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Biomass-derived dynamic covalent thermoset has been considered as a promising solution to the high dependence on fossil resources and the difficulty in recyclability after curing of conventional bisphenol A epoxy resins. However, the design and preparation of a dynamic covalent biobased epoxy thermoset with both comparable thermal and mechanical performances to bisphenol A epoxy resins and reprocessibility remains a significant challenge. Herein, based on imine chemistry, a novel Schiff base-containing dynamic covalent epoxy thermoset was facilely fabricated from biobased protocatechualdehyde and synthetic siloxane diamine. Due to the more reactive epoxides in the epoxy monomer than in bisphenol A epoxy oligomer, the thermoset exhibited a high cross-linking density, resulting in high thermal stability and glass transition temperature. The rigid aromatic Schiff base moieties endowed the thermoset with excellent mechanical properties: thanks to the plasticization of the flexible siloxane, the thermoset displayed high impact strength. Meanwhile, owing to the high segmental mobility, the fast exchange of imine bonds was guaranteed; and the thermoset was able to be recycled through reprocessing. Taking these features, this work provided great potential for designing and preparing sustainable substitutes for bisphenol A epoxy resins in the high-performance applications.

A new metal-organic framework {(Me2NH2)2[Co3(μ3-O)(btb)2(py)(H2O)]·(DMF)2(H2O)2}n (Cobtbpy) was solvothermal synthesized (H3btb = 1,3,5-tri(4-carboxylphenyl)benzene, py = pyridine, DMF = N,N-dimethylformamide). Cobtbpy shows a (3,6)-connected rtl 3D network with a point symbol of (4·62)2(42·610·83) based on the [Co3(μ3-O)] clusters. The obtained Cobtbpy has stable, accessible, dense active sites and can be applied in the potassium- and sodium-ion batteries. Through mixing with single-walled carbon nanotubes, the prepared composite anode material Cobtbpy-0.9 achieved a high reversible capability, delivering 416 mAh/g in the potassium-ion batteries and 379 mAh/g in the sodium-ion batteries at 0.05 A/g. The outstanding properties of Cobtbpy-0.9 in the batteries demonstrated that this MOFs-based carbon composite is a highly desirable electrode material candidate for high-performance potassium- and sodium-ion batteries.

Background The toxicity and inefficient delivery of triptolide (TPL) in tumor therapy have greatly limited the clinical application. Thus, we fabricated a CD44-targeting and tumor microenvironment pH/redox-sensitive nanosystem composed of hyaluronic acid-vitamin E succinate and poly (β-amino esters) (PBAEss) polymers to enhance the TPL-mediated suppression of breast cancer proliferation and lung metastasis. Results The generated TPL nanoparticles (NPs) had high drug loading efficiency (94.93% ± 2.1%) and a desirable average size (191 nm). Mediated by the PBAEss core, TPL/NPs displayed a pH/redox-dual-stimuli-responsive drug release profile in vitro. Based on the hyaluronic acid coating, TPL/NPs exhibited selective tumor cellular uptake and high tumor tissue accumulation capacity by targeting CD44. Consequently, TPL/NPs induced higher suppression of cell proliferation, blockage of proapoptotic and cell cycle activities, and strong inhibition of cell migration and invasion than that induced by free TPL in MCF-7 and MDA-MB-231 cells. Importantly, TPL/NPs also showed higher efficacy in shrinking tumor size and blocking lung metastasis with decreased systemic toxicity in a 4T1 breast cancer mouse model at an equivalent or lower TPL dosage compared with that of free TPL. Histological immunofluorescence and immunohistochemical analyses in tumor and lung tissue revealed that TPL/NPs induced a high level of apoptosis and suppressed expression of matrix metalloproteinases, which contributed to inhibiting tumor growth and pulmonary metastasis. Conclusion Collectively, our results demonstrate that TPL/NPs, which combine tumor active targeting and pH/redox-responsive drug release with proapoptotic and antimobility effects, represent a promising candidate in halting breast cancer progression and metastasis while minimizing systemic toxicity. Graphic Abstract

High Mountain Asia glaciers are currently ignored in the estimation of global greenhouse gas budgets (e.g., methane (CH4) and carbon dioxide (CO2)). Similar to the Asian Water Tower and Third Pole, the Tibetan Plateau (TP) hosts the largest volume of glaciers outside the polar regions. These glaciers contain large reservoirs of organic carbon that can influence glacial ecosystems under rapid melting. However, no data exist on the current footprint of CH4 and CO2 from glaciers in the TP. Here, we report in situ observations of CH4 and CO2 fluxes for glacial cryoconite holes, subglacial sediments, and proglacial river runoff across the TP. Our results indicate that cryoconite holes and subglacial sediments can accelerate the export of greenhouse gasses during the melting season due to intensive glacier melting. However, to some extent, proglacial river runoff can be a significant sink of atmospheric CO2; this fact was not identified in previous studies. Our findings suggest that variations (source or sink) of greenhouse gasses from TP glacial basins should be considered in regional CH4 and CO2 budgets under climate warming.

Epoxidized soybean oil (ESO)-based thermosets are attracting increasing attention because they are derived from renewable resources. To date, unfortunately, they have not been able to replace petroleum-based epoxy resins yet due to their poor mechanical properties and unsatisfactory thermal performances. To address the drawbacks, quercetin (QC) as a biobased polyphenol-type curing agent was chosen to increase the rigidity of ESO-QC thermosets. Meanwhile, three imidazole-type accelerators, including N-methylimidazole (N-MI), 4-methylimidazole (4-MI), and biobased histidine (His), were introduced to reduce the activation energy during curing and to tailor the network structures after curing. All ESO-QC thermosets possessed excellent thermal stabilities, thanks to the high rigidity and cross-linking density, among which the initial decomposition temperature of ESO-QC/His was up to 348 °C. Due to the different topological structures of ESO-QC thermosets resulted from different catalytic mechanisms of N-MI and 4-MI, superior tensile and flexural strengths of 44.7 and 81.8 MPa were obtained in ESO-QC/4-MI thermosets, respectively, while the ESO-QC/N-MI thermosets displayed outstanding tensile modulus of 1058 MPa, which could rarely be discovered in biobased systems. In addition, the Izod unnotched impact strength of ESO-QC/His thermosets reached 23.5 kJ·m–2, which was even higher than that of the commercial petroleum-based epoxy resins. These features provide great potential for the sustainable polymers for versatile applications.

A sensitive high-performance liquid chromatography–tandem mass spectrometry method was established for the simultaneous determination of sildenafil and N-desmethyl sildenafil in human plasma. The protein precipitation was used for extraction and the gradient elution of the mobile phase A of water (containing 0.01% formic acid) and the mobile phase B of acetonitrile, and methanol (V:V = 1:1, containing 0.01% formic acid) was used for chromatographic separation on a C18 column. Quantification was performed by multiple reaction monitoring mode to monitor the precursor-to-product ion transitions of m/z 475.4 → m/z 283.3 for sildenafil, m/z 461.4 → m/z 283.2 for N-desmethyl sildenafil, m/z 483.3 → m/z 108.1 for sildenafil-d8 (IS) and m/z 469.2 → m/z 283.3 for N-desmethyl sildenafil-d8 (IS) at the positive ionization mode. The intra- and inter-day relative standard deviations were less than 6.8% and 4.1% for sildenafil and N-desmethyl sildenafil, respectively. Accuracy at four levels ranged from 93.1% to 115.9% for sildenafil and 95.6% to 112.5% for N-desmethyl sildenafil. The present method was sensitive and reliable for simultaneous quantification of sildenafil and its active metabolite and was successfully applied to a pharmacokinetic study of an oral low dose of sildenafil in Chinese healthy volunteers.

Molecularly imprinted polymers (MIPs) have attracted tremendous attention as potential materials, but the conventional MIPs preparation limits its application. In this study, a novel strategy to synthesize pomegranate‐inspired hollow mesoporous molecularly imprinted nanoparticles (HMMINs) by organic‐organic self‐assembly of dopamine is reported. Benefiting from the unique chemical composition and architecture, the one‐pot synthesized HMMINs not only provide high imprinting efficiency and binding capacity, but possess biocompatibility, photothermal (PT) and sustained release effect, which indicates HMMIPDAs have great potential to be applied as a sorbent to increase the selectivity of analytes from complex matrices, and drug carrier for PT therapy to achieve sustained‐release of the drug.

Objective: Natural extracts, including nobiletin, have been reported to enhance the efficacy and sensitivity of chemotherapeutic drugs. However, whether and how nobiletin affects tumor growth and progression in renal cell carcinoma (RCC) are still unclear. Methods: Cell proliferation, cell cycle and apoptosis analyses, colony-formation assays, immunoblotting analysis, and qRT-PCR analysis were performed to investigate how nobiletin affected RCC cell proliferation in vitro. The nude mouse model was used to test the efficacy of nobiletin alone or in combination with palbociclib. Results: Nobiletin inhibited cell proliferation by inducing G1 cell cycle arrest and cell apoptosis in RCC cells. Mechanistically, nobiletin decreased SKP2 protein expression by reducing its transcriptional level. The downregulated SKP2 caused accumulation of its substrates, p27 and p21, which further inhibited the activity of the G1 phase-related protein, CDK2, leading to inhibition of cell proliferation and tumor formation. A higher SKP2 protein level indicated less sensitivity to the CDK4/6 inhibitor, palbociclib. A combination of nobiletin and palbociclib showed a synergistic tumor inhibition in vitro and in an in vivo model. Conclusions: Nobiletin downregulated the SKP2-p21/p27-CDK2 axis to inhibit tumor progression and showed synergistic tumor inhibition effects with the CDK4/6 inhibitor, palbociclib, on RCC, which indicates a potential new therapeutic strategy.

In this study, a series of new N-aryl-2-(2-hydroxyphenylamino)ethylenediamine derivatives has been designed, synthesized and evaluated for antifungal activity against six selected species of phytopathogenic fungi. Among the products, the most potent compound have demonstrated 97.7% inhibitory activity against S. sclerotiorum at the concentration of 50 μg/mL, which is higher than that of the positive control chlorothalonil.

A new N-cis-coumaroyltyramine derivative, fissistyramine (1), along with four known coumaroyltyramine derivatives (2–5), was isolated from the stems of Fissistigma oldhamii (Hemsl.) Merr. The structure of the new compound 1 was determined by 1D and 2D NMR as well as by HR-ESI-MS. The inhibitory effect of all the compounds on the proliferation of primary synovial cells was evaluated. Compounds 1, 2, and 5 exhibited inhibitory activity on synoviocytes, with IC50 values of 12.1, 13.8, and 15.6 μM.

Background & Aims The nuclear factor of activated T-cells (NFAT) family was first recognised to play an important role in the differentiation of T cells, but has since been shown to regulate multiple pathophysiological processes. However, whether it is involved in the pathogenesis of non-alcoholic steatohepatitis (NASH) remains unknown. Methods Hepatic NFATc expression and localisation were analysed in C57BL/6 mice on a methionine–choline-deficient diet, as well as in samples from non-alcoholic fatty liver disease patients. Gain- or loss-of-function approaches were used to investigate the role of NFATc4 in NASH. Results NFATc4 translocates from the cytoplasm to the nucleus in hepatocytes of both humans and rodents with NASH. NFATc4 knockdown resulted in decreased hepatic steatosis, inflammation, and fibrosis during NASH progression. Mechanistically, we found that activated NFATc4 directly bound to peroxisome proliferator-activated receptor α (PPARα) in the nucleus and negatively regulated its transcriptional activity, thereby impairing the hepatic fatty acid oxidation pathway and increasing lipid deposition in the liver. Moreover, NFATc4 activation increased the production and secretion of osteopontin (OPN) from hepatocytes, which subsequently enhanced the macrophage-mediated inflammatory response and hepatic stellate cell-mediated fibrosis progression via paracrine signalling. Conclusions Hepatic NFATc4 activation accelerates the progression of NASH by suppressing PPARα signalling and increasing OPN expression. Genetic or pharmacological inhibition of NFATc4 may have potential for future therapy of NASH. Lay summary NFATc4 is activated in the non-alcoholic steatohepatitis of mice and patients. Inhibition of NFATc4 activation alleviates lipid deposition, inflammatory response, and fibrosis progression in the liver.

Precise gene editing of model organisms is required for accurately modeling human diseases and deciphering gene functions. In this study, we used a pair of guide RNAs (sgRNAs), which in vitro transcribed along with other CRISPR RNA components, to generate two cleavage sites flanking pig GJB2 (pGJB2) CDS. By using long single-stranded DNAs (lssDNA) as homology-directed repair (HDR) templates, we efficiently obtained two gene-edited pigs, of which GJB2 CDS replaced with CDSs containing human GJB2 c.235delC mutation and orthologous human p.V37I mutation, respectively. These mutations were commonly observed in patients with hearing loss. Genetic analysis of the two gene-edited pigs showed that the HDR-derived gene-editing efficiency were as high as 80% (4/5) and 50% (2/4), respectively. While no mutation was observed in the group of single cutting with one sgRNA covering the 235th nucleotide C in pGJB2 CDS, using a short single-stranded oligo DNA containing c.235delC mutation as HDR template. Extra experiments proved that the intended mutations were successfully transmitted to offspring or extensively integrated into various tissues including gonad of founder pigs. Our work indicated that the new "double cutting with lssDNA template" gene editing method can expand sgRNA selection scope and avoids direct cutting of gene CDS. Additionally, can introduce precise mutations into mammalian genomic sites, especially those with unavailable proper protospacer sequence or being resistant to gene editing. Moreover, this method can be performed with CRISPR RNA reagents instead of CRISPR ribonucleoproteins applied in previous reports.

SUMOylation has long been recognized to regulate multiple biological processes in pancreatic beta cells, but its impact on proinsulin disulfide maturation and endoplasmic reticulum (ER) stress remains elusive. Herein, we conducted comparative proteomic analyses of SUMOylated proteins in primary mouse/human islets following proinflammatory cytokine stimulation. Cytokine challenge rendered beta cells to undergo a SUMOylation turnover manifested by the changes of SUMOylation substrates and SUMOylation levels for multiple substrates. Our data support that SUMOylation may play a crucial role to regulate proinsulin misfolding and ER stress at least by targeting Protein Disulfide Isomerase a3 (Pdia3). SUMOylation regulates Pdia3 enzymatic activity, subcellular localization, and protein binding ability. Furthermore, SUMOylation of Pdia3 exacerbated proinsulin misfolding and ER stress, and repressed Stat3 activation. In contrast, disruption of Pdia3 SUMOylation markedly rescued the outcomes. Collectively, our study expands the understanding how SUMOylation regulates ER stress in beta cells, which shed light on developing potential strategies against beta cell dysfunction., SCOPUS: ar.j, info:eu-repo/semantics/published

Localized surface plasmon resonance (LSPR) based nano-plasmonic biosensors have attracted great attentions due to rapid detection and label-free capability. Aiming to obtain a high performance LSPR...

Aims Global change factors (e.g. warming and nitrogen deposition) may influence biological invasions, but how these factors may influence the performance of invasive species and further mediate the interactions with native competitors remain still unknown. Methods Here, we conducted a 5-month greenhouse experiment to examine the effects of warming (using open-top chambers, +0.62°C) and N addition (adding NH4NO3 at a rate of 4.2 g m−2) on the performance of the native and invasive populations of an invasive species Plantago virginica in competition with a native Plantago asiatica. Important Findings Under warming treatment and its interaction with nitrogen addition treatment (W × N), invasive and native populations of P. virginica had different biomass allocation strategies to compete with native competitor P. asiatica. Native population of P. virginica (PV-Na) increased more below-ground biomass, whereas those from the invasive population (PV-In) increased more above-ground biomass. We also found that invasive species P. virginica had stronger responses to warming and N addition than the native species P. asiatica. The competitive ability of the invasive plants was significantly reduced by warming which indicated that the invasive plant were much stronger sensitivity to elevated temperature than native plant. Similarly, N addition and W × N reduced the competitive response of PV-In in below-ground biomass, but increased the competitive response of PV-Na in above-ground and total biomass when they grew with the P. asiatica. The results show that P. virginica have occurred differential biomass allocation strategies during its invasions and invasive population exhibit flexible competition ability to adapt to environmental changes (especially warming). These findings may potentially help to predict plant invasions and make management strategies in a world with changing climate.

Electrochemical nitrogen fixation techniques have emerged as a promisingly sustainable approach to face the challenge associated with nitrogen activation of ammonia synthesis by the Haber-Bosch process under ambient conditions. Herein, the performance of electrocatalytic nitrogen reduction for the production of α-Fe2 O3 nanospindles coated with mesoporous TiO2 with different crystallinity [denoted as α-Fe2 O3 @mTiO2 -X (X=300, 400, and 500 °C)] were investigated. The as-prepared α-Fe2 O3 @mTiO2 -400 composite exhibits a large NH3 yield (27.2 μg h-1 mgcat.-1 ) at -0. 5 V vs. the reversible hydrogen electrode and a high Faradaic efficiency (13.3 %) in 0.1 m Na2 SO4 , with excellent electrochemical durability. This work presents a novel avenue for the rational design of efficient unique hetero-phase nanocatalysts toward sustainable electrocatalytic N2 fixation.

As the power supply of the prosperous new energy products, advanced lithium ion batteries (LIBs) are widely applied to portable energy equipment and large-scale energy storage systems. To broaden the applicable range, considerable endeavours have been devoted towards improving the energy and power density of LIBs. However, the side reaction caused by the close contact between the electrode (particularly the cathode) and the electrolyte leads to capacity decay and structural degradation, which is a tricky problem to be solved. In order to overcome this obstacle, the researchers focused their attention on electrolyte additives. By adding additives to the electrolyte, the construction of a stable cathode-electrolyte interphase (CEI) between the cathode and the electrolyte has been proven to competently elevate the overall electrochemical performance of LIBs. However, how to choose electrolyte additives that match different cathode systems ideally to achieve stable CEI layer construction and high-performance LIBs is still in the stage of repeated experiments and exploration. This article specifically introduces the working mechanism of diverse electrolyte additives for forming a stable CEI layer and summarizes the latest research progress in the application of electrolyte additives for LIBs with diverse cathode materials. Finally, we tentatively set forth recommendations on the screening and customization of ideal additives required for the construction of robust CEI layer in LIBs. We believe this minireview will have a certain reference value for the design and construction of stable CEI layer to realize desirable performance of LIBs.

Supercritical CO2 appearing as bubbles in hydrothermal vents was identified in the south part of the Okinawa Trough using in situ Raman spectroscopy. Significantly, the N2 peak in supercritical CO2 is much larger than those in seawater and vent fluids, indicating that supercritical CO2 enriches N2 from the surrounding environment. Considering that the partial pressures of CO2 and N2 in the Earth’s proto-atmosphere were ~10–20 MPa, supercritical CO2 with high N2 was likely the dominant CO2 phase near the water-air interface in the early history of the Earth, which promoted the synthesis, pre-enrichment and preservation of amino acids and other organic matters that are essential to the origin of life.

Nano coir cellulose whiskersare materials abstracted from mesocarp of coconut shell which was modified by using KH570 as a coupling agent and modified nano coir cellulose whiskers need to be dispersed in chitosan/polyvinyl alcohol (CS/PVA) mixture solution. Because of regular structure and high crystallinity, nano coir cellulose whiskers could be applied in medical materials.In this paper, the results obtained with solution casting method by characterizing and analyzing structure, thermal properties, crystallization behavior and morphology of nano coir cellulose whiskers enhanced CS/PVA composite filmby FTIR, DSC, TG, XRD and SEM test. Different content of modified nano coir whiskers and CS/PVA composite film were preparedand themechanical properties of the composite film were also conducted. The results show that the tensile strength and Young's modulus of the CS/PVA composite film with modified nano coir whiskers are significantly improved, and Elongation break increases at first and then decreases, which indicates nano coir cellulose whiskers are good materials for medical purpose.

Heterogeneous magnesium matrix nanocomposites (Hetero-Mg-NCs) exhibited excellent strength-toughness synergy, but their damage behavior and toughness mechanism lacked of investigation. Here, atomic force microscopy was first employed to characterize the microstructure evolution and damage behavior of the Hetero-Mg-NCs after indentation. The heterogeneous structure comprised of pure Mg areas (soft phase) and Mg nanocomposite areas (hard phase) was revealed by the electrostatic force microscopy. Furthermore, the surface morphology and cracks of the deformed area were investigated with high resolution. The results indicated the soft phase undertook most of the deformation and played an important role in capturing and blunting the crack.

The objective of this project was to find a bronchodilatory compound from herbs and clarify the mechanism. We found that the ethanol extract of Folium Sennae (EEFS) can relax airway smooth muscle (ASM). EEFS inhibited ASM contraction, induced by acetylcholine, in mouse tracheal rings and lung slices. High-performance liquid chromatography assay showed that EEFS contained emodin. Emodin had a similar reversal action. Acetylcholine-evoked contraction was also partially reduced by nifedipine (a selective inhibitor of L-type voltage-dependent Ca2+ channels, LVDCCs), YM-58483 (a selective inhibitor of store-operated Ca2+ entry, SOCE), as well as Y-27632 (an inhibitor of Rho-associated protein kinase). In addition, LVDCC- and SOCE-mediated currents and cytosolic Ca2+ elevations were inhibited by emodin. Emodin reversed acetylcholine-caused increases in phosphorylation of myosin phosphatase target subunit 1. Furthermore, emodin, in vivo, inhibited acetylcholine-induced respiratory system resistance in mice. These results indicate that EEFS-induced relaxation results from emodin inhibiting LVDCC, SOCE, and Ca2+ sensitization. These findings suggest that Folium Sennae and emodin may be new sources of bronchodilators.

Leptolyngbya boryana (L. boryana) is a typical filamentous cyanobacterium that is widely distributed in aquatic ecosystems and is considered to play an important role in the arsenic biogeochemical cycle. Our results showed that L. boryana resisted arsenite (As(III)) and arsenate (As(V)) concentrations up to 0.25 mM and 5 mM, respectively. When exposed to 100 μM As(III) or As(V) for 4 weeks, L. boryana accumulated as much arsenic as 570.0 mg kg−1 and 268.5 mg kg−1, respectively. After the 4-week exposure to As(III) and As(V), organoarsenicals including dimethylarsenate (DMAs(V)) and oxo-arsenosugar-phosphate (Oxo-PO4) were detected in the cells of L. boryana, while inorganic arsenic, especially As(V), was still the main species in both the cells and medium. Furthermore, arsenic oxidation was observed to be solely caused by L. boryana cells and was considered the dominant detoxification pathway. In conclusion, due to its powerful arsenic accumulation, biotransformation, and detoxification abilities, L. boryana might play an important role in arsenic remediation in aquatic environments.

In the original published version of the article, the red squares in the figures which indicated the corrections.

The effects of nonuniform moving plasma on the polarization properties of electromagnetic (EM) waves were theoretically studied. Taking the ${L}$ -band right-hand circularly polarized (RHCP) wave as an example, based on the nonuniform moving plasma slab moving perpendicularly to the incident wave, the relationship between the polarization properties of the transmitted wave and the normalized velocity of the nonuniform plasma slab was analyzed. The results indicate that the polarization state of the transmitted wave is closely related to the normalized velocity of the nonuniform plasma slab. When the plasma slab approaches to the incident wave, its influence on the polarization properties is greater than that away from the incident wave. In addition, when the change of the polarization state reaches the maximum, the corresponding normalized velocity is mainly determined by the incident angle and the collision frequency. Various interesting features regarding polarization properties were obtained. The results are very important for applications in space exploration.

Electrochemical conversion of N2 to NH3 under ambient conditions is a promising and environmentally friendly route compared with the CO2-emitting and energy-intensive Haber-Bosch process. Nevertheless, due to ultrahigh stability of N2, it is urgent to explore efficient catalysts to weaken and activate the N≡N bond. Here, we report the Mo-doped iron phosphide (Mo-FeP) nanosphere as a valid transition-metal-based catalyst for electrochemical N2-to-NH3 fixation under ambient conditions. This catalyst exhibits excellent catalytic performance with a NH4+ yield rate (13.1 μg h-1 mg-1) and Faradaic efficiency (7.49%) at -0.3 and -0.2 V vs reversible hydrogen electrode (RHE), respectively. However, the FeP catalyst without doped Mo species displays weak catalytic performance. We found that the better catalytic performance of Mo-FeP might be due to the doping of Mo species, which is favorable for the polarization of adsorbed N2 molecules, making the N≡N bond more viable to dissociate.

As an important chemokine receptor, the role of CX3CR1 has been studied extensively on the migration of lymphocytes including T and B cells. Although CX3CR1+ B cells have immune suppressor properties, little is known about its role on the regulation of BCR signaling and B cell differentiation as well as the underlying molecular mechanism. We have used CX3CR1 KO mice to study the effect of CX3CR1 deficiency on BCR signaling and B cell differentiation. Interestingly, we found that proximal BCR signaling, such as the activation of CD19, BTK and SHIP was reduced in CX3CR1 KO B cells upon antigenic stimulation. However, the activation of mTORC signaling was enhanced. Mechanistically, we found that the reduced BCR signaling in CX3CR1 KO B cells was due to reduced BCR clustering, which is caused by the enhanced actin accumulation by the plasma membrane via increased activation of WASP. This caused an increased differentiation of MZ B cells in CX3CR1 KO mice and an enhanced generation of plasma cells (PC) and antibodies. Our study shows that CX3CR1 regulates BCR signaling via actin remodeling and affects B cell differentiation and the humoral immune response.

Background Rice ratooning has traditionally been an important component of the rice cropping system in China. However, compared with the rice of the first harvest, few studies on factors effecting ratoon rice yield have been conducted. Because ratoon rice is a one-season rice cultivated using axillary buds that germinate on rice stakes and generate panicles after the first crop’s harvest, its production is mainly affected by the growth of axillary buds. The objectives of this study were to evaluate the sprouting mechanism of axillary buds to improve the ratoon rice yield. Results First, we observed the differentiation and growth dynamics of axillary buds at different nodes of Shanyou 63, and found that they differentiated from bottom to top before the heading of the mother stem, and that they developed very slowly. After heading they differentiated from top to bottom, and the ones on the top, especially the top 2nd node, developed much faster than those at the other nodes. The average length and dry weight of the axillary buds were significantly greater than those at other nodes by the yellow ripe stage, and they differentiated into pistils and stamens by 6 d after the yellow ripe stage. The morphology of vegetative organs from regenerated tillers of Shanyou 63 also suggested the superior growth of the upper buds, which was regulated by hormones, in ratoon rice. Furthermore, a comprehensive proteome map of the rice axillary buds at the top 2nd node before and after the yellow ripe stage was established, and some proteins involved in steroid biosynthesis were significantly increased. Of these, four took part in brassinosteroid (BR) biosynthesis. Thus, BR signaling may play a role in the germination of axillary buds of ratoon rice. Conclusions The data provide insights into the molecular mechanisms underlying BR signaling, and may allow researchers to explore further the biological functions of endogenous BRs in the germination of axillary buds of ratoon rice.

It is important to effectively reduce carbon emissions and ensure the simultaneous adjustment of economic development and environmental protection. Therefore, we used Kaya identity to screen the factors influencing carbon emissions and conducted preliminary qualitative analyses, including grey relation analysis and linear regression analysis, on important variables to establish a vector autoregression (VAR) model based on their annual data to empirically analyze the influencing factors of carbon emissions. The results showed that economic growth effect, energy intensity effect and embodied carbon in foreign trade were the key factors affecting carbon emissions, among which the economic growth effect contributed the most. Accordingly, we propose countermeasures including technological innovation to reduce energy intensity, the development of new energy sources to improve energy structure, acceleration of industrial structure transfer, and optimization of trade structure.

Pancreatic beta cell failure is the hallmark of type 1 diabetes (T1D). Recent studies have suggested that pathogen recognizing receptors (PRRs) are involved in the survival, proliferation and function of pancreatic beta cells. So far, little is known about the role of alpha-protein kinase 1 (ALPK1), a newly identified cytosolic PRR specific for ADP-β-D-manno-heptose (ADP-heptose), in beta cell survival. In current study we aimed to fill the knowledge gap by investigating the role of Alpk1 in the apoptosis of MIN6 cells, a murine pancreatic beta cell line. We found that the expression of Alpk1 was significantly elevated in MIN6 cells exposed to pro-inflammatory cytokines, but not to streptozotocin, low-dose or high-dose glucose. Activation of Alpk1 by ADP heptose alone was insufficient to induce beta cell apoptosis. However, it significantly exacerbated cytokine-induced apoptosis in MIN6 cells. Mechanistic investigations showed that Alpk1 activation was potent to further induce the expression of tumor necrosis factor (TNF)-α and Fas after cytokine stimulation, possibly due to enhanced activation of the TIFA/TAK1/NF-κB signaling axis. Treatment of GLP-1 receptor agonist decreased the expression of TNF-α and Fas and improved the survival of beta cells exposed to pro-inflammatory cytokines and ADP heptose. In summary, our data suggest that Alpk1 sensitizes beta cells to cytokine-induced apoptosis by potentiating TNF-α signaling pathway, which may provide novel insight into beta cell failure and T1D development.

Physical review letters : PRL 127(15), 021101 (2021). doi:10.1103/PhysRevLett.127.021101, Published by American Physical Society, College Park, Md.

The accurate measurements of the galactic cosmic ray (GCR) fluxes as function of time and energy by the Alpha Magnetic Spectrometer (AMS) give us unique information to study the dynamics of solar modulation. To reproduce the observed data, a 3D time-dependent numerical model is established. The input parameters in the model (solar wind speed, tilt angle, magnetic intensity and polarity) are obtained by the observation near the Earth at the right time. The time varying parameters (diffusion coefficient, drift coefficient) is constrained by the proton and helium spectrum pair and obtained by Markov Chain Monte Carlo (MCMC) method. With the obtained coefficients, the proton and helium spectrum pair are reproduced with normalized mainly less than 1. Finally, the time variations of He/P at rigidity of 2.035 GV (fit well with AMS-02 observation) and 0.5 GV are studied. They show different behavior: The former one is mainly caused by the dependence of modulation on particle’s mass-to-charge ratio, the latter one is mainly caused by the difference of particle's local interstellar spectrum.

8-Shaped copolymers with two macrocycles connected together represent an interesting cyclic topology-derived polymer species due to the simultaneous incorporation of two cyclic moieties and the reported unique physical and chemical properties. To provide a proof-of-concept for a broad readership on biomedical polymers, a well-defined hetero-8-shaped amphiphilic copolymer, cyclic-poly(oligo(ethylene glycol)monomethyl ether methacrylate)-b-cyclic PCL (cPOEGMA-b-cPCL) is synthesized by an elegant integration of intrachain click cyclization and interchain click coupling. The potential of the self-assembled micelles of cPOEGMA-b-cPCL for controlled drug release is evaluated by in vitro drug loading and drug release, cellular uptake, cytotoxicity, and degradation studies. Most importantly, the micelles based on cPOEGMA-b-cPCL show much slower degradation profiles than the previously reported linear counterpart, POEGMA-b-PCL and tadpole-shaped analog, PEG-b-cPCL because of the presence of cyclic hydrophilic POEGMA segment. Therefore, this study not only develops a robust strategy for a universal precise synthesis of well-defined hetero-8-shaped copolymers based on diverse vinyl and ring-structured monomers, but also reveals the first modulation of polymer degradation property by topological control of the nondegradable moiety in the polymer construct through advanced macromolecular engineering.

In this study, Corydalis yanhusuo extract acts as a green inhibitor for J55 steel in 3.5% NaCl solution saturated with CO2. Rapid resolution liquid chromatography shows the concentrations of Palmatine to be 0.6358 g/L, Tetrahydropalmatine 0.7715 g/L, and Corydaline 0.3755 g/L. Potentiodynamic polarization results suggest that Corydalis yanhusuo extract is a mixed-type inhibitor. The inhibition efficiency of Corydalis yanhusuo extract increases with the increase of concentration and reaches 92.36% at 5%v/v but decrease with the increased temperature. The inhibition efficiency is 69% at 80°C. The protective film formed on the metal surface was confirmed by Fourier transforms infrared spectroscopy, UV–visible, scanning electrochemical microscope and scanning electron microscope methods. The quantum chemical calculations predicate that Palmatine acts as the major component for inhibition performance.

Efficient and convenient one-pot, three-component reactions of pyrrolidone, aromatic aldehydes and 1-phenyl-3-trifluoromethyl-5-pyrazolone afforded highly functionalized trifluoromethylated pyrazol-4-ylpyrrole-2,5-dione derivatives in good yields. The effect of solvents on the reaction efficiency and yield was briefly investigated. The structures of products were determined by spectral methods and X-ray diffraction analysis. The latter showed that the products formed have a strong intramolecular hydrogen bond, which made them particularly stable and the corresponding annulated products were not obtained by treatment with dehydrating reagents.

The efficacy of Fluorouracil (FU) in the treatment of colorectal cancer (CRC) is greatly limited by drug resistance. Autophagy has been implicated in chemoresistance, but the role of selective autophagic degradation in regulating chemoresistance remains unknown. In this study, we revealed a critical role of ABHD5 in charging CRC sensitivity to FU via regulating autophagic uracil yield. We demonstrated that ABHD5 localizes to lysosome and interacts with PDIA5 to prevent PDIA5 from interacting with RNASET2 and inactivating RNASET2. ABHD5 deficiency releases PDIA5 to directly interact with RNASET2 and leave RNASET2 in an inactivate state, which impairs RNASET2-mediated autophagic uracil yield and promotes CRC cells to uptake FU as an exogenous uracil, thus increasing their sensitivity to FU. Our findings for the first time reveal a novel role of ABHD5 in regulating lysosome function, highlighting the significance of ABHD5 as a compelling biomarker predicting the sensitivity of CRCs to FU-based chemotherapy., The mechanisms underlying differential chemotherapeutic response to 5-fluorouracil are not fully known. Here, the authors show that ABDH5 regulates sensitivity to 5-fluorouracil in colorectal cancer by regulating lysosome function.

Mounting evidence has illustrated the vital roles of long non‐coding RNAs (lncRNAs in gastric cancer (GC). Nevertheless, the majority of their roles and mechanisms in GC are still largely unknown. In this study, we investigate the roles of lncRNA SLC25A5‐AS1 on tumourigenesis and explore its potential mechanisms in GC. The results showed that the expressions of SLC25A5‐AS1 in GC were significantly lower than that of adjacent normal tissues, which were significantly associated with tumour size, TNM stage and lymph node metastasis. Moreover, SLC25A5‐AS1 could inhibit GC cell proliferation, induce G1/G1 cell cycle arrest and cell apoptosis in vitro, as well as GC growth in vivo. Dual‐luciferase reporter assay confirmed the direct interaction between SLC25A5‐AS1 and miR‐19a‐3p, rescue experiment showed that co‐transfection miR‐19a‐3p mimics and pcDNA‐SLC25A5‐AS1 could partially restore the ability of GC cell proliferation and the inhibition of cell apoptosis. The mechanism analyses further found that SLC25A5‐AS1 might act as a competing endogenous RNAs (ceRNA), which was involved in the derepression of PTEN expression, a target gene of miR‐19a‐3p, and regulate malignant phenotype via PI3K/AKT signalling pathway in GC. Taken together, this study indicated that SLC25A5‐AS1 was down‐regulated in GC and functioned as a suppressor in the progression of GC. Moreover, it could act as a ceRNA to regulate cellular behaviours via miR‐19a‐3p/PTEN/PI3K/AKT signalling pathway. Thus, SLC25A5‐AS1 might be served as a potential target for cancer therapeutics in GC.

Azithromycin (AZM) has been used for the treatment of asthma and chronic obstructive pulmonary disease (COPD); however, the effects and underlying mechanisms of AZM remain largely unknown. The effects of AZM on airway smooth muscles (ASMs) and the underlying mechanisms were studied using isometric muscle force measurements, the examination of lung slices, imaging, and patch-clamp techniques. AZM completely inhibited acetylcholine (ACH)-induced precontraction of ASMs in animals (mice, guinea pigs, and rabbits) and humans. Two other macrolide antibiotics, roxithromycin and Klaricid, displayed a decreased inhibitory activity, and the aminoglycoside antibiotics penicillin and streptomycin did not have an inhibitory effect. Precontractions were partially inhibited by nifedipine (selective inhibitor of L-type voltage-dependent Ca2+ channels (LVDCCs)), Pyr3 (selective inhibitor of TRPC3 and/or STIM/Orai channels, which are nonselective cation channels (NSCCs)), and Y-27632 (selective inhibitor of Rho-associated kinase (ROCK)). Moreover, LVDCC- and NSCC-mediated currents were inhibited by AZM, and the latter were suppressed by the muscarinic (M) 2 receptor inhibitor methoctramine. AZM inhibited LVDCC Ca2+ permeant ion channels, M2 receptors, and TRPC3 and/or STIM/Orai, which decreased cytosolic Ca2+ concentrations and led to muscle relaxation. This relaxation was also enhanced by the inhibition of Ca2+ sensitization. Therefore, AZM has potential as a novel and potent bronchodilator. The findings of this study improve the understanding of the effects of AZM on asthma and COPD.

Deciphering the molecular and cellular processes involved in foam cell formation is critical to understanding the pathogenesis of atherosclerosis. Interferon regulatory factor 1 (IRF1) was first identified as a transcriptional regulator of type-I interferons (IFNs) and IFN inducible genes. Our study aims to explore the role of IRF1 in atherosclerotic foam cell formation and understand the functional diversity of IRF1 in various cell types contributing to atherosclerosis. Methods: We induced experimental atherosclerosis in ApoE-/-IRF1-/- mice and evaluated the effect of IRF1 on disease progression and foam cell formation. Results: IRF1 expression was increased in human and mouse atherosclerotic lesions. IRF1 deficiency inhibited modified lipoprotein uptake and promoted cholesterol efflux, along with altered expression of genes implicated in lipid metabolism. Gene expression analysis identified scavenger receptor (SR)-AI as a regulated target of IRF1, and SR-AI silencing completely abrogated the increased uptake of modified lipoprotein induced by IRF1. Our data also explain a mechanism underlying endotoxemia-complicated atherogenesis as follows: two likely pro-inflammatory agents, oxidized low-density lipoprotein (ox-LDL) and bacterial lipopolysaccharide (LPS), exert cooperative effects on foam cell formation, which is partly attributable to a shift of IRF1-Ubc9 complex to IRF1- myeloid differentiation primary response protein 88 (Myd88) complex and subsequent IRF1 nuclear translocation. Additionally, it seems that improved function of vascular smooth muscle cells (VSMCs) also accounts for the diminished and more stable atherosclerotic plaques observed in ApoE-/-IRF1-/- mice. Conclusions: Our findings demonstrate an unanticipated role of IRF1 in the regulation of gene expression implicated in foam cell formation and identify IRF1 activation as a new risk factor in the development, progression and instability of atherosclerotic lesions.

In situ-derived boron-doped graphene quantum dots can significantly improve the activity of boron carbide nanosheets for artificial N2 fixation and reduction with superior electrocatalytic activity (NH3 yield: 28.6 μg h−1 mgcat.−1 at −0.45 V vs. RHE; faradaic efficiency: 16.7%), high electrochemical stability, and high selectivity in 0.1 M HCl under ambient conditions.

Temperature influences the physiological processes and ecology of both hosts and endophytes, however, it remains unclear how long noncoding RNAs (lncRNAs) modulate the consequences of temperature-dependent changes in host–pathogen interactions. To explore the role of lncRNAs in culm gall formation induced by the smut fungus Ustilago esculenta in Zizania latifolia, we employed RNA sequencing to identify lncRNAs and their potential cis-targets in Z. latifolia and U. esculenta under different temperatures. In Z. latifolia and U. esculenta, we identified 3194 and 173 lncRNAs as well as 126 and four potential target genes for differentially expressed lncRNAs, respectively. Further function and expression analysis revealed that lncRNA ZlMSTRG.11348 regulates amino acid metabolism in Z. latifolia and lncRNA UeMSTRG.02678 regulates amino acid transport in U. esculenta. The plant defence response was also found to be regulated by lncRNAs and suppressed in Z. latifolia infected with U. esculenta grown at 25 °C, which may result from the expression of effector genes in U. esculenta. Moreover, in Z. latifolia infected with U. esculenta, the expression of genes related to phytohormones was altered under different temperatures. Our results demonstrate that lncRNAs are important components of the regulatory networks in plant-microbe-environment interactions, and may play a part in regulating culm swelling in Z. latifolia plants.

While Cetuximab can be used to treat KRAS wild-type colon cancer cells by targeting EGFR and inhibiting the activation of downstream signaling pathways, it exhibits little therapeutic effect on KRAS mutant colon cancer cells. Natural killer (NK) cells are a class of powerful immune cells with anticancer activities. However, NK cells typically lack inherent tumor targeting abilities. Here, a new method is established to bestow NK-92 cells with tumor targeting abilities by installing cetuximab on the cell surface. Through metabolic glycoengineering, azide groups were introduced onto the surface of NK-92 cells. Bioorthogonal strain promoted the azide-alkyne cycloaddition click reaction of engineered NK-92 cells with alkyne modified cetuximab functionalized NK cells with the antibody. The resulting NK-92 cells were significantly more effective than the parent NK-92 cells in protecting against tumor development in a KRAS mutant mouse tumor model resistant to cetuximab treatment. Thus, NK cell functionalization with antibodies enabled by metabolic glycoengineering is a promising strategy to enhance anticancer immune therapy.