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1.
J Proteome Res ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38787199

RESUMEN

Bladder cancer (BCa) is the predominant malignancy of the urinary system. Herein, a comprehensive urine proteomic feature was initially established for the noninvasive diagnosis and recurrence monitoring of bladder cancer. 279 cases (63 primary BCa, 87 nontumor controls (NT), 73 relapsed BCa (BCR), and 56 nonrelapsed BCa (BCNR)) were collected to screen urinary protein biomarkers. 4761 and 3668 proteins were qualified and quantified by DDA and sequential window acquisition of all theoretical mass spectra (SWATH-MS) analysis in two discovery sets, respectively. Upregulated proteins were validated by multiple reaction monitoring (MRM) in two independent combined sets. Using the multi-support vector machine-recursive feature elimination (mSVM-RFE) algorithm, a model comprising 13 proteins exhibited good performance between BCa and NT with an AUC of 0.821 (95% CI: 0.675-0.967), 90.9% sensitivity (95% CI: 72.7-100%), and 73.3% specificity (95% CI: 53.3-93.3%) in the diagnosis test set. Meanwhile, an 11-marker classifier significantly distinguished BCR from BCNR with 75.0% sensitivity (95% CI: 50.0-100%), 81.8% specificity (95% CI: 54.5-100%), and an AUC of 0.784 (95% CI: 0.609-0.959) in the test cohort for relapse surveillance. Notably, six proteins (SPR, AK1, CD2AP, ADGRF1, GMPS, and C8A) of 24 markers were newly reported. This paper reveals novel urinary protein biomarkers for BCa and offers new theoretical insights into the pathogenesis of bladder cancer (data identifier PXD044896).

2.
Cell Metab ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38718794

RESUMEN

Although mechanical loading is essential for maintaining bone health and combating osteoporosis, its practical application is limited to a large extent by the high variability in bone mechanoresponsiveness. Here, we found that gut microbial depletion promoted a significant reduction in skeletal adaptation to mechanical loading. Among experimental mice, we observed differences between those with high and low responses to exercise with respect to the gut microbial composition, in which the differential abundance of Lachnospiraceae contributed to the differences in bone mechanoresponsiveness. Microbial production of L-citrulline and its conversion into L-arginine were identified as key regulators of bone mechanoadaptation, and administration of these metabolites enhanced bone mechanoresponsiveness in normal, aged, and ovariectomized mice. Mechanistically, L-arginine-mediated enhancement of bone mechanoadaptation was primarily attributable to the activation of a nitric-oxide-calcium positive feedback loop in osteocytes. This study identifies a promising anti-osteoporotic strategy for maximizing mechanical loading-induced skeletal benefits via the microbiota-metabolite axis.

3.
Chem Biodivers ; : e202400086, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619074

RESUMEN

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1H-NMR and 13C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI50 values of 4.87±0.23 µM and 9.97±1.44 µM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC50 value of 0.135±0.041 µM, and its activity was approximately 1/3 of the positive control Palbociclib.

4.
Circ Cardiovasc Interv ; 17(5): e013579, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38629273

RESUMEN

BACKGROUND: The prognostic impact of left atrial appendage (LAA) patency, including those with and without visible peri-device leak (PDL), post-LAA closure in patients with atrial fibrillation, remains elusive. METHODS: Patients with atrial fibrillation implanted with the WATCHMAN 2.5 device were prospectively enrolled. The device surveillance by cardiac computed tomography angiography was performed at 3 months post-procedure. Adverse events, including stroke/transient ischemic attack (TIA), major bleeding, cardiovascular death, all-cause death, and the combined major adverse events (MAEs), were compared between patients with complete closure and LAA patency. RESULTS: Among 519 patients with cardiac computed tomography angiography surveillance at 3 months post-LAA closure, 271 (52.2%) showed complete closure, and LAA patency was detected in 248 (47.8%) patients, including 196 (37.8%) with visible PDL and 52 (10.0%) without visible PDL. During a median of 1193 (787-1543) days follow-up, the presence of LAA patency was associated with increased risks of stroke/TIA (adjusted hazard ratio for baseline differences, 3.22 [95% CI, 1.17-8.83]; P=0.023) and MAEs (adjusted hazard ratio, 1.12 [95% CI, 1.06-1.17]; P=0.003). Specifically, LAA patency with visible PDL was associated with increased risks of stroke/TIA (hazard ratio, 3.66 [95% CI, 1.29-10.42]; P=0.015) and MAEs (hazard ratio, 3.71 [95% CI, 1.71-8.07]; P=0.001), although LAA patency without visible PDL showed higher risks of MAEs (hazard ratio, 3.59 [95% CI, 1.28-10.09]; P=0.015). Incidences of stroke/TIA (2.8% versus 3.0% versus 6.7% versus 22.2%; P=0.010), cardiovascular death (0.9% versus 0% versus 1.7% versus 11.1%; P=0.005), and MAEs (4.6% versus 9.0% versus 11.7% versus 22.2%; P=0.017) increased with larger PDL (0, >0 to ≤3, >3 to ≤5, or >5 mm). Older age and discontinuing antiplatelet therapy at 6 months were independent predictors of stroke/TIA and MAEs in patients with LAA patency. CONCLUSIONS: LAA patency detected by cardiac computed tomography angiography at 3 months post-LAA closure is associated with unfavorable prognosis in patients with atrial fibrillation implanted with WATCHMAN 2.5 device. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03788941.


Asunto(s)
Apéndice Atrial , Fibrilación Atrial , Cateterismo Cardíaco , Angiografía por Tomografía Computarizada , Ataque Isquémico Transitorio , Accidente Cerebrovascular , Humanos , Apéndice Atrial/fisiopatología , Apéndice Atrial/diagnóstico por imagen , Masculino , Femenino , Anciano , Fibrilación Atrial/fisiopatología , Fibrilación Atrial/mortalidad , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/terapia , Fibrilación Atrial/diagnóstico por imagen , Estudios Prospectivos , Factores de Riesgo , Ataque Isquémico Transitorio/etiología , Factores de Tiempo , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Anciano de 80 o más Años , Persona de Mediana Edad , Cateterismo Cardíaco/efectos adversos , Cateterismo Cardíaco/instrumentación , Medición de Riesgo , Hemorragia , Diseño de Prótesis
5.
Artículo en Inglés | MEDLINE | ID: mdl-38567538

RESUMEN

To reduce the cost of healthcare expenditures in China, the government has developed a centralised volume-based procurement (CVBP) policy for medicines and medical consumables. Based on tracking the development history of centralised procurement in China, this study explores China's CVBP model. By comparing the centralised procurement models and healthcare expenditure data among China, the United States (U.S), the United Kingdom (UK), and Singapore, we find that China still faces many challenges in implementing the CVBP policy. The main challenges are as follows. First, the policy cannot be guaranteed the effectiveness of implementation without a well-coordinated regulatory mechanism. Second, the CVBP rules and quality evaluation standards are imperfect. Third, the interests of healthcare companies cannot be guaranteed. Fourth, the policy affects the benefits of medical institutions, and the government has not built a compensation mechanism for medical institutions. Fifth, it poses a challenge to the operational capacity and innovation level of Chinese companies. Therefore, this paper posits a three-stage strategy and nine measures that could benefit China's progress in implementing the CVBP policy.

6.
Heliyon ; 10(6): e28299, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38545190

RESUMEN

Background: The Functional Movement Screen (FMS) is widely recognized by clinicians and trainers as a valuable tool for the prediction and prevention of training injuries in sports population. However, some studies suggested that FMS may not fully meet the needs of professional athletes. To address this, the Modified Functional Movement Screen (MFMS) has been specifically developed for athletes. Methods: A total of 527 male athletes in active service without prior training injuries 18.5 ± 1.2 years old) underwent the MFMS test, and their training injuries were monitored during a 2-year follow-up period. The ability of the MFMS to predict the risk of training injury was evaluated based on the receiver operating characteristic (ROC) curve of the total MFMS score. Binary logistic analysis was employed to examine the correlation between the 10 MFMS tests and the risk of training injury. Results: The injured group of athletes had significantly lower total MFMS scores compared to the healthy group (P < 0.001). The total MFMS score demonstrated a strong predictive ability for training injury risk, with an area under the ROC curve of 0.97 (P < 0.001). The calculated cut-off point was set at 22, yielding an odds ratio of 25.63, sensitivity of 0.94, and specificity of 0.88. Binary logistic regression analysis revealed a negative correlation between 6 MFMS tests and the risk of training injury. Conclusion: The MFMS can effectively predict the risk of training injuries. Athletes with a total MFMS score below 22 are more susceptible to experiencing injuries during training.

7.
Behav Brain Res ; 465: 114960, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38494129

RESUMEN

Cognitive behavioral therapy, rooted in exposure therapy, is currently the primary approach employed in the treatment of anxiety-related conditions, including post-traumatic stress disorder (PTSD). In laboratory settings, fear extinction in animals is a commonly employed technique to investigate exposure therapy; however, the precise mechanisms underlying fear extinction remain elusive. Casein kinase 2 (CK2), which regulates neuroplasticity via phosphorylation of its substrates, has a significant influence in various neurological disorders, such as Alzheimer's disease and Parkinson's disease, as well as in the process of learning and memory. In this study, we adopted a classical Pavlovian fear conditioning model to investigate the involvement of CK2 in remote fear memory extinction and its underlying mechanisms. The results indicated that the activity of CK2 in the medial prefrontal cortex (mPFC) of mice was significantly upregulated after extinction training of remote cued fear memory. Notably, administration of the CK2 inhibitor CX-4945 prior to extinction training facilitated the extinction of remote fear memory. In addition, CX-4945 significantly upregulated the expression of p-ERK1/2 and p-CREB in the mPFC. Our results suggest that CK2 negatively regulates remote fear memory extinction, at least in part, by inhibiting the ERK-CREB pathway. These findings contribute to our understanding of the underlying mechanisms of remote cued fear extinction, thereby offering a theoretical foundation and identifying potential targets for the intervention and treatment of PTSD.


Asunto(s)
Miedo , Trastornos por Estrés Postraumático , Animales , Ratones , Quinasa de la Caseína II/metabolismo , Condicionamiento Clásico/fisiología , Extinción Psicológica/fisiología , Miedo/fisiología , Corteza Prefrontal/metabolismo , Trastornos por Estrés Postraumático/metabolismo
8.
Front Immunol ; 15: 1338096, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495892

RESUMEN

Type III interferon (IFN-λ), a new member of the IFN family, was initially considered to possess antiviral functions similar to those of type I interferon, both of which are induced via the JAK/STAT pathway. Nevertheless, recent findings demonstrated that IFN-λ exerts a nonredundant antiviral function at the mucosal surface, preferentially produced in epithelial cells in contrast to type I interferon, and its function cannot be replaced by type I interferon. This review summarizes recent studies showing that IFN-λ inhibits the spread of viruses from the cell surface to the body. Further studies have found that the role of IFN-λ is not only limited to the abovementioned functions, but it can also can exert direct and/or indirect effects on immune cells in virus-induced inflammation. This review focuses on the antiviral activity of IFN-λ in the mucosal epithelial cells and its action on immune cells and summarizes the pathways by which IFN-λ exerts its action and differentiates it from other interferons in terms of mechanism. Finally, we conclude that IFN-λ is a potent epidermal antiviral factor that enhances the respiratory mucosal immune response and has excellent therapeutic potential in combating respiratory viral infections.


Asunto(s)
Interferón Tipo I , Virosis , Humanos , Interferón lambda , Quinasas Janus/metabolismo , Transducción de Señal , Factores de Transcripción STAT/metabolismo , Interferón Tipo I/metabolismo , Epitelio/metabolismo , Antivirales/farmacología , Antivirales/uso terapéutico
9.
Front Genet ; 15: 1333931, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482382

RESUMEN

Introduction: Post-transcriptional RNA modifications are crucial regulators of tumor development and progression. In many biological processes, N1-methyladenosine (m1A) plays a key role. However, little is known about the links between chemical modifications of messenger RNAs (mRNAs) and long noncoding RNAs (lncRNAs) and their function in bladder cancer (BLCA). Methods: Methylated RNA immunoprecipitation sequencing and RNA sequencing were performed to profile mRNA and lncRNA m1A methylation and expression in BLCA cells, with or without stable knockdown of the m1A methyltransferase tRNA methyltransferase 61A (TRMT61A). Results: The analysis of differentially methylated gene sites identified 16,941 peaks, 6,698 mRNAs, and 10,243 lncRNAs in the two groups. Gene ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the differentially methylated and expressed transcripts showed that m1A-regulated transcripts were mainly related to protein binding and signaling pathways in cancer. In addition, the differentially genes were identified that were also differentially m1A-modified and identified 14 mRNAs and 19 lncRNAs. Next, these mRNAs and lncRNAs were used to construct a lncRNA-microRNA-mRNA competing endogenous RNA network, which included 118 miRNAs, 15 lncRNAs, and 8 mRNAs. Finally, the m1A-modified transcripts, SCN2B and ENST00000536140, which are highly expressed in BLCA tissues, were associated with decreased overall patient survival. Discussion: This study revealed substantially different amounts and distributions of m1A in BLCA after TRMT61A knockdown and predicted cellular functions in which m1A may be involved, providing evidence that implicates m1A mRNA and lncRNA epitranscriptomic regulation in BLCA tumorigenesis and progression.

10.
J Ethnopharmacol ; 326: 117992, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38428654

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown. AIM OF THE STUDY: This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms. MATERIALS AND METHODS: The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders. RESULTS: The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders. CONCLUSIONS: The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.


Asunto(s)
Medicamentos Herbarios Chinos , Melatonina , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Ratones , Animales , Hipnóticos y Sedantes/farmacología , Hipnóticos y Sedantes/uso terapéutico , Triptófano , Serotonina/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Melatonina/farmacología , Trastornos del Inicio y del Mantenimiento del Sueño/tratamiento farmacológico
11.
J Chromatogr A ; 1720: 464808, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38471298

RESUMEN

Juices and beverages are produced by industry for long-distance distribution and shelf-stability, providing valuable nutrients. However, their nutritional value is often underestimated due to insufficient analytical methods. We have employed non-targeted analysis through a standardized analytical protocol, taking advantage of Data Independent Acquisition (DIA) technique and a novel Chromatographic Retention Behavior (CRB) data deconvolution algorithm. After analyzing 9 fruits and their products, correlations between fruits and their juices are accurately digitalized by similarities of their LC-MS fingerprints. We also specify non-targeted molecules primarily associate with nutrient loss in these analyzed juice products, including nitrogenous nutrients, flavonoids, glycosides, and vitamins. Moreover, we unveiled previously unreported fruit-characteristic metabolites, of which reconstituted-from-concentrate (RFC) juices contain over 40% of the content found in their fresh counterparts. Conclusively, our method establishes a quantitative benchmark for rational selection of RFC juices to substitute natural fruits.


Asunto(s)
Bebidas , Frutas , Frutas/química , Bebidas/análisis , Flavonoides/análisis , Jugos de Frutas y Vegetales/análisis
12.
ACS Nano ; 18(13): 9354-9364, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38517038

RESUMEN

Na3V2(PO4)3 (NVP) based on the multielectron reactions between V2+ and V5+ has been considered a promising cathode for sodium-ion batteries (SIBs). However, it still suffers from unsatisfactory stability, caused by the poor reversibility of the V5+/V4+ redox couple and structure evolution. Herein, we propos a strategy that combines high-entropy substitution and electrolyte optimization to boost the reversible multielectron reactions of NVP. The high reversibility of the V5+/V4+ redox couple and crystalline structure evolution are disclosed by in situ X-ray absorption near-edge structure spectra and in situ X-ray diffraction. Meanwhile, the electrochemical reaction kinetics of high-entropy substitution NVP (HE-NVP) can be further improved in the diglyme-based electrolyte. These enable HE-NVP to deliver a superior electrochemical performance (capacity retention of 93.1% after 2000 cycles; a large reversible capacity of 120 mAh g-1 even at 5.0 A g-1). Besides, the long cycle life and high power density of the HE-NVP∥natural graphite full-cell configuration demonstrated the superiority of HE-NVP cathode in SIBs. This work highlights that the synergism of high-entropy substitution and electrolyte optimization is a powerful strategy to enhance the sodium-storage performance of polyanionic cathodes for SIBs.

13.
Sensors (Basel) ; 24(5)2024 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-38475067

RESUMEN

This paper proposed a single-layer checkerboard metasurface with simultaneous wideband radar cross-section (RCS) reduction characteristics and low infrared (IR) emissivity. The metasurface consists of an indium tin oxide (ITO)-patterned film, a polyethylene terephthalate (PET) substrate and an ITO backplane from the top downwards, with a total ultra-thin thickness of 1.6 mm. This design also allows the metasurface to have good optical transparency and flexibility. Based on phase cancellation and absorption, the metasurface can achieve a wideband RCS reduction of 10 dB from 10.6 to 19.4 GHz under normal incidence. When the metasurface is slightly cylindrically curved, an RCS reduction of approximately 10 dB can still be achieved from 11 to 19 GHz. The polarization and angular stability of the metasurface have also been verified. The filling rate of the top ITO-patterned film is 0.81, which makes the metasurface have a low theoretical IR emissivity of 0.24. Both simulation and experimental results have verified the excellent characteristics of the proposed checkerboard metasurface, demonstrating its great potential application in radar-IR bi-stealth.

14.
Biomed Pharmacother ; 174: 116456, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552441

RESUMEN

Acute lung injury (ALI) is a common and critical respiratory disorder caused by various factors, with viral infection being the leading contributor. Dehydroandrographolide (DAP), a constituent of the Chinese herbal plant Andrographis paniculata, exhibits a range of activities including anti-inflammatory, in vitro antiviral and immune-enhancing effects. This study evaluated the anti-inflammatory effects and pharmacokinetics (PK) profile of DAP in ALI mice induced by intratracheal instillation of Poly(I:C) (PIC). The results showed that oral administration of DAP (10-40 mg/kg) effectively suppressed the increase in lung wet-dry weight ratio, total cells, total protein content, accumulation of immune cells, inflammatory cytokines and neutrophil elastase levels in bronchoalveolar lavage fluid of PIC-treated mice. DAP concentrations, determined by an LC-MS/MS method, in plasma after receiving DAP (20 mg/kg) were unchanged compared to those in normal mice. However, DAP concentrations and relative PK parameters in the lungs were significantly altered in PIC-treated mice, exhibiting a relatively higher maximum concentration, larger AUC, and longer elimination half-life than those in the lungs of normal mice. These results demonstrated that DAP could improve lung edema and inflammation in ALI mice, and suggested that lung injury might influence the PK properties of DAP, leading to increased lung distribution and residence. Our study provides evidence that DAP displays significant anti-inflammatory activity against viral lung injury and is more likely to distribute to damaged lung tissue.


Asunto(s)
Lesión Pulmonar Aguda , Antiinflamatorios , Líquido del Lavado Bronquioalveolar , Diterpenos , Poli I-C , Animales , Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios/farmacocinética , Antiinflamatorios/farmacología , Diterpenos/farmacocinética , Diterpenos/farmacología , Masculino , Ratones , Andrographis/química , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Pulmón/patología , Elastasa de Leucocito/metabolismo
15.
ACS Appl Mater Interfaces ; 16(9): 11767-11777, 2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38408283

RESUMEN

In addition to the donor-acceptor nano phases, the intermixed phase within the organic blends is crucial for the photovoltaic performance and stability of the bulk-heterojunction organic solar cells (OSCs). Here, the intermixed phase of a representative M-PhS:BTP-eC9 all-small-molecule organic solar cell was investigated by a concentration-dependent ultraviolet-visible (UV-vis) absorption spectroscopy method, where a shift of the absorption maximum wavelength was measured for the acceptor component with the increase of the acceptor concentration. The blend ratios of the acceptor to the donor in the intermixed phase, corresponding to the critical concentration for the formation of the acceptor nanophase (CAP), were determined to be 0.35, 0.20, and 0.15 for the as-cast, thermal annealing (TA), and the combined TA and solvent vapor annealing films. These results indicated that M-PhS and BTP-eC9 are kinetically well intermixed during spin coating, whereas TA and the following solvent annealing promote the crystallization of BTP-eC9 molecules out of the intermixed phase. The photovoltaic performance of the M-PhS:BTP-eC9 cells with different blend ratios was investigated. The formation of the BTP-eC9 nano phase in the blend film leads to stable VOC and fast increased JSC, which can be understood by the reduction of bimolecular charge recombination and the formation of electron transporting pathways within the photoactive layer. Similarly, the critical concentration for the formation of the donor phase was estimated to be 0.15 by measuring the stabilized VOC and increased JSC values of the cells with different donor blending ratios. More importantly, after a fast "burn-in" thermal degradation, the M-PhS:BTP-eC9 cell showed excellent thermal stability aging at 85 °C for over 1128 h, which is in good accordance with the unchanged intermixed phases measured by the UV-vis spectra of the annealed films. The current work demonstrates the feasibility of the spectroscopy method to investigate the intermixed phases for organic bulk-heterojunction solar cells and proves that all-small-molecule solar cells can be intrinsically very stable.

16.
J Med Chem ; 67(4): 2466-2486, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38316017

RESUMEN

Adenoviral E1A binding protein 300 kDa (p300) and its closely related paralog CREB binding protein (CBP) are promising therapeutic targets for human cancer. Here, we report the first discovery of novel potent small-molecule PROTAC degraders of p300/CBP against hepatocellular carcinoma (HCC), one of the most common solid tumors. Based upon the clinical p300/CBP bromodomain inhibitor CCS1477, a conformational restriction strategy was used to optimize the linker to generate a series of PROTACs, culminating in the identification of QC-182. This compound effectively induces p300/CBP degradation in the SK-HEP-1 HCC cells in a dose-, time-, and ubiquitin-proteasome system-dependent manner. QC-182 significantly downregulates p300/CBP-associated transcriptome in HCC cells, leading to more potent cell growth inhibition compared to the parental inhibitors and the reported degrader dCBP-1. Notably, QC-182 potently depletes p300/CBP proteins in mouse SK-HEP-1 xenograft tumor tissue. QC-182 is a promising lead compound toward the development of p300/CBP-targeted HCC therapy.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Proteína de Unión a CREB/química , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Dominios Proteicos , Factores de Transcripción p300-CBP/metabolismo
17.
Huan Jing Ke Xue ; 45(1): 354-363, 2024 Jan 08.
Artículo en Chino | MEDLINE | ID: mdl-38216485

RESUMEN

It is of great scientific significance in regulating plantation ecosystem restoration to investigate the effects of the nitrogen (N) deposition and litter manipulation on soil organic carbon components and enzyme activities. A micro-plot experiment was conducted with four nitrogen additions[CK (0 kg·hm-2·a-1, calculated by N), LN (50 kg·hm-2·a-1), MN (100 kg·hm-2·a-1), and HN (200 kg·hm-2·a-1)] and two litter treatments[LR (litter removal) and L (litter retained)] for tropical rubber plantations in western Hainan Island. The soil physico-chemical properties, soil organic carbon components, and enzyme activities in 0-10 cm and 10-20 cm depths were analyzed. The results showed that soil pH significantly decreased with elevated N addition and litter removal. The contents of NO3--N and NH4+-N significantly increased with elevated N addition. Moreover, there was a significant interaction between N addition and litter treatment on the contents of NO3--N and NH4+-N (P < 0.05). Compared to that with L, LR reduced SOC and its component contents; particularly, the largest decrease was in LFOC by 29.0%-81.4% in the 0-10 cm depth and 23.5%-58.4% in 10-20 cm, respectively. The contents of SOC and its components presented a trend of increasing first and then decreasing with elevated N addition irrespective of litter treatment, and those contents were significantly higher at LN than those at HN. There was a significant interaction between N addition and litter treatment on SOC, LFOC (0-10 cm), and HFOC contents. Compared with that under L, PPO activity was significantly reduced at LR under CK and LN but was significantly increased at LR under MN and HN, respectively. Variance analysis showed significant interactive effects between N addition and litter treatment on PPO and CBH (0-10 cm) activities, and the soil enzyme activity (BG, PPO, and CBH) responding to N addition was greater than that to the litter treatment. Pearson correlation analysis showed that SOC content was extremely positively correlated with MBC, POC, LFOC, and HFOC contents. To summarize, litter retained combined with low N deposition played an important synergistic role of improving SOC pool and soil enzyme activities for tropical rubber plantation systems.


Asunto(s)
Carbono , Suelo , Suelo/química , Carbono/análisis , Goma , Ecosistema , Nitrógeno/análisis , China
18.
J Adv Res ; 2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38295876

RESUMEN

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease worldwide, whereas there is no approved drug therapy due to its complexity. Studies are emerging to discuss the role of selective autophagy in the pathogenesis of NAFLD, because the specificity among the features of selective autophagy makes it a crucial process in mitigating hepatocyte damage caused by aberrant accumulation of dysfunctional organelles, for which no other pathway can compensate. AIM OF REVIEW: This review aims to summarize the types, functions, and dynamics of selective autophagy that are of particular importance in the initiation and progression of NAFLD. And on this basis, the review outlines the therapeutic strategies against NAFLD, in particular the medications and potential natural products that can modulate selective autophagy in the pathogenesis of this disease. KEY SCIENTIFIC CONCEPTS OF REVIEW: The critical roles of lipophagy and mitophagy in the pathogenesis of NAFLD are well established, while reticulophagy and pexophagy are still being identified in this disease due to the insufficient understanding of their molecular details. As gradual blockage of autophagic flux reveals the complexity of NAFLD, studies unraveling the underlying mechanisms have made it possible to successfully treat NAFLD with multiple pharmacological compounds that target associated pathways. Overall, it is convinced that the continued research into selective autophagy occurring in NAFLD will further enhance the understanding of the pathogenesis and uncover novel therapeutic targets.

19.
Small ; 20(6): e2307242, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37771206

RESUMEN

Photovoltaic thin film solar cells based on kesterite Cu2 ZnSn(S, Se)4 (CZTSSe) have reached 13.8% sunlight-to-electricity conversion efficiency. However, this efficiency is still far from the Shockley-Queisser radiative limit and is hindered by the significant deficit in open circuit voltage (VOC ). The presence of high-density interface states between the absorber layer and buffer or window layer leads to the recombination of photogenerated carriers, thereby reducing effective carrier collection. To tackle this issue, a new window structure ZnO/AgNW/ZnO/AgNW (ZAZA) comprising layers of ZnO and silver nanowires (AgNWs) is proposed. This structure offers a simple and low-damage processing method, resulting in improved optoelectronic properties and junction quality. The ZAZA-based devices exhibit enhanced VOC due to the higher built-in voltage (Vbi ) and reduced interface recombination compared to the usual indium tin oxide (ITO) based structures. Additionally, improved carrier collection is demonstrated as a result of the shortened collection paths and the more uniform carrier lifetime distribution. These advances enable the fabrication of the first ITO-free CZTSSe solar cells with over 10% efficiency without an anti-reflective coating.

20.
Adv Mater ; 36(7): e2305135, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37590909

RESUMEN

Sodium-ion batteries (SIBs) are a viable alternative to meet the requirements of future large-scale energy storage systems due to the uniform distribution and abundant sodium resources. Among the various cathode materials for SIBs, phosphate-based polyanionic compounds exhibit excellent sodium-storage properties, such as high operation voltage, remarkable structural stability, and superior safety. However, their undesirable electronic conductivities and specific capacities limit their application in large-scale energy storage systems. Herein, the development history and recent progress of phosphate-based polyanionic cathodes are first overviewed. Subsequently, the effective modification strategies of phosphate-based polyanionic cathodes are summarized toward high-performance SIBs, including surface coating, morphological control, ion doping, and electrolyte optimization. Besides, the electrochemical performance, cost, and industrialization analysis of phosphate-based polyanionic cathodes for SIBs are discussed for accelerating commercialization development. Finally, the future directions of phosphate-based polyanionic cathodes are comprehensively concluded. It is believed that this review can provide instructive insight into developing practical phosphate-based polyanionic cathodes for SIBs.

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