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Ground losses due to tunneling would induce settlement of nearby raft foundations. To study the change in behavior of the raft foundations over time due to tunnel excavation in soft clay, a series of centrifuge model tests were conducted. The results reveal that the raft stiffness has a significant influence on the development of the gap between the raft and the ground. The width of the gap beneath the flexible foundation would increase over time, leading to a further increase in tensile strain after excavation, whereas the gap for raft foundations with a large stiffness would reduce with time, causing a gradual decrease in tensile strain. The modification factor (MF) design approach is also evaluated with the test results and demonstrates that the MF design approach would underestimate the tensile strain of the flexible raft and provide a relatively conservative prediction for larger stiffnesses.

Abstract Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance. Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response. In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean.

Abstract We aimed to identify the severity and duration of COVID-19 infection on complications after allo-HSCT. Enrolled 179 hospitalized patients with COVID-19 were categorized into long-term infection (> 18 days, n = 90) or short-term infection group (≤ 18 days, n = 89) according to the median duration of COVID-19. The severity of COVID-19 was categorized as asymptomatic infection, mild, moderate, severe, and critical illness according to guidelines of National Institutes of Health. Particularly, severe illness and critical illness were classified as serious infection. Asymptomatic infection, mild illness and moderate illness were classified as non-serious infection. The 150-day probabilities of poor graft function (PGF), cytomegalovirus (CMV) pneumonia and non-relapse mortality (NRM) were significantly higher in long-term infection group. The 150-day probabilities of CMV pneumonia and NRM after COVID-19 were higher in serious infection group. The 150-day probabilities of overall survival (OS) was significantly lower in long-term and serious infection group. In multivariable analysis, the severity of COVID-19 was associated with NRM and OS, and the duration of COVID-19 was associated with PGF. In summary, our data reported that the severity and duration of COVID-19 were associated with several complications and contribute to poor outcomes after allo-HSCT.

The extracellular matrix (ECM) regulates carcinogenesis by interacting with cancer cells via cell surface receptors. Discoidin Domain Receptor 2 (DDR2) is a collagen‐activated receptor implicated in cell survival, growth, and differentiation. Dysregulated DDR2 expression has been identified in various cancer types, making it as a promising therapeutic target. Additionally, cancer cells exhibit mechanosensing abilities, detecting changes in ECM stiffness, which is particularly important for carcinogenesis given the observed ECM stiffening in numerous cancer types. Despite these, whether collagen‐activated DDR2 signaling and ECM stiffness‐induced mechanosensing exert similar effects on cancer cell behavior and whether they operate through analogous mechanisms remain elusive. To address these questions, we performed bulk RNA sequencing (RNA‐seq) on human SH‐SY5Y neuroblastoma cells cultured on collagen‐coated substrates. Our results show that DDR2 downregulation induces significant changes in the cell transcriptome, with changes in expression of 15% of the genome, specifically affecting the genes associated with cell division and differentiation. We validated the RNA‐seq results by showing that DDR2 knockdown redirects the cell fate from proliferation to senescence. Like DDR2 knockdown, increasing substrate stiffness diminishes cell proliferation. Surprisingly, RNA‐seq indicates that substrate stiffness has no detectable effect on the transcriptome. Furthermore, DDR2 knockdown influences cellular responses to substrate stiffness changes, highlighting a crosstalk between these two ECM‐induced signaling pathways. Based on our results, we propose that the ECM could activate DDR2 signaling and mechanosensing in cancer cells to orchestrate their cell fate through distinct mechanisms, with or without involving gene expression, thus providing novel mechanistic insights into cancer progression.

BackgroundInfant health among newborns with neonatal abstinence syndrome (NAS) has been understudied. We examined infant mortality and hospitalizations among infants diagnosed with NAS after birth.MethodsAll live births in British Columbia (BC), Canada, for fiscal years from 2004–2005 to 2019–2020, were included (N = 696,900). NAS was identified based on International Classification of Diseases, version 10, Canadian modification (ICD-10-CA) codes; the outcomes included infant death and hospitalizations during the first year of life, ascertained from BC linked administrative data. Generalized estimating equation models were used to adjust for maternal factors.ResultsThere were 2,439 infants with NAS (3.50 per 1,000 live births). Unadjusted for other factors, infant mortality was 2.5-fold higher in infants with vs. without NAS (7.79 vs. 3.08 per 1,000 live births, respectively) due to increased post-discharge mortality NAS (5.76 vs. 1.34 per 1,000 surviving infants, respectively). These differences diminished after adjustment: adjusted odds ratio (AOR) for infant death was 0.85 [95% confidence interval (CI): 0.52–1.39]; AOR for post-discharge death was 1.75 (95% CI 1.00–3.06). Overall, 22.3% infants with NAS had at least one hospitalization after post-neonatal discharge, this proportion was 10.7% in those without NAS. During the study period, discharge to foster care declined from 49.5% to 20.3% in infants with NAS.ConclusionUnadjusted for other factors, infants with NAS had increased post-discharge infant mortality and hospitalizations during the first year of life. This association diminished after adjustment for adverse maternal and socio-medical conditions. Infants with NAS had a disproportionately higher rate of placement in foster care after birth, although this proportion declined dramatically between 2004/2005 and 2019/2020. These results highlight the importance of implementing integrated care services to support infants born with NAS and their mothers during the first year of life and beyond, even though NAS itself is not independently associated with increased infant mortality.

Engraftment syndrome (ES) is one of the most common complications in the early phase after autologous hematopoietic stem cell transplantation (ASCT), and we aimed to evaluate the incidence and risk factors for ES patients receiving ASCT in the era of plerixafor-based mobilization. A total of 294 were enrolled, and 16.0% (n = 47) experienced ES after ASCT. The main clinical manifestations were fever (100%), diarrhea (78.7%), skin rash (23.4%), and hypoxemia/pulmonary edema (12.8%). Plerixafor-based mobilization was associated with higher counts of CD3+ cells, CD4+ cells, and CD8+ cells in grafts. In univariate analysis of the total cohort, age ≥60 years, receiving ASCT at complete remission (CR), higher number of mononuclear cell (MNC), CD3+ cell counts, CD4+ cells as well as CD8+ cells transfused and plerixafor-based mobilization were associated with ES after ASCT. Multivariate analysis showed that age ≥60 years (P = .0014), receiving ASCT at CR (P = .002), and higher number of MNC transfused (P = .026) were associated with ES in total cohort. In plasma cell disease subgroup, age ≥60 years (P = .013), plerixafor-based mobilization (P = .036), and receiving ASCT at CR (P = .002) were associated with ES. Patients with more risk factors had a higher risk of ES. The 1-year probabilities of relapse, non-relapse mortality, and survival were comparable between patients with and without ES. Thus, plerixafor-based mobilization may influence the composition of T lymphocytes in grafts and increase the risk of ES, particularly in patients with plasma cell disease.

Abstract Male infertility is one of the most common complications of diabetes mellitus (DM). Dapagliflozin is widely used to manage the type II DM. This study aimed to assess the dapagliflozin’s effects on the spermatogenesis by administering either dapagliflozin (Dapa) or vehicle (db) to male db/db mice, and using littermate male db/m mice as the control (Con). We further performed the integrative analyses of the cecal shotgun metagenomics, cecal/plasmatic/testicular metabolomics, and testicular proteomics. We found that dapagliflozin treatment significantly alleviated the diabetes-induced spermatogenic dysfunction by improving sperm quality, including the sperm concentration and sperm motility. The overall microbial composition was reshaped in Dapa mice and 13 species (such as Lachnospiraceae bacterium 3–1) were regarded as potential beneficial bacteria. Metabolites exhibited modified profiles, in which adenosine, cAMP, and 2′-deoxyinosine being notably altered in the cecum, plasma, and testis, respectively. Testicular protein expression patterns were similar between the Dapa and Con mice. In vivo results indicated that when compared with db group, dapagliflozin treatment alleviated apoptosis and oxidative stress in testis tissues by down-regulating 2′-deoxyinosine. This was further validated by in vitro experiments using GC-2 cells. Our findings support the potential use of dapagliflozin to prevent the diabetes-induced impaired sperm quality and to treat diabetic male infertility.

The stability of black rice anthocyanin microcapsules at high temperature, light and pH, and their release in simulated gastroenteric fluid were studied by emulsification and gelation of black rice anthocyanin microcapsules with calcium alginate as wall material. The stability of black rice anthocyanin in microcapsules prepared under the process parameters of sodium alginate concentration of 15 g/L, water oil volume ratio of 1∶3, wall to core ratio M (C3G)∶M (NaAlg) of 2∶1, and solution pH of 4.5 was significantly higher than that of uncoated free black ones under different pH, temperature, and light conditions. The microencapsulated anthocyanin could be kept for 4 hours in simulated gastric fluid, and the wall material was slowly decomposed and released in simulated intestinal fluid. The microencapsulation technology based on emulsified gel can improve the stability of anthocyanins, and achieve their intestinal delivery and sustained release in vivo.

ABSTRACTRapidly estimating post-disaster building damage via high-resolution remote sensing (HRRS) imagery is essential for initial disaster relief. However, the complex appearance of building damage poses challenges for existing methods. Specifically, relying solely on post-disaster images lacks building boundary guidance, while change detection methods using dual-temporal imageries are prone to introducing false changes. To address these issues, this paper presents a novel weakly supervised approach that leverages pre- and post-disaster HRRS images for building damage detection. The contributions of this paper are twofold. Firstly, a unique framework is proposed to utilize dual-temporal images. Precisely, the proposed method initially extracts fine-grained sub-building-level individuals from pre-disaster images by combining a fully convolutional neural network (FCN)-based method with superpixel segmentation. Then, these details serve as cues to effectively guide the detection of damaged building areas on post-disaster images, thereby enhancing accuracy. Secondly, we propose a weakly supervised method that solely relies on labeling building damage based on image patches but can ultimately yield pixel-level building damage results. Experiments conducted using HRRS images captured during the 2010 Haiti earthquake demonstrate that the proposed method outperforms existing methodologies. This effort of this paper will contribute to the sustainable development of cities and human settlements.

The paper focused on the Xining marginal area, providing the concept of land use competitive advantage, employing the PLUS and PFCI model to simulate production–living–ecological (PLE) land in 2030, and revealing the relationship between regional land interactions and sustainable land allocation. The results indicate that the following: (1) By 2030, the land use of the Xining marginal area is primarily production and ecological land, with approximately 0.1% of living land; however, living and production land will increase while ecological land will decrease in general, and the growth momentum of urban and other living space in government-seated regions is stronger. (2) The PLE land does not exhibit a piecemeal expansion pattern, as it is influenced by mountains and rivers. Agricultural production land and grassland ecological land have advantages for development, whereas urban living land has just development potential. (3) Developing the corresponding lands in the dominant regions can result in sustainable land allocation, and five nexus approaches are proposed for the sustainable allocation of PLE land in the Xining marginal region. The study addresses the interaction of different land use types across regions rather than examining them separately, and we provide significant insight into whether the Qinghai Tibet Plateau should be urbanized.

Objective: To investigate the short-term efficacy and safety of different chemotherapy regimens combined with thalidomide, in the treatment of low-income patients with newly diagnosed HIV-associated diffuse large B-cell lymphoma. Methods: A retrospective analysis was performed on 42 patients with HIV-DLBCL who were admitted to the Infectious Diseases Department of Yunnan Provincial Infectious Diseases Hospital from January 2018 to December 2020. 14 cases (including 1 case in stage II and 13 cases in stage III/IV) were treated with R-CHOP, 24 cases (including 1 case in stage II and 23 cases in stage III/IV) were treated with R-DAEPOCH, and 4 cases (including 1 case in stage II and 3 cases in stage III/IV) were treated with EPOCH. All patients were treated with thalidomide. The ART regimen was adjusted. At least 1 and up to 6 intrathecal injections were given during chemotherapy, and cotrimoxazole was taken orally to prevent infection. The clinical efficacy was evaluated after 4 cycles of chemotherapy, and adverse events were evaluated at each cycle of chemotherapy. Results: All patients received 1–8 cycles of chemotherapy. CR (64.2 %) was achieved in 9 patients in R-CHOP group, and 5 patients died. In the R-DAEPOCH group, 17 patients achieved CR (70.8 %) and 7 died. In the EPOCH group, 2 patients reached CR (50 %) and 2 died. The main adverse reactions were grade II and above myelosuppression. Conclusion: Combined treatment with thalidomide can improve the prognosis of low-income patients with newly diagnosed HIV-DLBCL.

The purpose of this study was to investigate the effect of brown rice and whole wheat on gut microbiota and lipid metabolism. Specific pathogen-free Sprague Dawley (SPF SD) rats were selected and randomly divided into six groups (n = 12 per group): control group, brown rice group, whole wheat group, HFD model group, brown rice + HFD group, and whole wheat + HFD group. After 12 weeks of feeding, the serum biochemical indicators of the rats were measured. The liver and colon tissues were examined pathologically, and the microbial community diversity in the colon was analyzed. The results showed that brown rice significantly inhibited the increase of body weight and lowered serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels. Brown rice also significantly alleviated inflammatory cell infiltration in colon tissue (P < 0.05). Whole wheat reduced serum free fatty acid (FFA) levels and inhibited hepatic lipid accumulation in rats (P < 0.05). In the normal maintenance diet groups, brown rice decreased the Firmicutes/Bacteroidetes ratio and increased the relative abundance of Blautia and Lactobacillus in the colon, while whole wheat increased the relative abundance of Blautia and Romboutsia (P < 0.05). In the HFD groups, the relative abundance of harmful bacteria such as Terrisporobacter, Pseudomonas, Psychrobacter, and Lachnoclostridium were reduced by brown rice and whole wheat, while brown rice increased the relative abundance of Bacteroides in the colon (P < 0.05). Taken together, the intake of brown rice and whole wheat had a healthy effect on regulating intestinal homeostasis. The results of this study can provide a scientific basis for formulating reasonable whole-grain cereals-related dietary guidelines and developing whole-grain-based healthy products.

Abstract Background Aging-related fertility decline is a prevalent concern globally. Male reproductive system aging is mainly characterized by a decrease in sperm quality and fertility. While it is known that intestinal physiology changes with age and that microbiota is shaped by physiology, the underlying mechanism of how the microbiota affects male reproductive aging is still largely unexplored. Results Here, we utilized fecal microbiota transplantation (FMT) to exchange the fecal microbiota between young and old mice. Cecal shotgun metagenomics and metabolomics were used to identify differences in gut microbiota composition and metabolic regulation during aging. Our results demonstrated that FMT from young to old mice alleviated aging-associated spermatogenic dysfunction through an unexpected mechanism mediated by a gut bacteria-derived metabolite, 3-hydroxyphenylacetic acid (3-HPAA). 3-HPAA treatment resulted in an improvement of spermatogenesis in old mice. RNA sequencing analysis, qRT-PCR and Western blot revealed that 3-HPAA induced an upregulation of GPX4, thereby restraining ferroptosis and restoring spermatogenesis. These findings were further confirmed by in vitro induction of ferroptosis and inhibition of GPX4 expression. Conclusions Our results demonstrate that the microbiome-derived metabolite, 3-HPAA, facilitates spermatogenesis of old mice through a ferroptosis-mediated mechanism. Overall, these findings provide a novel mechanism of dysregulated spermatogenesis of old mice, and suggest that 3-HPAA could be a potential therapy for fertility decline of aging males in clinical practice. Video Abstract

ABSTRACTBetacoronaviruses encode an internal (I) gene via an alternative reading frame within the nucleocapsid gene, called ORF8b for Middle-East respiratory syndrome coronavirus (MERS-CoV) and ORF9b for severe acute respiratory syndrome coronavirus (SARS-CoV) and SARS-CoV-2. Previous reports suggested that proteins 8b and 9b are involved in evading multiple innate immune signaling pathways. However, their roles in mediating pathogenesis in infected animals have not been determined. In this study, we abrogated the expression of protein 8b in MERS-CoV and protein 9b in SARS-CoV-2. Using mouse models of MERS-CoV and SARS-CoV-2 infection, we found that MERS-CoV lacking protein 8b expression was more virulent, while SARS-CoV-2 lacking protein 9b expression was attenuated compared with the respective wild-type viruses. Upon further analysis, we detected increased levels of type I interferon and enhanced infiltration of immune cells to the lungs of mice infected with MERS-CoV lacking protein 8b expression. These data suggest that the I protein of MERS-CoV plays a role in limiting pathogenesis while that of SARS-CoV-2 enhances disease severity.IMPORTANCEThe function of betacoronavirus internal protein has been relatively understudied. The earliest report on the internal protein of mouse hepatitis virus suggested that the internal protein is a structural protein without significant functions in virus replication and virulence. However, the internal proteins of severe acute respiratory syndrome coronavirus (SARS-CoV), Middle-East respiratory syndrome coronavirus, and SARS-CoV-2 have been shown to evade immune responses. Despite the reported functions of the internal protein in these highly pathogenic human coronaviruses, its role in mediating pathogenesis in experimentally infected animals has not been characterized. Our data indicated that despite the similar genomic location and expression strategy of these internal proteins, their effects on virulence are vastly different and virus specific, highlighting the complexity between host-virus interaction and disease outcome.

Summary: IGHV1-69 is frequently utilized by broadly neutralizing influenza antibodies to the hemagglutinin (HA) stem. These IGHV1-69 HA stem antibodies have diverse complementarity-determining region (CDR) H3 sequences. Besides, their light chains have minimal to no contact with the epitope. Consequently, sequence determinants that confer IGHV1-69 antibodies with HA stem specificity remain largely elusive. Using high-throughput experiments, this study reveals the importance of light-chain sequence for the IGHV1-69 HA stem antibody CR9114, which is the broadest influenza antibody known to date. Moreover, we demonstrate that the CDR H3 sequences from many other IGHV1-69 antibodies, including those to the HA stem, are incompatible with CR9114. Along with mutagenesis and structural analysis, our results indicate that light-chain and CDR H3 sequences coordinately determine the HA stem specificity of IGHV1-69 antibodies. Overall, this work provides molecular insights into broadly neutralizing antibody responses to influenza virus, which have important implications for universal influenza vaccine development.

Fluid dynamic calculations play a crucial role in understanding marine biochemical dynamic processes, impacting the behavior, interactions, and distribution of biochemical components in aquatic environments. The numerical simulation of fluid dynamics is a challenging task, particularly in real-world scenarios where fluid motion is highly complex. Traditional numerical simulation methods enhance accuracy by increasing the resolution of the computational grid. However, this approach comes with a higher computational demand. Recent advancements have introduced an alternative by leveraging deep learning techniques for fluid dynamic simulations. These methods utilize discretized learned coefficients to achieve high-precision solutions on low-resolution grids, effectively reducing the computational burden while maintaining accuracy. Yet, existing fluid numerical simulation methods based on deep learning are limited by their single-scale analysis of spatially correlated physical fields, which fails to capture the diverse scale characteristics inherent in flow fields governed by complex laws in different physical space. Additionally, these models lack an effective approach to enhance correlation interactions among dynamic fields within the same system. To tackle these challenges, we propose the Spatial Multi-Scale Feature Extract Neural Network based on Physical Heterogeneous Interaction (PHI-SMFE). The PHI module is designed to extract heterogeneity and interaction information from diverse dynamic fields, while the SMFE module focuses on capturing multi-scale features in fluid dynamic fields. We utilize channel-biased convolution to implement a separation strategy, reducing the processing of redundant feature information. Furthermore, the traditional solution module based on the finite volume method is integrated into the network to facilitate the numerical solution of the discretized dynamic field in subsequent time steps. Comparative analysis with the current state-of-the-art model reveals that our proposed method offers a 41% increase in simulation accuracy and a 12.7% decrease in inference time during the iterative evolution of unsteady flow. These results underscore the superior performance of our model in terms of both simulation accuracy and computational speedup, establishing it as a state-of-the-art solution.

Summary: The ability of the human immune system to generate antibodies to any given antigen can be strongly influenced by immunoglobulin V-gene allelic polymorphisms. However, previous studies have provided only limited examples. Therefore, the prevalence of this phenomenon has been unclear. By analyzing >1,000 publicly available antibody-antigen structures, we show that many V-gene allelic polymorphisms in antibody paratopes are determinants for antibody binding activity. Biolayer interferometry experiments further demonstrate that paratope allelic polymorphisms on both heavy and light chains often abolish antibody binding. We also illustrate the importance of minor V-gene allelic polymorphisms with low frequency in several broadly neutralizing antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus. Overall, this study not only highlights the pervasive impact of V-gene allelic polymorphisms on antibody binding but also provides mechanistic insights into the variability of antibody repertoires across individuals, which in turn have important implications for vaccine development and antibody discovery.

Objectives: Four seasonal coronaviruses, including human coronavirus (HCoV)-229E and HCoV-OC43, HCoV-NL63, and HCoV-HKU1 cause approximately 15-30% of common colds in adults. However, the full landscape of the immune trajectory to these viruses that covers the whole childhood period is still not well understood. Methods: We evaluated the serological responses against the four seasonal coronaviruses in 1886 children aged under 18 years by using enzyme-linked immunosorbent assay. The optical density values against each HCoV were determined from each sample. Generalized additive models were constructed to determine the relationship between age and seroprevalence throughout the whole childhood period. The specific antibody levels against the four seasonal coronaviruses were also tested from the plasma samples of 485 pairs of postpartum women and their newborn babies. Results: The immunoglobulin (Ig) G levels of the four seasonal coronaviruses in the mother and the newborn babies were highly correlated (229E: r = 0.63; OC43: r = 0.65; NL63: r = 0.69; HKU1: r = 0.63). The seroprevalences in children showed a similar trajectory in that the levels of IgG in the neonates dropped significantly and reached the lowest level after the age of around 1 year (229E: 1.18 years; OC43: 0.97 years; NL63: 1.01 years; HKU1: 1.02 years) and then resurgence in the children who aged older than 1 year. Using the lowest level from the generalized additive models as our cutoff, the seroprevalences for HCoV-229E, HCoV-OC43, HCoV-NL63, and HCoV-HKU1 were 98.11%, 96.23%, 96.23% and 94.34% at the age of 16-18 years. Conclusion: Mothers share HCoV-specific IgGs with their newborn babies and the level of maternal IgGs waned at around 1 year after birth. The resurgence of the HCoV-specific IgGs was found thereafter with the increase in age suggesting repeated infection occurred in children.

Building structural type (BST) information is vital for seismic risk and vulnerability modeling. However, obtaining this kind of information is not a trivial task. The conventional method involves a labor-intensive and inefficient manual inspection process for each building. Nowadays, a few methods have explored to use remote sensing images and some building-related knowledge (BRK) to realize automated BST recognition. However, these methods have many limitations, such as insufficient mining of multimodal information and difficulty obtaining BRK, which hinders their promotion and practical use. To alleviate the shortcomings above, we propose a deep multimodal fusion model, which combines satellite optical remote sensing image, aerial synthetic aperture radar image, and BRK (roof type, color, and group pattern) obtained by domain experts to achieve accurate automatic reasoning of BSTs. Specifically, first, we use a pseudo-siamese network to extract the image feature. Second, a knowledge graph (KG) based on the BRK is constructed, and then, we use a graph attention network to extract the semantic feature from the KG. Third, we propose a novel multistage gated fusion mechanism to fuse the image and semantic feature. Our method's best overall accuracy and kappa coefficient on the dataset collected in the study area are 90.35% and 0.83, which outperforms a series of existing methods. Through our model, high-precision BST information can be obtained for earthquake disaster prevention, reduction, and emergency decision making.

Building detection from panchromatic (PAN) and multispectral (MS) images is an essential task for many practical applications. In this article, a dual-stream asymmetric fusion network is proposed, named DAFNet. DAFNet can achieve effective information fusion at the feature level. It obtains better building detection performance from the following three perspectives: a two-stream network structure is designed to guarantee the ability to extract information from PAN and MS images; an asymmetric feature fusion module is proposed to fuse features efficiently and concisely; and two consistency regularization losses, i.e., PAN information preservation loss and cross-modal semantic consistency loss are applied to further explore the consistency between features for better fusion. The experiments are conducted on a challenging building detection dataset collected from GaoFen-2 satellite images. Comprehensive evaluations on 12 popular detection methods demonstrate the superiority of our DAFNet compared with the existing state-of-the-art fusion methods. We reveal that feature-level fusion is more suitable for building detection from PAN-MS images.

Fructose was popularly used in diet due to its high sweetness and low impact on blood sugar levels. High fructose diets are common in Western countries. With economic development, the per capita fructose intake in China has been increasing year by year, and the relationship between fructose and health has become a research hotspot. The absorption and metabolism of fructose in vivo can activate multiple signaling pathways including PI3K/Akt, NF- κ B, JAK-STAT, AMPK, MAPK and toll like receptors etc., which could down or up regulate the level of downstream signaling molecules, and cause the occurrence of metabolic syndrome such as obesity and non-alcoholic steatohepatitis. The absorption and metabolism molecular signal pathways involved in fructose induced metabolic syndrome were summarized and reviewed in this paper, which could provide reference for the rational consumption and further research of biological effects of fructose.

Mechanical cues from the tumor microenvironment (TME) can influence cell behaviors and have been indicated to play a pivotal role in tumor initiation, progression, and metastasis. The integration of microfluidics technologies, bioelectronics, and tissue engineering approaches have allowed the development of various in-vitro TME on-chip models. These models recapitulate and systematically simplify the intricate mechanical characteristics and interactions within tumors, enabling the study of the metastatic process with unprecedented detail. In this review, we will focus on shear flow, confinement, and stiffness and elucidate their mechanotransduction processes that contribute to the onset of metastatic cascade. Finally, novel Cancer-on-chip models are discussed along with an outlook on challenges and future perspectives of this emerging technology.

Lei et al. systematically characterized the epistasis among natural mutations in the neuraminidase of human influenza H3N2 virus, which provide insights into the biophysical constraints that shaped its evolution trajectory over the past half-century.

BACKGROUND: There are known differences in the risk of perinatal and maternal birth outcomes because of maternal factors, such as body mass index and maternal race. However, the association of maternal height with adverse birth outcomes and the potential differences in this relationship by race and ethnicity have been understudied. OBJECTIVE: This study aimed to examine the association between maternal stature and adverse perinatal outcomes and the potential modification of the association by race and ethnicity. STUDY DESIGN: This retrospective cohort study was conducted using data on all singleton births in the United States in 2016 and 2017 (N=7,361,713) obtained from the National Center for Health Statistics. Short and tall stature were defined as 90th percentiles of the maternal height distribution (172.7 cm, respectively). Race and ethnicity categories included non-Hispanic White, non-Hispanic Black, American Indian or Alaskan Native Asian or Pacific Islander, and Hispanic. The primary outcomes were preterm birth (

Land is the solid basis for human existence, living, and production activities [...]

Building detection is an important topic in remote sensing image applications. This study proposes a multiscale building detection method based on boundary preservation, to detect building roofs from a large number of high-resolution remote sensing images at a fast speed. A lightweight network extracts a feature map and a feature pyramid network (FPN) aggregates low- and high-level features. A multidimensional attention network (MDA) enhances building features and weakens the complex background information. The method uses four branches to extract buildings: classification, box, direction box, and mask. We manually labeled approximately 870,000 buildings of different types and selected about 300 1 ​km ​× ​1 ​km image plots of different ground objects without buildings, to construct positive and negative sample sets for 27 provinces in China. The accuracy and recall of test results of the proposed method are 12.4% and 3.6% higher than those of Mask R–CNN, respectively, while its accuracy and detection time of segmentation results are 6% and about 30% higher than those of Mask R–CNN, respectively. Pre-disaster buildings were extracted using the proposed method in several key provinces across the country, which were applied to quick assessment in emergency work for Yangbi earthquake. The method was used on post-disaster UAV images as well, achieving 95.61% precision and 91.36% recall of detection results. Experiments show that: the detection method and its results are beneficial to reduce manual interpretation time significantly, and detections on pre- and post-disaster images can be compared to help identification of damaged buildings.

Background Immune checkpoint inhibitors (ICIs) therapy targeting programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) shows promising clinical benefits. However, the relatively low response rate highlights the need to develop an alternative strategy to target PD-1/PD-L1 immune checkpoint. Our study focuses on the role and mechanism of annexin A1 (ANXA1)-derived peptide A11 degrading PD-L1 and the effect of A11 on tumor immune evasion in multiple cancers.Methods Binding of A11 to PD-L1 was identified by biotin pull-down coupled with mass spectrometry analysis. USP7 as PD-L1’s deubiquitinase was found by screening a human deubiquitinase cDNA library. The role and mechanism of A11 competing with USP7 to degrade PD-L1 were analyzed. The capability to enhance the T cell-mediated tumor cell killing activity and antitumor effect of A11 via suppressing tumor immune evasion were investigated. The synergistic antitumor effect of A11 and PD-L1 mAb (monoclonal antibody) via suppressing tumor immune evasion were also studied in mice. The expression and clinical significance of USP7 and PD-L1 in cancer tissues were evaluated by immunohistochemistry.Results A11 decreases PD-L1 protein stability and levels by ubiquitin proteasome pathway in breast cancer, lung cancer and melanoma cells. Mechanistically, A11 competes with PD-L1’s deubiquitinase USP7 for binding PD-L1, and then degrades PD-L1 by inhibiting USP7-mediated PD-L1 deubiquitination. Functionally, A11 promotes T cell ability of killing cancer cells in vitro, inhibits tumor immune evasion in mice via increasing the population and activation of CD8+ T cells in tumor microenvironment, and A11 and PD-1 mAb possess synergistic antitumor effect in mice. Moreover, expression levels of both USP7 and PD-L1 are significantly higher in breast cancer, non-small cell lung cancer and skin melanoma tissues than those in their corresponding normal tissues and are positively correlated in cancer tissues, and both proteins for predicting efficacy of PD-1 mAb immunotherapy and patient prognosis are superior to individual protein.Conclusion Our results reveal that A11 competes with USP7 to bind and degrade PD-L1 in cancer cells, A11 exhibits obvious antitumor effects and synergistic antitumor activity with PD-1 mAb via inhibiting tumor immune evasion and A11 can serve as an alternative strategy for ICIs therapy in multiple cancers.

Water-saving agriculture (WSA) is often introduced as an effective strategy to reduce water infiltration and mitigate irrigation-induced landslide risks. The effects highly rely on smallholder farmers, who often would rather suffer from landslides than adapt. This study focused on farmers’ adoption intention of WSA in general and drip irrigation and drought-tolerant crop in specific, representing changes in technology and farming systems. An integrative theoretical model was developed based on the extended theory of planned behavior (TPB) with elements from the norm activation model and technology acceptance model. Hypotheses were tested using data from a questionnaire survey with 363 farmers in Loess Plateau, Northwest China. The results of structural equation modeling showed that the most crucial factor bolstering farmers’ adoption intention was subjective norm, regardless of different measures. Attitude was more influential than perceived behavior control in drip irrigation and vice versa in drought-tolerant crop adoption, indicating that attitude was more important in technology change and capacity played a crucial role in farming system shift. In addition, awareness of environmental consequences contributed positively to subjective norm and attitude, and perceived ease-of-use improved perceived behavior control. Most notably, the extended TPB model has more explanatory power than the classical one. By considering the moral and technical aspects, the extended model enhanced the comprehensiveness of explaining drivers of farmers’ WSA adoption intention under the irrigation-induced landslide risks. The findings shed light on future disaster risk management for China and other countries under the landslide risk.

Abstract Background The therapeutic value of targeted therapies in patients with lung cancer is reduced when tumours acquire secondary resistance after an initial period of successful treatment. However, the molecular events behind the resistance to targeted therapies in lung cancer remain largely unknown. Aims To discover the important role and mechanism of lncRNA BC in promoting tumor metastasis and influencing clinical prognosis of LUAD. Materials & Methods: Microarrays were used to screen a comprehensive set of lncRNAs with differential expression profiles in lung cancer cells. The functional role and mechanism of lncRNA were further investigated by gain‐ and loss‐of‐function assays. RNA pull‐down, protein assays, and mass spectrometry were used to identify proteins that interacted with lncRNA. TaqMan PCR was used to measure lncRNA in lung adenocarcinoma and adjacent nontumor tissues from 428 patients. The clinical significance of lncRNA identified was statistically confirmed in this cohort of patients. Results In this study, we show that the long non‐coding RNA BC009639 (BC) is involved in acquired resistance to EGFR‐targeted therapies. Among the 235 long non‐coding RNAs that were differentially expressed in lung cancer cell lines, with different metastatic potentials, BC promoted growth, invasion, metastasis, and resistance to EGFR‐tyrosine kinase inhibitors (EGFR‐TKIs), both in vitro and in vivo. BC was highly expressed in 428 patients with lung adenocarcinoma (LUAD) and high BC expression correlated with reduced efficacy of EGFR‐TKI therapy. To uncover the molecular mechanism of BC‐mediated EGFR‐TKI resistance in lung cancer, we screened and identified nucleolin and hnRNPK that interact with BC. BC formed the splicing complex with nucleolin and hnRNPK to facilitate the production of a non‐protein‐coding inositol monophosphatase domain containing 1 (IMPAD1) splice variant, instead of the protein‐coding variant. The BC‐mediated alternative splicing (AS) of IMPAD1 resulted in the induction of the epithelial–mesenchymal transition and resistance to EGFR‐TKI in lung cancer. High BC expression correlated with clinical progress and poor survival among 402 patients with LUAD. Disscussion Through alternative splicing, BC boosted the non‐coding IMPAD1‐203 transcript variant while suppressing the IMPAD1‐201 variant. In order to control the processing of pre‐mRNA, BC not only attracted RNA binding proteins (NCL, IGF2BP1) or splicing factors (hnRNPK), but also controlled the formation of the splicing‐regulator complex by creating RNA‐RNA‐duplexes. Conclusion Our results reveal an important role for BC in mediating resistance to EGFR‐targeted therapy in LUAD through IMPAD1 AS and in implication for the targeted therapy resistance.

Abstract Background Myelodysplastic syndromes (MDS) are a group of heterogeneous myeloid clonal disorders characterized by ineffective haematopoiesis and immune deregulation. Emerging evidence has shown the effect of bone marrow (BM) endothelial progenitor cells (EPCs) in regulating haematopoiesis and immune balance. However, the number and functions of BM EPCs in patients with different stages of MDS remain largely unknown. Methods Patients with MDS (N = 30), de novo acute myeloid leukaemia (AML) (N = 15), and healthy donors (HDs) (N = 15) were enrolled. MDS patients were divided into lower-risk MDS (N = 15) and higher-risk MDS (N = 15) groups according to the dichotomization of the Revised International Prognostic Scoring System. Flow cytometry was performed to analyse the number of BM EPCs. Tube formation and migration assays were performed to evaluate the functions of BM EPCs. In order to assess the gene expression profiles of BM EPCs, RNA sequencing (RNA-seq) were performed. BM EPC supporting abilities of haematopoietic stem cells (HSCs), leukaemia cells and T cells were assessed by in vitro coculture experiments. Results Increased but dysfunctional BM EPCs were found in MDS patients compared with HDs, especially in patients with higher-risk MDS. RNA-seq indicated the progressive change and differences of haematopoiesis- and immune-related pathways and genes in MDS BM EPCs. In vitro coculture experiments verified that BM EPCs from HDs, lower-risk MDS, and higher-risk MDS to AML exhibited a progressively decreased ability to support HSCs, manifested as elevated apoptosis rates and intracellular reactive oxygen species (ROS) levels and decreased colony-forming unit plating efficiencies of HSCs. Moreover, BM EPCs from higher-risk MDS patients demonstrated an increased ability to support leukaemia cells, characterized by increased proliferation, leukaemia colony-forming unit plating efficiencies, decreased apoptosis rates and apoptosis-related genes. Furthermore, BM EPCs induced T cell differentiation towards more immune-tolerant cells in higher-risk MDS patients in vitro. In addition, the levels of intracellular ROS and the apoptosis ratios were increased in BM EPCs from MDS patients, especially in higher-risk MDS patients, which may be therapeutic candidates for MDS patients. Conclusion Our results suggest that dysfunctional BM EPCs are involved in MDS patients, which indicates that improving haematopoiesis supporting ability and immuneregulation ability of BM EPCs may represent a promising therapeutic approach for MDS patients.

Exploring the complex dynamic relationship between urban–rural integrated development and land-use efficiency can contribute to most efficient urban–rural land-use and the rational promotion of urban–rural integrated development. This study established an evaluation model of urban–rural integrated development, adopted the super-efficiency SBM model to measure land-use efficiency, and studied the evolution of the spatial–temporal patterns of urban–rural integrated development and land-use efficiency coupling in the Yellow River Basin. We also examined the factors affecting them with the help of the coupling coordination degree model, non-parametric kernel density estimation, and geographic probes. The results indicate the following: (1) Within the study period, the coupled coordination of urban–rural integrated development and land-use efficiency was similar to the spatial distribution characteristics of land-use efficiency, both showing a “high at both ends and low in the middle” trend. (2) The coupled coordination increased over time; however, a lagging land-use efficiency was a crucial impediment to improving the coupling coordination degree. (3) Carbon emissions, urbanization rate, and per capita GDP were key drivers. The results of this study can provide a reference for local governments in the Yellow River Basin and other similar areas to propose paths to optimize the allocation of urban and rural land-use.

In order to improve the surface friction, wear and high temperature oxidation resistance of TC4 titanium alloy, NiCrCoAlY+20%(mass fraction) Cr3C2 mixed powder was selected as the cladding powder to prepare NiCrCoAlY-Cr3C2 composite coating on the surface of TC4 titanium alloy by using laser cladding technology. The microstructure and phase composition of the coating were analyzed by OM, SEM, XRD, EDS, etc.The microhardness of the coating was measured by HXD-1000TB tester. MMG-500 three-body wear tester and WS-G150 smart muffle furnace were used to test the friction, wear and high temperature oxidation resistance of the coating and substrate. The results show that the laser cladding technology can be used to prepare the good composite coating on the surface of TC4 titanium alloy without cracks and pores. The microstructure of the cladding zone is dense, mostly needle-like crystals and dendrites.The microstructure of the bonding zone is mainly composed of planar crystals, cellular crystals and dendrites, which generates a variety of products including the carbides, oxides and intermetallic compounds that can improve wear resistance and high temperature oxidation resistance. The maximum microhardness of the composite coating is 1344HV, which is about 3.8 times of the 350HV of the titanium alloy substrate.The friction factor of the composite coating is 0.2-0.3, which is significantly lower than the friction factor of the titanium alloy substrate of 0.6-0.7. Under the same conditions, the wear mass loss of the composite coating is 0.00060 g, which is 0.9% of that of 0.06508 g of titanium alloy substrate. After oxidation at 850℃ for 100 h, the oxidation mass gain of the composite coating is 6.01 mg·cm-2, which is about 24% of that of 25.10 mg·cm-2 of titanium alloy substrate. Laser cladding technology effectively improves the friction and wear performance and high temperature oxidation resistance of the TC4 titanium alloy surface.

To provide reference for technical feasibility and process setting of physical cold disinfection of salad dressing, the commercial salad dressing was irradiated by electron beam at different doses of 0 kGy,1 kGy and 2 kGy. The disinfection effect of electron beam irradiation on salad dressing and the changes in terms of microorganism, color, texture, flavor, stability of irradiated salad dressing after storing for 40 days at room temperature were studied. The results showed that, electron beam irradiation had a good disinfection effect on Salmonella typhimurium, Escherichia coli, Staphylococcus aureus, the aerobic plate count, molds and yeasts of salad dressing. 1 kGy irradiation could reduce pathogenic bacteria by 3 log to 6 log, with no aerobic plate count, molds and yeasts found. After 40 days storage at room temperature, sensory evaluation showed that electron beam irradiation at 1 kGy had no significant effect on the color, texture, aroma and taste of salad dressing. There was no obvious difference in the results of electronic nose analysis, texture parameters and centrifugal resolution rate, but the taste score of 2 kGy irradiation was significantly lower than that of non-irradiation and 1 kGy irradiation. Significant difference of texture parameters was found between 2 kGy irradiation, non-irradiation, and 1 kGy irradiation. Therefore, we conclude electron beam irradiation can effectively control the pathogenic bacteria in salad dressing. The electron beam irradiation at doses of 1 kGy has no obvious undesirable effect on the color, texture, flavor, stability of the salad dressing, which could be used as a disinfection method for salad dressing.

During microbial infection, proteins are modified by the ubiquitin-like protein ISG15. Here, the authors uncover RNF213 as a sensor for ISGylated proteins on the surface of lipid droplets, showing that RNF213 has antiviral properties but also directly targets intracellular bacteria in infected cells.

ABSTRACT: Background: Livestock and poultry skeletal muscle development was regulated by a variety of genetic factors playing an essential role in this process. In our de novo sequencing, a missense mutation in ISPD exon 2 showed a selected signature for well-developed muscles. However, the relationship between this mutation and muscle phenotypes remains unclear. Results: Based on the genotype bias of this missense mutation in gamecock chickens, we compared the cross-section of muscle fibers among the individuals with different genotypes with the results showing a genotype preference of this missense mutation in the chickens with hypertrophic muscle fibers. Comparing TT- and CC-genotype ISPD showed that TT- genotype was associated with heavier skeletal muscle and a better effect on myogenesis and myofiber stability. At cellular level, ISPD was identified to inhibit myoblast proliferation, differentiation and antagonize of muscular atrophy. Conclusion: It can be concluded that the missense mutation of Arg84Lys in ISPD was associated with well-developed muscles and demonstrated to improve chicken muscles’ development.

Disorders of glucolipid metabolism is the main cause of obesity, cardiovascular diseases, diabetes and other chronic diseases. As our diet becomes increasingly refined, dietary is gaining attention from academia and people outside. Moreover, it has been recognized by the nutritional sciences as the seventh category of nutrients, which plays an important physiological role in regulating glucolipid metabolism. This paper briefly reviews the relationship between the physicochemical property of dietary fiber, the microbial-mediated regulatory mechanism and glucolipid metabolism, and predicts the future research topics and applications of dietary fiber. It aims to provide insights for further research and application of dietary fiber, as well as the prevention and early treatment of disorders of glucolipid metabolism.

Accurate and quick building damage assessment is an indispensable step after a destructive earthquake. Acquiring building damage information of the seismic area in a remotely sensed way enables a timely emergency response. Existing remote sensing building damage detection methods based on convolutional neural network (CNN) mainly need two-step processing or only use single post-event image, leading to low efficiency and inaccurate building boundary. Considering the practical needs of emergency rescue and post-disaster reconstruction, this study proposed a hierarchical building damage assessment workflow using CNN-based direct remote sensing change detection on superpixel level. First, vulnerable building areas close to the epicenter are extracted using extra feature enhancement bands (EFEBs) to narrow the extent of image processing. Then, fine scale building damage is detected in the extracted building areas based on a direct change detection method with pre-event superpixel constraint (PreSC) strategy to improve the precision and efficiency. Finally, a rapid remote sensing earthquake damage index (rRSEDI) is used to quantitatively assess the damage. Experimental results of the case study show that damaged buildings can be effectively and accurately localized and classified using the proposed workflow. Comparative experiments with single-temporal image and post-event segmentation further embody the superiority of the direct change detection. The damage assessment result matches the official report after Ludian earthquake, proving the reliability of the proposed workflow. For future natural hazard events, the workflow can contribute to formulating appropriate disaster management, prevention and mitigation policies.

Abstract Dysfunctional megakaryopoiesis hampers platelet production, which is closely associated with thrombocytopenia (PT). Macrophages (MФs) are crucial cellular components in the bone marrow (BM) microenvironment. However, the specific effects of M1 MФs or M2 MФs on regulating megakaryocytes (MKs) are largely unknown. In the current study, aberrant BM-M1/M2 MФ polarization, characterized by increased M1 MФs and decreased M2 MФs and accompanied by impaired megakaryopoiesis-supporting abilities, was found in patients with PT post-allotransplant. RNA-seq and western blot analysis showed that the PI3K-AKT pathway was downregulated in the BM MФs of PT patients. Moreover, in vitro treatment with PI3K-AKT activators restored the impaired megakaryopoiesis-supporting ability of MФs from PT patients. Furthermore, we found M1 MФs suppress, whereas M2 MФs support MK maturation and platelet formation in humans. Chemical inhibition of PI3K-AKT pathway reduced megakaryopoiesis-supporting ability of M2 MФs, as indicated by decreased MK count, colony-forming unit number, high-ploidy distribution, and platelet count. Importantly, genetic knockdown of the PI3K-AKT pathway impaired the megakaryopoiesis-supporting ability of MФs both in vitro and in a MФ-specific PI3K-knockdown murine model, indicating a critical role of PI3K-AKT pathway in regulating the megakaryopoiesis-supporting ability of M2 MФs. Furthermore, our preliminary data indicated that TGF-β released by M2 MФs may facilitate megakaryopoiesis through upregulation of the JAK2/STAT5 and MAPK/ERK pathways in MKs. Taken together, our data reveal that M1 and M2 MФs have opposing effects on MKs in a PI3K-AKT pathway-dependent manner, which may lead to new insights into the pathogenesis of thrombocytopenia and provide a potential therapeutic strategy to promote megakaryopoiesis.

The temperate steppe experienced degradation and desertification as a result of long-term heavy grazing and excessive reclamation. Some major ecological projects, such as the Grain for Green Program (GGP) and Grazing Exclosure (GE), have been implemented to promote ecological restoration in grassland ecosystems. With the goal of carbon neutrality, the effects of the GGP and GE on grassland carbon sequestration need to be further explored. Based on soil data from the second soil survey in the 1980s, a field survey in 2021, and the land-use/land-cover datasets of 2000–2018, we characterized the changes in soil C stock following grazing exclosure, analyzed the effect of GGP on land-use changes and soil C accumulation, and then estimated the overall grassland carbon sequestration in Ningxia on the Loess Plateau of China. From 2000 to 2018, GE increased the grassland SOCD from 49.60 Mg ha−1 to 90.71 Mg ha−1, and the C stock increased by 65.55 T g. Under the influence of the GGP, 347.62 km2 of cultivated land was converted into grasslands, increasing the grassland soil carbon sequestration by 1.31 T g. Subsequently, the grassland organic carbon storage increased by 66.86 T g, which accounted for approximately 4.26% of the grassland organic carbon storage in the Loess Plateau of China. In the southern Loess hilly area, which experienced high precipitation and low temperatures, grasslands increased by 95.55 km2; the average organic carbon density increased 46.95 Mg ha−1 due to a rate of increase of 2.61 Mg ha−1 yr−1; and the corresponding values for those in the middle arid zone were 36.25 Mg ha−1 and 2.01 Mg ha−1 yr−1, with grasslands decreasing by 147.41 km2. The follow-up policies of the GGP and GE should be implemented and improved according to local conditions to improve the carbon sink and ecological services in grassland ecosystems.

Using the data of China National Nutrition and Health Survey, we explored the relationship between dietary fructose intake and lipid indexes and dyslipidemia of 27 265 Chinese residents aged 45 and above. The level of serum total cholesterol (TC), triglycerides (TG) and high-density lipoprotein Cholesterol(HDL-C) were significantly lower in male while dietary fructose intake was lower in female (P < 0.001).With the increase of the dietary fructose quartile level, serum TG concentration was increased while HDL-C was decreased for male residents (Ptrend < 0.001). Among female residents, we only found serum TG concentration was increased (Ptrend < 0.001). Compared with the first quartile, the risk of low HDL cholesterolemia in the third (OR: 1.17; 95%CI: 1.03～1.33) and fourth (OR: 1.25; 95%CI: 1.08～1.43) quartile were increased after adjustment for confounding factor. There was no association between dietary fructose intake and hypercholesterolemia, hypertriglyceridemia, mixed hyperlipidemia, and dyslipidemia among female residents after adjustment for confounding factor (P > 0.001). There were gender differences for the effect of dietary fructose intake on lipid indexes and dyslipidemia.

Abstract Background This study aimed to quantify the dosimetric differences between the planned and delivered dose to tumor and normal organs in locally advanced non-small cell lung cancer (LANSCLC) treated with hypofractionated radiotherapy (HRT), and to explore the necessity and identify optimal candidates for adaptive radiotherapy (ART). Methods Twenty-seven patients with stage III NSCLC were enrolled. Planned radiation dose was 51Gy in 17 fractions with cone-beam CT (CBCT) acquired at each fraction. Virtual CT was generated by deformable image registration (DIR) of the planning CT to CBCT for dose calculation and accumulation. Dosimetric parameters were compared between original and accumulated plans using Wilcoxon signed rank test. Correlations between dosimetric differences and clinical variables were analyzed using Mann-Whitney U test or Chi-square test. Results Patients had varied gross tumor volume (GTV) reduction by HRT (median reduction rate 11.1%, range − 2.9-44.0%). The V51 of planning target volume for GTV (PTV-GTV) was similar between original and accumulated plans (mean, 88.2% vs. 87.6%, p = 0.452). Only 11.1% of patients had above 5% relative decrease in V51 of PTV-GTV in accumulated plans. Compared to the original plan, limited increase (median relative increase

Abstract Background In ruminants, dietary C18:3n-3 can be lost through biohydrogenation in the rumen; and C18:3n-3 that by-passes the rumen still can be lost through oxidation in muscle, theoretically reducing the deposition of C18:3n-3, the substrate for synthesis of poly-unsaturated fatty acids (n-3 LCPUFA) in muscle. In vitro studies have shown that rumen hydrogenation of C18:3n-3 is reduced by supplementation with palm oil (rich in cis-9 C18:1). In addition, in hepatocytes, studies with neonatal rats have shown that cis-9 C18:1 inhibits the oxidation of C18:3n-3. It therefore seems likely that palm oil could reduce both rumen biohydrogenation of C18:3n-3 and muscle oxidation of C18:3n-3. The present experiment tested whether the addition of palm oil to a linseed oil supplement for goat kids would prevent the losses of C18:3n-3 and thus improve the FA composition in two muscles, Longissimus dorsi and Biceps femoris. To investigate the processes involved, we studied the rumen bacterial communities and measured the mRNA expression of genes related to lipid metabolism in Longissimus dorsi. Sixty 4-month-old castrated male Albas white cashmere kids were randomly allocated among three dietary treatments. All three diets contained the same ingredients in the same proportions, but differed in their fat additives: palm oil (PMO), linseed oil (LSO) or mixed oil (MIX; 2 parts linseed oil plus 1 part palm oil on a weight basis). Results Compared with the LSO diet, the MIX diet decreased the relative abuandance of Pseudobutyrivibrio, a bacterial species that is positively related to the proportional loss rate of dietary C18:3n-3 and that has been reported to generate the ATP required for biohydrogenation (reflecting a decrease in the abundance of rumen bacteria that hydrogenate C18:3n-3 in MIX kids). In muscle, the MIX diet increased concentrations of C18:3n-3, C20:5n-3, C22:6n-3, and n-3 LCPUFA, and thus decreased the n-6/n-3 ratio; decreased the mRNA expression of CPT1β (a gene associated with fatty acid oxidation) and increased the mRNA expression of FADS1 and FADS2 (genes associated with n-3 LCPUFA synthesis), compared with the LSO diet. Interestingly, compared to Longissimus dorsi, Biceps femoris had greater concentrations of PUFA, greater ratios of unsaturated fatty acids/saturated fatty acids (U/S), and poly-unsaturated fatty acids/saturated fatty acids (P/S), but a lesser concentration of saturated fatty acids (SFA). Conclusions In cashmere goat kids, a combination of linseed and palm oils in the diet increases the muscle concentration of n-3 LCPUFA, apparently by decreasing the relative abundance of rumen bacteria that are positively related to the proportional loss rate of dietary C18:3n-3, by inhibiting mRNA expression of genes related to C18:3n-3 oxidation in muscle, and by up-regulating mRNA expression of genes related to n-3 LCPUFA synthesis in muscle, especially in Longissimus dorsi.

ObjectiveDespite the high efficiency of glucocorticoids (GCs), ~18–34% patients with myasthenia gravis (MG) may experience relapses of the disease. Here, we aim to identify clinical factors related to relapses during steroid tapering or after withdrawal in MG patients who were well-managed on steroid monotherapy.MethodsWe conducted a retrospective study on 125 MG patients from the Xuanwu Hospital MG Trial Database. Patients were treated with corticosteroids and achieved minimal manifestation status (MMS) or better. Patients were divided into steroid reduction subset (N = 74) and steroid withdrawal subset (N = 51). Clinical characteristics and therapeutic data were compared between patients with disease relapse and those who maintained clinical remission at the last follow-ups. Cox proportional hazards regression models were used to identify risk factors of relapse in each subset.ResultsThirty-seven (29.6%) patients experienced relapses during the follow-up periods. Relapse during the steroid reduction was significantly associated with drug reducing duration (HR = 0.81, 95%CI 0.74–0.89, P < 0.001). Risk of relapse was augmented if the drug reducing duration was

Abstract Background To investigate the loco-regional progression-free survival (LPFS) of intensity-modulated radiotherapy (IMRT) with different fraction sizes for locally advanced non-small-cell lung cancer (LANSCLC), and to apply a new radiobiological model for tumor control probability (TCP). Methods One hundred and three LANSCLC patients treated with concurrent radiochemotherapy were retrospectively analyzed. Factors potentially predictive of LPFS were assessed in the univariate and multivariate analysis. Patients were divided into group A (2.0 ≤ fraction size

With the rapid development of fructose industry, dietary fructose intake of Chinese residents has increased steadily.Thus, it is particularly critical to investigate the status of dietary fructose intake and its relationship to health.The relationship between dietary fructose and chronic non-communicable diseases,such as obesity, dyslipidemia, diabetes, hypertension and gout were reviewed in this paper.The aim of this study is to provide reference for the fundamental researches and applications of fructose.

Castor (Ricinus communis L.) is one of the world's top ten oil crops. China is the second largest producer of castor beans, but China's castor bean acreage has been declining. A principal reason for this decline is the prevalence of weeds and the absence of herbicide resistant varieties of castor plants. In this study, we used Agrobacterium-mediated gene transfer to introduce the EPSPS (5-enolpyruvylshikimate-3-phosphate synthase) gene, which confers resistance to glyphosate, and the Bar (phosphinothricin N-acetyltransferase) gene, encoding resistance to glufosinate, into castor 2129 (high stem excellent recovery line) and CSR 181 (dwarf stem excellent recovery line). The transgenic plants exhibited significantly increased expression of the EPSPS and Bar genes and significantly increased resistance to glyphosate and glufosinate. Proteomic analysis showed differences in the amounts of 20 proteins in the dwarf stem transgenic plants. Nine of these proteins are involved in photosynthesis and indirectly related to the mechanism of action of the Bar gene. Eight proteins are involved in defense, repair, stress response, oxidative phosphorylation, and metabolic pathways and are indirectly related to the mechanism of action of the EPSPS gene. These results provide a foundation for the preparation of high herbicide resistant castor varieties.

Abstract Background Ecological migration serves as an important measure for poverty eradication as well as for the protection, inheritance, and utilization of traditional ecological knowledge. This study investigated and cataloged the traditional forage plant resources and recorded the associated traditional knowledge of immigrant villages in Hongsibu District of Ningxia, China. The diversity of traditional forage plant resources and the changes in associated traditional ecological knowledge were compared among ecological immigrant villages from different emigration areas, with a hope of providing a reference for forage development, the conservation of wild forage plant resources, and the development of regional animal husbandry. Methods From March 2018 to May 2019, a field investigation was conducted in six villages in Ningxia. Through the snowball technique, a total of 315 immigrants were interviewed using various methods, including semistructured interviews and key person interviews, which included opportunities for free listing. The changes in the utilization of traditional forage plants were compared between the ecological migrants and the original inhabitants, and the causes underlying the changes were analyzed. In addition, the major forage plant species in the research area were investigated and evaluated. Results (1) The six investigated villages reported 224 traditional forage plant species that belong to 42 families and 150 genera. Compared with their original living areas, the number of traditional forage plant species used in the immigrant villages decreased with the increase in the relocation distance. (2) The utilization of traditional forage plants varied among the immigrants who moved to Hongsibu District from forest areas, loess hilly areas, and semiarid desertified areas. The smaller the difference was in ecological environment between the immigration and emigration areas, the more the traditional forage plant knowledge had been retained. (3) The diversity and associated knowledge of traditional forage plants retained by ecological migrants are closely correlated to gender, age, education level, and occupation. Conclusion This study revealed that the diversity of traditional forage plants and associated knowledge retained after migration vary among ecological immigrants from different areas; generally, the immigrants that relocated from a closer place retained more ecological knowledge. In the immigrant villages with significantly different natural resources and a long distance from the migrants’ original locations, the diversity of traditional forage plants decreased, and the traditional knowledge about forage plants showed signs of being forgotten and abandoned by the younger generation. Therefore, measures are urgently needed to document and protect the forage plant resources and preserve the traditional knowledge of ecological immigrants.