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The ketogenic diet (KD) has demonstrated benefits in numerous clinical studies and animal models of disease in modulating the immune response and promoting a systemic anti-inflammatory state. Here we investigate the effects of a KD on systemic toxicity in mice following SARS-CoV-2 infection. Our data indicate that under KD, SARS-CoV-2 reduces weight loss with overall improved animal survival. Muted multi-organ transcriptional reprogramming and metabolism rewiring suggest that a KD initiates and mitigates systemic changes induced by the virus. We observed reduced metalloproteases and increased inflammatory homeostatic protein transcription in the heart, with decreased serum pro-inflammatory cytokines (i.e., TNF-α, IL-15, IL-22, G-CSF, M-CSF, MCP-1), metabolic markers of inflammation (i.e., kynurenine/tryptophane ratio), and inflammatory prostaglandins, indicative of reduced systemic inflammation in animals infected under a KD. Taken together, these data suggest that a KD can alter the transcriptional and metabolic response in animals following SARS-CoV-2 infection with improved mice health, reduced inflammation, and restored amino acid, nucleotide, lipid, and energy currency metabolism. A systems-wide study of mice infected with SARS-CoV2 under ketogenic diet shows that this diet reprograms the transcriptional and metabolic response in animals following infection with improved health, reduced inflammation, and restored metabolism. [ABSTRACT FROM AUTHOR]

Purpose : Exposure to aggressive parenting is a well-established environmental risk factor for anxiety symptoms. Moreover, autonomic nervous system (ANS) activity, including activity in both parasympathetic and sympathetic nervous systems (PNS and SNS), may moderate the effects of aggressive parenting on anxiety. This study aims to examine the interactive effects of aggressive parenting and ANS activity (both PNS and SNS) in accounting for trait anxiety among emerging adults. Methods: Participants (n = 190, mean age = 19.29, 56% females) reported retrospectively on childhood aggressive parenting and trait anxiety. In addition, we measured resting respiratory sinus arrhythmia (RSA), an index of PNS, and resting skin conductance level (SCL), an index of SNS. Results: Regression analyses revealed that the three-way interaction between resting SCL, RSA, and aggressive parenting significantly accounted for trait anxiety. Simple slope analyses suggest that the relation between aggressive parenting and trait anxiety is stronger at lower conditional values of resting RSA and lower conditional values of resting SCL. Conclusion: Coinhibition, or relatively low activity across both systems, may exacerbate the link between aggressive parenting and trait anxiety. This study highlights the importance of considering the interaction effects of multiple physiological systems and environmental context on later psychological functioning. [ABSTRACT FROM AUTHOR]

Purpose: We aimed to synthesize insights from systems science approaches applied to domestic and gender-based violence. Methods: We conducted a systematic review of systems science studies (systems thinking, group model-building, agent-based modeling [ABM], system dynamics [SD] modeling, social network analysis [SNA], and network analysis [NA]) applied to domestic or gender-based violence, including victimization, perpetration, prevention, and community responses. We used blinded review to identify papers meeting our inclusion criteria (i.e., peer-reviewed journal article or published book chapter that described a systems science approach to domestic or gender-based violence, broadly defined) and assessed the quality and transparency of each study. Results: Our search yielded 1,841 studies, and 74 studies met our inclusion criteria (45 SNA, 12 NA, 8 ABM, and 3 SD). Although research aims varied across study types, the included studies highlighted social network influences on risks for domestic violence, clustering of risk factors and violence experiences, and potential targets for intervention. We assessed the quality of the included studies as moderate, though only a minority adhered to best practices in model development and dissemination, including stakeholder engagement and sharing of model code. Conclusions: Systems science approaches for the study of domestic and gender-based violence have shed light on the complex processes that characterize domestic violence and its broader context. Future research in this area should include greater dialogue between different types of systems science approaches, consideration of peer and family influences in the same models, and expanded use of best practices, including continued engagement of community stakeholders. [ABSTRACT FROM AUTHOR]

The use of insecticides remains important in managing pest insects. Over the years, many insects manifested physiological and behavioral modifications resulting in reduced efficacy of insecticides targeted against them. Emerging evidence suggests that bacterial symbionts could modulate susceptibility of host insects against insecticides. Here, we explore the influence of host microbiota in affecting the susceptibility of insect host against different insecticides in the blood-sucking bed bug, Cimex hemipterus. Rifampicin antibiotic treatment resulted in increased susceptibility to fenitrothion and imidacloprid, but not against deltamethrin. Meanwhile, the host fitness parameters measured in the present study were not significantly affected by rifampicin treatment, suggesting the role of bacterial symbionts influencing susceptibility against the insecticides. 16S metagenomics sequencing revealed a drastic shift in the composition of several bacterial taxa following rifampicin treatment. The highly abundant Alphaproteobacteria (Wolbachia > 90%) and Gammaproteobacteria (Yersinia > 6%) in control bed bugs were significantly suppressed and replaced by Actinobacteria, Bacilli, and Betaproteobacteria in the rifampicin treated F1 bed bugs, suggesting possibilities of Wolbachia mediating insecticide susceptibility in C. hemipterus. However, no significant changes in the total esterase, GST, and P450 activities were observed following rifampicin treatment, indicating yet unknown bacterial mechanisms explaining the observed phenomena. Re-inoculation of microbial content from control individuals regained the tolerance of rifampicin treated bed bugs to imidacloprid and fenitrothion. This study provides a foundation for a symbiont-mediated mechanism in influencing insecticide susceptibility that was previously unknown to bed bugs. [ABSTRACT FROM AUTHOR]

Genetic factors play a crucial role for the pathophysiology of treatment-resistant depression (TRD). It has been established that Catechol-O-methyltransferase (COMT) and cyclic amp-response element-binding protein (CREB) are associated with antidepressant response. The aim of this study was to explore the association between single nucleotide polymorphisms (SNPs) in COMT and CREB1 genes and TRD in a Chinese population. We recruited 181 patients with major depressive disorder (MDD) and 80 healthy controls, including 81 TRD patients. Depressive symptoms were assessed with the Hamilton Depression Rating Scale-17 (HDRS). Genotyping was performed using mass spectrometry. Genetic analyses were conducted by PLINK Software. The distribution of COMT SNP rs4818 allele and genotypes were significantly different between TRD and controls. Statistical differences in allele frequencies were observed between TRD and non-TRD groups, including rs11904814 and rs6740584 in CREB1 gene, rs4680 and rs4818 in COMT gene. There were differences in the distribution of HDRS total scores among different phenotypes of CREB1 rs11904814, CREB1 rs6740584, COMT rs4680 and rs4818. Gene–gene interaction effect of COMT–CREB1 (rs4680 × rs6740584) revealed significant epistasis in TRD. There findings indicate that COMT and CREB1 polymorphisms influence the risk of TRD and affect the severity of depressive symptoms of MDD. [ABSTRACT FROM AUTHOR]

To understand the molecular and genetic mechanisms related to the litter size in one species of two different populations (high litter size and low litter size), we performed RNA-seq for the oocytes and granulosa cells (GCs) at different developmental stages of follicle, and identified the interaction of genes from both sides of follicle (oocyte and GCs) and the ligand-receptor pairs from these two sides. Our data were very comprehensive to uncover the difference between these two populations regarding the folliculogenesis. First, we identified a set of potential genes in oocyte and GCs as the marker genes which can be used to determine the goat fertility capability and ovarian reserve ability. The data showed that GRHPR, GPR84, CYB5A and ERAL1 were highly expressed in oocyte while JUNB, SCN2A, MEGE8, ZEB2, EGR1and PRRC2A were highly expressed in GCs. We found more functional genes were expressed in oocytes and GCs in high fertility group (HL) than that in low fertility group (LL). We uncovered that ligand-receptor pairs in Notch signaling pathway and transforming growth factor-β (TGF-β) superfamily pathways played important roles in goat folliculogenesis for the different fertility population. Moreover, we discovered that the correlations of the gene expression in oocytes and GCs at different stages in the two populations HL and LL were different, too. All the data reflected the gene expression landscape in oocytes and GCs which was correlated well with the fertility capability. [ABSTRACT FROM AUTHOR]

H-steel all-bolted connection steel frame structures with heat preservation and decoration composite wall boards were investigated and the seismic performances of three scaled specimens were studied. The failure modes, hysteresis curves, bearing capacity, ductility, energy dissipation capacity, stiffness degradation and strain distribution were discussed. The calculation method of structural theoretical internal force was presented. The results showed that the overall structural seismic performance was better, and the structural ductility met the demands of elastic-plastic inter-story drift angle for seismic design. The H-steel weak-axis connection structure obtained better energy dissipation capacity, and its bearing capacity and stiffness were slightly different from the strong-axis connection. The heat preservation and decoration performance of composite wallboard and the all-bolted connection of the steel frame realized prefabrication during the whole construction period. The plastic hinge of the steel beam can be moved outwards because of the L-angles, which effectively avoids stress concentration in joint areas and expands the plastic hinge range. The errors between the theoretical structural capacity calculated by the plastic analysis method and the test results were within 2.44%. In addition, structural failure mechanisms and bearing capacities were verified by the finite element (FE) analysis, and the effects of the main parameters on the structures were investigated. The FE verification results were the same as in the test. The research results provide theoretical support and technical guidance for the application of thermal insulation and decorative composite wall panels in H-shaped steel all-bolted steel frames. [ABSTRACT FROM AUTHOR]

Glucose disturbances are a common comorbidity of major depressive disorder (MDD) patients and have been extensively studied in the past. However, few studies have explored glucose disturbances in first-episode drug-naïve (FEDN) MDD patients. The purpose of this study was to examine the prevalence and risk factors of glucose disturbances in FEDN MDD patients to understand the relationship between MDD and glucose disturbances in the acute early phase and provide important implications for therapeutic interventions. Using a cross-sectional design, we recruited a total of 1718 MDD patients. We collected their socio-demographic information, clinical data, and blood glucose indicators.17-item Hamilton Depression Rating Scale (HAMD), 14-item Hamilton Anxiety Rating Scale (HAMA), and the positive symptom subscale of the Positive and Negative Syndrome Scale (PANSS) were used to assess their depression, anxiety, psychotic symptoms, respectively. The prevalence of glucose disturbances in FEDN MDD patients was 13.6%. Depression, anxiety and psychotic symptoms, body mass index (BMI) levels and suicide attempts rates were higher in the group with glucose disorders than in the group without glucose disorders among patients with first-episode drug-naive MDD. Correlation analysis showed that glucose disturbances were associated with HAMD score, HAMA score, BMI, psychotic symptoms and suicide attempts. Furthermore, binary logistic regression showed that HAMD score and suicide attempts were independently associated with glucose disturbances in MDD patients. Our findings suggest that the prevalence of comorbid glucose disturbances is very high in FEDN MDD patients. Moreover, more severe depressive symptoms and higher suicide attempts are correlated with glucose disturbances in MDD FEDN patients in the early stage. [ABSTRACT FROM AUTHOR]

In order to achieve accurate fault diagnosis of rolling bearing under random noise, a new fault diagnosis method based on wavelet packet-variational mode decomposition (WP-VMD) and kernel extreme learning machine (KELM) optimized by particle swarm optimization (PSO) is proposed in this paper. Firstly, the time–frequency domain feature vectors of the original rolling bearing fault signals are effectively obtained by preprocessing of WMD and decomposition and reconstruction of VMD. Then, the extracted two-dimensional feature vector is input into the KELM neural network for fault identification, and combined with PSO, KELM parameters were optimized. The experimental results show that the proposed method can effectively diagnose the rolling bearing under random noise, with the features of fast speed, stable performance and high accuracy. By comparison, this paper obtains better accuracy and real-time performance with fewer features, which provides a simple and efficient solution for fault diagnosis of rolling bearings. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR) mutation is a reliable and sensitive biomarker for EGFR-TKI therapy in non-small-cell lung cancer (NSCLC). However, detection of EGFR mutation in tissues has obvious limitations. Circulating free DNA (cfDNA) has been reported as an alternative approach for the detection of EGFR mutations. This systematic review and meta-analysis was designed to assess the diagnostic performance of cfDNA, compared with tissues. True-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) values were extracted or calculated for each study. Pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were calculated. A summary receiver operating characteristic curve (SROC) and area under curve (AUC) were used to evaluate the overall diagnostic performance. 20 eligible studies involving 2012 cases were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were 0.674 (95%CI: 0.517-0.800), 0.935 (95%CI: 0.888-0.963), 10.307 (95%CI: 6.167-17.227), 0.348 (95%CI: 0.226-0.537), and 29.582 (95%CI: 4.582-60.012), respectively. The AUC was 0.93 (95% CI: 0.90-0.95). The meta-analysis suggests that detection of EGFR mutation by cfDNA is of adequate diagnostic accuracy and cfDNA analysis could be a promising screening test for NSCLC. [ABSTRACT FROM AUTHOR]

Epidemiological studies evaluating the association between the intake of vitamin C and lung cancer risk have produced inconsistent results. We conducted a meta-analysis to assess the association between them. Pertinent studies were identified by a search of PubMed, Web of Knowledge and Wan Fang Med Online through December of 2013. Random-effect model was used to combine the data for analysis. Publication bias was estimated using Begg's funnel plot and Egger's regression asymmetry test. Eighteen articles reporting 21 studies involving 8938 lung cancer cases were included in this meta-analysis. Pooled results suggested that highest vitamin C intake level versus lowest level was significantly associated with the risk of lung cancer [summary relative risk (RR) = 0.829, 95%CI = 0.734-0.937, I2 5 57.8%], especially in the United States and in prospective studies. Alinear dose-response relationship was found, with the risk of lung cancer decreasing by 7% for every 100 mg/day increase in the intake of vitamin C [summary RR = 0.93, 95%CI 5 0.88 = 0.98]. No publication bias was found. Our analysis suggested that the higher intake of vitamin C might have a protective effect against lung cancer, especially in the United States, although this conclusion needs to be confirmed. [ABSTRACT FROM AUTHOR]

Cerebral small vessel disease (CSVD) is increasingly being recognized as a leading contributor to cognitive impairment in the elderly. However, there is a lack of effective preventative or therapeutic options for CSVD. In this exploratory study, we investigated the interplay between neuroinflammation and CSVD pathogenesis as well as the cognitive performance, focusing on NLRP3 signaling as a new therapeutic target. Spontaneously hypertensive stroke-prone (SHRSP) rats served as a CSVD model. We found that SHRSP rats showed decline in learning and memory abilities using morris water maze test. Activated NLRP3 signaling and an increased expression of the downstream pro-inflammatory factors, including IL (interleukin)-6 and tumor necrosis factor α were determined. We also observed a remarkable increase in the production of pyroptosis executive protein gasdermin D, and elevated astrocytic and microglial activation. In addition, we identify several neuropathological hallmarks of CSVD, including blood-brain barrier breakdown, white matter damage, and endothelial dysfunction. These results were in correlation with the activation of NLRP3 inflammasome. Thus, our findings reveal that the NLRP3-mediated inflammatory pathway could play a central role in the pathogenesis of CSVD, presenting a novel target for potential CSVD treatment. [ABSTRACT FROM AUTHOR]

Objective: Green tea proposes anti-inflammatory properties which may attenuate chronic inflammation-induced fibrosis of vessels. This study evaluated whether green tea polyphenols (GTP) can avert fibrosis or vascular disruption along with mechanisms in rats with chronic inflammation. Treatments: Forty 3-month-old female rats were assigned to a 2 (placebo vs. lipopolysaccharide, administration) × 2 (no GTP vs. 0.5% GTP in drinking water) factorial design for 12 weeks. Methods: Masson's trichrome staining evaluated myocardial fibrosis in coronary vessels and surrounding myocardium. Whole blood specimens were counted for differentials. Spleen tumor necrosis factor-α (TNF-α) mRNA expression was determined by real-time RT-PCR. Data were analyzed by two-way analysis of variance (ANOVA) followed by mean separation procedures. Results: After 12 weeks, lipopolysaccharide administration induced myocardial fibrosis in vessels and surrounding myocardium, spleen TNF-α mRNA expression, and leukocytes, while GTP supplementation in drinking water significantly averted such observation. Conclusions: GTP attenuates myocardial fibrosis through a suppression of chronic inflammation and innate immune responses. [ABSTRACT FROM AUTHOR]

Let T be a bounded linear operator on a complex Hilbert space H. In this paper we introduce a new class denoted by l-*- A, of operators satisfying T*| T| T ≥ T*| T*| T, and we prove the basic properties of these operators. Using these results, we also prove that if T or T* ∈ l-*- A, then w( f( T)) = f( w( T)), σ( f( T)) = f( σ( T)) for every f ∈ H( σ( T)), where H( σ( T)) denotes the set of all analytic functions on an open neighborhood of σ( T). [ABSTRACT FROM AUTHOR]

Due to atypical clinical presentation, wide use of antibiotics and lack of specificity in diagnosis, misdiagnosis is common, and diagnosis of tubercular infection in a joint is increasingly difficult. The use of arthroscopy for the diagnosis and treatment of early-stage knee TB has rarely been reported. Through this case series we describe the usefulness of arthroscopy for the management of synovial tuberculosis of the knee joint. Synovectomy and synovial membrane biopsy were performed using arthroscopy in ten subjects suffering from synovial tuberculosis. This was combined with intra-articular isoniazid injection and systemic antituberculosis drugs. In all cases, continuous passive motion exercise was started 2 days after operation and they were followed up from 6 months to 3 years. The flexion angles 90° ± 5° preoperatively increased to 120° ± 14° in nine patients following surgery, the extension limit angle also improved from an average 20° ± 3° preoperatively to 5° ± 1° postoperatively. There was a significant difference in knee function index between preoperation and postoperation ( t = 6.9, t = 6.3, P < 0.01). Japanese Institute of Plastic Surgery synovial disease treatment success criteria was also improved from 44.4 ± 8.4 points before surgery to 81.5 ± 10.4 following surgery ( t = 8.749, P < 0.01) . The joint swelling disappeared or was relieved after 2 months. No relapse of tuberculosis was found at the time of follow-up. Combined use of arthroscopy and antituberculosis medication appears to be advantageous for the management of early-stage synovial tuberculosis of the knee joint. Arthroscopic removal of the pannus allows better nutrition of the cartilage and thus greatly improves the joint function. [ABSTRACT FROM AUTHOR]

Background: There is no optimal reconstruction method after proximal gastrectomy. The valvuloplastic esophagogastrostomy can reduce postoperative reflux esophagitis, but it is technically complex with a long operation time. The gastric tube anastomosis is technically simple, but the incidences of reflux esophagitis and anastomotic stricture are higher. Methods: We have devised a modified valvuloplastic esophagogastrostomy after laparoscopy-assisted proximal gastrectomy (LAPG), the arch-bridge anastomosis. After reviewing our prospectively maintained gastric cancer database, 43 patients who underwent LAPG from November 2021 to April 2023 were included in this cohort study, with 25 patients received the arch-bridge anastomosis and 18 patients received gastric tube anastomosis. The short-term outcomes were compared between the two groups to evaluate the efficacy of the arch-bridge anastomosis. Reporting was consistent with the STROCSS 2021 guideline. Results: The median operation time was 180 min in the arch-bridge group, significantly shorter than the gastric tube group (p = 0.003). In the arch-bridge group, none of the 25 patients experienced anastomotic leakage, while one patient (4%) experienced anastomotic stricture requiring endoscopic balloon dilation. The postoperative length of stay was shorter in the arch-bridge group (9 vs. 11, p = 0.034). None of the patients in the arch-bridge group experienced gastroesophageal reflux and used proton pump inhibitor (PPI), while four (22.2%) patients in the gastric tube group used PPI (p = 0.025). The incidence of reflux esophagitis (Los Angeles grade B or more severe) by endoscopy was lower in the arch-bridge group (0% vs. 25.0%). Conclusion: The arch-bridge anastomosis is a safe, time-saving, and feasible reconstruction method. It can reduce postoperative reflux and anastomotic stricture incidences in a selected cohort of patients undergoing laparoscopy-assisted proximal gastrectomy. [ABSTRACT FROM AUTHOR]

The distribution of nerve veins in oral and maxillofacial region is very rich and connected with many parts of the body. Once the infection occurs behind the mouth and maxilla, the effects will be widespread. Therefore, this study aims to explore the application of light enhanced medical imaging technology based on computer diagnosis in the analysis of infection factors in oral and maxillofacial surgery to improve the ability of early diagnosis and accurate treatment. The oral and maxillofacial surgical infection was recorded by using light enhanced medical imaging. The clinical data of patients were collected and analyzed, and the images were processed by computer diagnostic technology. It was found that the relaxation factor λ was 0.5 and the number of iterations was 25 times to improve the accuracy. Studies have also shown that plasma fibrin has an advantage in predicting oral infections. This study demonstrated the potential application value of light enhanced medical imaging technology based on computer diagnosis in the analysis of infection factors in oral and maxillofacial surgery. This technique is helpful for early diagnosis and accurate treatment of oral and maxillofacial surgical infection, improving the treatment effect and quality of life of patients. Further research should also consider expanding the sample size and improving the accuracy of the analysis algorithm. [ABSTRACT FROM AUTHOR]

Due to their complex molecular structures and interactions, phase behaviors of complex fluids are quite often difficult to be identified by common phase transition analysis methods. Percolation phase transition, on the other hand, only monitors the degree of connection among particles without strict geometric requirements such as translational or orientational order, and thus suitable for pinpointing phase transitions of complex fluids. As typical complex fluids, ionic liquids (ILs) exhibit phases beyond the description of simple liquid theories. In particular, with an intermediate cationic side-chain length, ILs can form the nanoscale segregated liquid (NSL) state, which will eventually transform into the ionic liquid crystal (ILC) structure when the side chains are adequately long. However, the microscopic mechanism of this transformation is still unclear. In this work, by means of coarse-grained molecular dynamics simulation, we show that, with increasing cationic side-chain length, some local pieces of non-polar domains are gradually formed by side chains aligned in parallel inside the NSL phase, before an abrupt percolation phase transition happens when the system transforms into the ILC phase. This work not only identifies that the NSL to ILC phase transition is a critical phenomenon, but also demonstrates the importance of percolation theory to complex fluids. [ABSTRACT FROM AUTHOR]

Apurinic/apyrimidinic endonuclease 1/redox-factor 1 (APE1/Ref-1) gene encodes a multifunctional protein involved in the DNA base excision repair (BER) pathway, which initiates repair of apurinic/apyrimidinic (AP) sites in DNA by catalyzing hydrolytic incision of the phosphodiester backbone. APE1/Ref-1 polymorphisms are related to the occurrence of neural tube defects (NTDs), but the association between APE1/Ref-1 polymorphisms and NTDs is not reported in Chinese Han population. The aim of the present study was to evaluate the association of APE1/Ref-1 polymorphism and the risk of NTD occurrence for Han population in a high-risk area of China. APE1/Ref-1 genotypes were determined by iPLEX Gold SNP genotyping. AP sites and folate level of brain tissues were measured. The results showed that three polymorphisms (rs3136817, rs77794916, and rs1760944) of APE1/Ref-1 were statistically associated with NTD subtypes. Allele C of rs3136817, allele T of rs77794916, and allele G of rs1760944 were associated with an increased risk for encephalocele (OR = 2.52, 95% CI [1.25–5.07], P < 0.01; OR = 1.80, 95% CI [1.04–3.12], P = 0.04; and OR = 1.96, 95% CI [1.12–3.45], P = 0.02), compared with those harboring the alleles T, C, and T, respectively. The folate level in NTDs was lower than that in controls. DNA AP sites in the encephalocele were significantly higher than the control (P < 0.01). The three polymorphisms of APE1/Ref-1 were significantly related to NTD occurrence, which indicated that APE1/Ref-1 might be a potential genetic risk factor for encephalocele in a high-risk area of NTDs in China. [ABSTRACT FROM AUTHOR]

Depressive symptoms are common in Parkinson's disease (PD). The relationships between autophagy and PD or depression have been documented. However, no studies explored the role of autophagy markers associated with depressive symptoms in PD. Our study aimed to investigate the relationships between autophagy markers, cognitive impairments and depressive symptoms in PD patients. A total of 163 PD patients aged 50–80 years were recruited. Plasma concentrations of autophagy markers (LC3-I, LC3-II and p62/SQSTM1) and glycolipid parameters were measured. Depressive symptoms, cognitive impairments, and motor function were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA), and the Movement Disorders Society Unified Parkinson's Rating Scale Part III (MDS-UPDRS-III), respectively. There were no significant differences between depressed and non-depressed PD patients for LC3-I, LC3-II, LC3-II/LC3-I and p62/SQSTM1. After controlling confounding variables, LC3-II/LC3-I showed an independent relationship with depressive symptoms in PD patients (Beta = 10.082, t = 2.483, p = 0.014). Moreover, in depressive PD patients, p62/SQSTM1 was associated with MoCA score (Beta = – 0.002, t = − 2.380, p = 0.020); Further, p62/SQSTM1 was related to naming ability; in addition, p62/SQSTM1 was independently associated with delayed recall (Beta = − 0.001, t = − 2.452, p = 0.017). LC3-II/LC3-I was related to depressive symptoms in PD patients. In depressive PD patients, p62/SQSTM1 was associated with cognitive function, especially naming ability and delayed recall. [ABSTRACT FROM AUTHOR]

Objective: To study the efficacy and safety of lasmiditan for acute treatment of migraine in patients using migraine preventive medications. Background: While lasmiditan has been proven to be an effective acute treatment for migraine, its effectiveness has not been examined when used concurrently with migraine preventives. Methods: SAMURAI and SPARTAN were similarly designed, double-blind, phase 3, placebo-controlled studies of patients 18 years or older with 3 to 8 migraine attacks per month. Patients were randomized to treat a migraine attack with oral lasmiditan 50 mg (SPARTAN only), 100 mg, 200 mg, or placebo. Migraine preventives were allowed as long as doses were stable for 3 months prior to screening and were unchanged during the study. Preventive medications with established or probable efficacy, as recommended by the American Academy of Neurology, the American Headache Society, and the European Headache Federation, plus botulinum toxin type A and candesartan, were included. Within the subgroups of patients using and not using preventive therapies, lasmiditan and placebo groups were analyzed for the outcome of pain-free at 2 h and other efficacy outcomes. The subgroups of patients using and not using preventive therapies were compared and interaction p-values were calculated for safety and efficacy outcomes. Results: In these trials, 698 of 3981 patients (17.5%) used migraine preventive treatments. Among patients using preventives, all lasmiditan doses resulted in significantly more patients being pain-free at 2 h, compared to placebo (p < 0.05). Primary efficacy outcome (pain-free at 2 h), key secondary outcome (most bothersome symptom-free at 2 h) and all other efficacy outcomes were not significantly different between patients using or not using migraine preventives (all interaction p-values ≥0.1). Rates of adverse events were similar for patients using and not using preventive medications. Conclusions: Lasmiditan was more effective than placebo for the acute treatment of migraine in patients concurrently using migraine preventive medications. Lasmiditan efficacy and safety measures were similar for patients using and not using preventive medications. Trial registration: SAMURAI (NCT02439320) and SPARTAN (NCT02605174). Registered 18 March 2015. [ABSTRACT FROM AUTHOR]

Although depressive symptoms are common in PD, few studies investigated sex and age differences in depressive symptoms. Our study aimed to explore the sex and age differences in the clinical correlates of depressive symptoms in patients with PD. 210 PD patients aged 50–80 were recruited. Levels of glucose and lipid profiles were measured. The Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MoCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III) assessed depressive symptom, cognition and motor function, respectively. Male depressive PD participants had higher fasting plasma glucose (FPG) levels. Regarding the 50–59 years group, depressive patients had higher TG levels. Moreover, there were sex and age differences in the factors associated with severity of depressive symptoms. In male PD patients, FPG was an independent contributor to HAMD-17 (Beta = 0.412, t = 4.118, p < 0.001), and UPDRS-III score was still associated with HAMD-17 in female patients after controlling for confounding factors (Beta = 0.304, t = 2.961, p = 0.004). Regarding the different age groups, UPDRS-III (Beta = 0.426, t = 2.986, p = 0.005) and TG (Beta = 0.366, t = 2.561, p = 0.015) were independent contributors to HAMD-17 in PD patients aged 50–59. Furthermore, non-depressive PD patients demonstrated better performance with respect to visuospatial/executive function among the 70–80 years group. These findings suggest that sex and age are crucial non-specific factors to consider when assessing the relationship between glycolipid metabolism, PD-specific factors and depression. [ABSTRACT FROM AUTHOR]

To study the influence of fluid solid coupling erosion on the joints of gas pipelines, the Fluent DPM model was first used to conduct finite element analysis on several commonly used gas pipeline joints through gas-solid coupling numerical simulation. Secondly, the reasons for erosion of four-way joints and fish tail joints were studied, and the effects of fluid velocity, particle mass, and particle diameter on erosion were compared and analyzed. Finally, two optimization schemes were proposed for these two types of joints. The results show that fish tail joint is generally lower than that of the three-way channel structure. The erosion rate of the fish tail pipe is caused by the large angle between the inlet and outlet channels, which causes particles to directly impact the projection direction of the inlet channel. The erosion rate increases with the increase in velocity and increases with the increase in particle diameter. The use of a double lobe guide structure in the four-ways joint and fish tail joint not only effectively optimizes the internal flow channel, but also reduces wall erosion and avoids large flow velocity zones. [ABSTRACT FROM AUTHOR]

Limbal melanocytes, located in the basal epithelial layer of the corneoscleral limbus, represent essential components of the corneal epithelial stem cell niche, but, due to difficulties in their isolation and cultivation, their biological roles and potential for stem cell-based tissue engineering approaches have not been comprehensively studied. Here, we established a protocol for the efficient isolation and cultivation of pure populations of human limbal melanocytes, which could be expanded at high yield by using recombinant laminin (LN)-511-E8 as culture substrate. Co-cultivation of limbal melanocytes with limbal epithelial stem/progenitor cells on fibrin hydrogels pre-incubated with LN-511-E8 resulted in multilayered stratified epithelial constructs within ten days. By reproducing physiological cell–cell and cell–matrix interactions of the native niche environment, these biomimetic co-culture systems provide a promising experimental model for investigating the functional roles of melanocytes in the limbal stem cell niche and their suitability for developing advanced epithelial grafts for ocular surface surface reconstruction. [ABSTRACT FROM AUTHOR]

In recent years, the exploration and development of shale oil and gas reservoirs has become a hot topic in various countries around the world. The mechanical properties of shale are an important basis for evaluating the mining effect. Previous studies have shown that shale swells with water, which greatly effects its mechanical properties. Based on the analysis of shale composition, a clay mineral swelling test and 3D compression test were carried out to analyze the influence of clay minerals on the mechanism of shale swelling and softening in water. The results show that hydration of clay minerals results in interlayer and intergranular swelling. Furthermore, an expansion force will be exerted on the rock skeleton. The clay minerals expansion will cause a decrease in the uniaxial compressive strength, decrease in the elastic modulus, and increase in the Poisson's ratio, both in normal and parallel directions to the shale plate bedding. The brittleness index calculated based on the elastic modulus and Poisson's ratio values also decreases. This work is significant for further engineering development of shale reservoirs. [ABSTRACT FROM AUTHOR]

To find the genetic markers related to the antipsychotic-induced weight gain (AIWG), we analyzed associations among candidate gene single-nucleotide polymorphisms (SNPs) and quantitative traits of weight changes and lipid profiles in a Chinese Han population. A total of 339 schizophrenic patients, including 86 first-episode patients (FEPs), meeting the entry criteria were collected. All patients received atypical antipsychotic drug monotherapy and hospitalization and were followed for 12 weeks. Forty-three SNPs in 23 candidate genes were calculated for quantitative genetic association with AIWG, performed by PLINK. The TOX gene SNP rs11777927 (P = 0.009) and the ADIPOQ gene SNP rs182052 (P = 0.019) were associated with AIWG (in body mass index, BMI). In addition, the BDNF SNP rs6265 (P = 0.002), BDAF SNP rs11030104 SNP (P = 0.001), and ADIPOQ SNPs rs822396 (P = 0.003) were significantly associated with the change of waist-to-hip ratio (WHR) induced by atypical antipsychotics. These results were still significant after age and gender adjustments. These findings provide preliminary evidence supporting the role of TOX, ADIPOQ and BDNF in weight and WHR gain induced by atypical antipsychotics. [ABSTRACT FROM AUTHOR]

Inositol is closely related to the occurrence of neural tube defects (NTDs). Inositol 1, 3, 4-trisphosphate 5/6-kinase (ITPK1) gene encoded an essential regulatory enzyme ITPK1, which is involved in inositol metabolism and has a critical role in the development of neural tube and axial mesoderm. It had been reported that some polymorphisms of critical genes in inositol pathways, including ITPK1, were associated with NTDs in Chinese pregnant women; however, the association between fetus ITPK1 polymorphisms and NTDs had not been reported. In a high incidence of NTDs region of China, a case–control study was performed to evaluate the association between fetal ITPK1 polymorphisms and NTDs. The ITPK1 polymorphisms were genotyped by iPLEX® Gold assay. Inositol levels in fetus brain tissues were analyzed. Three genetic polymorphisms of fetus ITPK1's, including rs3818175, rs2295394, and rs4586354, were statistically associated with spina bifida (NTD subtypes). A higher risk of spina bifida was associated with genotype GG of rs3818175, genotype CC of rs4586354, and genotype TT of rs2295394 (OR = 2.66, 95% CI [1.17–6.05], P = 0.017; OR = 2.22, 95% CI [1.02–4.80], P = 0.041; and OR = 2.33, 95% CI [1.00–5.48], P = 0.047), when compared with the other wild-type genotypes CC, TT, and CC, respectively. Decreased brain inositol level was found in NTDs fetuses, compared to normal controls. Inositol levels were found to significantly decrease with rs2295394 (CC genotype), rs4586354 (TT genotype), and rs3818175 (GC genotype) (P < 0.05). The polymorphisms of fetus ITPK1 were associated with the incidence of NTDs and might be a genetic risk factor for spina bifida. [ABSTRACT FROM AUTHOR]

The time-averaged serum potassium was more comprehensive to reflect the all-time changes of serum potassium levels during peritoneal dialysis (PD). However, the association of fluctuation of time-averaged serum potassium level with long-time survival of PD patients remains unknown. In this retrospective study, we included 357 incident PD patients in 2 centers from January 1, 2007 to October 31, 2012 with follow-up through October 31, 2014. Our data demonstrated that it was the lower time-averaged serum potassium level rather than baseline of serum potassium level that was associated with high risk of death. Patients with higher standard deviation (SD) had significantly poorer all-cause (p = 0.016) and cardiovascular mortality (p = 0.041). Among the patients with time-averaged serum potassium levels below 4.0 mEq/L, a lower mean value was more important than its SD to predict death risk. In contrast, the patients with time-averaged serum potassium levels above 4.0 mEq/L, those with serum potassium SD < 0.54 mEq/L, exhibited a higher 3-year and 5-year survival rate for both all-cause and cardiovascular mortality compared to the control groups. Our data clearly suggested both time-averaged serum potassium and its fluctuation contributed disproportionately to the high death risk in PD patients. [ABSTRACT FROM AUTHOR]

Chemotherapeutic agents such as methotrexate (MTX), raltitrexed (RTX), 5-fluorouracil (5-FU), hydroxyurea (HU), and retinoic acid (RA), and valproic acid (VPA), an antiepileptic drug, all can cause malformations in the developing central nervous system (CNS), such as neural tube defects (NTDs). However, the common pathogenic mechanisms remain unclear. This study aimed to explore the mechanisms of NTDs caused by MTX, RTX, 5-FU, HU, RA, and VPA (MRFHRV), based on network pharmacology and molecular biology experiments. The MRFHRV targets were integrated with disease targets, to find the potential molecules related to MRFHRV-induced NTDs. Protein–protein interaction analysis and molecular docking were performed to analyze these common targets. Utilizing the kyoto encyclopedia of genes and genomes (KEGG) signaling pathways, we analyzed and searched the possible causative pathogenic mechanisms by crucial targets and the signaling pathway. Results showed that MRFHRV induced NTDs through several key targets (including TP53, MAPK1, HSP90AA1, ESR1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN) and multiple signaling pathways such as PI3K/Akt pathway, suggesting that abnormal proliferation and differentiation could be critical pathogenic contributors in NTDs induced by MRFHRV. These results were further validated by CCK8 assay in mouse embryonic stem cells and GFAP staining in embryonic brain tissue. This study indicated that chemotherapeutic and antiepileptic agents induced NTDs might through predicted targets TP53, MAPK1, GRB2, HDAC1, EGFR, PIK3CA, RXRA, and FYN and multiple signaling pathways. More caution was required for the clinical administration for women with childbearing potential and pregnant. [ABSTRACT FROM AUTHOR]

The synthesis of diterpenoid tanshinones, which are some of the main bioactive ingredients of Danshen (the roots of Salvia miltiorrhiza), begins with the plastidial methylerythritol 4-phosphate (MEP) pathway. 1-Deoxy-d-xylulose-5-phosphate synthase (DXS) catalyzes the first step of the MEP pathway and is considered to be a key rate-limiting enzyme. To confirm the function of DXS genes, in this study two isoforms of DXS (SmDXS1 and SmDXS2) were isolated by rapid amplification of DNA ends from leaves of S. miltiorrhiza. Bioinformatic analyzes indicated that two SmDXSs had high homology with other plant DXSs. Tissue expression pattern analysis revealed that SmDXS1 and SmDXS2 exhibited distinct expression patterns in S. miltiorrhiza. SmDXS1 was expressed in all analyzed tissues; the highest expression was observed in leaves, followed by stems, with weak expression in roots. In contrast, SmDXS2 transcripts were predominantly detected in roots, but very weakly. Subcellular localization analysis revealed that SmDXS1 and SmDXS2 were both localized in the chloroplast. Agrobacterium-mediated transformation was used for induction of transgenic hairy root lines and tanshinone yield was assessed by high-performance liquid chromatography. Compared with the control, overexpression of SmDXS1 and SmDXS2 significantly enhanced tanshinone accumulation in transgenic roots, whereas only down-regulation of SmDXS2 led to a significant decrease. Our results indicated that SmDXS2 was an important rate-limiting gene in the MEP pathway involved in tanshinone biosynthesis and could be an effective regulatory target for controlling tanshinone accumulation in S. miltiorrhiza hairy root cultures. [ABSTRACT FROM AUTHOR]

Brain-derived neurotrophic factor (BDNF) and glycolipid metabolism have been implicated in cognitive impairments and depression among Parkinson’s disease (PD). However, the role of sex differences in this relationship remains elusive. This study aimed to investigate the potential sex differences in the link between serum BDNF levels, glycolipid metabolism and cognitive performance among depressive PD patients. PD patients comprising 108 individuals with depression and 108 without depression were recruited for this study. Cognitive function was assessed using the Montreal Cognitive Assessment Beijing version (MOCA-BJ). The severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale (HAMD-17), while motor symptoms were evaluated using the Revised Hoehn and Yahr rating scale (H-Y) and the Unified Parkinson’s Disease Rating Scale Part III (UPDRS-III). Laboratory testing and enzyme-linked immunosorbent assay (ELISA) are used to measure serum levels of glycolipid metabolism and BDNF. Females showed superior performance in delayed recall (all p < 0.05), male PD patients exhibited higher scores in naming tasks compared to females in non-depression group. There was no sex differences in serum BDNF levels between depression and non-depression groups. Liner regression analysis indicated BDNF as an independent risk factor for language deficits in male PD patients with depression (p < 0.05), while cholesterol (CHOL) emerged as a cognitive influencing factor, particularly in delayed recall among male PD patients with depression (p < 0.05). Our study reveals extensive cognitive impairments in PD patients with depression. Moreover, BDNF and CHOL may contribute to the pathological mechanisms underlying cognitive deficits, particularly in male patients with depression. [ABSTRACT FROM AUTHOR]

Depressive symptoms and abnormal glycolipid metabolisms are common in patients with Parkinson's disease (PD), but their relationship has not been fully reported. It is not clear whether glycolipid impairments lead to poor cognitive and motor function, and aggravate depressive symptoms. Therefore, we aimed to explore the relationships between glycolipid variables, cognition, motor and depressive symptoms in PD patients cross-sectionally. Two hundred ten PD patients were recruited. Glycolipid parameters and Uric acid (UA) were measured. Depressive symptoms, cognitive function and motor symptoms were assessed using the Hamilton Depression Rating Scale-17 (HAMD-17), the Montreal Cognitive Assessment (MOCA) and the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III). Depressive PD patients had significantly worse motor symptoms and higher levels of fasting plasma glucose (FPG) than those in non-depressive patients (F = 24.145, P < 0.001). Further, logistic regression analysis indicated that UPDRS-III (OR = 1.039, 95% CI 1.019–1.057, P = 0.044), FPG (OR = 1.447, 95% CI 1.050–1.994, P = 0.024) were independently associated with depression. In PD patients without depression, UA (β = − 0.068, t = − 2.913, P = 0.005) and cholesterol (CHOL) (β = − 3.941, t = − 2.518, P = 0.014) were independent predictors of the UPDRS-III score; in addition, UPDRS-III score was negatively associated with MOCA score (β = − 0.092, t = − 2.791, P = 0.007). FPG levels and motor symptoms were related to depressive symptoms in PD patients. Further, in non-depressive PD patients, UA and CHOL showed putative biomarkers of motor symptoms. [ABSTRACT FROM AUTHOR]

Bone marrow mesenchymal stem cells (BMSCs) have been shown to promote stroke recovery, however, the underlying mechanisms are not well understood. In this study naïve rats were intravenously injected with syngeneic BMSCs to screen for potential differences in brain metabolite spectrum versus vehicle-treated controls by capillary electrophoresis-mass spectrometry. A total of 65 metabolites were significantly changed after BMSC treatment. Among them, 5-oxoproline, an intermediate in the biosynthesis of the endogenous glutathione (GSH), was increased. To confirm the obtained results and investigate the metabolic pathways, BMSCs were injected into rats 24 h after middle cerebral artery occlusion (MCAO). Rats receiving vehicle solution and sham-operated animals served as controls. High performance liquid chromatography, reverse transcription-quantitative polymerase chain reaction, and Western blotting revealed that intravenous BMSC application increased the levels of 5-oxoproline and GSH in MCAO rats, as well as the expression of key enzymes involved in GSH synthesis including, gamma-glutamylcyclotransferase and gamma-glutamylcysteine ligase. Subsequent clinical investigation confirmed that acute ischemic stroke patients had higher plasma 5-oxoproline and GSH levels than age- and sex-matched non-stroke controls. The optimal cutoff value for 5-oxoproline diagnosing acute ischemic stroke (≤ 7d) was 3.127 µg/mL (sensitivity, 63.4 %; specificity, 81.2 %) determined by receiver characteristic operator curve. The area under the curve was 0.782 (95 % confidence interval: 0.718–0.845). Our findings indicate that BMSCs play a protective role in ischemic stroke through upregulation of GSH and 5-oxoproline is a potential biomarker for acute ischemic stroke. Ischemic stroke causes oxidative stress and induction of endogenous, glutathione-dependent anti-oxidative mechanisms. 5-oxoproline, an important metabolite in glutathione biosynthesis, could serve as a biomarker of acute ischemic stroke. Moreover, intravenous bone marrow mesenchymal stem cell (BMSC) treatment after experimental stroke upregulates the expression of key enzymes involved in glutathione synthesis, which results in better antioxidative defense and improved stroke outcome. [ABSTRACT FROM AUTHOR]

Hydro-mechanical continuously variable transmission is mainly composed of a pump-motor hydraulic transmission subsystem, a mechanical transmission subsystem, a power shunt device, and a power coupling device. Among them, the pump-motor hydraulic transmission subsystem, as a speed control element, has a serious effect on the speed control performance of hydro-mechanical continuously variable transmission. However, the poor controllability and stabilization of the output speed during variable speed input and load disturbance greatly limit the further development of the speed control performance of hydro-mechanical continuously variable transmission. To address these problems, this paper proposes an adaptive speed tracking compound control strategy that is based on neural network model reference adaptive control, seeker optimization algorithm, fuzzy control algorithm, and the PID controller. Simulation and testing results show that the control effect of the proposed strategy is more obvious than that of the traditional speed control strategies based on particle swarm optimization algorithm-PID and genetic algorithm-PID, and its applicability under the complicated working conditions is enhanced. This study can serve as a basis for the design and practical application of the pump-motor hydraulic transmission subsystem of hydro-mechanical continuously variable transmission in engineering and agricultural machinery. [ABSTRACT FROM AUTHOR]

Background: While pain freedom at 2 h is a key primary outcome for current trials for acute treatment of migraine, the relationship between the degree of head pain and other efficacy measures at 2 h has rarely been explored. Following lasmiditan treatment of a migraine attack with moderate or severe head pain, we contrast those who achieve pain freedom with those who achieve mild pain but not pain freedom 2 h post dosing. Methods: Patient-level data were pooled across studies and treatment arms from two Phase 3 trials comparing lasmiditan and placebo, SAMURAI and SPARTAN. This post hoc analysis assessed freedom from the most bothersome symptom (MBS), freedom from migraine-related functional disability (disability), and improved patient global impression of change (PGIC) in patients who achieved 2 h pain freedom compared to those who experienced 2 h mild pain. Mild pain differs from pain relief which is defined as either mild pain or pain freedom. Results: Patients who achieved 2 h pain freedom (N = 913), in comparison with those with 2 h mild pain (N = 864), were significantly more likely to experience MBS freedom (91.9% vs. 44.9%), disability freedom (87.1% and 13.4%), and improved PGIC (86.5% and 31.5%) (p < 0.001 for all combinations). In addition, more patients who were pain free experienced both 2 h MBS freedom and 2 h functional disability freedom (83.6%) compared to those with mild pain (10.8%; p < 0.001). The proportion of patients with pain freedom who did not achieve either MBS or disability freedom (4.6%) was lower than in patients with mild pain (52.4%). Lastly, 55.2% of patients experienced mild pain before disability freedom compared to 72.1% who experienced pain freedom and disability freedom at the same time. Conclusions: This study demonstrated that, at 2 h post treatment, patients who were pain free were more likely to achieve other outcomes including freedom from their MBS, freedom from migraine-related functional disability, and improved PGIC compared to those with mild pain, confirming that 2 h pain freedom is more robustly associated with other clinical outcomes than the 2 h mild pain endpoint. Trial Registration: SAMURAI (NCT02439320); SPARTAN (NCT02605174). [ABSTRACT FROM AUTHOR]

Guanine-rich DNA sequences commonly form helical quadruplex structures via Hoogsteen hydrogen bonds. The aggregation behavior of the nanoparticles, which are functionalized with four-guanine-terminated 27-base sequences at a nanoparticle-to-DNA ratio of 1:60, is investigated. To some extent, the guanine-quadruplex structures between the gold nanoparticles (GNPs) promote nanoparticle aggregation. However, the coordination site of the metal ion on the nanoparticle surface is partially passivated: the stability of guanine-rich DNA-GNPs is slightly lower than that of the usual DNA-GNPs, and the metal-ion specificity of nanoparticle assembly is substantially decreased. Thus, a mechanism for the aggregation of guanine-rich sequence-modified GNPs is proposed. It is possible to obtain a stable guanine-rich sequence-functionalized nanoparticle solution at high ionic strength by regulating guanine-rich DNA sequences. The controllability of guanine-rich sequence-modified nanoparticles makes the secondary structure of DNA a potentially useful candidate for DNA analysis and disease diagnostics. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

An optical-fiber sensor for colchicine has been fabricated. It is based on the use of the fluorescent dye N-vinylcarbazole, which contains a vinyl unit making it photo-copolymerizable in the presence of a monomer, 1,2-cyclohexanediol diacrylate, on a quartz surface of an optode slide. Prior to the photo-polymerization process the quartz surface was modified with γ-(methacryloxy)propyl trimethoxysilane to introduce vinyl units. A dye-incorporating optode membrane tightly immobilized on the quartz surface was prepared in this way. The spectral characteristics of the optode for sensing colchicines were evaluated, and the response mechanism was discussed. The optode membrane has a relatively long lifetime and short response and recovering time. The linear range of determining colchicine is from 1.0×10-6 to 4.0×10-3 mol L-1. The sensor was applied to determine the colchicine content in pharmaceutical tablets the results of which agreed with those obtained by the pharmacopoeia method. [ABSTRACT FROM AUTHOR]

Radiation therapy is a standard and effective non-surgical treatment for primary brain tumors and metastases. However, this strategy inevitably results in damage of normal brain tissue, causing severe complications, especially the late-delayed cognitive impairment. Due to the multifactorial and complex pathological effects of radiation, there is a lack of effective preventative and restorative treatments for the irradiated brain. Stem-cell therapy has held considerable promise for decades in the treatment of central nervous system (CNS) disorders because of its unique capacity for tissue repair and functional integrity. Currently, there is growing interest in using stem cells as a novel option to attenuate the adverse effects of irradiation. In the present review, we discuss recent studies evaluating stem-cell therapies for the irradiated brain and their therapeutic effects on ameliorating radiation-related brain injury as well as their potential challenges in clinical applications. We discuss these works in context of the pathogenesis of radiation-induced injury to CNS tissue in an attempt to elucidate the potential mechanisms of engrafted stem cells to reverse radiation-induced degenerative processes. [ABSTRACT FROM AUTHOR]

Background: Migraine is recognized as the second leading cause of disability globally. Lasmiditan is a novel, selective serotonin 5-HT1F receptor agonist developed for acute treatment of migraine. Here we analyzed effects of lasmiditan on migraine disability assessed with the Migraine Disability Assessment (MIDAS) scale for interim data from a long-term safety study. Methods: Completers of two single-attack parent studies were offered participation in the 1 year GLADIATOR study, that randomized participants to treatment with lasmiditan 100 mg or 200 mg taken as needed for migraine attacks of at least moderate severity. Changes in MIDAS were modeled using a mixed model repeated measures analysis. Results: The sample included 1978 patients who received ≥1 lasmiditan dose and were followed for a median of 288 days. Baseline mean MIDAS scores for the lasmiditan 100-mg and 200-mg groups were 29.4 and 28.9, respectively, indicating severe migraine-related disability. Relative to baseline, MIDAS total scores were significantly lower at 3, 6, 9, and 12 months for both dose groups. At 12 months, changes in MIDAS scores were − 12.5 and − 12.2 for lasmiditan 100 mg and 200 mg, respectively, with 49% and 53% of patients, respectively, achieving at least a 50% decrease in MIDAS total score. Statistically significant improvements were also seen for work and/or school absenteeism and presenteeism, monthly headache days, and mean headache pain intensity at all time points up to 1 year. Findings for patients who completed all visits versus those dropping out early were similar. Responses were generally similar for the lasmiditan 100 mg or 200 mg doses, between subgroups defined based on the number of baseline monthly migraine attacks (≤5 vs. >5), and also between subgroups defined by pain-free response (yes/no) during initial attacks. Conclusions: Long-term treatment with lasmiditan was associated with significant reductions in migraine-related disability, including both work or school absenteeism and presenteeism. The similarity of responses in completers and those who dropped out suggests that selective attrition does not account for the improvements. Benefits were significant at 3 months and maintained through 12 months. Trial registration: clinicaltrials.govNCT02565186; first posted October 1, 2015. [ABSTRACT FROM AUTHOR]

As one of the vital tectonic units of the Wulian Metamorphic Core Complex (MCC), the Wulian detachment fault zone (WDFZ), which developed in the Jiaodong peninsula, separates the lower plate of the ultrahigh pressure (UHP) metamorphic rocks in the Sulu orogenic belt from the upper plate of the early Cretaceous Zhucheng basin and the basin basement. The fault zone generally strikes NNE with a dip in the west along the southern portion of the MCC and strikes NE with a dip in the WNW along the northern portion. The fault zone displays a wavy-tile-shaped extension on the plane, principally composed of the fault breccias and mylonite and transits downward to the mylonitic gneiss As a whole, the detachment fault zone shows a top-to-west or a WNW extension. By calculating the harmonic mean, we obtain a Flynn index K of 0.98–2.0, and the mean value is approximately 1.35 in the fault zone. According to the polar Mohr construction, the extensional crenulation cleavage, the RS/θ, and the quartz C-axial fabric methods, we acquire mean kinematic vorticity values of 0.64–0.97, 0.76–0.93, 0.6–0.92, and 0.63–0.98 with mean values of 0.83, 0.80, 0.78 and 0.86, respectively, for mylonite and promylonite. The strain measurement results and the kinematic vorticity values indicate that the WDFZ is a normal ductile shear zone developed in the extensional setting. The kinematic track shows that the kinematic vorticity value decreases gradually from the NW to the SE as a whole. A simple shear dominates in the middle and upper parts of the shear zone, which is reflected by a higher vorticity value (>0.75, up to 0.98), a low thinning rate and a lower K value. In contrast, toward the footwall, the pure shear is increased significantly, showing a lower vorticity value (<0.70, low to 0.64), a relatively high thinning rate and a higher K value. Combined with the geotectonic background, the development and evolution of the WDFZ should respond to lithospheric thinning and the destruction of the North China Craton (NCC). As a result, the WDFZ can be defined as a thinning normal shear zone developed in the extension tectonic setting and the combined result of the simple shear caused by the crust extension and pure shear led by the rapid uplift of the footwall and magmatic upwelling. [ABSTRACT FROM AUTHOR]

Background: Dehydration is associated with a higher risk of poor outcome and venous thromboembolism in acute ischemic stroke patients. However, the relationship between dehydration and prognosis in patients with cerebral venous thrombosis (CVT) has not yet been investigated.Methods: Consecutive CVT patients at the First Affiliated Hospital of Zhengzhou University were retrospectively identified from November 2011 through January 2017. Dehydration was evaluated by blood urea/creatinine (U/Cr) ratio > 80. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3-6. Factors such as age, sex, coma, intracerebral hemorrhage, and straight sinus and/or deep CVT involved were adjusted to assess the relationship between dehydration, and prognosis at discharge and long-term follow-up in CVT patients.Results: A total of 220 CVT patients were included, and 85 patients (38.64%) were dehydrated. Multivariate logistic regression analysis indicated that patients with dehydration had a higher risk of mRS of 3-6 at discharge (adjusted odds ratio [OR] 3.629, 95% confidence intervals [CI] 1.526-8.633, P = 0.004) and long-term outcome (adjusted OR 3.831, 95% CI 1.597-9.190, P = 0.003). Subgroup analysis stratified by potential factors that might be associated with dehydration, such as infection, vomiting, pregnancy, and/or postpartum, showed similar results. Multivariate Cox regression analysis further demonstrated that dehydration was associated with higher mortality (adjusted hazard ratio [HR] = 2.301, 95% CI 1.025-5.166, P = 0.043).Conclusions: The present findings indicate that dehydration is an independent predictor for short-term and long-term unfavorable functional outcome in patients with CVT. [ABSTRACT FROM AUTHOR]

Background: Anemia is associated with unfavorable functional outcome in ischemic and hemorrhagic stroke. However, the relationship between anemia and prognosis in patients with cerebral venous thrombosis (CVT) has not been studied.Methods: Consecutive CVT patients were retrospectively identified from November 2011, through January 2017. Anemia was defined according to the World Health Organization criteria (non-pregnant female hemoglobin level < 120 g/L, pregnant female < 110 g/L and male < 130 g/L), which was further classified as mild, moderate, and severe anemia according to hemoglobin concentration, and as microcytic, normocytic, and macrocytic anemia according to mean corpuscular volume. Unfavorable outcome was defined as modified Rankin Scale (mRS) of 3-6. Factors such as age, sex, coma, malignancy, intracerebral hemorrhage, and straight sinus and/or deep CVT involved, premorbid mRS were adjusted to evaluate the relationship between anemia and prognosis in CVT patients.Results: A total of 238 CVT patients were included, among whom 73 patients (30.67%) were diagnosed with anemia. Multivariate logistic regression analysis showed that patients with anemia had a higher risk of mRS of 3-6 (OR = 3.62; 95% CI, 1.45-9.01; P = 0.006) and mortality (OR = 5.46; 95% CI, 1.90-15.70; P = 0.002). Subgroup analysis showed that severe anemia was independently associated with mRS of 3-6 (OR = 8.80; 95% CI, 1.90-40.81; P = 0.005) and mortality (OR = 9.82; 95% CI, 1.81-53.25; P = 0.010). Similarly, microcytic anemia increased the risk of mRS of 3-6 (OR = 4.64; 95% CI, 1.48-14.52; P = 0.008) and mortality (OR = 9.68; 95% CI, 2.61-35.91; P = 0.001). In addition, our study also revealed that lower hemoglobin level, evaluated as a continuous variable, was inversely associated with mRS of 3-6 (OR = 0.98; 95% CI, 0.96-0.99; P = 0.007) and mortality (OR = 0.97; 95% CI, 0.95-0.99; P = 0.005).Conclusions: Anemia was a significant and independent predictor of unfavorable functional outcome in patients with CVT. [ABSTRACT FROM AUTHOR]

The neural cell adhesion molecule (NCAM) plays a pivotal role in the development and maintenance of the nervous system via homophilic (NCAM-NCAM) and heterophilic (NCAM-other molecules) interactions. Many synthetic peptides have been engineered to mimic these interactions and induce NCAM-downstream signaling pathways. Such NCAM mimetics have displayed neuritogenic and neuroprotective properties, as well as synaptic modulation in vitro and in vivo. Furthermore, they have been used successfully in preclinical studies to treat neurological disorders including stroke, traumatic brain injury and Alzheimer’s disease. This review focuses on recent progress in the development of NCAM mimetic peptides, in particular, on establishing C3, plannexin, and FGL as therapeutic candidates for neurological disorders. [ABSTRACT FROM AUTHOR]

INTRODUCTION: To assess and compare per-day anti-diabetic medication costs for Chinese type-2 diabetes mellitus (T2DM) insulin-naïve patients between those who initiated premixed insulin analogs ("premixed group") and those who initiated long-acting insulin analogs ("long-acting group"). METHODS: Data were obtained from an electronic medical record database between 2010.01.01 and 2015.06.30 covering medical encounter records from all general hospitals in a district from Shanghai, China. Insulin-naïve T2DM patients who were aged ≥ 18 years, treated with an oral anti-diabetic drug (OAD) only during the baseline period (3 months prior to insulin initiation), and initiated premixed or long-acting insulin analogs were included. Patients were followed until index insulin discontinuation or 12 months after initiation, whichever came first. The t test and generalized linear models adjusting for propensity score (PS) (including baseline demographics, number of OAD classes, comorbidities, costs, and healthcare resource utilization) were used to examine the differences between the two insulin groups. RESULTS: A total of 570 and 185 patients were identified for the premixed and long-acting groups, with mean (SD) ages of 63.0 (12.8) and 61.1 (11.9) (P = 0.08) and male proportions of 47.4% and 51.4% (P = 0.35), respectively. During the baseline period, 19.3% of the premixed users had T2DM-related hospitalizations, while the rate was 12.4% in the long-acting group (P = 0.03). The mean number of T2DM-related outpatient visits was 0.98 and 1.23 for the premixed and long-acting groups, respectively (P = 0.07). During the follow-up period, the per-day insulin dose averaged 31.7 and 15.3 international units (IU) for the premixed and long-acting groups, respectively. Compared with the patients on premixed insulin, the mean per-day cost for patients on long-acting insulin was 37.3% higher [15.3 vs 11.2 Chinese yuan (RMB); mean difference (MD) (95% CI): 4.2 (3.2, 5.1)] for the overall anti-diabetes medication, 81.3% higher [3.3 vs 1.8 RMB; MD (95% CI): 1.5 (0.8, 2.2)] for OAD, and 28.6% higher [12.0 vs 9.3 RMB; MD (95% CI): 2.7 (2.1, 3.3)] for insulin. The results were consistent after adjusting for the PS. CONCLUSION: Among Chinese T2DM insulin-naïve patients, those who initiated premixed insulin had a lower per-day antidiabetic medication cost than those who initiated long-acting insulin. [ABSTRACT FROM AUTHOR]

A combined shape control procedure with optimality criterion and integrated structural electromagnetic concept for cable mesh reflector antennas is presented in this study. Using the optimality criterion, the shape control algorithm drives the distorted surface towards the ideal shape. The optimality criterion is implemented by pseudo inverse of sensitivity matrix of surface nodal displacements with respect to cable member dimensions to accelerate the iterative convergence. The following integrated structural electromagnetic design is performed to make good electromagnetic performance by a sequential quadratic programming optimization model. A distorted offset cable mesh reflector antenna is employed to show its effectiveness. [ABSTRACT FROM AUTHOR]

Motivated by previous experiences in identifying active reaction zones on plant pheophytins of the so-called semi- derivative morphology, for the catalytic decomposition of hydrogen gas, this current research aimed for similarly suggestive sites within DNA base pairs which exist in all living matters. Verified by the 1st-principle quantum mechanical simulations and subsequent wet and dry hydrogen fuel cell experiments, the feasibility of room-temperature DNA-catalyzed hydrogen oxidation reaction was unambiguously established. This implies that very low-cost DNA-catalyzed fuel cells, which contain no expensive, CO-sensitive platinum on the negative electrode side, can be put to work under room condition and thus might be practically available in every household in the very near future. [ABSTRACT FROM AUTHOR]

Ebola virus disease (EVD) has erupted many times in some zones since it was first found in 1976. The 2014 EVD outbreak in West Africa is the largest ever, which has caused a large number of deaths and the most serious country is Liberia during the outbreak period. Based on the data released by World Health Organization and the actual transmission situations, we investigate the impact of different transmission routes on the EVD outbreak in Liberia and estimate the basic reproduction number R0 = 2.012 in the absence of effective control measures. Through sensitivity and uncertainty analysis, we reveal that the transmission coefficients of suspected and probable cases have stronger correlations on the basic reproduction number. Furthermore, we study the influence of control measures (isolation and safe burial measures) on EVD outbreak. It is found that if combined control measures are taken, the basic reproduction number will be less than one and thus EVD in Liberia may be well contained. The obtained results may provide new guidance to prevent and control the spread of disease. [ABSTRACT FROM AUTHOR]

With the development of mobile networks, propagation characteristics and defense mechanism of the virus have attracted increasing research attention. But current researches are mainly concerned with static network topology or community structure and some studies focus on characteristics of virus and malware. Little attention is paid to the influence of dynamic changes of network topology to virus propagation. Meanwhile, many studies focus on the threshold rate of the infection (or the immunization rate) for virus outbreak. In this paper, we present a new way to assess and restrain virus propagation by proposing the concepts of propagation power and propagation structure. Three basic propagation structures are presented through which the infection risk can be quantified, and a framework is proposed to assess the impact of virus propagation in different network structures. The relationship between the speed of virus propagation and network structure is also explored. An algorithm is designed to assess the propagation power in a dynamic network with no need to redetect the community under the dynamic network which may significantly improve the efficiency of assessment in a large-scale dynamic network. This study offers a feasible approach for quantifying the risk of virus infection in the network community which is valuable for designing and optimizing the virus defense systems. [ABSTRACT FROM AUTHOR]

Sorting nexin 27 (SNX27), a brain-enriched PDZ domain protein, regulates endocytic sorting and trafficking. Here we show that Snx27−/− mice have severe neuronal deficits in the hippocampus and cortex. Although Snx27+/− mice have grossly normal neuroanatomy, we found defects in synaptic function, learning and memory and a reduction in the amounts of ionotropic glutamate receptors (NMDA and AMPA receptors) in these mice. SNX27 interacts with these receptors through its PDZ domain, regulating their recycling to the plasma membrane. We demonstrate a concomitant reduced expression of SNX27 and CCAAT/enhancer binding protein β (C/EBPβ) in Down's syndrome brains and identify C/EBPβ as a transcription factor for SNX27. Down's syndrome causes overexpression of miR-155, a chromosome 21-encoded microRNA that negatively regulates C/EBPβ, thereby reducing SNX27 expression and resulting in synaptic dysfunction. Upregulating SNX27 in the hippocampus of Down's syndrome mice rescues synaptic and cognitive deficits. Our identification of the role of SNX27 in synaptic function establishes a new molecular mechanism of Down's syndrome pathogenesis. [ABSTRACT FROM AUTHOR]

The key pathological feature of Parkinson's disease (PD) is selective degeneration of the neuromelanin (NM)-pigmented dopaminergic neurons in the substantia nigra (SN). NM, like other risk factors, such as oxidative stress (OS) and α-synuclein (α-syn), is involved in the pathogenesis of PD. But whether or not NM synergizes with α-syn or OS in the pathogenesis of PD remains unexplored. In the present study, we examined the effects of NM on cellular viability, apoptosis and free radical production in α-syn over-expressing human neuroblastoma cell line (SK-N-SH) in the presence or absence of the oxidizer Fenton's Reagent (FR). We showed that NM synergized with FR in suppressing cell viability, and in inducing apoptosis and hydroxyl radical production in all SK-N-SH cell lines. α-Syn over-expressing cells exhibited more pronounced effect, especially the A53T mutation. Our findings suggest that NM synergizes with both OS and α-syn in conferring dopaminergic vulnerability, adding to our understanding of the pathogenesis of PD. [ABSTRACT FROM AUTHOR]