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3-Isothiocyanato oxindoles are a class of important building blocks which have been widely used in the synthesis of structurally diverse enantioenriched spirooxindoles. In this short review, it is attempted to cover the recent synthetic aspects of 3-isothiocyanato oxindoles participated cascade cyclizations in the last few years (i.e., from 2017 to 2022), with an emphasis on formal [3+2] cycloaddition reactions.1 Introduction2 Organocatalyzed Formal [3+2] Cycloaddition of 3-Isothiocyanato Oxindoles3 Lewis Acid Catalyzed Formal [3+2] Cycloaddition of 3-Isothiocyanato Oxindoles4 Conclusions

Grip strength and walking pace have been linked to cognitive dysfunction. Their relationships, however, demand further clarification as the evidence is derived primarily from less-comprehensive investigations.A total of 340212 UK Biobank participants without dementia and cardiovascular diseases at baseline were analyzed. Cox proportional hazard models assessed the longitudinal associations.Over a mean follow-up of 8.51 ± 2.68 years, 2424 incident dementia cases were documented. A 5 kg increment of absolute grip strength was associated with lower risks of all-cause dementia (hazard ratio [HR] 0.857), Alzheimer's disease (HR 0.874), and vascular dementia (HR 0.788). The patterns of associations remained similar when grip strength was expressed in relative terms and quintiles. A slow walking pace demonstrated consistent associations with increased risks of all dementia types.Our findings provide amplified evidence and suggest that muscle fitness, reflected by objective grip strength measures and self-reported walking pace, may be imperative for estimating the risks of dementia.

Recent studies show that liver X receptor (LXR) agonists exert significant antitumor effects in a variety of tumor cell lines including hepatocellular carcinoma (HCC). But the molecular mechanisms underlying LXR antitumor activity are not fully understood. In this study we investigated the effect of LXR agonist T0901317 (T317) on HCC development and its relationship with RalA binding protein 1 (RALBP1)-associated EPS domain containing 2 (REPS2)/epidermal growth factor receptor (EGFR) signaling axis. We showed that T317 (0.1-0.5 μM) dose-dependently increased REPS2 expression in normal hepatocytes (BNLCL.2 and LO2) and HCC cells (HepG2 and Huh-7). Using promoter activity assay and chromatin immunoprecipitation (CHIP) assay we demonstrated that T317 enhanced REPS2 expression at the transcriptional level via promoting the binding of LXR protein to the LXR-response element (LXRE) in the REPS2 promoter region. We showed that the inhibitory effect of T317 on the proliferation and migration of HCC cells was closely related to REPS2. Moreover, we revealed that T317 (400 nM) increased expression of REPS2 in HepG2 cells, thus inhibiting epidermal growth factor (EGF)-mediated endocytosis of EGFR as well as the downstream activation of AKT/NF-κB, p38MAPK, and ERK1/2 signaling pathways. Clinical data analysis revealed that REPS2 expression levels were inversely correlated with the development of HCC and reduced REPS2 expression associated with poor prognosis, suggesting that REPS2 might be involved in the development of HCC. In conclusion, this study provides new insights into the potential mechanisms of LXR agonist-inhibited HCC.

A formal [4 + 1] cycloaddition reaction of Baylis–Hillman adducts with sulfur ylides has been developed for the first time.

Owing to an increase in the aging population, osteoporosis has become a severe public health concern, with a high prevalence among the elderly and postmenopausal adults. Osteoporosis-related fracture is a major cause of morbidity and mortality in elderly and postmenopausal adults, posing a considerable socioeconomic burden. However, existing treatments can only slow down the process of osteoporosis, reduce the risk of fractures, and repair fractures locally. Therefore, emerging methods for treating osteoporosis, such as mesenchymal stem cell transplantation, exosome-driving drug delivery systems, biomimetic materials, and 3D printing technology, have received increasing research attention, with significant progress. Mesenchymal stem cells (MSCs) are pluripotent stem cells that can differentiate into different types of functional cells. Exosomes play a key role in regulating cell microenvironments through paracrine mechanisms. Bionic materials and 3D printed scaffolds are beneficial for the reconstruction and repair of osteoporotic bones and osteoporosis-related fractures. Stem cells, exosomes, and biomimetic materials represent emerging technologies for osteoporosis treatment. This review summarizes the latest developments in these three aspects.

A visible-light-induced tandem radical brominative addition/spiro-cyclization/1,2-ester migration of activated alkynes with CBr

Alzheimer's disease (AD) is the most common neurodegenerative disorders presenting with the pathological hallmarks of amyloid plaques and tau tangles. Over the past few years, great efforts have been made to explore reliable biomarkers of AD. High-throughput omics are a technology driven by multiple levels of unbiased data to detect the complex etiology of AD, and it provides us with new opportunities to better understand the pathophysiology of AD and thereby identify potential biomarkers. Through revealing the interaction networks between different molecular levels, the ultimate goal of multi-omics is to improve the diagnosis and treatment of AD. In this review, based on the current AD pathology and the current status of AD diagnostic biomarkers, we summarize how genomics, transcriptomics, proteomics and metabolomics are all conducing to the discovery of reliable AD biomarkers that could be developed and used in clinical AD management.

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Prevention of dementia is a public health priority, and the identification of potential biomarkers may provide benefits for early detection and prevention. This study investigates the association of common serum laboratory tests with the risk of incident dementia. Among 407,190 participants from the UK Biobank (median follow-up of 9.19 years), we investigated the linear and nonlinear effects of 30 laboratory measures on the risk of all-cause dementia using Cox models and restricted cubic spline models. We found that dementia incidence was associated with low vitamin D concentration (hazard ratio 0.994, 95% confidence interval 0.993–0.996), indicators of endocrine disorders: IGF-1 level (P for non-linearity = 1.1E-05), testosterone level (P for non-linearity = 0.006); high sex-hormone-binding globulin level (HR 1.004, 95% CI: 1.003–1.006); reduced liver function: lower alanine aminotransferase (HR 0.990, 95% CI: 0.986–0.995); renal dysfunction: cystatin C level (P for non-linearity = 0.028); oxidative stress: lower urate level (HR 0.998, 95% CI: 0.998–0.999); lipids dysregulation: lower LDL (HR 0.918, 95% CI: 0.872–0.965) and triglycerides (HR 0.924, 95% CI: 0.882–0.967) concentrations; insulin resistance: high glucose (HR 1.093, 95% CI: 1.045–1.143) and HbA1c (HR 1.017, 95% CI: 1.009–1.025) levels; immune dysbiosis: C−reactive protein (P for non-linearity = 5.5E-09). In conclusion, markers of vitamin D deficiency, GH-IGF-1 axis disorders, bioactive sex hormone deficiency, reduced liver function, renal abnormalities, oxidation, insulin resistance, immune dysbiosis, and lipids dysregulation were associated with incident dementia. Our results support a contributory role of systemic disorders and diverse biological processes to onset of dementia.

Aza-ortho-quinone methides are important reactive intermediates that have found broad applications in synthetic chemistry. Recently, 1,4-elimination of ortho-chloromethyl aniline derivatives has emerged as a novel, powerful and convenient method for aza-ortho-quinone methide generation. This review will highlight the recent applications of aza-ortho-quinone methide precursors in annulation reactions to access various biologically important nitrogen-containing heterocycles. The general mechanisms are briefly discussed as well.1 Introduction2 [4+n] Annulation Reactions Using ortho-Chloromethyl Anilines as Aza-ortho-Quinone Methide Precursors2.1 [4+2] Annulation Reactions2.2 [4+1] Annulation Reactions2.3 [4+3] Annulation Reactions3 Conclusion and Perspective

Dynamic changes of traffic features in unstructured road networks challenge the scene-cognitive abilities of drivers, which brings various heterogeneous traffic behaviors. Modeling traffic with these heterogeneous behaviors would have significant impact on realistic traffic simulation. Most existing traffic methods generate traffic behaviors by adjusting parameters and cannot describe those heterogeneous traffic flows in detail. In this paper, a cognition-driven trafficsimulation method inspired by the theory of cognitive psychology is introduced. We first present a visual-filtering model and a perceptual-information fusion model to describe drivers’ heterogeneous cognitive processes. Then, logistic regression is used to model drivers’ heuristic decision-making processes based on the above cognitive results. Lastly, we apply the high-level cognitive decision-making results to low-level traffic simulation. The experimental results show that our method can provide realistic simulations for the traffic with those heterogeneous behaviors in unstructured road networks and has nearly the same efficiency as that of existing methods.

To investigate the effect of internal external fixator assisted O-arm navigation imaging in the treatment of unstable pelvic fractures.From May 2019 to November 2019, 15 patients with unstable pelvic fractures were treated by intraoperative O-arm navigation imaging using INFIX technology. There were 6 males and 9 females. The age ranged from 24 to 66 years old. The course of disease ranged from 2 to 14 days. According to Tile classification, there were 1 case of B1 type, 8 cases of B2 type, 3 cases of C1 type, and 3 cases of C2 type. According to Young-Burgess classification, there were 8 cases of LC, 1 case of APC, 4 cases of VS, 2 cases of CM. Preoperative routine pelvic anteroposterior film, entrance position, exit position and pelvic CT three-dimensional reconstruction were performed. Intraoperative O-arm navigation system three-dimensional reconstruction and triplane scanning imaging were used to evaluate the effect of intraoperative reduction. The anterior pelvic ring was fixed with internal external fixator, and the posterior ring was fixed with sacroiliac screw, plate screw or lumbar iliac screw. The operation time, intraoperative bleeding and nail placement were observed and recorded. The quality of fracture reduction was evaluated by Matta standard, and the postoperative function was evaluated by Majeed function score.Wound healing was good in all patients without vascular, nerve and local irritation complications. All the 15 patients were followed up for 10 to 16 months. The fracture reduction was evaluated according to the Matta scoring standard, 9 cases were excellent results, 5 cases were good, and 1 case was medium. The Majeed functional score was 0 to 95 points.The built-in external fixator assisted O-arm navigation imaging system in the treatment of unstable pelvic fractures. The reduction effect is evaluated in advance, the operation time is shortened, and the accuracy of internal fixation is improved. The operation is simple, safe and less bleeding. The operation is in line with the principles of minimally invasive medical treatment and precision medical treatment in orthopedics, which is conducive to the recovery of patients' postoperative function and rapid recovery.

To investigate the toxicity management and efficacy evaluation of BCMA-chimeric antigen receptor T cells(CART) in the treatment of relapsed and refractory multiple myeloma (MM).The efficacy and adverse reactions of 21 patients with MM who received BCMA-CART treatment at the First Affiliated Hospital of Wenzhou Medical University from December 2017 to September 2020 were evaluated, and the efficacy assessment and survival analysis for high-risk patients and non-high-risk patients were evaluated.After infusion of BCMA-CART cells in 21 MM patients, the number of effective cases was 17, of which the complete remission (sCR/CR) was 10, and the partial remission (VGPR/PR) was 7. The median OS time for all patients was 19.4 months, and the median PFS time was 7.9 months. The number of patients with extramedullary disease(EMD), high-risk genetics, and ISS stage Ⅲ were 5, 15 and 8, and the effective number was 3, 11 and 6, respectively. The treatment of 3 patients without high-risk factors was effective. The median OS and median PFS of patients with EMD were 14.2 and 2.5 months, respectively, which were shorter than those of patients without EMD (19.4 months and 8.9 months, respectively). The median OS and median PFS of patients with high-risk cytogenetic factors and ISS Ⅲ were not significantly different from those of non-high-risk patients. Cytokine release syndrane (CRS) occurred in 20 patients, of which 14 cases were Grade 1 CRS, while 6 were Grade 2, no CRS of Grade 3 or above occurred. IL-6 receptor inhibitors were used in 9 patients. All CRS were controlled effectively, and no patients had neurological toxicity.BCMA-CART is a certain curative effect in the treatment of relapsed and refractory multiple myeloma, and the adverse reactions can be well controlled through close monitoring and timely treatment.BCMA-CART治疗复发难治性多发性骨髓瘤的毒性管理及疗效评估.探讨BCMA-CART细胞治疗复发难治性多发性骨髓瘤(MM)的毒性管理及疗效评估.评估2017年12月至2020年9月在温州医科大学附属第一医院接受BCMA-CART治疗的21例MM患者的疗效及不良反应，对高风险患者和非高风险患者进行疗效评估和生存分析.21例复发难治性MM患者在输注BCMA-CART细胞后,有效例数为17例，其中完全缓解（sCR/CR）10例，部分缓解（VGPR/PR）7例。所有患者中位OS为19.4个月，中位PFS为7.9个月。具有髓外疾病、高风险遗传学和ISS Ⅲ期的患者分别为5、15和8例，有效例数分别为3、11和6例。3例无高危因素的患者治疗均有效。并发髓外疾病的MM患者中位OS和中位PFS分别为14.2和2.5个月，均短于无髓外疾病的患者（分别为19.4和8.9个月）。具有高风险细胞遗传学因素和ISS Ⅲ级的患者中位OS和中位PFS与非高危患者均无明显差异。20例患者发生细胞因子释放综合征（CRS），其中1级CRS 14例，2级6例，无≥3级病例。9例患者使用了IL-6受体抑制剂。所有患者的CRS均得到有效控制，没有患者发生神经系统毒性.BCMA-CART治疗复发难治性MM具有一定疗效，且不良反应可控。密切监测和及时处理有助于减少不良反应的发生发展.

Although sleep, physical activity and sedentary behavior have been found to be associated with dementia risk, findings are inconsistent and their joint relationship remains unclear. This study aimed to investigate independent and joint associations of these three modifiable behaviors with dementia risks. A total of 431,924 participants (median follow-up 9.0 years) without dementia from UK Biobank were included. Multiple Cox regressions were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Models fitted with restricted cubic spline were conducted to test for linear and nonlinear shapes of each association. Sleep duration, leisure-time physical activity (LTPA), and screen-based sedentary behavior individually associated with dementia risks in different non-linear patterns. Sleep duration associated with dementia in a U-shape with a nadir at 7 h/day. LTPA revealed a curvilinear relationship with dementia in diminishing tendency, while sedentary behavior revealed a J-shaped relationship. The dementia risk was 17% lower in the high LTPA group (HR[95%CI]: 0.83[0.76-0.91]) and 22% higher in the high sedentary behavior group (1.22[1.10-1.35]) compared to the corresponding low-level group, respectively. A combination of seven-hour/day sleep, moderate-to-high LTPA, and low-to-moderate sedentary behavior showed the lowest dementia risk (0.59[0.50-0.69]) compared to the referent group (longer or shorter sleep/low LTPA/high sedentary behavior). Notably, each behavior was non-linearly associated with brain structures in a pattern similar to its association with dementia, suggesting they may affect dementia risk by affecting brain structures. Our findings highlight the potential to change these three daily behaviors individually and simultaneously to reduce the risk of dementia.

Alcoholic liver damage is caused by long-term drinking, and it further develops into alcoholic liver diseases. In this study, we prepared a probiotic fermentation product of Grifola frondosa total active components (PFGF) by fermentation with Lactobacillus acidophilus, Lactobacillus rhamnosus, and Pediococcus acidilactici. After fermentation, the total sugar and protein content in the PFGF significantly decreased, while the lactic acid level and antioxidant activity of the PFGF increased. Afterward, we investigated the alleviating effect of PFGF on alcoholic liver injury in alcohol-fed mice. The results showed that the PFGF intervention reduced the necrosis of the liver cells, attenuated the inflammation of the liver and intestines, restored the liver function, increased the antioxidant factors of the liver, and maintained the cecum tissue barrier. Additionally, the results of the 16S rRNA sequencing analysis indicated that the PFGF intervention increased the relative abundance of beneficial bacteria, such as Lactobacillus, Ruminococcaceae, Parabacteroids, Parasutterella, and Alistipes, to attenuate intestinal inflammation. These results demonstrate that PFGF can potentially alleviate alcoholic liver damage by restoring the intestinal barrier and regulating the intestinal microflora.

BACKGROUND Midfoot deformity and injury can affect the internal pressure distribution of the foot. This study aimed to use 3D finite element and biomechanical analyses of midfoot von Mises stress levels in flatfoot, clubfoot, and Lisfranc joint injury. MATERIAL AND METHODS Normal feet, flatfeet, clubfeet (30 individuals each), and Lisfranc injuries (50 individuals) were reconstructed by CT, and 3D finite element models were established by ABAQUS. Spring element was used to simulate the plantar fascia and ligaments and set hyperelastic coefficients in encapsulated bone and ligaments. The stance phase was simulated by applying 350 N on the top of the talus. The von Mises stress of the feet and ankle was visualized and analyzed. RESULTS The von Mises stress on healthy feet was higher in the lateral metatarsal and ankle bones than in the medial metatarsal bone. Among the flatfoot group, the stress on the metatarsals, talus, and navicular bones was significantly increased compared with that on healthy feet. Among patients with clubfeet, stress was mainly concentrated on the talus, and stress on the lateral metatarsal and navicular bones was significantly lower. The von Mises stress on the fractured bone was decreased, and the stress on the bone adjacent to the fractured bone was higher in Lisfranc injury. During bone dislocation alone or fracture accompanied by dislocation, the von Mises stress of the dislocated bone tended to be constant or increased. CONCLUSIONS Prediction of von Mises stress distribution may be used clinically to evaluate the effects of deformity and injury on changes in structure and internal pressure distribution on the midfoot.

Three prokaryotic predator strains, BL9T, BL10 and BL28, were isolated with Vibrio alginolyticus from coastal seawater of PR China. Cells of the strains were Gram-negative, vibrioid-shaped and motile with a single sheathed flagellum (25–28 nm wide). Cells were around 0.3×0.5–1.0 µm in size. The three strains were obligate predators that exhibited a biphasic life cycle: a free-swimming attack phase and an intraperiplasmic growth phase within the prey. Bdelloplasts were formed. NaCl was required for growth. Optimum growth occurred at ~37 °C, with 2–4 % (w/v) NaCl and at pH 7.0–8.0. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the three strains shared 99.9 % similarity to each other, were affiliated with the genus Halobacteriovorax in the class Oligoflexia, and represented the same new species. Strain BL9T (=MCCC 1K03527T=JCM 32962T) was designated as the type strain. Genome sequencing of strain BL9T revealed a genome size of 3.14 Mb and a G+C content of 35.8 mol%. The estimated digital DNA–DNA hybridization (dDDH) values and the whole genome average nucleotide identity (gANI) values between the genome of strain BL9T and those of Bdellovibrionales and Bacteriovoracales were 12.5–19 and 63.49–76.15 %, respectively. On the basis of life cycle features, results of physiological analyses, gANI data and dDDH data, strain BL9T represents a new species within the genus Halobacteriovorax , for which the name Halobacteriovorax vibrionivorans sp. nov. is proposed.

In the course of screening for bacterial predator, a Gram-negative, non-flagellated, gliding, long rod-shaped and yellow-pigmented bacterium, designated strain HICWT, was isolated from coastal seawater of China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain HICWT represented a member of the genus Muricauda and showed the highest sequence similarity to M. aquimarina JCM11811T (98.8%) and M. ruestringensis DSM13258T (98.1%). NaCl was required for growth. Optimum growth occurred at 25–30 oC, 2.0–3.0% (w/v) NaCl with pH 7.0. Strain HICWT showed some similar characteristics to the nonobligate bactertal predators, the cells can attach the prey cells. Strain HICWT contained MK-6 as the predominant respiratory quinone and had iso-C15:0, iso-C15:1 G and iso-C17:0 3-OH as the major cellular fatty acids. The polar lipids contained phosphatidylethanolamine (PE), three unknown phospholipids (PL1–PL3), one unknown aminolipids (AL) and three unknown polar lipids (L1–L3). The genome size of strain HICWT was approximately 3.8 Mbp, with a G+C content of 41.4%. On the basis of the polyphasic evidence, strain HICWT is proposed as representing a new species of the genus Muricauda, for which the name Muricauda chongwuensis sp. nov. is proposed. The type strain is HICWT (=JCM 33643T=MCCC 1K03769T).

Background MicroRNA-122 (miR-122), a pivotal liver-specific miRNA, is frequently repressed in hepatocellular carcinoma (HCC) and associated with poor prognosis. Long non-coding RNA (lncRNA) HOTAIR has been proved to function as an oncogene in multiple cancers including HCC. However, the relationship between HOTAIR and miR-122 in HCC remains largely unknown. Methods We investigated the function of HOTAIR and miR-122 in HCC cell models and a xenograft mouse model. The regulatory network between HOTAIR and miR-122 was further detected following overexpression or knockdown of HOTAIR. DNA methylation status of miR-122 promoter region, as well as expression levels of DNMTs, EZH2 and Cyclin G1 were analyzed. Findings In this study, we found that HOTAIR was highly expressed whereas miR-122 was suppressed in HCC, and HOTAIR negatively regulated miR-122 expression in HCC cells. Furthermore, knockdown of HOTAIR dramatically inhibited HCC cell proliferation and induced cell cycle arrest in vitro and suppressed tumorigenicity in vivo by upregulating miR-122 expression. Mechanistically, a CpG island was located in the miR-122 promoter region. HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. Moreover, HOTAIR upregulated DNMTs expression via EZH2. In addition, suppression of miR-122 induced by HOTAIR directly reactivated oncogene Cyclin G1 expression. Collectively, our results suggest that HOTAIR epigenetically suppresses miR-122 expression via DNA methylation, leading to activation of Cyclin G1 and promotion of tumorigenicity in HCC, which provide new insight into the mechanism of HOTAIR-mediated hepatocarcinogenesis via suppressing miR-122., Highlights • HOTAIR is highly expressed in HCC, and negatively regulates miR-122 expression in HCC cells. • HOTAIR increased HCC cell proliferation and tumor growth through downregulating miR-122 expression. • HOTAIR epigenetically suppressed miR-122 expression via DNMTs-mediated DNA methylation. • HOTAIR upregulated DNMTs expression via EZH2. • HOTAIR increased cyclin G1 expression through repressing miR-122.

The long noncoding RNA, homeobox transcript antisense RNA (Hotair), has been demonstrated to have an important role in regulating various biological processes in various cancers, including hepatocellular carcinoma (HCC). However, the importance of Hotair in HCC proliferation and cell cycle progression remains to be elucidated. In the present study, knockdown of HOTAIR expression by RNA interference inhibited cell proliferation and induced G0/G1 cell cycle arrest in Huh7 hepatocellular carcinoma cells. In addition, the expression levels of CCND1 mRNA and its cyclin D1 protein product were reduced in Huh7 cells following knockdown of HOTAIR. Knockdown of HOTAIR reduced the expression of phosphorylated signal transducer and activator of transcription 3 (STAT3) and HOTAIR knockdown combined with STAT3 inhibition led to an additional decrease in cyclin D1 expression. The present study suggested that Hotair may have a critical role in the proliferation of HCC by regulating cell cycle, STAT3 activity and cyclin D1 expression. Therefore, Hotair may be a novel potential therapeutic target for HCC treatment.

Aim Aberrant expression of Snail, a mediator of epithelial-mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified. Methods HepG2 and Huh7 stable cell lines were established by transfection with pcDNA-HCVc. HepG2-HCVc and Huh7-HCVc cells were co-administered with AG490. Cell migration and invasiveness were tested. STAT3 and Snail expression was analyzed by Real-time PCR and Western blot. Results We found that HCV core is capable of increasing Snail expression and inducing EMT in hepatoma cells. HCV core-induced Snail expression was accompanied by activation of signal transducer and activator of transcription 3 (STAT3), inhibition of STAT3 abrogated HCV core-induced Snail expression and EMT. Furthermore, chromatin immunoprecipitation showed that phosphorylated STAT3 directly binds to the Snail promoter. Conclusion Collectively, these results suggest that HCV core would play a role in hepatocellular carcinoma invasiveness and metastasis by activating the STAT3 pathway, increasing Snail expression and subsequently triggering EMT. These findings would advance the understanding of HCV-mediated invasiveness and metastasis, and might provide a new potential therapeutic target for HCV-related hepatocellular carcinoma.

The draft genome sequence of the extracellular protease-producing bacterium Stenotrophomonas bentonitica VV6, isolated from Arctic seawater, was established. The genome size was approximately 4.365 Mb, with a G+C content of 66.54%, and it contains 3,871 predicted protein-coding sequences (CDSs) and 60 tRNAs.

Long non-coding RNA HOX transcript antisense RNA (HOTAIR) has been demonstrated to exhibit oncogenic activity in several types of cancer, including hepatocellular carcinoma (HCC). However, the association between HOTAIR and HCC multidrug resistance remains uncertain. The present study aimed to investigate the role of HOTAIR in HCC chemoresistance; it was found that knockdown of HOTAIR expression in HCC Huh7 cells resulted in decreased cell proliferation and increased chemosensitivity to cisplatin. Furthermore, expression levels of ATP binding cassette subfamily B member 1 (ABCB1) mRNA and protein were decreased in Huh7 cells upon HOTAIR-knockdown. In addition, HOTAIR-knockdown reduced the levels of phosphorylated signal transducer and activator of transcription 3 (STAT3), and inhibition of STAT3 phosphorylation reduced HOTAIR-mediated ABCB1 expression. Together, these findings indicated that knockdown of HOTAIR in Huh7 cells decreased STAT3 activity and ABCB1 expression, and increased chemosensitivity to cisplatin. Thus HOTAIR could serve as a novel potential therapeutic target to reverse multidrug resistance in HCC.

Cavities are important in clinical diagnosis of pulmonary tuberculosis (TB) infected by Mycobacterium tuberculosis. Although microRNAs (miRNAs) play a vital role in the regulation of inflammation, the relation between plasma miRNA and pulmonary tuberculosis with cavity remains unknown. In this study, plasma samples were derived from 89 cavitary pulmonary tuberculosis (CP-TB) patients, 89 non-cavitary pulmonary tuberculosis (NCP-TB) patients and 95 healthy controls. Groups were matched for age and gender. In the screening phase, Illumina high-throughput sequencing technology was employed to analyze miRNA profiles in plasma samples pooled from CP-TB patients, NCP-TB patients and healthy controls. During the training and verification phases, quantitative RT-PCR (qRT-PCR) was conducted to verify the differential expression of selected miRNAs among groups. Illumina high-throughput sequencing identified 29 differentially expressed plasma miRNAs in TB patients when compared to healthy controls. Furthermore, qRT-PCR analysis validated miR-769-5p, miR-320a and miR-22-3p as miRNAs that were differently present between TB patients and healthy controls. ROC curve analysis revealed that the potential of these 3 miRNAs to distinguish TB patients from healthy controls was high, with the area under the ROC curve (AUC) ranged from 0.692 to 0.970. Moreover, miR-320a levels were decreased in drug-resistant TB patients than pan-susceptible TB patients (AUC = 0.882). In conclusion, we identified miR-769-5p, miR-320a and miR-22-3p as potential blood-based biomarkers for TB. In addition, miR-320a may represent a biomarker for drug-resistant TB.

With the large-scale application of the prestressed concrete structure, the quality of the concrete component defects and pipeline grouting has increasingly become the focus of attention. The impact-echo scanner uses the nature of wave, which pass though different media at different velocities, to distinguish internal defects of concrete, pipe filling density and so on. In this paper, using the impact-echo method to detect the concrete block with prefabricated defects of shape, location, and size explores the effect of defect properties, parameter settings and detection environment to impact-echo preliminarily and also explores the relationship of pipeline filling status and impact-echo image. Based on this study, the article raised the problem met during this non-destructive testing methods applied to engineering, and accumulated a certain amount of available engineering data. The experiment results show that using the impact-echo method to identify the defects of concrete components and to test the quality of pipeline grouting is a more convenient and effective non-destructive testing method. Especially, with the radar method in the pipeline grouting quality inspection which complement each other to make up for the shortcomings the lightning wave in case of the metal medium total reflection phenomenon, cannot detect metal pipe grouting plumpness.

Universality is an important feature, but less researched in quantum communication protocols. In this paper, a kind of universal quantum secret sharing protocol is investigated. Firstly, we design a quantum secret sharing protocol based on the Borras-Plastino-Batle (BPB) state. Departing from previous research, our protocol has a salient feature in that participants in our protocol only need projective measurement instead of any unitary operations. It makes our protocol more flexible. Secondly, universality of quantum communication protocols is studied for the first time. More specifically, module division of quantum communication protocols and coupling between different modules are discussed. Our aforementioned protocol is analyzed as an example. On one hand, plenty of quantum states (the BPB-class states and the BPB-like-class states, which are proposed in this paper) could be used as carrier to perform our protocol. On the other hand, our protocol also could be regarded as a quantum private comparison protocol with a little revision. These features are rare for quantum communication protocols, and make our protocol more robust. Thirdly, entanglements of the BPB-class states are calculated in the Appendix.

To investigate the clinical efficacy of cannulated screw fixation with percutaneous Poking reduction for the treatment of Sanders II, III calcaneal fracture.From January 2012 to January 2014, 19 patients with Sanders II, III calcaneal fracture were treated with cannulated screw fixation with percutaneous Poking reduction. There were 14 males and 5 females, ranging in age from 19 to 58 years old, with an average age of (38.3 +/- 4.1) years old. The changes of Bohler angle and Gissane angle were measured and compared preoperatively and postoperatively to observe the recovery of the articular surface. The Maryland Foot Score was used to evaluate operation outcomes.All the patients were followed up, and the duration ranged from 12 to 28 months with a mean of (22.3 +/- 5.3) months. The Bohler angle and Gissane angle were improved significantly after operation compared with those before operation (P0.05). The Maryland score was 83.2 +/- 8.4.Treatment of calcaneal fractures with screw fixation with percutaneous Poking reduction has several advantages such as satisfactory outcome,less damage, fewer complications, quicker recovery, and shorter hospital stay,and it is one of the effective treatments for Sanders II and III calcaneal fractures.

Aberrant expression of Snail, a mediator of epithelial-mesenchymal transition (EMT), is crucial for cancer invasiveness and metastasis. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, the relationship between HCV core and Snail expression has not been clarified.HepG2 and Huh7 stable cell lines were established by transfection with pcDNA-HCVc. HepG2-HCVc and Huh7-HCVc cells were co-administered with AG490. Cell migration and invasiveness were tested. STAT3 and Snail expression was analyzed by Real-time PCR and Western blot.We found that HCV core is capable of increasing Snail expression and inducing EMT in hepatoma cells. HCV core-induced Snail expression was accompanied by activation of signal transducer and activator of transcription 3 (STAT3), inhibition of STAT3 abrogated HCV core-induced Snail expression and EMT. Furthermore, chromatin immunoprecipitation showed that phosphorylated STAT3 directly binds to the Snail promoter.Collectively, these results suggest that HCV core would play a role in hepatocellular carcinoma invasiveness and metastasis by activating the STAT3 pathway, increasing Snail expression and subsequently triggering EMT. These findings would advance the understanding of HCV-mediated invasiveness and metastasis, and might provide a new potential therapeutic target for HCV-related hepatocellular carcinoma.

Dianthus superbus L. is commonly used as a traditional Chinese medicine. We recently showed that ethyl acetate fraction (EE-DS) from ethanol extract of D. superbus exhibited the strongest antioxidant and cytotoxic activities. In this study, we examined apoptosis of HepG2 cells induced by EE-DS, and the mechanism underlying apoptosis was also investigated. Treatment of HepG2 cells with EE-DS (20–80μg/ml) for 48h led to a significant dose-dependent increase in the percentage of cells in sub-G1 phase by analysis of the content of DNA in cells, and a large number of apoptotic bodies containing nuclear fragments were observed in cells treated with 80μg/ml of EE-DS for 24h by using Hoechst 33258 staining. These data show that EE-DS can induce apoptosis of HepG2 cells. Immunoblot analysis showed that EE-DS significantly suppressed the expressions of Bcl-2 and NF-κB. Treatment of cells with EE-DS (80μg/ml) for 48h resulted in significant increase of cytochrome c in the cytosol, which indicated cytochrome c release from mitochondria. Activation of caspase-9 and -3 were also determined when the cells treated with EE-DS. The results suggest that apoptosis of HepG2 cells induced by EE-DS could be through the mitochondrial intrinsic pathway. High performance liquid chromatography (HPLC) data showed that the composition of EE-DS is complicated. Further studies are needed to find the effective constituents of EE-DS.

Nondestructive testing technology on prestressed pipe grouting is an important issue in recent years. Some research methods including Radar Method, Ray Method, and Impact Echo Method were contrasted and verified in this paper. The applicable scope and the defect detectable effect of these methods mentioned above was studied exploringly. The achievements obtained this paper were certain to be significant for the detection on pipeling grouting quality and defect inside concrete.

An input-output optimal control model is established under uncertain influence in environment. The objective function, terminal constraint of state variables and bound constraints of control variables are considered with fuzziness. The direct consumption coefficient matrix and investment coefficient matrix are regarded as stochastic variables. Membership function and chance constrained programming are applied to convert the uncertain model to a definite one. Penalty function and Particle Swarm Optimization are used to solve the model. The calculation results of an example demonstrate that the uncertain model has more practical value to decision makers compared to a definite one.

Considering the privacy issues on social network, a variety of anonymous techniques have been proposed, but these techniques neglect some differences among individuals in their demand for privacy protection. With the development of internet technology, the number of social network individuals increases yearly, and network data are poised for a massive change in trends. Motivated by this, we specify three levels of privacy information for victim individuals and propose a personalised k-degree-m-label (PKDML) anonymity model. Furthermore, we design and implement a distributed and personalised k-degree-m-lable (DPKDML) anonymisation algorithm, which takes advantage of the 'vertex-centric' GraphX programming model to complete the entire anonymous process by multiple message passing and node value updating. Finally, we conduct experiments on real social network datasets to evaluate the DPKDML, The experimental results show that our methods may overcome the shortcomings of traditional methods in processing massive data, and reduce anonymous costs and increase data utility.

An aged Al-5Zn-1.6Mg alloy with fine η' precipitates was grain refined to ~100 nm grain size by severe plastic deformation (SPD). Microstructure evolution during SPD and mechanical behaviour after SPD of the alloy were characterized by electron microscopy and tensile, compression as well as nanoindentation tests. The influence of η' precipitates on microstructure and mechanical properties of ultrafine grained Al-Zn-Mg alloy is discussed with respect to their effect on dislocation configurations and deformation mechanisms during processing of the alloy.

A wavelet energy method is presented to search the critical incidence of earthquake excitation in a multi-dimensional seismic response of offshore platforms. The total effective energy and the instantaneous effective energy input rate of an earthquake can be obtained by wavelet transformation to predict the critical incidence of the earthquake and then the maximum dynamic response of the platform can be calculated. The critical incidence is determined using this method for an actual platform and a group of single degree-of-freedom systems. Numerical results show that the application of wavelet transform in a multi-dimensional seismic response of structures is convenient and reliable.

A low-cost β type Ti-1.5Fe-6.8Mo-4.8Al-1.2Nd (mass fraction, %)(T12LCC) alloy was produced by blended elemental powder metallurgy(P/M) method and subsequent thermomechanical treatment. Low cycle fatigue(LCF) behavior of P/M T12LCC alloy before and after thermomechanical treatment was studied. The results show that the LCF resistance of P/M titanium alloy is significantly enhanced through the thermomechanical treatment. The mechanisms for the improvement of LCF behavior are attributed to the elimination of residual pores, the microstructure refining and homogenization.

A method was developed for the determination of 59 glucocorticoids, sex hormones, nonsteroidal anti-inflammatory drugs, antibiotics, and other contaminants in cosmetics simultaneously by ultra high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry. Acetonitrile was used to extract the sample, and the mixed sorbents were dispersed for purification. With the optimal conditions, the optimized pretreatment processes led to no significant interference on analysis from an extremely complicated sample matrix, and the linear ranges of 59 analytes were 0-480.0 μg/kg with the correlation coefficients above 0.99 and the limits of quantification (S/N≥10) were 5-40 μg/kg. Statistical evaluation revealed that the average recoveries were in the range of 61.2-131.2%, and relative standard deviations were in the range of 2.0-22.8%, meanwhile the interday precision ranged from 3.8 to 21.8%. This method is simple, fast, and credible, and it can be applied to simultaneous screening and determination of various classes of substances under investigations illegally presented in cosmetic products, covering a wide diversity of polarities, and pKa values.

A 5/6 nephrectomized (Nx) rat model was employed to address the impact of telmisartan on CKD related renal injury and the underlying molecular mechanisms. It was noted that telmisartan provided protection for rats against 5/6 Nx induced lethality. Telmisartan treated 5/6 Nx rats manifested improved renal function as characterized by the higher GFR but lower urinary albumin, BUN and Scr as compared with that of control rats. Telmisartan treatment also significantly decreased systolic blood pressure and alleviated glomerulosclerosis and interstitial fibrosis. Mechanistic studies revealed that telmisartan possesses the capability to increase NO generation in the kidney. Further studies demonstrated that telmisartan promotes PPARγ expression, by which it specifically enhances nNOS expression in the kidneys after 5/6 Nx insult. Particularly, blockade of PPARγ signaling by GW9662 abolished the protective effect conferred by telmisartan, indicating that telmisartan induction of renal nNOS expression along with NO generation is dependent on PPARγ signaling. Together, our data support that telmisartan could be a promising drug for treatment of chronic kidney diseases in diverse clinical settings.

Multidrug resistance (MDR) is one of the major reasons for the failure of liver cancer chemotherapy, and its suppression may increase the efficacy of chemotherapy. NANOG plays a key role in the regulation of embryonic stem cell self-renewal and pluripotency. Recent studies reported that NANOG was abnormally expressed in several types of tumors, indicating that NANOG is related to tumor development. However, the correlation between NANOG and liver cancer chemoresistance remains uncertain. In this study, RNA interfere technology was employed to knock down NANOG expression in HepG2 human liver cancer cells. We found that the knockdown of NANOG expression in NANOG siRNA-transfected HepG2 cells resulted in decreased colony formation rate and cell migration compared to control HepG2 cells. In addition, HepG2 cells were treated with doxorubicin to evaluate the chemosensitivity to doxorubicin. We found that the doxorubicin sensitivity of HepG2 cells was increased with downregulation of NANOG expression. The expression of MDR1 at both mRNA and protein levels was decreased in HepG2 cells when NANOG was knocked down. These findings suggest that the knockdown of NANOG in HepG2 human cells resulted in decreased MDR1 expression and increased doxorubicin sensitivity, and NANOG could be used as a novel potential therapeutic target to reverse multidrug resistance of liver cancer.

To construct a cDNA library from Streptomyces thermohydroscopicus and screen genes with virulence, obtain the recombinant fusion virulence proteins by prokaryotic expression system.The Streptomyces thermohydroscopicus cDNA library was constructed by switching mechanism at 5'end of RNA transcript approach. A total of 1020 clones randomly selected from the cDNA library were sequenced and these expressed sequence tags (EST) were further analyzed for the screen of antigen-specific genes. The two candidate genes were subcloned into expression vector pET-28a. The recombinants were transformed into BL2 and proteins were expressed by the induction of isopropyl-β-D-1-thiogalactopyranoside (IPTG).A high-quality cDNA library from Streptomyces thermohydroscopicus was constructed and a set of 978 valid sequences were obtained. Clustering and assembly of these cDNA sequences resulted in 347 unique genes, among which 2 potential antigen-specific genes were highly allied with outer membrane lipoprotein (51%) and transferring-binding protein B (42%) from Actinobacillus pleuropneumoniae serotype (APP). The open reading frame (ORF) of the two candidate genes are 1554 bp and 726 bp, which coded two peptides with 517 and 241 amino acids, respectively. The molecular weights of the recombinant fusion proteins were 63 000 and 30 000.The cDNA library of Streptomyces thermohydroscopicus reached the quality requirement of gene library. EST database in the library would greatly facilitate further screening of virulence genes.

To study the association between HLA-DRB1 alleles and familial hepatitis B.HLA-DRB1 alleles of 151 people in the familial hepatitis B families were detected,by using the the polymerase chain reaction-sequence specific oligonucleotide probing (PCR-SSOP) technique.The allele frequency of HLA-DRB1 * 0701 in the chronic hepatitis B (CHB) group was markedly higher than that in the normal control group (17.8% vs 7.4%), with significant correlation between them (P0.05, A = 1/0.367 approximately 2.725). The allele frequencies of HLA-DRB1 * 0401/0403/0405 and HLA-DRB1 * 1301/1302 in the normal control group (16.2%, 4.4% ) were markedly higher than that in the CHB group (5.1%, 0), with statistical significance (P0.05, A = 3.602; P0.05). The other alleles between the CHB group and the normal control group are no significant differences.HLA-DRB1 * 0701 is closely associated with the susceptibility to familial hepatitis B,and may be the susceptible or linkage gene. HLA-DRB1* 0401/0403/0405 and HLA-DRB1 * 1301/1302,in inverse proportion to the susceptibility to familial hepatitis B, may be the resistant gene. They may regulate the outcome of familial HBV infection in a patient.

Polycystic ovary syndrome (PCOS) may result from hypersensitivity to insulin, which is negatively regulated by uncoupling protein (UCP)-2. Because cholesterol side-chain cleavage enzyme (CYP11A1) is closely linked to PCOS, the expression of UCP-2 and CYP11A1 in ovarian tissues from PCOS patients was examined in the present study. Twelve PCOS patients with hyperandrogenaemia who underwent laparoscopic ovarian wedge resection and 12 age-matched control patients who underwent contralateral ovarian biopsy were enrolled in the study. UCP-2 expression in early stage (primordial, primary and secondary) and late stage (sinus and mature) follicles was examined using immunohistochemistry, whereas UCP-2 and CYP11A1 mRNA and protein levels in ovarian tissue were determined using quantitative reverse transcription–polymerase chain reaction and western blot analyses, respectively. UCP-2 expression increased significantly with follicular development in both control and PCOS tissue, with expression in early stage follicles from PCOS patients significantly greater than that in controls. In addition, both UCP-2 and CYP11A1mRNA and protein levels, mean fasting blood glucose concentrations and fasting serum insulin levels were significantly higher in PCOS patients compared with the control group. Finally, a significant correlation between UCP-2 and CYP11A1 expression was found in PCOS but not control patients. In conclusion, in PCOS patients, there was a correlation between UCP-2 and CYP11A1 expression, which was significantly higher than in the control group. These changes in UCP-2 and CYP11A1 expression may mediate follicle development in PCOS.

To investigate the inhibitory effect of nanoparticle-mediated endostatin gene therapy on hepatocellular carcinoma xenografts combined with local hyperthermia utilizing heat-inducible promoter.Heat-inducible HSP70B promoter and fusion gene of Endo/EGFP were cloned into pcDNA3.1 (+) plasmid, thus obtaining recombinant plasmid of pcDNA3.1 (+)/HSP70-Endo/EGFP using restriction endonucleases BglII/HindIII and EcoRI/SalI. The nanoparticles polylactide-grafted dextran copolymer (DEX-g-PLA) encapsulating the recombinant plasmid DNA were prepared by the method of emulsification and evaporation of organic solvent, and the surface shape of nanoparticles was observed by transmission electron microscope. Human hepatocellular cells of the lines HepG2 and ECV304 were cultured and transfected with the recombinant plasmid utilizing the nanoparticles. Following thermal induction at 37 degrees C, 39 degrees C, 41 degrees C, 43 degrees C, and 45 degrees C for 30 min, the expression of enhanced green fluorescent protein (EGFP) was detected by fluorescence microscope and flow cytometry. The concentration of endostatin protein in the supernatant was tested by ELISA, and the growth inhibition on the HepG2 and ECV304 cells was tested by MTT method. Balb/c nude mice were inoculated with HeG2 cells and then randomly divided into 2 groups to undergo intra-tumor injection of nanoparticles (heated or not heated), Lipofectamine 2000. Mice were used as controls without intra-tumor injection. Four weeks the mice were killed to observe the tumor inhibition rate.The nanoparticles encapsulating recombinant plasmid were of round or elliptical shape 90 approximately 120 nm in diameter. The efficiency of gene transfection mediated by nanoparticles was about 30.65%. The expression of Endo/EGFP gene in the HepG2 cells was up-regulated along with the increase of temperature, peaked at 43 degrees C (with the EGFP expression level 3.3 times as that at 37 degrees C). The concentration of endostatin protein in the supernatant of the 43 degrees C group was (177 +/- 28) microg/L, significantly higher than that of the 37 degrees C group [(41 +/- 10) microg/L]. MTT results indicated that endostatin inhibited the growth of ECV304 cells with a inhibition rate of 96.3% at the time point of 72 h in the 43 degrees C group, however, it did not show influence on HepG2 cells no matter what was the temperature The tumor inhibition rate in the mice of endostatin with thermal induction group was 58.5%, significantly higher than that of the 37 degrees C group (34.9%, P0.05).Low temperature thermal induction enhances the expression and secretion of endostatin in hepatocellular cells transfected by nanoparticles, and inhibits the growth of hepatocellular carcinoma xenografts.