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AIMS Alternaria longipes is a causal agent of brown spot of tobacco, which remains a serious threat to tobacco production. Herein, we established a detection method for A. longipes in tobacco samples based on the principle of time-resolved fluoroimmunoassay, in order to fulfil the requirement of rapid, sensitive and accurate detection in situ. METHODS AND RESULTS A monoclonal antibody against A. longipes was generated, and its purity and titration were assessed using western blot and ELISA. The size of europium (III) nanospheres was measured to confirm successful antibody conjugation. The method described here can detect A. longipes protein lysates as low as 0.78 ng ml-1 , with recovery rates ranging from 85.96% to 99.67% in spiked tobacco. The specificity was also confirmed using a panel of microorganisms. CONCLUSIONS The fluorescent strips allow rapid and sensitive onsite detection of A. longipes in tobacco samples, with high accuracy, specificity, and repeatability. SIGNIFICANCE AND IMPACT OF THE STUDY This novel detection method provides convenience of using crude samples without complex procedures, and therefore allows rapid onsite detection by end users and quick responses towards A. longipes, which is critical for disease control and elimination of phytopathogens.

Soil salinity is a widespread stress in semi-arid forests worldwide, but how to manage nitrogen (N) nutrition to improve plant saline tolerance remains unclear. Here, the cuttings of a widely distributed poplar from central Asia, Populus russikki Jabl., were exposed to either normal or low nitrogen (LN) concentrations for two weeks in semi-controlled greenhouse, and then they were added with moderate salt solution or not for another two weeks to evaluate their physiological, biochemical, metabolites and transcriptomic profile changes. LN-pretreating alleviated the toxicity caused by the subsequent salt stress in the poplar plants, demonstrated by a significant reduction in the influx of Na+ and Cl- and improvement of the K+/Na+ ratio. The other salt-stressed traits were also ameliarated, indicated by the variations of chlorophyll content, PSII photochemical activity and lipid peroxidation. Stress alleviation resulted from two different processes. First, LN pretreatment caused a significant increase of non-structural carbohydrates (NSC), allowed for an increased production of osmolytes and a higher potential fueling ion transport under subsequent salt condition, along with increased transcript levels of the cation/H+ ATPase. Second, LN pretreatment enhanced the transcript levels of stress signaling components and phytohormones pathway as well as antioxidant enzyme activities. The results indicate that early restrictions of N supply could enhance posterior survival under saline stress in poplar plants, which is important for plantation programs and restoration activities in semi-arid areas. This research was supported by Natural Science Foundation of China ( 31770644 and 31270660 ), Project of Innovation research team in Sichuan Education Administration in China (No. 13TD0023 ).

Self-germinated seedlings of Citrus sinensis and C. grandis were supplied with nutrient solution with 0 mM AlCl(3)·6H(2)O (control, −Al) or 1 mM AlCl(3)·6H(2)O (+Al) for 18 weeks. The DW (Dry weights) of leaf, stem, shoot and the whole plant of C. grandis were decreased and the ratio of root DW to shoot DW in C. grandis were increased by Al, whereas these parameters of C. sinensis were not changed by Al. Al treatment dramatically decreased the sulfur (S) content in C. grandis roots and the phosphorus (P) content in both C. sinensis and C. grandis roots. More Al was transported to shoots and leaves in C. grandis than in C. sinensis under Al treatment. Al treatment has more adverse effects on C. grandis than on C. sinensis, as revealed by the higher production of superoxide anion (O(2)(·−)), H(2)O(2) and thiobarbituric acid reactive substace (TBARS) content in C. grandis roots. Via the Illumina sequencing technique, we successfully identified and quantified 12 and 16 differentially expressed miRNAs responding to Al stress in C. sinensis and C. grandis roots, respectively. The possible mechanism underlying different Al tolerance of C. sinensis and C. grandis were summarized as having following aspects: (a) enhancement of adventitious and lateral root development (miR160); (b) up-regulation of stress and signaling transduction related genes, such as SGT1, PLC and AAO (miR477, miR397 and miR398); (c) enhancement of citrate secretion (miR3627); (d) more flexible control of alternative glycolysis pathway and TCA cycle (miR3627 and miR482); (e) up-regulation of S-metabolism (miR172); (f) more flexible control of miRNA metabolism. For the first time, we showed that root development (miR160) and cell wall components (cas-miR5139, csi-miR12105) may play crucial roles in Al tolerance in citrus plants. In conclusion, our study provided a comprehensive profile of differentially expressed miRNAs in response to Al stress between two citrus plants differing in Al tolerance which further enriched our understanding of the molecular mechanism underlying Al tolerance in plants. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12298-020-00895-y) contains supplementary material, which is available to authorized users.

Ionic liquids can be utilized in petroleum science. However, significant attention has been paid to the utilization of ionic liquids in petroleum science by researchers. In this work, the recent development of the utilization of ionic liquids in petroleum science is introduced. First of all, ionic liquids can be utilized as an additive in the oil & gas industry, such as a surfactant, corrosion inhibitor, demulsifier, and dispersant. In addition, ionic liquids can be utilized in the separation process of oil & gas processing. For example, ionic liquids can be utilized to remove naphthenic acids from oils, extract toluene from alkanes, dissolution of asphaltene in oils, extract phenol from model oil, and separate oil mixtures in a combination of membranes. Ionic liquids can also be utilized in novel technology development for enhanced oil recovery, and oil field scale control process. Moreover, utilization of ionic liquids in gasoline desulfurization process is important and crucial, which is greener, lower cost, and safer compared with the traditional processing technology. Furthermore, ionic liquids can be utilized as novel solvents to form micro-emulsion. Some ionic liquids have task-specific functional groups, which can reduce the cost and improve the separation efficiency. The utilization of ionic liquids in the catalysis process of the oil & gas industry is also introduced in this work. In the end, the utilization of ionic liquids in the oil sand treatment process and asphaltene precipitation inhibition process is discussed. This work will benefit the novel environmentally friendly technology development using ionic liquids for oil & gas production and processing.

Recently, lightweight and highly efficient electromagnetic interference (EMI) shielding composites are crucial but changing for the development of modern electronics and telecommunication. Here, a novel polyhedral Co/C particle embedded carbon nanofiber (CNF@Co/C) aerogels were synthesized via pyrolysis of bacterial cellulose wired zeolitic imidazolate frameworks-67 (ZIF-67) aerogel under argon. The flexible CNF@Co/C aerogels exhibit a high EMI shielding effectiveness (SE) is approaching 56.07 dB at a density of only 0.023 g cm−3 in the X band, and the average absorption coefficient is as high as 0.79, indicating 79% of electromagnetic (EM) waves are absorbed in shielding process. The remarkable performance results from the three-dimensional (3D) CNF-threaded porous structure with interconnected network and the magnetic Co/C particle strung by CNF, which contribute to a conduction loss and optimal impedance matching along with multiple polarization and strong magnetic loss. This work paves a promising way for the new generation of electronic device with lightweight and efficient EMI shielding.

Three-dimensional catalysts have attracted great attention in the field of the hydrogen evolution reaction (HER).However, great challenges remain in structural innovation and performance enhancement. Herein we designed and tailored a unique three-dimensional cross-linked neural network-like CoP-based composite, that is, carbon nanofibers inserted in CoP/NC polyhedra derived from in situ self-assembled bacterial cellulose (BC) wired ZIF-67 polyhedra via high-temperature carbonization and subsequent phosphorization. The obtained integrated catalyst (3-D CNF@CoP/NC) consists of CoP/NC polyhedra with abundant active sites as the “neurons” and carbon nanofibers as the “axons”, and displayed remarkable activity with an overpotential of 64.5 mV and 105.6 mV at 10 mA cm−2 in 0.5 M H2SO4 and 1 M KOH respectively and good stability with negligible current change after 80 h of chronoamperometric measurement or 4000 CV cycles. This work offers a high-performance HER catalyst and paves a new way for the rational engineering of unique 3-D interconnected hierarchical porous networks featuring ultrafast charge transfer and mass transport.

Transition metal phosphides (TMPs) demonstrate great potential for hydrogen evolution reaction (HER) electrocatalysis, but their activities need further improvement. Herein we report a novel Au incorporation strategy to boost the HER catalytic performance of CoP. As a proof of concept, heterostructured Au/CoP nanoparticles dispersed on nitrogen-doped carbon with unique porosity, denoted as Au/CoP@NC-3, are synthesized by thermal treatment of Au-nanoparticle-incorporated ZIF-67 precursor. It shows excellent HER activity as well as good durability in acidic and alkaline condition, respectively, greatly outperforming its Au-free analogue, namely, CoP@NC. In-depth analysis suggests that the improved HER activity of Au/CoP@NC-3 is attributed to the presence of Au nanoparticles which enlarge the electrochemical active surface areas and adjust the electronic structure of active CoP species to enhance the water adsorption and optimize H adsorption for the accelerated HER process.

D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS1000) is the most active water-soluble derivative of vitamin E and has been widely used as a carrier of solvents, plasticizers, emulsifiers, absorbent agents and refractory drug delivery systems. However, its anti-hepatocellular carcinoma (HCC) properties have not been explored. HCC cells were treated with different concentrations of TPGS1000. Cell survival was tested by CCK8 assay, and cell migration was tested by wound healing and Transwell assay. EdU staining verified cell proliferation, and signalling pathway was assayed by Western blot analysis. The BALB/c-nu mouse xenograft model was established to test HCC cell growth in vivo. In vitro TPGS1000 significantly inhibited the viability and mobility of HCC cells (HepG2, Hep3B and Huh7) in a dose-dependent manner. Cell cycle analysis indicated that TPGS1000 treatment arrested the HCC cell cycle in the G0/G1 phase, and induction of cell apoptosis was confirmed by TUNEL and Annexin V-7-AAD staining. Further pharmacological analysis indicated that collapse of the transmembrane potential of mitochondria, increased ROS generation, PARP-induced cell apoptosis and FoxM1-p21-mediated cell cycle arresting, were involved in the anti-HCC activity of TPGS1000. Moreover, treatment in vivo with TPGS1000 effectively impaired the growth of HCC xenografts in nude mice.

As a new anode material for sodium-ion batteries (SIBs), VS4 shows impressive energy storage potential due to its unique one-dimensional parallel chain structure, large chain spacing and high sulfur content. Here, poplar flower-like nitrogen-doped carbon nanotube@VS4 composites (NCNt@VS4) with a three-dimensional structure were successfully synthesized via a solvothermal reaction using nitrogen-doped carbon nanotube (NCNt) as a template. The unique three-dimensional structure can enhance the transmission of electrons and sodium ions, conducive to wetting of the electrolyte and buffering the huge volume change. Therefore, NCNt@VS4 delivers excellent sodium storage performance. It presents a reversible capacity of 430 mA h g−1 after 2000 cycles at 1 A g−1, and demonstrates a high initial coulombic efficiency (81.6%). At the same time, the electrode exhibits superior rate-performance (460 mA h g−1 at 5 A g−1) and high ability to tolerate current changes. This work develops a reliable method for the preparation of other 3D NCNt@transition metal sulfide composites, which exhibit great potential as an anode for SIBs.

Biomacromolecule therapeutic systems are intrinsically susceptible to degradation and denaturation. Nanoformulations are promising delivery vehicles for therapeutic biomacromolecules (antibodies, genes and so on). However, their applications in these areas still face many challenges including in vivo stability, premature leakage and accurate tumor recognition. In this study, a generally applicable new strategy for tumor-targeted delivery of biomacromolecules was developed through the hierarchical integration of degradable large-pore dendritic mesoporous silica nanoparticles (dMSNs) and cyclodextrin-modified polyamidoamine (PAMAM-CD) dendrimers. The orifice rim of the dMSNs was modified with ROS-responsive nitrophenyl-benzyl-carbonate (NBC) groups while disulfide-bonded azido ligands were subsequently grafted onto the inner channel walls via heterogeneous functionalization. The PAMAM-CD was then interred into the dendritic pores via click reactions and supramolecularly loaded with archetypal hydrophobic small-molecule anticancer model drug (SN-38) and therapeutic model gene (Bcl-2 siRNA), after which dMSNs were eventually coated with a 4T1 cancer cell membrane (CCM). Experimental evidence demonstrated that the synthesized nanocarriers could efficiently deliver therapeutic cargos to target cancer cells and release them in the tumor cytosol in a cascade-responsive manner. This biomimetic nanoplatform presents a novel strategy to efficiently deliver biomolecular therapeutics in a tumor-targeted manner.

A tumor redox-activatable micellar nanoplatform based on the naturally occurring biomacromolecule hyaluronic acid (HA) was developed for complementary photodynamic/chemotherapy against CD44-positive tumors. Here HA was first conjugated with l-carnitine (Lc)-modified zinc phthalocyanine (ZnPc) via disulfide linkage and then co-assembled with tirapazamine (TPZ) to afford the physiologically stable micellar nanostructure. The mitochondria-targeted photodynamic activity of ZnPc-Lc could efficiently activate the mitochondrial apoptosis cascade and deplete the oxygen in the tumor intracellular environment to amplify the hypoxia-dependent cytotoxic effect of TPZ.

Hydrogen evolution catalysts with effectively integrated structures at different length scales are promising to remarkably boost the efficiency of the hydrogen evolution reaction (HER), but their f...

Heterogeneity in sediment and aquifer is universal, resulting in preferential flows of injected materials in the high permeability regions and forming flow by-passed zones in the low permeability regions during in-situ subsurface remediation. This adverse effect can considerably delay the completion of remedial operations and significantly increase the cost. Column experiments were designed and conducted to study the transport of starch- and starch-xanthan gum modified Fe-Mn binary oxide particles (SFM and SXFM) in saturated heterogeneous porous media and to reveal the particles’ arsenic (As) stabilization performance. Fine-in-Coarse (FIC) and Coarse-in-Fine (CIF) patterns of heterogeneous packings were set up in the columns. Testing results demonstrated that starch-xanthan gum dual treatment on Fe-Mn binary oxides successfully improved the particles’ migration capability in heterogeneous porous media and their distribution uniformity attributed to the profound shear thinning behavior of xanthan gum solution. The addition of xanthan gum to the system increased the viscosity and shear thinning property of the SXFM suspension, making it a better candidate for delivery. Both SFM and SXFM stabilized As in heterogeneously packed sediment collected from a contaminated site, with SXFM showing better stabilization performance than SFM. The stabilization effects of SXFM were 90.7–97.0%, compared to 82.0–95.2% of SFM.

Macrophages play crucial roles in host tissue reaction to biomaterials upon implantation in vivo. However, the complexity of biomaterial degradation-related macrophage subpopulations that accumulate around the implanted biomaterials in situ is not fully understood. Here, using single cell RNA-seq, we analyze the transcriptome profiles of the various cell types around the scaffold to map the scaffold-induced reaction, in an unbiased approach. This enables mapping of all biomaterial degradation-associated cells at high resolution, revealing distinct subpopulations of tissue-resident macrophages as the major cellular sources of biomaterial degradation in situ. We also find that scaffold architecture can affect the mechanotransduction and catabolic activity of specific material degradation-related macrophage subpopulations in an Itgav-Mapk1-Stat3 dependent manner, eventually leading to differences in scaffold degradation rate in vivo. Our work dissects unanticipated aspects of the cellular and molecular basis of biomaterial degradation at the single-cell level, and provides a conceptual framework for developing functional tissue engineering scaffolds in future.

Ferroptosis is a new form of regulated cell death that shows promise for tumor treatment. Most current ferroptosis tumor therapies are based on the intrinsic pathological features of the malignancies, and it would be of clinical significance to develop ferroptosis-inducing strategies with improved tumor specificity and modulability. Here we report a polydopamine-based nanoplatform (FeII PDA@LAP-PEG-cRGD) for the efficient loading of Fe2+ and β-lapachone (LAP), which could readily initiate ferroptosis in tumor cells upon treatment with near-infrared light. PDA nanostructures could generate mild hyperthermia under NIR irritation and trigger the release of the ferroptosis-inducing Fe2+ ions. The NIR-actuated photothermal effect would also activate cellular heat shock response and upregulate the downstream NQO1 via HSP70/NQO1 axis to facilitate bioreduction of the concurrently released β-lapachone and enhance intracellular H2 O2 formation to promote the Fe2+ -mediated lipid peroxidation.

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures of arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cysteines within the DNA-binding domain, distal to the zinc-binding site. Arsenic binding stabilizes the DNA-binding loop-sheet-helix motif alongside the overall β-sandwich fold, endowing p53 mutants with thermostability and transcriptional activity. In cellular and mouse xenograft models, ATO reactivates mutant p53 for tumor suppression. Investigation of the 25 most frequent p53 mutations informs patient stratification for clinical exploration. Our results provide a mechanistic basis for repurposing ATO to target p53 mutations for widely applicable yet personalized cancer therapies.

This work presents a simple, rapid and green chiral analysis method for five triazole fungicides (penconazole, tebuconazole, triadimefon, myclobutanil, and triadimenol) in tobacco, by which the samples were cleaned up by the novel pass-through solid phase extraction and subsequently the stereoisomers were separated and determined by the supercritical fluid chromatography-tandem mass spectrometry (SFC-MS/MS). Optimized separation of the stereoisomers was achieved on an ACQUITY UPC2 Trefoil AMY 1 column within 6 min. Under fortified concentration levels of 0.1, 0.5 and 2.0 mg/kg, the mean recoveries were 82.8-106.6%, the intra-day relative standard deviations (RSDs) were 1.1-6.6%, and the inter-day RSDs were 2.5-5.6%. The correlation coefficient was greater than 0.9926 for all studied analytes within the range of 10-500 ng/mL. The limits of detection (LODs) for all stereoisomers ranged from 0.26 μg/kg to 3.24 μg/kg. The established method was subsequently successfully applied to analyze authentic samples, confirming that this method is a novel, rapid and environmentally friendly method for the stereoselective separation of triazole fungicides in tobacco.

Thermal interface material (TIM) is crucial for heat transfer from a heat source to a heat sink. A high-performance thermal interface material with solid&ndash, solid phase change properties was prepared to improve both thermal conductivity and interfacial wettability by using reduced graphene oxide (rGO)-coated polyurethane (PU) foam as a filler, and segmented polyurethane (SPU) as a matrix. The rGO-coated foam (rGOF) was fabricated by a self-assembling method and the SPU was synthesized by an in situ polymerization method. The pure SPU and rGOF/SPU composite exhibited obvious solid&ndash, solid phase change properties with proper phase change temperature, high latent heat, good wettability, and no leakage. It was found that the SPU had better heat transfer performance than the PU without phase change properties in a practical application as a TIM, while the thermal conductivity of the rGOF/SPU composite was 63% higher than that of the pure SPU at an ultra-low rGO content of 0.8 wt.%, showing great potential for thermal management.

A quick, green, and sensitive method for chiral separation and determination of fluazifop-butyl enantiomers in tobacco and soil was established by ultra-performance convergence chromatography with tandem mass spectrometry (UPC2 -MS/MS). The baseline separation was obtained on an ACQUITY UPC2 Trefoil CEL2 column in 4 minutes with CO2 and methanol as mobile phase. Column temperature, auto back pressure regulator pressure (ABPR), and modifier solvent were optimized to obtain the best separation efficiency. Under the optimal conditions, the recoveries of both enantiomers were 82.8% to 99.5% with relative standard deviations (RSDs) less than 5.5% at three different concentration levels in two matrices. Good coefficients of determination (R2 ≥ 0.9976) were achieved over the concentration range of 10 to 500 ng/mL. The limits of detection (LODs) for all enantiomers in the two matrices varied from 1.6 to 2.1 μg/kg, and the limits of quantification (LOQs) did not exceed 7.0 μg/kg. The proposed method was then successfully applied to analyze authentic samples, confirming that it was a green, convenient, and reliable strategy for the analysis of fluazifop-butyl enantiomers in tobacco and soil.

Hemp (Cannabis sativa L.) cultivars Yunma 5 (YM5, fiber-type) and Bamahuoma (BM, seed-type) were seriously affected by salt-alkali stress during germination, while the knowledge about the salt tolerance during seedling stage is deficient. Here, responses of hemp (Cannabis sativa L.) seedlings of the cultivars YM5 and BM to the stress of different concentrations of NaCl and Na2CO3 were investigated to explore the salt tolerance of hemp. Results showed that the plant height, dry weight and root length of YM5 and BM seedlings gradually decreased as the concentration of NaCl or Na2CO3 increased. Although physiological indices such as EC (Electrical conductivity), SOD (Superoxide dismutase) and Pro (Proline) increased as the salt concentration increased, the increase extent was significantly greater in YM5 than in BM. Under the conditions of 100 and 200 mM NaCl, BM had greater dry weight and root length, and lower Pro content than YM5. However, under the stress of 100 and 200 mM Na2CO3, the opposite results were recorded, with the exception for lower chlorophyll content and higher SOD activity in BM than in YM5. These findings indicated that BM had a stronger NaCl tolerance than YM5. Moreover, morphological indices of the two cultivars under Na2CO3 stress were stunted more than under NaCl stress, and the seedlings died when Na2CO3 concentration increased up to 300 mM. Some up-regulation of salt-tolerant genes were observed in the two hemp cultivars, a higher expression under NaCl stress than under Na2CO3 stress, and a higher expression in YM5 than in BM were recorded. Findings from the study indicated that hemp seedling is more sensitive to Na2CO3 stress, and the tolerance of hemp to salt stress varies with salt type and salt concentration, although both cultivars can withstand moderate doses of NaCl and Na2CO3.

Multicyclic polymers including bicyclic and tetracyclic polymers were constructed by combining atom transfer radical polymerization (ATRP) and a photo-induced coupling reaction of anthryl groups. First, 4-arm and 8-arm star polystyrenes were synthesized by ATRP using tetrafunctional and octafunctional initiators, respectively. Subsequently, after two-step modification of Br-terminated 4-arm and 8-arm star polystyrenes, including azidation and copper-catalyzed azide–alkyne cycloaddition (CuAAC) reactions with prop-2-yn-1-yl anthracene-9-carboxylate, the precursors with anthryl end groups were obtained. Finally, the photo-induced coupling reaction was conducted upon irradiation at 365 nm in a diluted solution of 4-arm and 8-arm star precursors, to produce bicyclic and tetracyclic polymers, respectively. Besides, the multicyclic polymers can convert back to the original precursors after heating at 150 °C. 1H NMR, FT-IR, GPC and UV-vis analyses were carried out to verify the resultant multicyclic structures and the topological conversion between multicyclic polystyrenes and their precursors.

Multicyclic polystyrene (PS) with hyperbranched structure was constructed in an efficient way. First, a seesaw-type PS was synthesized via atom transfer radical polymerization (ATRP) using a Y-shaped ATRP initiator containing one hydroxyl at center and bromine at each end. After azidation, the anthryl and hydroxyl groups were introduced to the ends of the polymer chain by click reaction with a trifunctional molecule bearing alkynyl, hydroxyl, and anthryl groups (alkynyl-OH-ant). By irradiation with 365 nm UV light in a highly dilute condition, cyclic polymer with three hydroxyl groups (c-PS-(OH)3) can be obtained; then it was converted to a cyclic polymer containing three azides (c-PS-(N3)3) by bromination of the hydroxyl groups and azidation. This “A3” cyclic macromonomer was then used to construct hyperbranched multicyclic polymers via self-accelerating click reaction with sym-dibenzo-1,5-cyclooctadiene-3,7-diyne (DBA). The properties of obtained polymer were characterized by NMR, FT-IR, MALDI-TOF MS, a...

The aim of this study was to investigate the effects of leucine on the stabilization and aerodynamic characteristics of spray-dried solid lipid nanoparticles (SLN). The stabilizing effects were evaluated in terms of the ability to inhibit particle growth, and to maintain the thermodynamic integrity and drug release characteristics of reconstituted SLN. The results showed that spray-drying drastically changed particle size of reconstituted SLN, whereas the presence of different excipients led to different extent of stabilization. Leucine appeared to be more effective in the stabilization of SLN than trehalose, sucrose, lactose and mannitol, with the former conferring the ability to maintain the particle size of spray-dried and reconstituted SLN being almost the same as that before spray drying. When the content of leucine was added to 40% w/w or higher, the fine particle fractions of spray-dried powders dispersed through a Cyclohaler were about 48%. The overall results demonstrated that the presence of leucine facilitated the stabilization of SLN during spray-drying, and improved the aerosolization properties of the spray-dried SLN for pulmonary delivery.

Background Ongoing neuropathic pain is difficult to treat. The authors examined whether dermorphin [D-Arg2, Lys4] (1–4) amide, a peripherally acting µ-opioid receptor agonist, attenuates ongoing pain-associated manifestations after nerve injury in rats and mice. Methods Using conditioned place preference assay, the authors tested whether animals show a preference to the environment associated with drug treatment. Wide-dynamic range and dorsal root ganglion neuronal activities were measured by electrophysiology recording and calcium imaging. Results Nerve-injured animals stayed longer in dermorphin [D-Arg2, Lys4] (1–4) amide–paired chamber after conditioning than during preconditioning (rats: 402.4 ± 61.3 vs. 322.1 ± 45.0 s, 10 mg/kg, n = 9, P = 0.009; mice: 437.8 ± 59.4 vs. 351.3 ± 95.9 s, 2 mg/kg, n = 8, P = 0.047). Topical ganglionic application of dermorphin [D-Arg2, Lys4] (1–4) amide (5 μM, 1 μl, n = 5) reduced the numbers of small-diameter dorsal root ganglion neurons that showed spontaneous activity (1.1 ± 0.4 vs. 1.5 ± 0.3, P = 0.044) and that were activated by test stimulation (15.5 ± 5.5 vs. 28.2 ± 8.2, P = 0.009) after injury. In neuropathic rats, dermorphin [D-Arg2, Lys4] (1–4) amide (10 mg/kg, n = 8) decreased spontaneous firing rates in wide-dynamic range neurons to 53.2 ± 46.6% of predrug level, and methylnaltrexone (5 mg/kg, n = 9) blocked dermorphin [D-Arg2, Lys4] (1–4) amide–induced place preference and inhibition of wide-dynamic range neurons. Dermorphin [D-Arg2, Lys4] (1–4) amide increased paw withdrawal threshold (17.5 ± 2.2 g) from baseline (3.5 ± 0.7 g, 10 mg/kg, n = 8, P = 0.002) in nerve-injured rats, but the effect diminished after repeated administrations. Conclusions Peripherally acting μ-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance.

A deep understanding of the basic geologic characteristics of the fine-grained shale layers in the Paleogene 1st sub-member of Kong 2 Member (Ek21) in Cangdong sag, Bohai Bay Basin, is achieved through observation of 140 m continuous cores and systematic analysis of over 1 000 core samples from two wells. Basic geological conditions for shale oil accumulation are proposed based on the unconventional geological theory of oil and gas. The shale rock system mainly developed interbedded formation of felsic shale, calcareous and dolomitic shale and carbonates; high quality hydrocarbon source rock formed in the stable and closed environment is the material base for shale oil enrichment; intergranular pores in analcite, intercrystalline pores in dolomite and interlayer micro-fractures make tight carbonate, calcareous and dolomitic shale and felsic shale effective reservoirs, with brittle mineral content of more than 70%; high abundance laminated shale rock in the lower section of Ek21 is rich in shale oil, with a total thickness of 70 m, burial depth between 2 800 to 4 200 m, an average oil saturation of 50%, a sweet spot area of 260 km2 and predicted resources of over 5×108 t. Therefore, this area is a key replacement domain for oil exploration in the Kongdian Formation of the Cangdong sag. At present, the KN9 vertical well has a daily oil production of 29.6 t after fracturing with a 2 mm choke. A breakthrough of continental shale oil exploration in a lacustrine basin is expected to be achieved by volume fracturing in horizontal wells. Key words: shale oil, fine grained deposits, horizontal well, volume fracturing, shale reservoir sweet spot, Paleogene Kongdian Formation, Cangdong sag, Bohai Bay Basin

Nano-sized iron sulfide (FeS) plays a vital role in heavy metal removal; However, FeS nanoparticles are easily agglomerated, oxidized, and deactivated due to their poor stability. In order to solve these problems, this work synthesized chitosan-coated zirconium–iron sulfide composite (CS@Zr-FeS) by the coprecipitation method using FeS, zirconia sol (ZrO2), and chitosan (CS) as the raw materials and tested it for enhancing the performance of molybdenum(VI) removal. The obtained CS@Zr-FeS exhibited a higher specific surface area (85.43 m2/g) than FeS (47.92 m2/g), with the maximum molybdenum(VI) adsorption capacity of 120.80 mg/g. The adsorption of molybdenum(VI) onto CS@Zr-FeS followed the pseudo-second-order kinetics and Langmuir isotherm. The adsorption process was partially inhibited by the competing anions (e.g., PO43− and HCO3−) and humic acids but was not influenced by dissolved oxygen. Moreover, the obtained CS@Zr-FeS had high stability. Spectroscopy analysis and density functional theory (DFT) calculations demonstrated that hydrogen bonding and surface complexation were the primary mechanisms for molybdenum(VI) removal. These results imply that the CS@Zr-FeS composite exhibits a higher potential for molybdenum(VI) removal from the aquatic solutions than the pristine FeS nanoparticles.

This study concerned the development and validation of a green and rapid method for the analysis of 23 pesticides in tobacco using ultra performance convergence chromatography-tandem mass spectrometry (UPC2-MS/MS) combined with modified QuEChERS. The sample was extracted with acetonitrile, purified by graphene, and then determined by UPC2-MS/MS. In this paper, optimization was made on factors affecting separation efficiency including chromatographic column, modifier, column temperature, and back pressure. With CO2-ethanol as mobile phase, all pesticides were adequately separated on a Viridis HSS C18 SB column, and the whole analysis process was completed within 6 min. Under optimal conditions, the calibration curves showed good linearity in the range of 10–200 ng/mL with the regression coefficients higher than 0.9946. The limit of detection and limit of quantification were 1.04–7.07 and 3.32–23.16 μg/kg, respectively. At three spiked levels (0.2, 1.0 and 2.0 mg/kg), mean recoveries for 23 pesticides were ranging from 80.2% to 110.6% and relative standard deviations were 2.2%–7.2%. The proposed method, being fast, sensitive, and practical, can be used for rapid detection of fungicides and carbamates in tobacco.

Silicon carbide (SiC) devices have attracted much attention due to their superior characteristics of high blocking voltage, high frequency and high operating temperature. In recent years, with the continuous development of SiC device technology, domestic and foreign high-voltage SiC devices have made certain breakthroughs. In this paper, a 6.5kV/400A SiC module is prepared using the 6.5kV SiC MOSFET chip and 6.5kV SiC SBD chip independently developed by the research group. The on-resistance of the module is 20.8mΩ at a junction temperature of 150°C, and the drain leakage current is 146μA under a voltage of 6.5kV, indicating that the module has excellent conduction and blocking characteristics. The switching characteristics of the 6.5kV/400A SiC module are tested and evaluated based on high-voltage SiC dynamic test platform. At a junction temperature of 150°C, the turn-on energy is 714.2mJ, and the turn-off energy Eoff is 448mJ, compared with the Si IGBT module of the same voltage and current, the SiC module has faster switching speed, lower switching loss, and has obvious advantages in high-voltage and high-frequency applications.

This paper describes the design of a D-band wide-band SPDT switch using 60nm GaN HEMT technology. The broadband characteristic has been realized by using the parasitic capacitance of the off-state HEMTs to form an artificial transmission line. The equivalent circuits of the on and off state HEMTs are developed and the design parameters of the traveling-wave switch have been calculated. The simulation results demonstrate that the insertion loss is less than 7dB, minimum Isolation on off state is 20dB over 130∼150GHz, the chip size is $1.5\text{mm}^{\ast}1.5\text{mm}$ .

Surgery is the mainstream treatment for melanoma, but its clinical implementation suffers from some major drawbacks including residual infiltrating melanoma cells at resection margins and severe tissue injury. In this study, a nanocomposite scaffold is developed for in-situ therapy after melanoma surgery as well as wound healing, which is fabricated by embedding photothermal-capable black phosphorus nanosheets (BPNSs) into bioresorbable Gelatin-PCL (GP) nanofibrous scaffold. GP scaffold is a clinically-tested biomaterial with temperature sensitivity and tissue-healing effect, while the BPNSs are loaded with the anticancer antibiotic of doxorubicin (DOX) and conjugated with NH2-PEG-FA for tumor-targeted delivery. The GP scaffold could undergo a sol-gel transition upon NIR irritation and release the BPNSs in situ. During this process, most of the BP-based nanoformulations were selectively internalized by the melanoma cells for the cooperative photothermal therapy and heat-triggerable DOX therapy, while some of the loaded DOX was released into the wound tissue to create a tumor-suppressive microenvironment. Moreover, BPNSs could be gradually degraded to phosphates/phosphonates and thus enhance tissue repair by activating the ERK1/2 and PI3K/Akt pathway. Meanwhile, the detached DOX molecules would also enter the wound tissues for continuous melanoma inhibition. Considering the anti-melanoma and wound healing effect of this composite scaffold, it may offer a facile strategy for the wound treatment after melanoma surgery.

In this paper, the design and implementation of a dual bands power amplifier using gallium nitride (GaN) high electron mobility transistor (HEMT) is presented. A methodology of realizing Class F and Inverse Class F dual bands power amplifier output topology is proposed. With simulation and measurement verification, the dual bands power amplifier gets good performances in L band and S band, 1.4GHz and 2.1GHz respectively. At the P −2 point, the output powers are higher than 41.3dBm and 41.2dBm, and generate more than 72% and 69% drain efficiency in the two 200MHz operation bands. Simulation and measurement results agree well with each other, verified the concept and method proposed in the paper.

N′-nitrosonornicotine (NNN) is one of the most prevalent and toxic tobacco-specific nitrosoamines. A chiral center at its 2′-position results in R and S enantiomers, the partial double bond character of the N N = O group also results in E and Z isomers, therefore, NNN can form a total of four absolute configurations (E-(R)-NNN, E-(S)-NNN, Z-(R)-NNN, and Z-(S)-NNN). This study investigated the resolution of R/S enantiomers and E/Z isomers of NNN by supercritical fluid chromatography tandem mass spectrometry (SFC-MS/MS). The baseline separation of E/Z-(R,S)-NNN isomers/enantiomers was accomplished through the optimization of chiral columns and co-solvents. Due to the lack of single standard of E/Z isomers, only R-NNN (sum of E-(R)-NNN and Z-(R)-NNN) and S-NNN (sum of E-(S)-NNN and Z-(S)-NNN) were further examined. Through the comprehensive optimization of SFC-MS/MS conditions, R-NNN and S-NNN were separated with a run time of 5 min, the developed method was validated, and its applicability to the determination of NNN enantiomers in burley tobacco samples was demonstrated. This study could be applied to preparative separation of single enantiomer and/or isomer of NNN, and could provide potential benefits to biologic activity studies on these enantiomers and isomers.

Adult mammalian cardiomyocytes may reenter the cell cycle and cause cardiac hypertrophy. Triptolide (TP) can regulate the expressions of various cell cycle regulators in tumor cells. However, its effects on cell cycle regulators in myocardial hypertrophy and mechanism are poorly understood. This study was designed to explore the profile of cell cycle of cardiomyocytes and the temporal expression of their regulators during cardiac hypertrophy, as well as the effects of TP. The hypertrophy models employed were neonatal rat ventricular myocytes (NRVMs) stimulated with angiotensin II (Ang II) for scheduled times (from 5 min to 48 h) in vitro and mice treated with isoprenaline (Iso) for from 1 to 21 days, respectively. TP was used in vitro at 1 μg/L and in vivo at 10 μg/kg. NRVMs were analyzed with flow cytometry to detect the cell cycle, and the expression levels of mRNA and protein of various cell cycle regulators were determined using real-time PCR and Western blot. It was found NRVM numbers in phases S and G2 increased, while that in the G1 phase decreased significantly after Ang II stimulation. The mRNA expression levels of p21 and p27 increased soon after stimulation, and thereafter, mRNA expression levels of all cell cycle factors showed a decreasing trend and reached their lowest levels in 1-3 h, except for cyclin-dependent kinase 1 (CDK1) and CDK4 mRNA. The expression levels of CDK1, p21, and p27 mRNA increased significantly after stimulation with Ang II for 24-48 h. In myocardium tissue, CDK and cyclin expression levels peaked in 3-7 days, followed by a decreasing trend, while those of p21 and p27 mRNA remained at a high level on day 21. All protein expression levels were consistent with the results of mRNA in NRVMs or mice. The influence of Ang II or Iso on protein expression was more obvious than that on mRNA. TP treatment effectively prevented the imbalance in the expression of cell cycle regulators in the hypertrophy model group. In Conclusion, an imbalance in the expression of cell cycle regulators occurs during cardiac hypertrophy, and triptolide corrects these abnormal expression levels and attenuates cardiac hypertrophy.

This study explores nitrogen removal performance, bioelectricity generation, and the response of microbial community in two novel tidal flow constructed wetland-microbial fuel cells (TFCW-MFCs) when treating synthetic wastewater under two different chemical oxygen demand/total nitrogen (COD/TN, or simplified as C/N) ratios (10:1 and 5:1). The results showed that they achieved high and stable COD, NH4 +-N, and TN removal efficiencies. Besides, TN removal rate of TFCW-MFC was increased by 5-10% compared with that of traditional CW-MFC. Molecular biological analysis revealed that during the stabilization period, a low C/N ratio remarkably promoted diversities of ammonia-oxidizing archaea (AOA) and ammonia-oxidizing bacteria (AOB) in the cathode layer, whereas a high one enhanced the richness of nitrite-oxidizing bacteria (NOB) in each medium; the dominant genera in AOA, AOB, and NOB were Candidatus Nitrosotenuis, Nitrosomonas, and Nitrobacter. Moreover, a high C/N ratio facilitated the growth of Nitrosomonas, while it inhibited the growth of Candidatus Nitrosotenuis. The distribution of microbial community structures in NOB was separated by space rather than time or C/N ratio, except for Nitrobacter. This is caused by the differences of pH, dissolved oxygen (DO), and nitrogen concentration. The response of microbial community characteristics to nitrogen transformations and bioelectricity generation demonstrated that TN concentration is significantly negatively correlated with AOA-shannon, AOA-chao, 16S rRNA V4-V5-shannon, and 16S rRNA V4-V5-chao, particularly due to the crucial functions of Nitrosopumilus, Planctomyces, and Aquicella. Additionally, voltage output was primarily influenced by microorganisms in the genera of Nitrosopumilus, Nitrosospira, Altererythrobacter, Gemmata, and Aquicella. This study not only presents an applicable tool to treat high nitrogen-containing wastewater, but also provides a theoretical basis for the use of TFCW-MFC and the regulation of microbial community in nitrogen removal and electricity production.

Ferroptosis is an emerging antitumor option and has demonstrated unique advantages against many tumor indications. However, its efficacy is potentially hindered by the endogenous lipid peroxide-scavenging mechanisms and the reliance on acidic pH. Herein, we have developed a nanointegrated strategy based on clinically-safe components to synergistically remodel glutathione and lactate metabolism in tumor cells for enhanced ferroptosis therapy. We first conjugated ferrocene on PEGylated polyamidoamine dendrimers via ROS-cleavable thioketal linkage, which would further self-assemble with the glutathione (GSH)-depleting agent diethyl maleate (DEM) and monocarboxylate transporter 4-inhibiting siRNA (siMCT4) to afford biostable nanoassemblies (siMCT4-PAMAM-PEG-TK-Fc@DEM). The nanoassemblies could be activated by the elevated ROS levels in tumor intracellular environment and readily release the incorporated therapeutic contents, afterwards DEM could directly conjugate to GSH to disrupt the glutathione peroxidase 4 (GPX4)-mediated antioxidant defense while siMCT4 could block the MCT4-mediated efflux of lactic acid and acidify the intracellular milieu, both of which could improve the ferrocene-catalyzed lipid peroxidation and induce pronounced ferroptotic damage. The siMCT4-PAMAM-PEG-TK-Fc@DEM nanoplatform demonstrated high ferroptosis-based antitumor potency and good biocompatibility in vitro and in vivo, which may offer new avenues for the development of more advanced antitumor therapeutics with improved translatability. This article is protected by copyright. All rights reserved.

Objectives Acute kidney injury (AKI) is a severe complication of rhabdomyolysis that significantly increases mortality. Unfortunately, the therapeutic approach is limited. Inflammation plays a critical role in the pathogenesis of rhabdomyolysis-induced AKI, which is a potential therapeutic target. Nicotinamide, a form of vitamin B3 and a precursor of nicotinamide adenine dinucleotide, has been shown to have potent antiinflammation effects. Klotho is a tubular highly expressed renoprotective protein. Therefore, we explored the effect of nicotinamide on rhabdomyolysis-induced AKI and the underlying mechanisms. Methods We intramuscularly injected glycerol to induce rhabdomyolysis, and intraperitoneally administrated nicotinamide to observe the effect on kidney injury. Interleukin-1 beta, tumor necrosis factor alpha, nuclear factor kappa B (NF-κB), and Klotho were determined by Western blot. Chromatin immunoprecipitation was used to assess the interaction of NF-κB, nuclear receptor corepressor, and histone deacetylase 1 with Klotho promoters. Small interfering RNA was used to evaluate the role of Klotho in nicotinamide-related renoprotection. Results The results showed that nicotinamide attenuated renal pathologic morphology, kidney functional abnormalities, and kidney inflammatory response in rhabdomyolysis. Moreover, nicotinamide effectively blocked the recruitment of NF-κB, nuclear receptor corepressor, and histone deacetylase 1 to the promoter of Klotho, and preserved Klotho expression. More importantly, the renoprotection effect of nicotinamide was abrogated when Klotho was knocked down by small interfering RNA in rhabdomyolysis mice. Conclusions Our study demonstrated that Klotho preservation is essential for the renoprotection effect of nicotinamide, and provides a new preventive strategy for rhabdomyolysis-induced AKI.

Metformin is a clinically-approved anti-diabetic drug with emerging antitumor potential, but its antitumor activity is highly susceptible to local glucose abundance. Herein, we construct a nanotherapeutic platform based on biocompatible constituents to sensitize tumor cells for metformin therapy via cooperative glucose starvation. The nanoplatform was synthesized through the spontaneous biomineralization of glucose oxidase (GOx) and metformin in amorphous calcium phosphate nanosubstrate, which was further modified with polyethylene glycol and cRGD ligands. This biomineralized nanosystem could efficiently deliver the therapeutic payloads to tumor cells in a targeted and bioresponsive manner. Here GOx could catalyze the oxidation of glucose into gluconic acid and H2O2, thus depleting the glucose in tumor intracellular compartment while accelerating the release of the entrapped therapeutic payloads. The selective glucose deprivation would not only disrupt tumor energy metabolism, but also upregulate the PP2A regulatory subunit B56δ and sensitize tumor cells to the metformin-induced CIP2A inhibition, leading to efficient apoptosis induction via PP2A-GSK3β-MCL-1 axis with negligible side effects. This study may offer new avenues for targeted tumor therapy in the clinical context.

Combining graphene composite with three-dimensional structure is an effective strategy to avoid the agglomeration of graphene nanosheets and significantly enhances the properties of composite at low graphene content. In this work, reduced graphene oxide coated polyurethane composite foams (RPFs) with different pore sizes were prepared by a simple and economical self-assembly method. The RPFs are found to have good structural integrity and excellent flexibility, with a remarkable ability to withstand large deformation of 90% and 3 orders of magnitude decrease of electrical resistance. The RPF composite with higher density and smaller pore size exhibits better elasticity and responsive piezoresistivity. The resistance-time curves of RPFs in compression and bending modes exhibits a quick response of loading and release procedures by 0.10 s and 0.74 s in compression, 1.14 s and 0.91 s in bending, respectively, showing a good potential application of flexible and highly sensitive strain sensors for large deformation.

Ferroptosis is a new form of regulated cell death with significant therapeutic prospect, but its application against drug-resistant tumor cells is challenging due to their ability to effuse antitumor agents via p-glycoprotein (P-gp) and anti-lipid peroxidation alkaline intracellular environment. Herein, an amorphous calcium phosphate (ACP)-based nanoplatform is reported for the targeted combinational ferroptosis/apoptosis therapy of drug resistant tumor cells by blocking the MCT4-mediated efflux of lactic acid (LA). The nanoplatform is fabricated through the biomineralization of doxorubicin-Fe2+ (DOX-Fe2+ ) complex and MCT4-inhibiting siRNAs (siMCT4) and can release them to the tumor cytoplasm after the hydrolysis of ACP and dissociation of DOX-Fe2+ in the acidic lysosomes. siMCT4 can inhibit MCT4 expression and force the glycolysis-generated lactic acid (LA) to remain in cytoplasm for rapid acidification. The nanoplatform-induced remodeling of the tumor intracellular environment can not only interrupt the ATP supply required for P-gp-dependent DOX effusion to enhance H2 O2 production, but also increase the overall catalytic efficiency of Fe2+ for the initiation and propagation of lipid peroxidation. These features could act in concert to enhance the efficacy of the combinational ferroptosis/chemotherapy and prolong the survival of tumor-bearing mice. This study may provide new avenues for the treatment of multidrug-resistant tumors.

The trade-off between plant growth and resistance to herbivory is thought to be at least partly mediated by the interactions between jasmonates and gibberellins (GAs). Insect herbivory activates jasmonate biosynthesis and signaling, and plant growth is concomitantly inhibited. Whether or not the herbivory-induced jasmonates suppress the accumulation of GAs and thus reduce plant growth, and which jasmonates are functional in this process, remain unclear. In this study, we show that herbivory-induced stunted growth of Nicotiana attenuata was completely dependent on allene oxide cyclase (AOC) and coronatine insensitive1 (COI1), which encode a JA biosynthetic enzyme and the receptor, respectively, but only partially dependent on jasmonic acid-isoleucine conjugate (JA-Ile), the bioactive jasmonate. Quantification of GAs and exogenous treatments indicated that herbivory-induced growth inhibition was caused by GA4 deficiency, and that the reduction in GA4 accumulation was strongly associated with both decreased concentrations of GA biosynthetic gene transcripts and transcriptional activation of GA catabolic genes. We further show that JA-Ile only positively regulated the levels of GA catabolic genes, while the accumulation of GA biosynthetic gene transcripts was controlled by certain AOC-derived jasmonate(s) rather than by JA-Ile. This work sheds light on the mechanisms by which plants adapt to herbivory by using intricate phytohormone signaling and transcriptional regulatory networks.

The chemotherapeutic efficacy of paclitaxel against hypoxic tumors is usually unsatisfactory, which is partially due to the so-called hypoxia-induced drug resistance. The mechanism of hypoxia-induced resistance is primarily associated with hypoxia-inducible factor 1α (HIF-1α), which is an oxygen-sensitive transcriptional activator coordinating the cellular response to hypoxia. Apigenin is a natural occurring HIF-1α inhibitor that can suppress the expression of HIF-1α through multiple pathways and reverse the hypoxia-induced resistance found in cancer cells. Here we report that the use of apigenin can suppress the HIF-1α expression in hypoxic tumors through the simultaneous inhibition of the AKT/p-AKT pathway and HSP90, which is beneficial for enhancing the anticancer activity of the co-administered paclitaxel. The potential synergistic effect of apigenin and paclitaxel was further validated on HepG2 cell line and tumor-bearing mouse models.

We present studies of protein (insulin) efflux rates from nano-sized core–shell systems with a gelled core and a lipid bilayer (nanolipogels). The efflux control mechanism is the manipulation of mesh size, and we show that diffusion control via crosslinking is the dominant mechanism for efflux control. The concept is inspired by the macromolecular crowding effect in human cells, which may be considered as a physical network of undefined mesh size. Our bio-inspired system is made of chemically crosslinked water-swellable poly(ethylene glycol) diacrylate cores, whose mesh size can be manipulated to yield a quantifiable crowding effect that then leads to predictable release rates for biomacromolecules.

Ferroptosis is a recently discovered form of programed cell death caused by the metabolically regulated lipid peroxidation and holds promise for cancer treatment, but its regulatory mechanisms remain elusive. In this study, we observe that lactate-rich liver cancer cells exhibit enhanced resistance to the ferroptotic damage induced by common ferroptosis inducers such as Ras-selective lethal small molecule 3 (RSL3) and Erastin and that the monocarboxylate transporter 1 (MCT1)-mediated lactate uptake could promote ATP production in hepatocellular carcinoma (HCC) cells and deactivate the energy sensor AMP-activated protein kinase (AMPK), leading to the upregulation of sterol regulatory element-binding protein 1 (SREBP1) and the downstream stearoyl-coenzyme A (CoA) desaturase-1 (SCD1) to enhance the production of anti-ferroptosis monounsaturated fatty acids. Additionally, blocking the lactate uptake via hydroxycarboxylic acid receptor 1 (HCAR1)/MCT1 inhibition promotes ferroptosis by activating the AMPK to downregulate SCD1, which may synergize with its acyl-coenzyme A synthetase 4 (ACSL4)-promoting effect to amplify the ferroptotic susceptibility. In vitro and in vivo evidence confirms that lactate regulates the ferroptosis of HCC cells and highlights its translational potential as a therapeutic target for ferroptosis-based tumor treatment. Published version

Citrus grandis seedlings were irrigated with nutrient solutions with four Al-P combinations [two Al levels (0 mM and 1.2 mM AlCl3·6H2O) × two P levels (0 μM and 200 μM KH2PO4)] for 18 weeks. Al dramatically inhibited the growth of C. grandis seedlings, as revealed by a decreased dry weight of roots and shoots. Elevating P level could ameliorate the Al-induced growth inhibition and organic acid (malate and citrate) secretion in C. grandis. Using a comparative proteomic approach revealed by the isobaric tags for relative and absolute quantification (iTRAQ) technique, 318 differentially abundant proteins (DAPs) were successfully identified and quantified in this study. The possible mechanisms underlying P-induced alleviation of Al toxicity in C. grandis were proposed. Furthermore, some DAPs, such as GLN phosphoribosyl pyrophosphate amidotransferase 2, ATP-dependent caseinolytic (Clp) protease/crotonase family protein, methionine-S-oxide reductase B2, ABC transporter I family member 17 and pyridoxal phosphate phosphatase, were reported for the first time to respond to Al stress in Citrus plants. Our study provides some proteomic details about the alleviative effects of P on Al toxicity in C. grandis, however, the exact function of the DAPs identified herein in response to Al tolerance in plants must be further investigated.