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Background Microsurgical clipping is effective for treating early rupture hemorrhage in intracranial aneurysm (IA) patients. We aimed to evaluate the therapeutic effects of microsurgical clipping at different time points on IA and to explore prognostic factors. Methods A total of 102 eligible patients were divided into good prognosis group (n = 87) and poor prognosis group (n = 15) according to Glasgow Outcome Scale (GOS) scores at discharge. The effects of microsurgical clipping at different time points (within 24 h, 48 h and 72 h) were compared. The incidence rates of postoperative complications in patients with different Hunt–Hess grades were compared. Prognostic factors were determined by multivariate logistic regression analysis. The nomogram prediction model was established based on independent risk factors and validated. Results The good recovery and success rates of complete aneurysm clipping were significantly higher in patients undergoing surgery within 24 h after rupture. The incidence rate of complications was significantly higher in patients with Hunt–Hess grade IV. Good and poor prognosis groups had significantly different age, history of hypertension, preoperative intracranial hematoma volume, aneurysm size, preoperative Hunt–Hess grade, later surgery, postoperative complications and National Institute of Health Stroke Scale (NIHSS) score, as independent risk factors for prognosis. The nomogram model predicted that poor prognosis rate was 14.71%. Conclusion Timing (within 24 h after rupture) microsurgical clipping benefits the prognosis of IA patients. Age, history of hypertension, preoperative intracranial hematoma volume, aneurysm size, preoperative Hunt–Hess grade, later surgery, postoperative complications and NIHSS score are independent risk factors for poor prognosis.

Temozolomide (TMZ) is the recommended drug for glioblastoma (GBM) treatment, but its clinical effect is restricted due to drug resistance. This research studies the effects of long non-coding RNA (lncRNA) ZBED3-AS1 and its related molecules on acquired TMZ resistance in glioblastoma (GBM). ZBED3-AS1 was identified to be downregulated in TMZ-resistant GBM cells by analyzing GSE113510 and GSE100736 datasets. ZBED3-AS1 downregulation was detected in TMZ-resistant GBM tissues and cell lines (U251/TMZ and U87/TMZ). ZBED3-AS1 knockdown promoted, whereas its overexpression suppressed TMZ resistance, viability and mobility, and glycolytic activity of TMZ-resistant cells. ZBED3-AS1 bound to Spi-1 proto-oncogene (SPI1) but did not affect its expression. Instead, it blocked SPI1-mediated transcriptional activation of thrombomodulin (THBD). SPI1 and THBD increased TMZ resistance and glycolysis in TMZ-resistant cells. Either ZBED3-AS1 overexpression or SPI1 knockdown in U87/TMZ cells blocked the growth of orthotopic and subcutaneous xenograft tumors in nude mice. In conclusion, this study demonstrates that ZBED3-AS1 downregulation and THBD activation is linked to increased TMZ resistance and glycolysis in GBM cells.

Endoplasmic reticulum stress (ERS) has been studied as critical factor during occurrence and development of ulcerative colitis (UC). However, the role of ERS in inflamed UC remains unclear. The purpose of this study was to analyze the role of inositol-requiring kinase 1 (IRE-1), a major regulator of ER, in regulating ERS and cell viability. In UC mucosa tissue, IRE-1, BiP, XBP-1s, CHOP caspase-12 and GADD34 mRNA were assayed by qRT-PCR. Then, human normal colon epithelial cell line (NCM-460) and colon fibroblast cell line (CCD-33Co) were cultured, and downregulated or upregulated IRE-1 expression. ERS was induced with 100 ng/mL of Interleukin 6 (IL-6). CCK8 assay was performed to analyze cell proliferation. Flow cytometry analysis was conducted to detect the apoptosis. Western blot assay was used to examine ERS markers. IRE-1, BiP, XBP-1s, caspase-12 and CHOP mRNA were highly expressed in UC mucosa tissue, and the expression of GADD34 mRNA significantly decreased. These results show that ERS-induced unfolded protein response was enhanced in UC mucosa tissue. In cells, silencing the expression of IRE-1 could suppress cell proliferation and promote apoptosis through activating unfolded protein response, while the over-expression of IRE-1 had the opposite effect. IL-6 could induce ERS and cells apoptosis. Furthermore, we demonstrated that shRNA IRE-1 could enhance the inhibition of IL-6 on cells viability. Inhibition of IRE-1 enhanced unfolded protein response and cells apoptosis and IL-6-induced ERS and suggested that IRE-1 might be a potential target of UC.

With the development of modern long-span cable-stayed bridges, due to the Parallel strand cable (PSC) being assembled on-site strand by strand, which has the advantages such as no need for large-scale equipment for cable-making, delivery, hoisting, traction, tensioning, and the corrosion protection of the cable is excellent, it is more and more favored by designers.OVM280 is a new type of cable system with high fatigue resistance and high durability developed based on OVM250 steel strand cable. By optimizing the anchoring unit of the steel strand cable, reducing the deviation angle of the steel strand in transition section, and improving the raw material quality of the steel strand at the same time, so that the comprehensive fatigue stress amplitude can be increased to 280MPa. According to the S-N curve of the cable fatigue test, the fatigue life is nearly 4 times that of the 200MPa stress amplitude and 1.71 times that of the 250MPa stress amplitude, and the anchoring performance and fatigue resistance performance are greatly improved.A new generation of double slip resistance saddle for OVM280DK strand cable has been developed, which solves the fretting wear problem in the saddle section. In addition, this saddle can be applied to the saddle with curvature radius less than 2 meters, which increases the ability of the saddle to adapt to different conditions.

Has_circ_0008583 is reported to be involved in the progression of hepatocellular carcinoma (HCC), while its biological role in HCC remains unclear. Here, the qRT-PCR was used to detect the expression of has_circ_0008583. The CCK-8 kit was performed to measure cell proliferation. The cell migration and invasion were evaluated by Transwell. A dual-luciferase reporter assay was performed to confirm the target combination between the genes in has_circ_0008583/miR-1301-3p/METTL3 axis. The in vivo role of has_circ_0008583 was verified by murine xenograft assay. Our data showed that hsa_circ_0008583 was upregulated in HCC tissues and cells. Hsa_circ_0008583 overexpression promoted Hep3B cell proliferation, migration and invasion, but hsa_circ_0008583 silencing had an opposing influence. MiR-1301-3p is directly bound to hsa_circ_0008583 and METTL3. MiR-1301-3p overexpression or METTL3 knockdown could partially counteract hsa_circ_0008583 overexpression-mediated influence on HCC cell behaviors. In addition, hsa_circ_0008583 depletion inhibits HCC tumor growth in vivo. In conclusion, hsa_circ_0008583 promotes HCC progression through the miR-1301-3p/METTL3 axis.

The joints between segments represent weak points and introduce discontinuity into structures, therefore they are particularly significant in precast concrete segmental bridges (PCSBs). In this study, a new steel shear key was designed, and 3 full-scale tests were conducted. Various shear keys were taken as experimental parameters to study crack development, failure mode, shear slip, ultimate bearing capacity, and the residual bearing capacity of various joints under direct shear force. The results show that the stiffness and bearing capacity of steel shear keyed joints is higher than concrete key joints, and the structural system is more stable than concrete key joints at the moment of cracking.

The occiput-axis crossing translaminar screw (C2LAM) fixation technique can help avoid vertebral injury, while the inclusion of offset connectors can facilitate implantation. This three-dimensional finite element (FE) study compared the stability of C2LAM using offset connectors (C2LAM + OF) with other methods.Occipital and cervical spine computed tomography images of a healthy 30-year-old man were selected to build the FE model. Four internal fixation instruments including occiput plate-C2 pedicle (C2P) and pars (C2Pars) screws, as well as C2LAM and C2LAM + OF were applied consecutively to the model respectively to establish four new models, which were subjected to all states of motion and physiological loads to simulate normal movement, including the four kinds of basic activities of human such as flexion, extension, lateral bending, and axial rotation. Physiological measures and comparison included the range of motion (ROM) and stress distribution in the model.ROM between the fixation techniques was comparable, and the stability of the C2LAM + OF fixation technique was similar to that of C2P. Screw entry points, offset connectors and rods were the main stress distribution regions in the C2LAM + OF system. The mean von Mises stress of the inner wall was significantly smaller than that of the outer wall in flexion, extension, and rotation (The results of this study indicate that the C2LAM + OF fusion technique can provide sufficient stability and can be used as an alternative to C2P under special circumstances.

Oscillatory activities within basal ganglia (BG) circuitry in L-DOPA induced dyskinesia (LID), a condition that occurs in patients with Parkinson disease (PD), are not well understood. The aims of this study were firstly to investigate oscillations in main BG input and output structures—the dorsolateral striatum (dStr) and substantia nigra pars reticulata (SNr), respectively— including the direction of oscillation information flow, and secondly to investigate the effects of 5-HT1A/B receptor agonism with eltoprazine on oscillatory activities and abnormal involuntary movements (AIMs) characteristic. To this end, we conducted local field potential (LFP) electrophysiology in the dStr and SNr of LID rats simultaneous with AIM scoring. The LFP data were submitted to power spectral density, coherence, and partial Granger causality analyses. AIM data were analyzed relative to simultaneous oscillatory activities, with and without eltoprazine. We obtained four major findings. 1) Theta band (5–8 Hz) oscillations were enhanced in the dStr and SNr of LID rats. 2) Theta power correlated with AIM scores in the 180-min period after the last LID-inducing L-DOPA injection, but not with daily summed AIM scores during LID development. 3) Oscillatory information flowed from the dStr to the SNr. 4) Chronic eltoprazine reduced BG theta activity in LID rats and normalized information flow directionality, relative to that in LID rats not given eltoprazine. These results indicate that dStr activity plays a determinative role in the causal interactions of theta oscillations and that serotonergic inhibition may suppress dyskinesia by reducing dStr-SNr theta activity and restoring theta network information flow.

Due to the limitation of system structure, UAV can not accurately locate itself. Once the positioning error accumulates to a certain extent, it may lead to mission failure. Therefore, the aircraft needs to go through several calibration points to correct vertical and horizontal error. In this paper, an improved ant colony optimization algorithm is used to realize path planning of the aircraft based on error correction. Firstly, mathematical model of path planning is established based on constraints of location error. Secondly, ant colony optimization is used to realize multi-objectives including maximizing success rate reaching the destination, minimizing the number of correction nodes and minimizing length of the path. To find feasible solutions for different problems, constraints are strengthened or relaxed and search strategies of the next node are set. Finally, the algorithm with adaptive parameters is verified by an example, the optimal path with 100% arrival rate, shorter length, and less correction nodes shows its effectiveness.

OBJECTIVE Percutaneous microballoon compression (PMC) is a simple and effective surgical procedure for the treatment of trigeminal neuralgia. The difficulty with this surgery is related to accurate and quick foramen ovale puncture. In this study, we compared the application of personalized 3D-printed guides and the traditional puncture method in trigeminal PMC surgery. METHOD Data from 40 patients with primary trigeminal neuralgia treated with PMC between June 2017 and August 2019 were analyzed retrospectively. Personalized 3D-printed jigs were used to assist foramen ovale puncture in 20 patients, and Hartel positioning was used for puncture in 20 patients. Three-dimensional reconstruction was performed preoperatively using 3DSlicer software to understand the size of the foramen ovale and positioning of related anatomical structures. Based on the reconstruction, personalized surgical paths were created for the jig plate-assisted treatment group, and the printed jig plate was applied to the surgery through 3D printing to explore the surgical effect. RESULTS Foramen ovale puncture was successful in all patients. Better results were achieved with guides than with the traditional method in terms of the foramen ovale puncture time (p

Recurrent epithelial erosion and refractory corneal ulcer are the clinical features of diabetic keratopathy (DK), which eventually lead to corneal scar and visual disturbance. In this study, we sought to determine the abnormalities of cell junction in diabetic corneal epithelial cells and the effect of high glucose on the β-catenin/E-cadherin complex. Corneal histology showed that corneal epithelial cells of high glucose mice were loosely arranged, and the immunohistochemistry showed that the expression of E-cadherin decreased, the levels of β-catenin increased in nuclear. High glucose-induced degradation and endocytosis of E-cadherin of corneal epithelial cells reduce the formation of β-catenin/E-cadherin complex and promote the nuclear translocation of β-catenin. Moreover, high glucose also activated the transcription and expression of matrix metallopeptidase and snail, which interfered with the adhesion of corneal epithelial cells to the basement membrane. These findings reveal that DK is associated with the dissociation of cell junctions. The maintenance of the stability of the β-catenin/E-cadherin complex may be a potential therapeutic target of refractory corneal ulcers in patients with diabetes.

At present, there are many excellent genome compression algorithms with high genome compression ratio. However, there is a lack of highly efficient compression algorithms for simultaneous compression of a large number of genomes. This manuscript presents an algorithm, which is called FastLNGC, for simultaneous compression of a large amount of genome data based on multi-thread concurrency. This algorithm is based on the LNGC (Large Number of Genomes Compressor) algorithm, and adopts multi-thread technology to achieve concurrent processing of genome data compression. A large number of experiments show that FastLNGC has better performance on compression of a large number of genes. The source code of FastLNGC is available at https://github.com/APandaThief/FastLNGC.

Recurrent pregnancy loss (RPL) is an important complication in reproductive health. About 50% of RPL cases are unexplained, and understanding the genetic basis is essential for its diagnosis and prognosis. Herein, we report causal KH domain containing 3 like (KHDC3L) mutations in RPL. KHDC3L is expressed in human epiblast cells and ensures their genome stability and viability. Mechanistically, KHDC3L binds to poly(ADP-ribose) polymerase 1 (PARP1) to stimulate its activity. In response to DNA damage, KHDC3L also localizes to DNA damage sites and facilitates homologous recombination (HR)-mediated DNA repair. KHDC3L dysfunction causes PARP1 inhibition and HR repair deficiency, which is synthetically lethal. Notably, we identified two critical residues, Thr145 and Thr156, whose phosphorylation by Ataxia-telangiectasia mutated (ATM) is essential for KHDC3L’s functions. Importantly, two deletions of KHDC3L (p.E150_V160del and p.E150_V172del) were detected in female RPL patients, both of which harbor a common loss of Thr156 and are impaired in PARP1 activation and HR repair. In summary, our study reveals both KHDC3L as a new RPL risk gene and its critical function in DNA damage repair pathways., Recurrent pregnancy loss is an important complication in reproductive health, and about 50% of cases remain unexplained. This study shows that KHDC3L safeguards the genomic stability of human early embryonic cells, and damaging mutations in its gene cause recurrent pregnancy loss in humans.

Oscillatory activity has been well-studied in many structures within cortico-basal ganglia circuits, but it is not well understood within the pedunculopontine nucleus (PPN), which was recently introduced as a potential target for the treatment of gait and postural impairments in advanced stages of Parkinson's disease (PD). To investigate oscillatory activity in the PPN and its relationship with oscillatory activity in cortico-basal ganglia circuits, we simultaneously recorded local field potentials in the PPN, primary motor cortex (M1), and subthalamic nucleus (STN) of 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats during resting and walking. After analysis of power spectral density, coherence, and partial Granger causality, three major findings emerged: 1) after 6-OHDA lesions, beta band oscillations were enhanced in all three regions during walking; 2) the direction of information flow for beta oscillations among the three structures was STN→M1, STN→PPN, and PPN→M1; 3) after the treatment of levodopa, beta activity in the three regions was reduced significantly and the flow of beta band was also abrogated. Our results suggest that beta activity in the PPN is transmitted from the basal ganglia and probably comes from the STN, and the STN plays a dominant role in the network of causal interactions for beta activity. Thus, the STN may be a potential source of aberrant beta band oscillations in PD. Levodopa can inhibit beta activity in the PPN of parkinsonian rats but cannot relieve parkinsonian patients' axial symptoms clinically. Therefore, beta oscillations may not be the major cause of axial symptoms.

Di(2-ethylhexyl) phthalate (DEHP), as a widespread environmental pollutant and an endocrine disruptor, can disturb the homeostasis of thyroid hormones (THs). In order to elucidate roles of the MAPK and PI3K/Akt pathways and hepatic enzymes in thyroid-disrupting effects of DEHP, Sprague-Dawley rats were dosed with DEHP by gavage for 30 consecutive days; Nthy-ori 3-1 cells were treated with DEHP with NAC, k-Ras siRNA or inhibitors (U0126 and wortmannin). Results showed that DEHP led to histopathologic changes in rat thyroid and liver, such as the decrease in thyroid follicular cavity diameter, hepatocyte edema. Triiodothyronine (T3), thyroxine (T4) and thyrotropin releasing hormone (TRH) were reduced. DEHP caused ROS production, oxidative stress and k-Ras upregulation, thereby activating the ERK and Akt pathways in vivo and in vitro. Moreover, TRH receptor (TRHr) level was elevated after the activation of the Akt pathway and was downregulated after the inhibition of the Akt pathway. However, TRHr was not modulated by the ERK pathway. Additionally, hepatic enzymes, including Ugt1a1, CYP2b1, Sult1e1, and Sult2b1, were significantly induced after DEHP exposure. Taken together, DEHP can perturb TH homeostasis and reduce TH levels. The activated Ras/Akt/TRHr pathway and induced hepatic enzymes play vital roles in thyroid-disrupting effects of DEHP.

Many patients of advanced Parkinson's disease (PD) suffer from intractable axial symptoms (severe gait and postural impairments), which were recently speculated to be more relevant to cholinergic degeneration in the brainstem than dopaminergic degeneration in the substantia nigra compacta (SNc). To investigate the role of the cholinergic cells of the pedunculopontine tegmental nucleus (PPTg) on motor deficits, especially the axial motor impairments, we measured and analyzed the gait performance of sham lesion rats, SNc dopaminergic lesion rats, PPTg cholinergic lesion rats, and combined lesion rats by using the CatWalk system. Motor performance of PPTg cholinergic lesion rats was also tested on the rotarod. Independent loss of cholinergic neurons in the PPTg did not induce gait disturbance in CatWalk, but PPTg lesion rats showed motor impairments on the rotarod when the demands of the motor task increased. Both SNc lesion rats and combined lesion rats displayed significant changes in many gait parameters, but the terminal dual stance increased much higher in combined lesion group than SNc lesion group. Furthermore, combined lesion rats showed more severe freezing of gait (FOG) than SNc lesion rats during behavioral re-evaluations after lesion. These results suggest that the PPTg cholinergic neurons play a vital role in the occurrence of FOG in PD.

Synchronized oscillatory neuronal activity in the beta frequency range has been reported in the basal ganglia (BG) of patients with Parkinson disease (PD) and PD animal models. The coherent abnormal oscillatory activities in the dorsolateral striatum (dStr) and substantia nigra pars reticulata (SNr) that accompany parkinsonian states have not been resolved. In this study, we recorded local field potentials (LFPs) in the dStr and SNr of 6-hydroxydopamine (6-OHDA)-induced dopamine (DA)-lesioned rats in an awake, resting state. Analyses of power spectral density and coherence data demonstrated augmented LFP power in the 24-36-Hz (high beta) range in both the dStr and SNr together with increased dStr-SNr coherence in the 24-36-Hz range, relative to sham controls; both effects were reversed by levodopa (L-dopa) treatment. Partial Granger causality analysis revealed a dStr→SNr propagation directionality of these beta oscillations. These findings support the involvement of increased synchronization of high beta activity in the dStr and the SNr, and suggest that dorsolateral striatal activity plays a determinant role in leading the coherent activity with the SNr in the development of parkinsonian pathophysiology.

Based on the transportation mode of high-speed trains and mid-speed trains operating on the same line, considering the delay time of different level trains influence the total late time differently and setting the double control parameters, the mathematical model of the train traffic control is built. According to the theory of genetic algorithm, the sectionalized structural optimization for chromosome coding is designed; model of solution algorithms is established. Using the adjusting algorithm based on genetic algorithm, a simulation system which was fit for the train traffic control of passenger dedicated railway is designed and by simulating the operation adjustment matter in an area of WuHan-GuangZhou passenger dedicated railway where it was from WuChang to YueYang, the feasibility of this method has been verified successfully.