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Despite the high efficiency of keyhole plasma arc welding (K-PAW), it still has several deficiencies, such as narrow welding parameter ranges, easily disturbed welding process and instability of welding quality, etc. It is a significant prerequisite to predict the keyhole/penetration status accurately for maintaining the welding process stability and improving the welding quality. Most researchers have focused on visual inspection techniques and convolutional neural networks (CNN), establishing a mathematical model of the correlation between weld pool images and penetration status. While CNN could extract the features of single weld pool images, it is difficult to predict the evolution trend of the incoming moments. In this paper, a novel model based on CNN and LSTM (long-short term memory) was developed to extract both the spatial and temporal features of topside weld pool images, and consequently the complex keyhole behaviors were predicted and described. The comparative study is carried out on different models, i.e. the single CNN model, the single LSTM model, and the CNN-LSTM model that integrates both spatial features of single images and temporal features of sequence. The keyhole initialization and establishing period, as the typical and critical welding scenario in full-penetration welding, is investigate and compared, resulting in a predicted value that is close to reality. Furthermore, ahead prediction of keyhole status was adopted, maintaining over 80% accuracy even when predicting keyhole behaviors 2 s into the future. Consequently, the unified CNN-LSTM model effectively improves the prediction accuracy of keyhole/penetration status, promising for intelligent K-PAW technology. [ABSTRACT FROM AUTHOR]

Although persistent efforts have identified and characterized a few candidate genes and related biological processes with potential functions in the adaptation of many species to extreme environments, few works have been conducted to determine the genomic basis of adaptation in endangered livestock breeds that have been living in extreme conditions for more than thousands of years. To fill this gap, we sequenced the whole genomes of nine individuals from three Chinese native endangered cattle breeds that are living in high‐altitude or arid environments. Phylogenetic and evolutionary history analyses of these three and other six breeds showed that the genetic structure of the cattle populations is primarily related to geographic location. Interestingly, we identified pervasive introgression from the yak to Zhangmu cattle (ZMC) that cover several genes (e.g., NOS2, EGLN1 and EPAS1) involved in the hypoxia response and previously identified as positive selection genes in other species, which suggested that the adaptive introgression from yak may have contributed to the adaptation of ZMC to high‐altitude environments. In addition, by contrasting the breeds in opposite living conditions, we revealed a set of candidate genes with various functions from hypoxia response, water metabolism, immune response and body shape change to embryo development and skeletal system development, etc., that may be related to high‐altitude or arid adaptation. Our research provides new insights into the recovery and adaptation of endangered native cattle and other species in extreme environments and valuable resources for future research on animal husbandry to cope with climate change. [ABSTRACT FROM AUTHOR]

To select candidate genes for goat prolificacy, we managed six multi- and six single-kid female goats at the same feeding level and in the same management mode over a 4-year period. These goats showed stable differences in litter size over five continuous parturition records. Whole-genome re-sequencing was used in all 12 to select candidate genes, namely, AURKA , ENDOG , SOX2 , RORA , GJA10 , RXFP2 , CDC25C , and NANOS3 , by the strength of their differentiation signals. Most of the selected genes were enriched in the coiled coil process and ovarian development, which suggests that the coiled coil process has a potential regulatory effect on fecundity. Detection of the distribution of variants and association analyses with litter size in 400 goats showed that NANOS3 exon mutations may lead to a transformation of the protein structure. The variation in CDC25C , ENDOG , and NANOS3 showed a significant association with litter size. These results can contribute to the improvement of reproduction traits in the artificial breeding of goats. • Some candidate genes, such as ENDOG, RORA, SMAD5, RXFP2, CDC25C and NANOS3 , was selected out by the strongest differentiation signals. • The coiled coil process and ovarian development enriched most genes at selective regions. • NANOS3 mutations may lead to the protein structure transformation, and variations in CDC25C, ENDOG and NANOS3 showed association with litter size [ABSTRACT FROM AUTHOR]

Abstract Due to the high order spatial derivatives and stiff reactions, severe temporal stability constraints on the time step are generally required when developing numerical methods for solving high order partial differential equations. Implicit integration method (IIF) method along with its compact form (cIIF), which treats spatial derivatives exactly and reaction terms implicitly, provides excellent stability properties with good efficiency by decoupling the treatment of reaction and spatial derivatives. One major challenge for IIF is storage and calculation of the potential dense exponential matrices of the sparse discretization matrices resulted from the linear differential operators. The compact representation for IIF (cIIF) was introduced to save the computational cost and storage for this purpose. Another challenge is finding the matrix of high order space discretization, especially near the boundaries. In this paper, we extend IIF method to high order discretization for spatial derivatives through an example of reaction diffusion equation with fourth order accuracy, while the computational cost and storage are similar to the general second order cIIF method. The method can also be efficiently applied to deal with other types of partial differential equations with both homogeneous and inhomogeneous boundary conditions. Direct numerical simulations demonstrate the efficiency and accuracy of the approach. [ABSTRACT FROM AUTHOR]

Background/Aims: Cisplatin-based treatment is first-line chemotherapy for several cancers including ovarian cancer. The development of cisplatin resistance results in treatment failure, but the underlying mechanisms are not fully understood. Histone deacetylases (HDACs) are a large family of enzymes that deacetylate lysine residues on histones and non-histone proteins. High expression of HDAC1 is associated with poor outcomes in ovarian cancer. Furthermore, resistance to chemotherapeutic agents is associated with HDAC1 overexpression in ovarian cancer cells. The goals of this study were to determine whether targeting HDAC1 can sensitize ovarian cancer cells to cisplatin and to explore the underlying mechanisms. Methods: Small interfering RNA (siRNA)-targeting HDAC1 was designed to silence HDAC1 in the cisplatin-resistant ovarian cancer cell line A2780CDDP and its cisplatin-sensitive cell line A2780. The effects of targeting HDAC1 on cell viability assay, colony formation, and apoptosis were detected. c-Myc re-expression or miR-34a inhibitors were used to examine the relationship among HDAC1, c-Myc, and miR-34a expression, which was assessed by western blot analysis and quantitative reverse transcription PCR. We established stable transfectants of A2780CDDP/HDAC1 short hairpin RNA (shRNA) and A2780/HDAC1 shRNA. The therapeutic effectiveness of cisplatin in murine xenograft models was assessed following shRNA-mediated HDAC1 silencing in A2780CDDP and A2780 cells. The mechanism of cell death was studied in tumor sections obtained from different mouse tumors. Results: In cisplatin-resistant A2780CDDP cells, HDAC1 knockdown by siRNA suppressed cell proliferation, and increased apoptosis and chemosensitivity by downregulating c-Myc and upregulating miR-34a. In cisplatin-sensitive A2780 cells, HDAC1 knockdown did not affect cell proliferation and apoptosis. Cisplatin treatment activated HDAC1 and c-Myc and inactivated miR-34a. Inhibition of HDAC1 with siRNA reduced c-Myc expression, increased miR-34a expression, and sensitized A2780 cells to cisplatin-induced apoptosis. c-Myc re-expression or miR-34a targeting by miR-34a inhibitors protected cells from apoptosis or reversed cisplatin resistance following HDAC1 knockdown or/and cisplatin exposure. Finally, in vivo studies showed that targeting HDAC1 inhibited A2780CDDP-induced xenograft tumor growth but not A2780-induced xenograft tumor growth. Targeting HDAC1 sensitized both A2780- and A2780CDDP-induced xenograft tumors to cisplatin treatment. Conclusions: Upregulation of HDAC1 is a crucial event in the development of drug resistance to current treatments in ovarian cancer. Thus, targeting HDAC1 by enhancing c-Myc-dependent miR-34a expression might be an effective strategy for increasing the efficacy of cisplatin treatment. [ABSTRACT FROM AUTHOR]

In their letter to the editor, the authors from the Karolinska Institute argue that, with the current available evidence of efficacy of mechanical thrombectomy for acute ischemic stroke, it is unethical to perform a trial in patients with basilar artery occlusion in which patients are at risk of being withheld this effective treatment. Good outcomes of a few selected patients after intra-arterial thrombolysis (IAT) were enough evidence for the stroke community to obviate the performance of a randomized trial of patients with basilar artery occlusion. Meta-analysis of retrospectively collected data of case series of selected patients showed no "obvious" difference in outcome between patients treated with intravenous thrombolysis (IVT) or IAT.[4]. [Extracted from the article]

The traditional bearingless permanent magnet synchronous motor has complex decoupling control problems. To overcome the drawbacks above, a novel hybrid permanent magnet type bearingless motor (HPMTBM) is proposed in this paper, which has integrated the merits of hybrid excitation permanent magnet motor and magnetic bearings. The main advantages of this HPMTBM are the simple control mechanism and the low power consumption. First, the principle and theoretical background of this motor are introduced. Then, the mathematical models of radial suspension force and torque are established using Maxwell stress tensor method, and air-gap magnetic fields, radial suspension forces are calculated by finite-element analysis. Finally, the prototype motor is designed and constructed. The radial suspension forces and rotor radial displacements are tested. The simulation and experimental results show the feasibility of the proposed HPMTBM. [ABSTRACT FROM AUTHOR]

Background: To determine the linear and non-linear interacting relationships between weather factors and hand, foot and mouth disease (HFMD) in children in Gansu, China, and gain further traction as an early warning signal based on weather variability for HFMD transmission.Method: Weekly HFMD cases aged less than 15 and meteorological information from 2010 to 2014 in Jiuquan, Lanzhou and Tianshu, Gansu, China were collected. Generalized linear regression models (GLM) with Poisson link and classification and regression trees (CART) were employed to determine the combined and interactive relationship of weather factors and HFMD in both linear and non-linear ways.Results: GLM suggested an increase in weekly HFMD of 5.9% [95% confidence interval (CI): 5.4%, 6.5%] in Tianshui, 2.8% [2.5%, 3.1%] in Lanzhou and 1.8% [1.4%, 2.2%] in Jiuquan in association with a 1 °C increase in average temperature, respectively. And 1% increase of relative humidity could increase weekly HFMD of 2.47% [2.23%, 2.71%] in Lanzhou and 1.11% [0.72%, 1.51%] in Tianshui. CART revealed that average temperature and relative humidity were the first two important determinants, and their threshold values for average temperature deceased from 20 °C of Jiuquan to 16 °C in Tianshui; and for relative humidity, threshold values increased from 38% of Jiuquan to 65% of Tianshui.Conclusion: Average temperature was the primary weather factor in three areas, more sensitive in southeast Tianshui, compared with northwest Jiuquan; Relative humidity's effect on HFMD showed a non-linear interacting relationship with average temperature. [ABSTRACT FROM AUTHOR]

The influence of socio-ecological factors on hand, foot and mouth disease (HFMD) were explored in this study using Bayesian spatial modeling and spatial patterns identified in dry regions of Gansu, China. Notified HFMD cases and socio-ecological data were obtained from the China Information System for Disease Control and Prevention, Gansu Yearbook and Gansu Meteorological Bureau. A Bayesian spatial conditional autoregressive model was used to quantify the effects of socio-ecological factors on the HFMD and explore spatial patterns, with the consideration of its socio-ecological effects. Our non-spatial model suggests temperature (relative risk (RR) 1.15, 95 % CI 1.01-1.31), GDP per capita (RR 1.19, 95 % CI 1.01-1.39) and population density (RR 1.98, 95 % CI 1.19-3.17) to have a significant effect on HFMD transmission. However, after controlling for spatial random effects, only temperature (RR 1.25, 95 % CI 1.04-1.53) showed significant association with HFMD. The spatial model demonstrates temperature to play a major role in the transmission of HFMD in dry regions. Estimated residual variation after taking into account the socio-ecological variables indicated that high incidences of HFMD were mainly clustered in the northwest of Gansu. And, spatial structure showed a unique distribution after taking account of socio-ecological effects. [ABSTRACT FROM AUTHOR]

Long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) are beneficial for human health. However, humans and mammals are unable to synthesize n-3 PUFAs because they lack the n-3 desaturase gene fat-1 and must therefore obtain this type of fatty acid through their diet. Through the production of fat-1 transgenic animals, it is possible to obtain animal products that are rich in n-3 PUFAs, such as meat and milk. The aim of this study was to analyze the gene expression profile and the mechanism of lipid metabolism in fat-1 transgenic cattle and to accumulate important basic data that are required to obtain more efficient fat-1 transgenic cattle. Transcriptome profiling of fat-1 transgenic and wild-type cattle identified differentially expressed genes that are involved in 90 biological pathways, eight pathways of which were related to lipid metabolism processes 36 genes of which were related to lipid metabolism. This analysis also identified 11 significantly enriched genes that were involved in the peroxisome proliferator-activated receptor signaling pathway. These findings were verified by quantitative polymerase chain reaction. The information obtained in this study indicated that the introduction of an exogenous fat-1 gene into cattle affects the gene expression profile and the process of lipid metabolism in these animals. These results may provide important insights into how an exogenous fat-1 gene synthesizes n-3 PUFAs in transgenic cattle and other mammals. [ABSTRACT FROM AUTHOR]

Aim: Mild cognitive impairment (MCI) is a prodrome for dementia. Alcohol drinking patterns may affect cognitive functions and the effects may accumulate to a significant level at an advanced age. This study investigated the relationship between alcohol consumption and risks for dementia in a cohort of elderly patients with MCI. Methods: Patients with suspected cognitive impairment were screened. One hundred and seventy-six patients who met the MCI criteria were enrolled. Lifetime and daily alcohol consumptions were assessed at baseline using a self-report questionnaire answered by patients and their caregivers. Patients were classified according to alcohol consumptions as abstainers, light–moderate and heavy drinkers. Global cognitive functions were assessed periodically with Mini-Mental State Examination (MMSE). Enrolled patients were followed for 2 years. Results: Of the 176 patients diagnosed as having MCI, 15 (8.5%) died, 13 (7.4%) were lost to follow up, and 66 (37.5%) developed dementia during follow up. Light–moderate alcohol drinkers had better MMSE performance than abstainers ( P < 0.05) and heavy drinkers ( P < 0.01) 2 years after MCI diagnosis. Patients who consumed a total of ≤300 kg alcohol prior to MCI diagnosis had less cognitive decline than patients who consumed no ( P < 0.05) or >300 kg alcohol ( P < 0.01). Heavy drinkers had a higher risk for dementia than abstainers ( P < 0.05) and light–moderate drinkers ( P < 0.05) 2 years after MCI diagnosis. Conclusions: A J-shaped relationship may exist between alcohol consumption and cognitive decline in MCI patients. Light–moderate alcohol drinking may be associated with decreased risks for dementia in elderly patients with MCI. [ABSTRACT FROM AUTHOR]

The eutectic cast Al–Si alloys with excellent high-temperature and casting performance are widely used in engine pistons. During frequent starts and stops, the thermo-mechanical fatigue (TMF) is the most important failure cause. Ultrasonic melt treatment (UT) was chosen to compare and investigate the influence of micro-structures on fatigue life and damage mechanisms of as-cast (AC) eutectic Al–Si alloys under TMF loading. After UT, the grain size, primary Si, and intermetallic particles are reduced significantly in the alloy; fatigue life increases obviously. As a result of pilling-up of dislocations, the competitive effects of the critical strain/stress for fatigue crack nucleation can be found. There are two different crack initiation mechanisms under TMF: one is primary Si fracture for AC alloys with limited critical strain/stress for fatigue crack nucleation at fractured Si particles, and the other is primary Si debonding for UT alloys with increasing critical fracture strain/stress. After the crack initiation, the fractured or debonded primary phases provide the advantages for the further development of main cracks for both alloys. The UT alloy (805 ± 253 cycles) has about twice the TMF life of the AC alloy (403 ± 98 cycles). The refinement of micro-structures is instrumental in improving the fatigue resistance and life of TMF for the UT alloy. [ABSTRACT FROM AUTHOR]

Background and Purpose Methods Results Conclusion This study aimed to investigate the effect of collateral circulation on the outcomes of thrombectomy versus medical management alone in basilar artery occlusion (BAO) patients with varying stroke severities.Data from the ATTENTION cohort were used to perform a post‐hoc analysis comparing the outcomes of thrombectomy with medical management in BAO patients with varying degrees of collateral circulation and stroke severity. Basilar Artery on Computed Tomography Angiography (BATMAN) scores were used to quantify the collateral circulation, and the effect was estimated through a primary outcome of 90‐day functional independence (modified Rankin Scale score, mRS ≤2). Favorable versus unfavorable BATMAN scores were analyzed as both continuous and categorical variables, and an adjusted multivariate regression model was applied.Among 221 BAO patients, thrombectomy significantly improved functional independence compared to medical management in patients with favorable BATMAN scores (aOR 7.75, 95% CI 2.78–26.1), but not in those with unfavorable BATMAN scores (aOR 1.33, 95% CI 0.28–6.92; pinteraction = 0.028). When treated as a continuous variable, increased BATMAN score was found to be associated with a higher likelihood of functional independence in the thrombectomy group (aOR 1.97, 95% CI 1.44–2.81; pinteraction = 0.053). In severe stroke patients with higher BATMAN scores (National Institutes of Health Stroke Scale (NIHSS) ≥21), we identified a significant interaction for treatment effect with thrombectomy compared to medical management (pinteraction = 0.042).An increased BATMAN score was significantly associated with a higher probability of functional independence after thrombectomy than after medical management, particularly in patients with severe BAO. [ABSTRACT FROM AUTHOR]

Background: CircRNAs are a class of noncoding RNAs with tissue- and development-specific expression characteristics. In many mammals, primordial follicle development begins in the embryonic stage. However, the study of circRNAs in primordial follicle development in mice has not been reported. Results: In this study, ovaries were collected from mouse foetuses at 15.5 days post coitus (dpc) and 17.5 dpc, which are two key stages of primordial follicle development. A total of 4785 circRNAs were obtained by using RNA-seq. Of these, 83 differentially expressed circRNAs were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that these differential circRNAs were mainly involved in the regulation of reproductive development. Through qRT-PCR, back-splice sequence detection and enzyme digestion protection experiments, we found that circ-009346, circ-014674, circ-017054 and circ-008296 were indeed circular. Furthermore, circ-009346, circ-014674 and circ-017054 were identified as three key circRNAs by analysing their expression in the ovaries of mice at different developmental stages. The circRNA-miRNA-mRNA interaction network was constructed and validated for target miRNA and mRNA using qRT-PCR. The interacting genes circ-009346, circ-014674, and circ-017054 were subjected to KEGG enrichment analysis. We found that circ-014674 may participate in the assembly and reserve of primordial follicles through oestrogen and the Janus kinase (JAK) signal transducer and activator of transcription (STAT) signalling pathway (JAK-SATA). Circ-009346 and circ-017054 may have similar functions and are involved in the activation and growth of primordial follicles through the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) signalling pathways. Conclusions: Based on our findings, three circRNAs associated with primordial follicle development were identified, and their potential mechanisms of regulating primordial follicle development were revealed. These findings will help us better understand the molecular mechanism of circRNAs in primordial follicles and provide important references and targets for the development of primordial follicles. [ABSTRACT FROM AUTHOR]

Multi-contrast magnetic resonance (MR) image registration is useful in the clinic to achieve fast and accurate imaging-based disease diagnosis and treatment planning. Nevertheless, the efficiency and performance of the existing registration algorithms can still be improved. In this paper, we propose a novel unsupervised learning-based framework to achieve accurate and efficient multi-contrast MR image registration. Specifically, an end-to-end coarse-to-fine network architecture consisting of affine and deformable transformations is designed to improve the robustness and achieve end-to-end registration. Furthermore, a dual consistency constraint and a new prior knowledge-based loss function are developed to enhance the registration performances. The proposed method has been evaluated on a clinical dataset containing 555 cases, and encouraging performances have been achieved. Compared to the commonly utilized registration methods, including VoxelMorph, SyN, and LT-Net, the proposed method achieves better registration performance with a Dice score of 0.8397± 0.0756 in identifying stroke lesions. With regards to the registration speed, our method is about 10 times faster than the most competitive method of SyN (Affine) when testing on a CPU. Moreover, we prove that our method can still perform well on more challenging tasks with lacking scanning information data, showing the high robustness for the clinical application. [ABSTRACT FROM AUTHOR]

Objectives: Idiopathic intracranial hypertension (IIH) is characterized by elevated intracranial pressure of unknown etiology and venous sinus stenting may be an optional treatment. We aimed to evaluate the effects of venous sinus stenting on visual function, intracranial pressure, and trans‐stenotic pressure gradient of the patients with IIH and to determine effects of baseline BMI or weight changes on subjective vision outcome and intracranial pressure. Methods: From July 2009 to Aug 2016, 88 eligible patients with IIH and venous sinus stenosis who underwent stenting were retrospectively studied. Results: In this study, 67 women and 21 men were included with an average age of 39.01 (18–60) years. The average BMI was 26.75 kg/m2. Here, 66 (75.9%) patients had papilledema, 39 had impaired vision before stenting; 57 patients were followed‐up, 48 (84.2%) showed significant subjective improvement or recovery in visual acuity, 4 (7.0%) patients reported no significant change in visual functions, and 5 (8.8%) suffered permanent vision loss. The cerebrospinal fluid opening pressure and trans‐stenotic pressure gradient were significantly decreased postoperatively. Baseline BMI was associated with pre‐and postoperative trans‐stenotic pressure gradients, as well as changes in cerebrospinal fluid opening pressure. However, baseline BMI and body weight changes during follow‐up were not necessarily associated with subjective visual outcomes after stenting. Stenting efficacy was limited in patients with severe preoperative optic symptoms. Conclusions: Venous sinus stenting represented an effective treatment for resolving visual dysfunction and intracranial pressure associated with venous sinus stenosis. BMI seemed to be associated with intracranial pressure but not subjective visual outcomes after stenting. [ABSTRACT FROM AUTHOR]

Objective: Risk stratification plays a critical role in patients with asymptomatic carotid atherosclerotic stenosis. Heavy macrophage infiltration (HMC) is an important factor of plaque destabilization. However, in vivo imaging technologies and screening criteria for HMC remain limited. We aimed to (i) introduce algorithms for in vivo detection of macrophage infiltrations using optical coherence tomography (OCT) and (ii) to investigate the threshold of HMC and its association with plaque vulnerability. Methods: Ex vivo OCT images were co‐registered with histopathology in 282 cross‐sectional pairs from 19 carotid endarterectomy specimens. Of these, 197 randomly selected pairs were employed to define the parameters, and the remaining 85 pairs were used to evaluate the accuracy of the OCT‐based algorithm in detecting macrophage infiltrations. Clinical analysis included 93 patients receiving carotid OCT evaluation. The prevalence and burden of macrophage infiltration were analyzed. Multivariable and subgroup analysis were performed to investigate the association between HMC and plaque rupture. Results: The sensitivity and specificity of algorithm for detecting macrophage infiltration were 88.0% and 74.9%, respectively. Of 93 clinical patients, ruptured plaques exhibited higher prevalence of macrophage infiltration than nonruptured plaques (83.7% [36/43] vs 32.0% [16/50], p < 0.001). HMC was identified when the macrophage index was greater than 60.2 (sensitivity = 74.4%, specificity = 84.0%). Multivariable analysis showed that HMC and multiple calcification were independent risk factors for non‐lipid‐rich plaque rupture. Interpretation: This study provides a novel approach and screening criteria for HMC, which might be valuable for atherosclerotic risk stratification. [ABSTRACT FROM AUTHOR]

The systems of reaction-diffusion equations coupled with moving boundaries defined by Stefan condition have been widely used to describe the dynamics of spreading population and with competition of two species. To solve these systems numerically, new numerical challenges arise from the competition of two species due to the interaction of their free boundaries. On the one hand, extremely small time steps are usually needed due to the stiffness of the system. On the other hand, it is always difficult to efficiently and accurately handle the moving boundaries especially with competition of two species. To overcome these numerical difficulties, we introduce a front tracking method coupled with an implicit solver for the 1D model. For the general 2D model, we use a level set approach to handle the moving boundaries to efficiently treat complicated topological changes. Several numerical examples are examined to illustrate the efficiency, accuracy and consistency for different approaches. [ABSTRACT FROM AUTHOR]

Invented decades ago, whirling is a machining process primarily employed for producing helical surfaces. In view of its cost-effectiveness, this paper proposes to adapt the whirling process for manufacturing airfoil blades. Considering that chatter often occurs during the whirling process due to the low stiffness of blade workpiece, which impairs the machining quality, theoretical issues in relation to chatter and its prediction for the blade whirling process are investigated. Firstly, the principle of blade whirling is briefly introduced and vibration components in the cutter-workpiece system are analyzed in order to identify the characteristics of blade whirling and establish a reasonable dynamic model. Then, a theoretical model for stability prediction in blade whirling is presented and verified, which fully considers the geometric immersion of the whirling cutter and the dynamic parameters of the workpiece system. In order to ensure accuracy of the prediction results, non-symmetric frequency response function (FRF) matrices are adopted in modeling the system and identifying the modal parameters. After that, the effect of material removal on machining stability is examined. Since a large proportion of material is to be removed, the whirling operation is divided into several steps for exploration. The results show that the material removal changes the natural frequency and modal shape of the system which causes the variation of the limit on cutting depth. Finally, the proposed approach is verified with a scaled propeller blade being machined as a case study. [ABSTRACT FROM AUTHOR]

Introduction: As a disorder of the brain in adults and children, traumatic brain injury (TBI) is considered the major cause of mortality and morbidity. As a serious complication of TBI, post-traumatic hydrocephalus (PTH) is commonly identified and significantly associated with neurocognitive impairment, motor dysfunction, and growth impairment. The long-term functional outcomes after shunt dependence are totally not clear. Methods: This study included 6279 patients between 2012 and 2022. To identify the unfavorable functional outcomes and the PTH-related factors, we carried out univariable logistic regression analyses. To identify the occurrence time of PTH, we conducted the log-rank test and Kaplan–Meier analysis. Results: Mean patient age was 51.03 ± 22.09 years. Of the 6279 patients with TBI, 327 developed PTH (5.2%). Several PTH development-associated factors, such as intracerebral hematoma, diabetes, longer initial hospital stay, craniotomy, low GCS (Glasgow Coma Scale), EVD (external ventricular drain), and DC (decompressive craniectomy) (p < 0.01), were identified. We also analyzed the factors of unfavorable outcomes after TBI including > 80 years, repeated operations, hypertension, EVD, tracheotomy, and epilepsy (p < 0.01). Ventriculoperitoneal shunt (VPS) itself is not an independent factor of the unfavorable outcome but shunt complication is a strong independent factor of unfavorable outcome (p < 0.05). Conclusion: We should emphasize the practices that can minimize the risks of shunt complications. Additionally, the rigorous radiographic and clinical surveillance will benefit those patients at high risk of developing PTH. Trial registration: ClinicalTrials.gov identifier, ChiCTR2300070016. [ABSTRACT FROM AUTHOR]

Background: Glycemic gap, as a novel index of acute glycemic excursion, is associated with poor prognosis of different diseases. This study aimed to explore the association of the glycemic gap with long‐term stroke recurrence in patients with ischemic stroke. Methods: This study included patients with ischemic stroke from the Nanjing Stroke Registry Program. The glycemic gap was calculated by subtracting the estimated average blood glucose from the blood glucose at admission. Multivariable Cox proportional hazards regression analysis was performed to explore the association between the glycemic gap and the risk of stroke recurrence. The Bayesian hierarchical logistic regression model was used to estimate the effects of the glycemic gap on stroke recurrence stratified by diabetes mellitus and atrial fibrillation. Results: Among 2734 enrolled patients, 381 (13.9%) patients experienced stroke recurrence during a median follow‐up of 3.02 years. In multivariate analysis, glycemic gap (high group vs. median group) was associated with significantly increased risk for stroke recurrence (adjusted hazard ratio, 1.488; 95% confidence interval, 1.140–1.942; p =.003) and had varying effects on stroke recurrence depending on atrial fibrillation. The restricted cubic spline curve showed a U‐shaped relationship between the glycemic gap and stroke recurrence (p =.046 for nonlinearity). Conclusion: Our study found that the glycemic gap was significantly associated with stroke recurrence in patients with ischemic stroke. The glycemic gap was consistently associated with stroke recurrence across subgroups and had varying effects depending on atrial fibrillation. [ABSTRACT FROM AUTHOR]

Background: Neuroinflammation is a vital pathophysiological process during ischemic stroke. Activated astrocytes play a major role in inflammation. Lipocalin-2 (LCN2), secreted by activated astrocytes, promotes neuroinflammation. Pyroptosis is a pro-inflammatory form of programmed cell death that has emerged as a new area of research in stroke. Nevertheless, the potential role of LCN2 in astrocyte pyroptosis remains unclear. Methods: An ischemic stroke model was established by middle cerebral artery occlusion (MCAO) in vivo. In this study, in vitro, oxygen–glucose deprivation and reoxygenation (O/R) were applied to cultured astrocytes. 24p3R (the LCN2 receptor) was inhibited by astrocyte-specific adeno-associated virus (AAV-GFAP-24p3Ri). MCC950 and Nigericin sodium salt (Nig) were used to inhibit or promote the activation of NLRP3 inflammasome pharmacologically, respectively. Histological and biochemical analyses were performed to assess astrocyte and neuron death. Additionally, the neurological deficits of mice were evaluated. Results: LCN2 expression was significantly induced in astrocytes 24 h after stroke onset in the mouse MCAO model. Lcn2 knockout (Lcn2−/−) mice exhibited reduced infarct volume and improved neurological and cognitive functions after MCAO. LCN2 and its receptor 24p3R were colocalized in astrocytes. Mechanistically, suppression of 24p3R by AAV-GFAP-24p3Ri alleviated pyroptosis-related pore formation and the secretion of pro-inflammatory cytokines via LCN2, which was then reversed by Nig-induced NLRP3 inflammasome activation. Astrocyte pyroptosis was exacerbated in Lcn2−/− mice by intracerebroventricular administration of recombinant LCN2 (rLCN2), while this aggravation was restricted by blocking 24p3R or inhibiting NLRP3 inflammasome activation with MCC950. Conclusion: LCN2/24p3R mediates astrocyte pyroptosis via NLRP3 inflammasome activation following cerebral ischemia/reperfusion injury. [ABSTRACT FROM AUTHOR]

1H NMR-based metabolic profiling combined with multivariate data analysis was used to explore the metabolic phenotype of functional dyspepsia (FD) in stressed rats and evaluate the intervention effects of the Chinese medicine Weikangning (WKN). After a 7-day period of model establishment, a 14-day drug administration schedule was conducted in a WKN-treated group of rats, with the model and normal control groups serving as negative controls. Based on 1H NMR spectra of urine and serum from rats, PCA, PLS-DA, and OPLS-DA were performed to identify changing metabolic profiles. According to the key metabolites determined by OPLS-DA, alterations in energy metabolism, stress-related metabolism, and gut microbiota were found in FD model rats after stress stimulation, and these alterations were restored to normal after WKN administration. This study may provide new insights into the relationship between FD and psychological stress and assist in research into the metabolic mechanisms involved in Chinese medicine. [ABSTRACT FROM AUTHOR]

CMYA1 is a protein that plays an important role in muscle development and contains a highly conserved Xin repeats region. However, the function of the Xin-repeats in CMYA1 is unknown, and there is little information regarding proteins that interact with the CMYA1/Xin-repeats in the bovine system. In this study, we generated a high-quality bovine muscle cDNA library and performed a yeast two-hybrid screen twice using both CMYA1 and the Xin-repeats as bait. There were 27 candidate-interacting proteins identified in this screen. Three of the 27 proteins (RPL35A, RPL21 and EIF3G) interacted with both CMYA1 and the Xin-repeats, and this interaction was further confirmed using one-to-one Y2H mating. These results showed that the three candidate proteins interacted with CMYA1/Xin-repeats and indicated that the Xin-repeats is a key region of CMYA1 required for protein interaction. In conclusion, our results provide new targets on the bovine CMYA1/Xin-repeats interacting proteins, and these findings provide an important reference for the study of how bovine muscle development is regulated. [ABSTRACT FROM AUTHOR]

Simple Summary: This study aimed to explore the possible role of histone deacetylase 1 (HDAC1), an epigenetic modifying enzyme, in the improvement of oocyte maturation recovered from the Tan sheep of China. We supplemented a specific inhibitor of HDAC1 to in vitro-cultured cumulus oocyte complexes (COCs). The results showed that the cumulus cell expansion and oocyte maturation ratio were impaired, while the production of the epidermal growth factor (EGF) was only slightly changed, despite the fact that the pan-acetylation levels of the histones were significantly elevated. This study implies that HDAC1 may participate in the maturation of oocytes in Tan sheep independently of the classic gonadotrophin-induction pathway. Previous studies have shown that some of the histone deacetylases (HDACs) play diverse roles in the regulation of ovarian somatic cell development, oocyte maturation and early embryonic development in different species including sheep. This study aimed to clarify whether HDAC1 also played pivotal roles in regulating oocyte maturation in Tan sheep. The results showed that HDAC1 was expressed in the nuclei of both the granulosa cells and oocytes of the growing follicles in the Tan sheep's ovaries. However, the level of HDAC1 was unaffected by luteinizing hormone (LH) induction in cultured granulosa cells. Meanwhile, the specific inhibition of HDAC1 using pyroxamide did not induce significant changes in the expression levels of EGF-like growth factors in vitro, whereas both the cumulus expansion and oocyte maturation of the cultured cumulus oocyte complexes (COCs) were significantly inhibited by pyroxamide. Additionally, the numbers of histone acetylation sites (H4K5, H4K12, H3K14 and H3K9) in ovarian granulosa cells were significantly increased. In conclusion, a constant expression of HDAC1 in the growing follicles of Tan sheep may be pivotal for supporting oocyte growth and maturation, although its action may not be closely correlated with LH induction, nor does it directly affect the expression of the EGF-like factors. Our study implies that there may exist diverse functions of the respective HDACs in modulating female reproduction in sheep. [ABSTRACT FROM AUTHOR]

Most cells involved in atherosclerosis release extracellular vesicles (EVs), which can carry bioactive substances to downstream tissues via circulation. We hypothesized that EVs derived from atherosclerotic plaques could promote atherogenesis in remote locations, a mechanism that mimics the blood metastasis of cancer. Ldlr gene knockout (Ldlr KO) rats were fed on a high cholesterol diet and underwent partial carotid ligation to induce local atherosclerosis. EVs were separated from carotid artery tissues and downstream blood of carotid ligation by centrifugation. MiRNA sequencing and qPCR were then performed to detect miRNA differences in EVs from rats with and without induced carotid atherosclerosis. Biochemical analyses demonstrated that EVs derived from atherosclerosis could increase the expression of ICAM-1, VCAM-1, and E-selectin in endothelial cells in vitro. EVs derived from atherosclerosis contained a higher level of miR-23a-3p than those derived from controls. MiR-23a-3p could promote endothelial inflammation by targeting Dusp5 and maintaining ERK1/2 phosphorylation in vitro. Inhibiting EV release could attenuate atherogenesis and reduce macrophage infiltration in vivo. Intravenously administrating atherosclerotic plaque-derived EVs could induce intimal inflammation, arterial wall thickening and lumen narrowing in the carotids of Ldlr KO rats, while simultaneous injection of miR-23a-3p antagomir could reverse this reaction. The results suggested that EVs may transfer atherosclerosis to remote locations by carrying proinflammatory factors, particularly miR-23a-3p. [ABSTRACT FROM AUTHOR]

Approximately 75% of diagnosed breast cancer tumors are estrogen-receptor-positive tumors and are associated with a better prognosis due to response to hormonal therapies. However, around 40% of patients relapse after hormonal therapies. Genomic analysis of gene expression profiles in primary breast cancers and tamoxifen-resistant cell lines suggested the potential role of miR-489 in the regulation of estrogen signaling and development of tamoxifen resistance. Our in vitro analysis showed that loss of miR-489 expression promoted tamoxifen resistance, while overexpression of miR-489 in tamoxifen-resistant cells restored tamoxifen sensitivity. Mechanistically, we found that miR-489 is an estrogen-regulated miRNA that negatively regulates estrogen receptor signaling by using at least the following two mechanisms: (i) modulation of the ER phosphorylation status by inhibiting MAPK and AKT kinase activities; (ii) regulation of nuclear-to-cytosol translocation of estrogen receptor α (ERα) by decreasing p38 expression and consequently ER phosphorylation. In addition, miR-489 can break the positive feed-forward loop between the estrogen-Erα axis and p38 MAPK in breast cancer cells, which is necessary for its function as a transcription factor. Overall, our study unveiled the underlying molecular mechanism by which miR-489 regulates an estrogen signaling pathway through a negative feedback loop and uncovered its role in both the development of and overcoming of tamoxifen resistance in breast cancers. [ABSTRACT FROM AUTHOR]

Objectives: This study aims at exploring the 3-month outcome predicting ability of delayed neurological improvement and the cause of delayed neurological improvement. Materials and methods: Early neurological improvement and delayed neurological improvement were calculated to represent the neurological improvements. Good functional outcome was defined as a 90-day modified Rankin Scale score 0–2. We used multivariant logistic regression to explore the influential factors of good functional outcome as well as delayed neurological improvement. We applied net reclassification improvement and integrated discrimination improvement to assess the quantitative improvement of the predictive model. Results: Early neurological improvement was observed in 50 (23%) patients and delayed neurological improvement exhibited in 67 (30%) patients. Early neurological improvement and delayed neurological improvement were both independent predictive factors to good functional outcome. In the basic model (adjusted for age, admission glucose level, baseline National Institute of Health Stroke Scale, and complications and number of retrieval attempts), early neurological improvement and delayed neurological improvement statistically improved the predictive ability (early neurological improvement: net reclassification improvement = 0.34, 95% confidence interval, 95% confidential interval (0.06, 0.69); integrated discrimination improvement = 0.05, p < 0.001; delayed neurological improvement: net reclassification improvement = 0.79, 95% confidential interval (0.47, 1.12); integrated discrimination improvement = 0.14, p < 0.001) delayed neurological improvement could predict clinical outcomes more accurately than early neurological improvement (early neurological improvement vs. delayed neurological improvement: integrated discrimination improvement = 0.09, p < 0.001). Moreover, delayed neurological improvement was affected by hypertension (odds ratio = 0.40, 95% CI (0.18, 0.88), p = 0.02), early neurological improvement (odds ratio = 20.10, 95% confidential interval (8.24, 19.02), p < 0.001), number of retrieval attempts (odds ratio = 0.39, 95% confidential interval (0.24, 0.66), p < 0.001), and complication (odds ratio = 0.25, 95% confidential interval (0.12, 0.54), p < 0.001). Conclusions: Delayed neurological improvement could predict clinical outcomes more accurately than early neurological improvement. Hypertension, early neurological improvement, numbers of retrieval attempts, and complications were all predicting factors to delayed neurological improvement. [ABSTRACT FROM AUTHOR]

Resistance to cisplatin-based chemotherapy is a major cause of treatment failure in advanced bladder cancer (BC) patients. There is increasing evidence that microRNAs are involved in the development and progression of BC. However, little is known about the function of microRNAs in predicting the effect of adjuvant chemotherapy on BC survival and regulating response to cisplatin. To address this issue, we employed RT-qPCR to evaluate the clinical significance of miR-203 expression in 108 tissues of BC patients receiving cisplatin-based adjuvant chemotherapy, and performed in vitro studies to explore chemotherapeutic sensitivity to cisplatin in miR-203 overexpressing BC cells. We found miR-203 levels were significantly lower in BC progression group than non-progression group (P<0.001). ROC curve analysis illustrated miR-203 could significantly distinguish progressed patients from those without progression (P<0.001), yielding an area under the ROC curve of 0.839 (95% CI, 0.756–0.903). Moreover, low miR-203 expression correlated with shortened progression free survival (PFS) and overall survival (OS) of BC patients, and was an independent prognostic factor. Overexpression of miR-203 in 5637 and T24 BC cells could decrease cell viability, enhance cisplatin cytotoxicity, and promote apoptosis. Western blotting and luciferase reporter assay showed Bcl-w and Survivin were direct downstream targets of miR-203. There was also a significant inverse association between miR-203 and Bcl-w or Survivin expression in BC tissues (r = -0.781, -0.740, both P<0.001). In conclusion, decreased miR-203 predicts progression and poor prognosis for BC patients treated with cisplatin-based chemotherapy while miR-203 overexpression can enhance cisplatin sensitization by promoting apoptosis via directly targeting Bcl-w and Survivin. [ABSTRACT FROM AUTHOR]

Photo-piezocatalysis based on homojunction emerges as an auspicious approach for the environmental crisis, while it is still in early stage with limited strategies and ambiguous reaction mechanisms. Herein, a heteroatom-free homojunction of ultrathin g-C 3 N 4 with N vacancies/pristine g-C 3 N 4 has been innovatively constructed through surface coupling effect. It achieves higher performance on both photo-piezocatalytic RhB degradation and H 2 O 2 production than solely piezocatalysis or photocatalysis. The underlying causes lie in the synergistic effects of the internal electric field constructed in the type II homojunction and the polarized electric field stimulated by the non-centrosymmetric structure, which cooperatively facilitate the driving force of the charge carriers. Notably, due to the unfixed polarization direction, the charge transfer pathways undergo transitions between type-II and Z-scheme mechanisms, which both promote the spatial separation and migration dynamics of electrons and holes. This work provides new insights into structural design and mechanism exploration for highly efficient photo-piezocatalytic applications. [Display omitted] • A heteroatom-free homojunction of ultrathin g-C 3 N 4 /pristine g-C 3 N 4 with stable surface coupling is flexibly constructed. • The photo-piezocatalytic RhB degradation efficiency reaches 99.0% in 2 h and H 2 O 2 production of 672.6 μmol in 1 h. • The dual-field coupling effect of internal electric field and polarized electric field synergistically facilitates the transfer of charge carriers. • The charge transfer dynamics undergo transitions between type-II and Z-scheme mechanisms. [ABSTRACT FROM AUTHOR]

Background: The association between non‐alcoholic fatty liver disease (NAFLD) and the risk of stroke is heterogeneous. Therefore, we aimed to examine any potential causal relationship between these two traits through Mendelian randomization. Methods: The genetic instruments associated with NAFLD were selected from a large genome‐wide association study in individuals of European ancestry (1483 cases and 17,781 controls, replicated in 559 cases and 945 controls). The genetic associations for stroke (40,585 cases and 406,111 controls) and ischemic stroke (34,217 cases and 406,111 controls) were selected from the MEGASTROKE consortium of European ancestry participants. The causal effects on ischemic stroke subtypes, including large artery atherosclerosis (LAA) (4373 cases and 146,392 controls), small vessel occlusion (SVO) (5386 cases and 192,662 controls), and cardioembolic stroke (7193 cases and 204,570 controls), were also analyzed. The inverse variant weighted method was performed to obtain the casual estimates. Heterogeneity and pleiotropy of individual single nucleotide polymorphisms were also tested for the robustness of the results. Results: NAFLD was not associated with stroke (odds ratio [OR] 1.015; 95% confidence interval [CI] 0.996–1.034; p = 0.121) and ischemic stroke (OR 1.017; 95% CI 0.997–1.037; p = 0.092). Regarding ischemic stroke subtypes, there were positive causal inferences on LAA (OR 1.065; 95% CI 1.004–1.129; p = 0.037) and SVO (OR 1.058; 95% CI 1.003–1.116; p = 0.037), while it was not significant for cardioembolic stroke (OR 1.026; 95% CI 0.983–1.071; p = 0.243). Conclusion: This study suggests that the potential causal effect of NAFLD on ischemic stroke may be confined to the LAA and SVO subtypes. [ABSTRACT FROM AUTHOR]

A common CCD camera was equipped with a specially designed filter to constitute a vision system, which was used to capture the weld pool and the keyhole images during plasma arc welding process. Through image processing and calibration, the shapes and sizes of both the keyhole and the weld pool were measured under different welding conditions. The dynamic variations of the keyhole/weld pool sizes with time and their relations with the main process parameters were experimentally determined. Six stages of the keyhole/weld pool evolution were observed during the whole welding process. The observation results lay solid foundation for optimizing the welding process parameters and implementing process control of plasma arc welding. [ABSTRACT FROM AUTHOR]

Background: Little research has been conducted on the spatio-temporal relationship between the severe cases and the enteroviruses infections of hand, foot and mouth disease (HFMD). This study aimed to investigate epidemic features and spatial clusters of HFMD incidence rates and assess the relationship between Enterovirus 71 (EV71) and Coxsackievirus A16 (CoxA16) and severe cases of HMFD in Gansu province, China.Methods: Weekly county-specific data on HFMD between 1st January and 31st December 2018 were collected from the China Infectious Disease Information System (CIDIS), including enterovirus type (EV71 and CoxA16), severe and non-severe cases in Gansu province, China. Temporal risk [frequency index (α), duration index (β) and intensity index (γ)] and spatial cluster analysis were used to assess epidemic features and identify high-risk areas for HFMD. Time-series cross-correlation function and regression model were used to explore the relationship between the ratios of two types of viruses (i.e. EV71/Cox16) (EC) and severe cases index (i.e. severe cases/non-severe cases) (SI) of HFMD.Results: Some counties in Dingxi City, Gansu were identified as a hot spot for the temporal risk indices. Time-series cross-correlation analysis showed that SI was significantly associated with EC (r = 0.417, P < 0.05) over a 4-week time lag. The regression analysis showed that SI was positively associated with EC (β = 0.04, 95% confidence interval (CI) 0.02-0.06).Conclusion: The spatial patterns of HFMD incidence were associated with enteroviruses in Gansu. The research suggested that the EC could be considered a potential early warning sign for predicting severe cases of HFMD in Gansu province. [ABSTRACT FROM AUTHOR]

This paper introduces a method of strengthening prestressed concrete continuous box-girder bridges with prestressed steel strands. Construction process monitoring, field load tests before and after reinforcement, and health monitoring after reinforcement were performed to verify the effectiveness of the external prestressed steel strand reinforcement method. During the construction monitoring process, the measured values of each tensioning step are basically consistent with the theoretical values, but the measured values are slightly less than the theoretical values. The results of the field load tests show that the bending strength and stiffness of the strengthened girder have been improved. During health monitoring, the strain value and deflection value data for some parts across the specified section were collected. According to the data, the strain and deflection values fluctuated within the specified limit, and the bridge was always in a safe state. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether stressful life events (SLEs) can predict post‐stroke fatigue (PSF) in patients with acute ischemic stroke (AIS). Methods: This prospective cohort study included data from patients with AIS who were followed up to 2‐year interview. PSF was assessed at admission and at 6 (n = 916), 12 (n = 880), and 24 (n = 857) months with the fatigue severity scale (FSS). SLEs were measured with the Social Readjustment Rating Scale questionnaire at 6, 12 and 24 months' interview. Results: A significant dose‐response association was found between SLEs and FSS score across all examined time‐points: compared with those did not experience SLEs, FSS score was higher for those experiencing SLEs ≥3 at 6 months (β 0.53, 95% CI 0.28–0.78), 12 months (β 0.54, 95% CI 0.30–0.78) and 24 months (β 0.48, 95% CI 0.29–0.68). Longitudinal analyses indicated a significantly positive relationship between the number of SLEs and FSS score (SLEs: ≥3 vs. 0, β 0.14, 95% CI 0.09–0.19). Moreover, a distinct interaction of follow‐up time and SLE numbers on FSS score was observed (p < 0.05), which means elevated exposure to SLEs during follow‐up was associated with a lower rate of fatigue decline. A similar association was found in SLE load analysis. Conclusion: Patients with severe fatigue were more likely to report increased number of SLEs in the previous 6 months, which could suggest that a non‐specific stressful event leads to an extra burden to an already vulnerable psychological system. [ABSTRACT FROM AUTHOR]

Background: Innate immunity can facilitate early brain injury (EBI) following subarachnoid hemorrhage (SAH). Numerous studies suggest that pyroptosis could exacerbate extracellular immune responses by promoting secretion of inflammatory cytokines. Transforming growth factor-β-activated kinase 1 (TAK1) is a quintessential kinase that positively regulates inflammation through NF-κB and MAPK signaling cascades. However, the effects of TAK1 on neuroinflammation in EBI following SAH are largely unknown.Methods: Two hundred and forty-six male C57BL/6J mice were subjected to the endovascular perforation model of SAH. A selective TAK1 inhibitor, 5Z-7-oxozeaenol (OZ) was administered by intracerebroventricular (i.c.v) injection at 30 min after SAH induction. To genetic knockdown of TAK1, small interfering RNA (siRNA) was i.c.v injected at 48 h before SAH induction. SAH grade, brain water content, BBB permeability, neurological score, western blot, real-time PCR, ELISA, transmission electron microscope, and immunofluorescence staining were performed. Long-term behavioral sequelae were evaluated by the rotarod and Morris water maze tests. Furthermore, OZ was added to the culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. The reactive oxygen species level was detected by DCFH-DA staining. Lysosomal integrity was assessed by Lyso-Tracker Red staining and Acridine Orange staining.Results: The neuronal phosphorylated TAK1 expression was upregulated following SAH. Pharmacologic inhibition of TAK1 with OZ could alleviate neurological deficits, brain edema, and brain-blood barrier (BBB) disruption at 24 h after SAH. In addition, OZ administration restored long-term neurobehavioral function. Furthermore, blockade of TAK1 dampened neuronal pyroptosis by downregulating the N-terminal fragment of GSDMD (GSDMD-N) expression and IL-1β/IL-18 production. Mechanistically, both in vivo and in vitro, we demonstrated that TAK1 can induce neuronal pyroptosis through promoting nuclear translocation of NF-κB p65 and activating nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. TAK1 siRNA treatment mitigated SAH-induced neurobehavioral deficits and restrained phosphorylated NF-κB p65 expression and NLRP3 inflammasome activation. TAK1 blockade also ameliorated reactive oxygen species (ROS) production and prevented lysosomal cathepsin B releasing into the cytoplasm.Conclusions: Our findings demonstrate that TAK1 modulates NLRP3-mediated neuronal pyroptosis in EBI following SAH. Inhibition of TAK1 may serve as a potential candidate to relieve neuroinflammatory responses triggered by SAH. [ABSTRACT FROM AUTHOR]

Background and Purpose. Ruptured tiny volume intracranial aneurysms (TVIAs) are associated with high risk of intraprocedural perforation. Aneurysm volume measuring is important for treatment planning and packing density calculation. We aim to assess the ability of the AngioSuite software in calculating TVIAs and guiding the selection of suitable coil. Methods. Thirty-three consecutive patients with 34 TVIAs were prospectively recruited and treated with endovascular techniques. The volume of TVIAs and the required length of coils were calculated by the AngioSuite software before embolization. The treatment efficacy of TVIAs was assessed using the Raymond scale (Rs) and the modified Rankin scale (mRs). Results. Of the 34 aneurysms with an average volume of 7.16 mm3, 13 aneurysms were treated with sole coil embolization, 19 by stent-assisted embolization, and 2 by balloon-assisted embolization. The average coil length was 5.32 cm, and the average packing density was 41.21%. The immediate DSA showed that total occlusion (Rs = 1) was achieved in 15 aneurysms, subtotal (Rs = 2) in 9, and partial (Rs = 3) in 11. Total occlusion was achieved in 30 aneurysms and subtotal in the other 4 aneurysms at 6-month follow-up. Baseline volume and diameter of aneurysms were significantly correlated with the coil length (r = 0.801 , P < 0.001 ; r = 0.711 , P < 0.001). Conclusions. Coil embolization of TVIAs was easy to achieve high packing density. According to the data from AngioSuite, relative few coils can increase the safety in procedure and stenting may reduce risk of aneurysmal recurrence. [ABSTRACT FROM AUTHOR]

Background and Aims: A reliable predictive score system to identify the risk of symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis (IVT) in acute ischemic stroke patients is of great essence. We aimed to develop a nomogram for predicting the risk of sICH after IVT in Chinese patients. Methods: We recruited acute ischemic stroke patients who were treated with IVT from five advanced stroke centers in China from April 2014 to November 2020. sICH was diagnosed according to the European Cooperative Acute Stroke Study II (ECASS-II) definition. Multivariable logistic regression was performed to construct the best-fit nomogram. The discrimination and calibration of the nomogram were evaluated by the area under the receiver operating characteristic curve (AUC-ROC) and calibration plot. Results: A total of 1200 patients were enrolled, of whom 66 (5.5%) developed sICH. In the multivariate logistic regression model, atrial fibrillation (odds ratio [OR] 3.25; 95% confidence interval [CI], 1.89− 5.60; P < 0.001), baseline glucose level (OR, 1.13; 95% CI, 1.07− 1.20; P < 0.001), neutrophil to lymphocyte ratio (OR, 1.05; 95% CI, 1.01− 1.09; P = 0.024) and baseline National Institute of Health Stroke Scale (NIHSS) (OR, 1.07; 95% CI, 1.04− 1.10; P < 0.001) were independent predictors for sICH and were used to generate the nomogram. The nomogram demonstrated good discrimination as the AUC-ROC value was 0.788 (95% CI, 0.737– 0.840). The calibration plot revealed good calibration. Conclusion: The nomogram consisted of atrial fibrillation, baseline glucose level, neutrophil to lymphocyte ratio, and NIHSS score may predict the risk of sICH in Chinese acute ischemic stroke patients treated with IVT. [ABSTRACT FROM AUTHOR]

Background and Purpose. The cause of in-stent restenosis (ISR) after vertebral artery ostium (VAO) stenting remains unclear. We evaluated factors associated with ISR in patients who underwent VAO stenting. We also assessed the feasibility of stenting for treating VAO stenosis (VAOS). Methods. Between January 2016 and October 2018, sixty-four consecutive patients who underwent a total of 66 stenting procedures were screened for symptomatic and asymptomatic atherosclerotic VAOS. Of these patients, 57 had complete follow-up data. The baseline patient demographics and morphological features of the VAO were recorded. Potential factors influencing ISR, including conventional cerebrovascular disease risk factors, were assessed, together with outcome events including recurrent transient ischemic attack (TIA), stroke, and vascular-related mortality. Results. The average follow-up period was 13.2 ± 4.6 months. Technical success was achieved in all interventions. The degree of stenosis was reduced from 77.2 ± 6.1 % to 13.7 ± 8.9 % after the procedure. ISR was detected in eight treated vessels (14.0%) and occlusion in two (5.3%) arteries. Of the 57 patients, one had an ischemic stroke and 5 had TIAs. The angle of the VAO at the subclavian artery was associated with the risk of restenosis (preoperative, P = 0.04 ; postoperative, P = 0.02). Conclusions. Stenting is a feasible and effective treatment for VAOS. The angle of the VAO at the subclavian artery may contribute to the development of ISR. [ABSTRACT FROM AUTHOR]

aiming Wang,1,4 Qin Yin,1 Xinfeng Liu11Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210000, People's Republic of China; 2Cerebrovascular Disease Treatment Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, 210000, People's Republic of China; 3Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, 210000, People's Republic of China; 4Department of Neurology, The 80th Group Army Hospital, Weifang, Shandong, 261000, People's Republic of China*These authors contributed equally to this workCorrespondence: Huaiming WangDepartment of Neurology, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of ChinaTel +86 2584801861Fax +86 2584805169Email wanghm89@163.comQin YinDepartment of Neurology, Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210002, Jiangsu Province, People's Republic of ChinaTel +86 2584801861Fax +86 2584805169Email yinqin9912@163.com Background and Aims: Albumin levels have been reported to be associated with all-cause and cardiovascular mortality. The aim of this study was to investigate the association between serum albumin and prognosis of ischemic stroke patients after endovascular thrombectomy (EVT) treatment. Methods: Patients with EVT due to large artery occlusion in anterior circulation were selected from ACTUAL (endovascular treatment for acute anterior circulation) ischemic stroke multicenter registry in China. Serum albumin levels were measured within 24 h of admission. The primary outcome was poor functional outcome (modified Rankin scale score of 3– 6) at three months. Secondary outcomes were symptomatic intracranial hemorrhage (sICH) and three-month mortality. Results: A total of 605 patients (mean age, 64.2 years; 59.3% male) were enrolled. Up to three months after stroke, 342 patients (56.5%) developed poor functional outcome. After multivariate adjustment for demographic characteristics, National Institutes of Health stroke score, and other potential confounders, the odds ratio for the lowest tertile of serum albumin levels was 2.43 (95%CI, 1.18− 5.01; P=0.046) for poor functional outcome, compared with the highest category. Restricted cubic spline regression demonstrated a linear association between albumin levels and poor functional outcome (P for linearity=0.017). Subgroup analyses further confirmed these results. Similar significant findings were also found in the association of serum albumin with mortality, but not with sICH. Conclusion: Decreased serum albumin levels were independently associated with poor prognosis at 90 days after acute large vessel occlusion stroke in anterior circulation treated with EVT. [ABSTRACT FROM AUTHOR]

The surface chemistry of colloidal quantum dots (CQD) play a crucial role in fabricating highly efficient and stable solar cells. However, as‐synthesized PbS CQDs are significantly off‐stoichiometric and contain inhomogeneously distributed S and Pb atoms at the surface, which results in undercharged Pb atoms, dangling bonds of S atoms and uncapped sites, thus causing surface trap states. Moreover, conventional ligand exchange processes cannot efficiently eliminate these undesired atom configurations and defect sites. Here, potassium triiodide (KI3) additives are combined with conventional PbX2 matrix ligands to simultaneously eliminate the undercharged Pb species and dangling S sites via reacting with molecular I2 generated from the reversible reaction KI3 ⇌ I2 + KI. Meanwhile, high surface coverage shells on PbS CQDs are built via PbX2 and KI ligands. The implementation of KI3 additives remarkably suppresses the surface trap states and enhances the device stability due to the surface chemistry optimization. The resultant solar cells achieve the best power convention efficiency of 12.1% and retain 94% of its initial efficiency under 20 h continuous operation in air, while the control devices with KI additive deliver an efficiency of 11.0% and retains 87% of their initial efficiency under the same conditions. [ABSTRACT FROM AUTHOR]

aiming Wang,1,5,6 Xinfeng Liu1,41Department of Neurology, Jinling Clinical College of Nanjing Medical University, Nanjing 210002, Jiangsu Province, People's Republic of China; 2Department of Cerebrovascular Disease Treatment Center, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing 210002, Jiangsu Province, People's Republic of China; 3Department of Neurology, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui Province, People's Republic of China; 4Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing 210002, Jiangsu Province, People's Republic of China; 5Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, People's Republic of China; 6Department of Neurology, The 80th Group Army Hospital of People's Liberation Army, Weifang, Shandong Province, People's Republic of China*These authors contributed equally to this workCorrespondence:Xinfeng LiuDepartment of Neurology, Jinling Clinical College of Nanjing Medical University, 305# East Zhongshan Road, Nanjing 210002, Jiangsu, People's Republic of ChinaTel +86-18951919349Fax +86-25-84801861Email xfliu2@vip.163.comHuaiming WangDepartment of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, Jiangsu Province, People's Republic of ChinaTel +86-18951919349Fax +86-25-84801861Email wanghm89@163.com Purpose: Malignant cerebral edema (MCE) in patients undergoing endovascular thrombectomy (EVT) is not uncommon and can reduce the benefit of EVT. We aimed to develop a nomogram model to predict the risk of MCE in ischemic stroke patients after EVT. Patients and Methods: We retrospectively collected patients treated with EVT caused by anterior circulation large vessel occlusion stroke at two comprehensive stroke centers. MCE was defined as midline shift > 5 mm at the septum pellucidum or pineal gland with obliteration of the basal cisterns or the need for early decompressive hemicraniectomy. A multivariate logistic model was utilized to construct the best-fit nomogram model. The discrimination and calibration of the nomogram were estimated using the area under the receiver operating characteristic curve (AUC-ROC) and Hosmer–Lemeshow test. Results: A total of 370 patients (mean age, 67.2± 11.9 years; male, 56.8%) were enrolled in the final analysis. Among them, 71 (19.2%) patients experienced MCE after EVT treatment. After adjustment for potential confounders, age, baseline National Institutes of Health Stroke Scale score, collateral circulation, fast blood glucose level and recanalization were independent predictors of MCE and were incorporated into the nomogram. The AUC-ROC value of the nomogram was 0.805 (95% confidence interval [CI]: 0.750– 0.860). The Hosmer–Lemeshow goodness-of-fit test showed good calibration of the nomogram (P = 0.681). Conclusion: The nomogram composed of age, baseline National Institutes of Health Stroke Scale score, blood glucose level, collateral circulation and recanalization may predict the probability of MCE in anterior circulation large vessel occlusion stroke patients treated with EVT. [ABSTRACT FROM AUTHOR]

• A novel lncRNA lnc403 was identified which mainly expressed in muscle cell nucleus. • Lnc403 inhibit myogenic differentiation of bovine skeletal muscle satellite cells. • Lnc403 negatively regulated gene Myf6 and positively regulated protein KRAS. Skeletal muscle, the most abundant and plasticity tissue in mammals, is essential for various functions such as movement, breathing, maintaining posture and metabolism. Myogenesis is a complex and precise process, which is regulated by the sequential expression of multiple transcription factors, and accumulating evidence have confirmed that multiple lncRNAs are involved in muscle development as the important transcriptional regulator. In this study, a novel lncRNA, named lnc403 was obtained, with a full-length 2689 bp, which had poor coding ability and was mainly expressed in the nucleus of myoblasts and myotubes. The expression of lnc403 was significantly different in the proliferation and differentiation stages of muscle cells. Then we successfully constructed lnc403 loss/gain-function cell models by transfecting silnc403 and pCDNA3.1-EGFP-lnc403 into satellite cells, respectively; and found that lnc403 inhibited skeletal muscle satellite cell differentiation but had no significant effect on cell proliferation, either in the case of lnc403 knockdown or overexpression. In order to further screen the target factors regulated by lncRNA in the process of myogenic differentiation, the RNA-pull down, mass spectrometry and bioinformatics analysis were performed. The results showed that lnc403 negatively regulated the expression of the adjacent gene Myf6 and positively regulated interaction proteins KRAS expression. The above results indicate that lnc403 affects skeletal muscle cell differentiation by affecting the expression of nearby genes and interacting proteins, implying lnc403 might participate in the bovine myoblasts differentiation through multi-pathway network regulation mode. This study provides a new perspective for further understanding of the regulation mechanism of lncRNAs on bovine myogenic process. [ABSTRACT FROM AUTHOR]

Background: Vascular angioplasty and stenting of middle cerebral artery (MCA) and basilar artery (BA) stenoses are associated with poor clinical outcomes and high mortality rates thought to be related to the abundance of perforating arteries in those segments. This study explores the use of Solitaire AB as an off-label vascular stent to treat stenoses in the MCA and BA. Methods: Solitaire AB stents were placed during angioplasty and stenting of MCA and BA stenoses in patients at our department between January 2015 and May 2017 with 6-36 months follow-up. Operative results were assessed by follow-up angiography and transcranial doppler after the procedure. Neurologic status was evaluated before and after treatment according to the modified Ranking Scale (mRS). Results: A total of 32 patients were included in the study. Seventeen (53.12%) patients presented with MCA stenosis and 15 (46.87%) with BA stenosis. The 30-day rate of procedure-related complications was 3.1% (1/32). Post-stenting residual stenosis degrees ranged from 0% to 40% (mean 13.44% ± 10.66%). Mean degree of residual stenosis in 26 patients followed up by DSA was 8.64% ± 9.67%. The mRS 0-2 was achieved in all (100%) patients at 6-12 months post-procedure. Conclusions: Our study indicates the off-label use of Solitaire AB for stenting is effective and safe for MCA and BA stenoses with high technical success and low complications. We recommend that lesion-specific therapy with an anatomically fitted stent design enables optimal treatment for intracranial stenosis. [ABSTRACT FROM AUTHOR]

Objectives: The accuracy of cognitive screening tools to detect poststroke cognitive impairment (PSCI) was investigated using various neuropsychological definitions. Methods: Hospital‐based stroke patients underwent a comprehensive neuropsychological assessment. The rate of PSCI was estimated using thresholds of 1, 1.5, or 2 standard deviations below the normal control and memory impairment defined by a single or multiple tests. Meanwhile, the diagnostic accuracy of cognitive screening through face‐to‐face assessment using the Mini‐Mental State Examination (MMSE) and the Montreal Cognitive Assessment Scale (MoCA), and telephone assessment using a 5‐minute NINDS‐Canadian Stroke Network (NINDS‐CSN) scale and a six‐item screener (SIS), was both tested under different definitions, with the optimal cutoff selected based on the highest Youden index. Results: In stroke patients, the rate of PSCI ranged from 46.3% to 76.3% upon different definitions. The face‐to‐face MoCA was more consistent with the comprehensive cognitive assessment compared to MMSE. The optimal cutoff of PSCI was MMSE ≤ 27 and MoCA ≤ 19. For the telephone tests, the 5‐minute NINDS‐CSN assessment was more reliable, and the optimal cutoff was ≤23, while for SIS ≤ 4. Conclusions: Cognitive screening tools including the face‐to‐face MMSE and MoCA, together with the telephone assessment of NINDS‐CSN 5‐minute protocol and SIS, were simple and effective for detecting PSCI in stroke patients. The corresponding threshold values for PSCI were 27 points, 19 points, 23 points, and 4 points. [ABSTRACT FROM AUTHOR]

Simple Summary: Individuals with hermaphroditism are a serious hazard to animal husbandry and production due to their abnormal fertility. The molecular mechanism of sheep intersex formation was unclear. This study was the first to locate the homologous sequence of the goat polled intersex syndrome (PIS) region in sheep and found that the intersex traits of Lanzhou fat-tailed sheep were not caused by the lack of this region. By detecting the selective sweep regions, vital genes associated with androgen biosynthesis and the follicle stimulating hormone response entry were found, including steroid 5 alpha-reductase 2 (SRD5A2), and pro-apoptotic WT1 regulator (PAWR). Additionally, the copy number variations of the four regions on chr9, chr1, chr4, and chr16 may affect the expression of the gonadal development genes, zinc finger protein, FOG family member 2 (ZFPM2), LIM homeobox 8 (LHX8), inner mitochondrial membrane peptidase subunit 2 (IMMP2L) and slit guidance ligand 3 (SLIT3), respectively, and further affect the formation of intersex traits. Intersex, also known as hermaphroditism, is a serious hazard to animal husbandry and production. The mechanism of ovine intersex formation is not clear. Therefore, genome-wide resequencing on the only two intersex and two normal Lanzhou fat-tailed (LFT) sheep, an excellent but endangered Chinese indigenous sheep breed, was performed. Herein, the deletion of homologous sequences of the goat polled intersex syndrome (PIS) region (8787 bp, 247747059–247755846) on chromosome 1 of the LFT sheep was not the cause of the ovine intersex trait. By detecting the selective sweep regions, we found that the genes related to androgen biosynthesis and follicle stimulating hormone response items, such as steroid 5 alpha-reductase 2 (SRD5A2), steroid 5 alpha-reductase 3 (SRD5A3), and pro-apoptotic WT1 regulator (PAWR), may be involved in the formation of intersex traits. Furthermore, the copy number variations of the four regions, chr9: 71660801–71662800, chr1: 50776001–50778000, chr4: 58119201–58121600, and chr16: 778801–780800, may affect the expression of the zinc finger protein, FOG family member 2 (ZFPM2), LIM homeobox 8 (LHX8), inner mitochondrial membrane peptidase subunit 2 (IMMP2L) and slit guidance ligand 3 (SLIT3) genes, respectively, which contribute to the appearance of intersex traits. These results may supply a theoretical basis for the timely detection and elimination of intersex individuals in sheep, which could accelerate the healthy development of animal husbandry. [ABSTRACT FROM AUTHOR]

Background: Preoperative neuroimaging assessment of collateral circulation is important for selecting acute ischemic stroke patients who are appropriate for endovascular treatment. We sought to validate the capillary index score system in an Asian population and compare its ability in predicting clinical outcomes with the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system. Methods: We continuously enrolled acute ischemic stroke patients from two neurological centers from March 2014 to March 2017. Multivariate analyses were performed to assess the capillary index score system with 90-day clinical outcome (modified Rankin scale score). The scoring systems were compared for predicting good (modified Rankin scale 0–2) and excellent (modified Rankin scale 0–1) functional outcomes using area under the receiver operating characteristic curves. Results: We identified 157 patients (median age, 65 years; 96 (61.1%) males), of whom 71 (45.2%) patients with 90-day good functional outcomes were selected. Capillary index score was independently associated with clinical outcome after endovascular treatment (OR 0.63; 95% CI 0.43–0.92; P = 0.016) with its predictive ability for good functional outcome (area under the receiver operating characteristic curve 0.755). For excellent functional outcome, the capillary index score system was not inferior to the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology grading system (area under the receiver operating characteristic curve 0.748 versus 0.793, P = 0.09). Conclusions: The capillary index score system is a potentially useful tool for predicting 90-day functional outcomes in acute ischemic stroke patients after endovascular treatment. [ABSTRACT FROM AUTHOR]

Background: Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive treatment for ischemic stroke. Astrocytes regulation has been suggested as one mechanism for rTMS effectiveness. But how rTMS regulates astrocytes remains largely undetermined. There were neurotoxic and neuroprotective phenotypes of astrocytes (also denoted as classically and alternatively activated astrocytes or A1 and A2 astrocytes) pertaining to pro- or anti-inflammatory gene expression. Pro-inflammatory or neurotoxic polarized astrocytes were induced during cerebral ischemic stroke. The present study aimed to investigate the effects of rTMS on astrocytic polarization during cerebral ischemic/reperfusion injury.Methods: Three rTMS protocols were applied to primary astrocytes under normal and oxygen-glucose deprivation/reoxygenation (OGD/R) conditions. Cell survival, proliferation, and phenotypic changes were assessed after 2-day treatment. Astrocytes culture medium (ACM) from control, OGD/R, and OGD/R + rTMS groups were mixed with neuronal medium to culture neurons for 48 h and 7 days, in order to explore the influence on neuronal survival and synaptic plasticity. In vivo, rats were subjected to middle cerebral artery occlusion (MCAO), and received posterior orbital intravenous injection of ACM collected from different groups at reperfusion, and at 3 days post reperfusion. The apoptosis in the ischemic penumbra, infarct volumes, and the modified Neurological Severity Score (mNSS) were evaluated at 1 week after reperfusion, and cognitive functions were evaluated using the Morris Water Maze (MWM) tests. Finally, the 10 Hz rTMS was directly applied to MCAO rats to verify the rTMS effects on astrocytic polarization.Results: Among these three frequencies, the 10 Hz protocol exerted the greatest potential to modulate astrocytic polarization after OGD/R injury. Classically activated and A1 markers were significantly inhibited by rTMS treatment. In OGD/R model, the concentration of pro-inflammatory mediator TNF-α decreased from 57.7 to 23.0 рg/mL, while anti-inflammatory mediator IL-10 increased from 99.0 to 555.1 рg/mL in the ACM after rTMS treatment. The ACM collected from rTMS-treated astrocytes significantly alleviated neuronal apoptosis induced by OGD/R injury, and promoted neuronal plasticity. In MCAO rat model, the ACM collected from rTMS treatment decreased neuronal apoptosis and infarct volumes, and improved cognitive functions. The neurotoxic astrocytes were simultaneously inhibited after rTMS treatment.Conclusion: Inhibition of neurotoxic astrocytic polarization is a potential mechanism for the effectiveness of high-frequency rTMS in cerebral ischemic stroke. [ABSTRACT FROM AUTHOR]