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Objectives: We aimed to characterize and investigate the safety and efficacy of Plonmarlimab, a novel anti‐granulocyte‐macrophage colony‐stimulating factor (anti‐GM‐CSF) neutralizing antibody, on the treatment of macrophage activation syndrome (MAS), a life‐threatening systemic inflammatory disease, in pre‐clinical models. Methods: The binding affinity was evaluated using Biacore. The neutralizing activity was measured through the blockade of ligand–receptor interaction, inhibition of STAT5 phosphorylation and suppression of TF‐1 cell proliferation. The efficacy of Plonmarlimab was evaluated in a humanized MAS model, which was established by engrafting human umbilical cord blood (UCB) cells into NOG‐EXL mice. Additionally, the safety profile of Plonmarlimab was investigated in cynomolgus monkeys. Results: At the molecular level, Plonmarlimab showed sub‐nanomolar binding affinity with human GM‐CSF and effectively blocked the binding of GM‐CSF to its receptor. At the cellular level, Plonmarlimab dose‐dependently inhibited intracellular STAT5 phosphorylation and suppressed GM‐CSF‐induced TF‐1 proliferation. In the UCB‐engrafted NOG‐EXL MAS mouse model, Plonmarlimab treatment significantly ameliorated disease progression, demonstrated by the improvements in body weight loss, anaemia and some histopathological features. Furthermore, Plonmarlimab was well tolerated up to 150 mg/kg weekly in monkeys with no reported adverse effects. Conclusions: Plonmarlimab is a highly potent GM‐CSF blocking antibody and has demonstrated promising efficacy in a pre‐clinical MAS model with a favourable safety profile, supporting its clinical development. [ABSTRACT FROM AUTHOR]

In the design and upkeep of canals in areas of seasonal permafrost, resistance to frost heave is a critical factor for ensuring the stability of water conveyance canals. Mechanical modeling is the key to frost heaving‐resistant design. In this study, the theory of elastic thin plates was used to build a mechanical model of frost heaving damage to rectangular canals. The model's plausibility was confirmed using a prototype canal as an example, and the canal's deformation, internal force, and stress distribution were examined. The findings demonstrate that, compared to beam theory, the internal forces and deformations computed by the model are not evenly distributed along the plate width; the base slab and side walls both saw their greatest deformations in the middle portion and two‐fifths from the canal's top, respectively; at the junction of the two, the bending moments and tensile stresses are maximum and distributions are consistent; transverse moments should be used as control moments in the structural design of canals, and stick feet should be placed at junctions to stop damage. In addition, the maximum normal frost heaving force and optimal thickness that four various canals can withstand were estimated, and the results were biased in favor of safety. The calculation's results can serve as a theoretical guide for antifreeze design concrete rectangular canals in places that experience seasonal freezing. [ABSTRACT FROM AUTHOR]

To improve the flame retardancy of 3D‐printed polypropylene (PP) parts, cyclic triphosphonitrile‐based hyperbranched charring agent (DHCCP) was innovatively synthesized and applied in flame‐retardant coatings. Thermogravimetric analysis (TGA) indicated that the residual char rate of DHCCP reached 64.33% at 700°C. When 5 wt% DHCCP was added to the coating, the limiting oxygen index of the composite reached 29.1%, and the vertical combustion (UL‐94) could reach V‐0 rating. In addition, cone calorimetry test measured a 54.10% reduction in peak exothermic rate, and the tensile strength of coated PP was improved. The morphology and chemical composition of the char residues were investigated by scanning electron microscopy, infrared spectroscopy, and laser Raman spectroscopy. After combustion, the coated PP formed a continuous and dense char layer, which could play the role of heat and oxygen insulation and anti‐drip, effectively improving the flame‐retardant of 3D‐printed PP parts. [ABSTRACT FROM AUTHOR]

Aiming at roadway rockbursts induced by near-field dynamic disturbances, this study explored the mechanical response and failure mechanism of anchored roadway surrounding rocks under this condition through the similarity simulation experiment and theoretical modeling analysis. Results show that the greater the disturbance energy is, the stronger mechanical response of surrounding rocks while the faster its attenuation. The starting acceleration amplitude is relatively smaller while the braking acceleration amplitude is larger in the bolt densification area, which has a better self-stabilizing ability. Anchored roadway surrounding rocks exhibit local impact failure characteristics, and the region facing disturbance is most seriously damaged. The bolt-mesh-cable support structure shows the good resistance to low-energy disturbances, while the impact failure is induced with damages inside support structure increasing abruptly under high-energy disturbances. The impact resistance of local surrounding rocks can be improved by bolt densification. Based on the failure criterion, the surrounding rocks only undergo impact failure in the region facing disturbance, while quasi-static failure occurs in remaining regions. The experimental and theoretical research results have been verified through in-situ measurements, which can provide an important reference for the mechanism and prevention of roadway rockburst under near-field dynamic disturbance. [ABSTRACT FROM AUTHOR]

An aluminum diethyl hypophosphite intercalation‐modified montmorillonite flame retardant (AlPi‐MMT) is successfully prepared and characterized by FT‐IR, SEM, and X‐ray diffraction. It is found that thermoplastic polyester elastomer (TPEE) composites incorporating 15 wt% AlPi‐MMT flame retardant exhibited better char formation and flame retardant properties compared to those incorporating 15 wt% (4:1, w:w) AlPi and MMT. And the char residual of TPEE/AlPi‐MMT at 700°C is 16.17%, which is higher than that of TPEE/AlPi‐MMT at 13.94%. and the former can pass UL‐94 V‐0 rating test while the latter can only pass UL‐94 V‐1 rating test. Afterwards, the combustion performance of TPEE composites is characterized, and it is found that the heat release and smoke release of TPEE/AlPi‐MMT are greatly reduced compared with those of pure TPEE and TPEE/AlPi/MMT, which is a flame retardant and smoke suppressant TPEE composite. Finally, by analyzing the residual char morphology and elements of TPEE composites after combustion, the mechanism of the flame retardant AlPi‐MMT to promote char formation and flame retardancy is demonstrated. [ABSTRACT FROM AUTHOR]

Lithium–sulfur batteries (Li–S) are recognized as the next generation of secondary batteries due to their satisfactory theoretical specific capacity and energy density. However, a series of problems such as disordered migration behavior, sluggish redox kinetics, and serious shuttle effect of lithium polysulfides (LiPSs) greatly limit the commercial application. Herein, nanoreactors encapsulate heterostructure to guarantee sulfur conversion in the hosts where the heterostructure consists of FeP with moderate adsorption ability, excellent catalytic active and low work function, and Fe3O4 with strong adsorption ability and high work function. This rational configuration of heterostructure controls the direction of the interface built‐in electric field (BIEF) between catalyst and adsorbent, realizing the successive "trapping‐directional migration‐conversion" reaction mechanism to sulfur species. Thanks to BIEF as a bridge to connect the trapping site and catalytic site, Fe3O4/FeP@C─S cathode delivers an ultrahigh initial specific capacity of 1402 mAh g−1 at 0.1 C and remains more than 450 mAh g−1 at 5 C after 350 cycles. Even with a sulfur loading of 5.20 mg cm−2, it displayed the initial specific capacity of 970 mAh g−1. This work provided an effective strategy to design high‐performance electrocatalysts for commercial Li–S batteries. [ABSTRACT FROM AUTHOR]

The appropriate excavation sequence can improve the overall stability of a foundation pit. In this study, eight schemes were created using FLAC3D to examine the impact of the excavation sequence on a foundation pit by analyzing a deep foundation pit in Nanjing, which had an irregular large rectangle shape. The results show that different excavation sequence schemes and different phases of the foundation pit can change the displacement values and the horizontal displacement type. The min–max normalization method was used to score the schemes in terms of six parameters and confirm the best excavation sequence scheme. In addition, the irregular shape of the foundation pit also leads to local differences in the stability of a foundation pit; the wide end is only slightly longer than the narrow end, but its displacement is significantly higher than that of the narrow end, so attention should be paid to reinforcing the weak parts when carrying out the support. This study can inform the selection of the excavation sequence for actual construction processes. [ABSTRACT FROM AUTHOR]

Background and aims: Liver fibrosis predicts adverse clinical outcomes, such as liver-related death (LRD) and hepatocellular carcinoma (HCC) in patients with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the accuracy of semi-automated quantification of collagen proportionate area (CPA) as an objective new method for predicting clinical outcomes. Method: Liver biopsies from patients with NAFLD underwent computerized image morphometry of Sirius Red staining with CPA quantification performed by ImageScope. Clinical outcomes, including total mortality, LRD, and combined liver outcomes (liver decompensation, HCC, or LRD), were determined by medical records and population-based data-linkage. The accuracy of CPA for predicting outcomes was compared with non-invasive fibrosis tests (Hepascore, FIB-4, APRI). Results: A total of 295 patients (mean age 50 years) were followed for a median (range) of 9 (0.2–25) years totalling 3253 person-years. Patients with CPA ≥ 10% had significantly higher risks for total death [hazard ratio (HR): 5.0 (1.9–13.2)], LRD [19.0 (2.0–182.0)], and combined liver outcomes [15.6 (3.1–78.6)]. CPA and pathologist fibrosis staging (FS) showed similar accuracy (AUROC) for the prediction of total death (0.68 vs. 0.70), LRD (0.72 vs. 0.77) and combined liver outcomes (0.75 vs. 0.78). Non-invasive serum markers Hepascore, APRI, and FIB-4 reached higher AUROC; however, they were not statistically significant compared to that of CPA except for Hepascore in predicting total mortality (0.86 vs. 0.68, p = 0.009). Conclusion: Liver fibrosis quantified by CPA analysis was significantly associated with clinical outcomes including total mortality, LRD, and HCC. CPA achieved similar accuracy in predicting outcomes compared to pathologist fibrosis staging and non-invasive serum markers. [ABSTRACT FROM AUTHOR]

To address the shortcomings of large porosity and insufficient mechanical properties of skeletonized Thermoplastic polyurethane (TPU) fabrications during the preparation of composite materials by selective laser sintering (SLS) technology. In this paper, SiO2@Si3N4ws‐GPTMS core‐shell structure filler was successfully prepared by first synthetically growing silicon dioxide (SiO2) nanospheres on the surface of silicon nitride whiskers (Si3N4ws) in situ by sol–gel method, and then modified with silane coupling agent Silane coupling agent (GPTMS). Then the filler was incorporated into the inner and outer surfaces of TPU skeletonized structural parts by vacuum dip coating using a water‐based polyurethane (PU) coating post‐treatment enhancement method, and the surface coating coating of TPU skeletonized structural parts was achieved by warming and curing. This composite filler coating structure greatly improved the mechanical properties of the SLS parts (tensile strength of 20.3 MPa and elongation at break of 338.9%, 163% higher tensile strength, 17.7% higher elongation at break, and 672% higher rebound dimension compared with the pure TPU sintered parts). In addition, the thermal stability of the SLS sintered parts was improved, which greatly enhanced the application of the sintered manufactured parts prepared by SLS technology in the field of rebound‐absorbing artificial wear. [ABSTRACT FROM AUTHOR]

We present a forecast study on the cross-correlation between cosmic shear tomography from the Chinese Survey Space Telescope (CSST) and cosmic microwave background (CMB) lensing from Ali CMB Polarization Telescope (AliCPT-1) in Tibet. The correlated galaxy and CMB lensing signals were generated from Gaussian realizations based on inputted auto and cross-spectra. To account for the error budget, we considered the CMB lensing reconstruction noise based on the AliCPT-1 lensing reconstruction pipeline; shape noise of the galaxy lensing measurement; CSST photo- z error; photo- z bias; intrinsic alignment (IA) effect; and multiplicative bias. The AliCPT-1 CMB lensing mock data were generated according to two experimental stages, namely the '4 modules*yr' and '48 modules*yr' cases. We estimate the cross-spectra in four tomographic bins according to the CSST photo- z distribution in the range of z ∈ [0, 4). After reconstructing the pseudo-cross-spectra from the realizations, we calculate the signal-to-noise ratio (SNR). By combining the four photo- z bins, the total cross-correlation SNR ≈ 15 (AliCPT-1 '4 modules*yr') and SNR ≈ 22 (AliCPT-1 '48 modules*yr'). Finally, we study the cosmological application of this cross-correlation signal. Excluding IA in the template fitting would lead to roughly a 0.6σ increment in σ8 due to the negative IA contribution to the galaxy lensing data. For AliCPT-1 first and second stages, the cross-correlation of CSST cosmic shear with CMB lensing gives errors on the clustering amplitude |$\sigma _{\sigma _8}=^{+0.043}_{-0.038}$| or |$\sigma _{S_8}=\pm 0.031$| and |$\sigma _{\sigma _8}=^{+0.030}_{-0.027}$| or |$\sigma _{S_8}=\pm 0.018$|⁠ , respectively. [ABSTRACT FROM AUTHOR]

The solution using built-in beam element method to increase the calculation efficiency of aqueduct pile foundations is studied in this work. The formulations of built-in beam element method based on the normal generalized displacement method of beam element are introduced in this work. Then, the validity of the built-in beam element method is checked by a static problem of a simplified aqueduct model. Furthermore, the solution to increase calculation efficiency by built-in beam element method for aqueduct pile foundations is introduced by studying the features of built-in beam element method and normal generalized displacement method of beam element in models with different grid density and foundation stiffness. Finally, a static problem of an arch aqueduct is solved using the summed solution. The results show that it is feasible to improve efficiency with sufficient accuracy by reasonably selecting the built-in beam element method and normal generalized displacement method in the analysis of aqueduct pile foundation. [ABSTRACT FROM AUTHOR]

Hong Kong International Airport (HKIA) is an important sea airdrome in China. The aim of this study is to evaluate the impacts of this reclamation on the water quality of the Northwestern Bay of Hong Kong (NWBHK). In all, 117 Landsat 5 TM and 44 Landsat 8 OLI images were preprocessed and matched with the marine water data of 18 in situ monitoring points, acquiring 458 and 119 sets of data, respectively. This study adopted BPNN Machine Learning methods to establish the retrieval algorithm. Based on the images, the construction of HKIA was divided into three stages: (1) the construction of the first and second runways from 1992 to 1995; (2) the construction of the Hong Kong Port from 2013 to 2016; and (3) the construction of the third runway from 2017 to 2020. The concentrations of suspended particulate matter, orthophosphate phosphorus, and dissolved inorganic nitrogen from 1986 to 2022 were retrieved. In this paper, it was found that (1) the construction activities led to an increase in SPM, PO4P, and DIN concentrations in adjacent water bodies; (2) the impact of the Tuen Mun River on the NWBHK increased, while the impact of the Tung Chung River on the NWBHK decreased; and (3) the interception impact of HKIA on the transportation of the Pearl River water became stronger. [ABSTRACT FROM AUTHOR]

Background: Non-invasive tests are widely used to diagnose fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), however, the optimal method remains unclear. We compared the accuracy of simple serum models, a serum model incorporating direct measures of fibrogenesis (Hepascore), and Fibroscan®, for detecting fibrosis in NAFLD. Methods: NAFLD patients undergoing liver biopsy were evaluated with Hepascore, NAFLD Fibrosis Score (NFS), FIB-4 and AST-platelet ratio index (APRI), with a subset (n = 131) undergoing Fibroscan®. Fibrosis on liver biopsy was categorized as advanced (F3–4) or cirrhosis (F4). Accuracy was determined by area under receiving operating characteristic curves (AUC). Indeterminate ranges were calculated using published cut-offs. Results: In 271 NAFLD patients, 83 (31%) had F3–4 and 47 (17%) cirrhosis. 6/131 (4%) had an unreliable Fibroscan®. For the detection of advanced fibrosis, the accuracy of Hepascore (AUC 0.88) was higher than FIB-4 (0.73), NFS (0.72) and APRI (0.69) (p < 0.001 for all). Hepascore had similar accuracy to Fibroscan® (0.80) overall, but higher accuracy in obese individuals (0.91 vs 0.80, p = 0.001). Hepascore more accurately identified patients with cirrhosis than APRI (AUC 0.85 vs 0.71, p = 0.01) and NFS (AUC 0.73, p = 0.01) but performed similar to FIB-4 and Fibroscan®. For the determination of F3-4, the proportion of patients in indeterminate area was lower for Hepascore (4.8%), compared to FIB-4 (42%), NFS (36%) and APRI (44%) (p < 0.001 for all). Conclusions: Hepascore has greater accuracy and a lower indeterminate range than simple serum fibrosis tests for advanced fibrosis in NAFLD, and greater accuracy than Fibroscan® in obese individuals. [ABSTRACT FROM AUTHOR]

To reduce the possibility of the TPU 3D‐printed workpiece causing a fire, a flame‐retardant coating containing phosphorus, nitrogen, silicon, and benzene rings was fabricated on the TPU workpiece surface. When the MSDS content in the coating is 30 phr, the coated TPU composites LOL reached 29.5%, achieved V‐0 rating at the UL‐94 test and its peak heat release rate was reduced by 71.3% in the cone calorimeter test. When the MSDS content was increased to 20 phr, a continuous char layer was observed. Moreover, the EP/PBz/PDMS coating improved the thermal stability and tensile strength of TPU 3D‐printed workpiece. When the coating burns, it forms a dense charcoal layer, which isolates oxygen. The substrate wrapped by the charcoal layer undergoes a carbonization reaction when heated, preventing the substrate from burning further, resulting in improved flame retardancy, smoke suppression and dripping resistance of TPU. [ABSTRACT FROM AUTHOR]

To propose the suitable diameter of calculus debris produced during flexible ureteroscopy lithotripsy (fURL). A glass tube was used to simulate the stone excretion process during Furl. Different stone diameters (0.50–1.00 mm, 0.25–0.50 mm, and 0.10–0.25 mm) with three sizes of flexible ureteroscopy (fURS) (7.5Fr, 8.7Fr, and 9.9Fr) and ureteral access sheath (UAS) (12/14Fr) with or without negative pressure suction were employed in the experiment. The intraoperative calculi excretion (ICE) was recorded according to the stones discharged from the gap between fURS and UAS. The ICE raised significantly in thinner fURS and UAS due to the smaller Ratio of Endoscope-Sheath Diameter (RESD). The gravel size ≤ 0.25 mm was conducive to drainage with traditional UAS, while using fURS with negative-pressure UAS could significantly improve ICE. The gravel size ≤ 0.5 mm was conducive to expulsion. We clarify that ICE during ureteroscopy relates to RESD and negative pressure suction. The proper size of the stone fragment is critical in ensuring the expulsion during fURL, ≤ 0.25 mm in traditional UAS and ≤ 0.50 mm in negative-pressure UAS, respectively. [ABSTRACT FROM AUTHOR]

Microglia are the main immune cells of the central nervous system (CNS) and comprise various model systems used to investigate inflammatory mechanisms in CNS disorders. Currently, shaking and mild trypsinization are widely used microglial culture methods; however, the problems with culturing microglia include low yield and a time-consuming process. In this study, we replaced normal culture media (NM) with media containing 25% fibroblast-conditioned media (F-CM) to culture mixed glia and compared microglia obtained by these two methods. We found that F-CM significantly improved the yield and purity of microglia and reduced the total culture time of mixed glia. The microglia obtained from the F-CM group showed longer ramified morphology than those from the NM group, but no difference was observed in cell size. Microglia from the two groups had similar phagocytic function and baseline phenotype markers. Both methods yielded microglia were responsive to various stimuli such as lipopolysaccharide (LPS), interferon-γ (IFN-γ), and interleukin-4 (IL-4). The current results suggest that F-CM affect the growth of primary microglia in mixed glia culture. This method can produce a high yield of primary microglia within a short time and may be a convenient method for researchers to investigate inflammatory mechanisms and some CNS disorders. [ABSTRACT FROM AUTHOR]

Maximizing the carbon sequestration of forested land is important for achieving carbon neutrality. Although some studies have discussed forest carbon sequestration efficiency (FCSE) from the perspective of total factor production, it is being increasingly recognized that forestland use regulates sequestration and emissions. When viewing forestland use as input and carbon emissions as output, there is a lack of empirical evidence on FCSE and its influencing factors. Here, a superefficiency slacks-based measurement model was applied to estimate FCSE for 66 counties in Zhejiang Province, China. The influencing factors and spatial spillover effects of FCSE were also analyzed using a spatial autocorrelation model. The findings showed that over the sample observation period, county FCSE ranged from 0.199 to 1.258, with considerable gaps. The global Moran's I index showed that county-level FCSE was markedly spatially autocorrelated. Spatially, forestland use, cutting, pests, and diseases had negative spatial spillover effects on FCSE, whereas average annual temperature and precipitation displayed positive spillover effects. These findings suggest that the overall coordination of forest resource supervision and management among counties should be strengthened. The implementation of forestry management models aimed at consolidating or increasing forest carbon sequestration should be emphasized to improve forest quality, thereby promoting FCSE enhancement. [ABSTRACT FROM AUTHOR]

CD47 expressed on cancer cells enables macrophage immune evasion. Blocking CD47 using anti‐CD47 monoclonal antibodies (mAbs) is a promising strategy. The anti‐CD47 mAb TJC4 has anti‐tumor activity but lacks hematological toxicity. Venetoclax, a B‐cell lymphoma 2 (BCL‐2) inhibitor for B‐cell malignancy, induces phosphatidylserine (PS) extracellular exposure, representing an "eat‐me" signal for macrophages. The present study aimed to explore whether TJC4‐Venetoclax combined therapy exerts synergistic anti‐cancer properties in B‐cell lymphoma. In vitro, flow cytometry and microscopy assessed whether TJC4 monotherapy or combination treatment could promote macrophage‐mediated phagocytosis of tumor cells. Induced PS exposure on the cell membrane was measured using flow cytometry with Annexin V‐FITC staining. In vivo, Venetoclax and TJC4's synergistic anti‐tumor effects were evaluated. B cell lymphoma cell lines express high levels of CD47 and patients with diffuse large B cell lymphoma expressing CD47 have a worse clinical prognosis. TJC4 eliminates tumor cells via macrophage‐mediated phagocytosis. In vitro and in vivo, the TJC4‐Venetoclax combination increased phagocytosis significantly compared with either agent alone, showing synergistic phagocytosis, and displayed synergistic anti‐cancer properties in B‐cell lymphoma. Our results support the TJC4‐Venetoclax combination as a promising therapy, and suppressing BCL‐2 and CD47 simultaneously could represent a novel therapeutic paradigm for B‐cell lymphoma. [ABSTRACT FROM AUTHOR]

Presently, layered double hydroxides (LDHs) are pervasively adopted as part of flame retardant polymer composite materials due to its favorable synergism effect with certain flame retardants. In addition, it is environmentally friendly. Meanwhile, selective laser sintering (SLS) is a powder‐based three‐dimensional (3D) printing technology, providing a novel path to manufacturing polymer composite materials with complex shapes. In this research, flame retardancy of thermoplastic polyurethane (TPU) was enhanced based on LDHs and intumescent flame retardant (IFR). Being prepared by SLS technology. First, TPU composite powders based on LDHs and IFR were obtained using a two‐stage mixing method. Morphology analysis revealed that IFR and LDHs were dispersed uniformly in TPU powder. Subsequently, flame retardant TPU composites were prepared with TPU composite powders using the SLS process under appropriate 3D printing parameters, thereby enabling flame retardant TPU parts to be obtained. With 23 wt% IFR and 2 wt% LDHs filler, the limiting oxygen index of TPU composite was reached to 31.7%, while passing the UL‐94 V‐0 level during the vertical burning test. The cone calorimeter test showed that the heat release rate, smoke production rate, as well as production of carbonic oxides, all decreased significantly following the addition of LDHs. Thermogravimetric analysis indicated that LDHs and IFR were characterized by a favorable synergism effect, with the TPU/23IFR/2LDHs possessing good thermal stability. Char residue analysis, including SEM, energy dispersive X‐ray, Fourier transform infrared, and Raman spectra, further testified that a synergism effect existed between LDHs and IFR in the TPU composite. Overall, in this study the TPU composites fabricated by SLS technology exhibited excellent flame retardant ability. [ABSTRACT FROM AUTHOR]

We demonstrate an efficient back-fire to forward wide-angle beam steering leaky-wave antenna (LWA) based on a large dispersion gradient planar spoof surface plasmon polariton (SSPP) transmission line (TL) with split-ring units. To convert the highly confined SSPP waveguiding mode to a radiation mode, two arrays of metallic patches are periodically arranged on both sides of the SSPP TL. The patches are designed as two combined half-elliptical shapes to mitigate the open stopband effect and enhance the radiation performance. We propose a theoretical method to interpret the mechanism and predict the directional pattern of the LWA. To verify the proposed method, the SSPP TL and LWA prototypes are fabricated and measured. The calculation, simulation, and experimental results match well and show that the main beam of the LWA can steer a wide range of 112° from back-fire (−90°) to the forward quadrant of 22° passing through the broadside in 6.3–11 GHz, demonstrating a large scanning rate of 2.07°/%. Furthermore, the LWA also possesses the advantages of low profile, high average gain (12 dBi), high average efficiency (95%), and low sidelobe level (<−13 dB). This work provides an alternative route to achieving wide-angle LWAs for promising microwave radar and wireless communication applications. [ABSTRACT FROM AUTHOR]

During the COVID-19 public health crisis, market failures such as shortage of supplies and soaring prices of anti-epidemic materials – with masks as the core – have occurred. In essence, such anti-epidemic materials have the dual nature of necessities with low elasticity of demand and private products with positive externalities. This research explores the understanding of anti-pandemic materials and how different initiatives, and evaluation to increase availability of necessary resources can be effective in curbing a pandemic. Market regulation results in a non-Pareto optimal allocation of resources and the difficulty of exerting the positive externalities of products. However, in China, the market failure of anti-epidemic materials was quickly resolved, due to the institutional advantages of socialism with Chinese characteristics, the social responsibility drive of domestic enterprises, and cultural genes that focus on equity and concern for the disadvantaged. The optimal allocation of anti-epidemic materials gave access to exerting efficiency and fairness effects, positive external effects, and public effects. [ABSTRACT FROM AUTHOR]

Background: Plants can recruit beneficial microbes to enhance their ability to defend against pathogens. However, in contrast to the intensively studied roles of the rhizosphere microbiome in suppressing plant pathogens, the collective community-level change and effect of the phyllosphere microbiome in response to pathogen invasion remains largely elusive. Results: Here, we integrated 16S metabarcoding, shotgun metagenomics and culture-dependent methods to systematically investigate the changes in phyllosphere microbiome between infected and uninfected citrus leaves by Diaporthe citri, a fungal pathogen causing melanose disease worldwide. Multiple microbiome features suggested a shift in phyllosphere microbiome upon D. citri infection, highlighted by the marked reduction of community evenness, the emergence of large numbers of new microbes, and the intense microbial network. We also identified the microbiome features from functional perspectives in infected leaves, such as enriched microbial functions for iron competition and potential antifungal traits, and enriched microbes with beneficial genomic characteristics. Glasshouse experiments demonstrated that several bacteria associated with the microbiome shift could positively affect plant performance under D. citri challenge, with reductions in disease index ranging from 65.7 to 88.4%. Among them, Pantoea asv90 and Methylobacterium asv41 identified as "recruited new microbes" in the infected leaves, exhibited antagonistic activities to D. citri both in vitro and in vivo, including inhibition of spore germination and/or mycelium growth. Sphingomonas spp. presented beneficial genomic characteristics and were found to be the main contributor for the functional enrichment of iron complex outer membrane receptor protein in the infected leaves. Moreover, Sphingomonas asv20 showed a stronger suppression ability against D. citri in iron-deficient conditions than iron-sufficient conditions, suggesting a role of iron competition during their antagonistic action. Conclusions: Overall, our study revealed how phyllosphere microbiomes differed between infected and uninfected citrus leaves by melanose pathogen, and identified potential mechanisms for how the observed microbiome shift might have helped plants cope with pathogen pressure. Our findings provide novel insights into understanding the roles of phyllosphere microbiome responses during pathogen challenge. BXFXiVHRdF5-go6BavLYay Video abstract [ABSTRACT FROM AUTHOR]

An innovative phosphorus‐silicone flame retardant (KAPP‐OGPOSS) was prepared by grafting octa (propyl glycidyl ether) polyhedral oligomeric silsesquioxane (OGPOSS) on ammonium polyphosphate (APP) through silane coupling agent (KH‐550). The chemical structure, morphology, flame retardancy, and mechanism of the obtained materials were comprehensively investigated. TG results demonstrated that EP with 15 wt% KAPP‐OGPOSS produced a char residue of 42.6% at 700°C, which is three times that of pure EP. The flame retardant tests showed that the limiting oxygen index value of EP/15 wt% KAPP‐OGPOSS was 30.6% (67.7% higher than that of neat EP) and its UL‐94 grade reached to V‐0 rating. Cone calorimeter testing indicated that the incorporation of 15 wt% KAPP‐OGPOSS to EP significantly reduced heat, smoke, CO, and CO2 release by 79%, 83%, 80%, and 82.5%, respectively. The modification of APP with OGPOSS was also beneficial for the improvement of the char yield and density of char. A flame retardant mechanism was revealed according to the investigation into the char residue. This modified approach provided an innovative yet practical means of enhancing the flame retardant properties of EP. [ABSTRACT FROM AUTHOR]

Background: After traumatic brain injury (TBI), an acute, robust inflammatory cascade occurs that is characterized by the activation of resident cells such as microglia, the migration and recruitment of peripheral immune cells and the release of inflammatory mediators that induce secondary cell death and impede neurological recovery. In addition, neuroinflammation can alter blood–brain barrier (BBB) permeability. Controlling inflammatory responses is considered a promising therapeutic approach for TBI. Hydroxychloroquine (HCQ) has already been used clinically for decades, and it is still widely used to treat various autoimmune diseases. However, the effects of HCQ on inflammation and the potential mechanism after TBI remain to be defined. The aim of the current study was to elucidate whether HCQ could improve the neurological recovery of mice post-TBI by inhibiting the inflammatory response via the TLR4/NF-κB signaling pathway. Methods: C57BL/6 mice were subjected to controlled cortical impact (CCI) and randomly divided into groups that received intraperitoneal HCQ or vehicle daily after TBI. TAK-242 (3.0 mg/kg), an exogenous TLR4 antagonist, was injected intraperitoneally 1 h before TBI. Behavioral assessments were performed on days 1 and 3 post-TBI, and the gene expression levels of inflammatory cytokines were analyzed by qRT-PCR. The presence of infiltrated immune cells was examined by flow cytometry and immunostaining. In addition, BBB permeability, tight junction expression and brain edema were investigated. Results: HCQ administration significantly ameliorated TBI-induced neurological deficits. HCQ alleviated neuroinflammation, the activation and accumulation of microglia and immune cell infiltration in the brain, attenuated BBB disruption and brain edema, and upregulated tight junction expression. Combined administration of HCQ and TAK-242 did not enhance the neuroprotective effects of HCQ. Conclusions: HCQ reduced proinflammatory cytokine expression, and the underlying mechanism may involve suppressing the TLR4/NF-κB signaling pathway, suggesting that HCQ is a potential therapeutic agent for TBI treatment. [ABSTRACT FROM AUTHOR]

The dodecyl sulfate intercalated CaMgAl‐hydrotalcites (layered double hydroxides [LDHs]) were successfully prepared by co‐precipitation method, and characterized by X‐ray diffraction analysis, infrared spectroscopy (Fourier transform infrared spectra [FT‐IR]), thermogravimetry (TG‐DTA), scanning electron microscope, and Brunner−Emmet−Teller (BET). The prepared LDHs were added to the intumescent flame retardant (IFR) polypropylene (PP) nanocomposites, and the limiting oxygen index method (LOI), vertical combustion method (UL‐94), cone calorimetry (CCT), and other test methods were used to study its thermal stability and combustion performance. The results showed that when the flame retardant was composed of 23 wt% IFR and 2 wt% O‐SDS‐LDHs, the LOI value of the material was increased to 31.5%, reaching the V‐0 level, and the flame retardant performance was significantly improved. The results also showed that there was a significant synergistic effect between IFR and O‐SDS‐LDHs, which could improve the thermal stability and graphitization degree of PP nanocomposites. In addition, the peak heat release rate, total heat release, and total smoke production of the PP/IFR/O‐SDS‐LDHs system were 177 kW/m2, 101 MJ/m2, and 15.4 m2, respectively, which were 82.2%, 51.0%, and 23.0% lower than those of pure PP, respectively. These improvements could be attributed to the presence of dense and continuous char layer formed by the synergistic effect. [ABSTRACT FROM AUTHOR]

In the rice blast fungus Magnaporthe oryzae, the cAMP signalling pathway plays a critical role in regulating leaf surface recognition and the initiation of appressorium development. Direct downstream targets of the cAMP signalling pathway are, however, not well‐characterised. The MoSom1 protein functions downstream of the cAMP dependent protein kinase A (cAMP‐PKA) and is essential for infection‐related morphogenesis and pathogenicity. In this study, we show that mutation of a putative PKA phosphorylation site in MoSom1 is essential for its role in appressorium differentiation and pathogenicity in M. oryzae. Mutation of serine 227 in MoSom1 by deletion or serine (S) substitution to alanine (A), valine (V) or tyrosine (Y), resulted in defects of conidiation, appressorium‐like structure formation and fungal pathogenicity. Western blot analysis confirmed that S227 in MoSom1 is a putative PKA phosphorylation site. Furthermore, a ΔMosom1 mutant showed reduced expression of PMK1 and was defective in Pmk1 phosphorylation, indicating that the Pmk1 mitogen‐activated protein kinase (MAPK) acts downstream of MoSom1 in M. oryzae. We conclude that the cAMP‐PKA pathway may regulate the Pmk1 MAPK pathway through MoSom1 during rice infection by the blast fungus. Take Aways: S227 is crucial for MoSom1 function in M. oryzae.S227 in MoSom1 was identified as a putative PKA phosphorylation site in M. oryzae.S227 is essential for infection‐related morphogenesis and pathogenicity in M. oryzae. [ABSTRACT FROM AUTHOR]

In this work, a multi‐contact Al2O3@AgNPs hybrid thermal conductive filler was synthesized by in‐situ growth method to fill high thermal conductivity polydimethylsiloxane (PDMS)‐based composites to prepare TIMs. And the thermal conductivity, electrical conductivity, and mechanical properties of the composite materials were studied. During the synthesis process of the multi‐contact hybrid filler, different concentrations of silver ions were reduced to generate silver nanoparticles and attached to the surface of Al2O3. Al2O3@AgNPs/PDMS thermally conductive composites were prepared by changing the filler addition. Using SEM, XPS, and XRD is used to characterize the morphology and chemical composition of Al2O3@AgNPs hybrid filler. The thermal conductivity of PDMS‐based composites with different AgNPs content under 70 wt% filler loading was studied. The results show that the thermal conductivity of PDMS‐based composites filled with 7owt%Al2O3@3AgNPs/PDMS multi‐contact hybrid filler is 0.67 W/m·K, which is 3.72 times that of pure PDMS, and is higher than that of unmodified Al2O3 with the same addition amount. /PDMS composite material has a high thermal conductivity of 24%. This work provides a new idea for the design and manufacture of high thermal conductivity hybrid fillers for TIMs. [ABSTRACT FROM AUTHOR]

Background:  Hunner's interstitial cystitis (HIC) is a complex disorder characterized by pelvic pain, disrupted urine storage, and Hunner lesions seen on cystoscopy. There are few effective diagnostic biomarkers. In the present study, we used the novel machine learning tool CIBERSORT to measure immune cell subset infiltration and potential novel diagnostic biomarkers for HIC.Methods: The GSE11783 and GSE57560 datasets were downloaded from the Gene Expression Omnibus for analysis. Ten HIC and six healthy samples from GSE11783 were analyzed using the CIBERSORT algorithm. Gene Set Enrichment Analysis (GSEA) was performed to identify biological processes that occur during HIC pathogenesis. Finally, expression levels of 11 T cell follicular helper cell (Tfh) markers were compared between three healthy individuals and four patients from GSE57560.Results: Six types of immune cells in HIC from GSE11783 showed significant differences, including resting mast cells, CD4+ memory-activated T cells (CD3+ CD4+ HLA-DR+ cells), M0 and M2 macrophages, Tfh cells, and activated natural killer cells. Except for plasma cells, there were no significant differences between Hunner's lesion and non-Hunner's lesion areas in HIC. The GSEA revealed significantly altered biological processes, including antigen-antibody reactions, autoimmune diseases, and infections of viruses, bacteria, and parasites. There were 11 Tfh cell markers with elevated expression in patients from GSE57560.Conclusion: This was the first demonstration of Tfh cells and CD3+ CD4+ HLA-DR+ cells with elevated expression in HIC. These cells might serve as novel diagnostic biomarkers. [ABSTRACT FROM AUTHOR]

Selective laser sintering (SLS) is an additive manufacturing technology that can provide a novel strategy to manufacture complex polymer‐based composites with tailored properties. In this study, polyamide 12 (PA12) composite powders based on Al2O3, boron nitride (BN), and carbon nanotubes (CNTs) were prepared via a two‐step mixing approach. Morphology characterization techniques indicated that the fillers were uniformly dispersed in the PA12 matrix as expected. Under the optimum 3D‐printing parameters, the fabrication of SLS parts with high filler loading could be obtained. With 40 wt% Al2O3, 8 wt% BN, and 2 wt% CNT hybrid fillers, the thermal conductivity of PA12 composites could reach 1.09 W/mK. It could be attributed to the synergistic effect of multi‐dimensional fillers to form dense and continuous thermal conduction paths. The factors influencing the performance of PA12 composites such as melting and crystallization behaviors, dielectric properties, and mechanical properties were also discussed. The results show that these composites have favorable dielectric and mechanical properties. Overall, the PA12 composites fabricated by SLS technology in this study exhibit excellent thermal management ability. [ABSTRACT FROM AUTHOR]

We demonstrate a new variety of spoof surface plasmon polariton (SSPP) waveguides and notch filters with periodic arrays of ultra-thin metallic meander-strip units for high-efficiency and strong confinement microwave SSPPs transmission and notch rejection. Firstly, the dispersion characteristics of the proposed SSPPs waveguide based on meander-strip units are investigated. The dispersion curve of the proposed waveguide presents a unique negative group velocity characteristic, and the asymptotic frequency greatly reduces to near half as that of SSPP waveguide based on traditional rectangular-grooved units with the same transverse size. To validate the proposed design, an SSPP waveguide prototype is fabricated and tested, showing good lowpass filtering performances with a high transmission coefficient ($\text {S}21 > {-}1$ dB) and a low reflection coefficient ($\text {S}11 < {-}15$ dB) below the asymptotic frequency of 5.2 GHz. Based on this waveguide structure, a notch filter is designed by loading a split ring resonator (SRR). The transmission coefficient (S21) of this filter is −18 dB at the notch frequency of 2.52 GHz. Furthermore, a PIN diode is integrated into the SRR of the notch filter to make the notch frequency switchable. As the PIN diode turns from the ON state to the OFF state, the notch frequency switches from 2.5 GHz to 3.5 GHz. The proposed waveguides and notch filters with electronically adjustable functionalities may have great potential applications in microwave integrated plasmon circuits and programmable systems. [ABSTRACT FROM AUTHOR]

Background: Cross-sectional studies suggest an association between metabolic syndrome (MetS) and knee osteoarthritis (KOA). We performed a meta-analysis to evaluate whether MetS is an independent risk factor for KOA. Methods: Prospective cohort studies evaluating the association between MetS and KOA in general population were retrieved from PubMed and Embase. Only studies with multivariate analyses were included. Data were pooled with a random-effect model, which is considered to incorporate heterogeneity among the included studies. Results: Five studies including 94,965 participants were included, with 18,990 people with MetS (20.0%). With a mean follow-up duration of 14.5 years, 2,447 KOA cases occurred. Pooled results showed that MetS was not significant associated with an increased risk of KOA after controlling of factors including body mass index (adjusted risk ratio [RR]: 1.06, 95% CI: 0.92~1.23, p = 0.40; I2 = 33%). Subgroup analysis showed that MetS was independently associated with an increased risk of severe KOA that needed total knee arthroplasty (RR = 1.16, 95% CI: 1.03~1.30, p = 0.02), but not total symptomatic KOA (RR = 0.84, 95% CI: 0.65~1.08, p = 0.18). Stratified analyses suggested that MetS was independently associated with an increased risk of KOA in women (RR = 1.23, 95% CI: 1.03~1.47, p = 0.02), but not in men (RR = 0.90, 95% CI: 0.70~1.14, p = 0.37). Conclusions: Current evidence from prospective cohort studies did not support MetS was an independent risk factor of overall KOA in general population. However, MetS may be associated with an increased risk of severe KOA in general population, or overall KOA risk in women. [ABSTRACT FROM AUTHOR]

Background and aim: Methotrexate (MTX) is routinely used for immunological disorders, and its long‐term use is associated with hepatotoxicity. The aim of this study was to investigate whether a serum liver fibrosis test (Hepascore) predicted the risk of adverse liver‐related outcomes and mortality. Methods: A total of 92 patients in Western Australia who had a long‐term MTX intake history,from 2004 to 2016, were recruited and followed up from the first Hepascore to death or end of the study. Clinical data, all deaths, and liver‐related outcomes (liver‐related death and decompensation) were obtained from hospital, PathWest, and WA Data Linkage Unit databases. Results: Nine deaths and four adverse liver‐related outcomes occurred during the follow up of 354 person‐years. The 5‐year survival was 86.1%. The liver‐related outcome free survival was 95.6%. Baseline Hepascore ≥0.84 was associated with advanced fibrosis on liver biopsy (P = 0.025). A baseline Hepascore ≥0.84 was significantly associated with higher risks for adverse liver‐related outcomes (P < 0.001) and all‐cause mortality (P = 0.001). Cox regression demonstrated that only baseline Hepascore ≥0.84 was independently associated with the increased risk of all‐cause mortality (7.91 [1.52–41.29], P = 0.014). Moreover, any Hepascore ≥0.84 found during follow up was independently associated with the increased risk of all‐cause mortality (86.18 [4.03–1844.83], P = 0.007). Conclusions: This study demonstrated the potential importance of Hepascore monitoring in long‐term MTX users. Patients with a Hepascore higher than 0.84 at any stage had increased mortality, but further studies are required to confirm this finding. [ABSTRACT FROM AUTHOR]

Immunocheckpoint proteins of tumor infiltrating lymphocytes play an important role in tumor prognosis in the course of tumor clinicopathology. PD‐1 (Programmed cell death protein 1) is an important immunosuppressive molecule. By binding to PD‐L1 (programmed cell death‐ligand 1), it blocks TCR and its costimulus signal transduction, inhibits the activation and proliferation of T cells, depletes the function of effector T cells, and enables tumor cells to achieve immune escape. In recent years, immunocheckpoint blocking therapy targeting the PD‐1/PD‐L1 axis has achieved good results in a variety of malignant tumors, pushing tumor immunotherapy to a new milestone, such as anti‐PD‐1 monoclonal antibody Nivolumab, Pembrolizumab, and anti‐PD‐L1 monoclonal antibody Atezolizumab, which are considered as potential antitumor drugs. It was found in clinical use that some patients obtained long‐term efficacy, but most of them developed drug resistance recurrence in the later stage. The high incidence of drug resistance (including primary and acquired drug resistance) still cannot be ignored, which limited its clinical application and became a new problem in this field. Due to tumor heterogeneity, current limited research shows that PD‐1 or PD‐L1 monoclonal antibody drug resistance may be related to the following factors: mutation of tumor antigen and antigen presentation process, multiple immune checkpoint interactions, immune microenvironment changes dynamically, activation of oncogenic pathways, gene mutation and epigenetic changes of key proteins in tumors, tumor competitive metabolism, and accumulation of metabolites, etc, mechanisms of resistance are complex. Therefore, it is the most urgent task to further elucidate the mechanism of immune checkpoint inhibitor resistance, discover multitumor universal biomarkers, and develop new target agents to improve the response rate of immunotherapy in patients. In this study, the mechanism of anti‐PD‐1/PD‐L1 drug resistance in tumors, the potential biomarkers for predicting PD‐1 acquired resistance, and the recent development of combination therapy were reviewed one by one. It is believed that, based on the complex mechanism of drug resistance, it is of no clinical significance to simply search for and regulate drug resistance targets, and it may even produce drug resistance again soon. It is speculated that according to the possible tumor characteristics, three types of treatment methods should be combined to change the tumor microenvironment ecology and eliminate various heterogeneous tumor subsets, so as to reduce tumor drug resistance and improve long‐term clinical efficacy. [ABSTRACT FROM AUTHOR]

Normally, the effective dispersion of thermal conductive fillers is a prerequisite for ensuring thermally conductive networks formed in polymer composites. In this work, a facile method was provided by using cellulose to alter the distribution state of boron nitride (BN) for the preparation of high thermally conductive polylactic acid (PLA). After powder mixing and hot‐pressing process, the Cellulose@BN was located at the boundaries of PLA granules to form consecutive thermally conductive networks with more compact structure. Morphology observation and FTIR spectra confirmed that BN edges absorbed on the cellulose surface under the intermolecular hydrogen bond interaction between PLA and BN. At the BN content of 25 wt%, contrasted with traditional BN/PLA segregated polymer composites (SPCs), thermal conductivity coefficient of Cellulose@BN/PLA SPCs improved by 53.5% from 0.71 to 1.09 Wm−1 K−1. This enhancement could be attributed to the reason that the cellulose regulated stripe aggregation allowed the BN connect with each other more compact, thus a thermal conduction networks with reduced phonon scattering were formed. [ABSTRACT FROM AUTHOR]

The sorting nexin Atg20/Snx42 plays an important role in autophagy. The wheat head blight pathogen Fusarium graminearum contains an FgAtg20 protein orthologous to Saccharomyces cerevisiae Atg20/Snx42, but its function remains largely unknown. Here, we report a role for FgAtg20 in regulating morphogenesis and fungal pathogenicity. Cytological observation and Western blot analysis revealed that ΔFgAtg20 mutants are defective in vacuolar transport and proteolysis of GFP‐FgAtg8, indicating that FgAtg20 is required for non‐selective macroautophagy. Furthermore, we found that FgATG20 is necessary for the maturation of FgApe1, an indicator of the cytoplasm‐to‐vacuole targeting (Cvt) pathway. Immunoblot analysis displayed lower level of FgPex14, a peroxisomal integral membrane protein in ΔFgAtg20 mutants, suggesting that pexophagy is impaired. Furthermore, we demonstrate that FgAtg20 forms a complex with FgAtg1, FgAtg11, FgAtg17 and FgAtg24. When considered together, we conclude that FgAtg20 plays a critical role in vegetative growth, conidiation and pathogenicity of the head blight pathogen, and is involved in the Cvt pathway, non‐selective macroautophagy and pexophagy. [ABSTRACT FROM AUTHOR]

Background: Increasing evidences indicated that diabetes might increase the incidence of gallbladder cancer. However, no sufficient data has ever clarified the impact of diabetes on the survival of patients with gallbladder cancer.Methods: We comprehensively searched PubMed, Embase, and the Cochrane Library databases through July 2019 in order to find sufficient eligible researches. The pooled hazard risks (HRs) and relative risks (RRs) with 95% confidence intervals (CIs) were calculated with either fix-effects or random-effects model. Due to the low gallbladder cancer mortality in general population, the RRs and standard mortality ratios (SMRs) were considered the similar estimates of the HRs.Results: Ten eligible studies were included in this meta-analysis. Analysis of eight cohorts found that diabetes was closely associated with the mortality of gallbladder cancer (HR = 1.10; 95% CI: 1.06-1.14; P < 0.00001). However, the mortality in male diabetes patients was not higher than female patients (RR = 1.08, 95%CI = 0.57-2.04, P = 0.80).Conclusions: These findings indicated that diabetes patients had a higher mortality of gallbladder cancer compared with non-diabetes. [ABSTRACT FROM AUTHOR]

This paper reports on an efficient lossless compression method for periodic signals based on adaptive dictionary predictive coding. Some previous methods for data compression, such as difference pulse coding (DPCM), discrete cosine transform (DCT), lifting wavelet transform (LWT) and KL transform (KLT), lack a suitable transformation method to make these data less redundant and better compressed. A new predictive coding approach, basing on the adaptive dictionary, is proposed to improve the compression ratio of the periodic signal. The main criterion of lossless compression is the compression ratio (CR). In order to verify the effectiveness of the adaptive dictionary predictive coding for periodic signal compression, different transform coding technologies, including DPCM, 2-D DCT, and 2-D LWT, are compared. The results obtained prove that the adaptive dictionary predictive coding can effectively improve data compression efficiency compared with traditional transform coding technology. [ABSTRACT FROM AUTHOR]

A triazine-based macromolecular hybrid charring agent containing zinc borate (MCA-K-ZB) was synthesized and combined with ammonium polyphosphate (APP) to improve the flame retardancy of polypropylene (PP). The flame retardancy and thermal properties of PP composites were investigated using limited oxygen index, vertical burning test, and thermogravimetric analysis. The results showed APP/MCA-K-ZB can improve the flame retardancy of PP compared with APP/MCA-K/ZB. The morphology of the char residues was investigated by scanning electron microscopy (SEM). The SEM result shows that MCA-K-ZB can improve the compactness and continuity of char residue compared with MCA-K/ZB, therefore improving the flame retardancy of PP composites. [ABSTRACT FROM AUTHOR]

Ubiquitination is a key regulatory mechanism that affects numerous important biological processes, including cellular differentiation and pathogenesis in eukaryotic cells. Attachment of proteins to ubiquitin is reversed by specialized proteases, deubiquitinating enzymes (DUBs), which are essential for precursor processing, maintaining ubiquitin homeostasis and promoting protein degradation by recycling ubiquitins. Here, we report the identification of a novel non-pathogenic T-DNA-tagged mutant T612 of Magnaporthe oryzae with a single insertion in the second exon of MoUBP4, which encodes a putative ubiquitin carboxyl-terminal hydrolase. Targeted gene deletion mutants of MoUBP4 are significantly reduced in mycelial growth, conidiation, and increased in tolerance to SDS and CR (Congo red) cell-wall damage. The ΔMoubp4 mutants are blocked in penetration and invasive growth, which results in the loss of pathogenicity. Many conidia produced by the ΔMoubp4 mutants are unable to form appressoria and mobilization and degradation of glycogen and lipid droplets are significantly delayed. Moreover, immunohybridization analysis revealed that total protein ubiquitination levels of the null mutants were significantly increased, indicating that MoUbp4 functions as a deubiquitination enzyme. Taken together, we conclude that MoUbp4 is required for deubiquitination, infection-related morphogenesis and pathogenicity in M. oryzae. [ABSTRACT FROM AUTHOR]

Background: Bile acids (BAs) are synthesized by the liver and modified by gut bacteria, and may play an intermediary role between the gut microbiome and liver in promoting fibrosis in non‐alcoholic fatty liver disease (NAFLD). We investigated the associations between serum and faecal BAs, gut microbiome and fibrosis in patients with and without NAFLD and examined the impact of diet and alcohol consumption on these relationships. Methods: Adult patients (n = 122) underwent liver biopsy and BAs characterization by high‐performance liquid chromatography/mass spectrometry. Gut microbiome composition was analysed using next‐generation 16S rRNA sequencing. Diet and alcohol intake were determined by 3‐day food diary. Results: Serum and faecal BA concentrations increased progressively among non‐NAFLD controls (n = 55), NAFLD patients with no/mild fibrosis (F0‐2, n = 58) and NAFLD with advanced fibrosis (F3/4, n = 9). Progressive increases in serum BAs were driven by primary conjugated BAs including glycocholic acid [GCA] and secondary conjugated BAs. In contrast, faecal BA increase was driven by secondary unconjugated BAs (predominately deoxycholic acid [DCA]). Serum GCA levels and faecal DCA levels correlated with the abundance of Bacteroidaceae and Lachnospiraceae, and stool secondary BAs with an unclassifiable family of the order Bacteroidales (Bacteroidales;other). These bacterial taxa were also associated with advanced fibrosis. Modest alcohol consumption was positively correlated with faecal DCA levels and relative abundance of Lachnospiracaea and Bacteroidales;other. Conclusions: Higher serum and faecal BA levels are associated with advanced fibrosis in NAFLD. Specific gut bacteria link alterations in BA profiles and advanced fibrosis, and may be influenced by low‐level alcohol consumption. [ABSTRACT FROM AUTHOR]

The B‐cell CLL/lymphoma 6 (Bcl6) oncogenic repressor is a master regulator of humoral immunity and B‐cell lymphomagenesis. Although much research has focused on its regulation and function of GC B cells and T cells, the role of Bcl6 in regulating the functions of innate immunity is not well defined. Here, we demonstrated that EAE is exacerbated in LysM Cre+/−Bcl6fl/fl mice. Although other cells such as neutrophils might be involved in this conditional mutant mouse model, we found that the disease pathology is mainly associated with a biased M1 macrophage activity and an enhanced encephalitogenic CD4+ Th17 cell response. In addition, LPS‐induced sepsis mice exhibited an enhanced M1 and inhibited M2 response, further confirming that Bcl6 has an important role in regulating macrophage polarization. Mechanistically, Bcl6 interacts with IκBζ and interferes its binding to the interleukin‐6 (Il‐6) promoter in macrophages, leading to a suppressed transcription of Il‐6. These findings have demonstrated that Bcl6 exerts its regulatory function mainly by repressing Il‐6 expression in macrophages. Thus, our study presents a novel role for Bcl6 in regulating immune response and inflammation. Interaction between Bcl6 and IκBζ in macrophages may provide a potential therapeutic target for autoimmune inflammatory disease. [ABSTRACT FROM AUTHOR]

The rice blast fungus Magnaporthe oryzae causes one of the most devastating crop diseases world-wide and new control strategies for blast disease are urgently required. We have used insertional mutagenesis in M. oryzae to define biological processes that are critical for blast disease. Here, we report the identification of LEU2A by T-DNA mutagenesis, which putatively encodes 3-isopropylmalate dehydrogenase (3-IPMDH) required for leucine biosynthesis, implicating that synthesis of this amino acid is required for fungal pathogenesis. M. oryzae contains a further predicted 3-IPMDH gene (LEU2B), two 2-isopropylmalate synthase (2-IPMS) genes (LEU4 and LEU9) and an isopropylmalate isomerase (IPMI) gene (LEU1). Targeted gene deletion mutants of LEU1, LEU2A or LEU4 are leucine auxotrophs, and severely defective in pathogenicity. All phenotypes associated with mutants lacking LEU1, LEU2A or LEU4 could be overcome by adding exogenous leucine. The expression levels of LEU1, LEU2A or LEU4 genes were significantly down-regulated by deletion of the transcription factor gene LEU3, an ortholog of Saccharomyces cerevisiae LEU3. We also functionally characterized leucine biosynthesis genes in the wheat pathogen Fusarium graminearum and found that FgLEU1, FgLEU3 and FgLEU4 are essential for wheat head blight disease, suggesting that leucine biosynthesis in filamentous fungal pathogens may be a conserved factor for fungal pathogenicity and, therefore, a potential target for disease control. [ABSTRACT FROM AUTHOR]

The target of rapamycin (TOR) signaling pathway plays critical roles in regulating vegetative development and virulence in Fusarium graminearum. Previously, we have demonstrated that the putative type 2A phosphatase FgPpg1, a downstream component of the pathway, is important for hyphal growth, sporulation, DON biosynthesis and virulence. Here, we report the identification of FgHLTF1 putatively encoding a histone-like transcription factor by the transcriptome analysis of an ΔFgppg1 mutant. The FgHLTF1 expression was significantly down-regulated by the deletion of FgPPG1 or treatment with rapamycin. Analysis of an F. graminearum strain expressing green fluorescent protein (GFP) revealed that FgHltf1-GFP fusion protein mainly localized to the nucleus. Targeted gene deletion mutants of FgHLTF1 exhibited a significant reduction in vegetative growth, sexual reproduction and virulence. Moreover, the growth of the ΔFghltf1 mutants was restricted by hyperosmotic stresses. Unlike the wild-type strain, the mutants showed anomalous subcellular translocation of FgHog1-GFP under hyperosmotic conditions, suggesting that FgHLTF1 is associated with the high osmolarity glycerol response pathway. Taken together, we conclude that FgHLTF1 is transcriptionally regulated by the TOR signaling pathway and plays important roles in regulating vegetative growth, sexual reproduction, virulence and hyperosmotic stresses in F. graminearum. [ABSTRACT FROM AUTHOR]

The tectonic regime and melting conditions of adakitic tonalitic‐trondhjemitic leucosomes and tonalite plutons from the North Qaidam terrane are evaluated through petrology, whole‐rock major, trace element and Sr‐Nd isotopic data and zircon U‐Pb data. Zircons from leucosomes and metabasites preserve distinct U‐Pb age populations: early Ordovician inherited zircon cores record a protolith age of ~470 Ma, whereas zircon rims preserve subsequent HP granulite facies metamorphism, anatexis, and magmatism between 437 and 433 Ma. Whole‐rock geochemistry suggests that three types of leucosomes and tonalite plutons have geochemical features similar to adakites. Type 1 leucosomes record high Sr contents and positive Eu anomalies representing an earlier period of plagioclase accumulation. The flat fractionated rare earth element patterns of type 2 leucosomes correspond to residues of HP mafic granulites, and the steep fractionated rare earth element patterns of type 3 leucosomes correspond to garnet‐ and clinopyroxene‐rich residues. Petrological observations with P‐T paths and experimentally constrained melting curves together infer that melting of the metagabbro were triggered by the breakdown of amphibole ± zoisite under high‐pressure conditions. Therefore, tonalite, trondhjemite, and granodiorite (TTG)‐adakitic magmas in the North Qaidam terrane were produced through partial melting of newly emplaced gabbroic rocks with an arc affinity under high‐pressure, granulite facies conditions in a thickened lower crust during continental collision. This model explains the origin of TTG‐adakitic rocks and related continental growth and crustal differentiation genetically associated with continental collision. Key Points: TTG‐like magmas in the North Qaidam were produced by partial melting of newly emplaced metagabbros under HP granulite facies conditionsMetagabbros possess a subduction‐related arc signature, whereas leucosomes and tonalite plutons record geochemical features similar to TTGsTTG‐like rocks and related continental growth genetically are associated with continental collision zones [ABSTRACT FROM AUTHOR]

At present, coal bursts in working faces of steeply inclined coal seams (SICSs) have rarely been investigated, and current research focuses on the influences of roof breaking and instability of overlying structures in goaf on coal bursts; however, the stress state of coal masses in working faces being subjected to coal bursts is rarely researched. To overcome the above defects, a model for analysing stresses on coal masses in horizontal section of SICSs was established based on the coal burst that occurred in LW5521-20, Yaojie No. 3 Coal Mine, Lanzhou, Gansu Province, China. Moreover, the mechanism underpinning such a coal burst in SICSs was analysed based on the superposition mechanism of dynamic and static loads. The results show that the side abutment pressure near the roof and floor under the horizontal sections of SICSs is asymmetrically distributed in the vertical direction in which the peak of side abutment pressure near the roof is closer to the working face and therefore is taken as the source of static loads for coal bursts in working faces. When the superimposed dynamic load caused by hanging roof breaking and high static load borne in the coal masses is larger than the critical load for coal burst inception, a coal burst will occur. Furthermore, the superimposed dynamic load induced by coal bursts on the support and the initial static load on the supports are larger than their limiting load, which leads to support collapse and eventually causes dynamic failure of the working face. The coal burst in working faces in horizontal sections of SICSs can be prevented by using deep-hole presplit blasting in a hard roof, destress blasting in coal masses, and support optimisation of working faces, showing a favourable preventative effect. [ABSTRACT FROM AUTHOR]

Abstract: In recent years, false smut disease of rice has been one of the most important diseases of cultivated rice in China. Ustilaginoidea virens is an ascomycete fungal pathogen that causes false smut in rice. There is always controversy about whether the pathogen can infect the rice root and cause the occurrence of false smut, mainly due to lack direct cytological evidence. In our study, we observed the cytological structure of rice root invaded by U. virens. The results showed that U. virens could attach to the surface of young roots and penetrate into the intercellular space of the root epidermis. The cellulose microfibrils in root epidermal cell wall are very loose and soft, and their structural features are similar to filaments of rice. After the fungus infected the roots, a large number of fungal secretions were accumulated outside of the cell walls. At 40 days, the fungus began to degrade, but pathogens still had not infected the sclerenchyma, in which the cells are arranged densely and the cell walls are thicker. U. virens could not cross the sclerenchyma layer into the endodermis and phloem of the root. To some extent, the U. virens infection affected the leaf and root growth of the rice. After inoculation, there was no fungal mycelium found in transverse sections of the rice young stem. These results suggested that root colonization of U. virens does not lead to systemic invasion in rice. [ABSTRACT FROM AUTHOR]

Rice false smut is heavily and increasingly occurring in subtropical zones in China in the past decades. The pathogen of the disease, Ustilaginoidea virens, can produce both chlamydospores and sclerotia, and the sclerotia seem to form frequently in temperate or high-altitude regions in China. Which of these structures play a dominant role in the pathogen's life cycle in subtropical zones remains unclear. Here we found that Ustilaginoidea virens could produce a great number of sclerotia in subtropical zones and the maximal number of sclerotia could reach to 2.25 million per hectare. In the year with relatively low autumn temperatures, the disease severity and sclerotia numbers of U. virens increased significantly. Although there was a few sclerotia in subtropical zones capable of overwintering successfully, one individual sclerotium could produce large numbers of ascospores. In the rice-growing paddy field, the ascospores could be trapped in both temperate and subtropical zones in May-September, when rice was at the booting stage, the critical infection period of rice false smut. This suggested that the sclerotia of rice false smut in subtropical zone played an important role in the life cycle of Ustilaginoidea virens and acted as the primary inoculum. Experiments in the laboratory showed that mature sclerotia of rice false smut remained dormant for about 2-5 months, and that light was essential for fruiting body differentiation. As with ergot, the fruiting bodies of Ustilaginoidea virens secreted sticky droplets on the stromata that prevented the ascospores from dispersing into the air, implying that the transfer of ascospores of Ustilaginoidea virens to rice plants in paddy field needed an intermediary vector. [ABSTRACT FROM AUTHOR]

14-3-3 Proteins are a family of highly conserved regulatory molecules expressed in all eukaryotic cells and regulate a diverse set of biological responses in plants. However, their functions in flowering of Phyllostachys violascens are poorly understood. In this study, four non∈ Pv14-3-3 genes from P. violascens were identified and named PvGF14b, PvGF14c, PvGF14e, and PvGF14f. qRT-PCR analyses revealed that PvGF14b and PvGF14e exhibited widely expressed in all tested bamboo tissues. PvGF14b was highest expression in root and lowest in immature leaf. Whereas PvGF14c and PvGF14f showed tissue-specific expression. PvGF14c was mainly expressed in immature and mature leaves. PvGF14f was highest expression in mature leaves. These four genes were not significantly differentially expressed in mature leaf before bamboo flowering and during flower development. PvGF14b and PvGF14c were not induced by circadian rhythm. PvGF14c displayed subcellular localization in the cytoplasm and PvFT in nucleus and cytoplasm. Yeast two-hybrid screening and bimolecular fluorescence complementation confirmed the interaction between PvGF14c and PvFT. The overexpression of PvGF14b, PvGF14c, and PvGF14e significantly delayed flowering time in transgenic Arabidopsis under long-day condition. These findings suggested that at least three PvGF14 genes are involved in flowering and may act as a negative regulator of flowering by interacting with PvFT in bamboo. [ABSTRACT FROM AUTHOR]