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The scaling of silicon metal-oxide-semiconductor field-effect transistors has followed Moore's law for decades, but the physical thinning of silicon at sub-ten-nanometre technology nodes introduces issues such as leakage currents1. Two-dimensional (2D) layered semiconductors, with an atomic thickness that allows superior gate-field penetration, are of interest as channel materials for future transistors2,3. However, the integration of high-dielectric-constant (κ) materials with 2D materials, while scaling their capacitance equivalent thickness (CET), has proved challenging. Here we explore transferrable ultrahigh-κ single-crystalline perovskite strontium-titanium-oxide membranes as a gate dielectric for 2D field-effect transistors. Our perovskite membranes exhibit a desirable sub-one-nanometre CET with a low leakage current (less than 10-2 amperes per square centimetre at 2.5 megavolts per centimetre). We find that the van der Waals gap between strontium-titanium-oxide dielectrics and 2D semiconductors mitigates the unfavourable fringing-induced barrier-lowering effect resulting from the use of ultrahigh-κ dielectrics4. Typical short-channel transistors made of scalable molybdenum-disulfide films by chemical vapour deposition and strontium-titanium-oxide dielectrics exhibit steep subthreshold swings down to about 70 millivolts per decade and on/off current ratios up to 107, which matches the low-power specifications suggested by the latest International Roadmap for Devices and Systems5.
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Cr2(NCN)3 is a potentially high-capacity and fast-charge Li-ion anode owing to its abundant and broad tunnels. However, high intrinsic chemical instability severely restricts its capacity output and electrochemical reversibility. Herein we report an effective crystalline engineering method for optimizing its phase and crystallinity. Systematic studies reveal the relevancy between electrochemical performance and crystalline structure; an optimal Cr2(NCN)3 with high phase purity and uniform crystallinity exhibits a high reversible capacity of 590 mAh g-1 and a stable cycling performance of 478 mAh g-1 after 500 cycles. In-operando heating XRD reveals its high thermodynamical stability over 600 °C, and in-operando electrochemical XRD proves its electrochemical Li storage mechanism, consisting of the primary Li-ion intercalation and subsequent conversion reactions. This study introduces a facile and low-cost method for fabricating high-purity Cr2(NCN)3, and it also confirms that the Li storage of Cr2(NCN)3 can be further improved by tuning its phase and crystallinity.
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The nonfused thiophene-benzene-thiophene (TBT) unit offers advantages in obtaining low-cost organic photovoltaic (OPV) materials due to its simple structure. However, OPV cells, including TBT-based acceptors, exhibit significantly lower energy conversion efficiencies. Here, we introduce a novel approach involving the design and synthesis of three TBT-based acceptors by substituting different position-branched side chains on the TBT unit. In comparison to TBT-10 and TBT-11, TBT-13, which exclusively incorporates α-position branched side chains with a large steric hindrance, demonstrates a more planar and stable conformation. When blended with the donor PBQx-TF, TBT-13-based blend film achieves favorable π-π stacking and aggregation characteristics, resulting in excellent charge transfer performance in the corresponding device. Due to the simultaneous enhancements in short-circuit current density and fill factor, the TBT-13-based OPV cell obtains an outstanding efficiency of 16.1%, marking the highest value for the cells based on fully nonfused acceptors. Our work provides a practical molecular design strategy for high-performance and low-cost OPV materials.
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BACKGROUND: To explore whether nobiletin has a protective effect on high-fat diet (HFD)-induced enteric nerve injury and its underlying mechanism. METHODS: An obesity model was induced by a HFD. Nobiletin (100 mg/kg and 200 mg/kg) and vehicle were administered by gastric gavage for 4 weeks. Lee's index, body weight, OGTT and intestinal propulsion assays were performed before sacrifice. After sampling, lipids were detected using Bodipy 493/503; lipid peroxidation was detected using MDA and SOD kits and the expression of PGP 9.5, Trem2, GFAP, ß-tubulin 3, Bax, Bcl2, Nestin, P75 NTR, SOX10 and EDU was detected using immunofluorescence. The GDNF, p-AKT, AKT, p-FOXO3a, FOXO3a and P21 proteins were detected using western blotting. The relative mRNA expression levels of NOS2 were detected via qPCR. Primary enteric neural stem cells (ENSCs) were cultured. After ENSCs were treated with palmitic acid (PA) and nobiletin, CCK-8 and caspase-3/7 activity assays were performed to evaluate proliferation and apoptosis. RESULTS: HFD consumption caused colon lipid accumulation and peroxidation, induced enteric nerve damage and caused intestinal motor dysfunction. However, nobiletin reduced lipid accumulation and peroxidation in the colon; promoted Trem2, ß-tubulin 3, Nestin, P75NTR, SOX10 and Bcl2 expression; inhibited Bax and GFAP expression; reduced NOS2 mRNA transcription; and regulated the GDNF/AKT/FOXO3a/P21 pathway. Nobiletin also promoted PA-induced impairment of ENSCs. CONCLUSIONS: Nobiletin restored HFD-induced enteric nerve injury, which may be associated with inhibiting enteric nerve apoptosis, promoting enteric nerve survival and regulating the GDNF/AKT/FOXO3a/P21 pathway.
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Dieta Alta en Grasa , Sistema Nervioso Entérico , Flavonas , Proteína Forkhead Box O3 , Factor Neurotrófico Derivado de la Línea Celular Glial , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Proteína Forkhead Box O3/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Dieta Alta en Grasa/efectos adversos , Transducción de Señal/efectos de los fármacos , Masculino , Flavonas/farmacología , Flavonas/uso terapéutico , Sistema Nervioso Entérico/metabolismo , Sistema Nervioso Entérico/efectos de los fármacos , Neuroglía/metabolismo , Neuroglía/efectos de los fármacos , Ratones , Modelos Animales de Enfermedad , Ratas , Obesidad/metabolismo , Obesidad/tratamiento farmacológico , Apoptosis/efectos de los fármacosRESUMEN
BACKGROUND: The circadian clock, also known as the circadian rhythm, is responsible for predicting daily and seasonal changes in the environment, and adjusting various physiological and developmental processes to the appropriate times during plant growth and development. The circadian clock controls the expression of the Lhcb gene, which encodes the chlorophyll a/b binding protein. However, the roles of the Lhcb gene in tea plant remain unclear. RESULTS: In this study, a total of 16 CsLhcb genes were identified based on the tea plant genome, which were distributed on 8 chromosomes of the tea plant. The promoter regions of CsLhcb genes have a variety of cis-acting elements including hormonal, abiotic stress responses and light response elements. The CsLhcb family genes are involved in the light response process in tea plant. The photosynthetic parameter of tea leaves showed rhythmic changes during the two photoperiod periods (48 h). Stomata are basically open during the day and closed at night. Real-time quantitative PCR results showed that most of the CsLhcb family genes were highly expressed during the day, but were less expressed at night. CONCLUSIONS: Results indicated that CsLhcb genes were involved in the circadian clock process of tea plant, it also provided potential references for further understanding of the function of CsLhcb gene family in tea plant.
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Camellia sinensis , Ritmo Circadiano , Fotosíntesis , Fotosíntesis/genética , Camellia sinensis/genética , Camellia sinensis/fisiología , Ritmo Circadiano/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genes de Plantas , Familia de Multigenes , Proteínas de Unión a Clorofila/genética , Proteínas de Unión a Clorofila/metabolismo , FotoperiodoRESUMEN
Non-fused electron acceptors have huge advantages in fabricating low-cost organic photovoltaic (OPV) cells. However, morphology control is a challenge as non-fused CâC single bonds bring more molecular conformations. Here, by selecting two typical polymer donors, PBDB-TF and PBQx-TF, the blend morphologies and its impacts on the power conversion efficiencies (PCEs) of non-fused acceptor-based OPV cells are studied. A selenium-containing non-fused acceptor named ASe-5 is designed. The results suggest that PBQx-TF has a lower miscibility with ASe-5 when compared with PBDB-TF. Additionally, the polymer networks may form earlier in the PBQx-TF:ASe-5 blend film due to stronger preaggregation performance, leading to a more obvious phase separation. The PBQx-TF:ASe-5 blend film shows faster charge transfer and suppressed charge recombination. As a result, the PBQx-TF:ASe-5-based device records a good PCE of 14.7% with a higher fill factor (FF) of 0.744, while the PBDB-TF:ASe-5-based device only obtains a moderate PCE of 12.3% with a relatively low FF of 0.662. The work demonstrates that the selection of donors plays a crucial role in controlling the blend morphology and thus improving the PCEs of non-fused acceptor-based OPV cells.
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Negative therapeutic feedback of inflammation would extensively attenuate the antitumor effect of photodynamic therapy (PDT). In this work, tumor homing chimeric peptide rhomboids (designated as NP-Mel) are fabricated to improve photodynamic performance by inhibiting PDT-upregulated cyclooxygenase-2 (COX-2). The hydrophobic photosensitizer of protoporphyrin IX (PpIX) and palmitic acid are conjugated onto the neuropilin receptors (NRPs) targeting peptide motif (CGNKRTR) to obtain tumor homing chimeric peptide (Palmitic-K(PpIX)CGNKRTR), which can encapsulate the COX-2 inhibitor of meloxicam. The well dispersed NP-Mel not only improves the drug stability and reactive oxygen species (ROS) production ability, but also increase the breast cancer targeted drug delivery to intensify the PDT effect. In vitro and in vivo studies verify that NP-Mel will decrease the secretion of prostaglandin E2 (PGE2) after PDT treatment, inducing the downregulation of IL-6 and TNF-α expressions to suppress PDT induced inflammation. Ultimately, an improved PDT performance of NP-Mel is achieved without inducing obvious systemic toxicity, which might inspire the development of sophisticated nanomedicine in consideration of the feedback induced therapeutic resistance.
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Ciclooxigenasa 2 , Péptidos , Fotoquimioterapia , Fotoquimioterapia/métodos , Ciclooxigenasa 2/metabolismo , Péptidos/química , Péptidos/farmacología , Animales , Humanos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Especies Reactivas de Oxígeno/metabolismo , Femenino , Meloxicam/farmacología , Meloxicam/uso terapéutico , Ratones , Protoporfirinas/química , Protoporfirinas/farmacología , Dinoprostona/metabolismoRESUMEN
Uncontrolled diabetes causes a catabolic state with multi-organic complications, of which impairment on skeletal muscle contributes to the damaged mobility. Kcnma1 gene encodes the pore-forming α-subunit of Ca2+ - and voltage-gated K+ channels of large conductance (BK channels), and loss-of-function mutations in Kcnma1 are in regards to impaired myogenesis. Herein, we observed a time-course reduction of Kcnma1 expression in the tibialis anterior muscles of leptin receptor-deficient (db/db) diabetic mice. To investigate the role of Kcnma1 in diabetic muscle atrophy, muscle-specific knockdown of Kcnma1 was achieved by mice receiving intravenous injection of adeno-associated virus-9 (AAV9)-encoding shRNA against Kcnma1 under the muscle creatine kinase (MCK) promoter. Impairment on muscle mass and myogenesis were observed in m/m mice with AAV9-shKcnma1 intervention, while this impairment was more obvious in diabetic db/db mice. Simultaneously, damaged mitochondrial dynamics and biogenesis showed much severer in db/db mice with AAV9-shKcnma1 intervention. RNA sequencing revealed the large transcriptomic changes resulted by Kcnma1 knockdown, and changes in mitochondrial homeostasis-related genes were validated. Besides, the artificial alteration of Kcnma1 in mouse C2C12 myoblasts was achieved with an adenovirus vector. Consistent results were demonstrated by Kcnma1 knockdown in palmitate-treated cells, whereas opposite results were exhibited by Kcnma1 overexpression. Collectively, we document Kcnma1 as a potential keeper of mitochondrial homeostasis, and the loss of Kcnma1 is a critical event in priming skeletal muscle loss in diabetes.
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Diabetes Mellitus Experimental , Canales de Potasio de Gran Conductancia Activados por el Calcio , Ratones , Animales , Canales de Potasio de Gran Conductancia Activados por el Calcio/metabolismo , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/metabolismo , Subunidades alfa de los Canales de Potasio de Gran Conductancia Activados por Calcio/genética , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , HomeostasisRESUMEN
Sepsis-induced myocardial depression (SIMD) is common in pediatric intensive care units and seriously threatens children's health. Recently, long noncoding RNAs (lncRNAs) have been showed to play important roles in various diseases; however, its role in SIMD is unclear. In this study, we used lipopolysaccharide (LPS)-treated rats and H9c2 cardiomyocytes to mimic SIMD in vivo and in vitro. We found that the expression of a novel lncRNA, we named lncRNA-AABR07066529.3, was elevated in LPS-induced rat heart tissue and H9c2 cardiomyocytes. In addition, LPS-induced inflammation, apoptosis, and pyroptosis were significantly exacerbated after lncRNA-AABR07066529.3 knockdown. Moreover, we found that myeloid differentiation factor 88 (MyD88) was upregulated in LPS-treated groups and was inhibited by lncRNA-AABR07066529.3. Besides, MyD88 knockdown abolished lncRNA-AABR07066529.3 silencing effects on inflammation, apoptosis, and pyroptosis induced by LPS in H9c2 cardiomyocytes. In our study, we found lncRNA-AABR07066529.3 exerted protective effects on LPS-induced cardiomyocytes by regulating MyD88 and might serve as a potential treatment target for SIMD.
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Cardiomiopatías , MicroARNs , ARN Largo no Codificante , Animales , Ratas , Apoptosis , Cardiomiopatías/metabolismo , Depresión , Inflamación/inducido químicamente , Inflamación/genética , Inflamación/metabolismo , Lipopolisacáridos/farmacología , MicroARNs/genética , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Miocitos Cardíacos/metabolismo , Piroptosis/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Inflammatory diseases, including infectious diseases, diabetes-related diseases, arthritis-related diseases, neurological diseases, digestive diseases, and tumor, continue to threaten human health and impose a significant financial burden despite advancements in clinical treatment. Pyroptosis, a pro-inflammatory programmed cell death pathway, plays an important role in the regulation of inflammation. Moderate pyroptosis contributes to the activation of native immunity, whereas excessive pyroptosis is associated with the occurrence and progression of inflammation. Pyroptosis is complicated and tightly controlled by various factors. Accumulating evidence has confirmed that epigenetic modifications and post-translational modifications (PTMs) play vital roles in the regulation of pyroptosis. Epigenetic modifications, which include DNA methylation and histone modifications (such as methylation and acetylation), and post-translational modifications (such as ubiquitination, phosphorylation, and acetylation) precisely manipulate gene expression and protein functions at the transcriptional and post-translational levels, respectively. In this review, we summarize the major pathways of pyroptosis and focus on the regulatory roles and mechanisms of epigenetic and post-translational modifications of pyroptotic components. We also illustrate these within pyroptosis-associated inflammatory diseases. In addition, we discuss the effects of novel therapeutic strategies targeting epigenetic and post-translational modifications on pyroptosis, and provide prospective insight into the regulation of pyroptosis for the treatment of inflammatory diseases.
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Epigénesis Genética , Inflamación , Procesamiento Proteico-Postraduccional , Piroptosis , Humanos , Piroptosis/efectos de los fármacos , Animales , Inflamación/genética , Inflamación/metabolismo , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
Di(2-ethylhexyl) phthalate (DEHP) is a widely used plasticizer that can interfere with the endocrine system and cause liver damage. However, the molecular mechanism of DEHP-induced liver injury is unclear. This study aimed to investigate the effects of DEHP on liver function and its relationship with thioredoxin-interacting protein (TXNIP) and mitochondrial oxidative stress pathway. We used C57BL/6â¯J mice and THLE-2 liver cells as in vivo and in vitro models, respectively, and treated them with different doses of DEHP, and measured the relevant biochemical indicators and molecular markers. We found that DEHP significantly increased the expression of TXNIP and NLRP3, while decreasing the expression of mitochondrial functional proteins, such as PGC-1α, TFAM, NRF1, NDUHA9, SDHA, MFN1. This resulted in mitochondrial dysfunction, manifested by reduced ATP generation, increased inflammatory factor release, elevated liver enzyme indicators, decreased mitochondrial membrane potential and increased oxidative stress. We further demonstrated that TXNIP upregulation activated NF-κB and MAPK signaling pathways, such as NF-κB, IκB, TAB2, TRAF6, ERK1, JNK, p38 MAPK, MEK1, which exacerbated oxidative stress and inflammation, leading to liver damage. Additionally, we found that treatment with the antioxidant MitoQ partially alleviated DEHP-induced liver toxicity, while silencing TXNIP more effectively restored mitochondrial function. Our study supports the hypothesis that DEHP induces mitochondrial oxidative stress through the TXNIP signaling pathway, resulting in liver dysfunction in mice, and suggests possible links between endocrine-disrupting chemicals and human diseases.
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Dietilhexil Ftalato , Fallo Hepático , Enfermedades Mitocondriales , Ácidos Ftálicos , Humanos , Ratones , Animales , Dietilhexil Ftalato/toxicidad , FN-kappa B/metabolismo , Ratones Endogámicos C57BL , Estrés Oxidativo , Tiorredoxinas/genética , Tiorredoxinas/metabolismo , Proteínas Adaptadoras Transductoras de SeñalesRESUMEN
Lead-based perovskites are highly susceptible to environmental influences, and their application in analytical chemistry, especially in aqueous solution, has been reported rarely. All-inorganic lead-free metal halide perovskites have been considered as a substitute for lead-based perovskites. Herein, a Cs2RbTbCl6 perovskite microcrystal (PMCs), which emits strong yellow-green fluorescence with a maximum emission wavelength at 547 nm, was for the first time synthesized and characterized. The Cs2RbTbCl6 PMCs could be well dispersed in N,N-dimethylacetamide (DMF), and its fluorescence could be significantly enhanced by the addition of norfloxacin (NOR) in the aqueous solution. We found that the Cs2RbTbCl6 PMCs can be used as fluorescent probes (excitation, 365 nm; emission, 547 nm) to selectively detect NOR in a concentration range from 10.0 to 200.0 µM with the limit of detection (LOD) being 0.04 µM. The Cs2RbTbCl6 PMCs could also be adsorbed on filter paper to fabricate as a fluorescent test paper for visual detection of NOR under 365-nm ultraviolet (UV) lamp irradiation. The proposed method has the potential to establish a new analytical method to visualize the detection of NOR in aqueous environments and also promotes the application of all-inorganic lead-free perovskites for analytical detection in aqueous environments.
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The circadian clock refers to the formation of a certain rule in the long-term evolution of an organism, which is an invisible 'clock' in the body of an organism. As one of the largest TF families in higher plants, the MYB transcription factor is involved in plant growth and development. MYB is also inextricably correlated with the circadian rhythm. In this study, the transcriptome data of the tea plant 'Baiyeyihao' were measured at a photoperiod interval of 4 h (24 h). A total of 25,306 unigenes were obtained, including 14,615 unigenes that were annotated across 20 functional categories within the GO classification. Additionally, 10,443 single-gene clusters were annotated to 11 sublevels of metabolic pathways using KEGG. Based on the results of gene annotation and differential gene transcript analysis, 22 genes encoding MYB transcription factors were identified. The G10 group in the phylogenetic tree had 13 members, of which 5 were related to the circadian rhythm, accounting for 39%. The G1, G2, G8, G9, G15, G16, G18, G19, G20, G21 and G23 groups had no members associated with the circadian rhythm. Among the 22 differentially expressed MYB transcription factors, 3 members of LHY, RVE1 and RVE8 were core circadian rhythm genes belonging to the G10, G12 and G10 groups, respectively. Real-time fluorescence quantitative PCR was used to detect and validate the expression of the gene transcripts encoding MYB transcription factors associated with the circadian rhythm.
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Camellia sinensis , Relojes Circadianos , Humanos , Camellia sinensis/genética , Filogenia , Ritmo Circadiano/genética , TéRESUMEN
Carrier-free self-assembly has gradually shifted the focus of research on natural products, which effectively improve the bioavailability and the drug-loading rate. However, in spite of the existing studies, the development of self-assembled natural phytochemicals that possess pharmacological effects still has scope for further exploration and enhancement. Herein, a nano-delivery system was fabricated through the direct self-assembly of Rhein and Matrine and was identified as a self-assembled Rhein-Matrine nanoparticles (RM NPs). The morphology of RM NPs was characterized by TEM. The molecular mechanisms of self-assembly were explored using FT-IR, 1H NMR, and molecular dynamics simulation analysis. Gelatin methacryloyl (GelMA) hydrogel was used as a drug carrier for controlled release and targeted delivery of RM NPs. The potential wound repair properties of RM NPs were evaluated on a skin wound-healing model. TEM and dynamic light scattering study demonstrated that the RM NPs were close to spherical, and the average size was approximately 75 nm. 1H NMR of RM NPs demonstrated strong and weak changes in the interaction energies during self-assembly. Further molecular dynamics simulation analysis predicted the self-assembly behavior. An in vivo skin wound-healing model demonstrated that RM NPs present better protection effect against skin damages. Taken together, RM NPs are a new self-assembly system; this may provide new directions for natural product applications.
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Alcaloides , Antraquinonas , Matrinas , Simulación de Dinámica Molecular , Nanopartículas , Quinolizinas , Cicatrización de Heridas , Alcaloides/química , Alcaloides/farmacología , Cicatrización de Heridas/efectos de los fármacos , Quinolizinas/química , Quinolizinas/farmacología , Nanopartículas/química , Antraquinonas/química , Antraquinonas/farmacología , Animales , Portadores de Fármacos/química , Ratones , Hidrogeles/química , HumanosRESUMEN
To meet the industrial requirements of organic photovoltaic (OPV) cells, it is imperative to accelerate the development of cost-effective materials. Thiophene-benzene-thiophene central unit-based acceptors possess the advantage of low synthetic cost, while their power conversion efficiency (PCE) is relatively low. Here, by incorporating a para-substituted benzene unit and 1st-position branched alkoxy chains with large steric hindrance, a completely non-fused non-fullerene acceptor, TBT-26, was designed and synthesized. The narrow band gap of 1.38â eV ensures the effective utilization of sunlight. The favorable phase separation morphology of TBT-26-based blend film facilitates the efficient exciton dissociation and charge transport in corresponding OPV cell. Therefore, the TBT-26-based small-area cell achieves an impressive PCE of 17.0 %, which is the highest value of completely non-fused OPV cells. Additionally, we successfully demonstrated the scalability of this design by fabricating a 28.8â cm2 module with a high PCE of 14.3 %. Overall, our work provides a practical molecular design strategy for developing high-performance and low-cost acceptors, paving the way for industrial applications of OPV technology.
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Sepsis-induced myocardial depression (SIMD), a common complication of sepsis, is one of the main causes of death in patients with sepsis. The pathogenesis of SIMD is complicated, and the process of SIMD remains incompletely understood, with no single or definitive mechanism fully elucidated. Notably, pyroptosis, as a pro-inflammatory programmed cell death, is characterized by Gasdermin-mediated formation of pores on the cell membrane, cell swelling, and cell rupture accompanied by the release of large amounts of inflammatory factors and other cellular contents. Mechanistically, pyroptosis is mainly divided into the canonical pathway mediated by caspase-1 and the non-canonical pathway mediated by caspase-4/5/11. Pyroptosis has been confirmed to participate in various inflammation-associated diseases. In recent years, more and more studies have shown that pyroptosis is also involved in the occurrence and development of SIMD. This article reviews the molecular mechanisms of pyroptosis and its research progress in SIMD, aiming to provide novel strategies and targets for the treatment of SIMD.
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Piroptosis , Sepsis , Humanos , Sepsis/complicaciones , Animales , Cardiomiopatías/etiologíaRESUMEN
Low-bandgap materials have achieved rapid development and promoted the enhancement of power conversion efficiencies (PCEs) of organic photovoltaic (OPV) cells. However, the design of wide-bandgap non-fullerene acceptors (WBG-NFAs), required by indoor applications and tandem cells, has been lagging far behind the development of OPV technologies. Here, we designed and synthesized two NFAs named ITCC-Cl and TIDC-Cl by finely optimizing ITCC. In contrast with ITCC and ITCC-Cl, TIDC-Cl can maintain a wider bandgap and a higher electrostatic potential simultaneously. When blending with the donor PB2, the highest dielectric constant is also obtained in TIDC-Cl-based films, enabling efficient charge generation. Therefore, the PB2:TIDC-Cl-based cell possessed a high PCE of 13.8% with an excellent fill factor (FF) of 78.2% under the air mass 1.5G (AM 1.5G) condition. Furthermore, an exciting PCE of 27.1% can be accomplished in the PB2:TIDC-Cl system under the illumination of 500 lux (2700 K light-emitting diode). Combined with the theoretical simulation, the tandem OPV cell based on TIDC-Cl was fabricated and exhibited an excellent PCE of 20.0%.
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The metabolism of glucose and lipids is essential for energy production in the body, and dysregulation of the metabolic pathways of these molecules is implicated in various acute and chronic diseases, such as type 2 diabetes, Alzheimer's disease, atherosclerosis (AS), obesity, tumor, and sepsis. Post-translational modifications (PTMs) of proteins, which involve the addition or removal of covalent functional groups, play a crucial role in regulating protein structure, localization function, and activity. Common PTMs include phosphorylation, acetylation, ubiquitination, methylation, and glycosylation. Emerging evidence indicates that PTMs are significant in modulating glucose and lipid metabolism by modifying key enzymes or proteins. In this review, we summarize the current understanding of the role and regulatory mechanisms of PTMs in glucose and lipid metabolism, with a focus on their involvement in disease progression associated with aberrant metabolism. Furthermore, we discuss the future prospects of PTMs, highlighting their potential for gaining deeper insights into glucose and lipid metabolism and related diseases.
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Diabetes Mellitus Tipo 2 , Glucosa , Humanos , Metabolismo de los Lípidos , Procesamiento Proteico-Postraduccional , Fosforilación , ProteínasRESUMEN
Photodynamic therapy (PDT) can generate reactive oxygen species (ROS) to cause cell apoptosis and induce immunogenic cell death (ICD) to activate immune response, becoming a promising antitumor modality. However, the overexpressions of indoleamine 2,3-dioxygenase (IDO) and programmed cell death ligand 1 (PD-L1) on tumor cells would reduce cytotoxic T cells infiltration and inhibit the immune activation. In this paper, a simple but effective nanosystem is developed to solve these issues for enhanced photodynamic immunotherapy. Specifically, it has been constructed a self-delivery biomedicine (CeNB) based on photosensitizer chlorine e6 (Ce6), IDO inhibitor (NLG919), and PD1/PDL1 blocker (BMS-1) without the need for extra excipients. Of note, CeNB possesses fairly high drug content (nearly 100%), favorable stability, and uniform morphology. More importantly, CeNB-mediated IDO inhibition and PD1/PDL1 blockade greatly improve the immunosuppressive tumor microenvironments to promote immune activation. The PDT of CeNB not only inhibits tumor proliferation but also induces ICD response to activate immunological cascade. Ultimately, self-delivery CeNB tremendously suppresses the tumor growth and metastasis while leads to a minimized side effect. Such simple and effective antitumor strategy overcomes the therapeutic resistance against PDT-initiated immunotherapy, suggesting a potential for metastatic tumor treatment in clinic.
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Neoplasias , Fotoquimioterapia , Porfirinas , Humanos , Línea Celular Tumoral , Inhibidores Enzimáticos , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Porfirinas/uso terapéutico , Microambiente TumoralRESUMEN
[Figure: see text].