroid2-related factor 2 (NRF2), a downstream target gene of Bmal1, and increased inflammatory response, oxidative stress reaction, and apoptosis of NP cells. In addition, NRF2 activation attenuated the dysfunction of NP cells induced by the dampened IVD clock and the degenerative process of NP tissues in an organotypic tissue-explant model. CONCLUSIONS: Taken together, our study extends the relationship between peripheral clock and IVD homeostasis and provides a potential therapeutic method for the prevention and recovery of IDD by targeting the clock-controlled gene Nrf2.

Decoding the annulus fibrosus cell atlas by scRNA-seq to develop an inducible composite hydrogel: A novel strategy for disc reconstruction.

Low back pain is one of the most serious public health problems worldwide and the major clinical manifestation of intervertebral disc degeneration (IVDD). The key pathological change during IVDD is dysfunction of the annulus fibrosus (AF). However, due to the lack of an in-depth understanding of AF biology, the methods to reconstruct the AF are very limited. In this study, the mice AF cell atlas were decoded by single-cell RNA sequencing to provide a guide for AF reconstruction. The results first identify a new population of AF cells, fibrochondrocyte-like AF cells, which synthesize both collagen I and collagen II and are potential functional cells for AF reconstruction. According to the dual features of the AF extracellular matrix, a composite hydrogel based on the acylation of methacrylated silk fibroin with methacrylated hyaluronic acid was produced. To obtain the ability to stimulate differentiation, the composite hydrogels were combined with a fibrochondrocyte-inducing supplement. Finally, reconstruction of the AF defects, by the novel AF stem cell-loaded composite hydrogel, could be observed, its amount of chondroid matrices recovered to 31.7% of AF aera which is significantly higher than that in other control groups. In summary, this study decodes the AF cell atlas, based on which a novel strategy for AF reconstruction is proposed.

Revealing the structure-activity relationship in woven covalent organic frameworks for the electrocatalytic oxygen reduction reaction.

Woven covalent organic frameworks (COFs) possess three-dimensional (3D) frameworks with well-dispersed variable metal centers, showing great promise in heterogeneous catalysis. Until now, woven COFs have not been exploited as catalysts. Herein, COF-112 (a typical woven COF) is utilized as an ORR catalyst to reveal the role of the metal center and linkage. Through metal center variation, the optimal COF-112Co with imine linkage exhibits superior ORR activity (Eonset = 0.87 V vs. RHE, n = 3.86, and JL = 5.78 mA cm-2). Experimental and theoretical studies demonstrate the non-metallic ORR active site and confirm the influence of metal variation in COF-112. A linkage conversion strategy reveals the importance of the imine linkage on the 4e- ORR. This work reveals the structure-activity relationship of woven COFs, which will broaden the application of COFs and extend the diversity of electrocatalysts.

Restoring the dampened expression of the core clock molecule BMAL1 protects against compression-induced intervertebral disc degeneration.

The circadian clock participates in maintaining homeostasis in peripheral tissues, including intervertebral discs (IVDs). Abnormal mechanical loading is a known risk factor for intervertebral disc degeneration (IDD). Based on the rhythmic daily loading pattern of rest and activity, we hypothesized that abnormal mechanical loading could dampen the IVD clock, contributing to IDD. Here, we investigated the effects of abnormal loading on the IVD clock and aimed to inhibit compression-induced IDD by targeting the core clock molecule brain and muscle Arnt-like protein-1 (BMAL1). In this study, we showed that BMAL1 KO mice exhibit radiographic features similar to those of human IDD and that BMAL1 expression was negatively correlated with IDD severity by systematic analysis based on 149 human IVD samples. The intrinsic circadian clock in the IVD was dampened by excessive loading, and BMAL1 overexpression by lentivirus attenuated compression-induced IDD. Inhibition of the RhoA/ROCK pathway by Y-27632 or melatonin attenuated the compression-induced decrease in BMAL1 expression. Finally, the two drugs partially restored BMAL1 expression and alleviated IDD in a diurnal compression model. Our results first show that excessive loading dampens the circadian clock of nucleus pulposus tissues via the RhoA/ROCK pathway, the inhibition of which potentially protects against compression-induced IDD by preserving BMAL1 expression. These findings underline the importance of the circadian clock for IVD homeostasis and provide a potentially effective therapeutic strategy for IDD.

Trace CO elimination in H2-rich streams with a wide operation temperature window: Co deposited CuO-CeO2 catalysts.

This work provides a new strategy to eliminate trace CO in H2-rich gas in a wide operation temperature window for the application of hydrogen fuel cells. We engineered Co deposited CuO-CeO2 catalysts with a Co/(Cu + Ce) molar ratio of 1/1 that manages to maintain the CO level at below 100 ppm from 85 to 240 °C in the H2-rich reformate stream. CO-PROX and CO methanation reaction respectively occurred in the low and high temperature ranges. Multiple characterization techniques demonstrate that the molar ratio of Co/(Cu + Ce) significantly affects the synergistic interactions between the Cu, Co and Ce species, and ultimately the CO oxidation and CO methanation reactions. At low reaction temperatures, the Cu-Ce interaction mainly dominates the CO-PROX process, while at high reaction temperatures, CO methanation reaction takes place due to the reduction of Co3O4 to Co0 and the Co-Ce interaction takes charge of the CO methanation. Moreover, the increment of Co/(Cu + Ce) from 1/2 to 1 gives rise to the reprecipitation of the partially dissolved Cu species on Co3O4, which strengthens the Cu-Co interaction and stabilizes surface Cu+ and Co3+, thus promoting the low temperature CO-PROX catalytic performance.

Elucidating the structure, redox properties and active entities of high-temperature thermally aged CuOx-CeO2 catalysts for CO-PROX.

CuOx-CeO2 catalysts with different copper contents are synthesized via a coprecipitation method and thermally treated at 700 °C. Various characterization techniques including X-ray diffraction (XRD) Rietveld refinement, N2 adsorption-desorption isotherms, X-ray photoelectron spectra (XPS), UV-Raman, high-resolution transmission electron microscopy (HRTEM), temperature-programmed reduction (TPR) and in situ diffuse reflectance infrared Fourier transform spectra (DRIFTs) were adopted to investigate the structure/texture properties, oxygen vacancies, Cu-Ce interaction and redox properties of the catalysts. After the thermal treatment, the catalysts exhibited outstanding catalytic properties for the preferential oxidation (PROX) of CO (with the T50% of 62 °C and the widest operation temperature window of 85-140 °C), which provided a new strategy for the design of Cu-Ce based catalysts with high catalytic performance. The characterization results indicated that moderately elevating the copper content (below 5%) increases the amount of highly dispersed Cu species in the catalysts, including highly dispersed surface CuOx species and strongly bonded Cu-[Ox]-Ce species, strengthening the Cu-Ce interaction, increasing oxygen vacancies and promoting redox properties, but a further increase in copper content causes the agglomeration of crystalline CuO and decreases the highly dispersed Cu species. This work also provides evidence from the perspective that the catalytic performance of CuOx-CeO2 catalysts for CO-PROX at low and high reaction temperatures is dependent on the redox properties of highly dispersed CuOx species and strongly bonded Cu-[Ox]-Ce species, respectively.

In-situ growth of NCNT and encapsulation of Co9S8/Co as a sustainable multifunctional electrocatalyst.

At present, the most effective catalytic materials are noble metals, which large-scale applications are strictly restricted by low reserve and high cost. For the development of sustainable energy, exploring cost-effective non-precious metal materials has therefore become an urgent task. As one of the promising candidates, the hybrid of transition metal sulfide and carbon-nitrogen skeleton attracts great attention due to variability, graded pore structure and high conductivity. Herein, a sustainable multifunctional electrocatalytic material has been designed and achieved by in-situ encapsulating Co9S8/Co in N-doped carbon nanotube (NCNT). Efficient multifunctional electrocatalysis towards oxygen reduction, oxygen evolution and hydrogen evolution reactions are realized. This work highlights the importance of rich Co-N and CoNC coupling centers generated by in-situ engineering transition metal sulfide into carbon-nitrogen skeleton for multifunctional catalytic conversion of sustainable energy. The results here may also be instructive for designing other complexes with perspective for catalysis, sensing, energy storage and conversion.

Doping effect of transition metals (Zr, Mn, Ti and Ni) on well-shaped CuO/CeO2(rods): nano/micro structure and catalytic performance for selective oxidation of CO in excess H2.

A series of CuO/CeM(rod) catalysts doped by transition metals were prepared and systematically characterized. The introduction of Mn and Ti plays a significant role in promoting the catalytic performance of the CuO/CeO2(rod) catalyst for the preferential oxidation of CO in H2-rich gas, while the doping with Zr basically maintains the same catalytic activity and Ni leads to a negative influence. Mn and Ti additives remarkably enrich the formation of defect structures and promote copper ion incorporation into the surface of CeM(rod), which greatly facilitates the generation of strong interfacial copper-ceria interaction in CuO/CeMn(rod) and CuO/CeTi(rod). In addition, CuO/CeMn(rod) possesses excellent surface oxygen mobility at low temperature due to the existence of manganese species with multiple valence states and todorokite species. The Ce-doped perovskite structure (Na0.5Ce0.5TiO3) further adjusts the oxygen vacancy in CuO/CeTi(rod) and anchors copper oxide species with strong interactions. Although a homogeneous solid solution is formed in CeZr(rod) with increased amounts of oxygen vacancies, the interaction between copper and ceria species in the interface of CuO/CeZr(rod) remains the same as with CuO/CeO2(rod). The addition of Ni impairs the dispersion of copper oxide and weakens the copper-ceria interaction, which damages the catalytic performance of CuO/CeNi(rod).

Direct electrochemical growth of amorphous molybdenum sulfide nanosheets on Ni foam for high-performance supercapacitors.

Crystalline molybdenum sulfides (MoSx) have gained much attention as electrode materials for supercapacitors due to their specific atomic structure and high theoretical specific capacitance. However, poor electric conductivity and few accessible active sites as well as strictly controlled synthetic processes limit their capacitive performances. In this work, amorphous MoSx (a-MoSx) nanosheets with porous structure was directly grown on Ni foam by a simple and low-cost electrodeposition technique. By using a-MoSx/Ni foam directly as the electrode material for supercapacitor, a high specific capacitance of 463 F/g was achieved at 1 A/g with good cycling stability at high rate. The isotropic and porous natures as well as ion reservoir function of the amorphous phase offers abundant active sites, transportation channels for ions and large electrode/electrolyte contact area, ensuring facile electrolyte diffusion within the active material. The strong adhesive of electrodeposited material to the underlying Ni foam substrate constructs an effective electron transport channel during the charging and discharging process. This work highlights the importance of electrodeposited amorphous MoSx for potential application in supercapacitors.

Polysaccharides from Ganoderma lucidum Promote Cognitive Function and Neural Progenitor Proliferation in Mouse Model of Alzheimer's Disease.

Promoting neurogenesis is a promising strategy for the treatment of cognition impairment associated with Alzheimer's disease (AD). Ganoderma lucidum is a revered medicinal mushroom for health-promoting benefits in the Orient. Here, we found that oral administration of the polysaccharides and water extract from G. lucidum promoted neural progenitor cell (NPC) proliferation to enhance neurogenesis and alleviated cognitive deficits in transgenic AD mice. G. lucidum polysaccharides (GLP) also promoted self-renewal of NPC in cell culture. Further mechanistic study revealed that GLP potentiated activation of fibroblast growth factor receptor 1 (FGFR1) and downstream extracellular signal-regulated kinase (ERK) and AKT cascades. Consistently, inhibition of FGFR1 effectively blocked the GLP-promoted NPC proliferation and activation of the downstream cascades. Our findings suggest that GLP could serve as a regenerative therapeutic agent for the treatment of cognitive decline associated with neurodegenerative diseases.

Neurogenesis-Promoting Natural Product α-Asarone Modulates Morphological Dynamics of Activated Microglia.

α-Asarone is an active constituent of Acori Tatarinowii, one of the widely used traditional Chinese Medicine to treat cognitive defect, and recently is shown to promote neurogenesis. Here, we demonstrated that low level (3 µM) of α-asarone attenuated LPS-induced BV2 cell bipolar elongated morphological change, with no significant effect on the LPS-induced pro-inflammatory cytokine expressions. In addition, time-lapse analysis also revealed that α-asarone modulated LPS-induced BV2 morphological dynamics. Consistently a significant reduction in the LPS-induced Monocyte Chemoattractant Protein (MCP-1) mRNA and protein levels was also detected along with the morphological change. Mechanistic study showed that the attenuation effect to the LPS-resulted morphological modulation was also detected in the presence of MCP-1 antibodies or a CCR2 antagonist. This result has also been confirmed in primary cultured microglia. The in vivo investigation provided further evidence that α-asarone reduced the proportion of activated microglia, and reduced microglial tip number and maintained the velocity. Our study thus reveals α-asarone effectively modulates microglial morphological dynamics, and implies this effect of α-asarone may functionally relate to its influence on neurogenesis.

A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation.

Aberrant neural progenitor cell (NPC) proliferation and self-renewal have been linked to age-related neurodegeneration and neurodegenerative disorders including Alzheimer's disease (AD). Rhizoma Acori tatarinowii is a traditional Chinese herbal medicine against cognitive decline. In this study, we found that the extract of Rhizoma Acori tatarinowii (AT) and its active constituents, asarones, promote NPC proliferation. Oral administration of AT enhanced NPC proliferation and neurogenesis in the hippocampi of adult and aged mice as well as that of transgenic AD model mice. AT and its fractions also enhanced the proliferation of NPCs cultured in vitro. Further analysis identified α-asarone and ß-asarone as the two active constituents of AT in promoting neurogenesis. Our mechanistic study revealed that AT and asarones activated extracellular signal-regulated kinase (ERK) but not Akt, two critical kinase cascades for neurogenesis. Consistently, the inhibition of ERK activities effectively blocked the enhancement of NPC proliferation by AT or asarones. Our findings suggest that AT and asarones, which can be orally administrated, could serve as preventive and regenerative therapeutic agents to promote neurogenesis against age-related neurodegeneration and neurodegenerative disorders.

The anti-spasticity drug baclofen alleviates collagen-induced arthritis and regulates dendritic cells.

Baclofen is used clinically as a drug that treats spasticity, which is a syndrome characterized by excessive contraction of the muscles and hyperflexia in the central nervous system (CNS), by activating GABA(B) receptors (GABA(B)Rs). Baclofen was recently reported to desensitize chemokine receptors and to suppress inflammation through the activation of GABA(B)Rs. GABA(B)Rs are expressed in various immune cells, but the functions of these receptors in autoimmune diseases remain largely unknown. In this study, we investigated the effects of baclofen in murine collagen-induced arthritis (CIA). Oral administration of baclofen alleviated the clinical development of CIA, with a reduced number of IL-17-producing T helper 17 (T(H)17) cells. In addition, baclofen treatment suppressed dendritic cell (DC)-primed T(H)17 cell differentiation by reducing the production of IL-6 by DCs in vitro. Furthermore, the pharmacological and genetic blockade of GABA(B)Rs in DCs weakened the effects of baclofen, indicating that GABA(B)Rs are the molecular targets of baclofen on DCs. Thus, our findings revealed a potential role for baclofen in the treatment of CIA, as well as a previously unknown signaling pathway that regulates DC function.