Search

Coaxial peaking capacitor is a key component in high-altitude electromagnetic pulse (EMP) simulators with fast front pulse output. It poses significant technical and engineering challenges in limiting radiation field amplitude and test space. This paper presents the design and testing of a 180 pF, 3 MV coaxial peaking capacitor with improved insulation performance. In the insulation design, the length of the dielectric film is extended to reduce the background electric field on the flashover path. The electric field threshold obtained from image diagnosis is used as a reference. During capacitor testing, the insulation characteristics are diagnosed using both direct and indirect methods. The voltage measured by a D-dot probe, the output waveform of the Marx generator in the primary source, and the radiation field waveform are analyzed to understand the flashover characteristics of the capacitor and to improve the reliability of the test results. The experimental results demonstrate that the peaking capacitor can operate stably at 3.0 MV. If flashover occurring on the dropping edge of the pulse is permitted, the operating voltage can be greater than 3.7 MV without significantly affecting the radiation field waveform. The analysis on the surface flashover morphology of the peaking capacitor reveals that the flashover mainly occurs at the dropping edge of the capacitor's waveform, indicating that the damage to the film is not serious. This research significantly increases the working voltage of coaxial peaking capacitors and contributes to the development of high-altitude EMP simulation technology. [ABSTRACT FROM AUTHOR]

The combined use of walnut meal peptides and ellagic acid demonstrated synergistic anti-inflammatory properties, which could be enhanced through encapsulation into nanoparticles to enhance their bioavailability. However, the specific anti-inflammatory mechanism of these nanoparticles remains unclear. Therefore, this study aimed to investigate the anti-inflammatory mechanism of nanoparticles composed of walnut meal peptides and ellagic acid using ELISA, Western Blot, and qRT-PCR techniques. The ELISA results revealed a significantly reduction in the secretion of nitric oxide and inflammatory factors upon treatment with the nanoparticles. Besides, the findings from the qRT-PCR analysis demonstrated a significant reduction in the mRNA expression of inducible nitric oxide synthase and inflammatory factors in RAW264.7 cells following treatment with the nanoparticles. Additionally, the Western Blot results indicated that the nanoparticles exerted inhibitory effects on the upstream signaling pathway of nuclear factor kappa-B and modulated the mitogen-activated protein kinases signaling pathway, resulting in the suppression of inflammatory factor expression. This study contributes to the foundational understanding of the potential application of these nanoparticles as anti-inflammatory agents in the context of health food. [ABSTRACT FROM AUTHOR]

As one economically important fish in the southeastern Himalayas, the giant devil catfish (Bagarius yarrelli) has been known for its extraordinarily large body size. It can grow up to 2 m, whereas the non- Bagarius sisorids only reach 10–30 cm. Another outstanding characteristic of Bagarius species is the salmonids-like reddish flesh color. Both body size and flesh color are interesting questions in science and also valuable features in aquaculture that worth of deep investigations. Bagarius species therefore are ideal materials for studying body size evolution and color depositions in fish muscles, and also potential organisms for extensive utilization in Asian freshwater aquaculture. In a combination of Illumina and PacBio sequencing technologies, we de novo assembled a 571-Mb genome for the giant devil catfish from a total of 153.4-Gb clean reads. The scaffold and contig N50 values are 3.1 and 1.6 Mb, respectively. This genome assembly was evaluated with 93.4% of Benchmarking Universal Single-Copy Orthologs completeness, 98% of transcripts coverage, and highly homologous with a chromosome-level-based genome of channel catfish (Ictalurus punctatus). We detected that 35.26% of the genome assembly is composed of repetitive elements. Employing homology, de novo, and transcriptome-based annotations, we annotated a total of 19,027 protein-coding genes for further use. In summary, we generated the first high-quality genome assembly of the giant devil catfish, which provides an important genomic resource for its future studies such as the body size and flesh color issues, and also for facilitating the conservation and utilization of this valuable catfish. [ABSTRACT FROM AUTHOR]

Background: DTL has been found to be related with multiple cancers. However, comprehensive analyses, which identify the prediction value of DTL in diagnosis, prognosis, immune infiltration and treatment, have rarely been reported so far. Methods: Combined with the data online databases, the gene expression, gene mutation, function enrichment and the correlations with the immunity status and clinical indexes of DTL were analyzed. Expression of DTL and the degree of immune cell infiltration were examined by immunofluorescence (IF) and immunohistochemistry (IHC) and analyzed by statistical analysis. Furthermore, the influences of DTL on the cell cycle, cell proliferation and apoptosis were detected by live cell imaging, IF and flow cytometric (FC) analysis. Genomic stability assays were conducted by chromosome slide preparation. Results: DTL was widely expressed in various cells and tissues, while it was overexpressed in tumor tissues except acute myeloid leukemia (LAML). Pan-cancer bioinformatics analysis showed that the expression of DTL was correlated with the prognosis, immunotherapy, and clinical indexes in various cancers. In addition, gene set enrichment analysis (GSEA) uncovered that DTL was enriched in oocyte meiosis, pyrimidine metabolism, the cell cycle, the G2M checkpoint, mTORC1 signaling and E2F targets. Furthermore, the overexpression of DTL, and its association with immune cell infiltration and clinical indexes in liver hepatocellular carcinoma (LIHC), bladder urothelial carcinoma (BLCA) and stomach adenocarcinoma (STAD) were verified in our study. It was also verified that overexpression of DTL could regulate the cell cycle, promote cell proliferation and cause genomic instability in cultured cells, which may be the reason why DTL plays a role in the occurrence, progression and treatment of cancer. Conclusions: Collectively, this study suggested that DTL is of clinical value in the diagnosis, prognosis and treatment of various cancers, and may be a potential biomarker in certain cancers. [ABSTRACT FROM AUTHOR]

An electrostatic calibration technique is highly flexible in producing a wide range of force and it is widely applied for nano-newton to micro-newton thrust stand calibration. This paper proposes a novel method for electrostatic comb implementation and related experiments have been carried out. Based on the printed circuit board and commercial fins, the comb can be realized flexibly with the output force conveniently extended. The force generated by this kind of comb is theoretically analyzed. Different from the traditional comb structure, the conductive area of the comb fixed plate is minimized to improve the force consistency over engagement. The influence of fin length, fin number, applied voltage, and engagement on the output force has been studied experimentally. The final comb system is capable of producing steady force in the range 13-5040 μN with the relative error within 5%. With a high voltage pulse generator, this system could produce calibration impulse bit in the range 1-1000 μN s for which the lowest level can be far more extended to the nanonewton range with a shorter pulse width, a lower voltage, and a reduced number of fins. Moreover, the calibrator has a rather flat force-engagement characteristic when the engagement is in the range of 6 mm–16 mm, while the variation of electrostatic force is within 5%. This calibrator has a wide output range and great consistency, and it is beneficial for the thrust stand calibration. [ABSTRACT FROM AUTHOR]

The capillary-based pulsed plasma thruster (PPT) has high-energy transfer efficiency, which provides potential to improve traditional PPT performance. In this paper, the discharge characteristics of a capillary-based PPT have been investigated. First, the typical process of voltage and current waveform is recognized. It is featured with a fast voltage drop (~25 ns) and a consequent damped sine wave oscillation discharge. Then based on the circuit analysis, the equivalent plasma resistance has been calculated. The current waveform is well fit with a linearly increasing resistance model. The influence of charging voltage has also been studied. The deposited energy increases while the transfer efficiency decreases with the increasing applied voltage. The cavity dimension has effects on the equivalent circuit parameters. The results show that longer cavity and smaller diameter lead to more deposited energy and higher transfer efficiency. The influence of voltage and capillary dimension on the mass shot characteristic has been discussed. Finally, the estimated impulse bit has been calculated and the impulse bit characteristics have been discussed. These results can contribute to the further optimization of PPT. [ABSTRACT FROM PUBLISHER]

Many studies have examined the beneficial effects of tea polyphenols (TP) and proanthocyanidins (PC) on the memory impairment in different animal models. However, the combined effects of them on synaptic, memory dysfunction and molecular mechanisms have been poorly studied, especially in the menopause-related memory decline in rats. In this rat study, TP and PC were used to investigate their protective effects on memory decline caused by inflammation. We characterized the learning and memory abilities, synaptic plasticity, AMPAR, phosphorylation of the p38 protein, TNF-ɑ, structural synaptic plasticity-related indicators in the hippocampus. The results showed that deficits of learning and memory in OVX + D-gal rats, which was accompanied by dendrites and synaptic morphology damage, and increased expression of Aβ1-42 and inflammation. The beneficial effects of TP and PC treatment were found to prevent memory loss and significantly improve synaptic structure and functional plasticity. TP+PC combination shows more obvious advantages than intervention alone. TP and PC treatment improved behavioral performance, the hippocampal LTP damage and the shape and number of dendrites, dendritic spines and synapses, reduced the burden of Aβ and decreased the inflammation in hippocampus. In addition, TP and PC treatment decreased the expressions of Iba-1, TNF-α, TNFR1, and TRAF2. These results provided a novel evidence TP combined with PC inhibits p38 MAPK pathway, suppresses the inflammation in hippocampus, and increase the externalization of AMPAR, which may be one of the mechanisms to improve synaptic plasticity and memory in the menopause-related memory decline rats. [ABSTRACT FROM AUTHOR]

In this paper, a torsional thrust balance with an asymmetrical arm is designed and tested which is effective for the microthruster performance evaluation in the vacuum facilities with limited space. An optimization design method for the key parameters of the thrust balance has been developed. By utilizing the asymmetrical arm, a great resolution can be obtained with a restrained arm length. A novel printed circuit board electrostatic comb has been applied to the thrust balance calibration. Experimental results show that the comb is capable of producing steady force in the range of about 30 μN–3300 μN and an impulse bit of 7 µNs–777 µNs which can be further extended to nano-Newton second range with a shorter pulse width and a lower voltage. The calibration results show that the thrust balance has a great repeatability and reliability. The total uncertainty of the thrust stand is estimated to be 3.33% in the 1 µNs range. [ABSTRACT FROM AUTHOR]

Megavolt-class pulsed gas switches play an important role in large pulsers as transfer switches. This article analyzes the breakdown process and characteristics of a megavolt self-triggered preionized switch under 100-ns pulses based on the optical diagnosis. It is discovered that the triggering spark illumination targeting the main cathode or anode can separately preionize the main gap. The discharge channel is likely to first form between trigger electrodes and the main anode. Based on the above deduction, the streamer velocity is calculated to be $0.54 \times 10^{6}$ – $2.34 \times 10^{6}$ m/s, proportional to the electric field. Also, parameters of the empirical formula for calculating the gas heating time are amended. Influence mechanisms of the switch jitter are also studied. Under pulsed preionization mode, the trigger gap breaks down when the main gap electric field is high enough, and the switch jitter is mainly determined by the self-triggering jitter. Nonetheless, the self-triggering jitter can be partly offset during the breakdown process if the changing rate of mean reduced electric field $d(E/p)$ / dt at the self-triggering time is higher than 1.0 $1.0\left(\mathrm{kV} \cdot \mathrm{ns}^{-1} \cdot \mathrm{cm}^{-1} \cdot \mathrm{MPa}^{-1}\right)$. Under sustaining preionization mode, the trigger gap breaks down prematurely, and the continuous arcing driven by switch leak current preionizes the main gap. Therefore, the influence of the self-triggering jitter on the switch jitter can be eliminated. [ABSTRACT FROM AUTHOR]

In order to further improve the insulation performance of fiber reinforce plastic (FRP) materials used in electromagnetic pulse (EMP) simulators, the flashover characteristics of FRP materials with different surface roughness and groove, i.e., those who are easily achieved and have a prominent effect, are investigated in 0.1 MPa SF6 under nanosecond pulse voltage with a rise time of 20–30 ns. The experimental results show that surfaces with different roughness have no significant influence on the flashover voltages of the FRP insulators, and both the convex grooves made of FRP and the convex grooves with nylon rings inlaid to form projections can improve the surface flashover voltage of epoxy FRP insulators under nanosecond pulse, in which the effect of the former surface is more obvious. For the insulators with convex grooves made of FRP, it is found that the root of the FRP protrusions breaks down after a number of shots with the occurrence of carbonization channels and spots, which is nonexistent for the nylon projections. Combined with the test results of surface characteristics, the surface roughness and the secondary electron emission yield (SEEY) are not key factors of flashover characteristics in SF6 under nanosecond pulse, arguably due to the fact that the energy needed for an incident electron to ionize an SF6 molecule is lower than that to excite two secondary electrons. Hence, the flashover performance cannot be improved by adjusting the surface roughness, and the flashover channel is principally governed by the macroscopic distribution of electrical field which can be changed by the convex groove. Breakdown phenomena of FRP protrusions indicate that the bulk insulation performance of resin FRP is weaker compared to pure resin because of its composite structure, as well as the impurities and voids introduced in the manufacturing process. The results are instructive for the design of FRP insulation structures in the compact EMP simulator. [ABSTRACT FROM AUTHOR]

The molecule of the title compound, C16H22N4S2, has a center of symmetry. The crystal packing is mainly stabilized by van der Waals forces. [ABSTRACT FROM AUTHOR]

Image segmentation methods have been utilized to determine the particle size distribution of crushed ores. Due to the complex working environment, high-powered computing equipment is difficult to deploy. At the same time, the ore distribution is stacked, and it is difficult to identify the complete features. To address this issue, an effective box-supervised technique with texture features is provided for ore image segmentation that can identify complete and independent ores. Firstly, a ghost feature pyramid network (Ghost-FPN) is proposed to process the features obtained from the backbone to reduce redundant semantic information and computation generated by complex networks. Then, an optimized detection head is proposed to obtain the feature to maintain accuracy. Finally, Lab color space (Lab) and local binary patterns (LBP) texture features are combined to form a fusion feature similarity-based loss function to improve accuracy while incurring no loss. Experiments on MS COCO have shown that the proposed fusion features are also worth studying on other types of datasets. Extensive experimental results demonstrate the effectiveness of the proposed method, which achieves over 50 frames per second with a small model size of 21.6 MB. Meanwhile, the method maintains a high level of accuracy 67.8 in A P 50 b o x and 47.7 in A P 50 m a s k compared with the state-of-the-art approaches on ore image dataset, even better than bounding box tightness prior (BBTP) by 10.4/1.3 on A P 50 b o x / A P 50 m a s k metrics with the ResNet50 as backbone. The source code is available at https://github.com/MVME-HBUT/OREINST. • A fusion feature combining Lab color space (Lab) and local binary pattern (LBP) texture features is proposed. • A Ghost-FPN and an optimized detection head are presented to reduce model size while increasing inference speed. • Experiments on MS COCO have shown that the proposed fusion features are also worth studying on other types of datasets. [ABSTRACT FROM AUTHOR]

The study was conducted between 2018 and 2020. From a cohort of 113 hearing impaired (HI), five non‐DFNB12 probands identified with heterozygous CDH23 variants were subjected to exome analysis. This resolved the etiology of hearing loss (HL) in four South Indian assortative mating families. Six variants, including three novel ones, were identified in four genes: PNPT1 p.(Ala46Gly) and p.(Asn540Ser), MYO15A p.(Leu1485Pro) and p.(Tyr1891Ter), PTPRQ p.(Gln1336Ter), and SLC12A2 p.(Pro988Ser). Compound heterozygous PNPT1 variants were associated with DFNB70 causing prelingual profound sensorineural hearing loss (SNHL), vestibular dysfunction, and unilateral progressive vision loss in one family. In the second family, MYO15A variants in the myosin motor domain, including a novel variant, causing DFNB3, were found to be associated with prelingual profound SNHL. A novel PTPRQ variant was associated with postlingual progressive sensorineural/mixed HL and vestibular dysfunction in the third family with DFNB84A. In the fourth family, the SLC12A2 novel variant was found to segregate with severe‐to‐profound HL causing DFNA78, across three generations. Our results suggest a high level of allelic, genotypic, and phenotypic heterogeneity of HL in these families. This study is the first to report the association of PNPT1, PTPRQ, and SLC12A2 variants with HL in the Indian population. [ABSTRACT FROM AUTHOR]

Clausena lansium (Lour.) Skeels (Rutaceae), recognized as wampee, is a widely distributed fruit tree which is utilized as a folk-medicine for treatment of several common diseases. However, the genomic information about this medicinally important species is still lacking. Therefore, we assembled the first genome of Clausena genus with a total length of 310.51 Mb and scaffold N50 of 2.24 Mb by using 10× Genomics technology. Further annotation revealed a total of 34,419 protein-coding genes, while repetitive elements covered 39.08% (121.36 Mb) of the genome. The Clausena and Citrus genus were found to diverge around 22 MYA, and also shared an ancient whole-genome triplication event with Vitis. Furthermore, multi-tissue transcriptomic analysis enabled the identification of genes involved in the synthesis of carbazole alkaloids. Altogether, these findings provided new insights into the genome evolution of Wampee species and highlighted the possible role of key genes involved in the carbazole alkaloids biosynthetic pathway. • First high-quality genome of Clausena genus (Clausena lansium). • Wampee genome encode 34,419 protein-coding genes, and 39.08% repetitive elements. • Clausena and Citrus diverged around 22 MYA. • C. lansium shared an ancient whole-genome triplication event with Vitis. • Key genes involved in the carbazole alkaloids biosynthesis pathways were identified. [ABSTRACT FROM AUTHOR]

Colorectal carcinoma (CRC) is often lethal when invasion and/or metastasis occur. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme involved in prostaglandin (including PGE2) bio-inactivation, is down-expressed in several epithelial malignancies including CRC. Although its role in the suppression of colon tumorigenesis has been well learned, little is known about the role of 15-PGDH in the process of tumor metastasis. Here, we tested the hypothesis that 15-PGDH over-expression in CRC cells results in decreased cell motility and invasion. In this study, 15-PGDH was re-expressed in SW480 cells by the use of gene transient transfection with eukaryotic expression vector pcDNA3.1-PGDH. We confirmed the over-expression of 15-PGDH protein by Western blot and enzymatic activity assay. The cell motility was tested by counting the number of cells crossing an 8-micron pore size PET membrane and by measuring cells migration distance through wound healing assay. Furthermore, cell invasive activity was evaluated by counting the number of cells invading through a Matrigel-coated membrane simulating basement membrane. The effects of 15-PGDH on the adhesion were investigated by MTT assay. Ectopic expression of 15-PGDH in SW480 cancer cells significantly inhibited the cell migratory and invasive capacity in vitro by approximately 1.9- and 8.4-fold, respectively. To test the hypothesis that 15-PGDH affects proteases and inactivates extracellular matrix (ECM), Western blot and gelatin zymography were performed by using serum-free conditioned medium. The results showed that re-expression of 15-PGDH suppresed matrix metalloproteinase-2 (MMP2) synthesis and secretion. In addition, the analysis of the MMP2 activity indicated that re-expression of 15-PGDH could inhibit activation of MMP2. Furthermore, we found that 15-PGDH inhibited cell adhesion to ECM and reduced CD44 expression in SW480 cell. Taken together, these results suggest that induced 15-PGDH expression may contribute to the inhibition of the invasive and metastatic capacity of colon cancer cells in vitro. [ABSTRACT FROM AUTHOR]

Tea is a rich source of pharmacologically active molecules that has been suggested to provide a variety of health benefits. However, its mechanism of action in aging-related intestinal flora dysbiosis mediated neuroinflammation is still unclear. This study aimed to explore whether tea polyphenols (TP) can improve memory by regulating intestinal flora mediated neuroinflammation in aging model rats. Ovariectomy (OVX) combined with D-galactose injection was used to establish aging rats related to menopause. The rats were divided into Sham control group, Aging model group, TP 75 mg/kg, 150 mg/kg, 300 mg/kg groups and VE group. After 12 weeks of intervention, the shuttle box test and Y maze test were used to check the memory of rats. The composition of intestinal flora was assessed by 16S rRNA sequencing technology. HE staining and ELISA were used to detect intestinal epithelial morphology and permeability, respectively. TLR4/NF-κB inflammation pathway related indicators were investigated by western blot, and the microglia activation in rat hippocampal tissue was checked by immunofluorescence. In the shuttle box test and the Y maze test, compared with the Sham control group, the memory of Aging model rats was significantly declined. It was observed that the intestinal flora of Aging model rats was dysbiosis, the permeability of the intestinal epithelium was increased. Further experimental results showed that the expression of TLR4/NF-κB inflammatory pathway related proteins in the hippocampus were increased, and the excessive activation of microglia was observed. The beneficial effects of TP intervention have been found to prevent memory decline and significantly improve brain inflammation induced by intestinal flora dysbiosis, and TP 300 mg/kg showed a more obvious advantage than TP 75 mg/kg. TP 300 mg/kg can significantly improve the behavior of rats, improve the composition and diversity of the intestinal flora, and the shape and function of the intestinal epithelium. By reversing the increased expression levels of TLR4, IRAK, p-IκBα and nuclear NF-κB p65 proteins in the hippocampus of Aging model rats, the activation of microglia in the CA1, CA3 and Dentate gyrus (DG) sub-regions of the hippocampus can be inhibited. TP inhibits the brain TLR4/NF-κB inflammatory signal pathway caused by the dysbiosis of intestinal flora, which may be one of the mechanisms to improve the memory decline in aging model rats. [Display omitted] • In this study, ovariectomy and D-galactose injection were used to establish aging model rats related to menopause. • The composition of the intestinal flora of aging rats was dysbiosis, which in turn triggered inflammation in the brain. • This study can provide laboratory evidence for the prevention of menopause-related memory decline. [ABSTRACT FROM AUTHOR]

Purpose: The applicability of laparoscopic-assisted radical gastrectomy for elderly patients with gastric cancer is still not well clarified. The aim of this double-center study was to explore the feasibility and effectiveness of laparoscopic-assisted radical gastrectomy on elderly patients with gastric cancer. Methods: We prospectively collected data of patients who underwent gastrectomy for cancer in two centers from June 2016 to December 2019. Propensity score matching was performed at a ratio of 1:1 to compare the laparoscopic-assisted radical gastrectomy group and open radical gastrectomy group. Univariate analyses and multivariate logistic regression analyses evaluating the risk factors for total, surgical, and medical complications were performed. Results: A total of 481 patients with gastric cancer met the inclusion criteria and were included in this study. After propensity score analysis, 258 patients were matched each other (laparoscopic-assisted radical gastrectomy (LAG) group, n = 129; open radical gastrectomy (OG) group, n = 129). LAG group had lower rate of surgical complications (P = 0.009), lower rate of severe complications (P = 0.046), shorter postoperative hospital stay (P = 0.001), and lower readmission rate (P = 0.039). Multivariate analyses revealed that anemia, Charlson comorbidity index, and combined resection were independent risk factors in the LAG group, whereas body mass index and American Society of Anesthesiology grade in the OG group. Conclusion: Laparoscopic-assisted radical gastrectomy was relative safe even effective in elderly gastric cancer patients. We should pay attention to the different risk factors when performing different surgical procedures for gastric cancer in elderly patients. [ABSTRACT FROM AUTHOR]

To verify the performance of longitudinal waves induced by laser phased arrays (LPA) for detection and quantitative evaluation in internal defects, the finite element method (FEM) is utilized to establish the models of LPA scanning processing. The interaction of longitudinal wave and internal defect is analyzed. Besides, the two components of the reflected longitudinal waves (the longitudinal wave component r LL and the shear wave component r LS r LS ) are focused on the imaging of defects with the synthetic aperture focusing technique (SAFT) and total focusing method (TFM) algorithms. It shows that the imaging of internal sub-millimeter defect is obtained using the LPA. The defect size and location are simultaneously calculated, with the relative error being 6.7% and 2.9%, respectively. The proposed longitudinal wave-based LPA is a promising method for the imaging and evaluation of internal micro defects. [ABSTRACT FROM AUTHOR]

Fibroblast-like synoviocytes (FLS) play a pathogenic role in rheumatoid arthritis (RA). STAT3 signaling is activated in FLS of RA patients (RA-FLS), which in turn causes RA-FLS hyperproliferation. RL is a traditional remedy for treating inflammatory diseases in China. It comprises Rosae Multiflorae Fructus and Lonicerae Japonicae Flos. A standardized ethanolic extract of RL (RLE) has been shown to exert anti-arthritic effects in collagen-induced arthritis (CIA) rats. Some constituents of RLE were reported to inhibit JAK2/STAT3 signaling in rat FLS. Here, we determined whether RLE inhibits FLS hyperproliferation, and explored the involvement of STAT3 signaling in this inhibition. In joints of CIA rats, RLE increased apoptotic FLS. In IL-6/sIL-6R-stimulated RA-FLS, RLE reduced cell viability and evoked cell apoptosis. In synovial tissues of CIA rats, RLE lowered the protein level of phospho-STAT3. In IL-6/sIL-6R-stimulated RA-FLS, RLE inhibited activation/phosphorylation of STAT3 and JAK2, decreased the nuclear localization of STAT3, and downregulated protein levels of Bcl-2 and Mcl-1. Over-activation of STAT3 diminished RLE's anti-proliferative effects in IL-6/sIL-6R-stimulated RA-FLS. In summary, RLE inhibits hyperproliferation of FLS in rat and cell models, and suppression of STAT3 signaling contributes to the underlying mechanisms. This study provides further pharmacological groundwork for developing RLE as a modern anti-arthritic drug. [ABSTRACT FROM AUTHOR]

Sarcopenia is a progressive systemic skeletal muscle disorder characterized by a pathological decline in muscle strength, quantity, and quality, which frequently affects the elderly population. The majority of cancer patients are of advanced age. Patients may already have sarcopenia prior to cancer development, and those with cancer are prone to developing sarcopenia due to hypercatabolism, inflammation, reduced physical fitness, anorexia, adverse effects, and stress associated with anticancer therapy. Based on the timing, sarcopenia in patients with cancer can be categorized into three: pre-existing sarcopenia before the onset of cancer, sarcopenia related to cancer, and sarcopenia related to cancer treatment. Sarcopenia not only changes the body composition of patients with cancer but also increases the incidence of postoperative complications, reduces therapeutic efficacy, impairs quality of life, and results in shortened survival. Different therapeutic strategies are required to match the cancer status and physical condition of patients with different etiologies and stages of sarcopenia. Here, we present a comprehensive review of the epidemiology and diagnosis of sarcopenia in patients with cancer, elucidate the complex interactions between cancer and sarcopenia, and provide evidence-based strategies for sarcopenia management in these patients. [Display omitted] • Cancer and sarcopenia mutually exacerbate, forming a vicious cycle. • Interventions vary depending on temporal occurrence of sarcopenia in cancer. • Early recognition and multimodal interventions are needed for sarcopenia in cancer. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a negative predictor for postoperative recovery. This study was performed to evaluate the short-term outcomes of laparoscopic surgery in colorectal cancer patients with sarcopenia.Methods: We conducted a study of patients who underwent curative surgeries for colorectal cancer in two centers from July 2014 to July 2018. In order to reduce selection bias, we conducted a propensity score matching analysis. Preoperative characteristics including age, gender, anemia, body mass index, hypoalbuminemia, America society of anesthesiology scores, epidural anesthesia, operative procedure, stoma, tumor location, and combined resection were incorporated in the model, and produced 58 matched pairs. The third lumbar skeletal muscle mass, handgrip strength, and 6 m usual gait speed were measured to define sarcopenia. Short-term outcomes were compared between the two groups.Results: In a total of 1136 patients, 272 had sarcopenia diagnosed, and 227 were further analyzed in this study. Among them, 108 patients underwent laparoscopic colorectal surgery and 119 underwent open colorectal surgery. In the matched cohort, the clinical characteristics of the two groups were well matched. The laparoscopic group had significantly reduced overall complications (15.5% vs. 36.2%, P = 0.016) and shorter postoperative hospital stays (10.5 vs. 14, P = 0.027). Subgroup analysis of postoperative complications showed that the incidence of surgical complications (P = 0.032) was lower in the laparoscopic group. Hospitalization costs (P = 0.071) and 30-day readmissions (P = 0.215) were similar between the two groups.Conclusion: Laparoscopic surgery for colorectal cancer is a safe and feasible option with better short-term outcomes in patients with sarcopenia. [ABSTRACT FROM AUTHOR]

Malignant melanoma is a fatal cancer. Signal transducer and activator of transcription 3 (STAT3) has been proposed as a therapeutic target of melanoma. An herbal formula Huai-Hua-San (HHS) comprising Sophorae Flos (SF) and Gardeniae Fructus (GF) is traditionally used for treating cancers including melanoma, but the pharmacological basis is unknown. This study aimed to investigate the anti-melanoma effects of an ethanolic extract of HHS (HHSE), and explore the involvement of STAT3 signaling in the effects. An UPLC-TOF/MS method was developed to control the quality of HHSE. A B16F10 allograft mouse model and three melanoma cell lines (B16F10, A375 and A2058) were used to determine the anti-melanoma effects of HHSE. Dacarbazine (DTIC) and Stattic were used as positive controls. Cell viability was detected using MTT and crystal violet staining assays. Cell apoptosis was analyzed by flow cytometry after the cells were stained with Annexin-V/PI. Cell invasive ability was examined using the transwell assay. Protein levels were determined by Western blotting. The contents of crocin I, crocin II, quercetin and kaempferol in HHSE were 0.59%, 0.98%, 4.66% and 1.15%, respectively. A clinically relevant dose of HHSE (0.1 g/kg/day, i.g. for 15 consecutive days) significantly suppressed B16F10 tumor growth in mice. HHSE dose-dependently reduced cell viability and dampened invasion of, and induced apoptosis in, melanoma cells. Mechanistic studies revealed that HHSE inhibited the phosphorylation/activation of STAT3 in B16F10 allografts and in cultured melanoma cells. In cell models, HHSE also inhibited the phosphorylation of STAT3 upstream kinases, JAK2 (Tyr1007/1008) and Src (Tyr416), lowered STAT3 nuclear levels, and down-regulated the protein levels of STAT3-targeted molecules. Over-activation of STAT3 in A375 cells significantly attenuated the cytotoxic effects of HHSE. HHSE exhibits anti-melanoma effects in cell and mouse models. Inhibition of STAT3 signaling contributes to the anti-melanoma mechanisms of HHSE. Our findings lay a groundwork for developing HHSE as a modern agent for melanoma management, and provide pharmacological justifications for the traditional use of HHS in treating melanoma. Image 1 [ABSTRACT FROM AUTHOR]

Background: Following acute infection, Herpes Simplex virus-1 (HSV-1) establishes lifelong latency and recurrent reactivation in the sensory neurons of trigeminal ganglia (TG). Infected tree shrew differs from mouse and show characteristics similar to human infection. A detailed transcriptomic analysis of the tree shrew model could provide mechanistic insights into HSV-1 infection in humans. Methods: We sequenced the transcriptome of infected TGs from tree shrews and mice, and 4 human donors, then examined viral genes expression up to 58 days in infected TGs from mouse and tree shrew, and compare the latency data with that in human TGs. Results: Here, we found that all HSV-1 genes could be detected in mouse TGs during acute infection, but 22 viral genes necessary for viral transcription, replication and viral maturation were not expressed in tree shrew TGs during this stage. Importantly, during latency, we found that LAT could be detected both in mouse and tree shrew, but the latter also has an ICP0 transcript signal absent in mouse but present in human samples. Importantly, we observed that infected human and tree shrew TGs have a more similar LAT region transcription peak. More importantly, we observed that HSV-1 spontaneously reactivates from latently infected tree shrews with relatively high efficiency. Conclusions: These results represent the first longitudinal transcriptomic characterization of HSV-1 infection in during acute, latency and recurrent phases, and revealed that tree shrew infection has important similar features with human infection. [ABSTRACT FROM AUTHOR]

Late stage melanoma is associated with a high mortality rate. Signal transducer and activator of transcription 3 (STAT3) is currently a target for melanoma treatment as it is constitutively activated with high frequency in melanoma. Dioscin is a natural steroid saponin that is present in several medical herbs. A previous study demonstrated that dioscin inhibits STAT3 signaling in a cerebral ischemia-reperfusion injury rat model. Furthermore, dioscin has been reported to exert anti-melanoma effects in B16 melanoma cells and a B16 allograft mouse model. The present study investigated whether inhibition of STAT3 signaling is involved in the anti-melanoma effects of dioscin. The results of the present study demonstrated that dioscin significantly decreased viability, induced apoptosis and suppressed migration of human A375 melanoma cells and murine B16F10 melanoma cells. Furthermore, dioscin inhibited the phosphorylation of STAT3 and Src (an upstream kinase of STAT3), and downregulated mRNA levels of STAT3-targeted genes, including B-cell lymphoma-2, cyclin D1 and matrix metalloproteinase-2. In addition, overexpression of STAT3 decreased the anti-proliferative effects of dioscin. Overall, the results of the present study indicate that inhibiting the Src/STAT3 signaling pathway contributes to the anti-melanoma molecular mechanisms of dioscin. These results provide further pharmacological groundwork for developing dioscin as a novel anti-melanoma agent. [ABSTRACT FROM AUTHOR]

Si-Jun-Zi-Tang (SJZT) is a traditional Chinese medicine formula used to treat chronic and debilitating diseases including melanoma. SJZT-based therapies have achieved good clinical outcomes in melanoma management. However, the pharmacological basis of SJZT for its clinical use in melanoma treatment is not fully understood. To investigate the anti-melanoma effects and mechanism of action of an ethanolic extract of SJZT. SJZT was extracted using 50% ethanol. A murine B16 melanoma-bearing mouse model was employed to investigate the anti-melanoma effects of SJZT. microRNA (miRNA) and mRNA levels were examined by RT-qPCR, and protein levels were measured by Western blotting. SJZT significantly inhibited B16 tumor growth in mice. Mechanistic investigations revealed that SJZT elevated miR-34b (a tumor suppressing miRNA), and lowered c-Met (a miR-34b target gene) and β-catenin (a downstream molecule of c-Met signaling) expression levels in the B16 tumors. In this study we found, for the first time, that SJZT exerts anti-melanoma effects and regulates the miR-34b/c-Met/β-catenin pathway in a melanoma mouse model. Our findings provide pharmacological justifications for the clinical use of SJZT in treating melanoma. Image 1 • An ethanolic extract of Si-Jun-Zi-Tang , a traditional Chinese medicine formula, suppresses B16 melanoma growth in mice. • Si-Jun-Zi-Tang regulates the miR-34b/c-Met/β-catenin pathway in B16 tumors. • This study provides pharmacological justifications for the traditional use of Si-Jun-Zi-Tang in treating melanoma. [ABSTRACT FROM AUTHOR]

Abstract Aim Mitochondrial dysfunction during aging is a key factor that contributes to sarcopenia. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been increasingly recognized to regulate mitochondrial function. The present study aimed to investigate the role of Nrf2 in the development of frailty and sarcopenia during aging, and to demonstrate whether Nrf2 contributes to the maintenance of muscle mass and function by regulation of mitochondrial biogenesis and dynamics during the aging process. Methods Young (5–6 months), middle-aged (11-13 months), old (20–24 months) Nrf2−/− (knockout, KO) mice and age-matched wild-type (WT) C57/BL6 mice were used in this study. Physical function of the mice in the 6 groups was assessed by grip strength test, four paw inverted hanging test, rotarod analysis, open field analysis, and treadmill endurance test. Muscle mass was measured by cross-sectional area (CSA) of tibialis anterior muscles and gastrocnemius muscle weight. The frailty status of the 25 old WT mice and 23 old KO mice were assessed based on the mouse frailty phenotype assessment. Expression levels of genes involved in mitochondrial biogenesis (nuclear respiratory factor 1 (Nrf1), peroxisome proliferative activated receptor, gamma, coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM)) and mitochondrial dynamics (optic atrophy protein 1 (Opa1), mitofusin 1 (Mfn1), mitofusin 2 (Mfn2), and dynamin-related protein 1 (Drp1)) were measured in the skeletal muscle. SDH staining was performed and mitochondrial DNA (mtDNA) copy number was measured. Transmission electron microscopy was used to measure the mitochondria number and morphology. Results Physical function and muscle mass decreased during aging. The mRNA expression levels of Nrf2 decreased with increasing frailty phenotype scores in the old WT mice. There were minimal differences in the physical function and muscle mass between the WT and KO mice in the young groups, whereas Nrf2 deficiency caused a declined physical function and muscle mass in the middle-aged and old mice, and exacerbated frailty in the old mice. The decreases of the physical function and muscle mass were accompanied by the reduced expression levels of genes involved in mitochondrial biogenesis and dynamics, as well as a reduction of mitochondrial number, mitochondrial content, mtDNA copy number, and an impaired mitochondria morphology in the skeletal muscle. Conclusion Nrf2 deficiency exacerbated frailty and sarcopenia during aging, at least partially by impairing skeletal muscle mitochondrial biogenesis and dynamics in an age-dependent manner. Highlights • Muscle mass/function and mitochondrial homeostasis are impaired during aging in mice. • Decline of muscle mass/function is linked with mitochondrial dysfunction during aging. • Nrf2 deficiency has few effect on frailty/sarcopenia and mitochondria in young mice. • Nrf2 deficiency worsens mitochondrial dysfunction, frailty/sarcopenia in older mice. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract A traditional Chinese medicine (TCM) formula (SL) comprising Sophorae Flos and Lonicerae Japonicae Flos was used for treating melanoma in ancient China. We have previously shown that an ethanolic extract of SL (SLE) possesses anti-melanoma effects and suppresses STAT3 signaling in vitro and in vivo. STAT3 has been linked to the development of melanoma immunosuppressive microenvironment. In this work, we investigated whether SLE inhibits melanoma growth by reprogramming the tumor microenvironment in mouse and co-culture cell models. In B16F10 melanoma-bearing mice, we found that intragastric administration of SLE (1.2 g/kg) dramatically inhibited tumor growth. This observation was associated with the downregulation of protein levels of phospho-STAT3 (Tyr 705) and STAT3-regulated immunosuppressive cytokines, and mRNA levels of STAT3-targeted genes involved in tumor growth and immune evasion. We also observed increased Th, Tc and dendritic cells in the melanomas and spleens in SLE-treated mice compared to that in control mice. In a co-culture system composed of B16F10 cells and mouse primary splenic lymphocytes, it was found that SLE not only inhibited STAT3 activation in B16F10 cells, but also downregulated mRNA levels of STAT3-targeted genes in the splenic lymphocytes. In this co-culture setting, SLE decreased the levels of STAT3-regulated immunosuppressive cytokines, increased the percentages of Th, Tc and dendritic cells as well. Furthermore, effects of SLE on STAT3 phosphorylation, cytokine levels and immune cell subtype percentages were significantly weaker in the B16STAT3C cells (stable cells harboring a constitutively active STAT3 variant STAT3C)/splenic lymphocytes co-culture system than in the B16V cells (cells stably transfected with the empty vector)/splenic lymphocytes co-culture system, indicating that STAT3 over-activation diminishes SLE's effects. In summary, our findings indicate that reprograming the immune microenvironment, partially mediated by inhibiting STAT3 signaling, contributes to the anti-melanoma mechanisms of SLE. This study provides further pharmacological groundwork for developing SLE as a modern agent for melanoma prevention/treatment, and supports the notion that reprograming immunosuppressive microenvironment is a viable anti-melanoma strategy. [ABSTRACT FROM AUTHOR]

Isentropic compression experiments (ICEs) are an important method to study the dynamic characteristics of materials at pressures, temperatures, and stress or strain rate not attainable in conventional shock experiments. Yet it makes high demands toward the precise current pulse tailoring capability of the source. The China Academy of Engineering Physics is now developing a 20-brick parallel discharge driver and a 256-brick parallel discharge driver (CQ-7) to improve the performance and flexibility of compact magnetic compression devices. The load current of ICEs is tailored by optimizing the switch trigger sequence and the brick charging voltage. This paper establishes the equivalent circuit model of the 20-brick parallel discharge driver, taking the distributed inductance, resistance, and capacitance of transmission plates into account based on the partial-element equivalent circuit method. Besides, the equivalent circuit model of discharge brick based on the switch arc resistance model is also established to study the influence of key structural parameters on the output current. Furthermore, by comparing the simulation and experimental results of simultaneous discharge of 20-brick driver, the accuracy of simulation model is confirmed. This paper is of great significance to the design and optimization of multibrick parallel discharge drivers. [ABSTRACT FROM AUTHOR]

Abstract Introduction Both Global Registry of Acute Coronary Events (GRACE) risk score and CYP2C19 metabolizer status can independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We investigated whether their combination could better predict MACE occurrence in patients with ACS undergoing PCI. Materials and methods This retrospective cohort study included 548 consecutive patients with ACS undergoing PCI. A cumulative MACE curve was calculated using the Kaplan-Meier method. Multivariate Cox regression was used to identify MACE predictors. The predictive value of GRACE risk score alone and CYP2C19 metabolizer status was estimated by the area under the receiver operating characteristic curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results In a median of 28.58 months, 17 patients (3%) were lost to follow-up, and 62 (11.3%) experienced MACEs. Multivariate Cox regression analysis showed that both GRACE score and CYP2C19 metabolizer status were independent MACE predictors (hazard ratio 1.019, 95% CI 1.011–1.027, p < 0.001; hazard ratio 2.383, 95% CI 1.601–3.547, p < 0.001, respectively). Kaplan-Meier analysis showed that CYP2C19 PM increased the MACE risk (log rank test = 10.848, p = 0.004). The GRACE score adjustment by CYP2C19 metabolizer status enhanced the predictive value (AUC increased from 0.682 for GRACE score alone to 0.731 for GRACE score plus CYP2C19 metabolizer). This result was further verified by IDI and NRI. Conclusions CYP2C19 metabolizer status and GRACE score are readily available predictive approaches for MACEs, and their combination derives a more accurate long-term MACE prediction in clopidogrel-treated patients with ACS undergoing PCI. Highlights • We show the role of combining CYP2C19 metabolizer with GRACE risk score for risk stratification in acute coronary syndromes. • CYP2C19 metabolizer is an independent predictor of MACE. • Combining CYP2C19 metabolizer with GRACE risk score improved predictive value by IDI and NRI analysis. [ABSTRACT FROM AUTHOR]

Abstract: Background: AnWj is a high‐incidence blood group antigen associated with three clinical disorders: lymphoid malignancies, immunologic disorders, and autoimmune hemolytic anemia. The aim of this study was to determine the genetic basis of an inherited AnWj‐negative phenotype. Methods: We identified a consanguineous family with two AnWj‐negative siblings and 4 additional AnWj‐negative individuals without known familial relationship to the index family. We performed exome sequencing in search for rare homozygous variants shared by the two AnWj‐negative siblings of the index family and searched for these variants in the four non‐related AnWj‐negative individuals. Results: Exome sequencing revealed seven candidate genes that showed complete segregation in the index family and for which the two AnWj‐negative siblings were homozygous. However, the four additional non‐related AnWj‐negative subjects were homozygous for only one of these variants, rs114851602 (R320Q) in the SMYD1 gene. Considering the frequency of the minor allele, the chance of randomly finding 4 consecutive such individuals is 2.56 × 10−18. Conclusion: We present genetic and statistical evidence that the R320Q substitution in SMYD1 underlies an inherited form of the AnWj‐negative blood group phenotype. The mechanism by which the mutation leads to this phenotype remains to be determined. [ABSTRACT FROM AUTHOR]

For human olfactory functional MRI studies, the primary olfactory cortex (POC) suffers severe magnetic susceptibility artifacts, which adversely influences the detectability and reproducibility of the olfactory fMRI data and its clinical applications. The goal of this work is to assess the impacts of the image artifacts on the detectability and reproducibility of the olfactory activation in the POC. The severity of artifacts in the POC were classified into three levels using a Subjective Artifact score (SA_score). The mean temporal signal-to-noise ratio (tSNR) of the fMRI data acquired by a given MRI sequence and olfactory activation (β value) in POC were evaluated and compared to the concurrent activations in the primary visual cortex (Brodmann area 17, BA17) by an odor-visual association paradigm using ninety-nine normal human subjects. Our study revealed that the mean tSNR in POC was above the threshold for reliable detection of the functional activation signal, and, consequently, the mean olfactory activations in the POC were not significantly different from those in BA17. The reproducibility of the activation in the POC was assessed by a random half-split stimulation of a test-retest experiment. The overlap of the activation maps for all the trials (n = 1000) in the POC were not statistically different from that observed in BA17. These results show that the detectability and reproducibility of olfactory activation in the presence of susceptibility artifacts in the POC was at similar level of that in the visual cortex. [ABSTRACT FROM AUTHOR]

Background: With the increased prevalence of obesity and sarcopenia, those patients with both visceral obesity and sarcopenia were at higher risk of adverse outcomes.Aim: The aim of this study was to ascertain the combined impact of visceral obesity and sarcopenia on short-term outcomes in patients undergoing colorectal cancer surgery.Methods: We conducted a prospective study from July 2014 to February 2017. Patients' demographic, clinical characteristics, physical performance, and postoperative short-term outcomes were collected. Patients were classified into four groups according to the presence of sarcopenia or visceral obesity. Clinical variables were compared. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed.Results: A total of 376 patients were included; 50.8 and 24.5% of the patients were identified as having "visceral obesity" and "sarcopenia," respectively. Patients with sarcopenia and visceral obesity had the highest incidence of total, surgical, and medical complications. Patients with sarcopenia or/and visceral obesity all had longer hospital stays and higher hospitalization costs. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Rectal cancer and visceral obesity were independent risk factors for surgical complications. Age ≥ 65 years and sarcopenia were independent risk factors for medical complications. Laparoscopy-assisted operation was a protective factor for total and medical complications.Conclusion: Patients with both visceral obesity and sarcopenia had a higher complication rate after colorectal cancer surgery. Age ≥ 65 years, visceral obesity, and sarcopenia were independent risk factors for total complications. Laparoscopy-assisted operation was a protective factor. [ABSTRACT FROM AUTHOR]

This paper presents the design and development of a trigger with a high repetition rate, low jitter, and compact structure for the pseudospark switch (PSS), which includes an improved Marx generator based on avalanche transistors and a corona-plasma trigger unit. The generator adopted a novel 3 × 12-stage Marx circuit based on avalanche transistors in which the failure rate of transistors in the first and second stages was significantly reduced by connecting the parallel capacitors compared to the previous similar generator. The reason for the improved performance was also discussed. The main parameters of output pulses were an amplitude of −7 kV, rise time of 6 ns, jitter of 0.2 ns, and repetition rate of 2 kHz. The corona-plasma trigger unit adopted BaTiO3 ceramics with high εr as the dielectric and was arranged in the hollow cathode of the PSS. The experiments of triggering a PSS prototype were conducted. The influence of anode voltage and pressure on the trigger delay and jitter was studied, and the minimum trigger jitter achieved <1 ns. This trigger worked for 107 shots at the repetition rate of 2 kHz continuously without obvious performance degradation and any failure of the generator. The main advantage of this trigger is the simultaneous combination of the high repetition rate, low jitter, long lifetime, and great simplicity in a compact structure. [ABSTRACT FROM AUTHOR]

Abstract: In this study, we aimed to investigate the anti‐melanoma effects and the JAK2/STAT3 pathway‐related mechanism of action of atractylenolide I in human melanoma cells. Our results showed that atractylenolide I effectively reduced viability, induced apoptosis and inhibited migration of melanoma cells. Meanwhile, atractylenolide I decreased the protein expression levels of phospho‐JAK2 and phospho‐STAT3, and in turn downregulated the mRNA levels of STAT3‐targeted genes, including Bcl‐xL, MMP‐2 and MMP‐9. Furthermore, the cytotoxic effect of atractylenolide I was attenuated in STAT3‐overactivated A375 cells. These findings indicate that inhibition of JAK2/STAT3 signalling contributes to the anti‐melanoma effects of atractylenolide I. [ABSTRACT FROM AUTHOR]

As a new member of lead-free Na 0.5 Bi 0.5 TiO 3 (NBT) ceramics based on bismuth layer-structured ferroelectrics (BLSFs), Bi x Ti 3 O 6+1.5 x ( x = 3.96, 3.98, 4.0, 4.02, 4.04) ceramics was prepared by a conventional mixed oxide route. In order to explore the ferroelectric and dielectric properties, we changed the content of Bi in the ceramics. XRD patterns of Bi x Ti 3 O 6+1.5 x demonstrated that the new material was a single phase of Bi-layered perovskite structure. Through impedance spectra analysis, we found that the Bi 4.02 Ti 3 O 12.03 ceramics sintered at 1100 °C showed excellent dielectric properties with a highest dielectric constant of 8967.49 and a lowest dielectric loss of 0.00298 measured under 10 kHz, which were enhanced much compared with Bi 4 Ti 3 O 12 prepared by the same means. Meantime, the Curie temperature of the whole samples was about 670 °C. In addition, the ferroelectric hysteresis loops of all the samples indicated that they were ferroelectric materials, and Bi 4 Ti 3 O 12 ceramics sintered at 1100 °C processed a remanent polarization (2 P r ) of 12.206 µC/cm 2 and a coercive field of 29.542 kV/cm. SEM can roughly describe the results of the dielectric spectrum and ferroelectricity with different Bi concentration through grain size mechanics. Because of the high dielectric constant, wide operating temperature and low dielectric loss, the Bi 4 Ti 3 O 12 ceramics have a broad application prospect in components, such as sensors, high-temperature capacitors and so on. [ABSTRACT FROM AUTHOR]

Background Gastrectomy results in a significant loss of body composition in the long term, but the acute skeletal muscle wasting after gastrectomy has been rarely investigated. Moreover, the association between postoperative muscle wasting and quality of life (QOL) has never been reported. In the present study, we aimed to investigate the risk factors for acute muscle wasting after gastric cancer surgery and its effect on QOL and short-term postoperative outcomes. Methods We conducted a prospective study of patients who underwent curative gastrectomy for gastric cancer between June 2015 and December 2015. Skeletal muscle mass was measured by computed tomography within 1 month before and 1 week after surgery. QOL was assessed 1, 3, and 6 months postoperatively. Univariate and multivariate analyses were performed to identify the risk factors for clinically relevant muscle wasting (muscle wasting ≥10%). Results A total of 110 patients were included, in which 35 patients had muscle wasting ≥10% within 1 week after surgery. Age ≥65 years and diabetes were independent risk factors for muscle wasting ≥10%. Patients with muscle wasting ≥10% had a poorer QOL in terms of fatigue and physical functioning at 1 and 3 months postoperatively, as well as a higher incidence of postoperative complications, a higher incidence of handgrip strength reduction ≥10%, longer hospital stays, and higher costs. Conclusions Age ≥65 years and diabetes were independently associated with clinically relevant muscle wasting within 1 week after gastric cancer surgery. Clinically relevant muscle wasting was associated with a poorer QOL and short-term outcomes after surgery. [ABSTRACT FROM AUTHOR]

Isolated familial hypoparathyroidism is an extremely rare disorder, which to date has been linked to several loci including mutations in CASR, GCM2, and PTH, as well as a rare condition defined as X-linked recessive hypoparathyroidism, previously associated with a 1.5 Mb region on Xq26-q27. Here, we report a patient with hypocalcemia-induced seizures leading to the diagnosis of primary hypoparathyroidism. Mutations in CASR, GCM2, and PTH were ruled out, while whole exome sequencing of the family suggested FHL1, located on chromosome Xq26, as the most likely causative gene variant ( FHL1, exon 4, c.C283T, p.R95W). Since FHL1 has not been linked to calcium regulation before, we provide evidence for its functional role in hypoparathyroidism by: (i) bioinformatics analysis coupling its action to known modulators of PTH function; (ii) observing strong expression of fhl1b in Corpuscles of Stannius, gland-like aggregates in zebrafish that function in calcium regulation similar to mammalian PTH; and (iii) implicating fhl1b and FHL1 as regulators of calcium homeostasis in zebrafish and human cells, respectively. Altogether, our data suggest that FHL1 is a novel regulator of calcium homeostasis and implicate it as the causative gene for X-linked recessive hypoparathyroidism. [ABSTRACT FROM AUTHOR]

Background A geriatric assessment is needed to identify high-risk elderly patients with gastric cancer. However, the current geriatric assessment has been considered to be either time-consuming or subjective. The present study aimed to investigate the predictive effect of sarcopenia on the postoperative complications for elderly patients who underwent radical gastrectomy. Materials and methods We conducted a prospective study of patients who underwent radical gastrectomy from August 2014 to December 2015. Computed tomography–assessed lumbar skeletal muscle, handgrip strength, and gait speed were measured to define sarcopenia. Results Sarcopenia was present in 69 of 240 patients (28.8%) and was associated with lower body mass index, lower serum albumin, lower hemoglobin, and higher nutritional risk screening 2002 scores. Postoperative complications significantly increased in the sarcopenic patients (49.3% versus 24.6%, P < 0.001), compared with nonsarcopenic patients. The multivariate analysis demonstrated that sarcopenia (odds ratio: 2.959, 95% CI: 1.629-5.373, P < 0.001) and the Charlson comorbidity index ≥2 (odds ratio: 3.357, 95% CI: 1.144-9.848, P = 0.027) were independent risk factors for postoperative complications. Conclusions Sarcopenia, presented as a new geriatric assessment factor, was a strong and independent risk factor for postoperative complications of elderly patients with gastric cancer. [ABSTRACT FROM AUTHOR]

Background Precise determination of the lymph node status is critical for determining appropriate treatment for early gastric cancer (EGC). This study attempted to establish a simple, effective risk scoring system to predict lymph node metastasis (LNM) in EGC by investigating the relationship between platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and EGC LNM. Materials and methods We retrospectively reviewed 312 operable patients with EGC. The clinical utility of PLR and NLR was tested by receiver operating characteristic curves. The scoring system was developed using independent risk factors. Finally, 89 EGC patients were collected from prospective database to validate the scoring system's accuracy. Results The optimal PLR and NLR cut-off values were 106 and 2.97, respectively. High NLR ( P = 0.009) and PLR ( P = 0.007) values were associated with LNM of EGC in univariate analyses, although only high PLR ( P = 0.025) was an independent risk factor in multivariate analyses, together with age ( P = 0.009), differentiation ( P = 0.017), invasive depth ( P < 0.001), and tumor size ( P = 0.003). The scoring system's accuracy for retrospective and prospective data was 0.781 (95% confidence interval: 0.721-0.841) and 0.817 (95% confidence interval 0.714-0.920), respectively. Conclusions Preoperative PLR and NLR correlate with EGC LNM. Our scoring system is reliable, accurate, and effective in predicting LNM in EGC patients. [ABSTRACT FROM AUTHOR]

Purpose: One-year mortality is vital for elderly oncologic patients undergoing surgery. Recent studies have demonstrated that sarcopenia can predict outcomes after major abdominal surgeries, but the association of sarcopenia and 1-year mortality has never been investigated in a prospective study. Methods: We conducted a prospective study of elderly patients (≥65 years) who underwent curative gastrectomy for gastric cancer from July 2014 to July 2015. Sarcopenia was determined by the measurements of muscle mass, handgrip strength, and gait speed. Univariate and multivariate analyses were used to identify the risk factors associated with 1-year mortality. Results: A total of 173 patients were included, in which 52 (30.1 %) patients were identified as having sarcopenia. Twenty-four (13.9 %) patients died within 1 year of surgery. Multivariate analysis showed that sarcopenia was an independent risk factor for 1-year mortality. Area under the receiver operating characteristic curve demonstrated an increased predictive power for 1-year mortality with the inclusion of sarcopenia, from 0.835 to 0.868. Solely low muscle mass was not predictive of 1-year mortality in the multivariate analysis. Conclusions: Sarcopenia is predictive of 1-year mortality in elderly patients undergoing gastric cancer surgery. The measurement of muscle function is important for sarcopenia as a preoperative assessment tool. [ABSTRACT FROM AUTHOR]

Purpose: This study was performed to determine the association of frailty and nutritional status with postoperative complications after total gastrectomy (TG) with D2 lymphadenectomy in patients with gastric cancer. Methods: Patients undergoing TG with D2 lymphadenectomy for gastric cancer between August 2014 and February 2016 were enrolled. Frailty was evaluated by sarcopenia which was diagnosed by a combination of third lumbar vertebra muscle index (L3 MI), handgrip strength, and 6-m usual gait speed. Nutritional status was evaluated by the nutritional risk screening 2002 (NRS 2002) score. Univariate and multivariate analyses evaluating the risk factors for postoperative complications were performed. Results: A total of 158 patients were analyzed, and 27.2 % developed complications within 30 days of surgery. One patient died within 30 days of the operation. In the univariate analyses, NRS 2002 score ≥3 (OR = 2.468, P = 0.012), sarcopenia (OR = 2.764, P = 0.008), and tumor located at the cardia (OR = 2.072, P = 0.046) were associated with the postoperative complications. Multivariable analysis revealed that sarcopenia (OR = 3.084, P = 0.005) and tumor located at the cardia (OR = 2.347, P = 0.026) were independent predictors of postoperative complications. Conclusions: This study showed a significant relationship between postoperative complications and geriatric frailty using sarcopenia in patients with gastric cancer after TG with D2 lymphadenectomy. Frailty should be integrated into preoperative risk assessment and may have implications in preoperative decisionmaking. [ABSTRACT FROM AUTHOR]

It is an often challenging but essential issue to develop a facile and cost-effective approach to additively manufacture crack-free and high-strength Al alloys for their wider commercial applications. However, efficient synergistic combination of advanced technology and material development is hardly likely to achieve without considering the extreme processing conditions during additive manufacturing. In this study, the addition of 4 wt% Ti-6Al-4V (TC4) alloy powders, the most commercially used Ti alloy powders, into the laser powder bed fusion (L -PBF) of 7075 Al alloy was performed and experimentally verified to be capable of eliminating the hot cracks while substantially refining the grains. The as-printed sample was crack-free and had a high relative density of up to 99.95%. Synergy effect of the in-situ formation of Al 3 (Ti x ,V 1−x) particles that act as the heterogeneous nucleation sites, and the solute effect of the elements Ti and V that possess a high grain growth restriction factor (Q value) in Al matrix can efficiently control the grain growth. After a direct ageing treatment, the resultant alloy displayed an excellent combination of the high ultimate tensile strength (441 ± 3 MPa) and large plasticity (10.1 ± 0.4%). Our work brings new insights between the grain refinement and crack elimination of additively manufactured Al alloys through addition of commercial Ti alloys, benefiting the tailoring and development of new crack-free and dense high-strength Al alloys for L -PBF. [Display omitted] • The addition of Ti-6Al-4 V alloy powders to laser powder bed fusion of 7075 Al alloy can eliminate the cracks. • The as-printed sample is crack-free and has a high relative density of up to 99.95%. • The grain refinement is due to the formation of Al 3 (Ti x ,V 1−x) particles and solute effect of the Ti and V. • The heat-treated sample shows a superior combination of high ultimate tensile strength and large plasticity. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the short- and long-term outcomes after total gastrectomy (TG) with D2 lymphadenectomy.Methods: Patients undergoing TG with D2 lymphadenectomy for gastric cancer between December 2008 and December 2011 were enrolled. Univariate and multivariate analyses were performed to evaluate the risk factors for the short- and long-term outcomes.Results: A total of 229 patients were analyzed, and 22.3 % developed complications within 30 days of surgery. No patient died within 30 days, while 2.6 % died within 90 days of the operation. In the multivariate analysis, age ≥65 years and cardiopulmonary comorbidities were associated with morbidity, whereas hypoproteinemia and tumor-node-metastasis (TNM) stage III were associated with the disease-free survival (DFS) and overall survival (OS). The number of preoperative risk factors stratified the morbidity from 10.3 % in those without any risk factors to 40.5 % in patients with both risk factors. Similarly, 5-year survival rates decreased from 68.9 % (DFS) and 71.1 % (OS) in those without risk factors to 20.2 % (DFS) and 22.9 % (OS) in patients with both risk factors.Conclusion: TG with D2 lymphadenectomy has acceptable short- and long-term outcomes. Patient risk stratification may allow for more rational selection of patients and therapeutic strategies for gastric resection. [ABSTRACT FROM AUTHOR]

The article focuses on findings of a study on relative abundance of β-thalassemia-related mutations in southern China correlates with geographical coordinates. It states relation between the graticule and the pathogenic genotype diversity, and mentions computation of the correlation coefficient between each genotype's frequency and geographic components. It notes analysis of pathogenic mutation carrier rate.

Gastritis can lead to ulcers and the development of gastric cancer. The rhizome of Atractylodes macrocephala Koidz. (Asteraceae), a traditional Chinese medicinal herb, is prescribed for the treatment of gastric disorders, hepatitis and rheumatism. Its bio-active compounds are considered to be particularly effective in this regard. However, the molecular processes of the herb's anti-inflammatory activity remain obscure. This study elucidates a mechanism upon which an ethanolic extract of this herb (Am-EE) exerts anti-inflammation effects in RAW264.7 macrophage cells (RAW cells) stimulated by lipopolysaccharide (LPS) treatment and HCl Ethanol-stimulated gastritis rats. To investigate the anti-gastritis activities of Am-EE and explore the mode of action. Ethanol (95%) was used to prepare Am-EE. The quality of the extract was monitored by HPLC analysis. The in vivo effects of this extract were examined in an HCl Ethanol-stimulated gastritis rat model, while LPS-stimulated RAW cells were used for in vitro assays. Cell viability and nitric oxide (NO) production were observed by MTT and Griess assays. Real-time PCR was used to examine mRNA expression. The PGE 2 ELISA kit was employed to detect prostaglandin E 2 (PGE 2). Enzyme activities and protein contents were examined by immunoblotting. Luciferase reporter gene assays (LRA) were employed to observe nuclear transcription factor (NF)-κB activity. The SPSS (SPSS Inc., Chicago, Illinois, United States) application was used for statistical examination. HPLC analysis indicates that Am-EE contains atractylenolide-1 (AT-1, 1.33%, w/w) and atractylenolide-2 (AT-2, 1.25%, w/w) (Additional Figure. A1). Gastric tissue damage (induced by HCl Ethanol) was significantly decreased in SD rats following intra-gastric application of 35 mg/kg Am-EE. Indistinguishable to the anti-inflammation effects of 35 mg/kg ranitidine (gastric medication). Am-EE treatment also reduced LPS-mediated nitric oxide (NO) and prostaglandin E 2 (PGE 2) production. The mRNA and protein synthesis of inducible cyclooxygenase (COX)-2 and NO synthase (iNOS) was down-regulated following treatment in RAW cells. Am-EE decreased NF-κB (p50) nuclear protein levels and inhibited NF-κB-stimulated LRA activity in RAW cells. Lastly, Am-EE decreased the up-regulated levels of phosphorylated IκBα and Akt proteins in rat stomach lysates and in LPS challenged RAW cell samples. Our study illustrates that Am-EE suppresses the Akt/IκBα/NF-κB pathway and exerts an anti-inflammatory effect. These novel conclusions provide a pharmacological basis for the clinical use of the A. macrocephala rhizome in the treatment and prevention of gastritis and gastric cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC -mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC -signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8 . In our combined cohort, we identified frequent inactivating mutations in AJUBA , ZNF750 , and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1 , in addition to known mutations. Functional analyses suggest roles for several genes ( CBX4 , CBX8 , AJUBA , and ZNF750 ) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets. [ABSTRACT FROM AUTHOR]

A complete picture of the evolution of miRNA combinatorial regulation requires the synthesis of information on all miRNAs and their targets. MiR156 and miR529 are two combinatorial regulators of squamosa promoter binding protein-like (SBP-box) genes. Previous studies have clarified the evolutionary dynamics of their targets; however, there have been no reports on the evolutionary patterns of two miRNA regulators themselves to date. In this study, we investigated the evolutionary differences between these two miRNA families in extant land plants. Our work found that miR529 precursor, especially of its mature miRNA sequence, has a higher evolutionary rate. Such accelerating evolution of miR529 has significantly effects on its structural stability, and sequence conservation against existence of itself. By contrast, miR156 evolves more rapidly in loop region of the stable secondary structure, which may contribute to its functional diversity. Moreover, miR156 and miR529 genes have distinct rates of loss after identical duplication events. MiR529 genes have a higher average loss rate and asymmetric loss rate in duplicated gene pairs, indicating preferred miR529 gene losses become another predominant mode of inactivation, that are implicated in the contraction of this family. On the contrary, duplicated miR156 genes have a low loss rate, and could serve as another new source for functional diversity. Taken together, these results provide better insight into understanding the evolutionary divergence of miR156 and miR529 family in miRNA combinational regulation network. [ABSTRACT FROM AUTHOR]