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Patients with anaplastic thyroid cancer (ATC) have a very poor prognosis. Immunotherapy is a potential treatment, while the current outcome is limited which may be due to the complicated tumor microenvironment (TME). Tumor associated macrophages (TAMs) is the most abundant cell in the TME of ATC. We aimed to clarify the novel indicators based on TAM in ATC.Transcriptome files were downloaded from the Gene Expression Omnibus (GEO) dataset. Weighted gene co-expression network analysis, cox regression, support vector machine, and random forest were utilized to identify TAM-related prognostic genes. Consensus clustering and principal component analysis were performed for integrated analysis. Moreover, external validation (Fudan University Shanghai Cancer Center cohort) was conducted in 23 ATC samples via immunohistochemistry.ATC patients with an abundance of TAMs had a poorer prognosis. Four TAM related genes (FZD6, RBBP8, PREX1, HSD3B7) were identified and a TAM-related prognostic index (TAMRPI) was constructed with high area under the curve (AUC). Next, high TAMRPI was related to the higher level of TAM infiltration and upregulation of several pathways, such as E2F targets, IL6-JAK-STAT3, and G2M checkpoint. Immune checkpoint TIM-3 and CSF1R were positively associated with TAMRPI, and dysfunction of T cells was increased in high TAMRPI subset. Moreover, in the external validation of protein level, strong expression of TAM related genes was related to poorer prognosis, which was further supported by time-dependent AUC analysis.TAM is negatively correlated to the prognosis of ATC. FZD6, RBBP8, PREX1, and HSD3B7 are potential biomarkers of ATC.

To observe the effect of electroacupuncture (EA) at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) on mental state, visceral sensitivity and protein expression of nerve growth factor (NGF), tyrosine kinase receptor A (TrkA) and transient receptor potential vanilloid 1 (TRPV1) of colonic tissue in diarrhea-predominant irritable bowel syndrome (IBS-D) rats, and to explore its possible mechanism on treating IBS-D.A total of 36 male SD rats of SPF grade were randomized into a blank group, a model group, an EA group and a western medication group, 9 rats in each group. In the model group, the EA group and the western medication group, IBS-D model was established by enema of dinitrobenzene sulfonic acid (DNBS) combined with chronic restraint stress method. In the EA group, EA was applied at "Tianshu" (ST 25) and "Shangjuxu" (ST 37), with disperse-dense wave, in frequency of 2 Hz/100 Hz, 20 min each time, once a day for 7 days. In the western medication group, pinaverium bromide suspension was given by gavage (15 mg•kgAfter model establishment, compared with the blank group, the body mass and 24 h food intake were decreased (Electroacupuncture at "Tianshu" (ST 25) and "Shangjuxu" (ST 37) can relieve the anxiety and depression-like behaviors in IBS-D rats, down-regulate the protein expression of NGF, TrkA, TRPV1 in colonic tissue, so as to reduce the visceral sensitivity and relieve symptoms.

To observe the effect of electroacupuncture (EA) of "Tianshu"(ST25) and "Shangjuxu"(ST37)on gastrointestinal motility, psychological abnormality and expression of RhoA and ROCK protein in rats with diarrhea predominant irritable bowel syndrome (IBS-D), so as to explore its underlying mechanism in improving IBS-D.Thirty-six male rats were randomly and equally divided into control, model, EA and medication groups (After modeling, the body mass, food consumption, sucrose preference index, the open-arm residence time ratio andlatency of colonic contraction waves were significantly decreased (EA can improve both colonic motility and psychological disorders in IBS-D rats with psychological disorder, which may be related to its function in down-regulating the expression of colonic RhoA and ROCK proteins.

Classical swine fever virus (CSFV), a member of the Flaviviridae enveloped RNA virus family, results in an epidemic disease that brings serious economic losses to the pig industry worldwide. Valosin-containing protein (VCP/p97), a multifunctional active protein in cells, is related to the life activities of many viruses. However, the role of VCP in CSFV infection remains unknown. In this study, it was first found that treatment of VCP inhibitors impaired CSFV propagation. Furthermore, overexpression or knockdown of VCP showed that it was essential for CSFV infection. Moreover, confocal microscopy and immunoprecipitation assay showed that VCP was recruited for intracellular transport from early endosomes to lysosomes. Importantly, knockdown of VCP prevented CSFV to release from early endosomes, suggesting that VCP is a key factor for CSFV trafficking. Taken together, our findings first demonstrate that the endocytosis of CSFV into PK-15 cells requires the participation of VCP, providing the alternative approach for the discovery of novel anti-flaviviridae drugs.

UVA irradiation induced ROS-mediated photo damage to the human skin leading to coarseness, wrinkling, pigmentation, and cutaneous malignancies. We investigated the dermatoprotective efficacies of submicromolar concentrations of ergothioneine (EGT, 0.125-0.5 μM), which occurs naturally as a sulfur-containing amino acid, in the mechanisms in human skin fibroblast (HSF) cells. UVA-induced AP-1 (c-Fos and c-Jun) translocation was found to be inhibited by EGT treatments with the parallel inhibition of the collagenolytic matrix metalloproteinase- (MMP-) 1 activation and type I procollagen degradation. Moreover, EGT mitigated UVA-induced ROS generation. An increase in the amount of antioxidant genes (HO-1, NQO-1, and γ-GCLC) from EGT and were associated with upregulated Nrf2 expressions in a dose-dependent or time-dependent manner. We confirmed this from Nrf2 translocation and increased nuclear ARE promoter activity that underlie EGT dermatoprotective activities. Also, glutathione (GSH) levels (from γ-GCLC) were significantly increased. Moreover, we showed that mediated by ERK, JNK, and PKC, signaling cascades mediate Nrf2 translocation. We confirmed this phenomenon by the suppressed nuclear Nrf2 activation in cells that were treated with respective inhibitors (PD98059, SP600125, and GF109203X). However, antioxidant protein expressions were impaired in Nrf2 knockdown cells to confirm that ARE/Nrf2 pathways and the inhibition of AP-1 had significant roles in EGT-mediated protective effects. We can conclude that ergothioneine ameliorated UVA-induced skin aging and is a useful food supplement for skin care products.

A network Meta-analysis based on Bayesian theory was used to evaluate efficacy and safety of acupuncture and moxibustion in the treatment of dry eye disease(DED), so as to provide evidence-based research basis for clinical application.Randomized controlled trials (RCT) for acupuncture and moxibustion treatment of DED published from the inception of database to November 25, 2020 were searched from PubMed, Embase, Cochrane Library, Web of Science, Sinomed, CNKI, Wanfang and VIP Database. Two reviewers independently screened the literatures, extracted the data. The quality of the included literature was evaluated, and network Meta-analysis was performed by using Stata14.0 and R4.0.3 software.A total of 71 literatures were identified, including 5 536 patients with DED, covering 11 different interventions. Network Meta-analysis showed that acupuncture+traditional Chinese medicine+artificial tears was the best treatment option in terms of the clinical effective rate, breakup time of tear film (BUT), Schirmer I test (SIT) with surface under cumulative ranking area value. Acupuncture+traditional Chinese medicine+artificial tears was better than artificial tears in the clinical effective rate (odds ratio［Acupuncture and moxibustion in the treatment of DED are generally better than artificial tears, and acupuncture-moxibustion combined with other traditional Chinese medicine therapy has the best effect.

Global climate change and local urban heat islands enhance urban heat stress. Studies focused at the urban neighborhood scale are limited. Wet-bulb temperature represents the combined effects of both temperature and humidity, and therefore can more accurately reflect human thermal comfort. In this study, air temperature, relative humidity and geographic information of different times, seasons, and sky conditions of the Nanjing Jiangbei New Area were obtained based on mobile measurements. The spatiotemporal variation of wet-bulb temperature at the urban neighborhood scale and the effects of sky conditions, land cover and urban morphology (sky view factor, SVF) were further analyzed. The results showed that: 1) the spatiotemporal variations of wet-bulb temperature at the Nanjing urban neighborhood scale were consistent with that of air temperature. Compared with vapor pressure, air temperature played a dominant role. The extremely high values of wet-bulb temperature in this area were mostly caused by the synergy between air temperature and vapor pressure. 2) The correlation between SVF and wet-bulb temperature was significantly positive in the daytime and negative at night. An increase in the vegetation fraction could reduce wet-bulb temperature, while impervious surfaces had the opposite effect. The wet-bulb temperature significantly decreased and its spatial distribution was much more homogeneous under overcast sky conditions. 3) The horizontal scale effect showed diurnal and seasonal differences and was more sensitive to sky conditions during nighttime than during daytime. Compared with vegetation, the horizontal effect of impervious surfaces was much larger in winter than in the other two seasons. The horizontal scale effects of vege-tation and impervious surfaces on wet-bulb temperature were similar to those of air temperature. These results could provide effective scientific support and a theoretical basis for improving and optimizing the thermal environment of urban neighborhoods, as well as alleviating urban heat stress.全球气候变化和局地城市热岛加剧了城市热胁迫问题,但针对城市街区的研究仍不多见。湿球温度指示气温和湿度的综合效应,能更准确地反映人体热舒适度。本研究以南京市江北新区为对象,在不同时段、季节和天空状况下,基于移动观测方法获取气温、相对湿度和地理信息等数据,分析了街区尺度湿球温度的时空分布特征;结合天空状况、地表覆盖和城市形态指标(天穹可见度),探究了城市街区湿球温度的影响机制。结果表明: 1)南京城市街区湿球温度的时空特征与气温较为一致;与水汽压相比,气温对湿球温度的变化起主导作用;该地区湿球温度的极端高值主要是由于气温和水汽压协同增长所致。2)天穹可见度在白天与湿球温度呈显著正相关,夜间为负相关关系。植被覆盖比率的增加能够降低湿球温度,不透水面则呈现相反的作用。阴天条件下,湿球温度明显降低并且空间分布更均匀。3)植被和不透水面对湿球温度的水平尺度效应存在昼夜和季节差异,并且在夜间这一效应对天空状况更敏感;与植被相比,冬季夜间不透水面的影响范围比夏、秋季更大;两者对湿球温度的水平尺度效应与气温一致。研究结果可为改善和优化城市街区热环境、缓解城市热胁迫提供有效的科学支持和理论依据。.

The present study aimed to regulate the market circulation of Caryophylli Flos and formulate standards for commodity specifications and grades of Caryophylli Flos. Market survey was carried out in four major medicinal material markets with 48 samples of Caryophylli Flos collected. The property, 100-seed weight, impurity percentage, moisture, and eugenol content in Caryophylli Flos of different specifications from different producing areas were determined and analyzed. The results showed that 27.1% of the samples surveyed on the markets did not meet the requirements of Chinese Pharmacopoeia(2020 edition). The 100-seed weight and the property are important factors for the classification of Caryophylli Flos specifications. There were significant differences in the property, 100-seed weight, impurity percentage, and eugenol content in Caryophylli Flos samples of different specifications from different producing areas, and also differences in the proportions of different specifications in Caryophylli Flos samples from different producing areas. The African-originated Xiaohong(medium grade) and Guangxi-originated Xiaohong(medium grade) accounted for 70% and 66.7% respectively, the Indonesian-originated Dahong(top grade) for 56.2%. In conclusion, there are many problems in the circulation of Caryophylli Flos at present, mainly including the loss of origin information, no standards for specifications, non-implementation of grade standards, excessive impurities, and no evidence for authenticity identification. According to the classification of Caryophylli Flos specifications in this study, the average eugenol content of Xiaohong is significantly higher than the Dahong by 4.74%.

The epithelial–mesenchymal transition (EMT) phenotype, whereby mature epithelial cells undergo phenotype transition and differentiate into motile, invasive cells, has been indicated in tumor metastasis. The melatonin hormone secreted by the pineal gland has an antioxidant effect and protects cells against carcinogenic substances that reduce tumor progression. However, the effects of melatonin in EMT and lung cancer metastasis are largely unknown. We found that melatonin down-regulated EMT by inhibiting Twist/Twist1 (twist family bHLH transcription factor 1) expression. This effect was mediated by MT1 receptor, PLC, p38/ERK and β-catenin signaling cascades. Twist expression was positively correlated with tumor stage and negatively correlated with MT1 expression in lung cancer specimens. Furthermore, melatonin inhibited EMT marker expression and lung cancer metastasis to liver in vivo. Finally, melatonin shows promise in the treatment of lung cancer metastasis and deserves further study.

Zinc oxide nanoparticles (ZnO NPs) have been widely investigated for applications in photocatalytic degradation of organic pollutants in wastewater. Despite the advantages of robust ZnO material, its photocatalytic activity is greatly affected by environmental factors. Halogen ions are commonly found in wastewater, which directly affect the pollutant aggregation and sedimentation, therefore it is necessary to discuss their effect on the photodegradation. The current study assesses the halogen ions effect on the photocatalytic degradation of bisphenol A (BPA) using different dosage of sodium chloride (NaCl) and sodium bromide (NaBr). The microstructural characterization of ZnO was conducted by transmission electron microscopy and hydrodynamic size was analyzed through dynamic light scattering. Degradation reactions of BPA with ZnO NPs followed pseudo-first-order kinetics. The increase of ZnO dosage from 0.01 g/L to 0.1 g/L enhanced the degradation rate constant of BPA up to 0.089 min− 1 (14.8 folds). In order to evaluate the the role halogen ions to degrade BPA, NaBr and NaCl were used. The degradation rate was reduced up to 26 folds (0.0034 min− 1) after the addition of NaBr, which was attributed to the increase in hydrodynamic particle size leading, thereby restricting the light adsorption capacity. Noteworthy, upon addition of NaCl from 10 mM to 500 mM concentration, there was only a slight decrease (2.4 folds, 0.037 min− 1) on the degradation rate of BPA. Therefore, this study unveils the role of chloride ions as an effective medium for BPA degradation by ZnO NPs, without aggregation, and provides a novel platform for the treatment of organic pollutants in saline water.

To observe the effect of acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) on intestinal flora and Toll-like receptors-4 (TLR4) in brain and intestinal tissue in rats with stress gastric ulcer (SGU), and to explore the possible mechanism of acupuncture for SGU.Thirty-one male SD rats were randomly divided into a blank group (Compared with the blank group, the gastric mucosal damage index was significantly increased in the model group (Acupuncture at "Guanyuan" (CV 4) and "Xiajuxu" (ST 39) could alleviate SGU in rats, and its mechanism may be related to increasing the diversity of intestinal flora, promoting the disorder of intestinal flora to normal, and reducing the overexpression of TLR4 in brain and intestinal tissues.

Zinc oxide (ZnO) nanoparticles have been widely investigated for applications in photocatalytic degradation of organic pollutants in wastewater. Despite the advantages of robust ZnO material, its photocatalytic activity is greatly affected by environmental factors. Halogen ions are commonly found in wastewater, which directly influence the pollutant aggregation and sedimentation, therefore it is necessary to discuss their effect on the photodegradation. The current study assesses the halogen ions effect on the photocatalytic degradation of BPA using different dosage of sodium chloride (NaCl) and sodium bromide (NaBr). The microstructural characterization of ZnO was conducted by transmission electron microscopy and hydrodynamic size was analyzed through dynamic light scattering. Degradation reactions of BPA with ZnO nanoparticles followed pseudo-first-order kinetics. The increase of ZnO dosage from 0.01 g/L to 0.1 g/L enhanced the degradation rate constant of BPA up to 0.089 min-1 (14.8 folds). In order to evaluate the the role halogen ions to degrade BPA, NaBr and NaCl were used. The degradation rate was reduced up to 26 folds (0.0034 min-1) after the addition of NaBr, which was attributed to the increase in hydrodynamic particle size leading, thereby restricting the light adsorption capacity. Noteworthy, upon addition of NaCl from 10 mM to 500 mM concentration, there was only a slight decrease (2.4 folds, 0.037 min-1) on the degradation rate of BPA. Therefore, this study unveils the role of chloride ions as an effective medium for BPA degradation by ZnO nanoparticles, without aggregation, and provides a novel platform for the treatment of organic pollutants in saline water.

Mandatory requirements for plasma pools containing a maximum concentration of human parvovirus B19 DNA will be established in Taiwan in the near future. To facilitate the implementation of the policy, a National Standard and working reagent were established for human parvovirus B19 DNA nucleic acid amplification techniques (NAT). The standards are intended to be used for the quality control of B19 NAT assays and as a quantitative reference material for B19 NAT testing. A collaborative study, including 10 laboratories from seven countries, was done in order to establish the National Standard and working reagent for B19 DNA NAT assays by calibration, in International Units (IU), against the WHO International Standard for B19 (99/800). Participants were requested to test the candidate materials and the WHO International Standard by the NAT assay in routine use in the laboratory. The mean B19 DNA content of the standards was determined by each laboratory in three independent assays and the results were analyzed statistically. Overall, a high level of agreement among results was achieved from different laboratories. Consequently, the first National Standard and working reagent for B19 DNA NAT assays with an assigned value of 1.9×10^6 IU/mL and 2.0×10^4 IU/mL, respectively, were established. The results of the stability analysis indicated that both reagents were stable for 4 weeks at 25℃, for 8 weeks at 4℃, for at least 18 months at -20°C or -80℃.

To investigate the effect of acupuncture on serum inflammatory cytokines and intestinal flora in rats with stress-induced gastric ulcer (SGU), and to explore the mechanism of acupuncture in the treatment of SGU.Sprague-Dawley rats were randomly divided into blank, model, acupuncture, and medication groups, with 7 rats in each group. Restraint water-immersion stress was used to establish the model of SGU. The rats in the acupuncture group were given acupuncture at "Zhongwan"(CV12) and bilateral "Zusanli"(ST36) for 20 min, once a day for 5 days, and those in the medication group were given 2 mL solution of Omeprazole enteric-coated tablets (0.2 mg/kg) by gavage, once a day for 5 days. The Guth method was used to calculate the gastric mucosa damage index, HE staining was used to observe the histopathological changes of the gastric mucosa, ELISA was used to measure the serum levels of interleukin-4 (IL-4) and interleukin-6 (IL-6), and 16S rDNA sequencing method was used to observe the change in intestinal flora.Compared with the blank group, the model group had a significant increase in gastric mucosa damage index (Acupuncture at CV12 and ST36 can down-regulate the content of serum IL-6, up-regulate the content of serum IL-4, maintain the relative homeostasis of inflammatory cytokines, and regulate the community structure of intestinal flora, and thus help to repair the damage of gastric mucosa.

To observe the effect of acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36) on intestinal flora in rats with stress gastric ulcer (SGU) , and to explore the mechanism of acupuncture promoting SGU recovery.Thirty-one SPF SD rats were randomly divided into a control group (7 rats), a model control group (8 rats), an acupuncture group (8 rats) and a medication group (8 rats). The rats in the model group, acupuncture group and medication group were selected to applied the improved restraint water-immersion stress method to establish the SGU model. After modeling, the rats in the control group and model group were fixed and restrained for 20 min every day for a total of 5 days; the rats in the acupuncture group were intervented with acupuncture at "Baihui" (GV 20), "Zhongwan" (CV 12) and "Zusanli" (ST 36), once a day, 20 min each time, and twisting needle for 30 s every 5 min for a total of 5 days; the rats in the medication group were gavaged by solution of omeprazole enteric-coated tablet (200 mg/mL), 2 mL for each rat, once a day. Guth method was used to calculate the gastric mucosal damage index (GMDI), HE staining was used to observe the pathological changes of gastric mucosa, and 16SrDNA identification was used to detect the structural abundance of intestinal flora.Compared with the control group, the GMDI of rats in the model group was increased (Acupuncture can effectively improve gastric mucosal injury of SGU, and the mechanism may be related to increasing the diversity of intestinal flora and promoting the correction of the disordered intestinal flora.

Acetyl coenzyme A (Ac-CoA)-dependent N-acetylation is performed by arylalkylamine N-acetyltransferase (AANAT) and is important in many biofunctions. AANAT catalyzes N-acetylation through an ordered sequential mechanism in which cofactor (Ac-CoA) binds first, with substrate binding afterward. No ternary structure containing AANAT, cofactor, and substrate was determined, meaning the details of substrate binding and product release remain unclear. Here, two ternary complexes of dopamine N-acetyltransferase (Dat) before and after N-acetylation were solved at 1.28 A and 1.36 A resolution, respectively. Combined with the structures of Dat in apo form and Ac-CoA bound form, we addressed each stage in the catalytic cycle. Isothermal titration calorimetry (ITC), crystallography, and nuclear magnetic resonance spectroscopy (NMR) were utilized to analyze the product release. Our data revealed that Ac-CoA regulates the conformational properties of Dat to form the catalytic site and substrate binding pocket, while the release of products is facilitated by the binding of new Ac-CoA. Wu et al. provide insight to the role of acetyl coenzyme A in regulating N-acetylation in insect AANAT using ITC and NMR methods. These results provide useful data on the structural function of insect AANATs.

Background: Immunotherapies have dramatically improved survival of melanoma patients. MUC16 encodes cancer antigen 125 (CA125), which is frequently mutated in melanoma. However, association of MUC16 mutation with tumor mutation load (TML), microenvironment, outcome and immunotherapeutic efficacy in melanoma remains elusive. Methods: We obtained 467 melanoma samples from the Cancer Genome Atlas (TCGA). We correlated MUC16 mutation status with TML, multiple immune-related signals in microenvironment, dysregulated pathways and outcome. An independent dataset containing 183 samples was used for validation. The association of MUC16 mutation with immune checkpoint inhibitor (ICI) efficacy was estimated with 144 ICI treated patients from a published study. Findings: MUC16 mutation exhibited the most significant correlation with TML in TCGA cohort. In both cohorts, patients with MUC16 mutations had significantly higher TML than those without MUC16 mutations. Enriched pro-inflammatory CD8 T cells and M1 macrophages, abundant total immune cells infiltration, enhanced interferon gamma (IFNγ) and T cell-inflamed signatures, and increased cytolytic activity were associated with MUC16 mutation. Immune-suppressive M2 macrophages was enriched in MUC16 wild-type patients. Immune checkpoints expression were also elevated in patients with MUC16 mutation. Patients with MUC16 mutations exhibited significantly better prognosis in both cohorts. For patients received ICI treatment, MUC16 mutation was associated with better response rate and survival outcome in male group but not in female and overall group. Interpretation: MUC16 mutation was associated with high TML, immune-activated microenvironment and favorable prognosis in melanoma. Male patients with MUC16 mutations had better ICI therapy efficacy. These findings provide new implications for tailoring immunotherapeutic strategies of melanoma patients. Funding Statement: This study was supported by the Program for Changjiang Scholars and Innovative Research Team in University in China [IRT_14R40 to K. C.], and the National Natural Science Foundation of China [no. 31801117 to X. L.]. Declaration of Interests: The authors stated: "None." Ethics Approval Statement: This study has been approved by the Tianjin Medical University Cancer Institute and Hospital.

Polybrominated diphenyl ethers (PBDEs) were commonly used flame retardants in the world, while some of PBDEs have been listed as persistent organic pollutants (POPs). Decabrominated diphenyl ether (BDE-209) was the most commercially used PBDEs. A farm near the factory located in Northern Taiwan was highly contaminated with BDE-209. Since PBDEs in the contaminated soils can be uptake by crops shown in our previous studies and could be potentially consumed by humans, it is very important to establish a feasible treatment method for PBDE remediation in this contaminated farm. Thermal treatment of PBDEs in soil was studied. The initial concentration of BDE-209 in contaminated soil was 1.472 mg/kg. A series of thermal experiments under different operating conditions including various temperature (105, 150, 200, 250, 300, 350, 400 and 450 °C), holding time (10, 20 and 30 min), heating rate (5, 10, 20 and 40 °C/min), and soil amount (10, 100, 1000 and 2000 g) were investigated. The optimal heating conditions for thermal treatment of contaminated soil were heating at 450 °C for 30 min with a heating rate of 10 °C/min. Under this condition, the removal of BDE-209 in the different weights of contaminated soil was tested. The soils in the contaminated farm were tested to further evaluate the feasibility of remediating the on-site PBDE contaminated soil through thermal treatment, suggesting that the holding time was extended to 2 h for the field-scale contaminated soil. The results showed that BDE-209 had been removed to below the detection limit in on-site soil. This investigation is the first study using thermal treatment to remediate soils really contaminated with PBDEs.

Objectives The aim of this study was to establish reference ranges for the corpus callosum in infancy and to clarify how sexual dimorphism evolves between the fetal stage and infancy. Methods Normal sonograms from cerebral ultrasonographic examinations of 1- to 6-month-old healthy full-term infants were selected. The length and thickness of the corpus callosum were determined, and the effect of sex on these values was analyzed. Studies on corpus callosum sexual dimorphism were reviewed. Results In total, sonograms from 236 1- to 6-month-old infants (120 male and 116 female) were collected, and the typical values (5th-95th percentiles) of the corpus callosum were determined for each group. During the first 2 months, with and without brain size adjustment, the corpus callosum in female infants was significantly thicker than that in male infants (mean thickness ± SD: 1 month, male infant, 1.8 ± 0.3 mm; female infant, 2.1 ± 0.3 mm; P = .005; 2 months, male infant, 1.8 ± 0.2 mm; female infant, 2.0 ± 0.3 mm; P = .002). The corpus callosum thickness of male and female infants had no significant differences after 2 months of age. Sexual dimorphism was not detected in corpus callosum length. Conclusions Our study provides reference data on typical corpus callosum development in infants. In the fetal period and early infancy, the corpus callosum in female infants is thicker than that in male infants. From 3 months onward, the corpus callosum sexual dimorphism becomes insignificant throughout childhood. The evolvement of corpus callosum sexual dimorphism suggests that maternal factors may influence brain development.

Chondrosarcoma is the second most prevalent general primary tumor of bone following osteosarcoma. Chondrosarcoma development may be linked to angiogenesis, which is principally elicited by vascular endothelial growth factor-A (VEGF-A). VEGF-A level has been recognized as a prognostic marker in angiogenesis. WNT1-inducible signaling pathway protein-3 (WISP)-3/CCN6 belongs to the CCN family and is involved in regulating several cellular functions, including cell proliferation, differentiation, and migration. Nevertheless, the effect of WISP-3 on VEGF-A production and angiogenesis in human chondrosarcoma remains largely unknown. This current study shows that WISP-3 promoted VEGF-A production and induced angiogenesis of human endothelial progenitor cells. Moreover, WISP-3-enhanced VEGF-A expression and angiogenesis involved the c-Src and p38 signaling pathways, while miR-452 expression was negatively affected by WISP-3 via the c-Src and p38 pathways. Our results illustrate the clinical significance of WISP-3, VEGF-A and miR-452 in human chondrosarcoma patients. WISP-3 may illustrate a novel therapeutic target in the metastasis and angiogenesis of chondrosarcoma.

The major goal of this study was to explore students' viewpoint toward the use of quick response codes in the pharmacology course in Taiwan. A total of 102 students were invited and agreed to take part in this project. The results indicated that a majority of students considered quick response codes easy to use and helpful with learning in a pharmacology course.

Canine parvovirus type 2 (CPV-2) is a severe enteric pathogen mainly affecting dogs. CPV-2 contains three antigenic variants (2a, 2b, and 2c) that are distributed internationally. Detection and characterization of the currently circulating CPV-2 strains are vital for the understanding of viral evolution, transmission, and the development of methods to control its spreading. Herein, we analyzed the strains in central Taiwan to provide information of local viral evolution, diversity, and epidemiology. Stool and blood samples from 24 dogs and 2 cats were genotyped by PCR amplification of strain-specific VP2 sequence collected during 2011–2013. 60% (16/26) of them were positive and 100% (16/16) of these positive samples were type 2b. Then, the full length VP2 gene was sequenced in 6 CPV-positive samples and a maximum-likelihood phylogenetic tree was constructed using both Taiwan and other strains worldwide. Surprisingly, all Taiwan CPVs showed high relatedness to type 2a. Recombination analysis revealed a recombination of VP2 gene between type 2a and 2b. This study demonstrates a recombination between CPV-2a and 2b in nature that contributes to the genetic diversity and evolution of CPV-2.

Lung cancer is one of the most frequently diagnosed malignancies and is associated with a poor survival rate in the Chinese Han population. Analysis of genetic variants could lead to improvements in prognosis following lung cancer therapy. High-mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein found in eukaryotic cells that participates in several biological functions including immune response, cell survival, apoptosis and cancer development. We investigated the effects of HMGB1 gene polymorphisms on the risk of lung cancer progression in a Chinese Han population. Our sample of 751 participants included 372 patients with lung cancer and 379 healthy controls. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene were examined by real-time polymerase chain reaction (RT-PCR). We found that the CT or CC+CT heterozygotes of the HMGB1 rs1045411 polymorphism reduced the risks for lung cancer, while the G/T/C haplotypes of three HMGB1 SNPs (rs1360485, rs1045411 and rs2249825) also reduced the risk for lung cancer by almost half (0.486-fold). The current study is the first to examine the risk factors associated with HMGB1 SNPs in lung cancer development in the Chinese Han population.

Lung cancers have a predilection for metastasizing to bone. The matricellular glycoprotein thrombospondin (TSP)-2 regulates multiple biological functions and has a critical role in tumor development and metastasis, although its effects are uncertain in lung cancer bone metastasis. This study demonstrates that TSP-2 expression is highly correlated with lung cancer tumor stage and that the TSP-2 neutralizing antibody reduces osteoclast formation in conditioned medium obtained from lung cancer cells. We also found that TSP-2 promotes osteoclastogenesis through the RANKL-dependent pathway and that TSP-2-mediated osteoclastogenesis involves the transactivation of nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) via the inhibition of miR-486-3p expression. Osteoblasts played a critical role in osteoclast differentiation and incubation of osteoblasts with TSP-2 altered the RANKL:OPG ratio. Furthermore, TSP-2 knockdown inhibited lung cancer osteolytic metastasis in vivo. TSP-2 appears to be worth targeting for the prevention of bone metastasis in lung cancer.

Background: Immune checkpoint blockade (ICB) therapies have revolutionized the treatment of human cancer including lung adenocarcinoma (LUAD). However, our understanding of the immune subtyping of LUAD and its association with clinical response of immune checkpoint inhibitor remains incomplete. Methods: We performed molecular subtyping of LUAD by analyzing immune infiltrating profiles of one LUAD cohorts from The Cancer Genome Atlas (TCGA) (discovery set) and 7 cohorts from Gene Expression Omnibus (GEO) (validation sets). Consensus molecular subtyping was performed using nonnegative matrix factorization (NMF). We used Tumor immune dysfunction and exclusion (TIDE) algorithm to predict potential response of ICB therapy and gene set enrichment analysis (GSEA) to identify dysregulated pathways. Findings: We identified 2 distinct subtypes of LUAD in TCGA cohorts that were characterized by significantly different immune infiltrating patterns and survival outcomes (i.e., high- and low-risk subtypes). The high-risk subtype was featured by upregulation of programmed death-ligand 1 (PD-L1) expression, higher infiltration of tumor infiltrating lymphocytes (TIL), and higher tumor mutation burden (TMB). Further analysis indicated the high-risk subtype harbored significantly activated cell cycle and TP53 mutation. These observations were validated in 7 additional independent LUAD cohorts. Interpretation: We identified 2 subtypes of LUAD featured by different immune infiltrating signatures and molecular mechanisms. Immune checkpoint blockade therapy may be efficacious for high-risk subtype of LUAD patients. Funding Statement: The study has been supported by the Program for Changjiang Scholars and Innovative Research Team in University in China (IRT_14R40) and National Natural Science Foundation of China (NSFC) (no. 31801117). Declaration of Interests: The authors state: "None reported." Ethics Approval Statement: Not required.

// Shuai Zhen 1, 2 , Yoichiro Takahashi 3 , Shunichi Narita 3 , Yi-Chen Yang 4 , Xu Li 1, 2 1 Center for Translational Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, P.R. China 2 Key Laboratory for Tumor Precision Medicine of Shaanxi Province, The First Affiliated Hospital of Xi’an Jiaotong University, P.R. China 3 Center for iPS Cell Research and Application (CiRA), Kyoto University, Kyoto, Japan 4 Tsinghua University, School of Life Sciences, Beijing, China Correspondence to: Xu Li, email: lixu56@mail.xjtu.edu.cn Keywords: CRISPR/Cas9 delivery, aptamer-liposome chimera, prostate cancer, prostate-specific membrane antigen (PSMA), polo-like kinase 1 (PLK1) Received: September 01, 2016 Accepted: December 06, 2016 Published: December 21, 2016 ABSTRACT The potent ability of CRISPR/Cas9 system to inhibit the expression of targeted gene is being exploited as a new class of therapeutics for a variety of diseases. However, the efficient and safe delivery of CRISPR/Cas9 into specific cell populations is still the principal challenge in the clinical development of CRISPR/Cas9 therapeutics. In this study, a flexible aptamer-liposome-CRISPR/Cas9 chimera was designed to combine efficient delivery and increased flexibility. Our chimera incorporated an RNA aptamer that specifically binds prostate cancer cells expressing the prostate-specific membrane antigen as a ligand. Cationic liposomes were linked to aptamers by the post-insertion method and were used to deliver therapeutic CRISPR/Cas9 that target the survival gene, polo-like kinase 1, in tumor cells. We demonstrate that the aptamer-liposome-CRISPR/Cas9 chimeras had a significant cell-type binding specificity and a remarkable gene silencing effect in vitro . Furthermore, silencing promoted a conspicuous regression of prostate cancer in vivo . Importantly, the approach described here provides a universal means of cell type–specific CRISPR/Cas9 delivery, which is a critical goal for the widespread therapeutic applicability of CRISPR/Cas9 or other nucleic acid drugs.

Lung cancer is one of the most common cancer in cancer-related deaths worldwide, which is characterized by its strong metastatic potential. The melatonin hormone secreted by the pineal grand has an antioxidant effect and protects cells against carcinogenic substances. However, the effects of melatonin in lung cancer stemness are largely unknown. We found that melatonin reduces CD133 expression by ~50% in lung cancer cell lines, while results of a sphere formation assay showed that melatonin inhibits lung cancer stemness. These effects of melatonin were reversed when the cell lines were incubated with phospholipase C (PLC), ERK/p38, and a β-catenin activator. Transfection with Twist siRNA augmented the inhibitory effects of melatonin, indicating that melatonin suppresses lung cancer stemness by inhibiting the PLC, ERK/p38, β-catenin, and Twist signaling pathways. We also found CD133 expression is positively correlated with Twist expression in lung cancer specimens. Melatonin shows promise in the treatment of lung cancer stemness and deserves further study.

This research looks at the service failure and recovery in the airline industry, a general service business vulnerable to failures such as losing baggage. Based on a real experience interacting with China Southern Airline, the study reviews existing literature and addresses that the service failure is detrimental to maintaining customer loyalty or long-term profitability, whereas a successful recovery is conducive to moderating the risk of losing revenue. Six potential solutions from current literature being evaluated, the study thereupon recommends three practicable strategies that assisting managers in getting further insight into service recovery and eventually minimizing potential losses.

Codonopsis taxa, as a traditional Chinese medicinal and edible plant, has found expanding domestic and foreign applications in recent decades. However, the poor management in germplasm resources market has inevitably caused an unnecessary hybrid of the provenances. In order to clarify the hybrid characteristics of germplasm resources in the main production area, the Codonopsis cultivars collected from the provinces Gansu, Shannxi, Shanxi, and Hubei of China were researched, using internal transcribed spacer (ITS) sequence technology. The confirmation of additive nucleotides based on the ITS sequencing of polymerase chain reaction (PCR) mixture was optimized and used to study the hybrid of Codonopsis cultivars. The results showed that when the ratio of PCR mixture increased up to 15 percent, the presence of a double peak in the sequencing electrophoresis map could be confirmed, suggesting the existence of additive nucleotides. According to the method above, 46 samples of Codonopsis cultivars collected during 2016 and 2017 were studied and compared with the samples collected from the year 2009 to 2010. All of the samples collected during 2016 and 2017 were hybridized and no genetic pure lines were found. In addition, the sites of variable base reduced greatly, concentrating at positions 122 and/or 226. These phenomena suggested that the genetic diversity of Codonopsis cultivars declined and the germplasm resources gradually converged. More attention should be paid to the reasonable exploitation and genetic breeding of Codonopsis taxa.

Background: Countries at higher latitudes have higher incidence rates of Kawasaki disease (KD) than do countries at lower latitudes in the Asian and West Pacific area. However, the precise influence of latitude on KD incidence rates requires further clarification. Methods: We searched the Longitudinal Health Insurance Database 2005 to retrieve patients’ medical records from 1996 to 2009. The patients with KD were categorized as living in northern, middle, and southern Taiwan; the period prevalence of KD for each area was determined. Climate variables, including temperature, sunshine duration, precipitation, and relative humidity, were collected from the Taiwan Central Weather Bureau. The effect of latitude on the period KD prevalence and the correlation between climate variables and KD prevalence were calculated. Results: After patients without complete data excluded, a total of 61,830 children up to 10 years old were retrieved, from which 404 patients with KD were recognized. The period prevalence of KD increased significantly with latitude (p = 0.0004). Climate variables associated with high temperature demonstrated a connection with KD prevalence; however, this correlation was not statistically significant. Conclusions: Our study demonstrated that higher latitude is associated with a higher KD prevalence in Taiwan.

Vaccination, which provides effective, safe infectious disease protection, is among the most important recent public health and immunological achievements. However, infectious disease remains the leading cause of death in developing countries because several vaccines require repeated administrations and children are often incompletely immunized. Microsphere-based systems, providing controlled release delivery, can obviate the need for repeat immunizations. Here, we review the function of sustained and pulsatile release of biodegradable polymeric microspheres in parenteral and mucosal single-dose vaccine administration. We also review the active-targeting function of polymeric particles. With their shield and co-delivery functions, polymeric particles are applied to develop single-dose and mucosally administered vaccines as well as to improve subunit vaccines. Because polymeric particles are easily surface-modified, they have been recently used in vaccine development for cancers and many infectious diseases without effective vaccines (e.g., human immunodeficiency virus infection). These polymeric particle functions yield important vaccine carriers and multiple benefits.

Background Corpus callosum atrophy has been associated with cognitive and motor deficits in elderly people. However, the role of the corpus callosum in infant development is unclear. The aim of this study was to assess the impact of corpus callosum size on motor development in infants. Methods We investigated cerebral ultrasonograms performed on healthy infants aged 4 to 6 months. The correlation between the development of rolling over and corpus callosum size was calculated for determining odds ratios. Covariates, including gestational age, sex, age in months, and head circumference were tested using logistic regression. Results We investigated 244 cerebral ultrasonograms performed on term infants from 2009 to 2011. The percentage of rolling over development in the examined infants increased with age (47.8%, 78.4%, and 97.5% at ages 4, 5, and 6 months, respectively). There was no significant difference in the development of rolling over between male (67.9%) and female (73.6%) children or among different gestational age groups. After the other covariates in the logistic model were adjusted, only age and corpus callosum size (length and thickness) were significantly associated with the development of rolling over: 3.86 times the odds (confidence interval, 2.1 to 7.0) for age in months, 1.14 times the odds (confidence interval, 1.0 to 1.3) for corpus callosum length, and 3.92 times the odds (confidence interval, 1.6 to 9.6) for corpus callosum thickness. Conclusions Corpus callosum size is positively associated with the development of rolling over in healthy term infants, independent of the gestational age, sex, age, and head circumference.