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Keywords Eutrophication; Cyanobacterial blooms; Quantile regression; Water depth; Chlorophyll a Highlights * Site-specific algal limiting factors were identified for the studied 54 freshwaters. * Algae in 16% and 84% sites were limited by nutrient and non-nutrient factors, respectively. * Algae in the studied freshwaters would be potentially P-limited with depths of >5.2 m. * Alleviating lake blooms by nutrient reduction requires different strategies depending on depths. Abstract Knowledge of phytoplankton limiting factors is essential for cost-efficient lake eutrophication management. Herein, we propose a statistical framework to explore site-specific phytoplankton limiting factors and their dependence on water depth (WD) in 54 lakes in the Chinese Eastern Plains ecoregion. First, the maximal chlorophyll a (Chla) response to total N (TN) or P (TP), representing a region-specific 'standard' model where phytoplankton were primarily N- or P-limited, was quantified using a 95% quantile regression. Second, site-specific limiting factors were identified using analogical residual analysis. N- or P-limitation was inferred if Fraction.sub.TN (i.e. fraction of Chla observed and predicted by the 'standard' model for a given TN) > 0.95 or Fraction.sub.TP >0.95; if both Fraction.sub.TN and Fraction.sub.TP 5.2 m can entail control of N, N+P, and P, respectively. This study provides essential information for formulating context-dependent bloom control for lakes in our study area and serves as a valuable reference for developing a cost-efficient eutrophication management framework for other regions. Author Affiliation: (a) Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing, 210008, PR China (b) Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, PR China (c) Jiangsu Provincial Key Laboratory of Environmental Engineering, Jiangsu Provincial Academy of Environmental Science, Nanjing, 210036, PR China (d) National Engineering Laboratory for Lake Pollution Control and Ecological Restoration, Chinese Research Academy of Environmental Sciences, Beijing, 100012, PR China * Corresponding author. Taihu Laboratory for Lake Ecosystem Research, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing, 210008, PR China. Article History: Received 3 April 2022; Revised 7 June 2022; Accepted 14 June 2022 Byline: Wei Zou (a), Guangwei Zhu [gwzhu@niglas.ac.cn] (a,*), Hai Xu (a), Mengyuan Zhu (a), Boqiang Qin (a), Yunlin Zhang (a), Yonghong Bi (b), Miao Liu (c), Tianhao Wu (d)

Keywords Eutrophication; Shallow lakes; Light limitation; Phytoplankton; Atmospheric stilling Highlights * Nitrogen and phosphorus reduction targets in Lake Taihu were proposed. * Increasing algal sensitivity to nutrients from 2005 to 2020 were observed in Lake Taihu. * A more stable water column led to the increasing annual peak Chla from 2005 to 2020. * Water stability promotes algal growth mainly by increasing light availability. Abstract Eutrophication and its associated algal blooms are principal environmental challenges confronting lakes worldwide. The empirical relationships between nutrient (total nitrogen, TN; total phosphorus, TP) and chlorophyll a (Chla) level are widely used as a theoretical basis for lake eutrophication management. Here, seasonal environmental variables and Chla from 2005 to 2020 in Chinese shallow eutrophic Lake Taihu were examined and Chla-nutrient equations in the entire period and annually from 2005 to 2020 were explored using 95% quantile regression model. The results showed robust linear relationships of logChla-logTN and logChla-logTP in the vast majority of cases. Based on Chla-nutrient equations in the entire study period, 0.69 mg/L TN and 52 [mu]g/L TP are recommended as nutrient threshold in Lake Taihu. Furthermore, the results revealed increasing Chla sensitivity to nutrient for each study month (i.e. February, May, August, and November) from 2005 to 2020, whose drivers included increase in water temperature and water level, decrease in wind speed, mass ratio of nitrogen to phosphorus, and grazing effect. It is noteworthy that atmospheric stilling is likely to be the key climatic factor promoting annual peak Chla in Lake Taihu. For one, the deviations of the sub-index of Trophic State Index indicated that light is a critical limiting factor of summer Chla in Lake Taihu. For another, calmer water mainly due to atmospheric stilling decreased near 40% non-algal turbidity and a substantially increased buoyant cyanobacteria during the study period, improving phytoplankton 'light niche'. Thus, increasing algal sensitivity to nutrient occurred until the additional algal-turbidity induce further light limitations or the exhaustion of TN (or TP) cause nutrient limitation. Given atmospheric stilling is a global phenomenon, this study would affect future algal bloom mitigation efforts in shallow lakes as temperature is always the focus in the recent literatures on global climate change. Author Affiliation: (a) Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, Nanjing 210008, PR China (b) University of Chinese Academy of Sciences, Beijing, 100049, PR China * Corresponding author. Taihu Laboratory for Lake Ecosystem Research, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 73 East Beijing Road, Nanjing, 210008, PR China. Tel.: +86 25 86882186; Fax: +86 25 57714759. Article History: Received 27 November 2021; Revised 30 December 2021; Accepted 7 January 2022 Byline: Wei Zou (a), Guangwei Zhu [gwzhu@niglas.ac.cn] (a,b,*), Hai Xu (a,b), Mengyuan Zhu (a), Yunlin Zhang (a,b), Boqiang Qin (a,b)

FLASH radiation therapy (FLASH-RT), delivered with ultrahigh dose rate (UHDR), may allow patients to be treated with less normal tissue toxicity for a given tumor dose compared with currently used conventional dose rate. Clinical trials are being carried out and are needed to test whether this improved therapeutic ratio can be achieved clinically. During the clinical trials, quality assurance and credentialing of equipment and participating sites, particularly pertaining to UHDR-specific aspects, will be crucial for the validity of the outcomes of such trials. This report represents an initial framework proposed by the NRG Oncology Center for Innovation in Radiation Oncology FLASH working group on quality assurance of potential UHDR clinical trials and reviews current technology gaps to overcome. An important but separate consideration is the appropriate design of trials to most effectively answer clinical and scientific questions about FLASH. This paper begins with an overview of UHDR RT delivery methods. UHDR beam delivery parameters are then covered, with a focus on electron and proton modalities. The definition and control of safe UHDR beam delivery and current and needed dosimetry technologies are reviewed and discussed. System and site credentialing for large, multi-institution trials are reviewed. Quality assurance is then discussed, and new requirements are presented for treatment system standard analysis, patient positioning, and treatment planning. The tables and figures in this paper are meant to serve as reference points as we move toward FLASH-RT clinical trial performance. Some major questions regarding FLASH-RT are discussed, and next steps in this field are proposed. FLASH-RT has potential but is associated with significant risks and complexities. We need to redefine optimization to focus not only on the dose but also on the dose rate in a manner that is robust and understandable and that can be prescribed, validated, and confirmed in real time. Robust patient safety systems and access to treatment data will be critical as FLASH-RT moves into the clinical trials. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ctim.2017.03.014 Byline: Hao Liu (a), Xiaowei Sun (b), Wei Zou (b), Mengtong Leng (a), Beng Zhang (b), Xiaoyu Kang (a), Tao He (a), Hui Wang (a) Abstract: * This is the first behavioral testing paper of acupuncture treatment with rat model of hemorrhagic stroke. * Scalp acupuncture could improve neurological deficits in a rat model of hemorrhagic stroke. * The observed behavioral effects were associated with improvement in pathological features and decreased markers of inflammation. Author Affiliation: (a) Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China (b) First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang Province, China Article History: Received 5 February 2017; Revised 21 March 2017; Accepted 21 March 2017

In this paper, we consider the (quasi-)copulas with a given curvilinear section, and then establish the best-possible bounds on the set of quasi-copulas with a common curvilinear section. The lower bound is shown to be the best-possible lower bound as well for the set of copulas with the given curvilinear section. A sufficient and necessary condition guaranteeing the upper bound to be a copula is provided, and it is shown that when the upper bound is a copula, it is the best-possible upper bound for the set of copulas with the given curvilinear section. The best-possible upper bound on the set of copulas which have a common curvilinear section and are symmetrical with respect to the given curve is also provided. Some properties of the best-possible bound copulas with the given curvilinear section are also discussed, such as the statistical characteristic, the concordance order, the nonparametric measure of association and the tail dependence. [ABSTRACT FROM AUTHOR]

The transition to sustainable diet has mitigated climate risks and improved human health. With the rapidly increasing demand for food and high carbon mitigation pressure, food consumption in rural China has emerged as a pivotal factor in the transition process. Although diet-related carbon footprint (DCF) has been widely discussed worldwide, little is known about intra-group differences in DCFs, particularly in rural regions. Additionally, a sustainable transition pathway is unclear because of the trade-offs between DCF, nutritional quality, and affordability. In this study, inequality in intra-rural food consumption and the associated carbon footprints of different food categories were revealed based on the latest and most updated social household survey data. Future transition pathways encompassing DCFs, affordability, and nutrition were comprehensively considered. The results revealed stark intragroup differences in the DCF of rural residents, and the consumption of animal-based food exhibited a more pronounced level of inequality than plant-based food. Compared with other groups, high-income households had a higher per capita DCF, larger emission share from animal-based food, and lower share from plant-based food. Based on future sustainable transition analysis, fully adopting optimized dietary patterns can reduce the DCF by 2.28–48.84% and improve nutritional quality, especially in low-income populations (16.98–38.62%). However, regardless of the transition pathway, affordability for low-income groups needs to be considered, which may hinder sustainable transitions in the future. Our study has implications for sustainable dietary transitions in rural areas, which will bring co-benefits to both humans and the environment. • The study reveals disparities in carbon footprints within various food categories at the household level. • A pronounced intra-discrepancy is evident in the diet-related carbon footprint among rural residents. • Increased attention is warranted for low-income households in fostering sustainable transitions. [ABSTRACT FROM AUTHOR]

During the early outbreak phase of COVID-19 in China, lockdowns prevailed as the only available policy tools to mitigate the spread of infection. To evaluate the impact of lockdown policies in the context of the first phase of COVID-19 pandemic, we leverage data on daily confirmed cases per million people and related characteristics of a large set of cities. The study analyzed 369 Chinese cities, among which 188 implemented lockdowns of varying severity levels from January 23 to March 31, 2020. We use nationwide Baidu Mobility data to estimate the impact of lockdown policies on mitigating COVID-19 cases through reducing human mobility. We adopt a heterogeneous treatment effect model to quantify the effect of lockdown policies on containing confirmed case counts. Our results suggest that lockdowns substantially reduced human mobility, and larger reduction in mobility occurred within-city compared to between-city. The COVID-19 daily confirmed cases per million people decreased by 9% - 9.2% for every ten-percentage point fall in within-city travel intensity in t+7 timeframe. We also find that one city's lockdowns can effectively reduce the spillover cases of the traveler's destination cities. We find no evidence that stricter lockdowns are more effective at mitigating COVID-19 risks. Our findings provide practical insights about the effectiveness of NPI during the early outbreak phase of the unprecedented pandemic. • Evaluate the effect of lockdowns in Chinese cities during the early outbreak phase of COVID-19. • Adopt a new DID estimator to identify the heterogeneous effects of lockdowns. • Estimated a 9% -9.2% decrease in COVID-19 confirmed cases per million people due to lockdowns. • Examine the spillover effects of lockdowns and its effect on infection of traveler's destination cities. [ABSTRACT FROM AUTHOR]

Hexagonal boron nitride (h -BN) nanomaterials have attracted numerous attentions for application in various fields, including environmental governance. Understanding the environmental implications of h -BN is a prerequisite for its safe and sustainable use; nevertheless, information on the negative effect of h -BN on aquatic organisms and the underlying toxicity mechanisms is scarce. The present study found that low exposure doses (0.1–1 μg/mL) of micron-sized h -BN lamella apparently suppressed (maximally 45.3%) the growth of Chlorella vulgaris (a freshwater alga) via membrane damages and metabolic reprogramming. Experimental and simulation results verified that h -BN can penetrate into and then extract phospholipids from the cell membrane of algae due to the strong hydrophobic interactions between h -BN nanosheets and lipids, resulting in membrane permeabilization and integrity reduction. Oxidative stress-triggered lipid peroxidation also contributes to membrane destruction of algae. Metabolomics assay demonstrated that h -BN down-regulated the CO 2 -fixation associated Calvin cycle and glycolysis/gluconeogenesis pathways in algae, thereby inhibiting energy synthesis and antioxidation process. Despite releasing soluble B inside cells, the B species exhibited negligible toxicity. These findings highlight the phenomena and mechanisms of h -BN toxicity in photosynthetic algae, which have great implications for guiding their safe use under the scenarios of global carbon neutrality. [Display omitted] • Low doses (0.1–1 μg/mL) of h -BN nanosheets notably inhibited the growth of algae. • h -BN extracted membrane phospholipids of algae due to hydrophobic interactions. • Cell membrane permeabilization and integrity reduction were induced by h -BN. • h -BN inhibited CO 2 -fixation in algae, affecting energy synthesis and antioxidation. [ABSTRACT FROM AUTHOR]

High energy efficiency and tracking accuracy are both vital for hydraulic lifting servo systems. However, the appropriate hardware configuration and its corresponding nonlinear controller is always a problem to be solved. To address this multi-objective task, an integrated energy-saving and position tracking controller is developed. Specifically, to reduce the substantial energy dissipation, a system configuration referring to the structure of the three-position-six-way valve is proposed. To ensure accurate tracking performance, a hybrid observer-based output feedback controller is developed. By doing so, the function of flow regeneration and the property of flow matching are achieved, and the tracking accuracy is guaranteed by using only position signal. To validate the effectiveness of the proposed method, a common Lyapunov function is used to prove the stability of the multi-model system, and case studies are conducted to demonstrate the system performance. • The multi-objective task is achieved. • System efficiency is improved by using the proposed scheme. • Tracking accuracy is guaranteed by the proposed controller. • Stability of the system is proved by common Lyapunov theory. • Estimates of states and unmatched uncertainties are obtained. [ABSTRACT FROM AUTHOR]

Two trials were conducted to determine the optimal replacement level of rice bran meal (RBM) as a substitute for kelp meal (KM) in the diet of the hybrid abalone Haliotis discus hannai ♀ × H. fulgens ♂. This study also investigated whether betaine as an attractant supplementation could be used to facilitate RBM as a replacement for KM. In Trial 1, RBM was used to replace 25%, 50%, and 100% of the dietary KM (RBM25, RBM50, and RBM100, respectively) based on a diet containing 30% KM (Con). In Trial 2, RBM50 was the same as in Trial 1, and betaine was supplemented in RBM50 at 0.2% (B1), 0.4% (B2), and 0.8% (B3) in the diets. Abalone (weight approximately 4 g) were randomly assigned to four groups replicated in triplicate (60 abalone/replicate). The abalone were fed the experimental diets for 10 weeks. In Trial 1, compared to the Con group, no significant differences were observed in final weight (FW), final shell length (FSL), specific growth rate (SGR), or daily increment in shell length (DISL) at 25% KM replacement by RBM. However, 50% KM replacement significantly reduced the FW, FSL, SGR, and DISL compared to the Con group. There were no significant differences in the proximate composition of the soft body tissues of the abalone. In Trial 2, growth performance parameters of the hybrid abalone were significantly improved with increasing levels of betaine in the diets compared to those fed diet RBM50, reaching the maximum value in the B2 group. Consistent with the feed intake results, the hormone concentrations of neuropeptide Y (NPY) and orexins in the digestive gland and cerebral ganglia of abalone were significantly increased when the supplementation level of betaine in the diets was increased to 0.2%. However, no apparent impacts were observed on NPY or orexin concentrations among the B1, B2, and B3 groups. Finally, we suggest 0.4% betaine supplementation along with replacing 50% of the KM with RBM in the hybrid abalone diet. The optimal diet is a cost-effective alternative feed formulation that can reduce the dependence on KM for abalone production in China. This study also demonstrates the potential of betaine as a feed attractant in abalone aquaculture. • 25% kelp meal (KM) can be replaced by rice bran meal (RBM) without obvious adverse impacts on the growth performance of the hybrid abalone. • The addition of 0.4% betaine in diets increased the replacement level of KM by RBM to 50% without negatively affecting the growth performance of the hybrid abalone. • Development of such diets will significantly reduce feed cost and reliance on KM for abalone feed company in China. [ABSTRACT FROM AUTHOR]

In multiple attribute group decision-making (MAGDM), a consensus exists that the psychological factors of decision makers (DMs) generally influence their choice of optimal alternatives. To quantify well the influence of DMs' risk attitudes on the group decision-making process, this paper develops a new approach to MAGDM by introducing DMs' utility functions into the aggregation process. First, the ordered weighted utility distance (OWUD) operator is constructed by introducing DMs' utility functions into the distance operator. As a novel operator, the OWUD operator not only satisfies both the basic features of distance measures and the desirable properties of aggregation operators, but also has some unique characteristics. Then, the linear risk tolerance (LRT) utility function is further used in the OWUD operator as the basic utility function, and a specific form of the OWUD operator, which is named as the ordered weighted-linear risk tolerance utility distance (OW-LRTUD) operator, is proposed. The OW-LRTUD operator can quantify well the influence of DMs' risk attitudes on the group decision-making process. It also has an analytically tractable form and includes many well-known distance measures and aggregation operators, and thus can be applied to many different kinds of decision-making problems. Subsequently, to determine the weights of the OW-LRTUD operator, an extension of the maximum Bayesian entropy method is proposed by incorporating the prior known weight information and different risk attitudes of all individual DMs. An approach to MAGDM based on the OW-LRTUD operator and the proposed weight determination method is developed. An application for determining the optimal alternative in the investment selection is provided to show the feasibility, effectiveness and robustness of our approach in practice, and the corresponding sensitive analysis illustrates the influence of DMs' risk attitudes on the group decision-making process. • This paper develops a class of distance operators, named as the ordered weighted utility distance operators, which can quantify the influence of DM's risk attitudes or the satisfaction degrees on the group decision-making process. • New weighting models for both attributes and DMs are provided respectively by combining the prior known weight information and subjective considerations of all individual DMs. • It is shown that the Arrow-Pratt measure of absolute/relative risk aversions of DMs significantly impact the optimal option of alternatives by numerical experiments and sensitivity analysis. [ABSTRACT FROM AUTHOR]

In this study, the optimal dietary protein levels for adult hybrid abalone (H. discus hannai♀ × H. fulgens♂) were evaluated at two representative temperatures, and the interactive influences of dietary protein and water temperature on abalone meat quality were examined. Six isoenergetic and isolipidic diets containing graded levels of protein (15%, 20%, 25%, 30%, 35%, and 40%) were fed to the hybrid abalone for 90 days. Based on the specific growth rate, the optimum dietary protein levels for adult hybrid abalone using a quadratic curve model were estimated to be 28.07% and 26.47% of the diet at 23 °C (optimum temperature) and 27 °C (high temperature), respectively. The amount of crude protein in the abalone body increased linearly with the dietary protein levels and water temperature. Antioxidation enzyme activities of abalone muscle, including GPx and GST were significantly affected by the interaction of dietary protein levels and water temperature. As for texture analysis, the abalone kept at 23 °C exhibited higher meat hardness than those fed the same diets at 27 °C. The n-3 PUFAs (particularly DHA and EPA) in abalone meat were significantly influenced by dietary protein levels, and the highest content was observed in the 30% dietary protein group. These levels were not affected by water temperature. In addition, higher dietary protein levels and water temperatures increased the total contents of free amino acids and flavor amino acids (Asp + Glu + Gly + Ala + Arg + Tau). The cooking loss of abalone meat was reduced with increased protein levels and was significantly lower in the 23 °C group, along with a higher meat postmortem pH value. The collagen fiber ratio and collagen content of abalone meat were higher in the 23 °C group. In summary, for multiple diet feeding strategies in practical production of abalone aquaculture, the balance between the seasonally specific feeds cost benefits and the abalone meat quality should be carefully evaluated. • The optimum dietary protein levels of adult hybrid abalone were estimated to be 28.07% and 26.47% of the diet by the quadratic curve model at 23 °C (optimum temperature) and 27 °C (high temperature), respectively. • Beyond 30% dietary protein, the growth performance declined, but relatively increased the nutritional, flavor quality, and hardness of abalone meat at both water temperatures. [ABSTRACT FROM AUTHOR]

• A CNN-GRU block is first designed and embedded into AE as fundamental structure to extract advanced, abstract, significant temporal features. • We introduced attention mechanism (AM) to highlight the meaningful features while reducing the weight of irrelevant information during the decoding process. • Different from existing methods, we design an encoding-decoding structure based on attention mechanism and skip connection. The skip link connects the decoder and encoder directly, allowing hierarchical features to be used more directly in the decoding process and improving the efficiency of information utilization. This paper proposes a method named AE-ACG for stock price movement prediction. In AE-ACG, the convolutional neural network (CNN) and gated recurrent unit (GRU) are combined to design a base layer, which is embedded in the autoencoder (AE) framework, to efficiently extract features from financial time series data. Furthermore, skip connection links encoding and decoding to leverage hierarchical features. Attention mechanism (AM) also distinguishes the importance of historical data across periods. Extensive experiments demonstrated that the proposed model is effective in predicting price movements, showing advantages over some mainstream methods. [ABSTRACT FROM AUTHOR]

Rhythmic behavior represents one of the most striking and ubiquitous manifestations of functional evolution for a wide class of natural and man-made systems. The emergence of diverse (ar)rhythmic dynamics can be well understood by models of coupled dynamical networks, where the interplay between the intrinsic dynamics of a single unit and the coupling functions plays a critical role in shaping a vast repertoire of collective behaviors. Under certain circumstances, all the individual dynamical systems may cease their oscillations totally when coupled, which results in the emergence of oscillation quenching in coupled oscillatory systems. Macroscopic oscillations of coupled dynamical networks can also be gradually weakened and even completely quenched via aging transition. Oscillation reviving, an inverse process of quenching and aging, refers to the restoration of rhythmic activity of coupled dynamical networks from the phenomena of quenching and aging. The study on quenching, aging, and reviving of rhythmic behaviors in coupled dynamical networks has developed into an active and rapidly evolving area of research with a wide variety of applications, where tremendous progresses with vital insights have been witnessed in the last decade. In this review, we endeavour to provide an exhaustive overview on the most important aspects of quenching, aging, and reviving in coupled dynamical networks ranging from theories to experiments and applications. The prevailing knowledge is integrated and pulled together to make the relevant results and methods more generally accessible for researchers in distinct communities of science and technology. Relevant open issues and challenges that deserve of special attentions are highlighted for future study. The present review should stimulate deeper investigations on the collapse and revival of macroscopic rhythmic behaviors, which will enlighten our understanding on evading irreversible failures of coupled dynamical networks and even guide us to identify the precursors of critical transitions. Our work will foster further studies on the physical principles of collective rhythms that robustly emerge in nature and real life. [ABSTRACT FROM AUTHOR]

To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1016/S0140-6736(16)00587-0 Byline: Dr Louis Fehrenbacher, MD [Lou.Fehrenbacher@kp.org] (a,*), Alexander Spira, MD (b,c), Marcus Ballinger, PhD (d), Marcin Kowanetz, PhD (d), Prof Johan Vansteenkiste, MD (e), Prof Julien Mazieres, MD (f), Prof Keunchil Park, MD (g), David Smith, MD (h,i), Angel Artal-Cortes, MD (j), Conrad Lewanski, MD (k), Fadi Braiteh, MD (l,m), Daniel Waterkamp, MD (d), Pei He, PhD (d), Wei Zou, PhD (d), Daniel S Chen, MD (d), Jing Yi, PhD (d), Alan Sandler, MD (d), Achim Rittmeyer, MD (n) for the POPLAR Study Group ([Dagger]) Summary Background Outcomes are poor for patients with previously treated, advanced or metastatic non-small-cell lung cancer (NSCLC). The anti-programmed death ligand 1 (PD-L1) antibody atezolizumab is clinically active against cancer, including NSCLC, especially cancers expressing PD-L1 on tumour cells, tumour-infiltrating immune cells, or both. We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC, analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population. Methods In this open-label, phase 2 randomised controlled trial, patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practices across 13 countries in Europe and North America. Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1, measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST v1.1), and adequate haematological and end-organ function. Patients were stratified by PD-L1 tumour-infiltrating immune cell status, histology, and previous lines of therapy, and randomly assigned (1:1) by permuted block randomisation (with a block size of four) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m.sup.2 once every 3 weeks. Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells (as percentage of PD-L1-expressing tumour cells TC3[greater than or equal to]50%, TC2[greater than or equal to]5% and Findings Patients were enrolled between Aug 5, 2013, and March 31, 2014. 144 patients were randomly allocated to the atezolizumab group, and 143 to the docetaxel group. 142 patients received at least one dose of atezolizumab and 135 received docetaxel. Overall survival in the intention-to-treat population was 12*6 months (95% CI 9*7--16*4) for atezolizumab versus 9*7 months (8*6--12*0) for docetaxel (hazard ratio [HR] 0*73 [95% CI 0*53--0*99]; p=0*04). Increasing improvement in overall survival was associated with increasing PD-L1 expression (TC3 or IC3 HR 0*49 [0*22--1*07; p=0*068], TC2/3 or IC2/3 HR 0*54 [0*33--0*89; p=0*014], TC1/2/3 or IC1/2/3 HR 0*59 [0*40--0*85; p=0*005], TC0 and IC0 HR 1*04 [0*62--1*75; p=0*871]). In our exploratory analysis, patients with pre-existing immunity, defined by high T-effector--interferon-[gamma]-associated gene expression, had improved overall survival with atezolizumab. 11 (8%) patients in the atezolizumab group discontinued because of adverse events versus 30 (22%) patients in the docetaxel group. 16 (11%) patients in the atezolizumab group versus 52 (39%) patients in the docetaxel group had treatment-related grade 3--4 adverse events, and one ( Interpretation Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC. Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells, suggesting that PD-L1 expression is predictive for atezolizumab benefit. Atezolizumab was well tolerated, with a safety profile distinct from chemotherapy. Funding F Hoffmann-La Roche/Genentech Inc. Author Affiliation: (a) Kaiser Permanente Medical Center, Vallejo, CA, USA (b) US Oncology Research, The Woodlands, TX, USA (c) Virginia Cancer Specialists Research Institute, Fairfax, VA, USA (d) Genentech, South San Francisco, CA, USA (e) University Hospitals KU Leuven, Leuven, Belgium (f) Toulouse University Hospital, Paul Sabatier University, Toulouse, France (g) Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, South Korea (h) US Oncology Research, The Woodlands, TX, USA (i) Compass Oncology, Vancouver, WA, USA (j) Servicio de Oncologia Medica, Hospital Universitario Miguel Servet, Zaragoza, Spain (k) Department of Oncology, Charing Cross Hospital, London, UK (l) US Oncology Research, The Woodlands, TX, USA (m) Comprehensive Cancer Centers of Nevada, Las Vegas, NV, USA (n) Lungenfachklinik Immenhausen, Immenhausen, Germany * Correspondence to: Dr Louis Fehrenbacher, Kaiser Permanente Medical Center Oncology Department, Vallejo, CA 94589, USA (footnote)[Dagger] The investigators in the POPLAR study are listed in the appendix

Graphene coatings generally cannot provide effective long-time protection for metal substrates. In this study, we developed a novel graphene coating that forms reciprocating carbon chains at the defects of graphene (FRCCDG). The FRCCDG coating deposited on Ni substrate exhibits excellent corrosion resistance over extended durations. Compared with conventional graphene coatings, FRCCDG coatings have lower defect density and higher crystallinity. They form a barrier at the defects of the graphene, thereby hindering the penetration of corrosive elements and improving the ability of graphene to inhibit corrosion. When exposed to air for a period of seven months, the degree of oxidation of FRCCDG-coated Ni foil is lower than that of uncoated substrate. This confirms that the FRCCDG coating has long-lasting corrosion and oxidation resistance. [ABSTRACT FROM AUTHOR]

• FLASH proton PBS has strong potential to be implemented for patient treatment. • Clinical proton PBS delivery parameters were extrapolated to high cyclotron current. • It is challenging to achieve >40Gy/s FLASH dose rate for field size >4x4 cm2. • Scanning magnet slew and energy switching times appear to be the limiting factors. • Portion of the local dose can be delivered at FLASH dose rate. Proton Pencil Beam Scanning (PBS) is an attractive solution to realize the advantageous normal tissue sparing elucidated from FLASH high dose rates. The mechanics of PBS spot delivery will impose limitations on the effective field dose rate for PBS. This study incorporates measurements from clinical and FLASH research beams on uniform single energy and the spread-out Bragg Peak PBS fields to extrapolate the PBS dose rate to high cyclotron beam currents 350, 500, and 800 nA. The impact of the effective field dose rate from cyclotron current, spot spacing, slew time and field size were studied. When scanning magnet slew time and energy switching time are not considered, single energy effective field FLASH dose rate (≥40 Gy/s) can only be achieved with less than 4 × 4 cm2 fields when the cyclotron output current is above 500 nA. Slew time and energy switching time remain the limiting factors for achieving high effective dose rate of the field. The dose rate-time structures were obtained. The amount of the total dose delivered at the FLASH dose rate in single energy layer and volumetric field was also studied. It is demonstrated that while it is difficult to achieve FLASH dose rate for a large field or in a volume, local FLASH delivery to certain percentage of the total dose is possible. With further understanding of the FLASH radiobiological mechanism, this study could provide guidance to adapt current clinical multi-field proton PBS delivery practice for FLASH proton radiotherapy. [ABSTRACT FROM AUTHOR]

• 10th & 11th edition of 4D Treatment Planning Workshop took place in Japan and Poland. • Clinical practice of 4D particle therapy has been currently implemented worldwide. • 4D imaging and artificial intelligence play a substantial role in 4D therapy progress. • FLASH and proton arc therapy shaping the future of 4D treatments. • Development of 4D particle therapy is framed by numerous consortia and committees. The 4D Treatment Planning Workshop for Particle Therapy, a workshop dedicated to the treatment of moving targets with scanned particle beams, started in 2009 and since then has been organized annually. The mission of the workshop is to create an informal ground for clinical medical physicists, medical physics researchers and medical doctors interested in the development of the 4D technology, protocols and their translation into clinical practice. The 10th and 11th editions of the workshop took place in Sapporo, Japan in 2018 and Krakow, Poland in 2019, respectively. This review report from the Sapporo and Krakow workshops is structured in two parts, according to the workshop programs. The first part comprises clinicians and physicists review of the status of 4D clinical implementations. Corresponding talks were given by speakers from five centers around the world: Maastro Clinic (The Netherlands), University Medical Center Groningen (The Netherlands), MD Anderson Cancer Center (United States), University of Pennsylvania (United States) and The Proton Beam Therapy Center of Hokkaido University Hospital (Japan). The second part is dedicated to novelties in 4D research, i.e. motion modelling, artificial intelligence and new technologies which are currently being investigated in the radiotherapy field. [ABSTRACT FROM AUTHOR]

The potential widespread applications in water processing have rendered the necessity for investigations of the fate and hazard of molybdenum disulfide (MoS 2) nanosheets. Herein, it was found that humic acid (HA) had better performances toward stabilizing pure 2H phase MoS 2 and chemical-exfoliated MoS 2 (ce-MoS 2) in electrolyte solutions than fulvic acid (FA), and molecular weight (MW)-dependent manners were disclosed due to steric repulsions. Compared with darkness, the extent to which the aggregation and sedimentation of ce-MoS 2 facilitated by visible light irradiation was greater in the presence of HA and FA fractions, likely due to the introduction of stronger plasmonic dipole-dipole interaction and Van der Waals attraction forces. HA-triggered structural disintegration of nanosheets was performed after irradiation and it was observed to be more significant with the increase in MWs, whereas the MW-dependent dissolution of MoS 2 caused by FA was much quicker than that by HA owing to the higher generation of singlet oxygen. Moreover, FA lowered the bioavailability of MoS 2 and relieved its toxicity to zebrafish more effectively than HA. Our findings boost the insights into the effects of organic molecules on the fates and hazards of MoS 2 , providing guidance for the MoS 2 -based nanotechnological development on environment. [Display omitted] HA exhibited better performance toward stabilizing 2H-MoS 2 and ce-MoS 2 than FA. Illumination remarkably accelerated the aggregation and sedimentation of ce-MoS 2. Low MW HA and FA fractions strengthened the light-assisted ce-MoS 2 aggregation. Higher 1O 2 production led to faster MW-dependent MoS 2 dissolution in FA than HA. FA reduced MoS 2 bioavailability and relieved its toxicity more effectively than HA. [ABSTRACT FROM AUTHOR]

Jiuqu, a saccharification and fermentation agent used in the production of baijiu, is rich in enzymes, microorganisms, and organisms that have essential effects on the flavor quality of baijiu. However, traditional Jiuqu has some deficiencies in quality or may require enhancement of specific functions at times. To address this, fortified Jiuqu has been developed and applied to enhance performance and improve baijiu quality. This review focused on the functional microorganisms and strengthening effects of fortified Jiuqu. Moreover, this review also discussed the limitations of current Jiuqu preparation and fortification and explored the roles of the core functional microbes and the synthetic microflora for fortified Jiuqu, which could improve the cleanliness, controllability, and food safety of Jiuqu production. [ABSTRACT FROM AUTHOR]

The marine economy needs high-quality development, as severe marine pollution has become a global concern and threatens human health worldwide. In the light of this, this study discusses the high-quality development of marine economy from 2006 to 2020 in 11 Chinese coastal provinces. Based on discussing the connotation and system operation mechanism of the high-quality development, this study builds a bidirectional multi-index comprehensive evaluation framework of "2+6+4" to measure the high-quality development of China's marine economy. It includes six development principles of "innovation, coordination, greenness, openness, sharing and security" and the four systems of "marine economic system, marine resource and environmental system, marine social system and marine institutional system". The entropy method is used to measure the comprehensive evaluation index, and the Kernel density estimation reveals the evolutionary trends and spatially unbalanced characteristics. Furthermore, the causes of the regional disparities are analyzed using the Dagum Gini coefficient. The results show that China's high-quality marine economic development level shows a steady improvement trend in both the connotation and system dimensions. It has formed a spatial disequilibrium pattern with Shandong and Guangdong as the two poles. From the perspective of the formation of regional disparities, improving the marine institution system and security levels are significant breakthroughs to reduce the differences. This study assists relevant decision-making departments in gaining an in-depth understanding of the high-quality development of China's marine economy and the outstanding contradictions. Some effective measures (e.g., targeted regional coordinated development strategy and implement preferential policies) are suggested to achieve high-quality development. Further, this evaluation framework is applicable to assess the other complex system worldwide that involve multiple factors, and the findings can help other countries improve their marine economy. • A new evaluation framework is constructed. • The high-quality development level has formed a spatial disequilibrium pattern. • The causes of the imbalance are analyzed. • The evaluation model of high-quality is applicable to other complex systems. [ABSTRACT FROM AUTHOR]

Platinum group metal (PGM)-free single atom catalysts (SACs) are highly desired to accelerate the sluggish oxygen reduction reaction (ORR) in acidic media, which has a critical role in renewable energy technologies. Herein, we report the direct transformation of commercial graphite into iron (Fe) single atom anchored graphitic flake via a combination of mechanochemical and thermochemical synthesis. By ball milling graphite with zirconium dioxide balls and capsule in the presence of dry ice, the graphite was mechanochemically functionalized and exfoliated into carboxylated graphitic flake (CGF). Subsequent heat-treatment of CGF with nitrogen containing additives formed nitrogenated graphitic flake (NGF) incorporated with Fe single atoms (Fe 1 NGF). Importantly, the existing Fe impurity in the pristine graphite was converted into value-added product without adding Fe sources. With an ultralow Fe content (0.4 wt%), the as-prepared Fe 1 NGF exhibited an acidic ORR performance comparable to Pt/C, including ultrahigh mass activity, surpassing the other reported outstanding Fe-based SACs. [Display omitted] • Demonstrated that the commercial graphite can be directly transformed into iron (Fe) single atom anchored graphitic flake. • Provided a fundamental insight into how Fe single atom active sites were formed and stabilized during the synthesis. • Achieved commercial Pt/C comparable catalytic performance towards acidic oxygen reduction, surpassing other reported outstanding Fe-based SACs. [ABSTRACT FROM AUTHOR]

Defects can be generated when growing diamond on heterogeneous substrates. The problem dampers the widespread use of diamond films. In this paper, a novel approach is proposed which grows diamond on graphene quasi-homogeneous epitaxial substrate. Results showed that high quality diamond was synthesized on a quasi homoepitaxial graphene substrate through sp2-sp3 hybridization and covalent bond transformation. Firstly, D peak-free graphene was synthesized on nickel metal surface. C–H and C C bonds were then exploited to produce dehydrogenation and coupling reaction which caused the transform of graphene to transform into diamond. In virtue of the superior intermiscibility and catalysis of nickel to carbon, few-layer graphene grew efficiently on nickel foil surface. An internal space microstructure network of carbon atoms was produced through different non-covalent interactions. At last, graphene is converted into diamond. This process can also be used to synthesize hydrophilic porous diamond film. It is a promising approach to the development of new graphene/diamond-based components in the future. [ABSTRACT FROM AUTHOR]

In the skeleton-based action recognition, mining information from the joints and limbs of human skeletons plays a key role. Previous studies treated the skeleton data as vectors and could not explicitly capture the joint interactions (e.g., RNN-based methods), or modeled the joint interactions in a local manner and may lose important cues without global response mapping (e.g., CNN and GCN (Graph Convolution Network) based methods). In this work, we address these problems by considering the potential relations of all the node pairs and edge pairs on the skeleton graphs. A dilation group-specific convolution module is proposed to aggregate relation messages of all the unit pairs on the skeleton graphs. By enumerating all the pair relations, the joint interactions could be learned explicitly and globally. It is then enhanced by introducing the attention pooling including temporal attention, spatial attention and channel attention. By stacking such several blocks, the relation messages of the node pairs are augmented by multi-layer propagation. Finally, the late fusion of four streams is used to combine the predictions of different inputs including node pairs, edge pairs and corresponding frame differences. The proposed method, termed conv-relation network, achieves competitive performance on two large scale datasets, NTU RGB+D and Kinetics. [ABSTRACT FROM AUTHOR]

The voltage fade of Li-rich layered oxide cathode material Li 1.2 Ni 0.13 Co 0.13 Mn 0.54 O 2 (LNCM) heavily hinders its application in Li-ion batteries. Herein, we revisit the origin of the voltage fade of LNCM and propose a solution to suppress this effect. It is demonstrated that the voltage fade of the LNCM cathode comes from the structural change of the crystal from layer structure to spinel structure, involving all the cations rearrangement. Such rearrangement of all the cations in LNCM is due to the high degree of delithiation and oxygen release at high cutoff voltage of 4.8 V. It is also evidenced that nickel and cobalt change from low valence to high valence at the discharged state, which not only inhibits the transport of lithium ions, but also leads to the loss of high voltage platforms. In particular, the cation rearrangement of Li/Mn causes valence change from Mn4+ to Mn3+, resulting in the decrease of discharge voltage platform at the cutoff voltage of 4.8 V much higher than at 4.6 V. The lower charge cutoff voltage can be a solution to suppress the voltage fade of LNCM cathode materials and have a good stability of LNCM cathode materials without compromising the battery performance. Image 1 • The voltage fade of Li 1.2 Ni 0.13 Co 0.13 Mn 0.54 O 2 comes from the layer to spinel structure. • All the cations rearrangement involves in the structure change. • Nickel and cobalt change from low valence to high valence at the discharged state. • The Mn4+ to Mn3+ in Mn rearrangement decreases the discharge voltage platform. • The lower charge cutoff voltage is a solution to suppress the voltage fade of Li 1.2 Ni 0.13 Co 0.13 Mn 0.54 O 2 without compromising the battery performance. [ABSTRACT FROM AUTHOR]

• Deamination as a C-polysaccharide degradation method to improve vaccine production. • C-polysaccharide removed from pneumococcal polysaccharides except serotype 1. • Proposed deamination mechanisms for C-polysaccharide and serotype 1 polysaccharide. Pneumococcal cell wall polysaccharide (C–PS), a contaminant in pneumococcal capsular polysaccharide (Pn-PS) vaccines is degraded by mild deamination of the 4-amino-2-acetamido-2,4,6-tri-deoxy-galactose (AAT) in C–PS, which was carried out by addition of 5% aqueous sodium nitrite to a solution of polysaccharide in 5% aqueous acetic acid. Glycosidic linkage and functional groups such as O-acetates, phosphodiesters, and pyruvates were preserved under the conditions. The small fragments from degraded C–PS were removed by ultrafiltration or dialysis to provide essentially C–PS free Pn-PS. Because of the presence of AAT in its structure the deamination is not suitable for the purification of type 1 Pn-PS. Meanwhile, the mass and NMR spectroscopic analysis on the deamination products suggests that both type 1 Pn-PS and C–PS degraded following a major pathway of 5,4-hydride shift, cleavage of AAT O5-C1 bond, C1 hemiacetal formation, and its hydrolysis to release neighboring GalA- in type 1 Pn-PS and GalNAc(6-O-PCho)- in C–PS. [ABSTRACT FROM AUTHOR]

Abstract Starch in pasta is slowly digested, which is nutritionally advantageous because it reduces post-prandial glycemia, a risk factor for type 2 diabetes. We examine the role of proteinaceous amylase inhibitors, providing insights into how wheat proteins slow starch digestion. Gluten samples were extracted in the laboratory and also commercially obtained, and incubated in water at 37 °C and 100 °C. The centrifuged supernatant and gluten pellet were incubated with porcine α-amylase, and enzymatic activity measurement revealed that the supernatant from gluten heated to 100 °C retained the capacity to significantly reduce amylolytic activity. Confocal microscopy showed that the gluten pellet had become porous following heat treatment. These results are consistent with an increased concentration of soluble proteins after cooking. Proteins in the soluble fraction and gluten pellet were identified with mass spectrometry proteomics, which screened a limited number of endogenous double-headed α-amylase/trypsin inhibitors (α-AI(s)), found to be enriched in the supernatant after cooking. Endogenous α-AI(s) play a role in slowing starch digestion by interacting with α-amylase as it penetrates the gluten network that entraps the starch, resulting in an immobilization of the enzyme onto the gluten network, so that the digestion of starch entrapped by the gluten network is inhibited. Graphical abstract Wheat gluten network contains highly thermally stable proteinaceous α-amylase inhibitors that interact and complex with the α-amylase to inhibit the starch digestion. Image 1 Highlights • Slow starch digestion in pasta is nutritionally advantageous. • Thermostable α-amylase inhibitors (α-AI(s)) present in gluten network. • Proteomics screened limited number of probable target α-AI(s). • Endogenous α-AI(s) slow starch digestion by interacting with α-amylase. [ABSTRACT FROM AUTHOR]

• The effects of abnormal arrivals were eliminated successfully using the analytical localization method. • The temporal and spatial errors caused by premeasured wave velocity were weakened efficiently with TD. • An effective collaborative localization method for MS/AE was proposed using analytical and TD methods. • The proposed CLMAI is a beneficial complement for the current localization methods of MS/AE. • The CLMAI is applicable to MS localization in the rockmass structure of dynamic underground mining. The localization of microseismic sources/acoustic emission in the rockmass structure can provide the basis for determining the potential areas of rockmass instability and rockburst in the underground mining. As the construction environment in deep mining is complex, the abnormal arrivals with different scales of errors may be recorded by the monitoring sensors, which can lead to large errors between the located results and the authentic coordinates. In addition, the average premeasured P -wave velocity through blasting tests (blasts) is widely used in the current localization methods, which are unsuitable for the mining environment with dynamic change of wave velocity in multi-level and multi-stope. To eliminate the effects of abnormal arrivals, the analytical localization method is used to remove abnormal arrivals since it has a stable solution with the high precision when the input data are accurate. To weaken errors induced by the dynamic wave velocity, the iterative solution without the need of premeasured P -wave velocity is used to improve the locating accuracy since it can optimize results using the advantage of multiple sensors. Therefore, a collaborative localization method using analytical and iterative solutions (CLMAI) was proposed, which combined with the arrivals of multi-sensor and inversion of the real-time average wave velocity, to seek the optimal locating results. Firstly, the analytical solutions using 6 sensors in unknown velocity system were resolved. The method to remove abnormal arrivals is developed by solving the logistic probability density function for the analytical solutions of different sensors combinations. Then, the iterative localization method based on the time differences was used to locate source coordinates with clear arrivals. Finally, the CLMAI is verified through locating coordinates of blasts and microseismic events (events) in Kaiyang phosphorous mine. Results show that the CLMAI can not only filter the abnormal arrivals by making use of the characteristic of analytical solutions, but also use the iterative method without premeasured average velocity to improve the locating accuracy significantly. The proposed method is a beneficial complement for the current iterative methods using premeasured velocity, which is applicable to microseismic sources localization under complex abnormal arrivals in the rockmass structure of dynamic underground mining. [ABSTRACT FROM AUTHOR]

Abstract A one-step strategy of preparing hierarchical porous poly (formaldehyde-melamine) monoliths (PFM) with high specific surface area was proposed. Based on the high internal phase emulsion (HIPE) template, the removal of dispersed phase (liquid paraffins) and the reaction-induced phase separation in continuous phase (the solution of parafomaldehyde and melamine) could generate the macropores, mesopores and micropores in PFM simultaneously. As a result, the highest specific surface areas of the prepared PFM could reach 210 m2/g, which was obviously higher than that of traditional polyHIPE. The effect of the constitution of the continuous phase of HIPE on the macroporous morphologies, specific surface areas, and micropore volume of PFM were investigated in detail. Moreover, the formation mechanism of micropores and mesopores by reaction-induced phase separation was proposed. Finally, the obtained PFM was applied as CO 2 absorbent and the adsorption properties were studied. Graphical abstract Image 10368 Highlights • High-nitrogen-content monoliths (PFM) possessed micropores, mesopores and macropores were prepared in one step. • The specific surface area of PFM could reach to 210 m2/g. • Reaction-induced phase separation mechanism for the formation of micro-and meso-pores in PFMs was proposed. [ABSTRACT FROM AUTHOR]

Highlights • Observed polysaccharide degradation during reductive amination as a common phenomenon in the synthesis of glycoconjugate vaccine. • Found the base-catalyzed β-elimination as the cause of degradation. • Established an optimal conjugation under a slightly acidic conditions. Abstract Reductive amination coupling an aldehyde-containing polysaccharide, generated by periodate oxidation, with the amino groups in protein has been widely used in the synthesis of glycoconjugate vaccines. The conjugation is often achieved under slightly basic conditions via a Schiff's base intermediate followed by its reduction with sodium cyanoborohydride. We observed that oxidized capsular polysaccharides such as Streptococcus pneumoniae type 6B (Pn-6B) and Haemophilus influenzae type a (HiA) underwent significant degradation during the conjugation in slightly basic media leading to sub-optimal glycoconjugates. Further study on oxidized Pn-3, Pn-6A, Pn-6C, Pn-2 polysaccharides and dextran provided evidence that the degradation is a result of base-catalysed β-elimination. In contrast to HiA, Pn-2, Pn-3, Pn-6B polysaccharides and dextran, oxidized Pn-6A and Pn-6C polysaccharides were stable under basic conditions due to lack of the leaving group at the β-position of the aldehyde. By performing conjugation of oxidized polysaccharides to bovine serum albumin (BSA) in phosphate buffer at pH 6.0, 6.8, 7.2 and 8.0, we concluded that the reductive amination proceeds best in slightly acidic media, particularly with those β-elimination susceptible polysaccharides. [ABSTRACT FROM AUTHOR]

Background: Salvia miltiorrhiza Bunge (S. miltiorrhiza), a traditional Chinese medicine, has demonstrated antioxidant, anti-inflammatory, and antibacterial activities. However, its effects against asthma that shows chronic inflammation and oxidative damage remain unknown.Purpose: To assess the effects of S. miltiorrhiza extracts on airway responsiveness, inflammation, and remodeling in ovalbumin (OVA)-induced asthmatic mice.Methods: Mice with ovalbumin (OVA)-induced allergic asthma were treated with S. miltiorrhiza extracts, and airway resistance (RL) to methacholine, inflammatory cell infiltration, Th1/Th2 cytokine levels, and airway remodeling were assessed. TGF-β1-induced BEAS-2B and MRC-5 cells were used to evaluate the effects of five S. miltiorrhiza compounds on epithelial-mesenchymal transition and fibrosis.Results: OVA-challenge resulted in remarkably increased RL, inflammatory cell infiltration, Th1/Th2 cytokine levels in BALF, goblet cell hyperplasia, collagen deposition, and airway wall thickening. Daily treatment with S. miltiorrhiza ethanolic (EE, 246 mg/kg) or water (WE, 156 mg/kg) extract significantly reduced OVA-induced airway inflammatory cell infiltration, Th1/Th2 cytokine amounts, and goblet cells hyperplasia. However, only WE remarkably decreased RL, collagen deposition, and airway wall thickening. Moreover, Chromatography showed that salvianic acid A and caffeic acid levels were much higher in WE than EE, while rosmarinic acid was slightly lower; salvianolic acid B and tanshinone IIA levels were much higher in EE than WE. Interestingly, caffeic acid and rosmarinic acid were more potent in reducing E-cadherin and vimentin levels in TGF-β1-induced BEAS-2B cells, and α-SMA and COL1A1 amounts in TGF-β1-induced MRC-5 cells.Conclusions: Both S. miltiorrhiza WE and EE alleviate airway inflammation in mice with OVA-sensitized allergic asthma. S. miltiorrhiza WE is more potent in reducing responsiveness and airway remodeling. [ABSTRACT FROM AUTHOR]

Abstract Purpose This study aimed to investigate the association between target volume margins and clinical outcomes for patients with inoperable non-small cell lung cancer (NSCLC) treated with concurrent chemoradiation therapy. Methods and materials We reviewed the records of 82 patients with inoperable NSCLC treated between 2009 and 2016 with concurrent chemoradiation. All patients received positron emission tomography–based treatment planning, 4-dimensional computed tomography simulation to define an internal target volume, and daily cone beam computed tomography. We quantified variations in target volume margins with a margin deviation index (MDI), calculated as the percentage change in equivalent uniform dose between the original planning target volume (PTV) and a standard reference PTV 10 mm beyond the original gross tumor volume, consistent with the minimum margins mandated by recent NSCLC trials. Greater MDIs equated to smaller effective target volume margins. We dichotomized patients by the upper tercile MDI value (5.8%). Endpoints included time to locoregional progression and time to grade ≥ 3 radiation esophagitis (RE3) or radiation pneumonitis (RP3), modelled with the Fine-Gray method. Results Median follow-up was 37.8 months (range, 5.9-58.1 months). Larger MDIs correlated with smaller clinical target volume (CTV) + PTV margins, larger gross tumor volumes, later treatment year, and intensity modulated radiation therapy use. The risk of locoregional progression did not differ for MDI ≥5.8% versus <5.8% (adjusted hazard ratio: 0.88; P =.76), but the risk of RE3 or RP3 was decreased for MDI ≥5.8% (adjusted hazard ratio: 0.27; P =.027). Patients with MDI ≥5.8% were treated with smaller CTV + PTV margins (median, 5.6 vs 8 mm; P <.0001) and a marginally lower volume of esophagus receiving ≥50 Gy (median, 31.1% vs 35.3%; P =.069). Conclusions Smaller margins were used for larger tumors but were not associated with an increase in locoregional failures. Additional studies could clarify whether smaller margins, when used alongside modern radiation therapy techniques, decrease treatment-related toxicity for inoperable NSCLC. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • P. akamusi and its effect on bioassessment were examined. • P. akamusi larvae present seasonally substantial vertical migration in the sediments. • Bioassessment based on grab samples may seriously overrate the water quality status. • Vertical migration of macroinvertebrates should be considered in developing bioassessment. Abstract Propsilocerus akamusi (Diptera: Chironomidae) is a dominant species in numerous eutrophic lakes and they could burrow into deep sediments (>30 cm) during summer months. However, common-used grab samplers are efficient in collecting surface-dwelling species (<20 cm), thus vertical migrations of dominant species may interfere bioassessment. Here, we monthly investigated the vertical sediment positioning of P. akamusi larvae and its influence on bioassessment. Our results indicated that, from late-April to October, most individuals aestivated at the sediment below 30 cm depth which maybe an adaptation to the thermal stress. As to other periods, the larvae were generally found in the depth of 10–30 cm. Moreover, Peterson grab samples collected only 0% and 12.6% of total P. akamusi individuals in summer and late-autumn, respectively, resulting in serious underestimation of the actual pollution status. This implied that vertical movements of dominant macroinvertebrates should be taken into account when designing of bioassessment protocols. For P. akamusi , Core-sampling for calibration were strongly encouraged, and the low-temperature period for Grab-sampling is also proposed. [ABSTRACT FROM AUTHOR]

Abstract Methylovorus sp. MP688 is a methylotrophic bacterium that can be used as a pyrroloquinolone quinone (PQQ) producer. To obtain a comprehensive understanding of its metabolic capabilities, we constructed a genome-scale metabolic model (i WZ583) of Methylovorus sp. MP688, based on its genome annotations, data from public metabolic databases, and literature mining. The model includes 772 reactions, 764 metabolites, and 583 genes. Growth of Methylovorus sp. MP688 was simulated using different carbon and nitrogen sources, and the results were consistent with experimental data. A core metabolic essential gene set of 218 genes was predicted by gene essentiality analysis on minimal medium containing methanol. Based on in silico predictions, the addition of aspartate to the medium increased PQQ production by 4.6- fold. Deletion of three reactions associated with four genes (MPQ_1150, MPQ_1560, MPQ_1561, MPQ_1562) was predicted to yield a PQQ production rate of 0.123 mmol/gDW/h, while cell growth decreased by 2.5%. Here, model i WZ583 represents a useful platform for understanding the phenotype of Methylovorus sp. MP688 and improving PQQ production. [ABSTRACT FROM AUTHOR]

Abstract Compacted soils are widely used as the subgrade layer for pavements. Knowledge of the mechanical properties of subgrade soils under cyclic and static loading conditions and their variation under the influence of environmental factors is required for the rational design of pavements based on mechanistic methods. This paper presents an experimental investigation of the cyclic and static moduli and the strength properties of seven different compacted Canadian subgrade soils considering the variation in the post-compaction moisture content. Cyclic triaxial tests were performed to reliably determine the resilient modulus (M R). Unconfined compression tests, which allow an unloading-reloading loop at 1% strain, were performed to determine the deviator stress (S u 1%) at 1% strain, the reloading elastic modulus (E 1%) at 1% strain and the unconfined compressive strength (q u) at failure. The physical properties, the chemical and mineralogical compositions, and the soil-water characteristics of these soils were also determined. Relationships were developed to predict the M R from the S u 1% , E 1% , q u and soil physical properties for the investigated subgrade soils because the experimental determination of M R is both expensive and time-consuming. The studies presented in this paper provide useful information and approaches that can be used to promote the implementation of mechanistic pavement design methods using simple techniques. [ABSTRACT FROM AUTHOR]

Background No index for non-invasive diagnosis of subclinical pelvic inflammatory disease (PID) is available at this time. Here we carried out a plasma metabolomic study to search for potential biomarkers to facilitate its non-invasive diagnosis. Method The metabolites in plasma were detected by using an LC-Q-TOF-MS method. The metabolic profiles of subclinical PID patients and healthy controls were discriminated by multivariate analysis. 30 patients and 28 controls were enrolled for PLS-DA model construction, and further 8 patients and 8 controls were employed for model validation. Univariate analysis was performed to evaluate potential biomarkers. Results The metabolic profiles of subclinical PID patients were different from those of healthy controls in a PLS-DA model, and this model was validated by permutation test and could accurately classify further 16 samples in T-prediction. Eleven differentiating metabolites, with the variable importance in the project >1 and corrected P  < 0.05, were found as potential biomarkers. These metabolites included eight lipids, p-cresol, 3-indolepropionic acid and indoxylsulfuric acid. Among them, lysophosphatidic acid (16,0/0:0) showed a highest AUC value of receiver operating characteristic curve (0.855), with sensitivity of 89.3% and specificity of 73.3%. Conclusion Through an LC-Q-TOF-MS based metabolomic analysis on subclinical PID, this study reports the potential plasma biomarkers which may be helpful for its non-invasive diagnosis. [ABSTRACT FROM AUTHOR]

According to the dissipative structure theory, this study establishes an indicator system and information entropy model to analyze the evolution of green development. The integrated weighting method is used to assess the level of green development. Finally, we analyze the level of green development from temporal and spatial perspectives. The results show that the total entropy of almost all provinces and cities in China has been reduced, indicating that the degree of order of the green development system has been strengthened. The level of green development has increased from 2000 to 2014 but overall was not high. From a temporal view, the level of green development converges with a big gap. From a spatial view, there are tremendous differences among the eastern, central, and western areas. Based on these findings, we put forth reasonable suggestions for promoting the level of green development in China. [ABSTRACT FROM AUTHOR]

Image guidance technology has evolved and seen widespread application in the past several decades. Advancements in the diagnostic imaging field have found new applications in radiation oncology and promoted the development of therapeutic devices with advanced imaging capabilities. A recent example is the development of linear accelerators that offer magnetic resonance imaging for real-time imaging and online adaptive planning. Volumetric imaging, in particular, offers more precise localization of soft tissue targets and critical organs which reduces setup uncertainty and permit the use of smaller setup margins. We present a review of the status of current imaging modalities available for radiation oncology and its impact on target margins and use for adaptive therapy. [ABSTRACT FROM AUTHOR]

The purpose of this research is to acquire knowledge and understanding of the value of marine ecosystem services in China's coastal regions. This evaluation involved combining existing research results, based on the theory of ecosystem services and emergy analysis, estimating marine ecosystem services values in 11 coastal provinces and cities for each year from 2005 to 2014, and analyzing the changes in marine ecosystem services values over time and across regions. The results showed that the values had in general increased during the time the study was conducted, and that Hainan, Guangdong, and Shandong accounted for most of the value. Applying the Theil index to analyze the regional differences of China's coastal marine ecosystem services values, we found that these disparities had shrunk; intra-region disparities were the primary cause of this shrinkage, but the developments of marine ecosystem services values of both intra- and inter-regions were unbalanced. Changes in the marine ecosystem services structure in China's coastal regions from 2005 to 2014 were analyzed using the information entropy theory. Over time, the information entropy and equilibrium degree of China's coastal marine ecosystem services structure consistently showed a fluctuating uptrend; across regions, the information entropy of the marine ecosystem services in the 11 coastal provinces and cities had larger discrepancies. Our results reveal emergy analysis is a helpful method for assessing marine ecosystem services, and our database can serve as a basis for more studies the future. Our research has also revealed the problems existing in the development of marine ecosystem services in China, such as the imbalance in the development of marine ecosystem service values between regions and the differences in the degree of development of various services, which is crucial to the future development of the ocean. [ABSTRACT FROM AUTHOR]

Water splitting hydrogen-oxygen evolution is the most promising way to solve the current energy crisis. Realizing the selective generation of hydrogen and oxygen via water splitting in a single photocatalyst is significant but still a challenge. Herein a layered ferroelectric material Bi 3 TiNbO 9 was synthesized by a modified molten-salt method and solid state method. The exposed facets of the nanosheets synthesized with the modified molten-salt method were {001} and {110}, and the ratio of which can be well-tuned by adjusting the synthesis temperature. Bi 3 TiNbO 9 nanosheets present both hydrogen and oxygen evolution via water splitting under illumination, and the hydrogen generation or oxygen generation can be selectively optimized by simply adjusting the ratio value of {001}/{110} exposed facets. The as-prepared samples with the highest {001} exposed facet displayed the highest hydrogen evolution activity (342.6 μmol h −1 g −1 ), while the samples with the highest {110} exposed facet showed the highest oxygen evolution activity (275.2 μmol h −1 g −1 ), indicating that the {001} and {110} facets of the Bi 3 TiNbO 9 were the active hydrogen generating facet and the active oxygen generating facet respectively. This research is very instructive in the rational design of highly efficient hydrogen generation or oxygen generation respectively in the similar photocatalyst. [ABSTRACT FROM AUTHOR]

Purpose Passive scattering proton radiotherapy utilizes beam-specific compensators to shape the dose to the distal end of the tumor target. These compensators typically require therapists to enter the treatment room to mount between beams. This study investigates a novel approach that utilizes a single patient-specific bolus to accomplish the role of multi-field compensators to improve the efficiency of the treatment delivery. Methods Ray-tracing from the proton virtual source was used to convert the beam-specific compensators (mounted on the gantry nozzle) into an equivalent bolus thickness on the patient surface. The field bolus contours were combined to create a single bolus. A 3D acrylic bolus was milled for a head phantom. The dose distribution of the compensator plan was compared to the bolus plan using 3D Gamma analysis and film measurements. Boluses for two clinical patients were also designed. Results The calculated phantom dose distribution of the original proton compensator plan was shown to be equivalent to the plan with the surface bolus. Film irradiations with the proton bolus also confirmed the dosimetric equivalence of the two techniques. The dose distribution equivalency of the bolus plans for the clinical patients were demonstrated. Conclusions We presented a novel approach that uses a single patient-specific bolus to replace patient compensators during passive scattering proton delivery. This approach has the potential to reduce the treatment time, the compensator manufacturing costs, the risk of potential collision between the compensator and the patient/couch, and the waste of compensator material. [ABSTRACT FROM AUTHOR]

Resilience has become an essential aspect of the high-quality development of the marine economy. This study considered multiple combinations of dimensions, including politics, economy, culture, society, ecology, and security, in developing marine economy resilience. Based on the adaptability theory, this study measures the resilience of China's marine economy by constructing an evaluation index system using the three resilience sub-dimensions of resistance, adaptability, and evolution from 2000 to 2020 in 11 Chinese coastal provinces. The evaluation index system also considers social factors such as institution, culture, and history. The new technical methods such as remote sensing interpretation and text analysis are used to obtain one-hand data. We use a fuzzy comprehensive evaluation (FCE) model to calculate the comprehensive evaluation index and determine the weight of each index using the entropy weight method, analytic hierarchy process, and the least square decision model. Furthermore, based on the Local Indicators of Spatial Association (LISA) time path and spatiotemporal transition probability matrix, we analyze the spatiotemporal characteristic evolution characteristics of marine economic resilience. The results reveal that (1) the resilience, resistance, adaptability, and evolution of the marine economy in 11 coastal provinces show an upward trend from 2000 to 2020. (2) The development speed of the resilience level differs in terms of resistance, adaptability, and evolution, but the overall level shows adaptability > evolution > resistance. (3) The analysis of the spatiotemporal interaction characteristics of resilience shows that the overall spatial characteristic of resilience is relatively stable. Therefore, some measurements are suggested to improve marine economic resilience. For example, government formulates marine plans, sea-related enterprises assume social responsibilities, and individuals actively participate in marine governance. The evaluation model of marine economic resilience applies to other complex systems with multiple factors. • Assess spatiotemporal characteristics of marine economic resilience. • A new compound asymmetric spatial vector weight matrix is constructed. • A new method explores the spatiotemporal evolution of marine economic resilience. • The evaluation model of resilience is applicable to other complex systems. [ABSTRACT FROM AUTHOR]

The increasing application of engineered nanomaterials (ENMs) unavoidably leads to environmental release and biological exposure. Understanding the potential hazards of ENMs on crops is essential for appropriate utilization and management. Herein, rice seedlings were hydroponically exposed to molybdenum sulfide (MoS 2 , a typical ENM) nanosheets at 5−20 mg/L for 7 days and then depurated for another 7 days in a fresh culture medium. Exposure to MoS 2 triggered irreversible reductions in root length (by 26.3%–69.9%) and tip number (by 22.2%–66.0%). Integration of biochemical assays, transcriptomic and metabolomics found that oxidative stress induced by MoS 2 in roots was persistent, whereas the activation of aquaporins, ionic transportation, and energy synthesis was normalized due to the recovery of nutrient uptake. The down-regulated levels of genes and metabolites associated with peroxidases, hemicellulose synthesis, expansins, and auxins caused persistent structural damages (sclerosis and rupture) of root cell walls. Approximately 64.5%–84.8% of internalized MoS 2 nanosheets were degraded, and the successive up-regulation of genes encoding cytochrome P450s and glutathione S -transferases reflected the biotransformation and detoxification of MoS 2 in the depuration period. These findings provide novel insights into the persistence and recovery of MoS 2 phytotoxicity, which will help advance the risk assessment of MoS 2 application on environment. [Display omitted] • MoS 2 exposure triggered irreversible reductions in root length and tip number. • Antioxidative genes were persistently down-regulated to adapt to the lowered ROS. • Activation of aquaporins, nutrient uptake, and energy synthesis was recoverable. • Inhibition on POD, hemicellulose, and expansins caused persistent cell wall damage. • Genes encoding CYP450 and GST were orderly activated for MoS 2 detoxification. [ABSTRACT FROM AUTHOR]

In this paper, a deformable registration network (DR-Net) and a multi-scale cascading strategy are designed for the registration of largely deformed 3D medical images. Our DR-Net appears as a U-shaped convolutional neural network with a pyramidal input module (PIM), a light weighted sequential Inception module and an SCAM convolutional attention module. Our multi-scale cooperative cascading strategy integrates the deformation field information within and between sub-networks at different scales to synthesize the cascaded deformation fields. To cooperatively train the cascaded network, not only the output of the final network layer but also the multi-scale outputs from different layers of the decoder in the last cascaded sub-network are used to calculate loss function. As compared with the VoxelMorph and IVTN, the average dice similarity coefficients (Dice) achieved with our DR-Net are 2.4% and 2.5% higher on the Sliver dataset and are 2.5% and 2.4% higher on the LiTS dataset. The average Dice coefficients achieved with our multi-scale cascading strategy of three DR-Nets are 1.6% and 1.9% higher than those of the VM-CR3 and are 1.5% and 1.7% higher than those of the IVTN-CR3 on these two datasets, respectively. These results show that not only our proposed DR-Net itself but also the cascade of them outperform the state-of-the-art methods and their cascades in registration accuracy. • A novel lightweight deformable registration network (DR-Net) with an SCAM convolutional attention module is proposed. • A multi-scale cascading strategy for synthesizing the cascaded deformation fields is proposed. • A cooperative training strategy is proposed to train the cascaded network. • Extensive experiments on large-scale public datasets from different medical center are conducted. [ABSTRACT FROM AUTHOR]