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Abstract Background The prognosis of non-small cell lung cancer (NSCLC) is substantially affected by lymph node metastasis (LNM), but there are no noninvasive, inexpensive methods of relatively high accuracy available to predict LNM in NSCLC patients. Methods Clinical data on NSCLC patients were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Risk factors for LNM were recognized LASSO and multivariate logistic regression. Six predictive models were constructed with machine learning based on risk factors. The area under the receiver operating characteristic curve (AUC) was used to assess the performance of the model. Subgroup analysis with different T-stages was performed on an optimal model. A webpage LNM risk calculator for optimal model was built using the Shinyapps.io platform. Results We enrolled 64,012 NSCLC patients, of whom 26,611 (41.57%) had LNM. Using multivariate logistic regression, we finally identified 10 independent risk factors for LNM: age, sex, race, histology, primary site, grade, T stage, M stage, tumor size, and bone metastases. GLM is the optimal model among all six machine learning models in both the training and validation cohorts. Subgroup analyses revealed that GLM has good predictability for populations with different T staging. A webpage LNM risk calculator based on GLM was posted on the shinyapps.io platform ( https://wubopredict.shinyapps.io/dynnomapp/ ). Conclusion The predictive model based on GLM can be used to precisely predict the probability of LNM in NSCLC patients, which was proven effective in all subgroup analyses according to T staging.

Abstract Background Selenium (Se) is essential for human health and is predominantly obtained from dietary sources, particularly rice in Hunan Province, a significant rice-producing region in southern China. Investigating the relationship between Se levels in paddy soil and rice grains, along with the associated influencing factors, is critical for enhancing Se-enriched food security. Results Analysis of 128,992 samples collected between 2019 and 2022 revealed that the soil Se concentration in Hunan exceeded the global average, with rice grains showing promising potential for Se enrichment. Various analytical methods, including statistical analyses, co-occurrence networks, and correlation heatmaps, were utilized to scrutinize the extensive dataset. Additionally, partial least squares path analysis elucidated the interactive effects of influencing factors on soil Se concentration, rice grain Se concentration, and Se bioconcentration factor (BCF). Soil parent materials significantly affected soil Se concentration, rice grain Se concentration, and Se BCF (p

Summary: Environmental stresses threaten global food security by reducing major crop productivity. MicroRNAs (miRNAs), a class of small non-coding RNAs, function as master regulators of gene expression in plants. In this study, we co-overexpressed three copper-miRNAs (miR397, miR408, and miR528) in three major food crops (referred to as 3miR-OE), which simultaneously silenced several target laccase genes, resulting in reduced lignin contents but increased flavonoid metabolites. Importantly, we observed that, compared to wild-type and single miRNA overexpression lines, the 3miR-OE transgenic Japonica and Indica rice exhibited significantly enhanced tolerance against cold and drought stresses throughout the growth period. In addition, 3miR-OE transgenic maize and wheat also exhibited robust resistance to cold and water-deficit conditions, suggesting that co-overexpressing three Cu-miRNAs is a powerful tool for improving resilience to abiotic stresses across diverse crops. Altogether, we have developed a bioengineering strategy to maintain crop growth and yield under unfavorable environmental conditions.

Brassinosteroid (BR), a plant hormone regulating growth, development, and stress responses, emerges as a promising tool for maintaining agricultural production under abiotic stress conditions. In this study, we conducted RNA-seq profiling and morpho-physiological analysis to investigate the molecular cross-talk involved in 24-epibrassinolide (EBR) mediating alleviation of chromium (Cr) stress. EBR inhibited Cr accumulation and reversed Cr-induced phytotoxicity, thereby promoting plant growth. The photosynthetic pigments, chlorophyll fluorescence a, electron transport rate (ETR) and non-photochemical quenching (NPQ) were significantly higher in EBR+Cr treated plants compared to Cr alone. EBR application facilitated the recovery from Cr-induced structural deformities, including the disintegration of cell walls and membranes. Furthermore, under Cr stress, EBR application reduced malondialdehyde (MDA) and reactive oxygen species (ROS) production and accumulation. The levels of glutathione reductase (GR) and the activities of antioxidant enzymes were notably higher in plants subjected to EBR application following Cr stress. In addition, we established a transcriptomic database comprising 2345 differentially expressed genes (DEGs) (1255 upregulated and 1090 downregulated) as a result of EBR application under Cr stress. The transcriptome analysis unveiled key DEGs and the associated pathways, emphasizing the importance of defense responses, genes encoding photosystem I and II, jasmonate signaling, aquaporins, ABC transporters, and cell wall biogenesis-related genes in the response of EBR to Cr stress.

Abstract The complete compound of gefitinib is effective in the treatment of lung adenocarcinoma. However, the effect on lung adenocarcinoma (LUAD) during its catabolism has not yet been elucidated. We carried out this study to examine the predictive value of gefitinib metabolism-related long noncoding RNAs (GMLncs) in LUAD patients. To filter GMLncs and create a prognostic model, we employed Pearson correlation, Lasso, univariate Cox, and multivariate Cox analysis. We combined risk scores and clinical features to create nomograms for better application in clinical settings. According to the constructed prognostic model, we performed GO/KEGG and GSEA enrichment analysis, tumor immune microenvironment analysis, immune evasion and immunotherapy analysis, somatic cell mutation analysis, drug sensitivity analysis, IMvigor210 immunotherapy validation, stem cell index analysis and real-time quantitative PCR (RT-qPCR) analysis. We built a predictive model with 9 GMLncs, which showed good predictive performance in validation and training sets. The calibration curve demonstrated excellent agreement between the expected and observed survival rates, for which the predictive performance was better than that of the nomogram without a risk score. The metabolism of gefitinib is related to the cytochrome P450 pathway and lipid metabolism pathway, and may be one of the causes of gefitinib resistance, according to analyses from the Gene Set Enrichment Analysis (GSEA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Immunological evasion and immunotherapy analysis revealed that the likelihood of immune evasion increased with risk score. Tumor microenvironment analysis found most immune cells at higher concentrations in the low-risk group. Drug sensitivity analysis found 23 sensitive drugs. Twenty-one of these drugs exhibited heightened sensitivity in the high-risk group. RT-qPCR analysis validated the characteristics of 9 GMlncs. The predictive model and nomogram that we constructed have good application value in evaluating the prognosis of patients and guiding clinical treatment.

Abstract MicroRNAs (miRNAs) play fundamental roles in many developmental and physiological processes in eukaryotes. MiRNAs in plants generally regulate their targets via either mRNA cleavage or translation repression; however, which approach plays a major role and whether these two function modes can shift remains elusive. Here, we identify a miRNA, miR408-5p that regulates AUXIN/INDOLE ACETIC ACID 30 (IAA30), a critical repressor in the auxin pathway via switching action modes in rice. We find that miR408-5p usually inhibits IAA30 protein translation, but in a high auxin environment, it promotes the decay of IAA30 mRNA when it is overproduced. We further demonstrate that IDEAL PLANT ARCHITECTURE1 (IPA1), an SPL transcription factor regulated by miR156, mediates leaf inclination through association with miR408-5p precursor promoter. We finally show that the miR156-IPA1-miR408-5p-IAA30 module could be controlled by miR393, which silences auxin receptors. Together, our results define an alternative auxin transduction signaling pathway in rice that involves the switching of function modes by miR408-5p, which contributes to a better understanding of the action machinery as well as the cooperative network of miRNAs in plants.

Backgrounds and purposes: Osteoporosis (OP) is a debilitating illness distinguished by a reduction in bone density and microstructure, which leads to fragility, fracture risk, and increased mortality, particularly in the elderly and postmenopausal women. Growing evidence suggests that various plant derivatives could be a potential therapy for osteoporosis. Ellagic acid is a phenolic found naturally in extracts from plants such as pomegranate, blackberry and berry. In earlier research, ellagic acid (EA) was reported to have certain benefits on osteoporosis, however, EA was limited by its weak bioactivity. Urolithin A (UA), an ellagic acid metabolite present in the intestinal bacteria, which had a greater bioavailability. However, its therapeutic effects and mechanisms in osteoporosis remain to be explored. Study design: In this work, we explored about how UA affected the molecular processes of osteoclasts differentiation in vitro. We also performed the ovariectomy-induced osteoporotic mice model in order to evaluate how UA impacted the bone loss of osteoporosis. Methods: 1. TRAP staining analysis to examine the impact of UA on osteoclast differentiation. 2. RT-PCR for evaluating UA's impact on the expression of genes relevant to osteoclasts. Bone resorption experiment and scan by electron microscope in order to determine the impact of UA on osteoclast function. 3.Using western blotting, investigate the impact of UA on the osteoclast differentiation-related signaling pathway. 4. Developed an osteoporosis mouse model for evaluating the preventative impact of UA on bone loss after an ovariectomy. Results: 1. UA reduced osteoclast development in a dosage manner without cytotoxicity. 2. UA suppresses osteoclast-related gene expression as well as the function of osteoclast bone resorption. 3. UA regulates osteoclast development by decreasing PI3K/AKT/mTOR signaling pathway phosphorylation as well as Nfatc1 transcription and translation. 4. Animal study demonstrated that UA reduced bone loss in ovariectomy-induced osteoporotic mice. Conclusion: UA reduced the development and bone resorption function of osteoclast, was shown as inhibiting expression of osteoclast-associated specific genes as well as the PI3K/AKT/mTOR signaling pathway and decreasing Nfatc1 expression. In vivo, UA prevented bone loss in ovariectomy-induced osteoporotic mice. Finally, UA shown tremendous promise in the prevention and treatment of osteoporosis.

BackgroundThere are various therapeutic methods for treating stage IA (T1N0M0) non-small cell lung cancer (NSCLC), but no studies have systematically assessed multiple treatments to determine the most effective therapy.MethodsStage IA NSCLC patient data collected between 2004 and 2018 were gathered from the Surveillance, Epidemiology, and End Results (SEER) database. Treatment modalities included observation, chemotherapy alone (CA), radiation alone (RA), radiation+chemotherapy (RC), surgery alone (SA), surgery+chemotherapy (SC), surgery+radiation (SR) and surgery+radiation+chemotherapy (SRC). Comparisons were made of overall survival (OS) and lung cancer-specific survival (LCSS) among patients based on different therapeutic methods by survival analysis.ResultsUltimately, 89147 patients with stage IA NSCLC between 2004 and 2018 were enrolled in this study. The order of multiple treatment modalities based on the hazard ratio (HR) for OS for the entire cohort revealed the following results: SA (HR: 0.20), SC (HR: 0.25), SR (HR: 0.42), SRC (HR: 0.46), RA (HR: 0.56), RC (HR: 0.72), CA (HR: 0.91) (PConclusionSA appeared to be the optimal treatment modality for patients with stage IA NSCLC, and lobectomy was associated with the best prognosis. There may be some indication and selection bias in our study, and the results of this study should be confirmed in a prospective study.

Background: Several studies have reported the association between osteoporosis and major depressive disorder (MDD) as well as the use of antidepressants. However, it remains to be elucidated whether these associations are related to exposure to antidepressants, a consequence of a disease process, or a combination of both. Methods: This study investigates the independent effect of the antidepressant duloxetine hydrochloride (DH) on ovariectomy-induced bone loss in mice. One week after ovariectomy, the treated mice received DH. To explore the mechanism underlying the rescue of bone loss, bone marrow cells were isolated from mouse femurs and tibias, and macrophages extracted from them were induced to become osteoclasts in vitro while being treated with DH. Subsequently, the osteoclasts underwent Bulk RNA-Seq to reveal the involved signaling pathways. The results of the bioinformatic analysis were then validated through in vitro experiments. Results: The in vivo experiments demonstrated that DH treatment compromised ovariectomy-induced bone loss after 7 weeks. The in vitro experiments suggested that DH treatment attenuated osteoclast differentiation via the MAPKs/NFATc1 signaling pathway. Conclusion: The findings from this study suggest that DH, instead of causing bone mass loss, may assist in alleviating postmenopausal osteoporosis. These results can serve as a reference for the clinical treatment of patients with perimenopausal or postmenopausal depression using antidepressants.

[Objective] The soil aggregates of Bingsugar orange orchards and the factors affecting them were characterized in order to reduce soil erosion and increase the water and fertility retention capacity of citrus orchards. [Methods] Soil samples were collected from weathered slate, weathered purple sandstone, sandstone, and weathered Quaternary laterite developed in a Bingsugar orange orchard. Related tillage and geographic information were collected simultaneously. ANOVA and correlation analysis were performed on the agglomerated data and their organic carbon contents using soil structural stability indexes R 0.25, GWD, MWD, fractal dimension (D), and soil erodibility K value. [Results] ① Agglomerates with particle sizes >0.25 mm accounted for 78%~85% of the total agglomerates. Graded soil content gradually decreased with decreasing agglomerate particle size. ② The GWD of the soils developed by the four matrices ranged from 0.536~0.797; MWD ranged from 0.890~1.208; fractal dimension (D) ranged from 2.434~2.480; and soil erodibility K value ranged from 0.060 8~0.0 697. ③ Organic carbon content decreased with increasing particle size and then increased, with an overall V-shaped distribution. Organic carbon content of the 0.250~0.053 mm microaggregates was the lowest. The relative contribution of organic carbon of large agglomerates was 82%~87%. ④ Soil structure stability indexes R0.25, GWD, and MWD significantly increased with increasing number of planting years and the continuous input of exogenous organic carbon. Fractal dimension (D) and soil erodibility K values significantly decreased at the same time, indicating increasing soil structure stability. [Conclusion] Soil stability was high with high content of large agglomerates in a Bingsugar orange orchard in Hu’nan Province. The soil stability of each parent material was at the same level. Sand content of the soil-forming parent material and anthropogenic disturbance directly affected the role of agglomerate stability, exogenous organic carbon, and planting years. Latitude and altitude jointly influence soil stability by organic colloidal material. The sand content of the parent material and anthropogenic disturbance directly contribute to the stability of the aggregates. Exogenous organic carbon, age of cultivation, latitude and altitude combine to influence soil stability through the organic cementing material.

Remote sensing-based techniques have been widely used for chlorophyll content (Cab) estimations, while they are challenging when transferred across different species. Sun-induced chlorophyll fluorescence (SIF) provides a new approach to address these issues. This research explores whether SIF has transferability for Cab estimation and to enhance between-species transferability. Here, three rice datasets and a rapeseed dataset were collected. Initially, direct transfer models were constructed using partial least squares regression (PLSR) based on SIF yield (SIFY) and reflectance, respectively. Subsequently, methods were employed within the rice datasets to improve the models’ transferability. Finally, the between-species transferability of two data sources was validated in the rapeseed dataset. Direct transfer models indicated that the reflectance-based model exhibited a higher accuracy in predicting Cab when the training dataset acquired sufficient features, whereas the SIFY-based model showed better performance with fewer features. Spectral preprocessing methods can enhance the transferability, especially for SIFY-based models. In addition, supplementing 10% of out-of-sample data significantly improved the transferability. The proposed methods only require a small amount of new data to extend the original model for predicting Cab in other species. Specifically, the new method reduced the average RMSE based on SIFY and reflectance models by 23.59% and 35.51%, respectively.

Vegetable production in Subtropical China is distinguished by excessive nitrogen (N) fertilization, frequent irrigation, and multiple crop rotations in a single year. The aforementioned variables are closely related to soil nitrous oxide (N2O) and methane (CH4) emissions. Hence, we conducted a field trial to measure N2O and CH4 emissions using static chamber–gas chromatograph. Four treatments were used: control (CK) with no fertilizer, 100% chemical N fertilization (CN), the conventional 30% chicken manure N plus 70%CN (CMN + CN), and 30% chicken manure biochar N plus 70%CN (CMBN + CN). The annual cumulative N2O emissions reached 12.4, 63.5, 111.8, and 44.1 kg N2O-N ha−1 for the CK, CN, CMN + CN, and CMBN + CN treatments, respectively. Compared to the CN and CMN + CN treatments, the CMBN + CN treatment reduced N2O emissions by 35.9%–65.7%, while it simultaneously increased the total vegetable yield by 16.1% compared to the CN treatment. Seven seasons mean N2O emission factors are 1.3% for CN, 3.8% for CMN + CN, and 0.9% for CMBN + CN. The CH4 emission was negligible, ranging from 0.07 kg CH4-C ha−1 for the CK treatment to 0.8 kg CH4-C ha−1 for the CN treatment. N2O emissions peaked under the conditions of an interior chamber temperature of around 31.9 °C and the water-filled pore space (WFPS) of the soil being approximately 60%. Future climate change will intensify, triggering higher N2O emissions from subtropical vegetable fields. CMB can be one of the best substitutes for direct chicken manure application as a soil supplement because it has a beneficial effect on improving vegetable yield and reducing N2O emissions in Subtropical China.

Abstract Neoantigens derived from non-synonymous somatic mutations are restricted to malignant cells and are thus considered ideal targets for T cell receptor (TCR)-based immunotherapy. Adoptive transfer of T cells bearing neoantigen-specific TCRs exhibits the ability to preferentially target tumor cells while remaining harmless to normal cells. High-avidity TCRs specific for neoantigens expressed on AML cells have been identified in vitro and verified using xenograft mouse models. Preclinical studies of these neoantigen-specific TCR-T cells are underway and offer great promise as safe and effective therapies. Additionally, TCR-based immunotherapies targeting tumor-associated antigens are used in early-phase clinical trials for the treatment of AML and show encouraging anti-leukemic effects. These clinical experiences support the application of TCR-T cells that are specifically designed to recognize neoantigens. In this review, we will provide a detailed profile of verified neoantigens in AML, describe the strategies to identify neoantigen-specific TCRs, and discuss the potential of neoantigen-specific T-cell-based immunotherapy in AML.

CRISPR-mediated genome editing has emerged as a powerful tool for creating targeted mutations in the genome for various applications, including studying gene functions, engineering resilience against biotic and abiotic stresses, and increasing yield and quality. However, its utilization is limited to model crops for which well-annotated genome sequences are available. Many crops of dietary and economic importance, such as wheat, cotton, rapeseed-mustard, and potato, are polyploids with complex genomes. Therefore, progress in these crops has been hampered due to genome complexity. Excellent work has been conducted on some species of Brassica for its improvement through genome editing. Although excellent work has been conducted on some species of Brassica for genome improvement through editing, work on polyploid crops, including U’s triangle species, holds numerous implications for improving other polyploid crops. In this review, we summarize key examples from genome editing work done on Brassica and discuss important considerations for deploying CRISPR-mediated genome editing more efficiently in other polyploid crops for improvement.

Purpose: Complex distal femoral fractures involve a challenging set of considerations that must be known to provide optimal management. This study aimed to determine the location and frequency of fracture lines and comminution zones in AO/OTA types 33A and 33C distal femoral fractures using three-dimensional computed tomography mapping.Methods: Seventy-four consecutive eligible patients were included. Fracture fragments for each patient were reconstructed, virtually reduced, and adjusted to match the distal femoral template. Then, all fracture lines and comminuted areas were extracted in transparent mode, and corresponding heat maps were constructed. Finally, these maps, along with the quantitative analysis findings of the counts and volumes of each fragment, were used to summarize the characteristics of the fractures.Results: Thirty-four females and 40 males [average age, 58 years (range, 18–92 years)] presented with a distal femoral fracture. There were 53 AO/OTA type 33A fractures, and 21 AO/OTA type 33C fractures. These two patterns differed significantly on fracture fragment count, comminuted zone fracture fragment count, and mean comminuted zone fracture fragment volume (p < 0.05). Most of the fracture line heat zones were in the femoral epiphysis, intercondylar notch of the femur, and patellofemoral joint. The comminuted area heat regions were mostly found on the lateral, anterior, and posterior femoral diaphysis, with less involvement on the medial side.Conclusion: Our findings may serve as a guide for the surgical approach selection of complex distal femur fractures, the placement strategy of the internal fixation, and the optimization of the osteotomy plan for biomechanical studies.

The excessive accumulation of cobalt (Co) in plant tissues severely impairs plant growth that ultimately reduces the yield. However, melatonin (MT) has been known to mediate the abiotic stress tolerance in plants. The present study aimed at investigating the protective mechanisms of exogenously applied MT (0, 50 and 100 μM) under Co (0, 100, 200 and 300 μM) stress by focusing on morpho-physiological, biochemical and cellular characterizations of Brassica napus plants. Cobalt (300 μM) alone treatment drastically inhibited the stomatal conductance, plant height (45%), leaf area (30%), free amino acid (139%), relative electrolyte leakage (109%), and total soluble sugars (71%), compared with the control. However, the exogenous supply of MT notably minimized the oxidative damage, lipid peroxidation and maintained the membrane integrity under Co-toxicity by restricting the overproduction of ROS (H2O2 and O2•), and MDA in leaves and roots. Melatonin significantly enhanced the activities of ROS-scavenging antioxidant enzymes, secondary metabolism-related phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), stress-responsive genes (heat shock protein as HSP-90, methyl transferase as MT) and regulated the Co-transporters, especially in roots. These findings indicated that an exogenous supply of MT improve the plant morphology, photosynthetic apparatus, osmotic adjustments, and antioxidant defense systems by enhancing the Co-detoxification in B. napus plants.

Improving yield in potato production with minimal environmental impact is of great significance for China’s potato staple food policy. Previous research has been limited by the absence of regional-scale parameters to evaluate the environmental costs of regional potato production. To address this gap, we utilized the input–output analysis method to offer a thorough estimation of nitrogen (N), phosphorus (P), and potassium (K) inputs and outputs in the potato production stage at a regional scale, leveraging a meta-analysis dataset from plenty of the literature. On this basis, we calculated the virtual N, P, and K factors (VNFs, VPFs, and VKFs) for different potato production regions, under both conventional and optimal management practices. China’s potato production suffered from excessive N and P inputs, while K inputs remained insufficient. Significant spatial heterogeneities were observed for the VNFs, VPFs, and VKFs across different potato production regions. Northeast China and northwest China emerged as the most suitable potato cultivation regions because they demonstrated high potato yields with relatively low inputs and, consequently, lower VNFs and VPFs. Southwest China was the most vital region where targeted efforts could lead to reducing VNF and VPF, thus significantly mitigating environmental N and P losses. In addition to reducing fertilizer inputs, site-specific and whole optimization measures are proposed to lower the environmental costs and promote the sustainable development of potato production.

Rapeseed is a significant oil crop, and the size and length of its pods affect its productivity. However, manually counting the number of rapeseed pods and measuring the length, width, and area of the pod takes time and effort, especially when there are hundreds of rapeseed resources to be assessed. This work created two state-of-the-art deep learning-based methods to identify rapeseed pods and related pod attributes, which are then implemented in rapeseed pots to improve the accuracy of the rapeseed yield estimate. One of these methods is YOLO v8, and the other is the two-stage model Mask R-CNN based on the framework Detectron2. The YOLO v8n model and the Mask R-CNN model with a Resnet101 backbone in Detectron2 both achieve precision rates exceeding 90%. The recognition results demonstrated that both models perform well when graphic images of rapeseed pods are segmented. In light of this, we developed a coin-based approach for estimating the size of rapeseed pods and tested it on a test dataset made up of nine different species of Brassica napus and one of Brassica campestris L. The correlation coefficients between manual measurement and machine vision measurement of length and width were calculated using statistical methods. The length regression coefficient of both methods was 0.991, and the width regression coefficient was 0.989. In conclusion, for the first time, we utilized deep learning techniques to identify the characteristics of rapeseed pods while concurrently establishing a dataset for rapeseed pods. Our suggested approaches were successful in segmenting and counting rapeseed pods precisely. Our approach offers breeders an effective strategy for digitally analyzing phenotypes and automating the identification and screening process, not only in rapeseed germplasm resources but also in leguminous plants, like soybeans that possess pods.

The control of a flexible beam using ionic polymer metal composites (IPMCs) is investigated in this paper. The mechanical flexible dynamics are modelled as a Timoshenko beam. The electric dynamics of the IPMCs are considered in the model. The port-Hamiltonian framework is used to propose an interconnected control model of the mechanical flexible beam and IPMC actuator. Furthermore, a passive and Hamiltonian structure-preserving linear quadratic Gaussian (LQG) controller is used to achieve the desired configuration of the system, and the asymptotic stability of the closed-loop system is shown using damping injection. An experimental setup is built using a flexible beam actuated by two IPMC patches to validate the proposed model and show the performance of the proposed control law.

Brown planthopper (BPH) is the most devastating pest of rice in Asia, causing substantial yield losses and has become a challenging task to be controlled under field conditions. Although extensive measures have been taken over the past decades, which resulted in the evolution of new resistant BPH strains. Therefore, besides other possible approaches, equipping host plants with resistant genes is the most effective and environment-friendly technique for BPH control. Here, we systematically analyzed transcriptome changes in the susceptible rice variety Kangwenqingzhan (KW) and the resistant near-isogenic line (NIL) KW-Bph36-NIL, through RNA-seq, depicting the differential expression profiles of mRNAs and long non-coding RNAs (lncRNAs) in rice before and after BPH feeding. We observed a proportion of genes (1.48%) and (2.74%) were altered in KW and NIL, respectively, indicating different responses of rice strains against BPH feeding. Nevertheless, we characterized 384 differentially expressed long non-coding RNAs (DELs) that can be impacted by the two strains by alternatively changing the expression patterns of the respective coding genes, suggesting their certain involvement in response to BPH feeding. In BPH invasion, KW and NIL responded differently by modifying the synthesis, storage, and transformation of intracellular substances, adjusting the nutrient accumulation and utilization inside and outside the cells. In addition, NIL expressed stronger resistance by acutely up-regulating genes and other transcription factors related to stress resistance and plant immunity. Altogether, our study elaborates valuable insights into the genome-wide DEGs and DELs expression profiles of rice under BPH invasion by high throughput sequencing and further suggests that NILs can be utilized in BPH resistance breeding programs in developing high-resistance rice lines.

Background: How to detect acute pancreatitis (AP) complicated with infection early and how to arrange the treatment time are still the main problems in the world. There are few reports on the potential relationship between extrapancreatic infections and AP. The purpose of this article was to investigate the characteristics, influencing factors and prognosis of extrapancreatic infection in AP patients with modified Marshall score ≥2 on admission. Materials and methods: We retrospectively analyzed AP admitted to emergency intensive care unit of Ruijin hospital within 72 h of onset from September 2019 to December 2021. In addition to the patients' baseline data, sites of infection and microorganisms outside the pancreas were collected. Microbial cultures were used to identify infections of the respiratory tract, blood, abdominal cavity, biliary tract, urinary tract and clostridium difficile in feces. Results: 144 patients with AP were included, of which extrapancreatic infection accounted for 40.28%. C-reactive protein, procalcitonin, blood urea nitrogen, serum creatinine, oxygenation index, modified Marshall score, BISAP score and APACHE II score were significantly increased in the extrapancreatic infection group. The risk factors of extrapancreatic infection included blood urea nitrogen, Modified Marshall score and duration of mechanical ventilation. The positive rates of pathogenic bacteria in sputum culture, blood culture, ascites culture and bile culture were significantly higher than those in the 1–3 days after admission. The infection begins to worsen as early as 4–7 days after the onset of symptoms. Extrapancreatic infection is associated with pancreatic necrosis, the rate of laparotomy, length of hospital stay and in-hospital mortality. Conclusion: Our research has confirmed the need to prevent and monitor extrapancreatic infection in the early stage.

The gamma-ray vortex burst in the nonlinear Thomson scattering when the laser wakefield accelerated electron bunch collides with an ultra-intense Laguerre–Gaussian laser that was reflected from the refocusing spiral plasma mirror. The orbit angular momentum of the scattering laser would be transferred to the gamma radiation through the scattering process. The 3-dimensional particle-in-cell simulations gave the electron dynamics in the scattering, which determines the characteristics of the vortical radiation. The radiation calculation results illustrated the burst of gamma-ray vortex and surprisingly revealed the radiation pattern distortion phenomenon due to the nonlinear effect. This scheme can not only simplify the experimental setup for the generation of twisted radiation but also boost the yield of vortical gamma photons. The peak brightness of the gamma-ray vortex was estimated to be 1 × 1022 photons/s/mm2/mrad2/0.1% BW at 1 MeV, which might pave the way for the researches on angular momentum-related nuclear physics.

Abstract Background The E75 and GP2 vaccines are the few therapeutic vaccines targeting HER2 currently under clinical research for patients with breast cancer. Methods Databases, including the Cochrane Library, PubMed, Medline, Embase, and Web of Science, were used to retrieve clinical studies on E75 and GP2 vaccines. Retrieval time was from the beginning of database construction until May 31st, 2021. Results A total of 24 clinical studies were included in this analysis, including 1704 patients in the vaccinated group and 1248 patients in the control group. For the E75 vaccine, there were significant differences between the vaccinated group and the control group in the delayed-type hypersensitivity reaction (SMD = 0.685 95% CI 0.52–0.85, PHeterogeneity = 0.186, PDTH 0.05) was not different between the two groups. Local and systemic toxicity assessments of the two vaccines showed minimal side effects. Conclusions The E75 vaccine was effective and safe in patients with breast cancer. The GP2 vaccine could elicit a strong immune response, but more trials are needed to confirm its clinical efficacy.

With the advantages of intrinsic safety, good affordability, environmental friendliness, moderate energy density, and large power density, aqueous zinc ion batteries (AZIBs) have gained considerable research interest. However, zinc dendrites, hydrogen evolution, inert byproducts, and zinc metal corrosion severely hinder practical applications of AZIBs. In order to address these issues, many research works have been carried out to modify the interface between zinc metal anode and aqueous electrolyte. In fact, the interface engineering takes effect at the surface and near the surface of separator. However, a specialized review on the separators of AZIBs is still lacking. Herein, basic requirements of separators and recent advances on the modification strategies including employment of functional groups, establishment of surface coatings, construction of hybrid architectures, regulations of porosity, and utilization of bipolar membrane are reviewed. Besides, the perspectives for further investigations on the separators of AZIBs are outlined. This review could offer useful guidance for the future explorations of separators for AZIBs.

A pervasive melatonin (N-acetyl-5-methoxytryptamine) reveals a crucial role in stress tolerance and plant development. Melatonin (MT) is a unique molecule with multiple phenotypic expressions and numerous actions within the plants. It has been extensively studied in crop plants under different abiotic stresses such as drought, salinity, heat, cold, and heavy metals. Mainly, MT role is appraised as an antioxidant molecule that deals with oxidative stress by scavenging reactive oxygen species (ROS) and modulating stress related genes. It improves the contents of different antioxidant enzyme activities and thus, regulates the redox hemostasis in crop plants. In this comprehensive review, regulatory effects of melatonin in plants as melatonin biosynthesis, signaling pathway, modulation of stress related genes and physiological role of melatonin under different heavy metal stress have been reviewed in detail. Further, this review has discussed how MT regulates different genes/enzymes to mediate defense responses and overviewed the context of transcriptomics and phenomics followed by the metabolomics pathways in crop plants.

Abstract Fluid resuscitation via colon (FRVC) is a complementary therapeutic procedure for early-stage cases of severe acute pancreatitis (SAP). The expression of intestinal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN) regulates systemic inflammation. This study aimed to investigate the effect of FRVC on the expression of DC-SIGN in the colon tissue of SAP rats and its effect on the early response of systemic inflammatory and multiple organ injury. SAP was induced in rats via retrograde injection of sodium taurocholate into the biliopancreatic duct. DC-SIGN expression of appeared in the proximal and distal colon. Histological characteristics and inflammatory cytokines were examined to compare the effect of FRVC and intravenous fluid resuscitation (IVFR). The results showed that DC-SIGN expression in the proximal colon increased in a time-dependent manner in the early-stage of SAP rats. FRVC inhibited DC-SIGN expression in the proximal colon. Both FRVC and IVFR alleviated histological injuries of the pancreas and colon. However, FRVC had an advantage over IVFR in alleviating lung injury and reducing serum TNF-α, IL-6 and LPS. These results suggest that FRVC treatment might help suppress systemic inflammation and prevent subsequent organ failure in early-stage SAP rats likely through inhibiting DC-SIGN expression in the proximal colon.

Abstract Severe acute pancreatitis (SAP) is a life-threatening disease. Fluid Resuscitation Via Colon (FRVC) may be a complementary therapy for early controlled fluid resuscitation. But its clinical application has not been reported. This study aims to explore the impact of FRVC on SAP. All SAP patients with the first onset within 72 h admitted to the hospital were included from January 2014 to December 2018 through electronic databases of Ruijin hospital and were divided into FRVC group (n = 103) and non-FRVC group (n = 78). The clinical differences before and after the therapy between the two groups were analyzed. Of the 181 patients included in the analysis, the FRVC group received more fluid volume and reached the endpoint of blood volume expansion ahead of the non-FRVC group. After the early fluid resuscitation, the inflammation indicators in the FRVC group were lower. The rate of mechanical ventilation and the incidence of hypernatremia also decreased significantly. Using pure water for FRVC was more helpful to reduce hypernatremia. However, Kaplan–Meier 90-day survival between the two groups showed no difference. These results suggest that the combination of FRVC might benefit SAP patients in the early stage of fluid resuscitation, but there is no difference between the prognosis of SAP patients and that of conventional fluid resuscitation. Further prospective study is needed to evaluate the effect of FRVC on SAP patients.

The HD-Zip transcription factors play a crucial role in plant development, secondary metabolism, and abiotic stress responses, but little is known about HD-Zip I genes in soybean. Here, a homeodomain-leucine zipper gene designated GmHdz4 was isolated. Chimeric soybean plants, GmHdz4 overexpressing (GmHdz4-oe), and gene-editing via CRISPR/Cas9 (gmhdz4) in hairy roots, were generated to examine the GmHdz4 gene response to polyethylene glycol (PEG)-simulated drought stress. Bioinformatic analysis showed GmHdz4 belonged to clade δ, and was closely related to other drought tolerance-related HD-Zip I family genes such as AtHB12, Oshox12, and Gshdz4. The GmHdz4 was located in the plant nucleus and showed transcriptional activation activity by yeast hybrid assay. Quantitative real-time PCR analysis revealed that GmHdz4 expression varied in tissues and was induced by PEG-simulated drought stress. The gmhdz4 showed promoted growth of aboveground parts, and its root system architecture, including the total root length, the root superficial area, and the number of root tips were significantly higher than those of GmHdz4-oe even the non-transgenic line (NT) on root tips number. The better maintenance of turgor pressure by osmolyte accumulation, and the higher activity of antioxidant enzymes to scavenge reactive oxygen species, ultimately suppressed the accumulation of hydrogen peroxide (H2O2), superoxide anion (O2−), and malondialdehyde (MDA), conferring higher drought tolerance in gmhdz4 compared with both GmHdz4-oe and NT. Together, our results provide new insights for future research on the mechanisms by which GmHdz4 gene-editing via CRISPR/Cas9 system could promote drought stress and provide a potential target for molecular breeding in soybean.

In the mining area affected by coal mining activities for a long time, heavy metal Zn pollution poses a serious threat to soil quality and human health, and direct evidence showing the relationship between Zn accumulation mechanism in soils and mining activities is lacking. In this study, the Zn content and isotopes composition (δ66Zn) from soil and environmental samples around mining area were determined and analyzed to clarify the Zn characteristics in soil. Moreover, the distribution and source of Zn content in soil of mining area were analyzed by mathematical statistics, correlation analysis and isotope mass mixing model. The results showed that: (1) the Zn content in soil ranged from 95 to 327 mg·kg−1 (mean: 233 mg·kg−1), exceeding the control point and the soil background value of Anhui Province; (2) the results of Zn isotope analysis showed that Zn in soil mainly derived from the wind dispersion input of fine particles in gangue and fly ash, followed by the natural weathering of parent material; (3) isotopic mass mixing model can be used to distinguish the contribution of anthropogenic and natural Zn sources. Mining input was the main contribution source of Zn in soil (mean: 67%), followed by natural background (mean: 33%). The employment of Zn isotopes can effectively evaluate the impact of anthropogenic and natural long-term processes on Zn in the soil of the mining area, and provide important information for the formulation of soil metal pollution control measures.

Purple-stem Brassica napus (B. napus) is a phenotype with unique color because of its high anthocyanins content. Anthocyanins are naturally occurring plant pigments that have antioxidants activity and play important role in plant defense against abiotic and biotic stresses. In the present study, drought induced effects on plants were investigated in hydroponically grown seedlings of green stem (GS) and purple stem (PS) genotypes of B. napus. The results of this study showed that the major function of anthocyanins accumulation during drought was to enhance the antioxidant capability and stress tolerance in B. napus plants. Our results showed that drought significantly inhibited the plant growth in terms of decreased biomass accumulation in both genotypes, although marked decline was observed in GS genotype. The reduction in photosynthetic attributes was more noticeable in the GS genotype, whereas the PS genotype showed better performance under drought stress. Under stressful conditions, both the genotype showed excessive accumulation of reactive oxygen species (ROS) and malondialdehyde (MDA), as well as higher levels of antioxidant enzymes activities. Under drought conditions, the GS genotype showed apparent damages on chloroplast deformation like in thylakoid membrane and grana structural distortion and fewer starch grains and bigger plastoglobuli. Moreover, during drought stress, the PS genotype exhibited maximum expression levels of anthocyanins biosynthesis genes and antioxidant enzymes accompanied by higher stress tolerance relative to GS genotype. Based on these findings, it can be concluded that GS genotype found more sensitive to drought stress than the PS genotype. Furthermore this research paper also provides practical guidance for plant biologists who are developing stress-tolerant crops by using anthocyanin biosynthesis or regulatory genes.

Abstract An AlInN/GaN superjunction fin‐gate high electron mobility transistor (SJFin‐HEMT) is proposed in this work. A superjunction region with GaN/AlInN/GaN/AlInN/GaN structure is defined between the gate and drain, and two‐dimensional‐hole‐gas/two‐dimensional‐electron‐gas/two‐dimensional‐hole‐gas/two‐dimensional‐electron‐gas (2DHG/2DEG/2DHG/2DEG) are respectively induced due to the polarization charges at the heterojunction interfaces. The 2DHGs and 2DEGs compensate each other, resulting a charge balanced superjunction in the gate‐drain spacing, thus inducing a uniform electric field distribution under off‐state maximizing the breakdown voltage. Additionally, because the current flows through both the 2DEGs, higher output current and lower on‐state resistance are observed in contrast to the conventional Fin‐HEMT. Simulation results show breakdown voltage of 2957 V (VGS = –6 V) and on‐state resistance of 0.31 mΩ·cm2 (VDS = 0.1 V, VGS = 0 V) for the SJFin‐HEMT, comparing with that of 241 V and 0.36 mΩ·cm2 for the conventional Fin‐HEMT.

Ammannia auriculata Willd. (eared redstem) has become one of the most troublesome weeds in paddy rice in China. Resistance to bensulfuron-methyl (BSM) has spread extensively in this species. Greenhouse and field experiments were conducted to determine how the eared redstem biotype and density affect competition against rice. In the greenhouse experiment, five treatments were tested: a BSM-susceptible biotype at low density (58 plants m−2, SL), a BSM-susceptible biotype at high density (288 plants m−2, SH), a BSM-resistant biotype at low density (RL), a BSM-resistant biotype at high density (RH), and a control without eared redstem (CK). Eared redstem grew slowly until 15 days after sowing (DAS); however, growth accelerated after 20 DAS, and the eared redstem plants were taller than the rice from 55 DAS on. The SH and RH treatments were associated with greater intraspecific competition: eared redstem plants in the SH and RH treatments had fewer branches, fewer capsules, and less shoot dry weight per individual plant relative to the SL and RL treatments. The SH and RH treatments also caused greater reductions in the rice yield. The dry weight of rice at 141 DAS was reduced by 73% in the SL treatment, 98% in the SH treatment, 51% in the RL treatment, and 82% in the RH treatment, all relative to the CK. At 141 DAS, BSM-resistant plants were smaller than BSM-susceptible plants, suggesting a fitness cost of herbicide resistance in the absence of a herbicide. In the field study, eared redstem densities as low as 5 plants m−2 reduced the rice yield by 22%. A density of 50 eared redstem plants m−2 reduced the rice yield by 70%. Overall, these findings demonstrate that eared redstem is a highly aggressive weed species and threatens the rice yield even at a low density. However, the findings also demonstrate that BSM-resistant populations are less competitive. There is an urgent need to develop integrated management programs for this aggressive weed, which may include tactics to shift competitive dynamics in favor of rice. Additionally, this research provides the theoretical basis for the damage level, resistance risk evaluation, and management strategy of eared redstem in rice cropping systems.

Abstract Background To investigate potential effects of herbicide phytotoxic on crops, a major challenge is a lack of non-destructive and rapid methods to detect plant growth that could allow characterization of herbicide-resistant plants. In such a case, hyperspectral imaging can quickly obtain the spectrum for each pixel in the image and monitor status of plants harmlessly. Method Hyperspectral imaging covering the spectral range of 380–1030 nm was investigated to determine the herbicide toxicity in rice cultivars. Two rice cultivars, Xiushui 134 and Zhejing 88, were respectively treated with quinclorac alone and plus salicylic acid (SA) pre-treatment. After ten days of treatments, we collected hyperspectral images and physiological parameters to analyze the differences. The score images obtained were used to explore the differences among samples under diverse treatments by conducting principal component analysis on hyperspectral images. To get useful information from original data, feature extraction was also conducted by principal component analysis. In order to classify samples under diverse treatments, full-spectra-based support vector classification (SVC) models and extracted-feature-based SVC models were established. The prediction maps of samples under different treatments were constructed by applying the SVC models using extracted features on hyperspectral images, which provided direct visual information of rice growth status under herbicide stress. The physiological analysis with the changes of stress-responsive enzymes confirmed the differences of samples under different treatments. Results The physiological analysis showed that SA alleviated the quinclorac toxicity by stimulating enzymatic activity and reducing the levels of reactive oxygen species. The score images indicated there were spectral differences among the samples under different treatments. Full-spectra-based SVC models and extracted-feature-based SVC models obtained good results for the aboveground parts, with classification accuracy over 80% in training, validation and prediction set. The SVC models for Zhejing 88 presented better results than those for Xiushui 134, revealing the different herbicide tolerance between rice cultivars. Conclusion We develop a reliable and effective model using hyperspectral imaging technique which enables the evaluation and visualization of herbicide toxicity for rice. The reflectance spectra variations of rice could reveal the stress status of herbicide toxicity in rice along with the physiological parameters. The visualization of the herbicide toxicity in rice would help to provide the intuitive vision of herbicide toxicity in rice. A monitoring system for detecting herbicide toxicity and its alleviation by SA will benefit from the remarkable success of SVC models and distribution maps.

Manganese (Mn) is an essential nutrient in most organisms. Establishing an effective regulatory system of Mn absorption is important for sustainable crop development. In this study, we selected sunflower as the model plant to explore the effects of 5-aminolevulinic acid (ALA) or salicylic acid (SA) combined with citric acid (CA) on Mn absorption. Six-leaf-old sunflower plants were exposed to 0.8 g kg−1 Mn for one week and then treated with chelating agents, i.e., CA (10 mmol kg−1), and different concentrations of ALA and SA for one week. The results showed that Mn-treated plants had significantly increased H2O2, O2− and MDA contents in leaves compared with the control. Under the Mn + CA treatment, ALA or SA2 significantly activated the antioxidant defense system by increasing SOD, POD and CAT activities in leaves. Moreover, the application of CA significantly increased the Mn uptake in sunflower roots compared with Mn treatment alone; however, did not accelerate the translocation efficiency of Mn from sunflower roots to shoots. Moreover, ultrastructural and RT-qPCR results further demonstrated that ALA/SA could recover the adverse impact of excessive Mn accumulation in sunflowers. Like a pump, ALA/SA regulated the translocation efficiency and promoted the transportation of Mn from roots to shoots. This study provides insights into the promotive role of ALA/SA combined with CA on sunflower growth by regulating Mn absorption, which would be beneficial for regulating Mn absorption in soil with an Mn deficit.

Myocardial metastasis of nasopharyngeal carcinoma (NPC) is rarely reported in the literature. Some autopsy studies found metastases in more than 10% of cases with malignant neoplasm. However, patients are often diagnosed during the postmortem because myocardial metastasis is often asymptomatic, and its Cardiac complications tend to be severe and fatal. Patients with Cardiac metastases are often treated with chemotherapy or surgical intervention, although the prognosis is poor. Immunotherapy with anti-programmed cell death receptor-1 or ligand-1 (PD-1 or PD-L1) inhibitors has recently been reported to be therapeutically significant in multiple cancers, including melanoma, nonsmall cell lung cancer, and NPC, but the treatment of myocardial metastasis of NPC has not been reported. This study described the case of a 50-year-old male patient who presented initially with NPC and received radiotherapy as first-line therapy. For 20 years, he had recurrent Cardiac metastasis of NPC. The pathological examination suggested tPD-L1 expression. Therefore, off-label sintilimab (200 mg every 21 days) was administered. After 10 cycles of treatment, myocardial metastasis shrank and the enlarged mediastinal lymph nodes disappeared. This case report demonstrated that Cardiac metastasis of NPC expressing PD-L1 might have a sustained response to PD-L1 inhibitor–directed therapy.

Cereals and pulses are consumed as a staple food in low-income countries for the fulfillment of daily dietary requirements and as a source of micronutrients. However, they are failing to offer balanced nutrition due to deficiencies of some essential compounds, macronutrients, and micronutrients, i.e., cereals are deficient in iron, zinc, some essential amino acids, and quality proteins. Meanwhile, the pulses are rich in anti-nutrient compounds that restrict the bioavailability of micronutrients. As a result, the population is suffering from malnutrition and resultantly different diseases, i.e., anemia, beriberi, pellagra, night blindness, rickets, and scurvy are common in the society. These facts highlight the need for the biofortification of cereals and pulses for the provision of balanced diets to masses and reduction of malnutrition. Biofortification of crops may be achieved through conventional approaches or new breeding techniques (NBTs). Conventional approaches for biofortification cover mineral fertilization through foliar or soil application, microbe-mediated enhanced uptake of nutrients, and conventional crossing of plants to obtain the desired combination of genes for balanced nutrient uptake and bioavailability. Whereas, NBTs rely on gene silencing, gene editing, overexpression, and gene transfer from other species for the acquisition of balanced nutritional profiles in mutant plants. Thus, we have highlighted the significance of conventional and NBTs for the biofortification of cereals and pulses. Current and future perspectives and opportunities are also discussed. Further, the regulatory aspects of newly developed biofortified transgenic and/or non-transgenic crop varieties via NBTs are also presented.

Allopolyploids play an essential role in plant evolution and confer apparent advantages on crop growth and breeding compared to low ploidy levels. A doubled haploid (DH) population derived from the cross between two artificially synthesized allohexaploid Brassica was created and self-crossed continuously. Morphological and yield-related traits showed considerable variation among different generations, different families and even within the same families. However, the flowering time, pollen viability and seed yield increased gradually during the selfing process. Ploidy level estimation and karyotyping analysis revealed that this population was chimeras with varied chromosome numbers within an identical plant. Chromosome translocations analysis showed that the B genome was more instable compared to the A and C genomes. The A genome was more prone to chromosome recombination than the C genome. Although some genomic regions were more likely to be duplicated, deleted, or rearranged, a consensus pattern was not shared between different progenies. This research deepened our understanding of the genetic variation of artificially synthesized allohexaploid Brassica. In addition, the allohexaploid Brassica can be used as a bridge to transfer some of the valuable traits blocked by reproductive barriers from wild Brassica species to cultivated species such as cold and drought resistance, etc.

Abstract Background The ubiquitous signaling molecule melatonin (N-acetyl-5-methoxytryptamine) (MT) plays vital roles in plant development and stress tolerance. Selenium (Se) may be phytotoxic at high concentrations. Interactions between MT and Se (IV) stress in higher plants are poorly understood. The aim of this study was to evaluate the defensive roles of exogenous MT (0 μM, 50 μM, and 100 μM) against Se (IV) (0 μM, 50 μM, 100 μM, and 200 μM) stress based on the physiological and biochemical properties, thiol biosynthesis, and antioxidant system of Brassica napus plants subjected to these treatments. Results Se (IV) stress inhibited B. napus growth and biomass accumulation, reduced pigment content, and lowered net photosynthetic rate (P n ) and PSII photochemical efficiency (Fv/Fm) in a dose-dependent manner. All of the aforementioned responses were effectively alleviated by exogenous MT treatment. Exogenous MT mitigated oxidative damage and lipid peroxidation and protected the plasma membranes from Se toxicity by reducing Se-induced reactive oxygen species (ROS) accumulation. MT also alleviated osmotic stress by restoring foliar water and sugar levels. Relative to standalone Se treatment, the combination of MT and Se upregulated the ROS-detoxifying enzymes SOD, APX, GR, and CAT, increased proline, free amino acids, and the thiol components GSH, GSSG, GSH/GSSG, NPTs, PCs, and cys and upregulated the metabolic enzymes γ-ECS, GST, and PCS. Therefore, MT application attenuates Se-induce oxidative damage in plants. MT promotes the accumulation of chelating agents in the roots, detoxifies Se there, and impedes its further translocation to the leaves. Conclusions Exogenous MT improves the physiological traits, antioxidant system, and thiol ligand biosynthesis in B. napus subjected to Se stress primarily by enhancing Se detoxification and sequestration especially at the root level. Our results reveal better understanding of Se-phytotoxicity and Se-stress alleviation by the adequate supply of MT. The mechanisms of MT-induced plant tolerance to Se stress have potential implications in developing novel strategies for safe crop production in Se-rich soils. Graphical abstract

Abstract Background Epidermal growth factor receptor (EGFR) and epidermal growth factor receptor pathway substrate 8 (Eps8) have been widely reported to be expressed in various tumors. Eps8 is an important active kinase substrate of EGFR that directly binds to the juxtamembrane (JXM) domain of EGFR to form an EGFR/Eps8 complex. The EGFR/Eps8 complex is involved in regulating cancer progression and might be an ideal target for antitumor therapy. This study focused on the screening of small-molecule inhibitors that target the EGFR/Eps8 complex in breast cancer and non-small cell lung cancer (NSCLC). Methods In silico virtual screening was used to identify small-molecule EGFR/Eps8 complex inhibitors. These compounds were screened for the inhibition of A549 and BT549 cell viability. The direct interaction between EGFR and Eps8 was measured using coimmunoprecipitation (CoIP) and JXM domain replacement assays. The antitumor effects of the inhibitors were analyzed in cancer cells and xenograft models. An acute toxicity study of EE02 was performed in a mouse model. In addition, the effect of the EE02 inhibitor on the protein expression of elements downstream of the EGFR/Eps8 complex was determined by western blotting and protein chip assays. Results In this study of nearly 390,000 compounds screened by virtual database screening, the top 29 compounds were identified as candidate small-molecule EGFR/Eps8 complex inhibitors and evaluated by using cell-based assays. The compound EE02 was identified as the best match to our selection criteria. Further investigation demonstrated that EE02 directly bound to the JXM domain of EGFR and disrupted EGFR/Eps8 complex formation. EE02 selectively suppressed growth and induced apoptosis in EGFR-positive and Eps8-positive breast cancer and NSCLC cells. More importantly, the PI3K/Akt/mTOR and MAPK/Erk pathways downstream of the EGFR/Eps8 complex were suppressed by EE02. In addition, the suppressive effect of EE02 on tumor growth in vivo was comparable to that of erlotinib at the same dose. Conclusions We identified EE02 as an EGFR/Eps8 complex inhibitor that demonstrated promising antitumor effects in breast cancer and NSCLC. Our data suggest that the EGFR/Eps8 complex offers a novel cancer drug target.

Chromium (Cr) is an important environmental constraint effecting crop productivity. Spermine (SPM) is a polyamine compound regulating plant responses to abiotic stresses. However, SPM-mediated tolerance mechanisms against Cr stress are less commonly explored in plants. Thus, current research was conducted to explore the protective mechanisms of SPM (0.01 mM) against Cr (100 µM) toxicity in two rice cultivars, CY927 (sensitive) and YLY689 (tolerant) at the seedling stage. Our results revealed that, alone, Cr exposure significantly reduced seed germination, biomass and photosynthetic related parameters, caused nutrient and hormonal imbalance, desynchronized antioxidant enzymes, and triggered oxidative damage by over-accretion of reactive oxygen species (ROS), malondialdehyde (MDA) and electrolyte leakage in both rice varieties, with greater impairments in CY927 than YLY689. However, seed priming with SPM notably improved or reversed the above-mentioned parameters, especially in YLY689. Besides, SPM stimulated the stress-responsive genes of endogenous phytohormones, especially salicylic acid (SA), as confirmed by the pronounced transcript levels of SA-related genes (OsPR1, OsPR2 and OsNPR1). Our findings specified that SPM enhanced rice tolerance against Cr toxicity via decreasing accumulation of Cr and markers of oxidative damage (H2O2, O2•− and MDA), improving antioxidant defense enzymes, photosynthetic apparatus, nutrients and phytohormone balance.

Emerging evidence suggests bright prospects of some natural antioxidants in the treatment of osteoporosis. 6′-O-Galloylpaeoniflorin (GPF), an antioxidant isolated from peony roots (one of very widely used Oriental medicines, with various anti-inflammatory, antitumor, and antioxidant activities), shows a series of potential clinical applications. However, its effects on osteoporosis remain poorly investigated. The current study aimed to explore whether GPF can attenuate osteoclastogenesis and relieve ovariectomy-induced osteoporosis via attenuating reactive oxygen species (ROS), and investigate the possible mechanism. After the culture of primary murine bone marrow-derived macrophages/monocytes were induced by the use of macrophage colony-stimulating factor (M-CSF) and the receptor activator of NF-κB ligand (RANKL) and then treated with GPF. Cell proliferation and viability were assessed by Cell Counting Kit-8 (CCK-8) assay. Thereafter, the role of GPF in the production of osteoclasts and the osteogenic resorption of mature osteoclasts were evaluated by tartrate-resistant acid phosphatase (TRAP) staining, podosome belt formation, and resorption pit assay. Western blotting and qRT-PCR examination were performed to evaluate proteins’ generation and osteoclast-specific gene levels, respectively. The ROS generation in cells was measured in vitro by 2′,7′-Dichlorodi-hydrofluorescein diacetate (DCFH-DA). Ovariectomy-induced osteoporosis mouse administered with GPF or vehicle was performed to explore the in vivo potential of GPF, then a micro-CT scan was performed in combination with histological examination for further analysis. GPF suppressed the formation of osteoclasts and podosome belts, as well as bone resorption when induced by RANKL through affecting intracellular ROS activity, MAPKs signaling pathway, and subsequent NFATc1 translocation and expression, as well as osteoclast-specific gene expression in vitro. In vivo study suggested that exposure to GPF prevented osteoporosis-related bone loss in the ovariectomized mice. These findings indicate that GPF attenuates osteoclastogenesis and relieves ovariectomy-induced osteoporosis by inhibiting ROS and MAPKs/c-Fos/NFATc1 signaling pathway. This suggested that GPF may be potentially used to treat bone diseases like periodontitis, rheumatoid arthritis, and osteoporosis associated with osteoclasts.

Cereals are the major contributors to global food supply, accounting for more than half of the total human calorie requirements. Sustainable availability of quality cereal grains is an important step to address the high-priority issue of food security. High concentrations of heavy metals specifically lead (Pb) in the soil negatively affect biochemical and physiological processes regulating grain quality in cereals. The dietary intake of Pb more than desirable quantity via food chain is a major concern for humans, as it can predispose individuals to chronic health issues. In plant systems, high Pb concentrations can disrupt several key metabolic processes such as electron transport chain, cellular organelles integrity, membrane stability index, PSII connectivity, mineral metabolism, oxygen-evolving complex, and enzymatic activity. Plant growth-promoting rhizobacteria (PGPR) has been recommended as an inexpensive strategy for remediating Pb-contaminated soils. A diverse group of Ascomycetes fungi, i.e., dark septate endophytes is successfully used for this purpose. A symbiotic relationship between endophytes and host cereal induces Pb tolerance by immobilizing Pb ions. Molecular and cellular modifications in plants under Pb-stressed environments are explained by transcription factor families such as bZIP, ERF, and GARP as a regulator. The role of metal tolerance protein (MTP), natural resistance-associated macrophage protein (NRAMP), and heavy metal ATPase in decreasing Pb toxicity is well known. In the present review, we provided the contemporary synthesis of existing data regarding the effects of Pb toxicity on morpho-physiological and biochemical responses of major cereal crops. We also highlighted the mechanism/s of Pb uptake and translocation in plants, critically discussed the possible management strategies and way forward to overcome the menace of Pb toxicity in cereals.

Arsenic (As) a non-essential element is of particular concern with respect to harmful effects on plant metabolism. While extensive studies have been conducted on the physiological responses of plants to increase As concentrations, however, molecular differences elucidating species-specific changes remain largely unknown. In the present experiment, two oilseed Brassica napus (B. napus) cultivars, ZS758 and ZD622, were treated by elevated As concentration. Their responses to the As stress have been investigated through pulse amplitude modulated fluorometer and isobaric tags based proteomic (iTRAQ) analysis. The chlorophyll fluorescence attributes showed that As stress significantly decrease the photochemical efficiency of photosystem II (PSII) and photosystem I (PSI) as well as the comparatively closed stomata observed under scanning electron microscopy (SEM). In this study, 65 proteins displayed increased abundance and 52 down-regulated were found in the control vs As comparison in cultivar ZS758, while 44 up and 67 down-regulated proteins were found in the control vs As comparison in ZD622. Metabolic pathways, followed by ribosome and biosynthesis of secondary metabolites were the dominant functional annotation categories among the differentially expressed protein (DEPs). Many genes involved in primary metabolism, stress and defense were found to be As-responsive DEPs and/or DEPs between these two cultivars. Based on these results, a schematic description of key processes involved in As tolerance in ZS758 and ZD622 is proposed, which suggests that higher tolerance in ZS758 depends on a multilevel coordination of efficient defense and energy metabolism. Real-time quantitative PCR supported the expression patterns of several genes encoding a protein similar to their corresponding DEPs. In addition, these findings could shed light in unraveling the molecular mechanisms of B. napus exposed to As stress and provide or improve essential understandings in the development of advanced B. napus cultivars against As resistance.

BackgroundThe administration of second- or third-generation anti-CD19 chimeric antigen receptor (CAR) T cells has remarkably improved the survival of patients with relapsed or refractory B cell malignancies. However, there are limited clinical results from fourth-generation CAR-T cell therapy, and the factors affecting response rate and survival have not been fully determined.MethodsLymphoma patients with progression or relapse after intensive treatments, including hematopoietic stem cell transplantation, and life expectancy >2 months were enrolled in the study. Peripheral lymphocytes were collected through apheresis, and magnetically selected T cells were lentivirally transduced with a 4th-generation CAR featuring an anti-CD19 CAR and the iCasp9 suicide switch (4SCAR19). The patients received 4SCAR19 T cell infusion after approximately seven days of expansion and a conditioning regimen comprising cyclophosphamide/fludarabine. The efficacy, safety, and risk factors were evaluated.ResultsA total of 21 patients with relapsed/refractory B cell non-Hodgkin lymphoma were enrolled and received 4SCAR19 T cell infusions at a median dose of 8.9×105 CAR-T cells/kg. The overall response rate was 67% [95% confidence interval (CI), 43 to 85], with 43% of patients achieving a complete response and 24% having a partial response. The overall and complete response rates were 58 and 33% in the diffuse large B-cell lymphoma (DLBCL) group and 78 and 56% in the non-DLBCL group, respectively. The median overall survival was 23.8 months (95% CI, not reached), with a median follow-up of 13.7 months. Factors affecting overall survival were International Prognostic Index (IPI), disease type, and remission status after CAR-T cell treatment. The most common adverse events of grade 3 or 4 during treatment were neutropenia (76%), leukopenia (71%), and thrombocytopenia (29%). The incidence of cytokine release syndrome (CRS) was 14%, and all cases were grade 1. One patient developed grade 3 neurotoxicity. No deaths were attributed to infusion of 4SCAR19 T cells, CRS, or neurotoxicity.ConclusionsIn this study, patients with relapsed or refractory B cell non-Hodgkin’s lymphoma who received 4SCAR19 T cell therapy had durable responses and few of adverse events. The IPI model is suitable for evaluating the prognosis of patients receiving CAR-T cell therapy.Trial registrationChinese Clinical Trial Registry (http://www.chictr.org.cn): ChiCTR-OOC-16007779.

Tolerance to metribuzin, a broad-spectrum herbicide, is an important trait for weed control in wheat breeding. However, the genetics of metribuzin tolerance in relation to the underlying quantitative trait loci (QTL) and genes is limited. This study developed F8 recombinant inbred lines (RILs) from a cross between a highly resistant genotype (Chuan Mai 25) and highly susceptible genotype (Ritchie), which were used for QTL mapping of metribuzin tolerance. Genotyping was done using a diversity arrays technology sequencing (DArTseq) platform, and phenotyping was done in controlled environments. Herbicide tolerance was measured using three traits, visual score (VS), reduction of chlorophyll content (RCC), and mean value of chlorophyll content for metribuzin-treated plants (MCC). A high-density genetic linkage map was constructed using 2,129 DArTseq markers. Inclusive composite interval mapping (ICIM) identified seven QTL, one each on chromosomes 2A, 2D, 3A, 3B, 4A, 5A, and 6A. Three major QTL—Qrcc.uwa.2AS, Qrcc.uwa.5AL, and Qrcc.uwa.6AL—explained 11.39%, 11.06%, and 11.45% of the phenotypic variation, respectively. The 5A QTL was further validated using kompetitive allele-specific PCR (KASP) assays in an F3 validation population developed from Chuan Mai 25 × Dagger. Blasting the single-nucleotide polymorphisms (SNPs) flanking the QTL in the wheat reference genome RefV1.0 revealed SNP markers within or very close to annotated genes which could be candidate genes responsible for metribuzin tolerance. Most of the candidate genes were related to metabolic detoxification, especially those of P450 pathway and xenobiotic transmembrane transporter activity, which are reportedly key molecules responsible for herbicide tolerance. This study is the first to use specially developed populations to conduct QTL mapping on the metribuzin tolerance trait. The three major QTL and candidate genes identified in this study could facilitate marker-assisted metribuzin breeding in wheat. The QTL could be fine-mapped to locate the genes responsible for metribuzin tolerance, which could be introgressed into elite wheat cultivars.

Background: Neonatal hypofibrinogenemia is often asymptomatic but can manifest as hemorrhage.Objective: This study was conducted to characterize clinical characteristics of neonates with hypofibrinogenemia and identify factors associated with hemorrhage.Methods: This was a retrospective study of neonates with plasma fibrinogen level (FIB) ≤1.0 g/L who were hospitalized at the Neonatology Department, People's Hospital, Chongqing, China, from January 2012 to December 2017. Based on severity, patients were grouped into severe, moderate, and mild hypofibrinogenemia (FIB < 0.5 g/L, 0.5 g/L ≤ FIB < 0.7 g/L, and 0.7 g/L ≤ FIB ≤ 1.0 g/L, respectively). Clinical characteristics associated with hemorrhage were analyzed.Results: Among 330 neonates, 52.7% showed mild hypofibrinogenemia, 25.5% had moderate hypofibrinogenemia, and 21.8% had severe hypofibrinogenemia. Severe hypofibrinogenemia was not associated with gestational age, but the mild form was frequent in neonates with low/normal birthweight (P = 0.018). Approximately 80.6% of neonates presented hypofibrinogenemia as variable combinations of thrombocytopenia or coagulopathies. Hemorrhage occurred in 38.8% of the cases, 60.9% of which were mild. Hemorrhage manifested as puncture site bleeding (47.7%) or spontaneous skin/mucous membrane bleeding (34.2%). The degree of hypofibrinogenemia was not associated with the severity or occurrence of hemorrhage. Among patients with hypofibrinogenemia and bleeding, 53.4% of the cases with coagulopathies showed mild hemorrhage, 85.7% of the cases with thrombocytopenia had moderate bleeding, while 53.8% of the cases with coagulopathy and thrombocytopenia showed severe hemorrhage.Conclusion: Neonatal hypofibrinogenemia is often comorbid and occurs with thrombocytopenia and/or coagulopathies. Although hemorrhage is not associated with the degree of hypofibrinogenemia, it may be severe when hypofibrinogenemia co-occurs with coagulopathies and/or thrombocytopenia.

With the advantages of intrinsic safety, low price, high output potential, and acceptable energy density, aqueous rechargeable Zn–MnO2 batteries are gradually emerging as promising energy storage devices in recent years. Unfortunately, the structural instability and poor electrical conductivity of manganese dioxides still hinder their further applications. To tackle these issues, we demonstrate a high-performance cathode material for Zn–MnO2 batteries by hybridizing lignin-derived porous carbon with δ-MnO2 (denoted as LPC/δ-MnO2). Benefiting from the high electrical conductivity of porous carbon, the LPC/δ-MnO2 cathode material can offer high discharge capacity of 332.3 mAh g–1 at 0.2 A g–1 and excellent high-rate capability (196.1 mAh g–1 at 5 A g–1). Meanwhile, the assembled Zn–MnO2 battery displays good long-term cycling stability (82% capacity retention after 1000 cycles). Such superior performances are attributed to the synergetic effect of nanostructured δ-MnO2 and porous carbon scaffold, which is in favor of rapid Zn2+ ion diffusion and large contribution ratio of pseudocapacitive Zn2+ ion intercalation. The results of this study show great prospects of hybridizing biomass-derived carbon framework with electrochemically active materials toward advanced energy storage materials.

It remains a great challenge for aqueous zinc-ion batteries to work at subzero temperatures, since the water in aqueous electrolytes would freeze and inhibit the transportation of electrolyte ions, inevitably leading to performance deterioration. In this work, we propose an anti-freezing gel electrolyte that contains polyacrylamide, graphene oxide, and ethylene glycol. The graphene oxide can not only enhance the mechanical properties of gel electrolyte but also help construct a three-dimensional macroporous network that facilitates ionic transport, while the ethylene glycol can improve freezing resistance. Due to the synergistic effect, the gel electrolyte exhibits high ionic conductivity (e.g., 14.9 mS cm−1 at −20 °C) and good mechanical properties in comparison with neat polyacrylamide gel electrolyte. Benefiting from that, the assembled flexible quasi-solid-state Zn-MnO2 battery exhibits good electrochemical durability and superior tolerance to extreme working conditions. This work provides new perspectives to develop flexible electrochemical energy storage devices with great environmental adaptability.

Crops frequently encounter abiotic stresses, and salinity is a prime factor that suppresses plant growth and crop productivity, globally. Ursolic acid (UA) is a potential signaling molecule that alters physiology and biochemical processes and activates the defense mechanism in numerous animal models; however, effects of UA in plants under stress conditions and the underlying mechanism of stress alleviation have not been explored yet. This study examined the effects of foliar application of UA (100 μM) to mitigate salt stress in three rice cultivars (HZ, 712, and HAY). A pot experiment was conducted in a climate-controlled greenhouse with different salt stress treatments. The results indicated that exposure to NaCl-induced salinity reduces growth of rice cultivars by damaging chlorophyll pigment and chloroplast, particularly at a higher stress level. Application of UA alleviated adverse effects of salinity by suppressing oxidative stress (H2O2, O2–) and stimulating activities of enzymatic and non-enzymatic antioxidants (APX, CAT, POD, GR, GSH, AsA, proline, glycinebutane), as well as protecting cell membrane integrity (MDA, LOX, EL). Furthermore, UA application brought about a significant increase in the concentration of leaf nitric oxide (NO) by modulating the expression of NR and NOS enzymes. It seems that UA application also influenced Na+ efflux and maintained a lower cytosolic Na+/K+ ratio via concomitant upregulation of OsSOS1 and OsHKT1;5 in rice cultivars. The results of pharmacological tests have shown that supply of the NO scavenger (PTI) completely reversed the UA-induced salt tolerance in rice cultivars by quenching endogenous NO and triggering oxidative stress, Na+ uptake, and lipid peroxidation. The PTI application with UA and sodium nitroprusside (SNP) also caused growth retardation and a significant increase in Na+ uptake and oxidative stress in rice cultivars. This suggests that UA promoted salt tolerance of rice cultivars by triggering NO production and limiting toxic ion and reactive oxygen species (ROS) accumulation. These results revealed that both UA and NO are together required to develop a salt tolerance response in rice.

OBJECTIVE:To determine whether the coexistence of carotid atherosclerosis plaque affects the neurological function of cerebral infarction. METHODS:A total of 1078 patients with acute cerebral infarction were enrolled, all patients were divided into carotid plaque group (n = 702) and non-carotid plaque group (n = 376). Meanwhile, all patients were divided into mild group (n = 624) and moderate to severe group (n = 454). The difference of the incidence of carotid plaque between the mild and moderate to severe group was analyzed. RESULTS:In the 1078 patients with cerebral infarction, the NIHSS score in the carotid plaque group was significantly higher than that in the non-carotid plaque group (P