Identifying SLC2A6 as the novel protective factor in breast cancer by TP53-related genes affecting M1 macrophage infiltration.

The high heterogeneity of breast cancer (BC) caused by pathogenic gene mutations poses a challenge to immunotherapy, but the underlying mechanism remains unknown. The difference in the infiltration of M1 macrophages induced by TP53 mutations has a significant impact on BC immunotherapy. The aim of this study was to develop a TP53-related M1 macrophage infiltration molecular typing risk signature in BC and evaluate the biological functions of the key gene to find new immunotherapy biomarkers. Weighted correlation network analysis (WGCNA) and negative matrix factorization (NMF) were used for distinguishing BC subtypes. The signature and the nomogram were both constructed and evaluated. Biological functions of the novel signature gene SLC2A6 were confirmed through in vitro and in vivo experiments. RNA-Sequencing and protein profiling were used for detecting the possible mechanism of SLC2A6. The results suggested that four BC subtypes were distinguished by TP53-related genes that affect M1 macrophage infiltration. The signature constructed by molecular typing characteristics could evaluate BC's clinical features and tumor microenvironment. The nomogram could accurately predict the prognosis. The signature gene SLC2A6 was found to have an abnormally low expression in tumor tissues. Overexpression of SLC2A6 could inhibit proliferation, promote mitochondrial damage, and result in apoptosis of tumor cells. The HSP70 family member protein HSPA6 could bind with SLC2A6 and increase with the increased expression of SLC2A6. In summary, the risk signature provides a reference for BC risk assessment, and the signature gene SLC2A6 could act as a tumor suppressor in BC.

Plasmonic Nanocubes with a Controllable "Crescent Arc" Facet: Tunable Hotspot Engineering for Highly Reliable and Sensitive SERS Detection.

The fine control of the nanogap and morphology of metal nanoparticles (NPs) has always been an obstacle, hindering the development and application of surface-enhanced Raman scattering (SERS) quantitative detection. Here, Au/4-mercaptobenzoic acid@Ag@Au-Ag bimetal core-shell nanocubes (NCs) with a "crescent arc" facet (C-Au/4MBA@Ag NCs) as a highly reliable and sensitive surface-enhanced Raman scattering SERS substrate is proposed for the first time. The bifunctional internal standard (IS) molecules (4MBA) govern the morphology of metal shells to maintain cubic configuration and provide calibration for SERS signals' flotation. In parallel, the controllable curvature of the C-Au/4MBA@Ag NCs is directly modulated by adjusting the relative rates of the galvanic replacement and co-reduction reaction, which generates a controllable interparticle nanogap to offer large depositing spaces for analytes and improve authoritative SERS signals' enhancement. The proposed C-Au/4MBA@Ag NCs exhibit an enhancement factor of up to 4.8 × 1010 and contribute to the ultralow RSD (7.9%). These C-Au/4MBA@Ag NCs also enable the detection of hazardous pesticide residues such as methamidophos and thiram in herbal plants with a complex matrix, with an average detection accuracy of up to 96%. In summary, this study achieves a fine control strategy of the "crescent arc" surface for improving SERS performance and explores the practical application potential for accurate and sensitive Raman detection of hazardous substances.

GRAS gene family in rye (Secale cereale L.): genome-wide identification, phylogeny, evolutionary expansion and expression analyses.

BACKGROUND: The GRAS transcription factor family plays a crucial role in various biological processes in different plants, such as tissue development, fruit maturation, and environmental stress. However, the GRAS family in rye has not been systematically analyzed yet. RESULTS: In this study, 67 GRAS genes in S. cereale were identified and named based on the chromosomal location. The gene structures, conserved motifs, cis-acting elements, gene replications, and expression patterns were further analyzed. These 67 ScGRAS members are divided into 13 subfamilies. All members include the LHR I, VHIID, LHR II, PFYRE, and SAW domains, and some nonpolar hydrophobic amino acid residues may undergo cross-substitution in the VHIID region. Interested, tandem duplications may have a more important contribution, which distinguishes them from other monocotyledonous plants. To further investigate the evolutionary relationship of the GRAS family, we constructed six comparative genomic maps of homologous genes between rye and different representative monocotyledonous and dicotyledonous plants. The response characteristics of 19 ScGRAS members from different subfamilies to different tissues, grains at filling stages, and different abiotic stresses of rye were systematically analyzed. Paclobutrazol, a triazole-based plant growth regulator, controls plant tissue and grain development by inhibiting gibberellic acid (GA) biosynthesis through the regulation of DELLA proteins. Exogenous spraying of paclobutrazol significantly reduced the plant height but was beneficial for increasing the weight of 1000 grains of rye. Treatment with paclobutrazol, significantly reduced gibberellin levels in grain in the filling period, caused significant alteration in the expression of the DELLA subfamily gene members. Furthermore, our findings with respect to genes, ScGRAS46 and ScGRAS60, suggest that these two family members could be further used for functional characterization studies in basic research and in breeding programmes for crop improvement. CONCLUSIONS: We identified 67 ScGRAS genes in rye and further analysed the evolution and expression patterns of the encoded proteins. This study will be helpful for further analysing the functional characteristics of ScGRAS genes.

Enhanced Tumor Site Accumulation and Therapeutic Efficacy of Extracellular Matrix-Drug Conjugates Targeting Tumor Cells.

The extracellular matrix (ECM) engages in regulatory interactions with cell surface receptors through its constituent proteins and polysaccharides. Therefore, nano-sized extracellular matrix conjugated with doxorubicin (DOX) is utilized to produce extracellular matrix-drug conjugates (ECM-DOX) tailored for targeted delivery to cancer cells. The ECM-DOX nanoparticles exhibit rod-like morphology, boasting a commendable drug loading capacity of 4.58%, coupled with acid-sensitive drug release characteristics. Notably, ECM-DOX nanoparticles enhance the uptake by tumor cells and possess the ability to penetrate endothelial cells and infiltrate tumor multicellular spheroids. Mechanistic insights reveal that the internalization of ECM-DOX nanoparticle is facilitated through clathrin-mediated endocytosis and macropinocytosis, intricately involving hyaluronic acid receptors and integrins. Pharmacokinetic assessments unveil a prolonged blood half-life of ECM-DOX nanoparticles at 3.65 h, a substantial improvement over the 1.09 h observed for free DOX. A sustained accumulation effect of ECM-DOX nanoparticles at tumor sites, with drug levels in tumor tissues surpassing those of free DOX by several-fold. The profound therapeutic impact of ECM-DOX nanoparticles is evident in their notable inhibition of tumor growth, extension of median survival time in animals, and significant reduction in DOX-induced cardiotoxicity. The ECM platform emerges as a promising carrier for avant-garde nanomedicines in the realm of cancer treatment.

In Situ Bioorthogonal Repair of the Vascular Endothelium Glycocalyx to Treat Acute Lung Injury.

In acute lung injury, destruction of the lung endothelial glycocalyx leads to vessel permeabilization and contributes to pulmonary edema and inflammation. Heparan sulfate, which accounts for >70% of glycosaminoglycans in the endothelial glycocalyx, plays a crucial physiological anti-inflammatory role. To treat acute lung injury, it is explored whether a two-step in vivo bioorthogonal chemistry strategy can covalently link intravenously administered heparan sulfate to the lung vascular endothelium and the damaged glycocalyx. First, fusogenic liposomes (EBP-Tz-FLs) carrying the reactive group tetrazine (Tz), and an E-selectin-binding peptide (EBP) to target the lung inflammatory endothelium are administered intravenously. This step aimed to anchor the tetrazine group to the membrane of inflammatory endothelial cells. Second, heparan sulfate (HS-TCO) conjugated to the trans-cyclooctene (TCO) group, which spontaneously reacts with Tz, is injected intravenously, leading to covalent heparan sulfate addition to the vascular endothelium. In a mouse model of acute lung injury, this approach substantially reduced vascular permeability and attenuated lung tissue infiltration. The EBP-Tz-FLs and HS-TCO showed favorable biocompatibility and safety both in vitro and in vivo. The proposed strategy shows good promise in acute lung injury therapy and covalently anchoring functional molecules onto the membrane of target cells.

Refractory lupus hepatitis successfully treated with telitacicept who failed to belimumab: A case report and literature review.

Background: Systemic lupus erythematosus (SLE)-associated hepatitis ("lupus hepatitis") was one of the most frequent causes of liver function abnormalities in patients with SLE. Lupus hepatitis (LH) is commonly treated with conventional treatment, including non-steroidal anti-inflammatory drugs, corticosteroids, and immunomodulators. However, in refractory cases, other treatment options may be required.Methodology: We report the case of a patient with lupus hepatitis refractory to both conventional therapy and belimumab who was successfully treated with telitacicept, a new dual B lymphocyte stimulator (BLyS)/APRIL (a proliferation-inducing ligand) inhibitor.Literature review was performed on PubMed search forum.Result: The specific search term was "telitacicept", 23 papers were searched, among them 10 case reports/series articles reporting telitacicept treatment were elected.Apart from our literature reporting the effectiveness of telitacicept in treating LH, there is no report on it in treating LH.Conclusion: This case suggests that telitacicept should be an effective and safe treatment for LH refractory, even to those who failed to belimumab based on the standard treatment, and can reduce the dosage of glucocorticoids.However, further investigations, particularly prospective randomized controlled trials, are warranted to verify our findings and ensure patient safety.

Plant-based proteins: advances in their sources, digestive profiles in vitro and potential health benefits.

Plant-based proteins (PBPs), which are environmentally friendly and sustainable sources of nutrition, can address the emerging challenges facing the global food supply due to the rapidly increasing population. PBPs have received much attention in recent decades as a result of high nutritional values, good functional properties, and potential health effects. This review aims to summarize the nutritional, functional and digestive profiles of PBPs, the health effects of their hydrolysates, as well as processing methods to improve the digestibility of PBPs. The diversity of plant protein sources plays an important role in improving the PBPs quality. Several types of models such as in vitro (the static and semi-dynamic INFOGEST) and in silico models have been proposed and used in simulating the digestion of PBPs. Processing methods including germination, fermentation, thermal and non-thermal treatment can be applied to improve the digestibility of PBPs. PBPs and their hydrolysates show potential health effects including antioxidant, anti-inflammatory, anti-diabetic, anti-hypertensive and anti-cancer activities. Based on the literature, diverse PBPs are ideal protein sources, and exhibit favorable digestive properties and health benefits that could be further improved by different processing technologies. Future research should explore the molecular mechanisms underlying the bioactivity of PBPs and their hydrolysates.

Quinoa greens as a novel plant food: a review of its nutritional composition, functional activities, and food applications.

Quinoa (Chenopodium quinoa Willd) is widely regarded as a versatile pseudo-cereal native to the Andes Mountains in South America. It has gained global recognition as a superfood due to its rich nutritional profile. While quinoa grains are well-known, there is an undiscovered potential in quinoa greens, such as sprouts, leaves, and microgreens. These verdant parts of quinoa are rich in a diverse array of essential nutrients and bioactive compounds, including proteins, amino acids, bioactive proteins, peptides, polyphenols, and flavonoids. They have powerful antioxidant properties, combat cancer, and help prevent diabetes. Quinoa greens offer comparable or even superior benefits when compared to other sprouts and leafy greens, yet they have not gained widespread recognition. Limited research exists on the nutritional composition and biological activities of quinoa greens, underscoring the necessity for thorough systematic reviews in this field. This review paper aims to highlight the nutritional value, bioactivity, and health potential of quinoa greens, as well as explore their possibilities within the food sector. The goal is to generate interest within the research community and promote further exploration and wider utilization of quinoa greens in diets. This focus may lead to new opportunities for enhancing health and well-being through innovative dietary approaches.

Nickel-Catalyzed Cross-Electrophile Vinylation of α-Chloro Phosphonates.

Herein, we report a general and efficient Ni-catalyzed reductive cross-coupling reaction of substituted vinyl bromides and α-chloro phosphonates to access a set of α-vinyl phosphonates using zinc as the terminal reductant. This reaction exhibits broad substrate adaptability and good functional group tolerance, which allows to afford diverse compounds including structurally complex motifs from natural products and drugs. Furthermore, the practicality was certificated through the gram-scale and transformation experiments. The preliminary mechanistic investigations support a radical chain process. The potential to realize enantiomeric control makes it more valuable for further exploration.

Copper-Catalyzed [4+1+1] Annulation of Ammonium Salts and Anthranils: Synthesis of 2,3-Diaroylquinolines.

A copper(I)-catalyzed protocol is developed for the synthesis of various 2,3-diaroylquinolines starting from achiral ammonium salts and anthranils through [4+1+1] annulation. Using copper(I) chloride as the sole catalyst, this reaction is featured with easily available starting materials, broad substrate scope, good yields and simple reaction conditions.

Electronic structures and quantum capacitance of twisted bilayer graphene with defects based on three-band tight-binding model.

Twisted bilayer graphene (tBLG) with C vacancies would greatly improve the density of states (DOS) around the Fermi level (EF) and quantum capacitance; however, the single-band tight-binding model only considering pz orbitals cannot accurately capture the low-energy physics of tBLG with C vacancies. In this work, a three-band tight-binding model containing three p orbitals of C atoms is proposed to explore the modulation mechanism of C vacancies on the DOS and quantum capacitance of tBLG. We first obtain the hopping integral parameters of the three-band tight-binding model, and then explore the electronic structures and the quantum capacitance of tBLG at a twisting angle of θ = 1.47° under different C vacancy concentrations. The impurity states contributed by C atoms with dangling bonds located around the EF and the interlayer hopping interaction could induce band splitting of the impurity states. Therefore, compared with the quantum capacitance of pristine tBLG (∼18.82 µF cm-2) at zero bias, the quantum capacitance is improved to ∼172.76 µF cm-2 at zero bias, and the working window with relatively large quantum capacitance in the low-voltage range is broadened in tBLG with C vacancies due to the enhanced DOS around the EF. Moreover, the quantum capacitance of tBLG is further increased at zero bias with an increase of the C vacancy concentration induced by more impurity states. These findings not only provide a suitable multi-band tight-binding model to describe tBLG with C vacancies but also offer theoretical insight for designing electrode candidates for low-power consumption devices with improved quantum capacitance.

Sirtuin 6 protects against podocyte injury by blocking the renin-angiotensin system by inhibiting the Wnt1/ß-catenin pathway.

Sirtuins (Sirts) are a family of nicotinamide adenine dinucleotide-dependent protein deacetylases that share diverse cellular functions. Increasing evidence shows that Sirts play a critical role in podocyte injury, which is a major determinant of proteinuria-associated renal disease. Membranous nephropathy (MN) is a typical glomerular disease in which podocyte damage mediates proteinuria development. In this study we investigated the molecular mechanisms underlying the regulatory roles of Sirt in podocyte injury in MN patients, rats with cationic bovine serum albumin (CBSA)-induced MN and zymosan activation serum (ZAS)-stimulated podocytes. Compared with healthy controls, MN patients showed significant reduction in intrarenal Sirt1 and Sirt6 protein expression. In CBSA-induced MN rats, significant reduction in intrarenal Sirt1, Sirt3 and Sirt6 protein expression was observed. However, only significant decrease in Sirt6 protein expression was found in ZAS-stimulated podocytes. MN patients showed significantly upregulated protein expression of Wnt1 and ß-catenin and renin-angiotensin system (RAS) components in glomeruli. CBSA-induced MN rats exhibited significantly upregulated protein expression of intrarenal Wnt1 and ß-catenin and their downstream gene products as well as RAS components. Similar results were observed in ZAS-stimulated podocytes. In ZAS-stimulated podocytes, treatment with a specific Sirt6 activator UBCS039 preserved the protein expression of podocin, nephrin and podocalyxin, accompanied by significant inhibition of the protein expression of ß-catenin and its downstream gene products, including Snail1 and Twist; treatment with a ß-catenin inhibitor ICG-001 significantly preserved the expression of podocyte-specific proteins and inhibited the upregulation of downstream ß-catenin gene products accompanied by significant suppression of the protein expression of RAS components. Thus, we demonstrate that Sirt6 ameliorates podocyte injury by blocking RAS signalling via the Wnt1/ß-catenin pathway. Sirt6 is a specific therapeutic target for the treatment of podocyte damage-associated renal disease.

Mitigating the effects of polyethylene microplastics on Pisum sativum L. quality by applying microplastics-degrading bacteria: A field study.

Polyethylene microplastics (PE-MPs) have been widely reported for their adverse effects on soil ecosystems. However, there are fewer field studies on addressing PE-MPs contamination in soil. This study investigated the effects of PE-MPs on soil properties, rhizosphere soil microorganisms, and pea (Pisum sativum L.) nutrient composition in a field experiment and mitigated the effects of PE-MPs by adding MPs-degrading bacteria. The results showed that the addition of MPs-degrading bacteria mitigated the effects of PE-MPs on the hydrolyzable nitrogen content in the soil. In addition, the introduction of MPs-degrading bacteria resulted in an increase in the Shannon indices of microorganisms in the soil. This also effectively regulates the structure of the soil microbial community to be closest to that of normal soil. Notably, the addition of MPs-degrading bacteria increased the protein, starch, cellulose, and chlorophyll contents of pea grains. This study demonstrated the ability to improve the nutrient content of peas affected by MPs by adding MPs-degrading bacteria. This study contributes to our understanding of the effects of PE-MPs on soil-microbe-plant systems and provides new insights into the bioremediation of PE-MPs in agricultural soils.

The characteristics of fungal responses to uranium mining activities and analysis of their tolerance to uranium.

The influence of uranium (U) mining on the fungal diversity (FD) and communities (FC) structure was investigated in this work. Our results revealed that soil FC richness and FD indicators obviously decreased due to U, such as Chao1, observed OTUs and Shannon index (P<0.05). Moreover, the abundances of Mortierella, Gibberella, and Tetracladium were notably reduced in soil samples owing to U mining activities (P<0.05). In contrast, the abundances of Cadophora, Pseudogymnoascus, Mucor, and Sporormiella increased in all soil samples after U mining (P<0.05). Furthermore, U mining not only dramatically influenced the Plant_Pathogen guild and Saprotroph and Pathotroph modes (P<0.05), but also induced the differentiation of soil FC and the enrichment of the Animal_Pathogen-Soil_Saprotroph and Endophyte guilds and Symbiotroph and Pathotroph Saprotroph trophic modes. In addition, various fungal populations and guilds were enriched to deal with the external stresses caused by U mining in different U mining areas and soil depths (P<0.05). Finally, nine U-tolerant fungi were isolated and identified with a minimum inhibitory concentration range of 400-600 mg/L, and their adsorption efficiency for U ranged from 11.6% to 37.9%. This study provides insights into the impact of U mining on soil fungal stability and the response of fungi to U mining activities, as well as aids in the screening of fungal strains that can be used to promote remediation of U mining sites on plateaus.

Geniposidic Acid Attenuates Chronic Tubulointerstitial Nephropathy Through Regulation of the NF-ƙB/Nrf2 Pathway Via Aryl Hydrocarbon Receptor Signaling.

Renal fibrosis is an outcome of chronic kidney disease, independent of the underlying etiology. Renal fibrosis is caused primarily by oxidative stress and inflammation. We identified the components of Plantaginis semen and elucidated their anti-fibrotic and anti-inflammatory mechanisms. The renoprotective components and underlying molecular mechanisms of P. semen were investigated in rats with adenine-induced chronic tubulointerstitial nephropathy (TIN) and in idole-3-acetic acid (IAA)-stimulated NRK-52E cells. Acetate and n-butanol extracts were found to be the bioactive fractions of P. semen. A total of 65 compounds including geniposidic acid (GPA), apigenin (APG), and acteoside (ATS) were isolated and identified. Among the seven main extract components, treatment with GPA, APG, and ATS reduced the serum levels of creatinine and urea in TIN rats. Mechanistically, GPA ameliorated renal fibrosis through repressing aryl hydrocarbon receptor (AHR) signaling and regulating redox signaling including inhibiting proinflammatory nuclear factor kappa B (NF-ƙB) and its target gene products as well as activated antioxidative nuclear factor-erythroid-2-related factor 2 (Nrf2) and its downstream target gene products in both TIN rats and IAA-stimulated NRK-52E cells. The inhibitory effect of GPA on AHR, NF-Ƙb, and Nrf2 signaling were partially abolished in IAA-stimulated NRK-52E cells treated with CH223191 compared with untreated IAA-stimulated NRK-52E cells. These data demonstrated that GPA alleviates oxidative stress and inflammation partly by suppressing AHR signaling.

Peptides Used for Heavy Metal Remediation: A Promising Approach.

In recent years, heavy metal pollution has become increasingly prominent, severely damaging ecosystems and biodiversity, and posing a serious threat to human health. However, the results of current methods for heavy metal restoration are not satisfactory, so it is urgent to find a new and effective method. Peptides are the units that make up proteins, with small molecular weights and strong biological activities. They can effectively repair proteins by forming complexes, reducing heavy metal ions, activating the plant's antioxidant defense system, and promoting the growth and metabolism of microorganisms. Peptides show great potential for the remediation of heavy metal contamination due to their special structure and properties. This paper reviews the research progress in recent years on the use of peptides to remediate heavy metal pollution, describes the mechanisms and applications of remediation, and provides references for the remediation of heavy metal pollution.

Mechanisms of Atomic Oxygen Erosion in Fluorinated Polyimides Investigated by Molecular Dynamics Simulations.

Traditional polyimides have highly conjugated structures, causing significant coloration under visible light. Fluorinated colorless polyimides, known for their light weight and excellent optical properties, are considered ideal for future aerospace optical lenses. However, their lifespan in low Earth orbit is severely limited by high-density atomic oxygen (AO) erosion, and the degradation behavior of fluorinated polyimides under AO exposure is not well understood. This study uses reactive molecular dynamics simulations to model two fluorinated polyimides, PMDA-TFMB and 6FDA-TFMB, with different fluorine contents, to explore their degradation mechanisms under varying AO concentrations. The results indicate that 6FDA-TFMB has slightly better resistance to erosion than PMDA-TFMB, mainly due to the enhanced chemical stability from its -CF3 groups. As AO concentration increases, widespread degradation of the polyimides occurs, with AO-induced cleavage and temperature-driven pyrolysis happening simultaneously, producing CO and OH as the main degradation products. This study uncovers the molecular-level degradation mechanisms of fluorinated polyimides, offering new insights for the design of AO erosion protection systems.

Traditional Chinese medicine improved diabetic kidney disease through targeting gut microbiota.

CONTEXT: Diabetic kidney disease (DKD) affects nearly 40% of diabetic patients, often leading to end-stage renal disease that requires renal replacement therapies, such as dialysis and transplantation. The gut microbiota, an integral aspect of human evolution, plays a crucial role in this condition. Traditional Chinese medicine (TCM) has shown promising outcomes in ameliorating DKD by addressing the gut microbiota. OBJECTIVE: This review elucidates the modifications in gut microbiota observed in DKD and explores the impact of TCM interventions on correcting microbial dysregulation. METHODS: We searched relevant articles from databases including Web of Science, PubMed, ScienceDirect, Wiley, and Springer Nature. The following keywords were used: diabetic kidney disease, diabetic nephropathy, gut microbiota, natural product, TCM, Chinese herbal medicine, and Chinese medicinal herbs. Rigorous criteria were applied to identify high-quality studies on TCM interventions against DKD. RESULTS: Dysregulation of the gut microbiota, including Lactobacillus, Streptococcus, and Clostridium, has been observed in individuals with DKD. Key indicators of microbial dysregulation include increased uremic solutes and decreased short-chain fatty acids. Various TCM therapies, such as formulas, tablets, granules, capsules, and decoctions, exhibit unique advantages in regulating the disordered microbiota to treat DKD. CONCLUSION: This review highlights the importance of targeting the gut-kidney axis to regulate microbial disorders, their metabolites, and associated signaling pathways in DKD. The Qing-Re-Xiao-Zheng formula, the Shenyan Kangfu tablet, the Huangkui capsule, and the Bekhogainsam decoction are potential candidates to address the gut-kidney axis. TCM interventions offer a significant therapeutic approach by targeting microbial dysregulation in patients with DKD.

Identification of the global diurnal rhythmic transcripts, transcription factors and time-of-day specific cis elements in Chenopodium quinoa.

BACKGROUND: Photoperiod is an important environmental cue interacting with circadian clock pathway to optimize the local adaption and yield of crops. Quinoa (Chenopodium quinoa) in family Amaranthaceae has been known as superfood due to the nutritious elements. As quinoa was originated from the low-latitude Andes, most of the quinoa accessions are short-day type. Short-day type quinoa usually displays altered growth and yield status when introduced into higher latitude regions. Thus, deciphering the photoperiodic regulation on circadian clock pathway will help breed adaptable and high yielding quinoa cultivars. RESULTS: In this study, we conducted RNA-seq analysis of the diurnally collected leaves of quinoa plants treated by short-day (SD) and long-day conditions (LD), respectively. We identified 19,818 (44% of global genes) rhythmic genes in quinoa using HAYSTACK analysis. We identified the putative circadian clock architecture and investigated the photoperiodic regulatory effects on the expression phase and amplitude of global rhythmic genes, core clock components and transcription factors. The global rhythmic transcripts were involved in time-of-day specific biological processes. A higher percentage of rhythmic genes had advanced phases and strengthened amplitudes when switched from LD to SD. The transcription factors of CO-like, DBB, EIL, ERF, NAC, TALE and WRKY families were sensitive to the day length changes. We speculated that those transcription factors may function as key mediators for the circadian clock output in quinoa. Besides, we identified 15 novel time-of-day specific motifs that may be key cis elements for rhythm-keeping in quinoa. CONCLUSIONS: Collectively, this study lays a foundation for understanding the circadian clock pathway and provides useful molecular resources for adaptable elites breeding in quinoa.

Coumarin-Based Fluorescent Inhibitors for Photocontrollable Bioactivation.

Activation of the IRE-1/XBP-1 pathway is related to many human diseases. Coumarin-based derivatives acting as both IRE-1 inhibitors and bright fluorophores are highly desirable to establish an integrated fluorescent inhibitor system. Here, we take insights into the aqueous stability of a photocaged IRE-1 inhibitor PC-D-F07 through a structure activity relationship. The substituent effects indicate that the electron-withdrawing -NO2 moiety in the photocage combined with the tricyclic coumarin fluorophore contribute to the structural stability of PC-D-F07. To optimize the photocage of PC-D-F07, we incorporate a 1-ethyl-2-nitrobenzyl or 2-nitrobenzyl photolabile moiety on the hydroxyl group of the IRE-1 inhibitor to generate RF-7 and RF-8. Upon photoactivation, both RF-7 and RF-8 present an increased fluorescence response, sequentially enabling the unlocking of the ortho-1,3-dioxane acetal for the release of active IRE-1 inhibitors. Moreover, RF-7 exhibits a high repolarization ratio of converting M2-type tumor-associated macrophages (M2-TAMs) to M1-type immune-responsive macrophages. This provides a novel prodrug strategy of modulating druggable fluorophore backbones to achieve spatiotemporally controllable drug release for precise cancer treatment.