Mage transposon: a novel gene delivery system for mammalian cells.

Transposons, as non-viral integration vectors, provide a secure and efficient method for stable gene delivery. In this study, we have discovered Mage (MG), a novel member of the piggyBac(PB) family, which exhibits strong transposability in a variety of mammalian cells and primary T cells. The wild-type MG showed a weaker insertion preference for near genes, transcription start sites (TSS), CpG islands, and DNaseI hypersensitive sites in comparison to PB, approaching the random insertion pattern. Utilizing in silico virtual screening and feasible combinatorial mutagenesis in vitro, we effectively produced the hyperactive MG transposase (hyMagease). This variant boasts a transposition rate 60% greater than its native counterpart without significantly altering its insertion pattern. Furthermore, we applied the hyMagease to efficiently deliver chimeric antigen receptor (CAR) into T cells, leading to stable high-level expression and inducing significant anti-tumor effects both in vitro and in xenograft mice models. These findings provide a compelling tool for gene transfer research, emphasizing its potential and prospects in the domains of genetic engineering and gene therapy.

Inhaled SARS-CoV-2 vaccine for single-dose dry powder aerosol immunization.

The COVID-19 pandemic has fostered major advances in vaccination technologies1-4; however, there are urgent needs for vaccines that induce mucosal immune responses and for single-dose, non-invasive administration4-6. Here we develop an inhalable, single-dose, dry powder aerosol SARS-CoV-2 vaccine that induces potent systemic and mucosal immune responses. The vaccine encapsulates assembled nanoparticles comprising proteinaceous cholera toxin B subunits displaying the SARS-CoV-2 RBD antigen within microcapsules of optimal aerodynamic size, and this unique nano-micro coupled structure supports efficient alveoli delivery, sustained antigen release and antigen-presenting cell uptake, which are favourable features for the induction of immune responses. Moreover, this vaccine induces strong production of IgG and IgA, as well as a local T cell response, collectively conferring effective protection against SARS-CoV-2 in mice, hamsters and nonhuman primates. Finally, we also demonstrate a mosaic iteration of the vaccine that co-displays ancestral and Omicron antigens, extending the breadth of antibody response against co-circulating strains and transmission of the Omicron variant. These findings support the use of this inhaled vaccine as a promising multivalent platform for fighting COVID-19 and other respiratory infectious diseases.

Dual Antiplatelet Therapy vs Alteplase for Patients With Minor Nondisabling Acute Ischemic Stroke: The ARAMIS Randomized Clinical Trial.

Importance: Intravenous thrombolysis is increasingly used in patients with minor stroke, but its benefit in patients with minor nondisabling stroke is unknown. Objective: To investigate whether dual antiplatelet therapy (DAPT) is noninferior to intravenous thrombolysis among patients with minor nondisabling acute ischemic stroke. Design, Setting, and Participants: This multicenter, open-label, blinded end point, noninferiority randomized clinical trial included 760 patients with acute minor nondisabling stroke (National Institutes of Health Stroke Scale [NIHSS] score ≤5, with ≤1 point on the NIHSS in several key single-item scores; scale range, 0-42). The trial was conducted at 38 hospitals in China from October 2018 through April 2022. The final follow-up was on July 18, 2022. Interventions: Eligible patients were randomized within 4.5 hours of symptom onset to the DAPT group (n = 393), who received 300 mg of clopidogrel on the first day followed by 75 mg daily for 12 (±2) days, 100 mg of aspirin on the first day followed by 100 mg daily for 12 (±2) days, and guideline-based antiplatelet treatment until 90 days, or the alteplase group (n = 367), who received intravenous alteplase (0.9 mg/kg; maximum dose, 90 mg) followed by guideline-based antiplatelet treatment beginning 24 hours after receipt of alteplase. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score of 0 or 1 (range, 0-6), at 90 days. The noninferiority of DAPT to alteplase was defined on the basis of a lower boundary of the 1-sided 97.5% CI of the risk difference greater than or equal to -4.5% (noninferiority margin) based on a full analysis set, which included all randomized participants with at least 1 efficacy evaluation, regardless of treatment group. The 90-day end points were assessed in a blinded manner. A safety end point was symptomatic intracerebral hemorrhage up to 90 days. Results: Among 760 eligible randomized patients (median [IQR] age, 64 [57-71] years; 223 [31.0%] women; median [IQR] NIHSS score, 2 [1-3]), 719 (94.6%) completed the trial. At 90 days, 93.8% of patients (346/369) in the DAPT group and 91.4% (320/350) in the alteplase group had an excellent functional outcome (risk difference, 2.3% [95% CI, -1.5% to 6.2%]; crude relative risk, 1.38 [95% CI, 0.81-2.32]). The unadjusted lower limit of the 1-sided 97.5% CI was -1.5%, which is larger than the -4.5% noninferiority margin (P for noninferiority <.001). Symptomatic intracerebral hemorrhage at 90 days occurred in 1 of 371 participants (0.3%) in the DAPT group and 3 of 351 (0.9%) in the alteplase group. Conclusions and Relevance: Among patients with minor nondisabling acute ischemic stroke presenting within 4.5 hours of symptom onset, DAPT was noninferior to intravenous alteplase with regard to excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03661411.

Effect of Argatroban Plus Intravenous Alteplase vs Intravenous Alteplase Alone on Neurologic Function in Patients With Acute Ischemic Stroke: The ARAIS Randomized Clinical Trial.

Importance: Previous studies suggested a benefit of argatroban plus alteplase (recombinant tissue-type plasminogen activator) in patients with acute ischemic stroke (AIS). However, robust evidence in trials with large sample sizes is lacking. Objective: To assess the efficacy of argatroban plus alteplase for AIS. Design, Setting, and Participants: This multicenter, open-label, blinded end point randomized clinical trial including 808 patients with AIS was conducted at 50 hospitals in China with enrollment from January 18, 2019, through October 30, 2021, and final follow-up on January 24, 2022. Interventions: Eligible patients were randomly assigned within 4.5 hours of symptom onset to the argatroban plus alteplase group (n = 402), which received intravenous argatroban (100 µg/kg bolus over 3-5 minutes followed by an infusion of 1.0 µg/kg per minute for 48 hours) within 1 hour after alteplase (0.9 mg/kg; maximum dose, 90 mg; 10% administered as 1-minute bolus, remaining infused over 1 hour), or alteplase alone group (n = 415), which received intravenous alteplase alone. Both groups received guideline-based treatments. Main Outcomes and Measures: The primary end point was excellent functional outcome, defined as a modified Rankin Scale score (range, 0 [no symptoms] to 6 [death]) of 0 to 1 at 90 days. All end points had blinded assessment and were analyzed on a full analysis set. Results: Among 817 eligible patients with AIS who were randomized (median [IQR] age, 65 [57-71] years; 238 [29.1%] women; median [IQR] National Institutes of Health Stroke Scale score, 9 [7-12]), 760 (93.0%) completed the trial. At 90 days, 210 of 329 participants (63.8%) in the argatroban plus alteplase group vs 238 of 367 (64.9%) in the alteplase alone group had an excellent functional outcome (risk difference, -1.0% [95% CI, -8.1% to 6.1%]; risk ratio, 0.98 [95% CI, 0.88-1.10]; P = .78). The percentages of participants with symptomatic intracranial hemorrhage, parenchymal hematoma type 2, and major systemic bleeding were 2.1% (8/383), 2.3% (9/383), and 0.3% (1/383), respectively, in the argatroban plus alteplase group and 1.8% (7/397), 2.5% (10/397), and 0.5% (2/397), respectively, in the alteplase alone group. Conclusions and Relevance: Among patients with acute ischemic stroke, treatment with argatroban plus intravenous alteplase compared with alteplase alone did not result in a significantly greater likelihood of excellent functional outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT03740958.

Neutralizing Antibodies against the SARS-CoV-2 Delta and Omicron BA.1 following Homologous CoronaVac Booster Vaccination.

Emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have reduced susceptibility to neutralization by vaccines. In response to the constantly updated variants, a global vaccine booster vaccination program has been launched. In this study, we detected neutralizing antibody levels against wild-type (WT), Delta (B1.617.2), and Omicron BA.1 viruses in serum after each dose of CoronaVac vaccination. We found that booster vaccination significantly increased the levels of neutralizing antibodies against WT, Delta, and Omicron BA.1. Compared with only one vaccination, neutralizing antibody levels increased by 19.2-21.6-fold after a booster vaccination, whilst two vaccinations only produced a 1.5-3.4-fold increase. Our results support the conclusion that the CoronaVac vaccine booster can increase neutralizing antibody levels and cross-reactivity and enhance the body's ability to effectively resist the infection of new coronavirus variants, emphasizing the need for booster vaccination.

First Report of Colletotrichum aenigma Causing Anthracnose of tree peony in China.

Tree peonies (Paeonia suffruticosa Andr. and hybrids) are well-known ornamental and medicinal plants cultivated in temperate and subtropical regions around the world. From June to September 2021, severe leaf spot disease was observed on 3 tree peony cultivars ('Luoyanghong', 'Moyushenghui', 'Roufurong') in Xinxiang (35º29´N, 113º95´E) and Luoyang (34º64´N, 112º49´E), Henan Province, China. Leaf spot incidence was as high as 28% ('Luoyanghong'), 45% ('Moyushenghui') and 67% ('Roufurong'), respectively. Symptoms appeared initially as small purple spots less than 1 mm in diameter in the middle and upper parts of the leaves, and then evolved to coalescent lesions, causing brown scorch ultimately. From each cultivar, 5 diseased leaves were collected. Leaflet tissues (3-4 mm2) cut from spot margins were surface sterilized in 75% alcohol for 45 s, washed 5 times with sterile distilled water, and then cultivated on potato dextrose agar (PDA) medium at 28 °C in the dark. Eleven isolates were obtained, and colonies grown from single conidia on PDA were 80-85 mm in diameter after 10 d, with scattered small, dark-based spikes on the surface of the colonies. The aerial mycelium was cottony, dense, and dark gray near the center on the reverse side. Conidia were cylindrical to clavate, with rounded apex and rounded base, and the conidia contents were granular, 8.44-14.06×3.60-4.31 µm (mean=11.28×3.69 µm, n=40). Appressoria were mostly subglobose or with a few broad lobes, pale to medium brown, 3.36-6.72×3.35-5.60 µm (mean=5.02×4.55 µm, n=20). Based on the culture representation and conidial morphology, the isolates were characterized as Colletotrichum gloeosporioides species complex (Weir et al. 2012; Fu et al. 2019). To further identity the species, the actin (ACT), calmodulin (CAL), chitin synthase (CHS-1), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and the ribosomal internal transcribed spacers (ITS) loci of isolates PSW0002, PSW0008 and PSW0009 were amplified using ACT-512F/ACT-783R, CL1C/CL2C, CHS-79F/CHS-345R, GDF/GDR, and ITS1/ITS4, primers (Weir et al. 2012; Schena et al; 2014; Kim et al. 2021; Li et al. 2021). Fifteen sequences were deposited in GenBank (ACT for OP225605, OP225606, and OP225607, CAL for OP225608, OP225609 and OP225610, CHS for OP225611, OP225612 and OP225613, GAPDH for ON321897, OP225614, and OP225615, and ITS for ON323473, OP214349 and OP214350 ), which showed 100% sequence similarity to Colletotrichum aenigma (JX009443 and JX009519 for ACT, JX009683 and JX009684 for CAL, JX009774 and JX009903 for CHS-1, JX010244 and JX009913 for GAPDH, JX010243 and JX010148 for ITS). Three isolates clustered with C. aenigma (ex-holotype culture ICMP 18608) in the multi-locus phylogenetic tree with a bootstrap value of 100%. To achieve Koch's postulates, pathogenicity was tested on 5-year-old healthy potted plants ('Luoyanghong'). Thirty leaves were inoculated with 10 µL conidial suspension (isolate PSW0002, 1×106 conidia/mL) and the controls were inoculated with sterile water. Plants were placed in a greenhouse at 28°C under conditions with 12 h photoperiod and 90% relative humidity. After 5 to 10 days, distinct spots were observed on the inoculated leaves, while the control leaves showed no symptoms. C. aenigma was reisolated from all inoculated leaves, but not from the control. C. aenigma has been reported to cause anthracnose on Pyrus pyrifolia (Weir et al. 2012), Camellia sasanqua (Chen et al. 2019), Juglans regia (Wang et al. 2020), Paeonia ostii (Ren et al. 2020), and Capsicum annuum (Sharma et al. 2022). A previous study reported C. gloeosporioides as a pathogen of anthracnose in tree peonies in China (Xuan et al. 2017), the typical symptoms were big necrotic lesions (5-10 mm diam) on leaves，which were significantly different from those caused by C. aenigma. To our knowledge, this is the first report of C. aenigma causing anthracnose in tree peonies in China. This finding may help to take effective control of anthracnose in tree peonies.

Screening for Active Compounds Targeting Human Natural Killer Cell Activation Identifying Daphnetin as an Enhancer for IFN-γ Production and Direct Cytotoxicity.

Natural killer (NK) cells are a potent weapon against tumor and viral infection. Finding active compounds with the capacity of enhancing NK cell effector functions will be effective to develop new anti-cancer drugs. In this study, we initially screened 287 commercially available active compounds by co-culturing with peripheral blood mononuclear cells (PBMCs). We found that five compounds, namely, Daphnetin, MK-8617, LW6, JIB-04, and IOX1, increased the IFN-γ+ NK cell ratio in the presence of IL-12. Further studies using purified human primary NK cells revealed that Daphnetin directly promoted NK cell IFN-γ production in the presence of IL-12 but not IL-15, while the other four compounds acted on NK cells indirectly. Daphnetin also improved the direct cytotoxicity of NK cells against tumor cells in the presence of IL-12. Through RNA-sequencing, we found that PI3K-Akt-mTOR signaling acted as a central pathway in Daphnetin-mediated NK cell activation in the presence of IL-12. This was further confirmed by the finding that both inhibitors of PI3K-Akt and its main downstream signaling mTOR, LY294002, and rapamycin, respectively, can reverse the increase of IFN-γ production and cytotoxicity in NK cells promoted by Daphnetin. Collectively, we identify a natural product, Daphnetin, with the capacity of promoting human NK cell activation via PI3K-Akt-mTOR signaling in the presence of IL-12. Our current study opens up a new potential application for Daphnetin as a complementary immunomodulator for cancer treatments.

Minocycline alleviates Gulf War Illness rats via altering gut microbiome, attenuating neuroinflammation and enhancing hippocampal neurogenesis.

Accumulating evidences suggest that deficits in neurogenesis, chronic inflammation and gut microbiome dysregulation contribute to the pathophysiology of Gulf War Illness (GWI). Minocycline has been demonstrated to be a potent neuroprotective agent and could regulate neuroinflammation. The present study intends to investigate whether the treatment of minocycline maintains better cognition and mood function in a rat model of GWI and the potential mechanism. Rats received 28 days of GWI-related chemical exposure and restraint stress, along with daily minocycline or vehicle treatment. Cognitive and mood function, neuroinflammation, neurogenesis and gut microbiota were detected. We found that minocycline treatment induces better cognitive and mood function in the GWI rat model, as indicated by open-field test, elevated plus maze test, novel object recognition test and forced swim test. Moreover, minocycline treatment reversed the altered gut microbiome, neuroinflammation and the decreased hippocampal neurogenesis of rats with GWI. Taken together, our study indicated that minocycline treatment exerts better cognitive and mood function in GWI rat model, which is possibly related to gut microbiota remodeling, restrained inflammation and enhanced hippocampal neurogenesis. These results may establish minocycline as a potential prophylactic or therapeutic agent for the treatment of GWI.

A combination of pirfenidone and TGF-ß inhibition mitigates cystic echinococcosis-associated hepatic injury.

Cystic echinococcosis (CE) occurs in the intermediate host's liver, assuming a bladder-like structure surrounded by the host-derived collagen capsule mainly derived from activated hepatic stellate cells (HSCs). However, the effect of CE on liver natural killer (NK) cells and the potential of transforming growth factor-ß (TGF-ß) signalling inhibition on alleviating CE-related liver damage remain to be explored. Here, by using the CE-mouse model, we revealed that the inhibitory receptors on the surface of liver NK cells were up-regulated, whereas the activating receptors were down-regulated over time. TGF-ß1 secretion was elevated in liver tissues and mainly derived from macrophages. A combination of TGF-ß signalling inhibitors SB525334 and pirfenidone could reduce the expression of TGF-ß1 signalling pathway-related proteins and collagen production. Based on the secretion of TGF-ß1, only the pirfenidone group showed a depressing effect. Also, the combination of SB525334 and pirfenidone exhibited a higher potential in effectively alleviating the senescence of the hepatocytes and restoring liver function. Together, TGF-ß1 may be a potential target for the treatment of CE-associated liver fibrosis.

Enhancing Thermoelectric Performance of Polyaniline/Single-Walled Carbon Nanotube Composites via Dimethyl Sulfoxide-Mediated Electropolymerization.

The fabrication of flexible high-performance organic/inorganic thermoelectric (TE) composite films has been a hot spot for researchers in recent years. In this work, dynamic 3-phase interfacial electropolymerization of aniline, together with physical mixing with single-walled carbon nanotubes (SWCNTs), was adopted to prepare polyaniline/SWCNT (PANI/SWCNT) TE composites. The dimethyl sulfoxide (DMSO) added into the electrochemical polymerization system affords strong capability in improving the TE performance of composite films. Moreover, varying loadings of SWCNTs can also conveniently tune the TE performance of composites. Hence, the resultant composites afford the highest power factor (PF) of 236.4 ± 5.9 µW m-1 K-2 at room temperature. This work demonstrates that the introduction of DMSO into the electrolyte and the electrochemical polymerization are highly effective in fabricating high-performance PANI/SWCNT TE composites.

Draft genome of the famous ornamental plant Paeonia suffruticosa.

Tree peony (Paeonia Sect. Moutan) is a famous ornamental plant, with huge historical, cultural, and economic significance worldwide. In this study, we reported the ~13.79 Gb draft genome of a wide-grown Paeonia suffruticosa cultivar "Luo shen xiao chun," representing the largest sequenced genome in dicots to date. Phylogenetic analyses based on genome sequences demonstrated that P. suffruticosa was placed as sister to Vitales, and they together formed a clade that was sister to Rosids, weakly supporting a relationship of ((Saxifragales and Vitales) and Rosids). The identification and expression analysis of MADS-box genes based on the genome assembly and de novo transcriptome assembly of P. suffruticosa revealed that the function of C class genes was restricted in flower development, which might be responsible for the stamen petalody in tree peony cultivars. Overall, the first sequenced genome in the family Paeoniaceae provides an important resource for the origin, domestication, and evolutionary study as well as cultivar breeding in tree peony.

[Study on effect of echinococcus granulosus protoscolices on fibrosis of bone marrow mesenchymal stem cells].

OBJECTIVE: To investigate the effect of echinococcus granulosus protoscolices on the differentiation of bone marrow mesenchymal stem cells (BMSCs) into fibroblasts. METHODS: Femur bone marrow of 4-week-old C57BL/6 mice was taken and BMSCs were isolated and cultured by adherent culture. Echinococcus granulosus protoscolices was extracted from the liver of sheep infected with echinococcus granulosus. The experiment was divided into two groups. The experimental group was co-cultured with the 3rd generation BMSCs and the echinococcus granulosus protoscolices, and the control group was the 3rd generation BMSCs. Before and after co-culture, the morphology of BMSCs and the activity of echinococcus granulosus protoscolices were observed by inverted microscope. After cultured for 1, 3, 5, and 7 days, the mRNA expressions of transforming growth factor ß 1 (TGF-ß 1), collagen type Ⅰ, and collagen type Ⅲ were detected by real-time fluorescent quantitative PCR, the protein expressions of TGF-ß 1, collagen type Ⅰ, collagen type Ⅲ, Smad7, and phosphorylated Smad2/3 were detected by Western blot, and the contents of collagen type Ⅰ and collagen type Ⅲ in the supernatant of the two groups were detected by ELISA. RESULTS: After 7 days of co-culture, the morphology of BMSCs changed into fusiform and irregular triangle, which was closer to the mouse fibroblasts. The relative mRNA expressions of TGF-ß 1, collagen type Ⅰ, and collagen type Ⅲ in the experimental group were significantly higher than those in the control group; the relative protein expressions of TGF-ß 1, collagen type Ⅰ, collagen type Ⅲ, and phosphorylated Smad2/3 in the experimental group were significantly higher than those in the control group, and the relative protein expression of Smad7 in the experimental group was significantly lower than that in the control group; the contents of collagen type Ⅰ and collagen type Ⅲ in the supernatant of the experimental group were significantly higher than those in the control group. The differences between the two groups were significant ( P<0.05). CONCLUSION: Echinococcus granulosus protoscolices may promote the secretion of collagen type Ⅰ, collagen type Ⅲ, and TGF-ß 1 by TGF-ß 1/Smad signal pathway, which can promote the fibrosis of BMSCs that related to the formation of fibrocystic wall by echinococcosis.

Estrogen and propofol combination therapy inhibits endoplasmic reticulum stress and remarkably attenuates cerebral ischemia-reperfusion injury and OGD injury in hippocampus.

AIM: Endoplasmic reticulum stress (ERS) is vital in inducing apoptosis via caspase-12 and C/EBP homologous protein (CHOP) apoptotic pathway in the hippocampus after ischemia-reperfusion injury. The study aimed to estimate the efficacy of estrogen and propofol combination therapy against ERS-induced apoptosis after cerebral ischemia-reperfusion injury and oxygen-glucose deprivation (OGD) injury in the hippocampus in vivo and in vitro. METHODS: Rat model of cerebral ischemia-reperfusion injury was generated by middle cerebral artery occlusion (MCAO) strategy with ischemic intervention for 90 min and reperfusion for 24 h. Propofol processing ischemia-reperfusion group (Propofol group) infused 50 mg/kg/h of propofol via the femoral vein at the onset of reperfusion for 30 min. Estrogen processing ischemia-reperfusion group (estrogen group) received 0.0125 mg/kg of estrogen via tail vein at 30 min prior to MCAO. Combination therapy for ischemia-reperfusion group (combination group) received simultaneous processing with propofol and estrogen. In vitro, brain slices were randomly exposed to dimethylsulfoxide (DSMO), 10 µm of propofol, 10 nm of estrogen, or propofol and estrogen. Changes in the orthodromic population spike (OPS) at the end of reoxygenation were recorded. Neurological deficit examination, Nissl staining, and 2,3,5-triphenyltetrazolium chloride (TTC) staining were employed to evaluate the level of cerebral ischemia-reperfusion injury. The expression of caspase-3, caspase-12, glucose-regulated protein 78 (GRP78), and CHOP were investigated by Western blot and immunofluorescence staining assays. Neural apoptotic rate in hippocampus was detected by the flow cytometry trial. RESULTS: Neurological deficit score, infarct volume, the expression of caspase-3 (P < 0.05), caspase-12, GRP78, CHOP, and neural apoptotic rate of I/R group increased markedly (P < 0.01). When obtaining drug treatment, neurological deficit score (P < 0.05), infarct volume, the expression levels of caspase-12 and GRP78, and neural apoptotic rate of the propofol group decreased significantly (P < 0.01). Furthermore, neurological deficit score, infarct volume, expression levels of caspase-3, caspase-12, GRP78, and CHOP (P < 0.05), and neural apoptotic rate decreased in the estrogen group (P < 0.01) and especially in the combination group (P < 0.01). Compared with the propofol group, the neurological deficit score (P < 0.05), infarct volume, caspase-3, caspase-12, GRP78, CHOP, and neural apoptotic rate of the combination group decreased (P < 0.01). Compared with the estrogen group, the infarct volume, caspase-3 (P < 0.05), GRP78, CHOP, and neural apoptotic rate (P < 0.05) of the combination group decreased (P < 0.01). Compared with the propofol group, the infarct volume, caspase-3, caspase-12 (P < 0.05), and GRP78 (P < 0.05) of the estrogen group decreased (P < 0.01). Propofol and estrogen treatment can delay the abolishing time of OPS and increase the recovery rate and amplitude of OPS, compared with OGD group (P < 0.01), especially in the combination therapy (P < 0.01). CONCLUSION: The neuroprotection of propofol and estrogen combination therapy inhibited excessive ERS-induced apoptosis against cerebral ischemia-reperfusion injury and OGD injury in the hippocampus of rats. Furthermore, the outcomes demonstrated that combination therapy yielded synergistic effects.

The efficacy and safety of high-dose statins in acute phase of ischemic stroke and transient ischemic attack: a systematic review.

Inconsistent findings in the studies have been observed concerning the higher dose of statins use in the acute phase of ischemic stroke and transient ischemic attack (TIA). Therefore, we performed a systematic review to assess this issue. A computerized literature search in PubMed, Cochrane Library databases, and EMBASE for randomized controlled trials (RCTs) was conducted. The efficacy outcome indicators were National Institutes of Health Stroke Scale (NIHSS) score, infarct volume, and recurrence of stroke; the safety outcome indicators were intracranial hemorrhage events, cardiovascular and cerebrovascular events, and all-cause death. Pre-specified subgroup analyses were carried out. A total of seven RCTs with 1089 patients were included. Six studies reported the results of the NHISS score. A great reduction was found in NIHSS score in the statins group, and the difference is statistically significant [mean difference (MD) -1.15, 95% confidence interval (CI) -1.64 to -0.66, P < 0.00001]. However, no significant differences in the effect on recurrence of stroke [odds ratio (OR) 1.05, 95% CI 0.65-1.69, P = 0.85] (available in 3 studies), infarct volume [std. mean difference (SMD) 0.04, 95% CI -0.55 to 0.63, P = 0.89] (available in 2 studies), intracerebral hemorrhage events (OR 3.25, 95% CI 0.34-31.52, P = 0.31) (available in 2 studies), cardiovascular and cerebrovascular events (OR 0.70, 95% CI 0.35-1.43, P = 0.33) (available in 2 studies), and all-cause death (OR 1.18, 95% CI 0.60-2.35, P = 0.63) (available in 2 studies) were found. High-dose statin therapy in the acute phase of ischemic stroke and TIA significantly reduce the NIHSS score and improve short-term functional outcome without increasing related adverse events.

Design and evaluation of an electrolarynx with tonal control function for Mandarin.

OBJECTIVE: To improve the speech quality of laryngectomized speakers of Mandarin, we designed an electrolarynx with tonal control function (tone-EL) by using the movement of a trackball. The performance of the tone-EL in producing Mandarin was evaluated. METHODS: The performance of tone-EL was evaluated via a listening experiment. The perceptual accuracies of monosyllabic words, different categories of phrases with different cues were measured and compared with that produced with a conventional EL. The acceptability of sentences was also measured. RESULTS: The perceptual accuracies of monosyllabic words and tones associated with the words produced with the tone-EL were significantly higher than those of monotonic EL speech. The perceptual accuracy of phrases was significantly higher than in monotonic EL speech when no categorical cue for listeners was provided, whereas they were at a close level when categorical information of the phrases was provided in advance. The acceptability of sentences was higher than that of monotonic EL speech. CONCLUSION: Using the tone-EL can produce Mandarin tones effectively and the quality of rehabilitated Mandarin is better than using a conventional-EL. To balance speech intelligibility and ease of use, a strategy -producing tonal speech when few informative cues are available to listeners is preferred.

[Ethanol production from sweet sorghum stalks by advanced solid state fermentation (ASSF) technology].

A robust strain of the species Saccharomyces cerevisiae CGMCC1949 was screened and identified, and advanced solid state fermentation (ASSF) technology for fuel ethanol production from sweet sorghum stalks was thus developed. The fermentation time was shortened to less than 30 h, and ethanol yield was 92% of its theoretical maximum. And in the meantime, the cost-effective storage was established for sweet sorghum stalks, with less than 5% sugar loss after 200 days of storage, making the plant operation could extend up to 200 days without feedstock shortage. With the fermentation kinetics and heat-mass transfer models, modeling of the ASSF process was investigated, and the rotating drum bioreactor was designed. Furthermore, the ASSF technology was successfully applied in the pilot plant in which the rotating drum bioreactor was scaled up to 127 m3, and ethanol yield of 91% was achieved. At the end, techno-economic analysis (TEA) conducted by ASPEN indicated that ethanol production from sweet sorghum stalks by the ASSF is economically competitive.