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Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza.

The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza.

Wind erosion is a geomorphic process in arid and semi-arid areas and has substantial implications for regional climate and desertification. In the Columbia Plateau of northwestern United States, the emissions from fine particles of loessial soils often contribute to the exceedance of inhalable particulate matter (PM) with an aerodynamic diameter of 10 µm or less (PM10) according to the air quality standards. However, little is known about the threshold friction velocity (TFV) for particles of different sizes that comprise these soils. In this study, soil samples of two representative soil types (Warden sandy loam and Ritzville silt loam) collected from the Columbia Plateau were sieved to seven particle size fractions, and an experiment was then conducted to determine the relationship between TFV and particle size fraction. The results revealed that soil particle size significantly affected the initiation of soil movement and TFV; TFV ranged 0.304–0.844 and 0.249–0.739 m/s for different particle size fractions of Ritzville silt loam and Warden sandy loam, respectively. PM10 and total suspended particulates (TSP) emissions from a bed of 63–90 µm soil particles were markedly higher for Warden sandy loam than for Ritzville silt loam. Together with the lower TFV of Warden sandy loam, dust emissions from fine particles (<100 µm in diameter) of Warden sandy loam thus may be a main contributor to dust in the region’s atmosphere, since the PM10 emissions from the soil erosion surfaces and its ensuing suspension within the atmosphere constitute an essential process of soil erosion in the Columbia Plateau. Developing and implementing strategic land management practices on sandy loam soils is therefore necessary to control dust emissions in the Columbia Plateau.

This paper proposed a new structure of highly-dense micro-jet arrays for hybrid jet-impingement/microchannel heat sinks (∼120 jet per cm2with jet width of 0.35 mm). Parametric study is performed to investigate the influence of structure and flow parameters on the convective heat transfer of water jet cooling in confined space. The simulation results show that the optimal jet width, jet spacing and impingement distance are around 0.2 mm, 0.2 mm and 0.3 mm, respectively, which can achieve a low thermal resistance as well as a relatively low pressure drop. The analysis of the heat transfer pathways shows that the micro-fin jet structures can extend the impinging heat transfer area and conduct a considerable proportion of heat, which can reach up to 38.9% with the Reynolds number ranging from 797.1 to 5602.2. The heat transfer characteristics in the heat sink will shift from impingement dominated heat transfer to the channel-convection dominated heat transfer as the jet impingement distance increases. A correlation is proposed to predict the average Nusselt number on the stagnation area for the heat sink with different structure parameters, and the deviations of predictions from the numerical results are less than 10%.

The use of handgrip strength (HGS) in clinical cancer research is surging. The association between HGS and outcomes in patients with cancer varied across studies, which might be due to the different measurement protocols for HGS. We aimed to answer three questions: (1) Did the use of various protocols for HGS, along with different numbers of repetitions, lead to significant differences in maximum HGS values? (2) If yes, were these differences clinically significant? (3) Did the differences in HGS protocols and repetitions affect the identification of HGS weakness or HGS asymmetry? We continuously recruited adult patients with solid tumours. Two protocols were used to measure HGS: Method A, following the American Society of Hand Therapists guidelines, and Method B, following the National Health and Nutrition Examination Survey guidelines. To analyse HGS, we used the maximal value obtained from either two or three repetitions of the dominant hand or four or six repetitions of both hands. We included 497 patients (326 men and 171 women, median age: 58 years). The maximal HGS values, measured with Method B, were significantly higher than those measured by Method A in both men and women, despite repetitions (all P< 0.05). The maximum HGS values were significantly different across the repetition groups, regardless of measurement protocols and sex (all P< 0.01). The protocol‐induced differences in maximal HGS values might be clinically meaningful in over 60% of men and 40% of women despite repetitions. The repetition‐induced difference was only clinically significant in 4.3–17.8% of men and 4.1–14.6% of women. To identify HGS weakness, using Method A (six repetitions) as the ‘gold’ standard, the other protocols demonstrated an overall accuracy of 0.923–0.997 in men and 0.965–1 in women. To identify HGS asymmetry, using Method A (six repetitions) as the ‘gold’ standard, Method B (six repetitions) demonstrated a diagnostic accuracy of 0.972 in men and 0.971 in women. Method A (four repetitions) showed a diagnostic accuracy of 0.837 in men and 0.825 in women, while Method B (four repetitions) showed a diagnostic accuracy of 0.825 in men and 0.807 in women. Both measurement protocols and repetitions significantly affect the maximal HGS values. The identification of HGS weakness is not significantly affected by either protocols or repetitions, while the identification of HGS asymmetry may be affected by different repetitions but not protocols.

•Two leukemic evolutionary patterns, “clonal shift” and “clonal drift” are unveiled in relapsed T-ALL via single-cell multiomics profiling.•High RNA-binding protein MSI2 level accounts for persistent clones at relapse through the posttranscriptional regulation of MYC in T-ALL.

With the widespread application of model averaging across various fields, the post-averaging inference for model averaging estimators has attracted more and more attention. In this article, the authors study the asymptotic properties of the parsimonious model averaging estimator in the case of heteroskedasticity, confirming the suitability of the estimator for statistical inference. When a correctly specified model exists in the candidate model set, it is proven that the method can assign the weight to the smallest correct model tending to 1, which further yields its consistency in variable selection and asymptotic normality. Simulation results show that the coverage of the confidence intervals constructed based on the parsimonious model averaging estimator can converge to the nominal level in both homoskedasticity and heteroskedasticity cases. As an illustrative example, the authors apply the method to the carbon emission data of prefecture-level cities in China for the year 2019.

A common view on meridional deflection of eddy propagation is poleward for cyclones and equatorward for anticyclones. This widely accepted polarity-sensitive pattern has been increasingly undermined given that it is systematically violated on both zonal and regional scales as recently reported. Here, we approach the problem by exploring these violations in terms of eddy effects of spatiotemporal geostrophy, thermal fading, and flow dragging, yielding the following main conclusions. (1) The polarity-dependent deflection discrepancy is a pseudo feature resulting from a biased fit to the normalized eddy tracks which are spatially asymmetric (though azimuthally symmetric) between the two signs; Instead, the primary pattern of eddy deflection appears to be geographically correlated and polarity independent. (2) Geostrophic adjustment plays a critical role in defining the meridional movement of an eddy. Specifically, a consistent poleward (equatorward) trajectory bending of spatially (temporally) ageostrophic eddies is observed irrespective of their polarity. (3) The mechanism of eddy deflection is also determined by its zonal propagation direction. Westward propagating eddies are substantially affected by thermal fading, while opposite ones by flow dragging. A realistic and comprehensive understanding of eddy deflection mechanisms serves as a significant contribution to the prediction of eddy trajectory, and the protection of ocean environment.

Ciprofol (HSK3486) is a novel intravenous agent for general anesthesia. In humans, HSK3486 mainly undergoes glucuronidation to form M4 [fraction of clearance (fCL): 62.6%], followed by the formation of monohydroxylated metabolites that further undergo glucuronidation and sulfation to produce M5-1, M5-2, M5-3, and M3 (summed fCL: 35.2%). However, the complete metabolic pathways of HSK3486 in humans remain unclear. In this study, by comparison with chemically synthesized reference standards, three monohydroxylated metabolites [M7-1, 4-hydroxylation with an unbound intrinsic clearance (CLint,u) of 2211 μl/min/mg; M7-2, ω-hydroxylation with a CLint,uof 600 μl/min/mg; and M7-3, (ω-1)-hydroxylation with a CLint,uof 78.4 μl/min/mg] were identified in human liver microsomes, and CYP2B6 primarily catalyzed their formation. In humans, M7-1 was shown to undergo glucuronidation at the 4-position and 1-position by multiple UDP-glucuronosyltransferases (UGTs) to produce M5-1 and M5-3, respectively, or was metabolized to M3 by cytosolic sulfotransferases. M7-2 was glucuronidated at the ωposition by UGT1A9, 2B4, and 2B7 to form M5-2. UGT1A9 predominantly catalyzed the glucuronidation of HSK3486 (M4). The CLint,uvalues for M4 formation in human liver and kidney microsomes were 1028 and 3407 μl/min/mg, respectively. In vitro to in vivo extrapolation analysis suggested that renal glucuronidation contributed approximately 31.4% of the combined clearance. In addition to HSK3486 glucuronidation (M4), 4-hydroxylation (M7-1) was identified as another crucial oxidative metabolic pathway (fCL: 34.5%). Further attention should be paid to the impact of CYP2B6- and UGT1A9-mediated drug interactions and gene polymorphisms on the exposure and efficacy of HSK3486.SIGNIFICANCE STATEMENTThis research elucidates the major oxidative metabolic pathways of HSK3486 (the formation of three monohydroxylated metabolites: M7-1, M7-2, M7-3) as well as definitive structures and formation pathways of these monohydroxylated metabolites and their glucuronides or sulfate in humans. This research also identifies major metabolizing enzymes responsible for the glucuronidation (UGT1A9) and oxidation (CYP2B6) of HSK3486 and characterizes the mechanism of extrahepatic metabolism. The above information is helpful in guiding the safe use of HSK3486 in the clinic.

Stereo Lithography Apparatus (SLA) has demonstrated improvements on surface-roughness and dimensional-accuracy of the precision casting prototypes in recent years, which however is still far from being satisfactory in industrial. One primary problem is the easy crack of the ceramic shell at sintering process originated from the high thermal expansion coefficient of the photosensitive resin. Herein, this paper aims to find a solution for the cracking problem of the SLA-prototyped ceramic shells. This paper introduces recent studies mainly focusing on the aspect of photosensitive resin modification, the hollow structure improvement inside the photosensitive resin prototype, the wax sheet pasting method on the weak part of ceramic shells, and the sintering process design of the photosensitive resin in ceramic shells. The performance of ceramic shells through these studies are evaluated, and a fundamental solution to the cracking problem of ceramic shells is thereafter prospected.

The alteration formed by the reaction of ore-bearing fluid and wall rock is often used as an important prospecting indicator, resulting in the dilution or enrichment of metals or related trace elements. A variety of rock-forming and metallogenic elements have been analyzed in regional stream sediments so that the relationship between the ore-bearing altered rock and the change in the geochemical elemental content can be obtained. Therefore, by using appropriate models, such as matched filtering, the abundance of the distribution of wall rock alteration, similar to the discovered deposits, can be modeled by using the distribution of geochemical elements in the region, and the areas with high distribution abundances are usually favorable prospecting targets. The alteration types related to gold mineralization in the Baiyun gold deposit are potassium feldspar alteration, silicification, pyritization, sericitization, and chloritization. In this paper, the geochemical data of the Qingchengzi ore field (1:200,000 and 1:50,000) have been used to form geochemical images through rasterization. In the three sections of the Baiyun gold deposit, binary-coded curves have been formed, revealing the differences in geochemical elements in stream sediments between altered rocks and the rocks surrounding the Baiyun gold mine. Among them, Au, W, and Mo are enriched elements, while Sn, Zn, and Hg are depleted elements. Several gold deposits are found in the predicted altered rock area by using the matched filtering method during fieldwork, which shows the effectiveness of the method.

Immunotherapy with programmed cell death 1 ligand 1 (PD-L1) blockade was effective in patients with NK/T-cell lymphoma. In addition to PD-L1, indoleamine 2,3-dioxygenase-1 (IDO1) is one of the most promising immunotherapeutic targets. High proportions of PD-L1 and IDO1 proteins were observed by immunohistochemistry (IHC) from 230 newly diagnosed patients with NK/T lymphoma with tissue samples from three cancer centers and were associated with poor overall survival (OS) in patients with NK/T lymphoma. Importantly, the coexpression of PD-L1 and IDO1 was related to poor OS and short restricted mean survival time in patients with NK/T lymphoma and was an independent prognostic factor in the training cohorts, and which was also validated in 58 NK/T lymphoma patients (GSE90597). Moreover, a nomogram model constructed with PD-L1 and IDO1 expression together with age could provide concise and precise predictions of OS rates and median survival time. The high-risk group in the nomogram model had a positive correlation with CD4 + T-cell infiltration in the validation cohort, as did the immunosuppressive factor level. Therefore, high PD-L1 and IDO1 expression was associated with poor OS in patients with NK/T lymphoma. PD-L1 and IDO1 might be potential targets for future immune checkpoint blockade (ICB) therapy for NK/T lymphoma.

The rhizosphere microbiome can regulate various plant biological activities; however, the composition of the rhizosphere microbiome is easily affected by the growing environment and plant genotype. To further explore the differences and the interaction mechanisms between the rhizosphere microbiome of different wheat cultivars planted in northern China, we systematically compared the rhizosphere microbiome of major wheat cultivars Jimai22 and Xiaoyan22 planted in the field in Jinan and Qingdao, Shandong Province. The rhizosphere microbiome data were obtained from Jimai22 and Xiaoyan22 at the three‐leaf stage by 16S rRNA gene amplicon sequencing and were compared based on diversity analysis, principal coordinates’ analysis, machine learning methods such as random forest, and network analysis. The results showed that the plant growing environment and genotype significantly affected the community structure of the wheat rhizosphere microbiome. Operational taxonomic units belonged to Actinobacteria, Bacteroidetes, Firmicutes, Acidobacteria, and Proteobacteria were differentially enriched between the two wheat genotypes. Moreover, random forest model could accurately (accuracy rate 96.4%) predict wheat genotype across locations based on differences in rhizosphere microbiome of Jimai22 and Xiaoyan22. The findings of this study provide supporting data and a theoretical basis for in‐depth understanding of the composition of the rhizosphere microbiome of wheat planted in northern China, which can be applied to improve wheat breeding from the perspective of root microbe–plant interaction. Environment and genotype affect wheat rhizosphere microbiome community structure.Different genotypes led to altered rhizosphere microbe composition and relationship.Root microbe could serve as biomarker to differentiate wheat genotype across fields.

Single-cell diagnosis of cancer drug resistance is highly relevant for cancer treatment, as it can be used to identify the subpopulations of drug-resistant cancer cells, reveal the sensitivity of cancer cells to treatment, and monitor the progress of cancer drug resistance. However, simple and effective methods for cancer drug resistance detection at the single-cell level are still lacking in laboratory and clinical studies. Inspired by the fact that nanoparticles with diverse physicochemical properties would generate distinct and specific interactions with drug-resistant and drug-sensitive cancer cells, which have distinctive molecular signatures, here, we have synthesized a library of fluorescent nanoparticles with various sizes, surface charges, and compositions (SiO2nanoparticles (SNPs), organic PS-co-PAA nanoparticles (ONPs), and ZIF-8 nanoparticles (ZNPs)), thus demonstrating that the composition has a critical influence on the interaction of nanoparticles with drug-resistant cancer cells. Furthermore, the clathrin/caveolae-independent endocytosis of ZNPs together with the P-glycoprotein-related decreased cell membrane fluidity resulted in a lower cellular accumulation of ZNPs in drug-resistant cancer cells, consequently causing the distinct cellular accumulation of ZNPs between the drug-resistant and drug-sensitive cancer cells. This difference was further quantified by detecting the fluorescence signals generated by the accumulation of nanoparticles at the single-cell level via flow cytometry. Our findings provide another insight into the nanoparticle–cell interactions and offer a promising platform for the diagnosis of cancer drug resistance of various cancer cells and clinical cancer samples at the single-cell level.

ABSTRACTTo study the impact of bus priority control (BPC) on traffic carbon emissions under the strategies of speed guidance, green extension (GE), and red truncation (RT), with consideration of the main influencing factors such as delay, stopping times, and speed, a combination optimization method was used to develop a bi-level optimization model for BPC. The optimal carbon-emission reductions of buses and social vehicles with different fuel types in the upstream section of the intersection and the intersection control area was the upper-level objective, and the optimal total passenger-delay reduction was the lower-level objective. The Gauss – Seidel iterative algorithm was used to solve the model. Finally, the model was applied to the analysis of calculation cases. The results indicated that after BPC was adopted under the guidance acceleration strategy, the reductions in the carbon emissions and total delay of passenger were optimal when the guidance speed was 38 km/h, i.e. 12.67% and 21.05%, respectively. Under the guidance acceleration and GE strategy, the reductions in the carbon emissions and total delay of passenger were optimal when the guidance speed was 39 km/h and the GE was 6 s, i.e. 27.49% and 38.62%, respectively. Under the guidance deceleration and RT strategy, the reductions in the carbon emissions and total delay of passenger were optimal when the guidance speed was 29 km/h and the RT was 6 s, i.e. 22.18% and 33.52%, respectively. The model reduced the carbon emissions and total delay of passenger in the upstream section of the intersection and the intersection control area to achieve the optimal overall traffic benefit for the intersection.

S/N/O tri-doped carbon nanospheres anode exhibits superior reversible capacity and ultra-long cycling stability for PIBs (397.4 mA h g−1at 100 mA g−1after 700 cycles; 123.1 mA h g−1at 3000 mA g−1after 16,500 cycles).

Aim: The quality of life (QoL) of disaster-exposed survivors has always been a topic of concern. The aims of the present study were to explore the role of mindfulness in QoL in a relatively large sample of disaster-exposed survivors and to examine whether social support and posttraumatic growth (PTG) could be mediators. Subject and methods: A total of 806 survivors were surveyed 10 years after the Wenchuan earthquake. A self-administered questionnaire was used to measure mindfulness, QoL, social support, PTG, and sociodemographic characteristics. Linear regressions and mediation analyses were performed to examine the associations between mindfulness, QoL, social support, and PTG. Results: Of the survivors surveyed, 7.8% still reported poor or very poor QoL 10 years later. Correlation analyses indicated QoL was positively correlated with mindfulness, social support, and PTG. The PROCESS macro revealed that social support and PTG played multiple mediating roles in the relationship between mindfulness and QoL. Moreover, the association between mindfulness and QoL was mediated sequentially by social support and PTG. Conclusions: QoL among disaster-exposed survivors can be improved through the enhancement of mindfulness, the provision of social support, and the promotion of PTG. Future clinical mindfulness-focused interventions for disaster-exposed survivors could also include intervening social support and PTG, which may have a synergistic effect on improving QoL.

We present a novel method using satellite and biogeochemical Argo (BGC-Argo) data to retrieve the 3-D structure of chlorophyll $a$ (Chla) in the northern Indian Ocean (NIO). The random forest (RF)-based method infers the vertical distribution of Chla using the near-surface and vertical features. The input variables can be divided into three categories: 1) near-surface features acquired by satellite products; 2) vertical physical properties obtained from temperature and salinity profiles collected by BGC-Argo floats; and 3) the temporal and spatial features, i.e., day of the year, longitude, and latitude. The RF-model is trained and evaluated using a large database including 9738 profiles of Chla and temperature-salinity properties measured by BGC-Argo floats from 2011 to 2021, with synchronous satellite-derived products. The retrieved Chla values and the validation dataset (including 1948 Chla profiles) agree fairly well, with $R^{2} = 0.962$ , root-mean-square error (RMSE) = 0.012, and mean absolute percent difference (MAPD) = 11.31%. The vertical Chla profile in the NIO retrieved from the RF-model is more accurate and robust compared to the operational Chla profile datasets derived from the neural network and numerical modeling. A major application of the RF-retrieved Chla profiles is to obtain the 3-D Chla structure with high vertical resolution. This will help to quantify phytoplankton productivity and carbon fluxes in the NIO more accurately. We expect that RF-model can be used to develop long-time series products to understand the variability of 3-D Chla in future climate change scenarios.

Predicting the trajectory of ocean eddies can promote the understanding of the transport of matter and energy in the ocean. However, accurately and rapidly predicting the trajectory of eddies poses a significant challenge due to their intricate nonlinear motion within a physical environment. Regrettably, existing data-driven methods primarily focus on the migration and combination of models, as well as the fusion processing of diverse observational data on oceanic eddies. These ways often overlook the crucial aspect of modeling the underlying motion mechanism of the eddies. We believe that the expeditious and precise prediction of eddies is closely intertwined with the physical mechanism and historical time series. Consequently, a medium-range eddy trajectory prediction neural network (ETPNet) compliant with the physical constraint is proposed, which embeds the physical regulation, intrinsic relations, and mutual interactions into the network via constraints. Then, a novel variant of the long short-term memory (LSTM) cell is designed to enhance the dynamic interaction and representation ability of the features, constraints, and knowledge. Finally, a geographically informed comprehensive loss function for marine tasks is formulated, namely mean absolute geodetic error (MAGE), which optimizes the network in Euclidean and sphere space. The proposed network is evaluated by predicting the future seven days trajectory of anticyclone eddies in the $15^{\circ }\text{N}$ to $40^{\circ }\text{N}$ . The extensive experiments and evaluations demonstrate that the proposed network guided by the comprehensive loss function can implement a state-of-the-art performance. The code is available at https://github.com/AI4Ocean/ETPNet

In this paper, we revisit state estimation and weak detectability verification for discrete event systems (DES) from a span-new perspective. Specifically, using the semi-tensor product (STP) technique, we construct two new matrix-based information structures called a current-state estimator (C-estimator) and an initial-state estimator (I-estimator) for computing three fundamental types of state estimates, namely, current-state estimate (CSE), initial-state estimate (ISE), and delayed-state estimate (DSE). The complexity of building C-estimator and I-estimator is polynomial time with respect to the size of a plant. A notion of weak delayed detectability is introduced, which captures that, after observing a $k_{1}$ -length sequence/string, whether or not one can always accurately determine the state of a plant at this moment after at most $k_{2}$ steps of delays for some trajectories. Further, using the proposed C-estimator and I-estimator, we discuss the different types of detectability verification problems, including, but not restricted to, weak current-state detectability (C-detectability), weak initial-state detectability (I-detectability), and weak delayed detectability. Accordingly, several necessary and sufficient criteria are derived for verifying the aforementioned different types of detectability. Our approaches are numerically tractable and only involve some basic matrix manipulations. Finally, some examples are given to illustrate the obtained results. Note to Practitioners—State estimation is one of the most fundamental problems in many practical engineering systems. For instance, one needs to infer the state of a manufacturing system before a failure occurs. For a communication system, can we guarantee that whether important information remains secret to outsiders for security requirements? Finding an alternative and efficient approach to capture the state of a plant based on imperfect observations is still crucial for engineers. To solve these problems, in this paper we develop a novel methodology to tackle simultaneously three fundamental categories of state estimation for practical engineering systems that are inherently abstracted as partially-observed discrete-event systems. Our approaches are technically quite different from the existing ones. The novel results obtained in this paper are all of matrix-based characterization, which can be implemented algorithmically by means of the user-friendly STP software package. We believe that the alternative methodology provides an innovative insight for engineers in the field of automatic control.

Background: Air pollution has aroused global concerns because of its adverse effects on individuals’ physical and psychological health and behavior. Although there has been substantial traditional consideration of the objective impact of air pollution, more knowledge is needed about perceived air quality (PAQ), its association with objective air pollution (OAP), and the relationship between OAP and PAQ with respect to pro-environmental behavior (PEB). Methods: To delineate and investigate the effect of air pollution on both perceived and objective perspectives of PEB and its underlying psychological mechanisms, this study distributed a survey questionnaire related to PAQ, the Positive and Negative Affect Schedule (PANAS), satisfaction with local governmental control of air quality (SAT), and the PEB scale. The monitored data of objective city-level air pollution and 391 samples of survey data were included in this study. Results: The results reveal that both PAQ and OAP increase individuals’ negative affect (NA) and decrease SAT, which sequentially restrains PEB. More importantly, PAQ, NA, and SAT played mediating roles in the relationship between OAP and PEB. Empirical testing for group difference also indicated that while there is no gender-related difference with respect to caring about SAT and PEB caused by air pollution, gender effects on NA were significantly different. Age-related differences exist among younger, medium, and older age groups with respect to NA, SAT, and PEB caused by air pollution, and there are also background differences with respect to NA, SAT, and PEB, although income does not generate a significant group difference effect on NA, SAT, and PEB. Conclusions: The findings corroborate the important roles of affect and SAT in activating public concern about air quality. We discuss the possible ways that affect and SAT might enhance PEB as well as the limitations of this study. More pollutants and mechanisms could be considered in future studies.

Electrical impedance tomography (EIT) is a promising functional and structural imaging method in process tomography. However, due to the “soft-field” nature and the high dependence on the prior information, it often suffers serious artifacts in quantitative analysis. Most recently, EIT image quality has significantly improved because of the state-of-the-art (SOTA) deep learning-based models in the aspect of solving the inverse problem, especially fully convolutional networks (FCNs) and V-Net variants. Despite their success, these deep convolutional neural networks (CNNs) have two limitations: 1) the long-range information transition is frequently lost and the reverse gradient often disappears in deep CNNs and 2) some novel skip connections, such as residual and dense connections, often occupy substantial computational resources. To overcome these two limitations, we propose $\text{V}^{2}\text{A}$ -Net, a new neural architecture based on redesigned feature transited connections by the terms of: 1) a prereconstructor based on the iterative Newton–Raphson (NR) method, which maps the nonlinear function between the measurements and the initial images; 2) dual cascaded V-Nets are combined, which play the role of an encoder and a decoder, respectively; 3) a new parallel attention mechanism via channel attention and coordinate attention to learn the conductivity distributions and boundary-shaped feature separately; and 4) the lightweight skip connections reduce the computational resources (or accelerate the inference speed) of EIT imaging. The $\text{V}^{2}\text{A}$ -Net is evaluated by using the multiphase flow industrial applications, and the results demonstrate that: 1) $\text{V}^{2}\text{A}$ -Net has a better performance in shape reconstruction with sharp “corner”; 2) $\text{V}^{2}\text{A}$ -Net could reconstruct the model accurately where it has some low-contrast conductivity distributions; 3) $\text{V}^{2}\text{A}$ -Net enhances the quality of interfaces with the stratified flow; and 4) the pruned $\text{V}^{2}\text{A}$ -Net achieves significant speedup compared with the VDD-Net or $\text{V}^{2}\text{D}$ -Net. The analyses show that the average relative error is 0.05, the average correlation coefficient (CC) is 0.92, and the average structural similarity (SSIM) is 0.92 on the testing datasets. In addition, the average relative cover ratio is 0.97, and the average relative contrast (RCo) ratio is 0.98 on the testing datasets.

In this study, our aim was to evaluate the discordance of programmed cell death ligand 1 (PD-L1) expression between 2 paired paraffin blocks from surgical nonsmall cell lung cancer (NSCLC) specimens, thus providing recommendations for choosing paraffin blocks for PD-L1 immunohistochemistry detection. A total of 460 paired paraffin blocks of surgical NSCLC specimens were analyzed using the 22C3-PD-L1 assay. PD-L1 expression between 2 paired paraffin blocks was calculated using 3 classification schemes, tumor proportion score (TPS)-based 3-level classification and TPS-based binary classification using TPS ≥1% or TPS ≥50% as the cutoff. Clinicopathological characteristics were analyzed for cases with discordant PD-L1 expression. PD-L1 expression in 2 paired paraffin blocks of surgical NSCLC specimens was highly correlated from a single tumor (R2=0.89) in the overall trend. The overall discordance rates were 10.9%, 7.4%, and 3.5% respectively when using TPS-based 3-level classification or binary classification. No statistical differences were observed in PD-L1 expression discordance rates when patients were stratified by age, sex, smoking status, histologic types, TNM stage, or years of paraffin blocks (P>0.05). The presence of a solid histologic pattern was associated with a higher PD-L1 expression discordance rate in adenocarcinomas (P<0.05). Twenty-five cases with discordant PD-L1 expression were divided into 2 categories: spatial heterogeneity without recognizable morphology difference (76%) and spatial heterogeneity with significantly different morphology (24%). The discordance rate in TPS scores was much higher in cases with different morphology than those without different morphology. One representative paraffin block containing adequate neoplastic tissue may be adequate to determine PD-L1 expression in most of the surgical specimens of NSCLC. In cases that harbored different morphology in different paraffin blocks, the dual-block immunohistochemistry assessment method is recommended due to the intratumoral heterogeneity.

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Over the past decade, dramatic progress has been made in dental research areas involving laser therapy. The photobiomodulatory effect of laser light regulates the behavior of periodontal tissues and promotes damaged tissues to heal faster. Additionally, photobiomodulation therapy (PBMT), a non-invasive treatment, when applied in orthodontics, contributes to alleviating pain and reducing inflammation induced by orthodontic forces, along with improving tissue healing processes. Moreover, PBMT is attracting more attention as a possible approach to prevent the incidence of orthodontically induced inflammatory root resorption (OIIRR) during orthodontic treatment (OT) due to its capacity to modulate inflammatory, apoptotic, and anti-antioxidant responses. However, a systematic review revealed that PBMT has only a moderate grade of evidence-based effectiveness during orthodontic tooth movement (OTM) in relation to OIIRR, casting doubt on its beneficial effects. In PBMT-assisted orthodontics, delivering sufficient energy to the tooth root to achieve optimal stimulation is challenging due to the exponential attenuation of light penetration in periodontal tissues. The penetration of light to the root surface is another crucial unknown factor. Both the penetration depth and distribution of light in periodontal tissues are unknown. Thus, advanced approaches specific to orthodontic application of PBMT need to be established to overcome these limitations. This review explores possibilities for improving the application and effectiveness of PBMT during OTM. The aim was to investigate the current evidence related to the underlying mechanisms of action of PBMT on various periodontal tissues and cells, with a special focus on immunomodulatory effects during OTM.

Hierarchical porous carbons equipped with heteroatoms and diffusion pores have a wide application prospect in adsorption. Herein, we report N-autodoped porous carbons (PTPACs), which were derived from rigid N-rich conjugated microporous poly(aniline)s (CMPAs) and show their all-around applicability in heavy metal adsorption. Their molecular structure could be delicately tuned from 3D organic networks to graphitic carbons through simply adjusting the pyrolysis temperature, affording unique hybrid features of hierarchical micro-meso-macroporosity and amount-tunable nitrogen defects, as validated by the enhanced CO2adsorption capacities reaching 5.0 mmol g–1, a 230% increase compared to the precursor (2.15 mmol g–1). They therefore show promising a Langmuir adsorption capacity of 434.8 mg g–1toward mercury ions, which could be rapidly achieved within a short 20 min. Based on the comprehensive experimental, characterization, and DFT calculation studies, we rationally reveal these impressive adsorptions arise from the hybrid function of chemisorption contributed by populated nitrogen defects and physical adsorption achieved by synergistic functions in the diffusion and storage pores. Outcomes mark the high merits of PTPACs in addressing recent global challenges in environmental engineering.

Background and aims COUNT score, PNI score, and GNRI scores are associated with cardiovascular events. This review identifies the most accurate malnutrition assessment tools based on these scores in predicting mortality and readmission outcomes in HF patients.Material and Methods PubMed via MEDLINE, EMBASE were searched to identify studies assessing malnutrition using CONUT, PNI and GNRI. A meta-analysis was carried out to pool the hazard ratios on mortality and readmission rates. The methodological quality was assessed using the Newcastle-Ottawa Scale.Results The mortality in HF patients with malnutrition assessed by CONUT showed pooled HR of 1.23. HF patients with all severe, moderate, and mild risk of malnutrition showed mortality with HR 3.56, 2.71 and 1.57 respectively. For malnutrition assessed with GNRI, HF patients with all severe, moderate, and mild risk of malnutrition showed mortality with HR 4.17, 2.73 and 1.73 respectively. No significance difference in association of CONUT score with pooled HR of readmission rate was observed HR 0.99. With PNI, HF patients with all severe and moderate risk of malnutrition showed mortality with HR 2.14 and HR 1.68 respectively, although they failed to achieve significance.Conclusion CONUT and GNRI are the superior prognostic indicator than PNI in prediction of mortality associated with risk of malnutrition.

ABSTRACTRNA 5-methylcytosine (m5C) is a widespread post-transcriptional modification involved in diverse biological processes through controlling RNA metabolism. However, its roles in uveal melanoma (UM) remain unknown. Here, we describe the biological roles and regulatory mechanisms of RNA m5C in UM. Initially, we identified significantly elevated global RNA m5C levels in both UM cells and tissue specimens using ELISA assay and dot blot analysis. Meanwhile, NOP2/Sun RNA methyltransferase family member 2 (NSUN2) was upregulated in both types of these samples, whereas NSUN2 knockdown significantly decreased RNA m5C level. Such declines inhibited UM cell migration and suppressed cell proliferation through cell cycle G1 arrest. Furthermore, bioinformatic analyses, m5C-RIP-qPCR, and luciferase assay identified β-Catenin (CTNNB1) as a direct target of NSUN2-mediated m5C modification in UM cells. Additionally, overexpression of miR-124a in UM cells diminished NSUN2 expression levels indicating that it is an upstream regulator of this response. Our study suggests that NSUN2-mediated RNA m5C methylation provides a potential novel target to improve the therapeutic management of UM pathogenesis.

In this instalment, we introduce a way of using high-resolution mass spectrometry (HR-MS) systems to characterize the structures of metabolites. This results in a general workflow for metabolism studies for [...]

Nuclear factor erythroid-2 related factor-2 (NFE2L2or NRF2) is a frequently mutated gene in esophageal squamous cell carcinoma (ESCC). However, the roles of NFE2L2alterations in ESCC remain elusive. In order to elucidate this issue, 130 ESCC patients who underwent esophagectomy were enrolled. The majority of tumor tissues were positive for NRF2, which was significantly enriched in the nucleus of the primary tumor tissues compared with the noncancerous mucosae. Primary ESCC tumors positive for NRF2 tended to be positive for NAD(P)H quinone oxidoreductase 1 (NQO1) as the downstream target of NRF2. There was a positive correlation between NRF2 and NQO1 expression level in primary tumors. NQO1 staining in primary tumors with NRF2 nuclear expression was significantly stronger than that with NRF2 cytoplasmic expression. In addition, high concordance for the status of NRF2 expression between primary tumors and corresponding metastatic lesions was observed. Next, we found high expression of nuclear NRF2 (the proportion of nuclear NRF2 expression >20% or nuclear NRF2 immunohistochemistry score >20) predicted shorter overall survival in patients with dual-positive expression of NRF2 and NQO1. Captured-based targeted sequencing revealed that NFE2L2somatic alterations were observed in 52.8% of ESCC patients with dual-positive expression of NRF2 and NQO1. NFE2L2amplification and mutations within the DLG/ETGE motifs were seen more frequently in ESCC tumors with nuclear or nucleocytoplasmic expression of NRF2 compared with those with cytoplasmic expression of NRF2. We also found high expression of nuclear NRF2 plus the status of NFE2L2alteration exhibited high performance in predicting prognosis of ESCC patients. Our study demonstrated that high nuclear NRF2 expression and NFE2L2alterations were associated with poor prognosis of ESCC patients. These findings suggest that NRF2 signaling pathway might play vital roles in ESCC malignancy and the aberrant activation of NRF2 pathway predicts unfavorable prognosis in ESCC.

Root microbiota affect the host plant's adaptation to adverse environments. The structure and function of plant root bacterial communities are affected by soil physicochemical properties and plant genotypes. Distant hybridization is a common breeding strategy to introgress the excellent genes of wild relatives into the crop genome. The effect of distant hybridization on the crop root microbiota has not been reported. In this study, the structure and function of root bacterial community of the somatic hybrid wheat introgression lines SR3 and SR4, which have been respectively reported to be tolerant to salt and saline‐alkali stress, and their parent wheat cultivar JN177 as well as common wheat cultivar Chinese Spring (CS) were analyzed using 16S rRNA high‐throughput sequencing technology. The results showed that distant hybridization altered the structure and function of wheat (Triticum aestivumL.) root bacterial community. Compared with the parent JN177, some bacterial genera related to plant growth and stress resistance showed higher abundance in SR3 and SR4. Intriguingly, compared with parent JN177, the root bacterial communities of SR3 and SR4 are more similar to that of CS. This indicated that the process of distant hybridization may alter key genes regulating wheat root microbiota. Distant somatic hybridization altered the structure of wheat root bacterial community.Bacterial genera related to stress resistance showed higher abundance in wheat introgression lines.The process of distant somatic hybridization may alter key genes regulating wheat root microbiota.Distant somatic hybridization alters the structure of wheat root bacterial microbiota.

Massive online open courses (MOOCs) are emerging as a disruptive innovation in the e-learning industry. Despite its rapid growth, MOOCs are challenged on its financial sustainability. In this paper, we focus on freemium, the predominant business model of MOOCs, and observe the emerging practice of nudging the learners toward completion. In the analytical model, the MOOC provider maximizes its profit by setting the price of the verified track and the effect of nudging the learners, and the learner decides to either enroll in the audit track or purchase to upgrade to the verified track based on the standalone utility from learning, the utility from peers and the prospective cost relating to dropout. We solve the joint optimization problem for the MOOC provider and perform sensitivity analysis. This paper contributes to theories of exploring the business side of MOOCs and implementing the freemium model in the context of MOOCs.

The pyrolysis carbon black (CBp) from waste tires accounts for more than 35% of pyrolysis products. Its poor reinforcing ability and low additional value limit heavily the wide application of thermal pyrolysis in resolving “the black pollution” problem caused by waste tires. In this study, the CBp was upgraded by hybridization with cellulose via ball milling of the CBp and microfibrillated cellulose (MFC). A series of characterizations show that the refinement of the CBp, nanofibrillation of MFC, and hybridization were simultaneously realized under the ball milling. The obtained CBp/nanocellulose hybrid (CNCH) has a bead-chain-like morphology, with the small CBp particles attached tightly to the cellulose nanofibers via hydrophobic and hydrogen-bond interactions. The aqueous suspension of CNCH was spray-dried and compounded with natural rubber (NR). CNCH showed a much higher reinforcing ability than the CBp and ball-milled CBp (mCBp), which was attributed to the unique bead-chain-like morphology, the fine dispersion of CNCH, the interlocking effect, and improved interface interaction between CNCH and NR molecular chains. Especially, NR reinforced by CNCH has very low hysteresis and higher antiabrasion ability, which means CNCH has obvious advantages to be used as reinforcing fillers in tires. The upgrading process is simple, environmentally friendly, and suitable for industrial applications. This work is expected to provide a theoretical basis and technical instruction for the use of the CBp in tires, accelerate the industrialization of pyrolysis, and resolve the black pollution problem.

Sulfur-doped hard carbon anode exhibits high reversible capacity and superior cycling stability for potassium-ion storage (298.1 mAh g−1at 100 mA g−1after 1000 cycles; 220.2 mAh g−1at 500 mA g−1after 5200 cycles).

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.cose.2006.11.001 Byline: Xiaoyan Chen, Bobby N.W. Ma, Cungang Yang Abstract: In secure multicast applications, members may join or leave frequently and key management is one of the most challenging problems. In this research, we proposed a modified CLIQUES key management protocol. It was the modification of CLIQUES that consisted of two stages: Static CLIQUES and Hierarchical CLIQUES. In Static CLIQUES, a static group controller was used to distribute the partial keys to group members. Compared with traditional CLIQUES, the Static CLIQUES was more secure for key storage, less complex, less processing requirement in the user machine, and easier to provide member privacy protection. In Hierarchical CLIQUES, a hierarchical structure was employed to support larger size of group members. Our experiments showed that the modified CLIQUES protocol was more scalable than CLIQUES. Also, it required less processing power than the Key Tree-Based approaches. Author Affiliation: Department of Electrical and Computer Engineering, Ryerson University, Toronto, Ont., Canada M5B 2K3 Article History: Received 21 August 2005; Revised 14 August 2006; Accepted 1 November 2006

In this paper, an S-type NCN/CdS heterojunction was formed by anchoring cadmium sulfide on nitrogen-doped carbon quantum dot-modified g-C3N4(abbreviated as NCN) via hydrothermal and calcination methods. The bifunctional properties of NCN/CdS for the detection and degradation of antibiotics [tetracycline (TC) and chlortetracycline (CTC)] were demonstrated. The S-type heterojunction has a strong redox capacity and effectively separates photogenerated e−-h+pairs, which improves photocatalytic performance. NCDs is located between cadmium sulfide and g-C3N4, which forms a charge-transport channel that accelerates the carrier transport between the interfaces of the S-type heterojunction. Good photocatalytic performance (TC: 98.0 % for 45 min; CTC: 100 % for 70 min) and excellent cycling stability were obtained. This study provides a new strategy for designing efficient, stable and bifunctional materials for environmental pollution treatment.

As urbanization rapidly progresses, rural areas are being increasingly recognized as havens for individuals seeking a slower pace of life. Despite the growing interest in slow tourism as a travel modality, there is a lack of rural destinations that have successfully established slow tourism as their primary image. This research focuses on Gaochun International Cittàslow in China, including a mixed-method approach to investigate how rural areas can cultivate a slow tourism image to attract visitors. This paper introduces a new conceptual framework for rural China's slow tourism image, termed the bullseye framework. This framework divides the image of slow tourism into three concentric layers: experiential foundation, interactive framework, and value resonance. Compositional analysis reveals a certain mismatch between the promotion of the image of slow tourism by the government and tourism companies and the perception of tourists. This mismatch is particularly evident in promoting an eco-original lifestyle, preserving folk culture, and creating a slow-paced living atmosphere. Therefore, the government and tourism companies must more accurately understand the needs of tourists to formulate more effective promotion strategies.

Ni/Co/SiO2hydrophobic coatings were fabricated by embedding SiO2nanoparticles into Ni/Co coatings using pulsed electrodeposition, followed by a liquid-phase hydrophobic treatment. Microstructure and morphology analysis of the composite coatings revealed that the SiO2nanoparticles were homogenously distributed in the Ni/Co coating, and the surfaces of the samples were close-grained without crack. Furthermore, the SiO2nanoparticles in the coating formed micro-nano structures on its surface, such that the contact angle reached 125° following the hydrophobic modification. The surface of the hydrophobic coating was found to be abrasion resistant and exhibited long-term stability in water. The corrosion inhibition efficiency of the Ni/Co/SiO2hydrophobic coatings on a Q235 carbon steel substrate in simulated seawater solution reached 98.6%, indicating optimal anti-corrosion performance.

The hydrological conditions near the soil surface influence the soil erosion process, as determined by the soil erodibility and critical shear stress. The soil erodibility and critical shear stress of saturated purple soil slopes were computed and compared with those of unsaturated purple soil slopes. The detachment capacities computed through the numerical method (NM), modified numerical method (MNM) and analytical method (AM), from rill erosion experiments on saturated purple soil slopes at different flow rates (2, 4, and 8 L min−1) and slope gradients (5, 10, 15, and 20°), were used to comparatively compute the soil erodibility and critical shear stress. The computed soil erodibilities and critical shear stresses were also compared with those of unsaturated purple soil slopes. At the different slope gradients ranging from 5° to 20°, there were no significant differences in the soil erodibilities of the saturated purple soil and also in those of the unsaturated purple soil. The critical shear stresses slightly varied with the slope gradients. The saturated purple soil was relatively significantly more susceptible to erosion. The NM overestimated the soil erodibility of both saturated and unsaturated soils by 31% and underestimated the critical shear stress. The MNM yielded the same soil erodibility and critical shear stress values as the AM. The results of this study supply parameters for modeling rill erosion of saturated purple soil slope.

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Minimal residual disease that persists after chemotherapy is the most valuable prognostic marker for haematological malignancies and solid cancers. Unfortunately, our understanding of the resistance elicited in minimal residual disease is limited due to the rarity and heterogeneity of the residual cells. Here we generated 161,986 single-cell transcriptomes to analyse the dynamic changes of B-cell acute lymphoblastic leukaemia (B-ALL) at diagnosis, residual and relapse by combining single-cell RNA sequencing and B-cell-receptor sequencing. In contrast to those at diagnosis, the leukaemic cells at relapse tended to shift to poorly differentiated states, whereas the changes in the residual cells were more complicated. Differential analyses highlighted the activation of the hypoxia pathway in residual cells, resistant clones and B-ALL with MLL rearrangement. Both in vitro and in vivo models demonstrated that inhibition of the hypoxia pathway sensitized leukaemic cells to chemotherapy. This single-cell analysis of minimal residual disease opens up an avenue for the identification of potent treatment opportunities for B-ALL.

Infertility affects about 15% of heterosexual couples and male factors account for ~45–50% of clinical cases. Genetic factors play an important role in male infertility and thus we try to develop a cost-effective method for screening the genetic factors in male infertility. In our retrospective proof-of-concept study, we employed the high-throughput ligation-dependent probe amplification (HLPA) to examine the copy number by 115 genomic loci covering the Y chromosome, and 5 loci covering the X chromosome-specific region. We identified 8 sex chromosome aneuploid people from the low sperm concentration (LSC) group, and Y chromosome-specific microdeletion/duplications in 211 samples from the LSC group, and in 212 samples from the control group. 35 samples showed complete loss of AZFc (BPY2to CDY1Bdeletion), which was not observed in controls. Nevertheless, a partial loss of AZFc (BPY2to BPY2Bdeletion) was detected at comparable frequencies in both groups (68/211 vs. 108/212, respectively). And we further found structural variations in 28.6 and 26.9% samples from infertility and fertility groups. Moreover, we found that there were lower copy numbers for heterochromatic sequences in men with LSC. Especially, we reported that ultra-low relative copy number (RCN) (<0.5) type and low RCN (0.5 to <0.75) type in Yq12 were more often in the LSC group for the first time. Our results not only shed light on the potential role of low RCN in Yq12 in male infertility but also showed that HLPA can be a powerful and cost-effective tool for clinical screening in male infertility.

Transition metal sulfides (TMSs) serve as anodes for potassium-ion batteries (PIBs) because of their high conductivity, high capacity, and requirement of cheap raw materials. However, their volume expansion, agglomeration, and crushing often lead to limited cycle life and inferior structural stability. Here, inspired by biological tree nodules, S, N-codoped carbon-coated Fe7S8particles (Fe7S8@SNC) originated from metalloporphyrins and were rationally designed for PIBs after being vulcanized by a one-pot method. Fe7S8@SNC as an anode delivered a high reversible capacity of 410 mAh g–1at 50 mA g–1, an extremely long cycle up to 2000 cycles with a capacity of 214 mAh g–1maintained at 1000 mA g–1, and excellent rate performances (287 mAh g–1at 500 mA g–1and 181 mAh g–1at 2000 mA g–1). Significantly, ex situ TEM can still capture the stable structure of Fe7S8after 500 cycles. In this unique structure, prominent Fe7S8particles reduce the mechanical stress and shorten the transport path of K+, alleviating the pulverization during repeated insertion/extraction of K+. The S, N-codoped carbon decoration protects the structural stability and inhibits the agglomeration of internal Fe7S8, alleviates the volume change caused by the K+reaction, and greatly improves the stability of PIBs. This study provides a new strategy for the realization of TMSs with ultralong cycling stability and lays a foundation for the commercial application of PIBs.

In the study of the number of limit cycles of near-Hamiltonian systems, the first order Melnikov function plays an important role. This paper aims to generalize Horozov-Iliev’s method to estimate the upper bound of the number of zeros of the function.

Excretion of [14C]HR011303-derived radioactivity showed significant species difference. Urine (81.50% of dose) was the main excretion route in healthy male subjects, whereas feces (87.16% of dose) was the main excretion route in rats. To further elucidate the underlying cause for excretion species differences of HR011303, studies were conducted to uncover its metabolism and excretion mechanism. M5, a glucuronide metabolite of HR011303, is the main metabolite in humans and rats. Results of a rat microsome incubation study suggested that HR011303 was metabolized to M5 in the rat liver. According to previous studies, M5 is produced in both human liver and kidney microsomes. We found that M5 in the human liver can be transported to the blood by multidrug resistance-associated protein (MRP) 3, and then the majority of M5 can be hydrolyzed to HR011303. HR011303 enters the human kidney or liver through passive diffusion, whereas M5 is taken up through organic anion transporter (OAT) 3, organic anion-transporting polypeptide (OATP) 1B1, and OATP1B3. When HR011303 alone is present, it can be metabolized to M5 in both sandwich-cultured rat hepatocytes (SCRH) and sandwich-cultured human hepatocytes (SCHH) and excreted into bile as M5 in SCRH. Using transporter inhibitors in sandwich-cultured model and membrane vesicles expressing MRP2 or Mrp2, we found that M5 was a substance of MRP2/Mrp2, and the bile efflux of M5 was mainly mediated by MRP2/Mrp2. Considering the significant role of MRP3/Mrp3 and MRP2/Mrp2 in the excretion of glucuronides, the competition between them for M5 was possibly the determinant for the different excretion routes in humans and rats.SIGNIFICANCE STATEMENTAnimal experiments are necessary to predict dosage and safety of candidate drugs prior to clinical trials. However, extrapolation results often differ from the actual situation. For HR011303, excretory pathways exhibited a complete reversal, through urine in humans and feces in rats. Such phenomena have been observed in several drugs, but no in-depth studies have been conducted to date. In the present study, the excretion species differences of HR011303 can be explained by the competition for M5 between MRP2/Mrp2 and MRP3/Mrp3.