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1.
Cell ; 182(5): 1271-1283.e16, 2020 09 03.
Artículo en Inglés | MEDLINE | ID: mdl-32795413

RESUMEN

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.


Asunto(s)
ARN Mensajero/genética , ARN Viral/genética , Vacunas Sintéticas/inmunología , Vacunas Virales/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , Sitios de Unión , Vacunas contra la COVID-19 , Chlorocebus aethiops , Infecciones por Coronavirus/genética , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/prevención & control , Femenino , Células HEK293 , Células HeLa , Humanos , Inmunogenicidad Vacunal , Inyecciones Intramusculares , Macaca fascicularis , Masculino , Ratones , Ratones Endogámicos ICR , Nanopartículas/química , ARN Mensajero/metabolismo , ARN Viral/metabolismo , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Células TH1/inmunología , Potencia de la Vacuna , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Células Vero , Vacunas Virales/administración & dosificación , Vacunas Virales/genética
2.
Nucleic Acids Res ; 52(17): 10400-10415, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39162233

RESUMEN

Circular RNAs (circRNAs) have emerged as a promising alternative to linear mRNA, owing to their unique properties and potential therapeutic applications, driving the development of novel approaches for their production. This study introduces a cis-splicing system that efficiently produces circRNAs by incorporating a ribozyme core at one end of the precursor, thereby eliminating the need for additional spacer elements between the ribozyme and the gene of interest (GOI). In this cis-splicing system, sequences resembling homologous arms at both ends of the precursor are crucial for forming the P9.0 duplex, which in turn facilitates effective self-splicing and circularization. We demonstrate that the precise recognition of the second transesterification site depends more on the structural characteristics of P9.0 adjacent to the ωG position than on the nucleotide composition of the P9.0-ωG itself. Further optimization of structural elements, like P10 and P1-ex, significantly improves circularization efficiency. The circRNAs generated through the cis-splicing system exhibit prolonged protein expression and minimal activation of the innate immune response. This study provides a comprehensive exploration of circRNA generation via a novel strategy and offers valuable insights into the structural engineering of RNA, paving the way for future advancements in circRNA-based applications.


Asunto(s)
Empalme del ARN , ARN Catalítico , ARN Circular , ARN Circular/química , ARN Circular/genética , ARN Circular/metabolismo , ARN Catalítico/metabolismo , ARN Catalítico/química , ARN Catalítico/genética , Humanos , ARN/genética , ARN/química , ARN/metabolismo , Conformación de Ácido Nucleico , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Mensajero/química , Células HEK293
3.
Small ; : e2403325, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39314054

RESUMEN

The solution-derived non-stoichiometric nickel oxide (NiOx) is a promising hole-injecting material for stable quantum dot light-emitting diodes (QLEDs). However, the carrier imbalance due to the misalignment of energy levels between the NiOx and polymeric hole-transporting layers (HTLs) curtails the device efficiency. In this study, the modification of the NiOx surface is investigated using either 3-cyanobenzoic acid (3-CN-BA) or 4-cyanobenzoic acid (4-CN-BA) in the QLED fabrication. Morphological and electrical analyses revealed that both 4-CN-BA and 3-CN-BA can enhance the work function of NiOx, reduce the oxygen vacancies on the NiOx surface, and facilitate a uniform morphology for subsequent HTL layers. Moreover, it is found that the binding configurations of dipole molecules as a function of the substitution position of the tail group significantly impact the work function of underlying layers. When integrated in QLEDs, the modification layers resulted in a significant improvement in the electroluminescent efficiency due to the enhancement of energy level alignment and charge balance within the devices. Specifically, QLEDs incorporating 4-CN-BA achieved a champion external quantum efficiency (EQE) of 20.34%, which is a 1.8X improvement in comparison with that of the devices utilizing unmodified NiOx (7.28%). Moreover, QLEDs with 4-CN-BA and 3-CN-BA modifications exhibited prolonged operational lifetimes, indicating potential for practical applications.

4.
Opt Express ; 32(2): 1325-1333, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38297687

RESUMEN

We demonstrate high-harmonic generation for the time-domain observation of the electric field (HHG-TOE) and use it to measure the waveform of ultrashort mid-infrared (MIR) laser pulses interacting with ZnO thin-films or WS2 monolayers. The working principle relies on perturbing HHG in solids with a weak replica of the pump pulse. We measure the duration of few-cycle pulses at 3200 nm, in reasonable agreement with the results of established pulse characterization techniques. Our method provides a straightforward approach to accurately characterize femtosecond laser pulses used for HHG experiments right at the point of interaction.

5.
Phys Chem Chem Phys ; 26(35): 22982-22989, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39171568

RESUMEN

The excitonic effect significantly influences the optoelectronic characteristics of halide perovskites. However, consensus on the temperature modulated exciton binding energy remains elusive, even for extensively studied materials like MAPbBr3 perovskites. In this study, we utilized UV-vis absorption spectra and the Elliott model to extract the exciton binding energies of MAPbBr3 in the range of 170-290 K. Elliott model fitted results reveal a linear increasing trend in bandgap and exciton binding energy for both cubic and tetragonal phases with temperature, with the tetragonal phase exhibiting a higher increasing rate. Additionally, we found that regardless of the temperature, the strongest absorption peaks are always dominated by the exciton absorption, and our fitted exciton absorption peak blue-shifts with the increase of temperature, accounting for the observed blue-shift of the strongest absorption peak for our fabricated MAPbBr3 sample. However, with the increase of temperature, the weight of continuum state absorption increases significantly, which widens the absorption tails to the longer wavelength, leading to the red-shift of Tauc-plotted optical bandgaps. This is the first work considering the temperature-modulated excitonic properties of halide perovskites, which offers valuable insights into the behavior of MAPbBr3 under varying temperature conditions. After a series of theoretical simulations on the temperature modulated electronic properties, including band structures, carrier effective masses, optical dielectric properties and Born effective charges, we provide rational interpretations for the experimentally observed temperature induced variation of the optical properties. These works are helpful to deepen our understanding of the temperature modulated optical properties of MAPbBr3 perovskites.

6.
Environ Res ; 260: 119612, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39004394

RESUMEN

Fish consumption can increase purine load in human body, and the enrichment of mercury in fish may affect the glomerular filtration function, both resulting in increased serum uric acid (SUA) levels. The data of blood mercury (BHg), fish consumption frequency and SUA levels of 7653 participants aged 18 years or older was from China National Human Biomonitoring (2017-2018). The associations between fish consumption frequency, ln-transformed BHg and SUA levels were explored through weighted multiple linear regressions. The mediating effect of BHg levels between fish consumption frequency and SUA levels was evaluated by mediation analysis. We found that both the fish consumption frequency and BHg were positively associated with SUA levels in both sexes. Compared to participants who had never consumed fish, participants who consumed fish once a week or more had higher SUA levels [ß (95% confidence interval, CI): 20.39 (2.16, 38.62) in males; ß (95% CI): 10.06 (0.76, 19.37) in females] and ln-transformed BHg [ß (95% CI): 0.97 (0.61, 1.34) in males; ß (95% CI): 0.84 (0.63, 1.05) in females]. Each 1-unit increase in ln-transformed BHg, the SUA levels rose by 4.78 (95% CI: 0.01, 9.54) µmol/L for males and 3.81 (95% CI: 1.60, 6.03) µmol/L for females. The association between fish consumption with SUA levels was mediated by ln-transformed BHg with the percent mediated of 34.66% in males and 26.58% in females. It revealed that BHg played mediating roles in the elevation of SUA levels caused by fish consumption. This study's findings could promote the government to intervene in mercury pollution in fish, so as to ensure the safety of fish consumption.


Asunto(s)
Mercurio , Alimentos Marinos , Ácido Úrico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Monitoreo Biológico , China , Dieta , Pueblos del Este de Asia , Contaminación de Alimentos/análisis , Mercurio/sangre , Ácido Úrico/sangre , Contaminantes Químicos del Agua/sangre
7.
Sensors (Basel) ; 24(16)2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39204900

RESUMEN

Impact craters are crucial for our understanding of planetary resources, geological ages, and the history of evolution. We designed a novel pseudo-spectral spatial feature extraction and enhanced fusion (PSEF) method with the YOLO network to address the problems encountered during the detection of the numerous and densely distributed meter-sized impact craters on the lunar surface. The illumination incidence edge features, isotropic edge features, and eigen frequency features are extracted by Sobel filtering, LoG filtering, and frequency domain bandpass filtering, respectively. Then, the PSEF images are created by pseudo-spectral spatial techniques to preserve additional details from the original DOM data. Moreover, we conducted experiments using the DES method to optimize the post-processing parameters of the models, thereby determining the parameter ranges for practical deployment. Compared with the Basal model, the PSEF model exhibited superior performance, as indicated by multiple measurement metrics, including the precision, recall, F1-score, mAP, and robustness, etc. Additionally, a statistical analysis of the error metrics of the predicted bounding boxes shows that the PSEF model performance is excellent in predicting the size, shape, and location of impact craters. These advancements offer a more accurate and consistent method to detect the meter-sized craters on planetary surfaces, providing crucial support for the exploration and study of celestial bodies in our solar system.

8.
Molecules ; 29(12)2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38930893

RESUMEN

The growing demand for wearable and attachable displays has sparked significant interest in flexible quantum-dot light-emitting diodes (QLEDs). However, the challenges of fabricating and operating QLEDs on flexible substrates persist due to the lack of stable and low-temperature processable charge-injection/-transporting layers with aligned energy levels. In this study, we utilized NiOx nanoparticles that are compatible with flexible substrates as a hole-injection layer (HIL). To enhance the work function of the NiOx HIL, we introduced a self-assembled dipole modifier called 4-(trifluoromethyl)benzoic acid (4-CF3-BA) onto the surface of the NiOx nanoparticles. The incorporation of the dipole molecules through adsorption treatment has significantly changed the wettability and electronic characteristics of NiOx nanoparticles, resulting in the formation of NiO(OH) at the interface and a shift in vacuum level. The alteration of surface electronic states of the NiOx nanoparticles not only improves the carrier balance by reducing the hole injection barrier but also prevents exciton quenching by passivating defects in the film. Consequently, the NiOx-based red QLEDs with interfacial modification demonstrate a maximum current efficiency of 16.1 cd/A and a peak external quantum efficiency of 10.3%. This represents a nearly twofold efficiency enhancement compared to control devices. The mild fabrication requirements and low annealing temperatures suggest potential applications of dipole molecule-modified NiOx nanoparticles in flexible optoelectronic devices.

9.
Semin Cancer Biol ; 86(Pt 3): 400-407, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35183412

RESUMEN

Colon cancer is a major human cancer accounting for about a tenth of all cancer cases thus making it among the top three cancers in terms of incidence as well as mortality. Metastasis to distant organs, particularly to liver, is the primary reason for associated mortality. Chemokines, the chemo-attractants for various immune cells, have increasingly been reported to be involved in cancer initiation and progression, including in colon cancer. Here we discuss the available knowledge on the role of several chemokines, such as, CCL2, CCL3, CCL5, CXCL1, CXCL2, CXCL8 in colon cancer progression. CCL20 is one chemokine with emerging evidence for its role in influencing colon cancer tumor microenvironment through the documents effects on fibroblasts, macrophages and immune cells. We focus on CCL20 and its receptor CCR6 as promising factors that affect multiple levels of colon cancer progression. They interact with several cytokines and TLR receptors leading to increased aggressiveness, as supported by multitude of evidence from in vitro, in vivo studies as well as human patient samples. CCL20-CCR6 bring about their biological effects through regulation of several signaling pathways, including, ERK and NF-κB pathways, in addition to the epithelial-mesenchymal transition. Signaling involving CCL20-CCR6 has profound effect on colon cancer hepatic metastasis. Combined with elevated CCL20 levels in colon tumors and metastatic patients, the above information points to a need for further evaluation of chemokines as diagnostic and/or prognostic biomarkers.


Asunto(s)
Quimiocinas , Neoplasias del Colon , Humanos , Neoplasias del Colon/genética , Neoplasias Hepáticas/secundario , FN-kappa B/metabolismo , Transducción de Señal , Microambiente Tumoral/genética
10.
New Phytol ; 237(1): 265-278, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36131553

RESUMEN

Caterpillar oral secretion (OS) contains active molecules that modulate plant defense signaling. We isolated an effector-like protein (Highly Accumulated Secretory Protein 1, HAS1) from cotton bollworm (Helicoverpa armigera) that is the most highly accumulated secretory protein of the nondigestive components in OS and belongs to venom R-like protein. Elimination of HAS1 by plant-mediated RNA interference reduced the suppression of OS on the defense response in plants. Plants expressing HAS1 are more susceptible to insect herbivory accompanied by the reduced expressions of multiple defense genes. HAS1 binds to the basic helix-loop-helix (bHLH) transcription factors, including GoPGF involved in pigmented gland formation and defense compounds biosynthesis in cotton and MYC3/MYC4 the main regulators in jasmonate (JA) signaling in Arabidopsis. The binding activity is required for HAS1 to inhibit the activation of bHLHs on plant defense gene expressions. Together with our previous study that another venom R-like protein HARP1 in cotton bollworm OS blocks JA signaling by interacting with JASMONATE-ZIM-domain repressors, we conclude that the venom R-like proteins in OS interfere with plant defense in a dual suppression manner. Considering the venom proteins in parasitic wasp assault the immune system of its host animal, our investigation reveals their conserved function in carnivorous and herbivorous insects.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Mariposas Nocturnas , Animales , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Proteínas de Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Transactivadores/metabolismo , Proteínas Represoras/metabolismo , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Plantas/metabolismo , Gossypium/genética , Gossypium/metabolismo
11.
Ann Surg Oncol ; 30(7): 4014-4025, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36566257

RESUMEN

BACKGROUND: Although the incidence of adenocarcinoma of the esophagogastric junction (AEG) has been increasing since the past decade, the proportion of AEG cases in two previous clinical trials (ACTS-GC and CLASSIC) that investigated the efficacy of adjuvant chemotherapy was relatively small. Therefore, whether AEG patients can benefit from adjuvant chemotherapy remains unclear. METHODS: Patients who were diagnosed with pathological stage II/III, Siewert II/III AEG, and underwent curative surgery at three high-volume institutions were assessed. Clinical outcomes were analyzed by using Kaplan-Meier curves, log-rank test, and Cox regression model. Propensity score matching (PSM) was used to reduce the selection bias. RESULTS: A total of 927 patients were included (the chemotherapy group: 696 patients; the surgery-only group: 231 patients). The median follow-up was 39.0 months. The 5-year overall survival was 63.1% (95% confidence interval [CI]: 59.0-67.6%) for the chemotherapy group and 50.2% in the surgery-only group (hazard ratio [HR] = 0.69, 95% CI: 0.54-0.88; p = 0.003). The 5-year, disease-free survival was 35.4% for the chemotherapy group and 16.6% for the surgery-only group (HR = 0.66, 95% CI: 0.53-0.83; p < 0.001). After PSM, the survival benefit of adjuvant chemotherapy for AEG was maintained. Multivariate analysis for overall survival and disease-free survival further demonstrated the survival benefit of adjuvant chemotherapy, with HRs of 0.63 (p < 0.001) and 0.52 (p < 0.001), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy was associated with improved overall survival and disease-free survival in patients with operable stage II or III AEG after D2 gastrectomy.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Humanos , Estudios Retrospectivos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Unión Esofagogástrica/cirugía , Unión Esofagogástrica/patología , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Gastrectomía , Quimioterapia Adyuvante
12.
Plant Cell ; 32(1): 226-241, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31649122

RESUMEN

Age and wounding are two major determinants for regeneration. In plants, the root regeneration is triggered by wound-induced auxin biosynthesis. As plants age, the root regenerative capacity gradually decreases. How wounding leads to the auxin burst and how age and wound signals collaboratively regulate root regenerative capacity are poorly understood. Here, we show that the increased levels of three closely-related miR156-targeted Arabidopsis (Arabidopsis thaliana) SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, SPL2, SPL10, and SPL11, suppress root regeneration with age by inhibiting wound-induced auxin biosynthesis. Mechanistically, we find that a subset of APETALA2/ETHYLENE RESPONSE FACTOR (AP2/ERF) transcription factors including ABSCISIC ACID REPRESSOR1 and ERF109 is rapidly induced by wounding and serves as a proxy for wound signal to induce auxin biosynthesis. In older plants, SPL2/10/11 directly bind to the promoters of AP2/ERFs and attenuates their induction, thereby dampening auxin accumulation at the wound. Our results thus identify AP2/ERFs as a hub for integration of age and wound signal for root regeneration.


Asunto(s)
Proteínas de Arabidopsis/metabolismo , Etilenos/metabolismo , Proteínas de Homeodominio/metabolismo , Raíces de Plantas/crecimiento & desarrollo , Regeneración/fisiología , Ácido Abscísico/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Homeodominio/genética , Ácidos Indolacéticos/metabolismo , MicroARNs/metabolismo , Proteínas Nucleares , Regiones Promotoras Genéticas , Regeneración/genética , Proteínas Represoras , Factores de Transcripción/metabolismo
13.
Mol Psychiatry ; 27(8): 3214-3222, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35668158

RESUMEN

Infectious disease epidemics have become more frequent and more complex during the 21st century, posing a health threat to the general public and leading to psychological symptoms. The current study was designed to investigate the prevalence of and risk factors associated with depression, anxiety and insomnia symptoms during epidemic outbreaks, including COVID-19. We systematically searched the PubMed, Embase, Web of Science, OVID, Medline, Cochrane databases, bioRxiv and medRxiv to identify studies that reported the prevalence of depression, anxiety or insomnia during infectious disease epidemics, up to August 14th, 2020. Prevalence of mental symptoms among different populations including the general public, health workers, university students, older adults, infected patients, survivors of infection, and pregnant women across all types of epidemics was pooled. In addition, prevalence of mental symptoms during COVID-19 was estimated by time using meta-regression analysis. A total of 17,506 papers were initially retrieved, and a final of 283 studies met the inclusion criteria, representing a total of 948,882 individuals. The pooled prevalence of depression ranged from 23.1%, 95% confidential intervals (95% CI: [13.9-32.2]) in survivors to 43.3% (95% CI: [27.1-59.6]) in university students, the pooled prevalence of anxiety ranged from 25.0% (95% CI: [12.0-38.0]) in older adults to 43.3% (95% CI: [23.3-63.3]) in pregnant women, and insomnia symptoms ranged from 29.7% (95% CI: [24.4-34.9]) in the general public to 58.4% (95% CI: [28.1-88.6]) in university students. Prevalence of moderate-to-severe mental symptoms was lower but had substantial variation across different populations. The prevalence of mental problems increased over time during the COVID-19 pandemic among the general public, health workers and university students, and decreased among infected patients. Factors associated with increased prevalence for all three mental health symptoms included female sex, and having physical disorders, psychiatric disorders, COVID infection, colleagues or family members infected, experience of frontline work, close contact with infected patients, high exposure risk, quarantine experience and high concern about epidemics. Frequent exercise and good social support were associated with lower risk for these three mental symptoms. In conclusion, mental symptoms are common during epidemics with substantial variation across populations. The population-specific psychological crisis management are needed to decrease the burden of psychological problem and improve the mental wellbeing during epidemic.


Asunto(s)
COVID-19 , Enfermedades Transmisibles , Trastornos del Inicio y del Mantenimiento del Sueño , Embarazo , Femenino , Humanos , Anciano , COVID-19/epidemiología , Pandemias , Trastornos del Inicio y del Mantenimiento del Sueño/epidemiología , Prevalencia , Depresión/epidemiología , Depresión/etiología , SARS-CoV-2 , Ansiedad/epidemiología , Ansiedad/etiología , Factores de Riesgo , Enfermedades Transmisibles/epidemiología
14.
Inorg Chem ; 62(46): 19043-19051, 2023 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-37939347

RESUMEN

Natural gas plays a crucial role in daily and industrial production, but the impurities contained in natural gas limit its further use. It is very important to develop adsorbents that can separate CH4 from multicomponent mixtures, but there are still many challenges and problems. Herein, a novel porous MOF {[Mn5(pbdia)2(CO3)(H2O)2] ↔ 5H2O ↔ 2DMF}n (pbdia = 2,2'-(5-carboxy-1,3-phenylene)bis(oxy) diterephthalic acid) was successfully synthesized based on a flexible pentacarboxylic acid ligand and a unique pentanuclear Mn5(COO)10CO3 cluster. The MOF reveals a 3D porous structure with 2D intersecting channels, which shows high C3H8, C2H6, and CO2 adsorption capacities and affinities over CH4. Moreover, the ideal adsorption solution theory selectivities of C3H8/CH4, C2H6/CH4, and CO2/CH4 can reach 263.0, 27.0, and 7.7, respectively, suggesting a potential for removing the low content of C3H8, C2H6, and CO2 from pipeline natural gas, which was further confirmed by breakthrough curves and GCMC simulations.

15.
Zhongguo Zhong Yao Za Zhi ; 48(17): 4675-4685, 2023 Sep.
Artículo en Zh | MEDLINE | ID: mdl-37802806

RESUMEN

The Compound Cheqian Tablets are derived from Cheqian Power in Comprehensive Recording of Divine Assistance, and they are made by modern technology with the combination of Plantago asiatica and Coptis chinensis. To investigate the material basis of Compound Cheqian Tablets in the treatment of diabetic nephropathy, in this study, the chemical components of Compound Cheqian Tablets were characterized and analyzed by UPLC-Q-TOF-MS/MS, and a total of 48 chemical components were identified. The identified chemical compounds were analyzed by network pharmacology. By validating with previous literature, six bioactive compounds including acteoside, isoacteoside, coptisine, magnoflorine, palmatine, and berberine were confirmed as the index components for qua-lity evaluation. Furthermore, the content of the six components in the Compound Cheqian Tablets was determined by the "double external standards" quantitative analysis of multi-components by single marker(QAMS), and the relative correction factor of isoacteoside was calculated as 1.118 by using acteoside as the control; the relative correction factors of magnoflorine, palmatine, and berberine were calculated as 0.729, 1.065, and 1.126, respectively, by using coptisine as the control, indicating that the established method had excellent stability under different conditions. The results obtained by the "double external standards" QAMS approximated those obtained by the external standard method. This study qualitatively characterized the chemical components in the Compound Cheqian Tablets by applying UPLC-Q-TOF-MS/MS and screened the pharmacodynamic substance basis for the treatment of diabetic nephropathy via network pharmacology, and primary pharmacodynamic substance groups were quantitatively analyzed by the "double external stan-dards" QAMS method, which provided a scientific basis for clarifying the pharmacodynamic substance basis and quality control of Compound Cheqian Tablets.


Asunto(s)
Berberina , Nefropatías Diabéticas , Medicamentos Herbarios Chinos , Humanos , Espectrometría de Masas en Tándem , Berberina/farmacología , Cromatografía Líquida de Alta Presión/métodos , Farmacología en Red , Medicamentos Herbarios Chinos/química , Control de Calidad , Comprimidos
16.
Ann Surg Oncol ; 29(13): 8214-8224, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35798893

RESUMEN

BACKGROUND: The benefit of adjuvant chemotherapy (AC) for patients with stage II gastric cancer remains controversial. This study aimed to explore the indications for adjuvant chemotherapy in patients with stage II gastric cancer by constructing an individual prediction model. PATIENTS AND METHODS: In this Chinese multicenter study, a total of 1012 patients with stage II gastric cancer after D2 radical gastrectomy were retrospectively analyzed. All patients were randomly assigned to a training cohort (n = 674) or a validation cohort (n = 338). A nomogram was constructed according to the training cohort. Concordance index (C-index), the area under the receiver operating characteristic (ROC) curves (AUC), calibration curves, and decision curve analysis (DCA) were applied to evaluate the performance of the nomogram. ROC curves and stratified survival were used to determine the patients' cutoff score for a benefit from adjuvant chemotherapy. An additional 338 patients were used as a validation cohort to validate the feasibility of using this nomogram to guide individualized therapy for patients with stage II gastric cancer. RESULTS: Univariate and multivariate analyses illustrated that age, sex, tumor location, size, carcinoembryonic antigen (CEA), hemoglobin (HB), and T stage were independent prognostic factors for overall survival (OS), and they were used to establish a nomogram. The cutoff value was determined by ROC curve analysis, and patients were divided into a high-risk group (< 239 points) and a low-risk group (≥ 239 points). There was no significant difference in the OS of low-risk patients in either the training cohort or the validation cohort. However, the OS of high-risk patients in the AC group was better than that of patients in the surgery-only group. CONCLUSIONS: This prediction model can be applied to guide treatment of patients with stage II gastric cancer. High-risk patients (< 239 points) are likely to benefit from AC after D2 radical gastrectomy.


Asunto(s)
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Estudios Retrospectivos , Gastrectomía/efectos adversos , Quimioterapia Adyuvante , Nomogramas , China
17.
Ann Surg Oncol ; 29(4): 2324-2331, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34796431

RESUMEN

BACKGROUND: Mismatch repair-deficient (dMMR) or microsatellite instability-high (MSI-H) status serves as a predictor of a poor response to adjuvant chemotherapy among stage 2 colon cancer patients. This study aimed to investigate the efficacy of adjuvant chemotherapy in dMMR/MSI-H gastric cancer (GC). METHODS: Clinical studies comparing adjuvant chemotherapy and surgery alone in dMMR/MSI-H GCs through June 2021 were retrieved to assess the survival of patients managed with both treatments. Two approaches were used to pool the hazard ratio (HR) of survival: (1) if Kaplan-Meier curves and number of patients at risk were provided, individual patient data were extracted. Cox models were used to calculate the HR with its 95% confidence interval (CI); (2) for study-level data, pooled HR was estimated using fixed/random-effects models. RESULTS: Seven clinical studies were assessed. For dMMR/MSI-H versus mismatch repair-proficient (pMMR)/microsatellite stable (MSS)/microsatellite instability-low (MSI-L) status, the estimated 5-year disease-free survival (DFS) rate was 74.2% versus 51.5% (HR, 0.44; 95% CI, 0.32-0.62; P < 0.001) and the estimated 5-year OS rate was 60.5% versus 49.1% (HR, 0.71; 95% CI, 0.60-0.85; P < 0.001). The study-level data showed pooled HRs of 0.42 for DFS (95% CI, 0.31-0.57; P < 0.001) and 0.65 for OS (95% CI, 0.38-1.11; P = 0.114). For adjuvant chemotherapy versus observation of dMMR/MSI-H, the estimated 5-year DFS rate was 76.1% versus 73.3% (HR, 0.72; 95% CI, 0.45-1.15; P = 0.171) and the estimated 5-year OS rate was 73.5% versus 59.7% (HR, 0.62; 95% CI, 0.46-0.83; P = 0.001). Significant survival differences also were observed at study level. CONCLUSIONS: The study findings confirm the benefit of adjuvant chemotherapy for dMMR/MSI-H GC patients.


Asunto(s)
Inestabilidad de Microsatélites , Neoplasias Gástricas , Neoplasias Encefálicas , Quimioterapia Adyuvante , Neoplasias Colorrectales , Reparación de la Incompatibilidad de ADN , Humanos , Estadificación de Neoplasias , Síndromes Neoplásicos Hereditarios , Pronóstico , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética
18.
Phys Chem Chem Phys ; 24(41): 25648-25655, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36255301

RESUMEN

Taking Cs2NaBiCl6, Cs2AgInCl6 and Cs2AgBiCl6 as examples of lead-free double perovskites (DPs), we study the photoluminescence (PL) properties of Mn-doped DPs. The electron localization function (ELF) reveals the more ionic nature of the Na-Cl bond in Cs2NaBiCl6 than that of the Ag-Cl bond in Cs2AgBiCl6. Bader charge calculations confirm the nominal +2 valence state of Mn ions in both DPs. Mn2+ ions introduce two defect levels in the band gap of the Cs2NaBiCl6 host, accounting for the d-d transition (4T1-6A1 transition) of Mn2+ and thus the subsequent orange PL. The changes of the crystal field and their influences on the emission energy of Mn2+ ions in different DPs are evaluated by calculating the Racah parameters (B and C) and the crystal field strength (Dq) obtained from energies of the terms of d5 in the Cs2NaBiCl6:Mn2+ and Cs2AgInCl6:Mn2+ systems. The results show that Dq in Cs2AgInCl6:Mn2+ is stronger than that in Cs2NaBiCl6:Mn2+. The analyses on bonding interactions of the Mn-Cl bond via ELF and the integrated projected pCOHP also confirm the stronger ionic bonding interactions and thus the boost of the crystal field strength in the Cs2AgInCl6:Mn2+ system, which results in the blue-shift of the Mn2+ introduced PL peak from Cs2AgInCl6 to Cs2NaBiCl6. Our results provide a new strategy to modulate the emission wavelengths, i.e., tuning the crystal field.

19.
Proc Natl Acad Sci U S A ; 116(28): 14331-14338, 2019 07 09.
Artículo en Inglés | MEDLINE | ID: mdl-31221756

RESUMEN

Insects have evolved effectors to conquer plant defense. Most known insect effectors are isolated from sucking insects, and examples from chewing insects are limited. Moreover, the targets of insect effectors in host plants remain unknown. Here, we address a chewing insect effector and its working mechanism. Cotton bollworm (Helicoverpa armigera) is a lepidopteran insect widely existing in nature and severely affecting crop productivity. We isolated an effector named HARP1 from H. armigera oral secretion (OS). HARP1 was released from larvae to plant leaves during feeding and entered into the plant cells through wounding sites. Expression of HARP1 in Arabidopsis mitigated the global expression of wounding and jasmonate (JA) responsive genes and rendered the plants more susceptible to insect feeding. HARP1 directly interacted with JASMONATE-ZIM-domain (JAZ) repressors to prevent the COI1-mediated JAZ degradation, thus blocking JA signaling transduction. HARP1-like proteins have conserved function as effectors in noctuidae, and these types of effectors might contribute to insect adaptation to host plants during coevolution.


Asunto(s)
Gossypium/genética , Interacciones Huésped-Parásitos/genética , Mariposas Nocturnas/patogenicidad , Enfermedades de las Plantas/genética , Animales , Arabidopsis/genética , Arabidopsis/crecimiento & desarrollo , Ciclopentanos/metabolismo , Resistencia a la Enfermedad/genética , Regulación de la Expresión Génica de las Plantas/genética , Gossypium/crecimiento & desarrollo , Gossypium/parasitología , Mariposas Nocturnas/metabolismo , Oxilipinas/metabolismo , Enfermedades de las Plantas/parasitología , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Transducción de Señal/genética
20.
J Asian Nat Prod Res ; : 1-7, 2022 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-35672871

RESUMEN

Two undescribed stilbenoid diglycosides, dendrosonside A and dendrosonside B (1 and 2), were isolated from the stems of Dendrobium 'Sonia'. Their structures were elucidated based on 1 D/2D NMR and HRESIMS. The glycosyls contained in the two isolates were determined as D-glucose by acid hydrolysis and GC-MS analyses. In addition, 1 and 2 were further tested for the inhibition of nitric oxide production.

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