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1.
Heliyon ; 10(10): e30904, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38765031

RESUMEN

Understanding the motion characteristics of cervical spine through biomechanical analysis aids in the identification of abnormal joint movements. This knowledge is essential for the prevention, diagnosis, and treatment of related disorders. However, the anatomical structure of the cervical spine is complex, and traditional medical imaging techniques have certain limitations. Capturing the movement characteristics of various parts of the cervical spine in vivo during motion is challenging. The dual fluoroscopic imaging system (DFIS) is able to quantify the motion and motion patterns of individual segments. In recent years, DFIS has achieved accurate non-invasive measurements of dynamic joint movements in humans. This review assesses the research findings of DFIS about the cervical spine in healthy and pathological individuals. Relevant study search was conducted up to October 2023 in Web of Science, PubMed, and EBSCO databases. After the search, a total of 30 studies were ultimately included. Among them, 13 studies focused on healthy cervical spines, while 17 studies focused on pathological cervical spines. These studies mainly centered on exploring the vertebral bodies and associated structures of the cervical spine, including intervertebral discs, intervertebral foramina, and zygapophyseal joints. Further research could utilize DFIS to investigate cervical spine motion in different populations and under pathological conditions.

2.
Cell Chem Biol ; 31(5): 920-931.e6, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38759618

RESUMEN

T cell receptor (TCR) plays a fundamental role in adaptive immunity, and TCR-T cell therapy holds great promise for treating solid tumors and other diseases. However, there is a noticeable absence of chemical tools tuning TCR activity. In our study, we screened natural sterols for their regulatory effects on T cell function and identified 7-alpha-hydroxycholesterol (7a-HC) as a potent inhibitor of TCR signaling. Mechanistically, 7a-HC promoted membrane binding of CD3ε cytoplasmic domain, a crucial signaling component of the TCR-CD3 complex, through alterations in membrane physicochemical properties. Enhanced CD3ε membrane binding impeded the condensation between CD3ε and the key kinase Lck, thereby inhibiting Lck-mediated TCR phosphorylation. Transient treatments of TCR-T cells with 7a-HC resulted in reduced signaling strength, increased memory cell populations, and superior long-term antitumor functions. This study unveils a chemical regulation of TCR signaling, which can be exploited to enhance the long-term efficacy of TCR-T cell therapy.


Asunto(s)
Hidroxicolesteroles , Receptores de Antígenos de Linfocitos T , Transducción de Señal , Transducción de Señal/efectos de los fármacos , Receptores de Antígenos de Linfocitos T/metabolismo , Receptores de Antígenos de Linfocitos T/inmunología , Humanos , Hidroxicolesteroles/química , Hidroxicolesteroles/metabolismo , Hidroxicolesteroles/farmacología , Animales , Ratones , Linfocitos T/efectos de los fármacos , Linfocitos T/inmunología , Linfocitos T/metabolismo , Ratones Endogámicos C57BL , Fosforilación/efectos de los fármacos
3.
Cell Biochem Biophys ; 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38722470

RESUMEN

Percutaneous coronary intervention (PCI) is the main treatment for patients with severe coronary vascular stenosis. However, In-stent neo-atherosclerosis (ISNA) is an important clinical complication in patients after PCI, which is mainly caused by a persistent inflammatory response and endothelial insufficiency. In the cardiovascular field, magnesium-based scaffolds stand out due to their properties. Magnesium plays a key role in regulating cardiovascular physiology. Magnesium deficiency can promote endothelial cell dysfunction, which contributes to the formation of atherosclerosis. Since astragaloside IV (AS­IV) has been proven to have potent cardioprotective effects, we asked whether high levels of magnesium cooperate with AS­IV might have effects on endothelial function and ISNA. We performed in vitro experiments on endothelial cells. Being treated with different concentrations of magnesium or/and AS-IV, the cell growth and migration were detected by CCK-8 and wound healing assay, respectively. The pro-inflammatory factors tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6), adhesion molecule vascular cell adhesion molecule-1 (VCAM-1), and NF-kB were determined by qRT-PCR, ELISA kits or western blot. Results showed that high magnesium and AS-IV improved endothelial function, including promoting cell migration and decreasing the content of TNF-α, IL-6, VCAM-1, and NF-kB. With the supplement of AS-IV, additive magnesium maintains cell proliferation, migration, and function of endothelial cells. In conclusion, these findings suggest that high magnesium and AS­IV could improve vascular endothelial dysfunction. Early detection and treatment for neo-atherosclerosis may be of great clinical significance for improving stent implantation efficacy and long-term prognosis.

4.
BMC Gastroenterol ; 24(1): 158, 2024 May 08.
Artículo en Inglés | MEDLINE | ID: mdl-38720308

RESUMEN

BACKGROUND: Primary sclerosing cholangitis (PSC) is a complex disease with pathogenic mechanisms that remain to be elucidated. Previous observational studies with small sample sizes have reported associations between PSC, dyslipidemia, and gut microbiota dysbiosis. However, the causality of these associations is uncertain, and there has been no systematic analysis to date. METHODS: The datasets comprise data on PSC, 179 lipid species, and 412 gut microbiota species. PSC data (n = 14,890) were sourced from the International PSC Study Group, while the dataset pertaining to plasma lipidomics originated from a study involving 7174 Finnish individuals. Data on gut microbiota species were derived from the Dutch Microbiome Project study, which conducted a genome-wide association study involving 7738 participants. Furthermore, we employed a two-step Mendelian randomization (MR) analysis to quantify the proportion of the effect of gut microbiota-mediated lipidomics on PSC. RESULTS: Following a rigorous screening process, our MR analysis revealed a causal relationship between higher levels of gene-predicted Phosphatidylcholine (O-16:1_18:1) (PC O-16:1_18:1) and an increased risk of developing PSC (inverse variance-weighted method, odds ratio (OR) 1.30, 95% confidence interval (CI) 1.03-1.63). There is insufficient evidence to suggest that gene-predicted PSC impacts the levels of PC O-16:1_18:1 (OR 1.01, 95% CI 0.98-1.05). When incorporating gut microbiota data into the analysis, we found that Eubacterium rectale-mediated genetic prediction explains 17.59% of the variance in PC O-16:1_18:1 levels. CONCLUSION: Our study revealed a causal association between PC O-16:1_18:1 levels and PSC, with a minor portion of the effect mediated by Eubacterium rectale. This study aims to further explore the pathogenesis of PSC and identify promising therapeutic targets. For patients with PSC who lack effective treatment options, the results are encouraging.


Asunto(s)
Colangitis Esclerosante , Microbioma Gastrointestinal , Lipidómica , Análisis de la Aleatorización Mendeliana , Humanos , Colangitis Esclerosante/sangre , Colangitis Esclerosante/microbiología , Colangitis Esclerosante/genética , Microbioma Gastrointestinal/genética , Masculino , Estudio de Asociación del Genoma Completo , Femenino , Fosfatidilcolinas/sangre , Disbiosis/sangre , Persona de Mediana Edad , Adulto
5.
Front Aging Neurosci ; 16: 1335122, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715962

RESUMEN

The expanding geriatric population, whose predisposition toward disabling morbidities and age-related diseases (ARD) is well-documented, has become a paramount social issue, exerting an onerous burden on both the healthcare industry and wider society. ARD manifest as the progressive deterioration of bodily tissues and organs, eventually resulting in the failure of these vital components. At present, no efficacious measures exist to hinder the onset of ARD. Copper, an essential trace element, is involved in a wide range of physiological processes across different cell types. In recent research, a novel variant of copper-dependent cell death, termed cuproptosis, has been identified. This mode of cellular demise stands apart from previously recognized types of cell death. Cuproptosis occurs when copper binds with acyl-CoA synthetase in the tricarboxylic acid (TCA) cycle, resulting in protein aggregation and protein toxicity stress, ultimately leading to cell death. In this paper, we provide a concise overview of the current understanding concerning the metabolism of copper, copper-related diseases, the hallmarks of copper toxicity, and the mechanisms that regulate copper toxicity. Additionally, we discuss the implications of cuproptosis mutations in the development of ARD, as well as the potential for targeting cuproptosis as a treatment for ARD.

6.
Hepatol Int ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38740698

RESUMEN

BACKGROUND: The Baveno VII consensus proposed criteria for the non-invasively diagnosis of clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease (cACLD). The performance of Baveno VII criteria for assessing CSPH by two-dimensional shear wave elastography (2D-SWE) had not been well validated. We aimed to validate the performance of Baveno VII criteria for rule-in and rule-out CSPH by 2D-SWE. METHOD: This is an international multicenter study including cACLD patients from China and Croatia with paired liver stiffness measurement (LSM), spleen stiffness measurement (SSM) by 2D-SWE, and hepatic venous pressure gradient (HVPG) were included. CSPH was defined as HVPG ≥ 10 mmHg. RESULT: A total of 146 patients with cACLD were enrolled, and finally 118 patients were included in the analysis. Among them, CSPH was documented in 79 (66.9%) patients. Applying the Baveno VII criteria for rule-out CSPH by 2D-SWE, [LSM ≤ 15 kPa and platelet count ≥ 150 × 109/L] OR SSM < 21 kPa, could exclude CSPH with sensitivity > 90% (93.5 or 98.7%) but negative predictive value < 90% (74.1 or 85.7%). Using the Baveno VII criteria for rule-in CSPH by 2D-SWE, LSM ≥ 25 kPa OR SSM ≥ 50 kPa, could diagnose CSPH with 100% specificity and 100% positive predictive values. CONCLUSION: Baveno VII criteria by 2D-SWE showed a good diagnostic performance for ruling in but not for ruling out CSPH, which might become an emerging non-invasive elastography tool to select the patients who needed non-selective beta blocker therapy.

7.
Anal Methods ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38742397

RESUMEN

A sensitive photoelectrochemical (PEC) biosensor for silver ions (Ag+) was developed based on Zn-Co doped C and CdS quantum dot (CdS QD) nanomaterials. Hydrophobic modified sodium alginate (HMA), which could stabilize and improve the PEC performance of CdS QDs, was also used for the construction of PEC sensors. Especially, Zn-Co doped C, CdS QDs and HMA were sequentially modified onto an electrode surface via the drop-coating method, and a C base rich DNA strand was then immobilized onto the modified electrode. As the C base in DNA specifically recognized Ag+, it formed a C-Ag+-C complex in the presence of Ag+, which created a spatial steric hindrance, resulting in a reduced PEC response. The sensing platform is sensitive to Ag+ in the range of 10.0 fM to 0.10 µM, with a limit of detection of 3.99 fM. This work offers an ideal platform to determine trace heavy metal ions in environmental monitoring and bioanalysis.

8.
Nat Rev Clin Oncol ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693335

RESUMEN

Novel strategies utilizing light in the second near-infrared region (NIR-II; 900-1,880 nm wavelengths) offer the potential to visualize and treat solid tumours with enhanced precision. Over the past few decades, numerous techniques leveraging NIR-II light have been developed with the aim of precisely eliminating tumours while maximally preserving organ function. During cancer surgery, NIR-II optical imaging enables the visualization of clinically occult lesions and surrounding vital structures with increased sensitivity and resolution, thereby enhancing surgical quality and improving patient prognosis. Furthermore, the use of NIR-II light promises to improve cancer phototherapy by enabling the selective delivery of increased therapeutic energy to tissues at greater depths. Initial clinical studies of NIR-II-based imaging and phototherapy have indicated impressive potential to decrease cancer recurrence, reduce complications and prolong survival. Despite the encouraging results achieved, clinical translation of innovative NIR-II techniques remains challenging and inefficient; multidisciplinary cooperation is necessary to bridge the gap between preclinical research and clinical practice, and thus accelerate the translation of technical advances into clinical benefits. In this Review, we summarize the available clinical data on NIR-II-based imaging and phototherapy, demonstrating the feasibility and utility of integrating these technologies into the treatment of cancer. We also introduce emerging NIR-II-based approaches with substantial potential to further enhance patient outcomes, while also highlighting the challenges associated with imminent clinical studies of these modalities.

9.
Front Rehabil Sci ; 5: 1384698, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38711832

RESUMEN

Background: In the previous research, the Disability Assessment Scale based on ICF had been constructed for LTC insurance in China. To apply this scale in further studies, it is essential to establish assessment standards for disability levels. Objective: To establish standardized disability classification criteria and identify the disability statuses and levels in older people. Methods: This is a cross-sectional study, in which 1,610 older individuals in 15 long-term care institutions in China were assessed by the disability assessment scale based on ICF. Cluster analysis was used for classification of the disability levels. Mean (SD) and median (IQR) were used to describe the scores for each item and each dimension. Results: The total scores of the disability assessment scale were classified into six disability levels. The overall disability level of the 1,610 participants was moderate-to-severe. The disability in the dimension of "self-care ability and activity" was the most obvious and severe. Conclusion: The Disability Assessment Scale is capable of identifying disability statuses and levels of older people, and it can serve as a valuable tool for investigating the disabilities among old people and for conducting cross-national comparisons of disability levels.

11.
BMC Genomics ; 25(1): 430, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693501

RESUMEN

BACKGROUND: Although multiple chicken genomes have been assembled and annotated, the numbers of protein-coding genes in chicken genomes and their variation among breeds are still uncertain due to the low quality of these genome assemblies and limited resources used in their gene annotations. To fill these gaps, we recently assembled genomes of four indigenous chicken breeds with distinct traits at chromosome-level. In this study, we annotated genes in each of these assembled genomes using a combination of RNA-seq- and homology-based approaches. RESULTS: We identified varying numbers (17,497-17,718) of protein-coding genes in the four indigenous chicken genomes, while recovering 51 of the 274 "missing" genes in birds in general, and 36 of the 174 "missing" genes in chickens in particular. Intriguingly, based on deeply sequenced RNA-seq data collected in multiple tissues in the four breeds, we found 571 ~ 627 protein-coding genes in each genome, which were missing in the annotations of the reference chicken genomes (GRCg6a and GRCg7b/w). After removing redundancy, we ended up with a total of 1,420 newly annotated genes (NAGs). The NAGs tend to be found in subtelomeric regions of macro-chromosomes (chr1 to chr5, plus chrZ) and middle chromosomes (chr6 to chr13, plus chrW), as well as in micro-chromosomes (chr14 to chr39) and unplaced contigs, where G/C contents are high. Moreover, the NAGs have elevated quadruplexes G frequencies, while both G/C contents and quadruplexes G frequencies in their surrounding regions are also high. The NAGs showed tissue-specific expression, and we were able to verify 39 (92.9%) of 42 randomly selected ones in various tissues of the four chicken breeds using RT-qPCR experiments. Most of the NAGs were also encoded in the reference chicken genomes, thus, these genomes might harbor more genes than previously thought. CONCLUSION: The NAGs are widely distributed in wild, indigenous and commercial chickens, and they might play critical roles in chicken physiology. Counting these new genes, chicken genomes harbor more genes than originally thought.


Asunto(s)
Pollos , Genoma , Anotación de Secuencia Molecular , Animales , Pollos/genética , Composición de Base , Telómero/genética , Cromosomas/genética , Genómica/métodos
12.
Heliyon ; 10(9): e29853, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38699038

RESUMEN

Liver disease is a severe public health concern worldwide. There is a close relationship between the liver and cytokines, and liver inflammation from a variety of causes leads to the release and activation of cytokines. The functions of cytokines are complex and variable, and are closely related to their cellular origin, target molecules and mode of action. Interleukin (IL)-20 has been studied as a pro-inflammatory cytokine that is expressed and regulated in some diseases. Furthermore, accumulating evidences has shown that IL-20 is highly expressed in clinical samples from patients with liver disease, promoting the production of pro-inflammatory molecules involved in liver disease progression, and antagonists of IL-20 can effectively inhibit liver injury and produce protective effects. This review highlights the potential of targeting IL-20 in liver diseases, elucidates the potential mechanisms of IL-20 inducing liver injury, and suggests multiple viable strategies to mitigate the pro-inflammatory response to IL-20. Genomic CRISPR/Cas9-based screens may be a feasible way to further explore the signaling pathways and regulation of IL-20 in liver diseases. Nanovector systems targeting IL-20 offer new possibilities for the treatment and prevention of liver diseases.

13.
ACS Appl Mater Interfaces ; 16(19): 24863-24870, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38706443

RESUMEN

Water evaporation-induced electricity generators (WEGs) have drawn widespread attention in the field of hydrovoltaic technology, which can convert atmospheric thermal energy into sustainable electric power. However, it is restricted in the wide application of WEGs due to the low power output, complex fabrication process, and high cost. Herein, we present a simple and effective approach to fabricate TiO2-carbon black film-based WEGs (TC-WEGs). A single TC-WEG device can sustainably output an open-circuit voltage of 1.9 V and a maximum power density of 40.9 µW/cm2. Moreover, it has been shown that TC-WEGs exhibit stable electrical energy output when operating in seawater, which can yield a short-circuit current of 1.2 µA. The superior electricity generation performance can be attributed to the intrinsic characteristics of the TC-WEGs, including hydrophilicity, porous structure, and electrical conductivity. This work provides an important reference for the constant harvesting of clean energy.

14.
J Photochem Photobiol B ; 255: 112923, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38692166

RESUMEN

Accurately visualizing the intracellular trafficking of upconversion nanoparticles (UCNPs) loaded with phthalocyanines and achieving precise photodynamic therapy (PDT) using near-infrared (NIR) laser irradiation still present challenges. In this study, a novel NIR laser-triggered upconversion luminescence (UCL) imaging-guided nanoparticle called FA@TPA-NH-ZnPc@UCNPs (FTU) was developed for PDT. FTU consisted of UCNPs, folic acid (FA), and triphenylamino-phenylaniline zinc phthalocyanine (TPA-NH-ZnPc). Notably, TPA-NH-ZnPc showcases aggregation-induced emission (AIE) characteristic and NIR absorption properties at 741 nm, synthesized initially via molybdenum-catalyzed condensation reaction. The UCL emitted by FTU enable real-time visualization of their subcellular localization and intracellular trafficking within ovarian cancer HO-8910 cells. Fluorescence images revealed that FTU managed to escape from lysosomes due to the "proton sponge" effect of TPA-NH-ZnPc. The FA ligands on the surface of FTU further directed their transport and accumulation within mitochondria. When excited by a 980 nm laser, FTU exhibited UCL and activated TPA-NH-ZnPc, consequently generating cytotoxic singlet oxygen (1O2), disrupted mitochondrial function and induced apoptosis in cancer cells, which demonstrated great potential for tumor ablation.


Asunto(s)
Indoles , Rayos Infrarrojos , Isoindoles , Lisosomas , Mitocondrias , Nanopartículas , Compuestos Organometálicos , Fotoquimioterapia , Compuestos de Zinc , Compuestos de Zinc/química , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Indoles/química , Indoles/farmacología , Lisosomas/metabolismo , Humanos , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Nanopartículas/química , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Oxígeno Singlete/metabolismo , Femenino , Ácido Fólico/química
15.
J Am Chem Soc ; 146(20): 14174-14181, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38723205

RESUMEN

Construction of robust heterogeneous catalysts with atomic precision is a long-sought pursuit in the catalysis field due to its fundamental significance in taming chemical transformations. Herein, we present the synthesis of a single-crystalline pyrazolate metal-organic framework (MOF) named PCN-300, bearing a lamellar structure with two distinct Cu centers and one-dimensional (1D) open channels when stacked. PCN-300 exhibits exceptional stability in aqueous solutions across a broad pH range from 1 to 14. In contrast, its monomeric counterpart assembled through hydrogen bonding displays limited stability, emphasizing the role of Cu-pyrazolate coordination bonds in framework robustness. Remarkably, the synergy of the 1D open channels, excellent stability, and the active Cu-porphyrin sites endows PCN-300 with outstanding catalytic activity in the cross dehydrogenative coupling reaction to form the C-O bond without the "compulsory" ortho-position directing groups (yields up to 96%), outperforming homogeneous Cu-porphyrin catalysts. Moreover, PCN-300 exhibits superior recyclability and compatibility with various phenol substrates. Control experiments reveal the synergy between the Cu-porphyrin center and framework in PCN-300 and computations unveil the free radical pathway of the reaction. This study highlights the power of robust pyrazolate MOFs in directly activating C-H bonds and catalyzing challenging chemical transformations in an environmentally friendly manner.

16.
Zhongguo Fei Ai Za Zhi ; 27(4): 266-275, 2024 Apr 20.
Artículo en Chino | MEDLINE | ID: mdl-38769829

RESUMEN

BACKGROUND: Cystic lung cancer, a special type of lung cancer, has been paid more and more attention. The most common pathological type of cystic lung cancer is adenocarcinoma. The invasiveness of cystic lung adenocarcinoma is vital for the selection of clinical treatment and prognosis. The aim of this study is to analyze the multiple clinical features of cystic lung adenocarcinoma, explore the independent risk factors of its invasiveness, and establish a risk prediction model. METHODS: A total of 129 cases of cystic lung adenocarcinoma admitted to the Department of Thoracic Surgery of the First Affiliated Hospital of Nanjing Medical University from January 2021 to July 2022 were retrospectively analyzed and divided into pre-invasive group [atypical adenomatous hyperplasia (AAH), adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA)] and invasive group [invasive adenocarcinoma (IAC)] according to pathological findings. There were 47 cases in the pre-invasive group, including 19 males and 28 females, with an average age of (51.23±14.96) years. There were 82 cases in the invasive group, including 60 males and 22 females, with an average age of (61.27±11.74) years. Multiple clinical features of the two groups were collected, including baseline data, imaging data and tumor markers. Univariate analysis, LASSO regression and multivariate Logistic regression analysis were used to screen out the independent risk factors of the invasiveness of cystic lung adenocarcinoma, and the risk prediction model was established. RESULTS: In univariate analysis, age, gender, smoking history, history of emphysema, neuron-specific enolase (NSE), number of cystic airspaces, lesion diameter, cystic cavity diameter, nodule diameter, solid components diameter, cyst wall nodule, smoothness of cyst wall, shape of cystic airspace, lobulation, short burr sign, pleural retraction, vascular penetration and bronchial penetration were statistically different between the pre-invasive group and invasive groups (P<0.05). The above variables were processed by LASSO regression dimensionality reduction and screened as follows: age, gender, smoking history, NSE, number of cystic airspaces, lesion diameter, cystic cavity diameter, cyst wall nodule, smoothness of cyst wall and lobulation. Then the above variables were included in multivariate Logistic regression analysis. Cyst wall nodule (P=0.035) and lobulation (P=0.001) were found to be independent risk factors for the invasiveness of cystic lung adenocarcinoma (P<0.05). The prediction model was established as follows: P=e^x/(1+e^x), x=-7.927+1.476* cyst wall nodule+2.407* lobulation, and area under the curve (AUC) was 0.950. CONCLUSIONS: Cyst wall nodule and lobulation are independent risk factors for the invasiveness of cystic lung adenocarcinoma, which have certain guiding significance for the prediction of the invasiveness of cystic lung adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , Humanos , Masculino , Femenino , Persona de Mediana Edad , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/cirugía , Neoplasias Pulmonares/patología , Estudios Retrospectivos , Anciano , Adulto , Factores de Riesgo , Invasividad Neoplásica
17.
Anal Chem ; 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38758357

RESUMEN

Singlet oxygen (1O2) plays imperative roles in a variety of biotic or abiotic stresses in crops. The change of its concentration within a crop is closely related to the crop growth and development. Accordingly, there is an urgent need to develop an efficient analytical method for on-site quantitative detection of 1O2 in crops. Here, we judiciously constructed a novel ratiometric fluorescent probe, SX-2, for the detection of 1O2 in crops. Upon treating with 1O2, probe SX-2 displayed highly selective ratiometric fluorescence response, which is favorable for the quantitative detection of 1O2. Concurrently, the fluorescence solution color of probe SX-2 was varied, obviously from blue to yellow, indicating that the probe is beneficial for on-site detection by the naked eye. Sensing reaction mechanism studies showed that the 2,3-diphenyl imidazole group in SX-2 could function as a new selective recognition group for 1O2. Probe SX-2 was utilized for the detection of photoirradiation-induced 1O2 and endogenous 1O2 in living cells. The changes in the 1O2 level in zebrafish were also tracked by fluorescence imaging. In addition, the production of 1O2 in crop leaves under a light source of different wavelengths was studied. The results demonstrated more 1O2 were produced under a light source of 365 nm. Furthermore, to achieve on-site quantitative detection, a mobile fluorescence analysis device has been made. Probe SX-2 and mobile fluorescence analysis device were capable of on-site quantitative detecting of 1O2 in crops. The method developed herein will be convenient for the on-site quantitative measurement of 1O2 in distinct crops.

18.
Eur J Med Chem ; 273: 116493, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38761790

RESUMEN

The emergence of multidrug-resistant bacteria along with a declining pipeline of clinically useful antibiotics has led to the urgent need for the development of more effective antibacterial agents to treat drug-resistant bacteria. We previously discovered compound OB-158 with potent antibacterial activity but exhibited poor oral bioavailability. Herein, a systematic structural optimization of OB-158 to improve pharmacokinetic profiles yielded 26 novel biaryloxazolidinone analogues, and their activities against Gram-positive S. aureus, multidrug resistant S. aureus and Enterococcus faecalis were evaluated. Remarkably, compound 8b was identified with potent antibacterial activity against S. aureus (MIC = 0.06 µg/mL), MSSA (MIC = 0.125 µg/mL), MRSA (MIC = 0.06 µg/mL), LRSA (MIC = 0.125 µg/mL) and LREFa (MIC = 0.5 µg/mL). Compound 8b was demonstrated as a promising candidate through druglikeness evaluation including metabolism in microsomes and plasma, Caco-2 cell permeability, plasma protein binding, cytotoxicity, and inhibition of CYP450 and human monoamine oxidase. Notably, compound 8b displayed excellent PK profile with appropriate T1/2 of 1.49 h, high peak plasma concentration (Cmax = 2320 ng/mL), high plasma exposure (AUC0-t = 8310 h ng/mL), and superior oral bioavailability (F = 68.1 %) in Sprague-Dawley rats. Ultimately, in vivo efficacy of compound 8b in a mouse model of LRSA systemic infection was also demonstrated. Taken together, compound 8b represents a promising drug candidate for the treatment of linezolid-resistant Gram-positive bacterial strains infection.

19.
Artículo en Inglés | MEDLINE | ID: mdl-38751677

RESUMEN

Background: Significant progress has been made in immunotherapy of breast cancer (BC) with the approval of multiple immune checkpoint inhibitors (ICIs), particularly in early and metastatic triple-negative breast cancer (TNBC) settings. Most guidelines have recommended immune therapy as the important approach in BC, yet several critical aspects still require further clarification, including proper patient selection, treatment duration, optimized chemotherapy partner, predictive biomarkers, and specific considerations for Chinese patients. Methods: (I) Establishment of expert group: the expert group consists of 32 experts from departments such as medical oncology, breast surgery, and pathology; (II) literature search: mainly conducted in English databases (such as PubMed, Embase, and Cochrane Library) and Chinese databases (such as China National Knowledge Infrastructure, China Biology Medicine disc, and Wanfang Database), with a search cutoff date of April 23, 2024; (III) assessment of evidence quality and recommendation strength: evidence quality and recommendation opinions are graded based on the evidence category and recommendation level of the Chinese Society of Clinical Oncology (CSCO) guidelines; (IV) consensus formulation: on the March 2, 2024, through online consensus meeting, the consensus content is thoroughly discussed, and opinions from all experts are solicited. Results: The consensus meeting has resulted in 15 detailed recommendations, providing clearer guidance on the clinical application of immunotherapy in BC management. The core suggestions are as follows: for early-stage II-III TNBC and metastatic TNBC (mTNBC) in the first-line setting, programmed cell death protein 1 (PD-1) inhibitors can be considered. However, for hormone receptor-positive/human epidermal growth factor receptor 2-negative BC (HR+/HER2- BC), HER2+ BC, and mTNBC in later lines of therapy, evidence is lacking to support the use of immunotherapy. Conclusions: This consensus provides a comprehensive overview of BC immunotherapy, including immunotherapy for early-stage BC and late-stage BC, immune related adverse event (irAE) management, biomarkers of immunotherapy, and future directions. The consensus consolidates these deliberations into 15 evidence-based recommendations, serving as a practical guide for clinicians to more scientifically and systematically manage the clinical application of immunotherapy.

20.
J Colloid Interface Sci ; 670: 288-296, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38763025

RESUMEN

Transition metal sulfides (TMSs) catalysts with high catalytic oxygen evolution reaction (OER) activity have been extensively studied, especially Fe and Co-based sulfides. Fe and Co active sites with a strong synergistic effect, which can adjust the electron density distribution and effectively improve the electrocatalytic OER activity. However, TMSs have poor stability in alkaline environment caused by metal ions and sulfur elements are facilitated to dissolve. In this work, TMSs was modified by polyaniline (PANI) to inhibit the precipitation of iron, cobalt, and sulfur elements and enhance its stability under alkaline conditions. Moreover, π-d structure can also be formed by the coating of PANI, which can further adjust its own electronic structure on the basis of stabilizing the TMSs structure, so as to improve the electrochemical performance, rendering them to stably operate at harsh environment for more than 90 h. These findings offer new guidance for improving the electrocatalytic stability of TMSs.

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