Association analyses between the variants of SNAP25, SV2C and ST3GAL2 and the efficacy of botulinum toxin A in the treatment of the primary Meige syndrome.

Objective: Individual differences were observed in the clinical efficacy of Botulinum toxin A (BoNT-A) in the treatment of the primary Meige syndrome. Our study aimed to explore the potential associations between the clinical efficacy of BoNT-A in the treatment of the primary Meige syndrome and variants of SNAP25, SV2C and ST3GAL2, which are involving in the translocation of the BoNT-A in vivo. Methods: Patients with the primary Meige syndrome treated with BoNT-A were enrolled. Clinical efficacy was evaluated by the maximum improvement rate of motor symptoms and the duration of efficacy. Variants of SNAP25, SV2C and ST3GAL2 were obtained by Sanger sequencing. Another cohort diagnosed with primary cervical dystonia was also enrolled in the replication stage. Results: Among the 104 primary Meige syndrome patients, 80 patients (76.9%) had a good efficacy (the maximum improvement rate of motor symptoms ≥30%) and 24 (23. 1%) had a poor (the maximum improvement rate of motor symptoms <30%). As to the duration of efficacy, 52 patients (50.0%) had a long duration of efficacy (≥4 months), and 52 (50.0%) had a short (<4 months). In terms of primary Meige syndrome, SNAP25 rs6104571 was found associating with the maximum improvement rate of motor symptoms (Genotype: P = 0.02, OR = 0.26; Allele: P = 0.013, OR = 0.29), and SV2C rs31244 was found associating with the duration of efficacy (Genotype: P = 0.024, OR = 0.13; Allele: P = 0.012, OR = 0.13). Besides, we also conducted the association analyses between the variants and BoNT-A-related adverse reactions. Although, there was no statistical difference between the allele of SV2C rs31244 and BoNT-A-related adverse reactions, there was a trend (P = 0.077, OR = 2.56). In the replication stage, we included 39 patients with primary cervical dystonia to further expanding the samples' size. Among the 39 primary cervical dystonia patients, 25 patients (64.1%) had a good efficacy (the maximum improvement rate of motor symptoms ≥50%) and 14 (35.9%) had a poor (the maximum improvement rate of motor symptoms <50%). As to the duration of efficacy, 32 patients (82.1%) had a long duration of efficacy (≥6 months), and 7 (17.9%) had a short (<6 months). Integrating primary Meige syndrome and primary cervical dystonia, SV2C rs31244 was still found associating with the duration of efficacy (Genotype: P = 0.002, OR = 0. 23; Allele: P = 0.001, OR = 0. 25). Conclusion: In our study, SNAP25 rs6104571 was associated with the maximum improvement rate of motor symptoms in patients with primary Meige syndrome treated with BoNT-A, and patients carrying this variant had a lower improvement rate of motor symptoms. SV2C rs31244 was associated with duration of treatment in patients with primary Meige syndrome treated with BoNT-A and patients carrying this variant had a shorter duration of treatment. Patients with primary Meige syndrome carrying SV2C rs31244 G allele have an increase likelihood of BoNT-A-related adverse reactions. Involving 39 patients with primary cervical dystonia, the results further verify that SV2C rs31244 was associated with duration of treatment and patients carrying this variant had a shorter duration of treatment.

Botulinum neurotoxin A ameliorates depressive-like behavior in a reserpine-induced Parkinson's disease mouse model via suppressing hippocampal microglial engulfment and neuroinflammation.

Depression is one of the common non-motor symptoms of Parkinson's disease (PD). In the clinic, botulinum neurotoxin A (BoNT/A) has been used to treat depression. In this study, we investigated the mechanisms underlying the anti-depressive effect of BoNT/A in a PD mouse model. Mice were administered reserpine (3 µg/mL in the drinking water) for 10 weeks. From the 10th week, BoNT/A (10 U·kg-1·d-1) was injected into the cheek for 3 consecutive days. We showed that chronic administration of reserpine produced the behavioral phenotypes of depression and neurochemical changes in the substantia nigra pars compacta (SNpc) and striatum. BoNT/A treatment significantly ameliorated the depressive-like behaviors, but did not improve TH activity in SNpc of reserpine-treated mice. We demonstrated that BoNT/A treatment reversed reserpine-induced complement and microglia activation in the hippocampal CA1 region. Furthermore, BoNT/A treatment significantly attenuated the microglial engulfment of presynaptic synapses, thus ameliorating the apparent synapse and spine loss in the hippocampus in the reserpine-treated mice. Moreover, BoNT/A treatment suppressed microglia-mediated expression of pro-inflammatory cytokines TNF-α and IL-1ß in reserpine-treated mice. In addition, we showed that BoNT/A (0.1 U/mL) ameliorated reserpine-induced complement and microglia activation in mouse BV2 microglial cells in vitro. We conclude that BoNT/A ameliorates depressive-like behavior in a reserpine-induced PD mouse model through reversing the synapse loss mediated by classical complement induced-microglial engulfment as well as alleviating microglia-mediated proinflammatory responses. BoNT/A ameliorates depressive-like behavior, and reverses synapse loss mediated by classical complement pathway-initiated microglia engulfment as well as alleviates microglia-mediated proinflammatory response in the reserpine-induced Parkinson's disease mouse model.

Magnetic Fe3O4 embedded chitosan-crosslinked-polyacrylamide composites with enhanced removal of food dye: Characterization, adsorption and mechanism.

The water solubility in acid solution, relative low adsorption capacities and unsatisfactory separation performance limit application of traditional chitosan-based adsorbents in wastewater treatment. To break the limitation, a hydrophilic magnetic Fe3O4 embedded chitosan-crosslinked-polyacrylamide composites (abbreviated as m-CS-c-PAM) were prepared by a two-step method. The m-CS-c-PAM composites were systematically characterized using SEM, XRD, FTIR, VSM, TGA and BET. Sunset yellow (SY) was selected as model food dye to investigate adsorption kinetics and thermodynamic parameters of food dye adsorption onto m-CS-c-PAM. Compared with magnetic Fe3O4/chitosan, m-CS-c-PAM can adapt to a wider range of pH (2-10) and resist the presence of inorganic salts. m-CS-c-PAM was proved to have high adsorption capacity (359.71 mg g-1) for SY dye at 298 K, much higher than magnetic Fe3O4/chitosan and many reported adsorbents. Moreover, m-CS-c-PAM could be rapidly and efficiently separated from treated solution within 15 s by an external magnet and regenerated by NaOH solution. With its excellent adsorption capacity, pH-independent adsorption capability for food dye, easy and convenient separation ability, satisfactory reusability, m-CS-c-PAM can be a promising material for food wastewater treatment.

Quzhi Formula Alleviates Nonalcoholic Steatohepatitis by Impairing Hepatocyte Lipid Accumulation and Inflammation via Bip/eIF2α Signaling.

Background and Aims: The Quzhi formula, a Chinese medicine compound prescription, relieves nonalcoholic steatohepatitis (NASH) symptoms. This study aimed to explore the mechanism of the Quzhi formula against NASH. Methods: A choline-deficient, L-amino acid-defined, high-fat diet induced a NASH mouse model and a free fatty acid-induced mouse hepatocyte cell model were used to evaluate the function of Quzhi formula in vivo and in vitro. Network pharmacology and molecular docking technology were performed to uncover the possible protective mechanisms of the Quzhi formula against NASH. Key factors in liver lipid metabolism and endoplasmic reticulum (ER) stress pathway were evaluated to verify the mechanism. Results: The positive contribution of the Quzhi formula on NASH was confirmed in vivo and in vitro. Abnormal accumulation of lipid in the liver and inflammatory responses were significantly decreased by the Quzhi formula. Network pharmacological analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that the Quzhi formula protected against NASH by regulating ER stress and inflammatory responses, which was enhanced by further molecular docking analysis. In addition, mechanism exploration showed that Quzhi formula mainly reduced ER stress by downregulating Bip/eIF2α signaling. Conclusions: The Quzhi formula protected against NASH by inhibiting lipid accumulation, ER stress, and inflammatory responses, which supports the potential use of Quzhi formula as an alternative treatment for NASH.

The Arabidopsis J-Protein AtDjC5 Facilitates Thermotolerance Likely by Aiding in the ER Stress Response.

AtDjC5 belongs to the J-protein family in Arabidopsis thaliana. Its biological functions remain unclear. In this study, we examined the roles of AtDjC5 in resisting heat stress using reverse genetic analysis. After the seedlings were exposed directly to 44 °C for 90 min, AtDjC5 knockout seedlings displayed decreases in the survival rate, membrane system stability, and cell vitality compared to WT seedlings, indicating that AtDjC5 is involved in plant basal thermotolerance. The AtDjC5 knockout seedlings pre-exposed to 37 °C for 30 min exhibited decreases in the survival rate and total chlorophyll contents and increased cell death when they were subsequently exposed to 45 °C compared to the WT seedlings, indicating that AtDjC5 plays an important role in plant acquired thermotolerance. AtDjC5 was found to localize to the endoplasmic reticulum. The expression of the AtDjC5 gene was induced by heat and TM (an ER stress inducer) treatment. Furthermore, we found that the knockout of AtDjC5 inhibited ER stress-induced autophagy and the expression of ER stress-related genes. Taken together, these results suggest that AtDjC5 facilitates thermotolerance, likely by aiding in the ER stress response.

A Comprehensive Evolutionary Study of Chloroplast RNA Editing in Gymnosperms: A Novel Type of G-to-A RNA Editing Is Common in Gymnosperms.

Although more than 9100 plant plastomes have been sequenced, RNA editing sites of the whole plastome have been experimentally verified in only approximately 21 species, which seriously hampers the comprehensive evolutionary study of chloroplast RNA editing. We investigated the evolutionary pattern of chloroplast RNA editing sites in 19 species from all 13 families of gymnosperms based on a combination of genomic and transcriptomic data. We found that the chloroplast C-to-U RNA editing sites of gymnosperms shared many common characteristics with those of other land plants, but also exhibited many unique characteristics. In contrast to that noted in angiosperms, the density of RNA editing sites in ndh genes was not the highest in the sampled gymnosperms, and both loss and gain events at editing sites occurred frequently during the evolution of gymnosperms. In addition, GC content and plastomic size were positively correlated with the number of chloroplast RNA editing sites in gymnosperms, suggesting that the increase in GC content could provide more materials for RNA editing and facilitate the evolution of RNA editing in land plants or vice versa. Interestingly, novel G-to-A RNA editing events were commonly found in all sampled gymnosperm species, and G-to-A RNA editing exhibits many different characteristics from C-to-U RNA editing in gymnosperms. This study revealed a comprehensive evolutionary scenario for chloroplast RNA editing sites in gymnosperms, and reported that a novel type of G-to-A RNA editing is prevalent in gymnosperms.

Melatonin inhibits angiotensin II-induced atrial fibrillation through preventing degradation of Ang II Type I Receptor-Associated Protein (ATRAP).

Angiotensin II (Ang II) induced Atrial fibrillation (AF) often accompanied with reduced ATRAP which is a negative modulator of Ang II type 1 receptor (AT1R). Melatonin can protect against AF, but the underlying molecular mechanism remains poorly understood. In this study, Ang II was used to induce AF, and AF inducibility and duration were documented telemetrically. Ang II-infused mice had a higher AF incidence, which was associated with atrial fibrosis, inflammation, and oxidative stress. Melatonin partially inhibited these effects, and enforced expression of siRNA-ATRAP in atria counteracted the beneficial role of melatonin. Specifically, melatonin inhibited expression of Ang II-induced proteasome and immunoproteasome subunits ß2, ß2i, ß5, and ß5i as well as their corresponding trypsin-like and chymotrypsin-like activities and blocked ATRAP degradation. In turn, this inhibited AT1R-mediated NF-κB signaling, transforming growth factor (TGF)-ß1/Smad signaling in the atria, and thereby affected atrial remodeling and AF. Melatonin receptor inhibition by the chemical inhibitor luzindole partially inhibited the inhibitory effects of melatonin on proteasome activity and also Ang II-induced pathological changes in the atria. Overall, our study demonstrates that melatonin protects against Ang II-induced AF by inhibiting proteasome activity and stabilizing ATRAP expression, and these effects are partially dependent on melatonin receptor activation.

Increased miR-155 in Microglial Exosomes Following Heat Stress Accelerates Neuronal Autophagy via Their Transfer Into Neurons.

Background: Heat stroke is the outcome of excessive heat stress, which results in core temperatures exceeding 40°C accompanied by a series of complications. The brain is particularly vulnerable to damage from heat stress. In our previous studies, both activated microglia and increased neuronal autophagy were found in the cortices of mice with heat stroke. However, whether activated microglia can accelerate neuronal autophagy under heat stress conditions is still unknown. In this study, we aimed to investigate the underlying mechanism that caused neuronal autophagy upregulation in heat stroke from the perspective of exosome-mediated intercellular communication. Methods: In this study, BV2 and N2a cells were used instead of microglia and neurons, respectively. Exosomes were extracted from BV2 culture supernatants by ultracentrifugation and then characterized via transmission electron microscopy, nanoparticle tracking analysis and Western blotting. N2a cells pretreated with/without miR-155 inhibitor were cocultured with microglial exosomes that were treated with/without heat stress or miR-155 overexpression and subsequently subjected to heat stress treatment. Autophagy in N2a cells was assessed by detecting autophagosomes and autophagy-related proteins through transmission electron microscopy, immunofluorescence, and Western blotting. The expression of miR-155 in BV2 and BV2 exosomes and N2a cells was measured using real-time reverse transcription polymerase chain reaction. Target binding analysis was verified via a dual-luciferase reporter assay. Results: N2a autophagy moderately increased in response to heat stress and accelerated by BV2 cells through transferring exosomes to neurons. Furthermore, we found that neuronal autophagy was positively correlated with the content of miR-155 in microglial exosomes. Inhibition of miR-155 partly abolished autophagy in N2a cells, which was increased by coculture with miR-155-upregulated exosomes. Mechanistic analysis confirmed that Rheb is a functional target of miR-155 and that microglial exosomal miR-155 accelerated heat stress-induced neuronal autophagy mainly by regulating the Rheb-mTOR signaling pathway. Conclusion: Increased miR-155 in microglial exosomes after heat stroke can induce neuronal autophagy via their transfer into neurons. miR-155 exerted these effects by targeting Rheb, thus inhibiting the activity of mTOR signaling. Therefore, miR-155 could be a promising target for interventions of neuronal autophagy after heat stroke.

Measuring of strain parameters reflects changes of right ventricular function before and after thrombolytic therapy in patients with acute pulmonary embolism.

Strain parameters on speckle tracking echocardiography (STE) have been proposed as effective indexes for evaluating right ventricular (RV) function. This pilot study investigated the role of STE-derived strain parameters in assessing global and regional RV myocardial mechanical changes in patients with acute pulmonary embolism (PE) before and after thrombolytic therapy. In this case-control study, a total of 73 PE patients, 34 with pulmonary hypertension (PH) and 39 without PH, who underwent thrombolytic therapy were included. Healthy volunteers were included as controls. The peak longitudinal systolic strain (PLSS) and time to PLSS (TTP) for the global and regional RV were analyzed by STE software immediately before and 14 days after thrombolytic therapy. Changes in STE-derived strain parameters and conventional ultrasound parameters were compared. PLSS and TTP decreased before treatment in PE patients compared with measurements in the control group, particularly in those with PH. Also, the strain parameters decreased more significantly for the free wall than for the septum wall (P < 0.05). Moreover, the RV diastolic diameter (RVDD) and RV/left ventricular (LV) diameter ratio increased, while RV fraction shortening (RVFS), RV fractional area change (RVFAC), tricuspid regurgitation pressure gradient (TRPG), and tricuspid annular peak systolic excursion (TAPSE) decreased (P < 0.05). The global strain parameters for the RV were positively correlated with RVDD and RV/LV diameter ratio, but negatively correlated with RVFS, RVFAC, TRPG, and TAPSE (P < 0.05). After treatment, the strain parameters differed significantly between PE patients with PH and controls but did not differ between PE patients without PH and controls. STE-derived parameters are effective for detecting changes in global and regional RV function in PE patients with or without acute PH.

Spatiotemporal Evolution of the Global Species Diversity of Rhododendron.

Evolutionary radiation is a widely recognized mode of species diversification, but its underlying mechanisms have not been unambiguously resolved for species-rich cosmopolitan plant genera. In particular, it remains largely unknown how biological and environmental factors have jointly driven its occurrence in specific regions. Here, we use Rhododendron, the largest genus of woody plants in the Northern Hemisphere, to investigate how geographic and climatic factors, as well as functional traits, worked together to trigger plant evolutionary radiations and shape the global patterns of species richness based on a solid species phylogeny. Using 3,437 orthologous nuclear genes, we reconstructed the first highly supported and dated backbone phylogeny of Rhododendron comprising 200 species that represent all subgenera, sections, and nearly all multispecies subsections, and found that most extant species originated by evolutionary radiations when the genus migrated southward from circumboreal areas to tropical/subtropical mountains, showing rapid increases of both net diversification rate and evolutionary rate of environmental factors in the Miocene. We also found that the geographically uneven diversification of Rhododendron led to a much higher diversity in Asia than in other continents, which was mainly driven by two environmental variables, that is, elevation range and annual precipitation, and were further strengthened by the adaptation of leaf functional traits. Our study provides a good example of integrating phylogenomic and ecological analyses in deciphering the mechanisms of plant evolutionary radiations, and sheds new light on how the intensification of the Asian monsoon has driven evolutionary radiations in large plant genera of the Himalaya-Hengduan Mountains.

Combined laparoscopic-endoscopic approach for gastric glomus tumor: A case report.

BACKGROUND: Gastric glomus tumor (GGT) is rare submucosal mesenchymal tumor that lacks specific clinical manifestations and is usually treated mainly by traditional surgical resection. This paper presents a case of a GGT, exhibited both intraluminally and extraluminally growth that was removed by laparoscopy-gastroscopy cooperative surgery. CASE SUMMARY: A 52-year-old male presented with epigastric discomfort accompanied by a sense of fullness for 3 mo. Upper gastrointestinal endoscopy identified a submucosal lump located in the gastric antrum. Endoscopic ultrasonography identified a 2.4 cm × 1.8 cm lump located in the gastric antrum. It originated from the muscularis propria and exhibited both intraluminally and extraluminally growth, with hypoechoicity on the periphery, hyperechoicity in the middle, and unclear boundaries. Computed tomography showed nodular thickening of 3.0 cm × 2.2 cm in the gastric wall of the gastric antrum, and after enhancement, the lesion exhibited obvious enhancement We suspected that it was a gastrointestinal stromal tumor (glomus tumor and schwannoma were not excluded) and planned to perform laparoscopy-gastroscopy cooperative surgery. Immunohistochemical staining after the operation revealed that spinal muscular atrophy (+), h-caldesmon (+), cluster of differentiation 34 (CD34) (+), 2% Ki-67-positive rate, CD56, melanoma antigen, CD117, discovered on GIST-1, leukocyte common antigen, caudal type homeobox 2, cytokeratin, and S-100 were all negative. The tumor was finally diagnosed as a GGT. CONCLUSION: GGTs are rare submucosal tumors of the stomach and should be considered in the differential diagnosis of gastric submucosal tumors. Laparoscopy-gastroscopy cooperative surgery is less invasive and more precise and could be an effective method for the treatment of GGTs.

The involvement of microglial CX3CR1 in heat acclimation-induced amelioration of adult hippocampal neurogenesis impairment in EMF-exposed mice.

Microglial CX3C chemokine receptor 1 (CX3CR1) has been implicated in numerous cellular mechanisms, including signalling pathways that regulate brain homoeostasis and adult hippocampal neurogenesis. Specific environmental conditions can impair hippocampal neurogenesis-related cognition, learning and memory. However, the role of CX3CR1 in the neurogenic alterations resulting from the cross-tolerance protection conferred by heat acclimation (HA) against the effects of electromagnetic field (EMF) exposure is less well understood. Here, we investigated the role of microglial CX3CR1 signalling in adult hippocampal neurogenesis induced by HA in EMF-exposed mice. We found that EMF exposure significantly decreased the number of proliferating and differentiating cells in the dentate gyrus (DG) of the hippocampus, resulting in a reduced neurogenesis rate. Moreover, alterations in the phenotypes of activated microglia and decreased expression levels of CX3CR1, but not sirtuin 1 (SIRT1), were observed in the brains of EMF-exposed mice. Remarkably, HA treatment improved microglial phenotypes, restored the expression of CX3CR1, and ameliorated the decrease in the adult hippocampal neurogenesis rate following EMF exposure. Moreover, pharmacological inhibition of CX3CR1 and SIRT1 failed to restore CX3CR1 expression and ameliorate hippocampal neurogenesis impairment following HA plus EMF stimulation. These results indicate that microglial CX3CR1 is involved in the cross-tolerance protective effect of HA on adult hippocampal neurogenesis upon EMF exposure.

Both Conifer II and Gnetales are characterized by a high frequency of ancient mitochondrial gene transfer to the nuclear genome.

BACKGROUND: Mitochondrial gene transfer/loss is common in land plants, and therefore the fate of missing mitochondrial genes has attracted more and more attention. The gene content of gymnosperm mitochondria varies greatly, supplying a system for studying the evolutionary fate of missing mitochondrial genes. RESULTS: Here, we studied the tempo and pattern of mitochondrial gene transfer/loss in gymnosperms represented by all 13 families, using high-throughput sequencing of both DNA and cDNA. All 41 mitochondrial protein-coding genes were found in cycads, Ginkgo and Pinaceae, whereas multiple mitochondrial genes were absent in Conifer II and Gnetales. In Conifer II, gene transfer from mitochondria to the nucleus followed by loss of the mitochondrial copy was common, but complete loss of a gene in both mitochondrial and nuclear genomes was rare. In contrast, both gene transfer and loss were commonly found in Gnetales. Notably, in Conifer II and Gnetales, the same five mitochondrial genes were transferred to the nuclear genome, and these gene transfer events occurred, respectively, in ancestors of the two lineages. A two-step transfer mechanism (retroprocessing and subsequent DNA-mediated gene transfer) may be responsible for mitochondrial gene transfer in Conifer II and Gnetales. Moreover, the mitochondrial gene content variation is correlated with gene length, GC content, hydrophobicity, and nucleotide substitution rates in land plants. CONCLUSIONS: This study reveals a complete evolutionary scenario for variations of mitochondrial gene transferring in gymnosperms, and the factors responsible for mitochondrial gene content variation in land plants.

Phylotranscriptomics reveals the complex evolutionary and biogeographic history of the genus Tsuga with an East Asian-North American disjunct distribution.

The disjunct distribution between East Asia and North America is one of the best established biogeographic patterns. A robust phylogeny is fundamental for understanding the biogeographic histories of taxa with this distribution pattern. Tsuga (hemlock) is a genus of Pinaceae with a typical intercontinental disjunct distribution in East Asia and eastern and western North America, and its phylogeny has not been completely reconstructed in previous studies. In this study, we reconstructed a highly resolved phylogeny of Tsuga using 881 nuclear genes, 60 chloroplast genes and 23 mitochondrial genes and explored its biogeographic and reticulate evolutionary history. The results of phylogenetic analysis, molecular dating and ancestral area reconstruction indicate that Tsuga very likely originated from North America in the late Oligocene and dispersed from America to East Asia via the Bering Land Bridge during the middle Miocene. In particular, we found complex reticulate evolutionary pattern among the East Asian hemlock species. T. sieboldii possibly originated from hybridization with the ancestor of T. chinensis from mainland China and T. forrestii as the paternal donor and the ancestor of T. diversifolia and T. ulleungensis as the maternal donor. T. chinensis (Taiwan) could have originated by hybridization together with T. sieboldii and then evolved independently after dispersal to the Taiwan Island, subsequently experiencing mitochondrial DNA introgression with T. chinensis from mainland China. Moreover, our study found that T. chinensis from western China is more closely related to T. forrestii than to T. chinensis from eastern China. The nonmonophyletic T. chinensis needs taxonomic reconsideration.

Two cyclometalated Pt(ii) complexes showing reversible phosphorescence switching due to grinding-induced destruction and crystallization-induced formation of supramolecular dimer structure.

Complexes [Pt(dfppy)(pbdtmi)]PF6 (1) and [Pt(ppy)(pbdtmi)]PF6 (2) have been constructed based on dithienylethene-based N^N ligand pbdtmi, showing supramolecular dimer structure in which two coordination cations connect each other through π⋯π stacking interaction. The crystalline state samples of both 1 and 2 reveal strong phosphorescence (emission peak: around 579 nm for 1, and 551 nm for 2). Interestingly, a grinding treatment for either 1 or 2 leads to phosphorescence switching from on-state to off-state. The subsequent crystallization with toluene recovers the initial on-state. This work discusses the relationship between the supramolecular dimer structures and the related phosphorescence switching behaviors in 1 and 2, and also explores the photochromism of pbdtmi, 1 and 2.

Vitamin D affects the neutrophil-to-lymphocyte ratio in patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: Chronic inflammation is an underlying feature of type 2 diabetes mellitus. Hypovitaminosis D is associated with type 2 diabetes mellitus, but whether it contributes to chronic inflammation is unclear. We examined the effects of vitamin D on various immune markers to evaluate its contribution to systemic inflammation in type 2 diabetes mellitus. MATERIALS AND METHODS: We retrospectively analyzed data from type 2 diabetes mellitus patients, people with prediabetes and control patients without diabetes (n = 9,746). Demographic and clinical variables were evaluated using descriptive statistics and generalized linear regression. A stratified analysis based on total serum vitamin D was also carried out. RESULTS: Neutrophil count was a significant predictor of 1,5-anhydroglucitol and glycated hemoglobin (HbA1c) in patients with prediabetes (1,5-anhydroglucitol: ß = -0.719, P < 0.001 and HbA1c: ß = -0.006, P = 0.002) and patients with diabetes (1,5-anhydroglucitol: ß = 0.207, P = 0.004 and HbA1c: ß = -0.067, P = 0.010). Lymphocyte count was a significant predictor of HbA1c in patients without diabetes (ß = 0.056, P < 0.001) and patients with prediabetes (ß = 0.038, P < 0.001). The neutrophil-to-lymphocyte ratio (NLR) was a significant predictor of HbA1c in patients without diabetes (ß = -0.001, P = 0.032). No immune markers differed significantly based on vitamin D level among patients without diabetes (P> 0.05 for all). Among patients with prediabetes, those who were vitamin D-deficient had the highest NLR (P = 0.040). Among patients with diabetes, those who were vitamin D-deficient had the highest neutrophil count (P = 0.001), lowest lymphocyte count (P = 0.016) and highest NLR (P < 0.001). CONCLUSIONS: The NLR is strongly influenced by serum vitamin D level. Given the high prevalence of hypovitaminosis D and elevated NLR among chronic disease patients and the elderly, our results suggest that clinical interpretation of NLR as a predictive marker of type 2 diabetes mellitus-related inflammation should consider vitamin D level, age and pre-existing morbidity.

The complete mitochondrial genome of Taxus cuspidata (Taxaceae): eight protein-coding genes have transferred to the nuclear genome.

BACKGROUND: Gymnosperms represent five of the six lineages of seed plants. However, most sequenced plant mitochondrial genomes (mitogenomes) have been generated for angiosperms, whereas mitogenomic sequences have been generated for only six gymnosperms. In particular, complete mitogenomes are available for all major seed plant lineages except Conifer II (non-Pinaceae conifers or Cupressophyta), an important lineage including six families, which impedes a comprehensive understanding of the mitogenomic diversity and evolution in gymnosperms. RESULTS: Here, we report the complete mitogenome of Taxus cuspidata in Conifer II. In comparison with previously released gymnosperm mitogenomes, we found that the mitogenomes of Taxus and Welwitschia have lost many genes individually, whereas all genes were identified in the mitogenomes of Cycas, Ginkgo and Pinaceae. Multiple tRNA genes and introns also have been lost in some lineages of gymnosperms, similar to the pattern observed in angiosperms. In general, gene clusters could be less conserved in gymnosperms than in angiosperms. Moreover, fewer RNA editing sites were identified in the Taxus and Welwitschia mitogenomes than in other mitogenomes, which could be correlated with fewer introns and frequent gene losses in these two species. CONCLUSIONS: We have sequenced the Taxus cuspidata mitogenome, and compared it with mitogenomes from the other four gymnosperm lineages. The results revealed the diversity in size, structure, gene and intron contents, foreign sequences, and mutation rates of gymnosperm mitogenomes, which are different from angiosperm mitogenomes.

Phylogenomics disentangles the evolutionary history of spruces (Picea) in the Qinghai-Tibetan Plateau: Implications for the design of population genetic studies and species delimitation of conifers.

A laborious and difficult task in current tree of life reconstruction is to resolve evolutionary relationships of closely related congeneric species that originated from recent radiations. This is particularly difficult for forest species with long generation times and large effective population sizes such as conifers. The Qinghai-Tibetan Plateau (QTP) and adjacent areas are considered a species diversity center of Picea, harboring 11 species (including 5 varieties) of this genus, but evolutionary relationships of these species are far from being resolved due to recent radiations, morphological convergence, and frequent interspecific gene flow. In this study, we use these spruce species to test whether phylotranscriptomic analysis, combined with population genetic analysis, can disentangle their evolutionary relationships, and to explore whether reticulate evolution has occurred among them. Phylogenomic analyses indicate that all spruce species in the QTP and neighboring areas, except P. asperata and P. crassifolia, cluster together, and in particular, nearly all taxa (including varieties) reflect reciprocally monophyletic lineages, although the two species P. likiangensis and P. brachytyla are not monophyletic. We found that, compared to herbaceous plants, many more genes (a minimum of 600 OGs for Picea) are required to resolve interspecific relationships of conifers. Contrary to previous studies, our data do not support a hybrid origin of P. purpurea, but suggests a hybrid origin for P. brachytyla var. brachytyla and P. likiangensis var. rubescens. We emphasize that the species or species complex used for population genetic and phylogeographical studies should be monophyletic.

Phylotranscriptomics resolves interspecific relationships and indicates multiple historical out-of-North America dispersals through the Bering Land Bridge for the genus Picea (Pinaceae).

A robust phylogeny is prerequisite to understand the evolution and biogeography of organisms. However, ancient and recent evolutionary radiations occurred in many plant lineages, which pose great challenges for phylogenetic analysis, especially for conifers characterized by large effective population sizes and long generation times. Picea is an important component of the dark coniferous forests in the Northern Hemisphere. Previous studies improved our understanding of its evolutionary history, but its interspecific relationships and biogeographic history remain largely unresolved. In the present study, we reconstructed a well-resolved phylogeny of Picea by comparative transcriptomic analysis based on a complete species sampling. The phylogenetic analysis, together with molecular dating and ancestral area reconstruction, further supports the North American origin hypothesis for Picea, and indicates that this genus experienced multiple out-of-North America dispersals by the Bering Land Bridge. We also found that spruces in the Japanese Archipelago have multiple origins, and P. morrisonicola from the Taiwan Island has a close relationship with species from the Qinghai-Tibetan Plateau and adjacent regions. Our study provides the first complete phylogeny of Picea at the genomic level, which is important for future studies of this genus.

MicroRNA-155 Promotes Heat Stress-Induced Inflammation via Targeting Liver X Receptor α in Microglia.

Background: The neuroinflammatory responses of microglial cells play an important role in the process of brain dysfunction caused by heat stroke. MicroRNAs are reportedly involved in a complex signaling network and have been identified as neuroinflammatory regulators. In this study, we determined the biological roles of microRNA-155 in the inflammatory responses in heat-stressed microglia and explored the underlying mechanisms. Methods: MicroRNA-155 mimic and inhibitor were used to separately upregulate or downregulate microRNA-155 expression. The activation state of BV-2 microglial cells (BV-2 cells) was assessed via immunoreactions using the microglial marker CD11b and CD68. Levels of induced interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using real-time reverse transcription polymerase chain reaction (RT-PCR) and enzyme linked immunosorbent assays (ELISAs). The activation of nuclear factor kappa B (NF-κB) signaling proteins was evaluated by Western blotting for inhibitory kappa B alpha (IκBα) and NF-κB p65 phosphorylation and indirect immunofluorescence analysis using a p65 phosphorylation antibody. A luciferase reporter assay was used to verify liver X receptor α (LXRα) as a target gene of microRNA-155. Results: Heat stress significantly induced IL-1ß, IL-6, and TNF-α release and increased the expression of CD11b and CD68. In addition, IκBα and NF-κB p65 phosphorylation were dramatically increased by heat stress, and microRNA-155 expression was also elevated. High expression of microRNA-155 in heat-stressed microglial cells was inversely correlated with LXRα expression. We then determined the role of microRNA-155 in the heat stress-induced inflammatory responses. The results revealed that by targeting LXRα, microRNA-155 enhanced NF-κB signaling activation and facilitated immune inflammation in heat stress-treated BV-2 cells. Conclusion: MicroRNA-155 promotes heat stress-induced inflammatory responses in microglia. The underlying mechanisms may include facilitating inflammatory factors expression by increasing NF-κB pathway activation via targeting LXRα.