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Some previous researches raised the possibility of a novel acute myeloid leukemia (AML) entity presenting cup-like cytomorphology with mutations of both FLT3 and NPM1 or one of them. However, the clinical implications of this subtype remain unknown. We describe a 63-year-old patient belonging to this distinct AML subtype, who presented similar features of acute promyelocytic leukemia (APL) including nuclear morphology, negative for CD34 and HLA-DR, and abnormal coagulation. He had no response to both arsenic trioxide and CAG regimen (cytarabine, aclarubicin, and G-CSF). Given that the patient carried the FLT3-ITD mutation, we switched to a pilot treatment of FLT3 inhibitor sorafenib combined with low-dose cytarabine (LDAC). To date, the patient achieved durable complete remission over 58 months. These findings suggest that AML with cup-like blasts and FLT3-ITD and NPM1 mutations mimic APL, and the prognosis of this subtype may be improved by sorafenib combined with LDAC.

Numerous studies have shown that over-nutritional obesity may lead to pre-diabetes, type 2 diabetes and cognitive decline. As the degree of metabolic disorders increases, the cognitive decline is getting worse. However, the cellular events that cause this cognitive dysfunction is yet to be clarified. We used a high-fat diet (HFD) consumption-induced obesity mouse model to test the effects of metformin on the hippocampal neurogenesis and learning and memory abilities of obese mice. 5-Bromo-2'-deoxyuridine (BrdU) labelling and retrovirus labeling were applied to detect hippocampal newborn neurons. Behavioral experiments were used to detect learning and memory abilities of mice. 16S rRNA gene sequencing was performed to detect the composition of gut microbiota. The positron emission tomography (PET) was conducted to detect the energy metabolism activity of different mouse brain regions. Our results reveal that metformin restores the impairment of neurogenesis in the dentate gyrus and finally prevents the cognitive decline of the obese mice. Moreover, the therapeutic effects of metformin are achieved by regulating the composition of gut microbiota of mice, which may inhibit microglia activation and neuroinflammation in the brain of obese mice. This study suggests that metformin may be taken as a promising candidate for the intervention of cognitive decline related to imbalance of gut microbiota caused by obesity.

Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders characterized by impairments activities without efficient pharmacological therapies in social interaction, speech and stereotypic patterns. Clinical studies have shown the efficacy of acupuncture as an alternative therapy for autism. The effectiveness of acupuncture as an alternative treatment for autism has been demonstrated through clinical trials. However, the molecular mechanisms that underlie these effects remain unclear. Due to its profound pro-social, anxiolytic, stress management effects, and its potential use for the treatment of psychiatric disorders associated with altered socioemotional competence, oxytocin (OT) released from the hypothalamus has attracted considerable interest. In the past decade, a number of clinical and animal studies have shown that OT administration effectively reduces core symptoms of ASD, especially social behavior deficits. Recently, the endocannabinoid system has emerged as a promising target for the treatment of autism. OT was found to facilitate the endocannabinoid-mediated social reward processes in the nucleus accumbens of the mouse brain. Furthermore, serotonin and dopamine are involved in the reward response mediated by OT. In view of these findings, we conclude that acupuncture may produce therapeutic effects on autism by triggering the hypothalamic oxytocin system, which in turn activates the release of neurotransmitters such as endocannabinoids, dopamine and serotonin. This would be a valuable guide for further research on the mechanism of treatment of autism with acupuncture.

Titanium alloys are widely used in the aerospace industry due to their superior properties such as high strength and low density. As a new titanium alloy with higher strength and lower heat conductivity, titanium alloy TC21 is very difficult to cut and the cutting mechanism of this alloy needs to be investigated deeply. In the paper, to observe the cutting phenomenon in the turning process of TC21 alloy, a series of turning experiments have been performed to investigate the turning process of TC21 alloy. Further, the influence of some important turning parameters (cutting speed, feed speed, depth of cut and rake angle) on cutting force and chip morphology is well analyzed through the experiments. In addition, a 3D finite element model for turning was established using the software ABAQUS for helping to analyze the turning process of TC21. Through simulation, cutting force, chip formation and temperature distribution of TC21 alloy in the turning process have been achieved. At the same time, simulated cutting forces and chip morphology were compared with the results of experiment. The results of experiments showed that the chip of TC21 alloy in turning process is serrated and the rake angle of tool has the obvious effect on the chip morphology.

The major risk factor for kidney stone disease is idiopathic hypercalciuria. Recent evidence implicates a role for defective calcium reabsorption in the renal proximal tubule. We hypothesized that claudin-2, a paracellular cation channel protein, mediates proximal tubule calcium reabsorption. We found that claudin-2–null mice have hypercalciuria due to a primary defect in renal tubule calcium transport and papillary nephrocalcinosis that resembles the intratubular plugs in kidney stone formers. Our findings suggest that a proximal tubule defect in calcium reabsorption predisposes to papillary calcification, providing support for the vas washdown hypothesis. Claudin-2–null mice were also found to have increased net intestinal calcium absorption, but reduced paracellular calcium permeability in the colon, suggesting that this was due to reduced intestinal calcium secretion. Common genetic variants in the claudin-2 gene were associated with decreased tissue expression of claudin-2 and increased risk of kidney stones in 2 large population-based studies. Finally, we describe a family in which males with a rare missense variant in claudin-2 have marked hypercalciuria and kidney stone disease. Our findings indicate that claudin-2 is a key regulator of calcium excretion and a potential target for therapies to prevent kidney stones.

Pitch length and surface braiding angle are two important parameters of braided composite preforms. In this paper, a method based on Faster R-CNN is proposed to measure the two parameters. First, after image acquisition, a fabric image database including initial cropped images, augmented images, and target images is established. Then, the target images are classified into four categories according to the gray change characteristics. Third, a Faster R-CNN fabric detection model is trained on the fabric image database. Fourth, targets are detected by the trained network, and corners are detected based on the detected targets. Finally, pitch lengths and surface braiding angles are measured based on the detected corners. Experimental results show that the proposed method achieves the automatic measurement of pitch lengths and surface braiding angles of 2D and 3D braided composite preforms with high accuracy.

Background Controversy exists around the locoregional management of the primary tumor for breast cancer associated with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM) due to the rarity of the disease and limited available data. This study aimed to compare outcomes of patients in the Surveillance, Epidemiology, and End Results (SEER) database with sISLM who underwent surgical resection and radiation of the primary tumor with those who did not. Methods This population-based retrospective study included breast cancer patients with sISLM without distant metastases from 2004 to 2016 in the SEER database. In this study, patients had been stratified by operative management, and propensity score matching (PSM) had been successfully applied. Results A total of 1172 breast cancer patients with sISLM were included in the study: 863 (73.6%) of patients underwent the primary tumor resection, and 309 (26.4%) patients did not undergo surgery. The median survival time in the surgery group was longer compared to the nonsurgery group in the overall cohort and the PSM cohort. We concluded that the primary tumor resection was associated with improved survival. Subgroup analysis further demonstrated that local surgery was not inferior to radical surgery. Conclusion For selected breast cancer patients with sISLM, surgery is a promising local intervention which may improve the survival.

Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder and characterized by early childhood-onset impairments in social interaction and communication, restricted and repetitive patterns of behavior or interests. So far there is no effective treatment for ASD, and the pathogenesis of ASD remains unclear. Genetic and epigenetic factors have been considered to be the main cause of ASD. It is known that endocannabinoid and its receptors are widely distributed in the central nervous system, and provide a positive and irreversible change toward a more physiological neurodevelopment. Recently, the endocannabinoid system (ECS) has been found to participate in the regulation of social reward behavior, which has attracted considerable attention from neuroscientists and neurologists. Both animal models and clinical studies have shown that the ECS is a potential target for the treatment of autism, but the mechanism is still unknown. In the brain, microglia express a complete ECS signaling system. Studies also have shown that modulating ECS signaling can regulate the functions of microglia. By comprehensively reviewing previous studies and combining with our recent work, this review addresses the effects of targeting ECS on microglia, and how this can contribute to maintain the positivity of the central nervous system, and thus improve the symptoms of autism. This will provide insights for revealing the mechanism and developing new treatment strategies for autism.

This paper shares our work on building a machine learning system to categorize transactions for Intuit's QuickBooks product. Transaction categorization is challenging due to the complexity of accounting, the need for personalization, and the diversity of customers. We have broken down this monolithic problem into smaller pieces based on customers' life-cycle stages, and tailored solutions to address customer pain-points for each. Modern machine learning technologies such as deep neural networks, transfer learning, and few-shot learning are adopted to enable accurate transaction categorization. Furthermore our system learns user actions in real-time to provide relevant and in-time category recommendations. This in-session learning capability reduces user workload, improves customer experience, and helps to cultivate confidence.

This paper aims to address the problem of oriented object detection under the complex background of remote sensing images. To this end, we propose a one-stage object detection method with feature fusion structure, and modify the loss function to enhance the detection of small objects. More specifically, on the basis of the end-to-end one-stage object detection model RetinaNet, the method of gliding the vertices of the horizontal bounding box is used to describe an oriented object. In order to obtain multi-scale context information, we design a feature fusion module. Besides, we propose a novel area-weighted loss function to pay more attention to small objects. Experimental results conducted on the DOTA dataset demonstrate that the proposed framework outperforms several state-of-the-art baselines.

Aiming at the concavity defects in the cross-wedge rolling (CWR) process, one new rolling method named as the twice closed–open joint CWR was presented to improve the use ratio of material in CWR of the axle parts. The new rolling method included three stages: the first closed rolling, the second closed rolling and the last open rolling. To investigate the flow of material in this rolling process, one 3D finite element model (FEM) of the twice closed–open joint CWR was established. The CWR process of one pump spindle part was simulated using the established 3D FEM. The formation, the flow law of metal materials and concavity defects of end were studied. In addition, the CWR experiments were carried out. The results of simulation agreed with the results of tests well. The results proved that the new method can decrease the extent of concavity and improve the material use ratio.

Fetal growth has been demonstrated to be an important predictor of perinatal and postnatal health. Although the effects of maternal exposure to air pollution during pregnancy on fetal growth have been investigated using ultrasound in many previous studies, the results were inconsistent and disputable. We aimed to qualitatively and quantitatively investigate the associations of air pollution exposure during different periods of pregnancy with fetal growth and anthropometric measurements at birth. We searched for all studies investigating the associations of air pollution exposure during pregnancy with fetal growth and birth anthropometric measurements in English and Chinese databases published before July 31, 2017. A random-effects model was employed in the meta-analysis to estimate the pooled effects of each 10 μg/m3 increment in air pollutant exposure. The ACROBAT-NRSI tool was applied to assess the quality of each included study, and the GRADE tool was employed to assess the overall quality of the meta-analysis. Maternal PM2.5 exposure (10 μg/m3) during the entire pregnancy was negatively associated with head circumference at birth (β = − 0.30 cm, 95% CI − 0.49, − 0.10), and NO2 exposure during the entire pregnancy was significantly linked to shorter length at birth (β = − 0.03 cm, 95% CI − 0.05, − 0.02). Maternal exposure to higher NO2 and PM2.5 during pregnancy may impair neonatal head circumference and length development, respectively. More studies are needed to confirm the effects of NO2 and PM2.5 and to identify the sources and major toxic components of PMs.

Magnetic fluid is a novel magnetorheological (MR) intelligent material consisting of magnetic particles, non-magnetic matrix, and additive agents. After applying the external magnetic field, magnetic particles will interact with each other due to the magnetic dipolar forces. The viscosity and yield stress of magnetic fluid could increase several orders of magnitude in milliseconds, which is called the MR effect. The controllable and reversible property makes magnetic fluid widely applied in drug targeting delivery, magnetic thermal therapy, commercial dampers, and polishing etc. In order to comprehend the mechanical behaviors of magnetic fluid, researchers developed several theoretical models for different flow conditions. However, due to the extensive calculation, theoretical models are only applicable for some special problems, such as 2-dimensional and axial symmetry. In recent years, with the development of computer performance, simulation has become an important method to investigate the MR mechanism of magnetic fluid. This paper reviews the recent progress in the theory and simulation of magnetic fluid. Firstly, theoretical models of magnetic fluid under shear mode, squeeze mode, and valve mode are introduced. Secondly, the existing simulation methods for magnetic fluid, such as molecular dynamics, particle-level dynamic simulation, and finite element method, are illustrated. The validity of the methods and their merits and drawbacks are discussed. Then, the research progress of the simulation of magnetic fluid is summarized from 3 aspects: Simulations of mechanical properties of novel magnetic fluid, simulations of complex mechanical behaviors of conventional magnetic fluid, and simulations of biomagnetic fluid. Finally, some future trends of simulation of magnetic fluid are proposed. The following 3 topics should be emphasized in the future work. First, a comprehensive theoretical model considering a variety of microscopic interactions is required. In order to prepare magnetic particles with high MR effect, excellent dispersibility, and low density, surface coating, modification, and additive agents are usually applied in experiments. Unfortunately, the influence of non-magnetic components on the MR effect is seldom considered in simulations. Second, current simulations could not simultaneously obtain the macroscopic mechanical properties and microstructures of magnetic fluid in complex flow. Finite element method and computational fluid dynamics are applicable for complex macroscopic problems but can not obtain the microstructures at the same time. Mesoscopic simulation methods can not exhibit large-scale aggregations of particles, which leads to the deviation compared with experiments. To establish multi-scale simulation methods and improve the accuracy of simulations have become an urgent requirement. Combining simulation methods with different spatial scales and reducing the time cost by using machine learning have become a possible approach. Third, multi-physics coupling simulation methods should be established. The magnetic field controlled electrical properties of magnetic fluid have attracted researchers interest in recent years. Magnetic fluid with this novel controllable property could be widely applied in battery and sensors. Investigations on other physical properties of magnetic fluid by using mechanical, electrical, and magnetic model together will be a future trend. These achievements will all contribute to the development of high-performance magnetic fluids and further enlarge the range of applications of magnetic fluid.

Background/Aims: Some adipokines, such as adiponectin and leptin, have been reported to be involved in the pathogenesis of nonalcoholic fatty liver disease (NAFLD), while the association of adipsin and visfatin with NAFLD still remains unclear. This study aimed to examine the association of circulating adipsin, visfatin, and adiponectin with NAFLD in Chinese adults. Methods: We recruited a total of 211 eligible subjects, including 100 NAFLD cases and 111 age and sex frequency-matched controls. Circulating adipsin, visfatin, and adiponection concentrations were measured by enzymatic immunoassay. Unconditional logistic regression was conducted to assess the associations between quartiles of adipokines and NAFLD. Results: Compared with the controls, NAFLD cases had higher levels of adipsin and lower levels of visfatin and adiponectin. By multivariate logistic analysis, adjusting for potential confounders, circulating adipsin levels were found to be positively associated with NAFLD risk, and circulating levels of visfatin and adiponectin were inversely associated with the risk of NAFLD (all p-trend < 0.05). The ORs were 3.76 (95% CI 1.27–11.08) for adipsin, 0.30 (95% CI 0.10–0.91) for visfatin, and 0.30 (95% CI 0.10–0.88) for adiponectin comparing subjects in the highest quartile with those in the lowest. After stratified by obesity status, the association of higher adipsin with increased risk of NAFLD was only observed in nonobese group. Additionally, the inverse association between adiponectin and NAFLD was found in both groups. Conclusions: These results indicated that increased circulating levels of adipsin and decreased circulating levels of visfatin and adiponectin were independently associated with the increased risk of NAFLD.

Post-stroke depression (PSD) is a common and complex post-stroke neuropsychiatric disorder, which not only delays functional recovery but also increases mortality, and which currently lacks effective drug therapy. The pathogenesis of PSD is associated with impairment of the subcortical neural circuits and alterations of synaptic plasticity and neurotransmitters, but the exact mechanisms of PSD remain unknown. Our previous work indicates that the death-associated protein kinase 1 (DAPK1) mediates neuronal death after stroke. Genetic deletion of DAPK1 gene or blocking DAPK1 signal in the PSD mouse model can not only alleviate cerebral ischemic injury but also relieve PSD-like behaviors. Our previous work has also demonstrated the following results. First, the neural circuit of dorsal CA1 (dCA1) to medial prefrontal cortex (mPFC) (dCA1-mPFC) is selectively impaired after stroke. Second, the DAPK1 signal is involved in the impairment of dCA1-mPFC neural circuit after stroke. Third, genetic deletion of the DAPK1 gene or blocking of the DAPK1 signal alleviates the injury of dCA1-mPFC neural circuit after stroke and improves PSD-like behaviors. In conclusion, we hypothesize that activated DAPK1 signal after stroke induces apoptosis in the hippocampal dCA1 neurons, leading to loss of the dCA1-mPFC glutamatergic projections, synaptic injury, decrease of glutamate release, inhibition of mPFC neurons, and finally onset of PSD. We hope to further replenish the mechanisms of PSD and provide new insights for PSD treatment.

Background Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear. Methods We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA. Results We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway. Conclusions Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

Background The study aims to investigate the performance of a metagenomic next-generation sequencing (NGS)-based diagnostic technique for the identification of potential bacterial and viral infections and effects of concomitant viral infection on the survival rate of intensive care unit (ICU) sepsis patients. Methods A total of 74 ICU patients with sepsis who were admitted to our institution from February 1, 2018 to June 30, 2019 were enrolled. Separate blood samples were collected from patients for blood cultures and metagenomic NGS when the patients' body temperature was higher than 38 °C. Patients' demographic data, including gender, age, ICU duration, ICU scores, and laboratory results, were recorded. The correlations between pathogen types and sepsis severity and survival rate were evaluated. Results NGS produced higher positive results (105 of 118; 88.98%) than blood cultures (18 of 118; 15.25%) over the whole study period. Concomitant viral infection correlated closely with sepsis severity and had the negative effect on the survival of patients with sepsis. However, correlation analysis indicated that the bacterial variety did not correlate with the severity of sepsis. Conclusions Concurrent viral load correlates closely with the severity of sepsis and the survival rate of the ICU sepsis patients. This suggests that prophylactic administration of antiviral drugs combined with antibiotics may be beneficial to ICU sepsis patients.

Background Alveolar epithelial cell apoptosis is implicated in the onset of ventilator-induced lung injury. Death-associated protein kinase 1 (DAPK1) is associated with cell apoptosis. The hypothesis was that DAPK1 participates in ventilator-induced lung injury through promoting alveolar epithelial cell apoptosis. Methods Apoptosis of mouse alveolar epithelial cell was induced by cyclic stretch. DAPK1 expression was altered (knockdown or overexpressed) in vitro by using a small interfering RNA or a plasmid, respectively. C57/BL6 male mice (n = 6) received high tidal volume ventilation to establish a lung injury model. Adeno-associated virus transfection of short hairpin RNA and DAPK1 inhibitor repressed DAPK1 expression and activation in lungs, respectively. The primary outcomes were alveolar epithelial cell apoptosis and lung injury. Results Compared with the control group, the 24-h cyclic stretch group showed significantly higher alveolar epithelial cell apoptotic percentage (45 ± 4% fold vs. 6 ± 1% fold; P < 0.0001) and relative DAPK1 expression, and this group also demonstrated a reduced apoptotic percentage after DAPK1 knockdown (27 ± 5% fold vs. 53 ± 8% fold; P < 0.0001). A promoted apoptotic percentage in DAPK1 overexpression was observed without stretching (49 ± 6% fold vs. 14 ± 3% fold; P < 0.0001). Alterations in B-cell lymphoma 2 and B-cell lymphoma 2–associated X are associated with DAPK1 expression. The mice subjected to high tidal volume had higher DAPK1 expression and alveolar epithelial cell apoptotic percentage in lungs compared with the low tidal volume group (43 ± 6% fold vs. 4 ± 2% fold; P < 0.0001). Inhibition of DAPK1 through adeno-associated virus infection or DAPK1 inhibitor treatment appeared to be protective against lung injury with reduced lung injury score, resolved pulmonary inflammation, and repressed alveolar epithelial cell apoptotic percentage (47 ± 4% fold and 48 ± 6% fold; 35 ± 5% fold and 34 ± 4% fold; P < 0.0001, respectively). Conclusions DAPK1 promotes the onset of ventilator-induced lung injury by triggering alveolar epithelial cell apoptosis through intrinsic apoptosis pathway in mice. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

INTRODUCTION: The treatment effects of antiviral agents, glucocorticoids, antibiotics, and intravenous immunoglobulin are controversial in patients with coronavirus disease 2019 (COVID­19). OBJECTIVES: This study aimed to evaluate the impact of drug therapy on the risk of death in patients with COVID­19. PATIENTS AND METHODS: The PubMed, Embase, Web of Science, Cochrane Library, and major preprint platforms were searched to retrieve articles published until April 7, 2020. Subsequently, the effects of specific drug interventions on mortality of patients with COVID­19 were assessed. Odds ratios (ORs) and relative risks (RRs) with corresponding 95% CIs were pooled using random effects models. RESULTS: Of 3421 references, 6 studies were included. Pooled results from retrospective studies revealed that antiviral agents may contribute to survival benefit (OR, 0.42; 95% CI, 0.17-0.99; P = 0.048; I2 = 82.8%), whereas a single randomized controlled trial found no effects of an antiviral agent on mortality (RR, 0.77; 95% CI, 0.45-1.3; P = 0.33). Glucocorticoid use led to an increased risk of death (OR, 2.43; 95% CI, 1.44-4.1; P = 0.001; I2 = 61.9%). Antibiotics did not significantly affect mortality (OR, 1.13; 95% CI, 0.67-1.89; P = 0.64; I2 = 0%). Similarly, intravenous immunoglobulin had a nonsignificant effect on mortality (OR, 2.66; 95% CI, 0.72-9.89; P = 0.14; I2 = 93.1%). CONCLUSIONS: With the varied heterogeneities across interventions, the current evidence indicated a probable survival benefit from antiviral agent use and a harmful effect of glucocorticoids in patients with COVID­19. Neither any of antibiotics nor intravenous immunoglobulin were associated with survival benefit in this population.

BACKGROUND Percutaneous transforaminal endoscopic surgery has been used as a surgical measure for lumbar lateral recess stenosis. However, the necessary decompressive range has never been clearly documented in detail. Here, we discuss the effectiveness of a percutaneous transforaminal endoscopic procedure with clearly defined decompressive range. MATERIAL AND METHODS The relevant data were retrospectively collected from a series of degenerative lateral recess stenosis patients who acquired a prospectively designed percutaneous transforaminal endoscopic procedure in our department. The decompressive procedure mainly included undercutting of superior articular process and intervertebral disk annuloplasty. Leg pain and back pain was evaluated using visual analogue scale (VAS). The functional status was assessed using Oswestry disability index (ODI). The clinical results were also evaluated using MacNab criteria. RESULTS From May 2014 to October 2018, a total of 33 patients who met our inclusion criteria were included for analysis. There were no perioperative complications. Leg pain VAS decreased from preoperative score of 6.18±2.38 to final follow-up score of 0.45±1.00 (P

Background Post-stroke pain (PSP) is generally a severe complication in stroke rehabilitation. It is always associated with allodynia and hyperalgesia to nociceptive stimuli. Previous studies believed that PSP was related with tissue injury at certain brain territory, possibly thalamic lesion. However, there is very little evidence that the risk of PSP has a salient association with the side of lesion location (left or right hemisphere). The aim of this study was to assess the relationship between the occurrence of PSP and the lesion location of stroke.Methods We selected relevant literatures by searching EMBASE, ISI Web of Science, PubMed, and systematically reviewed available publications according to predetermined inclusion criterion. Subgroup analyses were performed according to the subtype of PSP. The pooled risk estimates were calculated by using a randomized-effects model.Results A total of 19 studies involving 2038 patients suffered from cerebral stroke were included. Meta-analysis showed no significant relationship between brain lesion location and the risk of PSP (OR=0.95 95% CI 0.74–1.23). Subgroups analyses showed that the incidence of post-stroke shoulder pain (PSSP) or central post-stroke pain (CPSP) was also not associated with the side of brain lesion (PSSP: OR=0.91, 95% CI 0.57–1.46; CPSP: OR=0.99, 95% CI 0.70–1.40). The pooled result of prospective studies had similar result (RR=1.02, 95% CI 0.84-1.25). Evidence of publication bias has not been found using visual inspection of a funnel plot and Begg’s and Egger’s tests.Conclusions Our systematic meta-analysis suggests that the lesion location of stroke has no significant association with the incidence of post-stroke pain. Further studies are needed to detect the risk factors for PSP, which may contribute to the prevention, identification and management of PSP.

Background Grade V thoracic spondylolisthesis secondary to neurofibromatosis type 1 (NF-1), especially combined with vertebral fusion, is rare. We reported a case of a 26-year-old female diagnosed with grade V T2spondylolisthesis and T2-T5 autofusion secondary to NF-1, which caused severe kyphotic deformity and neurologic deficits, and she was treated with posterior decompression, internal fixation, and fusion. Case Description The right-handed patient admitted to the clinic due to weakness of her legs. An eye examination documented a sign of Lisch nodules in the iris. Cafe-au-lait macules, dermal neurofibroma of multiple forms, and rubbery bumps of varying sizes could be observed on her skin. Paresis with muscle strength of 2/5 in both lower extremities with increased muscle tone and decreased muscle mass could be observed. Radiographic results indicated grade V thoracic spondylolisthesis with vertebral fusion from T2-T5 level. To alleviate neurologic dysfunction, posterior decompression, internal fixation, and fusion were performed. She reported marked improvement in lower limb motor and sensory functions during the follow-up, and her muscle strength recovered to 5/5. Conclusions Grade V thoracic spondylolisthesis combined with vertebral fusion on T2-T5 level in NF-1 is rare. Early surgical intervention of posterior spinal decompression with internal fixation and fusion yielded satisfactory clinical outcomes.

Social media is believed as a privileged vehicle affording numerous ideas with multi-faceted insights from the crowds. In addition to the entertainment resource, social media, user-generated content (UGC) there, can also empower ideation and commercialization of innovation. We have proposed a novel approach to explore the pivotal role of social media in shaping corporation innovation performance in our article in 2018. In this commentary, we extend the literature review with more recent insights and identify the new possible directions to further inspire future research. Specifically, understanding the linkage between social media and organization innovation can be enriched via advancing deep learning methods, improving multi-modal data analysis, and fostering digital innovation.

Social media influences business practices such as innovation activities. This study is anchored in the theoretical paradigm of strategic information technology (IT) alignment and the literature on social media and its business value. We examine how the valence and volume of user-generated content (UGC) from social media influence firm-level innovation strategies. Based on an analysis of five years of panel data for 886 listed firms and their 6.2 million relevant microblogs, we observed three interesting results. First, the valence of social media UGC has a U-shaped relationship with firms’ innovation investments; and compared with neutral UGC, both negative and positive content lead to more innovation investment. Second, we found that this curvilinear relationship is mitigated as the volume of UGC increases. Third, we verified that increasing innovation investment improves firm performance. We then examined these findings using a series of strict robustness checks and discussed our study’s contribution to theory and practice.

An evaluation index system is developed to assess food safety supervision in the sales links of dairy products. Evaluation research is conducted using the fuzzy-ANP comprehensive evaluation model to assess the product safety supervision of dairy products in the sales link based on 307,705 survey data acquired from 1,501 online and offline dairy businesses in China. Evaluation results show that (1) the overall situation of dairy product safety supervision in the sales link is encumbered by the fact that the online situation of dairy product safety supervision in the sales link is general. It does not achieve a relatively good level; (2) the investment in food safety supervision of dairy products in the sales link is insufficient for the online e-commerce platforms. Especially, the processes of reviewing and approving relevant business sales qualification must be improved; (3) online business types do not directly determine the situation of dairy product safety supervision in the sales link, but the operating environment, sales staff quality, and warehousing management are common regulatory weaknesses; and (4) for offline provinces, the level of economic development can affect the situation of dairy product safety supervision in the sales link. Aside from emphasizing sales qualifications, economically backward provinces should improve the supervision of the operating environment, sales equipment, sanitary status of workers, and other aspects.

With the development of electronic science and technology, green landscape planning and design in urban landscape design has become a new trend and direction. The emergence of virtual reality assisted design technology and platforms has brought more innovation space for landscape designers and greatly reduced Time and workload. The mature application of virtualization technology and embedded network technology in various fields provides technical support for perfecting the concept of virtual reality. Based on virtual reality technology and embedded network, this thesis discusses green urban garden landscape design, and constantly strengthens user experience, expands the extension of garden landscape design. On the one hand, the development of virtual reality technology and embedded network makes garden landscape design the imagination of the teacher can be brought into play and realized. On the other hand, in the virtual scene, the landscape architect integrates the characteristics of different types of elements to design creative and innovative, open and shared garden landscapes. Using the Internet platform as a medium, refer to and learn from more representative works, and stimulate more creative landscape design concepts.

Efficacy of EGFR-targeted tyrosine kinase inhibitors (TKIs), such as erlotinib, to treat human non-small cell lung cancers (NSCLCs) with activating mutations in EGFR is not persistent due to drug resistance. Reprogramming in energy (especially glucose) metabolism plays an important role in development and progression of acquired resistance in cancer cells. We hypothesize that glucose metabolism in EGFR-TKI sensitive HCC827 cells and erlotinib-resistant sub-line of HCC827 (which we name it as erlotinib-resistant 6, ER6 cells in this study) is different and targeting glucose metabolism might be a treatment strategy for erlotinib-resistant NSCLCs. In this study, we found increased glucose uptakes, significant increase in glycolysis rate and overexpression of glucose transporter 1 in ER6 cells compared to its parental cells HCC827. We also found AKT and autophagy of ER6 cells were more activated than HCC827 cells after glucose starvation. Combining glucose deprivation and AKT or autophagy inhibitor could synergize and overcome the acquired resistance against EGFR-targeted therapy for NSCLCs. Our data suggest that the combinations of inhibitors of AKT or autophagy together with glucose deprivation could be novel treatment strategies for NSCLC with acquired resistance to targeted therapy.

The construction scale of high arch dams is large and the overall structure is complex. Numerical simulation results obtained only by quoting standard parameters or laboratory measurements are quite different from actual engineering conditions. Based on a set of temperature-stress coupling simulation system, the key thermodynamic parameters used in the simulation calculation are further optimized through monitoring data and experimental results, so as to be close to the actual engineering state and better for studying the working status of high arch dams. Combined with actual applications, it is shown that the optimized results of the method are consistent with the actual objective laws, can better reflect the real situation, reduce the “noise” interference in the data, and verify the correctness and feasibility of the method.

Functional failure of tau contributes to age-dependent, iron-mediated neurotoxicity, and as iron accumulates in ischemic stroke tissue, we hypothesized that tau failure may exaggerate ischemia-reperfusion-related toxicity. Indeed, unilateral, transient middle cerebral artery occlusion (MCAO) suppressed hemispheric tau and increased iron levels in young (3-month-old) mice and rats. Wild-type mice were protected by iron-targeted interventions: ceruloplasmin and amyloid precursor protein ectodomain, as well as ferroptosis inhibitors. At this age, tau-knockout mice did not express elevated brain iron and were protected against hemispheric reperfusion injury following MCAO, indicating that tau suppression may prevent ferroptosis. However, the accelerated age-dependent brain iron accumulation that occurs in tau-knockout mice at 12 months of age negated the protective benefit of tau suppression against MCAO-induced focal cerebral ischemia-reperfusion injury. The protective benefit of tau knockout was revived in older mice by iron-targeting interventions. These findings introduce tau-iron interaction as a pleiotropic modulator of ferroptosis and ischemic stroke outcome.

Artificial Immune System is used nowadays to solve complex problems, including medical problems. To overcome some flaws of traditional clonal selection algorithm in medical imaging applications, a novel clonal selection algorithm in intelligent adaptive enhancement design of magnetic resonance imaging (MRI) brain images is proposed. It is called the MRI-Clonal Selection Algorithm (MRI-CSA). The MRI-CSA uses three improvements for the Clonal Selection Algorithm. Firstly, instead of the simple binary coding, the real coding approach of the MRI brain image is designed. Secondly, the mutation distance is added into the mutation operator to better control the mutation progress and avoid any narrow local optimization. Finally, both the clone selection and the mutation are adjusted together in the Gauss distribution, the uniform distribution, and the chaotic distribution, rather than in only the Gauss distribution. In addition, the real MRI brain images are used in the image enhancement testing with our improved clonal selection algorithm. The experimental results show that the proposed approach outperforms the median filtering (MF) and the adaptive template filtering (ATF) in enhancing the MRI brain images.

Ischemic stroke, which accounts for 87% of all strokes, constitutes the leading cause of morbidity and mortality in China. Although the genetics and epigenetics of stroke have been extensively investigated, few studies have examined their relationships at different stages of stroke. This study assessed the characteristics of transcriptome changes at different stages of ischemic stroke using a mouse model of transient middle cerebral artery occlusion (tMCAO) and bioinformatics analyses. Cerebral cortex tissues from tMCAO mice at days 1, 3, 7, 14, and 28 were removed for RNA-Seq and small RNA-Seq library construction, sequencing, and bioinformatics analysis. We identified differentially expressed (DE) genes and miRNAs and revealed an association of the up-regulated or down-regulated DEmiRNAs with the correspondingly altered DEgene targets at each time point. In addition, different biological pathways were activated at different time points; thus, three groups of miRNAs were verified that may represent potential clinical biomarkers corresponding to days 1, 3, and 7 after ischemic stroke. Notably, this represents the first functional association of some of these miRNAs with stroke, e.g., miR-2137, miR-874-5p, and miR-5099. Together, our findings lay the foundation for the transition from a single-point, single-drug stroke treatment approach to multiple-time-point multi-drug combination therapies.

Electro-analytical (E-chem) biosensors offer unique advantages over widely used optical biosensors and can be considered ideal for low-cost, mass-deployable point-of-care (PoC) diagnostic devices [1]. They possess fully electronic and real-time transduction methods and require little or no external instrumentation. Despite these advantages, two fundamental challenges have hampered broad adoption of E-chem biosensors: 1C design and transducer (surface) material suitability. E-chem sensors require both low-noise and high detection dynamic range (DDR) front-end circuits and must also accommodate electrode-electrolyte interfaces with significant PVT variations and temporal drifts [2]–[5]. The absence of CMOS-compatible bio-electronic interfaces with adequate chemical and thermal stability has been another impediment [6].

Stroke activates microglia pro-inflammatory response that not only induces the early neuronal injuries but also causes the secondary brain infarction. Yet, the underlying mechanisms for how microglia become activated in stroke are still unknown. Here, using the next-generation of RNA sequencing we find a total of 778 genes increasingly expressed in brain of stroke mice. Of these, we identified Hmgb2 as a microglia pro-inflammatory mediator by promoting the transcription of Ctss. Inhibition of either Hmgb2 or Ctss blocks microglia pro-inflammatory response and protects against brain damages and improves the neurological functions of stroke mice. This study uncovers Hmgb2 and Ctss as the major microglia inflammatory response mediators in stroke and hence warrants the promising targets for stroke therapies.

// Rui-Min Chang 1 , Lei Pei 1 , Feng Fang 1 , Jiang-Feng Xu 1 , Hao Yang 1 , Chao-Hui Zuo 4 , Jian-Hua Zhou 2 , Geng-Qiu Luo 2 , Lian-Yue Yang 1, 3 1 Liver Cancer Laboratory, Xiangya Hospital, Central South University, Changsha 410008, China 2 Department of Pathology, Xiangya Hospital, Central South University, Changsha 410008, China 3 Department of Surgery, Xiangya Hospital, Central South University, Changsha 410008, China 4 Department of Abdominal Surgical Oncology, Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China Correspondence to: Lian-Yue Yang, email: lianyueyang@hotmail.com Keywords: YMO1, RhoC, PAX5, hepatocellular carcinoma, metastasis Received: November 21, 2015 Accepted: June 29, 2016 Published: July 27, 2016 ABSTRACT Previous studies have shown that 4.1 proteins, which are deregulated in many cancers, contribute to cell adhesion and motility. Yurt/Mosaic eyes-like 1 (YMO1) is a member of 4.1 protein family but it is unclear whether YMO1 plays a role in tumor invasion. This study aimed to investigate the effects of YMO1 on hepatocellular carcinoma (HCC) and attempted to elucidate the underlying molecular mechanisms. YMO1 expression in HCC tissues and its correlation with clinicopathological features and postoperative prognosis was analyzed. The results showed that YMO1 was down-regulated in the highly metastatic HCC cell line and in human tumor tissues. Underexpression of YMO1 indicated poor prognosis of HCC patients. Restoration of YMO1 expression caused a significant decrease in cell migration and invasiveness in vitro . In vivo study showed that YMO1 reduced liver tumor invasion and metastasis in xenograft mice. YMO1 directly inhibited RhoC activation. YMO1 expression in HCC was regulated by PAX5. Analysis of YMO1 expression levels in human HCC patients revealed a significant correlation of YMO1 expression with PAX5 and RhoC. Our findings revealed that YMO1 predicts favorable prognosis and the data suggest that YMO1 suppresses tumor invasion and metastasis by inhibiting RhoC activity.

Inflammation plays a crucial role in acute ischemic stroke pathogenesis. Macrophage-derived Maresin 1 (MaR1) is a newly uncovered mediator with potent anti-inflammatory abilities. Here, we investigated the effect of MaR1 on acute inflammation and neuroprotection in a mouse brain ischemia reperfusion (I/R) model. Male C57 mice were subjected to 1-h middle cerebral artery occlusion (MCAO) and reperfusion. By the methods of 2,3,5-triphenyltetrazolium chloride, haematoxylin and eosin or Fluoro-Jade B staining, neurological deficits scoring, ELISA detection, immunofluorescence assay and western blot analysis, we found that intracerebroventricular injection of MaR1 significantly reduced the infarct volume and neurological defects, essentially protected the brain tissue and neurons from injury, alleviated pro-inflammatory reactions and NF-κB p65 activation and nuclear translocation. Taken together, our results suggest that MaR1 significantly protects against I/R injury probably by inhibiting pro-inflammatory reactions.

Effective capacity-loss diagnosis and life-time prediction are the foundations of battery second-use technology and will play an important role in the development of the new energy industry. Of the two, the capacity-loss diagnostic, as a precondition of the life-time prediction, needs to be studied first. Performing a capacity-loss diagnosis for an aging cell consists of finding the decisive degradation mechanisms for the cell's capacity degradation. Because a cell's capacity just equals the span of the open-circuit voltage (OCV), when suspect degradation mechanisms affect a cell's capacity, they will leave corresponding and particular clues in the OCV curve. Taking a cell's OCV as the diagnostic indicator, a multi-mechanistic and non-destructive diagnostic method is developed in this paper. To establish an unambiguous relationship between OCV changes and the combinations of the decisive mechanisms, all the possible OCV changes under various aging situations are systematically analyzed based on a novel simultaneous coordinate system, in which the effects of each suspect capacity-loss mechanism on the OCV curve can be clearly represented. As a summary of the analysis results, a straightforward diagnostic flowchart is presented. By following the flowchart, an aging cell can be diagnosed within three steps by observation of the OCV changes.

Patients with triple negative breast cancer (TNBC) have a higher rate of distant recurrence and a poorer prognosis than those with other breast cancer subtypes. Therefore, it is important to study the mechanism of TNBC relapse. A retrospective immunohistochemical analysis of the expression of receptor protein tyrosine phosphatase ζ (PTPRZ1) and pleiotrophin (PTN) was performed for 325 cases of breast cancer. These samples included 66 cases of luminal A breast cancer, 67 cases of luminal B breast cancer, 78 cases of Her-2-enriched breast cancer, 78 cases of TNBC and 36 cases of relapsed TNBC (RTNBC). In addition, 30 control specimens and 30 cases of metastasized lymph nodes were examined. PTPRZ1 and PTN were highly expressed in the RTNBC group. Compared with the RTNBC group, significant differences in the expression of PTPRZ1 were observed between the TNBC, BC and control groups. A significant difference was observed in the expression of PTN in the BC group (P

Death-associated protein kinase 1 (DAPK1) is a key protein that mediates neuronal death in ischemic stroke. Although the substrates of DAPK1 and molecular signal in stroke have been gradually discovered, the modulation of DAPK1 itself is still unclear. Here we first reveal that Caytaxin, a brain-specific member of BCL2/adenovirus E1B -interacting protein (BNIP-2), increases and interacts with DAPK1 as early as 2 h after middle cerebral artery occlusion (MCAO) in the penumbra area of mouse brain. Furthermore, Caytaxin binds to DAPK1 at the presynaptic site and inhibits DAPK1 catalytic activity. Silencing Caytaxin by Caytaxin shRNA (Sh-Caytaxin) enhances DAPK1 activity, deteriorates neuronal apoptosis and brain injuries both in vivo and in vitro. Thus, elevating presynaptic Caytaxin could prevent neuronal apoptosis by inhibiting DAPK1 activation in the acute stage of ischemic stroke. Caytaxin may physiologically protect neuronal cells and represent a potential prevention and therapeutic target in the early phase of cerebral ischemic stroke.

Cardiovascular and respiratory diseases are among global leading causes of mortality. Insulators are at risk of these illnesses because of chronic exposure to asbestos and silica. Many insulators are habitual smokers, which confounds etiological diagnosis of disease. In this study, a retrospective analysis of non-smoking insulators examined the direct effects of occupational exposure. Unionized non-smoking insulators (n = 301) were recruited through a longitudinal surveillance program in Alberta (41 ± 14 years, 29 ± 5 kg/m2 BMI). Family, health, and work history, using validated questionnaires, and full physical assessments were collected. Insulators were assessed by pulmonary function tests (PFTs), chest X-rays, Framingham cardiac risk scores, and chronic obstructive pulmonary disease (COPD) assessment test (CAT) scores. For controls, a cohort of Royal Canadian Mounted Police (RCMP) officers was assessed (37 ± 9 years, 29 ± 6 kg/m2 BMI). Over half the insulators (54%) were exposed to asbestos in their working environment. No differences were found in PFT values from insulators and RCMP officers. While the CAT score for insulators (mean, 4 ± 4) was lower than that of RCMP (6 ± 5, p 13%. COPD and asbestos-related lung diseases (ARLD) were found in 18% of insulators. Our findings suggest an emerging public health crisis in the health of insulators independent of smoking habits. More needs to be done to protect the health of workers and prevent the onset of lung diseases.

Sepsis is a life-threatening state of organ dysfunction caused by infection and which can induce severe neurological disorders that lead to neuroinflammation and cognitive impairment. Inflammation has been reported to cause neuronal apoptosis in sepsis, which can finally lead to cognitive impairment. Previous studies have suggested that BML-111 can exhibit anti-inflammatory and proresolution activities. Additionally, silent information regulator 1 (SIRT1) can inhibit the NF-κB signaling pathway in an inflammation state. However, the role of the SIRT1/NF-κB signaling pathway in the protective effects of BML-111 against sepsis-induced neuroinflammation and cognitive impairment remains unclear. This study aimed to determine the effects of BML-111 on neuroinflammation and cognitive impairment induced by sepsis. Male C57BL/6J mice were subjected to cecal ligation and puncture (CLP) or a sham operation. BML-111 was administered via intracerebroventricular injection (0.1 mg/kg) immediately after CLP. Boc-2 (50 μg/kg) was administered intracerebroventricularly 30 min before CLP, and EX527 (10 μg) was administered every 2 days for a total of three times before CLP, also intracerebroventricularly. Some of the surviving mice underwent open-field, novel-object-recognition, and fear-conditioning behavioral tests at 7 days after surgery. Some of the other surviving mice were killed at 24 h after surgery to assess synaptic damage (PSD95 and Synapsin1), markers of inflammation [tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1β], cytoplasmic p65, nuclear p65, Ac- NF-κB and SIRT1. At 48 h after CLP, TUNEL and glia-activation by immunofluorescence investigations were performed on a separate cohort of surviving animals. The results suggested that sepsis resulted in cognitive impairment, which was accompanied by the decreased the expression of PSD95 and Synapsin1, increased amount of TUNEL-positive cells and the activation of glias, increased production of TNF-α and IL-1β, increased expression of nuclear p65, Ac- NF-κB, and decreased expression of SIRT1 and cytoplasmic p65. It is especially notable that these abnormalities could be reduced by BML-111 treatment. EX527, an SIRT1 inhibitor, abolished the effects of BML-111. These results demonstrate that BML-111 can reduce the neuroinflammation and cognitive impairment induced by sepsis via SIRT/NF-κB signaling pathway.

Nonalcoholic fatty liver disease has become a social health challenge of global concern. The term nonalcoholic steatohepatitis (NASH) is a more severe condition than simple steatosis and distinguishing NASH from nonalcoholic fatty liver disease is particularly important. Liver biopsy remains a gold standard in diagnosing NASH. Meanwhile, radiological techniques such as ultrasonography and MRI are also applied widely. However, the invasive and expensive examination is not suitable for screening, and there is a great need for reliable and appropriate biomarkers to screen patients for NASH. Based on the current studies of blood-based novel biomarkers, we attempt to summarize the latest findings on biomarkers for NASH, including blood biomarkers encompassing proteins, lipids and miRNAs; the correlation between extracellular vesicles and NASH; and treatment strategies for NASH.

Study design A retrospective study. Objective The aim of this study was to compare the clinical outcomes of continuous irrigation suction systems (CISS) or vacuum-assisted closure system (VACS) in early deep wound infection (DWI) after thoracolumbar instrumentation. Summary of background data DWI after thoracolumbar instrumentation is challenging and debridement followed by either CISS or VACS has been proven to be effective. So far, which one of the system has more advantages over the other remains unclear. Methods Patients after thoracolumbar instrumentation were evaluated at our spine surgery center from 2005 to 2015. Patients who were diagnosed with early deep DWI after spinal instrumentation and treated by meticulous debridement in the operating room followed by either CISS or VACS were included. Detailed information was obtained from the medical records, including clinical features, results of laboratory examinations, medical therapies, and outcomes. A follow-up was conducted to observe whether recurrent spinal infection or other complications happened. Results We identified 11 patients in the CISS group and 12 patients in the VACS group. There were no significant differences in terms of age, gender, follow-up duration, symptoms of infection, laboratory examinations, etc. The number of CISS or VACS replacement was 1.3 and 1.6, respectively, before wound healing (P > 0.05). And there were significant differences in terms of hospital stay and extra cost of infection treatment between the two groups. In the follow-up period, we observed sinus tract formation and low back pain in both groups and one patient in the VACS group died of pulmonary infection 4 years after the initial surgery. Conclusion Thorough debridement followed by CISS or VACS are comparable in treating early DWI after thoracolumbar instrumentation. The CISS treatment was statistically significant in comparison to the VACS treatment in terms of hospital stay and cost. Level of evidence 4.

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project., The authors would like to thank the European Union’s Seventh Framework Programme (BacHBerry, Project No. FP7-613793, and FP7-PEOPLE2013-COFUND, Project No. FP7-609405) for the financial support. AD, RF, MHHN, PG, SGS, and JF would also like to acknowledge the Novo Nordisk Foundation. We express our gratitude to Dr. Martha Cyert (Stanford School of Medicine, EUA), Dr. Hitoshi Shimoi (National Research Institute of Brewing, Japan) and Dr. Yoshio Araki (Graduate School of Biosphere Science, Hiroshima University, Japan) for providing the yeast strain YAA5. We also thank Dr. Ian Macraedie, RMIT University, Australia) for providing the plasmid p416_GPDprGFP-A42., info:eu-repo/semantics/publishedVersion

Fluoxetine, one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, has been thought to be effective for treating post-stroke depression (PSD). Recent work has shown that fluoxetine may exert an antidepressive effect through increasing the level of brain-derived neurotrophic factor (BDNF), but the underlying mechanism still remains unclear. In the present study, we successfully established the PSD model using male C57BL/6 J mice by photothrombosis of the left anterior cortex combined with isolatied-housing conditions. In the process, we confirmed that fluoxetine could improve the depression-like behaviors of PSD mice and upregulate the expression of BDNF in the hippocampus. However, depletion of BDNF by transfecting lentivirus-derived shBDNF in hippocampus suppressed the effect of fluoxetine. Furthermore, we demonstrated the epigenetic mechanisms involved in regulation of BDNF expression induced by fluoxetine. We found a statistically significant increase in DNA methylation at specific CpG sites (loci 2) of Bdnf promoter IV in the hippocampus of PSD mice. We also found that fluoxetine treatment could disassociate the MeCP2-CREB-Bdnf promoter IV complex via phosphorylation of MeCP2 at Ser421 by Protein Kinase A (PKA). Our research highlighted the importance of fluoxetine in regulating BDNF expression which could represent a potential strategy for preventing PSD.

Background Cervical sagittal alignment plays an important role in the pathogenesis of cervical spondylotic myelopathy (CSM), but there are limited studies on the cervical sagittal parameters in CSM patients and their correlations with myelopathy. The aim of this study is to investigate the correlations among the preoperative cervical sagittal alignment parameters and their correlations with the development of myelopathy in patients with CSM. Methods We retrospectively collected 212 patients with CSM who underwent surgical interventions. Gender, age, modified Japanese Orthopedic Association score (mJOA), cervical lordosis (CL), C2–C7 sagittal vertical axis (C2–C7 SVA), T1 slope (T1S), neck tilt (NT) and thoracic inlet angle (TIA) were collected before operation. Interobserver and intraobserver reliability were calculated for all measurements (intraclass correlation coefficient, ICC). Data were analyzed with Pearson and Spearman correlation tests and multiple linear regression analysis. Results A total of 212 patients with CSM were included in this study (male: 136, female: 76) with an average age of 54.5 ± 10.1 years old. Intraobserver and interobserver reliability for all included radiographic parameters presented good to excellent agreement (ICC > 0.7). No significant differences in demographic and radiological parameters have been observed between males and females (P > 0.05). We found statistically significant correlations among the following parameters: age with CL (r = 0.135, P = 0.049), age with T1S (r = 0.222, P = 0.001), CL with T1S (r = 0.291, P r = − 0.395, P r = − 0.274, P r = − 0.219, P T1S(r = − 0.171, p = 0.013). Linear regression analysis showed that C2–C7 SVA was the predictor of CL (adjusted R2 = 0.152, P R2 = 0.106, P Discussion There were significant correlations among certain preoperative cervical sagittal parameters in CSM patients. CL was the only predictor of C2–C7 SVA. Age combined with C2–C7 SVA could predict the severity of myelopathy.

The present study aimed to explore the importance of P53 and Cox-2 protein expression in esophageal cancer and assess their influence on prognosis. The expression of P53 and Cox-2 was assessed in esophageal cancer samples from 195 patients subjected to radical surgery at Changzhou First People's Hospital (Changzhou, China) between May 2010 and December 2011. Expression of P53 and Cox-2 proteins were detected in 60.5% (118/195) and 69.7% (136/195) of the samples, respectively, and were co-expressed in 43.1% (84/195) of the samples. A correlation was identified between P53 expression and overall survival (OS) (P=0.0351) as well as disease-free survival (DFS) (P=0.0307). In addition, the co-expression of P53 and Cox-2 also correlated with OS (P=0.0040) and DFS (P=0.0042). P53 expression (P=0.023), TNM staging (P