Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 166
Filtrar
Más filtros

Banco de datos
Tipo del documento
Intervalo de año de publicación
1.
Plant Cell ; 35(11): 4002-4019, 2023 Oct 30.
Artículo en Inglés | MEDLINE | ID: mdl-37648256

RESUMEN

Heading date (flowering time), which greatly influences regional and seasonal adaptability in rice (Oryza sativa), is regulated by many genes in different photoperiod pathways. Here, we characterized a heading date gene, Early heading date 5 (Ehd5), using a modified bulked segregant analysis method. The ehd5 mutant showed late flowering under both short-day and long-day conditions, as well as reduced yield, compared to the wild type. Ehd5, which encodes a WD40 domain-containing protein, is induced by light and follows a circadian rhythm expression pattern. Transcriptome analysis revealed that Ehd5 acts upstream of the flowering genes Early heading date 1 (Ehd1), RICE FLOWERING LOCUS T 1 (RFT1), and Heading date 3a (Hd3a). Functional analysis showed that Ehd5 directly interacts with Rice outermost cell-specific gene 4 (Roc4) and Grain number, plant height, and heading date 8 (Ghd8), which might affect the formation of Ghd7-Ghd8 complexes, resulting in increased expression of Ehd1, Hd3a, and RFT1. In a nutshell, these results demonstrate that Ehd5 functions as a positive regulator of rice flowering and provide insight into the molecular mechanisms underlying heading date.


Asunto(s)
Flores , Oryza , Ritmo Circadiano , Flores/genética , Flores/metabolismo , Regulación de la Expresión Génica de las Plantas/genética , Oryza/genética , Oryza/metabolismo , Fotoperiodo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Repeticiones WD40/genética
2.
BMC Genomics ; 25(1): 309, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528494

RESUMEN

BACKGROUND: Incubation behaviour, an instinct for natural breeding in poultry, is strictly controlled by the central nervous system and multiple neuroendocrine hormones and neurotransmitters, and is closely associated with the cessation of egg laying. Therefore, it is essential for the commercial poultry industry to clarify the molecular regulation mechanism of incubation behaviour. Here, we used high-throughput sequencing technology to examine the pituitary transcriptome of Changshun green-shell laying hen, a local breed from Guizhou province, China, with strong broodiness, in two reproductive stages, including egg-laying phase (LP) and incubation phase (BP). We also analyze the differences in gene expression during the transition from egg-laying to incubation, and identify critical pathways and candidate genes involved in controlling the incubation behaviour in the pituitary. RESULTS: In this study, we demonstrated that a total of 2089 differently expressed genes (DEGs) were identified in the pituitary, including 842 up-regulated and 1247 down-regulated genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that steroid biosynthesis pathway and neuroactive ligand-receptor interaction were significantly enriched based on DEGs commonly identified in pituitary. Further analysis revealed that SRC, ITGB4, ITGB3, PIK3R3 and DRD2 may play crucial roles in the regulation of incubation behaviour. CONCLUSIONS: We identified 2089 DEGs and the key signaling pathways which may be closely correlated with incubation in Changshun green-shell laying hens, and clarified the molecular regulation mechanism of incubation behaviour. Our results indicate the complexity and variety of differences in reproductive behaviour of different chicken breeds.


Asunto(s)
Pollos , Transcriptoma , Animales , Femenino , Pollos/metabolismo , Perfilación de la Expresión Génica , Hipófisis/metabolismo , Hormonas/metabolismo
3.
J Am Chem Soc ; 146(4): 2411-2418, 2024 01 31.
Artículo en Inglés | MEDLINE | ID: mdl-38234111

RESUMEN

Nanographene C222, which consists of a planar graphenic plane containing 222 carbon atoms, holds the record as the largest planar nanographene synthesized to date. However, its complete insolubility makes the processing of C222 difficult. Here we addressed this issue by introducing peripheral substituents perpendicular to the graphene plane, effectively disrupting the interlayer stacking and endowing C222 with good solubility. We also found that the electron-withdrawing substituents played a crucial role in the cyclodehydrogenation process, converting the dendritic polyphenylene precursor to C222. After disrupting the interlayer stacking, the introduction of only a few peripheral carboxylic groups allowed C222 to dissolve in phosphate buffer saline, reaching a concentration of up to 0.5 mg/mL. Taking advantage of the good photosensitizing and photothermal properties of the inner C222 core, the resulting water-soluble C222 emerged as a single-component agent for both photothermal and photodynamic tumor therapy, exhibiting an impressive tumor inhibition rate of 96%.


Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Terapia Fototérmica , Fotoquimioterapia/métodos , Neoplasias/tratamiento farmacológico
4.
Heart Fail Rev ; 29(1): 95-111, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37768435

RESUMEN

This review article offers a detailed examination of metabolic adaptations in pressure overload hypertrophic hearts, a condition that plays a pivotal role in the progression of heart failure with preserved ejection fraction (HFpEF) to heart failure with reduced ejection fraction (HFrEF). The paper delves into the complex interplay between various metabolic pathways, including glucose metabolism, fatty acid metabolism, branched-chain amino acid metabolism, and ketone body metabolism. In-depth insights into the shifts in substrate utilization, the role of different transporter proteins, and the potential impact of hypoxia-induced injuries are discussed. Furthermore, potential therapeutic targets and strategies that could minimize myocardial injury and promote cardiac recovery in the context of pressure overload hypertrophy (POH) are examined. This work aims to contribute to a better understanding of metabolic adaptations in POH, highlighting the need for further research on potential therapeutic applications.


Asunto(s)
Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/metabolismo , Metabolismo Energético , Volumen Sistólico , Cardiomegalia/metabolismo
5.
J Chem Inf Model ; 64(5): 1502-1511, 2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38413369

RESUMEN

Protein function prediction is essential for disease treatment and drug development; yet, traditional biological experimental methods are less efficient in annotating protein function, and existing automated methods fail to fully leverage protein multisource data. Here, we present MSF-PFP, a computational framework that fuses multisource data features to predict protein function with high accuracy. Our framework designs specific models for feature extraction based on the characteristics of various data sources, including a global-local-individual strategy for local location features. MSF-PFP then integrates extracted features through a multisource feature fusion model, ultimately categorizing protein functions. Experimental results demonstrate that MSF-PFP outperforms eight state-of-the-art models, achieving FMax scores of 0.542, 0.675, and 0.624 for the biological process (BP), molecular function (MF), and cellular component (CC), respectively. The source code and data set for MSF-PFP are available at https://swanhub.co/TianGua/MSF-PFP, facilitating further exploration and validation of the proposed framework. This study highlights the potential of multisource data fusion in enhancing protein function prediction, contributing to improved disease therapy and medication discovery strategies.


Asunto(s)
Proteínas , Programas Informáticos
6.
Brain ; 146(4): 1615-1623, 2023 04 19.
Artículo en Inglés | MEDLINE | ID: mdl-36200349

RESUMEN

We previously hypothesized that functional cognitive disorder is characterized by heightened subjective mental effort, exhausted attentional reserve and metacognitive failure. To test this hypothesis, we administered a Stroop colour-word task in which attentional demand was varied by task difficulty (congruent versus incongruent cues) and the presence of a secondary auditory stimulus (passive or active listening to an oddball-type paradigm). We measured subjective mental effort, objective performance (reaction times and accuracy), metacognition and EEG-based biomarkers of mental workload. We tested 19 functional cognitive disorder patients and 23 healthy controls. Patients reported higher levels of depression, anxiety, fatigue, pain, sleep disruption, dissociation and obsessiveness. They rated their memory as significantly poorer than healthy controls; however, accuracy did not differ between groups in any condition. In contrast to healthy controls, patients rated their performance as poorer on the congruent Stroop task with background noise compared to silent conditions. Functional cognitive disorder was consistently associated with slower reaction times but this was not exacerbated by increased attentional demand. Patients but not healthy controls reported greater mental workload in noisy conditions but EEG biomarkers were similar between groups, regardless of task difficulty. Functional cognitive disorder has significant syndromic overlap with mood disorders and chronic fatigue and pain. It is associated with global metacognitive failure whereas local (task-specific) metacognition is only selectively impaired. Patients were slower than healthy controls, which might contribute to the 'brain fog' reported in this condition. Although subjective mental effort was increased in noisy conditions, we found no evidence of attentional exhaustion in functional cognitive disorder. Our results indicate that functional cognitive disorder is a multisystem condition affecting reaction time, subjective mental effort and global metacognition.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Metacognición , Humanos , Tiempo de Reacción , Trastornos del Conocimiento/psicología , Biomarcadores
7.
Acta Paediatr ; 113(7): 1496-1505, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38647361

RESUMEN

AIM: Hypothermia poses a threat to the health and lives of newborns. Therefore, it is essential to identify the factors that influence neonatal hypothermia and provide targeted intervention suggestions for clinical practice to reduce its occurrence. METHODS: We conducted a literature search to identify factors influencing neonatal hypothermia and performed a meta-analysis to determine the prevalence of neonatal hypothermia and its associated factors. The Newcastle-Ottawa Scale (NOS) was used to assess the quality of cohort and case-control studies, while the Agency for Healthcare Research and Quality (AHRQ) was used to evaluate the quality of cross-sectional studies. RESULTS: Eighteen studies involving 44 532 newborns from 13 countries were included. The incidence of neonatal hypothermia was 52.5% (95% CI: 0.37, 0.68). Factors such as no skin-to-skin contact, prematurity, low birth weight, delayed breastfeeding, asphyxiation and resuscitation after birth, low APGAR score, not wearing a cap, and caesarean section were found to affect neonatal hypothermia. CONCLUSION: Multiple factors influence neonatal hypothermia, and clinicians can utilise these factors to develop targeted intervention measures to prevent and reduce the incidence of neonatal hypothermia.


Asunto(s)
Hipotermia , Humanos , Recién Nacido , Hipotermia/epidemiología , Hipotermia/etiología , Hipotermia/prevención & control , Incidencia , Factores de Riesgo
8.
J Electrocardiol ; 83: 21-25, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38241779

RESUMEN

BACKGROUND: The left bundle branch block (LBBB) is associated with ventricular septal mid-wall fibrosis (SMF) in patients with dilated cardiomyopathy (DCM). However, whether LBBB is also associated with SMF in patients with preserved left ventricular ejection fraction (LVEF) remains unclear. METHODS: We performed a retrospective study of 210 patients with preserved LVEF (male, n = 116; female, n = 94; mean age, 44 ± 17 years). LBBB was defined as QRS duration ≥140 ms for men or ≥ 130 ms for women, QS or rS in V1-V2, mid-QRS notching or slurring in at least two leads (V1, V2, V5, V6, I, and aVL). SMF determined by late gadolinium-enhancement cardiovascular magnetic resonance was defined as stripe-like or patchy mid-myocardial hyper-enhancement in the interventricular septal segments. RESULTS: SMF was detected in 24.8% (52/210) of these patients. The proportion of patients with SMF with LBBB was higher than the proportion of patients with SMF without LBBB (58.3% vs. 20.4%; P < 0.001). In the forward multivariate logistic analysis, LBBB (OR, 4.399; 95% CI, 1.774-10.904; P = 0.001) and age (OR, 1.028; 95% CI, 1.006-1.051; P = 0.011) were independently associated with SMF. The presence of LBBB showed a sensitivity of 27%%, specificity of 94%, positive predictive value of 58%%, and negative predictive value of 80% for the detection of SMF. CONCLUSION: LBBB was significantly associated with SMF in hospitalized patients with preserved LVEF. Screening with a resting 12­lead ECG may help to identify patients who are at a high risk of the presence of SMF.


Asunto(s)
Función Ventricular Izquierda , Tabique Interventricular , Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Volumen Sistólico , Bloqueo de Rama/diagnóstico , Electrocardiografía , Estudios Retrospectivos , Fibrosis
9.
Int J Neurosci ; : 1-7, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38712679

RESUMEN

OBJECTIVE: To explore the alleviating effect of standardized three-step nursing on perioperative pressure injury in patients with spinal fractures accompanied by spinal cord injury. METHODS: A retrospective analysis was conducted on the clinical data of 153 patients who underwent surgical treatment for spinal fracture accompanied by spinal cord injury in our hospital from January 2021 to January 2024. All patients met the criteria for inclusion and exclusion. According to the nursing interventions received during the perioperative period, the patients were divided into a control group (n = 76) and an observation group (n = 77). The control group received routine nursing interventions during the perioperative period, while the observation group received standardized three-step nursing interventions. The occurrence, severity, area, and pain [Visual Analog Scale (VAS)], coagulation indicators [prothrombin time (PT), fibrinogen (FIB), D-dimer (D-D)], activities of daily living [Barthel Index], and quality of life [General Quality of Life Inventory (GQOLI-74)] were compared between the two groups. RESULTS: (1) Occurrence and severity of perioperative pressure injury: in the control group, 18 cases of pressure injury occurred, including 5 cases of stage I, 11 cases of stage II, and 2 cases of stage III; in the observation group, 7 cases of pressure injury occurred, including 4 cases of stage I and 3 cases of stage II. The occurrence rate and severity of pressure injury in the observation group were lower than those in the control group (p < 0.05). (2) Area of injury and pain: The area of injury on the day of surgery and 5 days after surgery in the observation group was lower than that in the control group (p < 0.05); the VAS score 5 days after surgery in the observation group was lower than that in the control group (p < 0.05). (3) Coagulation indicators: 5 days after surgery, the levels of D-D and FIB in the observation group were lower than those in the control group, while PT was higher than that in the control group (p < 0.05). (4) Activities of daily living and quality of life: 3 months after surgery, the Barthel score and GQOLI-74 score in the observation group were higher than those in the control group (p < 0.05). CONCLUSION: Standardized three-step nursing can significantly reduce the occurrence rate, severity, and area of perioperative pressure injury in patients with spinal fracture accompanied by spinal cord injury, alleviate patient pain, improve coagulation function, and enhance levels of activities of daily living and quality of life.

10.
J Sci Food Agric ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619292

RESUMEN

Chickpea is a field crop that is playing an emerging role in the provision of healthy and sustainable plant-based value-added ingredients for the food and nutraceutical industries. This article reviews the characteristics of chickpea (composition, health properties, and techno-functionality) and chickpea grain that influence their use as whole foods or ingredients in formulated food. It covers the exploitation of traditional and emerging processes for the conversion of chickpea into value-added differentiated food ingredients. The influence of processing on the composition, health-promoting properties, and techno-functionality of chickpea is discussed. Opportunities to tailor chickpea ingredients to facilitate their incorporation in traditional food applications and in the expanding plant-based meat alternative and dairy alternative markets are highlighted. The review includes an assessment of the possible uses of by-products of chickpea processing. Recommendations are provided for future research to build a sustainable industry using chickpea as a value-added ingredient. © 2024 Society of Chemical Industry.

11.
Ann Surg Oncol ; 30(12): 7172-7180, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37543550

RESUMEN

BACKGROUND: Surgery is the primary treatment for locally advanced differentiated thyroid cancer (DTC). However, some locally advanced patients are not candidates for R0/1 resection. There is limited evidence of neoadjuvant treatment in locally advanced DTC. Surufatinib targets multiple kinases, which is efficient, tolerable, and safe in patients with radioiodine-refractory DTC. In addition, surufatinib plus toripalimab (an anti-PD-1 antibody) showed encouraging antitumor activity in advanced solid tumors. This study was designed to evaluate the efficacy and safety of surufatinib plus toripalimab in locally advanced DTC in the neoadjuvant setting. METHODS: In this single-arm, phase II study, patients with pathologically confirmed unresectable or borderline resectable DTC were eligible and received a combination of 250 mg of surufatinib (orally daily) with 240 mg of toripalimab (intravenous, every 3 weeks). Treatment continued until satisfied for curative surgery, disease progression, withdrawal of consent, unacceptable toxicity, or investigator decision. Primary endpoint was objective response rate (ORR). Secondary endpoints included R0/1 resection rate, adverse events (AEs), etc. RESULTS: Ten patients were enrolled and received at least 4 cycles of treatment. The ORR was 60%. Nine patients received R0/1 resections after neoadjuvant treatment. The median best percentage change in the sum of the target lesion diameter was 32%. Most adverse events (AEs) were grade 1 or 2. CONCLUSIONS: Surufatinib in combination with toripalimab as neoadjuvant therapy for locally advanced DTC was feasible, and the majority of patients achieved R0/1 resection. It represents a new option for locally advanced DTC and needs further investigation.

12.
Glob Chang Biol ; 29(15): 4430-4439, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37194010

RESUMEN

Microbial residues contribute to the long-term stabilization of carbon in the entire soil profile, helping to regulate the climate of the planet; however, how sensitive these residues are to climatic seasonality remains virtually unknown, especially for deep soils across environmental gradients. Here, we investigated the changes of microbial residues along soil profiles (0-100 cm) from 44 typical ecosystems with a wide range of climates (~3100 km transects across China). Our results showed that microbial residues account for a larger portion of soil carbon in deeper (60-100 cm) vs. shallower (0-30 and 30-60 cm) soils. Moreover, we find that climate especially challenges the accumulation of microbial residues in deep soils, while soil properties and climate share their roles in controlling the residue accumulation in surface soils. Climatic seasonality, including positive correlations with summer precipitation and maximum monthly precipitation, as well as negative correlations with temperature annual range, are important factors explaining microbial residue accumulation in deep soils across China. In particular, summer precipitation is the key regulator of microbial-driven carbon stability in deep soils, which has 37.2% of relative independent effects on deep-soil microbial residue accumulation. Our work provides novel insights into the importance of climatic seasonality in driving the stabilization of microbial residues in deep soils, challenging the idea that deep soils as long-term carbon reservoirs can buffer climate change.


Asunto(s)
Carbono , Microbiología del Suelo , Suelo , Carbono/análisis , China , Cambio Climático , Ecosistema , Suelo/química
13.
PLoS Comput Biol ; 18(4): e1009973, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35377873

RESUMEN

The drivers behind regional differences of SARS-CoV-2 spread on finer spatio-temporal scales are yet to be fully understood. Here we develop a data-driven modelling approach based on an age-structured compartmental model that compares 116 Austrian regions to a suitably chosen control set of regions to explain variations in local transmission rates through a combination of meteorological factors, non-pharmaceutical interventions and mobility. We find that more than 60% of the observed regional variations can be explained by these factors. Decreasing temperature and humidity, increasing cloudiness, precipitation and the absence of mitigation measures for public events are the strongest drivers for increased virus transmission, leading in combination to a doubling of the transmission rates compared to regions with more favourable weather. We conjecture that regions with little mitigation measures for large events that experience shifts toward unfavourable weather conditions are particularly predisposed as nucleation points for the next seasonal SARS-CoV-2 waves.


Asunto(s)
COVID-19 , SARS-CoV-2 , Austria/epidemiología , COVID-19/epidemiología , COVID-19/prevención & control , Humanos , Conceptos Meteorológicos , Tiempo (Meteorología)
14.
Eur Radiol ; 33(12): 9063-9073, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37439940

RESUMEN

OBJECTIVES: To establish a computed tomography (CT)-based scale to evaluate the resectability of locally advanced thyroid cancer. METHODS: This twin-centre retrospective study included 95 locally advanced thyroid cancer patients from the 1st centre as the training cohort and 31 patients from the 2nd centre as the testing cohort, who were categorised into the resectable and unresectable groups. Three radiologists scored the CT scans of each patient by evaluating the extension to the recurrent laryngeal nerve (RLN), trachea, oesophagus, artery, vein, soft tissue, and larynx. A 14-score scale (including all comprised structures) and a 12-score scale (excluding larynx) were developed. Receiver-operating characteristic (ROC) analysis was used to evaluate the performance of the scales. Stratified fivefold cross-validation and external verification were used to validate the scale. RESULTS: In the training cohort, compromised RLN (p < 0.001), trachea (p = 0.001), oesophagus (p = 0.002), artery (p < 0.001), vein (p = 0.005), and soft tissue (p < 0.001) were predictors for unresectability, while compromised larynx (p = 0.283) was not. The 12-score scale (AUC = 0.882, 95%CI: 0.812-0.952) was not inferior to the 14-score scale (AUC = 0.891, 95%CI: 0.823-0.960). In subgroup analysis, the AUCs of the 12-score scale were 0.826 for treatment-naïve patients and 0.976 for patients with prior surgery. The 12-score scale was further validated with a fivefold cross-validation analysis, with an overall accuracy of 78.9-89.4%. Finally, external validation using the testing cohort showed an AUC of 0.875. CONCLUSIONS: The researchers built a CT-based 12-score scale to evaluate the resectability of locally advanced thyroid cancer. Validation with a larger sample size is required to confirm the efficacy of the scale. CLINICAL RELEVANCE STATEMENT: This 12-score CT scale would help clinicians evaluate the resectability of locally advanced thyroid cancer. KEY POINTS: • The researchers built a 12-score CT scale (including recurrent laryngeal nerve, trachea, oesophagus, artery, vein, and soft tissue) to evaluate the resectability of locally advanced thyroid cancer. • This scale has the potential to help clinicians make treatment plans for locally advanced thyroid cancer.


Asunto(s)
Laringe , Neoplasias de la Tiroides , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodos , Neoplasias de la Tiroides/diagnóstico por imagen , Neoplasias de la Tiroides/cirugía
15.
Eur J Neurol ; 30(5): 1505-1514, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36719069

RESUMEN

BACKGROUND AND PURPOSE: Acute health events, including infections, can trigger the onset of functional neurological disorder (FND). It was hypothesized that a proportion of people with long COVID might be experiencing functional symptoms. METHODS: A systematic review of studies containing original data on long COVID was performed. The frequency and characteristics of neurological symptoms were reviewed, looking for positive evidence suggesting an underlying functional disorder and the hypothesized causes of long COVID. RESULTS: In all, 102 studies were included in our narrative synthesis. The most consistently reported neurological symptoms were cognitive difficulties, headaches, pain, dizziness, fatigue, sleep-related symptoms and ageusia/anosmia. Overall, no evidence was found that any authors had systematically looked for positive features of FND. An exception was three studies describing temporal inconsistency. In general, the neurological symptoms were insufficiently characterized to support or refute a diagnosis of FND. Moreover, only 13 studies specifically focused on long COVID after mild infection, where the impact of confounders from the general effects of severe illness would be mitigated. Only one study hypothesized that some people with long COVID might have a functional disorder, and another eight studies a chronic-fatigue-syndrome-like response. DISCUSSION: Neurological symptoms are prevalent in long COVID, but poorly characterized. The similarities between some manifestations of long COVID and functional disorders triggered by acute illnesses are striking. Unfortunately, the current literature is plagued by confounders, including the mixing of patients with initial mild infection with those with severe acute medical complications. The hypothesis that long COVID might in part correspond to a functional disorder remains untested.


Asunto(s)
COVID-19 , Trastornos de Conversión , Humanos , Síndrome Post Agudo de COVID-19 , COVID-19/complicaciones , Anosmia , Fatiga/etiología
16.
Bioorg Med Chem ; 78: 117153, 2023 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-36621179

RESUMEN

Several small-molecule covalent inhibitors of KRASG12C have made breakthrough progress in the treatment of KRAS mutant cancer. However, the clinical application of KRASG12C small-molecule inhibitors may be limited by adaptive resistance. Emerging PROTAC strategy can achieve complementary advantages with small molecule inhibitors and improve anti-tumor efficacy. Based on AMG-510, a series of novel KRASG12C-PROTACs were designed and synthesized. The protein degradation assay showed that PROTACs I-1, II-1, III-2 and IV-1 had binding and degradation ability to KRASG12C. III-2 and IV-1 showed potent inhibitory effect on downstream p-ERK and were more potent than AMG-510. Mechanistic studies demonstrated that PROTACs exerted degradation effects through the ubiquitin-proteasome pathway. Using cell lines sensitive to KRASG12C, anti-proliferative activities of compounds were assessed. PROTACs tested showed overall anti-proliferative activities. Besides,the structure-activity relationships (SARs) of KRASG12C-PROTACs were summarized. These results supported the use of the PROTAC strategy to degrade oncogene KRASG12C and provided clues for structural optimization of KRASG12C-PROTACs.


Asunto(s)
Neoplasias , Quimera Dirigida a la Proteólisis , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Proteolisis , Neoplasias/tratamiento farmacológico
17.
Appl Opt ; 62(13): 3380-3386, 2023 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-37132838

RESUMEN

This paper reports the method of generating a 355 nm ultraviolet (UV) quasicontinuous pulse laser by using two periodically poled Mg-doped lithium niobate (PPMgLN) crystals in a single-pass cascade. In the first PPMgLN crystal with a length of 20 mm and a first-order-poled period of 6.97 µm, the second-harmonic light of a 532 nm laser with 780 mW is generated from the 1064 nm laser with an average power of 2 W; After that, in the second PPMgLN crystal with a length of 15 mm and a third-order-poled period of 5.30 µm, the 532 nm laser generated was combined with the 1064 nm laser remaining through the first PPMgLN crystal to obtain a 355 nm UV laser with a maximum output average power of 20 mW, a repetition rate of 40 kHz, a pulse width of 49 ns, and a peak power of 10 W. Compared with existing reports, we have higher peak power and single pulse energy, which is an important application of the PPMgLN crystal. This paper will provide an important case for the realization of a 355 nm UV quasicontinuous or a continuous laser.

18.
Phytother Res ; 2023 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-37697721

RESUMEN

Metabolic dysfunction-associated fatty liver disease (MAFLD) is the main cause of chronic liver disease. Baicalin (Bai), a bioactive molecule found in Scutellaria baicalensis Georgi, possesses antioxidant and antiinflammatory properties. These activities suggest Bai could be a promising therapeutic agent against NAFLD; however, its specific effects and underlying mechanism are still not clear. This study aims to explore the effect of Bai to attenuate MAFLD and associated molecular mechanisms. Bai (50, 100 or 200 mg/kg) was orally administered to db/db mice with MAFLD for 4 weeks or db/m mice as the normal control. Bai markedly attenuated lipid accumulation, cirrhosis and hepatocytes apoptosis in the liver tissues of MAFLD mice, suggesting strong ability to attenuate MAFLD. Bai significantly reduced proinflammatory biomarkers and enhanced antioxidant enzymes, which appeared to be modulated by the upregulated p62-Keap1-Nrf2 signalling cascade; furthermore, cotreatment of Bai and all-trans-retinoic acid (Nrf2 inhibitor) demonstrated markedly weakened liver protective effects by Bai and its induced antioxidant and antiinflammatory responses. The present study supported the use of Bai in attenuating MAFLD as a promising therapeutic agent, and its strong mechanism of action in association with the upregulating the p62-keap1-Nrf2 pathway.

19.
Angew Chem Int Ed Engl ; 62(43): e202312076, 2023 Oct 23.
Artículo en Inglés | MEDLINE | ID: mdl-37667537

RESUMEN

The effective conversion of carbon dioxide (CO2 ) and nitrogen (N2 ) into urea by photocatalytic reaction under mild conditions is considered to be a more environmentally friendly and promising alternative strategies. However, the weak adsorption and activation ability of inert gas on photocatalysts has become the main challenge that hinder the advancement of this technique. Herein, we have successfully established mesoporous CeO2-x nanorods with adjustable oxygen vacancy concentration by heat treatment in Ar/H2 (90 % : 10 %) atmosphere, enhancing the targeted adsorption and activation of N2 and CO2 by introducing oxygen vacancies. Particularly, CeO2 -500 (CeO2 nanorods heated treatment at 500 °C) revealed high photocatalytic activity toward the C-N coupling reaction for urea synthesis with a remarkable urea yield rate of 15.5 µg/h. Besides, both aberration corrected transmission electron microscopy (AC-TEM) and Fourier transform infrared (FT-IR) spectroscopy were used to research the atomic surface structure of CeO2 -500 at high resolution and to monitor the key intermediate precursors generated. The reaction mechanism of photocatalytic C-N coupling was studied in detail by combining Density Functional Theory (DFT) with specific experiments. We hope this work provides important inspiration and guiding significance towards highly efficient photocatalytic synthesis of urea.

20.
Angew Chem Int Ed Engl ; 62(35): e202309073, 2023 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-37427886

RESUMEN

Macroscopic compass-like magnetic alignment at low magnetic fields is natural for ferromagnetic materials but is seldomly observed in paramagnetic materials. Herein, we report a "paramagnetic compass" that magnetically aligns under ∼mT fields based on the single-crystalline framework constructed by lanthanide ions and organic ligands (Ln-MOF). The magnetic alignment is attributed to the Ln-MOF's strong macroscopic anisotropy, where the highly-ordered structure allows the Ln-ions' molecular anisotropy to be summed according to the crystal symmetry. In tetragonal Ln-MOFs, the alignment is either parallel or perpendicular to the field depending on the easiest axis of the molecular anisotropy. Reversible switching between the two alignments is realized upon the removal and re-adsorption of solvent molecules filled in the framework. When the crystal symmetry is lowered in monoclinic Ln-MOFs, the alignments become even inclined (47°-66°) to the field. These fascinating properties of Ln-MOFs would encourage further explorations of framework materials containing paramagnetic centers.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA