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1.
Rev Cardiovasc Med ; 25(8): 284, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39228505

RESUMO

Background: Using fluid dynamic modeling, noninvasive fractional flow reserve (FFR) derived from coronary computed tomography angiography (CCTA) data provides better anatomic and functional information than CCTA, with a high diagnostic and discriminatory value for diagnosing hemodynamically significant lesions. Myocardial blood flow index (MBFI) based on CCTA is a physiological parameter that reflects myocardial ischemia. Thus, exploring the relationship between computed tomography derived fractional flow reserve (CT-FFR) and MBFI could be clinically significant. This study aimed to investigate the relationship between CT-FFR and MBFI and to analyze the feasibility of MBFI differing from CT-FFR in diagnosing suspected coronary artery disease (CAD). Methods: Data from 61 patients (35 males, mean age: 59.2 ± 10.02 years) with suspected CAD were retrospectively analyzed, including the imaging data of CCTA, CT-FFR, and data of invasive coronary angiography performed within one week after hospitalization. CT-FFR and MBFI were calculated, and the correlation between MBFI or CT-FFR and invasive coronary angiography (ICA) was evaluated. Using ICA (value ≥ 0.70) as the gold standard and determining the optimal cutoff value via a diagnostic test, the diagnostic performance of MBFI or CT-FFR was evaluated. Results: MBFI and CT-FFR were negatively correlated with ICA (r = -0.3670 and -0.4922, p = 0.0036 and 0.0001, respectively). Using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.115 for MBFI, and the area under the curve (AUC) was 0.833 (95% confidence interval [CI]: 0.716-0.916, Z = 5.357, p < 0.0001); using ICA (value of ≥ 0.70) the gold standard, the optimal cutoff value was 0.80 for CT-FFR, and the area under the curve (AUC) was 0.759 (95% CI: 0.632-0.859, Z = 3.665, p = 0.0002). No significant difference was observed between the AUCs of CT-FFR and MBFI (Z = 0.786, p = 0.4316). Conclusions: MBFI based on CCTA can be used to evaluate myocardial ischemia similar to CT-FFR in suspected CAD; however, it should be noted that CT-FFR is a functional index based on the anatomical stenosis of the coronary artery, whereas MBFI is a physiological index reflecting myocardial mass remodeling.

2.
J Craniofac Surg ; 2024 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-39248696

RESUMO

OBJECTIVE: Liposuction of the face and neck is a common treatment for fat deposition. If conventional methods are used for tumescent anesthesia, patients will experience pain, affecting their surgery experience. Using general anesthesia for liposuction of the face and neck can increase the cost to the patient and cause various adverse effects. METHODS: The authors selected appropriate parts of the patient's neck, angle of the mandible, and face as needle entry points, and performed nerve block in different directions. Afterward, we performed facial liposuction on these patients and evaluated their level of pain. RESULTS: This study included a total of 20 female participants who underwent facial liposuction after a nerve block. The Visual Analog Scale score of the 20 participants was 0.55 (±0.60). There were no significant adverse reactions during the treatment process, and all patients expressed satisfaction with this treatment. CONCLUSIONS: In this article, the authors present a method of tumescent anesthesia based on facial and cervical nerve block that significantly reduces the pain associated with facial and neck liposuction, eliminating the need for general anesthesia and enhancing the patient's comfort during the procedure.

3.
Ren Fail ; 46(2): 2397555, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39230066

RESUMO

BACKGROUND: Critically ill patients in the intensive care unit (ICU) often experience dysglycaemia. However, studies investigating the link between acute kidney injury (AKI) and dysglycaemia, especially in those with and without diabetes mellitus (DM), are limited. METHODS: We used the Medical Information Mart for Intensive Care IV database to investigate the association between AKI within 7 days of admission and subsequent dysglycaemia. The primary outcome was the occurrence of dysglycaemia (both hypoglycemia and hyperglycemia) after 7 days of ICU admission. Logistic regression analyzed the relationship between AKI and dysglycaemia, while a Cox proportional hazards model estimated the long-term mortality risk linked to the AKI combined with dysglycaemia. RESULTS: A cohort of 20,008 critically ill patients were included. The AKI group demonstrated a higher prevalence of dysglycaemia, compared to the non-AKI group. AKI patients had an increased risk of dysglycaemia (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.41-1.65), hypoglycemia (aOR 1.56, 95% CI 1.41-1.73), and hyperglycemia (aOR 1.53, 95% CI 1.41-1.66). In subgroup analysis, compared to DM patients, AKI showed higher risk of dysglycaemia in non-DM patients (aOR: 1.93 vs. 1.33, Pint<0.01). Additionally, the AKI with dysglycaemia group exhibited a higher risk of long-term mortality compared to the non-AKI without dysglycaemia group. Dysglycaemia also mediated the relationship between AKI and long-term mortality. CONCLUSION: AKI was associated with a higher risk of dysglycaemia, especially in non-DM patients, and the combination of AKI and dysglycaemia was linked to higher long-term mortality. Further research is needed to develop optimal glycemic control strategies for AKI patients.


Assuntos
Injúria Renal Aguda , Estado Terminal , Hiperglicemia , Hipoglicemia , Unidades de Terapia Intensiva , Humanos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/mortalidade , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/epidemiologia , Masculino , Estudos Retrospectivos , Feminino , Estado Terminal/mortalidade , Pessoa de Meia-Idade , Idoso , Hiperglicemia/complicações , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Hipoglicemia/complicações , Hipoglicemia/sangue , Hipoglicemia/epidemiologia , Hipoglicemia/mortalidade , Unidades de Terapia Intensiva/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Fatores de Risco , Modelos Logísticos , Modelos de Riscos Proporcionais , Glicemia/análise , Prevalência
4.
Urol Case Rep ; 56: 102813, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252846

RESUMO

Glomus tumors are rare mesenchymal tumors involving cells from the glomus body, smooth muscle, and vasculature, typically found in distal extremities' skin. This case describes a 54-year-old woman with a history of hypothyroidism and hyperlipidemia, incidentally discovered to have a four-centimeter calcified renal tumor. Surgery was performed due to suspected malignancy. Immunohistochemical staining confirmed a renal glomus tumor, positive for muscle actin and smooth muscle actin (SMA). The tumor was benign, and no adjuvant therapy was needed. The patient remained recurrence-free during follow-up. Renal glomus tumors are predominantly benign, with surgical resection as the primary treatment.

5.
EClinicalMedicine ; 75: 102779, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39252864

RESUMO

Background: Adolescent idiopathic scoliosis (AIS) is the most common spinal disorder in children, characterized by insidious onset and rapid progression, which can lead to severe consequences if not detected in a timely manner. Currently, the diagnosis of AIS primarily relies on X-ray imaging. However, due to limitations in healthcare access and concerns over radiation exposure, this diagnostic method cannot be widely adopted. Therefore, we have developed and validated a screening system using deep learning technology, capable of generating virtual X-ray images (VXI) from two-dimensional Red Green Blue (2D-RGB) images captured by a smartphone or camera to assist spine surgeons in the rapid, accurate, and non-invasive assessment of AIS. Methods: We included 2397 patients with AIS and 48 potential patients with AIS who visited four medical institutions in mainland China from June 11th 2014 to November 28th 2023. Participants data included standing full-spine X-ray images captured by radiology technicians and 2D-RGB images taken by spine surgeons using a camera. We developed a deep learning model based on conditional generative adversarial networks (cGAN) called Swin-pix2pix to generate VXI on retrospective training (n = 1842) and validation (n = 100) dataset, then validated the performance of VXI in quantifying the curve type and severity of AIS on retrospective internal (n = 100), external (n = 135), and prospective test datasets (n = 268). The prospective test dataset included 268 participants treated in Nanjing, China, from April 19th, 2023, to November 28th, 2023, comprising 220 patients with AIS and 48 potential patients with AIS. Their data underwent strict quality control to ensure optimal data quality and consistency. Findings: Our Swin-pix2pix model generated realistic VXI, with the mean absolute error (MAE) for predicting the main and secondary Cobb angles of AIS significantly lower than other baseline cGAN models, at 3.2° and 3.1° on prospective test dataset. The diagnostic accuracy for scoliosis severity grading exceeded that of two spine surgery experts, with accuracy of 0.93 (95% CI [0.91, 0.95]) in main curve and 0.89 (95% CI [0.87, 0.91]) in secondary curve. For main curve position and curve classification, the predictive accuracy of the Swin-pix2pix model also surpassed that of the baseline cGAN models, with accuracy of 0.93 (95% CI [0.90, 0.95]) for thoracic curve and 0.97 (95% CI [0.96, 0.98]), achieving satisfactory results on three external datasets as well. Interpretation: Our developed Swin-pix2pix model holds promise for using a single photo taken with a smartphone or camera to rapidly assess AIS curve type and severity without radiation, enabling large-scale screening. However, limited data quality and quantity, a homogeneous participant population, and rotational errors during imaging may affect the applicability and accuracy of the system, requiring further improvement in the future. Funding: National Key R&D Program of China, Natural Science Foundation of Jiangsu Province, China Postdoctoral Science Foundation, Nanjing Medical Science and Technology Development Foundation, Jiangsu Provincial Key Research and Development Program, and Jiangsu Provincial Medical Innovation Centre of Orthopedic Surgery.

6.
Adv Sci (Weinh) ; : e2404510, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39257029

RESUMO

Synovial Sarcomas (SS) are characterized by the presence of the SS18::SSX fusion gene, which protein product induce chromatin changes through remodeling of the BAF complex. To elucidate the genomic events that drive phenotypic diversity in SS, we performed RNA and targeted DNA sequencing on 91 tumors from 55 patients. Our results were verified by proteomic analysis, public gene expression cohorts and single-cell RNA sequencing. Transcriptome profiling identified three distinct SS subtypes resembling the known histological subtypes: SS subtype I and was characterized by hyperproliferation, evasion of immune detection and a poor prognosis. SS subtype II and was dominated by a vascular-stromal component and had a significantly better outcome. SS Subtype III was characterized by biphasic differentiation, increased genomic complexity and immune suppression mediated by checkpoint inhibition, and poor prognosis despite good responses to neoadjuvant therapy. Chromosomal abnormalities were an independent significant risk factor for metastasis. KRT8 was identified as a key component for epithelial differentiation in biphasic tumors, potentially controlled by OVOL1 regulation. Our findings explain the histological grounds for SS classification and indicate that a significantly larger proportion of patients have high risk tumors (corresponding to SS subtype I) than previously believed.

7.
PLoS Genet ; 20(9): e1011402, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264953

RESUMO

Nucleotide-binding domain and leucine-rich repeat (NLR) proteins play crucial roles in immunity against pathogens in both animals and plants. In solanaceous plants, activation of several sensor NLRs triggers their helper NLRs, known as NLR-required for cell death (NRC), to form resistosome complexes to initiate immune responses. While the sensor NLRs and downstream NRC helpers display diverse genetic compatibility, molecular evolutionary events leading to the complex network architecture remained elusive. Here, we showed that solanaceous NRC3 variants underwent subfunctionalization after the divergence of Solanum and Nicotiana, altering the genetic architecture of the NRC network in Nicotiana. Natural solanaceous NRC3 variants form three allelic groups displaying distinct compatibilities with the sensor NLR Rpi-blb2. Ancestral sequence reconstruction and analyses of natural and chimeric variants identified six key amino acids involved in sensor-helper compatibility. These residues are positioned on multiple surfaces of the resting NRC3 homodimer, collectively contributing to their compatibility with Rpi-blb2. Upon activation, Rpi-blb2-compatible NRC3 variants form membrane-associated punctate and high molecular weight complexes, and confer resistance to the late blight pathogen Phytophthora infestans. Our findings revealed how mutations in NRC alleles lead to subfunctionalization, altering sensor-helper compatibility and contributing to the increased complexity of the NRC network.

8.
Syst Rev ; 13(1): 238, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39300549

RESUMO

BACKGROUND: Arecae Semen is a traditional herbal medicine widely used in the medical service and food industry, but in recent years, the carcinogenesis of edible Arecae Semen chewing has aroused comprehensive attention, therefore it is necessary to evaluate its medicinal properties. Increasing evidence has shown that Arecae Semen Compounds (ASC) possess antidepressant ability. This study aimed to evaluate the effectiveness and safety of ASC in the treatment of depression. METHODS: We retrieved articles in eight databases from their inception to May 2024. Randomized controlled trials (RCTs) comparing the effects of ASC alone or combined with routine treatment in patients with depression were identified. The Cochrane risk of bias (ROB) tool (ROB 2) was used for assessing the ROB in the included trials. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to assess the certainty of the evidence for the review outcomes. The outcomes included Hamilton depression rating scale (HAMD) scores, depression-related symptoms, serum dopamine levels, and adverse events. Stata 14.0 was used for data analysis calculating standardized mean difference (SMD) for continuous outcomes and relative risk (RR) for binary outcomes, both with 95% confidence intervals (CI). RESULTS: Nine RCTs involving 787 patients were included in this review. ASC lowered HAMD scores (SMD - 3.43, 95% CI - 5.24 to - 1.61; I2 = 95.2%, P < 0.001), alleviated depression-related symptoms, increased serum dopamine levels, and reduced the incidence of adverse events slightly (RR 0.18, 95% CI 0.04 to 0.77; I2 = 0, P = 0.775) compared with the control group. Publication bias might account for the asymmetrical presentation of funnel plots. Meta-regression analysis revealed that regarding HAMD scores, there was no significant relationship with duration, sample size, or treatment strategy. The evidence of the outcomes was of very low certainty. CONCLUSIONS: ASC may achieve better therapeutic effects, alleviate depression-related symptoms with a lower incidence of adverse events, and provide a potentially effective and safe complementary therapy for patients with depression. However, the evidence is very uncertain so further researches are required to validate our results and explore clinical implications of Arecae Semen in depth. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022361150.


Assuntos
Depressão , Humanos , Depressão/tratamento farmacológico , Antidepressivos/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Fitoterapia , Extratos Vegetais/uso terapêutico , Resultado do Tratamento
9.
Adv Mater ; : e2408936, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39221549

RESUMO

Escalating energy demands of self-independent on-skin/wearable electronics impose challenges on corresponding power sources to offer greater power density, permeability, and stretchability. Here, a high-efficient breathable and stretchable monolithic hybrid triboelectric-piezoelectric-electromagnetic nanogenerator-based electronic skin (TPEG-skin) is reported via sandwiching a liquid metal mesh with two-layer topological insulator-piezoelectric polymer composite nanofibers. TPEG-skin concurrently extracts biomechanical energy (from body motions) and electromagnetic radiations (from adjacent appliances), operating as epidermal power sources and whole-body self-powered sensors. Topological insulators with conductive surface states supply notably enhanced triboelectric and piezoelectric effects, endowing TPEG-skin with a 288 V output voltage (10 N, 4 Hz), ∼3 times that of state-of-the-art devices. Liquid metal meshes serve as breathable electrodes and extract ambient electromagnetic pollution (±60 V, ±1.6 µA cm-2). TPEG-skin implements self-powered physiological and body motion monitoring and system-level human-machine interactions. This study provides compatible energy strategies for on-skin/wearable electronics with high power density, monolithic device integration, and multifunctionality.

10.
Mol Genet Genomic Med ; 12(9): e70004, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39219382

RESUMO

BACKGROUND: Marfan syndrome (MFS) is a complex genetic systemic connective tissue disorder. It is well known that genetic factors play a critical role in the progression of MFS, with nearly all cases attributed to variants in the FBN1 gene. METHODS: We investigated a Chinese family with MFS spanning two generations. Whole exome sequencing, in silico analysis, minigene constructs, transfection, RT-PCR, and protein secondary structure analysis were used to analyze the genotype of the proband and his father. RESULTS: The main clinical manifestations of the proband and his father were subluxation of the left lens and high myopia with pectus deformity. Whole exome sequencing identified a novel single nucleotide variant (SNV) in the FBN1 gene at a non-canonical splice site, c.443-3C>G. This variant resulted in two abnormal mRNA transcripts, leading to a frameshift and an in-frame insertion. Further in vitro experiments indicated that the c.443-3C>G variant in FBN1 was pathogenic and functionally harmful. CONCLUSION: This research identified a novel intronic pathogenic FBN1: c.443-3C>G gene variant, which led to two different aberrant splicing effects. Further functional analysis expands the variant spectrum and provides a strong indication and sufficient basis for preimplantation genetic testing for monogenic disease (PGT-M).


Assuntos
Fibrilina-1 , Heterozigoto , Íntrons , Síndrome de Marfan , Linhagem , Splicing de RNA , Humanos , Síndrome de Marfan/genética , Síndrome de Marfan/patologia , Fibrilina-1/genética , Masculino , Adulto , Feminino , Adipocinas
11.
Aging Dis ; 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39226169

RESUMO

Age-related hearing loss (ARHL) is a disease that impacts human quality of life and contributes to the progression of other neuronal problems. Various stressors induce an increase in free radicals, destroy mitochondria to further contribute to cellular malfunction, and compromise cell viability, ultimately leading to functional decline. Cisd2, a master gene for Marfan syndrome, plays an essential role in maintaining mitochondrial integrity and functions. As shown by our data, specific deletion of Cisd2 in the cochlea exacerbated the hearing impairment of ARHL in C57BL/6 mice. Increased defects in mitochondrial function, potassium homeostasis and synapse activity were observed in the Cisd2-deleted mouse models. These mechanistic phenotypes combined with oxidative stress contribute to cell death in the whole cochlea. Human patients with obviously deteriorated ARHL had low Cisd2 expression; therefore, Cisd2 may be a potential target for designing therapeutic methods to attenuate the disease progression of ARHL.

12.
Microsc Microanal ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39226242

RESUMO

As hydrogen is touted as a key player in the decarbonization of modern society, it is critical to enable quantitative hydrogen (H) analysis at high spatial resolution and, if possible, at the atomic scale. H has a known deleterious impact on the mechanical properties (strength, ductility, toughness) of most materials that can hinder their use as part of the infrastructure of a hydrogen-based economy. Enabling H mapping including local hydrogen concentration analyses at specific microstructural features is essential for understanding the multiple ways that H affect the properties of materials including embrittlement mechanisms and their synergies. In addition, spatial mapping and quantification of hydrogen isotopes is essential to accurately predict tritium inventory of future fusion power plants thus ensuring their safe and efficient operation. Atom probe tomography (APT) has the intrinsic capability to detect H and deuterium (D), and in principle the capacity for performing quantitative mapping of H within a material's microstructure. Yet, the accuracy and precision of H analysis by APT remain affected by complex field evaporation behavior and the influence of residual hydrogen from the ultrahigh vacuum chamber that can obscure the signal of H from within the material. The present article reports a summary of discussions at a focused workshop held at the Max-Planck Institute for Sustainable Materials in April 2024. The workshop was organized to pave the way to establishing best practices in reporting APT data for the analysis of H. We first summarize the key aspects of the intricacies of H analysis by APT and then propose a path for better reporting of the relevant data to support interpretation of APT-based H analysis in materials.

13.
World J Hepatol ; 16(8): 1145-1155, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39221100

RESUMO

BACKGROUND: Previous research has highlighted correlations between blood cell counts and chronic liver disease. Nonetheless, the causal relationships remain unknown. AIM: To evaluate the causal effect of blood cell traits on liver enzymes and nonalcoholic fatty liver disease (NAFLD) risk. METHODS: Independent genetic variants strongly associated with blood cell traits were extracted from a genome-wide association study (GWAS) conducted by the Blood Cell Consortium. Summary-level data for liver enzymes were obtained from the United Kingdom Biobank. NAFLD data were obtained from a GWAS meta-analysis (8434 cases and 770180 controls, discovery dataset) and the Fingen GWAS (2275 cases and 372727 controls, replication dataset). This analysis was conducted using the inverse-variance weighted method, followed by various sensitivity analyses. RESULTS: One SD increase in the genetically predicted haemoglobin concentration (HGB) was associated with a ß of 0.0078 (95%CI: 0.0059-0.0096), 0.0108 (95%CI: 0.0080-0.0136), 0.0361 (95%CI: 0.0156-0.0567), and 0.0083 (95%CI: 00046-0.0121) for alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase, and gamma-glutamyl transferase, respectively. Genetically predicted haematocrit was associated with ALP (ß = 0.0078, 95%CI: 0.0052-0.0104) and ALT (ß = 0.0057, 95%CI: 0.0039-0.0075). Genetically determined HGB and the reticulocyte fraction of red blood cells increased the risk of NAFLD [odds ratio (OR) = 1.199, 95%CI: 1.087-1.322] and (OR = 1.157, 95%CI: 1.071-1.250). The results of the sensitivity analyses remained significant. CONCLUSION: Novel causal blood cell traits related to liver enzymes and NAFLD development were revealed through Mendelian randomization analysis, which may facilitate the diagnosis and prevention of NAFLD.

14.
J Nanobiotechnology ; 22(1): 533, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39223666

RESUMO

The poor prognosis of hepatocellular carcinoma (HCC) is still an urgent challenge to be solved worldwide. Hence, assembling drugs and targeted short peptides together to construct a novel medicine delivery strategy is crucial for targeted and synergy therapy of HCC. Herein, a high-efficiency nanomedicine delivery strategy has been constructed by combining graphdiyne oxide (GDYO) as a drug-loaded platform, specific peptide (SP94-PEG) as a spear to target HCC cells, sorafenib, doxorubicin-Fe2+ (DOX-Fe2+), and siRNA (SLC7A11-i) as weapons to exert a three-path synergistic attack against HCC cells. In this work, SP94-PEG and GDYO form nanosheets with HCC-targeting properties, the chemotherapeutic drug DOX linked to ferrous ions increases the free iron pool in HCC cells and synergizes with sorafenib to induce cell ferroptosis. As a key gene of ferroptosis, interference with the expression of SLC7A11 makes the ferroptosis effect in HCC cells easier, stronger, and more durable. Through gene interference, drug synergy, and short peptide targeting, the toxic side effects of chemotherapy drugs are reduced. The multifunctional nanomedicine GDYO@SP94/DOX-Fe2+/sorafenib/SLC7A11-i (MNMG) possesses the advantages of strong targeting, good stability, the ability to continuously induce tumor cell ferroptosis and has potential clinical application value, which is different from traditional drugs.


Assuntos
Carcinoma Hepatocelular , Doxorrubicina , Ferroptose , Neoplasias Hepáticas , Nanomedicina , Peptídeos , Sorafenibe , Ferroptose/efeitos dos fármacos , Carcinoma Hepatocelular/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Doxorrubicina/farmacologia , Doxorrubicina/química , Nanomedicina/métodos , Sorafenibe/farmacologia , Sorafenibe/química , Linhagem Celular Tumoral , Animais , Peptídeos/química , Peptídeos/farmacologia , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Sinergismo Farmacológico , Sistema y+ de Transporte de Aminoácidos/metabolismo , Camundongos Nus , RNA Interferente Pequeno , Camundongos Endogâmicos BALB C , Sistemas de Liberação de Medicamentos/métodos
15.
J Med Chem ; 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231262

RESUMO

Inhibition of leucine-rich repeat kinase 2 is a genetically supported mechanism for the treatment of Parkinson's disease. We previously disclosed the discovery of an indazole series lead that demonstrated both safety and translational risks. The safety risks were hypothesized to be of unknown origin, so structural diversity in subsequent chemical matter was prioritized. The translational risks were identified due to a low brain Kpu,u in nonhuman primate studies, which raised concern over the use of an established peripheral biomarker as a surrogate for central target engagement. Given these challenges, the team sought to leverage structure- and property-based drug design and expanded efflux transporter profiling to identify structurally distinct leads with enhanced CNS drug-likeness. Herein, we describe the discovery of a "reinvented" indazole series with improved physicochemical properties and efflux transporter profiles while maintaining excellent potency and off-target kinase selectivity, which resulted in advanced lead, compound 23.

16.
J Prosthodont Res ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39231696

RESUMO

PURPOSE: The innate immune response, particularly the reaction of polymorphonuclear neutrophils (PMNs), is crucial in shaping the outcomes of chronic inflammation, fibrosis, or osseointegration following biomaterial implantation. Peri-implantitis or peri-mucositis, inflammatory conditions linked to dental implants, pose a significant threat to implant success. We developed a single-cell analysis approach using a murine model to assess the immune response to implant materials, offering a practical screening tool for potential dental implants. METHODS: We performed bioinformatics analysis and established a peri-implant inflammation model by inserting two titanium implants into the maxillary region, to examine the immune response. RESULTS: Bioinformatics analysis revealed that titanium implants triggered a host immune response, primarily mediated by PMNs. In the in vivo experiments, we observed a rapid PMN-mediated response, with increased infiltration around the implants and on the implant surface by day 3. Remarkably, PMN attachment to the implants persisted for 7 days, resembling the immune profiles seen in human implant-mediated inflammation. CONCLUSIONS: Our findings indicate that persistent attachment of the short-living PMNs to titanium implants can serve as an indicator or traits of peri-implant inflammation. Therefore, analyzing gingival tissue at the single-cell level could be a useful tool for evaluating the biocompatibility of candidate dental implants.

17.
Comput Biol Med ; 182: 109039, 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39232405

RESUMO

Alzheimer's disease (AD) severely impacts the lives of many patients and their families. Predicting the progression of the disease from the early stage of mild cognitive impairment (MCI) is of substantial value for treatment, medical research and clinical trials. In this paper, we propose a novel dual attention network to classify progressive MCI (pMCI) and stable MCI (sMCI) using both magnetic resonance imaging (MRI) and neurocognitive metadata. A 3D CNN ShuffleNet V2 model is used as the network backbone to extract MRI image features. Then, neurocognitive metadata is used to guide the spatial attention mechanism to steer the model to focus attention on the most discriminative regions of the brain. In contrast to traditional fusion methods, we propose a ViT based self attention fusion mechanism to fuse the neurocognitive metadata with the 3D CNN feature maps. The experimental results show that our proposed model achieves an accuracy, AUC, and sensitivity of 81.34%, 0.874, and 0.85 respectively using 5-fold cross validation evaluation. A comprehensive experimental study shows our proposed approach significantly outperforms all previous methods for MCI progression classification. In addition, an ablation study shows both fusion methods contribute to the high final performance.

18.
Brain Connect ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302050

RESUMO

BACKGROUND: Functional magnetic resonance imaging (fMRI) has not previously been used to localize the swallowing functional area in repetitive transcranial magnetic stimulation (rTMS) treatment for post-stroke dysphagia; Traditionally, the target area for rTMS is the hotspot, which is defined as the specific region of the brain identified as the optimal location for transcranial magnetic stimulation (TMS). This study aims to compare the network differences between the TMS hotspot and the saliva swallowing fMRI activation to determine the better rTMS treatment site and investigate changes in functional connectivity related to post-stroke dysphagia using resting-state fMRI. METHODS: Using an information-based approach, we conducted a single case study to explore neural functional connectivity in a patient with post-stroke dysphagia before, immediately after rTMS, and four weeks after rTMS intervention. 20 healthy participants underwent fMRI and TMS hotspot localization as a control group. Neural network alterations were assessed , and functional connections related to post-stroke dysphagia were examined using resting-state fMRI. RESULTS: Compared to the TMS-induced hotspots, the fMRI activation peaks were located significantly more posteriorly and exhibited stronger functional connectivity with bilateral postcentral gyri. Following rTMS treatment, this patient developed functional connection between the brainstem and the bilateral insula, caudate, anterior cingulate cortex, and cerebellum. CONCLUSION: The saliva swallowing fMRI activation peaks show more intense functional connectivity with bilateral postcentral gyri compared to the TMS hotspots. Activation peak-guided rTMS treatment improves swallowing function in post-stroke dysphagia. This study proposes a novel and potentially more efficacious therapeutic target for rTMS, expanding its therapeutic options for treating post-stroke dysphagia.

19.
ACS Nano ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302690

RESUMO

Artificial photomodulated channels represent a significant advancement toward practical photogated systems because of their remote noncontact stimulation. Ion transport behaviors in artificial photomodulated channels, however, still require further investigation, especially in multiple nanochannels that closely resemble biological structures. Herein, we present the design and development of photoswitchable ion nanochannels inspired by natural channelrhodopsins (ChRs), utilizing photoresponsive polymers grafted anodic aluminum oxide (AAO) membranes. Our approach integrates spiropyran (SP) as photoresponsive molecules into nanochannels through surface-initiated atom transfer radical polymerization (SI-ATRP), creating a responsive system that modulates ionic conductivity and hydrophilicity in response to light stimuli. A key design feature is the reversible ring-opening photoisomerization of spiropyran groups under UV irradiation. This transformation, observable at the molecular level and macroscopically, allows the surface inside the nanochannels to switch between hydrophobic and hydrophilic states, thus efficiently modulating ion transport via changing water wetting behaviors. The patternable and erasable polySP-grafted AAO, based on a controllable and reversible photochromic effect, also shows potential applications in anticounterfeiting. This study pioneers achieving macroscopic anticounterfeiting and photoinduced photoswitching through reversible surface chemistry and expands the application of polymer-grafted structures in multiple nanochannels.

20.
Adv Sci (Weinh) ; : e2405168, 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302846

RESUMO

Recycling of spent lead-acid batteries (LABs) is extremely urgent in view of environmental protection and resources reuse. The current challenge is to reduce high consumption of chemical reagents. Herein, a closed-loop spent LABs paste (SLBP) recovery strategy is demonstrated through Na2MoO4 consumption-regeneration-reuse. Experimental and DFT calculations verify that MoO4 2- competes Pb/Ca ions and weakens the metal-oxygen bond of PbSO4/CaSO4.2H2O in SLBP, facilitating PbMoO4/CaMoO4 formation and 99.13 wt% of SO4 2- elimination. Pb of 99.97 wt% is obtained as zero-carbon precursors (PbO2 and PbMoO4) by green leaching coupled with re-crystallization. The regeneration of Na2MoO4 is realized at 600 ℃ using LABs polypropylene shells and NaOH as reagents. Compared with the traditional smelting technologies, the temperature is reduced from >1000 to 600 °C. The extraction of Na2MoO4 require only water, and satisfactory re-used desulfurization efficiency (98.67 wt%) is achieved. For the residual Na2MoO4 after first SLBP desulfurization, the desulfurization efficiency remains above 97.36 wt% after adding fresh reagents for two running cycles. The new principle enables the reuse of 99.83 wt% of Na2MoO4 and the recycling of 95.27 wt% of Pb without generating wastewater and slags. The techno-economic analysis indicates this strategy is efficient, economical, and environmentally-friendly.

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