Expression analysis of squalene synthase gene in mevalonate pathway of <i>Sanghuangporus baumii</i>

Fungi produce a wide repertoire of secondary metabolites with pharmaceutical impacts on human health. However, the low expression of secondary metabolites limits their clinical application. Triterpenoids produced by Sanghuangporus baumii possess anti-cancer properties, however, their biosynthetic pathway and regulatory mechanism remain unclear. In this study, squalene synthase gene (SbSQS), a key gene involved in the mevalonate pathway, was cloned and analyzed. Sequence analysis identified SbSQS as a typical squalene synthase with three conserved catalytic structures related to binding and catalysis. The SbSQS gene encodes a 489 amino acid polypeptide with a predicted protein molecular weight of 55.05 kDa. The promoter of SbSQS contains cis-acting regulatory elements involved in the light, abscisic acid and MeJA responsiveness, which is consistent with the promoters of other genes in the mevalonate pathway. Furthermore, SbSQS was cloned into the pET-32a vector and overexpressed in Escherichia coli. During mycelium fermentation of S. baumii, the biomass increased as fermentation progressed, and peaked on day 18 (1.20 g/250 mL). The triterpenoid content did not accumulate during the fermentation process and was 20.8 mg · g−1 on day 18. The SbSQS expression and the triterpenoid content were peaked on day 6, suggesting a correlation between SbSQS expression level with triterpenoid content. This study proposes a key candidate gene for genetic manipulation of the triterpenoid synthesis to enhance the triterpenoid content in S. baumii.</p

Data_Sheet_1_Disease-modifying therapy in progressive multiple sclerosis: a systematic review and network meta-analysis of randomized controlled trials.PDF

BackgroundCurrently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive.ObjectivesThis systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs.MethodsMEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs).ResultsWe included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12–1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59–1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty).ConclusionDMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS.Systematic review registrationhttps://inplasy.com/?s=202320071, identifier: 202320071.</p

Formation Mechanism of Monocyclic Aromatic Hydrocarbons during Pyrolysis of Styrene Butadiene Rubber in Waste Passenger Car Tires

The production of aromatic hydrocarbons from the waste tire pyrolysis attracts more and more attention because of its tremendous potential. Based on styrene-butadiene rubber (SBR), which is the main rubber in the waste passenger car tires, this work studies the temperature influence on primary pyrolysis product distribution by experimental techniques (Py-GC/MS, TG–MS), and then, the formation mechanism of monocyclic aromatic hydrocarbons (MAHs) observed in the experiment was analyzed by first-principles calculations. The experimental results show that the MAHs during the pyrolysis mainly include styrene, toluene, and xylene, and subsequent calculations showed that these compounds were formed through a series of primary and secondary reactions. The formation pathways of these typical MAHs were studied via the reaction energy barrier analysis, respectively. It shows that the MAHs were not only derived from the benzene ring in the SBR chain but also generated from short-chain alkenes through the Diels–Alder reaction. The obtained pyrolysis reaction mechanism provides theoretical guidance for the regulation of the pyrolysis product distribution of MAHs

Lithiation Behavior of Individual Carbon-Coated Fe₃O₄ Nanowire Observed by in Situ TEM

Fe3O4 nanowires, as a typical transition-metal oxide (TMO), are being considered as promising anodes for lithium ion batteries (LIBs) due to their 1D structure and high specific capacity. However, their underlying mechanism and electrochemical behaviors are still poorly understood. Here, the dynamic behavior and the electrochemical reaction of the carbon-coated Fe3O4 (Fe3O4@C) nanowire have been investigated directly through assembling a nanoscale LIBs inside transmission electron microscope (TEM). The in situ TEM results reveal that the Fe3O4 nanowires undergo cracking and fracturing upon the first lithiation, but the carbon coatings still embrace the oxide cores well after lithiation and play a role in maintaining the mechanical and electrical integrity. Meanwhile the lithiation process involves the conversion of Fe3O4 nanowires to Fe nanograins and the formation of Li2O along the lithium ions diffusion direction. The delithiated product is FeO rather than the original phase of Fe3O4 after the first delithiation process. This irreversible phase conversion may be a major cause of capacity fading of the electrode in the first cycle. As for the Fe3O4 electrode, about 78% of the capacity loss can be attributed to the irreversible phase reaction in the first cycle. During the subsequent lithiation-delithiation cycles, the Fe3O4 electrode shows a reversible conversion between Fe and FeO nanograins, accounting for the good reversibility of Fe3O4 anodes for LIBs. Our in situ results provide important insights into the electrochemical behavior and conversion mechanism of TMO-based anodes in LIBs and are helpful for designing LIBs with outstanding performance

Lithiation Behavior of Individual Carbon-Coated Fe₃O₄ Nanowire Observed by in Situ TEM

Fe3O4 nanowires, as a typical transition-metal oxide (TMO), are being considered as promising anodes for lithium ion batteries (LIBs) due to their 1D structure and high specific capacity. However, their underlying mechanism and electrochemical behaviors are still poorly understood. Here, the dynamic behavior and the electrochemical reaction of the carbon-coated Fe3O4 (Fe3O4@C) nanowire have been investigated directly through assembling a nanoscale LIBs inside transmission electron microscope (TEM). The in situ TEM results reveal that the Fe3O4 nanowires undergo cracking and fracturing upon the first lithiation, but the carbon coatings still embrace the oxide cores well after lithiation and play a role in maintaining the mechanical and electrical integrity. Meanwhile the lithiation process involves the conversion of Fe3O4 nanowires to Fe nanograins and the formation of Li2O along the lithium ions diffusion direction. The delithiated product is FeO rather than the original phase of Fe3O4 after the first delithiation process. This irreversible phase conversion may be a major cause of capacity fading of the electrode in the first cycle. As for the Fe3O4 electrode, about 78% of the capacity loss can be attributed to the irreversible phase reaction in the first cycle. During the subsequent lithiation-delithiation cycles, the Fe3O4 electrode shows a reversible conversion between Fe and FeO nanograins, accounting for the good reversibility of Fe3O4 anodes for LIBs. Our in situ results provide important insights into the electrochemical behavior and conversion mechanism of TMO-based anodes in LIBs and are helpful for designing LIBs with outstanding performance

Lithiation Behavior of Individual Carbon-Coated Fe₃O₄ Nanowire Observed by in Situ TEM

Fe₃O₄ nanowires, as a typical transition-metal oxide (TMO), are being considered as promising anodes for lithium ion batteries (LIBs) due to their 1D structure and high specific capacity. However, their underlying mechanism and electrochemical behaviors are still poorly understood. Here, the dynamic behavior and the electrochemical reaction of the carbon-coated Fe₃O₄ (Fe₃O₄@C) nanowire have been investigated directly through assembling a nanoscale LIBs inside transmission electron microscope (TEM). The in situ TEM results reveal that the Fe₃O₄ nanowires undergo cracking and fracturing upon the first lithiation, but the carbon coatings still embrace the oxide cores well after lithiation and play a role in maintaining the mechanical and electrical integrity. Meanwhile the lithiation process involves the conversion of Fe₃O₄ nanowires to Fe nanograins and the formation of Li₂O along the lithium ions diffusion direction. The delithiated product is FeO rather than the original phase of Fe₃O₄ after the first delithiation process. This irreversible phase conversion may be a major cause of capacity fading of the electrode in the first cycle. As for the Fe₃O₄ electrode, about 78% of the capacity loss can be attributed to the irreversible phase reaction in the first cycle. During the subsequent lithiation-delithiation cycles, the Fe₃O₄ electrode shows a reversible conversion between Fe and FeO nanograins, accounting for the good reversibility of Fe₃O₄ anodes for LIBs. Our in situ results provide important insights into the electrochemical behavior and conversion mechanism of TMO-based anodes in LIBs and are helpful for designing LIBs with outstanding performance

Data_Sheet_1_The efficacy and safety of anti-Aβ agents for delaying cognitive decline in Alzheimer’s disease: a meta-analysis.DOCX

BackgroundThis meta-analysis evaluates the efficacy and safety of amyloid-β (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer’s disease (AD).MethodsPubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023.ResultsWe pooled 33,689 participants from 42 studies. The meta-analysis showed no difference between anti-Aβ drugs and placebo in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), and anti-Aβ drugs were associated with a high risk of adverse events [ADAS-Cog: MDs = −0.08 (−0.32 to 0.15), p = 0.4785; AEs: RR = 1.07 (1.02 to 1.11), p = 0.0014]. Monoclonal antibodies outperformed the placebo in delaying cognitive deterioration as measured by ADAS-Cog, Clinical Dementia Rating–Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL), without increasing the risk of adverse events [ADAS-Cog: MDs = −0.55 (−0.89 to 0.21), p = 0.001; CDR-SB: MDs = −0.19 (−0.29 to −0.10), p ConclusionCurrent evidence does not show that anti-Aβ drugs have an effect on cognitive performance in AD patients. However, monoclonal antibodies can delay cognitive decline in AD. Development of other types of anti-Aβ drugs should be cautious.Systematic Review RegistrationPROSPERO (https://www.crd.york.ac.uk/prospero/), identifier CRD42023391596.</p

Data_Sheet_1_The efficacy and safety of general anesthesia vs. conscious sedation for endovascular treatment in patients with acute ischemic stroke: a systematic review and meta-analysis.pdf

BackgroundEndovascular thrombectomy (EVT) is an important treatment for patients with acute ischemic stroke (AIS). A number of studies have suggested that anesthesia type (conscious sedation vs. general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes.MethodsPubMed, EMBASE, Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) that were performed to evaluate general anesthesia (GA) and conscious sedation (CS) up to May 30, 2023. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) were analyzed and calculated with a fixed effect model.ResultsWe pooled 930 patients from seven RCTs. We conducted a meta-analysis comparing the outcomes of GA and CS in the included trials. The rate of functional independence in the GA group was higher than that in the CS group (RR: 1.17, 95% CI: 1.00–1.35; P = 0.04; I2 = 16%). The GA group had a higher successful recanalization rate than the CS group (RR: 1.15, 95% CI: 1.08–1.22; P 2 = 26%). The GA group had a higher pneumonia rate than the CS group (RR: 1.69, 95% CI: 1.22–2.34; P = 0.002; I2 = 26%). In addition, there was no significant difference between GA and CS with respect to the National Institutes of Health Stroke Scale (NIHSS) score at 24 h (P = 0.62), Modified Rankin Scale (mRS) score at 90 days (P = 0.25), intracerebral hemorrhage (P = 0.54), and mortality at 3 months (P = 0.61).ConclusionGA demonstrated superiority over CS in achieving successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, it was also associated with a higher risk of pneumonia. Further studies, particularly those with long-term follow-ups, are necessary to identify precise strategies for selecting the appropriate anesthetic modality in EVT patients.Systematic review registrationINPLASY202370116.</p

Table_1_The efficacy and safety of general anesthesia vs. conscious sedation for endovascular treatment in patients with acute ischemic stroke: a systematic review and meta-analysis.docx

BackgroundEndovascular thrombectomy (EVT) is an important treatment for patients with acute ischemic stroke (AIS). A number of studies have suggested that anesthesia type (conscious sedation vs. general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes.MethodsPubMed, EMBASE, Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) that were performed to evaluate general anesthesia (GA) and conscious sedation (CS) up to May 30, 2023. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) were analyzed and calculated with a fixed effect model.ResultsWe pooled 930 patients from seven RCTs. We conducted a meta-analysis comparing the outcomes of GA and CS in the included trials. The rate of functional independence in the GA group was higher than that in the CS group (RR: 1.17, 95% CI: 1.00–1.35; P = 0.04; I2 = 16%). The GA group had a higher successful recanalization rate than the CS group (RR: 1.15, 95% CI: 1.08–1.22; P 2 = 26%). The GA group had a higher pneumonia rate than the CS group (RR: 1.69, 95% CI: 1.22–2.34; P = 0.002; I2 = 26%). In addition, there was no significant difference between GA and CS with respect to the National Institutes of Health Stroke Scale (NIHSS) score at 24 h (P = 0.62), Modified Rankin Scale (mRS) score at 90 days (P = 0.25), intracerebral hemorrhage (P = 0.54), and mortality at 3 months (P = 0.61).ConclusionGA demonstrated superiority over CS in achieving successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, it was also associated with a higher risk of pneumonia. Further studies, particularly those with long-term follow-ups, are necessary to identify precise strategies for selecting the appropriate anesthetic modality in EVT patients.Systematic review registrationINPLASY202370116.</p