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1.
Cancer Med ; 13(17): e70175, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39240166

RESUMEN

BACKGROUND: The therapeutic advantage of thoracic radiotherapy (tRT) as an adjunct to first-line immunotherapy and chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC) remains unclear. We sought to elucidate this in a retrospective cohort study comparing the effectiveness and safety of tRT in combination with first-line immunotherapy and chemotherapy. METHODS: Our retrospective study included patients with ES-SCLC, treated at the West China Hospital between January 2019 and December 2022. They received first-line immunotherapy and chemotherapy and were categorized into two cohorts based on the administration of tRT. The primary outcomes were overall survival (OS) and progression-free survival (PFS). Cox regression analysis was utilized to identify potential independent predictors of prognosis and to compare the treatment outcomes across various patient subgroups. Treatment-related toxicities across both cohorts were compared using the Chi-squared test. RESULTS: A total of 99patients were eligible for the study, out of which 55 received tRT. The medianduration of follow-up was 39 months. Remarkably, patients who received tRTdemonstrated superior OS and PFS in comparison to those who did not (P < 0.05). Subgroup analysis further confirmed these findings. Multivariate analysisidentified treatment group and liver metastasis as independent prognosticfactors (P < 0.05). The incidence of grade 3-4 adverse events showed nostatistically significant difference between the two cohorts. CONCLUSIONS: Thus, weconfirmed that the addition of tRT to the conventional regimen of first-linechemotherapy and immunotherapy yields better survival outcomes without asignificant increase in toxicity.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Carcinoma Pulmonar de Células Pequeñas/radioterapia , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/terapia , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Anciano , Resultado del Tratamiento , Adulto , Supervivencia sin Progresión , Inmunoterapia/métodos , Pronóstico , Terapia Combinada
2.
Small ; : e2404346, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39235385

RESUMEN

Magnetic 2D materials offer a promising platform for manipulating quantum states at the nanoscale. Recent studies have underscored the significant influence of 2D magnetic materials on the optical behaviors of transition-metal dichalcogenides (TMDs), revealing phenomena such as interlayer exciton-magnon interactions, magnetization-dependent valley polarization, and an enhanced Zeeman effect. However, the controlled manipulation of anisotropic optical properties in TMDs via magnetism remains challenging. Here, the magnetic ordering in FePS3 profoundly impacts the optical characteristics of WSe2, achieving a giant linear polarization degree of 5.1 in exciton emission is demonstrated. This is supported by a detailed analysis of low-temperature photoluminescence (PL) and Raman spectra from nL-FePS3/WSe2 heterostructures. These findings indicate that a phase transition in FePS3 from paramagnetic to antiferromagnetic enhances interlayer Coulomb interactions, inducing a transition from non-polar to polar behavior in the heterostructures. Additionally, valley-polarized PL spectra under magnetic fields from -9 to 9 T reveal the influence of FePS3 on valley polarization and Zeeman splitting of excitons in monolayer WSe2. These results present a novel strategy for tailoring the optoelectronic properties of 2D magnetic van der Waals heterostructures, paving the way for advancements in nanoscale device design.

3.
Artículo en Inglés | MEDLINE | ID: mdl-39298334

RESUMEN

Heterostructure engineering provides versatile platforms for exploring exotic physics and enhancing the device performance through interface coupling. Despite the rich array of physical phenomena presented by heterostructures composed of semiconductor and metal van der Waals materials, significant gaps remain in understanding their optical, thermal, and electronic properties. Here, we demonstrate that the valley pseudospin and electron-phonon coupling in monolayer WSe2 are significantly influenced by interface coupling with 1T-VSe2. The heterointerface alters the relaxation process of valley excitons, leading to a transition in magnetic-field-dependent valley polarization from a linear to a "V" shape. Furthermore, we uncover that enhanced electron-phonon coupling exacerbates variations in exciton and valley exciton behavior with temperature, involving higher phonon energies and a shift from acoustic to optical phonons. These findings highlight a promising pathway to manipulate valley excitons and investigate electron-phonon coupling through van der Waals interface interactions.

4.
Int J Ophthalmol ; 17(8): 1387-1395, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39156784

RESUMEN

AIM: To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fibroblasts (HPFs) and its correlation with the severity grades of pterygium. METHODS: Pterygium and normal conjunctival tissues were collected from the superior area of the same patient's eye (n=33). The correlation between pterygium severity and hsa_circ_0007482 expression using quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were analyzed. Three distinct siRNA sequences targeting hsa_circ_0007482, along with a negative control sequence, were transfected into HPFs. Cell proliferation was assessed using the cell counting kit-8. Expression levels of Ki67, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bax, B-cell lymphoma-2 (Bcl-2), and Caspase-3 were measured via RT-qPCR. Immunofluorescence staining was employed to detect Ki67 and vimentin expressions. Apoptosis was evaluated using flow cytometry. RESULTS: Hsa_circ_0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues (P<0.001). Positive correlations were observed between hsa_circ_0007482 expression and pterygium severity, thickness, and vascular density. Knockdown of hsa_circ_0007482 inhibited cell proliferation, reducing the mRNA expression of Ki67, PCNA, and Cyclin D1 in HPFs. Hsa_circ_0007482 knockdown induced apoptosis, increasing mRNA expression levels of Bax and Caspase-3, while decreasing Bcl-2 expression in HPFs. Additionally, hsa_circ_0007482 knockdown attenuated vimentin expression in HPFs. CONCLUSION: The downregulation of hsa_circ_0007482 effectively hampers cell proliferation and triggers apoptosis in HPFs. There are discernible positive correlations detected between the expression of hsa_circ_0007482 and the severity of pterygium.

5.
Nano Lett ; 24(30): 9186-9194, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-39012034

RESUMEN

The interaction between light and moiré superlattices presents a platform for exploring unique light-matter phenomena. Tailoring these optical properties holds immense potential for advancing the utilization of moiré superlattices in photonics, optoelectronics, and valleytronics. However, the control of the optical polarization state in moiré superlattices, particularly in the presence of moiré effects, remains elusive. Here, we unveil the emergence of optical anisotropy in moiré superlattices by constructing twisted WSe2/WSe2/SiP heterostructures. We report a linear polarization degree of ∼70% for moiré excitons, attributed to the spatially nonuniform charge distribution, corroborated by first-principles calculations. Furthermore, we demonstrate the modulation of this linear polarization state via the application of a magnetic field, resulting in polarization angle rotation and a magnetic-field-dependent linear polarization degree, influenced by valley coherence and moiré potential effects. Our findings demonstrate an efficient strategy for tuning the optical polarization state of moiré superlattices using heterointerface engineering.

6.
Small ; : e2403267, 2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-38982953

RESUMEN

Carbon-based perovskite solar cells (PSCs) coupled with solution-processed hole transport layers (HTLs) have shown potential owing to their combination of low cost and high performance. However, the commonly used poly(3-hexylthiophene) (P3HT) semicrystalline-polymer HTL dominantly shows edge-on molecular orientation, in which the alkyl side chains directly contact the perovskite layer, resulting in an electronically poor contact at the perovskite/P3HT interface. The study adopts a synergetic strategy comprising of additive and solvent engineering to transfer the edge-on molecular orientation of P3HT HTL into 3D molecular orientation. The target P3HT HTL possesses improved charge transport as well as enhanced moisture-repelling capability. Moreover, energy level alignment between target P3HT HTL and perovskite layer is realized. As a result, the champion devices with small (0.04 cm2) and larger areas (1 cm2) deliver notable efficiencies of 20.55% and 18.32%, respectively, which are among the highest efficiency of carbon-electrode PSCs.

7.
RSC Adv ; 14(31): 22582-22586, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39021454

RESUMEN

Most studies investigate the cyclable capacity fading mechanism of Li-rich layered oxides (LLOs) from the microscopic structure level, lacking discussions about how the structure degradation influences the performance of the pouch cell precisely and quantitatively. Based on the analysis of the evolution of key parameters during the whole cycling period, a new transition-type fading mechanism is proposed. From the early-to-middle stage of the cycling period, polarization increases, most of which is interface-related, causing about 67% of the whole capacity loss. From the middle-to-late stage of the cycling period, active material losses turn out to be the dominating factor, inducing about 61% of the total capacity loss. Diffusion-related polarization, replacing the interface type, is responsible for most of the increased overpotential. Relative analysis confirms that during the early stage, the increase of the charge transfer resistance, induced by CEI (cathode electrolyte interface) growth and initial surface layered-structure degradation, is the main source of interface polarization. As the cycling evolves to the late stage, severe bulky structure degradation, including lattice-oxygen release, Li/Ni mixture and generation of a new spinel phase, turns out to be the major factor, causing further capacity fading.

8.
Front Pharmacol ; 15: 1404119, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39021836

RESUMEN

Lycium ruthenicum Murray (LR), known as "black goji berry" or "black wolfberry", is widely utilized in chinese herbal medicine. LR fruit showed its antioxidant and/or anti-inflammation activity in treating cardiac injury, experimental colitis, nonalcoholic fatty liver disease, fatigue, and aging. Glaucoma is the leading cause of irreversible blindness. Besides elevated intraocular pressure (IOP), oxidative stress and neuroinflammation were recognized to contribute to the pathogenesis of glaucoma. This study investigated the treatment effects of LR water extract (LRE) on retinal ganglion cells (RGCs) threatened by sustained IOP elevation in a laser-induced chronic ocular hypertension (COH) mouse model and the DBA/2J mouse strain. The antioxidation and anti-inflammation effects of LRE were further tested in the H2O2-challenged immortalized microglial (IMG) cell line in vitro. LRE oral feeding (2 g/kg) preserved the function of RGCs and promoted their survival in both models mimicking glaucoma. LRE decreased 8-hydroxyguanosine (oxidative stress marker) expression in the retina. LRE reduced the number of Iba-1+ microglia in the retina of COH mice, but not in the DBA/2J mice. At the mRNA level, LRE reversed the COH induced HO-1 and SOD-2 overexpressions in the retina of COH mice. Further in vitro study demonstrated that LRE pretreatment to IMG cells could significantly reduce H2O2 induced oxidative stress through upregulation of GPX-4, Prdx-5, HO-1, and SOD-2. Our work demonstrated that daily oral intake of LRE can be used as a preventative/treatment agent to protect RGCs under high IOP stress probably through reducing oxidative stress and inhibiting microglial activation in the retina.

9.
Nano Lett ; 24(26): 8189-8197, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38904278

RESUMEN

IV-V two-dimensional materials have emerged as key contenders for polarization-sensitive and angle-resolved devices, given their inherent anisotropic physical properties. While these materials exhibit intriguing high-pressure quasi-particle behavior and phase transition, the evolution of quasi-particles and their interactions under external pressure remain elusive. Here, employing a diamond anvil cell and spectroscopic measurements coupled with first-principles calculations, we unveil rarely observed pressure-induced phonon-phonon coupling in layered SiP flakes. This coupling manifests as an anomalous phonon hardening behavior for the A1 mode within a broad wavenumber phonon softening region. Furthermore, we demonstrate the effective tuning of exciton emissions in SiP flakes under pressure, revealing a remarkable 63% enhancement in the degree of polarization (DOP) within the pressure range of 0-3.5 GPa. These findings contribute to our understanding of high-pressure phonon evolution in SiP materials and offer a strategic approach to manipulate the anisotropic performance of in-plane anisotropic 2D materials.

10.
Front Genet ; 15: 1405715, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38933921

RESUMEN

In recent years, burgeoning research has underscored the pivotal role of non-coding RNA in orchestrating the growth, development, and pathogenesis of various diseases across organisms. However, despite these advances, our understanding of the specific contributions of long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) to lens development remains notably limited. Clarifying the intricate gene regulatory networks is imperative for unraveling the molecular underpinnings of lens-related disorders. In this study, we aimed to address this gap by conducting a comprehensive analysis of the expression profiles of messenger RNAs (mRNAs), lncRNAs, and circRNAs at critical developmental time points of the mouse lens, encompassing both embryonic (E10.5, E12.5, and E16.5) and postnatal stages (P0.5, P10.5, and P60). Leveraging RNA-sequencing technology, we identified key transcripts pivotal to lens development. Our analysis revealed differentially expressed (DE) mRNAs, lncRNAs, and circRNAs across various developmental stages. Particularly noteworthy, there were 1831 co-differentially expressed (CO-DE) mRNAs, 150 CO-DE lncRNAs, and 13 CO-DE circRNAs identified during embryonic stages. Gene Ontology (GO) enrichment analysis unveiled associations primarily related to lens development, DNA conformational changes, and angiogenesis among DE mRNAs and lncRNAs. Furthermore, employing protein-protein interaction networks, mRNA-lncRNA co-expression networks, and circRNA-microRNA-mRNA networks, we predicted candidate key molecules implicated in lens development. Our findings underscore the pivotal roles of lncRNAs and circRNAs in this process, offering fresh insights into the pathogenesis of lens-related disorders and paving the way for future exploration in this field.

11.
Exp Eye Res ; 244: 109939, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38789021

RESUMEN

Transforming growth factor-ß2 (TGF-ß2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-ß2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-ß2-induced cell migration, and mitigated TGF-ß2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-ß2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-ß2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-ß2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-ß2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-ß2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.


Asunto(s)
Movimiento Celular , Proliferación Celular , Transducción de Señal , Silibina , Malla Trabecular , Humanos , Antioxidantes/farmacología , Western Blotting , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibrosis , Glaucoma de Ángulo Abierto/metabolismo , Glaucoma de Ángulo Abierto/tratamiento farmacológico , Glaucoma de Ángulo Abierto/patología , Janus Quinasa 2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Silibina/farmacología , Silimarina/farmacología , Factor de Transcripción STAT3/metabolismo , Malla Trabecular/efectos de los fármacos , Malla Trabecular/metabolismo , Malla Trabecular/patología , Factor de Crecimiento Transformador beta2/farmacología , Factor de Crecimiento Transformador beta2/metabolismo
12.
Nat Commun ; 15(1): 3079, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38594273

RESUMEN

Reconstructive phase transitions involving breaking and reconstruction of primary chemical bonds are ubiquitous and important for many technological applications. In contrast to displacive phase transitions, the dynamics of reconstructive phase transitions are usually slow due to the large energy barrier. Nevertheless, the reconstructive phase transformation from ß- to λ-Ti3O5 exhibits an ultrafast and reversible behavior. Despite extensive studies, the underlying microscopic mechanism remains unclear. Here, we discover a kinetically favorable in-plane nucleated layer-by-layer transformation mechanism through metadynamics and large-scale molecular dynamics simulations. This is enabled by developing an efficient machine learning potential with near first-principles accuracy through an on-the-fly active learning method and an advanced sampling technique. Our results reveal that the ß-λ phase transformation initiates with the formation of two-dimensional nuclei in the ab-plane and then proceeds layer-by-layer through a multistep barrier-lowering kinetic process via intermediate metastable phases. Our work not only provides important insight into the ultrafast and reversible nature of the ß-λ transition, but also presents useful strategies and methods for tackling other complex structural phase transitions.

13.
ACS Appl Mater Interfaces ; 16(15): 18980-18990, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38577916

RESUMEN

Although nonflammable electrolytes are beneficial for battery safety, they often adversely affect the electrochemical performance of lithium-ion batteries due to their poor compatibility with electrodes. Herein, we design a nonflammable electrolyte consisting of cyclic carbonate and 2,2-difluoroethyl acetate (DFEA) solvents paired with several surface-film-forming additives, significantly improving the safety and cycling performance of NMC811||SiOx/graphite pouch cells. The DFEA solvent exhibits not only good flame retardancy but also lower lowest unoccupied molecular orbital (LUMO) energy, promoting the formation of a robust inorganic-rich and gradient-architecture hybrid interface between the SiOx/graphite anode and electrolyte. The double insurance of good flame retardancy of the DFEA solvent and decreased exothermic effects of both bulk electrolyte and DFEA-derived solid electrolyte interphase (SEI) can ensure the high safety of the pouch cell. Moreover, the highly robust SEI can prevent the excessive reduction decomposition of the electrolyte and alleviate the structural decay of the anode, which can restrain the formation of lithium deposition on the anode surface and further suppress the structural decay of NMC materials. This contributes to the unprecedented cycling performance of the NMC811||SiOx/graphite pouch cells with a capacity retention of 80% after 1000 cycles at a 0.33C rate.

14.
Ann Med ; 56(1): 2331056, 2024 12.
Artículo en Inglés | MEDLINE | ID: mdl-38507901

RESUMEN

OBJECTIVES: To analyze the factors influencing myopia and construct a nomogram to forecast the risk of myopia among school-age children, providing a reference for identifying high-risk groups to aid prevention and control. METHODS: This case-control study enrolled 3512 students from three primary schools in Shenzhen using random cluster sampling for a questionnaire survey, myopia screening and ocular biometric parameter measurement. Logistic regression was used to analyze the influencing factors of myopia, and a nomogram was constructed to forecast myopia risk. Bootstrap resampling was used to verify the practicability of the nomogram. RESULTS: Older age (odds ratio[OR] = 1.164; 95% confidence interval [CI]: 1.111-1.219), female sex (OR = 2.405; 95% CI: 2.003-2.887), maternal myopia (OR = 1.331; 95% CI: 1.114-1.589), incorrect posture during reading and writing (OR = 1.283; 95% CI: 1.078-1.528) and axial length (OR = 7.708; 95% CI: 6.044-8.288) are risk factors for myopia, whereas an increase in corneal radius (OR = 0.036; 95% CI: 0.025-0.052) is a protective factor against myopia. The area under the receiver operating characteristic (ROC) curve of the nomogram was 0.857, and the net benefit was high when the risk threshold of the decision curve analyses (DCA) ranged from 0.20 to 1.00. The measured values were consistent with the prediction. CONCLUSION: The nomogram was accurate in predicting the risk of myopia among schoolchildren. This study provides a reference for screening high-risk students and for individualized myopia prevention and control.


Older age, female sex, maternal myopia, incorrect posture during reading and writing, and prolonged axial length are risk factors for myopia among primary school students.The nomogram constructed based on age, sex, maternal myopia, incorrect posture during reading and writing, axial length and corneal radius showed good predictive accuracy and practicability.The nomogram constructed in this study can be used for individualized myopia risk assessment.


Asunto(s)
Miopía , Nomogramas , Niño , Humanos , Femenino , Estudios de Casos y Controles , Estudiantes , Factores de Riesgo , Miopía/diagnóstico , Miopía/epidemiología , Miopía/prevención & control
15.
Front Biosci (Landmark Ed) ; 29(3): 91, 2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38538254

RESUMEN

OBJECTIVE: The morphology and functions of the human trabecular meshwork (HTM) are dysregulated in glaucoma, and the molecular mechanisms of this dysregulation remain unknown. According to an established in vitro model, whose function was to study the regulatory networks sustaining the response of HTM cells to the increased substrate stiffness, we systematically analyzed the expression pattern of long noncoding RNAs (lncRNAs), the important regulatory RNAs in cells. METHODS: Bioinformatics analysis was performed to identify the dysregulated lncRNAs in response to increased substrate stiffness using transcriptome sequencing data (RNA-seq). Then we interfered with the expression of several dysregulated lncRNAs in HTM cells to explore their molecular targets. The cross-linking immunoprecipitation and sequencing method (CLIP-seq) was used to identify enhancer of zeste homolog 2 (EZH2)-targeted RNAs in HTM cells. The chromatin IP and sequencing method (ChIP-seq) was used to identify the targets of EZH2 and histone H3 at lysine 27 (H3K27me3). RESULTS: The response of thousands of dysregulated lncRNAs to increased substrate stiffness was identified through RNA-seq. Functional prediction of these lncRNAs revealed that they potentially regulated key biological processes, including extracellular matrix (ECM) organization. By interfering with the expression of lncRNA SHNG8, ZFHX4-AS1, and RP11-552M11.4, the results demonstrated that those lncRNAs extensively regulated the expression levels of ECM-associated genes. Moreover, we found that EZH2 expression was significantly decreased at high substrate stiffness. Using CLIP-seq to identify EZH2-targeted RNAs in HTM cells, we found that SNHG8 was bound by EZH2. According to the CLIP-seq data of EZH2, we found that EZH2 binding sites were observed in the transcripts of SNHG8-regulated genes, but not in the ChIP-seq results of EZH2 and H3K27me3. CONCLUSION: Our results suggest that SNHG8 and EZH2 may cooperate to regulate the expression of a subset of genes by influencing their RNA abundance, explaining how they support HTM cell morphology and high density. This study contributes to the understanding of the alteration of HTM during the progression of glaucoma by identifying functional lncRNAs, especially SNHG8, and suggests novel therapeutic targets to treat glaucoma.


Asunto(s)
Glaucoma , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Histonas/metabolismo , Transcriptoma , Malla Trabecular/metabolismo , Cromatina/metabolismo , Biología Computacional/métodos , Glaucoma/genética , Glaucoma/metabolismo
16.
In Vitro Cell Dev Biol Anim ; 60(3): 278-286, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38485819

RESUMEN

Previous studies have implicated targeting Pim-1 proto-oncogene, serine/threonine kinase (PIM1) as a preventive measure against high glucose-induced cellular stress and apoptosis. This study aimed to reveal the potential role and regulatory mechanism of PIM1 in diabetic retinopathy. Human retinal microvascular endothelial cells (hRMECs) underwent high glucose induction, and fluctuations in PIM1 levels were assessed. By overexpressing PIM1, its effects on the levels of inflammatory factors, oxidative stress indicators, migration and tube formation abilities, tight junction protein expression levels, and ferroptosis in hRMECs were identified. Afterwards, hRMECs were treated with the ferroptosis-inducing agent erastin, and the effect of erastin on the above PIM1 regulatory functions was focused on. PIM1 was downregulated upon high glucose, and its overexpression inhibited the inflammatory response, oxidative stress, cell migration, and tube formation potential in hRMECs, whereas elevated tight junction protein levels. Furthermore, PIM1 overexpression reduced intracellular iron ion levels, lipid peroxidation, and levels of proteins actively involved in ferroptosis. Erastin treatment reversed the impacts of PIM1 on hRMECs, suggesting the mediation of ferroptosis in PIM1 regulation. The current study has yielded critical insights into the role of PIM1 in ameliorating high glucose-induced hRMEC dysfunction through the inhibition of ferroptosis.


Asunto(s)
Células Endoteliales , Ferroptosis , Humanos , Animales , Retina/metabolismo , Proteínas de Uniones Estrechas/metabolismo , Glucosa/toxicidad , Glucosa/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/farmacología
17.
CNS Neurosci Ther ; 30(2): e14594, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38332538

RESUMEN

BACKGROUND: With the rapidly increasing prevalence of metabolic diseases such as type 2 diabetes mellitus (T2DM), neuronal complications associated with these diseases have resulted in significant burdens on healthcare systems. Meanwhile, effective therapies have remained insufficient. A novel fatty acid called S-9-PAHSA has been reported to provide metabolic benefits in T2DM by regulating glucose metabolism. However, whether S-9-PAHSA has a neuroprotective effect in mouse models of T2DM remains unclear. METHODS: This in vivo study in mice fed a high-fat diet (HFD) for 5 months used fasting blood glucose, glucose tolerance, and insulin tolerance tests to examine the effect of S-9-PAHSA on glucose metabolism. The Morris water maze test was also used to assess the impact of S-9-PAHSA on cognition in the mice, while the neuroprotective effect of S-9-PAHSA was evaluated by measuring the expression of proteins related to apoptosis and oxidative stress. In addition, an in vitro study in PC12 cells assessed apoptosis, oxidative stress, and mitochondrial membrane potential with or without CAIII knockdown to determine the role of CAIII in the neuroprotective effect of S-9-PAHSA. RESULTS: S-9-PAHSA reduced fasting blood glucose levels significantly, increased insulin sensitivity in the HFD mice and also suppressed apoptosis and oxidative stress in the cortex of the mice and PC12 cells in a diabetic setting. By suppressing oxidative stress and apoptosis, S-9-PAHSA protected both neuronal cells and microvascular endothelial cells in in vivo and in vitro diabetic environments. Interestingly, this protective effect of S-9-PAHSA was reduced significantly when CAIII was knocked down in the PC12 cells, suggesting that CAIII has a major role in the neuroprotective effect of S-9-PAHSA. However, overexpression of CAIII did not significantly enhance the protective effect of S-9-PAHSA. CONCLUSION: S-9-PAHSA mediated by CAIII has the potential to exert a neuroprotective effect by suppressing apoptosis and oxidative stress in neuronal cells exposed to diabetic conditions. Furthermore, S-9-PAHSA has the capability to reduce fasting blood glucose and LDL levels and enhance insulin sensitivity in mice fed with HFD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Fármacos Neuroprotectores , Ácido Palmítico , Ácidos Esteáricos , Animales , Ratones , Ratas , Apoptosis , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Células Endoteliales/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Estrés Oxidativo , Anhidrasa Carbónica III/efectos de los fármacos , Anhidrasa Carbónica III/metabolismo
18.
Front Med (Lausanne) ; 11: 1351272, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38384405

RESUMEN

With the widespread application of Implantable Collamer Lens (ICL) implantation surgery in the field of myopia correction, a comprehensive understanding of its potential complications, especially those related to intraocular pressure (IOP), becomes crucial. This article systematically reviews various complications that may lead to IOP elevation after ICL surgery. Firstly, common complications after ICL surgery, including residual viscoelastic, steroid response, and excessive vault of the ICL, are detailed, emphasizing their potential impact on intraocular pressure. Regarding residual viscoelastic, we delve into its direct relationship with postoperative elevated IOP and possible preventive measures. For steroid response, we stress the importance of timely adjustment of steroid therapy and monitoring intraocular pressure. Additionally, excessive vault of the ICL is considered a significant potential issue, and we elaborate on its mechanism and possible management methods. In further discussion, we focus on relatively rare complications such as Toxic Anterior Segment Syndrome (TASS), Urrets-Zavalia Syndrome (UZS), Pigment Dispersion Syndrome (PDS), and malignant glaucoma. For these relatively rare complications, this review thoroughly explores their potential mechanisms, emphasizes the importance of prevention, and provides guidance for early diagnosis and treatment. This is a comprehensible review that aims to offer eye care professionals a comprehensive understanding and effective management guidance for complications of elevated IOP after ICL surgery, ultimately providing optimal care for patients' visual health.

19.
J Cardiothorac Surg ; 19(1): 57, 2024 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-38311778

RESUMEN

PURPOSE: To evaluate the efficacy and safety of selective aneurysmal sac neck-targeted embolization in endovascular aneurysm repair (EVAR) in patients with a hostile neck anatomy (HNA). MATERIALS AND METHODS: Between October 2020 and June 2022, patients with an abdominal aortic aneurysm (AAA) and HNA who underwent EVAR with a low-profile stent graft and a selective aneurysmal sac neck-targeted embolization technique were analysed. An HNA was defined by the presence of any of the following parameters: infrarenal neck angulation > 60°; neck length < 15 mm; conical neck; circumferential calcification ≥ 50%; or thrombus ≥ 50%. Before occluding the entire aneurysm during the procedure, a buddy wire was loaded prophylactically into the sac through the contralateral limb side. If a type Ia endoleak (ELIa) occurred and persisted despite adjunctive treatment such as balloon moulding or cuff extension, this preloaded wire could be utilized to enable a catheter to reach the space between the stent graft and sac neck to perform coil embolization. In the absence of ELIa, the wire was simply retracted. The primary outcome of this study was freedom from sac expansion and endoleak-related reintervention during the follow-up period; secondary outcomes included technical success and intraoperative and in-hospital postoperative complications. RESULTS: Among the 28 patients with a hostile neck morphology, 11 (39.5%) who presented with ELIa underwent intraprocedural treatment involving sac neck-targeted detachable coil embolization. Seventeen individuals (60.7%) of the total patient population did not undergo coiling. All patients in the coiling group underwent balloon moulding, and 2 patients additionally underwent cuff extension. In the noncoiling group, 14 individuals underwent balloon moulding as a treatment for ELIa, while 3 patients did not exhibit ELIa during the procedure. The coiling group showed longer operating durations (81.27 ± 11.61 vs. 70.71 ± 7.17 min, P < 0.01) and greater contrast utilization than the noncoiling group (177.45 ± 52.41 vs. 108.24 ± 17.49 ml, P < 0.01). In the entire cohort, the technical success rate was 100%, and there were no procedure-related complications. At a mean follow-up of 18.6 ± 5.2 months (range 12-31), there were no cases of sac expansion (19 cases of sac regression, 67.86%; 9 cases of stability, 32.14%) or endoleak-related reintervention. CONCLUSIONS: Selective aneurysmal sac neck-targeted embolization for the treatment of ELIa in AAA patients with an HNA undergoing EVAR is safe and may prevent type Ia endoleak and related sac expansion after EVAR.


Asunto(s)
Aneurisma de la Aorta Abdominal , Implantación de Prótesis Vascular , Procedimientos Endovasculares , Humanos , Aneurisma de la Aorta Abdominal/cirugía , Aneurisma de la Aorta Abdominal/complicaciones , Endofuga/etiología , Implantación de Prótesis Vascular/efectos adversos , Factores de Riesgo , Resultado del Tratamiento , Procedimientos Endovasculares/efectos adversos , Estudios Retrospectivos , Stents/efectos adversos
20.
Rev Sci Instrum ; 95(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38310639

RESUMEN

A specially designed experimental apparatus suitable for commercial superconductor magnet is used for solidification and in situ characterization of the nucleation behavior of high-melting metals. In order to carry out solidification experiments under a high magnetic field (HMF), the sample cell in the experimental device has two stations for repeated verification experiments of two same samples or comparative experiments of two different samples. Meanwhile, a metal specimen and a reference (α-Al2O3) are placed in the sample cell to characterize the nucleation behavior in situ. Using this experimental device, the nucleation behaviors of Al-7wt. %Si alloy and pure Cu under a HMF were investigated. The results show that the undercoolings of Al-7wt. %Si alloy and pure Cu increase under the HMF. Furthermore, the applied HMF decreases the activation energy of Al-7wt. %Si alloy and increases the nucleation work. Based on the magnetohydrodynamic effect, the change in undercooling and nucleation work could be partly attributed to the restrained thermal convection by the HMF in this study.

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