The apple bHLH transcription factor MdbHLH3 functions in determining the fruit carbohydrates and malate.

Changes in carbohydrates and organic acids largely determine the palatability of edible tissues of horticulture crops. Elucidating the potential molecular mechanisms involved in the change in carbohydrates and organic acids, and their temporal and spatial crosstalk are key steps in understanding fruit developmental processes. Here, we used apple (Malus domestica Borkh.) as research materials and found that MdbHLH3, a basic helix-loop-helix transcription factor (bHLH TF), modulates the accumulation of malate and carbohydrates. Biochemical analyses demonstrated that MdbHLH3 directly binds to the promoter of MdcyMDH that encodes an apple cytosolic NAD-dependent malate dehydrogenase, activating its transcriptional expression, thereby promoting malate accumulation in apple fruits. Additionally, MdbHLH3 overexpression increased the photosynthetic capacity and carbohydrate levels in apple leaves and also enhanced the carbohydrate accumulation in fruits by adjusting carbohydrate allocation from sources to sinks. Overall, our findings provide new insights into the mechanism of how the bHLH TF MdbHLH3 modulates the fruit quality. It directly regulates the expression of cytosolic malate dehydrogenase MdcyMDH to coordinate carbohydrate allocation and malate accumulation in apple.

Loss of GATA4 C-Terminus by p.S335X Mutation Modulates Coronary Artery Vascular Smooth Muscle Cell Phenotype.

Coronary artery disease (CAD) has been the leading cause of morbidity and mortality worldwide, and its pathogenesis is closely related with the proliferation and migration of vascular smooth muscle cell (VSMC). We previously reported a truncated GATA4 protein lacking C-terminus induced by p.S335X mutation in cardiomyocyte from ventricular septal defect (VSD) patients. However, it is still unclear whether GATA4 p.S335X mutation could influence the development of CAD. GATA4 wild-type (WT) and p.S335X mutant (MU) overexpression plasmids were constructed and transfected transiently into rat coronary artery smooth muscle cell (RCSMC) to observe the proliferative and migratory abilities by MTS and wound healing assay, respectively. PCR array was used to preliminarily detect the expression of phenotypic modulation-related genes, and QRT-PCR was then carried out to verify the screened differentially expressed genes (DEGs). The results showed that, when stimulated by fetal bovine serum (10%) for 24 h or tumor necrosis factor-α (10 or 30 ng/ml) for 10 or 24 h, deletion of GATA4 C-terminus by p.S335X mutation in GATA4 enhanced the proliferation of RCSMC, without alteration of the migration capability. Twelve DEGs, including Fas, Hbegf, Itga5, Aimp1, Cxcl1, Il15, Il2rg, Il7, Tnfsf10, Il1r1, Irak1, and Tlr3, were screened and identified as phenotypic modulation-related genes. Our data might be beneficial for further exploration regarding the mechanisms of GATA4 p.S335X mutation on the phenotypic modulation of coronary VSMC.

CmTCP20 Plays a Key Role in Nitrate and Auxin Signaling-Regulated Lateral Root Development in Chrysanthemum.

Lateral root (LR) formation and development play a vital role in plant development by permitting the establishment of branched root systems. It is well known that nutrient availability controls LR development. Moreover, LR development is fine-tuned by a myriad of hormonal signals. Many transcription factors (TFs) participate in LR development. Here, we discuss the TFs involved in the nitrate and auxin signaling pathways and how these function in the regulation of LR formation and development in chrysanthemum. AtTCP20 is a plant-specific TF, which can modulate LR development in response to nitrate. The roles of CmTCP20 in LR development were identified by overexpression in chrysanthemum and heterologous expression in Arabidopsis. Overexpression of CmTCP20 significantly increased the number and average length of LRs compared with the wild type in chrysanthemum and Arabidopsis. We also found that CmTCP20 positively influenced auxin accumulation in the LRs at least partly by improving auxin biosynthesis, transport and response, thereby promoting LR development. Moreover, we found that CmTCP20 interacts with an auxin response factor, CmARF8, which also can be induced by nitrate and combined to proximal sites in the upstream promoter region of CmCYCB1;1 to positively regulate the cell cycle. The CmTCP20-CmARF8 heterodimer links nitrate and auxin signaling and converts cell-cycle signals to regulate LR initiation and growth.

Molecular characterization of NBS-LRR genes in the soybean Rsv3 locus reveals several divergent alleles that likely confer resistance to the soybean mosaic virus.

KEY MESSAGE: The divergence patterns of NBS - LRR genes in soybean Rsv3 locus were deciphered and several divergent alleles ( NBS_C, NBS_D and Columbia NBS_E ) were identified as the likely functional candidates of Rsv3. The soybean Rsv3 locus, which confers resistance to the soybean mosaic virus (SMV), has been previously mapped to a region containing five nucleotide binding site-leucine-rich repeats (NBS-LRR) genes (referred to as nbs_A-E) in Williams 82. In resistant cultivars, however, the number of NBS-LRR genes in this region and their divergence from susceptible alleles remain unclear. In the present study, we constructed and screened a bacterial artificial chromosome (BAC) library for an Rsv3-possessing cultivar, Zaoshu 18. Sequencing two positive BAC inserts on the Rsv3 locus revealed that Zaoshu 18 possesses the same gene content and order as Williams 82, but two of the NBS-LRR genes, NBS_C and NBS_D, exhibit distinct features that were not observed in the Williams 82 alleles. Obtaining these NBS-LRR genes from eight additional cultivars demonstrated that the NBS_A-D genes diverged into two different alleles: the nbs_A-D alleles were associated with the rsv3-type cultivars, whereas the NBS_A-D alleles were associated with the Rsv3-possessing cultivars. For the NBS_E gene, the cultivar Columbia possesses an allele (NBS_E) that differed from that in Zaoshu 18 and rsv3-type cultivars (nbs_E). Exchanged fragments were further detected on alleles of the NBS_C-E genes, suggesting that recombination is a major force responsible for allele divergence. Also, the LRR domains of the NBS_C-E genes exhibited extremely strong signals of positive selection. Overall, the divergence patterns of the NBS-LRR genes in Rsv3 locus elucidated by this study indicate that not only NBS_C but also NBS_D and Columbia NBS_E are likely functional alleles that confer resistance to SMV.

A bean common mosaic virus (BCMV)-resistance gene is fine-mapped to the same region as Rsv1-h in the soybean cultivar Suweon 97.

KEY MESSAGE: In the soybean cultivar Suweon 97, BCMV-resistance gene was fine-mapped to a 58.1-kb region co-localizing with the Soybean mosaic virus (SMV)-resistance gene, Rsv1-h raising a possibility that the same gene is utilized against both viral pathogens. Certain soybean cultivars exhibit resistance against soybean mosaic virus (SMV) or bean common mosaic virus (BCMV). Although several SMV-resistance loci have been reported, the understanding of the mechanism underlying BCMV resistance in soybean is limited. Here, by crossing a resistant cultivar Suweon 97 with a susceptible cultivar Williams 82 and inoculating 220 F2 individuals with a BCMV strain (HZZB011), we observed a 3:1 (resistant/susceptible) segregation ratio, suggesting that Suweon 97 possesses a single dominant resistance gene against BCMV. By performing bulked segregant analysis with 186 polymorphic simple sequence repeat (SSR) markers across the genome, the resistance gene was determined to be linked with marker BARSOYSSR_13_1109. Examining the genotypes of nearby SSR markers on all 220 F2 individuals then narrowed down the gene between markers BARSOYSSR_13_1109 and BARSOYSSR_13_1122. Furthermore, 14 previously established F2:3 lines showing crossovers between the two markers were assayed for their phenotypes upon BCMV inoculation. By developing six more SNP (single nucleotide polymorphism) markers, the resistance gene was finally delimited to a 58.1-kb interval flanked by BARSOYSSR_13_1114 and SNP-49. Five genes were annotated in this interval of the Williams 82 genome, including a characteristic coiled-coil nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR, CNL)-type of resistance gene, Glyma13g184800. Coincidentally, the SMV-resistance allele Rsv1-h was previously mapped to almost the same region, thereby suggesting that soybean Suweon 97 likely relies on the same CNL-type R gene to resist both viral pathogens.

Complete nucleotide sequences of seven soybean mosaic viruses (SMV), isolated from wild soybeans (Glycine soja) in China.

Soybean mosaic virus (SMV) is a devastating plant virus classified in the family Potyviridae, and known to infect cultivated soybeans (Glycine max). In this study, seven new SMVs were isolated from wild soybean samples and analyzed by whole-genome sequencing. An updated SMV phylogeny was built with the seven new and 83 known SMV genomic sequences. Results showed that three northeastern SMV isolates were distributed in clade III and IV, while four southern SMVs were grouped together in clade II and all contained a recombinant BCMV fragment (~900 bp) in the upstream part of the genome. This work revealed that wild soybeans in China also act as important SMV hosts and play a role in the transmission and diversity of SMVs.

Interaction between RNA helicase ROOT INITIATION DEFECTIVE 1 and GAMETOPHYTIC FACTOR 1 is involved in female gametophyte development in Arabidopsis.

ROOT INITIATION DEFECTIVE 1 (RID1) is an Arabidopsis DEAH/RHA RNA helicase. It functions in hypocotyl de-differentiation, de novo meristem formation, and cell specification of the mature female gametophyte (FG). However, it is unclear how RID1 regulates FG development. In this study, we observed that mutations to RID1 disrupted the developmental synchrony and retarded the progression of FG development. RID1 exhibited RNA helicase activity, with a preference for unwinding double-stranded RNA in the 3' to 5' direction. Furthermore, we found that RID1 interacts with GAMETOPHYTIC FACTOR 1 (GFA1), which is an integral protein of the spliceosome component U5 small nuclear ribonucleoprotein (snRNP) particle. Substitution of specific RID1 amino acids (Y266F and T267I) inhibited the interaction with GFA1. In addition, the mutated RID1 could not complement the seed-abortion phenotype of the rid1 mutant. The rid1 and gfa1 mutants exhibited similar abnormalities in pre-mRNA splicing and down-regulated expression of some genes involved in FG development. Our results suggest that an interaction between RID1 and the U5 snRNP complex regulates essential pre-mRNA splicing of the genes required for FG development. This study provides new information regarding the mechanism underlying the FG developmental process.

Fine mapping of the Rsv1-h gene in the soybean cultivar Suweon 97 that confers resistance to two Chinese strains of the soybean mosaic virus.

KEY MESSAGE: The Rsv1 - h gene in cultivar Suweon 97, which confers resistance to SMVs, was mapped to a 97.5-kb location (29,815,195-29,912,667 bp on chromosome 13) in the Rsv1 locus, thereby providing additional insights into the molecular nature underlying variations in resistance alleles in this particular locus. Soybean mosaic virus (SMV) is a well-known devastating pathogen of soybean (Glycine max (L.) Merrill.) causing significant yield losses and seed quality deterioration. A single dominant allele, Rsv1-h, which confers resistance to multiple SMV strains, was previously reported in the cultivar Suweon 97, but its exact location is unknown. In the present study, Suweon 97 was crossed with a SMV-sensitive cultivar, Williams 82. Inoculating 267 F 2 individuals with two Chinese SMV strains (SC6-N and SC7-N) demonstrated that one single dominant gene confers SMV resistance. Another 1,150 F 2 individuals were then screened for two simple sequence repeat (SSR) markers (BARCSOYSSR_13_1103 and BARCSOYSSR_13_1187) that flank the Rsv1 locus. Seventy-four recombinants were identified and 20 additional polymorphic SSR markers within the Rsv1 region were then employed in genotyping these recombinants. F 2:3 and F 3:4 recombinant lines were also inoculated with SC6-N and SC7-N to determine their phenotypes. The final data revealed that in Suweon 97, the Rsv1-h gene that confers resistance to SC6-N and SC7-N was flanked by BARCSOYSSR_13_1114 and BARCSOYSSR_13_1115, two markers that delimit a 97.5-kb region in the reference Williams 82 genome. In such region, eight genes were present, of which two, Glyma13g184800 and Glyma13g184900, encode the characteristic CC-NBS-LRR type of resistance gene and were considered potential candidates for Rsv1-h.

White spot syndrome virus VP51 interact with ribosomal protein L7 of Litopenaeus vannamei.

The interaction between viral structural proteins and host plays key functions in viral infection. In previous studies, most research have been undertaken to explore the interaction of envelope structural proteins with host molecules. However, how the nucleocapsid proteins of WSSV interacted with host molecules remained largely unknown. In this study, the interaction of nucleocapsid protein VP51 and ribosomal protein L7 of Litopenaeus vannamei (LvRPL7) was reported. Furthermore, the mRNA transcriptional response of LvRPL7 to WSSV was investigated. The results showed that LvRPL7 was widely distributed in all analyzed tissues of L. vannamei. The high expression levels of LvRPL7 were found in the tissues of muscle and gills. The temporal expression of LvRPL7 in WSSV-challenged shrimp showed that LvRPL7 was up-regulated (P < 0.5) in the muscle at 8 h and 24 h post WSSV challenge and then restored to the normal levels. But the LvRPL7 expression was up-regulated (P < 0.5) in the hepatopancreas at 8 h post WSSV challenge and down-regulated at 12 h and 24 h post WSSV challenge. Indirect immunofluorescence assay indicated that LvRPL7 was mainly located on the surface and cytoplasm of hemocytes. Far-Western blotting showed that VP51 bound with LvRPL7. Moreover, ELISA results appeared that LvRPL7 interacted with VP51 in concentration dependent manner. Neutralization assay in vivo showed that anti-LvRPL7 antibody significantly delayed WSSV infection. Our results reveal that LvRPL7 was involved in WSSV infection.

White spot syndrome virus VP12 interacts with adenine nucleotide translocase of Litopenaeus vannamei.

White spot syndrome virus VP12 contains cell attachment motif RGD which is considered to be critical for host cell binding. Until now, the function of this protein remains undefined. In this study, we explored the interaction of VP12 with host cells. A new shrimp protein (adenine nucleotide translocase of Litopenaeus vannamei, LvANT) is selected by far-western overlay assay. Tissue distribution of adenine nucleotide translocase mRNA showed that it was commonly spread in all the tissues detected. Cellular localization of LvANT in shrimp hemocytes showed that it was primarily located in the cytoplasm of hemocytes and colocalized with mitochondria. ELISA and far-western blot assay confirmed that VP12 interacted with LvANT. In vivo neutralization assay showed that anti-LvANT antibody can significantly reduce the mortality of shrimp challenged by WSSV at 48h post-treatment. Our results collectively showed that VP12 is involved in host cell binding via interaction with adenine nucleotide translocase.

[Chemical constituents from the aerial part of Stauntonia obovatifoliola Hayata subsp. urophylla].

OBJECTIVE: To study the chemical constituents of the aerial part of Stauntonia obovatifoliola. METHODS: The chemical constituents of ethyl acetate fraction were isolated and purified by several chromatography. Their structures were elucidated by their physiochemical properties and spectral methods. RESULTS: Six known compounds were isolated and identified as lupeone(1), lupeol(2), stigmasterol(3),3beta-O-acetyloleanolic acid(4), resinone(5) and daucosterol(6). CONCLUSION: Compounds 1-6 are isolated from this plant for the first time.

[Spatial and Temporal Variations in PM1 Concentration and its Correlation with AOD in China from 2014 to 2017].

Based on the PM1 mass concentration data from all the air quality monitoring stations in China from 2014 to 2017, the temporal and spatial distribution characteristics of PM1 concentration were studied using the time series statistical and spatial hierarchical clustering methods, and the PM1 spatiotemporal evolution characteristics were revealed. Combined with AOD data of the MODIS remote-sensing satellite, the temporal and spatial variation in PM1-AOD correlation was analyzed on a fine scale. The results showed that, from 2014 to 2017, the annual average PM1 concentration in China decreased yearly, the seasonal PM1 concentration showed the characteristics of "high in winter and low in summer," and the monthly average PM1 concentration showed a "U"-shaped variation. An "M"-shaped PM1 variation pattern was presented before and after the holidays. Weekly variation showed that high PM1 values occurred on Mondays and Fridays, and low ones occurred on Sundays. Based on the spatial clustering method, the national average annual PM1 concentration in China was divided into seven categories, and the overall spatial distribution pattern was "high in the east and low in the west and high in the north and low in the south." The highest and the lowest values of average PM1 concentration occurred in central China(54.59 µg·m-3) and in Xinjiang-Qinghai-Xizang(11.37 µg·m-3), respectively. The PM1-AOD relationship was positively correlated as a whole, the highest correlation coefficient was 0.55 in central China, and the lowest value was 0.36 in central and southern China.

Comparative proteomic analysis reveals similar and distinct features of proteins in dry and wet stigmas.

Angiosperm stigma supports compatible pollen germination and tube growth, resulting in fertilization and seed production. Stigmas are mainly divided into two types, dry and wet, according to the absence or presence of exudates on their surfaces. Here, we used 2DE and MS to identify proteins specifically and preferentially expressed in the stigmas of maize (Zea Mays, dry stigma) and tobacco (Nicotiana tabacum, wet stigma), as well as proteins rinsed from the surface of the tobacco stigma. We found that the specifically and preferentially expressed proteins in maize and tobacco stigmas share similar distributions in functional categories. However, these proteins showed important difference between dry and wet stigmas in a few aspects, such as protein homology in "signal transduction" and "lipid metabolism," relative expression levels of proteins containing signal peptides and proteins in "defense and stress response." These different features might be related to the specific structures and functions of dry and wet stigmas. The possible roles of some stigma-expressed proteins were discussed. Our results provide important information on functions of proteins in dry and wet stigmas and reveal aspects of conservation and divergence between dry and wet stigmas at the proteomic level.

[Regulation of T-type Ca(2+) channel in lysophosphatidylcholine-stimulated cardiomyocytes].

OBJECTIVE: To study the effect of lysophosphatidylcholine (LPC) on T-type calcium channel currents (I(Ca.T)) in cardiomyocytes, and identify the mechanism by which LPC accumulation in intracellular and/or interstitial space may uptake tachycardia and various arrhythmias during cardiac ischemia. METHODS: Neonatal rat cardiomyocytes from 1 to 3-day-old Wistar rats and hypertrophied ventricular myocytes from Wistar rats were prepared. Human cardiac T-type calcium channel α1 subunits, Ca(V3.1) and Ca(V3.2), were stably expressed in HEK293 cells. In this study, cardiomyocytes and heterologous expression of human Ca(V3.1) and Ca(V3.2) components were measureed by whole-cell patch clamp to study the up-regulation of I(Ca.T) by LPC. RESULTS: LPC markedly accelerated the spontaneous beating rates of neonatal rat cardiomyocytes from (42±8) beats/min in control to (64 ±8) beats/min after LPC application for 5 min at the physiological [Ca(2+)](i) concentration (pCa=7.2). In neonatal cardiomyocytes, I(Ca.T) was significantly increased by 10 µmol/L LPC by 21.5% when [Ca(2+)](i) was high (pCa=7). Intracellular Ca(2+)-dependent augmentation of I(Ca.T) by LPC was confirmed not only in neonatal cardiomyocytes but also in adult ventricular myocytes from the hypertrophied hearts. In this experiment, I(Ca.T) was significantly increased by 10 µmol/L LPC by 23.5% when [Ca(2+)](i) was high (pCa=7), although it was unchanged when [Ca(2+)](i) was low (pCa=11), control: (3.8±0.2) pA/pF, n=16; LPC: (3.7±0.4) pA/pF, n=10. LPC exerted no effect on the Ca(V3.1) T-type Ca(2+) channel current (I(Ca(V)3.1)) regardless of the [Ca(2+)](i) concentration at a pCa of 7 or at a pCa of 11. In contrast, LPC up-regulated the Ca(V3.2) T-type Ca(2+) channel current (I(Ca(V)3.2)), which was much larger at a pCa of 7 [LPC=10 µmol/L: (68.8±2.1) pA/pF, n=10; LPC=50 µmol/L: (78.4±4.8) pA/pF, n=9)] than that at a pCa of 11 [(38.5±2.1) pA/pF, n=11]. CONCLUSION: The present study indicates that LPC up-regulates the cardiac I(Ca.T) in physiological or higher [Ca(2+)](i) concentration, which may accelerate the pathophysiological cardiac automaticity and trigger tachyarrhythmias as novel ischemia-related mechanism.

Deletion of Dcf1 Reduces Amyloid-ß Aggregation and Mitigates Memory Deficits.

BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disease. One of the pathologies of AD is the accumulation of amyloid-ß (Aß) to form senile plaques, leading to a decline in cognitive ability and a lack of learning and memory. However, the cause leading to Aß aggregation is not well understood. Dendritic cell factor 1 (Dcf1) shows a high expression in the entorhinal cortex neurons and neurofibrillary tangles in AD patients. OBJECTIVE: Our goal is to investigate the effect of Dcf1 on Aß aggregation and memory deficits in AD development. METHODS: The mouse and Drosophila AD model were used to test the expression and aggregation of Aß, senile plaque formation, and pathological changes in cognitive behavior during dcf1 knockout and expression. We finally explored possible drug target effects through intracerebroventricular delivery of Dcf1 antibodies. RESULTS: Deletion of Dcf1 resulted in decreased Aß42 level and deposition, and rescued AMPA Receptor (GluA2) levels in the hippocampus of APP-PS1-AD mice. In Aß42 AD Drosophila, the expression of Dcf1 in Aß42 AD flies aggravated the formation and accumulation of senile plaques, significantly reduced its climbing ability and learning-memory. Data analysis from all 20 donors with and without AD patients aged between 80 and 90 indicated a high-level expression of Dcf1 in the temporal neocortex. Dcf1 contributed to Aß aggregation by UV spectroscopy assay. Intracerebroventricular delivery of Dcf1 antibodies in the hippocampus reduced the area of senile plaques and reversed learning and memory deficits in APP-PS1-AD mice. CONCLUSION: Dcf1 causes Aß-plaque accumulation, inhibiting dcf1 expression could potentially offer therapeutic avenues.

Lewis acid promoted carbon-carbon double-bond formation via organozinc reagents and carbonyl compounds.

Using cheap and readily available AlCl(3) as Lewis acid, functionalized aldehydes react with organozinc reagents to give (E)-alkenes stereoselectively in high yields.

Proteomic profiling of root system development proteins in chrysanthemum overexpressing the CmTCP20 gene.

Plant root systems ensure the efficient absorption of water and nutrients and provide anchoring into the soil. Although root systems are a highly plastic set of traits that vary both between and among species, the basic root system morphology is controlled by inherent genetic factors. TCP20 has been identified as a key regulator of root development in plants, and yet its underlying mechanism has not been fully elucidated, especially in chrysanthemum. We found that overexpression of the CmTCP20 gene promoted both adventitious and lateral root development in chrysanthemum. To get further insight into the molecular mechanisms controlling root system development, we conducted a study employing tandem mass tag proteomic to characterize the differential root system development proteomes from CmTCP20-overexpressing and wild-type chrysanthemum root samples. Of the proteins identified, 234 proteins were found to be differentially abundant (>1.5-fold cut off, p < 0.05) in CmTCP20-overexpressing versus wild-type chrysanthemum root samples. Functional enrichment analysis indicated that the CmTCP20 gene may participate in "phytohormone signal transduction". Our findings provide a valuable perspective on the mechanisms of both adventitious and lateral root development via CmTCP20 modulation at the proteome level in chrysanthemum.

Homocysteine as a potential predictive factor for high major adverse cardiovascular events risk in female patients with premature acute coronary syndrome.

We aimed to investigate the correlation of homocysteine (Hcy) level with clinical characteristics, and explore its predictive value for major adverse cardiovascular events (MACE) risk in female patients with premature acute coronary syndrome (ACS).The serum Hcy level was detected from 1299 female patients with premature ACS. According to the tertile of Hcy level, patients were divided into 3 groups: lowest tertile group (≤9.1 µmol/L), middle tertile group (9.2-11.6 µmol/L) and highest tertile group (>11.6 µmol/L). MACE incidence was recorded and MACE-free survival was caculated with the median follow-up duration of 28.3 months.Increased Hcy correlated with older age (P < .001), higher creatinine level (P < .001), and enhanced uric acid level (P = .001), while reduced fasting glucose concentration (P < .001). MACE incidence was 10.7% and it was highest in highest tertile group (22.1%), followed by middle tertile group (7.7%) and lowest tertile group (2.4%) (P < .001). Receiver operating characteristic curve showed that Hcy distinguished MACE patients from non-MACE patients with the area under the curve of 0.789 (95% CI: 0.742-0.835). Kaplan-Meier curves revealed that MACE-free survival was shortest in Hcy highest tertile group, followed by middle tertile group and lowest tertile group (P < .001). Multivariate Cox analyses further showed that higher Hcy level was an independent predictive factor for poor MACE-free survival (middle tertile vs lowest tertile (P = .001, HR: 3.615, 95% CI: 1.661-7.864); highest tertile vs lowest tertile (P < .001, HR: 11.023, 95% CI: 5.356-22.684)).Hcy serves as a potential predictive factor for increased MACE risk in female patients with premature ACS.

A network meta-analysis of the efficacy and safety of baloxavir marboxil versus neuraminidase inhibitors for the treatment of influenza in otherwise healthy patients.

Objective: Baloxavir marboxil (baloxavir) is the first cap-dependent endonuclease inhibitor being studied for the treatment of influenza in single oral dosing regimen. This network meta-analysis (NMA) evaluated the efficacy and safety of baloxavir compared to other antivirals for influenza in otherwise healthy patients. Methods: A systematic literature review was performed on 14 November 2016 in Medline, Embase, CENTRAL, and ICHUSHI to identify randomized controlled trials assessing antivirals for influenza. A NMA including 22 trials was performed to compare the efficacy and safety of baloxavir with other antivirals. Results: The time to alleviation of all symptoms was significantly shorter for baloxavir compared to zanamivir (difference in median time 19.96 h; 95% CrI [3.23, 39.07]). The time to cessation of viral shedding was significantly shorter for baloxavir than zanamivir and oseltamivir (47.00 h; 95% CrI [28.18, 73.86] and 56.03 h [33.74, 87.86], respectively). The mean decline in virus titer from baseline to 24 h was significantly greater for baloxavir than for the other drugs. Other differences in efficacy outcomes were not significant. No significant differences were found between baloxavir and the other antivirals for safety, except total drug-related adverse events where baloxavir demonstrated a decrease compared to oseltamivir and laninamivir. Conclusions: The NMA suggests that baloxavir demonstrated better or similar efficacy results compared to other antivirals with a comparable safety profile. Baloxavir led to a significant decrease in viral titer versus zanamivir, oseltamivir and peramivir and decreased viral shedding versus zanamivir and oseltamivir.