Task-Oriented Training by a Personalized Electromyography-Driven Soft Robotic Hand in Chronic Stroke: A Randomized Controlled Trial.

BACKGROUND: Intensive task-oriented training has shown promise in enhancing distal motor function among patients with chronic stroke. A personalized electromyography (EMG)-driven soft robotic hand was developed to assist task-oriented object-manipulation training effectively. Objective. To compare the effectiveness of task-oriented training using the EMG-driven soft robotic hand. METHODS: A single-blinded, randomized controlled trial was conducted with 34 chronic stroke survivors. The subjects were randomly assigned to the Hand Task (HT) group (n = 17) or the control (CON) group (n = 17). The HT group received 45 minutes of task-oriented training by manipulating small objects with the robotic hand for 20 sessions, while the CON group received 45 minutes of hand-functional exercises without objects using the same robot. Fugl-Meyer assessment (FMA-UE), Action Research Arm Test (ARAT), Modified Ashworth Score (MAS), Box and Block test (BBT), Maximum Grip Strength, and active range of motion (AROM) of fingers were assessed at baseline, after intervention, and 3 months follow-up. The muscle co-contraction index (CI) was analyzed to evaluate the session-by-session variation of upper limb EMG patterns. RESULTS: The HT group showed more significant improvement in FMA-UE (wrist/hand, shoulder/elbow) compared to the CON group (P < .05). At 3-month follow-up, the HT group demonstrated significant improvements in FMA-UE, ARAT, BBT, MAS (finger), and AROMs (P < .05). The HT group exhibited a more significant decrease in muscle co-contractions compared to the CON group (P < .05). CONCLUSIONS: EMG-driven task-oriented training with the personalized soft robotic hand was a practical approach to improving motor function and muscle coordination. CLINICAL TRIAL REGISTRY NAME: Soft Robotic Hand System for Stroke Rehabilitation. CLINICAL TRIAL REGISTRATION-URL: https://clinicaltrials.gov/. UNIQUE IDENTIFIER: NCT03286309.

Research on the Low-Temperature Impact Toughness of a New 100-mm Ultra-Thick Offshore Steel Fabricated Using the Narrow-Gap Laser Wire Filling Welding Process.

Ultra-thick offshore steel, known for its high strength, high toughness, and corrosion resistance, is commonly used in marine platforms and ship components. However, when offshore steel is in service for an extended period under conditions of high pressure, extreme cold, and high-frequency impact loads, the weld joints are prone to fatigue failure or even fractures. Addressing these issues, this study designed a narrow-gap laser wire filling welding process and successfully welded a 100-mm new type of ultra-thick offshore steel. Using finite element simulation, EBSD testing, SEM analysis, and impact experiments, this study investigates the weld's microstructure, impact toughness, and fracture mechanisms. The research found that at -80 °C, the welded joint exhibited good impact toughness (>80 J), with the impact absorption energy on the surface of the weld being 217.7 J, similar to that of the base material (225.3 J), and the fracture mechanism was primarily a ductile fracture. The impact absorption energy in the core of the weld was 103.7 J, with the fracture mechanism mainly being a brittle fracture. The EBSD results indicated that due to the influence of the welding thermal cycle and the cooling effect of the narrow-gap process, the grains gradually coarsened from the surface of the welded plate to the core of the weld, which was the main reason for the decreased impact toughness at the joint core. This study demonstrates the feasibility of using narrow-gap laser wire filling welding for 100-mm new type ultra-thick offshore steel and provides a new approach for the joining of ultra-thick steel plates.

Identification of COQ2 as a regulator of proliferation and lipid peroxidation through genome-scale CRISPR-Cas9 screening in myeloma cells.

Multiple myeloma (MM) is the second most common malignant haematological disease with a poor prognosis. The limit therapeutic progress has been made in MM patients with cancer relapse, necessitating deeper research into the molecular mechanisms underlying its occurrence and development. A genome-wide CRISPR-Cas9 loss-of-function screening was utilized to identify potential therapeutic targets in our research. We revealed that COQ2 plays a crucial role in regulating MM cell proliferation and lipid peroxidation (LPO). Knockout of COQ2 inhibited cell proliferation, induced cell cycle arrest and reduced tumour growth in vivo. Mechanistically, COQ2 promoted the activation of the MEK/ERK cascade, which in turn stabilized and activated MYC protein. Moreover, we found that COQ2-deficient MM cells increased sensitivity to the LPO activator, RSL3. Using an inhibitor targeting COQ2 by 4-CBA enhanced the sensitivity to RSL3 in primary CD138+ myeloma cells and in a xenograft mouse model. Nevertheless, co-treatment of 4-CBA and RSL3 induced cell death in bortezomib-resistant MM cells. Together, our findings suggest that COQ2 promotes cell proliferation and tumour growth through the activation of the MEK/ERK/MYC axis and targeting COQ2 could enhance the sensitivity to ferroptosis in MM cells, which may be a promising therapeutic strategy for the treatment of MM patients.

Tight Junction Protein 1 Suppresses Kidney Renal Clear Cell Carcinoma Cells Proliferation by Inducing Autophagy.

TJP1, an adaptor protein of the adhesive barrier, has been found to exhibit distinct oncogenic or tumor suppressor functions in a cell-type dependent manner. However, the role of TJP1 in kidney renal clear cell carcinoma (KIRC) remains to be explored. The results showed a marked down-regulation of TJP1 in KIRC tissues compared to normal tissues. Low expression of TJP1 was significantly associated with high grade and poor prognosis in KIRC. Autophagosome aggregation and LC3 II conversion demonstrated that TJP1 may induce autophagy signaling in 786-O and OS-RC-2 cells. Knockdown of TJP1 led to a decrease in the expression of autophagy-related genes, such as BECN1, ATG3, and ATG7. Consistently, TJP1 expression showed a significant positive correlation with these autophagy-related genes in KIRC patients. Furthermore, the overall survival analysis of KIRC patients based on the expression of autophagy-related genes revealed that most of these genes were associated with a good prognosis. TJP1 overexpression significantly suppressed cell proliferation and tumor growth in 786-O cells, whereas the addition of an autophagy inhibitor diminished its inhibitory function. Taken together, these results suggest that TJP1 serves as a favorable prognostic marker and induces autophagy to suppress cell proliferation and tumor growth in KIRC.

In situ analysis of surface composition and meteorology at the Zhurong landing site on Mars.

The Zhurong rover of the Tianwen-1 mission landed in southern Utopia Planitia, providing a unique window into the evolutionary history of the Martian lowlands. During its first 110 sols, Zhurong investigated and categorized surface targets into igneous rocks, lithified duricrusts, cemented duricrusts, soils and sands. The lithified duricrusts, analysed by using laser-induced breakdown spectroscopy onboard Zhurong, show elevated water contents and distinct compositions from those of igneous rocks. The cemented duricrusts are likely formed via water vapor-frost cycling at the atmosphere-soil interface, as supported by the local meteorological conditions. Soils and sands contain elevated magnesium and water, attributed to both hydrated magnesium salts and adsorbed water. The compositional and meteorological evidence indicates potential Amazonian brine activities and present-day water vapor cycling at the soil-atmosphere interface. Searching for further clues to water-related activities and determining the water source by Zhurong are critical to constrain the volatile evolution history at the landing site.

Toward Feature-Preserving Vector Field Compression.

The objective of this work is to develop error-bounded lossy compression methods to preserve topological features in 2D and 3D vector fields. Specifically, we explore the preservation of critical points in piecewise linear and bilinear vector fields. We define the preservation of critical points as, without any false positive, false negative, or false type in the decompressed data, (1) keeping each critical point in its original cell and (2) retaining the type of each critical point (e.g., saddle and attracting node). The key to our method is to adapt a vertex-wise error bound for each grid point and to compress input data together with the error bound field using a modified lossy compressor. Our compression algorithm can be also embarrassingly parallelized for large data handling and in situ processing. We benchmark our method by comparing it with existing lossy compressors in terms of false positive/negative/type rates, compression ratio, and various vector field visualizations with several scientific applications.

Pediatric patients with familially inherited sitosterolemia: Two case reports.

Background: Sitosterolemia is a rare recessive genetic abnormality of hyperlipidemia; it is characterized by increased levels and accumulation of sitosterol in the plasma and local tissues. Case descriptions: The study subjects were two siblings (brother and sister) who had sitosterolemia with systemic multiple xanthomas as the main manifestation. The main clinical manifestations were hypercholesterolemia, premature atherosclerosis, arrhythmia, systemic multiple xanthomas, etc. After genetic testing, it was found that the patients had a compound heterozygous mutation of c.1324+1de1G in exon 7 and exon 9 of chromosome 2p21 of the adenosine triphosphate binding cassette transporter G family member 5(ABCG5) gene; the mutation at c.904+1G>A was of maternal origin, and the mutation at c. 1324+1de1G was of paternal origin. The compound heterozygous mutation of these two genes led to a metabolic disorder of plant sterols in vivo. Conclusion: Sitosterolemia is an autosomal recessive disease that could be effectively controlled after dietary control and oral lipid-lowering therapy with Ezetimibe. Xanthomas, which affects function and appearance, could be surgically removed, and primary wound healing could be achieved.

Case report: ISL2 is involved in malignant transformation in a patient with multiple relapsed oligodendroglioma.

The majority of oligodendrogliomas exhibit an intrinsic tendency to develop into malignant high-grade tumors. Angiogenesis is a major factor contributing to the malignant transformation of oligodendroglioma, and its molecular regulatory mechanism needs further study. We provide a case report of an oligodendroglioma patient with two recurrences whose disease progressed from WHO grade II to grade III. We showed that the expression of insulin gene enhancer protein (ISL2) and its angiogenic ability were positively correlated with the progression of oligodendroglioma. In Low-grade glioma (LGG) patients, including oligodendroglioma patients, overexpression of ISL2 was correlated with poor prognosis, and this correlation was not affected by gender or isocitrate dehydrogenase 1(IDH1) mutation status. ISL2 expression and ISL2-mediated angiogenic pathway activity are ideal biomarkers for the malignant transformation of oligodendroglioma. Anti-ISL2 therapy is also a potential treatment option for malignantly transformed oligodendroglioma.

Effective Aging Inhibition of the Thermoplastic Corn Starch Films through the Use of Green Hybrid Filler.

Recently, hybrid fillers have been widely used to improve the properties of biopolymers. The synergistic effects of the hybrid fillers can have a positive impact on biopolymers, including thermoplastic corn starch film (TPCS). In this communication, we highlight the effectiveness of hybrid fillers in inhibiting the aging process of TPCS. The TPCS, thermoplastic corn starch composite films (TPCS-C), and hybrid thermoplastic corn starch composite film (TPCS-HC) were stored for 3 months to study the effect of hybrid filler on the starch retrogradation. TPCS-C and TPCS-HC were prepared by casting method with 5 wt% of fillers: nanocellulose (NC) and bentonite (BT). The alteration of the mechanical properties, aging behavior, and crystalline structure of the films were analyzed through the tensile test, Fourier transform infrared (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and water absorption analysis. The obtained data were correlated to each other to analyze the retrogradation of the TPCS, which is the main factor that contributes to the aging process of the biopolymer. Results signify that incorporating the hybrid filler (NC + BT) in the TPCS/4BT1NC films has effectively prevented retrogradation of the starch molecules after being stored for 3 months. On the contrary, the virgin TPCS film showed the highest degree of retrogradation resulting in a significant decrement in the film's flexibility. These findings proved the capability of the green hybrid filler in inhibiting the aging of the TPCS.

Network Meta-analysis of efficacy and safety of oral Chinese patent medicines combined with conventional western medicine in treatment of hypertension / 中国中药杂志

This study aims to systematically evaluate the effect of oral Chinese patent medicines on hypertension with network Meta-analysis. Randomized controlled trials on the treatment of hypertension with oral Chinese patent medicine combined with conventional western medicine were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library(from establishment of the database to August 2021). Two researchers independently screened the articles, extracted the data, and evaluated article quality. Then R 4.1.0 was employed for data analysis. Finally, 195 eligible articles were screened out, involving 22 546 patients and 18 oral Chinese patent medicines. The results of the network Meta-analysis are as follows. In terms of reducing systolic blood pressure(SBP) and diastolic blood pressure(DBP), Xuesaitong, Qiangli Dingxuan Tablets, Songling Xuemaikang Capsules combined with conventional western medicine are superior. In improving blood lipids, the overall effects of Xinmaitong Capsules, Compound Xueshuantong Capsules, Ginkgo Folium preparations, Yindan Xinnaotong Soft Capsules, and Naoxintong Capsules combined with conventional western medicine are outstanding. In terms of regulating endothelial function, Yindan Xinnaotong Soft Capsules, Xinmaitong Capsules, Zhenju Jiangya Tablets, Compound Danshen Dripping Pills, Xuesaitong with conventional western medicine have certain advantages. As for the safety, the incidence of adverse reactions of conventional western medicine combined with oral Chinese patent medicines is lower than that of conventional western medicine alone. In summary, compared with conventional western medicine alone, the 18 oral Chinese patent medicines combined with conventional western medicine in the treatment of hypertension show advantages in improving blood pressure, blood lipids, and endothelial function. Among them, Xuesaitong, Qiangli Dingxuan Tablets, and Songling Xuemaikang Capsules may be the best oral Chinese patent medicines for lowering blood pressure. The conclusion needs to be further verified by more high-quality studies.

Clinical trials and evaluation of Chinese patent medicine for influenza / 中国中药杂志

The clinical randomized controlled trial(RCT) of Chinese patent medicine in the treatment of influenza were reviewed and analyzed to provide basic information for clinical decision and related research. On the basis of the collection in the Traditional Chinese Medicine(TCM) Clinical Evidence Database System(EVDS), CNKI, Wanfang, VIP, SinoMed, EMbase, PubMed, and Cochrane Library were searched for RCTs of Chinese patent medicine for influenza published from database inception to July 25, 2021. The publication time, sample size, intervention and control measures, course of treatment, outcome indicators, and methodological quality of the trials were analyzed and evaluated. Ninety-two RCTs of Chinese patent medicine for influenza published between 2005 and 2021, were included, among which 17 RCTs(18.48%) had a sample size higher than 200 and the average sample size was about 145. Twenty-seven Chinese patent medicines were involved, including twenty-one oral medicines and six injections. The Chinese patent medicines in trials reported in more than five papers included Lianhua Qingwen Capsules/Gra-nules, Tanreqing Injection, and Reduning Injection. Fourteen intervention protocols were reported, of which Chinese patent medicine+western medicine+conventional treatment vs western medicine+conventional treatment(20.65%) was the most frequently employed. Additionally, 85.87% of the RCTs reported the course of treatment, and 80.43% of the RCTs determined 3-7 d as the intervention course. Forty-five outcome indicators were extracted, which were used 434 times, including symptoms/signs, physicochemical detection, safety events, TCM symptoms/syndromes, quality of life, long-term prognosis, and economic evaluation. Symptoms/signs(61.52%) exhibited the highest frequency. Methodological problems were prevalent in the included trials. The findings reveal that there are few clinical trials on influenza treatment by Chinese patent medicine, and the methodological problems are prominent, affec-ting the reliability and practicability of the trials. In the future research, the value characteristics of Chinese patent medicine should be highlighted and the quality control in the whole process should be strengthened based on the scientific and rigorous design.

Analysis of outcome indexes in randomized controlled trials of traditional Chinese medicine for rheumatic heart disease / 中国中药杂志

The present study analyzed the efficacy evaluation indexes of the randomized controlled trials(RCTs) of Chinese medi-cine in the treatment of rheumatic heart disease to lay the foundation for the construction of the corresponding core outcome index set. Clinical RCTs with a definite diagnosis of rheumatic heart disease were retrieved from CNKI, Wanfang, VIP, Sino Med, Pub Med, EMbase, and Cochrane Library from January 1, 2010, to December 31, 2020. Thirty-five RCTs were included, involving 3 314 patients and 41 efficacy evaluation indexes, which covered seven domains [traditional Chinese medicine(TCM) symptoms/syndromes, symp-toms/signs, physical and chemical examination, quality of life, long-term prognosis, economic evaluation, and safety events]. Physi-cal and chemical examination(56. 91%) and symptoms/signs(29. 27%) were the more frequently applied. The number of indexes used in a single trial ranged from 1 to 15, with an average of 4. The measurement time points of the top five indexes in the frequency of use were as follows: total response rate was reported at five measurement time points, ranging from 14 days to 6 months; left ventri-cular ejection fraction was measured at eight time points ranging from 5 days to 6 months; left ventricular end systolic diameter was measured at six time points, ranging from 5 days to 6 months; interleukin-2(IL-2) and tumor necrosis factor-α(TNF-α) were repor-ted 28 days after treatment. At present, there are many problems in the efficacy outcome indexes of RCTs in the treatment of rheumatic heart disease with TCM, such as large difference in quantity, unclear primary and secondary indexes, unreasonable selection of " surro-gate indexes", insufficient attention to long-term prognostic indexes and safety event indexes, non-standard application of composite in-dexes, long measurement period, and lack of TCM characteristics. It is urgent to establish the core outcome set for TCM treatment of rheumatic heart disease.

Targeting hexokinase 2 increases the sensitivity of oxaliplatin by Twist1 in colorectal cancer.

Colorectal cancer (CRC) is the third most malignant tumour worldwide, with high mortality and recurrence. Chemoresistance is one of the main factors leading to metastasis and poor prognosis in advanced CRC patients. By analysing the Gene Expression Omnibus data set, we found higher hexokinase 2 (HK2) expression levels in patients with metastatic CRC than in those with primary CRC. Moreover, we observed higher enrichment in oxaliplatin resistance-related gene sets in metastatic CRC than in primary CRC. However, the underlying relationship has not yet been elucidated. In our study, HK2 expression was significantly elevated in CRC patients. Gene set enrichment analysis (GSEA) revealed multi-drug resistance and epithelial-mesenchymal transition (EMT) pathways related to high HK2 expression. Our results showed that knockdown of HK2 significantly inhibited vimentin and Twist1 expression and promoted TJP1 and E-cadherin expression in CRC cells. Additionally, transcriptional and enzymatic inhibition of HK2 by 3-bromopyruvate (3-bp) impaired oxaliplatin resistance in vitro and in vivo. Mechanistically, HK2 interacts with and stabilized Twist1 by preventing its ubiquitin-mediated degradation, which is related to oxaliplatin resistance, in CRC cells. Overexpression of Twist1 reduced the apoptosis rate by HK2 knockdown in CRC cells. Collectively, we discovered that HK2 is a crucial regulator that mediates oxaliplatin resistance through Twist1. These findings identify HK2 and Twist1 as promising drug targets for CRC chemoresistance.

On the Use of OPEFB-Derived Microcrystalline Cellulose and Nano-Bentonite for Development of Thermoplastic Starch Hybrid Bio-Composites with Improved Performance.

Thermoplastic starch (TPS) hybrid bio-composite films containing microcrystalline cellulose (C) and nano-bentonite (B) as hybrid fillers were studied to replace the conventional non-degradable plastic in packaging applications. Raw oil palm empty fruit bunch (OPEFB) was subjected to chemical treatment and acid hydrolysis to obtain C filler. B filler was ultra-sonicated for better dispersion in the TPS films to improve the filler-matrix interactions. The morphology and structure of fillers were characterized by scanning electron microscope (SEM), Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). TPS hybrid bio-composite films were produced by the casting method with different ratios of B and C fillers. The best ratio of B/C was determined through the data of the tensile test. FTIR analysis proved the molecular interactions between the TPS and the hybrid fillers due to the presence of polar groups in their structure. XRD analysis confirmed the intercalation of the TPS chains between the B inter-platelets as a result of well-developed interactions between the TPS and hybrid fillers. SEM images suggested that more plastic deformation occurred in the fractured surface of the TPS hybrid bio-composite film due to the higher degree of stretching after being subjected to tensile loading. Overall, the results indicate that incorporating the hybrid B/C fillers could tremendously improve the mechanical properties of the films. The best ratio of B/C in the TPS was found to be 4:1, in which the tensile strength (8.52MPa), Young's modulus (42.0 MPa), elongation at break (116.4%) and tensile toughness of the film were increased by 92%, 146%, 156% and 338%, respectively. The significantly improved strength, modulus, flexibility and toughness of the film indicate the benefits of using the hybrid fillers, since these features are useful for the development of sustainable flexible packaging film.

Corrigendum: Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity.

[This corrects the article DOI: 10.3389/fnmol.2018.00155.].

Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity.

Until now, the dopamine (DA) precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), remains the gold standard effective drug therapy for Parkinson's disease (PD) patients. Nevertheless, long-term chronic L-DOPA administration leads to the drug efficacy loss and severe adverse effects, such as L-DOPA-induced dyskinesia (LID). Icariin (ICA), a flavonoid that is extracted from Epimedium, has been proved to evoke neuroprotection against DA neuronal loss in PD animal models. Here, the present study detected the effects of ICA combined with L-DOPA on 6-hydroxydopamine (6-OHDA)-elicited DA neurotoxicity and L-DOPA-induced motor dysfunction as well. PC12 cells were applied to investigate the combination treatment of ICA and L-DOPA against 6-OHDA-lesioned neurotoxicity. In addition, rat substantia nigral stereotaxic injection of 6-OHDA-induced DA neuronal injury was performed to explore the neuroprotective effects mediated by ICA combined with L-DOPA. The pathological movement triggered by L-DOPA was determined by the abnormal involuntary movements (AIM) scores analysis. In PC12 cells, ICA combined with L-DOPA produced better neuroprotection from 6-OHDA-induced neurotoxicity than ICA or L-DOPA alone treatment. In parkinsonian 6-OHDA lesioned rats, ICA conferred DA neuroprotection as monotherapy and an enhancement benefit of L-DOPA treatment after daily administration of L-DOPA and ICA for 21 days. Moreover, ICA ameliorated the development of LID as evidenced by the lowered AIM scores without affecting L-DOPA-mediated efficacy. Furtherly, ICA attenuated neuroinflammation in 6-OHDA-induced DA neuronal loss and the development of LID in vivo. In conclusion, these findings suggest ICA might be a potential promising adjuvant to enhance L-DOPA efficacy and attenuate L-DOPA-produced adverse effects in PD.

Effects of a bone graft substitute consisting of porous gradient HA/ZrO2 and gelatin/chitosan slow-release hydrogel containing BMP-2 and BMSCs on lumbar vertebral defect repair in rhesus monkey.

Dense biomaterial plays an important role in bone replacement. However, it fails to induce bone cell migration into graft material. In the present study, a novel bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. The morphological characteristics of the BGS evaluated by a scanning electron microscope showed that it had a three-dimensional network structure with uniformly distributed chitosan microspheres on the surfaces of the graft material and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16 weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testing for bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed to examine the reparative efficacy of the BGS and PGHC. The BGS displayed excellent ability to repair the lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scanning, and histomorphological characterization showed that the newly formed bone volume in the interior of the pores in the BGS was significantly higher than in the PGHC. The results of biomechanical testing indicated that the vertebral body compression strength of the PGHC implant was lower than the other implants. Reverse-transcription polymerase chain reaction and western blot analyses showed that the expression of bone-related proteins in the BGS implant was significantly higher than in the PGHC implant. The BGS displayed reparative effects similar to autologous bone. Therefore, BGS use in vertebral bone defect repair appears promising.

Safety assessment of astaxanthin derived from engineered Escherichia coli K-12 using a 13-week repeated dose oral toxicity study and a prenatal developmental toxicity study in rats.

Astaxanthin is a natural carotenoid with strong antioxidant activity that has been used for decades as a nutrient/color additive and it has recently been marketed as a health supplement. Astaxanthin can be synthesized in a wide range of microalgae, yeast, and bacteria. As genes directing astaxanthin biosynthesis in various organisms have been cloned, this study assessed the safety of astaxanthin crystal produced by Escherichia coli K-12 harboring plasmids carrying astaxanthin biosynthetic genes. The astaxanthin crystal contains a total carotenoid content of 950 mg/g and an astaxanthin content of 795 mg/g. Subchronic oral toxicity and prenatal developmental toxicity of the astaxanthin in rats were conducted in accordance with the Guidelines of Health Food Safety Assessment promulgated by Food and Drug Administration of Taiwan which is based on OECD guidelines 408 and 414. Both male and female Sprague-Dawley (SD) rats (12 for each gender) receiving the astaxanthin crystal at 1.2, 240.0, or 750.0 mg/kg/day in olive oil via oral gavage for 90 days showed no changes in body weight gains, hematology and serum chemistry values and hepatic enzyme stability, organ integrity and organ weight. Except the higher food consumption observed in rats receiving 750.0 mg/g astaxanthin crystal, administration of the astaxanthin crystal to 25-27 pregnant female rats in each group throughout the period of organogenesis (G6-G15) produced no adverse effects on fetal organogenesis. Based on the results, we propose that the no-observable-adverse-effect level (NOAEL) of the astaxanthin crystal extracted from genetically modified E. coli K-12 is 750.0 mg/kg bw/day.

Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN) dopamine (DA) neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA), a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS)-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-κB (NF-κB) pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.

A study on the correlations study among HOMA-IR, obesity and inflammatory factors among middle aged and elderly population / 预防医学

Objective To investigate the distribution of insulin resistance (HOMA-IR) index and its influencing factorsamong middle and old aged people with normal glucose and to provide the basis for early screening and prevention of type 2diabetes. Methods A total of 229 residents were selected with health records showed normal blood glucose (fasting bloodglucose < 7.0mmol/L, postprandial 2h blood glucose<11.1 mmol/L) and more than 40 years old from July, 2012 to June,2015. Height, weight, waist and hip circumference, and the fasting plasma glucose (FPG), insulin (FINS), lowdensity lipoprotein (LDL), uric acid, tumor necrosis factor (TNF) and interleukin -6 (IL-6) were recorded to analyzethe distribution of HOMA-IR and its influencing factors. Results Totally 229 people were included, of which 113 were male(49.34%), 116 female(50.66%) . The average age was(63.58 + 8.85) years old. The average HOMA-IR index was 0.94(1.08) and there were 21 people that HOMA-IR exceed the standard (HOMA-IR≥2.68), accounting for 9.17%.TheHOMA-IR index of different gender, age, waist circumference, hip circumference, uric acid in the elderly had significantdifference (P < 0.05) .Multiple linear regression analysis showed that HOMA-IR index was positively correlated withfemale, waist circumference and IL-6 and was negatively correlated with age. Conclusion The possibility of IR was higherin women with relatively low age, female, central obesity and high IL-6 levels among the middle and old aged people withnormal blood glucose.