Search

Jinmeng Li, Xinjun Cai, Yingying Xu, Ruoying Zhang Department of Pharmacy, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310000, People’s Republic of ChinaCorrespondence: Ruoying Zhang, Department of Pharmacy, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310000, People’s Republic of China, Email hzhhzry@163.comAbstract: Aspergillus tubingensis spondylitis (AS) is a rare spinal infectious disease with severe clinical symptoms and a challenging diagnosis. Treatment of AS is challenging due to its prolonged duration, substantial side effects, and complex drug–drug interactions. However, there is a lack of experience in individualized pharmaceutical care of AS by clinical pharmacists, especially in the presence of rifampicin, which has sustained liver enzyme induction after discontinuation. Our case described an immunocompetent patient infected with Aspergillus tubingensis spondylitis. Clinical pharmacists proposed an individualized treatment regimen for AS, after considering the effects of sustained liver enzyme induction of rifampicin (after discontinuation) on voriconazole, and utilized caspofungin as a bridge-connection scheme. We also paid attention to changes in indicators during treatment and managed adverse reactions. Therapeutic drug monitoring of voriconazole was also used to optimize the dosing regimen. With the individualized pharmaceutical care of clinical pharmacists and the efforts of clinicians, the patient’s incision healed well after 33 days of hospitalization, and she was discharged with significant improvement. Therefore, individualized pharmaceutical care by a clinical pharmacist can help optimize the treatment of Aspergillus tubingensis spondylitis. In clinical practice, drug–drug and drug–diet interactions may affect voriconazole efficacy, and individualized dose adjustment using therapeutic drug monitoring (TDM) is critical to improve efficacy and reduce adverse reactions.Keywords: individualized pharmaceutical care, Aspergillus tubingensis spondylitis, enzyme-induction effect of rifampin, voriconazole, case report

Additional file 1: Figure S1.Relationship between ARHGAP39 expression and clinicopathological parameters. Figure S2. Kaplan-Meier curve ofARHGAP39 in breast cancer. Figure S3.ARHGAP39 promotes breast cancer cell colony formation and wound healingability. Figure S4. Subcellularlocation of ARHGAP39. Figure S5.Relationship between ARHGAP39 co-expressed genes and the immune cellinfiltration level. Figure S6.Relationship between ARHGAP39 and immune cell marker gene of macrophage inTIMER. Figure S7. The protein-protein interactions network of ARHGAP39.

Additional file 1. Original images of western blotting.

Inhalable messenger RNA (mRNA) has demonstrated great potential in therapy and vaccine development to confront various lung diseases. However, few gene vectors could overcome the airway mucus and intracellular barriers for successful pulmonary mRNA delivery. Apart from the low pulmonary gene delivery efficiency, nonnegligible toxicity is another common problem that impedes the clinical application of many non-viral vectors. PEGylated cationic peptide-based mRNA delivery vector is a prospective approach to enhance the pulmonary delivery efficacy and safety of aerosolized mRNA by oral inhalation administration. In this study, different lengths of hydrophilic PEG chains were covalently linked to an amphiphilic, water-soluble pH-responsive peptide, and the peptide/mRNA nano self-assemblies were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The in vitro mRNA binding and release, cellular uptake, transfection, and cytotoxicity were studied, and finally, a proper PEGylated peptide with enhanced pulmonary mRNA delivery efficiency and improved safety in mice was identified. These results showed that a proper N-terminus PEGylation strategy using 12-monomer linear monodisperse PEG could significantly improve the mRNA transfection efficiency and biocompatibility of the non-PEGylated cationic peptide carrier, while a longer PEG chain modification adversely decreased the cellular uptake and transfection on A549 and HepG2 cells, emphasizing the importance of a proper PEG chain length selection. Moreover, the optimized PEGylated peptide showed a significantly enhanced mRNA pulmonary delivery efficiency and ameliorated safety profiles over the non-PEGylated peptide and LipofectamineTM 2000 in mice. Our results reveal that the PEGylated peptide could be a promising mRNA delivery vector candidate for inhaled mRNA vaccines and therapeutic applications for the prevention and treatment of different respiratory diseases in the future. Schematic illustration of proper PEGylation strategy of pH-responsive LAH4-L1 peptide-mRNA nano self-assemblies enhances the pulmonary delivery efficiency of aerosolized mRNA.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of global cancer-related mortality and the most common form of liver cancer. REXO4 (RNA exonuclease 4 homolog) downregulation has previously been linked to enhanced chemosensitivity in breast cancer cells. The present study sought to comprehensively clarify the functional role of REXO4 in HCC. METHODS: REXO4 expression levels in HCC tumor tissues and control tissue samples were established by analyzing data from the Gene Expression Omnibus (GEO) database. The expression of REXO4 was then knocked down in HCC cell lines to explore its functional role in these cells, while a gene set enrichment analysis (GSEA) approach was used to assess the functional regulator network associated with REXO4, and the Cell type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) algorithm was used to determine the relationship between this gene and immune cell infiltration of tumor tissues. The relationship between REXO4 and metabolic pathway was analyzed by oil red O staining. Cell Counting Kit-8 assays, colony formation, wound-healing assay, and a nude mouse subcutaneous tumor model were used to evaluate the function of REXO4 in HCC. RESULTS: REXO4 was highly upregulated in HCC tumors and cell lines, and was an effective predictor of HCC patient prognosis. The results indicated that the knockdown of REXO4 inhibited the proliferation and progression of HCC in vitro and in vivo. GSEA approaches also revealed REXO4 to be associated with tumor progression. Furthermore, REXO4 was associated with the degree of increase of intratumoral immune cell infiltration in HCC tissues and cells, and this gene was also linked with altered lipid metabolism in HCC cells. CONCLUSIONS: In summary, these analyses revealed REXO4 to be upregulated in HCC and to be associated with poor patient prognosis. In addition, this gene was closely linked to key cancer hallmark pathways and was revealed to play an important role in the susceptibility of liver tumors to immune cell infiltration and activation. Thus, targeting REXO4 may be a promising approach to treating patients with HCC in the near future.

The aim of this study is to investigate the efficacy of treatment-combined electrocauterization after removal of apocrine sweat glands with ultrasound-guided (BOTOX) injection for adolescents with axillary bromhidrosis. From January 2015 to January 2018, 90 adolescents with axillary bromhidrosis were recruited and randomly divided into three groups (group A, B, and C). Patients in group A underwent electrocauterization after removal of apocrine sweat glands, patients in group B received ultrasound-guided BOTOX injection, and patients in group C had electrocauterization after the removal of apocrine sweat glands followed by ultrasound-guided BOTOX administration after two weeks. All patients were followed up for one year. The percentages of axillary malodor score at twelve months after treatments compared with pre-operation for group A, group B, and group C were 20.2%, 27.5%, and 12.5%, respectively. Significant statistical differences were observed in changes of axillary malodor score among the three groups at three, six, nine and twelve months postoperatively. Satisfaction rates of group A, group B, and group C were 90.0%, 93.3%, and 96.7%, respectively. The side effects after surgery in group A were similar to group C, and no side effect was observed in group B. One-year postoperative scar formation rate of group A was 16.7%, which was significantly higher than that of group B (0) and group C (6.66%). Combination of electrocauterization after removal of apocrine sweat glands with ultrasound-guided BOTOX injection showed better treatment effects.

Bladder cancer (BLCA) remains the leading cause of cancer‐related mortality among genitourinary malignancies worldwide. BLCA metastasis represents the primary reason for its poor prognosis. In this study, we report that decreased expression of partitioning defective 3 (Par3), a polarity protein (encoded by PARD3), is associated with tumor aggressive phenotypes and poor prognosis in BLCA patients. Consistently, ablation of Par3 promotes the metastasis and invasion of BLCA cells in vitro and in vivo. Further studies reveal that zinc finger protein Snail represses the expression of Par3 by binding to E2‐box (CAGGTG) of PARD3 promoter‐proximal. Inhibition of GSK‐3β promotes the expression and nuclear localization of Snail and then reduces the expression of Par3, resulting in the metastasis and invasion of BLCA cells. Moreover, we detected the interaction between Par3 (936‐1356 aa) and ZO‐1 (1372‐1748 aa), which is involved in the maintenance of tight junction. Together, our results demonstrate that the GSK‐3β/Snail/Par3/ZO‐1 axis regulates BLCA metastasis, and Snail is a major regulator for Par3 protein expression in BLCA., We report here that (a) polarity protein Par3 is frequently lost in BLCA patients and is associated with muscle‐invasive phenotypes and poor prognosis; (b) Par3 deficiency is required for BLCA invasion and metastasis in vitro and in vivo; (c) Snail suppresses Par3 expression through its binding to PARD3 E2‐box; and (d) overexpression of Par3 abolishes LiCl‐ or Snail‐induced BLCA metastatic behaviors, suggesting a role of the GSK‐3β/Snail/Par3 axis in regulating BLCA metastasis.

It is difficult to study the intestinal damage induced by space radiation to astronauts directly, and few prediction models exist. However, we can simulate it in patients with pelvic tumor radiotherapy (RT). Radiation-induced intestinal injury (RIII) is common in cancer patients who receieved pelvic and abdominal RT. We dynamically analyzed gut microbiota and metabolites alterations in 17 cervical and endometrial cancer patients after pelvic RT. In patients who later developed grade 2 RIII, dysbiosis of gut microbiota and metabolites were observed. Univariate analysis showed that Erysipelatoclostridium and ptilosteroid A were related to the occurrence of grade 2 RIII. Notably, a strong positive correlation between gut bacteria Erysipelatoclostridium relative abundance and gut metabolite ptilosteroid A expression was found. Furthermore, combinations of Erysipelatoclostridium and ptilosteroid A could provide good diagnostic markers for grade 2 RIII. In conclusion, gut bacteria Erysipelatoclostridium and its related metabolite ptilosteroid A may collaboratively predict RIII, and could be diagnostic biomarkers for RIII and space radiation injury.

Cone-Beam Computed Tomography (CBCT) has been proven useful in diagnosis, but how to shorten scanning time with lower radiation dosage and how to efficiently reconstruct 3D image remain as the main issues for clinical practice. The recent development of tomographic image reconstruction on sparse-view measurements employs deep neural networks in a supervised way to tackle such issues, whereas the success of model training requires quantity and quality of the given paired measurements/images. We propose a novel untrained Transformer to fit the CBCT inverse solver without training data. It is mainly comprised of an untrained 3D Transformer of billions of network weights and a multi-level loss function with variable weights. Unlike conventional deep neural networks (DNNs), there is no requirement of training steps in our approach. Upon observing the hardship of optimising Transformer, the variable weights within the loss function are designed to automatically update together with the iteration process, ultimately stabilising its optimisation. We evaluate the proposed approach on two publicly available datasets: SPARE and Walnut. The results show a significant performance improvement on image quality metrics with streak artefact reduction in the visualisation. We also provide a clinical report by an experienced radiologist to assess our reconstructed images in a diagnosis point of view. The source code and the optimised models are available from the corresponding author on request at the moment., 12 pages, 6 figures, 2 tables

Additional file 2: Figure S1. Small-molecule cocktails induced DE differentiation from hPSCs. Sequential morphologic changes in the differentiation of hPSCs into DE. Scale bars 100 μm. Figure S2. Small-molecule cocktails directed hepatic specification. Immunostaining analyses of AFP and HNF4α expression after different small molecule cocktails induced. Figure S3. Generation of HBs from human iPSC line. Immunostaining analyses results showed that human iPSC line (UC15) could sequentially differentiate into DE cells and HBs with high efficiency similarity as previous hESC line H1, and expressed stage specific markers.

Supplemental material, sj-pdf-1-cpj-10.1177_00099228221128375 for An Assessment of a Socioeconomic Risk Screening Tool for Telemedicine Encounters in Pediatric Primary Care: A Pilot Study by Elizabeth Ireson, Mary Carol Burkhardt, Dominick DeBlasio, Yingying Xu, Jessica Walters, Tasha Johnson and Melissa Klein in Clinical Pediatrics

Background. The NLRP3 inflammasome is overactivated in the brains of APP/PS1 transgenic mice and AD patients, and mitophagy has an obvious negative regulatory role on NLRP3 inflammasome activation. The protective effect of melatonin in AD may be related to the regulation of mitophagy and NLRP3 inflammasome activity. TFEB plays a critical role in maintaining autophagy/mitophagy. Studies have found that TFEB plays a protective role in AD. Methods. APP/PS1 transgenic mice were given melatonin in their drinking water for 3 months. Compared with mice without melatonin treatment, the mice given melatonin showed changes in the following features: (1) cognitive function, (2) mitophagy-related proteins in the brain, (3) ROS, (4) NLRP3 inflammasome and related proteins and the concentrations of inflammatory cytokines, and (5) Aβ deposition. In in vitro experiments, effects of melatonin on mitophagy, NLRP3 inflammasome activity, and TFEB in SH-SY5Y cells with Aβ25-35 were observed. TFEB knockdown was implemented in combination with Aβ25-35 and melatonin treatment, and the expressions of TFEB, Parkin, p62, IL-1β, caspase-1, ROS, and IL-18 were explored. Results. Melatonin improved cognitive function in APP/PS1 transgenic mice and decreased ROS and senile plaques. Melatonin promoted mitophagy in SH-SY5Y cells with Aβ25-35 and APP/PS1 transgenic mice. NLRP3 inflammasome activity was inhibited, and the concentrations of IL-18 and IL-1βwere clearly reduced. Compared with C57/BL6J mice, the amount of TFEB in the brain nucleus of APP/PS1 transgenic mice was decreased. Melatonin treatment increased the nuclear translocation of TFEB in SH-SY5Y cells. TFEB knockout was implemented in combination with Aβ25-35 and MT treatment; the expressions of Parkin, p62, caspase-1, IL-1β, IL-18, and ROS were accelerated. Conclusions. Melatonin promotes mitophagy by inducing TFEB nuclear translocation, downregulates NLRP3 inflammasome activation, and exerts protective effects in SH-SY5Y cells and APP/PS1 transgenic mice.

Spin flash drying equipment is widely used in chemical, food and other fields. Drying process consumes large amounts of energy and reduction in operating cost will be extremely beneficial for the industry. Therefore, in order to improve the efficiency of spin flash dryer. A three-dimensional CFD model of the drying process was established by computational fluid dynamics, and the flow field characteristics and heat transfer mechanism of the drying process were obtained. We studied the specific effects of different parameters on the drying process, and verified the results with calcium carbonate as raw material. The experimental results are basically consistent with the simulation results. The velocity, temperature and pressure in the drying chamber near the wall are greater than those in the central region, which generally decrease with height. The speed of the cutter set has a large effect on the tangential and radial velocity, but the influence on the pressure drop is not significant. Meanwhile the temperature and velocity of inlet air have a greater impact on distribution of flow field and material drying, the variable structure improves the stability of the drying process.

In order to depict the impact of rainfall on phreatic evaporation, this study analyzes phreatic evaporation and the phreatic evaporation coefficient between surface evaporation and soil depth in Shajiang black soil and Fluyo-aquic soil. We have improved the existing commonly used mathematical framework, established two rainless day phreatic evaporation calculation models, and then calculated the calculation model of the phreatic evaporation reduction on rainy days. Finally, rainy day evaporation calculation models on two soils were proposed. The results show that the evaporation coefficient is affected by both depth and the evaporation ability of the surface water. The evaporation reduction of Shajiang black soil increased with depth and the increasing trend gradually slowed down until it approached zero. The evaporation reduction of the Fluyo-aquic soil phreatic decreased first and then increased with depth, reaching a minimum at 0.4 m. The reduction of phreatic evaporation in both soils decreased with the increase in rainfall level and decreased with the increase in rainfall duration showing ‘inverted S-type’. In summary, the phreatic evaporation composite calculation models on rainy days and rainless days have good fitting and prediction results, which can improve the accuracy of phreatic evaporation calculations. HIGHLIGHTS How the water table depth and surface evaporation influence phreatic evaporation was determined.; The exponential calculation models of phreatic evaporation under rainless conditions were established.; The decrease in phreatic evaporation when the level of rainfall and rainfall duration increased.; The model of phreatic evaporation under rainfall conditions was established.

The product could not be effectively expanded and the puffing temperature was too high, which usually occurred during the explosion puffing drying process of fruits and vegetables. CO2 high-pressur...

Since the traditional methods such as statistical analysis are used to analyze the long-term nursing service strategy more, and no association rule method is used to solve the problems encountered in the development of long-term nursing service. This paper aims to provide some data support for the establishment of a scientific and reasonable long-term nursing information system by synthesizing the basic national conditions and drawing lessons from foreign experience. Therefore, in order to improve the analytical accuracy of multidimensional multi-model data, minimal rule which includes rules with single item as the consequent and the minimal number of items as the antecedent, can be introduced to derive the same decisions as other association rules without information loss, while the number of minimal rules is much less than of all rules. From these association rules, it can be known that diabetes has a strong association with coronary heart disease, hypertension, fatty liver, chronic arterial occlusive disease, abnormal lipid metabolism and other diseases; according to the analysis of the antecedent and consequence in the results table of the above association rules, it can be found that diabetes is highly likely to cause hypertension, coronary heart disease, abnormal lipid metabolism, fatty liver, and there is a close relationship between various complications.

Retroperitoneal liposarcoma (RPLS) is a very rare type of tumor, accounting for less than 1% of all malignancies, especially the “large retroperitoneal liposarcoma” (GRPLS) of more than 20 kg (kilograms). Herein, we describe the treatment experience in a case of recurrent GRPLS. A 70-year-old woman was admitted with an enlarged abdomen, and computed tomography (CT) showed a large, low-density, homogeneous retroperitoneal mass (40×37×26 cm). In laparotomy, this 55×40×20 cm liposarcoma was completely removed and pathologically diagnosed as low-grade myxoid liposarcoma. The patient did not receive any adjuvant therapy, and CT showed no evidence of recurrence during follow-up.

Objectives Our study aimed to explore the clinical therapeutic effects of ultrasound-guided five-point injection of botulinum toxin type A for patients with trapezius hypertrophy. Methods Twenty female patients diagnosed with trapezius hypertrophy were enrolled in this study. The thicknesses of the trapezius muscle were measured by using the ultrasound scanner to locate the thickest point of trapezius, followed by labelling the other four points around the first point. Botulinum toxin type A was injected bilaterally (50 IU/side, 5 points/side) in the trapezius muscle of these patients. The surgery effects were evaluated by thicknesses of the trapezius muscle, intramuscular needle electromyographic and electroneurographic examinations, appearance changes and patients’ satisfactions. Results Statistically significant differences in thicknesses of the trapezius muscle were observed at 4 weeks (p p p p = 0.011), 36 weeks (p = 0.022), and 44 weeks (p = 0.032) after surgery. The latencies of trapezius muscle became longer at 12 weeks after surgery (left: 2.40 ms, right: 2.53 ms vs. left: 1.75 ms, right: 2.00 ms). Electroneurographic results showed amplitude reduction of compound muscle action potentials (CMAPs) at 12 weeks after surgery (left: 1.91 uV, right: 3.10 uV vs. left: 15.00 uV, right: 15.40 uV). Obvious appearance changes were revealed at 12 weeks after surgery. All of 80% patients were very satisfied, 15% patients were relatively satisfied, and 5% patients were not satisfied with the surgery. Conclusion Ultrasound-guided five-point injection of botulinum toxin type A might be effective for patients with trapezius hypertrophy.

Purpose Paclitaxel, belongs to tubulin-binding agents (TBAs), showed a great efficacy against breast cancer via stabilizing microtubules. Drug resistance limits its clinical application. Here we aimed to explore a role of Polarity protein Par3 in improving paclitaxel effectiveness.Methods Breast cancer specimens from 45 patients were collected to study the relationship between Par3 expression and paclitaxel efficacy. The Kaplan–Meier method was used for survival analysis. Cell viability was measured in breast cancer cells (SK-BR-3 and T-47D) with Par3 over-expression or knockdown. The flow cytometry assays were performed to measure cell apoptosis and cell cycle. BrdU incorporation assay and Hoechst 33258 staining were performed to measure cell proliferation and cell apoptosis, respectively. Immunofluorescence was used to detect microtubule structures. Results Par3 expression is associated with good response of paclitaxel in breast cancer patients. Consistently, Par3 overexpression significantly sensitizes breast cancer cells to paclitaxel by promoting cell apoptosis and reducing cell proliferation. In Par3 overexpressing cells upon paclitaxel treatment, we observed intensified cell cycle arrests at metaphase. Further exploration showed that Par3 overexpression stabilizes microtubules of breast cancer cells in response to paclitaxel, and resists to microtubules instability induced by nocodazole, a microtubule-depolymerizing agent. Conclusion Par3 facilitates polymeric forms of tubulin and stabilizes microtubule structure, which aggravates paclitaxel-induced delay at the metaphase-anaphase transition, leading to proliferation inhibition and apoptosis of breast cancer cells. Par3 has a potential role in sensitizing breast cancer cells to paclitaxel, which may provide a more precise assessment of individual treatment and novel therapeutic targets.

This study aims to significantly improve the performance of the centrifugal pump by designing a wedge grooves on the outside of the impeller cover, and investigating the method for determining the blade outlet angle that plays important roles in the energy conversion. The solidliquid two-phase flow fields with the designed pump and an original pump were numerically simulated in the ANSYS-FLUENT. Compared with the original pump, reducing the blade outlet angle can effectively improve the sand-water wear on the blade surface and opening wedge grooves can slow down impeller ring wear. The head of the improved model pump decreases by about 1.5% and the efficiency increases by about 1.5%.

Large quantities of hazardous activated petroleum waste sludge and wastewaters are generated from petroleum refining. The present disposal of the sludge via incineration or landfill may cause secondary pollution as well as additional costs. Treatment of petroleum refinery wastewater (PRW) by catalytic ozonation process (COP) remains a great challenge of developing low-cost and high-efficiency catalysts. Use of waste sludge derived biochar as catalysts in COP of PRW not only solves the solid wastes and wastewaters problems but also improves profitability. The elements of carbon (C), silicon (Si) and metals originally found in activated petroleum waste sludge contribute to the formation of active sites during pyrolysis. The biochar contains functional C groups, Si O structures, and metallic oxides that promote oxidation through the formation of hydroxyl radicals ( OHs) mineralizing petroleum contaminants. Catalytic ozonation of PRW using this sludge biochar (SBC) doubles the total organic carbon removal (53.5%) relative to single ozonation (26.9%). Oxygen (Ox)-, nitrogen (NOx)- and sulfur (OxS)-containing contaminants were decreased by 33.4% (989 vs 659), 58.2% (912 vs 384) and 12.5% (384 vs 336). The present study shows the potential of a “wastes-treat-wastes” process for wastewater treatment.

Achieving an optimal cooling of the generator unit is indispensable for high working performance. In this work, computational fluid dynamics analysis on the flow field of the conventional type and silent type of the S688CCS series generator unit is conducted, and design optimization of the generator unit with poor cooling is studied based on flow field analysis results. Flow field simulation results indicate that the total cooling air quantity of the silent type generator unit is lower than that of the conventional type generator unit, and the cooling air quantity of the radiator is also lower than that of the conventional type generator unit, which is not conductive for the cooling of the silent type generator unit. The flow field optimization is achieved by adopting the single variable control method to improve the structure of the fan cover, silent components for silence, adjacent structure, and air inlet grille. The corresponding structure optimization scheme is put forward. After optimization, the air quantity for the cooling radiator of the silent type generator unit is 44.33% higher than that of its original structure, and the total cooling air quantity is higher than that of the conventional type generator unit. The research results in this work can provide a theoretical basis for the design of the cooling air flow path of generator units for achieving an optimal cooling performance.

Aiming at the problem of low efficiency and time-consuming of the traditional college attendance sign-in method, an attendance system based on face recognition, wireless network verification, fingerprint and voice verification was proposed and designed. This design splits the attendance system into four functions: wireless network list acquisition verification, face recognition, voice verification, fingerprint acquisition, and sign-in record storage. Based on this, a database for storing data and a graphical interface are designed to achieve The function of the time and attendance system.

BACKGROUND: Polybrominated diphenyl ethers (PBDEs) are persistent environmental pollutants used as flame retardants. Gestational PBDE exposure has been associated with a variety of behavior problems in children, but little is known about its impact into adolescence, particularly on social skills, which are important for achieving social competence, establishing identity, and forming lasting relationships. OBJECTIVE: We investigated associations between gestational exposure to PBDEs and social skills and problem behaviors in early adolescence in a longitudinal pregnancy and birth cohort in Cincinnati, Ohio (recruited 2003–2006). METHODS: We measured maternal serum concentrations of five PBDE congeners during gestation. At age 12, we collected social skills and problem behaviors scores from 243 adolescents and their caregivers using the Social Skills Improvement System (SSiS). We used multivariable linear regression models to estimate associations between maternal PBDE concentrations and SSiS outcomes, controlling for potential covariates. We report associations for the five congeners and a summary exposure variable (∑(5)BDE: the sum of BDE- 28, 47, 99, 100, and 153, n=197). RESULTS: We found sex-specific associations of ∑(5)BDE concentrations with adolescent-reported Problem Behaviors (∑(5)BDE × sex p(int)=0.02) and caregiver-reported Social Skills (∑(5)BDE × sex p(int)=0.02) despite higher ∑(5)BDE exposure among females (Male GM=35.30 ng/g lipid, GSE=1.09; Female GM=40.15 ng/g lipid, GSE=1.10). In sex-stratified models, log(10) transformed data revealed increased maternal ∑(5)BDE concentration among males was associated with decreased caregiver-reported Social Skills composite score (β=−10.2, 95% CI: −19.5, −1.0), increased adolescent-reported Problem Behaviors composite score (β=12.1, 95% CI: 5.4, 18.8), and increased caregiver-reported Problem Behaviors composite score (β=6.2, 95% CI: 0.7, 11.7). Further analysis on SSiS subscales revealed similar patterns in significant associations among males. There were no statistically significant associations in stratified models among females. DISCUSSION: We found gestational PBDE exposure in males was associated with poorer behavioral outcomes, extending previous findings among this cohort into early adolescence.

Oxidized low-density lipoprotein receptor 1 (OLR1), a key receptor for oxidized low-density lipoprotein (ox-LDL), plays a crucial role in cancer and inflammatory disease. However, the correlation between OLR1 expression and immune infiltration in breast cancer (BC) remain unclear. In this study, we comprehensively analyzed the expression level of OLR1 in BC tissues and explore the prognostic importance of OLR1 using quantitative real-time PCR, immunohistochemical analysis and different databases. The significantly enriched KEGG and GO pathways were used to identify the potential biological function of OLR1 via LinkedOmics analysis. Furthermore, we detected the correlation between OLR1 expression and a variety of immune infiltrating cells via Tumor Immune Estimation Resource database and GEPIA database. Our study revealed that OLR1 upregulation was observed in BC tissues and correlated with worse clinical outcomes and advanced clinicopathological factors. Meanwhile, OLR1 regulated various immunity-related pathways, especially the polarization of macrophages. Immunohistochemical analysis further confirmed the significant correlation between OLR1 expression and tumor infiltration of M2 macrophages as well as tumor-associated macrophages. OLR1 upregulation indicated poor prognosis in BC, possibly through inducing macrophage polarization and triggering immune evasion. Collectively, OLR1 may represent a potential therapeutic target for BC tailored therapy.

Litong Yao,1,2,* Yifan Zhong,3,* Lingzi He,1,* Yan Wang,4,* Jingyang Wu,3 Jin Geng,3 Yun Zhou,3 Jiahua Zhang,3 Jun Chen,3 Zhongyan Shan,5 Weiping Teng,5 Yingying Xu,2 Lei Chen,3 Lei Liu3 1China Medical University, Shenyang 110001, People’s Republic of China; 2Department of Breast Surgery, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 3Department of Ophthalmology, The First Hospital of China Medical University, Shenyang 110001, People’s Republic of China; 4Department of Radiology, General Hospital of Liaohe Oil Field, Panjin 124010, People’s Republic of China; 5Department of Endocrinology and Metabolism, Institute of Endocrinology, Liaoning Provincial Key Laboratory of Endocrine Diseases, The First Affiliated Hospital of China Medical University, Shenyang 110001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Chen; Lei Liu Email leichen51@hotmail.com; liuleijiao@163.comBackground: To investigate the association between serum carbohydrate antigen 125 (CA125) and the presence as well as severity of diabetes retinopathy (DR) in Chinese adult patients with type 2 diabetes.Methods: A hospital-based cross-sectional study was conducted from February 2012 to November 2018. DR was assessed using Early Treatment Diabetic Retinopathy Study criteria. Vision-threatening DR (VTDR) was diagnosed if subjects had severe non-proliferative DR (NPDR), proliferative DR (PDR), or clinically significant macular edema (CSME). Multivariate logistic regression models were applied to explore the associations.Results: Among the 2696 participants, the overall prevalence of DR was 25.1%, of which the prevalence of mild NPDR, moderate NPDR, and VTDR was 10.8%, 4.5%, and 9.9%, respectively. Serum CA125 level was significantly higher in participants with DR and increased with the severity of DR (P = 0.013). After accounting for age, gender, smoking, drinking, duration of diabetes, anti-diabetic agents use, systolic blood pressure, pulse pressure, weight, hemoglobin A1c and fasting plasma glucose levels, CA125 level was significantly associated with subjects in any-severity DR (odds ratio [OR] 1.006 [95% confidence interval CI: 1.002– 1.010], P = 0.006) and VTDR (1.008 [1.003– 1.013], P = 0.001). When CA125 was treated as categorized variables, the prevalence of VTDR might increase as improving CA125 quartiles (P value for trend = 0.017).Conclusion: In this study, serum CA125 level was associated with the presence and severity of DR in Chinese patients with type 2 diabetes. Further prospective studies should be warranted to validate the feasible role of CA125 as well as other biomarkers.Keywords: type 2 diabetes, diabetes retinopathy, tumor biomarker, CA125, association

Background A keloid is a benign human skin tumor that resulted by fibrous overgrowths during wound healing. Long noncoding RNAs (lncRNAs) are indicated to involve in the development of keloid. However, the role of lncRNA LINC01615 in regulating keloid development and the underlying mechanism are still unknown. Methods The expression levels of LINC01615, miR-590-3p and fibroblast growth factor 2 (FGF2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels of apoptosis-related proteins, α-smooth muscle actin (α-SMA), collagens and FGF2 were measured by western blot. The effect of LINC01615 on keloid development was assessed by cell proliferation, apoptosis and collagen deposition of keloid fibroblasts which were determined by Cell Counting Kit-8 (CCK-8), flow cytometry assay and the protein levels of collagens, respectively. The relationships between LINC01615 and miR-590-3p, miR-590-3p and FGF2 were predicated by online software and confirmed by dual-luciferase reporter assay and RNA pull-down assay. Results We first found that LINC01615 was upregulated in keloid tissues and fibroblasts, and LINC01615 promoted cell proliferation and collagen deposition and suppressed apoptosis in keloid fibroblasts. LINC01615 targeted miR-590-3p and downregulated miR-590-3p expression, and overexpression of miR-590-3p inhibited the development of keloid. Then, FGF2 was identified as a target of miR-590-3p. LINC01615 facilitated keloid development via regulating FGF2 expression through miR-590-3p. Conclusion Our study demonstrated that LINC01615 contributed to keloid development via the miR-590-3p/FGF2 axis.

En China existe una tradición milenaria de diseño de jardines que ha tenido como objetivo la búsqueda de integración con la naturaleza en armonía con ideas geománticas ancestrales. Durante la dinastía Míng (S.XIV-XVII) alcanzó su máximo explendor ya que constituyó un símbolo de prestigio social. En este contexto surgieron los primeros tratados sobre el jardín, siendo el más antiguo y completo el Yuányě, escrito en 1631 por Jì Chéng. En este artículo se realiza un análisis holístico del Yuányě con objeto de producir un relevante avance en la comprensión del jardín en relación a la cultura y el pensamiento chinos. There is a millenary tradition of garden design in China in a search for integration with nature in harmony with ancestral geomantic ideas. Garden design reached its maximum splendor during the Míng dynasty (14th-17th centuries) since it was a symbol of social prestige. In this context, the first treatises governing gardens appeared. The oldest and most complete is the Yuányě, written in 1631 by Jì Chéng. This article provides a holistic analysis of the Yuányě to produce a significant advance in understanding the garden in relation to Chinese culture and thought.

Background Colorectal cancer (CRC) is a malignant tumor, and the overall prognosis of patients with advanced CRC is still unsatisfactory. Circular RNAs (circRNAs) vesicle-associated membrane protein-associated protein A (circVAPA) could act as an underlying biomarker in CRC. This study aimed to explore the mechanism of circVAPA in the regulation of CRC growth. Methods CircVAPA level was measured in CRC tumor tissues. The expression levels of circVAPA, VAPA mRNA, microRNA-125a (miR-125a), and cAMP response element binding 5 (CREB5) in CRC cells were detected by RT-qPCR. Cell cycle progression, migration and invasion, extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by flow cytometry, transwell assays and Seahorse XF96 Glycolysis Analyzer, severally. The levels of glucose uptake, lactate and ATP production were examined by Glucose Uptake Colorimetric Assay kit, Lactate Assay kit and ATP Colorimetric Assay kit, respectively. The interaction between miR-125a and circVAPA or CREB5 was predicted by Starbase or DIANA TOOL, and verified by the dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. Results CircVAPA level was up-regulated in CRC tumor tissues. Expression levels of circVAPA and CREB5 were increased, and miR-125a was decreased in CRC cells. CircVAPA knockdown repressed CRC cells cycle progression, migration, invasion and glycolysis. CircVAPA acted as a miR-125a sponge to regulate CREB5 expression. Rescue assay confirmed that miR-125a deletion or CREB5 overexpression weakened the inhibitory effect of circVAPA knockdown on CRC growth. Conclusion Our studies disclosed that circVAPA knockdown suppressed CRC cells cycle progression, migration, invasion and glycolysis partly by modulating miR-125a/CREB5 axis, suggesting a potential therapeutic strategy for CRC treatment.

Plant leaf surface moisture is a frequent meteorological phenomenon that has complicated sources. As such, the determination of whether surface moisture is the input water or only the redistribution of water in the soil&ndash, plant&ndash, atmosphere ecosystem is of great importance. In this study, &delta, 18O and &delta, D characteristic values of dew, guttation, and soil waters in Buxus sinica var. parvifolia M. Cheng were monitored during the frost-free period (June&ndash, September 2017) in Changchun, China, to differentiate the hydraulic relationship among atmospheric vapor, rainwater, soil, dew, and guttation waters and quantitatively distinguish the leaf surface moisture on the canopy and bottom of plants. The water vapor sources of the leaf surface moisture on plants&rsquo, canopy and bottom were quantitatively verified in accordance with isotope fractionation and mass conservation principles. Results demonstrated that leaf surface moisture, atmospheric vapor, soil water, and dew were closely related. Leaf surface moisture was mainly the condensation of dew. The sources of canopy and bottom leaf surface moisture were basically the same. The proportions of canopy moisture from plant guttation, atmospheric vapor, and soil water were 2.4%&ndash, 2.5%, 79.8%&ndash, 92.4%, and 5.1%&ndash, 17.8%, respectively. By comparison, the proportions of bottom leaf surface moisture were 0.6%&ndash, 1.4%, 80.0%&ndash, 93.0%, and 6.4%&ndash, 18.6%, respectively. Leaf surface moisture is an important water input in urban systems. Moreover, the characteristic values of stable hydrogen and oxygen isotopes of urban dew are supplemented, and the transformation of atmospheric vapor, rainwater, and soil and dew waters is revealed.

Aiming at the problem that the mechanism of the moisture transfer in the nanopores of porous media has not been researched clearly. In this work, the molecular dynamics model of moisture diffusion in nano pores of porous media was established and the moisture diffusion process was analyzed by the molecular dynamics (MD) method. The Kelvin effect of water diffusion in nanopores of porous media was simulated and the model was validated by drying of potato slices. The results of simulation and verification showed that the molecular dynamics model could simulate and calculate the moisture diffusion coefficient of potato slices well. The maximum relative error of the diffusion coefficient between the simulation and experimental results is 8.6%. During the drying process, the temperature, pore size, wall roughness and the phase area fraction have important effects on the water diffusion in the nanopores. With the increase of the temperature, pore size and phase area fraction, and with the decrease of the wall roughness, the diffusion coefficients of porous media drying increased accordingly. (C) 2017 Elsevier Ltd. All rights reserved.

The detection of tunnel surface defects is the very important part to ensure tunnel safety. Traditional tunnel detection mainly relies on naked-eye inspection, which is time-consuming and error-prone. In the past few years, many defect detection methods based on computer vision have been introduced. However, these methods with manual feature extraction do not perform well in detecting tunnel defects due to the complicated background of tunnel surfaces. To address these problems, this paper proposes a novel tunnel defect inspection method based on the Mask R-CNN. To improve the accuracy of the network, we endow it with a path augmentation feature pyramid network (PAFPN) and an edge detection branch. These improvements are easy to implement, with subtle extra memory and computational overhead. In this paper, we perform a detailed study of the PAFPN and the edge detection branch, and the experiment results show their robustness and accuracy in tunnel defect detection and segmentation.

Fucosyllactoses, including 2'-fucosyllactose (2'-FL) and 3-fucosyllactose (3-FL), are important oligosaccharides in human milk that are commonly used as nutritional additives in infant formula due to their biological functions, such as the promotion of bifidobacteria growth, inhibition of pathogen infection, and improvement of immune response. In this study, we developed a synthetic biology approach to promote the efficient biosynthesis of 2'-FL and 3-FL in engineered Escherichia coli. To boost the production of 2'-FL and 3-FL, multiple modular optimization strategies were applied in a plug-and-play manner. First, comparisons of various exogenous α1,2-fucosyltransferase and α1,3-fucosyltransferase candidates, as well as a series of E. coli host strains, demonstrated that futC and futA from Helicobacter pylori using BL21(DE3) as the host strain yielded the highest titers of 2'-FL and 3-FL. Subsequently, both the availability of the lactose acceptor substrate and the intracellular pool of the GDP-L-fucose donor substrate were optimized by inactivating competitive (or repressive) pathways and strengthening acceptor (or donor) availability to achieve overproduction. Moreover, the intracellular redox regeneration pathways were engineered to further enhance the production of 2'-FL and 3-FL. Finally, various culture conditions were optimized to achieve the best performance of 2'-FL and 3-FL biosynthesizing strains. The final concentrations of 2'-FL and 3-FL were 9.12 and 12.43g/L, respectively. This work provides a platform that enables modular construction, optimization and characterization to facilitate the development of FL-producing cell factories.

The discharge of wastewater having recalcitrant chemical compositions can have significant and adverse environmental effects. The present study investigates the application of a catalytic ozonation treatment for the removal of recalcitrant organic chemicals (ROCs) from the water. Novel catalytic materials using vanadium (V) oxides deposited onto the surface of NaZSM-5 zeolites (V/ZSM) were found to be highly efficient for this purpose. The highly-dispersed V oxides (V4+ and V5+) and Si-OH-Al framework structures were determined to promote the surface reaction and generation of hydroxyl radicals. The constructed V1/ZSM450 (0.7 wt% of V loading and 450°C of calcination) exhibited the highest activity among the developed catalyst compositions. The V1/ZSM450-COP increased the mineralization rate of nitrobenzene and benzoic acid by 50 and 41% in comparison to single ozonation. This study demonstrates the enhanced potential of V/ZSM catalysts used with catalytic ozonation process (COP) for the treatment of chemical wastewaters.

Mobile Ad-hoc Network (MANET) is a self-configuring network that is widely used but vulnerable to the malicious jammers in practice. In this paper, we consider a jamming channel problem in MANET where a jammer intermittently interrupts the communication channels and the transmitter needs to determine which time slot to send data in order to avoid the interruption. Learning from the historical experience, a Deep Q-Network (DQN) based approach is proposed to generate transmission decisions at the transmitter. In addition, a variant of DQN, termed adaptive DQN, is introduced to cope with the change of jamming conditions. The simulation results demonstrate that the proposed scheme can learn an optimal policy to guide the transmitter to avoid jamming more quickly and efficiently than a Q-learning baseline. Moreover, the effectiveness and robustness of the adaptive DQN is also numerically verified.

Predicting time-to-event outcomes in large databases can be a challenging but important task. One example of this is in predicting the time to a clinical outcome for patients in intensive care units (ICUs), which helps to support critical medical treatment decisions. In this context, the time to an event of interest could be, for example, survival time or time to recovery from a disease/ailment observed within the ICU. The massive health datasets generated from the uptake of Electronic Health Records (EHRs) are quite heterogeneous as patients can be quite dissimilar in their relationship between the feature vector and the outcome, adding more noise than information to prediction. In this paper, we propose a modified random forest method for survival data that identifies similar cases in an attempt to improve accuracy for predicting time-to-event outcomes; this methodology can be applied in various settings, including with ICU databases. We also introduce an adaptation of our methodology in the case of dependent censoring. Our proposed method is demonstrated in the Medical Information Mart for Intensive Care (MIMIC-III) database, and, in addition, we present properties of our methodology through a comprehensive simulation study. Introducing similarity to the random survival forest method indeed provides improved predictive accuracy compared to random survival forest alone across the various analyses we undertook.

En China existe una tradición milenaria en el diseño de jardines que constituye una de sus manifestaciones culturales más significativas. El concepto de jardín apareció por primera vez durante la dinastía Shāng (s. XI a.C.) y alcanza su máximo esplendor en la dinastía Míng (s. XIV-XVII). En este último período, funcionarios y aristócratas competían con el diseño de sus jardines, debido a que constituía un símbolo de prestigio social y nivel cultural. Como consecuencia, el número y la calidad de los jardines privados aumentó considerablemente, sobre todo en la próspera región de Jiāngnán 江南, situada al sureste del país. En esta zona residían la mayor parte de literatos y eruditos, y constituyó por tanto el centro cultural de China durante esa época. En este contexto, aparecieron por primera vez tratados sobre el jardín que nos proporcionan valiosas reflexiones y descripciones. El más antiguo y completo es el Yuányě《园冶》, escrito en 1631 por Jì Chéng 计成, aunque también podemos destacar al "Tratado de Elementos Superfluos"《长物志》[Zhàngwù zhì] (1621) de Wén Zhènhēng ⽂震亨, o las "Notas ocasionales para ocio y percepción"《闲情偶寄》[Xiánqíng ǒujì] (1667) escrito por Lǐyú 李渔. Los jardines privados de esta región tuvieron una gran repercusión, ya que fueron utilizados posteriormente como modelos para la construcción de jardines privados e imperiales en otras zonas del país. La tesis se ha centrado por tanto en el estudio de los jardines privados Míng en Jiāngnán. Considerando pertinente estudiar el modo en que el contexto social, cultural y político de esta próspera región contribuyó al desarrollo del jardín, como su evolución a lo largo del período analizado. La investigación se ha basado en el estudio de fuentes originales tales como tratados de la época, pinturas paisajísticas, composiciones poéticas o análisis in situ de jardines que han perdurado hasta nuestros días. Además, las fuentes originales han sido complementadas mediante el análisis de investigaciones contemporáneas. Nos hemos centrado principalmente en el estudio del Yuányě, ya que es el tratado más antiguo y completo sobre el jardín en China, y se trata de un texto clave para entender el jardín clásico en el marco de la cultura y sociedad Míng. Por otro lado, este tratado refleja aspectos esenciales de la cultura y el pensamiento chino, y tiene gran importancia en la literatura clásica, debido a las numerosas referencias históricas y literarias que utiliza, así como el uso del estilo literario conocido como Piántǐ wén 骈 体⽂. Dada la importancia del Yuányě, hemos incluido una traducción anotada directamente desde el chino. De este modo, futuros investigadores podrán disponer del texto original, con aclaraciones o especificaciones pertinentes, para poder realizar su propia interpretación en función de sus objetivos o intereses de investigación. El Yuányě recoge conceptos o principios creativos que deben inspirar las diferentes escenas del jardín, y ofrece consejos prácticos para la construcción y ubicación de sus elementos arquitectónicos. En este sentido, aporta 235 ilustraciones que incluyen plantas de pabellones, tipos de ventanas y balaustradas, pavimentos y diseños decorativos de galerías o pasajes. Estos principios de diseño reflejan la búsqueda de una íntima relación entre el hombre y la naturaleza, y permiten arrojar nueva luz sobre como la arquitectura debe de relacionarse con su entorno para estar en armonía con el medio ambiente. Por otro lado, hemos analizado la relación del Yuányě con otras manifestaciones artísticas, tales como la pintura, literatura o poesía, así como con diferentes corrientes de pensamiento. En concreto, con el confucianismo, taoísmo, budismo e ideas de geomancia o fēngshuǐ. De este modo, queremos producir un relevante avance en la comprensión de las bases conceptuales en las que se fundamenta el arte del jardín en China. There is a millenary tradition of garden design in China that represents one of its most significant cultural expressions. The concept of gardens first appeared during the Shāng dynasty (11th century BC) and reached its maximum splendor in the Míng Dynasty (14th-17th centuries). During this period, officials and aristocrats competed in the design of gardens because it was a symbol of social and cultural prestige. As a result, the number and quality of private gardens considerably increased, more specifically in the prosperous Jiāngnan 江南region, located in the southeast of the country. The majority of literati and scholars resided in this area, and consequently, it was the cultural center of China at that time. In this context, the first treatises governing gardens appeared, which provided valuable reflections and descriptions. The oldest and most complete is the Yuányě《园冶》, written in 1631 by Jì Chéng 计成, although we can also highlight the "Treaty of Superfluous Elements"《长物志》[Zhàngwù zhì] (1621) by Wén Zhènhēng ⽂震亨and the "Occasional notes for leisure and perception"《闲情偶寄》[Xiánqíng ǒujì] (1667) written by Lǐyú 李渔. The private gardens of this region had a great impact, since they were later used as models for the construction of private and imperial gardens in other areas of China. Consequently, the thesis focuses on the study of Míng private gardens in Jiāngnán. We considered it pertinent to study the way in which the social, cultural and political context of this prosperous region contributed to the development of gardens and their evolution throughout this period. Our research has been based on the study of original sources such as treatises from the time, landscape paintings, poetic compositions or in situ analysis of gardens that have lasted to this day. Additionally, the original sources have been complemented by the analysis of contemporary research. We have focused the analysis on the study of Yuányě, since it is the oldest and most complete treatise on gardens in China, as well as being a key text to understand the classical garden within the framework of Míng culture and society. Furthermore, this important treatise reflects relevant values of Chinese culture and thought, and has great importance in classical literature, due to the numerous historical and literary references used, as well as the use of the literary style known as Piántǐ wén 骈体⽂. Given the importance of Yuányě, we have included an annotated translation directly from Chinese. Subsequently, future researchers will have access to the original text, with appropriate clarifications or specifications, to be able to carry out their interpretation according to their objectives or research interests. Yuányě includes concepts and creative principles that should inspire different garden scenes, and provides practical advice for the construction and location of architectural elements. In this sense, it contributes 235 illustrations that include designs for pavilions, types of windows and balustrades, pavements and decorative designs of galleries or passages. These design principles reflect the search for an intimate relationship between man and nature and allow us to shed new light on how architecture must relate to and harmonize with the natural environment. Moreover, we have analyzed the relationship of the Yuányě with additional artistic manifestations, such as painting, literature or poetry, as well as different currents of thought. In particular, its relationship with Confucianism, Taoism, Buddhism, and ideas of geomancy or fēngshuǐ. In this way, we want to produce a relevant advance in the understanding of the conceptual bases of the art of gardens in China.

Supplemental Digital Content is available in the text, Observational studies have reported that Vitamin D deficiency and the risk type 2 diabetes are associated, but the causation is unclear. Mendelian randomization (MR) involving genetic variants as instrument variables (IVs) overcomes the reverse-casualty and unmeasured confounding. However, with limited sample size and IVs, previous MR studies showed inconsistent results. Leveraging by a largely increased sample size for both stages, we aim to provide an updated and precise estimate for the causality between Vitamin D and type 2 diabetes. A 2-sample multi-IVs MR was performed. IVs for circulating 25-hydroxyvitamin D (25(OH)D) were obtained from a genome-wide association study from UK biobank involving 329,247 subjects of European ancestry. The causal effect of 25(OH)D and type 2 diabetes was estimated using traditional inverse variance weighting and MR pleiotropy residual sum and outlier (MR-PRESSO) framework which provides a robust estimate by systematically filtering out IVs identified with potential pleiotropy effects. A higher genetically instrumented 25(OH)D was causally linked to reduced risk of type 2 diabetes risk by MR-PRESSO [odds ratio (OR) per standard deviation (SD) = 0.950, 95% confidence interval (CI) = 0.913–0.988, P = .010] after removing 13 (13/193) invalid IVs. In addition, we confirmed the causal role Vitamin D using 2 synthesis-related single-nucleotide polymorphisms (SNPs) which are consistent with previous MR studies [OR per SD = 0.894, 95% CI = 0.816–0.979, P = .016]. With a largely improved sample size, our results confirmed that genetically increased 25(OH)D concentration reduced the risk of type 2 diabetes and provided a more precise estimate for the effect size. The updated result empowers the role of Vitamin D and provides nontrivial evidence for interventional studies.

Colorectal cancer (CRC) is a common gastrointestinal cancer with high mortality rate mostly due to metastasis. Ca2+-dependent activator protein for secretion 1 (CAPS1) was originally identified as a soluble factor that reconstitutes Ca2+-dependent secretion. In this study, we discovered a novel role of CAPS1 in CRC metastasis. CAPS1 is frequently up-regulated in CRC tissues. Increased CAPS1 expression is associated with frequent metastasis and poor prognosis of CRC patients. Overexpression of CAPS1 promotes CRC cell migration and invasion in vitro, as well as liver metastasis in vivo, without affecting cell proliferation. CAPS1 induces epithelial-mesenchymal transition (EMT), including decreased E-cadherin and ZO-1, epithelial marker expression, and increased N-cadherin and Snail, mesenchymal marker expression. Snail knockdown reversed CAPS1-induced EMT, cell migration and invasion. This result indicates that Snail is required for CAPS1-mediated EMT process and metastasis in CRC. Furthermore, CAPS1 can bind with Septin2 and p85 (subunit of PI3K). LY294002 and wortmanin, PI3K/Akt inhibitors, can abolish CAPS1-induced increase of Akt/GSK3β activity, as well as increase of Snail protein level. Taken together, CAPS1 promotes colorectal cancer metastasis through PI3K/Akt/GSK3β/Snail signal pathway-mediated EMT process.

We consider the statistical properties of interaction parameter estimates obtained by the direct coupling analysis (DCA) approach to learning interactions from large data sets. Assuming that the data are generated from a random background distribution, we determine the distribution of inferred interactions. Two inference methods are considered: the L2 regularized naive mean-field inference procedure (regularized least squares, RLS), and the pseudo-likelihood maximization (plmDCA). For RLS we also study a model where the data matrix elements are real numbers, identically and independently generated from a Gaussian distribution; in this setting we analytically find that the distribution of the inferred interactions is Gaussian. For data of Boolean type, more realistic in practice, the inferred interactions do not generally follow a Gaussian. However, extensive numerical simulations indicate that their distribution can be characterized by a single function determined by a few system parameters after normalization by the standard deviation. This property holds for both RLS and plmDCA and may be exploitable for inferring the distribution of extremely large interactions from simulations for smaller system sizes., 5 pages, 5 figures

Mozhi Wang,1,* Changwang Zhang,2,* Yongxi Song,2 Zhenning Wang,2 Yaojia Wang,1 Fang Luo,1 Yujie Xu,1 Yi Zhao,1 Zhonghua Wu,2 Yingying Xu1 1Department of Breast Surgery, 2Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, People’s Republic of China *These authors contributed equally to this work Abstract: Breast cancer (BC) is the most common malignant tumor among women, with high morbidity and mortality. Its onset, development, metastasis, and prognosis vary among individuals due to the interactions between tumors and host immunity. Many diverse mechanisms have been associated with BC, with immune evasion being the most widely studied to date. Tumor cells can escape from the body’s immune response, which targets abnormal components and foreign bodies, using different approaches including modification of surface antigens and modulation of the surrounding environment. In this review, we summarize the mechanisms and factors that impact the immunoediting process and analyze their functions in detail. Keywords: immune evasion, mechanism, breast cancer, cytokines, apoptosis, PD-L1

By referring to attribution theory, influence factor and internal mechanism of crisis brand generating two kinds of spillover effects are explored. In this paper, the influence mechanism on spillover effect is explored from the angles of network and industry information. Results show that high online review dispersion is easy to cause that consumer attributes the responsibility to the outside of the enterprise, while low online review dispersion is easy to cause that consumer attributes the responsibility to the inside of the enterprise; high industry base rate information is easy to cause that consumer attributes the responsibility to the outside of the enterprise, while low industry base rate information is easy to cause that consumer attributes the responsibility to the inside of the enterprise. When consumer attributes the responsibility to the outside of the enterprise, infectious network spillover is easy to occur. When consumer attributes the responsibility to the inside of the enterprise, contrast network spillover is easy to occur. Consumer’s existing brand knowledge regulates the influence of online review dispersion on responsibility attribution and the influence of industry base rate information on responsibility attribution. Research result could provide effective theoretic reference and management suggestion for crisis enterprise and even whole industry responding to product injury crisis.

Sleep patterns have been associated with the development of cancers, although the association between sleep duration and breast cancer remains controversial. The purpose of our study was to explore the relationship between sleep duration and breast cancer risk. The PubMed and Web of Science databases were searched, and restricted cubic splines were used to explore the dose-response relationship. Data from 415,865 participants were derived from 10 studies. A J-shaped nonlinear trend was found between sleep duration and breast cancer incidence (Pnon-linear = 0.012); compared with the reference hours (6 h or 7 h), with increasing sleep hours, the risk of breast cancer increased (Ptrend = 0.028). Moreover, a nonlinear relationship was found between sleep duration and estrogen receptor-positive breast cancer (Pnon-linear = 0.013); the risk of estrogen receptor-positive breast cancer increased with increasing sleep hours compared to the reference hours (Ptrend = 0.024). However, no nonlinear relationship was found between sleep duration and estrogen receptor-negative breast cancer; the risk of estrogen receptor-negative breast cancer was 1.035 for every additional sleep hour. Compared to women with the reference number of sleep hours, women with a longer sleep duration might have a significantly increased risk of breast cancer, especially estrogen receptor-positive breast cancer.

The potential impact that the intratumoral expression level of dihydropyrimidine dehydrogenase (DPD) has on chemotherapy sensitivity and long-term survival for gastric cancer (GC) patients remains controversial; therefore, this study seeks to clarify this issue. Our meta-analysis was performed using Review Manager (RevMan) 5.3 software. In vitro drug sensitivity tests, correlation coefficients between sensitivity to 5-fluorouracil (5-FU), and expression levels of intratumoral DPD were used as effective indexes to analyse. Overall survival (OS) and progression-free survival (PFS) were used as endpoints for patient outcome, and hazard ratios (HRs) and 95% confidence intervals (CIs) were noted as measures of effect. There were 15 eligible studies including 1805 patients for the final analysis. The analysis revealed a statistically significant difference between the expression level of intratumoral DPD activity, DPD mRNA levels, and sensitivity to 5-FU in GC patients, with high expression levels of intratumoral DPD resulting in low sensitivity to 5-FU. However, no matter what therapeutic regimens were used, there was no significant difference for patient outcomes between high and low DPD expression groups, either in OS or in PFS. In conclusion, high levels of intratumoral DPD expression have a negative impact on sensitivity to 5-FU in GC patients, but no prognostic value for long-term survival was uncovered.

The installation position of the external mirror, a very significant safety parts of vehicles, directly affects the driver’s field of view. To determine the position of the external mirror is a complicated task, factors need to be considered such as styling, ergonomic, safety, engineering design, etc. In the process of vehicle development, the external mirror is often arranged after the modeling schemes is determined. However, it is not easy to get a good visual field and human comfort subject to the constraints of the styling features. Therefore, it is necessary to give out the position of the external mirror and the field of vision in the early stage of modeling. In order to obtain a good view, the ideal position of the outside mirror is packaged considering of ergonomic, and the minimum visible dimension of the mirror is designed on the basis of vision conformance, which avoid the safety hazard and massive amounts of modification caused by improper design of the external mirror.

In view of the fact that the zone model for porous media drying cannot disclose the mechanism of liquid phase distribution effectively, a pore network model for the slow isothermal drying process of porous media was developed by applying the theories of pore network drying and transport-process, which fused the physical parameters of porous media, such as porosity, pore mean diameter, and pore size distribution into the model parameters, and a sand bed drying experiment was conducted to verify the validity of this model. The experiment and simulation results indicate that the pore network model could explain the slow isothermal drying process of porous media well. The pore size distributions of porous media have a great effect on the liquid phase distribution of the drying process. The dual-zone model is suitable for the porous media whose pore size distribution obeys Gaussian distribution, while the three-zone model is suitable for the porous media whose pore size distribution obeys the lognormal distribution when the drying analysis of porous media is conducted.

In this paper, we describe the formatting guidelines for ACM SIG Proceedings. In order to assure safety of Chinese Train Control System (CTCS), it is necessary to ensure the operational risk is acceptable throughout its life-cycle, which requires a pragmatic risk assessment required for effective risk control. Many risk assessment techniques currently used in railway domain are qualitative, and rely on the experience of experts, which unavoidably brings in subjective judgements. This paper presents a method that combines fuzzy reasoning and analytic hierarchy process approach to quantify the experiences of experts to get the scores of risk parameters. Fuzzy reasoning is used to obtain the risk of system hazard, analytic hierarchy process approach is used to determine the risk level (RL) and its membership of the system. This method helps safety analyst to calculate overall collective risk level of system. A case study of risk assessment of CTCS system is used to demonstrate this method can give quantitative result of collective risks without much information from experts, but can support the risk assessment with risk level and its membership, which are more valuable to guide the further risk management.