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1.
Artigo em Inglês | MEDLINE | ID: mdl-38574755

RESUMO

BACKGROUND AND OBJECTIVE: Stereo-electroencephalography (SEEG) electrodes are implanted using a variety of stereotactic technologies to treat refractory epilepsy. The value of SINO-robot for SEEG electrode implantation is rarely reported. The aim of the current study was to assess the value of SINO-robot in conjunction with Angio Render technology, in SEEG electrode implantation. We also assess its efficacy by examining factors such as localization error, operation time, and complications. METHODS: Between June 2018 and October 2020, we retrospectively reviewed 58 patients who underwent SEEG implantation to resect or ablate their epileptogenic zone (EZ) while minimizing the risk of hemorrhage. SINO-robot combined with Angio Render technology-assisted SEEG electrode implantation was used to visualize each patient' blood vessel in a 3D plane. The 3D view functionality was used to increase the safety and accuracy of the implantation, and reducing the risk of hemorrhage by avoiding said blood vessel. RESULTS: In this study, 634 SEEG electrodes were implanted in 58 patients. The mean 10.92(range 5- 18) leads per patient. The mean entry point localization error (EPLE) was 0.94 ± 0.23 mm (range: 0.39- 1.63 mm), and the mean target point localization error (TPLE) was 1.49 ± 0.37 mm (range: 0.80-2.78 mm). The mean operating time per lead (MOTPL) was 6. 18 ± 1.80 min (range: 3.02- 14.61 min). And the mean depth of electrodes was 56.96± 3.62 mm (range:27.23-124.85 mm). At a follow-up of at least one year, totally 81.57% (47/58) of patients achieved an Engel class I of seizure freedom. There were 2 patients with asymptomatic brain hematomas following SEEG placement, and no late complications or mortality in this cohort. CONCLUSIONS: SINO-robot in conjunction with Angio Render technology assist, in SEEG electrode implantation is safe and accurate in mitigating the risk of intracranial hemorrhage in patients suffering from drug-resistant epilepsy.

2.
Sci Adv ; 10(14): eadk8093, 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38578989

RESUMO

Trained immunity is one of the mechanisms by which BCG vaccination confers persistent nonspecific protection against diverse diseases. Genomic differences between the different BCG vaccine strains that are in global use could result in variable protection against tuberculosis and therapeutic effects on bladder cancer. In this study, we found that four representative BCG strains (BCG-Russia, BCG-Sweden, BCG-China, and BCG-Pasteur) covering all four genetic clusters differed in their ability to induce trained immunity and nonspecific protection. The trained immunity induced by BCG was associated with the Akt-mTOR-HIF1α axis, glycolysis, and NOD-like receptor signaling pathway. Multi-omics analysis (epigenomics, transcriptomics, and metabolomics) showed that linoleic acid metabolism was correlated with the trained immunity-inducing capacity of different BCG strains. Linoleic acid participated in the induction of trained immunity and could act as adjuvants to enhance BCG-induced trained immunity, revealing a trained immunity-inducing signaling pathway that could be used in the adjuvant development.


Assuntos
Vacina BCG , Tuberculose , Humanos , Ácido Linoleico , Imunidade Treinada , Multiômica , Adjuvantes Imunológicos/farmacologia
3.
Nat Commun ; 15(1): 2987, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38582870

RESUMO

Nipah virus (NiV) is a World Health Organization priority pathogen and there are currently no approved drugs for clinical immunotherapy. Through the use of a naïve human phage-displayed Fab library, two neutralizing antibodies (NiV41 and NiV42) targeting the NiV receptor binding protein (RBP) were identified. Following affinity maturation, antibodies derived from NiV41 display cross-reactivity against both NiV and Hendra virus (HeV), whereas the antibody based on NiV42 is only specific to NiV. Results of immunogenetic analysis reveal a correlation between the maturation of antibodies and their antiviral activity. In vivo testing of NiV41 and its mature form (41-6) show protective efficacy against a lethal NiV challenge in hamsters. Furthermore, a 2.88 Å Cryo-EM structure of the tetrameric RBP and antibody complex demonstrates that 41-6 blocks the receptor binding interface. These findings can be beneficial for the development of antiviral drugs and the design of vaccines with broad spectrum against henipaviruses.


Assuntos
Infecções por Henipavirus , Vírus Nipah , Humanos , Anticorpos Neutralizantes/metabolismo , Vírus Nipah/metabolismo , Anticorpos Antivirais
4.
Am J Perinatol ; 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38569506

RESUMO

OBJECTIVE: Error in birthweight prediction by sonographic estimated fetal weight (EFW) has clinical implications, such as avoidable cesarean or misclassification of fetal risk in labor. We aimed to evaluate optimal timing of ultrasound and which fetal measurements contribute to error in fetal ultrasound estimations of birth size at the extremes of birthweight. STUDY DESIGN: We compared differences in head circumference (HC), abdominal circumference (AC), femur length (FL), and EFW between ultrasound and corresponding birth measurements within 14 (n=1290) and 7 (n=617) days of birth for small (SGA, <10th percentile), appropriate (AGA, 10th-90th), and large-for-gestational age (LGA, >90th) newborns. RESULTS: Average differences between EFW and birthweight for SGA neonates were: -40.2g (CI -82.1, 1.6) at 14 days vs. 13.6g (CI -52.4, 79.7) at 7 days; for AGA, -122.4g (-139.6, -105.1) at 14 days vs.-27.2g (-50.4, -4.0) at 7 days; and for LGA, -242.8g (-306.5, -179.1) at 14 days vs. -72.1g (-152.0, 7.9) at 7 days. Differences between fetal and neonatal HC were larger at 14 versus 7 days, and similar to patterns for EFW and birthweight, differences were largest for LGA at both intervals. In contrast, differences between fetal and neonatal AC were larger at 7 versus 14 days, suggesting larger error in AC estimation closer to birth. CONCLUSIONS: Using a standardized ultrasound protocol, SGA neonates had ultrasound measurements closer to actual birth measurements compared to AGA or LGA neonates. LGA neonates had the largest differences between fetal and neonatal size, with measurements 14 days from delivery showing 3-4-fold greater differences from birthweight. Differences in EFW and birthweight may not be explained by a single fetal measurement; whether estimation may be improved by incorporation of other knowable factors should be evaluated in future research.

5.
Nat Prod Res ; : 1-8, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572741

RESUMO

The phytochemical study of the fruits of Melia azedarach (Meliaceae) led to the isolation and characterisation of two novel natural limonoids1-deoxy- 3, 20-dicinnamoyl-11-methoxy-meliacarpinin (1) and 12ß- O- methyl nimbolinin A (2), along with twelve known limonoids. Its structure was identified by 1D- and 2D-NMR, HR-ESI-MS and comparison with published data. The anti-inflammatory effect of the compounds was measured in vitro in RAW 264.7 cells by evaluating the production of NO stimulated by LPS. Compounds 1, 8 and 14 indicated significant anti-inflammatory effect with inhibition rate of 11.76, 8.45 and 6.59 µM, respectively. Limonoid 1 significantly inhibited the production of NO, TNF-α and IL-1ß in RAW 264.7 cells. Therefore, limonoid derivative may be a promising source of bioactive metabolite for inflammatory diseases.

6.
CNS Drugs ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38573471

RESUMO

BACKGROUND: Percutaneous endoscopic transforaminal discectomy (PETD) is an effective method for treating lumbar disc herniation, and is typically performed under local anesthesia. However, inadequate analgesia during the procedure remains a concern, prompting the search for a medication that can provide optimal pain control with minimal impact on the respiratory and circulatory systems. OBJECTIVES: The aim of this study was to observe the effects of different doses of esketamine combined with dexmedetomidine on reducing visual analog scale (VAS) scores during surgical interventions. METHODS: One hundred two patients who underwent PETD were randomly divided into a control group (group C: normal saline + dexmedetomidine), an E1 group (0.1 mg kg-1 esketamine + dexmedetomidine), and an E2 group (0.2 mg kg-1 esketamine + dexmedetomidine). The primary outcome was the maximum visual analogue scale (VAS) (score: 0 = no pain and 10 = worst pain) at six time points. The secondary outcomes included the Assessment of Alertness/Sedation Scale (OAA/S) score and mean arterial pressure (BP), heart rate (HR), respiratory rate (RR), and oxygen saturation (SpO2) at 11 time points. The incidence of adverse reactions during and 24 h after the operation and patient satisfaction with the anesthesia were also recorded. RESULTS: Compared with those in group C, the VAS scores of patients in groups E1 and E2 were lower at T6, T7, and T9 (P < 0.05). From T4 to T10, the OAA/S scores of the E1 and E2 groups were both lower than those of group C (P < 0.05), and at the T4-T6 time points, the OAA/S score of the E2 group was lower than that of group E1 (P < 0.05). At T4 and T5, the HR and BP of patients in groups E1 and E2 were greater than those in group C (P < 0.05). Compared with those in group C, the incidences of intraoperative illusion, floating sensation, postoperative dizziness, and hyperalgesia in groups E1 and E2 were significantly greater (P < 0.01). There was no significant difference in patient RR, SpO2, or postoperative satisfaction with anesthesia among the three groups (P > 0.05). CONCLUSION: The combination of esketamine and dexmedetomidine can reduce VAS scores during certain stages of this type of surgery; it has minimal impact on respiration and circulation. However, this approach is associated with increased incidences of postoperative dizziness and psychiatric side effects, which may also affect patients' compliance with surgical instructions from medical staff. Patient satisfaction was not greater with dexmedetomidine combined with esketamine than with dexmedetomidine alone. TRIAL REGISTRATION: http://www.chictr.org.cn . Identifier: ChiCTR2300068206. Date of registration: 10 February 2023.

8.
J Org Chem ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38579179

RESUMO

The total syntheses of (±)-quebrachamine and (±)-kopsiyunnanine D are reported. Key transformations include an intermolecular Horner-Wadsworth-Emmons olefination to merge the two fragments convergently and an intramolecular Mitsunobu reaction to introduce the synthetically challenging nine-membered azonane ring efficiently.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38564359

RESUMO

Medical multi-modal pre-training has revealed promise in computer-aided diagnosis by leveraging large-scale unlabeled datasets. However, existing methods based on masked autoencoders mainly rely on data-level reconstruction tasks, but lack high-level semantic information. Furthermore, two significant heterogeneity challenges hinder the transfer of pre-trained knowledge to downstream tasks, i.e., the distribution heterogeneity between pre-training data and downstream data, and the modality heterogeneity within downstream data. To address these challenges, we propose a Unified Medical Multi-modal Diagnostic (UMD) framework with tailored pre-training and downstream tuning strategies. Specifically, to enhance the representation abilities of vision and language encoders, we propose the Multi-level Reconstruction Pre-training (MR-Pretrain) strategy, including a feature-level and data-level reconstruction, which guides models to capture the semantic information from masked inputs of different modalities. Moreover, to tackle two kinds of heterogeneities during the downstream tuning, we present the heterogeneity-combat downstream tuning strategy, which consists of a Task-oriented Distribution Calibration (TD-Calib) and a Gradient-guided Modality Coordination (GM-Coord). In particular, TD-Calib fine-tunes the pre-trained model regarding the distribution of downstream datasets, and GM-Coord adjusts the gradient weights according to the dynamic optimization status of different modalities. Extensive experiments on five public medical datasets demonstrate the effectiveness of our UMD framework, which remarkably outperforms existing approaches on three kinds of downstream tasks.

10.
World J Gastroenterol ; 30(10): 1377-1392, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38596500

RESUMO

BACKGROUND: Crohn's disease (CD) is often misdiagnosed as intestinal tuberculosis (ITB). However, the treatment and prognosis of these two diseases are dramatically different. Therefore, it is important to develop a method to identify CD and ITB with high accuracy, specificity, and speed. AIM: To develop a method to identify CD and ITB with high accuracy, specificity, and speed. METHODS: A total of 72 paraffin wax-embedded tissue sections were pathologically and clinically diagnosed as CD or ITB. Paraffin wax-embedded tissue sections were attached to a metal coating and measured using attenuated total reflectance fourier transform infrared spectroscopy at mid-infrared wavelengths combined with XGBoost for differential diagnosis. RESULTS: The results showed that the paraffin wax-embedded specimens of CD and ITB were significantly different in their spectral signals at 1074 cm-1 and 1234 cm-1 bands, and the differential diagnosis model based on spectral characteristics combined with machine learning showed accuracy, specificity, and sensitivity of 91.84%, 92.59%, and 90.90%, respectively, for the differential diagnosis of CD and ITB. CONCLUSION: Information on the mid-infrared region can reveal the different histological components of CD and ITB at the molecular level, and spectral analysis combined with machine learning to establish a diagnostic model is expected to become a new method for the differential diagnosis of CD and ITB.


Assuntos
Doença de Crohn , Enterite , Tuberculose Gastrointestinal , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/patologia , Espectroscopia de Infravermelho com Transformada de Fourier , Diagnóstico Diferencial , Parafina , Tuberculose Gastrointestinal/diagnóstico , Tuberculose Gastrointestinal/patologia , Enterite/diagnóstico , Aprendizado de Máquina , Proteínas Mutadas de Ataxia Telangiectasia
11.
Fish Shellfish Immunol ; 148: 109511, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38499215

RESUMO

Lactobacillus rhamnosus is a probiotic, which not only promotes the growth of animals, but also has anti-inflammatory effects. However, the mechanism by which Lactobacillus rhamnosus regulates intestinal immunity is not well comprehended. Hence, the study aimed to research how Lactobacillus rhamnosus affects the intestinal immunity using juvenile grass carp (Ctenopharyngodon idella) as a model. We selected 1800 juvenile grass carp for testing. They were divided into six treatments and fed with six gradients of Lactobacillus rhamnosus GCC-3 (0.0, 0.5, 1.0, 1.5, 2.0, 2.5 g/kg) for 70 days. Enteritis was subsequently induced with dextroside sodium sulfate. Results indicated that dietary Lactobacillus rhamnosus GCC-3 addition improved growth performance. Meanwhile, appropriate levels of Lactobacillus rhamnosus GCC-3 alleviated excessive inflammatory response by down-regulating the expression of TLR4 and NOD receptors, up-regulating the expression of TOR, and then down-regulating the expression of NF-κB. Additionally, appropriate Lactobacillus rhamnosus GCC-3 improved intestinal immunity by reducing pyroptosis triggered by NLRP3 inflammasome and mediated by GSDME. Furthermore, 16 S rRNA sequencing showing appropriate levels of Lactobacillus rhamnosus GCC-3 increased Lactobacillus and Bifidobacterium abundance and decreased Aeromonas abundance. These results suggest that Lactobacillus rhamnosus GCC-3 can alleviate intestinal inflammation through down-regulating NF-κB and up-regulating TOR signaling pathways, as well as by inhibiting pyroptosis.


Assuntos
Carpas , Doenças dos Peixes , Lacticaseibacillus rhamnosus , Animais , NF-kappa B/metabolismo , Suplementos Nutricionais , Imunidade Inata , Carpas/metabolismo , Dieta/veterinária , Inflamação/veterinária , Ração Animal/análise , Proteínas de Peixes/genética
12.
J Org Chem ; 89(6): 4056-4066, 2024 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-38449357

RESUMO

An organo-photoredox catalyzed gem-difluoroallylation of glycine with α-trifluoromethyl alkenes via direct C(sp3)-H functionalization of glycine and C-F bond activation of α-trifluoromethyl alkenes has been described. As a consequence, a broad range of gem-difluoroalkene-containing unnatural amino acids are afforded in moderate to excellent yields. This reaction exhibits multiple merits such as readily available starting materials, broad substrate scope, and mild reaction conditions. The feasibility of this reaction has been highlighted by the late-stage modification of several peptides as well as the improved in vitro antifungal activity of compound 3v toward Valsa mali compared to that with commercial azoxystrobin.


Assuntos
Aminoácidos , Glicina , Alcenos , Peptídeos , Catálise
13.
J Clin Invest ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38451729

RESUMO

Development of effective strategies to manage the inevitable acquired resistance to osimertinib, an approved 3rd generation EGFR inhibitor for the treatment of EGFR mutant (EGFRm) non-small cell lung cancer (NSCLC), is urgently needed. This study reported that the DNA topoisomerase II (Topo II) inhibitors, doxorubicin and etoposide (VP-16) synergistically decreased cell survival with enhanced induction of DNA damage and apoptosis in osimertinib-resistant cells, suppressed the growth of osimertinib-resistant tumors, and delayed the emergence of osimertinib acquired resistance. Mechanistically, osimertinib decreased Topo IIα levels in EGFRm NSCLC cells by facilitating FBXW7-mediated proteasomal degradation, resulting in induction of DNA damage; these effects were lost in osimertinib-resistant cell lines possessing elevated levels of Topo IIα. Topo IIα elevation was also detected in the majority of EGFRm NSCLC tissues relapsed from EGFR-TKI treatment. Enforced expression of an ectopic TOP2A gene in sensitive EGFRm NSCLC cells conferred resistance to osimertinib, whereas knockdown of TOP2A in osimertinib-resistant cell lines restored their response to undergo osimertinib-induced DNA damage and apoptosis. Together, these results reveal an essential role of Topo IIα inhibition in mediating the therapeutic efficacy of osimertinib against EGFRm NSCLC, providing scientific rationale for targeting Topo II to manage acquired resistance to osimertinib.

14.
PLoS One ; 19(3): e0297960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38442091

RESUMO

In recent years, the intensification of global industrialization coupled with the enterprise's production and operating activities have caused pollution, increasing the current environmental pressure. Relevant government departments in China have instituted several stringent measures (environmental protection sensitization and awareness activities, training sessions, and exchange activities targeted towards enterprise managers) to address these rising environmental problems. Though these measures have gained traction over the years, there is a dearth of research on their effectiveness on the green innovation performance of enterprises. To bridge the gap, this research explores the effect of environmental awareness training, knowledge exchange activities, and commitment on green innovation performance with survey data from 285 medical equipment manufacturing companies in China. It further expands the theoretical application of environmental awareness training, commitment, and innovation performance from the lens of the Knowledge-Based View. The findings depict a positive relationship between environmental awareness training and innovation performance. It also finds a mediating influence of environmental commitment in the relationship between environmental awareness training and green innovation performance. Furthermore, environmental knowledge exchange activities positively moderate the relationship between environmental awareness training and environmental commitment. These findings offer valuable insights for the green development of medical equipment manufacturing enterprises and the government to formulate environmental protection policies.


Assuntos
Academias e Institutos , Comércio , China , Política Ambiental , Poluição Ambiental
15.
Protein Cell ; 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430542

RESUMO

Ferroptosis has been recognized as a unique cell death modality driven by excessive lipid peroxidation and unbalanced cellular metabolism. In this study, we established a protein interaction landscape for ferroptosis pathways through proteomic analyses, and identified choline/ethanolamine phosphotransferase 1 (CEPT1) as a lysophosphatidylcholine acyltransferase 3 (LPCAT3)-interacting protein that regulates LPCAT3 protein stability. In contrast to its known role in promoting phospholipid synthesis, we showed that CEPT1 suppresses ferroptosis potentially by interacting with phospholipases and breaking down certain pro-ferroptotic polyunsaturated fatty acid (PUFA)-containing phospholipids. Together, our study reveals a previously unrecognized role of CEPT1 in suppressing ferroptosis.

16.
Int Heart J ; 65(2): 279-291, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38556336

RESUMO

Myocardial ischemia/reperfusion (I/R) decreases cardiac function and efficiency. Accumulating evidence suggests that long noncoding RNAs (lncRNAs) have been linked to the cellular processes of myocardial I/R injury. The present investigation elucidated the function of lncRNA colon cancer-associated transcript 2 (CCAT2) in myocardial I/R injury and the related mechanisms.AC16 cardiomyocytes were exposed to hypoxia (16 hours) /reoxygenation (6 hours) (H/R) to mimic myocardial I/R models in vitro. CCAT2 and microRNA (miR) -539-3p expressions in AC16 cardiomyocytes were measured using real-time quantitative polymerase chain reaction. B-cell-specific Moloney murine leukemia virus insertion region 1 (BMI1) protein levels in AC16 cardiomyocytes were determined by western blotting. Cell viability, lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) levels, mitochondrial membrane potential, and apoptosis were detected using Counting Kit-8, LDH Assay Kit, dihydroethidium assay, 5,5',6,6'-tetrachloro1,1',3,3'-tetramethylbenzimidazolylcarbocyanine iodide staining, flow cytometry, and western blotting, respectively. The interactions between the molecules were confirmed using the dual-luciferase gene reporter. The wingless/integrated/beta-catenin (Wnt/ß-catenin) pathway under the H/R condition was detected by western blotting.CCAT2 and BMI1 mRNA expressions were reduced in H/R-exposed AC16 cardiomyocytes. CCAT2 overexpression exerted protective effects against H/R-induced cardiomyocyte injury, as demonstrated by increased cell viability and mitochondrial membrane potential and decreased LDH leakage, ROS levels, and apoptosis. In addition, CCAT2 positively regulated BMI1 expression by binding to miR-539-3p. CCAT2 knockdown or miR-539-3p overexpression restrained the protective effects of BMI1 against H/R-induced cardiomyocyte injury. In addition, miR-539-3p overexpression reversed the protective effects of CCAT2. Furthermore, CCAT2 activated the Wnt/ß-catenin pathway under the H/R condition via the miR-539-3p/BMI1 axis.Overall, this investigation showed the protective effects of the CCAT2/miR-539-3p/BMI1/Wnt/ß-catenin regulatory axis against cardiomyocyte injury induced by H/R.


Assuntos
Neoplasias do Colo , Doença da Artéria Coronariana , MicroRNAs , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , RNA Longo não Codificante , Animais , Humanos , Camundongos , Apoptose/fisiologia , beta Catenina/metabolismo , Neoplasias do Colo/metabolismo , Doença da Artéria Coronariana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Isquemia Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Complexo Repressor Polycomb 1/genética , Espécies Reativas de Oxigênio/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo
17.
Front Biosci (Landmark Ed) ; 29(3): 119, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38538250

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor in urgent need of novel diagnostics, prognostic markers, and treatments. Eukaryotic translation initiation factor 2 subunits (EIF2Ss), comprising Eukaryotic translation initiation factor 2 subunit alpha (EIF2S1), Eukaryotic translation initiation factor 2 subunit beta (EIF2S2), and Eukaryotic translation initiation factor 2 subunit gamma (EIF2S3), is a family of eukaryotic initiation factors that participate in early protein synthesis and are crucial for tumor initiation and progression. However, the role of EIF2Ss in PAAD has yet to be reported. The aim of this study was therefore to analyze EIF2Ss in relation to the diagnosis, prognosis, and treatment of PAAD. METHODS: The cancer genome atlas (TCGA) database was used to investigate gene expression and patient survival. Gene alterations, immune cell infiltration, and immune checkpoints in PAAD were also evaluated. Univariate and multivariate analysis, nomograms, calibration curves, and Decision Curve Analysis (DCA) diagrams were used to develop and evaluate a prediction model for patient outcome. Single-cell RNA-seq (scRNA) analysis, functional enrichment, co-IP assay, mass spectrometry, and western blot were used to study the relationship between EIF2Ss and c-myc in PAAD. RESULTS: EIF2Ss are over-expressed in PAAD tissue and are associated with poor prognosis. The frequency of EIF2S1, EIF2S2, and EIF2S3 gene alteration in PAAD was 0.2%, 0.4%, and 0.2%, respectively. High EIF2Ss expression was associated with Th2 cell infiltration, whereas low expression was associated with pDC infiltration. Moreover, EIF2Ss expression was positively correlated with the expression of the NT5E, ULBP1, PVR, CD44, IL10RB, and CD276 checkpoints. A prediction model developed using EIF2Ss and important clinicopathologic features showed good predictive value for the overall survival of PAAD patients. ScRNA-Seq data showed that EIF2Ss was associated with enrichment for endothelial cells, fibroblasts, malignant cells, and ductal cells. EIF2Ss expression was also correlated with adipogenesis, interferon-alpha response, epithelial-mesenchymal transition, myc targets, G2M checkpoint, oxidative phosphorylation, and hypoxia. Functional enrichment analysis of EIF2Ss showed a close correlation with the myc pathway, and interactions between EIF2Ss and c-myc were confirmed by co-IP assay and mass spectrometry. Importantly, knockdown of c-myc decreased the expression of EIF2S1, EIF2S2, and EIF2S3 in PAAD cells. CONCLUSIONS: EIF2Ss were found to have significant clinical implications for the prognosis and treatment of PAAD. Inhibition of c-myc caused the downregulation of EIF2S1, EIF2S2, and EIF2S3 expression.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Células Endoteliais , Fator de Iniciação 2 em Procariotos , Neoplasias Pancreáticas/genética , Genes myc/genética , Regulação Neoplásica da Expressão Gênica , Antígenos B7
18.
Int J Geriatr Psychiatry ; 39(3): e6076, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38488826

RESUMO

OBJECTIVES: The herbs in Tao Hong Si Wu Decoction (THSWD) are beneficial in the treatment of cognitive impairment. However, the underlying mechanisms of THSWD in treating diabetes-associated cognitive dysfunction (DACD) are not entirely explored. This study is aimed to investigate the therapeutic effects of THSWD in DACD model rats and the underlying mechanism. METHODS: Ultra-high-phase liquid chromatography was employed to identify the main compounds contained in the THSWD extract. DACD rat model was induced by feeding with a high-sugar and high-fat diet and injecting streptozotocin (35 mg/kg). DACD rats were gavaged with THSWD for 1 week. The learning and memory abilities of the rats were measured by using the Morris water maze. Western blotting was used to detect the changes in DACD rat targets. Statistical methods were used to evaluate the correlation between proteins. RESULTS: The results show that THSWD effectively reduced the escape latency, hippocampal neuron damage, glycosylated hemoglobin, type A1C, and blood lipid levels in DACD rats. Furthermore, DACD rats showed significantly increased amyloid precursor protein, ß-secretase, Aß1-40 , Aß1-42 , Tau phosphorylation, and advanced glycation end products (AGEs) expression. However, THSWD treatment can reverse this phenomenon. CONCLUSIONS: THSWD can improve the learning and memory abilities of DACD rats by inhibiting the expression of AEGs-AGE receptors pathway, which provides an experimental basis for the clinical application of THSWD. In addition, the experiment combines pharmacological and statistical methods, which offers a new perspective for the study of Chinese herbal medicine.


Assuntos
Disfunção Cognitiva , Diabetes Mellitus , Medicamentos de Ervas Chinesas , Humanos , Ratos , Animais , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos de Ervas Chinesas/farmacologia , Placa Amiloide , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/etiologia
19.
Biomater Sci ; 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38497247

RESUMO

Nanozymes, a distinctive class of nanomaterials endowed with enzyme-like activity and kinetics akin to enzyme-catalysed reactions, present several advantages over natural enzymes, including cost-effectiveness, heightened stability, and adjustable activity. However, the conventional trial-and-error methodology for developing novel nanozymes encounters growing challenges as research progresses. The advent of artificial intelligence (AI), particularly machine learning (ML), has ushered in innovative design approaches for researchers in this domain. This review delves into the burgeoning role of ML in nanozyme research, elucidating the advancements achieved through ML applications. The review explores successful instances of ML in nanozyme design and implementation, providing a comprehensive overview of the evolving landscape. A roadmap for ML-assisted nanozyme research is outlined, offering a universal guideline for research in this field. In the end, the review concludes with an analysis of challenges encountered and anticipates future directions for ML in nanozyme research. The synthesis of knowledge in this review aims to foster a cross-disciplinary study, propelling the revolutionary field forward.

20.
J Int Adv Otol ; 20(1): 26-29, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38454285

RESUMO

BACKGROUND: The precise treatment of iatrogenic cerebrospinal fluid (CSF) otorhinorrhea has been poorly studied. The purpose of the study was to investigate the clinical manifestation, surgical results, and management of CSF leak. METHODS: Electronic medical record database of iatrogenic CSF leaks after erebellopontine angle(CPA) surgery from 2019 to 2022 was retrospectively analyzed. Three patients returned to the hospital with the complication of CSF leak. After failed attempts of conservative strategies or reverse surgical repair, adipose tissue was applied to the mastoid cracks repair. RESULTS: With the techniques described above, the CSF leaks were successfully settled. The identified patients were observed for at least 10 months. and there was no recurrence or other complications. CONCLUSION: Conservative treatment and initial surgical methods for occult postoperative CSF leaks are prone to delay effective results, particularly in patients with well-evaporated temporal bone. This complication can be minimized with transmastoid closure utilizing autologous fat.


Assuntos
Neuroma Acústico , Humanos , Neuroma Acústico/cirurgia , Neuroma Acústico/complicações , Estudos Retrospectivos , Vazamento de Líquido Cefalorraquidiano/etiologia , Vazamento de Líquido Cefalorraquidiano/cirurgia , Osso Temporal , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Doença Iatrogênica , Resultado do Tratamento
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