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1.
J Chem Phys ; 161(9)2024 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-39230377

RESUMO

The pure rotational and rovibrational spectra of the ν27 -NH2 torsion of cyclopropylamine (CPA) in the far-infrared region were measured with a high-resolution Fourier transform infrared coupled to a synchrotron. The complex spectra reflect the presence of both trans and gauche conformers. Analysis of the pure rotational spectra (34-64 cm-1) yielded accurate rotational and centrifugal distortion constants of the ground and first two torsional excited states of trans-CPA. The fundamental, hot bands and weak overtones were identified and assigned in the 200-550 cm-1 range. Global analysis of over 19 000 transitions provides accurate energy levels of the torsional polyads up to vT = 3. The torsional levels and their rotational constants were in agreement with the theoretical results from quasiadiabatic channel reaction path Hamiltonian (RPH) calculations, emphasizing the need for molecular-specific theoretical treatments for large amplitude motions. Tunneling components of the torsional fundamental of gauche-CPA were assigned based on the RPH results and symmetry considerations, differing from previous experimental and theoretical work. This comprehensive spectroscopic characterization of CPA is crucial for its potential detection in the interstellar medium as a precursor to complex prebiotic molecules, providing essential data for future astronomical searches and advancing our understanding of nitrogen-containing organic molecules in space.

2.
Digit Health ; 10: 20552076241277735, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39233894

RESUMO

Background and Objective: The rapid development of computer technology has led to a revolutionary transformation in artificial intelligence (AI)-assisted healthcare. The integration of whole-slide imaging technology with AI algorithms has facilitated the development of digital pathology for lung cancer (LC). However, there is a lack of comprehensive scientometric analysis in this field. Methods: A bibliometric analysis was conducted on 197 publications related to digital pathology in LC from 502 institutions across 39 countries, published in 97 academic journals in the Web of Science Core Collection between 2004 and 2023. Results: Our analysis has identified the United States and China as the primary research nations in the field of digital pathology in LC. However, it is important to note that the current research primarily consists of independent studies among countries, emphasizing the necessity of strengthening academic collaboration and data sharing between nations. The current focus and challenge of research related to digital pathology in LC lie in enhancing the accuracy of classification and prediction through improved deep learning algorithms. The integration of multi-omics studies presents a promising future research direction. Additionally, researchers are increasingly exploring the application of digital pathology in immunotherapy for LC patients. Conclusions: In conclusion, this study provides a comprehensive knowledge framework for digital pathology in LC, highlighting research trends, hotspots, and gaps in this field. It also provides a theoretical basis for the application of AI in clinical decision-making for LC patients.

4.
J Phys Chem A ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292919

RESUMO

We report the coexistence of anti-conformers and energetically unfavorable syn-conformers of 2,3-, 2,4-, 2,5-, and 2,6-difluorobenzaldehyde in the gas phase using broadband chirped-pulse Fourier transform microwave (CP-FTMW) spectroscopy. The rotational spectra of monosubstituted 13C isotopologues of the anti-conformers have also been assigned in natural abundance, which were used to derive their vibrationally averaged geometries and semi-experimental equilibrium structures. The energy differences between anti- and syn-conformations are estimated to be 10.9, 11.3, and 12.9 kJ/mol for 2,3-, 2,4-, and 2,5-difluorobenzaldehyde, respectively, at the theoretical level of DLPNO-CCSD(T)/def2-TZVP. Despite the steric repulsion caused by the close proximity between the oxygen atom of the aldehyde group and the ortho-substituted fluorine atom, our experimental results indicate the planarity of the syn-conformations. The frequencies of the large amplitude torsion between the phenyl and aldehyde groups have been estimated by experimental inertial defects, which agree with theoretical calculation results.

5.
Adv Mater ; : e2406706, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39308291

RESUMO

Metal halide perovskites, a cost-effective class of semiconductos, hold great promise for display technologies that demand high-efficiency, color-pure light-emitting diodes (LEDs). Early research on three-dimensional (3D) perovskites showed low radiative efficiencies due to modest exciton binding energies. To inprove luminescence, reducing dimensionality or grain size has been a common approach. However, dividing the perovskite lattice into smaller units may hinder carrier transport, compromising electrical performance. Moreover, the increased surface area introduce additional surface trap states, leading to greater non-radiative recombination. Here, an ions-induced growth method is employed to assembe lattice-anchored perovskite nanocomposites for efficient LEDs with high color purity. This approach enables the nanocomposite thin films, composed of 3D CsPbBr3 and its variant of zero-dimensional (0D) Cs4PbBr6, to feature significant low trap-assisted nonradiative recombination, enhanced light out-coupling with a corrugated surface, and well-balanced charge carrier transport. Based on the resultant 3D/0D perovskite nanocomposites, the perovskite LEDs (PeLEDs) achieving an remarkable external quantum efficiency of 31.0% at the emission peak of 521 nm with a narrow full width at half-maximum of only 18 nm. This sets a new benchmark for color purity in high performance PeLED research, highlighting the significant advantage of this approach.

6.
Chin J Nat Med ; 22(9): 842-853, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39326978

RESUMO

Eight novel clerodane diterpenoids (1-8) were isolated from the twigs of Casearia graveolens. Their structures were elucidated through comprehensive nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), and electronic circular dichroism (ECD) analyses. In addition to structural determination, surface plasmon resonance (SPR) assays were conducted to investigate molecular interactions, revealing that compound 8 exhibited high affinity for vascular endothelial growth factor receptor 2 (VEGFR2), a key regulator of tumor angiogenesis. Subsequent in vivo experiments demonstrated that compound 8 effectively inhibited angiogenesis and displayed significant antitumor activity by suppressing tumor proliferation and metastasis in zebrafish xenograft models. These findings suggest that compound 8 holds promise as an anticancer lead compound targeting VEGFR-2 to obstruct tumor angiogenesis.


Assuntos
Inibidores da Angiogênese , Casearia , Receptor 2 de Fatores de Crescimento do Endotélio Vascular , Peixe-Zebra , Animais , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Humanos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/química , Inibidores da Angiogênese/isolamento & purificação , Estrutura Molecular , Casearia/química , Neovascularização Patológica/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Diterpenos/farmacologia , Diterpenos/química , Diterpenos/isolamento & purificação , Linhagem Celular Tumoral , Diterpenos Clerodânicos/farmacologia , Diterpenos Clerodânicos/química , Angiogênese
7.
Arch Sex Behav ; 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39327375

RESUMO

Mental health disparities in transgender and gender diverse (TGD) populations call for more research examining gender minority stressors (GMS) as antecedents to their psychological distress, especially for the long-underrepresented groups living in conservative societies towards gender minorities. Furthermore, some questions remain underexamined, including the relative, independent influences of various GMS on TGD people's mental well-being (i.e., uniqueness of each stressor); how these stressors would configurate with each other in distinctive patterns to characterize subgroups of TGD people (i.e., beyond-average heterogeneity); and how these stressors would constitute a psychological network and vary in their centrality in that network (i.e., holistic complexity). To narrow such gaps, we examined the links between GMS and TGD people's psychological distress, using survey data collected in 2023 from 410 Chinese TGD people (Meanage = 22.33 years, SD = 4.27; 306 transgender, 70 non-binary/gender-queer/gender-fluid, 26 agender/gender-neutral, 3 intersex, and 5 others). We approached such links from three perspectives. First, variable-centered analyses indicated that while different GMS were considered simultaneously, internalized transphobia, preoccupation with gender dysphoria, and gender-related victimization were uniquely associated with psychological distress. Second, person-centered analyses yielded a 3-profile solution. Psychological distress varied systematically across profiles. Last, network analyses revealed a 3-cluster structure: Distal, Proximal Internal, and TGD-Specific Stressors. Preoccupation with gender dysphoria was the most central node. These findings contribute to a more nuanced understanding of the implications of GMS for TGD people's mental well-being. GMS related to internal struggles with gender identity might be among the central intervention targets to prevent/reduce TGD people's psychological distress.

8.
Phytopathology ; 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39348563

RESUMO

Plant diseases impact the production of all kinds of crops, resulting in significant economic losses worldwide. Timely and accurate detection of plant pathogens is crucial for surveillance and management of plant diseases. In recent years, loop-mediated isothermal amplification (LAMP) has become a popular method for pathogen detection and disease diagnosis due to the advantages of its simple instrument requirement and constant reaction temperature. In this review, we provide an overview of current research on LAMP, including the reaction system, design of primers, selection of target regions, visualization of amplicons, and application of LAMP on the detection of all major groups of plant pathogens. We also discuss plant pathogens for which LAMP is yet to be developed, potential improvements of plant disease diagnosis, and disadvantages that need to be considered.

9.
Life (Basel) ; 14(8)2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39202756

RESUMO

Cnidarians are among the most important diploblastic organisms, elucidating many of the early stages of Metazoan evolution. However, Cnidarian fossils from Cambrian deposits have been rarely documented, mainly due to difficulties in identifying early Cnidarian representatives. Halysites, a tabulate coral from Silurian reef systems, serves as a crucial taxon for interpreting Cambrian cnidarians. Traditionally, the biological characteristics of Halysites have been analyzed using methods limited by pretreatment requirements (destructive testing) and the chamber size capacity of relevant analytical instruments. These constraints often lead to irreversible information loss and inadequate data extraction. This means that, to date, there has been no high-resolution three-dimensional mineralization analysis of Halysites. This study aims to introduce novel, non-destructive techniques to analyze the internal structure and chemical composition of Halysites. Furthermore, it seeks to elucidate the relationship between coral organisms and biomineralization in reef settings and to compare Silurian Tabulata with putative Cambrian cnidarians. Techniques such as micro-X-ray fluorescence spectrometry (micro-XRF), micro-X-ray computed tomography (micro-CT), and scanning electron microscopy (SEM) were employed in this research. With the help of high-resolution micro-CT scanning, we identify the growth pattern of Halysites, showing both lateral and vertical development. The lateral multiple-branching growth pattern of Halysites corals is first established herein. The flaggy corallite at the initial stage of branching is also observed. The micro-XRF mapping results reveal the occurrence of septa spines for Halysites, a trait previously thought rare or absent. Additionally, the ratio of coral volume to the surrounding rock was assessed, revealing that Halysites reefs were relatively sparse (volume ratio = ~30%). The cavities between Halysites likely provided more space for other organisms (e.g., rugose corals and bryozoans) when compared to other coral reef types. Additionally, we provide a comparative analysis of post-Cambrian colonial calcareous skeletons, offering insights into the structural features and growth patterns of early skeletal metazoans across the Ediacaran-Cambrian boundary.

10.
Arthritis Rheumatol ; 2024 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-39118347

RESUMO

OBJECTIVE: Mechanisms underlying the adolescent-onset and early-onset gout are unclear. This study aimed to discover variants associated with early-onset gout. METHODS: We conducted whole-genome sequencing in a discovery adolescent-onset gout cohort of 905 individuals (gout onset 12 to 19 years) to discover common and low-frequency single-nucleotide variants (SNVs) associated with gout. Candidate common SNVs were genotyped in an early-onset gout cohort of 2,834 individuals (gout onset ≤30 years old), and meta-analysis was performed with the discovery and replication cohorts to identify loci associated with early-onset gout. Transcriptome and epigenomic analyses, quantitative real-time polymerase chain reaction and RNA sequencing in human peripheral blood leukocytes, and knock-down experiments in human THP-1 macrophage cells investigated the regulation and function of candidate gene RCOR1. RESULTS: In addition to ABCG2, a urate transporter previously linked to pediatric-onset and early-onset gout, we identified two novel loci (Pmeta < 5.0 × 10-8): rs12887440 (RCOR1) and rs35213808 (FSTL5-MIR4454). Additionally, we found associations at ABCG2 and SLC22A12 that were driven by low-frequency SNVs. SNVs in RCOR1 were linked to elevated blood leukocyte messenger RNA levels. THP-1 macrophage culture studies revealed the potential of decreased RCOR1 to suppress gouty inflammation. CONCLUSION: This is the first comprehensive genetic characterization of adolescent-onset gout. The identified risk loci of early-onset gout mediate inflammatory responsiveness to crystals that could mediate gouty arthritis. This study will contribute to risk prediction and therapeutic interventions to prevent adolescent-onset gout.

11.
Artigo em Chinês | MEDLINE | ID: mdl-39118504

RESUMO

Objective:This study aims to identify the genetic etiology underlying late-onset hearing loss in two unrelated Chinese families. Methods:Detailed clinical data of recruited participants of two families were collected and analyzed using next-generation sequencing, combined with Sanger sequencing and bioinformatics tools. Results:Patients in both families manifested as down-sloping audiograms, mainly with severe mid-to-high frequency hearing loss as well as decreased speech recognition rate, both of which occurred during the second decade. Next-generation sequencing panels succeeded in identifying mutations in gene TMPRSS3, and three heterozygous mutations were screened out, among which c. 383T>C was the first reported mutation. In silico functional analysis and molecular modeling defined the five mutations as "pathogenic" or "likely pathogenic" according to official guideline. Conclusion:The novel mutation combinations in TMPRSS3 gene segregated with an exclusive auditory phenotype in the two pedigrees. Our results provided new data regarding the characteristic deafness caused by TMPRSS3 mutations during adolescent period when hearing should be closely monitored.


Assuntos
Perda Auditiva , Heterozigoto , Proteínas de Membrana , Serina Endopeptidases , Humanos , Idade de Início , Surdez/genética , Perda Auditiva/genética , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Membrana/genética , Mutação , Proteínas de Neoplasias , Linhagem , Serina Endopeptidases/genética , População do Leste Asiático/genética
12.
Int J Clin Pharmacol Ther ; 62(10): 460-478, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39120081

RESUMO

Pulmonary fibrosis (PF) is a chronic and progressive pulmonary interstitial disease of unknown etiology and is also a sequela in severe patients with the Coronavirus Disease 2019 (COVID-19). Seven databases were systematically searched to evaluate the preclinical evidence of Tanshinone IIA (Tan IIA) on PF. The quality of the included studies was assessed using a 10-item risk of bias tool, and data were analyzed using RevMan 5.3 software. 22 experiments from 12 studies on a total of 248 animals were included. The results showed that PF phenotype, such as fibrotic score, collagen I (Col-I), collagen III (Col-III), hydroxyproline (Hyp), in the group treated with Tan IIA were significantly lower than those in the model group (p < 0.00001). The potential mechanisms of Tan IIA improvement of PF involve reducing inflammation, antioxidation, and suppressing activation of transforming growth factor beta 1 (TGF-ß1). The subgroup analysis of different models, different rat species, and different dosage time showed significant reduction in fibrotic scores and Hyp levels with Tan IIA. The preclinical evidence indicated that Tan IIA might be a potent and promising agent for PF, but this conclusion should be further confirmed with more research.


Assuntos
Modelos Animais de Doenças , Fibrose Pulmonar , Fibrose Pulmonar/tratamento farmacológico , Animais , Humanos , Fenantrenos/administração & dosagem , Fenantrenos/farmacologia , Fenantrenos/uso terapêutico , Abietanos/farmacologia , Abietanos/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19 , Diterpenos/farmacologia , Diterpenos/administração & dosagem , Diterpenos/uso terapêutico , Ratos
13.
Front Med (Lausanne) ; 11: 1431578, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39086944

RESUMO

Although methods in diagnosis and therapy of hepatocellular carcinoma (HCC) have made significant progress in the past decades, the overall survival (OS) of liver cancer is still disappointing. Machine learning models have several advantages over traditional cox models in prognostic prediction. This study aimed at designing an optimal panel and constructing an optimal machine learning model in predicting prognosis for HCC. A total of 941 HCC patients with completed survival data and preoperative clinical chemistry and immunology indicators from two medical centers were included. The OCC panel was designed by univariate and multivariate cox regression analysis. Subsequently, cox model and machine-learning models were established and assessed for predicting OS and PFS in discovery cohort and internal validation cohort. The best OCC model was validated in the external validation cohort and analyzed in different subgroups. In discovery, internal and external validation cohort, C-indexes of our optimal OCC model were 0.871 (95% CI, 0.863-0.878), 0.692 (95% CI, 0.667-0.717) and 0.648 (95% CI, 0.630-0.667), respectively; the 2-year AUCs of OCC model were 0.939 (95% CI, 0.920-0.959), 0.738 (95% CI, 0.667-0.809) and 0.725 (95% CI, 0.643-0.808), respectively. For subgroup analysis of HCC patients with HBV, aged less than 65, cirrhosis or resection as first therapy, C-indexes of our optimal OCC model were 0.772 (95% CI, 0.752-0.792), 0.769 (95% CI, 0.750-0.789), 0.855 (95% CI, 0.846-0.864) and 0.760 (95% CI, 0.741-0.778), respectively. In general, the optimal OCC model based on RSF algorithm shows prognostic guidance value in HCC patients undergoing individualized treatment.

14.
Sci Adv ; 10(34): eadn4845, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39167645

RESUMO

Interleukin-4 (IL-4)-exposed microglia acquire neuroprotective properties, but their functions and regulation in Parkinson's disease (PD) are poorly understood. In this study, we demonstrate that IL-4 enhances anti-inflammatory microglia reactivity, ameliorates the pathological features of PD, and reciprocally affects expression of ß-arrestin 1 and ß-arrestin 2 in microglia in PD mouse models. We also show that manipulation of two ß-arrestins produces contrary effects on the anti-inflammatory states and neuroprotective action of microglia induced by IL-4 in vivo and in vitro. We further find that the functional antagonism of two ß-arrestins is mediated through sequential activation of sterile alpha motif domain containing 4 (Samd4), mammalian target of rapamycin (mTOR), and mitochondrial oxidative phosphorylation (OXPHOS). Collectively, these data reveal opposing functions of two closely related ß-arrestins in regulating the IL-4-induced microglia reactivity via the Samd4/mTOR/OXPHOS axis in PD mouse models and provide important insights into the pathogenesis and therapeutics of PD.


Assuntos
Modelos Animais de Doenças , Interleucina-4 , Microglia , Doença de Parkinson , Transdução de Sinais , Serina-Treonina Quinases TOR , Animais , Microglia/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Interleucina-4/metabolismo , Camundongos , Doença de Parkinson/metabolismo , Doença de Parkinson/patologia , Fosforilação Oxidativa , beta-Arrestinas/metabolismo , Mitocôndrias/metabolismo , Humanos , Masculino
15.
Laryngoscope ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39140234

RESUMO

OBJECTIVES: The relationship between the middle temporal (MTG) and occipital cortices in post-lingually deaf (PLD) individuals is unclear. This study aimed to investigate changes in the MTG and occipital cortices excitability and their effects on the occipital cortex in individuals with PLD after receiving a cochlear implant (CI). METHODS: Twenty-six individuals with severe-to-profound binaural sensorineural PLD were assessed clinically. Nine individuals had received a unilateral cochlear implant over 6 months, while 17 had not. Brodmann area 19 (BA19, extra-striate occipital cortex) and MTG (auditory-related area of cortex) were selected as regions of interest. The excitability of the ROI was observed and compared in the surgery and no-surgery groups by functional near-infrared spectroscopy (fNIRS) in the resting state, and correlations between connectivity of the MTG and occipital cortex, and as well as the duration of time that had elapsed following CI surgery, were investigated. RESULTS: fNIRS revealed enhanced global cortical connectivity in the BA19 and MTG on the operative side (p < 0.05) and the connectivity between BA19 and the MTG also increased (p < 0.05). The connectivity between the MTG and BA19 was positively correlated with the duration of cochlear implantation, as was the case for BA18. CONCLUSION: There was evidence for remodeling of the cerebral cortex: increased excitability was observed in the MTG and BA19, and their connectivity was enhanced, indicating a synergistic effect. Moreover, the MTG may further stimulate the visual cortex by strengthening their connectivity after CI. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

16.
RSC Adv ; 14(35): 25359-25368, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39144368

RESUMO

This study explored the preparation of a novel composite hydrogel based on deep eutectic solvent (DES) with lysine (Lys) and its application in pressure sensing and Fe3+ adsorption. DES was synthesized from acrylamide (AM) and urea (U) as hydrogen bond donors (HBD) with choline chloride (ChCl) as hydrogen bond acceptor (HBA), and Lys was used as a functional filler, and Lys/P(AM-U-ChCl) composite hydrogels were successfully prepared by frontal polymerization (FP) method. The structure of the hydrogels was characterized in depth using Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). The effects of Lys content on the mechanical properties, pH-responsive behavior, pressure-sensitive properties, and Fe3+ adsorption capacity of the hydrogels were further analyzed. It was found that the introduction of Lys significantly improved the compressive and pressure-sensitive properties of the hydrogels. The composite hydrogels exhibited excellent swelling equilibrium rates at different pH values. The capacitance change of the hydrogel with 0.5 wt% Lys at 200 g pressure was 2.12-fold higher than that of the hydrogel without Lys addition, and the adsorption efficiency of the hydrogel for Fe3+ was greatly enhanced. This study provides a new idea for the functionalized design of composite hydrogels and demonstrates their great application prospects in high-performance pressure sensors and heavy metal ion adsorption.

17.
BMC Neurosci ; 25(1): 34, 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39039434

RESUMO

The regulation of circadian rhythms and the sleep-wake states involves in multiple neural circuits. The suprachiasmatic nucleus (SCN) is a circadian pacemaker that controls the rhythmic oscillation of mammalian behaviors. The basal forebrain (BF) is a critical brain region of sleep-wake regulation, which is the downstream of the SCN. Retrograde tracing of cholera toxin subunit B showed a direct projection from the SCN to the horizontal limbs of diagonal band (HDB), a subregion of the BF. However, the underlying function of the SCN-HDB pathway remains poorly understood. Herein, activation of this pathway significantly increased non-rapid eye movement (NREM) sleep during the dark phase by using optogenetic recordings. Moreover, activation of this pathway significantly induced NREM sleep during the dark phase for first 4 h by using chemogenetic methods. Taken together, these findings reveal that the SCN-HDB pathway participates in NREM sleep regulation and provides direct evidence of a novel SCN-related pathway involved in sleep-wake states regulation.


Assuntos
Vias Eferentes , Optogenética , Núcleo Supraquiasmático , Animais , Núcleo Supraquiasmático/fisiologia , Masculino , Camundongos , Vias Eferentes/fisiologia , Camundongos Endogâmicos C57BL , Fases do Sono/fisiologia , Prosencéfalo Basal/fisiologia , Ritmo Circadiano/fisiologia , Eletroencefalografia
18.
Biol Direct ; 19(1): 57, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39039611

RESUMO

Laryngeal carcinoma (LC) is a common cancer of the respiratory tract. This study aims to investigate the role of RNA-binding motif protein 15 (RBM15) in the cisplatin (DDP) resistance of LC cells. LC-DDP-resistant cells were constructed. RBM15, lysine-specific demethylase 5B (KDM5B), lncRNA Fer-1 like family member 4 (FER1L4), lncRNA KCNQ1 overlapping transcript 1 (KCNQ1OT1), glutathione peroxidase 4 (GPX4), and Acyl-CoA synthetase long-chain family (ACSL4) was examined. Cell viability, IC50, and proliferation were assessed after RBM15 downregulation. The enrichment of insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3) and N6-methyladenosine (m6A) on KDM5B was analyzed. KDM5B mRNA stability was measured after actinomycin D treatment. A tumor xenograft assay was conducted to verify the role of RBM15 in LC. Results showed that RBM15 was upregulated in LC and its knockdown decreased IC50, cell viability, proliferation, glutathione, and upregulated iron ion content, ROS, malondialdehyde, ACSL4, and ferroptosis. Mechanistically, RBM15 improved KDM5B stability in an IGF2BP3-dependent manner, resulting in FER1L4 downregulation and GPX4 upregulation. KDM5B increased KCNQ1OT1 and inhibited ACSL4. KDM5B/KCNQ1OT1 overexpression or FER1L4 knockdown promoted DDP resistance in LC by inhibiting ferroptosis. In conclusion, RBM15 promoted KDM5B expression, and KDM5B upregulation inhibited ferroptosis and promoted DDP resistance in LC by downregulating FER1L4 and upregulating GPX4, as well as by upregulating KCNQ1OT1 and inhibiting ACSL4. Silencing RBM15 inhibited tumor growth in vivo.


Assuntos
Cisplatino , Resistencia a Medicamentos Antineoplásicos , Epigênese Genética , Ferroptose , Neoplasias Laríngeas , Proteínas de Ligação a RNA , Ferroptose/genética , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Linhagem Celular Tumoral , Camundongos , Animais , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Camundongos Nus , Regulação Neoplásica da Expressão Gênica , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/farmacologia , Coenzima A Ligases/genética , Coenzima A Ligases/metabolismo
19.
bioRxiv ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39005475

RESUMO

Motor cortical hyperexcitability is well-documented in the presymptomatic stage of amyotrophic lateral sclerosis (ALS). However, the mechanisms underlying this early dysregulation are not fully understood. Microglia, as the principal immune cells of the central nervous system, have emerged as important players in sensing and regulating neuronal activity. Here we investigated the role of microglia in the motor cortical circuits in a mouse model of TDP-43 neurodegeneration (rNLS8). Utilizing multichannel probe recording and longitudinal in vivo calcium imaging in awake mice, we observed neuronal hyperactivity at the initial stage of disease progression. Spatial and single-cell RNA sequencing revealed that microglia are the primary responders to motor cortical hyperactivity. We further identified a unique subpopulation of microglia, rod-shaped microglia, which are characterized by a distinct morphology and transcriptional profile. Notably, rod-shaped microglia predominantly interact with neuronal dendrites and excitatory synaptic inputs to attenuate motor cortical hyperactivity. The elimination of rod-shaped microglia through TREM2 deficiency increased neuronal hyperactivity, exacerbated motor deficits, and further decreased survival rates of rNLS8 mice. Together, our results suggest that rod-shaped microglia play a neuroprotective role by attenuating cortical hyperexcitability in the mouse model of TDP-43 related neurodegeneration.

20.
Plant Physiol Biochem ; 212: 108778, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38838570

RESUMO

The albino tea cultivar is one of the most important germplasms for key gene mining and high-quality tea producing. In order to elucidate the chlorophyll-deficient mechanism of albino cultivar 'Huangjinya' and its offspring, color difference, photosynthetic pigments and the relevant genes' expression of the tender shoots were comprehensively investigated in this study. Among the tested 16 offspring, 5 exhibited albino phenotype in spring and autumn, 3 showed albino phenotype in spring but normal green in autumn, while the rests were all normal green. The shoot of albino offspring had significantly higher lightness and/or yellowness than that of green ones, and possessed dramatically lower photosynthetic pigments and chlorophyll precursor protochlorophyllide (Pchlide), as well as higher chlorophyll a/chlorophyll b but lower chlorophylls/carotenoids in comparison with green ones. Among the tested genes involved in chlorophyll and carotenoid metabolism pathways, expression of the magnesium protoporphyrin IX monomethyl ester cyclase (CRD), 3,8-divinyl chlorophyllide 8-vinyl reductase (DVR), 5-aminolevulinate dehydratase 1 (HEMB1), 1-deoxy-D-xylulose 5-phosphate synthase 1 (DXS1) and 4-hydroxy-3-methylbut-2-enyl diphosphate reductase (ISPH) was remarkably down-regulated in shoots of the albino offspring. Color difference indices of the offspring were significantly correlated with the levels of photosynthetic pigments and Pchlide, and low level of chlorophylls in shoot of albino offspring was mainly due to conversion obstacle from magnesium protoporphyrin Ⅸ (Mg-Proto IX) to Pchlide which might be attributed to down-regulatory expression of CRD and DVR.


Assuntos
Clorofila , Fenótipo , Protoclorifilida , Protoporfirinas , Clorofila/metabolismo , Protoclorifilida/metabolismo , Protoporfirinas/metabolismo , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Fotossíntese
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