Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.215
Filtrar
Más filtros

Tipo del documento
Intervalo de año de publicación
1.
Cell ; 187(11): 2703-2716.e23, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38657602

RESUMEN

Antigen presentation defects in tumors are prevalent mechanisms of adaptive immune evasion and resistance to cancer immunotherapy, whereas how tumors evade innate immunity is less clear. Using CRISPR screens, we discovered that IGSF8 expressed on tumors suppresses NK cell function by interacting with human KIR3DL2 and mouse Klra9 receptors on NK cells. IGSF8 is normally expressed in neuronal tissues and is not required for cell survival in vitro or in vivo. It is overexpressed and associated with low antigen presentation, low immune infiltration, and worse clinical outcomes in many tumors. An antibody that blocks IGSF8-NK receptor interaction enhances NK cell killing of malignant cells in vitro and upregulates antigen presentation, NK cell-mediated cytotoxicity, and T cell signaling in vivo. In syngeneic tumor models, anti-IGSF8 alone, or in combination with anti-PD1, inhibits tumor growth. Our results indicate that IGSF8 is an innate immune checkpoint that could be exploited as a therapeutic target.


Asunto(s)
Inmunidad Innata , Inmunoterapia , Células Asesinas Naturales , Neoplasias , Animales , Femenino , Humanos , Ratones , Presentación de Antígeno , Línea Celular Tumoral , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Proteínas de la Membrana/metabolismo , Ratones Endogámicos C57BL , Neoplasias/inmunología , Neoplasias/terapia
2.
Immunity ; 54(9): 2042-2056.e8, 2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34407391

RESUMEN

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.


Asunto(s)
Quimiocina CCL1/metabolismo , Fibroblastos/metabolismo , Proteínas de la Membrana/metabolismo , Miofibroblastos/metabolismo , Fosfoproteínas/metabolismo , Fibrosis Pulmonar/metabolismo , Receptores del Factor Autocrino de Motilidad/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Diferenciación Celular/fisiología , Fibroblastos/patología , Humanos , Ratones , Miofibroblastos/patología , Fibrosis Pulmonar/patología , Transducción de Señal/fisiología
3.
Immunity ; 51(3): 522-534.e7, 2019 09 17.
Artículo en Inglés | MEDLINE | ID: mdl-31471107

RESUMEN

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Macrófagos/metabolismo , Fibrosis Pulmonar/metabolismo , Factores de Transcripción/metabolismo , Ubiquitina/metabolismo , Animales , Línea Celular , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Células HEK293 , Humanos , Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BL , Fosforilación/fisiología , Transducción de Señal/fisiología , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación/fisiología , Regulación hacia Arriba/fisiología
5.
Nano Lett ; 24(22): 6585-6591, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38785400

RESUMEN

The gallium-doped hafnium oxide (Ga-HfO2) films with different Ga doping concentrations were prepared by adjusting the HfO2/Ga2O3 atomic layer deposition cycle ratio for high-speed and low-voltage operation in HfO2-based ferroelectric memory. The Ga-HfO2 ferroelectric films reveal a finely modulated coercive field (Ec) from 1.1 (HfO2/Ga2O3 = 32:1) to an exceptionally low 0.6 MV/cm (HfO2/Ga2O3 = 11:1). This modulation arises from the competition between domain nucleation and propagation speed during polarization switching, influenced by the intrinsic domain density and phase dispersion in the film with specific Ga doping concentrations. Higher Ec samples exhibit a nucleation-dominant switching mechanism, while lower Ec samples undergo a transition from a nucleation-dominant to a propagation-dominant reversal mechanism as the electric field increases. This work introduces Ga as a viable dopant for low Ec and offers insights into material design strategies for HfO2-based ferroelectric memory applications.

6.
J Am Chem Soc ; 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38847614

RESUMEN

Axially chiral biaryls featuring a C-N axis are important functional molecules in diverse fields. The asymmetric Buchwald-Hartwig reaction represents a powerful strategy for these targets. Previous studies, however, have been predominantly restricted to intramolecular atroposelective coupling, likely due to the steric and entropic effects in the reductive elimination of Pd(II) species with sterically congested aryl and nitrogen groups. We now report two intermolecular Buchwald-Hartwig coupling systems of bulky NH lactams and halohydrocarbons enabled by rerouting the mechanism of C-N reductive elimination to one that accommodates sterically challenging substrates. Both atroposelective coupling systems exhibited functional group tolerance, excellent enantioselectivity, and high Z selectivity (if applicable), affording C-N atropisomeric biaryl and olefins through de novo construction of a C-N chiral axis. Experimental and computational studies were performed to elucidate the mechanism, and the switch of the reaction pathways is traced to the steric effect (ortho substituent) of the aryl halide substrate. A bulky 2,6-disubstituted aryl halide reorients the proximal lactamide ligand to its unusual O-ligation mode. With the amide oxygen participation, this intermediate undergoes C-N reductive elimination with an accessible barrier through a five-membered ring transition state, a pathway as well as a chiral induction mode that has been much underexplored in asymmetric catalysis.

7.
J Am Chem Soc ; 146(1): 250-262, 2024 01 10.
Artículo en Inglés | MEDLINE | ID: mdl-38147793

RESUMEN

We report the macrocyclic ring size-electronic structure-electrophilic reactivity correlation of mononuclear nonheme iron(III)-peroxo complexes bearing N-tetramethylated cyclam analogues (n-TMC), [FeIII(O2)(12-TMC)]+ (1), [FeIII(O2)(13-TMC)]+ (2), and [FeIII(O2)(14-TMC)]+ (3), as a model study of Rieske oxygenases. The Fe(III)-peroxo complexes show the same δ and pseudo-σ bonds between iron and the peroxo ligand. However, the strength of these interactions varies depending on the ring size of the n-TMC ligands; the overall Fe-O bond strength and the strength of the Fe-O2 δ bond increase gradually as the ring size of the n-TMC ligands becomes smaller, such as from 14-TMC to 13-TMC to 12-TMC. MCD spectroscopy plays a key role in assigning the characteristic low-energy δ → δ* LMCT band, which provides direct insight into the strength of the Fe-O2 δ bond and which, in turn, is correlated with the superoxo character of the iron-peroxo group. In oxidation reactions, reactivities of 1-3 toward hydrocarbon C-H bond activation are compared, revealing the reactivity order of 1 > 2 > 3; the [FeIII(O2)(n-TMC)]+ complex with a smaller n-TMC ring size, 12-TMC, is much more reactive than that with a larger n-TMC ring size, 14-TMC. DFT analysis shows that the Fe(III)-peroxo complex is not reactive toward C-H bonds, but it is the end-on Fe(II)-superoxo valence tautomer that is responsible for the observed reactivity. The hydrogen atom abstraction (HAA) reactivity of these intermediates is correlated with the overall donicity of the n-TMC ligand, which modulates the energy of the singly occupied π* superoxo frontier orbital that serves as the electron acceptor in the HAA reaction. The implications of these results for the mechanism of Rieske oxygenases are further discussed.


Asunto(s)
Ciclamas , Hierro , Hierro/química , Oxigenasas , Ligandos , Biomimética , Oxígeno/química , Hidrógeno , Compuestos Férricos
8.
Mol Cell Biochem ; 479(7): 1553-1570, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38856795

RESUMEN

Epigenetics encompasses reversible and heritable chemical modifications of non-nuclear DNA sequences, including DNA and RNA methylation, histone modifications, non-coding RNA modifications, and chromatin rearrangements. In addition to well-studied DNA and histone methylation, RNA methylation has emerged as a hot topic in biological sciences over the past decade. N6-methyladenosine (m6A) is the most common and abundant modification in eukaryotic mRNA, affecting all RNA stages, including transcription, translation, and degradation. Advances in high-throughput sequencing technologies made it feasible to identify the chemical basis and biological functions of m6A RNA. Dysregulation of m6A levels and associated modifying proteins can both inhibit and promote cancer, highlighting the importance of the tumor microenvironment in diverse biological processes. Gastrointestinal tract cancers, including gastric, colorectal, and pancreatic cancers, are among the most common and deadly malignancies in humans. Growing evidence suggests a close association between m6A levels and the progression of gastrointestinal tumors. Global m6A modification levels are substantially modified in gastrointestinal tumor tissues and cell lines compared to healthy tissues and cells, possibly influencing various biological behaviors such as tumor cell proliferation, invasion, metastasis, and drug resistance. Exploring the diagnostic and therapeutic potential of m6A-related proteins is critical from a clinical standpoint. Developing more specific and effective m6A modulators offers new options for treating these tumors and deeper insights into gastrointestinal tract cancers.


Asunto(s)
Adenosina , Neoplasias Gastrointestinales , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Adenosina/genética , Neoplasias Gastrointestinales/genética , Neoplasias Gastrointestinales/patología , Neoplasias Gastrointestinales/metabolismo , ARN Neoplásico/genética , ARN Neoplásico/metabolismo , Epigénesis Genética , Metilación
9.
Nanotechnology ; 35(19)2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38316045

RESUMEN

Molybdenum sulfide (MoS2) as an emerging optoelectronic material, shows great potential for phototransistors owing to its atomic thickness, adjustable band gap, and low cost. However, the phototransistors based on MoS2have been shown to have some issues such as large gate leakage current, and interfacial scattering, resulting in suboptimal optoelectronic performance. Thus, Al-doped hafnium oxide (Hf1-xAlx) is proposed to be a dielectric layer of the MoS2-based phototransistor to solve this problem because of the relatively higher crystallization temperature and dielectric constant. Here, a high-performance MoS2phototransistor with Hf1-xAlxO gate dielectric layer grown by plasma-enhanced atomic layer deposition has been fabricated and studied. The results show that the phototransistor exhibits a high responsivity of 2.2 × 104A W-1, a large detectivity of 1.7 × 1017Jones, a great photo-to-dark current ratio of 2.2 × 106%, and a high external quantum efficiency of 4.4 × 106%. The energy band alignment and operating mechanism were further used to clarify the reason for the enhanced MoS2phototransistor. The suggested MoS2phototransistors could provide promising strategies in further optoelectronic applications.

10.
Int J Med Sci ; 21(7): 1250-1256, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818475

RESUMEN

Background: Recovery time is a crucial factor in ensuring the safety and effectiveness of both patients and endoscopy centers. Propofol is often preferred due to its fast onset and minimal side effects. Remimazolam is a new intravenous sedative agent, characterized by its rapid onset of action, quick recovery and organ-independent metabolism. Importantly, its effect can be specifically antagonized by flumazenil. The primary goal of this study is to compare the recovery time of remimazolam besylate and propofol anesthesia during endoscopic procedures in elderly patients. Methods: 60 patients aged 65-95 years who underwent gastrointestinal endoscopy were randomly and equally assigned to two groups: the remimazolam group (Group R) and the propofol group (Group P). The primary measure was the recovery time, defined as the time from discontinuing remimazolam or propofol until reaching an Observer's Assessment of Alertness and Sedation scale (OAA/S) score of 5 (responds readily to name spoken in normal tone). The time required to achieve an OAA/S score of 3 (responds after name spoken loudly or repeatedly along with glazed marked ptosis) was also recorded and compared. Results: The recovery time for Group R (2.6 ± 1.6 min) was significantly shorter than that for Group P (10.8 ± 3.0 min), with a 95% confidence interval (CI): 6.949-9.431 min, p <0.001. Similarly, the time to attain an OAA/S score of 3 was significantly less in Group R (1.6 ± 0.9 min) compared to Group P (9.6 ± 2.6 min), with a 95% CI: 6.930-8.957 min, p <0.001. Conclusion: Our study demonstrated that remimazolam anesthesia combined with flumazenil antagonism causes a shorter recovery time for elderly patients undergoing gastrointestinal endoscopy compared to propofol. Remimazolam followed by flumazenil antagonism provides a promising alternative to propofol for geriatric patients, particularly during gastrointestinal endoscopy.


Asunto(s)
Periodo de Recuperación de la Anestesia , Benzodiazepinas , Endoscopía Gastrointestinal , Hipnóticos y Sedantes , Propofol , Humanos , Anciano , Propofol/administración & dosificación , Masculino , Femenino , Anciano de 80 o más Años , Endoscopía Gastrointestinal/métodos , Hipnóticos y Sedantes/administración & dosificación , Hipnóticos y Sedantes/efectos adversos , Benzodiazepinas/uso terapéutico
11.
BMC Pregnancy Childbirth ; 24(1): 2, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38166713

RESUMEN

BACKGROUND: This study aimed to assess whether maternal telomere length is a more accurate predictor of trisomy 21 than maternal age while also exploring the factors influencing maternal and fetal telomere length. METHODS: Forty mothers with fetuses carrying extra maternal copies of chromosome 21 were defined as trisomy 21 cases, and 18 mothers with normal karyotype fetuses were defined as controls. Telomere lengths of maternal blood lymphocytes and amniotic fluid cells were determined using real-time polymerase chain reaction. Fetal and maternal telomere lengths were compared between the two groups. Moreover, we analyzed the factors influencing maternal and fetal telomere length in the trisomy 21 pedigree. A logistic regression model was used to analyze the correlation between maternal telomere length and trisomy 21 risk. In addition, receiver operating characteristic (ROC) curve analysis was used to determine the accuracy of using maternal telomere length as an indicator of trisomy 21 risk. RESULTS: The study revealed that both maternal and fetal telomere lengths were significantly shorter in trisomy 21 cases than in the controls. In the trisomy 21 group, the maternal age, occupation, and nationality showed no significant correlation with their telomere length; fetal telomere length exhibited a positive correlation with maternal telomere length. Furthermore, maternal telomere length shortening is associated with trisomy 21 (OR = 0.311; 95% CI, 0.109-0.885, P < 0.05). The results of ROC curve analysis indicated that a combined assessment of maternal age and maternal telomere length predicted fetal chromosome trisomy more effectively than a single assessment (area under the curve 0.808, 95% CI, 0.674-0.941, P < 0.001). CONCLUSION: Maternal age combined with maternal telomere length proved to be a superior predictor of trisomy risk. Additionally, maternal telomere length was found to influence fetal telomere length.


Asunto(s)
Síndrome de Down , Trisomía , Femenino , Humanos , Trisomía/diagnóstico , Trisomía/genética , Síndrome de Down/diagnóstico , Síndrome de Down/genética , Acortamiento del Telómero , Aneuploidia , Feto , Sangre Fetal
12.
Artículo en Inglés | MEDLINE | ID: mdl-39320554

RESUMEN

Human reproduction is a complex process involving gamete maturation, fertilization, embryo cleavage and development, blastocyst formation, implantation, and live birth. If any of these processes are abnormal or arrest, reproductive failure will occur. Infertility is a state of reproductive dysfunction caused by various factors. Advances in molecular genetics, including cell and molecular genetics, and high-throughput sequencing technologies, have found that genetic factors are important causes of infertility. Genetic variants have been identified in infertile women or men and can cause gamete maturation arrest, poor quality gametes, fertilization failure, and embryonic developmental arrest during assisted reproduction technology (ART), and thus reduce the clinical success rates of ART. This article reviews clinical studies on repeated in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) failures caused by ovarian dysfunction, oocyte maturation defects, oocyte abnormalities, fertilization disorders, and preimplantation embryonic development arrest due to female genetic etiology, the accumulation of pathogenic genes and gene pathogenic loci, and the functional mechanism and clinical significance of pathogenic genes in gametogenesis and early embryonic development.

13.
Alzheimers Dement ; 20(4): 2516-2525, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38329281

RESUMEN

INTRODUCTION: The objective of this study is to investigate the incremental value of amyloid positron emission tomography (Aß-PET) in a tertiary memory clinic setting in China. METHODS: A total of 1073 patients were offered Aß-PET using 18F-florbetapir. The neurologists determined a suspected etiology (Alzheimer's disease [AD] or non-AD) with a percentage estimate of their confidence and medication prescription both before and after receiving the Aß-PET results. RESULTS: After disclosure of the Aß-PET results, etiological diagnoses changed in 19.3% of patients, and diagnostic confidence increased from 69.3% to 85.6%. Amyloid PET results led to a change of treatment plan in 36.5% of patients. Compared to the late-onset group, the early-onset group had a more frequent change in diagnoses and a higher increase in diagnostic confidence. DISCUSSION: Aß-PET has significant impacts on the changes of diagnoses and management in Chinese population. Early-onset cases are more likely to benefit from Aß-PET than late-onset cases. HIGHLIGHTS: Amyloid PET contributes to diagnostic changes and its confidence in Chinese patients. Amyloid PET leads to a change of treatment plans in Chinese patients. Early-onset cases are more likely to benefit from amyloid PET than late-onset cases.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Amiloide , Enfermedad de Alzheimer/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Proteínas Amiloidogénicas , Compuestos de Anilina , China , Péptidos beta-Amiloides , Disfunción Cognitiva/diagnóstico
14.
Behav Brain Sci ; 47: e169, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39311504

RESUMEN

This commentary examines the synergy between meta-learned models of cognition and integrative learning in enhancing animal and human learning outcomes. It highlights three integrative learning modes - holistic integration of parts, top-down reasoning, and generalization with in-depth analysis - and their alignment with meta-learned models of cognition. This convergence promises significant advances in educational practices, artificial intelligence, and cognitive neuroscience, offering a novel perspective on learning and cognition.


Asunto(s)
Cognición , Aprendizaje , Humanos , Animales , Cognición/fisiología , Aprendizaje/fisiología , Inteligencia Artificial , Modelos Psicológicos , Generalización Psicológica/fisiología
15.
Fa Yi Xue Za Zhi ; 40(1): 30-36, 2024 Feb 25.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-38500458

RESUMEN

OBJECTIVES: To establish a rapid screening method for 34 emerging contaminants in surface water by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF-MS). METHODS: The pretreatment conditions of solid phase extraction (SPE) were optimized by orthogonal experimental design and the surface water samples were concentrated and extracted by Oasis® HLB and Oasis® MCX SPE columns in series. The extracts were separated by Kinetex® EVO C18 column, with gradient elution of 0.1% formic acid aqueous solution and 0.1% formic acid methanol solution. Q-TOF-MS 'fullscan' and 'targeted MS/MS' modes were used to detect 34 emerging contaminants and to establish a database with 34 emerging contaminants precursor ion, product ion and retention times. RESULTS: The 34 emerging contaminants exhibited good linearity in the concentration range respectively and the correlation coefficients (r) were higher than 0.97. The limit of detection was 0.2-10 ng/L and the recoveries were 81.2%-119.2%. The intra-day precision was 0.78%-18.70%. The method was applied to analyze multiple surface water samples and 6 emerging contaminants were detected, with a concentration range of 1.93-157.71 ng/L. CONCLUSIONS: The method is simple and rapid for screening various emerging contaminants at the trace level in surface water.


Asunto(s)
Espectrometría de Masas en Tándem , Agua , Espectrometría de Masas en Tándem/métodos , Cromatografía Líquida de Alta Presión/métodos , Formiatos , Extracción en Fase Sólida/métodos
16.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 49(6): 914-920, 2024 Jun 28.
Artículo en Inglés, Zh | MEDLINE | ID: mdl-39311787

RESUMEN

OBJECTIVES: The expression of serum free light chain (FLC) is abnormal in various diseases, but its role in lung cancer remains unclear. This study aims to investigate the expression and diagnostic value of serum FLC in lung cancer. METHODS: A total of 80 lung cancer patients treated at Xiangdong Hospital, Hunan Normal University from January to December 2021 were selected as the lung cancer group. Another 80 healthy individuals undergoing routine physical examinations during the same period were chosen as the control group. General information and serum κFLC and λFLC levels were collected for all subjects. Clinical indicators such as serum carcinoembryonic antigen (CEA), cytokeratin fragment antigen 21-1 (CYFRA21-1) levels, tumor diameter, histological type, TNM stage, and lymph node metastasis status were recorded for lung cancer patients. The expression levels of serum FLC [κFLC, λFLC, and FLC (κ+λ)] were compared between the lung cancer group and the control group. Lung cancer patients were grouped based on gender, age, smoking history, tumor diameter, TNM stage, histological type, and lymph node metastasis to compare differences in serum κFLC and λFLC levels. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of serum FLC alone and in combination with other indicators in lung cancer. RESULTS: The expression levels of serum FLC (κ+λ) and κFLC were significantly higher in the lung cancer group than those in the control group (both P<0.001), while there was no significant difference in serum λFLC levels between the 2 groups (P>0.05). There were no significant differences in serum κFLC levels among lung cancer patients with different tumor diameters, histological types, or TNM stages (all P>0.05); however, serum κFLC levels were higher in lung cancer patients with lymph node metastasis than in those without, with statistical significance (P=0.033). There were no significant differences in serum λFLC levels based on tumor diameter or histological type (both P>0.05), but serum λFLC levels were higher in stage III+IV and lymph node metastatic lung cancer patients compared to stage I+II and non-metastatic patients, with statistical significance (P=0.033 and P=0.019, respectively). The area under the curve (AUC) for κFLC and CEA in diagnosing lung cancer showed no significant difference (P=0.333). The combination of κFLC+CYFRA21-1 had the highest diagnostic efficacy (AUC=0.875) and sensitivity (71.3%). The AUC for the combined diagnosis of κFLC+λFLC+CEA+CYFRA21-1 was 0.915 (95% CI 0.860 to 0.953, P<0.001). CONCLUSIONS: Serum FLC is highly expressed in lung cancer and is associated with its invasion and metastasis. Serum FLC, particularly κFLC, has diagnostic value for lung cancer, and the combined detection of FLC, CEA, and CYFRA21-1 offers the best diagnostic efficacy.


Asunto(s)
Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/diagnóstico , Masculino , Femenino , Metástasis Linfática , Antígeno Carcinoembrionario/sangre , Biomarcadores de Tumor/sangre , Queratina-19/sangre , Estadificación de Neoplasias , Antígenos de Neoplasias/sangre , Cadenas kappa de Inmunoglobulina/sangre , Cadenas lambda de Inmunoglobulina/sangre , Persona de Mediana Edad , Curva ROC
17.
Angew Chem Int Ed Engl ; 63(15): e202400308, 2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38299744

RESUMEN

The construction of the SCF3-containing 1,1-diaryl tertiary carbon stereocenters with high enantioselectivities is reported via a nickel-catalyzed asymmetric C-C coupling strategy. This method demonstrates simple operations, mild conditions and excellent functional group tolerance, with newly designed SCF3-containing synthon, which can be easily obtained from commercially available benzyl bromide and trifluoromethylthio anion in a two-step manner. Further substrate exploration indicated that the reaction system could be extended to diverse perfluoroalkyl sulfide (SC2F5, SC3F7, SC4F9, SCF2CO2Et)-substituted 1,1-diaryl compounds with excellent enantioselectivities. The synthetic utility of this transformation was further demonstrated by convenient derivatization to optical SCF3-containing analogues of bioactive compounds without an apparent decrease in enantioselectivity.

18.
Angew Chem Int Ed Engl ; 63(1): e202312923, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-37971168

RESUMEN

Axially chiral open-chained olefins are an underexplored class of atropisomers, whose enantioselective synthesis represents a daunting challenge due to their relatively low racemization barrier. We herein report rhodium(I)-catalyzed hydroarylative cyclization of 1,6-diynes with three distinct classes of arenes, enabling highly enantioselective synthesis of a broad range of axially chiral 1,3-dienes that are conformationally labile (ΔG≠ (rac)=26.6-28.0 kcal/mol). The coupling reactions in each category proceeded with excellent enantioselectivity, regioselectivity, and Z/E selectivity under mild reaction conditions. Computational studies of the coupling of quinoline N-oxide system reveal that the reaction proceeds via initial oxidative cyclization of the 1,6-diyne to give a rhodacyclic intermediate, followed by σ-bond metathesis between the arene C-H bond and the Rh-C(vinyl) bond, with subsequent C-C reductive elimination being enantio-determining and turnover-limiting. The DFT-established mechanism is consistent with the experimental studies. The coupled products of quinoline N-oxides undergo facile visible light-induced intramolecular oxygen-atom transfer, affording chiral epoxides with complete axial-to-central chirality transfer.

19.
Angew Chem Int Ed Engl ; 63(1): e202315230, 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-37938113

RESUMEN

The carbon-to-silicon switch in formation of bioactive sila-heterocycles with a silicon-stereogenic center has garnered significant interest in drug discovery. However, metal-catalyzed synthesis of such scaffolds is still in its infancy. Herein, a rhodium-catalyzed enantioselective formal [4+1] cyclization of benzyl alcohols and benzaldimines has been realized by enantioselective difunctionalization of a secondary silane reagent, affording chiral-at-silicon cyclic silyl ethers and sila-isoindolines, respectively. Mechanistic studies reveal a dual role of the rhodium-hydride catalyst. The coupling system proceeds via rhodium-catalyzed enantio-determining dehydrogenative OH silylation of the benzyl alcohol or hydrosilylation of the imine to give an enantioenriched silyl ether or silazane intermediate, respectively. The same rhodium catalyst also enables subsequent intramolecular cyclative C-H silylation directed by the pendent Si-H group. Experimental and DFT studies have been conducted to explore the mechanism of the OH bond silylation of benzyl alcohol, where the Si-O reductive elimination from a Rh(III) hydride intermediate has been established as the enantiodetermining step.

20.
Angew Chem Int Ed Engl ; : e202413600, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136072

RESUMEN

Achieving high energy density has always been the goal of lithium-ion batteries (LIBs). SiOx has emerged as a compelling candidate for use as a negative electrode material due to its remarkable capacity. However, the huge volume expansion and the unstable electrode interface during (de)lithiation, hinder its further development. Herein, we report a facile strategy for the synthesis of surface fluorinated SiOx (SiOx@vG-F), and investigate their influences on battery performance. Systematic experiments investigations indicate that the reaction between Li+ and fluorine groups promotes the in-situ formation of stable LiF-rich solid electrolyte interface (SEI) on the surface of SiOx@vG-F anode, which effectively suppresses the pulverization of microsized SiOx particles during the charge and discharge cycle. As a result, the SiOx@vG-F enabled a higher capacity retention of 86.4% over 200 cycles at 1.0 C in the SiOx@vG-F||LiNi0.8Co0.1Mn0.1O2 full cell. This approach will provide insights for the advancement of alternative electrode materials in diverse energy conversion and storage systems.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA