OsGA3ox genes regulate rice fertility and plant height by synthesizing diverse active GA.

Gibberellin (GA) is an important hormone, which is involved in regulating various growth and development. GA biosynthesis pathway and synthetase have been basically clarified. Gibberellin 3ß hydroxylase (GA3ox) is the key enzyme for the synthesis of various active GA. There are two GA3ox genes (OsGA3ox1 and OsGA3ox2) in rice, and their physiological functions have been preliminarily studied. However, it is not clear how they work together to synthesize active GA to regulate rice development. In this study, the knockout mutants ga3ox1 and ga3ox2 were obtained by CRISPR/Cas9 technology. The pollen fertility of ga3ox1 decreased significantly, while the plant height of ga3ox2 decreased significantly. It shows that OsGA3ox1 is necessary for normal pollen development, while OsGA3ox2 is necessary for stem and leaf elongation. Tissue expression analysis showed that OsGA3ox1 was mainly expressed in unopened flowers, while OsGA3ox2 was mainly expressed in unexpanded leaves. The GA in different tissues of wild type (WT), and two ga3ox mutants were detected. It was found that pollen fertility is most closely related to the content of GA7, and plant height is most closely related to the content of GA1. It was found that OsGA3ox1 catalyzes GA9 to GA7 in flowers, which is closely related to pollen fertility; OsGA3ox2 catalyzes the GA20 to GA1 in unexpanded leaves, thereby regulating plant height; OsGA3ox1 catalyzes the GA19 to GA20 in roots, regulating the generation of GA3. OsGA3ox1 and OsGA3ox2 respond to developmental and environmental signals, and cooperate to synthesize endogenous GA in different tissues to regulate rice development. This study provides a reference for clarifying its role in GA biosynthesis pathway and further understanding the function of OsGA3ox.

The sage genome provides insight into the evolutionary dynamics of diterpene biosynthesis gene cluster in plants.

The widely cultivated medicinal and ornamental plant sage (Salvia officinalis L.) is an evergreen shrub of the Lamiaceae family, native to the Mediterranean. We assembled a high-quality sage genome of 480 Mb on seven chromosomes, and identified a biosynthetic gene cluster (BGC) encoding two pairs of diterpene synthases (diTPSs) that, together with the cytochromes P450 (CYPs) genes located inside and outside the cluster, form two expression cascades responsible for the shoot and root diterpenoids, respectively, thus extending BGC functionality from co-regulation to orchestrating metabolite production in different organs. Phylogenomic analysis indicates that the Salvia clades diverged in the early Miocene. In East Asia, most Salvia species are herbaceous and accumulate diterpenoids in storage roots. Notably, in Chinese sage S. miltiorrhiza, the diterpene BGC has contracted and the shoot cascade has been lost. Our data provide genomic insights of micro-evolution of growth type-associated patterning of specialized metabolite production in plants.

Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL/6 mice and AC16 cells.

PURPOSE: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. METHODS: Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. RESULTS: PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-ß1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. CONCLUSION: PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1ß, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

Clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging.

BACKGROUND: Syphilitic myelitis caused by Treponema pallidum is an extremely rare disease. However, symptomatic neurosyphilis, especially syphilitic myelitis, and its clinical features have been infrequently reported. Only a few cases of syphilitic myelitis have been documented. To the best of our knowledge, there are only 19 reported cases of syphilitic myelitis. However, the clinical features of syphilitic myelitis with longitudinally extensive myelopathy have been still not clear. AIM: To explore the clinical features of syphilitic myelitis with longitudinally extensive myelopathy on spinal magnetic resonance imaging (MRI). METHODS: First, we report a patient who suffered from syphilitic myelitis with symptoms of sensory disturbance, with longitudinally extensive myelopathy with "flip-flop sign" on spinal MRI. Second, we performed a literature search to identify other reports (reviews, case reports, or case series) from January 1987 to December 2018, using the PubMed and Web of Science databases with the terms including "syphilis", "neurosyphilis", "syphilitic myelitis", "meningomyelitis", "central nervous system", and "spine". We also summarized the clinical features of syphilitic myelitis with longitudinally extensive myelopathy. RESULTS: A total of 16 articles of 20 cases were identified. Sixteen patients presented with the onset of sensory disturbance (80%), 15 with paraparesis (75%), and 9 with urinary retention (45%). Eleven patients had a high risk behavior (55%). Five patients had concomitant human immunodeficiency virus infection (25%). Serological data showed that 15 patients had positive venereal disease research laboratory test (VDRL)/treponema pallidum particle agglutination (TPHA), and 17 had positive VDRL/TPHA in cerebrospinal fluid (CSF). Seventeen patients were found to have elevated leukocytosis and protein in CSF. On MRI, 16 patients showed abnormal hyperintensities involved the thoracic spine, 6 involved the cervical spine, and 3 involved both the cervical and thoracic spine. There were 3 patients with the "flip-flop sign". All the patients were treated with penicillin, and 15 patients had a good prognosis. CONCLUSION: Our case further raises awareness of syphilitic myelitis as an important complication of neurosyphilis due to homosexuality, especially in developing countries such as China.

Clinical Correlation of Magnetic Resonance Imaging Features of Cerebral Small Vessel Disease.

OBJECTIVE: We have discussed the clinical features and neuroimaging findings and investigated the correlations between the clinical characteristics and different neuroradiologic phenotypes of cerebral small vessel disease (CSVD). METHODS: A total of 1106 patients with a diagnosis of CSVD were enrolled. The demographic data, medical history, laboratory test results, and neuroimaging findings were retrieved for analysis. The differences in clinical parameters between patient groups were examined. The relationships between the clinical parameters and neuroradiologic phenotypes (i.e., white matter lesions [WMLs] and enlarged perivascular spaces) were assessed. The magnetic resonance imaging features were clustered using the fast clustering algorithm. RESULTS: Approximately one third of our patients presented with a lacune, which was associated with atrial fibrillation (P = 0.029), lacunar syndrome (P < 0.001), periventricular WMLs (P = 0.001), cerebral WMLs (P = 0.021), basal ganglia perivascular space grade (P < 0.001) and severity (P = 0.001), and semiovale perivascular space grade (P = 0.010) and severity (P = 0.002). Hypertension was associated with periventricular WMLs (P = 0.048), centrum semiovale WMLs (P = 0.026), and basal ganglia perivascular space grade (P < 0.001) and severity (P < 0.001). A novel clustering algorithm was derived to stratify our cohort into 3 different groups according to the differing severity of the cerebral WMLs and perivascular space enlargement. CONCLUSION: The present study has provided a comprehensive analysis of the clinical correlation of characteristics and neuroradiologic phenotypes in patients with CSVD. The insights from these findings could be used to refine the management strategy for patients with CSVD.

Vertebrobasilar artery dissection manifesting as Millard-Gubler syndrome in a young ischemic stroke patient: A case report.

BACKGROUND: Millard-Gubler syndrome (MGS) is caused by a lesion in the brainstem at the level of the facial nerve nucleus, and it is also a rare ventral pontine syndrome. Vertebrobasilar artery dissection (VAD) is an uncommon cause of ischemic stroke. To the best of our knowledge, this is the first case report on the coexistence of MGS and VAD in a young acute ischemic stroke patient. CASE SUMMARY: We herein describe an unusual case of young acute ischemic stroke patient, presenting with acute right peripheral facial palsy, right abducens palsy, and contralateral hemihypesthesia, manifesting as MGS. After receiving dual antiplatelet therapy with aspirin and clopidogrel, as well as rosuvastatin, the patient recovered significantly. The high-resolution magnetic resonance imaging (MRI) indicated a diagnosis of VAD. CONCLUSION: Our finding further demonstrated that high-resolution MRI is a useful technique to early detect underlying dissection in posterior circulation ischemic stroke.

New clinical characteristics and risk factors of hand knob infarction.

Hand knob infarction (HKI) is a rare clinical condition which is often misdiagnosed as peripheral neuropathy. This study aimed to identify the clinical characteristics and risk factors of HKI. Nine HKI patients admitted between January 2013 and March 2016 were confirmed by magnetic resonance imaging. Their medical records were collected and analyzed. The modified Rankin Scale was used to assess clinical outcomes. Routine laboratory tests, electrocardiogram, echocardiography, cranial magnetic resonance imaging, magnetic resonance angiography, computed tomography angiography, and Doppler ultrasonography examinations were performed. Seven patients had uniform involvement of all digits. One patient with radial weakness had a lesion in the lateral area of hand knob, and another patient with ulnar weakness had a lesion distributed in the medial area of hand knob. Hyperhomocysteinemia was a most common risk factor for HKI. Most HKI patients had a benign disease course, but three patients (33.33%) with the stroke type of large artery atherosclerosis had disease recurrence. We characterized clinical characteristics and risk factors of HKI which will help the diagnosis and management of HKI.

Cu-Catalyzed Synthesis of Fluoroalkylated Isoxazoles from Commercially Available Amines and Alkynes.

A one-pot protocol for the construction of fluoroalkylated isoxazoles directly from commercially available amines and alkynes is described. The reaction is scalable, operationally simple, regioselective, mild, and tolerant of a broad range of functional groups. As such, it could be viewed as a "click synthesis" of fluoroalkylated isoxazoles. Preliminary mechanistic investigations reveal that the transformation involves an unprecedented Cu-catalyzed cascade sequence involving RfCHN2.

Nitrous oxide induced subacute combined degeneration with longitudinally extensive myelopathy with inverted V-sign on spinal MRI: a case report and literature review.

BACKGROUND: Nitrous oxide (N2O), a long-standing anesthetic, is also neurotoxic by interfering with the bioavailability of vitamin B12 if abused. A few case studies have reported the neurological and psychiatric complications of N2O. CASE PRESENTATION: Here, we reported a patient of N2O induced subacute combined degeneration (SCD) with longitudinally extensive myelopathy with inverted V-sign exhibiting progressive limb paresthesia and unsteady gait. CONCLUSIONS: This case raises the awareness of an important mechanism of neural toxicity of N2O, and clinical physicians should be well recognized this in the field of substance-related disorders.

Genetic variation in glia-neuron signalling modulates ageing rate.

The rate of behavioural decline in the ageing population is remarkably variable among individuals. Despite the considerable interest in studying natural variation in ageing rate to identify factors that control healthy ageing, no such factor has yet been found. Here we report a genetic basis for variation in ageing rates in Caenorhabditis elegans. We find that C. elegans isolates show diverse lifespan and age-related declines in virility, pharyngeal pumping, and locomotion. DNA polymorphisms in a novel peptide-coding gene, named regulatory-gene-for-behavioural-ageing-1 (rgba-1), and the neuropeptide receptor gene npr-28 influence the rate of age-related decline of worm mating behaviour; these two genes might have been subjected to recent selective sweeps. Glia-derived RGBA-1 activates NPR-28 signalling, which acts in serotonergic and dopaminergic neurons to accelerate behavioural deterioration. This signalling involves the SIR-2.1-dependent activation of the mitochondrial unfolded protein response, a pathway that modulates ageing. Thus, natural variation in neuropeptide-mediated glia-neuron signalling modulates the rate of ageing in C. elegans.

Disconnections of Cortico-Subcortical Pathways Related to Cognitive Impairment in Patients with Leukoaraiosis: A Preliminary Diffusion Tensor Imaging Study.

BACKGROUND: We aimed to explore the relation between the microstructural integrity of white matter using the technique of diffusion tensor imaging (DTI) and changes of cognition in leukoaraiosis (LA). METHODS: Fifty patients with LA and 50 age- and gender-matched controls were recruited consecutively. The average values of mean diffusivity (MD) and fractional anisotropy (FA) were quantified both within white matter lesions (WMLs) and normal-appearing white matter (NAWM) from the regions of interest (ROIs). RESULTS: We found significantly decreased FA and increased MD in WMLs at the 5 ROIs than that in NAWM and controls (p < 0.05). The values of FA in NAWM were significantly lower at centrum semiovale and posterior periventricular white matter than those of controls (p < 0.05). The values of MD in NAWM were significantly higher at the anterior periventricular white matter and corpus callosum than those of controls (p < 0.05). The values of FA in NAWM located at anterior periventricular white matter correlated inversely with the Z scores of executive function (r = -0.420, p = 0.028). CONCLUSIONS: DTI may provide some important information about the cognitive dysfunction in patients with LA, which may largely attribute to the "disconnection" of cortico-subcortical pathways, with the evidence of reduced FA and increased MD.

Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system, which has been associated with several vaccines such as rabies, diphtheria-tetanus-polio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, and the Hog vaccine. Here, we presented a case of 12-year-old child who suffered from ADEM three weeks after hepatitis B vaccination. He was admitted to our hospital with symptoms of weakness of limbs, high fever, and alteration of consciousness. Some abnormalities were also found in CSF. Treatment with high-dose corticosteroids and intravenous immunoglobulin had significant effect, with marked improvement of the clinical symptoms and the results of CSF. The findings of MRI also detected some abnormal lesions located in both brain and spinal cord. The clinical features, the findings of CSF and MRI, and therapeutic effect may contribute to such diagnosis of ADEM.

Isolation and Characterization of Three New Monoterpene Synthases from Artemisia annua.

Artemisia annua, an annual herb used in traditional Chinese medicine, produces a wealth of monoterpenes and sesquiterpenes, including the well-known sesquiterpene lactone artemisinin, an active ingredient in the treatment for malaria. Here we report three new monoterpene synthases of A. annua. From a glandular trichome cDNA library, monoterpene synthases of AaTPS2, AaTPS5, and AaTPS6, were isolated and characterized. The recombinant proteins of AaTPS5 and AaTPS6 produced multiple products with camphene and 1,8-cineole as major products, respectively, and AaTPS2 produced a single product, ß-myrcene. Although both Mg(2+) and Mn(2+) were able to support their catalytic activities, altered product spectrum was observed in the presence of Mn(2+) for AaTPS2 and AaTPS5. Analysis of extracts of aerial tissues and root of A. annua with gas chromatography-mass spectrometry detected more than 20 monoterpenes, of which the three enzymes constituted more than 1/3 of the total. Mechanical wounding induced the expression of all three monoterpene synthase genes, and transcript levels of AaTPS5 and AaTPS6 were also elevated after treatments with phytohormones of methyl jasmonate, salicylic acid, and gibberellin, suggesting a role of these monoterpene synthases in plant-environment interactions. The three new monoterpene synthases reported here further our understanding of molecular basis of monoterpene biosynthesis and regulation in plant.

Unearthing microbial diversity of Taxus rhizosphere via MiSeq high-throughput amplicon sequencing and isolate characterization.

The species variability and potential environmental functions of Taxus rhizosphere microbial community were studied by comparative analyses of 15 16S rRNA and 15 ITS MiSeq sequencing libraries from Taxus rhizospheres in subtropical and temperate regions of China, as well as by isolating laccase-producing strains and polycyclic aromatic hydrocarbon (PAH)-degrading strains. Total reads could be assigned to 2,141 Operational Taxonomic Units (OTUs) belonging to 31 bacteria phyla and 2,904 OTUs of at least seven fungi phyla. The abundance of Planctomycetes, Actinobacteria, and Chloroflexi was higher in T. cuspidata var. nana and T. × media rhizospheres than in T. mairei rhizosphere (NF), while Acidobacteria, Proteobacteria, Nitrospirae, and unclassified bacteria were more abundant in the latter. Ascomycota and Zygomycota were predominant in NF, while two temperate Taxus rhizospheres had more unclassified fungi, Basidiomycota, and Chytridiomycota. The bacterial/fungal community richness and diversity were lower in NF than in other two. Three dye decolorizing fungal isolates were shown to be highly efficient in removing three classes of reactive dye, while two PAH-degrading fungi were able to degrade recalcitrant benzo[a]pyrene. The present studies extend the knowledge pedigree of the microbial diversity populating rhizospheres, and exemplify the method shift in research and development of resource plant rhizosphere.

Efficacy of Cholinesterase Inhibitors in Vascular Dementia: An Updated Meta-Analysis.

BACKGROUND/AIMS: The objective of this study was to determine whether treatment with acetylcholinesterase inhibitors would provide cognitive benefit for patients with vascular dementia. METHODS: Studies in patients with vascular dementia, who had not taken acetylcholinesterase inhibitors or memantine for at least 6 weeks, were included. RESULTS: Twelve studies were included in the final analysis. Donepezil showed significant improvement in Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) as compared to placebo, at the doses tested, that is, 5 and 10 mg/day (difference in means -1.389 and -1.680, respectively, p ≤ 0.008), but not on the Mini Mental State Examination (MMSE) (p ≥ 0.259). Galantamine also improved the ADAS-cog in comparison to the placebo (difference in means -2.191, p < 0.001), whereas, rivastigmine did not show any benefit on ADAS-cog. However, the findings with rivastigmine are difficult to interpret, given there were only 2 studies. Treatment with cholinesterase inhibitors was associated with a twofold increase in the odds of discontinuation, due to adverse events (pooled OR 1.966, 95% CI 1.630-2.371, p < 0.001). CONCLUSION: The present results reveal the therapeutic benefits of donepezil and galantamine in patients with vascular dementia. Interestingly, the ADAS-cog and MMSE varied considerably in detecting cognitive improvement.