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Improving plants' ability to survive under drought is of great importance to the horticultural industry. The plant hormone gibberellic acid (GA) mediates diverse aspects of plant growth and development. The Arabidopsis gibberellin acid insensitive mutant gai-1 displays reduced plant height, altered GA response, and enhanced drought resistance. However, over-expression of gai-1 using the constitutive 35S promoter results in dwarf plants with drought resistance. Here, we tested the hypothesis that the temporary inhibition of cell growth caused by inducible expression of the gai-1 gene would lead to better drought resistance and improve crop productivity without an undesirable dwarf phenotype. We generated transgenic plants in which the gai-1 gene was over-expressed in petunia, under a stress-inducible RD29A promoter from Arabidopsis. When these plants were subjected to limited irrigation and drought treatments, transgenic plants showed phenotypes of darker green leaves and compact flowers compared to the wild type plants. Importantly, these transgenic plants recovered sooner than wild type and the empty vector-transformed control plants. This study provides evidence that temporary inhibition of cell growth caused by over-expression of the gai-1 mutant gene with a drought stress-inducible promoter leads to better drought resistance when the plants experience drought conditions.

A novel and efficient end-to-end learning model for automatic modulation classification is proposed for wireless spectrum monitoring applications, which automatically learns from the time domain in-phase and quadrature data without requiring the design of hand-crafted expert features. With the intuition of convolutional layers with pooling serving as the role of front-end feature distillation and dimensionality reduction, sequential convolutional recurrent neural networks are developed to take complementary advantage of parallel computing capability of convolutional neural networks and temporal sensitivity of recurrent neural networks. Experimental results demonstrate that the proposed architecture delivers overall superior performance in signal to noise ratio range above -10 dB, and achieves significantly improved classification accuracy from 80% to 92.1% at high signal to noise ratio range, while drastically reduces the average training and prediction time by approximately 74% and 67%, respectively. Response patterns learned by the proposed architecture are visualized to better understand the physics of the model. Furthermore, a comparative study is performed to investigate the impacts of various sequential convolutional recurrent neural network structure settings on classification performance. A representative sequential convolutional recurrent neural network architecture with the two-layer convolutional neural network and subsequent two-layer long short-term memory neural network is developed to suggest the option for fast automatic modulation classification.

H9N2 avian influenza viruses are widely prevalent in birds and pose an increasing threat to humans because of their enhanced virulence and transmissibility in mammals. Active surveillance on the prevalence and evolution of H9N2 viruses in different avian hosts will help develop eradication measures. We isolated 16 H9N2 viruses from chickens, green peafowls, and wild birds in eastern China from 2017 to 2019 and characterized their comparative genetic evolution, receptor-binding specificity, antigenic diversity, replication, and transmission in chickens and mice. The phylogenetic analysis indicated that the green peafowl viruses and swan reassortant shared the same ancestor with the poultry H9N2 viruses prevalent in eastern China, while the seven wild bird viruses belonged to wild bird lineage. The chicken, peafowl, and swan H9N2 viruses that belonged to the poultry lineage preferentially recognized α-2, 6-linked sialic acids (human-like receptor), but the wild bird lineage viruses can bind both α-2, 3 (avian-like receptor) and human-like receptor similarly. Interestingly, the H9N2 viruses of poultry lineage replicated well and transmitted efficiently, but the viruses of wild bird lineage replicated and transmitted with low efficiency. Importantly, the H9N2 viruses of poultry lineage replicated in higher titer in mammal cells and mice than the viruses of wild birds lineage. Altogether, our study indicates that co-circulation of the H9N2 viruses in poultry, wild birds, and ornamental birds increased their cross-transmission risk in different birds because of their widespread dissemination.

The highly pathogenic avian influenza H5N6 viruses are widely circulating in poultry and wild birds, and have caused 38 human infections including 21 deaths; however, the key genetic determinants of the pathogenicity of these viruses have yet to be fully investigated. Here, we characterized two H5N6 avian influenza viruses – A/duck/Guangdong/S1330/2016 (GD/330) and A/environment/Fujian/S1160/2016 (FJ/160) – that have similar viral genomes but differ markedly in their lethality in mice. GD/330 is highly pathogenic with a 50% mouse lethal dose (MLD50) of 2.5 log10 50% egg infectious doses (EID50), whereas FJ/160 exhibits low pathogenicity with an MLD50 of 7.4 log10 EID50. We explored the molecular basis for the difference in virulence between these two viruses. By using reverse genetics, we created a series of reassortants and mutants in the GD/330 background and assessed their virulence in mice. We found that the HA gene of FJ/160 substantially attenuated the virulence of GD/330 and that the mutation of glycine (G) to tryptophan (W) at position 225 (H3 numbering) in HA played a key role in this function. We further found that the amino acid mutation G225W in HA decreased the acid and thermal stability and increased the pH of HA activation, thereby attenuating the H5N6 virus in mice. Our study thus identifies a novel molecular determinant in the HA protein and provides a new target for the development of live attenuated vaccines and antiviral drugs against H5 influenza viruses.

Based on weather radar data, precipitation data from densified rainfall stations, hydrological data at Wucha hydrological station in Qijiang Catchment and ERA5 reanalysis data, we have conducted the analysis of a record-breaking flood event occurred in Qijiang Catchment from June 19 to 22 in 2020 including the spatial-temporal distribution of precipitation, the circulation background, the water vapor sources and the evolutional characteristics of mesoscale convective systems (MCSs). The results indicate that (1) this event is a persistent severe precipitation event with concentrated range and characterized by obvious periodic and diurnal variation. It can be divided into three stages. Severe precipitation mainly occurs at night. (2) Persistent heavy rainfall occurs under the circulation pattern of cold air guided by east-moving cold low pressure in the Ural Mountains moving southward to the northeast of Sichuan Basin, low trough in the mid-latitude maintaining for a long time in the eastern Sichuan-Chongqing-Guizhou area and the Western Pacific subtropical high being stable. (3) Low-level warm and moist southwest jet further increases the atmospheric stratification instability between northern Guizhou and southern Chongqing, and it conveys water vapor from South China Sea and Bengal Bay to Qijiang River Basin, providing abundant water vapor for the generation and persistence of heavy rainfall. (4) The occurrence and development of MCSs at the three severe precipitation stages show different features. At the first stage, MCSs in coherence with the strong radar echoes are situated in roughly north-south direction, moving eastward to affect the Qijiang Catchment, and the duration of heavy rainfall is therefore relatively short. Next, the MCSs present southwest-northeast direction, affecting Qijiang Catchment for a longer time, but the echo intensity is weak. At last stage, the MCSs present massive. And they are linearly distributed in the northwest-southeast direction when they mature, exhibiting "train effect", which affects Qijiang Catchment longest and cause the greater precipitation intensity.

Summary: Fusobacterium nucleatum (Fn) is primarily colonized in the oral cavity. Recently, Fn has been closely associated with the tumorigenesis of colorectal cancer (CRC). Here, we showed that the relative level of Fn DNA was increased in the saliva of the CRC group compared with the normal colonoscopy, hyperplastic polyp, and adenoma groups. Receiver operating characteristic curve analysis illustrated that Fn DNA was superior to carcinoembryonic antigen and carbohydrate antigen 19-9 in CRC diagnosis. Moreover, levels of Fn DNA were associated with the overall survival and disease-free survival of CRC patients, which was an independent factor for prognostic prediction. Transcriptome sequencing identified 1,287 differentially expressed mRNAs in tumor tissues between CRC patients with high-Fn and low-Fn infection. Kyoto encyclopedia of genes and genomes analysis showed that ECM-receptor interaction and focal adhesion were the top two significant pathways. Overall, salivary Fn DNA may be a noninvasive diagnostic and prognostic biomarker for CRC patients.

ABSTRACT H10Nx influenza viruses have caused increasing public concern due to their occasional infection of humans. However, the genesis and biological characteristics of H10 viruses in migratory wild birds are largely unknown. In this study, we conducted active surveillance to monitor circulation of avian influenza viruses in eastern China and isolated five H10N4 and two H10N8 viruses from migratory birds in 2020. Genetic analysis indicated that the hemagglutinin (HA) genes of the seven H10 viruses were clustered into the North American lineage and established as a novel Eurasian branch in wild birds in South Korea, Bangladesh, and China. The neuraminidase (NA) genes of the H10N4 and H10N8 viruses originated from the circulating HxN4 and H5N8 viruses in migratory birds in Eurasia. We further revealed that some of the novel H10N4 and H10N8 viruses acquired the ability to bind human-like receptors. Animal studies indicated that these H10 viruses can replicate in mice, chickens, and ducks. Importantly, we found that the H10N4 and H10N8 viruses can transmit efficiently among chickens and ducks but induce lower HA inhibition (HI) antibody titers in ducks. These findings emphasized that annual surveillance in migratory waterfowl should be strengthened to monitor the introduction of wild-bird H10N4 and H10N8 reassortants into poultry. IMPORTANCE The emerging avian influenza reassortants and mutants in birds pose an increasing threat to poultry and public health. H10 avian influenza viruses are widely prevalent in wild birds, poultry, seals, and minks and pose an increasing threat to human health. The occasional human infections with H10N8 and H10N3 viruses in China have significantly increased public concern about the potential pandemic risk posed by H10 viruses. In this study, we found that the North American H10 viruses have been successfully introduced to Asia by migratory birds and further reassorted with other subtypes to generate novel H10N4 and H10N8 viruses in eastern China. These emerging H10 reassortants have a high potential to threaten the poultry industry and human health due to their efficient replication and transmission in chickens, ducks, and mice.

Summary: The mechanism by which redox metabolism regulates the fates of acute myeloid leukemia (AML) cells remains largely unknown. Using a highly sensitive, genetically encoded fluorescent sensor of nicotinamide adenine dinucleotide phosphate (NADPH), iNap1, we find three heterogeneous subpopulations of AML cells with different cytosolic NADPH levels in an MLL-AF9-induced murine AML model. The iNap1-high AML cells have enhanced proliferation capacities both in vitro and in vivo and are enriched for more functional leukemia-initiating cells than iNap1-low counterparts. The iNap1-high AML cells prefer localizing in the bone marrow endosteal niche and are resistant to methotrexate treatment. Furthermore, iNap1-high human primary AML cells have enhanced proliferation abilities both in vitro and in vivo. Mechanistically, the MTHFD1-mediated folate cycle regulates NADPH homeostasis to promote leukemogenesis and methotrexate resistance. These results provide important clues for understanding mechanisms by which redox metabolism regulates cancer cell fates and a potential metabolic target for AML treatments.

Background and purpose: Fine particulate matter (PM2.5) has been associated with increased risks of stroke, but it remains unclear which specific size ranges and chemical constituents dominate the effects of PM2.5 on stroke. We aimed to evaluate the associations of size-segregated particles and various constituents of PM2.5 with daily emergency-room visits for stroke. Methods: We conducted a time-series study to investigate the associations of 5 particle size ranges from 0.01 to 2.5 µm and 35 constituents of PM2.5 with the daily emergency-room visits for stroke in Shanghai, from 2014 to 2019. Over-dispersed generalized additive models were used to estimate the associations. The robustness of these associations was evaluated by additionally controlling for PM2.5 mass. Results: For size ranges from 0.01 to 0.3 µm, there were significant positive associations between particle number concentrations and daily emergency-room visits for stroke with the strongest associations occurring for the size range 0.05–0.1 µm. The size-dependent pattern was not changed by adjusting for PM2.5 and gaseous pollutants. The associations of daily emergency-room visits for stroke also varied considerably by various PM2.5 constituents. After controlling for the simultaneous exposure to PM2.5 and gaseous pollutants in two-pollutant models, we identified 11 out of 35 constituents that had robust associations, these being organic carbon, elemental carbon, chlorine, magnesium, ammonium, nitrate, sulfate, copper, manganese, lead and zinc. Conclusion: Ultra-fine particles and some PM2.5 constituents (i.e., carbonaceous fractions, inorganic ions and some elements) may be mainly responsible for the excess risk of stroke induced by PM2.5.

ObjectiveSyndecan-2 (SDC2) methylation has been previously reported as a sensitive biomarker for the early detection of colorectal cancer (CRC). Droplet digital PCR (ddPCR) is the latest development of PCR technology. It can accurately detect and quantify the target sequence of nucleic acid. ddPCR is widely used in research and clinical diagnosis. In the present study, we aimed to develop a ddPCR method to detect SDC2 gene methylation and evaluate the diagnostic value of SDC2 gene methylation.MethodsFirst, a ddPCR method was developed to measure SDC2 methylation in stool samples collected from 51 cases of normal, 23 cases of adenoma, and 86 cases of CRC. Subsequently, a meta-analysis of existing studies was conducted to judge the diagnostic value of SDC2 gene methylation in CRC. PUBMED, EMBASE, Web of Science, and Scopus databases were searched for relative studies. Meta-analysis was performed using Meta Disc 1.4 and STATA 15.0 software.ResultsThe ddPCR showed that the linearity, sensitivity, and specificity for the detection of SDC2 gene methylation could be down to 0.1% methylation level and 5 ng of methylated DNA input. In 109 cases of CRC, 107 cases could be detected, and the sensitivity was 98.17%. The median value of the percentage of methylated reference (PMR) in colorectal adenoma and CRC patients was significantly higher compared with the normal individuals (p < 0.001). In addition, we found that the PMR value was associated with the clinical staging of CRC. The difference of PMR in stage II and stage IIIA was statistically significant (p < 0.05). Moreover, the meta-analysis showed that 11 out of 87 studies were identified to report the feasibility of SDC2 gene methylation as a method to diagnose early CRC. The pooled sensitivity and specificity of SDC2 gene methylation test for CRC were 0.80 [95% CI (0.68–0.88)] and 0.93 [95% CI (0.91–0.94)], respectively. The pooled diagnostic odds ratio (DOR) and area under curve (AUC) were 52.46 [95% CI (30.43–90.45)] and 0.94 [95% CI (0.92, 0.96)], respectively.ConclusionsThe ddPCR method was more sensitive and convenient to detect SDC2 gene methylation, and the pooled analysis showed that methylated SDC2 was a valuable biomarker for the non-invasive detection of CRC.

Various medicinal ingredients with different tastes are combined according to the theory of compatibility in Chinese materia medica to achieve a better efficacy, while the mechanism was not very clear. Here, the authors studied the interaction between ingredients and human transporters such as the kidney transporters OAT1 and OAT3, the liver transporters OATP1B1 and OATP1B3, and the intestine transporter OATP2B1 to discern the compatibility mechanism of ingredients with different tastes in the Yuanhuzhitong preparation (YHP) comprising Corydalis yanhusuo (CYH) and Angelica dahurica (AD), which could relieve pain by restraining the central system. The results show that tetrahydropalmatine (TDE), the major component of CYH, could be transported by OAT3 into kidney, OATP1B1 and OATP1B3 into liver, while imperatorin (IPT) and isoimperatorin (ISP), the two key components of AD, and AD extract showed strong inhibition to OAT1 and OAT3. What's more, AD extract also exerted strongly inhibition to human transporters OATP1B1 and OATP1B3. It was also detected that IPT, ISP, and AD extract significantly downregulated the expression of Oatp1a1, Oatp1a4, and Oatp1b2 of liver in mice. The in vivo results show that the concentration of TDE in liver and kidney significantly decreased, while the TDE concentration in blood and brain were both significantly enhanced in the presence of IPT, ISP, and AD extract. These results suggest that the ingredients in AD with pungent taste could enhance the exposure of TDE in blood and brain by inhibiting the uptake of TDE in liver and kidney. That is to say, TDE with bitter taste could “flood up” into the central nervous system to play its therapeutic effect by the cut-off of that into liver and kidney in the presence of ingredients within AD. This paper not only proves the meridian distribution of CYH in liver and kidney with the role of OAT3, OATP1B1, and OATP1B3, but also illustrates how to improve the efficacy of CYH by reasonable compatibility with AD. This study may offer a valuable clue to illustrate the mechanism of compatibility theory.

The ARPS3DVAR+WRF (Advanced Regional Prediction and 3-dimensional variational System)rapid assimilation model is used to simulate several heavy rainfall events in Sichuan and Chongqing areas occurred in recent years. Focusing on the strongest precipitation within 12 h. Neighborhood approach is adopted to the SSRAFS (Storm-Scale Rapid Assimilation and Forecast System)products to perform Neighborhood Mean(NM) forecast, Station Probability(SP) forecast and Neighborhood Probability(NP) forecast in the ranges of different upscale radius. Then the characteristics and effects are respectively analyzed, and the effect of increasing upscale window area to the precipitation forecast is particularly discussed. Finally, the optimum radius of the operational forecast is found by combining traditional and spatial verification results. The results show that the performance of the NM forecast is not stable in light rain and downpour. The improvementof the moderate rain is not obvious, However, it has a good effect on the prediction of heavy rainfall. The singlestation probability may be misleading, but NP forecast could serve as a remedy, by giving better classification information on the uncertainty of heavy rainfall prediction, and provide better reference to improve the capability of short-term operational forecast. FSS and AROC verification results based on NP prediction has a better consistency guidance than TS scores of NM prediction. It reveals that the size of 36 km upscale could eliminate the uncertainty of heavy precipitation to a certain extent while retaining the characteristics of convective feature, which should be selected as the optimal window region.

Abstract Background Lung cancer has been the leading cause of tumor related death, and 80% ~ 85% of it is non-small cell lung cancer (NSCLC). Even with the rising molecular targeted therapies, for example EGFR, ROS1 and ALK, the treatment is still challenging. The study is to identify credible responsible genes during the development of NSCLC using bioinformatic analysis, developing new prognostic biomarkers and potential gene targets to the disease. Methods Firstly, three genes expression profiles GSE44077, GSE18842 and GSE33532 were picked from Gene Expression Omnibus (GEO) to analyze the genes with different expression level (GDEs) between NSCLC and normal lung samples, and the cellular location, molecular function and the biology pathways the GDEs enriched in were analyzed. Then, gene function modules of GDEs were explored based on the protein-protein interaction network (PPI), and the top module which contains most genes was identified, followed by containing genes annotation and survival analysis. Moreover, multivariate cox regression analysis was performed in addition to the Kaplan meier survival to narrow down the key genes scale. Further, the clinical pathological features of the picked key genes were explored using TCGA data. Results Three GEO profiles shared a total of 664 GDEs, including 232 up-regulated and 432 down-regulated genes. Based on the GDEs PPI network, the top function module containing a total of 69 genes was identified, and 31 of 69 genes were mitotic cell cycle regulation related. And survival analysis of the 31 genes revealed that 17/31 genes statistical significantly related to NSCLC overall survival, including 4 spindle assembly checkpoints, namely NDC80, BUB1B, MAD2L1 and AURKA. Further, multivariate cox regression analysis identified NDC80 and MAD2L1 as independent prognostic indicators in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) respectively. Interestingly, pearson correlation analysis indicated strong connection between the four genes NDC80, BUB1B, MAD2L1 and AURKA, and their clinical pathological features were addressed. Conclusions Using bioinformatic analysis of GEO combined with TCGA data, we revealed two independent prognostic indicators in LUAD and LUSC respectively and analyzed their clinical features. However, more detailed experiments and clinical trials are needed to verify their drug targets role in clinical medical use.

Abstract Background Suicide is a global issue among the elderly. The number of older people committing suicide is proliferating, and the elderly suicide rate is the highest among all age groups in China. A better understanding of the possible protective factors against suicidal ideation is necessary to facilitate prevention and intervention efforts. The objectives of the present study are threefold. First, this study aims to examine the psychometric properties of the three-dimensional inventory of character strengths (TICS) with a sample of older adults. Second, this study intends to investigate correlations among suicide ideation, wellbeing, and character strengths. Third, the study seeks to explore the possible protective roles of the three character strengths and wellbeing in explaining suicidal ideation among older adults. Methods A cross-sectional study comprising 308 older adults aged at least 50 years old from nursing homes was conducted. Four questionnaires, namely, the TICS, the Geriatric Suicide Ideation Scale—10 items, the Brief Inventory of Thriving, and the Satisfaction with Life Scale, were used. Exploratory structural equation modeling, intraclass correlation coefficients, partial correlations, and sets of hierarchical regressions were adopted to estimate and report the results. Results TICS could be used to assess the character strengths (i.e., caring, inquisitiveness, and self-control) among older adults with an acceptable goodness-of-fit (chi square = 157.30, df = 63, p

Abstract Background Yellow-feathered chickens (YFCs) have a long history in China. They are well-known for the nutritional and commercial importance attributable to their yellow color phenotype. Currently, there is a huge paucity in knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these iconic chickens. This study aimed to uncover the genetic structure and the molecular underpinnings of the YFCs trademark coloration. Results The whole-genomes of 100 YFCs from 10 major traditional breeds and 10 Huaibei partridge chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed three geographically based clusters among the YFCs. Compared to other Chinese indigenous chicken genomes incorporated from previous studies, a closer genetic proximity within YFC breeds than between YFC breeds and other chicken populations is evident. Through genome-wide scans for selective sweeps, we identified RALY heterogeneous nuclear ribonucleoprotein (RALY), leucine rich repeat containing G protein-coupled receptor 4 (LGR4), solute carrier family 23 member 2 (SLC23A2), and solute carrier family 2 member 14 (SLC2A14), besides the classical beta-carotene dioxygenase 2 (BCDO2), as major candidates pigment determining genes in the YFCs. Conclusion We provide the first comprehensive genomic data of the YFCs. Our analyses show phylogeographical patterns among the YFCs and potential candidate genes giving rise to the yellow color trait of the YFCs. This study lays the foundation for further research on the genome-phenotype cross-talks that define important poultry traits and for formulating genetic breeding and conservation strategies for the YFCs.

Based on the hourly precipitation data from 34 automatic stations in Chongqing from 1991 to 2015, the temporal and spatial distribution characteristics have been analyzed from the aspects of precipitation ratio, percentage of heavy precipitation, frequency of heavy precipitation, heavy precipitation event, maximum heavy precipitation and threshold of extreme heavy precipitation. The results are as follows. (1) The spatial distribution of precipitation ratio, percentage of heavy precipitation, frequency of heavy precipitation, heavy precipitation events, maximum heavy precipitation and threshold of extreme heavy precipitation are consistent with each other. The high value areas are mainly distributed in the southeast and west, while the low value areas are mainly located in the northeast and central areas. (2) The annual changes of precipitation ratio, percentage of heavy precipitation, frequency of heavy precipitation and maximum precipitation have shown fluctuations, while the change in precipitation rate is relatively small, and the latter three show the change characteristic of the same phase. On the monthly changes, the precipitation ratio is characterized by a "double peak", while the latter three are consistently characterized by a "single peak". In terms of daily changes, the high frequency of heavy precipitation mainly occurs from 03:00 BT to 05:00 BT in the morning, while the low frequency times are mainly from 13:00 BT to 15:00 BT in the afternoon. (3) In the continuity of heavy rainfall events, the duration of heavy precipitation events is consistent with the spatial distribution of the time from the beginning of precipitation to the time of the heaviest precipitation. The high value areas are mainly concentrated in the northeast and southeast, while the low value areas are mainly distributed in the central and western areas. In general, the longer the duration, the more delayed the time to produce the strongest precipitation, and the long-lasting heavy precipitation event occurred mainly at 23:00 p.m. to 04:00 a.m. in the next day. (4) The 99th, 99.5th, 99.9th percentile thresholds and 5, 10, 20, 50, and 100-year return period thresholds of the generalized extreme value (GEV) distribution functions and the maximum observed values are all consistent with heavy precipitation in spatial distribution.

Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase expressed at early stages of normal development and in various cancers including ALK-positive anaplastic large cell lymphoma (ALK+ ALCL), in which it is the main therapeutic target. ALK tyrosine kinase inhibitors (ALK TKIs) have greatly improved the prognosis of ALK+ALCL patients, but the emergence of drug resistance is inevitable and limits the applicability of these drugs. Although various mechanisms of resistance have been elucidated, the problem persists and there have been relatively few relevant clinical studies. This review describes research progress on ALK+ ALCL including the application and development of new therapies, especially in relation to drug resistance. We also propose potential treatment strategies based on current knowledge to inform the design of future clinical trials.

The anisotropy feature is an important characteristic of granular materials in natural life and is caused by two facts: the anisotropy feature of particle shape, such as an elongated or flattened shape, and the anisotropy feature of the packing fabric, such as the preferable orientation of particle alignment. The discrete element method has been commonly used in the study of meso-mechanics of granular materials and is in our study to simulate the direct shear test with particles of various aspect ratios under different initial orientation alignment conditions for assessing the coupled influence of anisotropy from particle shape and fabric of particle packings on the shear behaviour of granular materials. Analysis results show that anisotropy from the particle shape has the most significant influence on the shear behaviour of a granular packing when the packing has the initial anisotropy fabric of an orientational alignment perpendicular to the shear direction. Moreover, the initial fabric anisotropy of a granular packing has an increasing influence with the rise in anisotropy of particle shape. A combined anisotropic factor is finally introduced to reflect the coupled influence of the shape anisotropy of particles and the fabric anisotropy of particle packings.

Background & ObjectivesPancreatic ductal adenocarcinoma remains an extremely malignant tumor having a poor prognosis. The 5-year survival rate of PDAC is related to its stage (about 80% for stage I vs 20% for other stages). However, detection of PDAC in an early stage is difficult due to the lack of effective screening methods. In this study, we aimed to construct a novel metabolic model for stage-I PDAC detection, using both serum and tissue samples.MethodsWe employed an untargeted technique, UHPLC-Q-TOF-MS, to identify the potential metabolite, and then used a targeted technique, GC-TOF-MS, to quantitatively validate. Multivariate and univariate statistics were performed to analyze the metabolomic profiles between stage-I PDAC and healthy controls, including 90 serum and 53 tissue samples. 28 patients with stage-I PDAC and 62 healthy controls were included in this study.ResultsA total of 10 potential metabolites presented the same expression levels both in serum and in tissue. Among them, a 2-metabolites-model (isoleucine and adrenic acid) for stage-I PDAC was constructed. The area under the curve (AUC) value was 0.93 in the discovery set and 0.90 in the independent validation set. Especially, the serum metabolite model had a better diagnostic performance than CA19-9 (AUC = 0.79). Pathway analysis revealed 11 altered pathways in both serum and tissue of stage-I PDAC.ConclusionsThis study developed a novel serum metabolites model that could early separate stage-I PDAC from healthy controls.

Based on the hourly precipitation data of 34 meteorological stations in Chongqing in the summers (June to August) from 1996 to 2015, the spatial distribution and daily variation of precipitation amount (PA), precipitation intensity (PI), precipitation frequency (PF), and precipitation extremes in Chongqing are analyzed. The results show that, from the perspective of spatial distribution, the precipitation amount (PA) in Chongqing presents a distribution pattern of more around and less in the middle; the area with high precipitation intensity (PI) is mainly located in the northeast of Chongqing; the large value centers of precipitation frequency (PF) are located in the south and west of Chongqing and near Chengkou. On the spatial distribution of hourly precipitation, the precipitation in most areas of Chongqing is mainly concentrated at night [0200–0900 BT (1800–0100 UTC)], and the rain belt spreads from west to east with the passage of time. On the whole, interannual evolution characteristics of summer precipitation amount, precipitation intensity, and precipitation frequency in Chongqing are basically the same, showing a fluctuation characteristic without obvious trend, but there are some peaks and valleys. From the perspective of diurnal cycle, a larger peak of PA in Chongqing appears near 0300 BT (1900 UTC), another lower peak around 1200 BT (0400 UTC), a larger peak of PI around 0300 BT (1900 UTC), another smaller peak around 1500 BT (0700 UTC), and only one peak of PF around 0700 BT (2300 UTC). The extreme precipitation of different duration in summer in Chongqing is closely related to the topographic characteristics and weather system, the extreme centers of each diachronic precipitation are mainly located near Shapingba, Kaizhou, Youyang, and Shizhu, and the time evolution characteristics of the extreme precipitation are not obvious, but the trend of the extreme precipitation accumulated in 1 h, 3 h, 6 h, or 12 h is basically the same.

CO is a significant product of electrochemical CO2 reduction (ECR) which can be mixed with H2 to synthesize numerous hydrocarbons. Membranes, as separators, can significantly influence the performance of ECR. Herein, a series of quaternized polybenzimidazole (QAPBI) anion exchange membranes with different quaternization degrees are prepared for application in ECR. Among all QAPBI membranes, the QAPBI-2 membrane exhibits optimized physico-chemical properties. In addition, the QAPBI-2 membrane shows higher a Faraday efficiency and CO partial current density compared with commercial Nafion 117 and FAA-3-PK-130 membranes, at −1.5 V (vs. RHE) in an H-type cell. Additionally, the QAPBI-2 membrane also has a higher Faraday efficiency and CO partial current density compared with Nafion 117 and FAA-3-PK-130 membranes, at −3.0 V in a membrane electrode assembly reactor. It is worth noting that the QAPBI-2 membrane also has excellent ECR stability, over 320 h in an H-type cell. This work illustrates a promising pathway to obtaining cost-effective membranes through a molecular structure regulation strategy for ECR application.

The clinical significance of necroptosis in gastric cancer (GC) has yet to be fully elucidated. The purpose of our study was to identify a necroptosis-relevant gene and to establish a prediction model to estimate the prognosis and therapeutic potential in GC. Here, we explored the expression profile of 76 necroptosis-related genes in TCGA-STAD patients. A six-gene risk score prediction model was established via regression analysis of the least absolute shrinkage and selection operator (LASSO) and validated in a separate cohort. Patients were separated into low- or high-risk groups according to the median risk score. We then compared and analyzed the biological process characteristics of two risk groups. Additionally, cell-to-cell communications and metabolic activity were analyzed in a single-cell solution. The in vitro experiments were conducted to explore the biological functions and drug sensitivity of necroptosis-related genes in gastric cancer. Our results identified that compared with the low-risk group, the high-risk group was associated with a higher clinical stage or grade and a worse prognosis. In addition, the low-risk group had higher levels of immunity and immune cell infiltration. Necroptosis was triggered by the TNF pathway in myeloid cells and the glycolysis pathway was altered. Necroptosis-related genes modulated the cell function, including proliferation and migration in vitro. Furthermore, the potential drugs’ sensitivity was higher in the low-risk subgroup. These findings could facilitate a better understanding and improve the treatment potential and prognosis of GC patients.

Regulation of neuroinflammation is critical to control the detrimental impact of chronic stress in the central nervous system. Neuroinflammation occurs in response to chronic stress, leading to enhanced neuronal damage in the brain. We investigated the regulatory effects of stress hormone corticosterone on neuroinflammation regulator, as well as amyloid-β and Beta-secretase 1 related signaling. We demonstrate that corticosterone can both positively and negatively regulate amyloid-β expression, which may be related to the ratio of neuroinflammation regulator and Beta-secretase 1 signaling in rat primary cortical neurons. Thirty minutes of treatment with 1 μM corticosterone significantly decreased the nuclear translocation of neuroinflammation mediator neuroinflammation regulator (Western Blot: P < 0.05, Immunofluorescence: P < 0.001) and production of Beta-secretase 1 enzyme (P < 0.01), which was accompanied by a reduction in amyloid-β1-42 levels (P < 0.01). In contrast, 1 µM corticosterone treatment over 3 days increased nuclear neuroinflammation regulator localization (P < 0.001), followed by the upregulation of Beta-secretase 1 (P < 0.01) and amyloid-β1-42 (P < 0.05) expression. This work is the first to demonstrate that the duration of corticosterone exposure can promote or inhibit amyloid-β production, and to link this effect with Beta-secretase 1 / neuroinflammation regulator signaling, together with providing valuable insight into the mechanisms of neuroinflammation and neuroprotection.

The objective of this study was to investigate the role of lncRNA XIST and its relationship with miR-133a in myocardial I/R injury. H9C2 cells treated by hypoxia/reoxygenation (H/R) were used to establish an in vitro I/R model. The small interfering RNA (siRNA) for XIST and miR-133 mimics, inhibitor, and suppressor of cytokine signaling (SOCS2) recombinant plasmids were used to transfect the cells. Cell apoptosis was determined by flow cytometry analysis, and cell viability was used for 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The dual-luciferase reporter assay was performed to confirm binding between XIST and miR-133a, as well as miR-133a and SOCS2. To inhibit or overexpress XIST, miR-133a, or SOCS2 in I/R mice, we used recombinant lentivirus vectors and adenovirus vectors for tail vein injection. The expression of XIST, miR-133a, and SOCS2 was determined by quantitative real-time PCR, and LC3 I/II and Beclin1 was determined by western blotting. The expression of XIST and SOCS2 was significantly upregulated, whereas the miR-133a level was remarkably downregulated in both H/R H9C2 cells and I/R mice myocardial tissues. In both H/R H9C2 cells and I/R mice, the inhibition of XIST led to decreased apoptosis and autophagy, and inhibition of miR-133a reversed these effects. Similarly, overexpression of miR-133a resulted in reduced apoptosis and autophagy, which were reversed by overexpression of SOCS2. The inhibition of XIST and overexpression of miR-133a also promote cell viability of H/R cells. The dual-luciferase reporter assay significantly showed that XIST directly targeted on miR-133a, and miR-133a directly targeted on SOCS2. The inhibition of XIST could improve myocardial I/R injury by regulation of the miR-133a/SOCS2 axis and inhibition of autophagy. Keywords: lncRNA XIST, myocardial ischemic-reperfusion injury, miR-133a, autophagy, SOCS2

Generally, air track planning is conducted in real time and takes modified track distance minimization as objective. Next-generation air transport systems provide aircrafts with more flexibility in track planning and more responsibilities in self-separation, which present a great challenge for aircraft optimal track planning, especially in some high-density airspaces and some complex conflict scenarios. This paper proposes a novel aircraft track planning method by taking aircraft conflict probability into consideration. First, the concepts of aircraft potential motion space and the estimation method for aircraft conflict probability is introduced. Then, taking conflict probability minimization as the objective, the classical ant colony algorithm (ACA) algorithm is improved to solve the model. Finally, an experimental study is conducted to illustrate the proposed method. Results show that the proposed method is able to provide a scientific and effective track planning approach considering the potential conflict probability of aircrafts, which is able to provide fundamental to the safety of entire air transport system.

Eastern and Western Asia were important centers for the domestication of plants and animals and they developed different agricultural practices and systems. The timing, routeway and mechanisms of the exchanges between the two centers have long been important scientific issues. The development of a mixed pastoral system (e.g., with the rearing of sheep, goats and cattle) and millet cultivation in the steppe region of northern China was the result of the link between the two cultures. However, little detailed information is available about the precise timing and mechanisms involved in this mixture of pastoralism and millet cultivation. To try to address the issue, we analyzed the pollen, fungal spores and phytolith contents of soil samples from the Bronze Age Zhukaigou site in the steppe area of North China, which was combined with AMS 14C dating of charcoal, millet and animal bones. A mixed pastoralism and millet agricultural system appeared at the site between 4,000 and 3,700 cal yr BP, and the intensity of animal husbandry increased in the later stage of occupation. Published data indicate that domestic sheep/goats appeared across a wide area of the steppe region of northern China after ∼4,000 cal yr BP. A comparison of records of sheep/goat rearing and paleoclimatic records from monsoon area in China leads us to conclude that the mixture of pastoralism and millet cultivation was promoted by the occurrence of drought events during 4,200–4,000 cal yr BP. Moreover, we suggest that mixed rainfed agriculture and animal husbandry increased the adaptability and resilience of the inhabitants of the region which enabled them to occupy the relatively arid environment of the monsoon marginal area of northern China.

Aviation resources in the post-pandemic era are still in short supply. The increasing air traffic flow aggravates flight delays and makes it difficult to ensure aviation safety. Instead of focusing on the economic benefits, this paper proposes a quantitative method for evaluating the safety of flight plans. A flight plan safety index system is constructed through airspace environment modelling and a conflict probability calculation. The proposed method provides a quantitative basis for the management and adjustment of flight plans at the strategic level. Improving the flight plan management strategy from the perspective of conflict avoidance is expected to fundamentally reduce the potential conflict and workload of controllers and pilots during flight and improve the safety level of the whole air transport system. Finally, the performance of the proposed flight plan safety evaluation method is demonstrated through an illustrative air traffic scenario.

Understanding the research lineage of rural landscape ecosystem services (RLESs) is of importance for improving rural landscapes and developing sustainable ecosystem services. However, there is currently no literature analysis on the scientific quantification and visualization of RLESs. In this study, 4524 articles related to RLESs from 1990 to 2021 were analyzed using the bibliometric method and ISI Web of Science database. The results show that RLES research hotspots have gradually shifted from the early keywords of “vegetation”, “land use change”, “agriculture”, “rural gradients” and “models” to the emerging “cultural ecosystem services”, “rural tourism”, “landscape preferences” and “policy guidance”. Scholars from developed and developing countries place different emphases on research hotspots in terms of research content, scale and methodology due to differences in their research backgrounds and other aspects. In addition, five categories of research fronts were obtained through literature co-citation analysis. Through burst word detection analysis, combined with basic research and research hotspots and frontier analysis, we concluded that future RLES research will focus on four areas: (1) the relationship and collaboration between and management of biodiversity and ecosystem services; (2) the landscape value of RLESs; (3) land-use changes and ecosystem service values; and (4) research methods for innovative RLESs. Our findings may contribute to better in-depth RLES research by providing a theoretical reference and practical help for future related research.

In this work, we demonstrate the implementation of a nonreciprocal perfect absorber (NPA) made of composite magnetic metamaterials (MMs) consisting of an array of dielectric core loaded (DCL) ferrite rods with either hollow or dielectric cores. The NPA can be functionalized as a PA for the incident beam at a specified direction, while at the symmetric direction the absorption is very weak so that a strong reflection is observed due to the excitation of nonreciprocal magnetic surface plasmon. Interestingly, it is shown that the material loss might be beneficial to the absorption, but it will result in the degradation of nonreciprocal performance. For the delicately designed MMs, only a very small material loss is necessary and simultaneously ensures the high nonreciprocal performance of NPA. To interpret the high quality of NPA, we developed a generalized effective-medium theory for the composite MMs, which shows the direct consequence of the DCL ferrite rods with optimized core size and core permittivity. The partial wave analysis indicates that the nonreciprocal dipole resonance in DCL ferrite rod plays a crucial role in improving the nonreciprocity. The narrow band feature and the angular sensitivity make the NPA promising for the diode-like functionalities. In addition, by controlling the magnitude and orientation of bias magnetic field both the operating frequency and the nonreciprocity can be flexibly controlled, adding an additional degree of freedom. The concept proposed in this research is promising for microwave photonics and integrated photonics.

BackgroundNasopharyngeal carcinoma is an endemic head and neck cancer in Southern China. The common metastases organs involve bone, lung, and liver. Metastases in the dura and at multiple locations in the brain after a diagnosis of nasopharyngeal carcinoma are extremely rare.Case PresentationWe present a case of a 66-year-old man who initially complained of nasal congestion, epistaxis, and hearing impairment. The biopsy of the nasopharynx lesion showed basaloid squamous cell carcinoma. Eight months after conventional therapy, the patient was admitted to our hospital again with the complaint of a headache. A PET/CT scan was performed, revealing multiple metastases. A biopsy of subcutaneous soft tissue from the right upper arm was consistent with the previous biopsy. Palliative chemotherapy was administered. Thereafter, the patient had sudden dysfunction of the right side of the body. MRI demonstrated dural and multiple brain metastases. The therapeutic regimen then consisted of whole-brain radiotherapy, anti-angiogenesis therapy, and immunotherapy.ConclusionsThis case highlights the diagnosis and treatment of uncommon metastases of nasopharyngeal carcinoma. Clinicians should remain vigilant for metastases during the treatment and follow-up periods.

BackgroundTo establish a machine-learning-derived nomogram based on radiomic features and clinical factors to predict post-surgical 2-year progression-free survival (PFS) in patients with lung adenocarcinoma.MethodsPatients with >2 years post-surgical prognosis results of lung adenocarcinoma were included in Hospital-1 for model training (n = 100) and internal validation (n = 50), and in Hospital-2 for external testing (n = 50). A total of 1,672 radiomic features were extracted from 3D segmented CT images. The Rad-score was established using random survival forest by accumulating and weighting the top-20 imaging features contributive to PFS. A nomogram for predicting PFS was established, which comprised the Rad-score and clinical factors highly relevant to PFS.ResultsIn the training, internal validation, and external test groups, 69/100 (69%), 37/50 (74%) and 36/50 (72%) patients were progression-free at two years, respectively. According to the Rad-score, the integral of area under the curve (iAUC) for discriminating high and low risk of progression was 0.92 (95%CI: 0.77-1.0), 0.70 (0.41-0.98) and 0.90 (0.65-1.0), respectively. The C-index of Rad-score was 0.781 and 0.860 in the training and external test groups, higher than 0.707 and 0.606 for TNM stage, respectively. The nomogram integrating Rad-score and clinical factors (lung nodule type, cM stage and histological type) achieved a C-index of 0.845 and 0.837 to predict 2-year PFS, respectively, significantly higher than by only radiomic features (all p < 0.01).ConclusionThe nomogram comprising CT-derived radiomic features and risk factors showed a high performance in predicting post-surgical 2-year PFS of patients with lung adenocarcinoma, which may help personalize the treatment decisions.

Aim: A new simulation model and training curriculum for laparoscopic bilioenteric anastomosis has been developed. Currently, this concept lacks evidence for the transfer of skills from simulation to clinical settings. This study was conducted to determine whether training with a three-dimensional (3D) bilioenteric anastomosis model result in greater transfer of skills than traditional training methods involving video observation and a general suture model. Methods: Fifteen general surgeons with no prior experience in laparoscopic biliary-enteric anastomosis were included in this study and randomised into three training groups: video observation only, practice using a general suture model, and practice using a 3D-printed biliary-enteric anastomosis model. Following five training sessions, each surgeon was asked to perform a laparoscopic biliary-enteric anastomosis procedure on an isolated swine organ model. The operative time and performance scores of the procedure were recorded and compared among the three training groups. Results: The operation time in the 3D-printed model group was significantly shorter than the suture and video observation groups (P =0.040). Furthermore, the performance score of the 3D-printed model group was significantly higher than those of the suture and video observation groups (P= 0.001). Finally, the goal score for laparoscopic biliary-enteric anastomosis in the isolated swine organ model was significantly higher in the 3D model group than in the suture and video observation groups (P =0.004). Conclusions: The utilisation of a novel 3D-printed model for simulation training in laparoscopic biliary-enteric anastomosis facilitates improved skill acquisition and transferability to an animal setting compared with traditional training techniques. [ABSTRACT FROM AUTHOR]

Micro plastics have recently emerged as a major biohazard that has a considerable impact on the environment. Moreover, of the detrimental capabilities of micro plastics, a hope of controlling efforts of micro plastics has been in the headlines. microplastics have gained notoriety due to their adverse effects on the environment and wildlife. Controlling these minuscule yet harmful particles requires effective monitoring, detection, and management strategies. This analysis delves into the diverse techniques and technologies available for tracking and mitigating microplastic pollution. Therefore, the following analysis has aimed at analysing the monitoring technologies and methods for micro plastics. Additionally, the monitoring methods are observed along with the advantages and disadvantages. For the development of the analysis, a secondary qualitative method was used in the process. Additionally, the graphical representation of the efforts for controlling the novel pollutant is analysed along with relevant problems. Hence, a coherent discussion is presented in the following analysis. This research contributes to the broader understanding of microplastic pollution and its monitoring while underlining the need for enhanced control measures. It provides a valuable resource for policymakers, environmentalists, and researchers working toward a cleaner, more sustainable environment. As microplastics continue to infiltrate ecosystems worldwide, comprehensive monitoring and control efforts are of paramount importance. [ABSTRACT FROM AUTHOR]

Abstract Background Despite decades of research, the horse domestication scenario in East Asia remains poorly understood. Results The study identified 16 haplogroups with fine-scale phylogenetic resolution using mitochondrial genomes of 317 horse samples. The time to the most recent common ancestor of the 16 haplogroups ranges from [0.8–3.1] thousand years ago (KYA) to [7.9–27.1] KYA. With combined analyses of the mitochondrial control region for 35 extant Przewalski’s horses, 3544 modern and 203 ancient horses across the world, researchers provide evidence for that East Asian prevalent haplogroups Q and R were indigenously domesticated or they were involved in numerous distinct genetic components from wild horses in the southern part of East Asia. These events of haplotypes Q and R occurred during 4.7 to 16.3 KYA and 2.1 to 11.5 KYA, respectively. The diffusion of preponderant European haplogroups L from west to East Asia is consistent with the external gene input. Furthermore, genetic differences were detected between northern East Asia and southern East Asia cohorts by Principal Component Analysis, Analysis of Molecular Variance test, the χ2 test and phylogeographic analyses. Conclusions All results suggest a complex picture of horse domestication, as well as geographic pattern in East Asia. Both local origin and external input occurred in East Asia horse populations. And besides, there are at least two different domestication or hybridization centers in East Asia.

Abstract Background Lung cancer has been a common malignant tumor with a leading cause of morbidity and mortality, current molecular targets are woefully lacking comparing to the highly progressive cancer. The study is designed to identify new prognostic predictors and potential gene targets based on bioinformatic analysis of Gene Expression Omnibus (GEO) database. Methods Four cDNA expression profiles GSE19188, GSE101929, GSE18842 and GSE33532 were chosen from GEO database to analyze the differently expressed genes (DEGs) between non-small cell lung cancer (NSCLC) and normal lung tissues. After the DEGs functions were analyzed, the protein–protein interaction network (PPI) of DEGs were constructed, and the core gene in the network which has high connectivity degree with other genes was identified. We analyzed the association of the gene with the development of NSCLC as well as its prognosis. Lastly we explored the conceivable signaling mechanism of the gene regulation during the development of NSCLC. Results A total of 92 up regulated and 214 down regulated DEGs were shared in four cDNA expression profiles. Based on their PPI network, TOP2A was connected with most of other genes and was selected for further analysis. Kaplan–Meier overall survival analysis (OS) revealed that TOP2A was associated with worse NSCLC patients survival. And both GEPIA analysis and immunohistochemistry experiment (IHC) confirmed that TOP2A was aberrant gain of expression in cancer comparing to normal tissues. The clinical significance of TOP2A and probable signaling pathways it involved in were further explored, and a positive correlation between TOP2A and TPX2 expression was found in lung cancer tissues. Conclusion Using bioinformatic analysis, we revealed that TOP2A could be adopted as a prognostic indicator of NSCLC and it potentially regulate cancer development through co-work with TPX2. However, more detailed experiments are needed to clarify its drug target role in clinical medical use.

Structural variations in gastric cancer impact progression. Here, the authors perform whole-genome sequencing on 168 gastric cancer patients and identified tandem-duplications of super-enhancer ZFP36L2 in 10% of gastric cancer, and mutational signatures in tumors with cadherin 1 mutations that associated with poor prognoses.

Summary: Background: Platelet parameters play an important role in thrombosis. This study investigates the role of platelet parameters in the occlusion of modified Blalock Taussig (BT). Objectives: To investigate the association between mean platelet volume (MPV), platelet distribution width (PDW) and BT conduit obstruction and to evaluate the role of MPV and PDW in BT conduit obstruction. Methods: 388 patients with modified BT shunt in the Pediatric Heart Center, Anzhen Hospital From January 1, 2008 to December 30, 2014 were divided into BT obstruction group (OBS) 11 cases and BT non-obstruction group (N-OBS) 377 cases according to whether the BT tube was occluded. The platelet count, mean platelet volume and platelet distribution width in the both groups were measured. The BT pipe occlusion related risk factors were analyzed. Results: There was no significant difference in PC value of OBS group [(221 ± 28.4) × 109/L] and that of N-OBS group [(198 ± 69.1) × 109/L). MPV [(15 ± 6.8) fL] and PDW (20 ± 6.4)% in OBS group were significantly higher than those in N-OBS group [(8 ± 3.2) fL, (15 ± 2.1)%] (P 0.05). Abnormal increases of MPV and PDW increased the risk of ductal occlusion [(OR = 2.1, 95%CI:1.47–2.49, P