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1.
Nature ; 632(8027): 1032-1037, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39198671

RESUMEN

Superconductivity in a highly correlated kagome system has been theoretically proposed for years (refs. 1-5), yet the experimental realization is hard to achieve6,7. The recently discovered vanadium-based kagome materials8, which exhibit both superconductivity9-11 and charge-density-wave orders12-14, are nonmagnetic8,9 and weakly correlated15,16. Thus these materials are unlikely to host the exotic superconductivity theoretically proposed. Here we report the discovery of a chromium-based kagome metal, CsCr3Sb5, which is contrastingly featured with strong electron correlations, frustrated magnetism and characteristic flat bands close to the Fermi level. Under ambient pressure, this kagome metal undergoes a concurrent structural and magnetic phase transition at 55 K, with a stripe-like 4a0 structural modulation. At high pressure, the phase transition evolves into two transitions, possibly associated with charge-density-wave and antiferromagnetic spin-density-wave orderings. These density-wave-like orders are gradually suppressed with pressure and, remarkably, a superconducting dome emerges at 3.65-8.0 GPa. The maximum of the superconducting transition temperature, Tcmax = 6.4 K, appears when the density-wave-like orders are completely suppressed at 4.2 GPa, and the normal state exhibits a non-Fermi-liquid behaviour, reminiscent of unconventional superconductivity and quantum criticality in iron-based superconductors17,18. Our work offers an unprecedented platform for investigating superconductivity in correlated kagome systems.

2.
Nature ; 588(7839): 693-698, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33177715

RESUMEN

Despite its success in achieving the long-term survival of 10-30% of treated individuals, immune therapy is still ineffective for most patients with cancer1,2. Many efforts are therefore underway to identify new approaches that enhance such immune 'checkpoint' therapy3-5 (so called because its aim is to block proteins that inhibit checkpoint signalling pathways in T cells, thereby freeing those immune cells to target cancer cells). Here we show that inhibiting PCSK9-a key protein in the regulation of cholesterol metabolism6-8-can boost the response of tumours to immune checkpoint therapy, through a mechanism that is independent of PCSK9's cholesterol-regulating functions. Deleting the PCSK9 gene in mouse cancer cells substantially attenuates or prevents their growth in mice in a manner that depends on cytotoxic T cells. It also enhances the efficacy of immune therapy that is targeted at the checkpoint protein PD1. Furthermore, clinically approved PCSK9-neutralizing antibodies synergize with anti-PD1 therapy in suppressing tumour growth in mouse models of cancer. Inhibiting PCSK9-either through genetic deletion or using PCSK9 antibodies-increases the expression of major histocompatibility protein class I (MHC I) proteins on the tumour cell surface, promoting robust intratumoral infiltration of cytotoxic T cells. Mechanistically, we find that PCSK9 can disrupt the recycling of MHC I to the cell surface by associating with it physically and promoting its relocation and degradation in the lysosome. Together, these results suggest that inhibiting PCSK9 is a promising way to enhance immune checkpoint therapy for cancer.


Asunto(s)
Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Inhibidores de PCSK9 , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Neutralizantes/farmacología , Anticuerpos Neutralizantes/uso terapéutico , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Antígenos de Histocompatibilidad Clase I/inmunología , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Lisosomas/metabolismo , Ratones , Neoplasias/metabolismo , Neoplasias/patología , Proproteína Convertasa 9/deficiencia , Proproteína Convertasa 9/genética , Proproteína Convertasa 9/inmunología , Linfocitos T Citotóxicos/citología , Linfocitos T Citotóxicos/inmunología , Ensayos Antitumor por Modelo de Xenoinjerto
3.
Plant Physiol ; 2024 Aug 22.
Artículo en Inglés | MEDLINE | ID: mdl-39172695

RESUMEN

The carboxysome is a natural proteinaceous organelle for carbon fixation in cyanobacteria and chemoautotrophs. It comprises hundreds of protein homologs that self-assemble to form a polyhedral shell structure to sequester cargo enzymes, ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) and carbonic anhydrases. How these protein components assemble to construct a functional carboxysome is a central question in not only understanding carboxysome structure and function but also synthetic engineering of carboxysomes for biotechnological applications. Here, we determined the structure of the chaperone protein CcmS, which has recently been identified to be involved in ß-carboxysome assembly, and its interactions with ß-carboxysome proteins. The crystal structure at 1.99 Å resolution reveals CcmS from Nostoc sp. PCC 7120 forms a homodimer, and each CcmS monomer consists of five α-helices and four ß-sheets. Biochemical assays indicate that CcmS specifically interacts with the C-terminal extension of the carboxysome shell protein CcmK1, but not the shell protein homolog CcmK2 or the carboxysome scaffolding protein CcmM. Moreover, we solved the structure of a stable complex of CcmS and the C-terminus of CcmK1 at 1.67 Å resolution and unveiled how the CcmS dimer interacts with the C-terminus of CcmK1. These findings allowed us to propose a model to illustrate CcmS-mediated ß-carboxysome assembly by interacting with CcmK1 at the outer shell surface. Collectively, our study provides detailed insights into the accessory factors that drive and regulate carboxysome assembly, thereby improving our knowledge of carboxysome structure, function, and bioengineering.

4.
J Am Chem Soc ; 146(13): 9335-9346, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38501695

RESUMEN

Controlling product selectivity in successive reactions of the same type is challenging owing to the comparable thermodynamic and kinetic properties of the reactions involved. Here, the synergistic interaction of the two phosphoryl groups in bisphosphine dioxides (BPDOs) with a bromo-phosphonium cation was studied experimentally to provide a practical tool for substrate-catalyst recognition. As the eventual result, we have developed a phosphonium-catalyzed monoreduction of chiral BPDOs to access an array of synthetically useful bisphosphine monoxides (BPMOs) with axial, spiro, and planar chirality, which are otherwise challenging to synthesize before. The reaction features excellent selectivity and impressive reactivity. It proceeds under mild conditions, avoiding the use of superstoichiometric amounts of additives and metal catalysts to simplify the synthetic procedure. The accessibility and scalability of the reaction allowed for the rapid construction of a ligand library for optimization of asymmetric Heck-type cyclization, laying the foundation for a broad range of applications of chiral BPMOs in catalysis.

5.
Cell Physiol Biochem ; 58(4): 418-430, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39172137

RESUMEN

BACKGROUND/AIMS: After 9/11, multiple government agencies instituted programs aimed at developing medical radiation countermeasures (MRCs) for two syndromes lethal within weeks of a limited nuclear attack; the hematopoietic-acute radiation syndrome (H-ARS) and the higher-dose gastrointestinal-acute radiation syndrome (GI-ARS). While re-purposing drugs that enhance marrow repopulation treats H-ARS, no mitigator protects GI tract. METHODS: We recently reported anti-ceramide 6B5 single-chain variable fragment (scFv) pre-treatment abrogates ongoing small intestinal endothelial apoptosis to rescue Lgr5+ stem cells, preventing GI-ARS lethality in C57B/L6J mice. Here, with US Department of Defense support, we provide evidence that humanized anti-ceramide scFv (CX-01) is a promising prophylactic MRC for first responders, who risk exposure upon entering a radiation-contaminated site. RESULTS: CX-01, when delivered up to 90 min before irradiation, is highly-effective in preventing small intestinal endothelial apoptosis in mice and lethality in both sexes. Unexpectedly, females require an ~2-fold higher CX-01 dose than males for full protection. CX-01 is effective subcutaneously and intramuscularly, a property critical for battlefield use. Increasing the maximally-effective dose 5-fold does not extend duration of bioeffectiveness. CONCLUSION: While CX-01 prevents GI-ARS lethality, structural modification to extend half-life may be necessary to optimize first responder prophylaxis.


Asunto(s)
Apoptosis , Ceramidas , Ratones Endogámicos C57BL , Anticuerpos de Cadena Única , Animales , Anticuerpos de Cadena Única/inmunología , Femenino , Ratones , Masculino , Ceramidas/metabolismo , Apoptosis/efectos de los fármacos , Síndrome de Radiación Aguda/patología , Síndrome de Radiación Aguda/tratamiento farmacológico , Síndrome de Radiación Aguda/prevención & control , Humanos , Armas Nucleares , Protectores contra Radiación/farmacología , Protectores contra Radiación/uso terapéutico , Intestino Delgado/patología , Intestino Delgado/efectos de los fármacos , Intestino Delgado/efectos de la radiación
6.
Small ; 20(29): e2309863, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38368256

RESUMEN

Research on flexible thermoelectric (TE) materials has typically focused on conducting polymers and conducting polymer-based composites. However, achieving TE properties comparable in magnitude to those exhibited by their inorganic counterparts remains a formidable challenge. This study focuses on the synthesis of silver selenide (Ag2Se) nanomaterials using solvothermal methods and demonstrates a significant enhancement in their TE properties through the synergistic dual doping of sulfur and copper. Flexible TE thin films demonstrating excellent flexibility are successfully fabricated using vacuum filtration and hot-pressing techniques. The resulting thin films also exhibited outstanding TE performance, with a high Seebeck coefficient (S = -138.5 µV K-1) and electrical conductivity (σ = 1.19 × 105 S m-1). The record power factor of 2296.8 µW m-1 K-2 at room temperature is primarily attributed to enhanced carrier transport and interfacial energy filtration effects in the composite material. Capitalizing on these excellent TE properties, the maximum power output of flexible TE devices reached 1.13 µW with a temperature difference of 28.6 K. This study demonstrates the potential of Ag2Se-based TE materials for flexible and efficient energy-harvesting applications.

7.
J Transl Med ; 22(1): 829, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39252063

RESUMEN

BACKGROUND: CT-detected Extramural venous invasion (EMVI) is known as an independent risk factor for distant metastasis in patients with advanced gastric cancer (GC). However, the molecular basis is not clear. In colorectal cancer, M2 macrophages plays a vital role in determining EMVI. This study aimed to investigate the relationship between CT-detected EMVI and the M2 macrophages as well as prognosis predictionusing a radiogenomic approach. METHOD: We utilized EMVI-related genes (from mRNA sequencing of 13 GC samples correlated with EMVI score by spearman analysis, P < 0.01) to overlap the co-expression genes of WGCNA module and M2 macrophages related genes (from mRNA data of 371 GC patients in TCGA database), generating a total of 136 genes. An EMVI-M2-prognosis-related hub gene signature was constructed by COX and least absolute shrinkage and selection operator (LASSO) analysis from a training cohort TCGA database (n = 371) and validated it in a validation cohort from GEO database (n = 357). High- and low-risk groups were divided by hub gene (EGFLAM and GNG11) signature-derived risk scores. We assessed its predictive ability through Kaplan-Meier (K-M) curve and COX analysis. Furthermore, we utilized ESTIMATE to detect tumor mutation burden (TMB) and evaluate sensitivity to immune checkpoint inhibitors (ICIs). Expression of hub genes was tested using western blotting and immunohistochemistry (IHC) analysis. RESULTS: The overall survival (OS) was significantly reduced in the high-risk group (Training/Validation: AUC = 0.701/0.620; P < 0.001/0.003). Furthermore, the risk score was identified as an independent predictor of OS in multivariate COX regression analyses (Training/Validation: HR = 1.909/1.928; 95% CI: 1.225-2.974/1.308-2.844). The low-risk group exhibited significantly higher TMB levels (P = 1.6e- 07) and greater sensitivity to ICIs. Significant higher expression of hub-genes was identified on multiple GC cell lines and original samples. Hub-genes knockdown in gastric cancer cell lines inhibited their proliferation, metastatic and invasive capacity to varying degrees. In vivo experiments indicate that EGFLAM, as one of the hub genes, its high expression can serve as a biomarker for low response to immunotherapy. CONCLUSION: Our study demonstrated EMVI-M2 gene signature could effectively predict the prognosis of GC tissue, reflecting the relationship between EMVI and M2 macrophages.


Asunto(s)
Regulación Neoplásica de la Expresión Génica , Macrófagos , Invasividad Neoplásica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , Macrófagos/metabolismo , Macrófagos/patología , Masculino , Femenino , Pronóstico , Persona de Mediana Edad , Tomografía Computarizada por Rayos X , Estimación de Kaplan-Meier , Análisis de Supervivencia , Transcriptoma/genética , Animales , Línea Celular Tumoral , Perfilación de la Expresión Génica , Reproducibilidad de los Resultados , Anciano
8.
Opt Lett ; 49(16): 4729-4732, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39146146

RESUMEN

We theoretically study the second-harmonic generation (SHG) of two-dimensional (2D) materials excited by a Laguerre-Gaussian (LG) beam at normal incidence and provide a method to distinguish SHG induced by the electric dipole (ED) interaction and SHG induced by the electric quadrupole and magnetic dipole (EQ-MD) interaction by their different dependence on the LG beam parameters, including the effective spot area v02 and the order of orbital angular momentum (OAM) m. In an approximation of neglecting reflection and taking a beam radius to infinity, the intensity of the ED induced SHG is proportional to F m/v02 with Fm = 2-2|m|(2|m|)!/(π(|m|!)2), while the EQ-MD induced one is proportional to (4|m|+2)F m/v04. An in-plane isotropic substrate can strongly affect the signal amplitude but slightly change the v0 and m dependence. Our results provide an all-optical way to detect the OAM by SHG, as well as a theoretical basis for studying the EQ-MD induced SHG by the LG beams.

9.
Opt Lett ; 49(11): 2886-2889, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38824284

RESUMEN

Light field (LF) imaging has gained significant attention in the field of computational imaging due to its unique capability to capture both spatial and angular information of a scene. In recent years, super-resolution (SR) techniques based on deep learning have shown considerable advantages in enhancing LF image resolution. However, the inherent challenges of obtaining rich structural information and reconstructing complex texture details persist, particularly in scenarios where spatial and angular information are intricately interwoven. This Letter introduces a novel, to the best of our knowledge, approach for Disentangling LF Image SR Network (DLISN) by leveraging the synergy of dual learning and Fourier channel attention (FCA) mechanisms. Dual learning strategies are employed to enhance reconstruction results, addressing limitations in model generalization caused by the difficulty in acquiring paired datasets in real-world LF scenarios. The integration of FCA facilitates the extraction of high-frequency information associated with different structures, contributing to improved spatial resolution. Experimental results consistently demonstrate superior performance in enhancing the resolution of LF images.

10.
Chemistry ; 30(33): e202400995, 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38600034

RESUMEN

Introduction of the trifluoromethyl (CF3) group into organic compounds has garnered substantial interest because of its significant role in pharmaceuticals and agrochemicals. Here, we report a hydroxylamine-mediated radical process for C(sp2)-H trifluoromethylation of terminal alkenes. The reaction shows good reactivity, impressive E/Z selectivity (up to >20 : 1), and broad functional group compatibility. Expansion of this approach to perfluoroalkylation and late-stage trifluoromethylation of bioactive molecules demonstrates its promising application potential. Mechanistic studies suggest that the reaction follows a radical addition and subsequent elimination pathway.

11.
BMC Cancer ; 24(1): 156, 2024 Jan 31.
Artículo en Inglés | MEDLINE | ID: mdl-38291366

RESUMEN

BACKGROUND: Lactate dehydrogenase (LDHs) is an enzyme involved in anaerobic glycolysis, including LDHA, LDHB, LDHC and LDHD. Given the regulatory role in the biological progression of certain tumors, we analyzed the role of LDHs in pan-cancers. METHODS: Cox regression, Kaplan-Meier curves, Receiver Operating Characteristic (ROC) curves, and correlation of clinical indicators in tumor patients were used to assess the prognostic significance of LDHs in pan-cancer. The TCGA, HPA, TIMER, UALCAN, TISIDB, and Cellminer databases were used to investigate the correlation between the expression of LDHs and immune subtypes, immune checkpoint genes, methylation levels, tumor mutational load, microsatellite instability, tumor-infiltrating immune cells and drug sensitivity. The cBioPortal database was also used to identify genomic abnormalities of LDHs in pan-cancer. A comprehensive assessment of the biological functions of LDHs was performed using GSEA. In vitro, HepG2 and Huh7 cells were transfected with LDHD siRNA and GFP-LDHD, the proliferation capacity of cells was examined using CCK-8, EdU, and colony formation assays; the migration and invasion of cells was detected by wound healing and transwell assays; western blotting was used to detect the levels of MMP-2, MMP-9, E-cadherin, N-cadherin and Akt phosphorylation. RESULTS: LDHs were differentially expressed in a variety of human tumor tissues. LDHs subtypes can act as pro-oncogenes or anti-oncogenes in different types of cancer and have an impact on the prognosis of patients with tumors by influencing their clinicopathological characteristics. LDHs were differentially expressed in tumor immune subtypes and molecular subtypes. In addition, LDHs expression correlated with immune checkpoint genes, tumor mutational load, and microsatellite instability. LDHD was identified to play an important role in the prognosis of HCC patients, according to a comprehensive analysis of LDHs in pan-cancer. In HepG2 and Huh7 cells, knockdown of LDHD promoted cell proliferation, migration, and invasion, promoted the protein expression levels of MMP-2, MMP-9, N-cadherin, and Akt phosphorylation, but inhibited the protein expression level of E-cadherin. In addition, LDHD overexpression showed the opposite changes. CONCLUSION: LDHs subtypes can be used as potential prognostic markers for certain cancers. Prognostic and immunotherapeutic analysis indicated that LDHD plays an important role in the prognosis of HCC patients. In vitro experiments revealed that LDHD can affect HCC proliferation, migration, and invasion by regulating MMPs expression and EMT via Akt signaling pathway, which provides a new perspective on the anti-cancer molecular mechanism of LDHD in HCC.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Cadherinas/genética , Carcinoma Hepatocelular/genética , L-Lactato Deshidrogenasa , Neoplasias Hepáticas/genética , Metaloproteinasa 2 de la Matriz , Metaloproteinasa 9 de la Matriz , Inestabilidad de Microsatélites , Pronóstico , Proteínas Proto-Oncogénicas c-akt
12.
Artículo en Inglés | MEDLINE | ID: mdl-38864839

RESUMEN

A Gram-stain-positive, strictly anaerobic, endospore-forming and rod-shaped (0.6-0.8×2.7-13.1 µm) bacterium, designated as 5 N-1T, was isolated from a yellow water sample collected from the manufacturing process of Nongxiangxing baijiu in the Yibin region of Sichuan, PR China. Growth occurred at 15-40 °C (optimum growth at 37 °C), at pH 6.0-9.0 (optimum growth at pH 7.0) and in NaCl concentrations of 0-1 % (w/v) and ethanol concentrations of 0-2 % (v/v). The major fatty acids in strain 5 N-1T were C16 : 0, C18 : 0 and C14 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unidentified aminophospholipids and one unidentified lipid. Phylogenetic analysis of its 16S rRNA gene sequence indicated that strain 5 N-1T was most closely related to Clostridium weizhouense YB-6T (97.70 %) and Clostridium uliginosum DSM 12992T (97.56 %). The average nucleotide identity and digital DNA‒DNA hybridization values between strain 5 N-1T and the above two type strains were 80.89 and 80.05 % and 25.80 and 25.30 %, respectively, which were all below the species thresholds. The genome size of strain 5 N-1T was 3.5 Mbp and the DNA G+C content was 27.5 mol%. Based on the results of phenotypic and genotypic analyses, strain 5 N-1T represents a novel species of the genus Clostridium, for which the name Clostridium aquiflavi sp. nov. is proposed. The type strain is Clostridium aquiflavi 5 N-1T (=CICC 24886T=JCM 35355T).


Asunto(s)
Técnicas de Tipificación Bacteriana , Composición de Base , Clostridium , ADN Bacteriano , Ácidos Grasos , Hibridación de Ácido Nucleico , Filogenia , ARN Ribosómico 16S , Análisis de Secuencia de ADN , China , ARN Ribosómico 16S/genética , Ácidos Grasos/análisis , ADN Bacteriano/genética , Clostridium/genética , Clostridium/aislamiento & purificación , Clostridium/clasificación , Microbiología del Agua , Fosfolípidos/análisis
13.
Eur Radiol ; 34(3): 1659-1666, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37672054

RESUMEN

OBJECTIVE: To report the results of a dose survey conducted across 31 provinces in mainland China from 2017 to 2018 and to analyse the dose level to determine the national diagnostic reference levels (DRLs) for paediatric CT procedures. METHODS: At least ten patients for each age group (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) and each procedure (head, chest and abdomen) for each CT scanner were selected from four to eight hospitals in each province. The dose information (CTDIvol and DLP) was collected from the HIS or RIS-PACS systems. The median values in each CT scanner were considered the representative dose values for the paediatric patients in CT scanning. The national DRLs were estimated based on the 75th percentile distribution of the median values. RESULTS: A total of 24,395 patients and 319 CT scanners were investigated across 262 hospitals. For paediatric CT scanning in 4 different age groups, the median (P50) and the 75th percentile (P75) of CTDIvol and DLP for each scanning procedure were calculated and reported. National DRLs were then proposed for each procedure and age group. CONCLUSION: The dose level of CT scanning for children in mainland China was reported for the first time. The DRLs for paediatric CT in the present study are similar to those in some Asian countries but higher than those in European countries. CLINICAL RELEVANCE STATEMENT: The paediatric CT is an extensively used tool in diagnosing paediatric disease; however, children are more sensitive to radiation. Establishing the diagnostic reference level of paediatric CT examination is necessary to reduce the dose of CT in children and promote the optimisation of medical exposure. KEY POINTS: • The DRLs for 3 paediatric CT procedures (head, chest and abdomen) and 4 age groups (0- < 1, 1- < 5, 5- < 10, 10- < 15 years) were proposed in mainland China first time. • The examination parameter and dose for children need to be further optimised in China, especially to lower the tube voltage in paediatric CT.


Asunto(s)
Tórax , Tomografía Computarizada por Rayos X , Niño , Humanos , Adolescente , Dosis de Radiación , Valores de Referencia , Tomografía Computarizada por Rayos X/métodos , China/epidemiología
14.
Mol Cell ; 64(4): 673-687, 2016 11 17.
Artículo en Inglés | MEDLINE | ID: mdl-27840030

RESUMEN

Distinctive from their normal counterparts, cancer cells exhibit unique metabolic dependencies on glutamine to fuel anabolic processes. Specifically, pancreatic ductal adenocarcinoma (PDAC) cells rely on an unconventional metabolic pathway catalyzed by aspartate aminotransferase, malate dehydrogenase 1 (MDH1), and malic enzyme 1 to rewire glutamine metabolism and support nicotinamide adenine dinucleotide phosphate (NADPH) production. Here, we report that methylation on arginine 248 (R248) negatively regulates MDH1. Protein arginine methyltransferase 4 (PRMT4/CARM1) methylates and inhibits MDH1 by disrupting its dimerization. Knockdown of MDH1 represses mitochondria respiration and inhibits glutamine metabolism, which sensitizes PDAC cells to oxidative stress and suppresses cell proliferation. Meanwhile, re-expression of wild-type MDH1, but not its methylation-mimetic mutant, protects cells from oxidative injury and restores cell growth and clonogenic activity. Importantly, MDH1 is hypomethylated at R248 in clinical PDAC samples. Our study reveals that arginine methylation of MDH1 by CARM1 regulates cellular redox homeostasis and suppresses glutamine metabolism of pancreatic cancer.


Asunto(s)
Carcinoma Ductal Pancreático/genética , Regulación Neoplásica de la Expresión Génica , Glutamina/metabolismo , Malato-Deshidrogenasa (NADP+)/genética , Neoplasias Pancreáticas/genética , Proteína-Arginina N-Metiltransferasas/genética , Arginina/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patología , Línea Celular Tumoral , Proliferación Celular , Células HEK293 , Humanos , Malato-Deshidrogenasa (NADP+)/antagonistas & inhibidores , Malato-Deshidrogenasa (NADP+)/metabolismo , Metilación , Mitocondrias/genética , Mitocondrias/metabolismo , Mitocondrias/patología , Modelos Moleculares , NADP/biosíntesis , Oxidación-Reducción , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patología , Multimerización de Proteína , Estructura Secundaria de Proteína , Proteína-Arginina N-Metiltransferasas/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Transducción de Señal
15.
Prenat Diagn ; 44(1): 81-87, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38148006

RESUMEN

To report two novel TTN variants associated with fetal recessive titinopathy, thereby broadening the range of TTN variants that can lead to titinopathy. Clinical information on the fetus and parents was gathered, and genomic DNAs were extracted from the fetal tissue and family members' peripheral blood samples. Exome sequencing on fetal DNA was performed and following bioinformatics analysis, the suspected pathogenic variants were confirmed through Sanger sequencing. Prenatal ultrasound performed at 29 weeks of gestation revealed hydrops fetalis, decreased fetal movements, multiple joint contractures and polyhydramnios. Intrauterine fetal death was noted in the third trimester. Exome sequencing revealed compound heterozygous variants in the TTN gene: a paternally inherited allele c.101227C>T (p.Arg33743Ter) and a maternally inherited c.104254C>T (p.Gln34752Ter) allele. These variants have not been previously reported and are evaluated to be likely pathogenic according to the American College of Medical Genetics and Genomics guidelines. We report a fetus with hydrops fetalis and arthrogryposis multiplex congenita associated with a compound heterozygote in the TTN gene. Our report broadens the clinical and genetic spectrum associated with the TTN-related conditions.


Asunto(s)
Artrogriposis , Hidropesía Fetal , Embarazo , Femenino , Humanos , Hidropesía Fetal/diagnóstico por imagen , Hidropesía Fetal/genética , Exones , Artrogriposis/diagnóstico por imagen , Artrogriposis/genética , Tercer Trimestre del Embarazo , Feto/diagnóstico por imagen , Conectina/genética
16.
BMC Public Health ; 24(1): 1411, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38802825

RESUMEN

BACKGROUND: Preterm birth (PTB) is an important predictor of perinatal morbidity and mortality. Previous researches have reported a correlation between air pollution and an increased risk of preterm birth. However, the specific relationship between short-term and long-term exposure to carbon monoxide (CO) and preterm birth remains less explored. METHODS: A population-based study was conducted among 515,498 pregnant women in Chongqing, China, to assess short-term and long-term effects of CO on preterm and very preterm births. Generalized additive models (GAM) were applied to evaluate short-term effects, and exposure-response correlation curves were plotted after adjusting for confounding factors. Hazard ratios (HR) and 95% confidence intervals (CI) were calculated using COX proportional hazard models to estimate the long-term effect. RESULTS: The daily incidence of preterm and very preterm birth was 5.99% and 0.41%, respectively. A positive association between a 100 µg/m³ increase in CO and PTB was observed at lag 0-3 days and 12-21 days, with a maximum relative risk (RR) of 1.021(95%CI: 1.001-1.043). The exposure-response curves (lag 0 day) revealed a rapid increase in PTB due to CO. Regarding long-term exposure, positive associations were found between a 100 µg/m3 CO increase for each trimester(Model 2 for trimester 1: HR = 1.054, 95%CI: 1.048-1.060; Model 2 for trimester 2: HR = 1.066, 95%CI: 1.060-1.073; Model 2 for trimester 3: HR = 1.007, 95%CI: 1.001-1.013; Model 2 for entire pregnancy: HR = 1.080, 95%CI: 1.073-1.088) and higher HRs of very preterm birth. Multiplicative interactions between air pollution and CO on the risk of preterm and very preterm birth were detected (P- interaction<0.05). CONCLUSIONS: Our findings suggest that short-term exposure to low levels of CO may have protective effects against preterm birth, while long-term exposure to low concentrations of CO may reduce the risk of both preterm and very preterm birth. Moreover, our study indicated that very preterm birth is more susceptible to the influence of long-term exposure to CO during pregnancy, with acute CO exposure exhibiting a greater impact on preterm birth. It is imperative for pregnant women to minimize exposure to ambient air pollutants.


Asunto(s)
Contaminantes Atmosféricos , Monóxido de Carbono , Nacimiento Prematuro , Humanos , Femenino , Embarazo , Nacimiento Prematuro/epidemiología , China/epidemiología , Monóxido de Carbono/análisis , Adulto , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/efectos adversos , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Recién Nacido , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricos , Factores de Tiempo , Adulto Joven , Factores de Riesgo
17.
Ren Fail ; 46(1): 2330629, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38494199

RESUMEN

Acetaminophen (APAP)-induced acute kidney injury (APAP-AKI) has turned into one of reasons for clinic obtained renal insufficiency. Magnesium hydride (MgH2), as a solid-state hydrogen source, might be potentially applied in clinical practice. The current study aimed to investigate the protective effect of MgH2 against APAP-AKI. The results showed that MgH2 improved renal function and histological injury in mice of APAP-AKI. MgH2 also had protective effects on APAP-induced cytotoxicity in HK-2 cells. In addition, the increased level of reactive oxygen species (ROS) and expressions of inflammatory cytokines (TNF-α and IL-1ß) and pro-apoptotic factors (Bad, Bax, Caspase3, and CytC) induced by APAP were downregulated with MgH2 treatment. Furthermore, the expressions of molecules related to TXNIP/NLRP3/NF-κB pathway (TXNIP, NLRP3, NF-κB p65 and p-NF-κB p65) in renal tissues and HK-2 cells were enhanced by APAP overdose, which were reduced by MgH2 administration. Collectively, this study indicated that MgH2 protects against APAP-AKI by alleviating oxidative stress, inflammation and apoptosis via inhibition of TXNIP/NLRP3/NF-κB signaling pathway.


Asunto(s)
Lesión Renal Aguda , Enfermedad Hepática Inducida por Sustancias y Drogas , Ratones , Animales , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Acetaminofén/toxicidad , Magnesio , Estrés Oxidativo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/prevención & control
18.
J Asian Nat Prod Res ; 26(8): 892-899, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38600044

RESUMEN

Two new triterpene fatty acid esters, 3ß-palmityloxy-12,27-cyclofriedoolean-14-en-11α-ol (1) and 3ß-palmityloxy-19α-hydroxyursane (2), together with 3ß-hydroxy-11-oxo-olean-12-enyl palmitate (3) were isolated from the potent anti-inflammatory active fraction of the petroleum ether-soluble part of Cirsium setosum ethanol extract. Compound 1 was found to be a rare 12,27-cyclopropane triterpenoid. Their structures were determined through spectral data analysis combined with literature reports. Furthermore, in vitro experiment, compounds 1-3 exhibited significant inhibitory effects on nitric oxide production in lipopolysaccharide-activated mouse RAW264.7 macrophages.


Asunto(s)
Antiinflamatorios , Cirsium , Ésteres , Lipopolisacáridos , Óxido Nítrico , Triterpenos , Animales , Ratones , Cirsium/química , Triterpenos/farmacología , Triterpenos/química , Triterpenos/aislamiento & purificación , Estructura Molecular , Óxido Nítrico/biosíntesis , Óxido Nítrico/antagonistas & inhibidores , Células RAW 264.7 , Antiinflamatorios/farmacología , Antiinflamatorios/química , Lipopolisacáridos/farmacología , Ésteres/farmacología , Ésteres/química , Macrófagos/efectos de los fármacos
19.
Molecules ; 29(11)2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38893354

RESUMEN

Metal halide perovskites have attracted considerable attention as novel optoelectronic materials for their excellent optical and electrical properties. Inorganic perovskites (CsPbX3, X = Cl, Br, I) are now viable alternative candidates for third-generation photovoltaic technology because of their high photoelectric conversion efficiency, high carrier mobility, good defect tolerance, simple preparation method and many other advantages. However, the toxicity of lead is problematic for practical implementation. Thus, the fabrication of lead-free perovskite materials and devices has been actively conducted. In this work, the energy band and photoelectric properties of inorganic perovskites CsBX3 (B = Pb, Sn, Ge, X = Cl, Br, I) have been investigated with the first principles calculation, and the possible defect energy levels and their formation energies in different components, in particular, have been systematically studied. The advantages and disadvantages of Sn and Ge as replacement elements for Pb have been demonstrated from the perspective of defects. This study provides an important basis for the study of the properties and applications of lead-free perovskites.

20.
Molecules ; 29(16)2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39202889

RESUMEN

Kombucha is a well-known fermented beverage traditionally made from black tea infusion. Recent studies have focused on finding alternative materials to create novel kombucha beverages with various health benefits. In this study, we prepared and evaluated two novel kombucha beverages using Rhodiola rosea and Salvia miltiorrhiza as materials. The effects of fermentation with the residue of these plants on the kombucha were also investigated. The antioxidant activities, total phenolic contents, and concentrations of the bioactive compounds of the kombucha beverages were determined by the Trolox equivalent antioxidant capacity test, ferric-reducing antioxidant power test, Folin-Ciocalteu method, and high-performance liquid chromatography, respectively. The results revealed that the kombucha beverages made with Rhodiola rosea and Salvia miltiorrhiza had strong antioxidant capacities and abundant phenolic contents. Additionally, the kombucha fermented with Rhodiola rosea residue had higher FRAP, TEAC and TPC values than that fermented without residue. On the other hand, the Salvia miltiorrhiza kombucha fermented with residue had similar FRAP and TEAC values but lower TPC values compared to that fermented without residue. The correlation analysis showed that gallic acid, salidroside, and tyrosol were responsible for the antioxidant abilities and total phenolic contents of the Rhodiola rosea kombucha, and salvianolic acid A and salvianolic acid B contributed to the antioxidant abilities of the Salvia miltiorrhiza kombucha. Furthermore, the kombucha fermented with Rhodiola rosea residue had the highest sensory scores among the kombucha beverages studied. These findings suggest that Rhodiola rosea and Salvia miltiorrhiza are suitable for making novel kombucha beverages with strong antioxidant abilities and abundant phenolic contents, which can be used in preventing and managing oxidative stress-related diseases.


Asunto(s)
Antioxidantes , Fermentación , Fenoles , Rhodiola , Salvia miltiorrhiza , Antioxidantes/química , Rhodiola/química , Salvia miltiorrhiza/química , Fenoles/análisis , Fenoles/química , Bebidas/análisis , Extractos Vegetales/química , Extractos Vegetales/farmacología , Levaduras/metabolismo , Bacterias/efectos de los fármacos , Fitoquímicos/química , Fitoquímicos/análisis , Cromatografía Líquida de Alta Presión
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