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Soil and water conservation (SWC) measures are among the most important ways to control soil erosion in mountainous areas. However, little is known about the application of SWC measures on soil erosion over large areas. We developed a new framework for investigating the distribution of engineering measures by using high-resolution remote sensing images at a large scale, and we assessed the soil conservation effects of those measures on the Yunnan Plateau (YP) in China using the Chinese Soil Loss Equation (CSLE). We detected 43,398 km2 of soil conservation measures on the YP, accounting for 53% of farmland. The area of conservation measures decreased with an increase in slope gradient. Different types of engineering measures had different spatial distribution patterns, and together they conserved 5.08 × 108 t of soil each year on the YP. The effects of engineering measures on soil erosion decreased with an increase in slope. Furthermore, more than 82% of soil loss from farmlands was attributed to areas without engineering measures, and steep-slope farmland without such measures was the main source of soil erosion on the YP. Our results suggest that engineering measures were effective in soil conservation, but the effects varied with topography on the YP. We suggest that further studies focus on the relationships between the soil erosion and grain supply of farmlands without engineering measures to provide a basis for the formulation of land use planning policy in China.

In this study, a mathematical model of axial ultrasonic vibration enhanced friction stir welding is developed to predict the effect of ultrasonic vibration during friction stir welding of aluminum alloys 6061. The research focuses on the effect of with/without axial ultrasonic vibration in friction stir welding by the temperature distribution and material flow characteristics. Results indicate that the addition of axial ultrasonic vibration can reduce the heat generation rate and the temperature of contact surface between the rotating tool tip and the workpiece during the welding process, and improve the flow rate of the plastic metal material near the rotating tool tip. Under the same process parameters, when the vibration frequency is constant, as the vibration amplitude increases, the peak temperature of the welding decreases gradually, and the flow rate of the plastic metal material gradually increases

A 316L/Q345R stainless steel-clad plate after hot rolling was subjected to three heat treatments: rapid cooling, rapid cooling and tempering, high-temperature rapid cooling, and low-temperature slow cooling to improve its microstructure and properties. Its specimens were prepared by of an hot rolling evacuated package. Optical microscopy and energy dispersive spectroscopy were applied to examine the microstructure and constituents of the specimens. The mechanical properties under different treatments were evaluated in shear, tensile, and impact tests. The results demonstrate grain refinement and improved properties after heat treatment. After rapid cooling the microstructure of the specimen is mainly composed of martensite, strength increases, ductility is poor, and elongation is relatively low, only 12.7%. The microstructure and ductility are certainly at their optimum after rapid cooling and tempering, elongation tends to 16.7%, but performance still does not meet the practical requirements. After high-temperature rapid cooling plus low-temperature slow cooling, the microstructure mainly consists of bainite, fine ferrite, and a small amount of pearlite. The clad plate exhibits excellent performance due to the combined soft and hard phase structure, shear strength reaches 397 MPa, and elongation is 22.2%, both fulfill the requirements.

Sweet cherry (Prunus avium L.) was firstly introduced into China in 1871. Initially, it was only planted in temples and home gardens in northern China, mainly distributed in Bohai Bay region. With the rapid development of China’s economy, cultivation area and production of sweet cherry have increased significantly since the 1980s. By 2016, the total sweet cherry plantation area reached about 180,000 ha, the harvested area and greenhouse cultural area are approximately 100,000 and 10,000 ha, with the production of 700,000 and 90,000 t, respectively. Greenhouses provide better conditions for tree growth and thus produces cherries with earlier harvest, better quality and higher yield. Nowadays, the major cultivation regions of sweet cherry are mainly distributed in Bohai Bay region and along the Longhai railway line. The major cultivars include ‘Hongdeng’, ‘Krupnoplodnaja’, ‘Tieton’, ‘Brooks’, ‘Van’, ‘Rainier’, ‘Lapins’, ‘Summit’, ‘Sunburst’, ‘Regina’, etc. ‘Hongdeng’ is the most popular cultivar in China, which has many attractive traits such as early maturity (‘Burlat’ +2~3), red color, larger fruit size (8 g), higher SSC and tasty flavor. Major rootstocks are mostly derived from P. pseudoceresus, P. serrulata, P. cerasus, P. mahaleb, and interspecific hybrids. The main training systems include traditional type (small and sparse canopy shape), central leader, bush and wall trellis, etc.

BACKGROUND: Calcification was recently found to be present in the majority of cerebral aneurysms, though how calcification and the presence or absence of co-localized lipid pools affect failure properties is still unknown. OBJECTIVE: The primary objective is to quantify the biomechanical effect of a macro-calcification with surrounding Near-Calcification Region (NCR) of varying mechanical properties on tissue failure behavior. METHODS: We utilized a structurally informed finite element model to simulate pre-failure and failure behavior of a human cerebral tissue specimen modeled as a composite containing a macro-calcification and surrounding NCR, embedded in a fiber matrix composite. Data from multiple imaging modalities was combined to quantify the collagen organization and calcification geometry. An idealized parametric model utilizing the calibrated model was used to explore the impact of NCR properties on tissue failure. RESULTS: Compared to tissue without calcification, peak stress was reduced by 82% and 49% for low modulus (representing lipid pool) and high modulus (simulating increase in calcification size) of the NCR, respectively. Failure process strongly depended on NCR properties with lipid pools blunting the onset of complete failure. When the NCR was calcified, the sample was able to sustain larger overall stress, however the failure process was abrupt with nearly simultaneous failure of the loaded fibers. CONCLUSIONS: Failure of calcified vascular tissue is strongly influenced by the ultrastructure in the vicinity of the calcification. Computational modeling of failure in fibrous soft tissues can be used to understand how pathological changes impact the tissue failure process, with potentially important clinical implications.

To explore the factors influencing the short-term efficacy of percutaneous transforaminal endoscopic lumbar discectomy in the treatment of lumbar disc herniation is the main objective. 100 patients with lumbar disc herniation who were treated in our hospital from February 2017 to February 2019 were selected as the control group (n=85, effective) and observation group (n=15, ineffective), the effective rate of treatment was statistically analyzed. Visual analogue scale and Japanese orthopaedic association scores were compared before surgery, 3 mo after surgery and 6 mo after surgery. The influencing factors of lumbar disc herniation treatment effect were analyzed. The effective rate of lumbar disc herniation patients treated by percutaneous transforaminal endoscopic lumbar discectomy surgery was 85.00 %. Compared with that before surgery, the visual analogue scale score of lumbar disc herniation patients was significantly decreased 3 mo after surgery and 6 mo after surgery, but the Japanese orthopaedic association score was significantly increased (p

This work analyzed the spatial and temporal variations of the extreme precipitation over China during the period 1982 to 2019, based on GPCC data. Meanwhile, the spatially clustering characteristic of China is evaluated based on the trends of summer precipitation through K-means. This is the first to clustering based on the trend of summer precipitation. The results indicated that the spatial distribution of MK trends for the summer precipitation indices over China during 1982 ~ 2019 shows increasing and decreasing trends in different regions. The extreme precipitation has been found mainly in Pearl River Basin, Southeastern River Basin, Huaihe River Basin, and the lower reaches of the Yangtze River. The risk of floods in SERB (the Southeastern River Basin), especially those caused by short-term heavy precipitation, may increase in recent decades. Four clusters are identified through K-means, which can be named as stable (59%), extreme wetter (5%), dryer (19%), and wetter (17%) zones. Combining the spatial distribution of the multi-year average of precipitation indicators and four clusters, the ‘wet to wetter and dry to dryer’ is found in China summer precipitation.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Aims For a given passively-distributed lipophilic drug, the extent of in vivo distribution (pharmacokinetic volume of distribution, Vd ) in obese individuals increases in relation to the degree of obesity. The present study had the objective of evaluating drug distribution in relation to in vitro lipophilicity, and the relative increase in Vd associated with obesity across a series of drugs. Methods Cohorts of normal-weight control and obese subjects received single doses of drugs ranging from hydrophilic (acetaminophen, salicylate) to lipophilic (imipramine, verapamil). Lipid solubility was measured by the log-transformed values of the high-pressure liquid chromatographic (HPLC) retention index (Log10 (HPLC)), and the octanol-water partition coefficient (LogP). Results Among normal-weight controls, Vd normalized for protein binding was highly correlated with Log10 (HPLC) (R2 = .65) and with LogP (R2 = .78). Vd of all drugs was increased in the obese cohort, but the relative increase (compared to controls) for individual drugs was disproportionately greater as lipid solubility increased. Since clearance was unrelated to lipophilicity, the increased Vd produced a parallel disproportionate increase in elimination half-life in the obese cohort that was associated with Log10 (HPLC) (R2 = .62). Conclusion Lipophilicity is a principal correlate of in vivo Vd , as well as the increased Vd of drugs in obese patients. The consequent prolongation of half-life in obesity has clinical safety implications in terms of delayed drug accumulation and washout during and after chronic dosage. The magnitude and importance of this effect for a given drug depends on the degree of obesity, as well as the lipid-solubility of the specific drug.

Wa Na Qi(), is a traditional-curing male impotence medicinal. We have made several conclusions through a field investigation to Antarctica, material medica literature research, and current market investigation. Throughout history, Wa Na Qi (also known ashaigou shen) was a word of vague connotation which was not the meaning of a specific product. However, the most common meaning of Wa Na Qi was the penises of several different species of seals. The name Wa Na Qi was adapted from a foreign word, and it is believed to sound like walrus, which has also been credited as a source for Wa Na Qi. In Chinese, Wa Na was a reference to the roundness of the walrus but eventually became a general description of heaviness. Later, it became a name for fur seals. The Song Dynasty Materia Medica腽肭脐为一味传统的补肾壮阳药，通过本草考证、香港及内地市场及生产厂家的调查，南极半岛及南设得兰群岛海域的实地考察，提出以下结论：腽肭脐(海狗肾)在历史上其实是一个比较笼统的概念，主要指源自海狗、海豹类几种海洋动物的外肾。腽肭脐一词，属于古代的外来语，其读音贴近海狗肾来源之一的海象Walrus一词。因为海象的肥耎，汉语中出现了一个音译词"腽肭"。最初宋代的《本草图经》与明代的《本草品汇精要》描述的原动物为海豹类。《本草纲目》(金陵版)所绘者与有鬃毛的海狗(毛皮海狮)的特征比较符合。《补遗雷公炮制便览》及此后本草书中，加入了主观臆想成分，进而以讹传讹。通过在南极周边海域的实地考察，了解到历史上腽肭脐可能源自海狗(毛皮海狮)及海豹类，这与现今药材市场海狗与海豹两大种群基本吻合。经对现今中国内地与香港市场品种实地考察，以海狗肾之名售卖者，包括海狗、海象、海豹类外生殖器。.

The oral direct-acting antiviral drug (DAA) offers tremendous opportunities to eliminate hepatitis C. We analyzed the market trends, price trends and global treatment progress of DAA drugs by reviewing the guidelines recommended by the World Health Organization for the treatment of hepatitis C, and discusses the current accessibility of DAA treatment and its influencing factors. The results show that WHO recommends the use of DAA for treatment of hepatitis C, but the price of DAA is expensive. Although some countries have taken measures to lower prices and improve accessibility, the advancement of DAA treatment has been unsatisfactory and coverage is still not high. In addition to price, factors such as strategy, health system, accessibility and service provision need to be considered, and public health methods should be adopted to promote DAA treatment to achieve the elimination of hepatitis C.全口服直接抗病毒药物（DAA）的上市为消除丙肝带来巨大机遇。本文通过梳理世界卫生组织近年更新的关于丙肝治疗的指南建议，并分析DAA药品的市场动态、价格趋势以及全球治疗进展，探讨目前DAA药物价格情况，治疗的可及性及其影响因素。结果显示WHO推荐使用DAA进行治疗，但DAA的价格昂贵，虽然各国采取措施降低价格，提高可及性，但DAA治疗的推进却不尽如人意，覆盖面依然不高。除了价格以外，还需考虑策略、卫生系统、可及性和服务提供等因素，采用公共卫生方法，推进DAA治疗，以实现丙肝的消除。.

This study investigated the effects of supplemented l-arginine (l-Arg) in broiler breeder hens' diets on the embryonic development and physiological changes of offspring during the hatching period. A total of 480 35-wk-old healthy female Arbor Acres broiler breeders were randomly divided into 6 groups and fed a corn and soybean meal diet with 6 digestible Arg levels (0.96%, 1.16%, 1.35%, 1.55%, 1.74%, and 1.93%). After a 10-wk experiment, eggs were collected for incubation. At embryonic day (E) 11 to E21, eggs, embryos, and organs (liver, breast muscle, and thigh muscle) were weighed. Total protein, urea nitrogen, creatinine, cholesterol, and triglyceride in plasma, were measured. Plasma level of immunoglobulin G (IgG), immunoglobulin M (IgM), and nitric oxide synthase (NOS) were measured at E13, E17, and E21. Messenger RNA expression of carbamoyl phosphate synthase I (CPS1), ornithine transcarbamylase (OTC), and argininosuccinate synthase (ASS) in liver and breast muscle tissues was assessed at E13, E17, and E21. The results showed that 1.16% Arg in maternal diet increased egg weight (P < 0.05). The level of Arg in maternal diet has a significant effect on organ index and embryo weight of multiple embryonic days (P < 0.05). Embryonic plasma total protein concentration was significantly affected by maternal dietary Arg level (P < 0.05) and exhibited quadratic responses at E11, E15, E17, and E21 (P < 0.01). Plasma urea nitrogen, creatinine, triglyceride, and cholesterol level were also significantly affected by the level of maternal Arg at different embryonic ages (P < 0.05). Dietary digestible Arg levels quadratically influenced plasma urea nitrogen level at E21 (P < 0.05) and cholesterol concentration at E17 and E19 (P < 0.01). L-Arg supplementation in maternal diet significantly improved the IgG level at E17 and E21 (1.16%, 1.35%, 1.55%, and 1.74%; P < 0.05), the IgM level at E13 (1.35%, 1.55%, 1.74%, and 1.93%) and E17 (P < 0.05) and the NOS level at E13, E17, and E21 (P < 0.05). Maternal dietary L-Arg supplementation significantly improved the expression of CPS1 gene, OTC gene (1.16%, 1.35%, and 1.55%), and ASS gene (1.35% and 1.55%) in the liver (P < 0.05), and also enhanced the CPS1 gene (except 1.35%) and OTC gene (1.55% and 1.74%) expression in the breast muscle (P < 0.05). In conclusion, maternal Arg level affected the embryonic development of offspring and regulated the apparent metabolic programming and immunity state of the embryo. Arginine level of 1.55% in hens' diet was beneficial to the protein synthesis and immunity of the offspring in the embryonic period, and it was recommended to obtain healthy offspring.

Making use of Hilbert-pair-based digital filtering, intensity modulation and passive optical coupling, optical filter- and O-E-O conversion-free flexible ROADMs are, for the first time, experimentally demonstrated to perform DSP-enabled dynamic add/drop operations at wavelength, sub-wavelength and spectrally overlapped sub-band levels. Extensive experimental explorations of physical-layer add/drop operation performances and their robustness to variations in both differential optical power dynamic range and drop RF signal power are also undertaken in IMDD-based optical network nodes. It is shown that the ROADM add/drop operation performances are independent of the sub-band spectral location, and that the add/drop operations introduce optical power penalties of ≤ 1.8 dB. In addition, for a total optical power as low as −12 dBm, the add operation still can tolerate a differential optical power dynamic range of > 2 dB. Whilst for the drop operation, an optical power penalty of 2 dB is observed over a drop RF signal power variation range of 7.1 dB. Experimental results indicate that the add/drop operations of DSP-switched ROADMs have excellent performance robustness to considerably relax stringent requirements on network components.

Newly proposed DSP-enabled ROADMs free from O − E − O conversions offer an excellent opportunity of utilising advanced DSP techniques to greatly simplify complicated conventional ROADM configurations, to introduce more highly desired networking functionalities and to create a programmable environment capable of addressing elastic 5G slicing and supporting the SDN paradigm. In this paper, detailed analytical and numerical investigations are performed, for the first time, of DSP-enabled ROADM drop operation performances in coherent systems. Two simple but effective drop operation approaches are proposed analytically and validated numerically, which, compared to the previously published quadrature-point-biased Mach–Zehnder modulator-based ROADM drop element subject to a standard drop RF signal, can not only improve the minimum required OSNR requirements by approximately 10 dB, but also considerably enhance the drop operation performance robustness to modulation index variations.

Background: Pathological complete response (pCR) is accepted by FDA as a surrogate endpoint for accelerated approval of targeted agents in combination with chemotherapy based on better long-term outcomes compared to residual disease (Cortazar 2014). Methods: The multi-center, adaptively-randomized I-SPY2 platform trial uses pCR as the primary endpoint to identify investigational agents that will improve outcomes in women with stage 2/3 breast cancer with high risk of early recurrence, across all signatures, based on hormone receptor (HR), HER2, and 70-gene (MammaPrint) status. For patients with HR+ HER2- tumors, only 70-gene (Mammaprint) high-risk patients are enrolled. To date, 1200+ patients have been randomized to one of 14 arms: control (paclitaxel followed by AC); veliparib/carboplatin; neratinib; MK2206; trebananib; trastuzumab/pertuzumab; ado-trastuzumab emtansine/pertuzumab; pembrolizumabx4; ganitumab/metformin; ganetespib; PLX-3397. 7 agents graduated in at least one signature (> 85% probability of success in a 300-patient phase III confirmatory trial); 2 did not graduate; 1 stopped for toxicity, and 3 are enrolling (patritumab/trastuzumab, talazoparib/irinotecan, pembrolizumabx8). Local pathologists were centrally trained using the Residual Cancer Burden (RCB) assessment to ensure uniform evaluation and response classification; RCB 0 = pCR. Results: We evaluated the relationship between pCR and event free (EFS) and distant disease free survival (DDFS) in the first 522 pts (median follow-up:2.5 years). 180 pts achieved pCR (36%) while 338 did not (RCB=1-3). There were 82 EFS and 65 DRFS events. Over the entire group (including all arms), pCR was highly associated with 3-year EFS (p 3-year survival (pCR group)Hazard Ratio OverallOverallHR+/HER2-HER2+TNBCEFS97%0.08 (0.03-0.23)0.14 (0.02-1.04)0 (NA)0.11 (0.03-0.37)DDFS98%0.08 (0.03-0.26)0.17 (0.01-1.23)0 (NA)0.09 (0.02-0.40) Conclusions: The first long-term efficacy results from the I-SPY2 TRIAL demonstrate that achieving pCR is a very strong surrogate endpoint for improved EFS and DDFS in a high-risk population, across all treatment arms, regardless of subtype. I-SPY2 shows substantially lower estimated EFS hazards for patients achieving pCR, compared to the 5 yr EFS hazard ratio for pCR vs not in Cortazar (hazard ratio 0.49), demonstrating important differences between a metaanalysis compared to a platform trial with uniform high-risk eligibility, standardized pathology assessment, and multiple targeted therapies. Our data support the use of pCR as a primary endpoint for accelerated approval of new drugs if EFS is evaluated in the same population. Based on these findings, the I-SPY2 TRIAL will test whether therapy can be deescalated or escalated for individual patients with the goal of achieving pCR for all. Citation Format: Yee D, DeMichele A, Isaacs C, Symmans F, Yau C, Albain KS, Hylton NM, Forero-Torres A, van't Veer LJ, Perlmutter J, Rugo HS, Melisko M, Chen Y-Y, Balassanian R, Krings G, Datnow B, Hasteh F, Tipps A, Weidner N, Zhang H, Tickman R, Thornton S, Ritter J, Amin K, Klein M, Chen B, Keeney G, Ocal T, Feldman M, Klipfel N, Sattar H, Mueller J, Gwin K, Baker G, Kallakury B, Zeck J, Duan X, Ersahin C, Gamez R, Troxell M, Mansoor A, Grasso LeBeau L, Sams S, Wisell J, Wei S, Harada S, Vinh T, Stamatakos MD, Tawfik O, Fan F, Adams A, Rendi M, Minton S, Magliocco A, Sahoo S, Fang Y, Hirst G, Singhrao R, Asare SM, Wallace AM, Chien AJ, Ellis ED, Han HS, Clark AS, Boughey JC, Elias AD, Nanda R, Korde L, Murthy R, Lang J, Northfelt D, Khan Q, Edmiston KK, Viscusi R, Haley B, Kemmer K, Zelnak A, Berry DA, Esserman LJ. Pathological complete response predicts event-free and distant disease-free survival in the I-SPY2 TRIAL [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS3-08.

This meta-analysis aimed to clarify the actual association between the phosphodiesterase type 5 inhibitors (PDE5-Is) use and the risk of melanoma in erectile dysfunction (ED) patients. A systematic literature search was conducted in online databases in October, 2016 to identify studies focusing on the association between PDE5-Is use and the risk of melanoma. Summarized multivariate adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were calculated to assess the strength of associations. A total of six clinical trials containing more than one million participants were included. ED patients using PDE5-Is shared a significant high risk of melanoma (RR=1.12, 95% CI=1.03-1.21, p=0.006). Positive associations were observed in all kinds of prescriptions: single prescription (RR=1.20, 95% CI=1.06-1.35, p=0.003), medium number of prescription (RR=1.15, 95% CI=1.01-1.30, p=0.03), and high number of prescription (RR=1.18, 95% CI=1.05-1.34, P=0.006). Additionally, PDE5-Is were also found to be significantly associated with increased risk of basal cell carcinoma (RR=1.14, 95% CI=1.09-1.19, p

Although Flotillin 1 (FLOT1) is highly expressed in various human cancers, its relationship with ovarian cancer (OC) remains unknown. This study determines FLOT1 expression in human ovarian tumors and examines its effect on OC cell proliferation. FLOT1 protein expression was assessed in a tissue microarray by immunohistochemical staining. We found that 81.48% malignant and 50% borderline tumors were FLOT1 protein-positive, whereas benign tumors and normal ovarian tissues were negative. The staining was strongest in serous malignant tumor and transitional cell carcinoma and weakest in mucinous tumor. Differentially expressed FLOT1 in freshly isolated serous tumors was confirmed by Western blot and we then evaluated FLOT1 expression association with OC patients' clinical characteristics. Histological typing established that FLOT1 protein expression was significantly associated with serous tumor (P Keywords: cell proliferation, epithelial ovarian cancer, FLOT1, miRNA, therapeutic target, tumorigenesis.

The Aktobe project is the largest oil and gas producing area of PetroChina in Central Asia. However, after years of exploitation, the pressure of the reservoir has dropped, making it difficult to increase the production of a single well. Both the Kenkyak block and North Troyes block of the project have induced fractured leakage, and frequent leakage affects safe and efficient drilling and completion operations and production. Therefore, the research on leakage prevention and control technology is very necessary. This article focuses on the characteristics of the cracks in the high-pressure area of the Kenkyak block and the cracks in the low-pressure area of the North Troyes block. Aiming at the fracture characteristics of the high-pressure zone in the Kenkyak block and the low-pressure zone in North Troyes block, and taking advantage of the synergistic effect of supramolecules, a supramolecular plugging-while-drilling agent was developed based on the deformable fiber composite gel. It forms a strong adhesion plugging layer on the inner wall of the leakage channel through the strong adhesion force, and it achieves a good plugging effect. The 300-500mD sand disc bearing pressure could reach 700psi when adding 3% agent, and the bearing pressure of 3-5D permeability sand disc could reach above 450psi. A supramolecular static plugging agent was also developed based on the dilatant gel. It is rich in strong shear reversible gel with supramolecular structure, which guarantees its pumpability and plugging performance. The effective rate of one-time plugging is over 80%, and the viscosity is greatly reduced after the gel is broken for 72hr, which benefits the reservoir protection.

We aimed to determine whether high-resolution specimen-positron emission mammography (PEM) using fluorodeoxyglucose (18F-FDG) can reveal extension of breast cancer in breast-conserving surgery (BCS), and assess the safety of radiation exposure to medical staff. Sixteen patients underwent positron emission tomography, and then BCS with intraoperative frozen section analysis on the same day. Resected specimens with remaining 18F-FDG accumulation were scanned by high-resolution PEM. At least 1 day after surgery, tumour extension was evaluated by three independent experienced readers and by binarized images from the specimen-PEM data. Intraoperative exposure of medical staff to 18F-FDG was measured. Specimen-PEM evaluations of binarized images and the three investigators detected all (100 %, 12/12) invasive lesions and 94.4 % (17/18) of in situ lesions using both methods. The positive predictive value of the accumulated lesions was 74.4 % (29/39) for the binarized images and 82.9 % (29/35) for the three investigators. Analysis of intraoperative frozen sections detected 100 % (2/2) of the margin-positive cases, also detected by both specimen-PEM evaluation methods with no false-positive margin cases. The mean exposure of the medical staff to 18F was 18 μSv. Specimen-PEM detected invasive and in situ lesions with high accuracy and allowable radiation exposure. • Specimen-PEM detected invasive and in situ lesions with high accuracy. • Specimen-PEM predicted complete resection with the same accuracy as frozen section analysis. • Breast-conserving surgery after fluorodeoxyglucose injection was performed with low medical staff exposure.

The impacts of the channel frequency response roll-off effect on upstream optical OFDM transmission performance in digital filter multiple access (DFMA) passive optical networks (PONs) based on intensity modulation and direct detection (IMDD) are investigated, in terms of BER versus received optical power performance, optical network unit (ONU) transmission capacity, ONU launch power variation (LPV) range, and inter-ONU sample timing offset. The effect of signal bandwidth is also explored by comparing tolerance with the channel roll-off effect for two different signal bandwidths. Over all of the aforementioned aspects, good agreements are obtained between numerical simulations and experimental measurements. The results provide important insights into channel roll-off-induced performance dependencies to facilitate cost-effective designs of both DFMA transceivers and IMDD DFMA PONs.

Micro-dystrophins are highly promising candidates for treating Duchenne muscular dystrophy, a lethal muscle disease caused by dystrophin deficiency. Here, we report robust disease rescue in the severe DBA/2J-mdx model with a neuronal nitric oxide synthase (nNOS)-binding micro-dystrophin vector. 2 × 1013 vector genome particles/mouse of the vector were delivered intravenously to 10-week-old mice and were evaluated at 6 months of age. Saturated micro-dystrophin expression was detected in all skeletal muscles and the heart and restored the dystrophin-associated glycoprotein complex and nNOS. In skeletal muscle, therapy substantially reduced fibrosis and calcification and significantly attenuated inflammation. Centronucleation was significantly decreased in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles but not in the quadriceps. Muscle function was normalized in the TA and significantly improved in the EDL muscle. Heart histology and function were also evaluated. Consistent with the literature, DBA/2J-mdx mice showed myocardial calcification and fibrosis and cardiac hemodynamics was compromised. Surprisingly, similar myocardial pathology and hemodynamic defects were detected in control DBA/2J mice. As a result, interpretation of the cardiac data proved difficult due to the confounding phenotype in control DBA/2J mice. Our results support further development of this microgene vector for clinical translation. Further, DBA/2J-mdx mice are not good models for Duchenne cardiomyopathy.

A novel magnetic composite coagulant, prepared from nano-Fe3O4 and poly-aluminum chloride, was introduced to pre-treat mature landfill leachate. The coagulation performance of the coagulant as well as its microstructural morphology was discussed. Coagulation experimental results revealed that the coagulation performance of the landfill leachate using the new coagulant was better than that using poly-aluminum chloride alone, with COD and color removals above 60 and 68%, respectively. Based on the analysis of three-dimensional excitation–emission matrix spectrum, the fluorescence signals of treated leachate are totally reduced by the magnetic composite coagulant. The components of dissolved organic matters in the wastewater are removed in different degrees. Fourier transform infrared spectra analysis shows that the magnetic composite coagulant, which is a multi-core polymer with hydroxyl ligands and nano-Fe3O4, has a complex valence and crystal structure. Besides, X-ray diffraction pattern analysis indicates that the chemical composition of the magnetic composite coagulant is not changed significantly, which has comprehensively combined the chemical characteristics of both nano-Fe3O4 and poly-aluminum chloride, whereas the specific surface area of the novel magnetic composite coagulant effectively increased by nano-Fe3O4 particles under the analysis of scanning electron microscope spectral. The specific surface area analysis indicates that the magnetic composite coagulant is interconnected by narrow cracks and holes and has a high specific surface area and developed pore structure, which is also similar to the typical porous-type materials. Therefore, the nano-Fe3O4 compounded with poly-aluminum chloride leads to a larger specific surface, smaller average pore diameter, and more pore volume of the novel coagulant.

Summary Epstein–Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing–remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS.

CRISPR editing of muscle stem cells (MuSCs) with adeno-associated virus serotype-9 (AAV9) holds promise for sustained gene repair therapy for muscular dystrophies. However, conflicting evidence exists on whether AAV9 transduces MuSCs. To rigorously address this question, we used a muscle graft model. The grafted muscle underwent complete necrosis before regenerating from its MuSCs. We injected AAV9.Cre into Ai14 mice. These mice express tdTomato upon Cre-mediated removal of a floxed stop codon. About 28%–47% and 24%–89% of Pax7(+) MuSCs expressed tdTomato in pre-grafts and regenerated grafts (p > 0.05), respectively, suggesting AAV9 efficiently transduced MuSCs, and AAV9-edited MuSCs renewed successfully. Robust MuSC transduction was further confirmed by delivering AAV9.Cre to Pax7-ZsGreen-Ai14 mice in which Pax7(+) MuSCs are genetically labeled by ZsGreen. Next, we co-injected AAV9.Cas9 and AAV9.gRNA to dystrophic mdx mice to repair the mutated dystrophin gene. CRISPR-treated and untreated muscles were grafted to immune-deficient, dystrophin-null NSG.mdx4cv mice. Grafts regenerated from CRISPR-treated muscle contained the edited genome and yielded 2.7-fold more dystrophin(+) cells (p = 0.015). Importantly, increased dystrophin expression was not due to enhanced formation of revertant fibers or de novo transduction by residual CRISPR vectors in the graft. We conclude that AAV9 effectively transduces MuSCs. AAV9 CRISPR editing of MuSCs may provide enduring therapy.

Amelogenesis imperfecta (AI) is a group of genetic disorders of defective dental enamel. Mutation of

e14006 Background: Previous studies have shown that brain metastases of non-small cell lung cancer (NSCLC) with positive driver genes have poor prognosis. There is still lack of prospective studies on the efficacy and safety of targeted therapy combined with concurrent radiotherapy for brain metastases(BM). Methods: NSCLC patients, with ECOG score 0-2, having MRI confirmed brain or meningeal metastases were eligible. Patients must have driver gene mutation and received corresponding targeted therapy. The intracranial radiotherapy regimen was SRS or whole brain radiotherapy. The primary objective was iPFS (intracranial progression-free survival); Secondary objectives were: iORR (intracranial objective response rate), PFS (progression-free survival), OS (overall survival). MMSE (Mini Mental State Examination) and FACT-Br was carried out before/after weekly radiotherapy and during systematic treatment. Treatment-related toxicities were assessed according RTOG/EORTC criteria. Tumor responses were evaluated using RECIST V1.1 criteria. Survival analysis was performed using the Graphprism version 6.0 by Kaplan-Meier method and log-rank test. Results: 23 NSCLC with BM was included. Among them, 10 patients were newly diagnosed with NSCLC BM. 2 patients’ BM progressed after targeted therapy. 11 NSCLC patients were newly diagnosed with BM after targeted therapy. 91.3% of patients presented an EGFR mutation, including primarily EGFR 19-exon deletion, EGFR 21-L8585R. 11.5% presented with c-MET mutation. Median age was 58.34 yrs(44-71yrs). Patients were mostly treated with Erolotinib and Gefitinib. All patients were adenocarcinoma. At last follow-up, for patients newly diagnosed with NSCLC BM, 8 patients had achieved intracranial progression, and 7 patients had reached OS, of which 1 died before completing WBRT. The median iPFS was 9.3m(95%CI:0.571-4.055) and the median OS was 11.9m (95%CI:0.2752 -2.732). As for patients who progressed after targeted therapy, one patient’s OS was 4.4m, iPFS of the other patient was 3.9m. Among NSCLC patients who were newly diagnosed with BM after targeted therapy, 8 patients had achieved intracranial progression and 5 patients had reached OS. The median iPFS was 6.13m (95%CI:0.247-1.751) and the mOS was 13.8m (95%CI:0.3660-3.634). Common adverse effects include dry skin, fatigue, dizziness, headache, anorexia, and grade I myelosuppression and no serious adverse events (SAEs); MMSE and FACT-Br scores were no significant differences at baseline and follow-up. Conclusions: In stage IV brain metastatic NSCLC with driver gene mutation, targeted therapy combined with concurrent radiotherapy for BM is tolerable, and there is no significant impact on the quality of life and cognitive function after radiotherapy. The evaluation of efficacy requires further follow-up. Support:LC2019ZD009,81972853 and 81572279.

The cDNA sequence of the growth hormone receptor (GHR) from the black Muscovy duck was obtained and compared to the mRNA expression of growth hormone (GH) in the breast and leg muscles during 2-13 weeks of age using quantitative RT-PCR. The cDNA sequence of the Muscovy duck GHR gene is 1903 bp in length, with an 1830 bp coding region that encodes 609 amino acids. It exhibits > 92.9% homology with the poultry GHR cDNA and amino acid sequences. Overall, GHR mRNA expression was the highest at 2 weeks and the lowest at 13 weeks of age, exhibiting different profiles in different muscles. In the breast muscles, the GHR mRNA level declined sharply at 2-4 weeks, maintained at a plateau at 4-10 weeks and decreased slightly at 10-13 weeks. In the leg muscles, a gradual and slow decrease was observed during the whole period of 2-13 weeks. Robust extra-pituitary GH mRNA expression was detected in the muscles and the expression profile was highly correlated with that of GHR mRNA, in contrast to the inverse correlation between the pituitary GH and tissue GHR levels shown previously. These data suggest that the locally synthesised GH in the muscles, rather than the pituitary GH, is more closely associated with GHR and may be more critical for the regulation of muscle growth and contribute to the tissue-specific effects of GH.