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Green synthesis of Ag nanoparticles (AgNPs) by using the plant extract is a very important strategy to gain efficient antimicrobial agents with strong antimicrobial activity and low toxicity. In this study, jujube seed extract (JSE) is utilized to green synthesis of AgNPs by both hydrothermal process and solution‐based approaches. UV–vis absorption spectroscopy and infrared spectroscopy (FTIR) spectra confirm that jujube seed extract functionalized Ag nanoparticles are formed by both approaches and jujube seed extract covered on the surface of Ag nanoparticles. Transmission electron microscopy (TEM) images indicate that the JSE‐AgNPs are spherical with the average diameter of 17.7 and 14.2 nm for the hydrothermal process and solution‐based approaches, respectively. X‐ray diffraction (XRD) results indicate that the JSE‐AgNPs prepared by both approaches have face‐centered cubic crystal structure. The antimicrobial activity test reveals that minimum inhibitory concentrations (MIC) of JSE‐AgNPs by the solution‐based method are 62.5, 125, and 62.5 µg mL−1 against Escherichia coli, Staphylococcus aureus, and Candida albicans, respectively. These results imply that the JSE‐AgNPs have potential to be developed as efficient antimicrobial agents. [ABSTRACT FROM AUTHOR]

Self‐charging power systems (SCPSs) are envisioned as promising solutions for emerging electronics to mitigate the increasing global concern about battery waste. However, present SCPSs suffer from large form factors, unscalable fabrication, and material complexity. Herein, a type of highly stable, eco‐friendly conductive inks based on poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) are developed for direct ink writing of multiple components in the SCPSs, including electrodes for miniaturized spacer‐free triboelectric nanogenerators (TENGs) and microsupercapacitors (MSCs), and interconnects. The principle of "one ink, multiple functions" enables to almost fully print the entire SCPSs on the same paper substrate in a monolithic manner without post‐integration. The monolithic fabrication significantly improves the upscaling capability for manufacturing and reduces the form factor of the entire SCPSs (a small footprint area of ≈2 cm × 3 cm and thickness of ≈1 mm). After pressing/releasing the TENGs for ≈79000 cycles, the 3‐cell series‐connected MSC array can be charged to 1.6 V while the 6‐cell array to 3.0 V. On‐paper SCPSs are promising to serve as lightweight, thin, sustainable, and low‐cost power supplies. [ABSTRACT FROM AUTHOR]

Harvesting renewable mechanical energy is envisioned as a promising and sustainable way for power generation. Many recent mechanical energy harvesters are able to produce instantaneous (pulsed) electricity with a high peak voltage of over 100 V. However, directly storing such irregular high‐voltage pulse electricity remains a great challenge. The use of extra power management components can boost storage efficiency but increase system complexity. Here utilizing the conducting polymer PEDOT:PSS, high‐rate metal‐free micro‐supercapacitor (MSC) arrays are successfully fabricated for direct high‐efficiency storage of high‐voltage pulse electricity. Within an area of 2.4 × 3.4 cm2 on various paper substrates, large‐scale MSC arrays (comprising up to 100 cells) can be printed to deliver a working voltage window of 160 V at an ultrahigh scan rate up to 30 V s−1. The ultrahigh rate capability enables the MSC arrays to quickly capture and efficiently store the high‐voltage (≈150 V) pulse electricity produced by a droplet‐based electricity generator at a high efficiency of 62%, significantly higher than that (<2%) of the batteries or capacitors demonstrated in the literature. Moreover, the compact and metal‐free features make these MSC arrays excellent candidates for sustainable high‐performance energy storage in self‐charging power systems. [ABSTRACT FROM AUTHOR]

The southern waters of the Sumatra‐Java Islands, within the Indo‐Pacific Warm Pool, are highly susceptible to global climate change impacts. Understanding particulate inorganic carbon (PIC) dynamics and environmental responses in this region is critical for assessing climate change effects on marine ecosystems. Utilizing two decades of remote sensing PIC data (2003–2022), we identified five sub‐regions via K‐means clustering: the Sunda Strait, southern coastal/offshore waters of Sumatra Island, and southern coastal/offshore waters of Java Island. Self‐Organizing Map explored interannual PIC variations, while Generalized Additive Models delineated driving factors. In the Sunda Strait, PIC dynamics are influenced by water exchanges between the Indonesian Seas (ISs) and eastern Indian Ocean (EIO). Seasonally, PIC concentrations peak during the east monsoon (boreal summer); decreasing during positive Indian Ocean Dipole (+IOD) and El Niño events. Along the southern Sumatra, PIC variations positively correlate with rainfall and photosynthetically active radiation (PAR). Along the southern Sumatra, upwelling drives PIC variations, with higher concentrations during mature summer monsoon induced upwelling periods. PIC increases during +IOD and decreases during El Niño. Our study highlights the nexus between nutrients, physical factors (e.g., rainfall), and climatic events (e.g., El Niño) on PIC concentrations. Climate‐induced changes in oceanic physical processes modulate nutrient concentrations, thereby governing PIC variations. We propose a mechanistic model to elucidate PIC variations in upwelling areas. Findings suggest that prospective climate variability, encompassing alterations in climate events, rainfall, and temperature, may escalate PIC concentrations within the study area, advocating PIC as a forward‐looking climate change indicator. Plain Language Summary: Understanding the response of particulate inorganic carbon (PIC)—a primary form of oceanic carbon ‐ to environmental changes in the vulnerable southern waters of the Sumatra‐Java Islands is crucial for assessing the marine ecosystem. We used satellite image data to examine the variability of PIC, from 2003 to 2022. Our research showed that PIC concentrations varied across the area. In the Sunda Strait, a narrow body of water between land masses, water movement between the Indonesian Seas and eastern Indian Ocean influences PIC concentrations. In the southern waters of Sumatra Island, we discovered that increased rainfall and sunlight contribute to higher PIC concentrations. In the southern waters of Java Island, upwelling, an ocean physical process that brings nutrient‐rich water to the surface, plays a significant role. Our study delineates the interplay between nutrients, physical factors (e.g., rainfall), and climatic events (e.g., El Niño) on coccolithophore biomass. Climate changes drive alterations in oceanic physical processes, which in turn affect nutrient availability, thereby governing the growth of coccolithophores. Findings suggest prospective climate variability, inclusive of alterations in climate events, rainfall, and temperature, may escalate PIC concentrations within the study area, advocating PIC concentrations alterations as a forward‐looking climate change indicator. Key Points: Climate alters oceanic physical processes, thereby modulating nutrient availability, which in turn directly governs Particulate Inorganic Carbon (PIC) variationsA 20‐year analysis identified three core mechanisms driving PIC spatiotemporal variations in the study areaRising PIC under future climates predicts higher carbon sedimentation rates, marking PIC as a key climate indicator [ABSTRACT FROM AUTHOR]

Green extraction of the active lignans from Schisandra chinensis has received considerable attention due to their promising applications in the biomedical field. In this study, microwave‐assisted deep eutectic solvent method was used to simultaneously extract five lignans: Schizandrol A, Schizandrol B, Schisantherin A, Schisandrin A and Schizandrin B. The extraction parameters were optimized according to the calculated comprehensive score obtained from the analytic hierarchy process combined with the entropy weight method. The optimal extraction conditions were that the molar ratio of choline chloride and glycolic acid is 4:1, water content is 30% (V/V), solid–liquid ratio is 1:20 (Wg:VmL), extraction time is 20 min, and extraction temperature is 70°C, under which the extraction rate of the five lignans were 10.89, 8.616, 4.019, 4.893, and 5.318 mg/g. These results confirmed that our extraction method is efficient and feasible for green extraction of lignans from S. chinensis. [ABSTRACT FROM AUTHOR]

The limited oxygen barrier of polyethylene (PE) films has restricted their further application in food packaging, like emergency foods. Although its oxygen barrier property can be improved by applying a polyvinyl alcohol (PVA) coating, the application of PVA/PE composite films in high‐humidity environments is still challenging. Hence, this study aimed to enhance the oxygen barrier properties of PVA/PE composite films in high‐humidity environments. Specifically, PVA coatings were modified by the itaconic acid (IA) and magnesium‐aluminum layered double hydroxides (LDH), and then applied to PE films as bilayer coating. Because of the unique bilayer coating on the PE surface, the oxygen barrier property of PVA/PE composite film (IA/LDH‐p) in high‐humidity environments has been further improved. The results confirmed that IA/LDH‐p had an oxygen permeability coefficient of 1.92 ± 0.16 × 10−16 cm3 cm/(cm2 s Pa) under a high‐humidity environment test, 82.42% better than that of single‐layer coating coated on PE surface. After being stored at RH 90% for 36 h, the tensile strength and elongation at break values of IA/LDH‐p were 27.20 MPa and 919.63%, respectively. Overall, this obtained PVA/PE composite films showed great potential for application in emergency foods packaging, particularly in high‐humidity environments. [ABSTRACT FROM AUTHOR]

Non‐small‐cell lung cancer (NSCLC) is a highly lethal tumor that often develops resistance to targeted therapy. It is shown that Tank‐binding kinase 1 (TBK1) phosphorylates AGO2 at S417 (pS417‐AGO2), which promotes NSCLC progression by increasing the formation of microRNA‐induced silencing complex (miRISC). High levels of pS417‐AGO2 in clinical NSCLC specimens are positively associated with poor prognosis. Interestingly, the treatment with EGFR inhibitor Gefitinib can significantly induce pS417‐AGO2, thereby increasing the formation and activity of oncogenic miRISC, which may contribute to NSCLC resistance to Gefitinib. Based on these, two therapeutic strategies is developed. One is jointly to antagonize multiple oncogenic miRNAs highly expressed in NSCLC and use TBK1 inhibitor Amlexanox reducing the formation of oncogenic miRISC. Another approach is to combine Gefitinib with Amlexanox to inhibit the progression of Gefitinib‐resistant NSCLC. This findings reveal a novel mechanism of oncogenic miRISC regulation by TBK1‐mediated pS417‐AGO2 and suggest potential therapeutic approaches for NSCLC. [ABSTRACT FROM AUTHOR]

Due to their atomically dispersed active centers, single‐atom nanozymes (SAzymes) have unparalleled advantages in cancer catalytic therapy. Here, loaded with chlorin e6 (Ce6), a hydrothermally mass‐produced bimetallic silicate‐based nanoplatforms with atomically dispersed manganese/gadolinium (Mn/Gd) dual sites and oxygen vacancies (OVs) (PMnSAGMSNs‐V@Ce6) is constructed for tumor glutathione (GSH)‐triggered chemodynamic therapy (CDT) and O2‐alleviated photodynamic therapy. The band gaps of silica are significantly reduced from 2.78 to 1.88 eV by doping with metal ions, which enables it to be excited by a 650 nm laser to produce electron‐hole pairs, thereby facilitating the generation of reactive oxygen species. The Gd sites can modulate the local electrons of the atom‐catalyzed Mn sites, which contribute to the generation of superoxide and hydroxyl radicals (•OH). Tumor GSH‐triggered Mn2+ release can convert endogenous H2O2 to •OH and realize GSH‐depletion‐enhanced CDT. Significantly, the hydrothermally generated OVs can not only capture Mn and Gd atoms to form atomic sites but also can elongate and weaken the O‐O bonds of H2O2, thereby improving the efficacy of Fenton reactions. The degraded Mn2+/Gd3+ ions can be used as tumor‐specific magnetic resonance imaging contrast agents. All the experimental results demonstrate the great potential of PMnSAGMSNs‐V@Ce6 as cancer theranostic agent. [ABSTRACT FROM AUTHOR]

Summary: Glycine‐rich RNA‐binding proteins (GRPs) have been implicated in the responses of plants to environmental stresses, but the function of GRP genes involved in salt stress and the underlying mechanism remain unclear. In this study, we identified BpGRP1 (glycine‐rich RNA‐binding protein), a Betula platyphylla gene that is induced under salt stress. The physiological and molecular responses to salt tolerance were investigated in both BpGRP1‐overexpressing and suppressed conditions. BpGRF3 (growth‐regulating factor 3) was identified as a regulatory factor upstream of BpGRP1. We demonstrated that overexpression of BpGRF3 significantly increased the salt tolerance of birch, whereas the grf3‐1 mutant exhibited the opposite effect. Further analysis revealed that BpGRF3 and its interaction partner, BpSHMT, function upstream of BpGRP1. We demonstrated that BpmiR396c, as an upstream regulator of BpGRF3, could negatively regulate salt tolerance in birch. Furthermore, we uncovered evidence showing that the BpmiR396c/BpGRF3 regulatory module functions in mediating the salt response by regulating the associated physiological pathways. Our results indicate that BpmiR396c regulates the expression of BpGRF3, which plays a role in salt tolerance by targeting BpGRP1. [ABSTRACT FROM AUTHOR]

Summary: Aluminium (Al) toxicity decreases crop production in acid soils in general, but many crops have evolved complex mechanisms to resist it. However, our current understanding of how plants cope with Al stress and perform Al resistance is still at the initial stage. In this study, the citrate transporter CcMATE35 was identified to be involved in Al stress response. The release of citrate was increased substantially in CcMATE35 over‐expression (OE) lines under Al stress, indicating enhanced Al resistance. It was demonstrated that transcription factor CcNFYB3 regulated the expression of CcMATE35, promoting the release of citrate from roots to increase Al resistance in pigeon pea. We also found that a Long noncoding RNA Targeting Citrate Synthase (CcLTCS) is involved in Al resistance in pigeon pea. Compared with controls, overexpression of CcLTCS elevated the expression level of the Citrate Synthase gene (CcCS), leading to increases in root citrate level and citrate release, which forms another module to regulate Al resistance in pigeon pea. Simultaneous overexpression of CcNFYB3 and CcLTCS further increased Al resistance. Taken together, these findings suggest that the two modules, CcNFYB3‐CcMATE35 and CcLTCS‐CcCS, jointly regulate the efflux and synthesis of citrate and may play an important role in enhancing the resistance of pigeon pea under Al stress. [ABSTRACT FROM AUTHOR]

Summary: As a multifunctional hormone‐like molecule, melatonin exhibits a pleiotropic role in plant salt stress tolerance. While actin cytoskeleton is essential to plant tolerance to salt stress, it is unclear if and how actin cytoskeleton participates in the melatonin‐mediated alleviation of plant salt stress. Here, we report that melatonin alleviates salt stress damage in pigeon pea by activating a kinase‐like protein, which interacts with an actin‐depolymerizing factor. Cajanus cajan Actin‐Depolymerizing Factor 9 (CcADF9) has the function of severing actin filaments and is highly expressed under salt stress. The CcADF9 overexpression lines (CcADF9‐OE) showed a reduction of transgenic root length and an increased sensitivity to salt stress. By using CcADF9 as a bait to screen an Y2H library, we identified actin depolymerizing factor‐related phosphokinase 1 (ARP1), a novel protein kinase that interacts with CcADF9. CcARP1, induced by melatonin, promotes salt resistance of pigeon pea through phosphorylating CcADF9, inhibiting its severing activity. The CcARP1 overexpression lines (CcARP1‐OE) displayed an increased transgenic root length and resistance to salt stress, whereas CcARP1 RNA interference lines (CcARP1‐RNAi) presented the opposite phenotype. Altogether, our findings reveal that melatonin‐induced CcARP1 maintains F‐actin dynamics balance by phosphorylating CcADF9, thereby promoting root growth and enhancing salt tolerance. [ABSTRACT FROM AUTHOR]

Molybdenum (Mo)‐based nanozymes have been attracting increasingly extensive attention in photocatalytic antitumor field due to their versatile physicochemical properties, whereas the limited light capture rate and high recombination rate of photogenerated carriers seriously impedes their further development. Herein, MoO3‐starring silica nanozymes with hyaluronic acid modification (HMMSNs@HA) are innovated by hydrogenation to simultaneously achieve oxygen vacancies (OVs) engineering and tumor adaptive accumulation for the second near‐infrared (NIR‐II, 1064 nm) light‐potentiated thermal‐catalytic therapy. The hydrogenation‐regulated OVs can narrow the band gap of HMMSNs from 2.66 to 1.16 eV, achieving optimal optical absorption in NIR‐II region. Additionally, HMMSNs hold high separation efficacy of electron‐hole pairs to facilitate the generation of reactive oxygen species under laser irradiation. Significantly, HMMSNs@HA are stable in tumor microenvironment, while can degrade in normal physiological conditions, thereby offering tumor‐adaptive accumulation. Synchrotron radiation‐based extended X‐ray absorption fine structure spectroscopy reveals that OVs enabling the Mo4+ and Mo5+ formation, which can react with tumor endogenous H2O2 to produce hydroxyl radicals. Furthermore, OVs‐induced localized surface plasmon resonance effect endows the nanozymes with photothermal conversion efficacy of 32.3%, which affords NIR‐II‐excited photonic hyperthermia‐enhances catalytic therapy. All the experimental results demonstrate the high safety and superiorities of HMMSNs@HA for NIR‐II‐initiate therapy. [ABSTRACT FROM AUTHOR]

MYB transcription factor (TF) is one of the largest superfamilies that play a vital role in multiple plant biological processes. However, the MYB family has not been comprehensively identified and functionally verified in Cajanus cajan, which is the sixth most important legume crop. Here, 170 CcR2R3‐MYBs were identified and divided into 43 functional subgroups. Segmental and tandem duplications and alternative splicing events were found and promoted the expansion of the CcR2R3‐MYB gene family. Functional prediction results showed that CcR2R3‐MYBs were mainly involved in secondary metabolism, cell fate and identity, developmental processes, and responses to abiotic stress. Cis‐acting element analysis of promoters revealed that stress response elements were widespread in the above four functional branches, further suggesting CcR2R3‐MYBs were extensively involved in abiotic stress response. The transcriptome data and qRT‐PCR results indicated that most of the CcR2R3‐MYB genes responded to various stresses, of which the expression of CcMYB107 was significantly induced by drought stress. Overexpression of CcMYB107 enhanced antioxidant enzyme activity and increased proline and lignin accumulation, thus improving the drought resistance of C. cajan. Furthermore, Overexpression of CcMYB107 up‐regulated the expression of stress‐related genes and lignin biosynthesis genes after drought stress. Our findings established a strong foundation for the investigation of biological function of CcR2R3‐MYB TFs in C. cajan. [ABSTRACT FROM AUTHOR]

Single‐atom nanozymes (SAzymes) can effectively mimic the metal active centers of natural enzymes at the atomic level owing to their atomically dispersed active sites, thereby maximizing atom utilization efficiency and density of active sites. Hence, SAzymes can be considered the most promising candidates to replace natural enzymes. Herein, a PEGylated mesoporous Mn‐based single‐atom nanozyme (PmMn/SAE) employing a coordination‐assisted polymerization pyrolysis strategy that uses polydopamine for photothermal‐augmented nanocatalytic therapy is designed. PmMn/SAE exhibits excellent multiple enzymatic performance, including catalase‐like, oxidase‐like, and peroxidase (POD)‐like performance, due to the atomically dispersed Mn active species. As a result, PmMn/SAE not only catalyzes the decomposition of endogenous H2O2 to generate O2 for relieving hypoxia inside the tumor but also transfers electrons to O2 to produce superoxide radicals to kill tumor cells. Meanwhile, PmMn/SAE is able to trigger Fenton‐like reactions to generate highly toxic hydroxyl radicals to induce cancer cell apoptosis. The POD‐like catalytic mechanism of mMn/SAE is revealed using experimental results and density functional theory. Furthermor, PmMn/SAE shows good photothermal conversion efficiency (η = 22.1%) in the second near‐infrared region (1064 nm). Both the in vitro and in vivo experimental results indicate that PmMn/SAE can effectively kill cancer cells through photothermal‐enhanced catalytic therapy. [ABSTRACT FROM AUTHOR]

Summary: Cyanobacteria have an inherited advantage in phosphonate phytoremediation. However, studies on phosphonate metabolism in cyanobacteria are rare and mostly focus on physiology and ecology. Here, C‐P lyase gene cluster regulation in an undomesticated thermophilic Synechococcus OS‐B′ was examined in Synechocystis sp. PCC6803, a unicellular cyanobacterial model. Phylogenetic and cluster synteny analysis of C‐P lyase genes revealed a closer relationship between Syn OS‐B′ and Thermus thermophilus, than with other cyanobacteria. Pho boxes were identified in the 5′‐end‐flanking region of the C‐P lyase gene cluster, through which the downstream gene expression was regulated in a phosphate concentration‐dependent manner. Unexpectedly, the phosphate concentration that thoroughly inhibited Pho boxes was almost two orders of magnitude higher than that of any natural or anthropogenic wastewater reported so far. The Pho boxes mediated regulation was achieved through the Pho regulon two‐component system, and the absence of either SphS or SphR ablated the cell's ability to sense ambient phosphate changes. The three tandems of Pho boxes maintained inequivalent roles, of which the third tandem was not essential; however, it played a role in adjusting Pho boxes response in both positive and negative manner under phosphorus limitation. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) metastasizes mainly to the liver, which accounts for the majority of CRC‐related deaths. Here it is shown that metastatic cells undergo specific chromatin remodeling in the liver. Hepatic growth factor (HGF) induces phosphorylation of PU.1, a pioneer factor, which in turn binds and opens chromatin regions of downstream effector genes. PU.1 increases histone acetylation at the DPP4 locus. Precise epigenetic silencing by CRISPR/dCas9KRAB or CRISPR/dCas9HDAC revealed that individual PU.1‐remodeled regulatory elements collectively modulate DPP4 expression and liver metastasis growth. Genetic silencing or pharmacological inhibition of each factor along this chromatin remodeling axis strongly suppressed liver metastasis. Therefore, microenvironment‐induced epimutation is an important mechanism for metastatic tumor cells to grow in their new niche. This study presents a potential strategy to target chromatin remodeling in metastatic cancer and the promise of repurposing drugs to treat metastasis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Chemosensory proteins (CSPs) play important roles in chemical communication, but their precise physiological functions are still unclear. Cylas formicarius is the most serious pest attacking sweet potato around the world. At present, there is no effective way to control this pest. RESULTS: Our results showed that CforCSP1, 5 and 6 genes were highly expressed in the antennae of both sexes of C. formicarius. In addition, results from a fluorescence competitive binding assay showed that the CforCSP1, 5 and 6 proteins had high binding affinities for 17 plant volatiles including eight host plant volatiles. This indicated that the three proteins may be involved in the detection of host plant volatiles. Furthermore, results from four‐arm olfactometer bioassays showed that there was a significant tendency for C. formicarius to be attracted to eucalyptol, β‐carotene, benzaldehyde, vanillin and phenethyl alcohol, while it was repelled by β‐ionone. Finally, the levels of expression of the three CforCSPs in C. formicarius were successfully inhibited by RNA interference (RNAi). Behavioral experiments showed that CforCSP1, 5 and 6‐deficient C. formicarius were partly anosmic to β‐cyclocitral, benzaldehyde, octyl aldehyde, and β‐ionone and exhibited a reduced ability to locate the host plant volatiles β‐carotene and vanillin. CONCLUSION: Our data suggest that CforCSP1, 5 and 6 likely are involved in the chemical communication between C. formicarius and host plant volatiles, which may play pivotal roles in oviposition and feeding site preferences. More importantly, these results could provide information for the development of monitoring and push‐pull strategies for the control of C. formicarius. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Metal‐coordinated supramolecular nanoassemblies have recently attracted extensive attention as materials for cancer theranostics. Owing to their unique physicochemical properties, metal‐coordinated supramolecular self‐assemblies can bridge the boundary between traditional inorganic and organic materials. By tailoring the structural components of the metal ions and binding ligands, numerous multifunctional theranostic nanomedicines can be constructed. Metal‐coordinated supramolecular nanoassemblies can modulate the tumor microenvironment (TME), thus facilitating the development of TME‐responsive nanomedicines. More importantly, TME‐responsive organic–inorganic hybrid nanomaterials can be constructed in vivo by exploiting the metal‐coordinated self‐assembly of a variety of functional ligands, which is a promising strategy for enhancing the tumor accumulation of theranostic molecules. In this review, recent advancements in the design and fabrication of metal‐coordinated supramolecular nanomedicines for cancer theranostics are highlighted. These supramolecular compounds are classified according to the order in which the coordinated metal ions appear in the periodic table. Furthermore, the prospects and challenges of metal‐coordinated supramolecular self‐assemblies for both technical advances and clinical translation are discussed. In particular, the superiority of TME‐responsive nanomedicines for in vivo coordinated self‐assembly is elaborated, with an emphasis on strategies that enhance the accumulation of functional components in tumors for an ideal theranostic outcome. [ABSTRACT FROM AUTHOR]

SUMMARY: Calcineurin B‐like (CBL)‐interacting protein kinases (CIPKs) play a central role in Ca2+ signalling and promote drought tolerance in plants. The CIPK gene family in pigeon pea (Cajanus cajan L.), a major food crop affected by drought, has not previously been characterised. Here, we identified 28 CIPK genes in the pigeon pea genome. Five CcCIPK genes were strongly upregulated in roots upon drought treatment and were selected for further characterisation. Overexpression of CcCIPK13 and CcCIPK14 increased survival rates by two‐ to three‐fold relative to controls after 14 days of drought. Furthermore, the three major flavonoids, genistin, genistein and apigenin, were significantly upregulated in the same transgenic plants. Using CcCIPK14 as bait, we performed a yeast two‐hybrid screen and identified six interactors, including CcCBL1. CcCIPK14 exhibited autophosphorylation and phosphorylation of CcCBL1 in vitro. CcCBL1‐overexpressed plants displayed higher survival rates upon drought stress as well as higher expression of flavonoid biosynthetic genes and flavonoid content. CcCIPK14‐overexpressed plants in which CcCBL1 transcript levels were reduced by RNA interference had lower survival rates, which indicated CcCBL1 in the same pathway as CcCIPK14. Together, our results demonstrate a role for the CcCIPK14‐CcCBL1 complex in drought stress tolerance through the regulation of flavonoid biosynthesis in pigeon pea. Significance Statement: This study systematically elucidates the mechanism by which the CIPK‐CBL complex regulates flavonoid accumulation and drought resistance in pigeon pea, which lays a foundation for in‐depth exploration of relevant molecular mechanisms in plants. [ABSTRACT FROM AUTHOR]

Bone modelling evaluation is important for monitoring idiopathic condylar resorption (ICR) progress. To compare condylar modelling in ICR patients treated with or without stabilisation splints (SSs). Eighty‐four condyles from 84 ICR patients were studied: 42 received SS therapy (SS group); 42 received conventional therapy (control group). Cone‐beam computed tomography images at diagnosis (T0) and after at least 6 months (T1) were used for three‐dimensional reconstruction. Volume differences between T0 and T1 (δV) were used to evaluate the amount of modelling. Percentage of growth area (PCT) was used to assess the condylar surface growth tendency. No significant change in condylar volume was found in the SS group, whereas that in the control group was significantly decreased at T1 (P <.0001). The amount of modelling differed among condylar subregions within the SS group: among 6 subregions (P =.0137), between anterior and posterior regions (P =.0336) and between lateral, intermediate and medial regions (P =.0275). Control group condylar subregions showed no significant differences in the amount of modelling. The anabolic modelling tendency of the total condylar surface in the SS group was greater than that in the control group (P =.0251); however, there were no statistical differences in PCTs among condylar subregions in either group. SS therapy effectively reduced further bone destruction and promoted condylar modelling. Three‐dimensional morphological analysis is a novel method that can accurately evaluate the amount of bone modelling and growth tendency in ICR patients. [ABSTRACT FROM AUTHOR]

Direct quantification of exhausted T cells in human cancer is lacking, and its predictive value for checkpoint‐based treatment remains poorly investigated. We sought to systematically characterize the pan‐cancer landscape and molecular hallmarks of T‐cell dysfunction for the purpose of precision immunotherapy. Here, we defined a transcriptional signature for T‐cell exhaustion through analyzing differential gene expression between PD‐1‐high and PD‐1‐negative CD8+ T lymphocytes from primary non‐small cell lung cancer (NSCLC), followed by positive correlation tests with PDCD1 in TCGA lung carcinomas. A 78‐gene signature for exhausted CD8+ T cells (GET) was identified and validated to reflect dysfunctional immune state spanning different species and disease models. We discovered that GET estimation significantly correlated with intratumoral immune cytolytic activity (CYT) and T‐cell‐inflamed gene expression profile (GEP) across 30 solid tumor types. Miscellaneous tumor‐intrinsic and ‐extrinsic properties, in particular leukocyte proportions, genomic abnormalities, specific mutational signatures, and signaling pathways, were notably associated with GET levels. Furthermore, higher GET expression predicted an increased likelihood of clinical response to immune checkpoint inhibitors. These findings highlight the interrelation between T‐cell exhaustion and immune cytolytic activity at the pan‐cancer scale. The resulting inflamed tumor microenvironment may further crosstalk with other molecular and clinicopathological factors, which should be properly considered during immunotherapy biomarker development. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary: For non‐model plants, functional characterization of genes is still hampered by lack of efficient stable transformation procedures. Here, we report a simple, fast and efficient transformation technique with Agrobacterium rhizogenes for generating stable transgenic roots in living plants to facilitate functional studies in vivo. We showed that injection of A. rhizogenes into stems of various plant species lead to stable transgenic root generation, which can sustain plant growth after the original, non‐transgenic roots were cut off. A transformation system was established for pigeon pea, a major woody food crop, after optimizing the selection of A. rhizogenes strains, bacterium concentration, injection position and seedling age. RT‐PCR and fluorescence observation indicated a transgenic root induction efficiency of about 39% in pigeon pea. Furthermore, induction of hairy roots was achieved in nine out of twelve tested economically important plants at an efficiency of 15–39%. As proof of concept, bimolecular fluorescence complementation (BiFC) assay was applied to test the interaction between CcCIPK14 and CcCBL1/2 in pigeon pea. Additionally, ectopic expression of the bZIP transcription factor MdHY5 from apple confirmed the utility of the transformation technique for engineering anthocyanin synthesis in roots. Taken together, we show that this method allows fast in vivo studies of gene function in a wide range of plant species. [ABSTRACT FROM AUTHOR]

The objective of this research was twofold: first, to optimize the extraction process of Lonicera japonica polyphenols using a response surface methodology, and second, to study the antioxidant activity and tyrosinase inhibitory capacity of the polyphenols of different purities. High‐speed shearing homogenization extraction was used to extract the polyphenols from L. japonica. The antioxidant activity and the effect of polyphenols on tyrosinase activity were studied using free radical scavenging assay and the tyrosinase method, respectively. The optimal extraction conditions with an extraction yield of 6.96% for polyphenols were determined as follows: ethanol volume fraction 57%, shearing time 3.30 min, and solid–liquid ratio 1:58. Lonicera japonica polyphenols exhibited potent scavenging activity on 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2, 2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), and inhibitory capacity on tyrosinase. The results suggested that L. japonica polyphenols could be explored as a natural antioxidant and tyrosinase inhibitor. [ABSTRACT FROM AUTHOR]

Somatic KEAP1‐NRF2 pathway alterations are frequently detected in both lung adenocarcinomas and squamous cell carcinomas. However, the biological characteristics and molecular subtypes of KEAP1/NRF2‐mutant lung cancer remain largely undefined. Here, we performed a stepwise, integrative analytic and experimental interrogation of primary tumors and cancer cell lines harboring KEAP1 or NFE2L2 (encoding NRF2) gene mutations. First, we discovered that KEAP1/NRF2‐mutant lung cancer presented APOBEC‐mediated mutational signatures, impaired tumor angiogenesis, elevated hypoxic stress and deficient immune‐cell infiltrates. Second, gene expression‐based subtyping revealed three molecular subsets of KEAP1/NRF2‐mutant lung adenocarcinomas and two molecular subsets of KEAP1/NRF2‐mutant lung squamous cell carcinomas, each associated with distinguishing genetic, differentiation, immunological and clinicopathological properties. Third, single‐sample prediction allowed for de novo identification of KEAP1/NRF2‐active tumors within KEAP1/NRF2‐wild‐type samples. Our data demonstrate that KEAP1/NRF2‐mutant lung cancer is a microenvironmentally distinct, biologically heterogeneous, and clinically underestimated disease. These new pathological and molecular insights may accelerate the development of efficacious therapeutic strategies against human malignancies featured by KEAP1‐NRF2 pathway activation. What's new? The stress‐sensor KEAP1 and transcription factor NRF2 serve a key cooperative role in cytoprotection against oxidative stress. In lung cancer, these proteins frequently are mutated, though the functional consequences remain unknown. Here, comprehensive analysis of primary lung tumors harboring genetic mutations in KEAP1 or the NRF2‐encoding gene NFE2L2 identifies KEAP1/NRF2‐mutant lung cancer as a pathologically distinct disease. Moreover, tumors exhibited unique mutation profiles, which were differentiated into transcriptional subtypes and associated with diverse disease patterns. The data suggest that KEAP1/NRF2‐mutant lung cancer is a clinically relevant disease, warranting further investigation into possible avenues for targeted therapeutic intervention. [ABSTRACT FROM AUTHOR]

Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques were used to estimate the enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC50 > 100 μ m). In the induction studies, PI had minimal effects on CYP1A2, CYP2B6and CYP3A4 activity. Based on these results, PI would not be expected to cause clinically significant CYP450 inhibition or induction. [ABSTRACT FROM AUTHOR]

We evaluated an ionic-liquid-based ultrasound/microwave-assisted extraction method for the extraction of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one and 6-methoxy-benzoxazolin-2-one from etiolated maize seedlings. We performed single-factor and central composite rotatable design experiments to optimize the most important parameters influencing this technique. The best results were obtained using 1.00 M 1-octyl-3-methylimidazolium bromide as the extraction solvent, a 50°C extraction temperature, a 20:1 liquid/solid ratio (mL/g), a 21 min treatment time, 590 W microwave power, and 50 W fixed ultrasonic power. We performed a comparison between ionic-liquid-based ultrasound/microwave-assisted extraction and conventional homogenized extraction. Extraction yields of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one and 6-methoxy-benzoxazolin-2-one by the ionic-liquid-based ultrasound/microwave-assisted extraction method were 1.392 ± 0.051 and 0.205 ± 0.008 mg/g, respectively, which were correspondingly 1.46- and 1.32-fold higher than those obtained by conventional homogenized extraction. All the results show that the ionic-liquid-based ultrasound/microwave-assisted extraction method is therefore an efficient and credible method for the extraction of 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one and 6-methoxy-benzoxazolin-2-one from maize seedlings. [ABSTRACT FROM AUTHOR]

A method based on matrix solid-phase dispersion extraction followed by ultra high performance liquid chromatography with tandem mass spectrometry is presented for the extraction and determination of phenolic compounds in Equisetum palustre. This method combines the high efficiency of matrix solid-phase dispersion extraction and the rapidity, sensitivity, and accuracy of ultra high performance liquid chromatography with tandem mass spectrometry. The influential parameters of the matrix solid-phase dispersion extraction were investigated and optimized. The optimized conditions were as follows: silica gel was selected as dispersing sorbent, the ratio of silica gel to sample was selected to be 2:1 (400/200 mg), and 8 mL of 80% methanol was used as elution solvent. Furthermore, a fast and sensitive ultra high performance liquid chromatography with tandem mass spectrometry method was developed for the determination of nine phenolic compounds in E. palustre. This method was carried out within <6 min, and exhibited satisfactory linearity, precision, and recovery. Compared with ultrasound-assisted extraction, the proposed matrix solid-phase dispersion procedure possessed higher extraction efficiency, and was more convenient and time saving with reduced requirements on sample and solvent amounts. All these results suggest that the developed method represents an excellent alternative for the extraction and determination of active components in plant matrices. [ABSTRACT FROM AUTHOR]

Our previous study has shown that ampelopsin ( AMP), a flavonol mainly found in Ampelopsis grossedentata, could induce cell death in human breast cancer cells via reactive oxygen species generation and endoplasmic reticulum ( ER) stress pathway. Here, we examined whether autophagy is activated in AMP-treated breast cancer cells and, if so, sought to find the exact role and underlying molecular profile of autophagy in AMP-induced cell death. Our results showed that AMP treatment activated autophagy in MDA- MB-231 and MCF-7 breast cancer cells, as evidenced by the accumulation of autophagosomes, an increase of microtubule-associated protein 1 light chain 3 beta-2 ( LC3 B- II) and the conversion of LC3 B- I to LC3 B- II, the degradation of the selective autophagic target p62/ SQSTM1, and the formation of green fluorescent protein ( GFP)- LC3 puncta. Blockage of autophagy augmented AMP-induced cell death, suggesting that autophagy has cytoprotective effects. Meanwhile, AMP treatment suppressed Akt-mammalian target of rapamycin (m TOR) pathway as evidenced by dose- and time-dependent decrease of the phosphorylation of Akt, m TOR and ribosomal protein S6 kinase (p70 S6 K), whereas Akt activator insulin-like growth factor-1 ( IGF-1) pretreatment partially restored Akt-m TOR pathway inhibited by AMP and decreased AMP-inuduced autophagy, signifying that AMP activated autophagy via inhibition of the Akt-m TOR pathway. Additionally, blocking ER stress not only reduced autophagy induction, but also alleviated inhibition of the Akt-m TOR pathway induced by AMP, suggesting that activation of ER stress was involved in induction of autophagy and inhibition of the Akt-m TOR pathway. Taken together, these findings indicate that AMP induces protective autophagy in human breast cancer cells through Akt-m TOR pathway via ER stress. [ABSTRACT FROM AUTHOR]

In the present study, the main natural estrogen-agonist/antagonist from Pigeonpea roots was studied by the estrogen receptor α-dependent signaling pathway in human prostate cancer cell. First, the natural products with estrogenic activity in Pigeonpea roots were screened by pER8-GFP transgenic Arabidopsis, and cajanol (5-hydroxy-3-(4-hydroxy-2-methoxyphenyl)-7-methoxychroman-4-one) was confirmed as the active compound. Further study showed that cajanol significantly arrested the cell cycle in the G1 and G2/M phase and induced nuclei condensation, fragmentation and the formation of apoptotic bodies. Western blotting showed that cajanol modulated the ERα-dependent PI3K pathway and induced the activation of GSK3 and CyclinD1 closely following the profile of PI3K activity. Based on above results, we proposed a mechanism through which cajanol could inhibit survival and proliferation of estrogen-responsive cells (PC-3 cells) by interfering with an ERα-associated PI3K pathway, following a process that could be dependent of the nuclear functions of the ERα. Above all, we conclude that cajanol represents a valuable natural phytoestrogen source and may potentially be applicable in health food industry. [ABSTRACT FROM AUTHOR]

Tensile load is known to regulate the osteogenesis of mesenchymal stem cells (MSCs) and osteogenic progenitors; therefore it is widely used in clinical treatment and tissue engineering. Meanwhile, in vitro, both published studies and our lab data demonstrate that the application of intermittent tensile loading which stimulates cells several minutes or hours each day for several days has promoted the osteogenic differentiation of MSCs. Whereas, for clinic trails, it is important to know accurately how and how long mechanical tension should be applied. Hence, it is necessary to investigate different kinds of mechanical tension on osteogenesis of MSCs. Until now, during the osteogenesis, there has been no research on the effect of continuous cyclic mechanical tension (CCMT) which provides continuous stimulation throughout the study period. We firstly figure out CCMT inhibiting the expression of osteogenic genes such as key transcription factor Runx2. It is known that RhoA regulates cell differentiation in response to mechanical stimuli. MAPK signaling acts as a downstream effector of RhoA. So, we ask in MSCs, if CCMT regulates the osteogenic master gene Runx2 through RhoA-ERK1/2 pathway. And then, we find out there is a decrease in RhoA activity after CCMT stimulation. Pre-treatment of CCMT-loaded MSCs with LPA, a RhoA activator, restores ALP activity and significantly rescues Runx2 expression, while pre-treatment with C3 toxin, a RhoA inhibitor, further decreases the activity of ALP and down-regulates the expression of Runx2. Following results indicate that the inhibition of Runx2 expression after CCMT stimulation is mediated by RhoA-ERK1/2 pathway. J. Cell. Physiol. 226: 2159-2169, 2011. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Ab initio calculations at MP2 level of theory were used to study the proton transfer at the carboxylic sites of amino acids, in the isolated, mono- and di-hydrated forms. In the case of water dimer, two interaction modes with glycine neutral structures (see Fig. 3) were explored, corresponding to the concerted and stepwise reaction pathways. Their transition states can be described as (H2O&bond;H&bond;OH2)+ [Fig. 4(a)] and (H2O---H&bond;OH2)+ [Fig. 4(b)], respectively. The energy analysis indicated that the concerted pathway is preferred. In the isolated, mono- and di-hydrated glycine complexes, the activation barriers of the proton transfer at the carboxylic sites were calculated to be 34.49, 16.59, and 13.36 kcal mol-1, respectively. It was thus shown that the proton transfer is significantly assisted and catalyzed by water monomer so that it can take place at room temperature. Instead, the further addition of water molecules plays solvent effects rather than catalytic effects to this proton transfer process. The above results obtained with discrete water molecules were supported by the solvent continuum calculated data. It was also observed that the heavy dependence of the solvent continuum models on dipole moments may produce misleading results. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009 [ABSTRACT FROM AUTHOR]

The adsorption of his-tag green fluorescent protein (GFPH6) onto the mica surfaces has been studied by atomic force microscopy (AFM) and laser confocal fluorescence microscopy. By controlling the adsorption conditions, separated single GFPH6 and GFPH6 monolayer can be adsorbed and formed on mica surfaces. In present experiments, based on the AFM measurement, we found that the adsorbed GFPH6 was bound on the mica surface with its β-sheets. The formed GFPH6 monolayer on mica surfaces was flat, uniform, and stable. Some applications of the formed monolayer have been demonstrated. The formed monolayer can be used as a substrate for DNA imaging and AFM mechanical lithography. Microsc. Res. Tech., 2008. © 2008 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

In the present study, the antimicrobial activity of the essential oils from clove (Syzygium aromaticum (L.) Merr. et Perry) and rosemary (Rosmarinus officinalis L.) was tested alone and in combination. The compositions of the oils were analysed by GC/MS. Minimum inhibitory concentrations (MIC) against three Gram-positive bacteria, three Gram-negative bacteria and two fungi were determined for the essential oils and their mixtures. Furthermore, time-kill dynamic processes of clove and rosemary essential oils against Staphylococcus epidermidis, Escherichia coli and Candida albicans were tested. Both essential oils possessed significant antimicrobial effects against all microorganisms tested. The MICs of clove oil ranged from 0.062% to 0.500% (v/v), while the MICs of rosemary oil ranged from 0.125% to 1.000% (v/v). The antimicrobial activity of combinations of the two essential oils indicated their additive, synergistic or antagonistic effects against individual microorganism tests. The time-kill curves of clove and rosemary essential oils towards three strains showed clearly bactericidal and fungicidal processes of (1)/(2) x MIC, MIC, MBC and 2 x MIC. [ABSTRACT FROM AUTHOR]