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1.
Mol Cell ; 83(12): 2137-2147.e4, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37244256

RESUMEN

Biological energy currency ATP is produced by F1Fo-ATP synthase. However, the molecular mechanism for human ATP synthase action remains unknown. Here, we present snapshot images for three main rotational states and one substate of human ATP synthase using cryoelectron microscopy. These structures reveal that the release of ADP occurs when the ß subunit of F1Fo-ATP synthase is in the open conformation, showing how ADP binding is coordinated during synthesis. The accommodation of the symmetry mismatch between F1 and Fo motors is resolved by the torsional flexing of the entire complex, especially the γ subunit, and the rotational substep of the c subunit. Water molecules are identified in the inlet and outlet half-channels, suggesting that the proton transfer in these two half-channels proceed via a Grotthus mechanism. Clinically relevant mutations are mapped to the structure, showing that they are mainly located at the subunit-subunit interfaces, thus causing instability of the complex.


Asunto(s)
Adenosina Trifosfato , ATPasas de Translocación de Protón , Humanos , Microscopía por Crioelectrón , Adenosina Trifosfato/metabolismo , ATPasas de Translocación de Protón/química , Conformación Proteica
2.
Nature ; 612(7939): 259-265, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36443603

RESUMEN

The unique topology and physics of chiral superlattices make their self-assembly from nanoparticles highly sought after yet challenging in regard to (meta)materials1-3. Here we show that tetrahedral gold nanoparticles can transform from a perovskite-like, low-density phase with corner-to-corner connections into pinwheel assemblies with corner-to-edge connections and denser packing. Whereas corner-sharing assemblies are achiral, pinwheel superlattices become strongly mirror asymmetric on solid substrates as demonstrated by chirality measures. Liquid-phase transmission electron microscopy and computational models show that van der Waals and electrostatic interactions between nanoparticles control thermodynamic equilibrium. Variable corner-to-edge connections among tetrahedra enable fine-tuning of chirality. The domains of the bilayer superlattices show strong chiroptical activity as identified by photon-induced near-field electron microscopy and finite-difference time-domain simulations. The simplicity and versatility of substrate-supported chiral superlattices facilitate the manufacture of metastructured coatings with unusual optical, mechanical and electronic characteristics.


Asunto(s)
Oro , Nanopartículas del Metal , Electrónica , Física
3.
Proc Natl Acad Sci U S A ; 121(25): e2313193121, 2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38857390

RESUMEN

Renewable Portfolio Standards (RPSs) are one of the most prevalent and impactful clean energy policies implemented by states in the United States. This paper investigates the regional spillover effect of RPS policies using a directed dyad panel dataset of renewable electricity generation in US states from 1991 to 2021. Regional spillover effect is measured in two ways: by considering the influence of an RPS enacted in neighboring states and in states in the same regional transmission organization or independent system operator region. We use dyadic fixed effects estimation and conclude that the neighboring state's RPS stringency score is a strong determinant of a state's total renewable electricity generation. For states without an RPS, the positive influence of an RPS in a neighboring state is larger when the non-RPS state has more abundant renewable energy resources than the neighboring RPS state. Our findings suggest that past RPS policy evaluation research using a confined within-state focus may have underestimated the holistic impact of an RPS, as the impacts of an RPS policy can extend beyond the enacting state's borders. Overall, this study contributes to an improved understanding of the holistic impact of state RPS policies.

4.
Proc Natl Acad Sci U S A ; 120(18): e2216713120, 2023 05 02.
Artículo en Inglés | MEDLINE | ID: mdl-37098072

RESUMEN

Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of this molecular machine. Here, we have determined the structure of human complex II in the presence of ubiquinone at 2.86 Å resolution by cryoelectron microscopy, showing it comprises two water-soluble subunits, SDHA and SDHB, and two membrane-spanning subunits, SDHC and SDHD. This structure allows us to propose a route for electron transfer. In addition, clinically relevant mutations are mapped onto the structure. This mapping provides a molecular understanding to explain why these variants have the potential to produce disease.


Asunto(s)
Estructura Cuaternaria de Proteína , Humanos , Modelos Moleculares , Mutación , Microscopía por Crioelectrón
5.
Chem Rev ; 123(5): 2276-2310, 2023 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-35522923

RESUMEN

Liquid flowing around a solid edge, i.e., overflow, is a commonly observed flow behavior. Recent research into surface wetting properties and microstructure-controlled overflow behavior has attracted much attention. Achieving controllable macroscale liquid dynamics by manipulating the micro-nanoscale liquid overflow has stimulated diverse scientific interest and fostered widespread use in practical applications. In this review, we outline the evolution of overflow and present a critical survey of the mechanism of surface wetting properties and microstructure-controlled liquid overflow in multilength scales ranging from centimeter to micro and even nanoscale. We summarize the latest progress in utilizing the mechanisms to manipulate liquid overflow and achieve macroscale liquid dynamics and in emerging applications to manipulate overflow for sustainable development in various fields, along with challenges and perspectives.

6.
Nano Lett ; 24(8): 2589-2595, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38252875

RESUMEN

Surface topography, or height profile, is a critical property for various micro- and nanostructured materials and devices, as well as biological systems. At the nanoscale, atomic force microscopy (AFM) is the tool of choice for surface profiling due to its capability to noninvasively map the topography of almost all types of samples. However, this method suffers from one drawback: the convolution of the nanoprobe's shape in the height profile of the samples, which is especially severe for sharp protrusion features. Here, we report a deep learning (DL) approach to overcome this limit. Adopting an image-to-image translation methodology, we use data sets of tip-convoluted and deconvoluted image pairs to train an encoder-decoder based deep convolutional neural network. The trained network successfully removes the tip convolution from AFM topographic images of various nanocorrugated surfaces and recovers the true, precise 3D height profiles of these samples.

7.
J Cell Mol Med ; 28(3): e18075, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38213100

RESUMEN

The prevalence of chronic kidney disease (CKD) is highly increasing. Renal fibrosis is a common pathological feature in various CKD. Previous studies showed tubular cell senescence is highly involved in the pathogenesis of renal fibrosis. However, the inducers of tubular senescence and the underlying mechanisms have not been fully investigated. C-X-C motif chemokine receptor 4 (CXCR4), a G-protein-coupled seven-span transmembrane receptor, increases renal fibrosis and plays an important role in tubular cell injury. Whereas, whether CXCR4 could induce tubular cell senescence and the detailed mechanisms have not studied yet. In this study, we adopted adriamycin nephropathy and 5/6 nephrectomy models, and cultured tubular cell line. Overexpression or knockdown of CXCR4 was obtained by injection of related plasmids. We identified CXCR4 increased in injury tubular cells. CXCR4 was expressed predominantly in renal tubular epithelial cells and co-localized with adipose differentiation-related protein (ADRP) as well as the senescence-related protein P16INK4A . Furthermore, we found overexpression of CXCR4 greatly induced the activation of ß-catenin, while knockdown of CXCR4 inhibited it. We also found that CXCR4 inhibited fatty acid oxidation and triggered lipid deposition in tubular cells. To inhibit ß-catenin by ICG-001, an inhibitor of ß-catenin, could significantly block CXCR4-suppressed fatty acid oxidation. Taken together, our results indicate that CXCR4 is a key mediator in tubular cell senescence and renal fibrosis. CXCR4 promotes tubular cell senescence and renal fibrosis by inducing ß-catenin and inhibiting fatty acid metabolism. Our findings provide a new theory for tubular cell injury in renal fibrosis.


Asunto(s)
Riñón , Receptores CXCR4 , Insuficiencia Renal Crónica , beta Catenina , beta Catenina/metabolismo , Senescencia Celular , Células Epiteliales/metabolismo , Ácidos Grasos/metabolismo , Fibrosis , Riñón/patología , Insuficiencia Renal Crónica/patología , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Animales , Ratones
8.
J Am Chem Soc ; 146(15): 10498-10507, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38590084

RESUMEN

Metastable compounds have greatly expanded the synthesizable compositions of solid-state materials and have attracted enormous amounts of attention in recent years. Especially, mechanochemically enabled metastable materials synthesis has been very successful in realizing cation-disordered materials with highly simple crystal structures, such as rock salts. Application of the same strategy for other structural types, especially for non-close-packed structures, is peculiarly underexplored. Niobium tungsten oxides (NbWOs), a class of materials that have been under the spotlight because of their diverse structural varieties and promising electrochemical and thermoelectric properties, are ideally suited to fill such a knowledge gap. In this work, we develop a new series of metastable NbWOs and realize one with a fully cation-disordered structure. Furthermore, we find that metastable NbWOs transform to a cation-disordered cubic structure when applied as a Li-ion battery anode, highlighting an intriguing non-close-packed-close-packed conversion process, as evidenced in various physicochemical characterizations, in terms of diffraction, electronic, and vibrational structures. Finally, by comparing the cation-disordered NbWO with other trending cation-disordered oxides, we raise a few key structural features for cation disorder and suggest a few possible research opportunities for this field.

9.
Small ; 20(11): e2306910, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37926698

RESUMEN

Heterogeneous membranes play a crucial role in osmotic energy conversion by effectively reducing concentration polarization. However, most heterogeneous membranes mitigate concentration polarization through an asymmetric charge distribution, resulting in compromised ion selectivity. Herein, hetero-nanochannels with asymmetric wettability composed of 2D mesoporous carbon and graphene oxide are constructed. The asymmetric wettability of the membrane endows it with the ability to suppress the concentration polarization without degrading the ion selectivity, as well as achieving a diode-like ion transport feature. As a result, enhanced osmotic energy harvesting is achieved with a power density of 6.41 W m-2 . This represents a substantial enhancement of 102.80-137.85% when compared to homogeneous 2D membranes, surpassing the performance of the majority of reported 2D membranes. Importantly, the membrane can be further used for high-performance ionic power harvesting by regulating ion transport, exceeding previously reported data by 89.1%.

10.
Drug Metab Dispos ; 52(3): 210-217, 2024 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-38195521

RESUMEN

Valproic acid (VPA) is a first-line antiepileptic drug with broad efficacy. Due to significant individual differences in its metabolism, therapeutic drug monitoring is commonly used. However, the recommended therapeutic range (50-100 µg/mL) is inadequate for predicting clinical outcomes. Additionally, the relationship between VPA metabolites and clinical outcomes remains unclear. In this retrospective study, 485 Chinese Southern Han epilepsy patients receiving VPA monotherapy were analyzed after reaching steady-state levels. Plasma concentrations of VPA and its five main metabolites were determined by liquid chromatography-mass spectrometry (LC-MS). We assessed the relevance of the recommended therapeutic VPA range for clinical outcomes and explored the association between VPA/metabolites levels and treatment efficacy/adverse effects. Vitro experiments were conducted to assess 4-ene-VPA hepatotoxicity. The therapeutic range of VPA exhibited no significant correlation with clinical outcomes, and plasma concentrations of VPA failed to serve as predictive indicators for treatment response/adverse effects. Treatment responders had higher 2-PGA concentrations (median, 26.39 ng/mL versus 13.68 ng/mL), with a threshold of 36.5 ng/mL for optimal epilepsy treatment. Patients with abnormal liver function had a higher 4-ene-VPA median concentration (6.41 µg/mL versus 4.83 µg/mL), and the ratio of 4-ene-VPA to VPA better predicted VPA-induced hepatotoxicity (area under the curve, 0.718) than 4-ene-VPA concentration. Vitro experiments revealed that 4-ene-VPA was more hepatotoxic than VPA in HepaRG and L02 cell lines. Total plasma VPA concentration does not serve as a predictor of clinical outcomes. 2-PGA concentrations may be associated with efficacy, whereas the ratio of 4-ene-VPA to VPA may be considered a better biomarker (threshold 10.03%) for VPA-induced hepatotoxicity. SIGNIFICANCE STATEMENT: This was the first and largest observational cohort in China to explore the relationship between patients' parent and metabolites concentrations of VPA and clinical outcomes during the maintenance of VPA monotherapy in epileptic patients. This study provided feasible references of VPA for epilepsy clinical treatment with a larger sample of patients compared with previous studies for a more definitive conclusion based on real-world situations. We found two potential biomarkers in predicting efficacy and liver injury, respectively. This breakthrough has the potential to assist in the rational use of VPA.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Epilepsia , Humanos , Anticonvulsivantes/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/tratamiento farmacológico , Monitoreo de Drogas , Epilepsia/tratamiento farmacológico , Estudios Retrospectivos , Ácido Valproico/efectos adversos
11.
Mol Reprod Dev ; 91(2): e23731, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38404010

RESUMEN

Premature ovarian insufficiency (POI) patients experience a decline in ovarian function and a reduction in serum reproductive hormones, leading to a significant impact on the outcomes of assisted reproductive technology. Despite the absence of an effective clinical treatment to restore fertility in POI patients, recent research has indicated that cord blood plasma (CBP) derived from human umbilical cord blood (hUCB) may offer therapeutic benefits for various degenerative diseases. The primary aim of this study is to explore approaches for enhancing ovarian function and serum reproductive hormones through the administration of CBP in a murine model. Initially, hUCB was utilized to obtain CBP (CBP), which was subsequently analyzed for cytokine and growth factor profiles in comparison to adult blood plasma (ABP) by use of flow cytometry. Subsequently, POI mouse models were established through the induction of 4-vinylcyclohexene diepoxide, followed by the injection of CBP into the tail. At 7, 14, and 21 days posttreatment, mouse ovaries and blood were collected, and their estrus cycle, body weight, and ovarian weights were evaluated using precise electronic balance. Finally, ovarian morphology and follicle number were assessed through HE staining, while serum levels of anti-Müllerian hormone (AMH), estradiol (E2) and follicle-stimulating hormone (FSH) were determined by ELISA. Our study revealed that individuals with CBP exhibited significantly lower concentrations of proinflammatory cytokines, including IL-ß (p < 0.01) and IL-2 (p < 0.05), while displaying elevated levels of anti-inflammatory cytokines and chemokines, such as IL-2, IL-4, IL-6, IL-8, IL-12P70, IL-17A, IP-10, interferon-γ, and tumor necrosis factor-α (p < 0.01). Furthermore, CBP demonstrated remarkably higher levels of growth factors, including transforming growth factor-ß1, vascular endothelial growth factor, and insulin-like growth factor-1 (p < 0.01) than ABP. Notably, our investigation also revealed that CBP restored the content of serum reproductive hormones, such as AMH, E2, and FSH (p < 0.05), and increased the number of primordial and primary follicles (p < 0.01) and decreased the number of luteal and atretic follicles (p < 0.01) in vivo. Our findings suggested that CBP-secreted cytokines and growth factors could be restored POI ovarian function, enhanced serum reproductive hormones and rescued follicular development in vivo. These findings further support the potential of CBP as a promising strategy in clinical applications for POI related infertility.


Asunto(s)
Citocinas , Insuficiencia Ovárica Primaria , Femenino , Adulto , Humanos , Ratones , Animales , Sangre Fetal , Factor A de Crecimiento Endotelial Vascular , Interleucina-2 , Insuficiencia Ovárica Primaria/terapia , Insuficiencia Ovárica Primaria/patología , Estradiol , Hormona Folículo Estimulante , Péptidos y Proteínas de Señalización Intercelular , Plasma
12.
Artículo en Inglés | MEDLINE | ID: mdl-38714595

RESUMEN

Providencia genus is known to harbor certain opportunistic pathogens capable of causing human infections. Here, we report two strains of multidrug-resistant bacteria initially identified as Providencia rettgeri by mass spectrometry, but genome analysis revealed their ANI (79.84-84.20%) and dDDH (21.1-25.6%) values to fall below the accepted species threshold for known Providencia species. We therefore propose that these isolates be recognized as a novel species, Providencia xianensis sp. nov. Alarmingly, both strains, isolated from locations far apart, exhibited resistance to last-resort antibiotics, indicating their possible wide distribution, underscoring the urgency for immediate attention and enhanced surveillance for this emerging multidrug-resistant pathogen.

13.
Analyst ; 149(13): 3522-3529, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787653

RESUMEN

Bioinspired nanochannel-based sensors have elicited significant interest because of their excellent sensing performance, and robust mechanical and tunable chemical properties. However, the existing designs face limitations due to material constraints, which hamper broader application possibilities. Herein, a heteromembrane system composed of a periodic mesoporous organosilica (PMO) layer with three-dimensional (3D) network nanochannels is constructed for glutathione (GSH) detection. The unique hierarchical pore architecture provides a large surface area, abundant reaction sites and plentiful interconnected pathways for rapid ionic transport, contributing to efficient and sensitive detection. Moreover, the thioether groups in nanochannels can be selectively cleaved by GSH to generate hydrophilic thiol groups. Benefiting from the increased hydrophilic surface, the proposed sensor achieves efficient GSH detection with a detection limit of 1.2 µM by monitoring the transmembrane ionic current and shows good recovery ranges in fetal bovine serum sample detection. This work paves an avenue for designing and fabricating nanofluidic sensing systems for practical and biosensing applications.


Asunto(s)
Glutatión , Límite de Detección , Compuestos de Organosilicio , Glutatión/química , Glutatión/análisis , Glutatión/sangre , Porosidad , Compuestos de Organosilicio/química , Animales , Bovinos , Técnicas Biosensibles/métodos , Membranas Artificiales , Técnicas Electroquímicas/métodos
14.
Analyst ; 149(5): 1464-1472, 2024 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-38284827

RESUMEN

Copper ions (Cu2+), as a crucial trace element, play a vital role in living organisms. Thus, the detection of Cu2+ is of great significance for disease prevention and diagnosis. Nanochannel devices with an excellent nanoconfinement effect show great potential in recognizing and detecting Cu2+ ions. However, these devices often require complicated modification and treatment, which not only damages the membrane structure, but also induces nonspecific, low-sensitivity and non-repeatable detection. Herein, a 2D MXene-carboxymethyl chitosan (MXene/CMC) freestanding membrane with ordered lamellar channels was developed by a super-assembly strategy. The introduction of CMC provides abundant space charges, improving the nanoconfinement effect of the nanochannel. Importantly, the CMC can chelate with Cu2+ ions, endowing the MXene/CMC with the ability to detect Cu2+. The formation of CMC-Cu2+ complexes decreases the space charges, leading to a discernible variation in the current signal. Therefore, MXene/CMC can achieve highly sensitive and stable Cu2+ detection based on the characteristics of nanochannel composition. The linear response range for Cu2+ detection is 10-9 to 10-5 M with a low detection limit of 0.095 nM. Notably, MXene/CMC was successfully applied for Cu2+ detection in real water and fetal bovine serum samples. This work provides a simple, highly sensitive and stable detection platform based on the properties of the nanochannel composition.


Asunto(s)
Quitosano , Nitritos , Oligoelementos , Elementos de Transición , Cobre , Quitosano/química , Iones/química
15.
Acta Pharmacol Sin ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38789496

RESUMEN

Renal tubular epithelial cell senescence plays a critical role in promoting and accelerating kidney aging and age-related renal fibrosis. Senescent cells not only lose their self-repair ability, but also can transform into senescence-associated secretory phenotype (SASP) to trigger inflammation and fibrogenesis. Recent studies show that mitochondrial dysfunction is critical for renal tubular cell senescence and kidney aging, and calcium overload and abnormal calcium-dependent kinase activities are involved in mitochondrial dysfunction-associated senescence. In this study we investigated the role of mitochondrial calcium overload and mitochondrial calcium uniporter (MCU) in kidney aging. By comparing the kidney of 2- and 24-month-old mice, we found calcium overload in renal tubular cells of aged kidney, accompanied by significantly elevated expression of MCU. In human proximal renal tubular cell line HK-2, pretreatment with MCU agonist spermine (10 µM) significantly increased mitochondrial calcium accumulation, and induced the production of reactive oxygen species (ROS), leading to renal tubular cell senescence and age-related kidney fibrosis. On the contrary, pretreatment with MCU antagonist RU360 (10 µM) or calcium chelator BAPTA-AM (10 µM) diminished D-gal-induced ROS generation, restored mitochondrial homeostasis, retarded cell senescence, and protected against kidney aging in HK-2 cells. In a D-gal-induced accelerated aging mice model, administration of BAPTA (100 µg/kg. i.p.) every other day for 8 weeks significantly alleviated renal tubuarl cell senescence and fibrosis. We conclude that MCU plays a key role in promoting renal tubular cell senescence and kidney aging. Targeting inhibition on MCU provides a new insight into the therapeutic strategy against kidney aging.

16.
Proc Natl Acad Sci U S A ; 118(16)2021 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-33853951

RESUMEN

Encapsulins containing dye-decolorizing peroxidase (DyP)-type peroxidases are ubiquitous among prokaryotes, protecting cells against oxidative stress. However, little is known about how they interact and function. Here, we have isolated a native cargo-packaging encapsulin from Mycobacterium smegmatis and determined its complete high-resolution structure by cryogenic electron microscopy (cryo-EM). This encapsulin comprises an icosahedral shell and a dodecameric DyP cargo. The dodecameric DyP consists of two hexamers with a twofold axis of symmetry and stretches across the interior of the encapsulin. Our results reveal that the encapsulin shell plays a role in stabilizing the dodecameric DyP. Furthermore, we have proposed a potential mechanism for removing the hydrogen peroxide based on the structural features. Our study also suggests that the DyP is the primary cargo protein of mycobacterial encapsulins and is a potential target for antituberculosis drug discovery.


Asunto(s)
Proteínas Bacterianas/ultraestructura , Mycobacterium smegmatis/ultraestructura , Peroxidasas/ultraestructura , Proteínas Bacterianas/metabolismo , Microscopía por Crioelectrón/métodos , Mycobacterium smegmatis/metabolismo , Mycobacterium smegmatis/patogenicidad , Orgánulos/metabolismo , Orgánulos/fisiología , Peroxidasas/metabolismo
17.
J Insect Sci ; 24(1)2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38412293

RESUMEN

The butterfly genus of Teinopalpus, endemic to Asia, embodies a distinct species of mountain-dwelling butterflies with specific habitat requirements. These species are rare in the wild and hold high conservation and research value. Similar to other protected species, the genetic analysis of the rare Teinopalpus aureus poses challenges due to the complexity of sampling. In this study, we successfully extracted DNA and amplified mitochondrial genomic DNA from various noninvasive sources such as larval feces, larval exuviae, larval head capsules, pupal exuviaes, and filamentous gland secretions, all integral parts of butterfly metamorphosis. This was conducted as part of a research initiative focused on the artificial conservation of T. aureus population in Jinggang Shan Nature Reserve. Our findings illustrated the successful extraction of DNA from multiple noninvasive sources, achieved through modified DNA extraction methodologies. Although the DNA concentration obtained from noninvasive samples was lower than that from muscle tissues of newly dead larvae during rearing, all samples met the requirements for PCR amplification and sequencing, yielding complete circular sequences. These sequences are pivotal for both interspecific and intraspecific genetic relationship analysis. Our methods can be extended to other insects, especially scarce species.


Asunto(s)
Mariposas Diurnas , Genoma Mitocondrial , Lepidópteros , Animales , Mariposas Diurnas/genética , Lepidópteros/genética , Filogenia , Análisis de Secuencia de ADN , ADN Mitocondrial/genética , Larva/genética
18.
Phytochem Anal ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740517

RESUMEN

INTRODUCTION: Sulfur-fumigation of Paeoniae Radix Alba (PRA) could induce the chemical transformation of its bioactive component paeoniflorin into a sulfur-containing derivative paeoniflorin sulfite, and thus alter the quality, bioactivities, pharmacokinetics, and toxicities of PRA. However, how sulfur-fumigated PRA (S-PRA) affects the quality of PRA-containing complex preparations has not been intensively evaluated. OBJECTIVES: We intend to evaluate the influence of S-PRA on the overall quality of three kinds of Si-Wu-Tang (SWT) formulations, i.e., decoction (SWT-D), granule (SWT-G), and mixture (SWT-M). MATERIAL AND METHODS: An UPLC-DAD multi-components quantification method was used to compare the transfer rates of paeoniflorin sulfite and other 10 bioactive components between S-PRA-containing and NS-PRA-containing SWT formulations. An UPLC-QTOF-MS/MS-based target metabolomics approach was applied to explore the differential sulfur-containing derivatives in S-PRA-containing SWT formulations. RESULTS: The transfer rates of paeoniflorin sulfite in three S-PRA-containing SWT formulations were all higher than 100%. Moreover, S-PRA also increased the transfer rate of 5-hydroxymethylfurfural, 1,2,3,4,6-O-pentagalloylglucose, whereas decreased that of paeoniflorin, albiflorin, and ferulic acid in three SWT formulations. Six pinane monoterpene glucoside sulfites originally identified in S-PRA, were also detectable in three S-PRA-containing SWT formulations. In addition, seven phenolic acid sulfites including (3Z)-6-sulfite-ligustilide, (3E)-6-sulfite-ligustilide, 6,8-disulfite-ligustilide, ferulic acid sulfite, neochlorogenic acid sulfite, chlorogenic acid sulfite, and angelicide sulfite (or isomer) were newly identified in these three S-PRA-containing formulations. CONCLUSION: S-PRA could differentially affect the transfer rate of paeoniflorin sulfite and other bioactive components during the preparation of three SWT formulations and subsequently the overall quality thereof.

19.
Phytochem Anal ; 35(4): 733-753, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38219286

RESUMEN

INTRODUCTION: Zishui-Qinggan decoction (ZQD) is a classical traditional Chinese medicine formula (TCMF) for alleviating menopausal symptoms (MPS) induced by endocrine therapy in breast cancer patients. In the production of TCMF modern preparations, ethanol precipitation (EP) is a commonly but not fully verified refining process. OBJECTIVES: Chemical profiling/serum pharmacochemistry and network pharmacology approaches were integrated for exploring the rationality of the EP process in the production of ZQD modern preparations. MATERIAL AND METHODS: Ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS/MS) was applied to identify the chemical profiles and absorbed components of ZQD. Network pharmacology was used to identify targets and pathways related to MPS-relieving efficacy. RESULTS: The chemicals of ZQDs without/with EP process (referred to as ZQD-W and ZQD-W-P, respectively) were qualitatively similar with 89 and 87 components identified, respectively, but their relative contents were different; 51 components were detectable in the serum of rats orally administered with ZQD-W, whereas only 19 were detected in that administered with ZQD-W-P. Key targets, such as AKT1, and pathways, such as the PI3K-Akt signalling pathway, affected by ZQD-W and ZQD-W-P were similar, while the neuroactive ligand-receptor interaction pathway among others and the MAPK signalling pathway among others were specific pathways affected by ZQD-W and ZQD-W-P, respectively. The specifically absorbed components of ZQD-W could combine its specific key targets. CONCLUSION: The EP process quantitatively altered the chemical profiles of ZQD, subsequently affected the absorbed components of ZQD, and then affected the key targets and pathways of ZQD for relieving MPS. The EP process might result in variation of the MPS-relieving efficacy of ZQD, which deserves further in vivo verification.


Asunto(s)
Medicamentos Herbarios Chinos , Etanol , Farmacología en Red , Espectrometría de Masas en Tándem , Medicamentos Herbarios Chinos/química , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Animales , Etanol/química , Ratas Sprague-Dawley , Ratas , Precipitación Química , Medicina Tradicional China
20.
Angew Chem Int Ed Engl ; : e202407491, 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38735853

RESUMEN

Ion-selective nanochannel membranes assembled from two-dimensional (2D) nanosheets hold immense promise for power conversion using salinity gradient. However, they face challenges stemming from insufficient surface charge density, which impairs both permselectivity and durability. Herein, we present a novel vacancy-engineered, oxygen-deficient NiCo layered double hydroxide (NiCoLDH)/cellulose nanofibers-wrapped carbon nanotubes (VOLDH/CNF-CNT) composite membrane. This membrane, featuring abundant angstrom-scale, cation-selective nanochannels, is designed and fabricated through a synergistic combination of vacancy engineering and interfacial super-assembly. The composite membrane shows interlayer free-spacing of ~3.62 Å, which validates the membrane size exclusion selectivity. This strategy, validated by DFT calculations and experimental data, improves hydrophilicity and surface charge density, leading to the strong interaction with K+ ions to benefit the low ion transport resistance and exceptional charge selectivity. When employed in an artificial river water|seawater salinity gradient power generator, it delivers a high-power density of 5.35 W/m2 with long-term durability (20,000s), which is almost 400 % higher than that of the pristine NiCoLDH membrane. Furthermore, it displays both pH- and temperature-sensitive ion transport behavior, offering additional opportunities for optimization. This work establishes a basis for high-performance salinity gradient power conversion and underscores the potential of vacancy engineering and super-assembly in customizing 2D nanomaterials for diverse advanced nanofluidic energy devices.

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