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1.
J Infect Dis ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995029

RESUMO

BACKGROUND: Respiratory syncytial virus (RSV) is a leading cause of acute respiratory illness (ARI) in older adults. Optimizing diagnosis could improve understanding of RSV burden. METHODS: We enrolled adults ≥50 years of age hospitalized with ARI and adults of any age hospitalized with congestive heart failure or chronic obstructive pulmonary disease exacerbations at two hospitals during two respiratory seasons (2018-2020). We collected nasopharyngeal (NP) and oropharyngeal (OP) swabs (n=1558), acute and convalescent sera (n=568), and expectorated sputum (n=153) from participants, and recorded standard-of-care (SOC) NP results (n=805). We measured RSV antibodies by two immunoassays and performed BioFire testing on respiratory specimens. RESULTS: Of 1,558 eligible participants, 92 (5.9%) tested positive for RSV by any diagnostic method. Combined NP/OP PCR yielded 58 positives, while separate NP and OP testing identified 11 additional positives (18.9% increase). Compared to Study NP/OP PCR alone, the addition of paired serology increased RSV detection by 42.9% (28 vs 40) among those with both specimen types, while the addition of SOC swab RT-PCR results increased RSV detection by 25.9% (47 vs 59). CONCLUSIONS: The addition of paired serology testing, SOC swab results, and separate testing of NP and OP swabs improved RSV diagnostic yield in hospitalized adults.

3.
J Cancer ; 15(14): 4467-4476, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39006074

RESUMO

Anti-HER2 therapy has significantly improved the survival rates of patients with HER2+ breast cancer. However, a subset of these patients eventually experience treatment failure, and the underlying genetic mechanisms remain largely unexplored. This underscores the need to investigate the genomic heterogeneity of HER2+ breast cancer. In this study, we focus on HER2+/HR- breast cancer, as it differs from HER2+/HR+ breast cancer in terms of genetic and biological characteristics. We performed gene-targeted genome sequencing on 45 HER2+/HR- breast cancer samples and identified 650 mutations across 268 cancer-related genes. TP53 (71.1%) and PIK3CA (35.6%) were the most frequently mutated genes in our sample. Additionally, ERBB2 (77.8%), CDK12 (42.2%), and MYC (11.1%) exhibited a high frequency of copy number amplifications (CNAs). Comparative analysis with two other HER2+/HR- breast cancer cohorts revealed that our cohort had higher genetic variation rates in ARID1A, PKHD1, PTPN13, FANCA, SETD2, BRCA2, BLM, STAG2, FAT1, TOP2A, POLE, ATM, KMT2B, FGFR4, and EPAS1. Notably, in our cohort, NF1 and ATM mutations were more prevalent in trastuzumab-resistant patients (NF1, p=0.016; ATM, p=0.006) and were associated with primary trastuzumab resistance (NF1, p=0.042; ATM, p=0.021). Moreover, patients with NF1 mutations (p=0.009) and high histological grades (p=0.028) were more likely to experience early relapse. Ultimately, we identified a unique cancer-related gene mutation profile and a subset of genes associated with primary resistance to trastuzumab and RFS in patients with HER2+/HR- breast cancer in Northwest China. These findings could lay the groundwork for future studies aimed at elucidating the mechanisms of resistance to trastuzumab and improving HER2-targeted treatment strategies.

4.
Ecotoxicol Environ Saf ; 281: 116653, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38964066

RESUMO

Nitrite is the most common nitrogen-containing compound in nature. It is widely used in food processing like in pickled foods so it has caused widespread public concern about the safety of nitrites due to the formation of nitrosamine, a carcinogen, during the food process. Recent research has shown nitrite has therapeutic potential for cardiovascular disease due to its similar function to NO, yet the safety of oral nitrite and the physiological and biochemical responses induced after oral administration still require further validation. In addition, the relationship between nitrite and glycolipid metabolism still needs to be elucidated. As aquatic animals, fish are more susceptible to nitrite compared to mammals. Herein, we utilized tilapia (Oreochromis niloticus) as an animal model to explore the relationship between nitrite and glycolipid metabolism in organisms. In the present study, we found that nitrite elicited a hypoxic metabolic response in tilapia and deepened this metabolic response under the co-stress of the pathogenic bacterium S.ag (Streptococcus agalactiae). In addition, nitrite-induced elevation of MetHb (Methemoglobin) and its by-product heme was involved in the metabolic response to nitrite-induced hypoxia through the HO/CO pathway, which has not yet been mentioned in previous studies. Moreover, heme affected hepatic metabolic responses through the ROS-ER stress-VLDL pathway. These findings, for the first time, reveal that nitrite exposure leads to glycolipid metabolic disorder via the heme-HO pathway in teleost. It not only provides new insights into the results of nitrite on the body but also is beneficial for developing healthy strategies for fish farming.


Assuntos
Glicolipídeos , Heme , Nitritos , Animais , Nitritos/toxicidade , Ciclídeos/metabolismo , Doenças Metabólicas/induzido quimicamente , Poluentes Químicos da Água/toxicidade
5.
Front Pharmacol ; 15: 1408135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38939844

RESUMO

Background: Tivozanib, a vascular endothelial growth factor tyrosine kinase inhibitor, has demonstrated efficacy in a phase III clinical trials for the treatment of renal cell carcinoma. However, comprehensive evaluation of its long-term safety profile in a large sample population remains elusive. The current study assessed Tivozanib-related adverse events of real-world through data mining of the US Food and Drug Administration Adverse Event Reporting System FDA Adverse Event Reporting System. Methods: Disproportionality analyses, utilizing reporting odds ratio proportional reporting ratio Bayesian confidence propagation neural network and multi-item gamma Poisson shrinker (MGPS) algorithms, were conducted to quantify signals of Tivozanib-related AEs. Weibull distribution was used to predict the varying risk incidence of AEs over time. Results: Out of 5,361,420 reports collected from the FAERS database, 1,366 reports of Tivozanib-associated AEs were identified. A total of 94 significant disproportionality preferred terms (PTs) conforming to the four algorithms simultaneously were retained. The most common AEs included fatigue, diarrhea, nausea, blood pressure increased, decreased appetite, and dysphonia, consistent with prior specifications and clinical trials. Unexpected significant AEs such as dyspnea, constipation, pain in extremity, stomatitis, and palmar-plantar erythrodysaesthesia syndrome was observed. The median onset time of Tivozanib-related AEs was 37 days (interquartile range [IQR] 11.75-91 days), with a majority (n = 127, 46.35%) occurring within the initial month following Tivozanib initiation. Conclusion: Our observations align with clinical assertions regarding Tivozanib's safety profile. Additionally, we unveil potential novel and unexpected AE signatures associated with Tivozanib administration, highlighting the imperative for prospective clinical studies to validate these findings and elucidate their causal relationships. These results furnish valuable evidence to steer future clinical inquiries aimed at elucidating the safety profile of Tivozanib.

6.
Int J Biol Macromol ; 272(Pt 1): 132639, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38834116

RESUMO

Layer-by-layer (LBL) self-assembly is an effective strategy for constructing fire-resistant coatings on flexible polyurethane foam (FPUF), while the efficiency of fire-resistant coatings remains limited. Therefore, this study proposes an in situ flame retardancy modification combined with LBL self-assembly technology to enhance the efficiency of flame retardant coatings for FPUF. Initially, polydopamine (PDA) and polyethyleneimine (PEI) were employed to modify the FPUF skeleton, thereby augmenting the adhesion on the surface of the skeleton network. Then, the self-assembly of MXene and phosphorylated cellulose nanofibers (PCNFs) via the LBL technique on the foam skeleton network formed a novel, sustainable, and efficient flame retardant system. The final fire-protective coatings comprising PDA/PEI and MXenes/PCNF effectively prevented the collapse of the foam structure and suppressed the melt dripping of the FPUF during combustion. The peak heat release rate, the peak CO production rate and peak CO2 production rate were reduced by 68.6 %, 61.1 %, and 68.4 % only by applying a 10-bilayer coating. In addition, the smoke release rate and total smoke production were reduced by 83.3 % and 57.7 %, respectively. This work offers a surface modification approach for constructing highly efficient flame retardant coatings for flammable polymeric materials.


Assuntos
Celulose , Retardadores de Chama , Indóis , Polímeros , Poliuretanos , Poliuretanos/química , Indóis/química , Celulose/química , Polímeros/química , Fosforilação , Nanofibras/química , Incêndios/prevenção & controle
7.
Front Endocrinol (Lausanne) ; 15: 1399274, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38894746

RESUMO

Gonadotropin-releasing hormone (GnRH) is a key stimulator for gonadotropin secretion in the pituitary and its pivotal role in reproduction is well conserved in vertebrates. In fish models, GnRH can also induce prolactin (PRL) release, but little is known for the corresponding effect on PRL gene expression as well as the post-receptor signalling involved. Using grass carp as a model, the functional role of GnRH and its underlying signal transduction for PRL regulation were examined at the pituitary level. Using laser capture microdissection coupled with RT-PCR, GnRH receptor expression could be located in carp lactotrophs. In primary cell culture prepared from grass carp pituitaries, the native forms of GnRH, GnRH2 and GnRH3, as well as the GnRH agonist [D-Arg6, Pro9, NEt]-sGnRH were all effective in elevating PRL secretion, PRL mRNA level, PRL cell content and total production. In pituitary cells prepared from the rostral pars distalis, the region in the carp pituitary enriched with lactotrophs, GnRH not only increased cAMP synthesis with parallel CREB phosphorylation and nuclear translocation but also induced a rapid rise in cytosolic Ca2+ by Ca2+ influx via L-type voltage-sensitive Ca2+ channel (VSCC) with subsequent CaM expression and NFAT2 dephosphorylation. In carp pituitary cells prepared from whole pituitaries, GnRH-induced PRL secretion was reduced/negated by inhibiting cAMP/PKA, PLC/PKC and Ca2+/CaM/CaMK-II pathways but not the signalling events via IP3 and CaN/NFAT. The corresponding effect on PRL mRNA expression, however, was blocked by inhibiting cAMP/PKA/CREB/CBP and Ca2+/CaM/CaN/NFAT2 signalling but not PLC/IP3/PKC pathway. At the pituitary cell level, activation of cAMP/PKA pathway could also induce CaM expression and Ca2+ influx via VSCC with parallel rises in PRL release and gene expression in a Ca2+/CaM-dependent manner. These findings, as a whole, suggest that the cAMP/PKA-, PLC/PKC- and Ca2+/CaM-dependent cascades are differentially involved in GnRH-induced PRL secretion and PRL transcript expression in carp lactotrophs. During the process, a functional crosstalk between the cAMP/PKA- and Ca2+/CaM-dependent pathways may occur with PRL release linked with CaMK-II and PKC activation and PRL gene transcription caused by nuclear action of CREB/CBP and CaN/NFAT2 signalling.


Assuntos
Cálcio , Carpas , Proteínas Quinases Dependentes de AMP Cíclico , AMP Cíclico , Hormônio Liberador de Gonadotropina , Hipófise , Prolactina , Proteína Quinase C , Fosfolipases Tipo C , Animais , Carpas/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Prolactina/metabolismo , Hipófise/metabolismo , Hipófise/citologia , Proteína Quinase C/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Cálcio/metabolismo , Fosfolipases Tipo C/metabolismo , Fosfolipases Tipo C/genética , AMP Cíclico/metabolismo , Transdução de Sinais/efeitos dos fármacos , Calmodulina/metabolismo , Células Cultivadas , Expressão Gênica/efeitos dos fármacos
8.
Int J Biol Macromol ; 273(Pt 1): 132929, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866279

RESUMO

In order to more efficiently utilize the abundant cellulose resources in nature, increase the utilization rate of cellulose in aquaculture, implement precise feeding and save aquaculture costs, we have conducted research on cellulase genes related to the spotted knifejaw (Oplegnathus punctatus). Cellulose, as the most abundant renewable resource, is a cornerstone in the intricate ecological balance of diverse ecosystems. While herbivorous fish are recognized for their utilization of proteins, sugars, and fats, the extent of cellulose utilization by carnivorous and omnivorous fish remains an enigma. Here, through field sampling and behavioural observations, O. punctatus' omnivorous diet has been demonstrated (stomach contents contain approximately several species of algae in the Bacillariophyta (1.12 %), Streptomyces (0.55 %), Chlorophyta (0.35 %), Rhodophyta (0.16 %), and Euglenophyta (0.19 %) phylum). Additionally, the high cellulase activity in the intestine of O. punctatus has been detected first discovery (enzyme activity up to 4800.15 U/g), indicating its ability to digest cellulose. By employing whole-genome scanning and high-throughput sequencing, a single cellulase gene (ß-glucosidase) within the genome of O. punctatus, suggesting the absence of a complete cellulose digestive system. However, microbiological analysis revealed the three crucial role of microorganisms, including Actinobacteria (25.80 %), Bacteroidetes (18.93 %), and Firmicutes phylum (0.82 %), were found to play a crucial role in the decomposition of plant cell walls, thereby facilitating plant material digestion to help the host to complete the process of cellulose digestion. Expression patterns and proteomic analysis of the ß-glucosidase were notably high in the gonads. In situ hybridization confirmed the expression of the ß-glucosidase gene in the intestinal contents and gonads, highlighting its role in supplying energy of gonads. These discoveries shed light on the dietary habits of O. punctatus and its cellulose utilization, offering insights that can inform the development of customized feeding strategies to enhance aquaculture sustainability and minimize resource expenditure.


Assuntos
Peixes , beta-Glucosidase , Animais , beta-Glucosidase/genética , beta-Glucosidase/metabolismo , Peixes/genética , Filogenia , Celulose/metabolismo , Carnivoridade
10.
Clin Ophthalmol ; 18: 1457-1465, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38818525

RESUMO

Purpose: To compare Barrett TK Universal II and Barrett Universal II TCRP calculations in the power calculations for 3 presbyopia-correcting intraocular lenses (PC-IOL). Methods: This observational study involved 64 eyes from 64 patients who prepared to undergo extraction of crystalline lenses combined with PC-IOL (Symfony ZXR00, PanOptix TFNT00, or AT LISA tri 839MP) implantation. All eyes underwent ocular biometric measurements with IOLMaster 700 and Pentacam HR, and the interdevice agreement of measurements including total keratometry (TK, IOLMaster 700) and total corneal refractive power (TCRP, Pentacam HR) was evaluated. IOL power calculations were performed using TK-based Barrett TK Universal II and TCRP-based Barrett Universal II calculations, respectively. Results: Paired t-tests showed that the differences in white-to-white diameter, central corneal thickness, anterior chamber depth, and mean TK between IOLMaster 700 and Pentacam HR were slight but significant (all P<0.05), and the differences in recommended IOL power for emmetropia between two Barrett calculations were also significant in 3 PC-IOLs (all P<0.05). The ROC curve showed that the AUC was 0.917 (95% CI, 0.820-0.971) for the absolute value of the difference between TK and TCRP in discriminating the difference of ≥ ±0.5 D in predicted IOL power with best cutoff values of 0.4 D. Conclusion: The novel Barrett TK Universal II formula built in IOLMaster 700 is comparable to TCRP-based Barrett Universal II calculation for IOL power calculation of PC-IOLs, and the convenience of using the Barrett TK Universal II formula should be founded on measurement consistency between devices.

11.
J Org Chem ; 89(11): 7770-7779, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38738957

RESUMO

A visible-light-enabled photoredox radical cascade cyclization of 2-vinyl benzimidazole derivatives is developed. This chemistry is applicable to a wide range of N-aroyl 2-vinyl benzimidazoles as acceptors, and halo compounds, including alkyl halides, acyl chlorides and sulfonyl chlorides, as radical precursors. The Langlois reagent also serves as an effective partner in this photocatalytic oxidative cascade process. This protocol provides a robust alternative for rendering highly functionalized benzo[4,5]imidazo[1,2-b]isoquinolin-11(6H)-ones.

12.
Transl Psychiatry ; 14(1): 228, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816357

RESUMO

Depression and obesity are prevalent disorders with significant public health implications. In this study, we used a high-fat diet (HFD)-induced obese mouse model to investigate the mechanism underlying HFD-induced depression-like behaviors. HFD-induced obese mice exhibited depression-like behaviors and a reduction in hippocampus volume, which were reversed by treatment with an indoleamine 2,3-dioxygenase (IDO) inhibitor 1-methyltryptophan (1-MT). Interestingly, no changes in IDO levels were observed post-1-MT treatment, suggesting that other mechanisms may be involved in the anti-depressive effect of 1-MT. We further conducted RNA sequencing analysis to clarify the potential underlying mechanism of the anti-depressive effect of 1-MT in HFD-induced depressive mice and found a significant enrichment of shared differential genes in the extracellular matrix (ECM) organization pathway between the 1-MT-treated and untreated HFD-induced depressive mice. Therefore, we hypothesized that changes in ECM play a crucial role in the anti-depressive effect of 1-MT. To this end, we investigated perineuronal nets (PNNs), which are ECM assemblies that preferentially ensheath parvalbumin (PV)-positive interneurons and are involved in many abnormalities. We found that HFD is associated with excessive accumulation of PV-positive neurons and upregulation of PNNs, affecting synaptic transmission in PV-positive neurons and leading to glutamate-gamma-aminobutyric acid imbalances in the hippocampus. The 1-MT effectively reversed these changes, highlighting a PNN-related mechanism by which 1-MT exerts its anti-depressive effect.


Assuntos
Depressão , Dieta Hiperlipídica , Modelos Animais de Doenças , Matriz Extracelular , Hipocampo , Camundongos Endogâmicos C57BL , Triptofano , Animais , Camundongos , Triptofano/análogos & derivados , Triptofano/farmacologia , Depressão/tratamento farmacológico , Depressão/etiologia , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/efeitos dos fármacos , Obesidade/tratamento farmacológico , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Comportamento Animal/efeitos dos fármacos , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Rede Nervosa/efeitos dos fármacos
13.
Sci Rep ; 14(1): 10507, 2024 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714727

RESUMO

Glioma, particularly glioblastomas (GBM), is incurable brain tumor. The most targeted receptor tyrosine kinase (RTKs) drugs did not bring benefit to GBM patients. The mechanism of glioma growth continues to be explored to find more effective treatment. Here, we reported that Ser/Thr protein kinase YANK2 (yet another kinase 2) is upregulated in glioma tissues and promotes the growth and proliferation of glioma in vitro and in vivo. Further, we confirmed that oncogene Fyn directly activated YANK2 through phosphorylation its Y110, and Fyn-mediated YANK2 phosphorylation at Y110 site promotes glioma growth by increasing its stability. Finally, YANK2 was proved to be a novel upstream kinase of p70S6K and promotes glioma growth by directly phosphorylating p70S6K at T389. Taken together, we found a new mTOR-independent p70S6K activation pathway, Fyn-YANK2-p70S6K, which promotes glioma growth, and YANK2 is a potential oncogene and serves as a novel therapeutic target for glioma.


Assuntos
Proliferação de Células , Glioma , Proteínas Proto-Oncogênicas c-fyn , Proteínas Quinases S6 Ribossômicas 70-kDa , Transdução de Sinais , Serina-Treonina Quinases TOR , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/genética , Humanos , Proteínas Proto-Oncogênicas c-fyn/metabolismo , Proteínas Proto-Oncogênicas c-fyn/genética , Serina-Treonina Quinases TOR/metabolismo , Glioma/metabolismo , Glioma/patologia , Glioma/genética , Animais , Linhagem Celular Tumoral , Fosforilação , Carcinogênese/genética , Carcinogênese/metabolismo , Camundongos , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Camundongos Nus , Regulação Neoplásica da Expressão Gênica
14.
Heliyon ; 10(9): e30491, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38756593

RESUMO

Aim: The aim of this study was to confirm the presence of the form deprivation myopia (FDM) guinea pig eye-gut axis and investigate the relationship between serum vasoactive intestinal peptide (VIP), lipopolysaccharides (LPS), specific gut microbiota and their metabolites. Method: 20 specific-pathogen-free (SPF) guinea pigs were divided into the FDM and the control(Con) group. Following model induction, serum levels of VIP and LPS were quantified. A combination of 16S ribosomal ribosomal Ribonucleic Acid (rRNA) gene sequencing, non-targeted metabolomics and bioinformatics analysis were employed to identify disparities in gut microbiota and metabolites between the two groups of guinea pigs. Result: Compared to the control group, FDM guinea pigs exhibited a significant trend towards myopia, along with significantly elevated concentrations of LPS and VIP (p < 0.0001). Furthermore, Ruminococcus_albus emerged as the predominant bacterial community enriched in FDM (p < 0.05), and demonstrated positive correlations with 10 metabolites, including l-Glutamic acid, Additionally, Ruminococcus_albus exhibited positive correlations with VIP and LPS levels (p < 0.05). Conclusion: The findings suggest that the Ruminococcus_Albus and glutamate metabolic pathways play a significant role in myopia development, leading to concurrent alterations in serum VIP and LPS levels in FDM guinea pigs. This underscores the potential of specific gut microbiota and their metabolites as pivotal biomarkers involved in the pathogenesis of myopia.

16.
Gen Comp Endocrinol ; 354: 114530, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-38657738

RESUMO

Prolactin is involved in regulating various physiological activities of vertebrates and is one of the most momentous pituitary hormones. However, not enough attention is currently paid to prolactin, especially in teleost. This paper aims to gather, organize, and analyze recent studies on the regulation and functions of prolactin. By comparing with other animal groups, it highlights the significant role of prolactin in fish reproduction, immunity, growth, and osmotic pressure regulation, as well as the upstream and downstream factors that may be involved in the regulation of prolactin functions were introduced to provide a theoretical basis for the in-depth study and potential practical application of prolactin.


Assuntos
Peixes , Prolactina , Animais , Prolactina/metabolismo , Peixes/metabolismo , Peixes/fisiologia , Reprodução/fisiologia
17.
Quant Imaging Med Surg ; 14(4): 3086-3106, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38617147

RESUMO

Background: Parkinson's disease (PD) is an irreversible, chronic degenerative disease of the central nervous system, potentially associated with cerebral white matter (WM) lesions. Investigating the microstructural alterations within the WM in the early stages of PD can help to identify the disease early and enable intervention to reduce the associated serious threats to health. Methods: This study selected 227 cases from the Parkinson's Progression Markers Initiative (PPMI) database, including 152 de novo PD patients and 75 normal controls (NC). Whole-brain voxel analysis of the WM was performed using the tract-based spatial statistics (TBSS) method. The WM regions with statistically significant differences (P<0.05) between the PD and NC groups were identified and used as masks. The mask was applied to each case's fractional anisotropy (FA) image to extract voxel values as feature vectors. Geometric dimensionality reduction was then applied to eliminate redundant values in the feature vectors. Subsequently, the cases were randomly divided into a training group (158 cases, including 103 PD patients and 55 NC) and a test group (69 cases, including 49 PD patients and 20 NC). The least absolute shrinkage and selection operator (LASSO) regression algorithm was employed to extract the minimal set of relevant features, then the random forest (RF) algorithm was utilized for classification using 5-fold cross validation. The resulting model was further integrated with clinical factors to create a comprehensive prediction model. Results: In comparison to the NC group, the FA values in PD patients exhibited a statistically significant decrease (P<0.05), indicating the presence of widespread WM lesions across multiple brain regions. Moreover, the PD prediction model, constructed based on these WM lesion regions, yielded prediction accuracy (ACC) and area under the receiver operating characteristic (ROC) curve (AUC) values of 0.778 and 0.865 in the validation set, and 0.783 and 0.831 in the test set, respectively. Furthermore, the performance of the integrated model showed some improvement, with ACC and AUC values in the test set reaching 0.804 and 0.844, respectively. Conclusions: The quantitative calculation of WM lesion area on FA images using the TBSS method can serve as a neuroimaging biomarker for diagnosing and predicting early PD at the individual level. When integrated with clinical variables, the predictive performance improves.

18.
Cancer Lett ; 591: 216849, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38621458

RESUMO

Branched-chain amino acid transferase 1 (BCAT1) is highly expressed in multiple cancers and is associated with poor prognosis, particularly in glioblastoma (GBM). However, the post-translational modification (PTM) mechanism of BCAT1 is unknown. Here, we investigated the cross-talk mechanisms between phosphorylation and ubiquitination modifications in regulating BCAT1 activity and stability. We found that BCAT1 is phosphorylated by branched chain ketoacid dehydrogenase kinase (BCKDK) at S5, S9, and T312, which increases its catalytic and antioxidant activity and stability. STUB1 (STIP1 homology U-box-containing protein 1), the first we found and reported E3 ubiquitin ligase of BCAT1, can also be phosphorylated by BCKDK at the S19 site, which disrupts the interaction with BCAT1 and inhibits its degradation. In addition, we demonstrate through in vivo and in vitro experiments that BCAT1 phosphorylation inhibiting its ubiquitination at multiple sites is associated with GBM proliferation and that inhibition of the BCKDK-BCAT1 axis enhances the sensitivity to temozolomide (TMZ). Overall, we identified novel mechanisms for the regulation of BCAT1 modification and elucidated the importance of the BCKDK-STUB1-BCAT1 axis in GBM progression.


Assuntos
Proliferação de Células , Glioblastoma , Ubiquitina-Proteína Ligases , Ubiquitinação , Glioblastoma/patologia , Glioblastoma/metabolismo , Glioblastoma/genética , Humanos , Fosforilação , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Animais , Linhagem Celular Tumoral , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/genética , Progressão da Doença , Camundongos , Camundongos Nus , Proteólise , Temozolomida/farmacologia , Células HEK293
19.
PLoS One ; 19(3): e0297230, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38489304

RESUMO

PURPOSE: To determine whether pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for rhegmatogenous retinal detachment (RRD) could get better functional and anatomical outcomes. METHODS: A comprehensive literature search was performed to find relevant studies. A meta-analysis was conducted by comparing the weighted mean differences (WMD) in the mean change of best corrected visual acuity (BCVA) from baseline and calculating the odd ratios (OR) for rates of epiretinal membrane (ERM) formation and recurrence of retinal detachment (RD). RESULTS: Fourteen studies were selected, including 2259 eyes (825 eyes in the ILM peeling group and 1434 eyes in the non-ILM peeling group). There was no significant difference in terms of mean change in BCVA from baseline and the rate of RD recurrence (WMD = 0.02, 95% CI, -0.20 to 0.24, P = 0.86, and OR = 0.55, 95% CI, 0.24 to 1.26, P = 0.16), but ILM peeling was associated with a significantly lower frequency of postoperative ERM formation (OR = 0.13, 95% CI, 0.06 to 0.26, P<0.00001). Similar results were obtained in a sub-analysis based on macula-off RRD. CONCLUSION: ILM peeling results in similar BCVA, with same rate of RD recurrence, but lower rate of postoperative ERM development. ILM peeling could be considered in selected cases with risk factors that are likely to develop an ERM.


Assuntos
Membrana Epirretiniana , Macula Lutea , Descolamento Retiniano , Anormalidades da Pele , Humanos , Descolamento Retiniano/etiologia , Retina , Membrana Epirretiniana/etiologia , Membrana Basal/cirurgia , Vitrectomia/métodos , Estudos Retrospectivos , Tomografia de Coerência Óptica
20.
ACS Omega ; 9(9): 10929-10936, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38463324

RESUMO

Chongqing Chengkou manganese deposit is a large carbonate-type manganese deposit in the upper reaches of the Yangtze River, located in Gaoyan Town, Chengkou County, Chongqing. In order to improve the recovery rate of low-grade manganese ore and concentrate grade index, achieve efficient utilization of mineral resources, and sustainable development of Gaoyan manganese ore deposit in Chengkou, Chongqing, China, in this paper, by means of optical microscope analysis, high-resolution X-ray tomography technology, three-dimensional image analysis technology, X-ray diffraction analysis, X-ray fluorescence spectrum analysis, and technical and economic analysis, the occurrence state and process mineralogy of manganese are studied, and the technical and economic analysis of flotation, high-intensity magnetic separation, and gravity separation are carried out. It provides a reference for other mining enterprises to choose the most suitable beneficiation method according to the specific mineral species.

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