Rhythmic cilia changes support SCN neuron coherence in circadian clock.

The suprachiasmatic nucleus (SCN) drives circadian clock coherence through intercellular coupling, which is resistant to environmental perturbations. We report that primary cilia are required for intercellular coupling among SCN neurons to maintain the robustness of the internal clock in mice. Cilia in neuromedin S-producing (NMS) neurons exhibit pronounced circadian rhythmicity in abundance and length. Genetic ablation of ciliogenesis in NMS neurons enabled a rapid phase shift of the internal clock under jet-lag conditions. The circadian rhythms of individual neurons in cilia-deficient SCN slices lost their coherence after external perturbations. Rhythmic cilia changes drive oscillations of Sonic Hedgehog (Shh) signaling and clock gene expression. Inactivation of Shh signaling in NMS neurons phenocopied the effects of cilia ablation. Thus, cilia-Shh signaling in the SCN aids intercellular coupling.

Total Flavonoids of Astragalus Inhibit Activated CD4[Formula: see text] T Cells and Regulate Differentiation of Th17/Th1/Treg Cells in Experimental Autoimmune Encephalomyelitis Mice by JAK/STAT and NF[Formula: see text]B Signaling Pathways.

Multiple sclerosis (MS) is a neuroinflammatory disease characterized by CD4[Formula: see text] T cell-mediated immune cell infiltration and demyelination in the central nervous system (CNS). The subtypes of CD4[Formula: see text] T cells are T helper cells 1 (Th1), Th2, Th17, and regulatory T cells (Treg), while three other types of cells besides Th2 play a key role in MS and its classic animal model, experimental autoimmune encephalomyelitis (EAE). Tregs are responsible for immunosuppression, while pathogenic Th1 and Th17 cells cause autoimmune-associated demyelination. Therefore, suppressing Th1 and Th17 cell differentiation and increasing the percentage of Treg cells may contribute to the treatment of EAE/MS. Astragali Radix (AR) is a representative medicine with immunoregulatory, anti-inflammatory, antitumor, and neuroprotective effects.The active ingredients in AR include astragalus flavones, polysaccharides, and saponins. In this study, it was found that the total flavonoids of Astragus (TFA) could effectively treat EAE in mice by ameliorating EAE motor disorders, reducing inflammatory damage and demyelination, inhibiting the proportion of Th17 and Th1 cells, and promoting Tregs differentiation by regulating the JAK/STAT and NF[Formula: see text]B signaling pathways. This novel finding may increase the possibility of using AR or TFA as a drug with immunomodulatory effects for the treatment of autoimmune diseases.

Astragaloside IV ameliorates metabolic disorder in db/db obese mice as a PPARγ antagonist.

Metabolic disorder is highly related to obesity, insulin resistance, hypertension, and hyperlipidemia. The present study found that astragaloside IV (ASI) attenuated metabolic disorder related symptoms and modulated hepatic lipid metabolism associated gene mRNA expression in db/db mice. ASI inhibited rosiglitazone-induced adipocyte differentiation of 3T3-L1 cells, and lipid accumulation in palmitic acid (PA)-induced HepG2 cells with down-regulated mRNA expression of lipogenesis-related genes. In addition, it was predicted to bind to the ligand binding domain (LBD) of PPARγ and inhibit its transactivity. Collectively, our study suggested that ASI improves lipid metabolism in obese mice probably through suppressing PPARγ activity.

LUBAC regulates ciliogenesis by promoting CP110 removal from the mother centriole.

Primary cilia transduce diverse signals in embryonic development and adult tissues. Defective ciliogenesis results in a series of human disorders collectively known as ciliopathies. The CP110-CEP97 complex removal from the mother centriole is an early critical step for ciliogenesis, but the underlying mechanism for this step remains largely obscure. Here, we reveal that the linear ubiquitin chain assembly complex (LUBAC) plays an essential role in ciliogenesis by targeting the CP110-CEP97 complex. LUBAC specifically generates linear ubiquitin chains on CP110, which is required for CP110 removal from the mother centriole in ciliogenesis. We further identify that a pre-mRNA splicing factor, PRPF8, at the distal end of the mother centriole acts as the receptor of the linear ubiquitin chains to facilitate CP110 removal at the initial stage of ciliogenesis. Thus, our study reveals a direct mechanism of regulating CP110 removal in ciliogenesis and implicates the E3 ligase LUBAC as a potential therapy target of cilia-associated diseases, including ciliopathies and cancers.

Effects of Eucommia ulmoides extract against renal injury caused by long-term high purine diets in rats.

Diets of overloaded purine-rich foods for a long time are one of the important reasons to cause renal lesions. Eucommia ulmoides is one of the traditional Chinese medicine herbs, which has been used to recover functions of the kidney. However, its mechanism remains unclear. The aim of this study was to explore the effects and protective mechanism of Eucommia ulmoides extract on renal injury caused by long-term high purine diets in rats. SD rats underwent an intragastric adenine (200 mg kg-1 d-1) administration for 9 weeks and were treated for 15 weeks. The results demonstrated that Eucommia ulmoides extract significantly reduced serum Cre and BUN levels in rats. H&E and Masson's trichrome stains showed notable lowering of the infiltration of inflammatory cells, the formation of fibrous tissues and collagen fibers, and improvement in the pathological morphology of kidneys. It also suppressed the protein and mRNA expressions of TGF-ß1 and α-SMA and enhanced E-cadherin expression. Meanwhile, Eucommia ulmoides extract prominently inhibited the mRNA expression of Col I, Col III, Col IV, TIMP-1, and TIMP-2 and promoted expressions of MMP-1, MMP-2 and MMP-9. Through our study, it is the first time to prove that Eucommia ulmoides extract could ameliorate renal interstitial fibrosis and may involve in the regulation of the extracellular matrix (ECM) degradation enzyme (MMPs/TIMPs) system, promotion of the expression of E-cadherin, and suppression of expressions of TGF-ß1 and α-SMA. The results provide a significant implication for the utilization of Eunomia Ulmoides extract as functional foods to enhance renal functions and improve renal injury caused by high purine diets.

LPA signaling acts as a cell-extrinsic mechanism to initiate cilia disassembly and promote neurogenesis.

Dynamic assembly and disassembly of primary cilia controls embryonic development and tissue homeostasis. Dysregulation of ciliogenesis causes human developmental diseases termed ciliopathies. Cell-intrinsic regulatory mechanisms of cilia disassembly have been well-studied. The extracellular cues controlling cilia disassembly remain elusive, however. Here, we show that lysophosphatidic acid (LPA), a multifunctional bioactive phospholipid, acts as a physiological extracellular factor to initiate cilia disassembly and promote neurogenesis. Through systematic analysis of serum components, we identify a small molecular-LPA as the major driver of cilia disassembly. Genetic inactivation and pharmacological inhibition of LPA receptor 1 (LPAR1) abrogate cilia disassembly triggered by serum. The LPA-LPAR-G-protein pathway promotes the transcription and phosphorylation of cilia disassembly factors-Aurora A, through activating the transcription coactivators YAP/TAZ and calcium/CaM pathway, respectively. Deletion of Lpar1 in mice causes abnormally elongated cilia and decreased proliferation in neural progenitor cells, thereby resulting in defective neurogenesis. Collectively, our findings establish LPA as a physiological initiator of cilia disassembly and suggest targeting the metabolism of LPA and the LPA pathway as potential therapies for diseases with dysfunctional ciliogenesis.

CEP55 promotes cilia disassembly through stabilizing Aurora A kinase.

Primary cilia protrude from the cell surface and have diverse roles during development and disease, which depends on the precise timing and control of cilia assembly and disassembly. Inactivation of assembly often causes cilia defects and underlies ciliopathy, while diseases caused by dysfunction in disassembly remain largely unknown. Here, we demonstrate that CEP55 functions as a cilia disassembly regulator to participate in ciliopathy. Cep55-/- mice display clinical manifestations of Meckel-Gruber syndrome, including perinatal death, polycystic kidneys, and abnormalities in the CNS. Interestingly, Cep55-/- mice exhibit an abnormal elongation of cilia on these tissues. Mechanistically, CEP55 promotes cilia disassembly by interacting with and stabilizing Aurora A kinase, which is achieved through facilitating the chaperonin CCT complex to Aurora A. In addition, CEP55 mutation in Meckel-Gruber syndrome causes the failure of cilia disassembly. Thus, our study establishes a cilia disassembly role for CEP55 in vivo, coupling defects in cilia disassembly to ciliopathy and further suggesting that proper cilia dynamics are critical for mammalian development.

[Clinical features of coronavirus disease 2019 in children aged <18 years in Jiangxi, China: an analysis of 23 cases].

OBJECTIVE: To study the clinical features of coronavirus disease 2019 (COVID-19) in children aged <18 years. METHODS: A retrospective analysis was performed from the medical data of 23 children, aged from 3 months to 17 years and 8 months, who were diagnosed with COVID-19 in Jiangxi, China from January 21 to February 29, 2020. RESULTS: Of the 23 children with COVID-19, 17 had family aggregation. Three children (13%) had asymptomatic infection, 6 (26%) had mild type, and 14 (61%) had common type. Among these 23 children, 16 (70%) had fever, 11 (48%) had cough, 8 (35%) had fever and cough, and 8 (35%) had wet rales in the lungs. The period from disease onset or the first nucleic acid-positive detection of SARS-CoV-2 to the virus nucleic acid negative conversion was 6-24 days (median 12 days). Of the 23 children, 3 had a reduction in total leukocyte count, 2 had a reduction in lymphocytes, 2 had an increase in C-reactive protein, and 2 had an increase in D-dimer. Abnormal pulmonary CT findings were observed in 12 children, among whom 9 had patchy ground-glass opacities in both lungs. All 23 children received antiviral therapy and were recovered. CONCLUSIONS: COVID-19 in children aged <18 years often occurs with family aggregation, with no specific clinical manifestation and laboratory examination results. Most of these children have mild symptoms and a good prognosis. Epidemiological history is of particular importance in the diagnosis of COVID-19 in children aged <18 years.

[Correlation between color of Scutellariae Radix pieces and content of five flavonoids after softening and cutting by different methods].

Scutellariae Radix is one of the commonly used heat-clearing and damp-drying drugs in clinical practice. Establishment of the quality evaluation system for Scutellariae Radix is of great significance to ensure safety and effectiveness of clinical drug use.Scutellariae Radix pieces were prepared under different processing conditions with 3 softening methods: boiling,atmospheric steaming and pressurized steaming. High performance liquid chromatography( HPLC) method was used to determine the content of five flavonoids in Scutellariae Radix,and L*,a*,b*values representing color chromaticity of Scutellariae Radix powder were measured by colorimeter,then total color value E*was calculated. Simple correlation and canonical correlation analysis was used to explore the correlation between color of Scutellariae Radix powder and content of five flavonoids. The results showed that the contents of baicalin and wogonoside were significantly positively correlated with L*,b*and E*values,but negatively correlated with a*value. The contents of wogonin,apigenin,and melaleuca A were positively correlated with a*value,but negatively correlated with L*,b*,and E*values( P<0. 01). There was a significant negative correlation between the content of flavonoid glycosides and flavonoid aglycones( P<0. 01).All of these indicated that the color of Scutellariae Radix powder was significantly correlated with content of five flavonoids. The experiment results proved that when color difference between Huangqin pieces and medicinal materials was kept at ΔL*<6,Δb*<3,ΔE*<6,the total amount of the two glycosides in the pieces was about ±1. 5% of the medicinal materials; in this case,the total amount of the two glycosides was relatively high and stable,indicating that the color of Huangqin decoction pieces is a concrete manifestation of its intrinsic quality,and the chromaticity value detected by colorimeter can be used as a means to quickly evaluate the quality of Scutellariae Radix pieces. The results provide a new detection index for the characteristic quality evaluation system of Scutellariae Radix pieces.

Rab7 regulates primary cilia disassembly through cilia excision.

The primary cilium is a sensory organelle that protrudes from the cell surface. Primary cilia undergo dynamic transitions between assembly and disassembly to exert their function in cell signaling. In this study, we identify the small GTPase Rab7 as a novel regulator of cilia disassembly. Depletion of Rab7 potently induced spontaneous ciliogenesis in proliferating cells and promoted cilia elongation during quiescence. Moreover, Rab7 performs an essential role in cilia disassembly; knockdown of Rab7 blocked serum-induced ciliary resorption, and active Rab7 was required for this process. Further, we demonstrate that Rab7 depletion significantly suppresses cilia tip excision, referred to as cilia ectocytosis, which has been identified as required for cilia disassembly. Mechanically, the failure of F-actin polymerization at the site of excision of cilia tips caused suppression of cilia ectocytosis on Rab7 depletion. Overall, our results suggest a novel function for Rab7 in regulating cilia ectocytosis and cilia disassembly via control of intraciliary F-actin polymerization.

[Edge effect of the plant community structure on land-bridge islands in the Thousand Island Lake].

The research was conducted on 29 land-bridge islands in the Thousand Island Lake (TIL), where long-term monitoring plots were set up during 2009-2010. The community attributes including species richness, Shannon index, plant mean height, plant mean diameter at breast height (DBH) and plant density along the edge-interior gradient from edge to interior forest were calculated to investigate the edge effect. The results showed that the species richness and Shannon index were affected through the whole gradient (larger than 50 m), while the range of edge effect was 20-30 m on mean plant height, and 10 m on plant density and mean DBH. Community attributes differed significantly among the edge gradients. The species richness and Shannon index peaked at the intermediate edge gradient. Plant density decreased and plant mean height increased along the edge to interior gradient. All five community attributes were significantly associated with the edge gradient, also different functional groups, evergreen or deciduous species, trees or shrubs, shade tolerant or shade intolerant species, were differentially influenced by the edge effect. It was demonstrated the influence of edge effect on the fragmented forest community varied with community attributes and functional groups.

[Dynamics of soil arthropod community structure and its responses to forest fragmentation during the decomposition of Castanopsis eyrei leaf litter].

Five evergreen broad-leaved forests (one continuous forest and four fragmented forests) in the mountain areas in the juncture of Zhejiang, Fujian, and Jiangxi Provinces, East China were selected as test objects to study the dynamics of soil arthropod community structure and its responses to forest fragmentation during the decomposition of dominant tree species Castanopsis eyrei leaf litter. A total of 899 soil arthropods were collected, belonging to 9 classes and 25 orders. Lepidoptera was the dominant taxon, accounting for 10% of the individual, while Hymenoptera, Collembola, Diptera, Prostigmata, and Geophilomorpha were the common taxa. The decomposition rate of C. eyrei leaf litter was the highest in August and lower in April-June and December, which was in accordance with the seasonal dynamics of the taxa number and individual number of soil arthropods. Meanwhile, the taxa number, individual number, and species diversity of soil arthropods differed between continuous forest and fragmented forests, suggesting that both area effect and edge effect affected the dynamics of soil arthropod community structure during the decomposition of C. eyrei leaf litter.

[Decomposition of Schima superba leaf litter and dynamics change of soil meso-micro arthropods community structure in evergreen broad-leaved forest fragments].

Taking four evergreen broad-leaved forest fragments within the adjacent mountainous region of Zhejiang, Fujian, and Jiangxi provinces as study objects, and the continuous forest in Gutianshan National Natural Reserve as the control, an investigation was made by litter bag method from June 2004 to April 2006, aimed to understand the community structure and its dynamics change of soil meso-micro arthropods during the decomposition of Schima superba leaf litter. A total of 1050 soil meso-micro arthropods belonging to 8 classes and 23 orders were collected, among which, Lepidoptera, Hymenoptera, Collembola and Diptera were the dominant taxa. The impact of habitat fragmentation on the community composition of soil arthropods was mainly manifested in the differences of rare taxa, and the dominance of different taxa at different decomposition stages of S. superba leaf litter varied with the functions of the taxa in litter decomposition. After two-year decomposition, the mass loss of S. superba leaf litter was 60%-70%, and the species diversity indices of soil arthropods showed certain changes, being different between forest fragments and continuous forest.