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1.
Neural Regen Res ; 20(4): 1042-1057, 2025 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38989936

RESUMEN

Spinal cord injuries impose a notably economic burden on society, mainly because of the severe after-effects they cause. Despite the ongoing development of various therapies for spinal cord injuries, their effectiveness remains unsatisfactory. However, a deeper understanding of metabolism has opened up a new therapeutic opportunity in the form of metabolic reprogramming. In this review, we explore the metabolic changes that occur during spinal cord injuries, their consequences, and the therapeutic tools available for metabolic reprogramming. Normal spinal cord metabolism is characterized by independent cellular metabolism and intercellular metabolic coupling. However, spinal cord injury results in metabolic disorders that include disturbances in glucose metabolism, lipid metabolism, and mitochondrial dysfunction. These metabolic disturbances lead to corresponding pathological changes, including the failure of axonal regeneration, the accumulation of scarring, and the activation of microglia. To rescue spinal cord injury at the metabolic level, potential metabolic reprogramming approaches have emerged, including replenishing metabolic substrates, reconstituting metabolic couplings, and targeting mitochondrial therapies to alter cell fate. The available evidence suggests that metabolic reprogramming holds great promise as a next-generation approach for the treatment of spinal cord injury. To further advance the metabolic treatment of the spinal cord injury, future efforts should focus on a deeper understanding of neurometabolism, the development of more advanced metabolomics technologies, and the design of highly effective metabolic interventions.

2.
J Med Chem ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39250558

RESUMEN

Triggering ferroptosis represents a promising anticancer therapeutic strategy, but the development of a selective ferroptosis inducer for cancer-specific therapy remains a great challenge. Herein, a H2S-responsive iridium(III) complex NA-Ir has been well-designed as a ferroptosis inducer. NA-Ir could selectively light up H2S-rich cancer cells, primarily localize in mitochondria, intercalate into mitochondrial DNA (mtDNA), and induce mtDNA damage, exhibiting higher anticancer activity under light irradiation. Mechanistic studies showed that NA-Ir-mediated PDT triggered lipid peroxidation and glutathione peroxidase 4 downregulation through ROS production and GSH depletion, resulting in ferroptosis through multiple pathways. Moreover, the intense mtDNA damage can activate the cyclic GMP-AMP synthase-stimulator of the interferon gene (cGAS-STING) pathway, leading to ferritinophagy and further ferroptosis. RNA-sequencing analysis showed that NA-Ir-mediated PDT mainly affects the expression of genes related to ferroptosis, autophagy, and cancer immunity. This study demonstrates the first cancer-specific example with ferroptosis and cGAS-STING activation, which provides a new strategy for multimodal synergistic therapy.

3.
Nat Commun ; 15(1): 7843, 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245687

RESUMEN

Pompe disease (PD) is a rare autosomal recessive glycogen storage disorder that causes proximal muscle weakness and loss of respiratory function. While enzyme replacement therapy (ERT) is the only effective treatment, biomarkers for disease monitoring are scarce. Following ex vivo biomarker validation in phantom studies, we apply multispectral optoacoustic tomography (MSOT), a laser- and ultrasound-based non-invasive imaging approach, in a clinical trial (NCT05083806) to image the biceps muscles of 10 late-onset PD (LOPD) patients and 10 matched healthy controls. MSOT is compared with muscle magnetic resonance imaging (MRI), ultrasound, spirometry, muscle testing and quality of life scores. Next, results are validated in an independent LOPD patient cohort from a second clinical site. Our study demonstrates that MSOT enables imaging of subcellular disease pathology with increases in glycogen/water, collagen and lipid signals, providing higher sensitivity in detecting muscle degeneration than current methods. This translational approach suggests implementation in the complex care of these rare disease patients.


Asunto(s)
Enfermedad del Almacenamiento de Glucógeno Tipo II , Glucógeno , Imagen por Resonancia Magnética , Técnicas Fotoacústicas , Humanos , Enfermedad del Almacenamiento de Glucógeno Tipo II/diagnóstico por imagen , Enfermedad del Almacenamiento de Glucógeno Tipo II/metabolismo , Enfermedad del Almacenamiento de Glucógeno Tipo II/patología , Glucógeno/metabolismo , Técnicas Fotoacústicas/métodos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Estudios de Casos y Controles , Ultrasonografía/métodos , Fantasmas de Imagen
4.
Sci Rep ; 14(1): 20896, 2024 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-39245685

RESUMEN

The purpose of this study is to evaluate whether the periprostatic adipose tissue thickness (PPATT) is an independent prognostic factor for prostate cancer patients after laparoscopic radical prostatectomy (LRP). This retrospective cohort study included consecutive prostate cancer patients who underwent LRP treatment at Wuhan Union Hospital from June 2, 2016, to September 7, 2023. PPATT was defined as the thickness of periprostatic fat and was obtained by measuring the shortest vertical distance from the pubic symphysis to the prostate on the midsagittal T2-weighted MR images. Subcutaneous adipose tissue thickness (SATT) was obtained by measuring the shortest vertical distance from the pubic symphysis to the skin at the same slice with PPATT. The primary outcome of the study was biochemical recurrence (BCR), and the secondary outcome was overall survival (OS). Multivariable Cox regression analysis was used to identify independent prognostic factors for prostate cancer survival and prognosis. Based on the optimal cutoff value, 162 patients were divided into a low PPATT/SATT group (n = 82) and a high PPATT/SATT group (n = 80). During the entire follow-up period (median 23.5 months), 26 patients in the high PPATT/SATT group experienced BCR (32.5%), compared to 18 in the low PPATT/SATT group (22.0%). Kaplan-Meier curve analysis indicated that the interval to BCR was significantly shorter in the high PPATT/SATT group (P = 0.037). Multivariable Cox regression analysis revealed that an increase in the PPATT/SATT ratio was associated with BCR (hazard ratio: 1.90, 95% CI, 1.03-3.51; P = 0.040). The PPATT/SATT ratio is a significant independent risk factor for BCR after LRP for prostate cancer patients.


Asunto(s)
Imagen por Resonancia Magnética , Próstata , Prostatectomía , Neoplasias de la Próstata , Grasa Subcutánea , Humanos , Masculino , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/diagnóstico por imagen , Persona de Mediana Edad , Anciano , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/patología , Imagen por Resonancia Magnética/métodos , Factores de Riesgo , Estudios Retrospectivos , Próstata/patología , Próstata/cirugía , Próstata/diagnóstico por imagen , Pronóstico , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología
5.
Adv Sci (Weinh) ; : e2405997, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287090

RESUMEN

Radiotherapy is a curative arsenal for prostate cancer (PCa), but radioresistance seriously compromises its effectiveness. Dysregulated RNA splicing factors are extensively involved in tumor progression. Nonetheless, the role of splicing factors in radioresistance remains largely unexplored in PCa. Here, 23 splicing factors that are differentially expressed between PCa and adjacent normal tissues across multiple public PCa databases are identified. Among those genes, polypyrimidine tract binding protein 1 (PTBP1) is significantly upregulated in PCa and is positively associated with advanced clinicopathological features and poor prognosis. Gain- and loss-of-function experiments demonstrate that PTBP1 markedly reinforces genomic DNA stability to desensitize PCa cells to irradiation in vitro and in vivo. Mechanistically, PTBP1 interacts with the heterogeneous nuclear ribonucleoproteins (hnRNP) associated with lethal yellow protein homolog (RALY) and regulates exon 5 splicing of DNA methyltransferase 3b (DNMT3B) from DNMT3B-S to DNMT3B-L. Furthermore, upregulation of DNMT3B-L induces promoter methylation of dual-specificity phosphatase-2 (DUSP2) and subsequently inhibits DUSP2 expression, thereby increasing radioresistance in PCa. The findings highlight the role of splicing factors in inducing aberrant splicing events in response to radiotherapy and the potential role of PTBP1 and DNMT3B-L in reversing radioresistance in PCa.

6.
Artículo en Inglés | MEDLINE | ID: mdl-39269425

RESUMEN

A novel multidimensional electromagnetic wave-absorbing material was developed by combining carboxylated carbon nanotubes (CNT) with graphene oxide (GO) through multidimensional design, and cobalt/nickel-based metal organic frameworks (Co/Ni-MOF) were subsequently loaded onto the GO surface via its rich functional groups to form the composite absorbing material CNT-rGO-Co/Ni-MOF. Incorporating 25 wt % of CNT-rGO-Co/Ni-MOF into the paraffin matrix led to a remarkable RLmin value of -43 dB at 16.4 GHz, with an effective absorbing bandwidth (EAB) exceeding 4 GHz, all within a thickness of just 1.5 mm, showcasing its "lightweight, broadband, and high efficiency" characteristics. The exceptional electromagnetic wave absorption performance was attributed to multi-interface polarization loss, resistance loss, and magnetic medium loss. Furthermore, when incorporating 10 wt % of CNT-rGO-Co/Ni-MOF, the heat release capacity and peak heat release rate of EP/CNT-rGO-Co/Ni-MOF10 decreased by 59.2 and 52.6%, respectively.

7.
Artículo en Inglés | MEDLINE | ID: mdl-39250401

RESUMEN

Room-scale immersive data visualisations provide viewers a wide-scale overview of a large dataset, but to interact precisely with individual data points they typically have to navigate to change their point of view. In traditional screen-based visualisations, focus-and-context techniques allow visualisation users to keep a full dataset in view while making detailed selections. Such techniques have been studied extensively on desktop to allow precise selection within large data sets, but they have not been explored in immersive 3D modalities. In this paper we develop a novel immersive focus-and-context technique based on a "magic portal" metaphor adapted specifically for data visualisation scenarios. An extendable-hand interaction technique is used to place a portal close to the region of interest. The other end of the portal then opens comfortably within the user's physical reach such that they can reach through to precisely select individual data points. Through a controlled study with 12 participants, we find strong evidence that portals reduce overshoots in selection and overall hand trajectory length, reducing arm and shoulder fatigue compared to ranged interaction without the portal. The portals also enable us to use a robot arm to provide haptic feedback for data within the limited volume of the portal region. In a second study with another 12 participants we found that haptics provided a positive experience (qualitative feedback) but did not significantly reduce fatigue. We demonstrate applications for portal-based selection through two use-case scenarios.

8.
Ann Med ; 56(1): 2399759, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39258876

RESUMEN

BACKGROUND: The status of BRCA1/2 genes plays a crucial role in the treatment decision-making process for multiple cancer types. However, due to high costs and limited resources, a demand for BRCA1/2 genetic testing among patients is currently unmet. Notably, not all patients with BRCA1/2 mutations achieve favorable outcomes with poly (ADP-ribose) polymerase inhibitors (PARPi), indicating the necessity for risk stratification. In this study, we aimed to develop and validate a multimodal model for predicting BRCA1/2 gene status and prognosis with PARPi treatment. METHODS: We included 1695 slides from 1417 patients with ovarian, breast, prostate, and pancreatic cancers across three independent cohorts. Using a self-attention mechanism, we constructed a multi-instance attention model (MIAM) to detect BRCA1/2 gene status from hematoxylin and eosin (H&E) pathological images. We further combined tissue features from the MIAM model, cell features, and clinical factors (the MIAM-C model) to predict BRCA1/2 mutations and progression-free survival (PFS) with PARPi therapy. Model performance was evaluated using area under the curve (AUC) and Kaplan-Meier analysis. Morphological features contributing to MIAM-C were analyzed for interpretability. RESULTS: Across the four cancer types, MIAM-C outperformed the deep learning-based MIAM in identifying the BRCA1/2 genotype. Interpretability analysis revealed that high-attention regions included high-grade tumors and lymphocytic infiltration, which correlated with BRCA1/2 mutations. Notably, high lymphocyte ratios appeared characteristic of BRCA1/2 mutations. Furthermore, MIAM-C predicted PARPi therapy response (log-rank p < 0.05) and served as an independent prognostic factor for patients with BRCA1/2-mutant ovarian cancer (p < 0.05, hazard ratio:0.4, 95% confidence interval: 0.16-0.99). CONCLUSIONS: The MIAM-C model accurately detected BRCA1/2 gene status and effectively stratified prognosis for patients with BRCA1/2 mutations.


Asunto(s)
Mutación , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Humanos , Femenino , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Masculino , Proteína BRCA1/genética , Proteína BRCA2/genética , Pronóstico , Persona de Mediana Edad , Supervivencia sin Progresión , Neoplasias Ováricas/genética , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Terapia Molecular Dirigida/métodos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/tratamiento farmacológico , Adulto
9.
Medicine (Baltimore) ; 103(22): e38432, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-39259061

RESUMEN

Acute myeloid leukemia (AML), an uncommonly low 5-year survival and high mortality rate, is a potentially catastrophic diagnosed subtype of leukemia. The development of new prognostic markers is urgently needed to guide its treatment. Necroptosis is a newly defined biological process for regulating cell death, and previous studies have confirmed that the abnormality of the physical function can lead to multiple malignancies. Here, we performed necroptosis-related genes (NRGs) to build a predictive model in the Cancer Genome Atlas (TCGA)-AML patients, thus exploring the correlation between the NRG prognosis signature (NRG score) of this model and immune infiltration, pathway activity, clinical features, and immunotherapy. Besides, we computed the statistical measure Spearman rank correlation between the NRG score and the Log IC50 values of therapeutic agents. Subsequently, we divided the TCGA-AML cohort into 2 groups, one with high scores and the other with low scores depending on the model score. AML patients with high NRG scores exhibited a lower estimated overall survival (OS) rate than those with low NRG scores, which was confirmed in the validation set. The prognostic value of the constructed NRG signature to the AML, independent of other variables, was demonstrated by uni- and multivariate stepwise regression analysis. When comparing the infiltrating states of specialized cells associated with immune system from the 2 groups, B cells naive, Plasma cells, and monocytes represented significant differences among various subgroups of samples. Moreover, the 30 hallmark-related pathways related to necroptosis characteristics were remarkably different between the high/low NRG score groups. And patients showed remarkable NRG score distribution in clinical features of bone marrow lymphocyte, category, and FAB classifications. Besides, we found that the BIRB0796, VX680, Vorinostat, and Axitinib positively related with NRG score, whereas CI. 1040, PD. 0325901, Z.L LNle. CHO, and AZD6244 negatively correlated with the NRG score. These drugs may provide a reference for subsequent treatment.


Asunto(s)
Leucemia Mieloide Aguda , Necroptosis , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamiento farmacológico , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/mortalidad , Pronóstico , Necroptosis/genética , Masculino , Femenino , Persona de Mediana Edad , Biomarcadores de Tumor/genética , Anciano , Adulto
10.
Cancer Lett ; 604: 217240, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39265800

RESUMEN

Nuclear Bcl-xL is found to promote cancer metastasis independently of its mitochondria-based anti-apoptotic activity. How Bcl-xL is translocated into the nucleus and how nuclear Bcl-xL regulates histone H3 trimethyl Lys4 (H3K4me3) modification have yet to be understood. Here, we report that C-terminal Binding Protein 2 (CtBP2) binds to Bcl-xL via its N-terminus and translocates Bcl-xL into the nucleus. Knockdown of CtBP2 by shRNA decreases the nuclear portion of Bcl-xL and reverses Bcl-xL-induced invasion and metastasis in mouse models. Furthermore, knockout of CtBP2 not only reduces the nuclear portion of Bcl-xL but also suppresses Bcl-xL transcription. The binding between Bcl-xL and CtBP2 is required for their interaction with MLL1, a histone H3K4 methyltransferase. Pharmacologic inhibition of the MLL1 enzymatic activity reverses Bcl-xL-induced H3K4me3 and TGFß mRNA upregulation, as well as invasion. Moreover, the cleavage under targets and release using nuclease (CUT&RUN) assay coupled with next-generation sequencing reveals that H3K4me3 modifications are particularly enriched in the promotor regions of genes encoding TGFß and its signaling pathway members in cancer cells overexpressing Bcl-xL. Altogether, the metastatic function of Bcl-xL is mediated by its interaction with CtBP2 and MLL1 and this study offers new therapeutic strategies to treat Bcl-xL-overexpressing cancer.

11.
Adv Mater ; : e2409025, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39267409

RESUMEN

Monolithic integration of color-conversion materials onto blue-backlight micro-light-emitting-diodes (micro-LEDs) has emerged as a promising strategy for achieving full-color microdisplay devices. However, this approach still encounters challenges such as the blue-backlight leakage and the poor fabrication yield rate due to unsatisfied quantum dot (QD) material and fabrication process. Here, the monolithic integration of 0.39-inch micro-display screens displaying colorful pictures and videos are demonstrated, which are enabled by creating interfacial chemical bonds for wafer-scale adhesion of sub-5 µm QD-pixels on blue-backlight micro-LED wafer. The ligand molecule with chlorosulfonyl and silane groups is selected as the synthesis ligand and surface treatment material, facilitating the preparation of high-efficiency QD photoresist and the formation of robust chemical bonds for pixel integration. This is a leading record in micro-display devices achieving the highest brightness larger than 400 thousand nits, the ultrahigh resolution of 3300 PPI, the wide color gamut of 130.4% NTSC, and the ultimate performance of service life exceeding 1000 h. These results extend the mature integrated circuit technique into the manufacture of micro-display device, which also lead the road of industrialization process of full-color micro-LEDs.

12.
ACS Omega ; 9(36): 37585-37595, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39281958

RESUMEN

Novel t-butyloxycarbonyl-protected molecular glass photoresists with pyrene as the core (Pyr-8Boc and Pyr-4Boc) were designed and synthesized. The thermal stability and film-forming ability were measured to assess their applicability for lithography. Pyr-Boc (Pyr-8Boc and Pyr-4Boc) photoresists were evaluated by high-resolution electron beam lithography (EBL), acting as chemically amplified resists. Pyr-4Boc showed a better lithography performance, achieving 25 nm line/space patterns at the dose of 50 µC/cm2. Under SF6/O2 plasma, the etch selectivity of the Pyr-4Boc photoresist to silicon was 12.3, which is twice that of the commercially available poly(methyl methacrylate) photoresist (950 k). The lithography mechanism of EBL was further investigated. Theoretical calculations of HOMO/LUMO orbital energies, cyclic voltammetry, and fluorescence quenching experiments were conducted to confirm the electron-transfer reactions between the Pyr-Boc and photoacid generator. The study provides an option of high sensitivity and etch-resistant photoresist for EBL.

13.
Front Oncol ; 14: 1397273, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286018

RESUMEN

Background and purpose: Radiotherapy is a primary therapeutic approach for breast cancer following breast-conserving surgery. The TaiChiB dual-modality radiotherapy system combining X-ray and focused γ-ray, offers a new approach to reduce the radiation dose of organs at risk (OARs) and has the potential to mitigate the adverse effects of radiotherapy. Currently, there are few studies on the dosimetric characteristics of the TaiChiB dual-modality system for actual treatment plans for specific diseases. The purpose of this work is to study the dosimetric advantages of dual-modal systems for right breast patients after breast-conserving surgery. Material and methods: Treatment plans for 20 patients with right breast cancer were generated for a linear accelerator (LINAC) based system and the TaiChiB dual-modality system, respectively. Volumetric modulated arc therapy plans with simultaneous integrated boost (VMAT-SIB) were made for the LINAC. Focused γ-ray was used to deliver the boost dose with the dual-modality system. The dosimetric parameters of the target and OARs were evaluated and compared between the treatment plans generated for the two systems. Results: The TaiChiB dual-modality plans exhibit a higher conformal index (CI) and lower gradient index (GI) for the PGTV and PTV compared with the LINAC-based VMAT-SIB plans. Compared to VMAT-SIB plans, the PTV Dmax, PTV Dmean, PTV V110, PGTV Dmax, and PGTV Dmean of the TaiChiB dual-modality plans are significantly lower. Meanwhile, the dose to OARs, such as the Dmean of the heart, the V5 of liver, the Dmean of ipsilateral lung, the V30 of ipsilateral lung, the V20 of ipsilateral lung, the V5 of ipsilateral lung, the Dmean of contralateral lung, Dmax of contralateral breast and the Dmean of contralateral breast are significantly reduced. Conclusions: Our study demonstrates the dosimetric advantages of the novel TaiChiB dual-modality radiotherapy system for the treatment of right-sided breast cancer. Overall, for the TaiChiB dual-modality radiotherapy system, the radiation dose outside the target region decreases rapidly, thereby minimizing radiation exposure to neighboring organs and ensuring the conformity of the target area. Our research confirms the potential of the TaiChiB dual-modality system for future radiotherapy.

14.
Front Neurol ; 15: 1450221, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39286804

RESUMEN

Background: Parkinson's disease (PD) is a prevalent disorder of the central nervous system, marked by the degeneration of dopamine (DA) neurons in the ventral midbrain. In the pathogenesis of PD, inflammation hypothesis has been concerned. This study aims to investigate clinical indicators of peripheral inflammation in PD patients and to explore the diagnostic value of neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen ratio (AFR), and lymphocyte-to-monocyte ratio (LMR) in assessing PD risk. Methods: This study included 186 patients with PD and 201 matched healthy controls (HC) with baseline data. Firstly, the differences of hematological indicators between PD group and healthy participants were compared and analyzed. Univariate and multivariate regression analyses were then conducted. Smooth curve fitting was applied to further validate the relationships between NLR, LMR, AFR, and PD. Subsequently, subgroup analysis was conducted in PD group according to different duration of disease and Hoehn and Yahr (H&Y) stage, comparing differences in clinical indicators. Finally, the receiver operating characteristic (ROC) curve was employed to assess the diagnostic value of NLR, LMR, and AFR in PD. Results: Compared to the HC group, the PD group showed significantly higher levels of hypertension, diabetes, neutrophil count, monocyte count, CRP, homocysteine, fibrinogen, and NLR. Conversely, levels of LMR, AFR, lymphocyte count, HDL, LDL, TG, TC, uric acid, and albumin were significantly lower. The multivariate regression model indicated that NLR (OR = 1.79, 95% CI: 1.39-2.31, p < 0.001), LMR (OR = 0.75, 95% CI: 0.66-0.85, p < 0.001), and AFR (OR = 0.79, 95% CI: 0.73-0.85, p < 0.001) were significant factors associated with PD. Smooth curve fitting revealed that NLR was positively linked to PD risk, whereas AFR and LMR were inversely associated with it. In ROC curve analysis, the AUC of AFR was 0.7290, the sensitivity was 63.98%, and the specificity was 76.00%. The AUC of NLR was 0.6200, the sensitivity was 50.54%, and the specificity was 71.50%. The AUC of LMR was 0.6253, the sensitivity was 48.39%, and the specificity was 73.00%. The AUC of the combination was 0.7498, the sensitivity was 74.19%, and the specificity was 64.00%. Conclusion: Our findings indicate that NLR, LMR, and AFR are significantly associated with Parkinson's disease and may serve as diagnostic markers.

15.
Front Psychol ; 15: 1408396, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39291173

RESUMEN

Background: Non-suicidal self-injury (NSSI) is a worldwide mental health problem that deserves thorough investigation. This study aims to explore the effect of parenting styles, attachment to parents, and self-compassion on the occurrence of non-suicidal self-injury (NSSI) behavior in adolescents and whether these factors influence their recovery motivation. Methods: A total of 132 adolescents who had engaged in NSSI within the last year and 72 adolescents who had never engaged in NSSI were recruited from the Shenzhen Kangning Hospital and from primary and secondary schools and communities. Differences in the Hamilton Depression Scale (HAMD), Inventory of Parent and Peer Attachment (IPPA), Egma Minn av. Bardndosnauppforstran (EMBU), and Self-Compassion Scale (SCS) of participants were compared. A binary logistic model was established to measure the odds ratios of these variables on the occurrence of NSSI. In the NSSI adolescent sample, separate binary logistic models were created with NSSI impulse inhibition, NSSI resistance activity, and NSSI recovery motivation as dependent variables and with parenting styles, attachment to parents, and self-compassion as independent variables. Results: Compared with adolescents with no NSSI behavior, those who had engaged in NSSI within the past year had higher scores on the HAMD, as well as higher EMBU-negative father parental behavior (punishment, excessive interference, rejection, and overprotection), EMBU-negative mother parental behavior (excessive interference, rejection, and punishment), and SCS negative self-compassion scores. Moreover, adolescents with NSSI had lower EMBU-father emotional warmth, EMBU-mother emotional warmth, IPPA-attachment to father, IPPA-attachment to mother, and SCS positive self-compassion scores. Current depressive symptoms and maternal punishment are risk factors for NSSI in adolescents, while positive self-compassion was a protective factor. Positive self-compassion can positively predict NSSI impulse inhibition, NSSI resistance activity, and NSSI recovery motivation. However, we unexpectedly found that the father's emotional warmth negatively predicts NSSI resistance activity. Conclusion: This study found that positive self-compassion has a significant impact on the prevention of and recovery from NSSI behavior in adolescents.

16.
Liver Int ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291973
17.
J Virol ; : e0112924, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287389

RESUMEN

Because host kinases are key regulators of multiple signaling pathways in response to viral infections, we previously screened a kinase inhibitor library using rhabdomyosarcoma cells and human intestinal organoids in parallel to identify potent inhibitors against EV-A71 infection. We found that Rho-associated coiled-coil-containing protein kinase (Rock) inhibitor efficiently suppressed the EV-A71 replication and further revealed Rock1 as a novel EV-A71 host factor. In this study, subsequent analysis found that a variety of vascular endothelial growth factor receptor (VEGFR) inhibitors also had potent antiviral effects. Among the hits, Pazopanib, with a selectivity index as high as 254, which was even higher than that of Pirodavir, a potent broad-spectrum picornavirus inhibitor targeting viral capsid protein VP1, was selected for further analysis. We demonstrated that Pazopanib not only efficiently suppressed the replication of EV-A71 in a dose-dependent manner, but also exhibited broad-spectrum anti-enterovirus activity. Mechanistically, Pazopanib probably induces alterations in host cells, thereby impeding viral genome replication and transcription. Notably, VEGFR2 knockdown and overexpression suppressed and facilitated EV-A71 replication, respectively, indicating that VEGFR2 is a novel host dependency factor for EV-A71 replication. Transcriptome analysis further proved that VEGFR2 potentially plays a crucial role in combating EV-A71 infection through the TSAd-Src-PI3K-Akt pathway. These findings expand the range of potential antiviral candidates of anti-enterovirus therapeutics and suggest that VEGFR2 may be a key host factor involved in EV-A71 replication, making it a potential target for the development of anti-enterovirus therapeutics. IMPORTANCE: As the first clinical case was identified in the United States, EV-A71, a significant neurotropic enterovirus, has been a common cause of hand, foot, and mouth disease (HFMD) in infants and young children. Developing an effective antiviral agent for EV-A71 and other human enteroviruses is crucial, as these viral pathogens consistently cause outbreaks in humans. In this study, we demonstrated that multiple inhibitors against VEGFRs effectively reduced EV-A71 replication, with Pazopanib emerging as the top candidate. Furthermore, Pazopanib also attenuated the replication of other enteroviruses, including CVA10, CVB1, EV-D70, and HRV-A, displaying broad-spectrum anti-enterovirus activity. Given that Pazopanib targets various VEGFRs, we narrowed the focus to VEGFR2 using knockdown and overexpression experiments. Transcriptomic analysis suggests that Pazopanib's potential downstream targets involve the TSAd-Src-PI3K-Akt pathway. Our work may contribute to identifying targets for antiviral inhibitors and advancing treatments for human enterovirus infections.

18.
Clin Oral Investig ; 28(10): 529, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287813

RESUMEN

OBJECTIVES: This study aims to investigate the changes in alveolar bone following the simultaneous performance of labial and lingual augmented corticotomy (LLAC) in patients with insufficient alveolar bone thickness on both the labial and lingual sides of the mandibular anterior teeth during presurgical orthodontic treatment. MATERIALS AND METHODS: Thirth-five surgical patients with skeletal Class III malocclusion were included: 19 (LLAC group) accepted LLAC surgery during presurgical orthodontic treatment, and 16 (non-surgery group, NS) accepted traditional presurgical orthodontic treatment. Cone-beam computed tomography (CBCT) scans were obtained before treatment (T0) and at the completion of presurgical orthodontic treatment (T1). The amount of vertical alveolar bone and contour area of the alveolar bone in the labial and lingual sides of mandibular incisors were measured. RESULTS: After presurgical orthodontic treatment, the contour area of the alveolar bone at each level on the lingual side and alveolar bone level on both sides decreased significantly in the NS group (P < 0.001). However, the labial and lingual bone contour area at each level and bone level increased significantly in the LLAC group (P < 0.001). The bone formation rate in the lingual apical region was the highest, significantly different from other sites (P < 0.001). CONCLUSIONS: During presurgical orthodontic treatment, LLAC can significantly increase the contour area of the labio-lingual alveolar bone in the mandibular anterior teeth to facilitate safe and effective orthodontic decompensation in skeletal Class III patients. CLINICAL RELEVANCE: This surgery has positive clinical significance in patients lacking bone thickness (< 0.5 mm) in the labial and lingual sides of the lower incisors.


Asunto(s)
Proceso Alveolar , Tomografía Computarizada de Haz Cónico , Maloclusión de Angle Clase III , Mandíbula , Humanos , Maloclusión de Angle Clase III/cirugía , Maloclusión de Angle Clase III/diagnóstico por imagen , Masculino , Femenino , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Proceso Alveolar/diagnóstico por imagen , Proceso Alveolar/cirugía , Adulto , Incisivo/diagnóstico por imagen , Resultado del Tratamiento , Ortodoncia Correctiva/métodos , Adolescente
19.
J Mater Chem B ; 12(36): 8897-8901, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39248138

RESUMEN

The exploration of noble metal-free nanoarrays as high-activity catalytic electrodes for glucose biosensing holds great significance. Herein, we propose a Ni nanoparticle-decorated TiO2 nanoribbon array on a titanium plate (Ni@TiO2/TP) as an effective non-enzymatic glucose biosensing electrode. The as-prepared Ni@TiO2/TP electrode demonstrates rapid glucose response, a wide linear response range (1 µM to 1 mM), a low detection limit (0.08 µM, S/N = 3), and high sensitivity (10 060 and 3940 µA mM-1 cm-2), with good mechanical flexibility and stability. Moreover, it proves efficient in glucose biosensing in real human blood serum and cell culture fluid. Thus, it is highly promising for practical applications.


Asunto(s)
Técnicas Biosensibles , Electrodos , Níquel , Titanio , Titanio/química , Níquel/química , Humanos , Glucosa/análisis , Nanotubos de Carbono/química , Técnicas Electroquímicas , Glucemia/análisis , Propiedades de Superficie
20.
Water Res ; 266: 122433, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39276477

RESUMEN

Anthropogenic enrichment of phosphorus (P) in water environment can cause eutrophication, harmful algal blooms, and water quality deterioration. Adsorbents are often used for the removal and recovery of P from water, however, P is highly susceptible to re-release in anoxic benthic environments. As a response, this study prepared oxygen-carrying iron-rich biochar (O-Fe-BC) as an effective oxygen micro-nanobubble carrier (Q = 8.7024 cm³/g STP at 1.5 MPa) and P adsorbent (qm = 16.7097 mg P/g, q0.1 = 3.1974 mg P/g). Over the 90-day experimental period with O-Fe-BC, dissolved oxygen (DO) levels in the overlying water could maintain at ∼4 mg/L (peaking at ∼9.5 mg/L), and total phosphorus (TP) and soluble reactive phosphorus (SRP) levels decreased by over 96 %. The higher inorganic phosphorus content in the surface sediment-biochar mixture, along with the lower labile P and Fe concentration in the sediment pore water in the O-Fe-BC group compared to other groups, suggested the enhanced P immobilization. Further mechanism exploration revealed the combined roles of adsorption and microbial response, in which O-Fe-BC achieved efficient phosphate adsorption primarily through inner-sphere complexation via ligand exchange and keystone taxa (particularly Candidatus Electronema) played a crucial role in driving water chemistry divergence. Specially, these cable bacteria could provide large pools of Fe oxides in the surface sediment, binding with P to prevent its release, as supported by significant correlations between Ca. Electronema abundance and oxidation-reduction potential (ORP), TP, SRP, and sediment Fe-P variations. Additionally, a pot experiment with mung bean seedlings showed that the recovered O-Fe-BC significantly promoted the seed germination and growth, indicating its potential as a novel material for removing and recovering P from eutrophic waters. Taken together, our work provided a promising strategy for sustainable anoxia and P pollution mitigation, and also highlighted the indispensable roles of inner-sphere adsorption in P recovery and microbial keystone taxa in P cycling regulation.

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