5-(Pyridin-2-yl)-3,3′-bi(1H-1,2,4-triazole)

In the title mol­ecule, C9H7N7, the two triazole rings are twisted by an angle of 3.8 (5)°; the central triazole ring is twisted by 32.3 (6)° with respect to the pyridyl ring. The crystal packing consists of layers generated by inter­molecular N—H⋯N hydrogen bonds

10-Benzyl-10H-phenothia­zine 9-oxide. Corrigendum

Corrigendum to Acta Cryst. (2009), E65, o1799

10-Benzyl-10H-phenothia­zine 9-oxide

In the title compound, C19H15NOS, the butterfly angle between the mean planes defined by the S, N and phenyl C atoms of the two wings of the phenothiazine unit is 23.4 (1)°. In the crystal, a supra­molecular two-dimensional arrangement arises from weak inter­molecular C—H⋯O inter­actions

Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress

Atherosclerosis is a progressive disease leading to loss of vascular homeostasis and entails fibrosis, macrophage foam cell formation, and smooth muscle cell proliferation. Recent studies have reported that epidermal growth factor receptor (EGFR) is involved vascular pathophysiology and in the regulation of oxidative stress in macrophages. Although, oxidative stress and inflammation play a critical role in the development of atherosclerosis, the underlying mechanisms are complex and not completely understood. In the present study, we have elucidated the role of EGFR in high-fat diet-induced atherosclerosis in apolipoprotein E null mice. We show increased EGFR phosphorylation and activity in atherosclerotic lesion development. EGFR inhibition prevented oxidative stress, macrophage infiltration, induction of pro-inflammatory cytokines, and SMC proliferation within the lesions. We further show that EGFR is activated through toll-like receptor 4. Disruption of toll-like receptor 4 or the EGFR pathway led to reduced inflammatory activity and foam cell formation. These studies provide evidence that EGFR plays a key role on the pathogenesis of atherosclerosis, and suggests that EGFR may be a potential therapeutic target in the prevention of atherosclerosis development

Features and influencing mechanisms of gaseous elemental mercury over the equatorial Pacific and their differences with the Southern Ocean

Due to the harmful impacts on the ecosystem and even human health, mercury (Hg) compounds in the environment deserve serious concern. Atmospheric mobilization and exchange at the air-sea interface are important processes in biogeochemical cycling of Hg. Relying on the 30th (2013/2014), 31st (2014/2015), and 33rd (2016/2017) Chinese National Antarctic Research Expedition aboard R/V Xuelong, we found significant rising gaseous elemental mercury (GEM) concentrations over the equatorial Central Indo-Pacific region. Excluding the contribution of anthropogenic, volcanic and biomass burning emissions, the enhanced GEM in marine boundary layer was likely due to the combined actions of two driving factors drove by the Inter-Tropical Conversion Zone (ITCZ): (1) intense wet deposition of Hg, followed by subsequent rapid photoreduction and vast evasion from the surface sea; and (2) the regional low-level convergence of airflow that caused the mass accumulation of GEM in air. In addition, apparently higher GEM concentration level in the equatorial Central Indo-Pacific than in the Southern Ocean was observed in one cruise. Further investigation suggests that apart from the ITCZ corresponded mechanisms, the effects of spatial differences in anthropogenic emissions and more significant GEM oxidation in Antarctic sea should play roles in this phenomenon

Mechanical thrombectomy with intra-arterial alteplase provided better functional outcomes for AIS-LVO: a meta-analysis

BackgroundSeveral clinical trials have shown that intra-arterial thrombolysis using alteplase during mechanical thrombectomy (MT) has a better outcome than MT alone in ischemic stroke management. We performed the current meta-analysis to estimate the efficacy and safety of MT with intra-arterial alteplase therapy.MethodsThe MEDLINE, Embase, Cochrane Library, and ClinicalTrials.gov databases were searched up to Mar. 2022 to identify the clinical trials that compared MT alone versus MT with intra-arterial alteplase therapy. STATA 16.0 was used for statistical analysis. The odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated with a random effect model.ResultsSeven studies involving 1,083 participants were included. The primary outcomes were better functional outcomes, defined as a modified Rankin Scale (mRS) score between 0 and 2 at 90  days, and successful recanalization, defined as a modified thrombolysis in cerebral infarction (mTICI) score  ≥  2b. Compared to MT alone, MT with intra-arterial alteplase did not lead to higher mTICI scores (OR 1.58, 95%CI 0.94 to 2.67, p = 0.085, I2 = 16.8%) but did lead to better mRS (OR 1.37, 95%CI 1.01 to 1.86, p = 0.044). There was no increase in mortality or bleeding events in the overall or subgroup analyses.ConclusionMT with intra-arterial alteplase did not improve the recanalization rate but provided better functional outcomes. The intervention did not increase adverse effects in any subgroup at the same time.Clinical trial registrationhttp://inplasy.com, identifier INPLASY202240027

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

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 < 0.0001; MMSE: MDs = 0.19 (0.00 to 0.39), p = 0.05; ADCS-ADL: MDs = 1.26 (0.84 to 1.68), p < 0.00001]. Intravenous immunoglobulin and γ-secretase modulators (GSM) increased cognitive decline in CDR-SB [MDs = 0.45 (0.17 to 0.74), p = 0.002], but had acceptable safety profiles in AD patients. γ-secretase inhibitors (GSI) increased cognitive decline in ADAS-Cog, and also in MMSE and ADCS-ADL. BACE-1 inhibitors aggravated cognitive deterioration in the outcome of the Neuropsychiatric Inventory (NPI). GSI and BACE-1 inhibitors caused safety concerns. No evidence indicates active Aβ immunotherapy, MPAC, or tramiprosate have effects on cognitive function and tramiprosate is associated with serious adverse events.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

Ecological responses of typical Antarctic marine organisms to climate change and anthropogenic impacts

To improve our understanding and ability to predict biological responses to global climate change, it is important to be able to distinguish the influences of natural forcing from anthropogenic impacts. In the ice-free areas of Antarctica, lake and terrestrial sediments that contain penguin guanos, seal excrement and other biological remains provide natural archives of ecological, geological and climatic information that range from hundreds to thousands of years old. Our review focuses on the paleoecology of typical Antarctic marine organisms (penguins, seals and Antarctic krill) and their responses to climate change and human activities over centennial and millennial timescales. Land-based seabirds and marine mammals play an important role in linking the marine and terrestrial ecosystems and act as bio-vectors, transporting large amounts of nutrients and contaminants from ocean to land

Rapid pathway prototyping and engineering using <i>in vitro</i> and <i>in vivo</i> synthetic genome SCRaMbLE-in methods

AbstractExogenous pathway optimization and chassis engineering are two crucial methods for heterologous pathway expression. The two methods are normally carried out step-wise and in a trial-and-error manner. Here we report a recombinase-based combinatorial method (termed “SCRaMbLE-in”) to tackle both challenges simultaneously. SCRaMbLE-in includes an in vitro recombinase toolkit to rapidly prototype and diversify gene expression at the pathway level and an in vivo genome reshuffling system to integrate assembled pathways into the synthetic yeast genome while combinatorially causing massive genome rearrangements in the host chassis. A set of loxP mutant pairs was identified to maximize the efficiency of the in vitro diversification. Exemplar pathways of β-carotene and violacein were successfully assembled, diversified, and integrated using this SCRaMbLE-in method. High-throughput sequencing was performed on selected engineered strains to reveal the resulting genotype-to-phenotype relationships. The SCRaMbLE-in method proves to be a rapid, efficient, and universal method to fast track the cycle of engineering biology.</jats:p

Early tissue and healing responses after maxillary sinus augmentation using horizontal platelet rich fibrin bone blocks.

BACKGROUND The effects of horizontal platelet-rich fibrin (H-PRF) bone block on the healing and immune response during sinus augmentation have not been fully investigated histologically at early time points. METHODS Eighteenth male New Zealand white rabbits underwent bilateral sinus augmentation and were divided into two groups: deproteinized bovine bone mineral (DBBM) alone and H-PRF + DBBM (H-PRF bone block) group. Maxilla samples were collected at 3, 7 and 14 days post sinus augmentation procedures and analyzed using histological staining for the number of inflammatory cells, new blood vessels and evidence for early osteoclast bone turnover/remodeling. Furthermore, the effects of H-PRF bone blocks on the migration of osteoblasts and THP-1 macrophages were evaluated using a Transwell assay in vitro. RESULTS A higher number of immune cells were found in the H-PRF bone block group at 3 and 7 days post-surgery when compared to the DBBM alone group,most notably in the regions close to the mucosal lining and bone plates. Furthermore, a significantly greater number of new blood vessel formations and early signs of osteoclast development were found in the H-PRF bone block group at 14 days. The in vitro transwell assay further confirmed that culture medium from H-PRF bone block markedly promote the migration of osteoblasts and THP-1 macrophages. CONCLUSIONS The findings from this study have shown that H-PRF bone block is capable of increasing early immune cell infiltration leading to the acceleration of neovascularization and speeding the process of bone metabolism in vivo following maxillary sinus grafting with DBBM