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Abstract Background Peritoneal metastases frequently occur in epithelial ovarian cancer (EOC), resulting in poor prognosis and survival rates. Tumor-associated-macrophages (TAMs) massively infiltrate into ascites spheroids and are multi-polarized as protumoral M2-like phenotype, orchestrating the immunosuppression and promoting tumor progression. However, the impact of omental conditioned medium/ascites (OCM/AS) on TAM polarization and its function in tumor progression remains elusive. Methods The distribution and polarization of TAMs in primary and omental metastatic EOC patients’ tumors and ascites were examined by m-IHC, FACS analysis, and immunofluorescence. QPCR, immunofluorescence, FACS analysis, lipid staining assay, ROS assay, and Seahorse real-time cell metabolic assay characterized TAMs as being polarized in the ascites microenvironment. The oncogenic role of TAMs in tumor cells was demonstrated by co-cultured migration/invasion, proliferation, and spheroid formation assays. Mechanistic studies of the regulations of TAM polarization were performed by using RNA-Seq, GTPase pull-down, G-LISA activation assays, and other biochemical assays. A Yap1 macrophages (MФs) conditional knockout (cKO) mouse model demonstrated the roles of YAP1 in TAM polarization status and its pro-metastatic function. Finally, the anti-metastatic potential of targeting TAMs through restoring YAP1 by pharmacological agonist XMU MP1 was demonstrated in vitro and in vivo. Results Abundant polyunsaturated fatty acids (PUFAs) in OCM/AS suppressed RhoA-GTPase activities, which, in turn, downregulated nuclear YAP1 in MФs, leading to increased protumoral TAM polarization accompanied by elevated OXPHOS metabolism. Abolishment of YAP1 in MФs further confirmed that a higher M2/M1 ratio of TAM polarization could alleviate CD8+ T cell infiltration and cytotoxicity in vivo. Consistently, the loss of YAP1 has been observed in EOC metastatic tissues, suggesting its clinical relevance. On the contrary, restoration of YAP1 expression by pharmaceutical inhibition of MST1/2 induced conversion of M2-to-M1-like polarized MФs, elevating the infiltration of CD8+ T cells and attenuating tumor growth. Conclusion This study revealed that PUFAs-enriched OCM/AS of EOC promotes M2-like TAM polarization through RhoA-YAP1 inhibition, where YAP1 downregulation is required for accelerating protumoral M2-like TAM polarization, thereby causing immunosuppression and enhancing tumor progression. Conversion of M2-to-M1-like polarized MФs through Yap1 activation inhibits tumor progression and contributes to developing potential TAMs-targeted immunotherapies in combating EOC peritoneal metastases.

Non-Intrusive Load Monitoring (NILM) represents a technique for energy monitoring that is adept at discerning the quantity, type, and operational status of appliances through the analysis of aggregate power data within a specified area. This method facilitates the disaggregation of total energy consumption into the power usage of individual appliances. Recent advancements in deep learning have led to the application of various neural networks in the context of NILM. However, the presence of multiple appliances operating concurrently in various states, coupled with significant disparities in appliance switching behavior, poses challenges to the efficacy of disaggregation models. To mitigate these challenges, this study introduces a novel load-energy disaggregation algorithm, dubbed GTA-BT, which integrates Gated Recurrent Units (GRU) and a bidirectional Transformer architecture featuring time-aware self-attention. This approach aims to enhance disaggregation accuracy for appliances that exhibit multi-stage operational patterns and low utilization rates. The bidirectional Transformer is employed to capture local feature dependencies across different segments of the power consumption sequence, while the integration of GRU facilitates effective modeling of temporal sequences. In alignment with NILM task requirements, this model incorporates a device time state variable within the self-attention mechanism to augment focus on active appliances and extends the local receptive field through convolutional layer expansion. Moreover, a novel masking strategy, predicated on the operational state of devices, has been developed to heighten the model’s responsiveness to transitions in multi-stage appliance states. Comparative evaluations of this method against leading NILM algorithms using the REDD and UK-DALE datasets demonstrate its superior performance, evidenced by a 25% reduction in Mean Absolute Error (MAE) across all appliances, a 20% enhancement in F1-Score, and overall improved disaggregation capability.

Plastic products are widely used in various fields, and the discarded plastics in the environment can be degraded into microplastics (MPs) or even nanoplastics (NPs), which significantly increases the risk of organism exposure. MPs/NPs have been found in aquatic organisms, birds of prey, and even humans. The detection of plastic particles in biological samples is more complicated than that in environmental samples. Biological samples are mainly composed of various organic substances such as proteins and lipids, which makes the pretreatment process particularly critical. Effective detection and accurate quantification of MPs/NPs are crucial to health risk assessment. In this paper, the exposure levels and composition of MPs/NPs in different tissues and organs of the human body, aquatic organisms, and birds of prey were reviewed. The digestion of biological samples (acids, bases, enzymes, and hydrogen peroxide digestion protocols) and MPs/NPs identification methods (spectroscopy and chromatography) were compared and their advantages and disadvantages were assessed, providing a methodological basis for plastic exposure risk assessment and pollution control.

Taking inspiration from a popular online English test, this study first documents the development of an achievement test containing a newly developed C-test and pseudo-character test for beginner-level Chinese learners. Then, based on the test results collected from 53 university learners and using statistical tools, analyses were conducted on its content validity, construct validity, criterion-related validity, difficulty, discrimination power, and reliability. Results indicate that this new achievement test has relatively satisfactory reliability and validity, with only minor issues that need to be addressed in future studies. Situated in the context of language assessment, the study sheds light on the application of the C-test and a pseudo-character section in both face-to-face and at-distance Chinese as a foreign language (CFL) classrooms. Furthermore, the study also provides practical and applicable methods for CFL teachers to develop their own assessments.

Nanoparticles (NPs) can be extremely effective in the early diagnosis and treatment of cancer due to their properties. The nanotechnology industry is developing rapidly. The number of multifunctional NPs has increased in the market and hundreds of NPs are in various stages of preclinical and clinical development. Thus, the mechanism underlying the effects of NPs on biological systems has received much attention. After NPs enter the body, they interact with plasma proteins, tumour cell receptors, and small biological molecules. This interaction is closely related to the size, shape, chemical composition and surface modification properties of NPs. In this review, the effects of the size, shape, chemical composition and surface modification of NPs on the biological effects of NPs were summarised, including the mechanism through which NPs enter cells, the resulting oxidative stress response, and the interaction with proteins. This review of the biological effects of NPs can not only provide theoretical support for the preparation of safer and more efficient NPs but also lay the foundation for their clinical application.

Increasing amounts of nanoplastics (NPs) in the environment are a great threat to human health, causing intestinal inflammation when consumed through seafood and water. There is, however, still a lack of understanding of the immunomodulatory role of NPs in immune cells, especially the early signal events behind inflammation resulting from NPs ingestion. In this study, we explored the dynamic internalization of polystyrene NPs and their carboxy and amino-functionalized products (PS, PS-COOH and PS-NH2) followed by activation of ROS-MAPK/NF-κB signaling pathways in macrophage RAW 264.7. The inflammatory and cytotoxic potentials of NPs were evaluated by ELISA and apoptosis assays. Results showed that PS-COOH accumulated most in cells and induced more pronounced ROS and apoptosis than PS, PS-NH2 and PS-μm. PS-COOH and PS-NH2 showed stronger MAPK/NF-κB activation potential to at a low concentration of 10 μg/mL than unmodified PS, followed by production of IL-6 and TNF-α cytokines. Furthermore, PS-COOH induced MAPK/NF-κB activation and cytokine secretion could be inhibited by NAC, indicating that ROS was responsible for signal dysregulation and immunogenicity of PS-COOH, but not for PS-NH2. The results suggested that the MAPK and NF-κB pathways were involved in NPs-induced macrophage inflammation, which was influenced by surface functionalization of NPs, with carboxylated PS NPs exhibiting a greater pro-inflammatory and cytotoxic potential.

The combined use of ductile cast iron and alloy steel is beneficial, however, this technique causes some difficulties in welding due to the different properties of these two materials. In the present work, magnetically impelled arc butt (MIAB) welding a solid-state joining process, was employed to weld GGG40 ductile cast iron tube and an E355 + N alloy steel tube (each one had a thickness of 6 mm). The microstructure and mechanical properties of the resultant joints along different positions of the weld tube were systematically investigated. The heating during MIAB welding was non-uniform, causing significant changes in the microstructure, microhardness, and tensile stress of the welds. The maximum hardness of the welds (482 HV) was much higher than that of the base metal. The average (334.4 MPa) and maximum tensile strengths (382.4 MPa) of the welds were 83.6% and 95.6% of those of the base metal, respectively. These results show that MIAB is an effective method for welding ductile cast iron/alloy steel dissimilar materials.

Objective To explore the feasibility of picture naming training in improving naming ability of patients with semantic dementia (SD). Methods A total of 14 cases of semantic dementia whose the first symptom was semantic memory impairment were given picture naming training 30 min/time, twice a day, for 5 d from October 2018 to December 2020 at Xuanwu Hospital, Capital Medical University. One day before and one day after the end of training, Picture Naming Test and Boston Naming Test (BNT) were used to evaluate the naming ability. Results After training, Picture Naming Test score (65.79 ± 34.54 vs. 49.79 ± 30.85; t = ⁃ 3.297, P = 0.001) and BNT score [6.50 (4.75, 14.00) vs. 5.00 (3.00, 11.50); Z = ⁃ 2.007, P = 0.045] were higher than before training. Conclusions Picture naming training can effectively improve the naming ability of patients with semantic dementia.

Molecular diversity of proprioceptive neuron types (Ia, Ib and II PNs) is unclear. Here, the authors characterized the functional organization and development of eight subtypes of PNs in mice. Importantly, Ia subtypes are plastic, suggesting a role in adaptive proprioception during motor behavior.

This study aimed to investigate the prevalence of age-related macular degeneration (AMD) in patients with diabetes mellitus (DM) and diabetic retinopathy (DR) and analyze whether DR is a risk factor for AMD. This population-based epidemiological study included 14,440 people from the Kailuan Eye Study in 2016, of whom 1,618 were patients with type 2 DM aged over 50 years, and 409 had DM with DR. We analyzed whether there were differences in the prevalence of AMD between DM with DR and DM without DR, and conducted a hierarchical statistical analysis according to different stages of DR. Using variable regression analysis, we explored whether DR constituted a risk factor for AMD. In the DM population, the prevalence of wet AMD in patients with DM with and without DR was 0. 3 and 0.2%, respectively, with no significant difference (P = 0.607). Meanwhile, the prevalence of dry AMD in patients with DM with and without DR was 20.8 and 16.0%, respectively, with a significant difference. In the subgroup analysis of dry AMD, the prevalence of early, middle, and late dry AMD in DM with DR was 14.4, 5.9, and 0.5%, respectively. In DM without DR, the prevalence of early, middle, and late dry AMD was 10.5, 4.8, and 0.7%, respectively (P = 0.031). In the subgroup analysis of DR staging, statistical analysis could not be performed because of the limited number of patients with PDR. In the variable regression analysis of risk factors for dry AMD, after adjusting for age, sex, body mass index, hypertension, and dyslipidemia, DR constituted the risk factor for dry AMD. In conclusion, DM did not constitute a risk factor for AMD, and the prevalence of wet AMD and dry AMD in patients with DM and DR was higher than that in patients with DM without DR (among which dry AMD was statistically significant). Multivariate regression analysis confirmed that DR is an independent risk factor for dry AMD. Reasonable control of DM and slowing down the occurrence and development of DR may effectively reduce the prevalence of AMD in patients with DM.

Abstract Background During the course of gene transfection, the interaction kinetics between liposomes and DNA is speculated to play very important role for blood stability, cellular uptake, DNA release and finally transfection efficiency. Results As cationic peptide liposomes exhibited great gene transfer activities both in vitro and in vivo, two peptide lipids, containing a tri-ornithine head (LOrn3) and a mono-ornithine head (LOrn1), were chosen to further clarify the process of liposome-mediated gene delivery in this study. The results show that the electrostatically-driven binding between DNA and liposomes reached nearly 100% at equilibrium, and high affinity of LOrn3 to DNA led to fast binding rate between them. The binding process between LOrn3 and DNA conformed to the kinetics equation: y = 1.663631 × exp (− 0.003427x) + 6.278163. Compared to liposome LOrn1, the liposome LOrn3/DNA lipoplex exhibited a faster and more uniform uptake in HeLa cells, as LOrn3 with a tri-ornithine peptide headgroup had a stronger interaction with the negatively charged cell membrane than LOrn1. The efficient endosomal escape of DNA from LOrn3 lipoplex was facilitated by the acidity in late endosomes, resulting in broken carbamate bonds, as well as the “proton sponge effect” of the lipid. Conclusions The interaction kinetics is a key factor for DNA transfection efficiency. This work provided insights into peptide lipid-mediated DNA delivery that could guide the development of the next generation of delivery systems for gene therapeutics.

Objective(s): In this study, a stable bear bile-loaded pH sensitive in-situ eye drop gel was prepared for sustain delivery and enhanced therapeutic application. Materials and Methods: Bear bile-loaded in-situ ocular gels with different Carbopol/Hydroxypropyl methylcellulose (HPMC) ratios were prepared and their stability was tested in PBS at a series of pH at 40 °C. The morphology was observed by SEM examination and rheology was observed by Rheometer equipped with a 60-mm cone-plate at apex angle of 1°. Gel erosion and release kinetics of Tauroursodeoxycholic acid (TUDCA) was determined by HPLC. While, the in vivo dwelling time was obtained after administering the fluorescent-loaded gel in ocular disease-free New Zealand rabbits. Finally, biocompatibility and toxicity was observed by irritation test and H&E staining of eye-ball tissues, respectively. Results: The bear bile-loaded in-situ ocular gel showed excellent stability at different pH (pH 5.0, 5.5, 6.0, 6.5, 7.0 and 8.0) up to 5 days, and bear bile extract significantly attenuated the gelling ability of the in-situ gel. The viscosity of in-situ gels formulation was decreased with increase in shear rate (0.01 to 100 s-1), and morphological examination of freeze-dried preparation showed three-dimensional reticular structure at physiological pH. The in-situ ocular gel exhibited promising sustained drug release up to 160 min in vitro, and showed prolonged retention time up to 3-folds in vivo. Finally, the biocompability data confirmed that the formulation did not induce any toxic effects and was completely compatible with eye tissues.Conclusion: pH sensitive in-situ ocular gel provides new research opportunities to efficiently treat eye diseases.

In order to improve the effect of rural garden landscape design, this paper combines virtual simulation technology to design rural garden landscape and evaluates its design effect. Moreover, this paper proposes an optical modulation system for the application of virtual simulation in rural garden landscape design. In addition, before the target is modulated, this paper converts the two-dimensional image on the detector target surface into a one-dimensional stretched modulation image so that the beam emitted by each object point is stretched and flattened on the detector target surface. Finally, this paper explores the influence of lens spacing and field of view on the modulation image of the target surface and the characteristics of projected intensity attenuation after modulation and designs a modulation model that optimizes attenuation. The research results show that the garden landscape design based on virtual reality technology proposed in this paper has a good effect and is of great significance to the effect of rural garden landscape design.

Background: Pancreatic cancer is a malignancy with poor prognosis. Importin 7 (IPO7) is a soluble nuclear transport factor, which has been linked to the pathogenesis of several human diseases. However, its role and underlying mechanism in pancreatic cancer are still obscure.Methods: Immunohistochemical staining and quantitative real-time polymerase chain reaction (qPCR) were performed to determine IPO7 expression in pancreatic cancer tissues and adjacent tissues. Western blot was used to measure IPO7 expression at the protein level in cell lines. Cell Counting Kit-8 (CCK-8), 5-bromo-2′-deoxyuridine (BrdU), flow cytometry, and Transwell assays were employed to explore the biological functions of IPO7. Subcutaneous xenograft transplanted tumor model and caudal vein injection model in mice were also established to validate the oncogenic role of IPO7. Western blot and qPCR were utilized to detect the regulatory function of IPO7 on p53 and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), respectively. Interaction between MALAT1 and miR-129-5p and interaction between miR-129-5p and IPO7 were verified by bioinformatics prediction, qPCR, dual-luciferase reporter gene experiment, RNA immunoprecipitation (RIP), and pull-down assay.Results: Upregulation of IPO7 in pancreatic cancer tissues was associated with adverse prognosis of the patients with pancreatic cancer. Knocking down IPO7 remarkably suppressed cancer cell proliferation and metastasis, while it promoted apoptosis. Overexpression of IPO7 facilitated the malignant phenotypes of pancreatic cancer cells. Mechanistically, IPO7 could repress the expression of p53 and induce the expression of MALAT1 but reduce miR-129-5p expression. Furthermore, miR-129-5p was identified as a posttranscriptional regulator for IPO7, and its inhibition led to IPO7 overexpression in pancreatic cancer cells.Conclusion: IPO7 is a novel oncogene for pancreatic cancer, and IPO7/p53/MALAT1/miR-129-5p positive feedback loop facilitates the progression of this deadly disease.

Background: In the literature, obesity is discussed as a determinant of high oxidative stress (OS). Hence, prevention or reduction of obesity could prevent high OS and subsequently serve as a target for “healthy aging.” Methods: Diacron’s reactive oxygen metabolites test (D-ROM) and total thiol levels (TTL), a marker of antioxidant defense capacity, were measured in 1,734 participants of a population-based cohort study of older adults (age range: 57–83 years) at 2 time points 3 years apart. The longitudinal associations of body mass index, waist-to-hip ratio, and waist circumference with D-ROM and TTL were assessed with multivariable adjusted generalized linear models. Dose-response analyses were conducted with restricted cubic splines. Results: D-ROM was not significantly associated with any of the weight measures. On the contrary, TTL showed statistically significant, inverse linear associations with all weight measures. Conclusion: A healthy body weight seems to be highly relevant for the antioxidative defense capacity of human beings. In contrast, D-ROM levels were independent of the study participant’s weight. Clinical trials are needed to corroborate if loss of weight by obese individuals can effectively increase TTL and subsequently also life expectancy.

Hydrogels are basic materials widely used in various fields, especially in biological engineering and medical imaging. Hydrogels consist of a hydrophilic three-dimensional polymer network that rapidly expands in water and can hold a large volume of water in its swelling state without dissolving. These characteristics have rendered hydrogels the material of choice in drug delivery applications. In particular, carboxymethyl cellulose (CMC) hydrogels have attracted considerable research attention for the development of safe drug delivery carriers because of their non-toxicity, good biodegradability, good biocompatibility and low immunogenicity. Aiming to inspire future research in this field, this review focuses on the current preparation methods and applications of CMC gels and highlights future lines of research for the further development of diverse applications.

The unique bactericidal mechanism of metal nanoparticles (MNPs) is considered to be an effective strategy to deal with antibiotic resistance, but the oxidative stress damage caused by excessive accumulation of MNPs to normal cells cannot be ignored. Achieving on-demand release of nano-drugs in specific infection environments is highly attractive. Herein, we constructed a “core-shell” nanogel (G@CuS) based on a copper sulfide (CuS) antimicrobial agent and gelatin for targeted drug release and bacterial clearance in a gelatinase infected microenvironment. G@CuS produced heat and reactive oxygen species (ROS) under the irradiation of a laser, which together with the released Cu2+ cause irreversible and efficient physical damage to the bacteria. Moreover, the encapsulation of gelatin not only limits the biotoxicity of CuS nanodots (NDs), but also effectively promotes the proliferation of mammalian cells. Under the synergy of multiple mechanisms, G@CuS eradicated the colonized bacteria in the wound of mice infected with Staphylococcus aureus (S. aureus) and accelerated wound healing. The proposed application strategy of nanogel is expected to provide a new idea for clinical transformation.

Abstract Background Reactive oxygen species may be involved in epigenetic gene activation or silencing. We aimed to identify CpG sites, at which DNA methylation is related to urinary 8-isoprostane levels (biomarker of lipid peroxidation) and cancer or mortality outcomes. This investigation was based on a German, population-based cohort with linkage to cancer and mortality registry data (2000–2016). Results Blood DNA methylation in promoter regions of 519 genes, known to be involved in pathways from oxidative stress (OS) to cancer, was obtained at the cohort's baseline examination. Inverse associations of DNA methylation at cg25365794 (ALOXE3) and cg08862778 (MTOR) with 8-isoprostane levels were observed in a derivation set (n = 1000) and validated in two independent subsets of the cohort (n = 548 and n = 741). Multivariate regression models were used to evaluate the associations of DNA methylation at the two CpG sites with lung, colorectal, prostate, breast, and overall cancer incidence as well as CVD, cancer, and all-cause mortality. DNA methylation at cg25365794 (ALOXE3) was inversely associated with lung and prostate cancer incidence. DNA methylation at cg08862778 (MTOR) was associated with a 43% lower breast cancer incidence in the top vs. bottom tertile. Conclusion The finding for ALOXE3 may not be causal. As ALOXE3 is mainly expressed in skin tissue, the observed association might reflect the fact that both DNA methylation at the ALOXE3 gene and urinary 8-isoprostane concentrations depend on the level of OS in tissues. Contrarily, the finding for the MTOR gene and breast cancer is biologically plausible because the MTOR protein plays an important role in PI3K/Akt signaling, which is a pathway related to cancer development and cell senescence.

In order to solve the considerable issues of air pollution, climate warming and fossil energy shortage, many governments around the world have formulated policies to encourage the development of electric vehicles over the past decade. This paper proposes a three-level dual-active-bridge (DAB) converter with blocking capacitors for bidirectional electric vehicle charger. In the proposed three-level DAB converter, two blocking capacitors are placed in series with the two windings of the transformer, respectively. Both of the two three-level bridges can operate in four modes, and generate square waves with four kinds of amplitude. Therefore, the proposed three-level DAB converter can adapt to the wide voltage range of electric vehicle. A working mode selection algorithm is developed to minimize the transformer RMS current of the three-level DAB converter. The optimal working mode can be selected in real time according to the voltage ratio and the active power. Finally, experimental results are presented to verify the feasibility and the advantage of the proposed three-level DAB converter.

Objective: The aim of this study is to describe the technique and to evaluate the outcome of single-incision laparoscopic (SILC) approach for linea alba hernia in children. Materials and Methods: A 2 cm vertical umbilical incision was made and stretched horizontally. A 5-mm trocar was inserted through middle port for the telescope. Another extra-long 5-mm 30° trocar was inserted through the lateral port, 5 mm beside the middle port. The extraperitoneal fat was removed, and the defect of linea alba was repaired after hernial sac was excised. The peritoneum was reconstructed with interrupted suture. Results: From May 2014 to May 2015, eight children with linea alba hernia underwent SILC. Pre-operative abdominal ultrasound showed the average diameter of hernia ring was 3.2 ± 0.7 cm. Mean operation time was 32.5 min (range = 30–45 min). Oral intake was resumed during anaesthesia recovery period. All could endure pain and discharge on the post-operative 12 h. There was no post-operative wound infection. The follow-up period was 1–12 months, no recurrence and other complications occurred. Conclusions: SILC approach for linea alba hernia is a safe and effective, minimally invasive new technology. The linea alba hernia could be repaired with a cosmetic outcome.

ObjectiveOur objective is to identify the potential factors associated with serum Diacron’s reactive oxygen metabolites test (D-ROM) levels of patients with type 2 diabetes mellitus (T2DM) by conducting cross-sectional and longitudinal analyses in two large cohorts and further strengthening these results by performing a meta-analysis.MethodsSerum D-ROM concentrations were measured in 1045 and 1101 patients with T2DM from two independent cohort studies from Germany at baseline and repeatedly 3–4 years later. The cross-sectional and longitudinal associations of various potential determinants with D-ROM levels were assessed with a backwards selection algorithm in multivariable adjusted models.ResultsIn the meta-analysis of the cross-sectional analysis, female sex, low education, obesity, smoking, high total cholesterol, hemoglobin A1c ≥7%, no diabetes medication, a history of myocardial infarction, heart failure, a history of cancer and C reactive protein levels (CRP) >3 mg/L were statistically significantly associated with increased D-ROM levels in patients with T2DM. The meta-analysis of the longitudinal analysis revealed that old age, female sex, obesity, smoking, physical inactivity, high alcohol consumption, ≥5 years since diabetes diagnosis and CRP levels between 3 mg/L and 10 mg/L were statistically significantly associated with D-ROM levels measured 3–4 years later.Conclusions (validity, limitations and clinical applicability)This comprehensive analysis confirmed that several modifiable risk factors are being associated with oxidative stress in patients with T2DM within an observational study design. We discuss potential prevention measures against these risk factors that might help to reduce oxidative stress and to prevent some cases of premature mortality in patients with T2DM.

Abstract Background This study aimed to explore hyper-O-linked N-acetylglucosaminylation (O-GlcNAcylation) with an elevation of the expression of O-linked-β-N-acetylglucosamine transferase (OGT) in human bladder cancer. Methods Immunohistochemical staining for OGT and O-GlcNAcylation was performed in 20 paired human bladder cancer and adjacent normal tissues, as well as in human bladder cancer tissue microarrays (N = 169). The expression level of OGT and O-GlcNAcylation in cell lines were detected using the Western blot analysis. The effects of O-GlcNAcylation on the cell proliferation of bladder cancer were detected using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and clone formation assays. Cell apoptosis and cell cycle analysis were detected using flow cytometry. The autophagy of bladder cancer cells was investigated using the Western blot analysis, and GFP–LC3 plasmid was used to detect the autophagic flux. MTT assay was performed to detect the sensitivity of bladder cancer cells to cisplatin after OGT knockdown. Results The expression of OGT and the O-GlcNAcylation were upregulated in bladder cancer tissues and cell lines. O-GlcNAcylation and OGT were observed in nucleus and cytoplasm and found to be higher in muscle-invasive bladder cancer (MIBC) than in non-muscle-invasive bladder cancer (NMIBC). Reducing hyper-O-GlcNAcylation by OGT knockdown inhibited the proliferation of bladder cancer cells in vitro and xenograft tumor growth in vivo, triggered apoptosis, as well as led to cell cycle arrest. It also increased autophagy in bladder cancer cells. This study demonstrated increased autophagy pro-survival, but not pro-death. Reducing hyper-O-GlcNAcylation by OGT knockdown facilitated the chemosensitivity of bladder cancer cells to cis-platinum. Conclusions The data indicated that hyper-O-GlcNAcylation enhanced oncogenic phenotypes and was involved in DNA damage response in bladder cancer.

Abstract Background Ag2S has the characteristics of conventional quantum dot such as broad excitation spectrum, narrow emission spectrum, long fluorescence lifetime, strong anti-bleaching ability, and other optical properties. Moreover, since its fluorescence emission is located in the NIR-II region, has stronger penetrating ability for tissue. Ag2S quantum dot has strong absorption during the visible and NIR regions, it has good photothermal and photoacoustic response under certain wavelength excitation. Results 200 nm aqueous probe Ag2S@DSPE-PEG2000-FA (Ag2S@DP-FA) with good dispersibility and stability was prepared by coating hydrophobic Ag2S with the mixture of folic acid (FA) modified DSPE-PEG2000 (DP) and other polymers, it was found the probe had good fluorescent, photoacoustic and photothermal responses, and a low cell cytotoxicity at 50 μg/mL Ag concentration. Blood biochemical analysis, liver enzyme and tissue histopathological test showed that no significant influence was observed on blood and organs within 15 days after injection of the probe. In vivo and in vitro fluorescence and photoacoustic imaging of the probe further demonstrated that the Ag2S@DP-FA probe had good active targeting ability for tumor. In vivo and in vitro photothermal therapy experiments confirmed that the probe also had good ability of killing tumor by photothermal. Conclusions Ag2S@DP-FA was a safe, integrated diagnosis and treatment probe with multi-mode imaging, photothermal therapy and active targeting ability, which had a great application prospect in the early diagnosis and treatment of tumor.

Abstract Background N-myc (and STAT) interactor (NMI) plays vital roles in tumor growth, progression, and metastasis. In this study, we identified NMI as a potential tumor suppressor in lung cancer and explored its molecular mechanism involved in lung cancer progression. Methods Human lung cancer cell lines and a mouse xenograft model was used to study the effect of NMI on tumor growth. The expression of NMI, COX-2 and relevant signaling proteins were examined by Western blot. Tissue microarray immunohistochemical analysis was performed to assess the correlation between NMI and COX-2 expression in lung cancer patients. Results NMI was highly expressed in normal lung cells and tissues, but lowly expressed in lung cancer cells and tissues. Overexpression of NMI induced apoptosis, suppressed lung cancer cell growth and migration, which were mediated by up-regulation of the cleaved caspase-3/9 and down-regulation of phosphorylated PI3K/AKT, MMP2/MMP9, β-cadherin, and COX-2/PGE2. In contrast, knockdown of NMI promoted lung cancer cell colony formation and migration, which were correlated with the increased expression of phosphorylated PI3K/AKT, MMP2/MMP9, β-cadherin and COX-2/PGE2. Further study showed that NMI suppressed COX-2 expression through inhibition of the p50/p65 NF-κB acetylation mediated by p300. The xenograft lung cancer mouse models also confirmed the NMI-mediated suppression of tumor growth by inhibiting COX-2 signaling. Moreover, tissue microarray immunohistochemical analysis of lung adenocarcinomas also demonstrated a negative correlation between NMI and COX-2 expression. Kaplan-Meier analysis indicated that the patients with high level of NMI had a significantly better prognosis. Conclusions Our study showed that NMI suppressed tumor growth by inhibiting PI3K/AKT, MMP2/MMP9, COX-2/PGE2 signaling pathways and p300-mediated NF-κB acetylation, and predicted a favorable prognosis in human lung adenocarcinomas, suggesting that NMI was a potential tumor suppressor in lung cancer.

The 14-pods Cu7S4 hollow microcages wholly exposed with nanotwinned building blocks were successfully prepared by an ethanol-assisted sacrificial Cu2O template approach. Its photocatalytic activity for the degradation of methylene blue (MB) was determined. The results suggest that the Cu7S4 microcages with nanotwinned building blocks possess higher catalytic activity than the Cu7S4 microcages without the nanotwinned structures, suggesting that the special nanotwinned components can improve the catalytic performance of the multipod framework. Further investigate reveals that the nanotwins inside the Cu7S4 microcages can facilite the transport of free charges, decrease the recombination of photoinduced electrons and holes, and elongate the lifetime of the electron–hole pairs. Our work will provide powerful evidence that the nanotwinned building blocks of the synthesized Cu7S4 microcages play a crucial role for the high catalytic activity.

A previous study by our group found that inhibition of nischarin promotes neurite outgrowth and neuronal regeneration in Neuro-2a cells and primary cortical neurons. In recent years, more and more studies have shown that nanomaterials have good prospects in treatment of spinal cord injury. We proposed that small interfering RNA targeting nischarin (Nis-siRNA) delivered by polyethyleneimine-alginate (PEI-ALG) nanoparticles promoted motor function recovery in rats with spinal cord injury. Direct microinjection of 5 μL PEI-ALG/Nis-siRNA into the spinal cord lesion area of spinal cord injury rats was performed. From day 7 after surgery, Basso, Beattie and Bresnahan score was significantly higher in rats from the PEI-ALG/Nis-siRNA group compared with the spinal cord injury group and PEI-ALG/Control-siRNA group. On day 21 after injection, hematoxylin-eosin staining showed that the necrotic area was reduced in the PEI-ALG/Nis-siRNA group. Immunohistochemistry and western blot assay results confirmed successful inhibition of nischarin expression and increased protein expression of growth-associated protein-43 in the PEI-ALG/Nis-siRNA group. These findings suggest that a complex of PEI-ALG nanoparticles and Nis-siRNA effectively suppresses nischarin expression, induces expression of growth-associated protein-43, and accelerates motor function recovery after spinal cord injury.

Background Almost 39% of US construction workers (CWs) smoke. Hispanic/Latino CWs represent 23% of the US CWs, and they have lower access to cessation services mainly due to their transient and lack of culturally-sensitive intervention. One potential strategy is the provision of a work-based culturally-tailored smoking cessation services. This study aimed to gain insight into the construction site management's current practices related to anti-smoking policies and smoking cessation services. It also sought views on “ideal” workplace cessation services, implementation commitment, and anticipated challenges. Methods We conducted semi-structured, 45-minute interviews with 25 key personnel at five construction sites in South Florida. Interviews were recorded, transcribed and analyzed thematically using Braun's six phases approach. Results Participants were all males and represented a range of professions including construction executive, senior/safety manager, and contractor/subcontractor. Smoking was prohibited only inside the construction buildings and participants perceived most workers as adherent to the policy. Although employers were concerned about the effects of smoking on productivity loss, safety, and insurance costs, nothing was provided to help smokers quit smoking. Only one-quarter of participants believed that worksite management would support implementing smoking cessation services. The majority considered distributing self-help materials with free medications as the most appropriate service and recommended providing the service in Spanish during lunch/breakfast breaks. Challenges to integrate services were smokers' low interest in quitting, time restriction, and cost. Recommendations to support implementing services were local or state government mandate, obtaining company approval, involving safety managers and subcontractors in the process, and providing services during employment orientation training. Conclusions Tailoring sustainable onsite smoking cessation services in the construction sector presents unique, but not insurmountable challenges. Involvement of key stakeholder groups including policymakers as well as construction management, supervisors, and subcontractors is necessary to support integrating smoking cessation services in this setting.

Based on biomimetic technology, wellbore strengthener GBFS-1 and shale inhibitor YZFS-1 were synthesized imitating the mussel protein which has super adhesion. A new drilling fluid system centering on the two biomimetic agents was designed and prepared in order to enhance the strength of shale rocks near wellbore and maintain wellbore stability. Various inhibition evaluation tests show that YZFS-1 can strongly inhibit clay hydrated swelling and the resulting shale dispersion, due to the adsorption and self-polymerization of YZFS-1 molecules in the interlayer of clay. Besides the ability of controlling fluid loss, GBFS-1 can also adhere to shale rock, produce dense and water impermeable biomimetic shell that has relative strong cohesion strength after spontaneous cure. The shear strength tests show that the shear strength of two shale pieces glued together by the biomimetic shell in aqueous environment is obviously stronger than glued by several commonly-used binders. Through compatibility evaluation and dosage optimization of the additives, the formula of biomimetic drilling fluid was established, and its performance was evaluated and compared with another anti-caving drilling fluid. The results show the biomimetic drilling fluid is better in all basic performances than the anti-caving drilling fluid on the whole, and can effectively inhibit shale swelling and dispersion. Key words: wellbore stability, biomimetic technology, wellbore strengthener, shale inhibitor, drilling fluid