Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 548
Filtrar
1.
J Chromatogr A ; 1732: 465231, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39133951

RESUMEN

Macrocycles play vital roles in supramolecular chemistry and chromatography. 1,1'-Bi-2-naphthol (BINOL)-based chiral polyimine macrocycles are an emerging class of chiral macrocycles that can be constructed by one-step aldehyde-amine condensation of BINOL derivatives with other building blocks. These macrocycles exhibit good characteristics, such as facile preparation, rigid cyclic structures, multiple chiral centers, and defined molecular cavities, that make them good candidates as new chiral recognition materials for chromatographic enantioseparations. In this study, a BINOL-based [2+2] chiral polyimine macrocycle was synthesized by one-step condensation of enantiopure (S)-2,2'-dihydroxy-[1,1'-binaphthalene]-3,3'-dicarboxaldehyde with (1R,2R)-1,2-diaminocyclohexane. The product was modified with 5-bromo-1-pentene and then attached to thiolated silica using click chemistry to construct a new chiral stationary phase (CSP). The enantioselectivity of the new CSP was explored by separating various racemates under normal phase (NP) and reversed phase (RP) high performance liquid chromatography (HPLC). Thirteen racemates and eight racemates were enantioseparated under the two separation modes, respectively, including chiral alcohols, phenols, esters, ketones, amines, and organic acids. Among them, nine racemates achieved baseline separation under NP-HPLC and seven racemates achieved baseline separation under RP-HPLC. High resolution separation was observed with benzoin (Rs = 5.10), epinephrine (Rs = 4.98), 3-benzyloxy-1,2-propanediol (Rs = 4.42), and 4,4'-dimethylbenzoin (Rs = 4.52) in NP-HPLC, and with 4-methylbenzhydrol (Rs = 4.72), benzoin ethyl ether (Rs = 3.79), 1-phenyl-1-pentanol (Rs = 3.68), and 1-(3-bromophenyl)ethanol (Rs = 3.60) in RP-HPLC. Interestingly, the CSP complemented Chiralcel OD-H, Chiralpak AD-H, and CYCLOBOND I 2000 RSP columns for resolution of these test racemates, separating several racemic compounds that could not be well separated by the three commercially available columns. The influences of injected sample amount on separation were also evaluated. It was found that the column exhibited excellent stability and reproducibility after hundreds of injections, and the relative standard deviations (n = 5) of the retention time and resolution were less than 0.49% and 0.69%, respectively. This study indicates that the BINOL-based chiral macrocycle has great potential for HPLC enantioseparation.


Asunto(s)
Compuestos Macrocíclicos , Naftoles , Dióxido de Silicio , Cromatografía Líquida de Alta Presión/métodos , Estereoisomerismo , Naftoles/química , Naftoles/aislamiento & purificación , Compuestos Macrocíclicos/química , Compuestos Macrocíclicos/aislamiento & purificación , Dióxido de Silicio/química
2.
Microbiol Res ; 288: 127839, 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39141971

RESUMEN

The evolution of hypervirulent and carbapenem-resistant Klebsiella pneumoniae can be categorized into three main patterns: the evolution of KL1/KL2-hvKp strains into CR-hvKp, the evolution of carbapenem-resistant K. pneumoniae (CRKp) strains into hv-CRKp, and the acquisition of hybrid plasmids carrying carbapenem resistance and virulence genes by classical K. pneumoniae (cKp). These strains are characterized by multi-drug resistance, high virulence, and high infectivity. Currently, there are no effective methods for treating and surveillance this pathogen. In addition, the continuous horizontal transfer and clonal spread of these bacteria under the pressure of hospital antibiotics have led to the emergence of more drug-resistant strains. This review discusses the evolution and distribution characteristics of hypervirulent and carbapenem-resistant K. pneumoniae, the mechanisms of carbapenem resistance and hypervirulence, risk factors for susceptibility, infection syndromes, treatment regimens, real-time surveillance and preventive control measures. It also outlines the resistance mechanisms of antimicrobial drugs used to treat this pathogen, providing insights for developing new drugs, combination therapies, and a "One Health" approach. Narrowing the scope of surveillance but intensifying implementation efforts is a viable solution. Monitoring of strains can be focused primarily on hospitals and urban wastewater treatment plants.

3.
Materials (Basel) ; 17(15)2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-39124315

RESUMEN

Pressure sensors prepared from sapphire exhibit excellent characteristics, including high-temperature resistance, high hardness, and resistance to electromagnetic interference. A Fast Fourier Transform and Mean Square Error (FFT-MSE) demodulation algorithm was employed to demodulate a sapphire sandwich-structure Fabry-Perot (F-P) pressure sensor. Through simulation analysis, the experimental results indicated that the demodulation error of the air cavity length in the range of 206 µm to 216 µm was less than 0.0008%. Compared to single demodulation methods and combined demodulation methods based on FFT or Minimum Mean Square Error (MMSE), the method proposed in this work reduced the demodulation error by more than three times and increased accuracy by more than six times. The algorithm was utilized to demodulate the sapphire sandwich-structure F-P pressure sensor, and the test results indicated that the fitting error of the sensor was less than 0.025% within the pressure range of 0 MPa to 10 MPa. The repeatability error was less than 0.066%, the zero-point deviation was 1.26%, and the maximum stability deviation was 0.0063% per 30 min. The algorithm effectively demodulated the actual cavity length variation in the sapphire sandwich-structure F-P pressure sensor, providing a solution for the performance evaluation of the sapphire sandwich-structure F-P pressure sensor.

4.
Rheumatol Int ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39168871

RESUMEN

Systemic lupus erythematosus (SLE) affects many populations. This study aims to develop a predictive model and create a nomogram for assessing the risk of end-stage renal disease (ESRD) in patients diagnosed with SLE. Data from electronic health records of SLE patients treated at the Affiliated Hospital of North Sichuan Medical College between 2013 and 2023 were collected. The dataset underwent thorough cleaning and variable assignment procedures. Subsequently, variables were selected using one-way logistic regression and lasso logistic regression methods, followed by multifactorial logistic regression to construct nomograms. The model's performance was assessed using calibration, receiver operating characteristic (ROC), and decision curve analysis (DCA) curves. Statistical significance was set at P < 0.05. The predictive variables for ESRD development in SLE patients included anti-GP210 antibody presence, urinary occult blood, proteinuria, white blood cell count, complement 4 levels, uric acid, creatinine, total protein, globulin, glomerular filtration rate, pH, specific gravity, very low-density lipoprotein, homocysteine, apolipoprotein B, and absolute counts of cytotoxic T cells. The nomogram exhibited a broad predictive range. The ROC area under the curve (AUC) was 0.886 (0.858-0.913) for the training set and 0.840 (0.783-0.897) for the testing set, indicating good model performance. The model demonstrated both applicability and significant clinical benefits. The developed model presents strong predictive capabilities and considerable clinical utility in estimating the risk of ESRD in patients with SLE.

5.
Ecotoxicol Environ Saf ; 284: 116906, 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39182283

RESUMEN

BACKGROUND: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. METHODS: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. RESULTS: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database (GTRD)and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. CONCLUSION: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

6.
Int J Surg ; 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954666

RESUMEN

BACKGROUND: Artificial intelligence (AI) technologies, particularly large language models (LLMs), have been widely employed by the medical community. In addressing the intricacies of urology, ChatGPT offers a novel possibility to aid in clinical decision-making. This study aimed to investigate the decision-making ability of LLMs in solving complex urology-related problems and assess its effectiveness in providing psychological support to patients with urological disorders. MATERIALS AND METHODS: This study evaluated the clinical and psychological support capabilities of ChatGPT 3.5 and 4.0 in the field of urology. A total of 69 clinical and 30 psychological questions were posed to the AI models, and their responses were evaluated by both urologists and psychologists. As a control, clinicians from Chinese medical institutions provided responses under closed-book conditions. Statistical analyses were conducted separately for each subgroup. RESULTS: In multiple-choice tests covering diverse urological topics, ChatGPT 4.0, performed comparably to the physician group, with no significant overall score difference. Subgroup analyses revealed variable performance, based on disease type and physician experience, with ChatGPT 4.0 generally outperforming ChatGPT 3.5 and exhibiting competitive results against physicians. When assessing the psychological support capabilities of AI, it is evident that ChatGPT4.0 outperforms ChatGPT3.5 across all urology-related psychological problems. CONCLUSIONS: The performance of LLMs in dealing with standardized clinical problems and providing psychological support has certain advantages over clinicians. AI stands out as a promising tool for potential clinical aid.

7.
Int Immunopharmacol ; 139: 112662, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39038385

RESUMEN

OBJECTIVE: Sarcopenia manifests as a chronic, low-level inflammation along with multiple inflammatory cells infiltration. Interleukin (IL)-25 can regulate the function of macrophages. However, the specific role and mechanisms through which IL-25 functions in sarcopenia are still not fully understood and require further investigation. METHODS: Aged mice were utilized as sarcopenia models and examined the expression of inflammatory factors. To investigate the effects of IL-25 on sarcopenia, the model mice received IL-25 treatment and underwent in vivo adoptive transfer of IL-25-induced macrophages. Meanwhile, RAW264.7 cells, bone marrow-derived macrophages, satellite cells and C2C12 cells were used in vitro. Shh insufficiency was induced through intramuscular administration of SHH-shRNA adenoviruses. Then, various assays including scratch wound, cell counting kit-8 and Transwell assays, as well as histological staining and molecular biological methods, were conducted. RESULTS: Aged mice exhibited an accelerated decline in muscle strength and mass, along with an increased muscle lipid droplets and macrophage infiltration, and decreased IL-25 levels compared to the young group. IL-25 therapy and the transfer of IL-25-preconditioned macrophages could improve these conditions by promoting M2 macrophage polarization in vivo as well as in vitro. M2 macrophage conditioned medium enhanced satellite cell proliferation and migration, as well as the vitality, migration, and differentiation of C2C12 cells in vitro. Furthermore, IL-25 enhanced Shh expression in macrophages in vitro, and activated the Shh signaling pathway in muscle tissue of aged mice, which could be suppressed by either the inhibitor cyclopamine or Shh knockdown. Mechanistic studies showed that Shh insufficiency suppressed the activation of Akt/mTOR signaling pathway in muscle tissue of aged mice. CONCLUSION: IL-25 promotes the secretion of Shh by M2 macrophages and activates the Shh/Akt/mTOR signaling pathway, which improves symptoms and function in sarcopenia mice. This suggests that IL-25 has potential as a therapeutic agent for treating sarcopenia.


Asunto(s)
Proteínas Hedgehog , Macrófagos , Ratones Endogámicos C57BL , Músculo Esquelético , Regeneración , Sarcopenia , Transducción de Señal , Animales , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Ratones , Macrófagos/inmunología , Macrófagos/efectos de los fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/efectos de los fármacos , Células RAW 264.7 , Masculino , Interleucina-17/metabolismo , Modelos Animales de Enfermedad , Humanos , Proliferación Celular/efectos de los fármacos
8.
J Am Med Dir Assoc ; 25(9): 105128, 2024 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-38977200

RESUMEN

OBJECTIVE: Reliable identification of high-risk older adults who are likely to develop sarcopenia is essential to implement targeted preventive measures and follow-up. However, no sarcopenia prediction model is currently available for community use. Our objective was to develop and validate a risk prediction model for calculating the 1-year absolute risk of developing sarcopenia in an aging population. METHODS: One prospective population-based cohort of non-sarcopenic individuals aged 60 years or older were used for the development of a sarcopenia risk prediction model and model validation. Sarcopenia was defined according to the 2019 Asian Working Group for Sarcopenia consensus. Stepwise logistic regression was used to identify risk factors for sarcopenia incidence within a 1-year follow-up. Model performance was evaluated using the area under the receiver operating characteristics curve (AUROC) and calibration plot, respectively. RESULTS: The development cohort included 1042 older adults, among whom 87 participants developed sarcopenia during a 1-year follow-up. The PRE-SARC (PREdiction of SARCopenia Risk in community older adults) model can accurately predict the 1-year risk of sarcopenia by using 7 easily accessible community-based predictors. The PRE-SARC model performed well in predicting sarcopenia, with an AUROC of 87% (95% CI, 0.83-0.90) and good calibration. Internal validation showed minimal optimism, with an adjusted AUROC of 0.85. The prediction score was categorized into 4 risk groups: low (0%-10%), moderate (>10%-20%), high (>20%-40%), and very high (>40%). The PRE-SARC model has been incorporated into an online risk calculator, which is freely accessible for daily clinical applications (https://sarcopeniariskprediction.shinyapps.io/dynnomapp/). CONCLUSIONS: In community-dwelling individuals, the PRE-SARC model can accurately predict 1-year sarcopenia incidence. This model serves as a readily available and free accessible tool to identify older adults at high risk of sarcopenia, thereby facilitating personalized early preventive approaches and optimizing the utilization of health care resources.

9.
Hum Vaccin Immunother ; 20(1): 2382502, 2024 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-39081126

RESUMEN

It was common to see that older adults were reluctant to be vaccinated for coronavirus disease 2019 (COVID-19) in China. There is a lack of practical prediction models to guide COVID-19 vaccination program. A nationwide, self-reported, cross-sectional survey was conducted from September 2022 to November 2022, including people aged 60 years or older. Stratified random sampling was used to divide the dataset into derivation, validation, and test datasets at a ratio of 6:2:2. Least absolute shrinkage and selection operator and multivariable logistic regression were used for variable screening and model construction. Discrimination and calibration were assessed primarily by area under the receiver operating characteristic curve (AUC) and calibration curve. A total of 35057 samples (53.65% males and mean age of 69.64 ± 7.24 years) were finally selected, which constitutes 93.73% of the valid samples. From 33 potential predictors, 19 variables were screened and included in the multivariable logistic regression model. The mean AUC in the validation dataset was 0.802, with sensitivity, specificity, and accuracy of 0.732, 0.718 and 0.729 respectively, which were similar to the parameters in the test dataset of 0.755, 0.715 and 0.720, respectively, and the mean AUC in the test dataset was 0.815. There were no significant differences between the model predicted values and the actual observed values for calibration in these groups. The prediction model based on self-reported characteristics of older adults was developed that could be useful for predicting the willingness for COVID-19 vaccines, as well as providing recommendations in improving vaccine acceptance.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Autoinforme , Humanos , Estudios Transversales , Masculino , Anciano , Femenino , COVID-19/prevención & control , Vacunas contra la COVID-19/administración & dosificación , China , Persona de Mediana Edad , Vacunación/estadística & datos numéricos , SARS-CoV-2/inmunología , Modelos Logísticos , Anciano de 80 o más Años , Curva ROC , Pueblos del Este de Asia
10.
Sensors (Basel) ; 24(14)2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39065984

RESUMEN

There are various indoor fingerprint localization techniques utilizing the similarity of received signal strength (RSS) to discriminate the similarity of positions. However, due to the varied states of different wireless access points (APs), each AP's contribution to RSS similarity varies, which affects the accuracy of localization. In our study, we analyzed several critical causes that affect APs' contribution, including APs' health states and APs' positions. Inspired by these insights, for a large-scale indoor space with ubiquitous APs, a threshold was set for all sample RSS to eliminate the abnormal APs dynamically, a correction quantity for each RSS was provided by the distance between the AP and the sample position to emphasize closer APs, and a priority weight was designed by RSS differences (RSSD) to further optimize the capability of fingerprint distances (FDs, the Euclidean distance of RSS) to discriminate physical distance (PDs, the Euclidean distance of positions). Integrating the above policies for the classical WKNN algorithm, a new indoor fingerprint localization technique is redefined, referred to as FDs' discrimination capability improvement WKNN (FDDC-WKNN). Our simulation results showed that the correlation and consistency between FDs and PDs are well improved, with the strong correlation increasing from 0 to 76% and the high consistency increasing from 26% to 99%, which confirms that the proposed policies can greatly enhance the discrimination capabilities of RSS similarity. We also found that abnormal APs can cause significant impact on FDs discrimination capability. Further, by implementing the FDDC-WKNN algorithm in experiments, we obtained the optimal K value in both the simulation scene and real library scene, under which the mean errors have been reduced from 2.2732 m to 1.2290 m and from 4.0489 m to 2.4320 m, respectively. In addition, compared to not using the FDDC-WKNN, the cumulative distribution function (CDF) of the localization errors curve converged faster and the error fluctuation was smaller, which demonstrates the FDDC-WKNN having stronger robustness and more stable localization performance.

11.
Eur J Surg Oncol ; 50(9): 108513, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38968854

RESUMEN

INTRODUCTION: Comparative studies on surgical treatments with time-to-event endpoints have provided substantial evidence for clinical practice, but the accurate use of survival data analysis and the control of confounding bias remain big challenges. METHODS: This was a survey of surgical studies with survival outcomes published in four general medical journals and five general surgical journals in 2021. The two most concerned statistical issues were evaluated, including confounding control by propensity score analysis (PSA) or multivariable analysis and testing of proportional hazards (PH) assumption in Cox model. RESULTS: A total of 74 studies were included, comprising 63 observational studies and 11 randomized controlled trials. Among the observational studies, the proportion of studies utilizing PSA in surgical oncology and non-oncology studies was similar (40.9 % versus 36.8 %, P = 0.762). However, the former reported a significantly lower proportion of PH assumption assessments compared to the latter (13.6 % versus 42.1 %, P = 0.020). Twenty-five observational studies (25/63) used PSA methods, but two-thirds of them (17/25) showed unclear balance of baseline data after PSA. And the proportion of PH assumption testing after PSA was slightly lower than that before PSA, but the difference was not statistically significant (24.0 % versus 28.0 %, P = 0.317). Comprehensive suggestions were given on confounding control in survival analysis and alternative resolutions for non-compliance with PH assumption. CONCLUSION: This study highlights suboptimal reporting of PH assumption evaluation in observational surgical studies both before and after PSA. Efforts and consensus are needed with respect to the underlying assumptions of statistical methods.

13.
Diabetes ; 2024 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-39058664

RESUMEN

Maturation of postnatal ß cells is regulated in a cell-autonomous manner, and metabolically stressed ß cells regress to an immature state, ensuring defective ß-cell function and the onset of type 2 diabetes. The molecular mechanisms connecting the nutritional transition to ß-cell maturation remain largely unknown. Here, we report a miR-203/ZBTB20/MAFA regulatory axis that mediates the ß-cell maturation process. We show that miR-203 level in ß cells changes during the nutritional transition and that miR-203 inhibits ß-cell maturation at the neonatal stage and under high-fat diet (HFD) conditions. Using single-cell RNA sequencing, we demonstrated that miR-203 elevation promoted the transition of immature ß cells into CgBHi endocrine cells, while suppressing gene expressions associated with ß-cell maturation in a ZBTB20/MAFA-dependent manner. ZBTB20 is an authentic target of miR-203 and transcriptionally upregulates MAFA expression. Manipulating the miR-203/ZBTB20/MAFA axis may therefore offer a novel strategy for boosting functional ß-cell numbers to alleviate diabetes.

14.
J Nanobiotechnology ; 22(1): 432, 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39034393

RESUMEN

Rheumatoid arthritis (RA) involves chronic joint inflammation. Combining acupuncture and medication for RA treatment faces challenges like spatiotemporal variability, limited drug loading in acupuncture needles, and premature or untargeted drug release. Here, we designed a new type of tubular acupuncture needles, with an etched hollow honeycomb-like structure to enable the high loading of therapeutics, integrating the traditional acupuncture and drug repository into an all-in-one therapeutic platform. In these proof-of-concept experiments, we fabricated injectable hollow honeycomb electroacupuncture needles (HC-EA) loaded with melittin hydrogel (MLT-Gel), enabling the combination treatment of acupuncture stimulation and melittin therapy in a spatiotemporally synchronous manner. Since the RA microenvironment is mildly acidic, the acid-responsive chitosan (CS)/sodium beta-glycerophosphate (ß-GP)/ hyaluronic acid (HA) composited hydrogel (CS/GP/HA) was utilized to perform acupuncture stimulation and achieve the targeted release of injected therapeutics into the specific lesion site. Testing our therapeutic platform involved a mouse model of RA and bioinformatics analysis. MLT-Gel@HC-EA treatment restored Th17/Treg-mediated immunity balance, reduced inflammatory factor release (TNF-α, IL-6, IL-1ß), and alleviated inflammation at the lesion site. This novel combination of modified acupuncture needle and medication, specifically melittin hydrogel, holds promise as a therapeutic strategy for RA treatment.


Asunto(s)
Terapia por Acupuntura , Artritis Reumatoide , Hidrogeles , Meliteno , Agujas , Animales , Meliteno/farmacología , Meliteno/química , Ratones , Artritis Reumatoide/terapia , Artritis Reumatoide/tratamiento farmacológico , Hidrogeles/química , Terapia por Acupuntura/métodos , Quitosano/química , Ácido Hialurónico/química , Masculino , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL
15.
Proc Natl Acad Sci U S A ; 121(28): e2320870121, 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38959033

RESUMEN

Efficient storage and sharing of massive biomedical data would open up their wide accessibility to different institutions and disciplines. However, compressors tailored for natural photos/videos are rapidly limited for biomedical data, while emerging deep learning-based methods demand huge training data and are difficult to generalize. Here, we propose to conduct Biomedical data compRession with Implicit nEural Function (BRIEF) by representing the target data with compact neural networks, which are data specific and thus have no generalization issues. Benefiting from the strong representation capability of implicit neural function, BRIEF achieves 2[Formula: see text]3 orders of magnitude compression on diverse biomedical data at significantly higher fidelity than existing techniques. Besides, BRIEF is of consistent performance across the whole data volume, and supports customized spatially varying fidelity. BRIEF's multifold advantageous features also serve reliable downstream tasks at low bandwidth. Our approach will facilitate low-bandwidth data sharing and promote collaboration and progress in the biomedical field.


Asunto(s)
Difusión de la Información , Redes Neurales de la Computación , Humanos , Difusión de la Información/métodos , Compresión de Datos/métodos , Aprendizaje Profundo , Investigación Biomédica/métodos
17.
Aging Cell ; : e14236, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38838088

RESUMEN

Sarcopenia is a significant geriatric syndrome that involves the loss of skeletal muscle mass and strength. Due to its substantial endocrine role, the metabolic microenvironment of skeletal muscle undergoes changes with age. Examining the pathogenesis of sarcopenia through focusing on metabolic dysregulation could offer insights for developing more effective intervention strategies. In this study, we analyzed the transcriptomics data to identify specific genes involved in the regulation of metabolism in skeletal muscle during the development of sarcopenia. Three machine learning algorithms were employed to screen key target genes exhibiting strong correlations with metabolism, which were further validated using RNA-sequencing data and publicly accessible datasets. Among them, the metabolic enzyme nicotinamide N-methyltransferase (NNMT) was elevated in sarcopenia, and predicted sarcopenia with an area under the curve exceeding 0.7, suggesting it as a potential therapeutic target for sarcopenia. As expected, inhibition of NNMT improved the grip strength in aging mice and alleviated age-related decline in the mass index of the quadriceps femoris muscles and whole-body lean mass index. Additionally, the NNMTi treatment increased the levels of nicotinamide adenine dinucleotide (NAD+) content, as well as PGC1α and p-AMPK expression in the muscles of both the D-galactose-treated mouse model and naturally aging mouse model. Overall, this work demonstrates NNMT as a promising target for preventing age-related decline in muscle mass and strength.

18.
Biochem Pharmacol ; 226: 116375, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38906227

RESUMEN

Fat mass and obesity-associated protein (FTO) is an N6-methyladenosine (m6A) demethylase and plays critical oncogenic roles in multiple cancers. Here we show that FTO is an effective target in hepatocellular carcinoma (HCC). FTO is highly expressed in patients with HCC. Genetic depletion of Fto dramatically attenuated HCC progression in mice. Pharmacological inhibition of FTO by FB23/FB23-2 markedly suppressed the proliferation and migration of HCC cell lines in vitro and inhibited HCC tumorigenicity in xeno-transplanted mice. Mechanistically, FB23-2 suppressed the expression of Erb-b2 receptor tyrosine kinase 3 (ERBB3) and human tubulin beta class Iva (TUBB4A) by increasing the m6A level in these mRNA transcripts. The decrease in ERBB3 expression resulted in the inhibition of Akt-mTOR signaling, which subsequently impaired the proliferation and survival of HCC cells. Moreover, FB23-2 disturbed the stability of the tubulin cytoskeleton, whereas overexpression of TUBB4A rescued the migration of HCC cells. Collectively, our study demonstrates that FTO plays a critical role in HCC by maintaining the proliferation and migration of cells and highlights the potential of FTO inhibitors for targeting HCC.


Asunto(s)
Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato , Carcinoma Hepatocelular , Neoplasias Hepáticas , Receptor ErbB-3 , Tubulina (Proteína) , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/metabolismo , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/genética , Dioxigenasa FTO Dependiente de Alfa-Cetoglutarato/antagonistas & inhibidores , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/genética , Humanos , Animales , Ratones , Tubulina (Proteína)/metabolismo , Receptor ErbB-3/metabolismo , Receptor ErbB-3/genética , Receptor ErbB-3/antagonistas & inhibidores , Línea Celular Tumoral , Ratones Desnudos , Masculino , Proliferación Celular/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/efectos de los fármacos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...