Novel Social Stimulation Ameliorates Memory Deficit in Alzheimer's Disease Model through Activating α-Secretase.

As the most common form of dementia in the world, Alzheimer's disease (AD) is a progressive neurological disorder marked by cognitive and behavioral impairment. According to previous researches, abundant social connections shield against dementia. However, it is still unclear how exactly social interactions benefit cognitive abilities in people with AD and how this process is used to increase their general cognitive performance. In this study, we found that single novel social (SNS) stimulation promoted c-Fos expression and increased the protein levels of mature ADAM10/17 and sAPPα in the ventral hippocampus (vHPC) of wild-type (WT) mice, which are hippocampal dorsal CA2 (dCA2) neuron activity and vHPC NMDAR dependent. Additionally, we discovered that SNS caused similar changes in an AD model, FAD4T mice, and these alterations could be reversed by α-secretase inhibitor. Furthermore, we also found that multiple novel social (MNS) stimulation improved synaptic plasticity and memory impairments in both male and female FAD4T mice, accompanied by α-secretase activation and Aß reduction. These findings provide insight into the process underpinning how social interaction helps AD patients who are experiencing cognitive decline, and we also imply that novel social interaction and activation of the α-secretase may be preventative and therapeutic in the early stages of AD.

Experimental study on pore structure characteristics and thermal conductivity of fibers reinforced foamed concrete.

The pore structure characteristics and thermal conductivity of foamed concrete (FC) reinforced with glass fibers (GF), polyvinyl alcohol fibers (PVAF) and polypropylene fibers (PPF) were investigated experimentally in this article. Firstly, GF, PVAF or PPF with different mass fractions (0%, 1%, 1.5% and 2%) were added to the Portland cement, fly ash and plant protein foaming agent to prepare the FC. Then, SEM tests, dry density tests, porosity tests, and thermal conductivity tests were carried out on FRFC. Later, the adhesion of GF, PVAF and FFF with different mass fractions to the cementitious base was investigated by SEM images of FRFC. The pore size distribution, shape factor and porosity of FRFC were analyzed using Photoshop software and Image Pro Plus (IPP) software. Finally, the effects of different mass fractions and lengths of three types of fibers on the thermal conductivity of FRFC were discussed. The results indicated that proper fiber mass fraction can play a role of refining small pores and separating large pores, improving the structural compactness, reducing the pore collapse phenomenon and optimizing the pore structure of FRFC. The three types of fibers can promote the optimization of cellular roundness and increase the proportion of pores with diameters below 400 µm. The FC with larger porosity had smaller dry density. As the fiber mass fraction increased, the thermal conductivity performed a phenomenon of first decrease and then increase. The three types of fibers with 1% mass fraction achieved relatively low thermal conductivity. Compared with the FC without fibers, the thermal conductivities of GF reinforced FC, PVAF reinforced FC and PPF reinforced FC with 1% mass fraction were decreased by 20.73%, 18.23% and 7.00%, respectively.

Trophic Dynamics and Feeding Ecology of Skipjack Tuna (Katsuwonus pelamis) off Eastern and Western Taiwan.

The skipjack tuna (Katsuwonus pelamis) is a mesopredator fish species with seasonal abundance in waters off Taiwan. Regional ecological and life-history information has been historically lacking for this species. In recent years, stable isotope analysis (SIA) of carbon and nitrogen has been used to assess predator feeding ecology and broader ecosystem trophic dynamics. This study evaluated comparative skipjack feeding ecology in distinct regions off Taiwan, combining traditional stomach content analysis with SIA of individuals off western (n = 43; 2020) and eastern (n = 347; 2012-2014 and n = 167; 2020) Taiwan. The stomach content analysis showed the most important prey to be ponyfish (Photopectoralis bindus) in western Taiwan and epipelagic squids (Myopsina spp.) and carangids (Decapterus macrosoma;) in eastern Taiwan from 2012 to 2014 and epipelagic carangids (Decapterus spp.) and flying fishes (Cheilopogon spp.) in eastern Taiwan in 2020, suggesting that the skipjack tuna is a generalist predator across regions. In contrast, time-integrated diet estimates from Bayesian mixing models indicated the importance of cephalopods and crustaceans as prey, potentially demonstrating more mesopelagic feeding in less productive waters during skipjack migrations outside the study regions. Skipjack off western Taiwan had a slightly higher estimated trophic position than in the waters off eastern Taiwan, potentially driven by the varying nutrient-driven pelagic food web structures. Skipjack SI values increased with body size off eastern Taiwan but not in western waters, suggesting that opportunistic predation can still result in different predator-prey size dynamics between regions.

Versatile lifestyles of Edwardsiella: Free-living, pathogen, and core bacterium of the aquatic resistome.

Edwardsiella species in aquatic environments exist either as individual planktonic cells or in communal biofilms. These organisms encounter multiple stresses, include changes in salinity, pH, temperature, and nutrients. Pathogenic species such as E. piscicida, can multiply within the fish hosts. Additionally, Edwardsiella species (E. tarda), can carry antibiotic resistance genes (ARGs) on chromosomes and/or plasmids, that can be transmitted to the microbiome via horizontal gene transfer. E. tarda serves as a core in the aquatic resistome. Edwardsiela uses molecular switches (RpoS and EsrB) to control gene expression for survival in different environments. We speculate that free-living Edwardsiella can transition to host-living and vice versa, using similar molecular switches. Understanding such transitions can help us understand how other similar aquatic bacteria switch from free-living to become pathogens. This knowledge can be used to devise ways to slow down the spread of ARGs and prevent disease outbreaks in aquaculture and clinical settings.

Distribution of antibiotic resistance genes in the environment.

The prevalence of antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) in the microbiome is a major public health concern globally. Many habitats in the environment are under threat due to excessive use of antibiotics and evolutionary changes occurring in the resistome. ARB and ARGs from farms, cities and hospitals, wastewater treatment plants (WWTPs) or as water runoffs, may accumulate in water, soil, and air. We present a global picture of the resistome by examining ARG-related papers retrieved from PubMed and published in the last 30 years (1990-2020). Natural Language Processing (NLP) was used to retrieve 496,640 papers, out of which 9374 passed the filtering test and were further analyzed to determine the distribution and diversity of ARG subtypes. The papers revealed seven major antibiotic families together with their respective ARG subtypes in different habitats on six continents. Asia, especially China, had the highest number of ARGs related papers compared to other countries/regions/continents. ARGs belonging to multidrug, glycopeptide, and ß-lactam families were the most common in reports from hospitals and sulfonamide and tetracycline families were common in reports from farms, WWTPs, water and soil. We also highlight the 'omics' tools used in resistome research, describe some factors that shape the development of resistome, and suggest future work needed to better understand the resistome. The goal was to show the global nature of ARB and ARGs in order to encourage collaborate research efforts aimed at reducing the negative impacts of antibiotic resistance on the One Health concept.

Determinants of Tourism Stocks During the COVID-19: Evidence From the Deep Learning Models.

This paper examines the determinants of tourism stock returns in China from October 25, 2018, to October 21, 2020, including the COVID-19 era. We propose four deep learning prediction models based on the Back Propagation Neural Network (BPNN): Quantum Swarm Intelligence Algorithms (QSIA), Quantum Step Fruit-Fly Optimization Algorithm (QSFOA), Quantum Particle Swarm Optimization Algorithm (QPSO) and Quantum Genetic Algorithm (QGA). Firstly, the rough dataset is used to reduce the dimension of the indices. Secondly, the number of neurons in the multilayer of BPNN is optimized by QSIA, QSFOA, QPSO, and QGA, respectively. Finally, the deep learning models are then used to establish prediction models with the best number of neurons under these three algorithms for the non-linear real stock returns. The results indicate that the QSFOA-BPNN model has the highest prediction accuracy among all models, and it is defined as the most effective feasible method. This evidence is robust to different sub-periods.

Novel strategies for the biocontrol of noctuid pests (Lepidoptera) based on improving ascovirus infectivity using Bacillus thuringiensis.

Identifying novel biocontrol agents and developing new strategies are urgent goals in insect pest biocontrol. Ascoviruses are potential competent insect viruses that may be developed into bioinsecticides, but this aim is impeded by their poor oral infectivity. To improve the per os infectivity of ascovirus, Bacillus thuringiensis kurstaki (Btk) was employed as a helper to damage the midgut of lepidopteran larvae (Helicoverpa armigera, Mythimna separata, Spodoptera frugiperda, and S. litura) in formulations with Heliothis virescens ascovirus isolates (HvAV-3h and HvAV-3j). Btk and ascovirus mixtures (Btk/HvAV-3h and Btk/HvAV-3j) were fed to insect larvae (3rd instar). With the exception of S. frugiperda larvae, which exhibited low mortality after ingesting Btk, the larvae of the other tested species showed three types of response to feeding on the formulas: type I, the tested larvae (H. armigera) were killed by Btk infection so quickly that insufficient time and resources remained for ascoviral invasion; type II, both Btk and the ascovirus were depleted by their competition, such that neither was successfully released or colonized the tissue; type III, Btk was eliminated by the ascovirus, and the ascovirus achieved systemic infection in the tested larvae. The feeding of Btk/ascovirus formulas led to a great reduction in larval diet consumption and resulted in a significant decrease in the emergence rate of H. armigera, M. separata, and S. litura larvae, which suggested that the formulas exerted marked oral control effects on both the contemporary individuals and the next generation of these tested pest species.

Angiotensin II Decreases Endothelial Nitric Oxide Synthase Phosphorylation via AT1R Nox/ROS/PP2A Pathway.

Increasing evidences suggest that angiotensin (Ang) II participates in the pathogenesis of endothelial dysfunction (ED) through multiple signaling pathways, including angiotensin type 1 receptor (AT1R) mediated NADPH oxidase (Nox)/reactive oxygen species (ROS) signal transduction. However, the detailed mechanism is not completely understood. In this study, we reported that AngII/AT1R-mediated activated protein phosphatase 2A (PP2A) downregulated endothelial nitric oxide synthase (eNOS) phosphorylation via Nox/ROS pathway. AngII treatment reduced the levels of phosphorylation of eNOS Ser1177 and nitric oxide (NO) content along with phosphorylation of PP2Ac (PP2A catalytic subunit) Tyr307, meanwhile increased the PP2A activity and ROS production in human umbilical vein endothelial cells (HUVECs). These changes could be impeded by AT1R antagonist candesartan (CAN). The pretreatment of 10-8 M PP2A inhibitor okadaic acid (OA) reversed the levels of eNOS Ser1177 and NO content. Similar effects of AngII on PP2A and eNOS were also observed in the mesenteric arteries of Sprague-Dawley rats subjected to AngII infusion via osmotic minipumps for 2 weeks. We found that the PP2A activity was increased, but the levels of PP2Ac Tyr307 and eNOS Ser1177 as well as NO content were decreased in the mesenteric arteries. The pretreatments of antioxidant N-acetylcysteine (NAC) and apocynin (APO) abolished the drop of the levels of PP2Ac Tyr307 and eNOS Ser1177 induced by AngII in HUVECs. The knockdown of p22phox by small interfering RNA (siRNA) gave rise to decrement of ROS production and increment of the levels of PP2Ac Tyr307 and eNOS Ser1177. These results indicated that AngII/AT1R pathway activated PP2A by downregulating its catalytic subunit Tyr307 phosphorylation, which relies on the Nox activation and ROS production. In summary, our findings indicate that AngII downregulates PP2A catalytic subunit Tyr307 phosphorylation to activate PP2A via AT1R-mediated Nox/ROS signaling pathway. The activated PP2A further decreases levels of eNOS Ser1177 phosphorylation and NO content leading to endothelial dysfunction.

Blood Pressure Variability during Angiography in Patients with Ischemic Stroke and Intracranial Artery Stenosis.

Our aim was to investigate factors predicting blood pressure (BP) variability during diagnostic cerebral angiography and associations between BP variability and clinical outcomes in patients with acute and subacute ischemic stroke and intracranial artery stenosis. 114 patients with ischemic stroke and intracranial artery stenosis (stenosis rate >50%) were recruited. Patients who underwent cerebral angiography within 3 days and 3-14 days of disease onset are referred to be Group A and Group S, respectively. BP variability in Group A was defined as the coefficient of variance (CV) of BP. Univariate and multivariate regression analyses were used to identify predictors of CV of BP and associations between CV of BP and clinical outcomes at discharge. In Group A patients, advanced age was associated with increased CV of SBP and diastolic blood pressure (DBP), and antihypertensive use was associated with lower CV of SBP. Male was associated with lower CV of DBP. In Group S, higher CV of SBP was associated with hypertension and antihypertensive use. Males had lower CV of SBP than females. The calcium channel blocker was associated with lower CV of DBP. Higher scores of the Stroke Scale at admission were significantly associated with poor clinical outcomes for both groups, while BP variability was not. Factors associated with BP variability are significantly different between stroke patients undergoing angiography within 3 days vs. 3-14 days after disease onset. BP variability is not significantly associated with clinical outcomes at discharge.

Azo dye degrading bacteria tolerant to extreme conditions inhabit nearshore ecosystems: Optimization and degradation pathways.

Nearshore ecosystems are transitional zones, and they may harbor a diverse microbial community capable of degrading azo dyes under extreme environmental conditions. In this study, thirteen bacterial strains capable of degrading eight azo dyes were isolated in nearshore environments and characterized using high throughput 16 S rRNA sequencing. The results of this study demonstrate that the biodegradability of azo dyes was influenced by their chemical structure and position of functional groups as well as the type of bacteria. The decolorization rate of Methyl Orange (95%) was double that of the heavier and sterically hindered Reactive Yellow 84 (<40%). Shewanella indica strain ST2, Oceanimonas smirnovii strain ST3, Enterococcus faecalis strain ST5, and Clostridium bufermentans strain ST12 demonstrated potential application in industrial effluent treatment as they were tolerant to a wide range of environmental parameters (pH: 5-9, NaCl: 0-70 g L-1, azo dye concentration: 100-2000 mg L-1) including exposure to metals. Analysis of the transformation products using GC-MS revealed that different bacterial strains may have different biotransformation pathways. This study provides critical insight on the in-situ biotransformation potential of azo dyes in marine environments.

High Throughput Sediment DNA Sequencing Reveals Azo Dye Degrading Bacteria Inhabit Nearshore Sediments.

Estuaries and coastal environments are often regarded as a critical resource for the bioremediation of organic pollutants such as azo dyes due to their high abundance and diversity of extremophiles. Bioremediation through the activities of azoreductase, laccase, and other associated enzymes plays a critical role in the removal of azo dyes in built and natural environments. However, little is known about the biodegradation genes and azo dye degradation genes residing in sediments from coastal and estuarine environments. In this study, high-throughput sequencing (16S rRNA) of sediment DNA was used to explore the distribution of azo-dye degrading bacteria and their functional genes in estuaries and coastal environments. Unlike laccase genes, azoreductase (azoR), and naphthalene degrading genes were ubiquitous in the coastal and estuarine environments. The relative abundances of most functional genes were higher in the summer compared to winter at locations proximal to the mouths of the Hanjiang River and its distributaries. These results suggested inland river discharges influenced the occurrence and abundance of azo dye degrading genes in the nearshore environments. Furthermore, the azoR genes had a significant negative relationship with total organic carbon, Hg, and Cr (p < 0.05). This study provides critical insights into the biodegradation potential of indigenous microbial communities in nearshore environments and the influence of environmental factors on microbial structure, composition, and function which is essential for the development of technologies for bioremediation in azo dye contaminated sites.

DNA Methylation Analysis Identifies Differentially Methylated Sites Associated with Early-Onset Intracranial Atherosclerotic Stenosis.

AIM: Studies have suggested that genetic and environmental factors do not account for all risks and mechanisms of intracranial atherosclerotic stenosis (ICAS). DNA methylation may play a role in the progression of ICAS. METHODS: DNA methylation profiles of peripheral blood leucocytes from 7 patients with early-onset ICAS and 7 perfectly matched controls were interrogated for the first time using the Illumina Infinium Human MethylationEPIC BeadChip. Afterward, functional analysis for differentially methylated genes was conducted. In addition, pyrosequencing verification was performed in an independent cohort comprising 21 patients with early-onset ICAS and 21 age- and gender-matched controls. RESULTS: A total of 318 cytosine-phosphate-guanine sites were found to be differentially methylated based on the established standards. Functional analysis annotated differentially methylated sites to atherosclerosis-related processes and pathways, such as the negative regulation of hydrolase activity (GO 0051346), type II diabetes mellitus (KEGG hsa04930), and the insulin signaling pathway (KEGG hsa04910). In addition, a differentially methylated site was also validated, cg22443212 in gene Rnf213, which showed significant hypermethylation in patients with early-onset ICAS compared with controls 59.56% (49.77%, 88.55%) vs. 44.65% (25.07%, 53.21%), respectively; P=0.010). Receiver operating characteristic curve analysis showed that the area under the curve value of cg22443212 was 0.744 (95% confidence interval, 0.586-0.866; P=0.002). CONCLUSIONS: We revealed that altered DNA methylation may play a role in the occurrence and development of ICAS. These results provided new epigenetic insights into ICAS.

Altered Spontaneous Activity and Functional Connectivity in the Posterior Pons of Patients With Migraine Without Aura.

The brainstem has been discussed as the main player in the pathogenesis of migraine. Dysfunctional brainstem nuclei and their abnormal connections to other key brain centers may contribute to headache and other symptoms of migraine. In the present study, 32 patients with migraine without aura (MWoA) and 32 age- and sex-matched healthy controls (HCs) underwent resting-state fMRI scans. We used masked independent analysis (mICA) to investigate whether patients with MWoA exhibited abnormal brainstem nuclei-cortical functional connectivity (FC). The mICA can suppress adjacent physiological noise and prevent results from being driven by the much stronger signals of the surrounding structures. Regional homogeneity (ReHo) was used to investigate whether the brainstem regions with abnormal FC to other brain areas exhibited abnormal regional neuronal activity. Patients with MWoA showed significantly weaker FC between the posterior pons and the left superior parietal lobule, the left middle temporal gyrus, and the left middle frontal gyrus. Furthermore, patients with MWoA exhibited significantly decreased ReHo values in the posterior pons compared with HCs, and the posterior pons ReHo value was significantly negatively correlated with HIT-6 scores in the MWoA group. Patients with MWoA exhibited functional abnormalities in the posterior pons and weakened connections between the posterior pons and several key cortical brain areas involved in pain processing during the resting state. PERSPECTIVE: This study provided increased evidence that the pons is involved in the pathophysiological mechanism of migraine, and weakened connections suggest that the touch and pain sensation of migraine sufferers may not be properly relayed to cortical processing areas, which may be associated with the pathogenesis of MWoA.

Higher Platelet-to-Lymphocyte Ratio Is Associated With Worse Outcomes After Intravenous Thrombolysis in Acute Ischaemic Stroke.

Objective: The platelet-to-lymphocyte ratio (PLR) is a new marker of atherosclerotic inflammation and has been identified as a predictive factor in cardiovascular diseases, but its significance in patients with acute ischaemic stroke (AIS) who have undergone intravenous thrombolysis (IVT) is still unknown. Methods: Consecutive patients who were treated with IVT using recombinant tissue plasminogen activator (rtPA) for AIS were included from May 2012 to August 2018. The PLR was calculated according to platelet and lymphocyte counts within 24 h after thrombolysis therapy. Functional outcomes were assessed by the modified Rankin Scale (mRS) at 3 months after thrombolysis. Stroke severity was assessed by National Institutes of Health Stroke Scale (NIHSS) scores. The primary endpoint was an unfavorable outcome (mRS > 2), and the secondary endpoint was death at 3 months. Results: A total of 286 patients were included in the study. The median age was 69.5 (59.0-80.0) years, and 59.1% of patients were men. A total of 120 (42.0%) patients had an unfavorable outcome, and 38 (13.2%) died. Patients with an unfavorable outcome had significantly higher PLR values compared with those with a favorable outcome [172.5 (105.3-239.0) vs. 139 (97.0-194.5), P = 0.008], and the PLR values of the patients who died at 3 months were higher than those of the surviving patients [189.5 (127.5-289.0) vs. 142.0 (98.0-215.5), P = 0.006]. After adjustment for other variables, the PLR was independently associated with the two endpoints: unfavorable outcome (OR 2.220, 95% CI 1.245-3.957, P = 0.007) and death (OR 2.825, 95% CI 1.050-7.601, P = 0.040) at 3 months after thrombolysis. In addition, PLR was correlated with the NIHSS score (R = 0.230, P < 0.001). Conclusions: Higher PLR levels were independently associated with an unfavorable outcome and death at 3 months in AIS patients treated with IVT.

Structural changes of cerebellum and brainstem in migraine without aura.

BACKGROUND: Increasing evidence has suggested that the cerebellum is associated with pain and migraine. In addition, the descending pain system of the brainstem is the major site of trigeminal pain processing and modulation and has been discussed as a main player in the pathophysiology of migraine. Cerebellar and brainstem structural changes associated with migraineurs remain to be further investigated. METHODS: Voxel-based morphometry (VBM) (50 controls, 50 migraineurs without aura (MWoAs)) and diffusion tensor imaging (DTI) (46 controls, 46 MWoAs) were used to assess cerebellum and brainstem anatomical alterations associated with MWoAs. We utilized a spatially unbiased infratentorial template toolbox (SUIT) to perform cerebellum and brainstem optimized VBM and DTI analysis. We extracted the average diffusion values from a probabilistic cerebellar white matter atlas to investigate whether MWoAs exhibited microstructure alterations in the cerebellar peduncle tracts. RESULTS: MWoAs showed decreased fractional anisotropy (FA) in the vermis VI extending to the bilateral lobules V and VI of the cerebellum. We also found higher axial diffusivity (AD), mean diffusivity (MD), and radial diffusivity (RD) in the right inferior cerebellum peduncle tract in MWoAs. MWoAs exhibited both reduced gray matter volume and increased AD, MD and RD in the spinal trigeminal nucleus (SpV). CONCLUSION: MWoAs exhibited microstructural changes in the cerebellum and the local brainstem. These structural differences might contribute to dysfunction of the transmission and modulation of noxious information, trigeminal nociception, and conduction and integration of multimodal information in MWoAs. These findings further suggest involvement of the cerebellum and the brainstem in the pathology of migraine without aura.

Increased plasma levels of miR-124-3p, miR-125b-5p and miR-192-5p are associated with outcomes in acute ischaemic stroke patients receiving thrombolysis.

BACKGROUND AND AIMS: Circulating microRNAs (miRNAs) have recently emerged as promising biomarkers for acute ischaemic stroke (AIS). However, the expression profiles of miRNAs in AIS patients receiving intravenous thrombolysis, and their associations with outcome have not been investigated. METHODS: In a prospective cohort study, a total of 84 AIS patients, who received intravenous thrombolysis (21.4% received combined reperfusion therapy) and completed 3 month follow-up visits, were included. Favourable and unfavourable outcomes were defined as modified Rankin Scale (mRS) scores of 0-1 and 2-6, respectively. Plasma samples were collected at 24 h after thrombolysis. We used RNA sequencing to study miRNA profiles in 5 patients with unfavourable outcomes and 5 matched patients with favourable outcomes. Differentially expressed miRNAs were further validated in all cohorts using quantitative real-time polymerase chain reaction assays. RESULTS: After identification and validation, we found that miR-124-3p, miR-125b-5p and miR-192-5p levels were higher in patients with unfavourable outcomes than in patients with favourable outcomes. Logistic regressions and receiver-operating characteristic curve analyses demonstrated that these altered miRNAs may function as predictive biomarkers for outcome in AIS patients receiving thrombolysis, whether combined with endovascular thrombectomy or not. In addition, miR-124-3p and miR-125b-5p were closely associated with stroke severity. CONCLUSIONS: A set of circulating microRNAs (miR-124-3p, miR-125b-5p and miR-192-5p) are associated with unfavourable 3 month outcomes and might have clinical utility in AIS patients receiving thrombolysis.

Lack of Correlation Between Intracranial Carotid Artery Modified Woodcock Calcification Score and Prognosis of Patients With Acute Ischemic Stroke After Intravenous Thrombolysis.

There have been few studies about the association between intracranial carotid artery calcification (ICAC) and acute ischemic stroke (AIS) prognosis after intravenous thrombolysis (IVT). We aimed to analyze the association between ICAC and prognosis (including symptomatic intracranial hemorrhage (sICH), functional outcome and death) of AIS patients treated with IVT. In this retrospective study, we consecutively included 232 AIS patients treated with IVT between April 2012 and December 2018. ICAC was evaluated using the modified Woodcock calcification visual score on non-enhanced cranial computed tomography scans. Poor functional outcome was defined as a modified Rankin Scale score > 2 at 3 months. We found that the modified Woodcock calcification score was associated with ICH, poor outcome, and death in univariable analyses on the symptomatic side and/or bilaterally. However, after adjustment for other different covariates, the results showed no significant difference. We documented that the presence and severity of ICAC did not significantly modify the beneficial effects of rtPA treatment in AIS.

Cathepsin K Knockout Exacerbates Haemorrhagic Transformation Induced by Recombinant Tissue Plasminogen Activator After Focal Cerebral Ischaemia in Mice.

Severe haemorrhagic transformation (HT), a common complication of recombinant tissue plasminogen activator (rtPA) treatment, predicts poor clinical outcomes in acute ischaemic stroke. The search for agents to mitigate this effect includes investigating biomolecules involved in neovascularization. This study examines the role of Cathepsin K (Ctsk) in rtPA-induced HT after focal cerebral ischaemia in mice. After knockout of Ctsk, the gene encoding Ctsk, the outcomes of Ctsk+/+ and Ctsk-/- mice were compared 24 h after rtPA-treated cerebral ischaemia with respect to HT severity, neurological deficits, brain oedema, infarct volume, number of apoptotic neurons and activated microglia/macrophage, blood-brain barrier integrity, vascular endothelial growth factor (VEGF) expression and Akt-mTOR pathway activation. We observed that haemoglobin levels, brain oedema and infarct volume were significantly greater and resulted in more severe neurological deficits in Ctsk-/- than in Ctsk+/+ mice. Consistent with our hypothesis, the number of NeuN-positive neurons was lower and the number of TUNEL-positive apoptotic neurons and activated microglia/macrophage was higher in Ctsk-/- than in Ctsk+/+ mice. Ctsk knockout mice exhibited more severe blood-brain barrier (BBB) disruption, with microvascular endothelial cells exhibiting greater VEGF expression and lower ratios of phospo-Akt/Akt and phospo-mTOR/mTOR than in Ctsk+/+ mice. This study is the first to provide molecular insights into Ctsk-regulated HT after cerebral ischaemia, suggesting that Ctsk deficiency may disrupt the BBB via Akt/mTOR/VEGF signalling, resulting in neurological deficits and neuron apoptosis. Ctsk administration has the potential as a novel modality for improving the safety of rtPA treatment following stroke.

Distribution of microbial communities in metal-contaminated nearshore sediment from Eastern Guangdong, China.

Nearshore environments are a critical transitional zone that connects the marine and terrestrial/freshwater ecosystems. The release of anthropogenic chemicals into nearshore ecosystems pose a human and environmental health risk. We investigated the microbial diversity, abundance and function in metal-contaminated sediments collected from the Rongjiang, Hanjiang and Lianjiang River estuaries and adjacent coastal areas using high throughput sequencing. The concentration of nutrients (NO3-N, NO2-N, NH4-N, PO4-P) and metal (Cu, Zn, Cd, Pb, As, Hg) contaminants were higher at the mouth of the rivers compared to the coastal lines, and this was confirmed using cluster analysis. Estimates obtained using geoaccumulation index showed that about 38.9% of the sites were contaminated with Pb and the pollution load index showed that sediment from the mouth of Hanjiang River Estuary was moderately polluted with metals. In the nearshore sediment samples collected, Proteobacteria, Bacteroidetes, Planctomycetes, Chloroflexi, Acidobacteria were the dominant phylum with relative abundances of 46.6%, 8.05%, 6.47%, 5.26%, and 4.59%, respectively. There was no significant correlation between environmental variables and microbial abundance and diversity except for total organic carbon (TOC) (diversity; r = 0.569, p < 0.05) and Cr (diversity; r = 0.581, p < 0.05). At phyla level, Nitrospirae had a significant negative correlation with all metals except Cr, while OD1 had a significant positive correlation with all the metals. Overall, changes in nearshore sediment microbial communities by environmental factors were observed, and these may affect biogeochemical cycling.