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Background Melanoma is an aggressive malignant skin tumor endangering the health of patients. Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) have been increasingly reported to be implicated in the carcinogenesis of melanoma. Long intergenic non-coding RNA 00665 (LINC00665) has been found to exert important regulatory roles in some cancers, yet its function in melanoma remains to be investigated. Methods QRT-PCR analysis was conducted to evaluate the relative expression of RNAs. Functional experiments in vitro including colony formation, EdU, wound-healing and transwell assays, as well as in vivo xenograft assays, were utilized to study the role of LINC00665 in melanoma. Mechanical experiments were implemented to probe into the molecular linkage of LINC00665, miR-224-5p and VMA21. Results LINC00665 was abnormally highly expressed in melanoma cells. Silencing LINC00665 could inhibit the proliferation and migration of melanoma cells. LINC00665 sponged miR-224-5p to up-regulate VMA21. VMA21 knockdown exerted similarly interfering effects on above biological processes in melanoma cells. However, VMA21 overexpression abolished the in vitro and in vivo outcomes of LINC00665 silencing. Conclusion LINC00665 promotes proliferative and migrating abilities of melanoma cells via targeting miR-224-5p/VMA21 axis.

Background Noonan syndrome (NS) is a multisystem disorder resulting from pathogenic mutations in more than 15 genes, among which LZTR1 is newly discovered. However, its role in NS pathogenesis remains unclear, including its inheritance pattern. Methods We herein report a family with LZTR-related NS. We collected clinical data of the proband and her families. Four of them completed the whole exon sequencing. Results Two children with NS inherited the same heterozygous LZTR1 variant, c.1149 + 1G > T, from their affected mother. Moreover, the proband was diagnosed as NS accompanied by growth hormone deficiency (GHD) without other associated gene mutations. Conclusion The variant c.1149 + 1G > T of LZTR1 was previously reported in autosomal recessive NS, but this is the first report of an autosomal dominant form. Our reported cases provided evidence for a more complex inheritance pattern resulting from LZTR1 c.1149 + 1G > T mutation. Occasionally, NS patients can have GHD.

Ascorbic acid is often used to enhance iron absorption in nutritional interventions, but it produces pro-oxidant effects in the presence of iron. This study aimed to evaluate ascorbate's role in iron toxicity on intestinal resistance against foodborne pathogens during iron supplementation/fortification. In polarized Caco-2 cell monolayers, compared to the iron-alone treatment, the iron-ascorbate co-treatment caused more than 2-fold increase in adhesion, invasion and translocation of

In this study, we successfully synthesized a thin-slice layer of graphitic carbon nitride (g-C3N4) with abundant irregular holes by a facile two-step method using Pluronic P123 as a template (CN-P1...

Developing efficient and robust materials for emerging electrodegradation of organic pollutants has attracted broad interests. In this study, a novel controlled pyrolysis approach was employed to fabricate a quasi-MOF derivative-based electrode by pyrolyzing MIL-101(Fe) anchored on a polyaniline-modified carbon fiber paper at 400 °C. The construction of the accessible Fe-O sites, and the in situ generation of Fe3O4 nanoparticles with graphene-like carbon layers coated, would enhance the electro-Fenton activity of the electrode, which was used as the cathode. The results showed that 100 % of 50 mg L−1 p-nitrophenol and 52 % total organic carbon were removed in 120 min under a current density of 5 mA cm-2, suggesting that the prepared electrode had a more efficient mineralization current efficiency and less energy consumption compared with electrodes before pyrolysis. Notably, the stability of the electrode was greatly improved, maintaining its outstanding performance even after ten runs. The plausible reaction mechanism and degradation pathway were also proposed. This new pyrolysis strategy is expected to serve as a paradigm for designing efficient electrode in electro-Fenton remediation field.

Objective The prediction of survival of gastric neuroendocrine tumours (g-NETs) is controversial. Prognostic effects of the metastatic lymph node ratio (LNR) in patients with g-NET were explored, and a nomogram was plotted to predict the survival rates of patients. Methods A longitudinal study conducted on the basis of the Surveillance, Epidemiology, and End Results database. The association between LNR and survival were investigated by using Pearson correlation and Cox regression. Overall survival (OS) and cancer-specific survival (CSS) rates were predicted with the help of nomograms. Results A total of 315 patients with g-NET diagnosed from 2004 to 2015 were included in this study. LNR was discovered to have a negative correlation with OS and CSS (Pearson correlation coefficients: 0.343 (p

In this work, the bimetallic iron oxide self-supported electrode was prepared by a simple solvothermal as well as thermal method. CoFe2O4 magnetic nanoparticles were grown in situ on the CFP surface and characterized to reveal the morphology, composition, and electrochemical properties of the electrode. Compared to CFP and CFP@Co-Fe, CFP@CoFe2O4 equipped more efficient mineralization current efficiency and lower energy consumption due to the improved electrocatalytic capacity of CoFe2O4 properly grown on the conductive substrate surface. Further studies showed that the manufactured electrode maintained a high level of stability after continuous operation. According to the free radical trapping experiment, EPR, and liquid mass spectrometry analysis, the rational reaction mechanism of p-nitrophenol was finally proposed, in which ·OH and SO4·- were considered as the main active oxidants. This work demonstrated the great potential of establishing an electro-Fenton system based on CoFe2O4 immobilized self-supporting cathode for environmental remediation.

In this study, in order to prevent the failure of hemipelvic arthroplasty using a patient-specific Computer-Aided Design (CAD) and Additive Manufacturing (AM) approach, a new design for modular hemipelvic prosthesis was developed. Moreover, the biomechanical properties of the new design were determined. The 3D printed pelvic prosthesis with a sacrum portion that completely matches the back surface of the patient’s sacrum offers more potential for bone ingrowth between the host bone and prosthesis. The new approach integrated the capabilities of digital medical imaging techniques, CAD and metal AM to realize a modular hemipelvic prosthesis. The patient’s pelvic Digital Imaging and Communication in Medicine (DICOM) data were imported into Mimics software to construct a digital representative patient model for design of the prosthesis. A physical model was obtained using a Stereolithography (SLA) 3D printer for preoperative planning. The final customized implant was designed by using UG NX 10.0 software. Then a surgically modular hemipelvic prosthesis was fabricated from the Ti6Al4V titanium alloy by electron beam melting technology. The operation was performed according to the preoperative planning. The outcome of the operation was good at the 6-month follow-up. Also, the stress distribution and the relative micromotion revealed positive results based on a finite element model built to detect prosthesis stability. The 3D printed modular hemipelvic prosthesis provided good resolution for the failure of hemipelvic arthroplasty. Personal customization will be important in future surgeries aiming at improving the anatomy and function of the implant.

Solar driven photoelectrochemical (PEC) hydrogen production has attracted considerable attention, but the design of highly efficient, robust and low-cost photocathode still remains a significant challenge. Herein, we report a novel SiNWs@Co3O4Z-scheme heterojunction photocathode with carbon quantum dots eco-friendly derived from sludge (SCQDs) as the co-catalyst. The photocathode not only leads to effective separation of electron-hole pair, lower transmission resistance, and longer lifetime of charge carriers, but also elevates the stability by preventing direct contact between the SiNWs and the electrolyte as well as the self-oxidation. Simultaneously, the excellent electron transport properties of the SCQDs further improved the PEC performance. Correspondingly, a maximum current density of 14.88 mA·cm-2 was obtained at -0.67 V with the applied bias photon-to-current efficiency (ABPE) achieving 8.4% under visible light irradiations at pH = 7. This work provides a promising scheme for Si-based photocathodes for PEC hydrogen production with a high performance, reliable stability, and low-cost.

Iron fortification has been associated with a modest increase in diarrhea risk among children. Herein, we investigate the correction for this unwanted side effect with probiotic/prebiotic supplementation in weaning mice. Iron fortification with 250 ppm and 500 ppm ferrous sulfate for 30 days significantly increased the species richness of the mouse gut microbiota compared to controls. The 500 ppm-FeSO4 diet caused a significantly decreased abundance of potentially beneficial Lactobacillus. During infection with the foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium), mice on the 500 ppm-FeSO4 diet showed earlier appearance of poisoning symptoms, higher rates of weight and appetite loss, and lower survival rates, all of which were effectively reversed by supplementation with a probiotic (Lactobacillus acidophilus) or a prebiotic (inulin) for 7 days before infection. Iron fortification with 500 ppm ferrous sulfate also increased fecal shedding and spleen and liver load of viable S. Typhimurium, suggesting its promoting effect on pathogen colonization and translocation, and this negative effect was found to be well corrected by supplementation with Lactobacillus acidophilus or inulin. Light and transmission electron microscopic observation on the ileal villus structure revealed the histopathological impairment of the intestine by iron fortification with both 250 ppm and 500 ppm ferrous sulfate, and the intestinal lesions were markedly alleviated by supplementation with Lactobacillus acidophilus or inulin. These results provide experimental evidence for the increased diarrhea risk upon iron fortification with high pathogen load, and demonstrate that probiotic or prebiotic supplementation can be used to eliminate the potential harm of iron fortification on gut health.

Background: Medulloblastoma (MB) is a central nervous system malignancy that rarely affects adult. Epidemiological trends of adult MB are limited. This study aimed to explore population-level trends in the incidence of adult MB and to examine potential predictors for overall survival (OS). Methods: Data for patients from 1973 to 2015 were extracted from the Surveillance, Epidemiology and End Results (SEER) database. Age-adjusted incidence rates (AAIR) were calculated for groups divided on the basis of age, gender, and ethnicity. Propensity-score matching was used to compensate for potential selection biases. Cox proportional hazard models were used to examine potential predictors for OS. Results: AAIR was stable among MB patients ≥20 yr of age. The AAIR was slightly higher in males than that in females (0.065 vs. 0.049 per 100,000). Compared to whites, the incidence was nearly doubled in individuals of black ethnicity (0.063 vs. 0.033 per 100,000). Incidence was also lower among patients ≥40 yr of age, compared to those 20-39 yr of age (0.025 vs. 0.107 per 100,000). Multivariate Cox analysis indicated that age (p

Additional file 1: Table S1. Association between vascular risk factor burden and severe COVID-19 illness adjusted for comorbidity, and sensitivity analyses using the E-value approach. Table S2. Association between vascular risk factor burden and severe COVID-19 illness adjusted for laboratory and chest CT findings, and sensitivity analyses using the E-value approach. Figure S1. Bias Plots

Coordination between multiple agents can be found in many areas of industry or society. Despite a few recent advances, this problem remains challenging due to its combinatorial nature. First, with an exponentially scaling action set, it is challenging to search effectively and find the right balance between exploration and exploitation. Second, performing maximization over all agents’ actions jointly is computationally intractable. To tackle these challenges, we exploit the side information and loose couplings, i.e., conditional independence between agents, which is often available in coordination tasks. We make several key contributions in this paper. First, the repeated multi-agent coordination problem is formulated as a multi-agent contextual bandit problem to balance the exploration-exploitation trade-off. Second, a novel algorithm called MACUCB is proposed, which uses a modified zooming technique to improve the context exploitation process and a variable elimination technique to efficiently perform the maximization through exploiting the loose couplings. Third, two enhancements to MACUCB are proposed with improved theoretical guarantees. Fourth, we derive theoretical bounds on the regrets of each of the algorithms. Finally, to demonstrate the effectiveness of our methods, we apply MACUCB and its variants to a realistic cloudlet resource rental problem. In this problem, cloudlets must coordinate their computation resources in order to optimize the quality of service at a low cost. We evaluate our approaches on a real-world dataset and the results show that MACUCB and its variants significantly outperform other benchmarks.

In the intestine, several phenols and aromatic acids are generated by microbiota and are highly related to the formation of uremic toxins. Herein, we developed a new derivatization reagent, 2-bromo-1-[4-(dimethylamino)phenyl] ethyl ketone (BDAPE), that reacted simultaneously with phenols and aromatic acids. Following a reaction within 2 h at 60 °C in the presence of 200 mM potassium carbonate (K2CO3), the obtained BDAPE derivatives were separated on a reversed-phase C18 column and quantified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in positive electrospray ionization mode. This method allowed a lower limit of quantification (LLOQ) of 0.090 μΜ for 3-indolepropionic acid (3IPA), indole-3-acetic acid (3IAA), p-cresol (PC), benzoic acid (BA), and phenol (PN); 0.30 μΜ for phenylacetic acid (PAA); 0.45 μΜ for 4-hydroxyphenylacetic acid (4HPAA); and 0.60 μΜ for 3-phenylpropionic acid (PPA). Methodological validation further demonstrated acceptable accuracy (%RE

Rationale Short-chain fatty acids (SCFAs) are associated with intestinal microbiota and diseases in humans. SCFAs have a low response in mass spectrometry, and in order to increase sensitivity, reduce sample consumption, shorten analysis time, and simplify sample preparation steps, a derivatization method was developed. Methods We converted seven SCFAs into amide derivatives with 4-aminomethylquinoline. The reaction occurred for 20 min at room temperature. The analytes were separated on a reversed-phase C18 column and quantitated in the positive ion electrospray ionization mode using multiple reaction monitoring. Acetic acid-d4 was used as the stable-isotope-labeled surrogate analyte for acetic acid in the working solutions, while the other stable-isotope-labeled standards were used as internal standards (ISs). Results Method validation showed that the intra-day and inter-day precision of quantitation for the seven SCFAs over the whole concentration range was ≤3.8% (n = 6). The quantitation accuracy ranged from 85.5% to 104.3% (n = 6). Most important, the collected feces were vortexed immediately with ethanol. Conclusions This study provides a new derivatization method for a precise, accurate, and rapid quantitation of SCFAs in human feces using ultra-performance liquid chromatography/tandem mass spectrometry. This method successfully determined the concentration of SCFAs in human feces and could assist in the exploration of intestinal microbiota and diseases.

In this study, we report a novel magnetic biomimetic nanozyme (Fe3O4@Cu/GMP (guanosine 5′-monophosphate)) with high laccase-like activity, which could oxidize toxic o-phenylenediamine (OPD) and remove phenolic compounds. The magnetic laccase-like nanozyme was readily obtained via complexed Cu2+ and GMP that grew on the surface of magnetic Fe3O4 nanoparticles. The prepared Fe3O4@Cu/GMP catalyst could be magnetically recycled for at least five cycles while still retaining above 70% activity. As a laccase mimic, Fe3O4@Cu/GMP had more activity and robust stability than natural laccase for the oxidization of OPD. Fe3O4@Cu/GMP retained about 90% residual activity at 90°C and showed little change at pH 3–9, and the nanozyme kept its excellent activity after long-term storage. Meanwhile, Fe3O4@Cu/GMP had better activity for removing phenolic compounds, and the removal of naphthol was more than 95%. Consequently, the proposed Fe3O4@Cu/GMP nanozyme shows potential for use as a robust catalyst for applications in environmental remediation.

Self-supporting electrodes have triggered great interests in improving electro-Fenton (EF) system for degradation of refractory organic pollutants. In this work, a novel self-supporting carbon fiber paper (CFP) electrode modified by transition metals, e.g. Fe and Mn, was fabricated and employed as a heterogeneous EF cathode. The prepared electrode exhibited excellent degradation for a number of typical organic pollutants along with superior stability. Remarkably, a high removal efficiency was achieved in the EF treatment of shale gas fracturing flowback wastewater. Results indicated that 65.2% TOC and 74.8% COD were eliminated after 4 h degradation. The residual COD value of the real wastewater was 80 mg L−1, meeting the emission requirement of the integrated wastewater discharge standard (COD ＜ 100 mg L−1) with a low specific energy consumption of 6.9 kWh kg−1 COD−1. This work demonstrates a competing alternative for efficient decontamination of real wastewater using an electro-Fenton strategy with a low-cost electrode.

Using nanomaterials to achieve functional enzyme mimics (nanozymes) is attractive for both applied and fundamental research. Laccases are multicopper oxidases highly important for biotechnology and environmental remediation. In this work, we report an exceptionally simple yet functional laccase mimic based on guanosine monophosphate (GMP) coordinated copper. It forms an amorphous metal–organic framework (MOF) material. The ratio of copper and GMP is 3:4 as determined by isothermal titration calorimetry. It has excellent laccase-like activity and converts a diverse range of phenol containing substrates such as hydroquinone, naphthol, catechol and epinephrine. Comparative work shows that the activity is originated from guanosine coordination instead of phosphate binding in GMP. Cu2+ is required and cannot be substituted by other metal ions. At the same mass concentration, the Cu/GMP nanozyme has a higher Vmax and similar Km compared to the protein laccase. To achieve the same catalytic efficiency, the cost ...

1. Among the different in vitro studies recommended by the regulatory agencies, no gold-standard model can easily and directly measure the quantitative CYP450 contributions to drug biotransformation. In this article, we propose an original strategy, called SilensomesTM, to produce human liver microsomes silenced for one specific CYP450, thanks to specific mechanism-based inhibitors (MBI). 2. Using azamulin as a specific CYP3A4 MBI, we demonstrated the proof of concept that CYP3A4 can be totally, specifically (even against 3A5) and permanently (at least for six years) inhibited by our process. Thus, comparing clearance in control and CYP3A4-SilensomesTM, CYP3A4 contributions were determined for 11 CYP3A4 substrates which correlated with known in vivo contributions and revealed accuracy with less than 10% error. In comparison, contributions determined using recombinant human CYP450 (rhCYP450s) were less accurate (more than 10% error for 30% of the tested CYP3A4 substrates). 3. This easy and ready-to-use in vitro method combines the advantages of existing models (specificity of rhCYP450s and representativeness of HLM) without their drawbacks. The same strategy could be used to silence other major CYP450s one-by-one to provide a complete direct CYP450 quantitative phenotyping kit.

Purpose To characterize the pattern of post-mastectomy supraclavicular lymph node (LN) metastases in patients with breast cancer (BC) and to provide insights for individualized clinical target volume delineation for radiotherapy. Methods We retrospectively analyzed 88 patients with BC who developed post-mastectomy regional LN metastases. The affected regional LNs were categorized as the ipsilateral medial supraclavicular LN area (IMSC-LN), ipsilateral lateral supraclavicular LN area (ILSC-LN), ipsilateral infraclavicular LN area (IIC-LN), and ≥2 groups in the ipsilateral clavicular LN area (MMIC-LN). Clinical characteristics were included in a multivariate analysis to identify risk factors for clavicular LN metastases. Results The ILSC-LNs (68.2%) were the most common metastatic site. IMSC-LN metastases showed a significant association with estrogen-receptor (ER) negative status, left-sided BC, and positive axillary LNs. Tumor size ≥2.4 cm and Her2 type were predictors of ILSC-LN metastases. Additionally, tumor size ≥2.4 cm, and level I ipsilateral axillary metastases were associated with MMIC-LN metastasis. Conclusion ILSC-LN was the most frequently affected group of supraclavicular lymph nodes. ER-negative status, left-sided BC, tumor size, and positive ipsilateral axillary LNs are potentially associated with the pattern of supraclavicular LN metastatic involvement.

Recently, increasing evidence has suggested the association between gut dysbiosis and Alzheimer's disease (AD) progression, yet the role of gut microbiota in AD pathogenesis remains obscure. Herein, we provide a potential mechanistic link between gut microbiota dysbiosis and neuroinflammation in AD progression. Using AD mouse models, we discovered that, during AD progression, the alteration of gut microbiota composition leads to the peripheral accumulation of phenylalanine and isoleucine, which stimulates the differentiation and proliferation of pro-inflammatory T helper 1 (Th1) cells. The brain-infiltrated peripheral Th1 immune cells are associated with the M1 microglia activation, contributing to AD-associated neuroinflammation. Importantly, the elevation of phenylalanine and isoleucine concentrations and the increase of Th1 cell frequency in the blood were also observed in two small independent cohorts of patients with mild cognitive impairment (MCI) due to AD. Furthermore, GV-971, a sodium oligomannate that has demonstrated solid and consistent cognition improvement in a phase 3 clinical trial in China, suppresses gut dysbiosis and the associated phenylalanine/isoleucine accumulation, harnesses neuroinflammation and reverses the cognition impairment. Together, our findings highlight the role of gut dysbiosis-promoted neuroinflammation in AD progression and suggest a novel strategy for AD therapy by remodelling the gut microbiota.

Vascular depression can respond poorly to antidepressants. This study aimed to explore the efficacy and safety of tandospirone plus escitalopram for treating vascular depression with anxiety. This pilot randomized controlled trial included consecutive inpatients/outpatients with vascular depression/anxiety at the Department of Neurology, Fujian Medical University Union Hospital, China (January 2014 to December 2016). Among 157 patients screened, 100 were randomly divided into the tandospirone + escitalopram (combination therapy) and escitalopram (monotherapy) groups equally, and then followed for 8 weeks. Efficacy was evaluated using the Hamilton Depression (HAMD), Hamilton Anxiety (HAMA), Clinical Global Impression (CGI) and Mini-Mental State examination (MMSE) scales. Adverse events (AEs) were assessed with the Treatment Emergent Symptom Scale (TESS). HAMD and HAMA scores decreased progressively, showing reductions versus baseline at 1, 2, 4 and 8 weeks in both groups (P 0.001). HAMD and HAMA scores were lower in the tandospirone + escitalopram group than those in the escitalopram group at 1 and 2 weeks (P 0.001), but not at 4 and 8 weeks. Improvements in CGI scores (severity, improvement and efficacy indexes) were greater in the tandospirone + escitalopram group than that in the escitalopram group at 1 and 2 weeks (P 0.01), but not at 4 and 8 weeks. The tandospirone + escitalopram group had higher MMSE scores than that in the escitalopram group at 4 and 8 weeks (P 0.01). All AEs were mild, and the rates were comparable between groups. Augmentation of escitalopram with tandospirone accelerates the onset of anti-depressive and anxiolytic effects and improves cognitive function in patients with vascular depression and anxiety.

Xueqing Zhang,1,* Jinluan Li,1,* Qingqin Peng,2 Yunxia Huang,1 Lirui Tang,1 Qingyang Zhuang,1 Feifei Lin,1 Xijin Lin,1 Kaixin Du,3 Junxin Wu1 1Department of Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou 350014, China; 2Department of Radiation Oncology, First Hospital of Quanzhou Affiliated to Fujian Medical University, Quanzhou 362000, China; 3Department of Radiation Oncology, Xiamen Humanity Hospital, Xiamen 361000, China *These authors contributed equally to this work Purpose: The inflammatory status of patients with cancer appears to affect cancer progression and patient prognosis. We examined the characteristics of cancer-associated systemic and local inflammation and its impact on the overall survival (OS) of patients with locally advanced rectal cancer (LARC) who received neoadjuvant radiotherapy (nRT). Patients and methods: Seventy-six consecutive LARC patients who received nRT from February 2012 to September 2015 were retrospectively analyzed. The peripheral neutrophil-to-lymphocyte ratio (NLR) was determined at diagnosis, and the CD8+ T-cell count was determined from surgical specimens. Factors associated with OS were identified by univariate and multivariate Cox regression. Results: The median follow-up time was 23.0 months (range: 2–59), and the overall 5-year OS rate was 68.6% (95% CI =46.06–91.14). Patients with a high NLR (≥2.0) and a low CD8+ T-cell count (

To evaluate whether high biologically effective dose (BED) radiotherapy improves local control and survival outcomes for patients with brain metastases (BMs) from small-cell lung cancer (SCLC) and to determine possible prognostic factors. From January 1998 to June 2018, 250 patients with BM from SCLC were retrospectively analyzed. The Cutoff Finder program was used to classify patients by BED. Overall survival (OS) and BM progression-free survival (BM-PFS) were analyzed using the Kaplan-Meier method and log-rank test. A Cox regression model was used to calculate the hazard ratio and 95% CI for prognostic factors for OS among the study population and propensity score (PS)–matched patients. A BED of 47.4 was taken as the optimal cutoff value. Both OS and BM-PFS were significantly improved in the high-BED (>47.4 Gy) than in the low-BED (≤47.4 Gy) group (median OS: 17.5 months vs 9.5 months, P < .001, median BM-PFS: 14.4 months vs 8.3 months, P < .001). Biologically effective dose ( P < .001), Eastern Cooperative Oncology Group performance status ( P = .047), smoking ( P = .005), and pleural effusion ( P = .004) were independent prognostic factors for OS. Propensity score matching with a ratio of 1:2 resulted in 57 patients in the high-BED group and 106 patients in the low-BED group. In the PS-matched cohort, OS and BM-PFS were significantly prolonged in the high-BED group compared with the low-BED group ( P < .001). Biologically effective dose >47.4 Gy improves survival among patients with BM from SCLC. Eastern Cooperative Oncology Group score, smoking, and pleural effusion independently affect OS of SCLC patients with BM.

A great number of studies have demonstrated functional abnormalities in children with attention-deficit/hyperactivity disorder (ADHD), although conflicting results have also been reported. And few studies analyzed homotopic functional connectivity between hemispheres. In this study, resting-state functional magnetic resonance imaging (MRI) data were recorded from 45 medication-naïve ADHD children and 26 healthy controls. The regional homogeneity (ReHo), degree centrality (DC) and voxel-mirrored homotopic connectivity (VMHC) values were compared between the two groups to depict the intrinsic brain activities. We found that ADHD children exhibited significantly lower ReHo and DC values in the right middle frontal gyrus and the two values correlated with each other; moreover, lower VMHC values were found in the bilateral occipital lobes of ADHD children, which was negatively related with anxiety scores of Conners' Parent Rating Scale (CPRS-R) and positively related with completed categories of Wisconsin Card Sorting Test (WCST). Our results might suggest that less spontaneous neuronal activities of the right middle frontal gyrus and the bilateral occipital lobes in ADHD children.注意缺陷多动障碍（ADHD）儿童的大脑功能异常已经被广泛报道，但是其结果存在不一致性，且半球间功能连接相关研究较少。本研究纳入了 45 名首发未用药 ADHD 儿童和 26 名正常对照儿童，进行静息态功能磁共振扫描。采用局部一致性（ReHo）、度中心性（DC）和镜像同伦功能连接（VMHC）三种测量指标对两组受试的静息态脑活动进行比较分析。发现与正常儿童相比，ADHD 儿童 ReHo 值和 DC 值在右侧额中回区域降低，且两者呈正相关；VMHC 值在双侧枕叶降低，且该改变与 Conners 父母用量表焦虑得分呈负相关，与威斯康星卡片测验正确分类数呈正相关。本研究结果提示了 ADHD 儿童右侧额中回及双侧枕叶自发神经活动的异常。.

Background Medulloblastoma (MB) is a rare central nervous system malignancy in adult. For its rarity, most previous studies are limited on patient populations and ascertainment bias. We aimed to explore the population-level trends in incidence and assess potential predictors of overall survival (OS). Methods We utilized the Surveillance, Epidemiology and End Results Program (SEER) database between 1973 and 2015, to estimate the epidemiological trends of adult MB in the United States. Propensity-score matching was used to balance potential selection biases and Cox proportional hazard modeling was used to determine predictors of OS. Results The age-adjusted incidence was stable in MB patients aged 20 years old and elder in total (annual percent change (APC)=0.15). The age-adjusted incidence rate in males was slightly higher than that in females (0.065 vs. 0.049 per 100,000). Compared to whites, the rate was nearly doubled to blacks (0.063 vs. 0.033 per 100,000). There was obvious differ between the younger group and the elder group (aged 20-39: 0.107 vs. aged≥40: 0.025 per 100,000). According to multivariable Cox analysis, age (P Conclusions From the SEER database, race, gender and age disparities were found in incidence of adult MB patients. The survival analysis demonstrated the benefits of the GTR and younger patients. As for patients without GTR, radiotherapy and chemotherapy may improve the long-term survival. Legal entity responsible for the study Feifei, Lin. Funding The Fujian Province Natural Science Foundation (2017J01260), Joint Funds for the Innovation of Science and Technology, Fujian province (2017Y9074), and the Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing (2017 Open Project-9). Disclosure All authors have declared no conflicts of interest.

1. We have applied the concept of using MBIs to produce CYP-Silensomes to quantify the contribution of the major CYPs to drug metabolism (fmCYP). 2. The target CYPs were extensively and selectivity inhibited by the selected MBIs, while non-target CYPs were inhibited by less than 20% of the homologous control activities. Only CYP2D6-Silensomes exhibited a CYP2B6 inhibition that could be easily and efficiently encountered by subtracting the fm

Graphitic carbon nitride (g-C3N4) possess great potential applications in photocatalytic wastewater purification and hydrogen production. However, its activity is moderate because of the sluggish electron transfer and insufficient light absorption. Here, a series of hydroxyl carbon quantum dots modified with fiber-like carbon nitride composites (OH-CQDs/CNF) were synthesized by a solvothermal approach to enhance the photocatalytic activity. Compared to g-C3N4, the prepared OH-CQDs/CNF exhibited significantly improved visible light absorption (UV-VIS), low recombination electron-hole pairs (PL), and dramatically enhanced conductivity (EIS). Therefore, the optimized OH-CQDs/CNF-4 composite (derived from 4 mL OH-CQDs) displayed excellent photodegradation activity, and its rate constant for tetracycline degradation was 11.3 times higher than that in the presence of g-C3N4, even higher than some noble metal or metal oxides modified g-C3N4. In addition, OH-CQDs/CNF-4 rendered around 4 times H2 evolution rate than CNF, mainly because the OH-CQDs were highly dispersed on the CNF surface and formed an intact interface through hydrogen bond interactions. Quenching experiments and ESR results indicated that ·O2− and h+ were the main free radicals generated during TC degradation. This study provides guidance for the design of hydrogen bonding-based metal-free photocatalysts for wastewater purification and hydrogen evolution.

Background To compare the effects of high biologically effective dose (BED) and low BED radiotherapy for small cell lung cancer (SCLC) with brain metastases (BMs), and identify the prognostic factors of survival. Methods A total of 250 consecutive SCLC (stage II-IV) with BMs patients in our institution were retrospectively analyzed, from January 1998 to June 2018. Preliminary screening of the prognostic factors was accomplished by Kaplan-Meier univariate analysis. Baseline covariates were balanced by a propensity score model. And survival curves between the two groups were compared by the log-rank test. The Cox regression model was used to analyze factors associated with prognosis. Results The Cutoff Finder program exported an optimal BED cutoff value of 47 for all patients. The high-BED (>47 Gy) group had a significantly better OS than low-BED (≤47 Gy) group (median OS: 17.5 vs. 9.5, P Conclusions BED, smoking, ECOG score, age were observed to affect the OS of SCLC patients with BMs. High BED radiotherapy (>47 Gy) might improve long-term survival. Legal entity responsible for the study Qingyang, Zhuang. Funding The Fujian Province Natural Science Foundation (2017J01260), Joint Funds for the Innovation of Science and Technology, Fujian province (2017Y9074), and the Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education/Beijing (2017 Open Project-9). Disclosure All authors have declared no conflicts of interest.

The 0.50-mm-thick Fe81Ga19 sheets were produced by rolling procedure, and texture evolution was investigated using macro- and microtexture analyses. The recrystallization texture dominated with strong η fiber (〈001〉//RD) was successfully obtained through sheet thickness by primary recrystallization annealing. The η fiber development can be attributed to the advantage in both grain number and grain size derived from the specially applied rolling process.

Iron titanium oxide (Fe 1.5 Ti 0.5 O 3 ) nanoparticles with the diameter of about 150 nm were prepared by hydrothermal process and further heat treatment at 300 °C for 2 h. The morphology, structure and electrochemical performance of Fe 1.5 Ti 0.5 O 3 nanoparticles as anode material for lithium-ion batteries were investigated by scanning electron microscopy, X-ray diffraction and a variety of electrochemical testing techniques. It was found that, compared with TiO 2 and Fe 2 O 3 , the iron titanium oxide electrode exhibited higher specific capacity of 734.9 mAh g −1 after 50 cycles at the current density of 50 mA g −1 , good cycle stability and high-rate performance, suggesting that the Fe 1.5 Ti 0.5 O 3 nanoparticle synthesized by this method is a promising anode material for lithium-ion batteries.

To explore the smoking status and related influence factors among female sex workers (FSW) and general migrant women (GMW) in Shanghai City, and provide references for health intervention.A total of 721 FSW and 675 GMW, recruited by a multiple stage cluster sampling method from Minhang District, Shanghai city, were interviewed. Socio-demographic characteristics and the smoking status were collected by questionnaire interview, while the quality of life (QOL) among participants were evaluated by WHOQOL-BREF.The smoking rate within FSW (39. 1%) was significantly higher than GMW (2.7%). When compared with GMW, QOL scores among FSW were signifiantly lower in four domains ( physio-domain F = 55. 50, P0. 001, psychi-domain F =59. 07, P0. 001, social relationship domain F = 157. 46, P0. 001 and environmental domain F = 65. 08, P0. 001). The multivariate analysis showed that higher score of psychi-domain (OR = 0. 893, 95% CI 0. 839 - 0. 950), married (OR =0. 590, 95% CI 0. 395 - 0. 880), older age group (OR =0. 590, 95% CI 0. 395 - 0. 880) and GMW (OR = 0. 077, 95% CI 0. 043 - 0. 141.) were protecting factors for smoking, whereas not having a permant partner (OR = 1. 610, 95% CI 1. 114 - 2. 328), staying in Shanghai ≤ 1 year (OR = 1. 537, 95% CI 1. 109 - 2. 132) and low income group (OR = 1. 956, 95% CI 1. 445 - 2. 650) were risk factors for smoking.The rate of smoking is significantly higher in FSW, when compared: with GMW. The effective preventive strategies which concentrate on the influence factors should be taken to reduce smoking in the target population.

Background HIV related stigma is a recognized barrier to early detection of HIV and causes great suffering for those affected. However, data regarding HIV related stigma among female sex workers (FSW) in China was limited, with none for comparison between FSW and general migrant women (GMW). Therefore, the aim of this study was to examine HIV related stigma among FSW and GMW in Shanghai, China. Methods A community based cross-sectional study with face-to-face interviews was conducted in Shanghai (September 2011 through December 2012), using a structured questionnaire.HIV related stigma scores were examined graphically using boxplot. A logistic regression analysis with the proportional odds model was employed to identify factors affecting HIV related stigma scores. Results A total of 1,396 subjects, including 721 FSW and 675 GMW, were recruited in the present study. Both groups had substantial misconceptions about HIV/AIDS, although FSW had slightly higher scores on average. Both groups showed a medium level of HIV related stigma (38.34 ± 6.21 and 38.35 ± 6.86 for FSW and GMW, respectively). For the FSW, higher levels of stigma were observed for those who were in the older age groups (age 26-35 years, OR, 2.06, 95% CI 1.06-4.01), those who were married (OR, 1.62, 95% CI 1.03-2.54), and those who were working at lower-level sex service sites (OR, 1.60, 95% CI 1.06-2.43). Conversely, HIV knowledge was inversely associated with the level of HIV related stigma (OR, 0.93, 95% CI 0.87-0.98).Among GMW participating in the study, those age in the 26-35 years were more likely to show higher level of stigma (OR, 2.61, 95% CI 1.03-2.54), and HIV knowledge was found to be inversely associated with the HIV related stigma level as well (OR, 0.89, 95% CI 0.84-0.95). Conclusions The present study suggests that there is an urgent need for the development of appropriate education strategies to reduce HIV related stigma among FSW and GMW in Shanghai, China. In particular, older women, less educated women, and women that have lived in Shanghai a relatively long time should be targeted in future stigma reduction programs. Electronic supplementary material The online version of this article (doi:10.1186/s12905-014-0160-3) contains supplementary material, which is available to authorized users.

The aim was to investigate the relationship between apparent diffusion coefficient (ADC) values measured by diffusion-weighted magnetic resonance imaging (DW MRI) and the split glomerular filtration rate (GFR) in infants with congenital hydronephrosis. Diffusion-weighted imaging (DWI) (b = 0 and 700 seconds/mm(2)) was performed with a General Electric Company (GE) Signa 1.5T MR unit in 46 infants suffering single congenital hydronephrosis and in 30 healthy infants as normal control group. The ADCs were calculated with regions of interest (ROIs) positioned in the renal parenchyma. The 46 obstructed kidneys were classified into four groups according to the GFR level: renal dysfunction compensated group, renal dysfunction decompensated group, renal failure group, and uremia group. The renal ADCs in six groups (normal kidneys in control group, contralateral kidneys, and four groups of hydronephrotic kidneys) were compared statistically using analysis of variance (ANOVA), and the correlative relationship between ADCs and GFR was examined by Pearson's correlation test. There were statistically significant differences in renal ADCs among the six groups. The ADCs of hydronephrotic kidneys were lower than that of the normal kidneys. There was a moderate positive correlation between the ADCs of hydronephrotic kidneys and split GFR (r = 0.744). This study indicated that the ADCs of congenital hydronephrotic kidneys were lower than that of normal renal parenchyma, and there was a positive correlation between the ADCs and split renal GFR, which demonstrates that the ADCs can reflect the filtration function of hydronephrotic kidneys and may provide some reference to help clinical physician to explore a novel noninvasive approach to evaluate the single renal function.

Background Limited information on epidemiologic patterns of KSHV, with none focusing on heterosexual transmission, is available in mainland China. To clarify this, a cross-sectional study was conducted among a group of female sex workers (FSW) and general population women (GW) in Shanghai, China. Methods An anonymous questionnaire interview was administrated among 600 FSW and 600 GW. Blood samples were collected and tested for antibodies to KSHV, HSV-2, HIV, syphilis and HBsAg. Correlates of KSHV and HSV-2 were examined using multiple logistic regression analysis. Results None of the study participants were tested positive for HIV. The seroprevalence of KSHV, HSV-2 , HBV and syphilis was 10.0%, 52.2%, 12.3% and 10.5%, respectively for FSW, and was 11.0%, 15.3%, 9.8% and 2.8%, respectively for GW. KSHV seropositivity was not associated with syphilis and HSV-2 infection as well as sexual practices among either FSW or GW. Nevertheless, HSV-2 infection among FSW was independently associated with being ever married (OR = 1.59; 95%CI: 1.04-2.45), >5 years of prostitution (OR = 2.06; 95%CI: 1.16-3.68) and being syphilis positive (OR = 2.65; 95%CI: 1.43-4.93). HSV-2 infection among GW was independently associated with an age of >35 years (OR = 2.29; 95%CI: 1.07-4.93), having had more than 2 sex partners in the prior 12 months (OR = 6.44; 95%CI: 1.67-24.93) and being syphilis positive (OR = 3.94; 95%CI: 1.38-11.23). A gradual increase of prevalence with the prostitution time group was also detected for HSV-2 and syphilis, but not for KSHV. Conclusions KSHV is moderately and equivalently prevalent among FSW and GW. Heterosexual contact is not a predominant route for KSHV transmission among Chinese women.

We have critically examined the kinetics of latex film formation using an atomic force microscope to obtain corrugation height data as a function of time, temperature, molecular weight, particle size, etc. The results show that the film forming process obeys viscoelastic time/ temperature superposition principles, thus indicating a direct relationship between the kinetics of film formation and rheological properties. Film formation kinetics are examined under ‘wet’ and ‘dry’ conditions, with film formation occurring almost ten-times faster under wet conditions than dry. This proves for the latex system examined that capillary pressure from the water meniscus is the dominant driving stress for film formation. Past theories for latex film formation are reviewed, and problems and deficiencies are noted. A new theory for film formation from a dry latex system is presented, which is based on the use of the Boltzmann Superposition Principle to relate the changing stress and strain fields as the latex particles deform. The predictions of theory and the experimental data show excellent agreement over nearly four decades of time.

In this second paper of a series dealing with the film-forming behavior of latex systems, we show the relationship between the kinetics of film formation and rheological properties. The kinetics of...

BACKGROUND: Transplantation with bone marrow-derived mesenchymal stem cells (BMSCs) improves the survival of neurons and axonal outgrowth after stroke remains undetermined. Here, we investigated whether PI3K/AKT signaling pathway is involved in these therapeutic effects of BMSCs. METHODOLOGY/PRINCIPAL FINDINGS: (1) BMSCs and cortical neurons were derived from Sprague-Dawley rats. The injured neurons were induced by Oxygen-Glucose Deprivation (OGD), and then were respectively co-cultured for 48 hours with BMSCs at different densities (5×10(3), 5×10(5)/ml) in transwell co-culture system. The average length of axon and expression of GAP-43 were examined to assess the effect of BMSCs on axonal outgrowth after the damage of neurons induced by OGD. (2) The injured neurons were cultured with a conditioned medium (CM) of BMSCs cultured for 24 hours in neurobasal medium. During the process, we further identified whether PI3K/AKT signaling pathway is involved through the adjunction of LY294002 (a specific phosphatidylinositide-3-kinase (PI3K) inhibitor). Two hours later, the expression of pAKT (phosphorylated AKT) and AKT were analyzed by Western blotting. The length of axons, the expression of GAP-43 and the survival of neurons were measured at 48 hours. RESULTS: Both BMSCs and CM from BMSCs inreased the axonal length and GAP-43 expression in OGD-injured cortical neurons. There was no difference between the effects of BMSCs of 5×10(5)/ml and of 5×10(3)/ml on axonal outgrowth. Expression of pAKT enhanced significantly at 2 hours and the neuron survival increased at 48 hours after the injured neurons cultured with the CM, respectively. These effects of CM were prevented by inhibitor LY294002. CONCLUSIONS/SIGNIFICANCE: BMSCs promote axonal outgrowth and the survival of neurons against the damage from OGD in vitro by the paracrine effects through PI3K/AKT signaling pathway.

We discuss mechanisms that have been proposed for film formation from latex systems and point out that major problems exist, in that the relative role played by the water/air, the polymer/air, and the polymer/water interfacial tensions in promoting film formation has not been established. Even the relative role played by plasticization of latex polymers by water has remained as an unanswered question. In order to clarify this problem, we have investigated the rate of film formation of wet and dry latex systems by atomic force microscopy. The role of the water surface tension (in creating a capillary pressure) was clearly revealed by forming a wet latex system through condensation of water into the interstitial space of initially dry latex particles. Poly(iso-butyl methacrylate) (PiBMA) was used as the model latex because of its appropriate glass transition temperature, T g ∼ 65 °C, and its hydrophobic character. The rate of film formation (at 70°C) was found to be approximately 10-times faster under wet conditions than when dry. Separate experiments showed that T g of PiBMA was unaffected by water, and hence plasticization was not a factor in the enhanced rate. These results clearly show in this system that the dominant factor in promoting film formation was the water surface tension and resulting negative capillary pressure. Furthermore, it is shown that the capillary pressure in wet systems can be of sufficient magnitude to explain the observed deformation of the latex particles at 50 °C, i.e., 15 °C below T g . Capillary pressures and forces increase with decreasing amounts of water in the interstitial regions of spherical particles, and capillary pressures can reach very high values with seemingly insignificant amounts of water. The equilibrium between the amount of interstitial water and the relative humidity of the atmospheric water is shown, and it indicates that even with low relative humidities the capillary pressures can still be quite large. We maintain that capillary pressure typically is the dominant driving force for film formation. These results are in contrast to the conclusions of others.

Background This study was performed to determine whether injury induced by cerebral ischemia could be further improved by transplantation with bone marrow-derived mesenchymal stem cells (MSCs) modified by Survivin (SVV). Methods MSCs derived from bone marrow of male Sprague-Dawley rats were infected by the self-inactive lentiviral vector GCFU carrying green fluorescent protein (GFP) gene and SVV recombinant vector (GCFU-SVV). In vitro, vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected in infected MSCs supernatants under hypoxic conditions by ELSIA. In vivo, experiments consisted of three groups, one receiving intravenous injection of 500 μl of phosphate-buffered saline (PBS) without cells (control group) and two groups administered the same volume solution with either three million GFP-MSCs (group GFP) or SVV/GFP-MSCs (group SVV). All animals were submitted to 2-hour middle cerebral artery occlusion (MCAO) and then reperfusion. Differentiation and survival of the transplanted MSCs were determined by confocal microscope. Western blot was used to detect the expression of VEGF and bFGF in ischemic tissue. A 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to assess the infarct volume. Evaluation of neurological function was performed using a modified Neurological Severity Score (mNSS). Results In vitro, modification with SVV further increased secretion of VEGF and bFGF under hypoxic condition. In vivo, only very few transplantated cells co-expressed GFP and NeuN. The survival transplanted cells in the group SVV was 1.3-fold at 4 days after transplantation and 3.4-fold higher at 14 days after transplantation, respectively, when compared with group GFP. Expression of VEGF and bFGF in the ischemic tissue were further up-regulated by modification with SVV. Moreover, modification with SVV further reduced the cerebral infarct volume by 5.2% at 4 days after stroke and improved post-stroke neurological function at 14 days after transplantation. Conclusion Modification with SVV could further enhance the therapeutic effects of MSCs possibly through improving the MSCs survival capacity and up-regulating the expression of protective cytokines in the ischemic tissue.