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Due to the limitations imposed by urban power grid outages for maintenance, on‐line harmonic current detection technology for distribution network cables is expected to become an effective supplement to traditional offline diagnostic methods, enhancing the real‐time diagnosis of distribution network cable insulation conditions. This study established a 10 kV distribution network cable test platform and prepared typical defective cables subjected to moisture and long‐term thermal aging. Using COMSOL finite element electromagnetic simulation, the magnetic flux evolution laws of the cable insulation under typical defects were obtained. Experimental tests provided the harmonic current characteristics and statistical features of cables with typical defects. Based on these data, a method for analysing the degradation degree of distribution network cables was constructed using least absolute shrinkage and selection operator (LASSO) regression analysis. Furthermore, a defect‐type identification method based on cluster analysis was proposed. Results indicate that the odd harmonics and the 4th harmonic of the distribution network cable's harmonic current are closely related to the cable's degradation state. A model integrating principal component analysis (PCA) data dimensionality reduction and expectation‐maximization clustering analysis achieved a recognition accuracy of up to 75.64% in distinguishing between moisture‐affected and normal cable states. The proposed on‐line detection and evaluation methods can effectively identify high‐risk cables with latent defects. [ABSTRACT FROM AUTHOR]

Background: Monoamine oxidase B (MAOB), a flavin monoamine oxidase, regulates biogenic and xenobiotic amine oxidative deaminization. We demonstrate MAOB expression in head and neck epithelium and its biological importance in head and neck squamous cell carcinoma (HNSCC) development. Methods: First, we found a possible MAOB downregulation in HNSCC using bioinformatic analysis. Second, we validated MAOB expression changes in vitro and assessed its tumorigenicity in HNSCC. Finally, preclinical xenograft models further confirmed our findings. Results: Results proved that MAOB was significantly reduced in HNSCC tissues and cell lines. By comparing MAOB localization in patient specimens, we found that epithelial basal cells express MAOB and that it changes throughout HNSCC development. We observed that MAOB overexpression inhibited HNSCC cell malignancy via lentiviral transfection. We additionally discovered that selegiline partly counter‐regulated MAOB overexpression‐induced phenotypes in HNSCC cells. Conclusions: We found that MAOB is a potent biomarker and a unique and essential indication of HNSCC carcinogenesis. [ABSTRACT FROM AUTHOR]

Increasing evidence suggests that DNA phosphorothioate (PT) modification serves several purposes in the bacterial host, and some restriction enzymes specifically target PT‐DNA. PT‐dependent restriction enzymes (PDREs) bind PT‐DNA through their DNA sulfur binding domain (SBD) with dissociation constants (KD) of 5 nM~1 μM. Here, we report that SprMcrA, a PDRE, failed to dissociate from PT‐DNA after cleavage due to high binding affinity, resulting in low DNA cleavage efficiency. Expression of SBDs in Escherichia coli cells with PT modification induced a drastic loss of cell viability at 25°C when both DNA strands of a PT site were bound, with one SBD on each DNA strand. However, at this temperature, SBD binding to only one PT DNA strand elicited a severe growth lag rather than lethality. This cell growth inhibition phenotype was alleviated by raising the growth temperature. An in vitro assay mimicking DNA replication and RNA transcription demonstrated that the bound SBD hindered the synthesis of new DNA and RNA when using PT‐DNA as the template. Our findings suggest that DNA modification‐targeting proteins might regulate cellular processes involved in DNA metabolism in addition to being components of restriction‐modification systems and epigenetic readers. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel diseases (IBDs) pose significant challenges in terms of treatment non‐response, necessitating the development of novel therapeutic approaches. Although biological medicines that target TNF‐α (tumour necrosis factor‐α) have shown clinical success in some IBD patients, a substantial proportion still fails to respond. Methods: We designed bispecific nanobodies (BsNbs) with the ability to simultaneously target human macrophage‐expressed membrane TNF‐α (hmTNF‐α) and IL‐23. Additionally, we fused the constant region of human IgG1 Fc (hIgG1 Fc) to BsNb to create BsNb‐Fc. Our study encompassed in vitro and in vivo characterization of BsNb and BsNb‐Fc. Results: BsNb‐Fc exhibited an improved serum half‐life, targeting capability and effector function than BsNb. It's demonstrated that BsNb‐Fc exhibited superior anti‐inflammatory effects compared to the anti‐TNF‐α mAb (infliximab, IFX) combined with anti‐IL‐12/IL‐23p40 mAb (ustekinumab, UST) by Transwell co‐culture assays. Notably, in murine models of acute colitis brought on by 2,4,6‐trinitrobenzene sulfonic acid（TNBS) and dextran sulphate sodium (DSS), BsNb‐Fc effectively alleviated colitis severity. Additionally, BsNb‐Fc outperformed the IFX&UST combination in TNBS‐induced colitis, significantly reducing colon inflammation in mice with colitis produced by TNBS and DSS. Conclusion: These findings highlight an enhanced efficacy and improved biostability of BsNb‐Fc, suggesting its potential as a promising therapeutic option for IBD patients with insufficient response to TNF‐α inhibition. Key points: A bispecific nanobody (BsNb) was created to target TNF‐α and IL‐23p19, exhibiting high affinity and remarkable stability.BsNb‐Fc inhibited the release of cytokines in CD4+T cells during co‐culture experiments.BsNb‐Fc effectively alleviated colitis severity in mouse model with acute colitis induced by DSS or TNBS, outperforming the IFX&UST combination. [ABSTRACT FROM AUTHOR]

Despite the success of small interfering RNA (siRNA) in clinical settings and its potential value in human immunodeficiency virus (HIV) therapy, the rapid clearance and absence of precise delivery to target cells still hinder the therapeutic effect of siRNA. Herein, a new system, which can escape immune recognition, has HIV‐1 neutralizing capacity, and the ability to deliver siRNA specifically into HIV‐1‐infected cells, is constructed by functionalizing siRNA delivery lipid nanoparticles with the lymphocyte membrane and 12p1. The constructed system is shown to escape uptake by the mononuclear phagocyte system. The constructed system exhibits strong binding ability with gp120, thus displaying distinguished neutralizing breadth and potency. The constructed system neutralizes all tested HIV‐1 pseudotyped viruses with a geometric mean 80% inhibitory concentration (IC80) of 29.75 µg mL−1 and inhibits X4‐tropic HIV‐1 with an IC80 of 64.20 µg mL−1, and R5‐tropic HIV‐1 with an IC80 of 16.39 µg mL−1. The new system also specifically delivers siRNA into the cytoplasm of HIV‐1‐infected cells and exhibits evident gene silencing of tat and rev. Therefore, this new system can neutralize HIV‐1 and deliver siRNA selectively into HIV‐1‐infected cells and may be a promising therapeutic candidate for the precise therapy of HIV. [ABSTRACT FROM AUTHOR]

The human colon plays a critical role in fluid and salt absorption and harbors the largest immune compartment. There is a widespread need for in vitro models of human colon physiology with its innate immune system. A method is described to produce a cassette with a network of struts supporting a suspended, non‐chemically cross‐linked collagen hydrogel scaffold compatible with the co‐culture of primary gastrointestinal epithelium and migratory inflammatory cells. The epithelial monolayer cultured on the suspended collagen possesses a population of polarized and differentiated cells similar to that present in vivo. This epithelial layer displays proper barrier function with a transepithelial electrical resistance (TEER) ≥ 1,500 Ω cm2 and an apparent permeability ≤10−5 cm2 s−1. Immune cells plated on the basal face of the scaffold transmigrated over a period of 24 h to the epithelial layer in response to epithelial production of IL‐8 induced by luminal stimulation of Clostridium difficile Toxin A. These studies demonstrate that this in vitro platform possesses a functional primary colonic epithelial layer with an immune cell compartment capable of recruitment in response to pro‐inflammatory cues coming from the epithelium. [ABSTRACT FROM AUTHOR]

Both environmental and economic factors have driven the development of degradable resin for carbon fiber (CF) recycling under mild conditions. However, the vast majority of thermosetting materials are difficult to recycle. This paper presents bio‐based polyimine vitrimers to fully recycle the CF. The effect of vitrimers fine structures on the thermal, mechanical, solvent resistance, and degradation properties is carefully investigated. The tensile strength at break and Young's Modulus of pure polyimine vitrimers reach ≈80.3 MPa and 2.89 GPa. Importantly, the mechanical property of isophoronediamine‐based polyimine vitrimers/two‐layers CF exhibits a slightly inferior value to that of bisphenol A epoxy. Polyimine vitrimers are easily degradable under acid solution at 60 °C for 24 h. The surface morphology and chemical structure of CF are not changed after recycling. This work on mildly degradable polyimine vitrimers from vanillin and readily recycling of CF is desirable for the development of eco‐friendly CF composites and lignin functional materials. [ABSTRACT FROM AUTHOR]

This paper proposes a Gaussian Distance Intersection over Union (GDIoU) loss function‐based YOLOv4 deep learning network to solve the problem of slow speed and low accuracy insulator location in power facilities health inspection. In the scheme, A GDIoU loss function is designed to accelerate the convergence speed of the YOLOv4 deep learning network; at the same time, the GDIoU loss is added as one part of the network propagation loss, and the insulator's location accuracy is accordingly improved. Moreover, a re‐location scheme for tilt insulators correction is proposed to enhance the location accuracy of the insulators in different spatial angle states. Large amounts of field insulator images were gathered as training and testing samples to evaluate the performance of the proposed scheme. The experimental results have demonstrated that the GDIoU‐based YOLOv4 deep learning network combined with the tilt correction scheme can improve the insulator location speed by three times compared with the peer schemes, and the average precision is increased by 7.37% compared with the naive YOLOv4 network. The performance of the proposed scheme meets the requirement of online insulator location adequately. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the most common malignant tumor diagnosed in women. It is the second leading cause of cancer‐related death among women in the world. Aberrant expression of microRNAs (miRNAs) have been identified to be involved in the development and progression of breast cancer. The aim of this study was to investigate the function of miR‐223‐3p in breast cancer progression and metastasis. Methods: qRT‐PCR was used to analyze the expression levels of miR‐223‐3p in breast cancer tissues and cell lines. Wound healing and Matrigel assays were used to examine cell motility and invasiveness. FBXW7 3′‐UTR construct and luciferase reporter assays were performed for the target gene. Results: miR‐223‐3p was overexpressed in breast cancer tissue and cell lines. A high level of miR‐223‐3p was associated with poor prognosis in breast cancer patients. In addition, overexpressed miR‐223‐3p promoted the migration and invasion of breast cancer cells in vitro and in vivo. Mechanistically, we found that tumor suppressor gene FBXW7 is a target of miR‐223‐3p. Luciferase activity reporter assay indicated miR‐223‐3p could directly bind with the 3′‐UTR of FBXW7. miR‐223‐3p exhibited its oncogenic role partly by decreasing FBXW7 expression, and consequently promoted the invasion and metastasis of breast cancer cells. Conclusions: Our study revealed a physical and functional relationship among miR‐223‐3p and FBXW7. By negatively regulating FBXW7 expression, miR‐223‐3p exerts a tumor promotion role promoting cell invasion and metastasis in breast cancer. [ABSTRACT FROM AUTHOR]

We characterized horizontal hydraulic conductivity (K) of a fractured granitic aquifer using single‐ and cross‐hole hydraulic tests to evaluate "scale effect." For selected boreholes, K estimates were obtained using single‐hole FLUTe liner and slug tests. Several cross‐hole pumping tests were carried out at various durations. Drawdown responses were first interpreted using analytical well‐test solutions to obtain an effective horizontal conductivity (Keff) assuming a homogeneous and infinite aquifer. The same drawdowns were then numerically inverted using transient hydraulic tomography (THT) to delineate spatial distributions of K and storativity in the area encompassing the boreholes. Papadopulos (1965) and a nonlinear least squares minimization method produced a similar principal Keff direction that is consistent with the dominant fracture strike observed from outcrop and borehole televiewer data. However, principal direction and magnitude of this Keff depend on the pumping test duration and the number of monitoring boreholes used in the interpretation. As a group, K obtained from cross‐hole tests is larger than that obtained from single‐hole tests. However, because cross‐hole tests stressed the aquifer at both interwell and larger scales, Keff obtained from interpreting cross‐hole data is observed to decrease with pumping time, likely due to the dominance of less permeable fractures at larger scale. This lateral reduction of mean K is also revealed by THT as low K zones surrounding the test boreholes. Overall, K is found to increase from single‐hole to the interwell scale and then decrease at larger scale, exhibiting a non‐monotonic scale effect. Plain Language Summary: Knowledge of hydrological properties, particularly hydraulic conductivity (K), which controls groundwater flow in aquifers, is limited by the lack of subsurface data. Scientists have long observed that K estimated using field‐testing methods that stimulate different volumes of aquifers can vary by several orders of magnitude, which creates a conundrum for how groundwater flow should be analyzed. To determine if scale effect is apparent in a fractured granitic aquifer in the Laramie Range, Wyoming, testing methods that stressed the aquifer with different water volumes were employed. Our results indicate that K increases from single‐hole to the interwell scale but decreases at larger scale, with an overall nonmonotonic, albeit mild, scale effect. Compared to similar studies performed at other fractured rock sites, scale effect appears to be site‐specific and is not generally transferable across different aquifers. Key Points: In a granitic aquifer, K anisotropy identified from cross‐hole drawdown data is consistent with site geological dataAnalytical and hydraulic tomography interpretations of cross‐hole data suggest a reduced mean K at large scaleK increases from single‐hole to the interwell scale and then decreases at a larger scale, exhibiting a nonmonotonic scale effect [ABSTRACT FROM AUTHOR]

Background: Vascular smooth muscle cells (VSMC) switch to macrophage‐like cells after cholesterol loading, and this change may play an important role in atherogenesis. Muscleblind‐like splicing regulator 1 (MBNL1) is a well‐known splicing factor that has been implicated in many cellular processes. However, the role of MBNL1 in VSMC macrophage‐like transdifferentiation is largely unknown. In this study, we aim to characterize the role of MBNL1‐induced gene splicing during atherogenesis. Methods: The expression of MBNL1 and Abelson interactor 1 (Abi1) splice variants (Abi1‐e10 and Abi1‐Δe10) was compared between artery tissues from healthy donors and atherosclerosis patients. Regulatory mechanisms of MBNL1‐induced Abi1 gene splicing were studied, and the signal pathways mediated by Abi1 splice variants were investigated in VSMC. Results: Loss of MBNL1 was found in the macrophage‐like VSMC (VSMC‐M) in artery wall from atherosclerosis patients. In vitro and in vivo evidence confirmed that Abi1 is one of the MBNL1 target genes. Loss of MBNL1 significantly induces the Abi1‐Δe10 isoform expression. Compared to the known actin organization activities of the Abi1 gene, we discovered a novel action of Abi1‐Δe10, whereby Abi1‐Δe10 activates Rac1 independent of upstream stimulation and triggers the Rac1‐NOX1‐ROS pathway, which results in increased expression of transcription factor Kruppel‐like factor 4 (KLF4). While Abi1‐Δe10 inhibits contractile VSMC biomarkers expression and cell contraction, it stimulates VSMC proliferation, migration and macrophage‐like transdifferentiation. Conclusion: Loss‐of‐function of MBNL1 activates VSMC‐M transdifferentiation to promote atherogenesis through regulating Abi1 RNA splicing. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM)‐induced glucolipotoxicity is a factor strongly contributing to alveolar bone deficiency. Parathyroid hormone (PTH) has been identified as a main systemic mediator to balance physiological calcium in bone. This study aimed to uncover PTH's potential role in ameliorating the osteogenic capacity of human bone marrow mesenchymal stem cells (HBMSCs) against glucolipotoxicity. Optimal PTH concentrations and high glucose and palmitic acid (GP) were administered to cells, followed by alkaline phosphatase (ALP) staining and ALP activity assay. Quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) and Immunoblot were carried out for assessing mRNA and protein amounts, respectively. Cell counting kit‐8 (CCK‐8) and flow cytometry were performed for quantitating cell proliferation. Osteogenesis and oxidative stress were determined, and the involvement of mitogen‐activated protein kinase (MAPK) signaling was further verified. About 1–50 mmol/ml GP significantly inhibited the osteogenic differentiation of HBMSCs. 10−9 mol/L PTH was found to be the optimal concentration for HBMSC induction. PTH had no effects on HBMSC proliferation, with or without GP treatment. PTH reversed inadequate osteogenesis and excessive oxidative stress in GP‐treated HBMSCs. Mechanistically, PTH activated p38 MAPK signaling, while inhibiting p38 MAPK‐suppressed PTH's beneficial impacts on HBMSCs. Collectively, PTH promotes osteogenic differentiation in HBMSCs against glucolipotoxicity via p38 MAPK signaling. [ABSTRACT FROM AUTHOR]

Introduction: Cyclic adenosine monophosphate (AMP)‐responsive element‐binding protein H (CREBH), an endoplasmic reticulum‐anchored transcription factor essential for lipid metabolism and inflammation in nonalcoholic fatty liver disease (NAFLD), is covalently modified by N‐acetylglucosamine. Glycosylation is a ubiquitous type of protein involved in posttranslational modifications, and plays a critical role in various biological processes. However, the mechanism of glycosylated CREBH remains poorly understood in NAFLD. Methods: CREBH glycosylation mutants were obtained by site‐mutation methods. After transfection with plasmids, AML‐12, LO2, or HepG2 cells were treated with palmitic acid (PA) proteolysis, tunicamycin (Tm), or their combination. Glycosyltransferase V (GnT‐V) was used induce hyperglycosylation to further understand the effect of CREBH. In addition, glycosylation mutant mice and hyperglycosylated mice were generated by lentivirus injection to construct two kinds of NAFLD animal models. The expression of NAFLD‐related factors was detected to further verify the role of N‐linked glycosylation of CREBH in lipid and sterol metabolism, inflammation, and lipotoxicity. Results: N‐glycosylation enhanced the ability of CREBH to activate transcription and modulated the production of peroxisome proliferator‐activated receptor alpha (PPARα) and stearoyl‐CoA desaturase‐1 (SCD‐1) activity by affecting their promoter‐driven transcription activity and protein interactions, leading to reduce lipid deposition and attenuate lipotoxicity. Deglycosylation of CREBH induced by Tm could inhibit the proteolysis of CREBH induced by PA. The addition of unglycosylated CREBH to cells upregulates gene and protein expression of lipogenesis, lipotoxicity, and inflammation, and aggravates liver damage by preventing glycosylation in cells, as well as in mouse models of NAFLD. Furthermore, increased N‐glycosylation of CREBH, as achieved by overexpressing GnT‐V could significantly improve liver lesion caused by unglycosylation of CREBH. Conclusion: These findings have important implications for the role of CREBH N‐glycosylation in proteolytic activation, and they provide the first link between N‐glycosylation of CREBH, lipid metabolism, and lipotoxicity processes in the liver by modulating PPARα and SCD‐1. These results provide novel insights into the N‐glycosylation of CREBH as a therapeutic target for NAFLD. [ABSTRACT FROM AUTHOR]

Recent research has highlighted the importance of cultivating the ethical climate of a firm with implications for ethical decision making and consumer confidence. However, there are important lessons still to be gleaned from firms responsible for generating ethical failures. Based on a case study of the Sanlu melamine milk powder scandal in China, this article analyzes the key factors that have affected consumer confidence in Sanlu and highlights main reasons for Chinese consumers' continued distrust of state dairy enterprises. We explore the causes of business distrust in the Sanlu case from the perspective of Chinese product consumers. We further recommend solutions to repair a crisis of consumer confidence and trust in the domestic dairy industry by considering these stakeholders' perspectives. [ABSTRACT FROM AUTHOR]

Human adipose‐derived stem cells (HASCs) represent pluripotent cells capable of differentiating into the bone tissue. Meanwhile, human amnion‐derived mesenchymal stem cells (HAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. This work assessed the osteogenic effects exerted by HAMSCs on the potential of HASCs to form bone cells. Cell growth was evaluated flow‐cytometrically. Differentiation into osteoblasts and mineral formation were assessed by chromogenic alkaline phosphatase activity substrate assay and Alizarin red S staining. Adiponectin (APN), the adipocytokine secreted by adipocytes, was evaluated by enzyme‐linked immunosorbent assay. In this study, HAMSCs concentration‐dependently induced growth, osteoblastic differentiation, and APN excretion in HASCs. Mechanistically, immunofluorescence and immunoblot revealed HAMSCs promoted cytosolic translocation of leucine zipper motif (APPL1) from the nucleus and induced extracellular signaling‐regulated kinase 1/2 (ERK1/2) phosphorylation in HASCs. Furthermore, HAMSC effects were markedly blunted by pretreatment with APPL1 siRNA and U0126, an ERK1/2 signaling inhibitor with high selectivity. These results suggested that APN excretion is not suppressed by APPL1 knockdown in HASCs, but by ERK1/2 inhibition. These findings collectively indicate that HAMSCs induce the osteogenesis of HASCs by promoting APN excretion through APPL1‐ERK1/2 activation. [ABSTRACT FROM AUTHOR]

Our previous studies indicated that a coculture system containing human amnion‐derived mesenchymal stem cells (HAMSCs) and human bone marrow mesenchymal stem cells (HBMSCs) has the potential of application for bone regeneration. However, there is currently no enough comparative investigation between HAMSCs/HBMSCs transwell and mixed coculture systems. This study aimed to assess the phenotype and mechanisms regulated by indirect and direct coculture systems, respectively. Two in vitro models were employed with HAMSCs and HBMSCs at a ratio of 3:1, and then were analyzed by a series of processes, including flow cytometry, alkaline phosphatase (ALP) substrate assays, Alizarin red S staining, quantitative reverse transcription polymerase chain reaction (RT‐qPCR), and Western blot analysis. We found that cell proliferation, ALP activity, mineralized matrix formation, and osteoblast‐related mRNA expression were accelerated in transwell coculture system compared with mixed coculture system. Conditioned medium from transwell coculture system achieved an elevated level of vascular endothelial growth factor and induced more vascular structures in human umbilical vein endothelial cells than those of mixed coculture system. Moreover, we observed that transwell coculture system, promoted osteogenesis and angiogenesis by maintaining stemness through extracellular regulated protein kinases 1/2 (ERK1/2) mitogen‐activated protein kinase (MAPK) signaling pathway. U0126, a selective inhibitor of ERK1/2 MAPK signaling, significantly suppressed maintaining of the stemness‐based effects on transwell coculture system. Taken together, our results compared the merits of two different models and clarified the role of HAMSCs/HBMSCs transwell coculture system in the development of bone tissue engineering. © 2019 IUBMB Life, 2019 [ABSTRACT FROM AUTHOR]

Aim: This study examined the total peripheral vascular resistance (TPVR) and cardiac output changes due to the head-up tilt test (HUTT) in children with vasovagal syncope (VVS).Methods: From December 2013 to January 2016, we recruited 77 children diagnosed with VVS group at Peking University First Hospital, China, and 28 children without VVS provided the control group. Heart rate, blood pressure, TPVR, cardiac output and baroreflex sensitivity were monitored during the HUTT.Results: In the supine position, TPVR and baroreflex sensitivity were higher in the patients with VVS than the controls, but cardiac output did not differ between the two groups. There were obvious increases in the VVS patients from TPVR in the supine position to the prepositive response period (p < 0.05), then the positive response period (p < 0.01). However, we noted the opposite trend in cardiac output, from the supine position to the prepositive response period (p < 0.01) then the positive response period (p < 0.01).Conclusion: During HUTT, children with VVS demonstrated increases in TPVR but decreases in cardiac output, during the transition from the supine position to the positive response. This response might be involved in the pathogenesis of VVS. [ABSTRACT FROM AUTHOR]

Abstract: To add the growing literature on baseline of high‐risk human papillomavirus (HR‐HPV) genotype distribution in cervical intraepithelial neoplasia (CIN) before the widespread using of HPV vaccines in Chinese mainland and to improve risk stratification of HR‐HPV–positive women. Retrospectively, the data of age, cervical HPV genotypes, cytology, and pathology were collected from 1166 patients who received loop electrosurgical excision procedure (LEEP). HPV genotypes were analyzed with Flowcytometry Fluorescence Hybridization Method. And then HPV prevalence, HR‐HPV genotype distribution and the correlation of HR‐HPV genotypes with CIN2+ (CIN2 or severer) were analyzed. The role of multiple HR‐HPV types infection with or without HPV16/18 in the pathogenesis of CIN2+ was also analyzed. The 6 most common HR‐HPV genotypes were HPV16, 58, 52, 33, 18, and 31 in descending order. Compared to HR‐HPV–negative women, HPV16, 33 or 58 positive women had higher risk of CIN2+ (OR = 5.10, 95% CI = 2.68‐9.70; OR = 3.09, 95% CI = 1.39‐6.84; OR = 3.57, 95% CI = 1.85‐6.89, respectively). And women who were infected by multiple HR‐HPV types infection with HPV16/18 also had higher risk of CIN2+ (OR = 2.58, 95% CI = 1.35‐4.92). However, multiple HR‐HPV types infection without HPV16/18 did not increase the risk significantly (P = .08). Compare to bivalent Cervarix® and quadrivalent Gardasil®, HPV prophylactic vaccine targeting HPV31, 33, 52, and 58 might provide women more protection from HPV‐induced cervical cancer in China. The women who infected by HPV16, 33, 58, or multiple HR‐HPV types with HPV16/18 have higher risk of CIN2+ and need to be paid more attention in screening processes. And the role of multiple HR‐HPV types infection without HPV16/18 needs be further identified in more studies. [ABSTRACT FROM AUTHOR]

Gefitinib, an epidermal growth factor receptor–tyrosine kinase inhibitor (EGFR‐TKI), is an effective treatment for non‐small‐cell lung cancer (NSCLC) with EGFR activating mutations, but inevitably, the clinical efficacy is impeded by the emergence of acquired resistance. The tumor suppressor gene FBXW7 modulates chemosensitivity in various human cancers. However, its role in EGFR‐TKI therapy in NSCLC has not been well studied. Here, we demonstrate that the mice with deficient Fbxw7 have greater susceptibility to urethane‐induced lung tumor development. Through analysis of The Cancer Genome Atlas data, we show that deletion of FBXW7 occurs in 30.9% of lung adenocarcinomas and 63.5% of lung squamous cell carcinomas, which significantly leads to decrease in FBXW7 mRNA expression. The reduction in FBXW7 mRNA level is associated with poor overall survival in lung cancer patients. FBXW7 knockdown dramatically promotes epithelial–mesenchymal transition, migration, and invasion in NSCLC cells. Moreover, with silenced FBXW7, EGFR‐TKI‐sensitive cells become resistant to gefitinib, which is reversed by the mammalian target of rapamycin inhibitor, rapamycin. Furthermore, xenograft mouse model studies show that FBXW7 knockdown enhances tumorigenesis and resistance to gefitinib. Combination of gefitinib with rapamycin treatment suppresses tumor formation of gefitinib‐resistant (GR) FBXW7‐knockdown cells. In conclusion, our findings suggest that loss of FBXW7 promotes NSCLC progression as well as gefitinib resistance and combination of gefitinib and rapamycin may provide an effective therapy for GR NSCLC. [ABSTRACT FROM AUTHOR]

Abstract: The existence of Th17 cells and IL‐17 was recently shown in several types of infectious diseases, but their distribution and functions in cervical lesions with high‐risk human papillomavirus (HPV) infection have not been fully elucidated. In this study, the frequency of Th17 cells in peripheral blood samples obtained from 28 cervical squamous cell carcinoma patients, 26 CIN1 patients, 30 CIN2 patients, 29 CIN3 patients, 25 high‐risk HPV‐infected women with normal cervical cytology, and 30 healthy controls was determined by flow cytometry. Besides, the levels of IL‐17 in peripheral blood samples as well as in supernatant of cervical tissue homogenate were assessed by enzyme‐linked immunosorbent assay (ELISA) simultaneously. We found that during the disease progression of cervical lesions, the proportion of Th17 cells in the total CD4+ cells showed a gradually increased tendency compared with the controls (P < 0.05). Moreover, levels of IL‐17 in serum and supernatant of cervical tissue homogenate showed the same tendency as the proportion of Th17 cells (P < 0.05). When compared in pairs, the levels of IL‐17 in supernatant differed significantly among the study groups and the control group (P < 0.05), but no significant difference was observed in serum (P > 0.05). In conclusions, the results indicate that Th17 cells and IL‐17 may play a role of immune enhancement in the infection of high‐risk HPV especially in the cervical microenvironment, which contribute to the disease progression of its associated cervical lesions. [ABSTRACT FROM AUTHOR]

Oxygen deprivation induces a range of cellular adaptive responses that enable to drive cancer progression. Here, we report that lysine-specific demethylase 1 ( LSD1) upregulates hypoxia responses by demethylating RACK1 protein, a component of hypoxia-inducible factor ( HIF) ubiquitination machinery, and consequently suppressing the oxygen-independent degradation of HIF-1α. This ability of LSD1 is attenuated during prolonged hypoxia, with a decrease in the cellular level of flavin adenine dinucleotide ( FAD), a metabolic cofactor of LSD1, causing HIF-1α downregulation in later stages of hypoxia. Exogenously provided FAD restores HIF-1α stability, indicating a rate-limiting role for FAD in LSD1-mediated HIF-1α regulation. Transcriptomic analyses of patient tissues show that the HIF-1 signature is highly correlated with the expression of LSD1 target genes as well as the enzymes of FAD biosynthetic pathway in triple-negative breast cancers, reflecting the significance of FAD-dependent LSD1 activity in cancer progression. Together, our findings provide a new insight into HIF-mediated hypoxia response regulation by coupling the FAD dependence of LSD1 activity to the regulation of HIF-1α stability. [ABSTRACT FROM AUTHOR]

Colon cancer-associated transcript-1 (CCAT1) is a highly conserved long noncoding RNA that is deregulated in several cancers. However, its role in gastric carcinoma and its post-transcriptional regulation remain poorly understood. In this study, we provide the first evidence that CCAT1 regulates miR-490 in gastric cancer (GC) cells. Interestingly, miR-490 can also repress CCAT1 expression. CCAT1 expression was significantly upregulated, and miR-490 expression was downregulated in GC. The negative correlation between miR-490 and CCAT1 expression was observed in GC tissues. Importantly, CCAT1 contains a putative miR-490-binding site, and deletion of this binding site abolishes their miR-490 responsiveness. Post-transcriptional CCAT1 silencing by miR-490 significantly suppressed GC cell migration. Furthermore, miR-490 directly bound to the hnRNPA1 mRNA 3′-UTR to repress its translation. Inhibition of miR-490 rescued CCAT1 siRNA-mediated suppression of cell migration. hnRNPA1 expression was significantly upregulated in GC specimens, and there was a negative correlation between miR-490 and hnRNPA1 expression and also a positive correlation between hnRNAP1 expression level and CCAT1 level. Taken together, we show for the first time that the CCAT1/miR-490/hnRNPA1 axis promotes GC migration, and it may have a possible diagnostic and therapeutic potential in GC. © 2016 IUBMB Life, 68(3):201-210, 2016 [ABSTRACT FROM AUTHOR]

Background Cisplatin-based chemotherapy is the standard first-line treatment for non-small-cell lung cancers (NSCLCs); however, the long-term therapeutic effect is reduced by chemoresistance. Brain and reproductive organ-expressed (BRE) proteins are overexpressed in several cancers and have an anti-apoptotic function. However, their biological role in the development of the chemoresistant phenotype of human NSCLC remains unknown. We investigate the differential expression of the BRE gene in human lung adenocarcinoma cell lines A549 and the cisplatin-resistant variant A549/cisplatin (DDP), and the mechanisms of cisplatin-resistance induced by the BRE gene. Methods Cell counting kit-8 assay was employed to determine the sensitivity of A549 and A549/DDP cell lines to cisplatin. BRE expression was measured using quantitative real time-polymerase chain reaction and western blot analysis. The apoptosis rate of lung adenocarcinoma cells was determined by flow cytometry. Results BRE expression in A549 cells, derived from human lung cells, was markedly decreased compared with parental cisplatin-resistant A549/DDP cells at messenger ribonucleic acid and protein levels. BRE overexpression in A549 significantly decreased sensitivity to DDP by inhibiting cell apoptosis. Conversely, BRE knockdown in A549/DDP cells increased their chemosensitivity. Importantly, we demonstrate that BRE overexpression induces the expression of phosphoprotein kinase B (p-Akt) in lung cancer cells, while BRE silencing inhibits p-Akt expression. Furthermore, downregulation of p-Akt by LY294002 reversed the DDP resistance induced by BRE by increasing apoptosis. BRE enhances the DDP resistance of lung cancer cells through the Akt signaling pathway. Conclusion Our findings provide new insight into the mechanism of DDP resistance in NSCLC cells and suggest BRE as an attractive new target for NSCLC treatment. [ABSTRACT FROM AUTHOR]

Primary hyperparathyroidism ( PHPT) is a common endocrine neoplastic disorder caused by a failure of calcium sensing secondary to tumour development in one or more of the parathyroid glands. Parathyroid adenomas are comprised of distinct cellular subpopulations of variable clonal status that exhibit differing degrees of calcium responsiveness. To gain a clearer understanding of the relationship among cellular identity, tumour composition and clinical biochemistry in PHPT, we developed a novel single cell platform for quantitative evaluation of calcium sensing behaviour in freshly resected human parathyroid tumour cells. Live-cell intracellular calcium flux was visualized through Fluo-4- AM epifluorescence, followed by in situ immunofluorescence detection of the calcium sensing receptor ( CASR), a central component in the extracellular calcium signalling pathway. The reactivity of individual parathyroid tumour cells to extracellular calcium stimulus was highly variable, with discrete kinetic response patterns observed both between and among parathyroid tumour samples. CASR abundance was not an obligate determinant of calcium responsiveness. Calcium EC50 values from a series of parathyroid adenomas revealed that the tumours segregated into two distinct categories. One group manifested a mean EC50 of 2.40 mM (95% CI: 2.37-2.41), closely aligned to the established normal range. The second group was less responsive to calcium stimulus, with a mean EC50 of 3.61 mM (95% CI: 3.45-3.95). This binary distribution indicates the existence of a previously unappreciated biochemical sub-classification of PHPT tumours, possibly reflecting distinct etiological mechanisms. Recognition of quantitative differences in calcium sensing could have important implications for the clinical management of PHPT. [ABSTRACT FROM AUTHOR]

Background Anti-angiogenesis has been demonstrated to have a critical role in lung cancer pathogenesis. Here, we characterized the effect of the small-molecule angiogenesis inhibitor pazopanib on non-small cell lung cancer ( NSCLC) cells. Methods NSCLC cells were tested for viability and migration after incubation with varying concentrations of pazopanib. Further, the phosphorylation status of extracellular signal-regulated kinase, protein kinase B, and MEK were assessed in vitro. For in vivo testing, mice grafted with NSCLC cell lines L9981 and A549 were treated orally with pazopanib. Results Pazopanib inhibits signaling pathways in tumor cells, thus blocking NSCLC cell growth and migration in vitro and inducing tumor cell arrest at G0/ G1 phase. We show that pazopanib could inhibit tumor cell growth, decrease metastases, and prolong survival in two mouse xenograft models of human NSCLC. Conclusion These preclinical studies of pazopanib show the possibility of clinical application and, ultimately, improvement in patient outcome. [ABSTRACT FROM AUTHOR]

To assess the role of p27kip1 in regulating dental formation and alveolar bone development, we compared the teeth and mandible phenotypes of homozygous p27kip1-deficient (p27−/−) mice with their wild-type littermates at 2 weeks of age. At 2 weeks of age, dental mineral density, dental volume and dentin sialoprotein-immunopositive areas were increased significantly, whereas the predentin area : total dentin area and biglycan-immunopositive area : dentin area ratios were decreased significantly in p27−/− mice compared with their wild-type (WT) littermates. Mandible mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive areas, osteoblast number and activity and mRNA expression of Runt-related transcription factor 2 ( Runx2), alkaline phosphatase ( ALP), osteocalcin and bone morphogenetic protein ( bmp2) were all significantly increased in the mandibles, as was the number and surface of tartrate-resistant acid phosphatase-positive osteoclasts in the alveolar bone of p27−/− mice compared with their WT littermates. Furthermore, the percentage of proliferating cell nuclear antigen-positive cells in Hertwig's epithelial root sheath and protein expression of cyclin E and cyclin-dependent kinase 2 were increased significantly in p27−/− mice relative to their WT littermates. The results from this study indicate that p27 plays a negative regulatory role in dentin formation and alveolar bone development. [ABSTRACT FROM AUTHOR]

Under mild conditions, optically active 2,3-allenoates were synthesized from enantioenriched propargylic mesylates with moderate to excellent yields and high efficiency of chirality transfer by using palladium(0) bis(dibenzylideneacetone) (3 mol%) with ( S)-(−)-5,5′-bis(diphenylphosphino)-4,4′-bi-1,3-benzodioxole [( S)-SEGPHOS] (3 mol%) as the catalyst and diammonium hydrogen phosphate (1.1 equiv .) as the base. [ABSTRACT FROM AUTHOR]

Kallikrein (KLK) 5 and KLK7 were reported to be overexpressed in several cancers, but underexpressed in prostate and breast cancers. However, the expression levels of KLK5 and KLK7 in benign breast tissues and metastases, and the relationship between KLK5 and KLK7, have not been reported. In addition, the value of KLK5 and KLK7 in the diagnosis and prognosis prediction of breast cancer patients is far from clear. To further determine their role and clinical significance in breast cancer and to explore the relationship between KLK5 and KLK7, the mRNA levels of KLK5 and KLK7 in normal breast tissues, benign breast tissues, primary tumors, and lymph node metastases were detected by real-time reverse transcription–polymerase chain reaction and microarray. The relationship between KLK5 and KLK7 expression and clinicopathological parameters, and the correlation between the mRNA levels of KLK5 and KLK7 as well as the 5′-uncoding regions of KLK5 and KLK7 were analyzed. The mRNA levels of KLK5 and KLK7 were both downregulated in breast cancers relative to normal and benign tissues, and downregulated in metastases compared to primary cancers. Underexpression of KLK5 and KLK7 was correlated with postmenopausal status and positive estrogen receptor status. The mRNA levels of KLK5 and KLK7 were positively correlated in breast malignancies. Moreover, four homologous sequences and 10 transcription factors as potential regulators were found on the control regions of both KLK5 and KLK7. Thus, KLK5 and KLK7 were underexpressed in parallel, potentially with the same regulation pathways, in breast malignancies, which might contribute to the carcinogenesis and development of breast cancer. They are potential biomarkers for breast cancer. ( Cancer Sci 2009; 100: 601–607) [ABSTRACT FROM AUTHOR]

Superhydrophobic (SH) surfaces have held great promise during the last decade because of their diverse potential applications as self‐cleaning surfaces, in microfluidics, microarrays, etc. Recently, reactive SH surfaces combining their liquid‐repellency with the possibility for convenient postfunctionalization and patterning were introduced. However, current concepts for making reactive SH materials have very limited selection of "hydrophobic as well as reactive" groups. Here a novel reparable SH surface with hidden reactivity (SuSHiR) based on photodynamic properties of disulfides is reported. Reactive hydrophobic, SH, as well as superhydrophilic surfaces are fabricated using this method. The method allows the use of diverse end functionalities (reactive or nonreactive, hydrophobic, or hydrophilic), while keeping the same reactive disulfides "hidden" in the middle of the functional surface‐grafted chains. The photoreactivity of the disulfide bond allows for the functionalization and patterning of various molecules through UV irradiation. The obtained SuSHiR exhibits better stability compared to conventional reactive SH surfaces, and the reversibility of the disulfide–disulfide exchange reaction enables reversible patterning as well as photorestoration of damaged functionalities. A new strategy to fabricate superhydrophobic surfaces with hidden reactivity is presented. Reactive surfaces with various peripheral functional groups can be fabricated using this strategy, allowing for convenient postfunctionalization and patterning. The surface exhibits high stability and the ability to repair its functionality after damage. [ABSTRACT FROM AUTHOR]

A diagram is presented which explains the asymmetric synthesis of allenes at East China Normal University (ECNU).

The reaction allows to introduce various alkyl-, allyl- and benzyl substituents in the desired optically active allene derivatives. [ABSTRACT FROM AUTHOR]

To assess the role of p27(kip1) in regulating dental formation and alveolar bone development, we compared the teeth and mandible phenotypes of homozygous p27(kip1) -deficient (p27(-/-) ) mice with their wild-type littermates at 2 weeks of age. At 2 weeks of age, dental mineral density, dental volume and dentin sialoprotein-immunopositive areas were increased significantly, whereas the predentin area : total dentin area and biglycan-immunopositive area : dentin area ratios were decreased significantly in p27(-/-) mice compared with their wild-type (WT) littermates. Mandible mineral density, cortical thickness, alveolar bone volume, type I collagen and osterix-immunopositive areas, osteoblast number and activity and mRNA expression of Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin and bone morphogenetic protein (bmp2) were all significantly increased in the mandibles, as was the number and surface of tartrate-resistant acid phosphatase-positive osteoclasts in the alveolar bone of p27(-/-) mice compared with their WT littermates. Furthermore, the percentage of proliferating cell nuclear antigen-positive cells in Hertwig's epithelial root sheath and protein expression of cyclin E and cyclin-dependent kinase 2 were increased significantly in p27(-/-) mice relative to their WT littermates. The results from this study indicate that p27 plays a negative regulatory role in dentin formation and alveolar bone development., (© 2014 Wiley Publishing Asia Pty Ltd.)

In the title mol-ecule, C(15)H(12)BrClO(2), the two benzene rings form a dihedral angle of 69.30 (3)°. In the crystal structure, weak inter-molecular C-H⋯O hydrogen bonds link mol-ecules into chains propagating along the b axis.