α-Vitamin E derivative, RRR-α-tocopheryloxybutyric acid inhibits the proliferation of prostate cancer cells

Aim： To investigate the activity of RRR-α-tocopheryloxybutyric acid （TOB）, an ether analog of RRR-α-tocopheryl succinate （VES）, in prostate cancer cells. Methods： VES and TOB were used to treat prostate cancer LNCaP, PC3, and 22Rvl cells and primary-cultured prostate fibroblasts. The proliferation rates were determined by MTT assay, the cell viabilities were determined by trypan blue exclusion assay, and the cell deaths were evaluated by using Cell Death Detection ELISA kit. The protein expression levels were determined by Western blot analysis. Results： The MTT growth assay demonstrated that TOB could effectively suppress the proliferation of prostate cancer cells, but not normal prostate fibroblasts. Mechanism dissections revealed that TOB reduced cell viability and induced apoptosis in prostate cancer cells similar to VES. In addition, both TOB and VES suppressed prostate-specific antigen （PSA） at the transcriptional level leading to reduced PSA protein expression. Furthermore, vitamin D receptor （VDR） expression increased after the addition of TOB. Conclusion： Our data suggests that the VES derivative, TOB, is effective in inhibiting prostate cancer cell proliferation, suggesting that TOB could be used for both chemopreventive and chemotherapeutic purposes in the future.

Role of Rehabilitation Counseling and Psychology in Working with Individuals with Work-related Chronic Pain Injuries: An Interdisciplinary Approach-Chronic Pain and Work Injuries in the United States

This paper addresses the topic of an interdisciplinary approach of chronic pain management from a biopsychosocial perspective. The first section provides an introduction to the definitions and theories of chronic pain and the various contributing factors (psychological, interpersonal/environmental and social support, and vocational). The second section presents the role of various health care professions (medical doctors, nurses, physical therapists, occupational therapists, psychologists and rehabilitation counselors) and the evidence of their treatment effectiveness. The third section discusses the concept of an interdisciplinary pain rehabilitation program (IPRP) and its evidence to support its effectiveness. Finally, the clinical implications of rehabilitation counseling and psychology as part of the inter-disciplinary program in treating individuals with chronic pain will be highlighted.

Mechanistic considerations for the use of monoclonal antibodies for cancer therapy

Since the approval of rituximab in 1997, monoclonal antibodies(mAbs) have become an increasingly important component of therapeutic regimens in oncology. The success of mAbs as a therapeutic class is a result of great strides that have been made in molecular biology and in biotechnology over the past several decades. Currently, there are 14 approved mAb products for oncology indications, and there are ten additional mAbs in late stages of clinical trials. Compared to traditional chemotherapeutic agents, mAbs have several advantages, including a long circulating half-life and high target specificity. Antibodies can serve as cytotoxic agents when administered alone, exerting a pharmacologic effect through several mechanisms involving the antigen binding(Fab) and/or Fc domains of the molecule, and mAbs may also be utilized as drug carriers, targeting a toxic payload to cancer cells. The extremely high affinity of mAbs for their targets, which is desirable with respect to pharmacodynamics(i.e., contributing to the high therapeutic selectivity of mAb), often leads to complex, non-linear, target-mediated pharmacokinetics. In this report, we summarize the pharmacokinetic and pharmacodynamics of mAbs that have been approved and of mAbs that are nearing approval for oncology indications, with particular focus on the molecular and cellular mechanisms responsible for their disposition and efficacy.

Gut microbiota contributes to the distinction between two traditional Chinese medicine syndromes of ulcerative colitis

BACKGROUND Ulcerative colitis(UC)is considered to be closely associated with alteration of intestinal microorganisms.According to the traditional Chinese medicine(TCM)theory,UC can be divided into two disease syndromes called Pi-Xu-Shi-Yun(PXSY)and Da-Chang-Shi-Re(DCSR).The relationships among gut microbiota,TCM syndromes,and UC pathogenesis have not been well investigated.AIM To investigate the role of gut microbiota in UC and the distinction of microbiota dysbiosis between PXSY and DCSR syndromes.METHODS From May 2015 to February 2016,UC patients presenting to LongHua Hospital who met the established inclusion and exclusion criteria were enrolled in this retrospective study.Fresh stool specimens of UC patients with PXSY or DCSR were collected.The feces of the control group came from the health examination population of Longhua Hospital.The composition of gut bacterial communities in stool samples was determined by the pyrosequencing of 16S ribosomal RNA.The high-throughput sequencing reads were processed with QIIME,and biological functions were predicted using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States.RESULTS The composition of gut bacterial communities in 93 stool samples(30 healthy controls,32 patients with PXSY syndrome,and 31 patients with DCSR syndrome)was determined by the pyrosequencing of 16S ribosomal RNA.Beta diversity showed that the composition of the microbiota was different among the three groups.At the family level,Porphyromonadaceae,Rikeneliaceae,and Lachnospiraceae significantly decreased while Enterococcus,Streptococcus,and other potential pathogens significantly increased in UC patients compared to healthy subjects.At the genus level,Parabacteroides,Dorea,and Ruminococcus decreased while Faeca-libacterium showed increased abundance in UC compared to healthy controls.Five differential taxa were identified between PXSY and DCSR syndromes.At the genus level,a significantly increased abundance of Streptococcus was observed in DCSR patients,while Lachnoclostridium increased in PXSY patients.The differential functional pathways of the gut microbiome between the PXSY and DCSR groups mainly included lipid metabolism,immunity,and the metabolism of polypeptides.CONCLUSION Our study suggests that the gut microbiota contributes to the distinction between the two TCM syndromes of UC.

Effects of climate change on phenology and primary productivity in the desert steppe of Inner Mongolia

Variations in temperature and precipitation affect local ecosystems. Considerable spatial and temporal heterogeneity exists in arid ecosystems such as desert steppes. In this study, we analyzed the spatiotemporal dy- namics of climate and vegetation phenology in the desert steppe of Inner Mongolia, China using meteorological data （1961-2010） from 11 stations and phenology data （2004-2012） from 6 ecological observation stations. We also estimated the gross primary production for the period of 1982-2009 and found that the annual mean tem- perature increased at a rate of 0.47~C/decade during 1961-2010, with the last 10 years being consistently warmer than the 50 years as an average. The most significant warming occurred in winters. Annual precipitation slightly decreased during the 50-year period, with summer precipitation experiencing the highest drop in the last 10 years, and spring precipitation, a rise. Spatially, annual precipitation increased significantly in the northeastern and eastern central areas next to the typical steppe. From 2004 to 2012, vegetation green-up and senescence date advanced in the study area, shortening the growing season. Consequently, the primary productivity of the desert steppe de- creased along the precipitation gradient from southeast to northwest. Temporally, productivity increased during the period of 1982-1999 and significantly decreased after 2000. Overall, the Last decade witnessed the most dramatic climatic changes that were likely to negatively affect the desert steppe ecosystem. The decreased primary produc- tivity, in particular, decreases ecosystem resilience and impairs the livelihood of local farmers and herdsmen.

Characterization of the salivary microbiome in healthy Thai children

Objective: To investigate the composition of the salivary microbiome of 50 healthy Thai children. Methods: A total 76 provinces in Thailand are grouped into 5 geographical clusters based on unique economics, foods and lifestyles. Geographical locations and the results of an oral assessment were also considered. Genomic DNA was extracted from stimulated saliva samples. Subsequently, amplicon libraries were prepared by 16 S Metagenomic Sequencing Library Preparation. The amplicons were sequenced using an Illumina Miseq platform followed by bioinformatics and statistical analyses.Results: The correlation between oral hygiene status and caries history varied from r^2=0.887 to r^2=0.999 in the geographical groups, suggesting oral hygiene status a strong association between caries history. Twenty taxonomic groups were found in all subjects and constituted 93.6%-96.5% of the microbiome. Of these, genus Veillonella and Prevotella showed significant differences in their proportions between the geographical groups(P<0.05). Furthermore, the proportion of Veillonella parvula, as well as Rothia aeria and Rothia dentocariosa tended to increase with worse oral hygiene status, which was also related to higher dental caries history.Conclusions: The differences in the salivary microbiome as related to geographic regions suggest that environmental factors, which may include dietary habits, could influence the predominant bacteria found in the mouth of Thai children, especially the genus Veillonella and Prevotella. The ratio of Veillonella parvula, Rothia aeria and Rothia dentocariosa may be indicators of worse oral hygiene status and future caries in this population.

Deletion of IFT20 in early stage T lymphocyte differentiation inhibits the development of col agen-induced arthritis

IFT20 is the smallest member of the intraflagellar transport protein（IFT） complex B. It is involved in cilia formation. Studies of IFT20 have been confined to ciliated cells. Recently, IFT20 was found to be also expressed in non-ciliated T cells and have functions in immune synapse formation and signaling in vitro. However, how IFT20 regulates T-cell development and activation in vivo is still unknown. We deleted the IFT20 gene in early and later stages of T-cell development by crossing IFT20flox/flox（IFT20f/f） mice with Lck-Cre and CD4-Cre transgenic mice, and investigated the role of IFT20 in T-cell maturation and in the development of T cell-mediated collagen-induced arthritis（CIA）. We found that both Lck-Cre/IFT20f/f and CD4-Cre/IFT20f/f mice were indistinguishable from their wild-type littermates in body size, as well as in the morphology and weight of the spleen and thymus. However, the number of CD4- and CD8-positive cells was significantly lower in thymus and spleen in Lck-Cre/IFT20f/f mice. Meanwhile, the incidence and severity of CIA symptoms were significantly decreased, and inflammation in the paw was significantly inhibited in Lck-Cre/IFT20f/f mice compared to Lck-Cre/IFT201/1littermates. Deletion IFT20 in more mature T cells of CD4-Cre/IFT20f/f mice had only mild effects on the development of T cells and CIA. The expression of IL-1b, IL-6 and TGF-b1 were significantly downregulated in the paw of Lck-Cre/IFT20f/f mice, but just slight decreased in CD4-Cre/IFT20f/f mice. These results demonstrate that deletion of IFT20 in the early stage of T-cell development inhibited CIA development through regulating T-cell development and the expression of critical cytokines.

Thermally insulating and fire-retardant bio-mimic structural composites with a negative Poisson's ratio for battery protection

Battery safety has attracted considerable attention worldwide due to the rapid development of wearable electronics and the steady increase in the production and use of electric vehicles.As battery failures are often associated with mechanical-thermal coupled behaviors,protective shielding materials with excellent mechanical robustness and flame-retardant properties are highly desired to mitigate thermal runaway.However,most of the thermal insulating materials are not strong enough to protect batteries from mechanical abuse,which is one of the most critical scenarios with catastrophic consequences.Here,inspired by wood,we have developed an effective approach to engineer a hierarchical nanocomposite via self-assembly of calcium silicate hydrate and polyvinyl alcohol polymer chains(referred as CSH wood).The versatile protective material CSH wood demonstrates an unprecedented combination of light weight(0.018 g cm-3),high stiffness(204 MPa in the axial direction),negative Poisson's ratio(-0.15),remarkable toughness(6.67×105 J m-3),superior thermal insulation(0.0204 W m-1 K-1 in the radial direction),and excellent fire retardancy(UL94-V0).When applied as a protective cover or a protective layer within battery packages,the tough CSH wood can resist high-impact load and block heat diffusion to block or delay the spread of fire,therefore significantly reducing the risk of property damage or bodily injuries caused by battery explosions.This work provides new pathways for fabricating advanced thermal insulating materials with large scalability and demonstrates great potential for the protection of electronic devices.

Identification and Biological Activities of the Phenolic Compounds in <i>Eisenia arborea</i>

Four polyphenols were isolated and purified from a brown alga Eisenia arborea. These phlorotannin compounds showed strong radical scavenging and some enzyme inhibitory activities. All of the compounds showed strong antioxidative, acetylcholinesterase and butyrylcholinesterase inhibitory, and tyrosinase inhbibitory activities at 100 μg/mL. Dieckol and PFF inhibited butyrylcholinesterase, a new target for the treatment of Alzheimer’s disease, very strongly even at 10 μg/mL, more strongly than AChE. These two compounds also effectively inhibited tyrosinase. These results support the potential of developing natural antioxidants and antidementia agents from the brown alga.

The Power-Energy Coupling Effect of Mixed Hard-Carbon/Graphite Anode

As the anode materials of lithium-ion battery, the hard carbon has the higher power performance while the graphite has the higher energy performance, respectively. In this work, novel mixed hard carbon/graphite anodes are presented showing the coupling effect of power and mixed anodes was investigated at the varying charging rates, showing the tunable behaviors dependent on the hard carbon/graphite ratios. By studying the specific capacity evolution in different split potential ranges, we found that the mixed anodes with a higher proportion of hard carbon were advantageous when working in the cut-off potential greater than 0.10 V. The electrochemical impedance spectroscopy was measured at various anode potentials, which depicted the evolution of cell resistance with the state of charge. With the aid of electrochemical impedance spectroscopy, we found that the capacity evolution with mixed ratio is attributed to the lithiation-level induced difference of charge transfer resistance and Warburg resistance. A coupling effect was discovered showing a great potential in balancing the power-energy performance of mixed anode by simply controlling the ratio of hard-carbon/graphite.

Alpha-synuclein in mitochondrial dysfunction:opportunities or obstacles

Recent work suggests a link betweenα-synuclein(α-syn)and mitochondrial dysfunction;however,the mechanisms of howα-syn influences mitochondrial function are still unclear.Most notably,whetherα-syn plays a direct role during mitochondrial function and/or whether diseasedα-syn-mediated mitochondrial dysfunction is a potential modifiable risk factor in Parkinson’s disease(PD)is unknown.To date,mutations in more than eight genes cause familial PD(fPD)and have functions in diverse pathways including synaptic homeostasis,mitochondria maintenance,autophagy/lysosome,and ubiquitin-proteasome pathways.

Application of platelet-rich plasma with stem cells in bone and periodontal tissue engineering

Presently, there is a high paucity of bone grafts in the United States and worldwide. Regenerating bone is of prime concern due to the current demand of bone grafts and the increasing number of diseases causing bone loss. Autogenous bone is the present gold standard of bone regeneration. However, disadvantages like donor site morbidity and its decreased availability limit its use. Even allografts and synthetic grafting materials have their own limitations. As certain specific stem cells can be directed to differentiate into an osteoblastic lineage in the presence of growth factors(GFs), it makes stem cells the ideal agents for bone regeneration.Furthermore, platelet-rich plasma(PRP), which can be easily isolated from whole blood, is often used for bone regeneration, wound healing and bone defect repair. When stem cells are combined with PRP in the presence of GFs, they are able to promote osteogenesis. This review provides in-depth knowledge regarding the use of stem cells and PRP in vitro, in vivo and their application in clinical studies in the future.

Stereotactic body radiation therapy for non-small cell lung cancer:A review

Stereotactic body radiation therapy(SBRT) is the treatment of choice for medically inoperable patients with early stage non-small cell lung cancer(NSCLC). A literature search primarily based on PubMed electronic databases was completed in July 2018. Inclusion and exclusion criteria were determined prior to the search, and only prospective clinical trials were included. Nineteen trials from 2005 to 2018 met the inclusion criteria, reporting the outcomes of 1434 patients with central and peripheral early stage NSCLC. Patient eligibility,prescription dose and delivery, and follow up duration varied widely. Threeyears overall survival ranged from 43% to 95% with loco-regional control of up to 98% at 3 years. Up to 33% of patients failed distantly after SBRT at 3 years. SBRT was generally well tolerated with 10%-30% grade 3-4 toxicities and a few treatment-related deaths. No differences in outcomes were observed between conventionally fractionated radiation therapy and SBRT, central and peripheral lung tumors, or inoperable and operable patients. SBRT remains a reasonable treatment option for medically inoperable and select operable patients with early stage NSCLC. SBRT has shown excellent local and regional control with toxicity rates equivalent to surgery. Decreasing fractionation schedules have been consistently shown to be both safe and effective. Distant failure is common, and chemotherapy may be considered for select patients. However, the survival benefit of additional interventions, such as chemotherapy, for early stage NSCLC treated with SBRT remains unclear.

Phase transformation in suspension roasting of oolitic hematite ore

Suspension roasting followed by magnetic separation is a promising method to upgrade oolitic hematite ore.An oolitic hematite ore was roasted using suspension roasting technology at different temperatures.The phase transformation for iron minerals was investigated by XRD and Mossbauer spectrum,and the characteristics of roasted product were analyzed by VSM and SEM-EDS.Results indicate that the magnetic concentrate is of 58.73% Fe with iron recovery of 83.96% at 650 °C.The hematite is rapidly transformed into magnetite during the roasting with transformation ratio of 92.75% at 650 °C.Roasting temperature has a significant influence on the phase transformation of hematite to magnetite.The transformation ratio increases with increased temperature.After roasting,the magnetic susceptibility is significantly improved,while iron ore microstructure is not altered significantly.

Clinical guidelines of non-alcoholic fatty liver disease: A systematic review

AIM To perform a systematic review to grade guidelines and present recommendations for clinical management of non-alcoholic fatty liver disease(NAFLD).METHODS A database search was conducted on Pub Med for guidelines published before May 2016, supplemented by reviewing relevant websites. The Appraisal of Guidelines for Research and Evaluation(ARGEE) instrument Ⅱ was a tool designed to appraise the methodological rigor and transparency in which a clinical guideline is developed and it is used internationally. it was used to appraise the quality of guidelines in this study. The inclusion criteria include: clinical NAFLD guidelines for adults, published in English, and released by governmental agencies or key organizations.RESULTS Eleven guidelines were included in this study. Since 2007, guidelines have been released in Asia(3 in China, 1 in South Korea, and 1 in Japan), Europe(1 in italy),America(1 in United States and 1 in Chile) and three international agencies [European associations joint, Asia-Pacific Working Party and World Gastroenterology Organization(WGO)]. Using the ARGEE Ⅱ instrument, we found US 2012 and Europe 2016 had the highest scores, especially in the areas of rigor of development and applicability. Additionally, italy 2010 and Korea 2013 also presented comprehensive content, rigorous procedures and good applicability. And WGO 2014 offered various algorithms for clinical practice. Lastly, a practical algorithm for the clinical management was developed, based on the recommended guidelines.CONCLUSION This is the first systematic review of NAFLD guidelines. it may yield insights for physicians and policy-makers in the development and application of guidelines.

Modeling and cyclic behavior of segmental bridge column connected with shape memory alloy bars

This paper examines the quasi-static cyclic behavior, lateral strength and equivalent damping capacities of a system of post-tensioned segmental bridge columns tied with large diameter martensitic Shape Memory Alloy （SMA） link-bars. Moment-curvature constitutive relationships are formulated and analysis tools are developed for the PT column, including a modified four-spring model prepared for the SMA bars. The suggested system is exemplified using a column with an aspect ratio of 7.5 and twelve 36.5 mm diameter NiTi martensitic SMA bars. A post-tensioning force of 40% to 60% of the tendon yield strength is applied in order to obtain a self re-centering system, considering the residual stress of the martensitie SMA bars. The cyclic response results show that the lateral strength remains consistently around 10% of the total vertical load and the equivalent viscous damping ratios reach 10%-12% of critical. When large diameter NiTi superelastic SMA bars are incorporated into the column system, the cyclic response varies substantially. The creep behavior of the superelastic SMA bar is accounted for since it affects the re-centering capability of the column. Two examples are presented to emphasize the modeling sensitivities for these special bars and quantify their cyclic behavior effects within the column assembly.

Long-term outcomes of interventions for radiation-induced xerostomia:A review

Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen,submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine(three); cevimeline(one); amifostine(eleven);submandibular gland transfer(five); acupuncture like transcutaneous electrical nerve stimulation(ALTENS)(one); hyperbaric oxygen(one); and acupuncture(one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical.The use of intensity-modulated radiation therapy, in addition to dose deescalation in select patients, may result in fewer patients with late xerostomia,reducing the need for additional interventions.