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1.
Front Vet Sci ; 11: 1340849, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721154

RESUMEN

Introduction: Pigs are often used to study the intestinal development of newborns, particularly as preterm pig models that mimic the intestinal growth of human preterm infants. Neonatology's study of delivery mode's impact on neonatal development is crucial. Methods: We established 14 newborn pigs delivered via cesarean sections (C-section, at 113 days of gestational age, CS group) and 8 naturally born pigs were used as controls (at 114 days of gestational age, NF group). The impact of two alternative delivery procedures (C-section and natural birth) on the levels of short-chain fatty acids (SCFAs) and organic acids in the hepatic and intestines of newborn pigs were compared using metabolomics. The underlying molecular pathways are examined at the "protein-metabolite" level by integrating proteomic data. Results: The findings demonstrated that the mode of delivery changed the metabolism of SCFAs in newborn pigs, perhaps by affecting the physiology levels of cyclic intermediates such as lactate and malate in the pyruvate metabolic pathway. Additionally, by participating in the fatty acid metabolism pathway, two distinct proteins (FASN and HSD17B4) may impact the physiological concentration of these tiny metabolites. Discussion: In conclusion, this study provided reliable animal model data for understanding the physiological SCFA metabolic information and its affecting mechanism of large-gestational age preterm infants.

2.
J Adv Res ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38718895

RESUMEN

INTRODUCTION: Tissues maintain their function through interaction with microenvironment. During aging, both hair follicles and blood vessels (BV) in skin undergo degenerative changes. However, it is elusive whether the changes are due to intrinsic aging changes in hair follicles or blood vessels respectively, or their interactions. OBJECTIVE: To explore how hair follicles and blood vessels interact to regulate angiogenesis and hair regeneration during aging. METHODS: Single-cell RNA-sequencing (scRNA-seq) analyses were used to identify the declined ability of dermal papilla (DP) and endothelial cells (ECs) during aging. CellChat and CellCall were performed to investigate interaction between DP and ECs. Single-cell metabolism (scMetabolism) analysis and iPATH were applied to analyze downstream metabolites in DP and ECs. Hair-plucking model and mouse cell organoid model were used for functional studies. RESULTS: During aging, distance and interaction between DP and ECs are decreased. DP interacts with ECs, with decreased EDN1-EDNRA signaling from ECs to DP and CTF1-IL6ST signaling from DP to ECs during aging. ECs-secreted EDN1 binds to DP-expressed EDNRA which enhances Taurine (TA) metabolism to promote hair regeneration. DP-emitted CTF1 binds to ECs-expressed IL6ST which activates alpha-linolenic acid (ALA) metabolism to promote angiogenesis. Activated EDN1-EDNRA-TA signaling promotes hair regeneration in aged mouse skin and in organoid cultures, and increased CTF1-IL6ST-ALA signaling also promotes angiogenesis in aged mouse skin and organoid cultures. CONCLUSIONS: Our finding reveals reciprocal interactions between ECs and DP. ECs releases EDN1 sensed by DP to activate TA metabolism which induces hair regeneration, while DP emits CTF1 signal received by ECs to enhance ALA metabolism which promotes angiogenesis. Our study provides new insights into mutualistic cellular crosstalk between hair follicles and blood vessels, and identifies novel signaling contributing to the interactions of hair follicles and blood vessels in normal and aged skin.

3.
Front Neurol ; 15: 1387399, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707999

RESUMEN

Background: Infant, junior, and adult patients with neuronal intranuclear inclusion disease (NIID) present with various types of seizures. We aimed to conduct a systematic literature review on the clinical characteristics of NIID with seizures to provide novel insight for early diagnosis and treatment and to improve prognosis of these patients. Methods: We used keywords to screen articles related to NIID and seizures, and data concerning the clinical characteristics of patients, including demographic features, disease characteristics of the seizures, treatment responses, imaging examinations, and other auxiliary examination results were extracted. Results: The included studies comprised 21 patients with NIID with seizures. The most common clinical phenotypes were cognitive impairment (76.20%) and impaired consciousness (57.14%), and generalized onset motor seizures (46.15%) represented the most common type. Compared with infantile and juvenile cases, the use of antiepileptic drugs in adults led to significant seizure control and symptom improvement, in addition to providing a better prognosis. The number of GGC sequence repeats in the NOTCH2NLC gene in six NIID patients with seizures who underwent genetic testing ranged 72-134. Conclusion: The most common clinical phenotypes in patients with NIID with seizures were cognitive impairment and consciousness disorders. Patients with NIID presented with various types of seizures, with the most common being generalized onset motor seizures. Adult patients had a better prognosis and were relatively stable. The early diagnosis of NIID with seizures is of great significance for treatment and to improve prognosis.

4.
BMJ Open ; 14(5): e079955, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760055

RESUMEN

OBJECTIVES: This study aims to predict the risk of noise-induced hearing loss (NIHL) through a back-propagation neural network (BPNN) model. It provides an early, simple and accurate prediction method for NIHL. DESIGN: Population based, a cross sectional study. SETTING: Han, China. PARTICIPANTS: This study selected 3266 Han male workers from three automobile manufacturing industries. PRIMARY OUTCOME MEASURES: Information including personal life habits, occupational health test information and occupational exposure history were collected and predictive factors of NIHL were screened from these workers. BPNN and logistic regression models were constructed using these predictors. RESULTS: The input variables of BPNN model were 20, 16 and 21 important factors screened by univariate, stepwise and lasso-logistic regression. When the BPNN model was applied to the test set, it was found to have a sensitivity (TPR) of 83.33%, a specificity (TNR) of 85.92%, an accuracy (ACC) of 85.51%, a positive predictive value (PPV) of 52.85%, a negative predictive value of 96.46% and area under the receiver operating curve (AUC) is: 0.926 (95% CI: 0.891 to 0.961), which demonstrated the better overall properties than univariate-logistic regression modelling (AUC: 0.715) (95% CI: 0.652 to 0.777). The BPNN model has better predictive performance against NIHL than the stepwise-logistic and lasso-logistic regression model in terms of TPR, TNR, ACC, PPV and NPV (p<0.05); the area under the receiver operating characteristics curve of NIHL is also higher than that of the stepwise and lasso-logistic regression model (p<0.05). It was a relatively important factor in NIHL to find cumulative noise exposure, auditory system symptoms, age, listening to music or watching video with headphones, exposure to high temperature and noise exposure time in the trained BPNN model. CONCLUSIONS: The BPNN model was a valuable tool in dealing with the occupational risk prediction problem of NIHL. It can be used to predict the risk of an individual NIHL.


Asunto(s)
Automóviles , Pérdida Auditiva Provocada por Ruido , Industria Manufacturera , Redes Neurales de la Computación , Enfermedades Profesionales , Exposición Profesional , Humanos , Pérdida Auditiva Provocada por Ruido/diagnóstico , Pérdida Auditiva Provocada por Ruido/epidemiología , Pérdida Auditiva Provocada por Ruido/etiología , Estudios Transversales , Masculino , China/epidemiología , Adulto , Persona de Mediana Edad , Medición de Riesgo/métodos , Enfermedades Profesionales/epidemiología , Enfermedades Profesionales/etiología , Exposición Profesional/efectos adversos , Ruido en el Ambiente de Trabajo/efectos adversos , Modelos Logísticos , Factores de Riesgo , Curva ROC , Pueblos del Este de Asia
5.
Artículo en Inglés | MEDLINE | ID: mdl-38597685

RESUMEN

The development and application of micropatterning technology play a promising role in the manipulation of biological substances and the exploration of life sciences at the microscale. However, the universally adaptable micropatterning method with user-friendly properties for acceptance in routine laboratories remains scarce. Herein, a green, facile, and rapid microcontact printing method is reported for upgrading popularization and diversification of biological patterning. The three-step printing can achieve high simplicity and fidelity of additive-free polydimethylsiloxane (PDMS) micropatterning and chip fabrication within 8 min as well as keep their high stability and diversity. A detailed experimental report is provided to support the advanced microcontact printing method. Furthermore, the applications of easy-to-operate PDMS-patterned chips are extensively validated to complete microdroplet array assembly with spatial control, cell pattern formation with high efficiency and geometry customization, and microtissue assembly and biomimetic tumor construction on a large scale. This straightforward method promotes diverse micropatternings with minimal time, effort, and expertise and maximal biocompatibility, which might broaden its applications in interdisciplinary scientific communities. This work also offers an insight into the establishment of popularized and market-oriented microtools for biomedical purposes such as biosensing, organs on a chip, cancer research, and bioscreening.

6.
Diabetes Obes Metab ; 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38618979

RESUMEN

AIM: To assess the use of non-insulin antidiabetic medicines in China. MATERIALS AND METHODS: We analysed the national procurement data for 29 non-insulin antidiabetic medicines from nine subgroups in China from 2015 to 2022. We estimated the number of defined daily doses (DDDs) procured per year in seven regions of China for nine subgroups and adjusted the data by the number of patients with diabetes. For each subgroup, the regional ratio was calculated by comparing the procurement per patient in each region with the procurement nationwide. The regional disparity was the difference between the highest and lowest regional ratios. We compared the medication patterns across regions. RESULTS: Nationally, between 2015 and 2022, the number of DDDs per patient increased from 14.45 to 47.37. The two most commonly used categories were sulphonylurea and biguanides, which increased from 7.04 to 15.39 (119%) and 3.28 to 11.11 (239%) DDDs per patient, respectively. The procurement of new drugs (dipeptidyl peptidase-4 inhibitors, sodium-glucose cotransporter type 2 inhibitors and glucagon-like peptide-1 receptor agonists) increased quickly and had >5000% relative changes. Particularly for sodium-glucose cotransporter type 2 inhibitors, it increased from 0.08 to 5.03 DDDs (6662%). The southwest region had the highest relative change (319%), while the southern region had the lowest (118%). Biguanide and thiazolidinediones had the lowest (1.19) and highest level (2.21) of regional disparity in 2022, respectively. CONCLUSION: The procurement of non-insulin antidiabetic medicines in China has increased a lot from 2015 to 2022. In terms of DDDs per patient, sulphonylurea ranked first, followed by metformin. The procurement of new drugs increased greatly. A large regional disparity existed in medicine usage and patterns.

7.
Front Cell Infect Microbiol ; 14: 1334581, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38644963

RESUMEN

Ischemic stroke (IS) is a serious central nervous system disease. Post-IS complications, such as post-stroke cognitive impairment (PSCI), post-stroke depression (PSD), hemorrhagic transformation (HT), gastrointestinal dysfunction, cardiovascular events, and post-stroke infection (PSI), result in neurological deficits. The microbiota-gut-brain axis (MGBA) facilitates bidirectional signal transduction and communication between the intestines and the brain. Recent studies have reported alterations in gut microbiota diversity post-IS, suggesting the involvement of gut microbiota in post-IS complications through various mechanisms such as bacterial translocation, immune regulation, and production of gut bacterial metabolites, thereby affecting disease prognosis. In this review, to provide insights into the prevention and treatment of post-IS complications and improvement of the long-term prognosis of IS, we summarize the interaction between the gut microbiota and IS, along with the effects of the gut microbiota on post-IS complications.


Asunto(s)
Eje Cerebro-Intestino , Microbioma Gastrointestinal , Accidente Cerebrovascular Isquémico , Humanos , Accidente Cerebrovascular Isquémico/complicaciones , Accidente Cerebrovascular Isquémico/microbiología , Eje Cerebro-Intestino/fisiología , Animales , Disbiosis , Encéfalo/microbiología , Traslocación Bacteriana , Disfunción Cognitiva/microbiología , Disfunción Cognitiva/etiología
8.
Plants (Basel) ; 13(6)2024 Mar 07.
Artículo en Inglés | MEDLINE | ID: mdl-38592745

RESUMEN

Under abiotic stress, plant root exudates can improve plant growth performance. However, studies on the effect of root exudates on the stress resistance of another plant are insufficient. In this study, root exudates (REs) were extracted from Suaeda glauca to explore their effect on alfalfa seedlings under salt stress. The results showed that the plant height and fresh weight of alfalfa significantly increased by 47.72% and 53.39% after 7 days of RE treatment at a 0.4% NaCl concentration. Under 1.2% salt stress, REs reduced the Malondialdehyde content in alfalfa by 30.14% and increased the activity of its antioxidant enzymes (peroxidase and catalase) and the content of its osmotic regulators (soluble sugar and proline) by 60.68%, 52%, 45.67%, and 38.67%, respectively. Soil enzyme activity and the abundance of soil-beneficial bacteria were increased by REs. Spearman analysis showed that urease and neutral phosphatase were related to the richness of beneficial bacteria. Redundancy analysis confirmed that urease affected the composition of the soil bacterial community. The partial least squares structural equation model (PLS-SEM) revealed that REs had a direct positive effect on alfalfa growth under salt stress by regulating the plant's injury and antioxidant systems, and the soil bacterial community had an indirect positive effect on alfalfa growth through soil enzyme activity.

9.
Artículo en Inglés | MEDLINE | ID: mdl-38676634

RESUMEN

Conductive hydrogels are ideal materials for intelligent medical devices, human-machine interfaces, and flexible bioelectrodes due to their adjustable mechanical properties and electrical responsiveness, whereas it is still a great challenge to achieve the integration of excellent flexibility and biocompatibility into one hydrogel sensor while also incorporating self-healing, self-adhesion, environmental tolerance, and antimicrobial properties. Here, a nanocomposite conductive organohydrogel was constructed by using collagen (Col), alginate-derived carbon quantum dots (OSA-CQDs), poly(acrylic acid) (PAA), ethylene glycol reduced AgNPs, and Fe3+ ions. Depending on OSA-CQDs with multiple chemical binding sites and high specific surface area as cross-linkers, while coupling highly biologically active Col chains and PAA chains are serving as an energy dissipation module, the resulting organohydrogel exhibited excellent flexibility (795% of strain, 193 kPa of strength), high cell compatibility (>95% survival rate), self-healing efficiency (HE = 79.5%), antifreezing (-20 °C), moisturizing (>120 h), repeatable adhesion (strength >20 kPa, times >10), inhibitory activity against Escherichia coli and Staphylococcus aureus (9 and 21.5 cm2), conductivity, and strain sensitivity (σ = 1.34 S/m, gauge factor (GF) = 11.63). Based on the all-in-one integration of multifunction, the organohydrogel can collaboratively adapt to the multimode of strain sensing and electrophysiological sensing to realize wireless real-time monitoring of human activities and physiological health. Therefore, this work provides a new and common platform for the design and sensing of next-generation hydrogel-based smart wearable sensors.

10.
Bioresour Technol ; 399: 130608, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38499202

RESUMEN

A novel porous manganese and nitrogen co-doped biochar (Mn-N@SBC) was synthesized via one-step pyrolysis, utilizing loofah agricultural waste as the precursor and NaHCO3 as the activator. The behavior of bisphenol A adsorbed on Mn-N@SBC was evaluated using static batch adsorption experiments. Compared to direct manganese-nitrogen co-doping, co-doping based on NaHCO3 activation significantly increased the specific surface area (231 to 1027 m2·g-1) and adsorption capacity (15 to 351 mg·g-1). Wide pH (2-10) and good resistance to cation/anion, humic acid and actual water demonstrated the robust adaptability of Mn-N@SBC to environmental factors. The significantly reduced specific surface area after adsorption, adverse effects of ethanol and phenanthrene on the removal of bisphenol A, and theoretically predicted interaction sites indicated the primary adsorption mechanisms involved pore filling, hydrophobicity, and π-π-electron-donor-acceptor interaction. This work presented an approach to create high-efficiency adsorbents from agricultural waste, offering theoretical and practical guidance for the removal of pollutants.


Asunto(s)
Compuestos de Bencidrilo , Manganeso , Fenoles , Contaminantes Químicos del Agua , Bicarbonato de Sodio , Nitrógeno/química , Teoría Funcional de la Densidad , Carbón Orgánico/química , Adsorción , Contaminantes Químicos del Agua/química , Cinética
11.
Eur J Med Chem ; 269: 116310, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38479166

RESUMEN

Hematopoietic progenitor kinase 1 (HPK1) is a negative regulator of T-cell receptor signaling. While HPK1 is considered as a promising target for cancer immunotherapy, no small-molecule HPK1 inhibitors have been approved for cancer treatment. Herein, we report the discovery of a series of new HPK1 inhibitors with a 5-aminopyrido[2,3-d]pyrimidin-7(8H)-one scaffold. The most potent compound 9f inhibited HPK1 kinase activity with an IC50 of 0.32 nM in the time-resolved fluorescence resonance energy transfer (TR-FRET) assays, while displayed reasonable selectivity in a panel of 416 kinases. Cellular engagement of HPK1 by compound 9f was confirmed through the nano-bioluminescence resonance energy transfer (Nano-BRET) experiments. Compound 9f effectively reduced the phosphorylation of the downstream protein SLP-76 in primary peripheral blood mononuclear cells (PBMCs) and human T lymphocytic leukemia Jurkat cells. Compound 9f also enhanced the IL-2 and IFN-γ secretion in PBMCs. Furthermore, the binding mode of compound 9f with HPK1 was confirmed by the resolved cocrystal structure. Taken together, this study provides HPK1 inhibitors with a novel scaffold and clear binding mode for further development of HPK1-targeted therapeutic agents.


Asunto(s)
Leucocitos Mononucleares , Proteínas Serina-Treonina Quinasas , Humanos , Leucocitos Mononucleares/metabolismo , Transducción de Señal , Fosforilación
12.
Opt Lett ; 49(5): 1157-1160, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38426962

RESUMEN

High-power femtosecond pulses delivered at a high-repetition rate will aid machining throughput and improve signal-to-noise ratios for sensitive measurements. Here we demonstrate a Kerr-lens mode-locked femtosecond Yb:YAG ring-cavity thin-disk oscillator with a multi-pass scheme for the laser beam. With four passes through the thin disk, 175-fs pulses were delivered from the oscillator at an average power of 71.5 W and a repetition rate of 65.3 MHz. The corresponding intra-cavity peak power of 110 MW is ample for intra-cavity nonlinear conversion into more exotic wavelength ranges. With six passes, the average output power reached 101.3 W. To the best of our knowledge, this is the highest average output power of any mode-locked ring laser. These results confirm the viability of using multi-pass configuration on a thin-disk ring oscillator for high-throughput femtosecond applications.

13.
Sensors (Basel) ; 24(4)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38400262

RESUMEN

Intelligent workshop UAV inspection path planning is a typical indoor UAV path planning technology. The UAV can conduct intelligent inspection on each work area of the workshop to solve or provide timely feedback on problems in the work area. The sparrow search algorithm (SSA), as a novel swarm intelligence optimization algorithm, has been proven to have good optimization performance. However, the reduction in the SSA's search capability in the middle or late stage of iterations reduces population diversity, leading to shortcomings of the algorithm, including low convergence speed, low solution accuracy and an increased risk of falling into local optima. To overcome these difficulties, an improved sparrow search algorithm (namely the chaotic mapping-firefly sparrow search algorithm (CFSSA)) is proposed by integrating chaotic cube mapping initialization, firefly algorithm disturbance search and tent chaos mapping perturbation search. First, chaotic cube mapping was used to initialize the population to improve the distribution quality and diversity of the population. Then, after the sparrow search, the firefly algorithm disturbance and tent chaos mapping perturbation were employed to update the positions of all individuals in the population to enable a full search of the algorithm in the solution space. This technique can effectively avoid falling into local optima and improve the convergence speed and solution accuracy. The simulation results showed that, compared with the traditional intelligent bionic algorithms, the optimized algorithm provided a greatly improved convergence capability. The feasibility of the proposed algorithm was validated with a final simulation test. Compared with other SSA optimization algorithms, the results show that the CFSSA has the best efficiency. In an inspection path planning problem, the CFSSA has its advantages and applicability and is an applicable algorithm compared to SSA optimization algorithms.

14.
J Biochem Mol Toxicol ; 38(2): e23648, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38348705

RESUMEN

Chronic liver diseases caused by various factors may develop into liver fibrosis (LF). Early stage of LF could be reversible. Tanshinone IIA (Tan IIA), an extract from Salvia miltiorrhiza, has been reported to be hepatoprotective. However, the potential targets and mechanism of Tan IIA in the treatment of LF are still unclear. Our study aims at the anti-LF mechanism of Tan IIA through network pharmacological analysis combined with LF-related experiments. Serum biochemical indicators and histopathological examination showed that Tan IIA could ameliorate the process of LF in the CCl4 -induced mouse model. Western blot and immunohistochemical assays showed that Tan IIA decreased the expression of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositide 3-kinases/protein kinase B (PI3K/Akt), and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1). Compared with the model group, the Tan IIA groups increased the decreased superoxide dismutase activity and glutathione content, while decreasing the increased malondialdehyde content. These results indicate that Tan IIA may play an antioxidant role by inhibiting the expression of KRAS, PI3K/Akt, and Nrf2/HO-1 to ameliorate the progression of LF, which to some extent explains the pharmacological mechanism of Tan IIA in LF. In conclusion, our study demonstrates that Tan IIA could regulate LF via PI3K/Akt and Nrf2/HO-1 signaling pathways. It may be an effective therapeutic compound for the treatment of LF.


Asunto(s)
Abietanos , Factor 2 Relacionado con NF-E2 , Proteínas Proto-Oncogénicas c-akt , Animales , Ratones , Hemo Oxigenasa (Desciclizante)/metabolismo , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/tratamiento farmacológico , Ratones Endogámicos C57BL , Factor 2 Relacionado con NF-E2/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas p21(ras)/metabolismo , Transducción de Señal
15.
Environ Sci Pollut Res Int ; 31(13): 20311-20329, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38369662

RESUMEN

The synthesis of iron-based nanoparticles (Fe NPs) using traditional preparation methods suffered from the disadvantages of high cost, environmental harm, and easy agglomeration. In this study, a novel eco-friendly method was proposed for the synthesis of iron nanomaterials (ML-Fe NPs): using antioxidant components extracted from mulberry leaf to reduce divalent iron (II). The preparation conditions of ML-Fe NPs were optimized by orthogonal tests. The prepared ML-Fe NPs exhibited an amorphous core-shell structure, displaying excellent dispersion and stability. During the synthesis process of ML-Fe NPs, the polyphenol molecules in mulberry leaf extract played a dominant role. A possible synthetic mechanism involving complexation, reduction, and encapsulation was proposed. Furthermore, the ML-Fe NPs were utilized to construct an ML-Fe NPs/peroxymonosulfate catalytic system for the degradation of Rhodamine B dye wastewater. The ML-Fe NPs demonstrated remarkable catalytic potential, achieving a 99% degradation efficiency for Rhodamine B within a span of 40 min.


Asunto(s)
Nanopartículas del Metal , Morus , Nanopartículas , Hierro/química , Extractos Vegetales/química , Nanopartículas/química , Aguas Residuales , Nanopartículas del Metal/química
16.
Bioengineering (Basel) ; 11(2)2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38391617

RESUMEN

Oxygen extraction fraction (OEF), the fraction of oxygen that tissue extracts from blood, is an essential biomarker used to directly assess tissue viability and function in neurologic disorders. In ischemic stroke, for example, increased OEF can indicate the presence of penumbra-tissue with low perfusion yet intact cellular integrity-making it a primary therapeutic target. However, practical OEF mapping methods are not currently available in clinical settings, owing to the impractical data acquisitions in positron emission tomography (PET) and the limitations of existing MRI techniques. Recently, a novel MRI-based OEF mapping technique, termed QQ, was proposed. It shows high potential for clinical use by utilizing a routine sequence and removing the need for impractical multiple gas inhalations. However, QQ relies on the assumptions of Gaussian noise in susceptibility and multi-echo gradient echo (mGRE) magnitude signals for OEF estimation. This assumption is unreliable in low signal-to-noise ratio (SNR) regions like disease-related lesions, risking inaccurate OEF estimation and potentially impacting clinical decisions. Addressing this, our study presents a novel multi-echo complex QQ (mcQQ) that models realistic Gaussian noise in mGRE complex signals. We implemented mcQQ using a deep learning framework (mcQQ-NET) and compared it with the existing QQ-NET in simulations, ischemic stroke patients, and healthy subjects, using identical training and testing datasets and schemes. In simulations, mcQQ-NET provided more accurate OEF than QQ-NET. In the subacute stroke patients, mcQQ-NET showed a lower average OEF ratio in lesions relative to unaffected contralateral normal tissue than QQ-NET. In the healthy subjects, mcQQ-NET provided uniform OEF maps, similar to QQ-NET, but without unrealistically high OEF outliers in areas of low SNR, such as SNR ≤ 15 (dB). Therefore, mcQQ-NET improves OEF accuracy by more accurately reflecting realistic Gaussian noise in complex mGRE signals. Its enhanced sensitivity to OEF abnormalities, based on more realistic biophysics modeling, suggests that mcQQ-NET has potential for investigating tissue variability in neurologic disorders.

17.
Curr Med Chem ; 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38231075

RESUMEN

HER3 (Human Epidermal Growth Factor Receptor 3) is frequently overexpressed in various cancers, including non-small cell lung cancer (NSCLC), with a prevalence of 83% in primary tumors. Its involvement in tumorigenesis and resistance to targeted therapies makes HER3 a promising target for cancer treatment. Despite being initially considered "undruggable" due to its lack of catalytic activity, significant progress has been made in the development of anti-HER3 therapeutics. Monoclonal antibodies such as lumretuzumab, seribantumab, and patritumab have shown potential in targeting HER3 to overcome resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). Additionally, antibody-drug conjugates (ADCs) like HER3-DXd (patritumab deruxtecan) are new drug candidates that have demonstrated selective delivery of cytotoxic chemicals to NSCLC cells by exploiting HER3's widespread expression, minimizing cytotoxicity. This review aims to evaluate the efficacy of current HER3 therapeutics in development and their therapeutic potential in NSCLC, incorporating evidence from clinical trials.

18.
Gut Microbes ; 16(1): 2307581, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38277136

RESUMEN

The role of gut microbiota in insulin resistance (IR), Metabolic Syndrome (MetS), and Type 2 Diabetes Mellitus (T2DM) is rapidly gaining recognition. However, the mechanisms and implications of gut bacteria in these conditions remain enigmatic. This commentary not only highlights the findings of a recent multi-omics study by Takeuchi et al. but also offers a unique perspective by integrating personal opinions and insights. The discussion revolves around the intricate connection between gut microbes and IR, suggesting novel therapeutic potential in targeting gut microbial carbohydrate metabolism for improved IR management and metabolic health.


Asunto(s)
Diabetes Mellitus Tipo 2 , Microbioma Gastrointestinal , Resistencia a la Insulina , Síndrome Metabólico , Humanos , Diabetes Mellitus Tipo 2/microbiología , Insulina
20.
J Minim Access Surg ; 20(2): 187-195, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-36695243

RESUMEN

OBJECTIVE: The aim of this study was to evaluate the effect of adding dexmedetomidine to ropivacaine on pain relief and quality of recovery in older patients undergoing open inguinal hernia repair surgeries. METHODS: This was a prospective and randomised clinical trial of 102 patients aged over 65 years who received an ultrasound-guided transversus open mesh herniorrhaphy abdominis plane (TAP) block with either 0.375% ropivacaine 20 ml (Group R, n = 47) or 0.375% ropivacaine combined with 1 µg/kg dexmedetomidine 20 ml (Group RD, n = 45) in the pre-anaesthesia care unit before elective open inguinal hernia surgeries. The primary outcome measure was Visual Analogue Scale (VAS) pain scores at rest and on movement at 2, 4, 8, 12 and 24 h and at 1 and 3 months' postoperatively. The secondary outcome measures were the incidence of post-operative delirium (POD), nausea and vomiting and the occurrence of side effects or complications on post-operative day 1. RESULTS: Group RD had lower VAS scores at rest and on movement at 8 and 12 h postoperatively and a lower incidence of POD on the post-operative day 1 than Group R. Transient bradycardia was more frequent in Group RD than in Group R, and side effects or post-operative complications were reported in either group. CONCLUSION: The addition of dexmedetomidine to ropivacaine in a TAP block enhances postoperative analgesia during hospitalisation and improves the quality of recovery without affecting chronic pain in older patients undergoing open inguinal hernia repair surgery.

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