Developing a tactical irrigation and nitrogen fertilizer management strategy for winter wheat through drip irrigation.

Introduction: Agricultural activities in the North China Plain are often challenged by inadequate irrigation and nutrient supply. Inadequate and improper resource utilization may impose negative impacts on agricultural sustainability. To counteract the negative impacts, a deeper understanding of the different resource management strategies is an essential prerequisite to assess the resource saving potential of crops. Methods: We explored plausible adaptation strategies including drip irrigation lateral spacings of 40 and 80 cm (hereafter referred to as LS40 and LS80, respectively), irrigating winter wheat after soil water consumption of 20 and 35 mm (hereafter represented as IS20 and IS35, respectively), and nitrogen fertilization scheme of a) applying 50% nitrogen as a basal dose and 50% as a top-dressing dose (NS50:50), b) 25% nitrogen as a basal dose and 75% as a topdressing dose (NS25:75), and c) no nitrogen application as a basal dose and 100% application as a top-dressing dose (NS0:100). Results and discussion: The consecutive 2 years (2017-2018 and 2018-2019) of field study results show that growing winter wheat under LS40 enhanced the water use efficiency (WUE), grain yield, 1,000-grain weight, and number of grains per spike by 15.04%, 6.95%, 5.67%, and 21.59% during the 2017-2018 season, respectively. Additionally, the corresponding values during the 2018-2019 season were 12.70%, 7.17%, 2.66%, and 19.25%, respectively. Irrigation scheduling of IS35 treatment improved all the growth-related and yield parameters of winter wheat. Further, treating 25% nitrogen as a basal dose and application of 75% as a top-dressing dose positively influenced the winter wheat yield. While NS0:100 increased the plant height, leaf area index (LAI), and aboveground biomass as compared to the other application strategies, but high nitrogen was observed in deeper soil layers. Regarding soil environment, the lowest soil moisture and nitrate nitrogen contents were observed in LS80 during both growing seasons. Overall, coupling the IS35 with NS25:75 under 40-cm lateral spacing is a suitable choice for sustainable winter wheat production in theNorth China Plain. The results of our study may be helpful in advancing the knowledge of the farmer community for winter wheat production. The findings can also aid in advancing new insights among scientists working on soil water and nitrogen distribution in drip irrigation for better productivity.

Corrigendum: Retrieving rice (Oryza sativa L.) net photosynthetic rate from UAV multispectral images based on machine learning methods.

[This corrects the article DOI: 10.3389/fpls.2022.1088499.].

Metformin attenuates fibroblast activation during pulmonary fibrosis by targeting S100A4 via AMPK-STAT3 axis.

Fibroblasts activation is a crucial process for development of fibrosis during idiopathic pulmonary fibrosis pathogenesis, and transforming growth factor (TGF)-ß1 plays a key regulatory role in fibroblast activation. It has been reported that metformin (MET) alleviated bleomycin (BLM)-induced pulmonary fibrosis (PF) by regulating TGF-ß1-induced fibroblasts activation, but the underlying mechanisms still deserve further investigations. In this study, MET blocked α-smooth muscle actin (α-SMA) accumulation in vivo accompanied with S100A4 expression and STAT3 phosphorylation inhibition, resulting in attenuating the progression of lung fibrosis after BLM administration. We determined that S100A4 plays critical roles in fibroblasts activation in vitro, evidenced by siRNA knockdown of S100A4 expression downregulated TGF-ß1 induced α-SMA production in Human fetal lung fibroblast (HFL1) cells. Importantly, we found for the first time that the expression of S100A4 in fibroblasts was regulated by STAT3. Stattic, an effective small molecule inhibitor of STAT3 phosphorylation, reduced S100A4 level in TGF-ß1- treated HFL1 cells accompanied with less α-SMA production. We further found that MET, which inhibits STAT3 phosphorylation by AMPK activation, also inhibits fibroblasts activation by targeting S100A4 in vitro. Together all these results, we conclude that S100A4 contributes to TGF-ß1- induced pro-fibrogenic function in fibroblasts activation, and MET was able to protect against TGF-ß1-induced fibroblasts activation and BLM-induced PF by down-regulating S100A4 expression through AMPK-STAT3 axis. These results provide a useful clue for a clinical strategy to prevent PF.

Melatonin ameliorates bleomycin-induced pulmonary fibrosis via activating NRF2 and inhibiting galectin-3 expression.

Pulmonary fibrosis (PF) is a chronic interstitial lung disease with no effective therapies. Galectin-3 (Gal-3), a marker of oxidative stress, plays a key role in the pathogenesis of PF. Fibroblast-myofibroblast differentiation (FMD) is an important source of fibrotic cells in PF. Previous studies showed that melatonin (MT) exerted anti-fibrotic effect in many diseases including PF through its antioxidant activity. In the present study we investigated the relationships among Gal-3, NRF2, ROS in FMD and their regulation by MT. We established an in vitro model of FMD in TGF-ß1-treated human fetal lung fibroblast1 (HFL1) cells and a PF mouse model via bleomycin (BLM) intratracheal instillation. We found that Gal-3 expression was significantly increased both in vitro and in vivo. Knockdown of Gal-3 in HFL1 cells markedly attenuated TGF-ß1-induced FMD process and ROS accumulation. In TGF-ß1-treated HFL1 cells, pretreatment with NRF2-specific inhibitor ML385 (5 µM) significantly increased the levels of Gal-3, α-SMA and ROS, suggesting that the expression of Gal-3 was regulated by NRF2. Treatment with NRF2-activator MT (250 µM) blocked α-SMA and ROS accumulation accompanied by reduced Gal-3 expression. In BLM-induced PF model, administration of MT (5 mg·kg-1·d-1, ip for 14 or 28 days) significantly attenuated the progression of lung fibrosis through up-regulating NRF2 and down-regulating Gal-3 expression in lung tissues. These results suggest that Gal-3 regulates TGF-ß1-induced pro-fibrogenic responses and ROS production in FMD, and MT activates NRF2 to block FMD process by down-regulating Gal-3 expression. This study provides a useful clue for a clinical strategy to prevent PF. Graphic abstract of the mechanisms. MT attenuated BLM-induced PF via activating NRF2 and inhibiting Gal-3 expression.

High-resolution crop yield and water productivity dataset generated using random forest and remote sensing.

Accurate and high-resolution crop yield and crop water productivity (CWP) datasets are required to understand and predict spatiotemporal variation in agricultural production capacity; however, datasets for maize and wheat, two key staple dryland crops in China, are currently lacking. In this study, we generated and evaluated a long-term data series, at 1-km resolution of crop yield and CWP for maize and wheat across China, based on the multiple remotely sensed indicators and random forest algorithm. Results showed that MOD16 products are an accurate alternative to eddy covariance flux tower data to describe crop evapotranspiration (maize and wheat RMSE: 4.42 and 3.81 mm/8d, respectively) and the proposed yield estimation model showed accuracy at local (maize and wheat rRMSE: 26.81 and 21.80%, respectively) and regional (maize and wheat rRMSE: 15.36 and 17.17%, respectively) scales. Our analyses, which showed spatiotemporal patterns of maize and wheat yields and CWP across China, can be used to optimize agricultural production strategies in the context of maintaining food security.

Dang Gui Bu Xue Tang, a conventional Chinese herb decoction, ameliorates radiation-induced heart disease via Nrf2/HMGB1 pathway.

Introduction: Radiation-induced heart disease (RIHD), characterized by cardiac dysfunction and myocardial fibrosis, is one of the most common complications after cardiothoracic radiotherapy. Dang Gui Bu Xue Tang (DBT) is a conventional Chinese herb decoction composed of Radix Astragali membranaceus (RAM) and Radix Angelicae sinensis (RAS) at a ratio of 5:1, famous for its "blood-nourishing" effect. In this study, we aimed to investigate the cardioprotective effect of DBT on RIHD. Methods: C57BL mice at 8 weeks of age were divided into five groups, namely Control, Radiation, RDBT51 (Radiation with DBT, RAM:RAS = 5:1), RDBT11 (Radiation with DBT, RAM:RAS = 1:1), and RDBT15 (Radiation with DBT, RAM:RAS = 1:5). Results: We mainly found that radiation in the cardiothoracic region led to significant left ventricular systolic dysfunction, myocardial fibrotic lesions and cardiac injury accompanied by abnormally increased myocardial HMGB1 protein levels. Administration of conventional DBT significantly ameliorated left ventricular systolic dysfunction, alleviated myocardial fibrosis, and counteracted cardiac injury, all of which supported the protective effect of DBT on RIHD, involving upregulation of myocardial Nrf2 protein levels and downregulation of HMGB1 protein levels as underlying mechanisms. Conclusions: DBT exerts a significant protective effect on RIHD, and the Nrf2/ HMGB1 pathway probably plays an important role in this protective effect.

Retrieving rice (Oryza sativa L.) net photosynthetic rate from UAV multispectral images based on machine learning methods.

Photosynthesis is the key physiological activity in the process of crop growth and plays an irreplaceable role in carbon assimilation and yield formation. This study extracted rice (Oryza sativa L.) canopy reflectance based on the UAV multispectral images and analyzed the correlation between 25 vegetation indices (VIs), three textural indices (TIs), and net photosynthetic rate (Pn) at different growth stages. Linear regression (LR), support vector regression (SVR), gradient boosting decision tree (GBDT), random forest (RF), and multilayer perceptron neural network (MLP) models were employed for Pn estimation, and the modeling accuracy was compared under the input condition of VIs, VIs combined with TIs, and fusion of VIs and TIs with plant height (PH) and SPAD. The results showed that VIs and TIs generally had the relatively best correlation with Pn at the jointing-booting stage and the number of VIs with significant correlation (p< 0.05) was the largest. Therefore, the employed models could achieve the highest overall accuracy [coefficient of determination (R 2) of 0.383-0.938]. However, as the growth stage progressed, the correlation gradually weakened and resulted in accuracy decrease (R 2 of 0.258-0.928 and 0.125-0.863 at the heading-flowering and ripening stages, respectively). Among the tested models, GBDT and RF models could attain the best performance based on only VIs input (with R 2 ranging from 0.863 to 0.938 and from 0.815 to 0.872, respectively). Furthermore, the fusion input of VIs, TIs with PH, and SPAD could more effectively improve the model accuracy (R 2 increased by 0.049-0.249, 0.063-0.470, and 0.113-0.471, respectively, for three growth stages) compared with the input combination of VIs and TIs (R 2 increased by 0.015-0.090, 0.001-0.139, and 0.023-0.114). Therefore, the GBDT and RF model with fused input could be highly recommended for rice Pn estimation and the methods could also provide reference for Pn monitoring and further yield prediction at field scale.

Progranulin as a Potential Therapeutic Target in Immune-Mediated Diseases.

Progranulin (PGRN), a secretory glycoprotein consisting of 593 amino acid residues, is a key actor and regulator of multiple system functions such as innate immune response and inflammation, as well as tissue regeneration. Recently, there is emerging evidence that PGRN is protective in the development of a variety of immune-mediated diseases, including rheumatoid arthritis (RA), inflammatory bowel disease (IBD), type 1 diabetes mellitus (T1DM) and multiple sclerosis (MS) by regulating signaling pathways known to be critical for immunology, particularly the tumor necrosis factor alpha/TNF receptor (TNF-α/TNFR) signaling pathway. Whereas, the role of PGRN in psoriasis, systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) is controversial. This review summarizes the immunological functions of PGRN and its role in the pathogenesis of several immune-mediated diseases, in order to provide new ideas for developing therapeutic strategies for these diseases.

Estimating leaf area index using unmanned aerial vehicle data: shallow vs. deep machine learning algorithms.

Measuring leaf area index (LAI) is essential for evaluating crop growth and estimating yield, thereby facilitating high-throughput phenotyping of maize (Zea mays). LAI estimation models use multi-source data from unmanned aerial vehicles (UAVs), but using multimodal data to estimate maize LAI, and the effect of tassels and soil background, remain understudied. Our research aims to (1) determine how multimodal data contribute to LAI and propose a framework for estimating LAI based on remote-sensing data, (2) evaluate the robustness and adaptability of an LAI estimation model that uses multimodal data fusion and deep neural networks (DNNs) in single- and whole growth stages, and (3) explore how soil background and maize tasseling affect LAI estimation. To construct multimodal datasets, our UAV collected red-green-blue, multispectral, and thermal infrared images. We then developed partial least square regression (PLSR), support vector regression, and random forest regression models to estimate LAI. We also developed a deep learning model with three hidden layers. This multimodal data structure accurately estimated maize LAI. The DNN model provided the best estimate (coefficient of determination [R2] = 0.89, relative root mean square error [rRMSE] = 12.92%) for a single growth period, and the PLSR model provided the best estimate (R2 = 0.70, rRMSE = 12.78%) for a whole growth period. Tassels reduced the accuracy of LAI estimation, but the soil background provided additional image feature information, improving accuracy. These results indicate that multimodal data fusion using low-cost UAVs and DNNs can accurately and reliably estimate LAI for crops, which is valuable for high-throughput phenotyping and high-spatial precision farmland management.

Activated AMPK by metformin protects against fibroblast proliferation during pulmonary fibrosis by suppressing FOXM1.

Pulmonary fibrosis (PF) is a progressive and devastating lung disease of unknown etiology, excessive fibroblast proliferation serves as a key event to promote PF. Transcription factor forkhead box M1 (FOXM1) is not only a well-known proto-oncogene, but also an essential driver of cell proliferation. Recently, 5'-AMP-activated protein kinase (AMPK) is reported to reduce the incidence of PF. However, it remains elusive whether have an underlying relationship between AMPK and FOXM1 in fibroblast proliferation-mediated PF. Here, the progression of lung fibroblast proliferation and the expression levels of AMPK and FOXM1 were observed by intratracheally instilled of bleomycin (BLM) and intraperitoneal injection of metformin in C57BL/6 J mice. Meanwhile, human fetal lung fibroblast1 (HFL1) cells were respectively treated with AMPK activator metformin or AMPK inhibitor Compound C, or FOXM1 depletion by transfected small interfering RNA (siRNA) to unveil roles of AMPK, FOXM1 and the link between them on platelet-derived growth factor (PDGF)-induced fibroblast proliferation. Our results demonstrated that AMPK activated by metformin could down-regulate FOXM1 and alleviate BLM-induced mouse PF model. In vitro, activation of AMPK attenuated PDGF-induced fibroblast proliferation accompanied by the down-regulation of FOXM1. In contrast, inhibition of AMPK enhanced PDGF-induced fibroblast proliferation along with activating FOXM1. These findings suggest that AMPK can ameliorate the progression of fibroblast proliferation during PF via suppressing the expression of FOXM1 and provide new insight into seek PF treatment approaches.

Protective effect of dimethyl itaconate against fibroblast-myofibroblast differentiation during pulmonary fibrosis by inhibiting TXNIP.

Fibroblast-myofibroblast differentiation (FMD) is a critical cellular phenotype during the occurrence and deterioration of pulmonary fibrosis (PF). FMD can increase with an elevated level of reactive oxygen species (ROS) on fibroblasts under oxidative stress. Thioredoxin-interacting protein (TXNIP) is an α-arrestin family protein that regulates the level of intracellular ROS. Nuclear factor erythroid 2-related factor 2 (Nrf2) can protect against FMD in PF. However, the relationship between Nrf2 and TXNIP in FMD remains elusive. Therefore, we established TGF-ß1-induced FMD in vitro and bleomycin (BLM)-induced mouse PF model in vivo to explore whether the activation of Nrf2 can inhibit TXNIP-mediated FMD in PF. Dimethyl itaconate (DMI) was selected to activate Nrf2. Our results showed that TXNIP was elevated and FMD was aggravated in mice lung tissues after BLM administration compared with the saline group. Inversely, Nrf2 decreased TXNIP expression and alleviated FMD in PF. In vitro, TXNIP overexpression enhanced FMD and increased the level of ROS. In contrast, TXNIP deficiency by small interfering RNA (siRNA) attenuated TGF-ß1-induced FMD and reduced ROS. An increase in ROS by H2 O2 can upregulate TXNIP expression. Moreover, Nrf2 also inhibited TGF-ß1-induced FMD and the increase of ROS, with reducing expression of TXNIP, and the inhibitory effect was better than TXNIP siRNA. These results suggest that activation of Nrf2 by DMI can protect against PF via inhibiting TXNIP expression. Our study may provide new therapeutic targets and treatment approaches for PF.

Sodium Houttuyfonate Inhibits Bleomycin Induced Pulmonary Fibrosis in Mice.

Pulmonary fibrosis (PF) could severely disrupt the normal lung architecture and function with fatal consequences. Currently, there is no effective treatment for PF or idiopathic pulmonary fibrosis (IPF). The aim of this study was to investigate the effects of Sodium Houttuyfonate (SH) on bleomycin (BLM) induced PF mice model. Our results indicated that SH could attenuate BLM induced lung injury by reducing the inflammation, fibrogenesis and lung/body weight ratio. The proposed mechanisms for the protective effects of SH include: 1) improvement of pulmonary function in BLM mice, for instance, it can elevate the vital capacity (VC), increase the forced expiratory flow at 50% of forced vital capacity (FEF50) and improve other pulmonary function indices; 2) inhibition of collagen formation in BLM mice; 3) attenuation of the elevation of inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α), which are triggered by BLM administration; 4) reduction of the mRNA level and protein production of transforming growth factor-ß1 (TGF-ß1) in BLM mice. Furthermore, it was found that the protective effects of SH against BLM induced PF in mice was comparable to that of prednisone acetate (PA) tablets, a widely used drug for immunological diseases. Although Houttuynia Cordata Thunb has been widely used in China for lung infection and inflammation, the mechanism has not yet been fully elucidated. Our study provides the evidence that SH is an effective compound against pulmonary injury, irritation and fibrogenesis.

Natural products action on pathogenic cues in autoimmunity: Efficacy in systemic lupus erythematosus and rheumatoid arthritis as compared to classical treatments.

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by self-perpetuating inflammation and tissue/organ damage, resulting from the failure of lymphocyte auto-tolerance, cause morbidity and mortality worldwide. The current drugs or therapies including conventional non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying anti-rheumatic drugs (DMARDs), as well as several biologic therapies such as B cell-targeted, T cell-targeted, cytokines-targeted and cytokines receptors-targeted therapy, cannot completely cure SLE and RA, and are always accompanied by unexpected side effects. Therefore, more studies have explored new methods for therapy and found that the herbal medicine as well as its natural products (NPs) exhibited promising therapeutic value through exerting effects of immunomodulation, anti-inflammation, anti-oxidation, and anti-apoptosis, etc. via regulating abnormal responses in kidney, innate and adaptive immune systems, intestine, synoviocytes, as well as bone system including chondrocytes, osteoclasts, joints and paw tissues. In the present review, we will elucidate the current mainstream drugs and therapies for SLE and RA, and summarize the efficacy and mechanisms of NPs in the treatment of SLE and RA based on available findings including in vitro and in vivo animal models, as well as clinical studies, and further analyze the existing challenges, in order to provide comprehensive evidence for improvement of SLE and RA therapy by NPs and to promote management of these two autoimmune diseases.