Comparison of microstructure, mechanical property, and degradation rate of Mg-1Li-1Ca and Mg-4Li-1Ca alloys.

Mg-1 wt.% Li-1 wt.% Ca (LX11) and Mg-4 wt.% Li-1 wt.% Ca (LX41) alloys share the same hexagonal closed-packed crystalline structure. However, the differences in microstructure, mechanical properties, and degradation rates between the two alloys are not well understood. Hereby, the above three aspects of LX11 and LX41 alloys were studied via optical microscopy, tensile tests, and electrochemical polarization and electrochemical impedance spectroscopy, together with hydrogen evolution. The concentration of the released Mg2+, Ca2+, and Li+ ions was analyzed using a flame atomic absorption spectrophotometer. Results demonstrated that the LX11 alloy was composed of finer α-Mg grains, fewer twins, and smaller volume fractions of the intermetallic phases Mg2Ca than the LX41 alloy. The increasing Li concentration generated a weak decrease in the yield strength of the Mg-Li-Ca alloys, a remarkable increase in elongation to failure, and a stable ultimate tensile strength. The LX11 alloy had better corrosion resistance than the LX41 alloy. The release rate of the cations (Mg2+, Ca2+, and Li+) varied significantly with time. The release rate of metallic ions in Hank's solution cannot reflect the true corrosion rate of Mg-Li-Ca alloys due to the formation of the precipitated corrosion products and their difference in solubility. The dealloying corrosion mechanism of the Mg2Ca phase in Mg-Li-Ca alloys was proposed.

Clinical outcomes and prognostic risk factors of Langerhans cell histiocytosis in children: Results from the BCH-LCH 2014 protocol study.

Langerhans cell histiocytosis (LCH) is a rare myeloid neoplasm mainly affecting young children. This study aimed to evaluate the outcomes of 449 pediatric patients enrolled in the BCH-LCH 2014 study. 52.6% of patients were classified with single-system (SS) LCH, 28.1% with multisystem (MS) risk organ negative (RO-) LCH, and 19.4% with MS RO+ LCH. Three hundred ninety-six patients (88.2%) were initially treated with first-line therapy based on the vindesine-prednisone combination. One hundred thirty-nine patients who lacked a response to initial treatment were shifted to second-line therapy, 72 to intensive treatment Arm S1 (a combination of cytarabine, cladribine, vindesine, and dexamethasone), and 67 to Arm S2 (without cladribine). The 5-year overall survival (OS), progression-free survival (PFS), and relapse rates were 98.2% (median: 97.6 months), 54.6% (median: 58.3 months), and 29.9%, respectively. MS RO+ patients had the worst prognosis among the three clinical subtypes. For the patients initially treated with first-line therapy, the 5-year OS, PFS, and relapse rates were 99.2%, 54.5%, and 29.3%, respectively. Patients in Arm S1 had a significantly better prognosis than patients in Arm S2 (5-year PFS: 69.2% vs. 46.5%, p = .042; relapse rate: 23.4% vs. 44.2%, p = .031). Multivariate analysis revealed that early treatment response, the involvement of RO, skin, and oral mucosa, as well as laboratory parameters, including CRP and γ-GT, were independent risk factors for the PFS of LCH. Thus, the prognosis of LCH in children has been improved significantly with stratified chemotherapy, and progression and relapse remained the challenges, especially for RO+ patients.

Lipid Droplets in Lung Cancers Are Crucial for the Cell Growth and Starvation Survival.

For rapid and unlimited cell growth and proliferation, cancer cells require large quantities of nutrients. Many metabolic pathways and nutrient uptake systems are frequently reprogrammed and upregulated to meet the demand from cancer cells, including the demand for lipids. The lipids for most adult normal cells are mainly acquired from the circulatory system. Whether different cancer cells adopt identical mechanisms to ensure sufficient lipid supply, and whether the lipid demand and supply meet each other, remains unclear, and was investigated in lung cancer cells. Results showed that, despite frequent upregulation in de novo lipogenesis and the lipid transporter system, different lung cancer cells adopt different proteins to acquire sufficient lipids, and the lipid supply frequently exceeds the demand, as significant amounts of lipids stored in the lipid droplets could be found within lung cancer cells. Lipid droplet surface protein, PLIN3, was found frequently overexpressed since the early stage in lung cancer tissues. Although the expression is not significantly associated with a specific gender, age, histology type, disease stage, and smoking habit, the frequently elevated expression of PLIN3 protein indicates the importance of lipid droplets for lung cancer. These lipid droplets are not only for nutrient storage, but are also crucial for tumor growth and proliferation, as well as survival in starvation. These results suggest that manipulation of lipid droplet formation or TG storage in lung cancer cells could potentially decrease the progression of lung cancer. Further exploration of lipid biology in lung cancer could help design novel treatment strategies.

The potential and limitation of targeted chromosomal breakpoint sequencing for the ROS1 fusion gene identification in lung cancer.

ROS1 fusion genes are rare but important driver genes in lung cancer. Owing to their rarity, many clinicopathological features and treatment responses for each ROS1 fusion variant are still largely unknown and require further investigation. RNA is the preferable template for the ROS1 fusion gene screening, but deterioration of RNA in FFPE often makes the detection challenging. To resolve the difficulty, a targeted chromosomal breakpoint sequencing method was developed for searching the ROS1 fusion gene, and was compared with fluorescence in situ hybridization, immunohistochemistry, RT-qPCR using 260 lung cancer samples of Southern Taiwan. The results showed that ROS1-altered cases were present at low frequencies, did not share distinct clinicopathological features, and often carried other driver mutations. The performance of the targeted sequencing assay was superior to the RT-qPCR in ROS1 fusion gene identification when the cDNAs were from FFPE samples, but long-read DNA sequencing and fresh-frozen samples would be better to revolve all fusion genes. Precise determination of all ROS1 fusion variants and concomitant driver mutations using both genomic DNA and RNA would be required to help improve the treatment of patients with ROS1 alterations.

A highly sensitive and specific real-time quantitative PCR for BRAF V600E/K mutation screening.

Mutations that lead to constitutive activation of key regulators in cellular processes are one of the most important drivers behind vigorous growth of cancer cells, and are thus prime targets in cancer treatment. BRAF V600E mutation transduces strong growth and survival signals for cancer cells, and is widely present in various types of cancers including lung cancer. A combination of BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) has recently been approved and significantly improved the survival of patients with advanced NSCLC harboring BRAF V600E/K mutation. To improve the detection of BRAF V600E/K mutation and investigate the incidence and clinicopathological features of the mutation in lung cancer patients of southern Taiwan, a highly sensitive and specific real-time quantitative PCR (RT-qPCR) method, able to detect single-digit copies of mutant DNA, was established and compared with BRAF V600E-specific immunohistochemistry. Results showed that the BRAF V600E mutation was present at low frequency (0.65%, 2/306) in the studied patient group, and the detection sensitivity and specificity of the new RT-qPCR and V600E-specific immunohistochemistry both reached 100% and 97.6%, respectively. Screening the BRAF V600E/K mutation with the RT-qPCR and V600E-specific immunohistochemistry simultaneously could help improve detection accuracy.

[The regulation of ubiquitination in milk fat synthesis in bovine].

Ubiquitination signaling is the main pathway of protein degradation in eukaryotic cells. Ubiquitin-proteasome system degrades the ubiquitinated cytoplasmic proteins and lysosome pathway mainly degrades the ubiquitinated membrane proteins. Previous studies have shown that ubiquitination signaling plays a critical role in fatty acids synthesis. In the process of fatty acids import, disruption of ubiquitination could prevent the degradation of fatty acid transport proteins, thereby promoting fatty acids import and milk fat synthesis in bovine primary mammary epithelial cells. In this review, we summarize the signal transduction and regulation mechanism of ubiquitination signaling in milk fat synthesis, which may provide references and new ideas for future research on milk fat traits in dairy cows.

Knock-down Sox5 suppresses porcine adipogenesis through BMP R-Smads signal pathway.

Adipogenesis, a differentiation process that transitions preadipocytes to adipocytes, is key to understanding the biology of fat accumulation and obesity. During this process, there many crucial transcription factors, such as PPARγ and the C/EBP family. Here we show a transcription factor in preadipocytes --- Sox5, that has a function in porcine adipogenesis. In our porcine subcutaneous-derived preadipocyte differentiation model, we found Sox5 expression displayed a significant upregulation after initial induction and decreased afterwards, which resembles the PPARγ expression pattern. siRNA knockdown of Sox5 in porcine preadipocytes significantly promoted cell growth and accelerated cell cycle progression. After inducing differentiation, knockdown of Sox5 notably down-regulated the expression of adipogenic marker genes: PPARγ, aP2, FAS and impaired lipid accumulation. Mechanistically, the deletion of Sox5 down-regulated the BMP R-Smads signal pathway, a crucial signal pathway for controlling preadipocyte fate commitment and adipogenesis. After using BMP4 recombinant protein to activate the BMP R-Smads signal, Sox5 function was partially rescued. In conclusion, our findings uncovered a function of Sox5 in porcine adipogenesis and reveal an interaction between Sox5 and BMP signaling.

Differences between porcine longissimus thoracis and semitendinosus intramuscular fat content and the regulation of their preadipocytes during adipogenic differentiation.

Intramuscular fat (IMF) plays an important role in pork quality. However, differences in the adipogenic regulation of IMF content between pig longissimus thoracis (LT) and semitendinosus (ST) remain unclear. Here, we found that IMF content of 180-day-old pig LT was greater than that of pig ST. Furthermore, lipid accumulation was earlier and greater in LT intramuscular preadipocytes (L-IMA) than in ST intramuscular preadipocytes (S-IMA) during differentiation. Interestingly, glucose consumption was lower in L-IMA than in S-IMA. Moreover, monounsaturated fatty acid content was greater in L-IMA than in S-IMA, whereas polyunsaturated fatty acid content was lower. Levels of the expression of key adipogenic genes were higher in L-IMA than S-IMA. Compared with S-IMA, adipogenic signals were more activated in L-IMA after adipogenic induction. In conclusion, IMF deposition differences between pig LT and ST were due to different glucose consumption, fatty acid composition, expression of key adipogenic genes and level of activating adipogenic signals between S-IMA and L-IMA during adipogenesis.

[Regulation of VPS28 gene knockdown on the milk fat synthesis in Chinese Holstein dairy].

In a previous genome-wide association study on milk production traits in Chinese Holstein population, we discovered VPS28 gene was highly expressed in mammary gland tissue. Further, a -58C>T mutantion at the 5°-UTR of the gene was significantly associated with milk fat content traits. However, its regulation on milk fat content is still uncertain. In this study, we explored the effect of this -58C>T mutation on VPS28, and found that it could significantly reduce promoter activity of VPS28 gene. To identify the potential function of this SNP, we performed RNAi experiments to knockdown VPS28 gene in BMECs and examined the general effects of VPS28 knockdown on BMECs. The results showed that VPS28 knockdown could decrease the mRNA expression of genes in ubiquitination-lysosome and ubiquitination- proteasome pathways, increase the mRNA expression of genes in milk fat synthesis pathway and promote triglyceride synthesis in BMECs. Our data indicate that VPS28 gene could regulate milk fat synthesis pathway; and promote triglyceride synthesis in BMECs. Our data indicate that VPS28 gene could regulate milk fat synthesis through modulating the ubiquitination-lysosome and ubiquitination-proteasome systems. Our results demonstrate the molecular mechanism of VPS28 on regulation of milk synthesis in dairy cattle through the ubiquitination signaling pathway, thereby supporting a relationship between milk fat synthesis and ubiquitination and laying the molecular foundation in breeding of dairy cattle in the future.

Impact of putamen stroke on task context updating: Evidence from P300 brain waves.

According to the context updating theory, the oddball P300 component indexes brain activities underlying revision of the mental representation induced by incoming stimuli. It involves an attention-driven comparison process that evaluates the representation of the previous event in working memory. Delayed latencies have been reported for various types of stroke such as unilateral thalamic stroke. We investigated memory updating effects in patients with putamen stroke. Two groups of patients with putamen and thalamic stroke were recruited along with two control groups of young and old healthy participants. Auditory and visual P300 were elicited respectively in a two-stimulus oddball paradigm. The auditory P300 peak latencies were significantly longer in patients with a putamen lesion than in the aged and young control groups and the same pattern was found in the thalamus-lesioned patient. The delayed auditory P300 component in both patient groups but neither control group suggests impairment of memory updating in patients with putamen stroke comparable with thalamic stroke. Our study illustrates the important role of subcortical structures subserved in context updating.

miR-425-5p Inhibits Differentiation and Proliferation in Porcine Intramuscular Preadipocytes.

Intramuscular fat (IMF) content affects the tenderness, juiciness, and flavor of pork. An increasing number of studies are focusing on the functions of microRNAs (miRs) during porcine intramuscular preadipocyte development. Previous studies have proved that miR-425-5p was enriched in porcine skeletal muscles and played important roles in multiple physiological processes; however, its functions during intramuscular adipogenesis remain unclear. To explore the role of miR-425-5p in porcine intramuscular adipogenesis, miR-425-5p agomir and inhibitor were used to perform miR-425-5p overexpression and knockdown in intramuscular preadipocytes, respectively. Our results showed that the agomir of miR-425-5p dramatically inhibited intramuscular adipogenic differentiation and downregulated the expression levels of adipogenic marker genes PPARγ, FABP4, and FASN, whereas its inhibitor promoted adipogenesis. Interestingly, the agomir repressed proliferation of porcine intramuscular preadipocytes by downregulation of cyclin B and cyclin E. Furthermore, we demonstrated that miR-425-5p inhibited adipogenesis via targeting and repressing the translation of KLF13. Taken together, our findings identified that miR-425-5p is a novel inhibitor of porcine intramuscular adipogenesis possibly through targeting KLF13 and subsequently downregulating PPARγ.

miR-429 Inhibits Differentiation and Promotes Proliferation in Porcine Preadipocytes.

MicroRNAs (miRNAs) are crucial regulatory molecules for adipogenesis. They contribute to the controlling of proliferation and differentiation of preadipocytes. Previous studies revealed an important role of miR-429 in cell invasion, migration, and apoptosis. Our previous work has shown that the expression of miR-429 in subcutaneous fat can be observed in newly born (3-day-old) Rongchang piglets rather than their adult counterparts (180-day-old). This expression pattern suggests that miR-429 might be functionally related to postnatal adipogenesis. However, we currently lack a mechanistic understanding of miR-429 within the context of preadipocyte differentiation. In this study, we investigated the function of miR-429 in porcine subcutaneous and intramuscular preadipocyte proliferation and differentiation. In our porcine preadipocyte differentiation model, miR-429 expression decreased remarkably upon adipogenic induction. Overexpression of miR-429 notably down-regulated the expression of adipogenic marker genes: PPARγ, aP2, FAS and impaired the triglyceride accumulation, while the expression of lipolytic gene ATGL was not affected. In addition, we observed that miR-429 significantly promoted the proliferation of porcine preadipocytes. We also found that miR-429 could directly bind to the 3'-UTRs of KLF9 and p27, which have been well documented to promote preadipocyte differentiation and repress cell cycle progression. Taken together, our data support a novel role of miR-429 in regulating porcine preadipocyte differentiation and proliferation, and KLF9 and p27 are potent targets of miR-429 during these processes.

Occurrence of Hexabromocyclododecane in soil and road dust from mixed-land-use areas of Shanghai, China, and its implications for human exposure.

Herein, the occurrence of three Hexabromocyclododecane (HBCDD) diastereoisomers in soil and road dust from the mixed-land-use areas in Shanghai was investigated. The total concentrations of HBCDDs (∑HBCDDs) in soil ranged from 0.30 to 249ngg(-1)dw, with a median level of 5.14ngg(-1)dw. For the road dust samples, the ΣHBCDD concentrations varied from 4.11 to 508ngg(-1)dw, with a median level of 23.4ngg(-1)dw. The levels of HBCDDs varied in different mixed-land-use areas. In soil, the levels of HBCDDs increased in the following sequence: residential area & agricultural area (R&A)

Use of and Self-Perceived Need for Assistive Devices in Individuals with Disabilities in Taiwan.

Assistive devices (ADs) can help individuals with disabilities achieve greater independence, and it can enhance the quality of their lives. This study investigated the use of and self-perceived need for ADs in individuals with disabilities, and determined the influence of gender, age as well as type and degree of disability on the use of and self-perceived need for ADs. This descriptive study utilized a cross-sectional survey design with a convenience sample of participants. A total of 1018 subjects with disabilities who visited an exhibition of assistive technology and two ADs research and development centers completed a questionnaires either by themselves or via a caregiver who completed the questionnaire on behalf of the subject or via interviewers trained specifically for this study. The Mann-Whitney U test and Kruskal-Wallis test were used to determine the influence of participant characteristics on the use of ADs. The results showed that 77.2% and 83.3% of the participants reported that they used and needed AD(s) to engage in activities of daily living. The mean quantity of the use of and self-perceived need for total types of ADs were 3.0 and 5.3, respectively. Participants with different disabilities reported different percentages of the use of various types of ADs. No difference was found between genders and among the age groups in the use of quantity of ADs. Individuals with different types and degrees of disability used different quantities of ADs. Participants with physical, visual and multiple disabilities used significantly more ADs compared to participants with intellectual disability. The total quantity of ADs used increased significantly with increased severity of disability. The mean use of assistive devices was lower compared to the mean need of individuals with disabilities. Further study is required to determine why patients feel the need for but not currently use a specific assistive device.

Expression of Beclin Family Proteins Is Associated with Tumor Progression in Oral Cancer.

BACKGROUND: Beclin 1 and Beclin 2 are autophagy-related proteins that show similar amino acid sequences and domain structures. Beclin 1 established the first connection between autophagy and cancer. However, the role of Beclin 2 in cancer is unclear. The aims of this study were to analyze Beclin 1 and Beclin 2 expressions in oral cancer tissues and in cell lines, and to evaluate their possible roles in cancer progression. METHODS: We investigated Beclin 1 and Beclin 2 expressions by immunohistochemistry in 195 cases of oral cancer. The prognostic roles of Beclin 1 and Beclin 2 were analyzed statistically. In vitro, overexpression and knockdown of Beclin proteins were performed on an oral cancer cell line, SAS. The immunofluorescence and autophagy flux assays confirmed that Beclin proteins were involved in autophagy. The impacts of Beclin 1 and Beclin 2 on autophagy and tumor growth were evaluated by conversion of LC3-I to LC3-II and by clonogenic assays, respectively. RESULTS: Oral cancer tissues exhibited aberrant expressions of Beclin 1 and Beclin 2. The cytoplasmic Beclin 1 and Beclin 2 expressions were unrelated in oral cancer tissues. In survival analyses, high cytoplasmic Beclin 1 expression was associated with low disease specific survival, and negative nuclear Beclin 1 expression was associated with high recurrent free survival. Patients with either high or low cytoplasmic Beclin 2 expression had significantly lower overall survival and disease specific survival rates than those with moderate expression. In oral cancer cells, overexpression of either Beclin 1 or Beclin 2 led to autophagy activation and increased clonogenic survival; knockdown of Beclin 2 impaired autophagy and increased clonogenic survival. CONCLUSIONS: Our results indicated that distinct patterns of Beclin 1 and Beclin 2 were associated with aggressive clinical outcomes. Beclin 1 overexpression, as well as Beclin 2 overexpression and depletion, contributed to tumor growth. These findings suggest Beclin proteins are associated with tumorigenesis.

Effect of Anterior Ankle-Foot Orthoses on Weight Shift in Persons With Stroke.

OBJECTIVE: To examine the effects of an anterior ankle-foot orthosis (AAFO) on the speed and accuracy of weight shift in persons with stroke. DESIGN: Cross sectional, repeated measures. SETTING: Neurologic rehabilitation department. PARTICIPANTS: People with stroke (N=24) who were unable to voluntarily dorsiflex the foot against gravity. INTERVENTION: The weight-shift performance was measured with and without the AAFO. MAIN OUTCOME MEASURES: The speed and accuracy of sustained and cyclic bilateral weight shift were measured using the computerized dynamic posturography. The movement velocity, maximum excursion, and directional control of sustained weight shift were calculated using the limits of stability test. The on-axis velocity gap, directional control, and stability of cyclic bilateral weight shift were calculated using the rhythmic weight shift test. RESULTS: For sustained weight shift, the maximum excursion of weight shift to the affected side was greater with the AAFO (P=.002). For cyclic bilateral weight shift, the on-axis velocity gap in the mediolateral (ML) direction was smaller at a fast speed (P=.004). The stability of the ML and anteroposterior weight shift was higher at slow (P=.002 and P<.001, respectively) and fast (P=.001 and P<.001, respectively) speeds when wearing the AAFO. CONCLUSIONS: The findings demonstrated that persons with stroke who wear an AAFO might improve the excursion of the sustained weight shift to the affected side and the speed and stability of cyclic bilateral weight shift in the ML direction.

User satisfaction with orthotic devices and service in taiwan.

User satisfaction is afforded considerable importance as an outcome measurement in evidence-based healthcare and the client-centered approach. Several studies have investigated user satisfaction with orthoses. Few studies have investigated user satisfaction with orthoses in Taiwan. Therefore, the purpose of this study was to investigate the user satisfaction with orthotic devices and service using the Taiwanese version of Quebec User Evaluation of Satisfaction with Assistive Technology. We conducted a cross-sectional study of 280 subjects who had used orthoses and received services. The results showed that the mean satisfaction score was 3.74 for the devices and 3.56 for service. Concerning the participants, 69.1% and 59.6% were quite satisfied or very satisfied with their devices and service, respectively. The satisfaction score of orthotic service was lower than that of the devices. Regarding demographic characteristics, participants living in different areas differed only in service score (p = 0.002). The participants living in eastern area and offshore islands were the least satisfied with the orthotic service. For clinical characteristics, there was a significant difference in satisfaction scores among severity of disability (all p = 0.015), types of orthoses (all p = 0.001), and duration of usage (all p = 0.001). The participants with mild disability, wearing the pressure garment and using the orthosis for less than one year, were the most satisfied with their orthotic devices and service. There is a need for improved orthotic devices and services, especially with respect to the comfort of the devices and the provision of subsidy funding.

Effects of an anterior ankle-foot orthosis on walking mobility in stroke patients: get up and go and stair walking.

OBJECTIVE: To examine the effects of an anterior ankle-foot orthosis (AAFO) on walking mobility in stroke patients. DESIGN: Cross-sectional and repeated-measures study design. SETTING: A university's neurologic rehabilitation department. PARTICIPANTS: Ambulant stroke patients (N=21). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking mobility was measured by the Timed Up and Go (TUG) test and the Timed Up and Down Stairs (TUDS) test. The paired t test was used to determine the difference between the mobility performances measured with and without the AAFO. RESULTS: There were significant differences between mobility performances with and without an AAFO in the TUG test (P=.038) and the TUDS test (P=.000). CONCLUSIONS: This study supports the effect of an AAFO on walking mobility in stroke patients. The findings demonstrate that stroke patients wearing an AAFO may ambulate with greater speed and safety on level surfaces and stairs.

[Spring food selection by Rhinopithecus bieti at Mt. Lasha in relation to phytochemical components].

Food selection by folivorous primates is thought to relate to macronutrients, micronutrients and plant secondary metabolites. However, few studies explain their effects on food choices. This study was designed to clarify the effect of phytochemical components on Rhinopithecus bieti food choice by analyzing the chemical composition of food samples collected from March to May in 2010 and 2011 at Mt. Lasha in northwest Yunnan, China. Compared with non-foods, there was more phosphorous and crude protein, less total sugar and a lower ratio of calcium to phosphorus in selected foods. However, no differences were found in crude fat, crude ash, calcium and tannin content between foods and non-foods. Phytochemical constituents may influence food choices; the monkeys preferred foods with high phosphorus and low Ca/P, low calcium, low sugar and low tannins. Rhinopithecus bieti foraged high quality foods such as buds and young leaves to meet their nutritional needs after a long winter. Therefore, if tannin content in food did not exceed the enduring threshold of R. bieti, the nutrient intake was prioritized by phosphorus and calcium regulation when the need for macronutrients dominated by protein was satisfied.