The Use of Simple Laboratory Parameters in the Differential Diagnosis of Acute-Phase Zika and Dengue Viruses.

BACKGROUND: Differential diagnosis between acute-phase Zika and dengue is challenging because of a similar clinical presentation and the lack of available molecular diagnosis tools in most of endemic areas. OBJECTIVES: Our study aimed to evaluate the use of simple laboratory parameters to differentiate these infections. METHODS: We retrospectively compared simple hematology and biochemistry values in 81 and 341 patients with confirmed Zika and dengue, respectively, collected from June 2013 to March 2014 during the French Polynesia outbreaks. RESULTS: Thrombocytopenia, neutropenia, leukopenia, lymphopenia, and elevated aspartate aminotransaminases were significantly more frequent in dengue than in Zika (p < 0.001). Platelets <100 × 109/L, neutrophils <0.5 × 109/L, lymphocytes <0.5 × 109/L, and aspartate aminotransaminases >100 IU/mL were found in dengue but not in Zika. The positive predictive value of the -association of leukocytes <4 × 109/L + lymphocytes <1 × 109/L + aspartate aminotransaminases >40 IU/mL for the diagnosis of dengue was 90%, with an accuracy of 82.4%. CONCLUSION: For the differential diagnosis between acute-phase Zika and dengue, there is no specific standard laboratory pattern. We identified cutoff values and a combination of laboratory parameters that are a strong argument against Zika and in favor of dengue.

Molecular detection of Zika virus in blood and RNA load determination during the French Polynesian outbreak.

Zika virus (ZIKV) viremia is reported as low and transient; however, these estimates rely on limited data. We report RNA loads in sera collected from symptomatic patients during the 2013-2014 French Polynesian ZIKV outbreak. We performed molecular detection of ZIKV RNA in sera from 747 patients presenting with suspected acute phase ZIKV infection. Among patients with confirmed infection, we analyzed the duration of viremia, assessed viral RNA loads and recorded the main clinical symptoms. A total of 210/747 (28.1%) sera tested positive using a ZIKV-specific RT-PCR. Viral RNA loads in symptomatic patients that ranged from 5 to 3.7 × 106 copies/mL (mean 9.9 × 104 copies/mL) were not related to a particular clinical presentation, and were significantly lower than those previously obtained from asymptomatic ZIKV infected blood donors. The rate of detection of ZIKV RNA in sera from suspected cases of acute phase ZIKV infection was low. ZIKV RNA loads were lower in symptomatic patients compared to asymptomatic blood donors and were lower than RNA loads usually reported in dengue infections. As there is no abrupt onset of symptoms in ZIKV infections, we suggest that infected patients sought for medical attention when viremia was already decreasing or had resolved.

Detection of chikungunya virus in saliva and urine.

BACKGROUND: Saliva and urine have been used for arthropod-borne viruses molecular detection but not yet for chikungunya virus (CHIKV). We investigated the use of saliva and urine for molecular detection of CHIKV during the French Polynesian outbreak. METHODS: During the French Polynesian chikungunya outbreak (2014-2015), we collected the same day blood and saliva samples from 60 patients with probable chikungunya (47 during the 1st week post symptoms onset and 13 after), urine was available for 39 of them. All samples were tested using a CHIKV reverse-transcription PCR. RESULTS: Forty eight patients had confirmed chikungunya. For confirmed chikungunya presenting during the 1st week post symptoms onset, CHIKV RNA was detected from 86.1 % (31/36) of blood, 58.3 % (21/36) of saliva and 8.3 % (2/24) of urine. Detection rate of CHIKV RNA was significantly higher in blood compared to saliva. For confirmed chikungunya presenting after the 1st week post symptoms onset, CHIKV RNA was detected from 8.3 % (1/12) of blood, 8.3 % (1/12) of saliva and 0 % (0/8) of urine. CONCLUSIONS: In contrast to Zika virus (ZIKV), saliva did not increased the detection rate of CHIKV RNA during the 1st week post symptoms onset. In contrast to ZIKV, dengue virus and West Nile virus, urine did not enlarged the window of detection of CHIKV RNA after the 1st week post symptoms onset. Saliva can be used for molecular detection of CHIKV during the 1st week post symptoms onset only if blood is impossible to collect but with a lower sensitivity compared to blood.

Effect of Culture Conditions on Metabolite Production of Xylaria sp.

Seeking a strategy for triggering the cryptic natural product biosynthesis to yield novel compounds in the plant-associated fungus Xylaria sp., the effect of culture conditions on metabolite production was investigated. A shift in the production of five known cytochalasin-type analogues 1-5 to six new α-pyrone derivatives, xylapyrones A-F (compounds 6-11), from a solid to a liquid medium was observed. These compounds were identified by analysis of 1D and 2D NMR and HRMS data. Compounds 1-3 showed moderate cytotoxicity against HepG2 and Caski cancer cell lines with IC50 values ranging from 25 to 63 µM and compounds 4-11 were found to be inactive, with IC50 values>100 µM.

Emergence of Zika virus.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) of the family Flaviviridae, genus Flavivirus, transmitted by the bite of infected mosquitoes. ZIKV was first isolated from a non-human primate in 1947, ZIKV infections in humans were sporadic during 60 years before emerging in the Pacific in 2007 and 2013 and in Brazil in 2015. Due to a non-specific clinical presentation, Zika fever can be misdiagnosed with other arboviruses such as dengue and chikungunya. ZIKV infections were associated with mild illness before the large French Polynesia outbreak in 2013-2014 in which severe neurological complications were reported. Routine laboratory diagnosis of Zika fever relies on the detection of specific ZIKV RNA by PCR. Serological diagnosis is complicated due to cross reactivity with other flaviviruses. ZIKV adapted to an urban cycle involving humans and domestic mosquito vectors that are widely distributed, such as Aedes aegypti and Ae. albopictus. This adaptation highlights the potential for ZIKV to emerge in tropical, intertropical and also temperate areas.

Pestalafuranones F-J, five new furanone analogues from the endophytic fungus Nigrospora sp. BM-2.

Five new 2(5H)-furanone-type derivatives, pestalafuranones F-J (compounds 3-7), together with two known compounds, pestalafuranones A (1) and B (2), were isolated from the ethyl acetate extract from the fermentation broth of the endophytic fungus Nigrospora sp. BM-2 in a hypersaline medium. The structures of these metabolites were elucidated by EIMS, HREIMS and NMR spectroscopic data. Compounds 1-7 exhibited no cytotoxic activities against the MDA-MB-231 and Caski cancer cell lines.

Idiopathic hypereosinophilic syndrome presenting as capsular warning syndrome: A case report and literature review.

RATIONALE: Few reports of idiopathic hypereosinophilic syndrome exist presenting as ischemic cerebrovascular disease, and the majority are watershed infarction. We report the first case of idiopathic hypereosinophilic syndrome that has clinical features of capsular warning syndrome lasting 6 weeks. PATIENT CONCERNS: A 26-year-old man complained of recurrent right limb weakness, accompanying slurred speech, and right facial paresthesia. DIAGNOSES: The patient was diagnosed with idiopathic hypereosinophilic syndrome (IHES). INTERVENTIONS: Adequate glucocorticoid and anticoagulant treatments were given. OUTCOMES: The patient's motor ability improved, and he was discharged 2 weeks later. Muscle strength in the right-side extremities had fully recovered at a 3-month follow-up after discharge. LESSONS: This case suggests that idiopathic hypereosinophilic syndrome should be considered as a cause of capsular warning syndrome, and the dose of glucocorticoid and the efficacy evaluation index needs to be reevaluated for the treatment of ischemic cerebrovascular disease associated with idiopathic hypereosinophilic syndrome.

Optimization of Hydrogenobyrinic Acid Synthesis in a Cell-Free Multienzyme Reaction by Novel S-Adenosyl-methionine Regeneration.

Hydrogenobyrinic acid, a modified tetrapyrrole composed of eight five-carbon compounds, is a key intermediate and central framework of vitamin B12. Synthesis of hydrogenobyrinic acid requires eight S-adenosyl-methionine working as the methyl group donor catalyzed by 12 enzymes including six methyltransferases, causing the great shortage of S-adenosyl-methionine and accumulation of S-adenosyl-homocysteine, which is uneconomic and unsustainable for the cascade reaction. Here, we report a cell-free synthetic system for producing hydrogenobyrinic acid by integrating 12 enzymes using 5-aminolevulininate as a substrate and develop a novel S-adenosyl-methionine regeneration system to steadily supply S-adenosyl-methionine and avoid the accumulated inhibition of S-adenosyl-homocysteine by consuming a cheaper substrate (l-methionine and polyphosphate). By combination of the reaction system optimization and S-adenosyl-methionine regeneration, the titer of hydrogenobyrinic acid was improved from 0.61 to 29.39 mg/L in a 12 h reaction period, representing an increase of 48.18-fold, raising an efficient and rapidly evolutional alternative method to produce high-value-added compounds and intermediate products.

Remediation of lindane contaminated soil by fluidization-like dielectric barrier discharge.

This study proposed the fluidization-like dielectric barrier discharge (DBD) plasma for the remediation of lindane contaminated soil and integrated physical and chemical reaction pathway. Soil particle distribution within the reactor was simulated with Euler-Euler and Gidaspow drag models, and a bipolar pulsed power supply was applied to energize the DBD reactor after full fluidized. The effect of soil particles movement on electric features was discussed in terms of voltage waveforms and Lissajous figures. Lindane degradation was found to be related to electrics parameters and soil properties. Soil samples before and after treatment were analyzed by XRD and SEM methods. A 95.98% lindane decomposition and 0.66 mgLindane/h average reaction rate were obtained with 3 wt% CaO injection by pulse power drove fluidization-like DBD after 32 min treatment. Ozone was proved to play a major role during lindane degrading by plasma. The reaction potential pathway of lindane decomposition contains 4 steps, including dehydrogen, dehydrochlorination, and dechlorination, respectively.

Saccharothrix yanglingensis sp. nov., an antagonistic endophytic actinomycete isolated from cucumber plant.

An endophytic actinomycete strain, designated Hhs.015(T), was isolated from roots of cucumber seedlings. The endophytic isolate was identified by means of a polyphasic taxonomic approach. On the basis of 16S rRNA gene sequence similarities, strain Hhs.015(T) was closely related to members of the genus Saccharothrix. DNA-DNA hybridization with the four closest relatives, Saccharothrix longispora NRRL B-16116(T), Saccharothrix xinjiangensis NRRL B-24321(T), Saccharothrix autraliensis CGMCC 4.1355(T) and Saccharothrix espanaensis CGMCC 4.1714(T), gave similarity values of 33.8, 28.2, 44.1 and 29.5%, respectively, which indicated that strain Hhs.015(T) represents a novel species of the genus Saccharothrix. This is consistent with the morphological, physiological and chemotaxonomic data. As a whole, these results suggest that strain Hhs.015(T) represents a novel Saccharothrix species. The name Saccharothrix yanglingensis sp. nov. is proposed, with the type strain Hhs.015(T) (=CGMCC 4.5627(T) = KCTC 19722(T)).

Understanding the role of self-organizations in disaster relief during COVID-19: A case study from the perspective of co-production.

This article examines the role of self-organizations, the spontaneous emergence of order in natural and physical systems in disaster relief during the outbreak of COVID-19 in Wuhan China. By investigating a selection of involved self-organizations, it adopts a co-production perspective by focusing on two cases during the process of delivering emergency responses with the government and citizens to combat the health crisis. Observations and case analysis have found that both government and citizen channel play a role in delivering disaster responses. In particular, self-organizations emerged in the process of delivering relief services are observed as a critical actor of change in terms of mobilizing resources and collaborating citizens to achieve personal safety and community resilience. First, government channels are primarily manifested in residential communities in obeying emergency orders and tasks. Second, citizen channels are practiced through the co-production of disaster responses mainly delivered by residents, nonprofit organizations and enterprises. The finding suggests that self-organizations in the co-production of disaster responses with the government and residents in Wuhan has been effective that eventually brought the health crisis under control. Policy implications generated from this health crisis may provide insightful lessons for government policy making and disaster management.

MicroRNA-140-5p exacerbates vascular cognitive impairment by inhibiting neurogenesis in the adult mouse hippocampus after global cerebral ischemia.

Vascular cognitive impairment (VCI) is the most common type of dementia after Alzheimer's disease (AD). Effective treatments for VCI are currently lacking. MicroRNA (miR)- 140-5p is associated with cerebral ischemia and poststroke depression, but its relationship with VCI remains unknown. A VCI model was established by bilateral common carotid artery occlusion (BCCAO) for 17 min in mice. Neurogenesis was evaluated by immunostaining for Nestin/bromodeoxyuridine (BrdU), NeuN/BrdU, and doublecortin (DCX)/BrdU. Neuroplasticity was assessed by quantifying synapsin-I and postsynaptic density protein 95 (PSD-95) protein levels. Predicted target genes were screened and verified using the dual luciferase reporter gene system. MiR-140-5p was upregulated in the hippocampus of the BCCAO mice 2 weeks following ischemia. Compared with control groups, the AAV-miR-140-5p group exhibited poorer cognitive performance alongside lower numbers of DCX/BrdU and NeuN/BrdU and less synapsin-I and PSD-95 in the dentate gyrus (P < 0.05). MiR-140-5p overexpression decreased the predicted target gene Prox1. Dual luciferase reporter system confirmed that Prox1 was a direct target site for miR-140-5p. In conclusion, our results suggest that miR-140-5p inhibits neurogenesis and neuroplasticity via downregulation of Prox1 and aggravates VCI. Our findings highlight that miR-140-5p is involved in the pathological process of VCI and provides information for the development of new treatments, which may need further inhibition tests to verify.

Periventricular White Matter Hyperintensity in Males is Associated with Post-Stroke Depression Onset at 3 Months.

OBJECTIVE: This study aimed to explore the correlation between white matter hyperintensity (WMH) and post-stroke depression (PSD) at 3 months, and to further investigate sex differences in the pathogenesis of PSD. METHODS: A total of 238 consecutive patients with acute cerebral infarction were recruited. PSD was assessed at 2 weeks and at 3 months after stroke onset. All stroke cases were divided into four subgroups according to the diagnosis of depression at two time nodes: continuous depression; depression remission; late-onset PSD; and continuous non-depression. The Fazekas and Scheltens visual rating scales were adopted to assess WMH. RESULTS: Logistic regression revealed that the presence of periventricular white matter hyperintensity (PVWMH) at baseline in male patients was an independent risk factor for PSD at 3 months. Further subgroup analysis revealed that PVWMH was associated with late-onset PSD in males, but not with continuous depression 3 months after stroke. Male acute stroke patients with PVWMH at baseline were more likely to develop PSD at 3 months, especially late-onset PSD. CONCLUSION: Our data suggest that sex differences may influence the pathogenesis of PSD.

Genome-Wide Association Mapping of Salinity Tolerance at the Seedling Stage in a Panel of Vietnamese Landraces Reveals New Valuable QTLs for Salinity Stress Tolerance Breeding in Rice.

Rice tolerance to salinity stress involves diverse and complementary mechanisms, such as the regulation of genome expression, activation of specific ion-transport systems to manage excess sodium at the cell or plant level, and anatomical changes that avoid sodium penetration into the inner tissues of the plant. These complementary mechanisms can act synergistically to improve salinity tolerance in the plant, which is then interesting in breeding programs to pyramidize complementary QTLs (quantitative trait loci), to improve salinity stress tolerance of the plant at different developmental stages and in different environments. This approach presupposes the identification of salinity tolerance QTLs associated with different mechanisms involved in salinity tolerance, which requires the greatest possible genetic diversity to be explored. To contribute to this goal, we screened an original panel of 179 Vietnamese rice landraces genotyped with 21,623 SNP markers for salinity stress tolerance under 100 mM NaCl treatment, at the seedling stage, with the aim of identifying new QTLs involved in the salinity stress tolerance via a genome-wide association study (GWAS). Nine salinity tolerance-related traits, including the salt injury score, chlorophyll and water content, and K+ and Na+ contents were measured in leaves. GWAS analysis allowed the identification of 26 QTLs. Interestingly, ten of them were associated with several different traits, which indicates that these QTLs act pleiotropically to control the different levels of plant responses to salinity stress. Twenty-one identified QTLs colocalized with known QTLs. Several genes within these QTLs have functions related to salinity stress tolerance and are mainly involved in gene regulation, signal transduction or hormone signaling. Our study provides promising QTLs for breeding programs to enhance salinity tolerance and identifies candidate genes that should be further functionally studied to better understand salinity tolerance mechanisms in rice.

MicroRNA-140-5p: A novel circulating biomarker for early warning of late-onset post-stroke depression.

We aimed to explore the circulating microRNAs biomarkers in the acute stage following cerebral ischemia to earlier warn late-onset post-stroke depression (PSD). A total of 251 consecutive patients with acute ischemic stroke were recruited. They were divided into three groups depending on whether PSD had occurred at 2 weeks or 3 months since stroke: early-onset PSD, late-onset PSD, and non-depressed group. Microarray assay was conducted to identify the different expression profiles of plasma miRNAs. Comprehensive bioinformatics analysis for their integrating putative target genes was performed. The key miRNA was validated in a larger cohort and its function was further studied in ischemic mice brain. We screened three differentially expressed miRNAs in the late-onset PSD individuals, miR-140-5p and miR-221-3p were significantly upregulated while miR-1246 was downregulated. The bioinformatics analysis demonstrated that their predicted target genes were mainly enriched in axon development and Ras signaling pathway. Logistic regression analysis revealed that miR-140-5p was an independent risk factor for late-onset PSD (P = 0.017, OR = 2.313, 95%CI 1.158 to 4.617). The miR-140-5p expression on admission was significantly positively correlated with HDRS scores assessed at 3 months after stroke (P = 0.0007). The predictive value of miR-140-5p for late-onset PSD is 83.3% sensitivity and 72.6% specificity (AUC = 0.8127, P < 0.0001). AAV-mediated overexpression of miR-140-5p decreased the protein level of IL1rap, IL1rapl1, VEGF, and MEGF10 in the ischemic mouse hippocampus and inhibited neurogenesis and capillary density. MiR-140-5p might be involved in the pathogenesis of late-onset PSD and used as a novel early warning biomarker.