The (re)hemorrhage in patients with sporadic cerebral cavernous malformations (CCM) was the primary aim for CCM management. However, accurately identifying the potential (re)hemorrhage among sporadic ...CCM patients in advance remains a challenge. This study aims to develop machine learning models to detect potential (re)hemorrhage in sporadic CCM patients. This study was based on a dataset of 731 sporadic CCM patients in open data platform Dryad. Sporadic CCM patients were followed up 5 years from January 2003 to December 2018. Support vector machine (SVM), stacked generalization, and extreme gradient boosting (XGBoost) were used to construct models. The performance of models was evaluated by area under receiver operating characteristic curves (AUROC), area under the precision-recall curve (PR-AUC) and other metrics. A total of 517 patients with sporadic CCM were included (330 female 63.8%, mean SD age at diagnosis, 42.1 15.5 years). 76 (re)hemorrhage (14.7%) occurred during follow-up. Among 3 machine learning models, XGBoost model yielded the highest mean (SD) AUROC (0.87 0.06) in cross-validation. The top 4 features of XGBoost model were ranked with SHAP (SHapley Additive exPlanations). All-Elements XGBoost model achieved an AUROCs of 0.84 and PR-AUC of 0.49 in testing set, with a sensitivity of 0.86 and a specificity of 0.76. Importantly, 4-Elements XGBoost model developed using top 4 features got a AUROCs of 0.83 and PR-AUC of 0.40, a sensitivity of 0.79, and a specificity of 0.72 in testing set. Two machine learning-based models achieved accurate performance in identifying potential (re)hemorrhages within 5 years in sporadic CCM patients. These models may provide insights for clinical decision-making.
Global warming has obtained more and more attention because the global mean surface temperature has increased since the late 19th century. As more than 50% of the human population lives in cities, ...urbanization has become an important contributor for global warming. Pearl River Delta (PRD) in Guangdong Province, southern China, is one of the regions experiencing rapid urbanization that has resulted in remarkable Urban Heat Island (UHI) effect, which will be sure to influence the regional climate, environment, and socio-economic development. In this study, Landsat TM and ETM+ images from 1990 to 2000 in the PRD were selected to retrieve the brightness temperatures and land use/cover types. A new index, Normalized Difference Bareness Index (NDBaI), was proposed to extract bare land from the satellite images. Additionally, Shenzhen, which has experienced the fastest urbanization in Guangdong Province, was taken as an example to analyze the temperature distribution and changes within a large city as its size expanded in the past decade. Results show that the UHI effect has become more prominent in areas of rapid urbanization in the PRD region. The spatial distribution of heat islands has been changed from a mixed pattern, where bare land, semi-bare land and land under development were warmer than other surface types, to extensive UHI. Our analysis showed that higher temperature in the UHI was located with a scattered pattern, which was related to certain land-cover types. In order to analyze the relationship between UHI and land-cover changes, this study attempted to employ a quantitative approach in exploring the relationship between temperature and several indices, including the Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI), Normalized Difference Bareness Index (NDBaI) and Normalized Difference Build-up Index (NDBI). It was found that correlations between NDVI, NDWI, NDBaI and temperature are negative when NDVI is limited in range, but positive correlation is shown between NDBI and temperature.
Subduction initiation is one of the key processes in the operation of plate tectonics. Our understanding of this process is largely derived from geochemical studies of basaltic rocks in ophiolites at ...continental margins. Because of the petrological inheritance in forearc basalts, it is important to acquire geochemical signatures for fluid metasomatism of the nascent mantle wedge at forearc depths. This may be provided by the study of peridotite in ophiolites, which is least affected by tectonic emplacement of the ophiolites onto continental margins. For this purpose, we have carried out a comprehensive study of whole-rock and mineral geochemical compositions for harzburgites from the Xigaze ophiolites in the Yarlung Zangbo suture zone, southern Tibet. The results provide insights into the forearc metasomatism during subduction initiation before the closure of Neo-Tethyan Ocean for the India-Asia continental collision in the Cenozoic. The harzburgites show high spinel Cr# values and strong whole-rock depletion in CaO, Al2O3 and REE, suggesting high degrees of melt extraction (~10–20%) during seafloor spreading to form the Neo-Tethyan mid-ocean ridge basalts. They exhibit positive LILE anomalies in trace element distribution patterns, indicating metasomatism by subduction zone fluids. This is supported by the occurrence of tremolite and dolomite in some of the harzburgites. Based on the presence or absence of carbonate minerals, two types of metasomatic fluids are distinguished. One is the aqueous solutions, leading to the formation of tremolite and the enrichment of LILE in clinopyroxene. The other is the carbonate-bearing fluids, resulting in the formation of dolomites, tremolite and low Mg# (79–82) olivine. The metasomatism also results in the high contents of structural hydroxyl in pyroxenes and elevated δ18O values for the harzburgites. It is inferred that the fluid metasomatism was induced by incipient subduction of the juvenile Neo-Tethyan oceanic slab to forearc depths shortly after conversion of the Neo-Tethyan mid-ocean ridge into the trench. During this period of subduction initiation, the fluids were produced by heating dehydration of the sinking ridge crust to the forearc depths. It is these fluids that would metasomatize the overlying nascent mantle wedge, leading to superimposition of the geochemically enriched signature on the lithochemically depleted harzburgites in the ophiolites. Therefore, the forearc metasomatism of peridotite in ophiolite can be used as a geochemical proxy for subduction initiation. Furthermore, the Xigaze ophiolites were produced by the ridge-trench conversion for subduction initiation in the Mesozoic and they were emplaced onto the southern margin of the Asian continent in the Cenozoic.
•The harzburgite experienced melt extraction at the mid-ocean ridge;•The harzburgite was metasomatized by two types of subduction zone fluids;•The fluid metasomatism is closely associated with subduction initiation;•The Xigaze ophiolites were generated through the ridge-trench conversion.
Ginsenosides are major bioactive compounds found in
that exhibit various pharmaceutical properties. Dammarenediol-II, the nucleus of dammarane-type ginsenosides, is a promising candidate for ...pharmacologically active triterpenes. Dammarenediol-II synthase (DDS) cyclizes 2,3-oxidosqualene to produce dammarenediol-II. Based on the native terpenoids synthetic pathway, a dammarane-type ginsenosides synthetic pathway was established in
by introducing
, CYP450 enzyme (
), or/and
NADPH-cytochrome P450 reductase gene (
), which is responsible for producing dammarane-type ginsenosides. To enhance productivity, strategies such as "gene loading" and "culture optimizing" were employed. Multiple copies of transgene expression cassettes were introduced into the genome to increase the expression of the key rate-limiting enzyme gene,
, significantly improving the titer of dammarenediol-II to approximately 0.2 mg/L. Following the culture optimization in an opt2 medium supplemented with 1.5 mM methyl jasmonate under a light:dark regimen, the titer of dammarenediol-II increased more than 13-fold to approximately 2.6 mg/L. The
strains engineered in this study constitute a good platform for the further production of ginsenosides in microalgae.
Constraint-induced movement therapy (CIMT) improves functional outcome in patients with stroke possibly through structural plasticity. We hypothesized that CIMT could enhance axonal growth by ...overcoming the intrinsic growth-inhibitory signals, leading eventually to improved behavioral performance in stroke rats.
Focal cerebral ischemia was induced by intracerebral injection of endothelin-1. Adult Wistar rats were divided into a sham-operated group, an ischemic group, and an ischemic group treated with CIMT. CIMT started at postoperative day 7 and continued for 3 weeks. Biotinylated dextran amine was injected into the contralateral sensorimotor cortex at postoperative day 14 to trace crossing axons at the cervical spinal cord. The expressions of Nogo-A, Nogo receptor, RhoA, and Rho-associated kinase in the peri-infarct cortex, and the expressions of biotinylated dextran amine, growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated spinal cord were measured by immunohistochemistry and Western blots. Behavioral recovery was analyzed at postoperative days 29 to 32.
Infarct volumes were not different between groups after stroke. CIMT significantly increased the length and the number of midline crossings of contralateral corticospinal axons to the denervated cervical spinal cord. CIMT significantly decreased the expressions of Nogo-A/Nogo receptor and RhoA/Rho-associated kinase in the peri-infarct cortex, and increased the expressions of growth associated protein-43, synaptophysin, vGlut1, and postsynaptic density-95 in the denervated cervical spinal cord. Behavioral performances assessed by the beam-walking test and the water maze test were improved significantly by CIMT.
CIMT promoted poststroke synaptic plasticity and axonal growth at least partially by overcoming the intrinsic growth-inhibitory signaling, leading to improved behavioral outcome.
Alzheimer's disease (AD) is the most prevalent form of neurodegenerative disorders, yet no major breakthroughs have been made in AD human trials and the disease remains a paramount challenge and a ...stigma in medicine. Here we eliminate the toxicity of amyloid beta (Aβ) in a facile, high-throughput zebrafish (Danio rerio) model using casein coated-gold nanoparticles (βCas AuNPs). βCas AuNPs in systemic circulation translocate across the blood brain barrier of zebrafish larvae and sequester intracerebral Aβ
and its elicited toxicity in a nonspecific, chaperone-like manner. This is evidenced by behavioral pathology, reactive oxygen species and neuronal dysfunction biomarkers assays, complemented by brain histology and inductively coupled plasma-mass spectroscopy. We further demonstrate the capacity of βCas AuNPs in recovering the mobility and cognitive function of adult zebrafish exposed to Aβ. This potent, safe-to-use, and easy-to-apply nanomedicine may find broad use for eradicating toxic amyloid proteins implicated in a range of human diseases.
An efficient diastereo- and enantioselective Mannich-type/cyclization cascade reaction of α-substituted isocyanoacetates and cyclic trifluoromethyl ketimines cooperatively catalyzed by cinchona ...alkaloid-derived multi-hydrogen-bonding donor squaramide and AgOAc has been investigated, affording the optically active trifluoromethyl-substituted tetrahydroimidazo1,5-cquinazoline derivatives in excellent yields (up to 99%) and good to excellent stereoselectivities (up to >15:1 dr, up to 98% ee) under mild conditions.
Adipic acid is an important dicarboxylic acid mainly used for the production of nylon 6–6 fibers and resins. Previous studies focused on the biological production of adipic acid directly from ...different substrates, resulting in low yields and titers. In this study, a five-step reverse adipate-degradation pathway (RADP) identified in Thermobifida fusca has been reconstructed in Escherichia coli BL21 (DE3). The resulting strain (Mad136) produced 0.3 g L−1 adipic acid with a 11.1% theoretical yield in shaken flasks, and we confirmed that the step catalyzed by 5-Carboxy-2-pentenoyl-CoA reductase (Tfu_1647) as the rate-limiting step of the RADP. Overexpression of Tfu_1647 by pTrc99A carried by strain Mad146 produced with a 49.5% theoretical yield in shaken flasks. We further eliminated pathways for major metabolites competing for carbon flux by CRISPR/Cas9 and deleted the succinate-CoA ligase gene to promote accumulation of succinyl-CoA, which is the precursor for adipic acid synthesis. The final engineered strain Mad123146, which could achieve 93.1% of the theoretical yield in the shaken flask, was able to produce 68.0 g L−1 adipic acid by fed-batch fermentation. To the best of our knowledge, these results constitute the highest adipic acid titer reported in E. coli.
•A five-step reverse adipate-degradation pathway (RADP) was reconstructed in Escherichia coli.•5-Carboxy-2-pentenoyl-CoA reductase was the rate-limiting step of the RADP.•Strain Mad123146 achieved 93.1% of the theoretical yield in the shaken flask.•A high production of 68.0 g L−1 adipic acid was produced by fed-batch fermentation.
Cardiovascular diseases are associated with platelet hyperactivity, and downregulating platelet activation is one of the promising antithrombotic strategies. This study newly extracted two ...polysaccharides (purified exopolysaccharides, EPSp and purified intercellular exopolysaccharides, IPSp) from Cordyceps sinensis Cs-4 mycelial fermentation powder, and investigated the effects of the two polysaccharides and their gut bacterial metabolites on platelet functions and thrombus formation. EPSp and IPSp are majorly composed of galactose, mannose, glucose, and arabinose. Both EPSp and IPSp mainly contain 4-Galp and 4-Glcp glycosidic linkages. EPSp and IPSp significantly inhibited human platelet activation and aggregation with a dose-dependent manner, and attenuated thrombus formation in mice without increasing bleeding risk. Furthermore, the EPSp and IPSp after fecal fermentation showed enhanced platelet inhibitory effects. The results have demonstrated the potential value of Cs-4 polysaccharides as novel protective ingredients for cardiovascular diseases.
A lateral size effect of reinforcement on mechanical properties is investigated for aluminum matrix nanolaminated composites reinforced with reduced graphene oxide (rGO). rGO sheets with remarkably ...different lateral size are chosen to cover the critical value estimated by the shear lag model. Tensile tests with loading along the in-plane direction of the nanolaminated structure demonstrate that lateral size has significant influence on mechanical properties. A good balance between strength and ductility is realized by the largest lateral size of rGO.
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