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1.
BMC Nurs ; 23(1): 267, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38658935

RESUMO

BACKGROUND: As the largest group of healthcare professionals, nurses play an indispensable and crucial role in disaster response. The enhancement of nurses' disaster literacy is imperative for effective disaster emergency management. However, there is currently a lack of knowledge regarding nurses' disaster literacy. This study represents the first attempt to explore the key components and characteristics of disaster literacy among nurses. METHODS: A qualitative descriptive design was employed, and the reporting followed the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines (refer to File S1). The purposive sampling method was utilized. Thirty-one rescue nurses from 31 medical institutions across 25 provinces and regions in China were recruited to participate in the study. The respondents were requested to share their experiences and insights regarding disaster rescue operations. Inductive content analysis was employed for data examination. RESULTS: The results indicated that rescue nurses universally recognized that there was a pressing need to enhance the level of disaster literacy among nurses. The disaster literacy of nurses encompasses nine dimensions: physical and mental quality, disaster rescue general knowledge, professional and technical competence, professional ethics, teamwork, emotional ability, information literacy, leadership, and knowledge transformation. CONCLUSIONS: To ensure national sustainability, government departments, healthcare organizations, and hospital administrators can accurately evaluate the disaster literacy of individual clinical nurses, groups, and the workforce as a whole through nine dimensions, which also can provide evidence to support the development of precision strategies to strengthen the disaster literacy of nurses.

3.
Front Med (Lausanne) ; 11: 1338947, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633306

RESUMO

Background: Interstitial lung disease (ILD) is a common complication of idiopathic inflammatory myopathy (IIM), which is one of the connective tissue diseases (CTD). It can lead to poor prognosis and increased mortality. However, the distribution and role of the lower respiratory tract (LRT) microbiome in patients with IIM-ILD remains unclear. This study aimed to investigate the microbial diversity and community differences in bronchoalveolar lavage fluid (BALF) in patients with IIM-ILD. Methods: From 28 June 2021 to 26 December 2023, 51 individual BALF samples were enrolled, consisting of 20 patients with IIM-ILD, 16 patients with other CTD-ILD (including 8 patients with SLE and 8 with RA) and 15 patients with CAP. The structure and function of microbiota in BALF were identified by metagenomic next-generation sequencing (mNGS). Results: The community evenness of LRT microbiota within the IIM-ILD group was marginally lower compared to the other CTD-ILD and CAP groups. Nonetheless, there were no noticeable differences. The species community structure was similar among the three groups, based on the Bray-Curtis distance between the samples. At the level of genus, the IIM-ILD group displayed a considerably higher abundance of Pseudomonas and Corynebacterium in comparison to the CAP group (p < 0.01, p < 0.05). At the species level, we found that the relative abundance of Pseudomonas aeruginosa increased significantly in the IIM-ILD group compared to the CAP group (p < 0.05). Additionally, the relative abundance of Prevotella pallens was significantly higher in other CTD-ILD groups compared to that in the IIM-ILD group (p < 0.05). Of all the clinical indicators examined in the correlation analysis, ferritin level demonstrated the strongest association with LRT flora, followed by Serum interleukin-6 level (p < 0.05). Conclusion: Our research has identified particular LRT microorganisms that were found to be altered in the IIM-ILD group and were significantly associated with immune function and inflammatory markers in patients. The lower respiratory tract microbiota has potential in the diagnosis and treatment of IIM-ILD.

4.
J Ginseng Res ; 48(2): 236-244, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465211

RESUMO

Background: Fusarium oxysporum (F. oxysporum) is the primary pathogenic fungus that causes Panax notoginseng (P. notoginseng) root rot disease. To control the disease, safe and efficient antifungal pesticides must currently be developed. Methods: In this study, we prepared and characterized a nanoemulsion of Foeniculum vulgare essential oil (Ne-FvEO) using ultrasonic technology and evaluated its stability. Traditional Foeniculum vulgare essential oil (T-FvEO) was prepared simultaneously with 1/1000 Tween-80 and 20/1000 dimethyl sulfoxide (DMSO). The effects and inhibitory mechanism of Ne-FvEO and T-FvEO in F. oxysporum were investigated through combined transcriptome and metabolome analyses. Results: Results showed that the minimum inhibitory concentration (MIC) of Ne-FvEO decreased from 3.65 mg/mL to 0.35 mg/mL, and its bioavailability increased by 10-fold. The results of gas chromatography/mass spectrometry (GC/MS) showed that T-FvEO did not contain a high content of estragole compared to Foeniculum vulgare essential oil (FvEO) and Ne-FvEO. Combined metabolome and transcriptome analysis showed that both emulsions inhibited the growth and development of F. oxysporum through the synthesis of the cell wall and cell membrane, energy metabolism, and genetic information of F. oxysporum mycelium. Ne-FvEO also inhibited the expression of 2-oxoglutarate dehydrogenase and isocitrate dehydrogenase and reduced the content of 2-oxoglutarate, which inhibited the germination of spores. Conclusion: Our findings suggest that Ne-FvEO effectively inhibited the growth of F. oxysporum in P. notoginseng in vivo. The findings contribute to our comprehension of the antifungal mechanism of essential oils (EOs) and lay the groundwork for the creation of plant-derived antifungal medicines.

5.
ChemSusChem ; : e202400211, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38547358

RESUMO

The reductive amination of 1,6-hexanediol with ammonia is one of the most promising green routes for synthesis of 1,6-hexanediamine. Herein, we developed a phosphorous modified Ni catalyst of Ni-P/Al2O3. It presented satisfactory improved selectivity to 1,6-hexanediamine in the reductive amination of 1,6-hexanediol compared to the Ni/Al2O3 catalyst. The phosphorous tended to interact with Al2O3 to form AlPOx species, induced Ni nanoparticle to be flatter, and the decrease of strong acid sites, the new-formed Ni-AlPOx-Al2O3 interface and the flatter Ni nanoparticle were the key to switch the dominating product from hexamethyleneimine to 1,6-hexanediamine. This work develops an efficient catalyst for production of 1,6-hexanediamine from the reductive amination of 1,6-hexanediol, and provides a point of view about designing selective non-noble metal catalysts for producing primary diamines via reductive amination of diols.

6.
Heliyon ; 10(5): e26553, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38455558

RESUMO

Objective: The study aims to evaluate and compare the efficacy and safety between ticagrelor and clopidogrel in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Methods: We searched MEDLINE (via PubMed), Cochrane, Embase, and the Cochrane library databases for eligible citations (the last search was up to December 2021). Subgroup analyses were performed based on region, study design, dose, and single-center/multicenter. Meta regressions were conducted to explore the source of heterogeneity. A sensitivity analysis was conducted to assess the robustness of the results. Funnel plots and Egger's test were preformed to test publication bias of the meta-analysis. Results: A total of 29 studies were included, totaling 165,981 patients. Ticagrelor reduced the overall incidence rate of major adverse cardiovascular events (MACEs) (HR 0.74; 95% CI, 0.62, 0.89; P = 0.001; I2 = 88.3%, P < 0.001) and all-cause mortality (HR 0.85; 95% CI, 0.75, 0.97; P = 0.019; I2 = 39.7%, P = 0.052) compared with clopidogrel. However, there was a higher risk of major bleeding (HR 1.21; 95% CI, 1.02,1.44; P = 0.026, I2 = 59.3%, P = 0.012) and all bleeding (HR 1.42; 95% CI, 1.24, 1.62; P < 0.001, I2 = 76.4%, P < 0.001) with ticagrelor compared to clopidogrel. The stability of the results was demonstrated by sensitivity analysis. Furthermore, subgroup analyses and meta-regression revealed that the heterogeneity in the study may stem from factors such as whether it was conducted in a single-center or multicenter setting, as well as the geographical region. Conclusion: Ticagrelor has demonstrated superior efficacy compared to clopidogrel in ACS patients undergoing PCI, particularly in Asia and Europe. Nevertheless, it is crucial to acknowledge that the utilization of ticagrelor is linked to a heightened risk of bleeding. To provide guidance for clinical decision-making regarding the use of ticagrelor, future multicenter randomized trials that are relevant and encompass longer follow-up periods are necessary. The category of the manuscript a meta-analysis: PROSPERO registration number CRD42021274198.

7.
Cell Prolif ; : e13633, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38528645

RESUMO

Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs. AAV-Pcolce2 facilitated SC re-entry into the cell cycle both in cultured cochlear organoids and in the postnatal cochlea. In the neomycin-damaged model, regenerated HCs were detected after overexpression of Pcolce2, and these were derived from SCs that had re-entered the cell cycle. These findings reveal that Pcolce2 may serve as a therapeutic target for the regeneration of HCs to treat hearing loss.

8.
J Med Internet Res ; 26: e49312, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38407951

RESUMO

BACKGROUND: Virtual reality-based exercise rehabilitation (VRER) is a promising intervention for patients with cancer-related dysfunctions (CRDs). However, studies focusing on VRER for CRDs are lacking, and the results are inconsistent. OBJECTIVE: We aimed to review the application of VRER in patients with CRDs. METHODS: This scoping review was conducted following the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) checklist framework. Publications were included from the time of database establishment to October 14, 2023. The databases were PubMed, Embase, Scopus, Cochrane, Web of Science, ProQuest, arXiv, IEEE Xplore, MedRxiv, CNKI, Wanfang Data, VIP, and SinoMed. The population included patients with cancer. A virtual reality (VR) system or device was required to be provided in exercise rehabilitation as an intervention. Eligible studies focused on VRER used for CRDs. Study selection and data extraction were performed by 2 reviewers independently. Extracted data included authors, year, country, study type, groups, sample size, participant age, cancer type, existing or potential CRDs, VR models and devices, intervention programs and durations, effectiveness, compliance, satisfaction, and safety. RESULTS: We identified 25 articles, and among these, 12 (48%) were randomized clinical trials, 11 (44%) were other experimental studies, and 2 (8%) were observational studies. The total sample size was 1174 (range 6-136). Among the 25 studies, 22 (88%), 2 (8%), and 1 (4%) included nonimmersive VR, immersive VR, and augmented reality, respectively, which are models of VRER. Commercial game programs (17/25, 68%) were the most popular interventions of VRER, and their duration ranged from 3 to 12 weeks. Using these models and devices, VRER was mostly applied in patients with breast cancer (14/25, 56%), leukemia (8/25, 32%), and lung cancer (3/25, 12%). Furthermore, 6 CRDs were intervened by VRER, and among these, postmastectomy syndromes were the most common (10/25, 40%). Overall, 74% (17/23) of studies reported positive results, including significant improvements in limb function, joint range of motion, edema rates, cognition, respiratory disturbance index, apnea, activities of daily living, and quality of life. The compliance rate ranged from 56% to 100%. Overall, 32% (8/25) of studies reported on patient satisfaction, and of these, 88% (7/8) reported satisfaction with VRER. Moreover, 13% (1/8) reported mild sickness as an adverse event. CONCLUSIONS: We found that around half of the studies reported using VRER in patients with breast cancer and postmastectomy dysfunctions through nonimmersive models and commercial game programs having durations of 3-12 weeks. In addition, most studies showed that VRER was effective owing to virtualization and interaction. Therefore, VRER may be an alternate intervention for patients with CRDs. However, as the conclusions were drawn from data with acknowledged inconsistencies and limited satisfaction reports, studies with larger sample sizes and more outcome indictors are required.


Assuntos
Neoplasias da Mama , Medicina , Humanos , Feminino , Atividades Cotidianas , Qualidade de Vida , Mastectomia
9.
Metabolism ; 154: 155818, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38369056

RESUMO

BACKGROUND: Cardiac glucose oxidation is decreased in heart failure with reduced ejection fraction (HFrEF), contributing to a decrease in myocardial ATP production. In contrast, circulating ketones and cardiac ketone oxidation are increased in HFrEF. Since ketones compete with glucose as a fuel source, we aimed to determine whether increasing ketone concentration both chronically with the SGLT2 inhibitor, dapagliflozin, or acutely in the perfusate has detrimental effects on cardiac glucose oxidation in HFrEF, and what effect this has on cardiac ATP production. METHODS: 8-week-old male C57BL6/N mice underwent sham or transverse aortic constriction (TAC) surgery to induce HFrEF over 3 weeks, after which TAC mice were randomized to treatment with either vehicle or the SGLT2 inhibitor, dapagliflozin (DAPA), for 4 weeks (raises blood ketones). Cardiac function was assessed by echocardiography. Cardiac energy metabolism was measured in isolated working hearts perfused with 5 mM glucose, 0.8 mM palmitate, and either 0.2 mM or 0.6 mM ß-hydroxybutyrate (ßOHB). RESULTS: TAC hearts had significantly decreased %EF compared to sham hearts, with no effect of DAPA. Glucose oxidation was significantly decreased in TAC hearts compared to sham hearts and did not decrease further in TAC hearts treated with high ßOHB or in TAC DAPA hearts, despite ßOHB oxidation rates increasing in both TAC vehicle and TAC DAPA hearts at high ßOHB concentrations. Rather, increasing ßOHB supply to the heart selectively decreased fatty acid oxidation rates. DAPA significantly increased ATP production at both ßOHB concentrations by increasing the contribution of glucose oxidation to ATP production. CONCLUSION: Therefore, increasing ketone concentration increases energy supply and ATP production in HFrEF without further impairing glucose oxidation.


Assuntos
Compostos Benzidrílicos , Glucosídeos , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Masculino , Camundongos , Animais , Insuficiência Cardíaca/metabolismo , Glucose/metabolismo , Volume Sistólico , Miocárdio/metabolismo , Oxirredução , Trifosfato de Adenosina/metabolismo , Cetonas/farmacologia , Cetonas/metabolismo
10.
Regen Biomater ; 11: rbad115, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38313824

RESUMO

Metal-organic frameworks (MOFs) have a high specific surface area, adjustable pores and can be used to obtain functional porous materials with diverse and well-ordered structures through coordination and self-assembly, which has intrigued wide interest in a broad range of disciplines. In the arena of biomedical engineering, the functionalized modification of MOFs has produced drug carriers with excellent dispersion and functionalities such as target delivery and response release, with promising applications in bio-detection, disease therapy, tissue healing, and other areas. This review summarizes the present state of research on the functionalization of MOFs by physical binding or chemical cross-linking of small molecules, polymers, biomacromolecules, and hydrogels and evaluates the role and approach of MOFs functionalization in boosting the reactivity of materials. On this basis, research on the application of functionalized MOFs composites in biomedical engineering fields such as drug delivery, tissue repair, disease treatment, bio-detection and imaging is surveyed, and the development trend and application prospects of functionalized MOFs as an important new class of biomedical materials in the biomedical field are anticipated, which may provide some inspiration and reference for further development of MOF for bio-medical applications.

11.
J Fungi (Basel) ; 10(2)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38392772

RESUMO

Nigrospora oryzae is one of several fungal pathogens known to cause brown streaks, leaf spots, and latent infections in rice. In this study, the entire 42.09-Mb genome of N. oryzae was sequenced at a depth of 169× using the Oxford Nanopore Technologies platform. The draft genome sequence was comprised of 26 scaffolds, possessed an average GC content of 58.83%, and contained a total of 10,688 protein-coding genes. Analysis of the complete genome sequence revealed that CAZyme-encoding genes account for 6.11% of all identified genes and that numerous transcription factors (TFs) associated with diverse biological processes belong predominantly to Zn-clus (22.20%) and C2H2 (10.59%) fungal TF classes. In addition, genes encoding 126 transport proteins and 3307 pathogen-host interaction proteins were identified. Comparative analysis of the previously reported N. oryzae reference strain GZL1 genome and the genome of a representative strain ZQ1 obtained here revealed 9722 colinear genes. Collectively, these findings provide valuable insights into N. oryzae genetic mechanisms and phenotypic characteristics.

12.
Cell Prolif ; : e13620, 2024 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-38400824

RESUMO

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research. In this study, we found that AAV-ie-mediated Gpm6b overexpression promoted SC-derived organoid expansion. Enhanced Gpm6b prevented the normal decrease in SC plasticity as the cochlea develops by supporting cells re-entry cell cycle and facilitating the SC-to-HC transformation. Also, overexpression of Gpm6b in the organ of Corti through the round window membrane injection facilitated the trans-differentiation of Lgr5+ SCs into HCs. In conclusion, our results suggest that Gpm6b overexpression promotes HC regeneration and highlights a promising target for hearing repair using the inner ear stem cells combined with AAV.

13.
Innovation (Camb) ; 5(2): 100561, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38379784

RESUMO

Helicobacter pylori infection is associated with the risk of gastrointestinal (GI) cancers; however, its impact on immunotherapy for GI cancers remains uncertain. In this study, we included 10,122 patients who underwent 13C-urea breath tests. Among 636 patients with Epstein-Barr virus-negative microsatellite-stable gastric cancer (GC) who were treated with anti-PD-1/PD-L1 therapy, H. pylori-positive patients exhibited significantly longer immune-related progression-free survival (irPFS) compared with H. pylori-negative patients (6.97 months versus 5.03 months, p < 0.001, hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.62-0.95, p = 0.015). Moreover, the H. pylori-positive group demonstrated a trend of 4 months longer median immune-related overall survival (irOS) than the H. pylori-negative group. H. pylori-positive GC displayed higher densities of PD-L1+ cells and nonexhausted CD8+ T cells, indicative of a "hot" tumor microenvironment. Transcriptomic analysis revealed that H. pylori-positive GC shared molecular characteristics similar to those of immunotherapy-sensitive GC. However, H. pylori-positive patients with DNA mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) colorectal adenocarcinoma and esophageal squamous cell carcinoma (ESCC) had shorter irPFS compared with H. pylori-negative patients (16.13 months versus not reached, p = 0.042, HR 2.26, 95% CI 1.13-4.50, p = 0.021 and 5.57 months versus 6.97 months, p = 0.029, HR 1.59, 95% CI 1.14-2.23, p = 0.006, respectively). The difference in irOS between H. pylori-positive and -negative patients had the same trend as that between dMMR/MSI-H colorectal adenocarcinoma and ESCC patients. We also identified a trend of shorter irPFS and irOS in H. pylori-positive liver cancer and pancreatic cancer patients. In summary, our findings supported that H. pylori infection is a beneficial factor for GC immunotherapy by shaping hot tumor microenvironments. However, in dMMR/MSI-H colorectal adenocarcinoma and ESCC patients, H. pylori adversely affects the efficacy of immunotherapy.

14.
Cardiovasc Res ; 120(4): 360-371, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38193548

RESUMO

AIMS: Heart failure with preserved ejection fraction (HFpEF) is a prevalent disease worldwide. While it is well established that alterations of cardiac energy metabolism contribute to cardiovascular pathology, the precise source of fuel used by the heart in HFpEF remains unclear. The objective of this study was to define the energy metabolic profile of the heart in HFpEF. METHODS AND RESULTS: Eight-week-old C57BL/6 male mice were subjected to a '2-Hit' HFpEF protocol [60% high-fat diet (HFD) + 0.5 g/L of Nω-nitro-L-arginine methyl ester]. Echocardiography and pressure-volume loop analysis were used for assessing cardiac function and cardiac haemodynamics, respectively. Isolated working hearts were perfused with radiolabelled energy substrates to directly measure rates of fatty acid oxidation, glucose oxidation, ketone oxidation, and glycolysis. HFpEF mice exhibited increased body weight, glucose intolerance, elevated blood pressure, diastolic dysfunction, and cardiac hypertrophy. In HFpEF hearts, insulin stimulation of glucose oxidation was significantly suppressed. This was paralleled by an increase in fatty acid oxidation rates, while cardiac ketone oxidation and glycolysis rates were comparable with healthy control hearts. The balance between glucose and fatty acid oxidation contributing to overall adenosine triphosphate (ATP) production was disrupted, where HFpEF hearts were more reliant on fatty acid as the major source of fuel for ATP production, compensating for the decrease of ATP originating from glucose oxidation. Additionally, phosphorylated pyruvate dehydrogenase levels decreased in both HFpEF mice and human patient's heart samples. CONCLUSION: In HFpEF, fatty acid oxidation dominates as the major source of cardiac ATP production at the expense of insulin-stimulated glucose oxidation.


Assuntos
Insuficiência Cardíaca , Masculino , Humanos , Animais , Camundongos , Trifosfato de Adenosina/metabolismo , Miocárdio/metabolismo , Volume Sistólico , Camundongos Endogâmicos C57BL , Ácidos Graxos/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Cetonas
15.
Adv Sci (Weinh) ; 11(11): e2306788, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38189623

RESUMO

Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno-associated virus (AAV)-mediated OTOF gene replacement therapy is extensively validated in Otof-deficient mice. However, the clinical safety and efficacy of AAV-OTOF is not reported. Here, AAV-OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non-human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV-OTOF is delivered into one cochlea of a 5-year-old deaf patient and into the bilateral cochleae of an 8-year-old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure-tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5-year-old patient can be restored to the normal range at 1 month after AAV-OTOF injection, while the 8-year-old patient can hear the conversational sounds. Most importantly, the 5-year-old patient can hear and recognize speech only through the AAV-OTOF-injected ear. This study is the first to demonstrate the safety and efficacy of AAV-OTOF in patients, expands and optimizes current OTOF-related gene therapy and provides valuable information for further application of gene therapies for deafness.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Humanos , Animais , Camundongos , Dependovirus/genética , Perda Auditiva Neurossensorial/genética , Perda Auditiva Neurossensorial/terapia , Audição , Surdez/genética , Surdez/terapia , Terapia Genética
16.
Sci Rep ; 14(1): 1193, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216627

RESUMO

High rates of cardiac fatty acid oxidation during reperfusion of ischemic hearts contribute to contractile dysfunction. This study aimed to investigate whether lysine acetylation affects fatty acid oxidation rates and recovery in post-ischemic hearts. Isolated working hearts from Sprague Dawley rats were perfused with 1.2 mM palmitate and 5 mM glucose and subjected to 30 min of ischemia and 40 min of reperfusion. Cardiac function, fatty acid oxidation, glucose oxidation, and glycolysis rates were compared between pre- and post-ischemic hearts. The acetylation status of enzymes involved in cardiac energy metabolism was assessed in both groups. Reperfusion after ischemia resulted in only a 41% recovery of cardiac work. Fatty acid oxidation and glycolysis rates increased while glucose oxidation rates decreased. The contribution of fatty acid oxidation to ATP production and TCA cycle activity increased from 90 to 93% and from 94.9 to 98.3%, respectively, in post-ischemic hearts. However, the overall acetylation status and acetylation levels of metabolic enzymes did not change in response to ischemia and reperfusion. These findings suggest that acetylation may not contribute to the high rates of fatty acid oxidation and reduced glucose oxidation observed in post-ischemic hearts perfused with high levels of palmitate substrate.


Assuntos
Lisina , Miocárdio , Ratos , Animais , Miocárdio/metabolismo , Lisina/metabolismo , Ratos Sprague-Dawley , Acetilação , Ácidos Graxos/metabolismo , Coração/fisiologia , Isquemia/metabolismo , Glicólise/fisiologia , Glucose/metabolismo , Oxirredução , Palmitatos/metabolismo
17.
Sensors (Basel) ; 24(1)2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38203167

RESUMO

Robot arm monitoring is often required in intelligent industrial scenarios. A two-stage method for robot arm attitude estimation based on multi-view images is proposed. In the first stage, a super-resolution keypoint detection network (SRKDNet) is proposed. The SRKDNet incorporates a subpixel convolution module in the backbone neural network, which can output high-resolution heatmaps for keypoint detection without significantly increasing the computational resource consumption. Efficient virtual and real sampling and SRKDNet training methods are put forward. The SRKDNet is trained with generated virtual data and fine-tuned with real sample data. This method decreases the time and manpower consumed in collecting data in real scenarios and achieves a better generalization effect on real data. A coarse-to-fine dual-SRKDNet detection mechanism is proposed and verified. Full-view and close-up dual SRKDNets are executed to first detect the keypoints and then refine the results. The keypoint detection accuracy, PCK@0.15, for the real robot arm reaches up to 96.07%. In the second stage, an equation system, involving the camera imaging model, the robot arm kinematic model and keypoints with different confidence values, is established to solve the unknown rotation angles of the joints. The proposed confidence-based keypoint screening scheme makes full use of the information redundancy of multi-view images to ensure attitude estimation accuracy. Experiments on a real UR10 robot arm under three views demonstrate that the average estimation error of the joint angles is 0.53 degrees, which is superior to that achieved with the comparison methods.

18.
Angew Chem Int Ed Engl ; 63(5): e202316425, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38061013

RESUMO

Photoactivated chemotherapy (PACT) is a promising cancer treatment modality that kills cancer cells via photochemical uncaging of a cytotoxic drug. Most ruthenium-based photocages used for PACT are activated with blue or green light, which penetrates sub-optimally into tumor tissues. Here, we report amide functionalization as a tool to fine-tune the toxicity and excited states of a terpyridine-based ruthenium photocage. Due to conjugation of the amide group with the terpyridine π system in the excited state, the absorption of red light (630 nm) increased 8-fold, and the photosubstitution rate rose 5-fold. In vitro, red light activation triggered inhibition of tubulin polymerization, which led to apoptotic cell death both in normoxic (21 % O2 ) and hypoxic (1 % O2 ) cancer cells. In vivo, red light irradiation of tumor-bearing mice demonstrated significant tumor volume reduction (45 %) with improved biosafety, thereby demonstrating the clinical potential of this compound.


Assuntos
Antineoplásicos , Neoplasias , Rutênio , Animais , Camundongos , Rutênio/farmacologia , Rutênio/química , Polimerização , Antineoplásicos/farmacologia , Antineoplásicos/química , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêutico , Microtúbulos
19.
Mol Ther ; 32(1): 204-217, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-37952086

RESUMO

Inner ear hair cells detect sound vibration through the deflection of mechanosensory stereocilia. Cytoplasmic protein TPRN has been shown to localize at the taper region of the stereocilia, and mutations in TPRN cause hereditary hearing loss through an unknown mechanism. Here, using biochemistry and dual stimulated emission depletion microscopy imaging, we show that the TPRN, together with its binding proteins CLIC5 and PTPRQ, forms concentric rings in the taper region of stereocilia. The disruption of TPRN rings, triggered by the competitive inhibition of the interaction of TPRN and CLIC5 or exogenous TPRN overexpression, leads to stereocilia degeneration and severe hearing loss. Most importantly, restoration of the TPRN rings can rescue the damaged auditory function of Tprn knockout mice by exogenously expressing TPRN at an appropriate level in HCs via promoter recombinant adeno-associated virus (AAV). In summary, our results reveal highly structured TPRN rings near the taper region of stereocilia that are crucial for stereocilia function and hearing. Also, TPRN ring restoration in stereocilia by AAV-Tprn effectively repairs damaged hearing, which lays the foundation for the clinical application of AAV-mediated gene therapy in patients with TPRN mutation.


Assuntos
Surdez , Perda Auditiva , Animais , Humanos , Camundongos , Surdez/genética , Audição/genética , Perda Auditiva/genética , Perda Auditiva/terapia , Camundongos Knockout , Proteínas/metabolismo , Proteínas Tirosina Fosfatases Classe 3 Semelhantes a Receptores/metabolismo , Estereocílios/metabolismo
20.
J Xray Sci Technol ; 32(1): 157-171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37424493

RESUMO

BACKGROUND: Early diagnosis of breast cancer is crucial to perform effective therapy. Many medical imaging modalities including MRI, CT, and ultrasound are used to diagnose cancer. OBJECTIVE: This study aims to investigate feasibility of applying transfer learning techniques to train convoluted neural networks (CNNs) to automatically diagnose breast cancer via ultrasound images. METHODS: Transfer learning techniques helped CNNs recognise breast cancer in ultrasound images. Each model's training and validation accuracies were assessed using the ultrasound image dataset. Ultrasound images educated and tested the models. RESULTS: MobileNet had the greatest accuracy during training and DenseNet121 during validation. Transfer learning algorithms can detect breast cancer in ultrasound images. CONCLUSIONS: Based on the results, transfer learning models may be useful for automated breast cancer diagnosis in ultrasound images. However, only a trained medical professional should diagnose cancer, and computational approaches should only be used to help make quick decisions.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Humanos , Feminino , Detecção Precoce de Câncer , Redes Neurais de Computação , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Tecnologia
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