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Abnormal expression in long noncoding RNAs (lncRNAs) is closely associated with cancers. Herein, a novel CRISPR/Cas13a-enhanced photocurrent-polarity-switching photoelectrochemical (PEC) biosensor was engineered for the joint detection of dual lncRNAs, using deep learning (DL) to assist in cancer diagnosis. After target lncRNA-activated CRISPR/Cas13a cleaves to induce DNAzyme bidirectional walkers with the help of cofactor Mg2+, nitrogen-doped carbon-Cu/Cu2O octahedra are introduced into the biosensor, producing a photocurrent in the opposite direction of CdS quantum dots (QDs). The developed PEC biosensor shows high specificity and sensitivity with limits of detection down to 25.5 aM for lncRNA HOTAIR and 53.1 aM for lncRNA MALAT1. More importantly, this platform for the lncRNA joint assay in whole blood can successfully differentiate cancers from healthy people. Furthermore, the DL model is applied to explore the potential pattern hidden in data of the established technology, and the accuracy of DL cancer diagnosis can acquire 93.3%. Consequently, the developed platform offers a new avenue for lncRNA joint detection and early intelligent diagnosis of cancer.
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Técnicas Biossensoriais , Aprendizado Profundo , RNA Longo não Codificante , RNA Longo não Codificante/genética , Humanos , Pontos Quânticos/química , Técnicas Eletroquímicas , Sistemas CRISPR-Cas/genética , Neoplasias/diagnóstico , Neoplasias/genética , Compostos de Cádmio/química , Sulfetos/química , Limite de Detecção , Processos FotoquímicosRESUMO
Encapsulation of transition metals represents a crucial method for modifying the electronic structure and regulating the reactivity of fullerene, thereby expanding its applications. Herein, we present calculations with density functional theory methods to investigate the mechanisms of the Diels-Alder (DA) reactions of cyclopentadiene and La@C60 or Gd@C60 as well as their tricationic derivatives. Our findings indicate that the encapsulation of La and Gd into the C60 cage is thermodynamically favorable. The DA reactions are favored by the presence of La and Gd, with lower barriers, though the regioselectivity, favoring 6-6 bonds in the fullerene, is not affected. The effect of external electric fields has been also considered.
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The field of artificial photosynthesis, which focuses on harnessing solar light for the conversion of CO2 to economically valuable chemical products, remains a captivating area of research. In this study, we developed a series of photocatalysts based on Earth abundant elements (Fe, Co, Ni, Cu, and Zn) incorporated into 2D metalloporphyrin-conjugated organic polymers known as MTBPP-BEPA-COPs. These photocatalysts were utilized for the photoreduction of CO2 employing only H2O as the electron donor, without the need for any sacrificial agents or precious-metal cocatalysts. Remarkably, all of the synthesized MTBPP-BEPA-COPs exhibited an exceptional CO2 photoreduction performance only irradiated by visible light. Particularly, upon optimizing the metal ion coordinated with porphyrin units, ZnTBPP-BEPA-COP outperformed the other MTBPP-BEPA-COPs in terms of photocatalytic activity, achieving an impressive CO reduction yield of 152.18 µmol g-1 after just 4 h of irradiation. The electrostatic potential surfaces calculated by density functional theory suggest the potential involvement of metal centers as binding and catalytic sites for the binding of CO2. The calculated adsorption energy of CO2 with ZnTBPP-BEPA-COP exhibited one of the two smallest values. This may be the reason for the excellent catalytic effect of ZnTBPP-BEPA-COP. Thus, the present study not only demonstrates the potential of porphyrin-based conjugated polymers as highly efficient photocatalysts for CO2 reduction but also offers valuable insights into the rational design of such materials in the future.
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Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.
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Lycium , Extratos Vegetais , Lycium/química , Extratos Vegetais/química , Antocianinas/química , Humanos , Flavonoides/química , Antioxidantes/química , Antioxidantes/farmacologia , Polifenóis/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Polissacarídeos/químicaRESUMO
KEY MESSAGE: We proposed a working model of BR to promote leaf size through cell expansion. In the BR signaling pathway, GhBES1 affects cotton leaf size by binding to and activating the expression of the E-box element in the GhEXO2 promoter region. Brassinosteroid (BR) is an essential phytohormone that controls plant growth. However, the mechanisms of BR regulation of leaf size remain to be determined. Here, we found that the BR deficient cotton mutant pagoda1 (pag1) had a smaller leaf size than wild-type CRI24. The expression of EXORDIUM (GhEXO2) gene, was significantly downregulated in pag1. Silencing of BRI1-EMS-SUPPRESSOR 1 (GhBES1), inhibited leaf cell expansion and reduced leaf size. Overexpression of GhBES1.4 promoted leaf cell expansion and enlarged leaf size. Expression analysis showed GhEXO2 expression positively correlated with GhBES1 expression. In plants, altered expression of GhEXO2 promoted leaf cell expansion affecting leaf size. Furthermore, GhBES1.4 specifically binds to the E-box elements in the GhEXO2 promoter, inducing its expression. RNA-seq data revealed many down-regulated genes related to cell expansion in GhEXO2 silenced plants. In summary, we discovered a novel mechanism of BR regulation of leaf size through GhBES1 directly activating the expression of GhEXO2.
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Brassinosteroides , Gossypium , Gossypium/metabolismo , Brassinosteroides/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Regiões Promotoras Genéticas/genética , Folhas de Planta/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
Sensing systems based on cholinesterase and carboxylesterase coupled with different transduction technologies have emerged for pesticide screening owing to their simple operation, fast response, and suitability for on-site analysis. However, the broad spectrum and specificity screening of pyrethroids over organophosphates and carbamates remains an unmet challenge for current enzymatic sensors. Human serum albumin (HSA), a multifunctional protein, can promote various chemical transformations and show a high affinity for pyrethroids, which offer a route for specific and broad-spectrum pyrethroid screening. Herein, for the first time, we evaluated the catalytic hydrolysis function of human serum albumin (HSA) on the coumarin lactone bond and revealed that HSA can act as an enzyme to catalyze the hydrolysis of the coumarin lactone bond. Molecular docking and chemical modifications indicate that lysine 199 and tyrosine 411 serve as the catalytic general base and contribute to most of the catalytic activity. Utilizing this enzymatic activity, a broad specific ratiometric fluorescence pyrethroids sensing system was developed. The binding energetics and binding constants of pesticides and HSA show that pyrethroids bind to HSA more easily than organophosphates and carbamates, which is responsible for the specificity of the sensing system. This study provides a general sensor platform and strategy for screening pesticides and reveals the catalytic activity of HSA on the hydrolysis of the coumarin lactone bond, which may open innovative horizons for the chemical sensing and biomedical applications of HSA.
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Praguicidas , Piretrinas , Humanos , Albumina Sérica Humana/metabolismo , Hidrólise , Piretrinas/química , Simulação de Acoplamento Molecular , Cumarínicos/química , Carbamatos , Organofosfatos , Lactonas , Ligação Proteica , Espectrometria de FluorescênciaRESUMO
Reproductive hormones play vital roles in reproductive health and can be used to assess a woman's ovarian function and diagnose diseases associated with reproductive endocrine disorders. As these hormones are important biomarkers for reproductive health monitoring and diagnosis, a rapid, high-throughput, and low-invasive detection and simultaneous assessment of the levels of multiple reproductive hormones has important clinical applications. In this work, a quadruplex ultrasensitive immunoassay was developed for simultaneous assessment of 4 human reproductive hormone proteins (follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), and anti-Müllerian hormone (AMH)) in a variety of human biofluid samples. This assay takes advantage of single-molecule imaging of microwell arrays and capture antibody beads as a reaction interface to construct multiplex bead array immunoassays. The analyte-bound beads can easily be parsed to individual wells and detected via fluorophores, emitting distinct wavelengths associated to the beads. As a result, this proposed quadruplex immunoassay exhibits four good 4-parameter logistic calibration curves ranging from 2.7 to 2000, 1.6 to 1200, 1.8 to 1300, and 0.3 to 220 pg/mL with limits of detection of 0.32, 0.28, 0.14, and 0.02 pg/mL for FSH, LH, PRL, and AMH, respectively. Furthermore, the developed quadruplex immunoassay was used to test clinical venous serum samples where it showed remarkable consistency with clinical test results in methodological comparison and the diagnosis of polycystic ovary syndrome. In addition, we successfully applied the ultrasensitive capability of this assay to the simultaneous testing and evaluation of four proteins in fingertip blood as well as urine samples, in which the urinary AMH level (1.42-156 pg/mL) was measured and assessed quantitatively for the first time.
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Hormônio Luteinizante , Síndrome do Ovário Policístico , Feminino , Humanos , Hormônio Foliculoestimulante , Síndrome do Ovário Policístico/diagnóstico , Hormônio Antimülleriano , ImunoensaioRESUMO
A convenient and efficient visible-light-induced method has been developed for the construction of sulfonated and selenylated indolo[1,2-a]quinolines through sulfonyl or selenyl radical-initiated tandem cyclization of unactivated alkynes with sodium sulfinates or diaryl diselenides under mild conditions. This protocol, which simply utilizes visible light as the safe and eco-friendly energy source and an inexpensive and nontoxic organic dye as a photocatalyst without the aid of an external photocatalyst, provides various sulfonyl- and selenyl-containing indolo[1,2-a]quinolines in moderate to good yields.
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Fluorescent probes that emit in the far-red (600-700 nm), first near-infrared (NIR-I, 700-900 nm), and second NIR (NIR-II, 900-1700 nm) regions possess unique advantages, including low photodamage and deep penetration into biological samples. Notably, NIR-II optical imaging can achieve tissue penetration as deep as 5-20 mm, which is critical for biomedical sensing and clinical applications. Much research has focused on developing far-red to NIR-II dyes to meet the needs of modern biomedicine. Flavylium compounds are natural colorants found in many flowers and fruits. Flavylium-inspired dyes are ideal platforms for constructing fluorescent probes because of their far-red to NIR emissions, high quantum yields, high molar extinction coefficients, and good water solubilities. The synthetic and structural diversities of flavylium dyes also enable NIR-II probe development, which markedly advance the field of NIR-II in vivo imaging. In the last decade, there have been huge developments in flavylium-inspired dyes and their applications as far-red to NIR fluorescent probes for biomedical applications. In this review, we highlight the optical properties of representative flavylium dyes, design strategies, sensing mechanisms, and applications as fluorescent probes for detecting and visualizing important biomedical species and events. This review will prompt further research not only on flavylium dyes, but also into all far-red to NIR fluorophores and fluorescent probes. Moreover, this interest will hopefully spillover into applications related to complex biological systems and clinical treatments, ranging in focus from the sub-organelle to whole-animal levels.
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Corantes Fluorescentes , Imagem Óptica , Animais , Corantes Fluorescentes/química , Imagem Óptica/métodosRESUMO
Epimedium is a classical Chinese herbal medicine, which has been used extensively to treat various diseases, such as sexual dysfunction, osteoporosis, cancer, rheumatoid arthritis, and brain diseases. Flavonoids, such as icariin, baohuoside I, icaritin, and epimedin C, are the main active ingredients with diverse pharmacological activities. Currently, most Epimedium flavonoids are extracted from Epimedium plants, but this method cannot meet the increasing market demand. Biotransformation strategies promised huge potential for increasing the contents of high-value Epimedium flavonoids, which would promote the full use of the Epimedium herb. Complete biosynthesis of major Epimedium flavonoids by microbial cell factories would enable industrial-scale production of Epimedium flavonoids. This review summarizes the structures, pharmacological activities, and biosynthesis pathways in the Epimedium plant, as well as the extraction methods of major Epimedium flavonoids, and advancements in the biotransformation and complete microbial synthesis of Epimedium flavonoids, which would provide valuable insights for future studies on Epimedium herb usage and the production of Epimedium flavonoids.
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Medicamentos de Ervas Chinesas , Epimedium , Osteoporose , Epimedium/química , Biotransformação , Medicamentos de Ervas Chinesas/uso terapêutico , Flavonoides/química , Osteoporose/tratamento farmacológicoRESUMO
Although membrane separation technology has been widely used in the treatment of oily wastewater, the complexity and high cost of the membrane preparation, as well as its poor stability, limit its further development. In this study, via the vacuum-assisted suction filtration method, polydopamine (PDA)-coated TiO2 nanoparticles were tightly attached and embedded on both sides of laboratory filter paper (FP). The resultant FP possessed the typical wettability of high hydrophilicity in the air with the water contact angle (WCA) of 28°, superoleophilicity with the oil contact angle (OCA) close to 0°, underwater superoleophobicity with the underwater OCA greater than 150°, and superhydrophobicity under the water with the underoil WCA over 150° for five kinds of organic solvents (carbon tetrachloride, toluene, n-hexane, n-octane, and iso-octane). The separation efficiency of immiscible oil/water, oil-in-water, and water-in-oil emulsions using the modified FP is higher than 99%. After 17 cycles of emulsion separation, a high separation efficiency of 99% was still maintained for the FP, along with good chemical and mechanical stability. In addition, successful separation and purification were also realized for the oil-in-water emulsion that contained the methylene blue (MB) dye, along with the complete degradation of MB in an aqueous solution under UV irradiation.
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Exosomal microRNAs (miRNAs) are reliable biomarkers of disease progression, allowing for non-invasive detection. However, detection of exosomal miRNAs in situ remains a challenge due to low abundance, poor permeability of the lipid bilayers, and slow kinetics of previous methods. Herein, an accelerated DNA nanoprobe was implemented for fast, in situ monitoring of miRNA in exosomes by employing a spatial confinement strategy. This nanoprobe not only detects miRNA in exosomes but also distinguishes tumor exosomes from those derived from normal cells with high accuracy, paving the way toward exosomal miRNA bioimaging and disease diagnosis. Furthermore, the fast response allows for this nanoprobe to be successfully utilized to monitor the process of exosomes endocytosis, making it also a tool to explore exosome biological functions.
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Biomarcadores Tumorais , DNA , Exossomos , MicroRNAs , Neoplasias , Biomarcadores Tumorais/genética , DNA/genética , Sondas de DNA , Exossomos/genética , Humanos , MicroRNAs/genética , Nanoestruturas , Neoplasias/genéticaRESUMO
Skin is the largest organ in the human body, and the interplay between the environment factors and human skin leads to some skin diseases, such as acne, psoriasis, and atopic dermatitis. As the first line of human immune defense, skin plays significant roles in human health via preventing the invasion of pathogens that is heavily influenced by the skin microbiota. Despite being a challenging niche for microbes, human skin is colonized by diverse commensal microorganisms that shape the skin environment. The skin microbiota can affect human health, and its imbalance and dysbiosis contribute to the skin diseases. This review focuses on the advances in our understanding of skin microbiota and its interaction with human skin. Moreover, the potential roles of microbiota in skin health and diseases are described, and some key species are highlighted. The prevention, diagnosis and treatment strategies for microbe-related skin diseases, such as healthy diets, lifestyles, probiotics and prebiotics, are discussed. Strategies for modulation of skin microbiota using synthetic biology are discussed as an interesting venue for optimization of the skin-microbiota interactions. In summary, this review provides insights into human skin microbiota recovery, the interactions between human skin microbiota and diseases, and the strategies for engineering/rebuilding human skin microbiota.
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Dermatite Atópica , Microbiota , Dermatopatias , Disbiose , Humanos , PeleRESUMO
A visible-light-induced persulfate-promoted cascade phosphorylation/cyclization reaction to access various phosphorylated pyrrolo[1,2-a]indolediones under mild conditions was developed. Notably, the transformation was carried out with diethyl carbonate/H2O as a green medium at room temperature. More impressively, traditional metal catalysts and photocatalysts could be effectively avoided. The reactions are simple to operate, easy to scale up, and have good functional group tolerance.
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A visible-light-induced metal-free cascade cyclization of cyclic N-sulfonyl ketimines with N-arylglycines for the construction of N-sulfonamide-fused imidazolidines was developed. The procedure employed 3 mol% of eosin Y as the photocatalyst at room temperature under visible light irradiation, providing various N-sulfonamide-fused imidazolidines in good yields (32 examples, up to 86% yields).
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A photoexcited sulfenylation of C(sp3)-H bonds in amides is developed for the synthesis of sulfenyl amides using thiosulfonates as a sulfur source. In the presence of easily available and inexpensive Na2-eosin Y, TBHP and K2CO3, various sulfenyl amides can be obtained under the irradiation of blue light at room temperature.
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Amidas , Enxofre , Amidas/química , Enxofre/químicaRESUMO
A turn-on fluorescent sensor based on CdTe quantum dots (QDs) is designed for highly sensitive and selective ascorbic acid (AA) detection. CdTe shows a strong emission centered at 578 nm. When assembled with poly(sodium 4-styrenesulfonate) (PSS) and methyl viologen (Mv2+) through electrostatic interaction, the emission is found to be effectively quenched. In the presence of AA, Mv2+ is reduced to Mv+, making the fluorescence of CdTe QDs restored. Under the optimal conditions, the proposed AA sensing method shows a linear proportional response from 0.8 µM to 20 µM, with the detecting limit as low as 50 nM. The developed method was successfully applied in the analysis of AA in human serum samples and cell lysates with satisfactory results.
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Compostos de Cádmio , Pontos Quânticos , Ácido Ascórbico , Fluorescência , Humanos , Limite de Detecção , Oxirredução , Paraquat , Espectrometria de Fluorescência/métodos , TelúrioRESUMO
The main protease is regarded as an essential drug target for treating Coronavirus Disease 2019. In the present study, 13 marketed drugs were investigated to explore the possible binding mechanism, utilizing molecular docking, molecular dynamics simulation, and MM-PB(GB)SA binding energy calculations. Our results suggest that fusidic acid, polydatin, SEN-1269, AZD6482, and UNC-2327 have high binding affinities of more than 23 kcal mol-1. A descriptor was defined for the energetic occupancy of the subpocket, and it was found that S4 had a low occupancy of less than 10% on average. The molecular optimization of ADZ6482 via reinforcement learning algorithms was carried out to screen out three lead compounds, in which slight structural changes give more considerable binding energies and an occupancy of the S4 subpocket of up to 43%. The energetic occupancy could be a useful descriptor for evaluating the local binding affinity for drug design.
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Proteases 3C de Coronavírus , Inibidores de Proteases , SARS-CoV-2 , Humanos , COVID-19 , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Proteases 3C de Coronavírus/antagonistas & inibidoresRESUMO
The mechanistic understanding of catalytic radical reactions currently lags behind the flourishing development of new types of catalytic activation. Herein, an innovative single electron transfer (SET) model has been expanded by using the nonadiabatic crossing integrated with the rate-determining step of 1,5-hydrogen atom transfer (HAT) reaction to provide the control mechanism of radical decay dynamics through calculating excited-state relaxation paths of a paradigm example of the amide-directed distal sp3 C-H bond alkylation mediated by Ir-complex-based photocatalysts. The stability of carbon radical intermediates, the functional hindrance associated with the back SET, and the energy inversion between the reactive triplet and closed-shell ground states were verified to be key factors in improving catalytic efficiency via blocking radical inhibition. The expanded SET model associated with the dynamic behaviors and kinetic data could guide the design and manipulation of visible-light-driven inert bond activation by the utilization of photocatalysts bearing more or less electron-withdrawing groups and the comprehensive considerations of kinetic solvent effects and electron-withdrawing effects of substrates.
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2,4,5,6-Tetrakis(3,6-di-tert-butyl-9H-carbazol-9-yl)isophthalonitrile (4CzIPN-tBu) was developed as a photocatalyst for the phosphorus-radical-initiated cascade cyclization reaction of isocyanides. By using 4CzIPN-tBu as catalyst, we developed a visible-light-induced proton-coupled electron transfer strategy for the generation of phosphorus-centered radicals, via which a wide range of phosphorylated phenanthridines, quinolines, and benzothiazoles were successfully constructed.