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1.
Data Brief ; 56: 110829, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39252782

RESUMEN

This data report presents prokaryotic metagenome-assembled genomes (MAGs) from a hot spring stream with temperatures between 64 and 100°C. The stream water was filtered and the extracted total DNA was sequenced using the Illumina HiSeq 2500 platform. Approximately 80 Gb of raw data were generated, which were subsequently assembled using MEGAHIT v1.2.9. The MAGs were generated using MetaWRAP with binning approaches of MetaBAT2, CONCOCT and MaxBin2. We constructed 25 medium-quality and 24 high-quality archaeal MAGs, and 152 medium-quality and 112 high-quality bacterial MAGs. The fasta files of these MAGs are available in the NCBI database as well as Mendeley Data. Major phyla identified include Bacteroidota, Chloroflexota, Desulfobacterota, Firmicutes, Patescibacteria, Proteobacteria, Spirochaetota, Verrucomicrobiota, Armatimonadota, Nitrospirota, Acidobacteriota, Elusimicrobiota, Planctomycetota, Candidate division WOR-3, Aquificota, Thermoproteota, and Micrarchaeota. This dataset is valuable for studies on thermophilic genomes, reconstruction of biochemical pathways and gene discovery.

2.
World J Cardiol ; 16(8): 458-468, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39221191

RESUMEN

BACKGROUND: Cardio-oncology has received increasing attention especially among older patients with colorectal cancer (CRC). Cardiovascular disease (CVD)-specific mortality is the second-most frequent cause of death. The risk factors for CVD-specific mortality among older patients with CRC are still poorly understood. AIM: To identify the prognostic factors and construct a nomogram-based model to predict the CVD-specific mortality among older patients with CRC. METHODS: The data on older patients diagnosed with CRC were retrieved from The Surveillance, Epidemiology, and End Results database from 2004 to 2015. The prognostic factors and a nomogram-based model predicting the CVD-specific mortality were assessed using least absolute shrinkage and selection operator and Cox regression. RESULTS: A total of 141251 eligible patients with CRC were enrolled, of which 41459 patients died of CRC and 12651 patients died of CVD. The age at diagnosis, sex, marital status, year of diagnosis, surgery, and chemotherapy were independent prognostic factors associated with CVD-specific mortality among older patients with CRC. We used these variables to develop a model to predict CVD-specific mortality. The calibration curves for CVD-specific mortality probabilities showed that the model was in good agreement with actual observations. The C-index value of the model in the training cohort and testing cohort for predicting CVD-specific mortality was 0.728 and 0.734, respectively. CONCLUSION: The proposed nomogram-based model for CVD-specific mortality can be used for accurate prognostic prediction among older patients with CRC. This model is a potentially useful tool for clinicians to identify high-risk patients and develop personalized treatment plans.

3.
J Insect Sci ; 24(4)2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-39225032

RESUMEN

Poplar is a valuable tree species that is distributed all over the world. However, many insect pests infest poplar trees and have caused significant damage. To control poplar pests, we transformed a poplar species, Populus davidiana × P. bolleana Loucne, with the dsRNA of the chitinase gene of a poplar defoliator, Clostera anastomosis (Linnaeus) (Lepidoptera: Notodontidae), employing an Agrobaterium-mediated approach. The transgenic plant has been identified by cloning the T-DNA flanking sequences using TAIL-PCR and quantifying the expression of the dsRNA using qPCR. The toxicity assay of the transgenic poplar lines was carried out by feeding the target insect species (C. anastomosis). The results showed that, in C. anastomosis, the activity of chitinase was significantly decreased, consistent with the expression on mRNA levels, and the larval mortality was significantly increased. These results suggested that the transgenic poplar of dsRNA could be used for pest control.


Asunto(s)
Quitinasas , Larva , Mariposas Nocturnas , Plantas Modificadas Genéticamente , Populus , ARN Bicatenario , Animales , Populus/genética , Quitinasas/genética , Quitinasas/metabolismo , Mariposas Nocturnas/genética , Mariposas Nocturnas/crecimiento & desarrollo , Larva/crecimiento & desarrollo , Larva/genética , Control Biológico de Vectores , Proteínas de Insectos/genética , Proteínas de Insectos/metabolismo
4.
J Eval Clin Pract ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39291807

RESUMEN

AIM: Faecal immunochemical testing (FIT) is used to triage people with signs or symptoms of a colorectal cancer (CRC). Recent guidelines have recommended further research to improve access, uptake and return of FIT. This systematic scoping review aims to understand the barriers and facilitators to FIT testing in symptomatic patients. METHOD: Qualitative, quantitative and mixed-methods studies published after September 2013 were included. MEDLINE, EMBASE and PsycINFO databases were searched to identify publications examining barriers and facilitators to FIT. Initially, the data underwent thematic analysis, and subsequently, factors were aligned to components of the Capability, Opportunity, Motivation, Behaviour model. All outcomes are presented in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: One thousand two hundred thirty-two papers were identified; 11 met the inclusion criteria. Barriers and facilitators were identified at the patient (e.g., knowledge), provider (e.g., general practitioner awareness) and service level (e.g., method of providing FIT kits). Factors were categorised into the subcomponents of the model: psychological capability (e.g., lack of FIT knowledge), reflective motivation (e.g., beliefs regarding FIT sampling and faeces being unhygienic) and automatic motivation (e.g., embarrassment, scary, anxiety provoking). Gaps in knowledge emerged in three domains: (1) patient experience, (2) FIT pathway and (3) healthcare professionals experience of FIT. CONCLUSION: This systematic scoping review provides a summary of the literature on FIT uptake, and identified factors across multiple levels and components. To increase adherence to FIT completion within primary care, a multifaceted theory and evidence-based approach is needed to underpin future behavioural science interventions.

5.
J Gastrointest Oncol ; 15(4): 1789-1795, 2024 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-39279936

RESUMEN

Background: Despite advances made in pancreatic cancer treatment, the extent of progress made in pancreatic cancer mortality at the population level remains unclear. Our cross-sectional study sought to measure trends in pancreatic cancer mortality in the United States in the last 2 decades. Methods: Patients with pancreatic cancer mortality from 1999 to 2020 were analyzed from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER). Age-adjusted mortality rates (AAMRs) per 100,000 individuals were measured. We used joinpoint trend analysis to determine average annual percent change (AAPC) in AAMR trends. Results: From 1999 to 2020, pancreatic cancer accounted for 809,197 deaths. Overall, the AAMRs of pancreatic cancer increased from 20.74 per 100,000 individuals in 1999 to 21.60 per 100,000 individuals in 2020. The highest AAMR was recorded in non-Hispanic Black males (30.11 per 100,000 individuals), and the lowest, in non-Hispanic White females (18.51 per 100,000 individuals). Patients aged 75-84 years had the highest AAMR (6.87 per 100,000 individuals) compared to the younger patients. The highest AAMR was observed in the Northeast region (22.07 per 100,000 individuals) and rural regions (21.29 per 100,000 individuals). Conclusions: There was no improvement in pancreatic cancer mortality in the last two decades. These findings emphasize the importance of efforts to increase access to multidisciplinary cancer care with the realization that without it, improvements in treatment standards will not translate to lower cancer mortality at the population level.

6.
Sci Rep ; 14(1): 17942, 2024 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095513

RESUMEN

Glycogen storage, conversion and utilization in astrocytes play an important role in brain energy metabolism. The conversion of glycogen to lactate through glycolysis occurs through the coordinated activities of various enzymes and inhibition of this process can impair different brain processes including formation of long-lasting memories. To replenish depleted glycogen stores, astrocytes undergo glycogen synthesis, a cellular process that has been shown to require transcription and translation during specific stimulation paradigms. However, the detail nuclear signaling mechanisms and transcriptional regulation during glycogen synthesis in astrocytes remains to be explored. In this report, we study the molecular mechanisms of vasoactive intestinal peptide (VIP)-induced glycogen synthesis in astrocytes. VIP is a potent neuropeptide that triggers glycogenolysis followed by glycogen synthesis in astrocytes. We show evidence that VIP-induced glycogen synthesis requires CREB-mediated transcription that is calcium dependent and requires conventional Protein Kinase C but not Protein Kinase A. In parallel to CREB activation, we demonstrate that VIP also triggers nuclear accumulation of the CREB coactivator CRTC2 in astrocytic nuclei. Transcriptome profiles of VIP-induced astrocytes identified robust CREB transcription, including a subset of genes linked to glucose and glycogen metabolism. Finally, we demonstrate that VIP-induced glycogen synthesis shares similar as well as distinct molecular signatures with glucose-induced glycogen synthesis, including the requirement of CREB-mediated transcription. Overall, our data demonstrates the importance of CREB-mediated transcription in astrocytes during stimulus-driven glycogenesis.


Asunto(s)
Astrocitos , Proteína de Unión a Elemento de Respuesta al AMP Cíclico , Glucógeno , Péptido Intestinal Vasoactivo , Astrocitos/metabolismo , Glucógeno/metabolismo , Glucógeno/biosíntesis , Animales , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , Péptido Intestinal Vasoactivo/metabolismo , Transcripción Genética , Células Cultivadas , Proteína Quinasa C/metabolismo , Regulación de la Expresión Génica , Ratones , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Núcleo Celular/metabolismo
7.
Sci Rep ; 14(1): 18645, 2024 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134563

RESUMEN

Telemedicine has gained popularity due to the increasing use of technology in our lives. However, no studies have explored the demographic factors affecting acceptability, desirability and adherence (ADA) to telemedicine in Singapore. Our study aims to evaluate the level of ADA of telemedicine services within demographic factors and to explore the association of potential demographic factors with the degree of acceptability, desirability and adherence of telemedicine among older adults in Singapore. A cross-sectional study was conducted with Singapore citizens or permanent residents aged 40-99 years, who were able to provide informed consent. Interviewers conducted door-to-door surveys in 67 Blocks of Housing & Development Board flats in Singapore, offering a self-administered electronic questionnaire available in four languages. Random sampling without replacement determined the order of blocks, floors and units visited. The questionnaire utilised Qtelemediab scoring and covered sociodemographic data, usage of telemedicine, as well as ADA towards telemedicine. A total of 324 valid responses were analysed. Increased age was associated with a significant decrease across all three domains of ADA namely acceptability (ß = - 0.02, 95%CI - 0.03; - 0.02, p-value = 0.002), desirability (ß = - 0.02, 95%CI - 0.02; - 0.02, p-value < 0.001) and adherence (ß = - 0.02, 95%CI - 0.03; - 0.0.02, p-value < 0.001). Additionally, lower education was associated with a decrease in all domains of ADA. Conversely, employment and increased household income were associated with higher ADA scores across all three domains. These associations were independent of gender, chronic health conditions and smoking history. Older participants with lower income and lesser education demonstrated lower levels of acceptability, desirability and adherence towards telemedicine. Our study highlights the importance of considering these factors in the implementation and promotion of telemedicine solutions.


Asunto(s)
Telemedicina , Humanos , Singapur , Anciano , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Anciano de 80 o más Años , Adulto , Encuestas y Cuestionarios , Aceptación de la Atención de Salud/estadística & datos numéricos
8.
Angew Chem Int Ed Engl ; : e202413661, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39166420

RESUMEN

Single-atom nanozymes (SAzymes) with ultrahigh atom utilization efficiency have been extensively applied in reactive oxygen species (ROS)-mediated cancer therapy. However, the high energy barriers of reaction intermediates on single-atom sites and the overexpressed antioxidants in the tumor microenvironment restrict the amplification of tumor oxidative stress, resulting in unsatisfactory therapeutic efficacy. Herein, we report a multi-enzyme mimetic MoCu dual-atom nanozyme (MoCu DAzyme) with various catalytic active sites, which exhibits peroxidase, oxidase, glutathione (GSH) oxidase, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase mimicking activities. Compared with Mo SAzyme, the introduction of Cu atoms, formation of dual-atom sites, and synergetic catalytic effects among various active sites enhance substrate adsorption and reduce the energy barrier, thereby endowing MoCu DAzyme with stronger catalytic activities. Benefiting from the above enzyme-like activities, MoCu DAzyme can not only generate multiple ROS, but also deplete GSH and block its regeneration to trigger the cascade amplification of oxidative stress. Additionally, the strong optical absorption in the near-infrared II bio-window endows MoCu DAzyme with remarkable photothermal conversion performance. Consequently, MoCu DAzyme achieves high-efficiency synergistic cancer treatment incorporating collaborative catalytic therapy and photothermal therapy. This work will advance the therapeutic applications of DAzymes and provide valuable insights for nanocatalytic cancer therapy.

9.
Invest Ophthalmol Vis Sci ; 65(10): 4, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087932

RESUMEN

Purpose: Local recurrence predicts dismal prognosis in eyelid sebaceous carcinoma (SC). Recurrence predictors vary across studies. Accurate recurrence estimation is essential for individualized therapy in eyelid SC. This study aims to identify recurrence predictors and develop a nomogram for personalized prediction in eyelid SC. Methods: We conducted a multicenter retrospective cohort study. Chart reviews were performed in 418 consecutive patients with eyelid SC. All patients were followed up after their initial surgery. Multivariate Cox regression was used to explore the independent predictors of recurrence. A nomogram for recurrence prediction was developed and validated with bootstrap resampling. The predictive accuracy and discriminative ability were compared with the Tumor, Node, Metastasis (TNM) staging system. Results: Over a median of 60-month follow-up, 167 patients (40%) had local recurrence. The median time from diagnosis to recurrence was 14 months. The 1-year cumulative recurrence rate was 18%. Diagnostic delay (hazard ratio [HR] = 1.01, 95% confidence interval [CI] = 1.00-1.01, P = 0.001), orbital involvement (HR = 4.47, 95% CI = 3.04-6.58, P < 0.001), Ki67 (HR = 1.01, 95% CI = 1.00-1.02, P = 0.008) and initial surgery of Mohs micrographic surgery with intraoperative frozen section control (HR = 0.53, 95% CI = 0.35-0.80, P = 0.003) were independent influencing factors of recurrence. A nomogram integrating these four factors combined with pagetoid spread displayed satisfactory discriminative ability (C-index = 0.80-0.83; area under the curve [AUC] = 0.82-0.84), which compared favorably than TNM staging (all P < 0.05). Conclusions: The recurrence rate is high in eyelid SC. Early detection and primary resection with Mohs micrographic surgery are recommended in controlling recurrence. Patients with orbital involvement, high Ki67 expression, and pagetoid spread may require adjuvant measures. This nomogram offers more accurate recurrence estimates, aiding in therapeutic decision making.


Asunto(s)
Adenocarcinoma Sebáceo , Neoplasias de los Párpados , Recurrencia Local de Neoplasia , Nomogramas , Neoplasias de las Glándulas Sebáceas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Neoplasias de los Párpados/patología , Neoplasias de los Párpados/diagnóstico , Neoplasias de las Glándulas Sebáceas/patología , Neoplasias de las Glándulas Sebáceas/diagnóstico , Persona de Mediana Edad , Anciano , Adenocarcinoma Sebáceo/patología , Adenocarcinoma Sebáceo/diagnóstico , Estudios de Seguimiento , Estadificación de Neoplasias , Anciano de 80 o más Años , Adulto , Pronóstico
10.
Heart Fail Clin ; 20(4): 373-386, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39216923

RESUMEN

The conventional sequence of guideline-directed medical therapy (GDMT) initiation in heart failure with reduced ejection fraction (HFrEF) assumes that the effectiveness and tolerability of GDMT agents mirror their order of discovery, which is not true. In this review, the authors discuss flexible GDMT sequencing that should be permitted in special populations, such as patients with bradycardia, chronic kidney disease, or atrial fibrillation. Moreover, the initiation of certain GDMT medications may enable tolerance of other GDMT medications. Most importantly, the achievement of partial doses of all four pillars of GDMT is better than achievement of target dosing of only a couple.


Asunto(s)
Insuficiencia Cardíaca , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/efectos de los fármacos , Quimioterapia Combinada , Antagonistas de Receptores de Angiotensina/uso terapéutico , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico
11.
Math Biosci Eng ; 21(6): 6289-6335, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-39176427

RESUMEN

Hyperparameter optimization (HPO) has been well-developed and evolved into a well-established research topic over the decades. With the success and wide application of deep learning, HPO has garnered increased attention, particularly within the realm of machine learning model training and inference. The primary objective is to mitigate the challenges associated with manual hyperparameter tuning, which can be ad-hoc, reliant on human expertise, and consequently hinders reproducibility while inflating deployment costs. Recognizing the growing significance of HPO, this paper surveyed classical HPO methods, approaches for accelerating the optimization process, HPO in an online setting (dynamic algorithm configuration, DAC), and when there is more than one objective to optimize (multi-objective HPO). Acceleration strategies were categorized into multi-fidelity, bandit-based, and early stopping; DAC algorithms encompassed gradient-based, population-based, and reinforcement learning-based methods; multi-objective HPO can be approached via scalarization, metaheuristics, and model-based algorithms tailored for multi-objective situation. A tabulated overview of popular frameworks and tools for HPO was provided, catering to the interests of practitioners.

12.
Life Sci ; 355: 122980, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39147312

RESUMEN

Testicular organoids have great potential for maintaining male fertility and even restoring male infertility. However, existing studies on generating organoids with testis-specific structure and function are scarce and come with many limitations. Research on cryopreservation of testicular organoids is even more limited, and inappropriate cryopreservation methods may result in the loss of properties in resuscitated or regenerated organoids, rendering them unsuitable for clinical or research needs. In this paper, we investigated the effects of mouse age and cell number on the self-aggregation of testicular cells into spheres in low-adsorption plates. Various media compositions, culture systems, and cell numbers were used to culture cell spheres for 14 days to form testicular organoids, and the self-organization of the organoids was assessed by histological and immunofluorescence staining. We determined the appropriate cryopreservation conditions for testicular cells, cell spheres, and tissues. Subsequently, organoids derived from cryopreserved testicular tissues, testicular cells, and testicular cell spheres were compared and evaluated by histological and immunofluorescence staining. The results indicate that testicular cell spheres consisting of 30 × 104 testicular cells from 2-week-old mice were able to form organoids highly similar to the luminal structure and cell distribution of natural mouse testicular tissues. This transformation occurred over 14 days of incubation in α-MEM medium containing 10 % knockout serum replacer (KSR) using an agarose hydrogel culture system. Additionally, the Sertoli cells were tightly connected to form a blood-testis barrier. The relative rates of tubular area, germ cells, Sertoli cells, and peritubular myoid cells were 36.985 % ± 0.695, 13.347 % ± 3.102, 47.570 % ± 0.379, and 27.406 % ± 1.832, respectively. The optimal cryopreservation protocol for primary testicular cells involved slow freezing with a cryoprotectant consisting of α-MEM with 10 % dimethyl sulfoxide (DMSO). Slow freezing with cryoprotectants containing 5 % DMSO and 5 % ethylene glycol (EG) was optimal for all different volumes of testicular cell spheres. Compared to testicular organoids generated from frozen testicular tissue and cell spheres, freezing testicular cells proved most effective in maintaining organoid differentiation characteristics and cell-cell interactions. The findings of this study contribute to a "universal" testicular organoid in vitro culture protocol with promising applications for fertility preservation and restoration in prepubertal cancer patients and adult infertile patients.


Asunto(s)
Criopreservación , Organoides , Testículo , Animales , Masculino , Criopreservación/métodos , Organoides/citología , Ratones , Testículo/citología , Células de Sertoli/citología , Ratones Endogámicos C57BL , Técnicas de Cultivo de Célula/métodos , Barrera Hematotesticular
13.
J Blood Med ; 15: 331-339, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39132283

RESUMEN

Purpose: Our study aims to describe the mortality trends and disparities among individuals with thalassemia in the United States (US). Patients and Methods: We used CDC WONDER database to calculate the age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and used the Joinpoint Regression Program to measure the average annual percent change (AAPC). Subgroup evaluations were performed by sex, age, race, census region, and urbanization level. Results: From 1999 to 2020, there were 2797 deaths relatd to thalassemia in the US. The AAMR of thalassemia-related death showed a decreasing trend from 0.50 (95% CI, 0.41-0.58) in 1999 to 0.48 (95% CI, 0.41-0.55) in 2020 with the AAPC of -1.42 (95% CI, -2.42, -0.42). Asians have the highest AAMR (1.34 [95% CI, 1.20-1.47]), followed by non-Hispanic Blacks (0.65 [95% CI, 0.59-0.71]), non-Hispanic Whites (0.32 [95% CI, 0.30-0.33]), and Hispanics (0.11 [95% CI, 0.08-0.14]). Cardiovascular disease remains the leading cause of death among individuals with thalassemia. The urban population has a higher AAMR than the rural population (0.43 [95% CI, 0.41-0.45] vs 0.29 [95% CI, 0.26-0.32]). Conclusion: Our study calls for targeted interventions to address the racial and geographic disparities existed among individuals of thalassemia in the US.

14.
Curr Oncol Rep ; 2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39002054

RESUMEN

PURPOSE OF REVIEW: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities. RECENT FINDINGS: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively.

15.
World J Gastroenterol ; 30(25): 3155-3165, 2024 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-39006389

RESUMEN

BACKGROUND: Due to similar clinical manifestations and imaging signs, differential diagnosis of primary intestinal lymphoma (PIL) and Crohn's disease (CD) is a challenge in clinical practice. AIM: To investigate the ability of radiomics combined with machine learning methods to differentiate PIL from CD. METHODS: We collected contrast-enhanced computed tomography (CECT) and clinical data from 120 patients form center 1. A total of 944 features were extracted single-phase images of CECT scans. Using the last absolute shrinkage and selection operator model, the best predictive radiographic features and clinical indications were screened. Data from 54 patients were collected at center 2 as an external validation set to verify the robustness of the model. The area under the receiver operating characteristic curve, accuracy, sensitivity and specificity were used for evaluation. RESULTS: A total of five machine learning models were built to distinguish PIL from CD. Based on the results from the test group, most models performed well with a large area under the curve (AUC) (> 0.850) and high accuracy (> 0.900). The combined clinical and radiomics model (AUC = 1.000, accuracy = 1.000) was the best model among all models. CONCLUSION: Based on machine learning, a model combining clinical data with radiologic features was constructed that can effectively differentiate PIL from CD.


Asunto(s)
Enfermedad de Crohn , Neoplasias Intestinales , Aprendizaje Automático , Curva ROC , Tomografía Computarizada por Rayos X , Humanos , Enfermedad de Crohn/diagnóstico por imagen , Femenino , Diagnóstico Diferencial , Masculino , Persona de Mediana Edad , Adulto , Neoplasias Intestinales/diagnóstico por imagen , Neoplasias Intestinales/patología , Tomografía Computarizada por Rayos X/métodos , Estudios Retrospectivos , Linfoma/diagnóstico por imagen , Linfoma/patología , Anciano , Sensibilidad y Especificidad , Medios de Contraste/administración & dosificación , Adulto Joven , Radiómica
16.
Colloids Surf B Biointerfaces ; 242: 114096, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39053031

RESUMEN

Cryopreserved testicular tissue offers a promising method to restore fertility in male infertility patients. Current protocols rely on high concentrations of penetrating cryoprotectants (pCPAs), such as dimethyl sulfoxide (DMSO), which necessitating complex washing procedures and posing risks of toxicity. Hydrogel encapsulation presents a non-toxic alternative for cellular cryopreservation. This study investigates the effects of various types, concentrations, and thicknesses of hydrogel encapsulation on the cryopreservation of mouse testicular tissue. Testicular tissues loaded with varying concentrations of DMSO were encapsulated in alginate or gelatin-methacryloyl (GelMA) hydrogels. We evaluated hydrogels as potential CPAs to reduce pCPA concentrations and determine optimal combinations for cryopreservation. Post-cryopreservation, tissues were cultured using organ culture methods to assess spermatogenesis progression. Cryomicroscopy and differential scanning calorimetry (DSC) were used to examine ice crystal formation, melting enthalpy, and non-freezing water content in different hydrogels during cooling. Results indicate that 3 % alginate or 5 % GelMA hydrogel with thin encapsulation optimally preserves mouse testicular tissue. Using 20 % DMSO in 5 % GelMA thin encapsulation showed comparable apoptosis rates, improved morphology, higher mitochondrial activity, and enhanced antioxidant capacity compared to conventional 30 % DMSO without encapsulation. This suggests that hydrogel encapsulation reduces pCPA concentration by 10 %, thereby mitigating toxic damage. Hydrogel encapsulation can reduce basement membrane shrinkage of testicular tissue during cryopreservation. Moreover, frozen tissues remained viable with preserved germ cells after being cultured for one week on alginate methacryloyl (AlgMA) hydrogel using the gas-liquid interphase method. Cryomicroscopy and DSC studies confirmed the hydrogel's ability to inhibit ice crystal growth. In conclusion, this study introduces novel strategies for male fertility preservation and advances cryopreservation technology for clinical applications in assisted reproduction.


Asunto(s)
Criopreservación , Crioprotectores , Hidrogeles , Testículo , Animales , Masculino , Crioprotectores/química , Crioprotectores/farmacología , Ratones , Testículo/efectos de los fármacos , Criopreservación/métodos , Hidrogeles/química , Hidrogeles/farmacología , Alginatos/química , Alginatos/farmacología , Dimetilsulfóxido/química , Dimetilsulfóxido/farmacología , Gelatina/química , Rastreo Diferencial de Calorimetría , Metacrilatos
17.
J Med Chem ; 67(14): 12439-12458, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38996004

RESUMEN

The discovery of effective and safe antiobesity agents remains a challenging yet promising field. Our previous studies identified Bouchardatine derivatives as potential antiobesity agents. However, the 8a-aldehyde moiety rendered them unsuitable for drug development. In this study, we designed two series of novel derivatives to modify this structural feature. Through a structure-activity relationship study, we elucidated the role of the 8a-aldehyde group in toxicity induction. We identified compound 14d, featuring an 8a-N-acylhydrazone moiety, which exhibited significant lipid-lowering activity and reduced toxicity. Compound 14d shares a similar lipid-lowering mechanism with our lead compound 3, but demonstrates improved pharmacokinetic properties and safety profile. Both oral and injectable administration of 14d significantly reduced body weight gain and ameliorated metabolic syndrome in diet-induced obese mice. Our findings identify 14d as a promising antiobesity agent and highlight the potential of substituting the aldehyde group with an N-acylhydrazone to enhance drug-like properties.


Asunto(s)
Aldehídos , Fármacos Antiobesidad , Hidrazonas , Obesidad , Animales , Fármacos Antiobesidad/farmacología , Fármacos Antiobesidad/síntesis química , Fármacos Antiobesidad/farmacocinética , Fármacos Antiobesidad/uso terapéutico , Fármacos Antiobesidad/química , Hidrazonas/farmacología , Hidrazonas/química , Hidrazonas/síntesis química , Hidrazonas/farmacocinética , Hidrazonas/uso terapéutico , Ratones , Relación Estructura-Actividad , Aldehídos/química , Masculino , Obesidad/tratamiento farmacológico , Ratones Endogámicos C57BL , Dieta Alta en Grasa/efectos adversos , Humanos , Ratones Obesos , Estructura Molecular
18.
J Agric Food Chem ; 72(26): 14557-14569, 2024 Jul 03.
Artículo en Inglés | MEDLINE | ID: mdl-38957088

RESUMEN

This study aimed to investigate the mechanisms by which dark septate endophytes (DSE) regulate salt tolerance and the accumulation of bioactive constituents in licorice. First, the salt stress tolerance and resynthesis with the plant effect of isolated DSE from wild licorice were tested. Second, the performance of licorice inoculated with DSE, which had the best salt-tolerant and growth-promoting effects, was examined under salt stress. All isolated DSE showed salt tolerance and promoted plant growth, withCurvularia lunata D43 being the most effective. Under salt stress, C. lunata D43 could promote growth, increase antioxidant enzyme activities, enhance glycyrrhizic acid accumulation, improve key enzyme activities in the glycyrrhizic acid synthesis pathway, and induce the expression of the key enzyme gene and salt tolerance gene of licorice. The structural equation model demonstrated that DSE alleviate the negative effects of salt stress through direct and indirect pathways. Variations in key enzyme activities, gene expression, and bioactive constituent concentration can be attributed to the effects of DSE. These results contribute to revealing the value of DSE for cultivating medicinal plants in saline soils.


Asunto(s)
Endófitos , Glycyrrhiza , Ácido Glicirrínico , Estrés Salino , Ácido Glicirrínico/metabolismo , Glycyrrhiza/química , Glycyrrhiza/metabolismo , Glycyrrhiza/microbiología , Endófitos/metabolismo , Endófitos/genética , Tolerancia a la Sal , Ascomicetos/metabolismo , Ascomicetos/crecimiento & desarrollo , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulación de la Expresión Génica de las Plantas
19.
Cryobiology ; 116: 104942, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39032528

RESUMEN

Cryopreservation of biological samples is an important technology for expanding their applications in the biomedical field. However, the quality and functionality of samples after rewarming are limited by the toxicity of commonly used cryoprotectant agents (CPAs). Here, we developed a novel preservation system by combining the natural amino acid l-proline (L-Pro) with gelatin methacryloyl (GelMA) hydrogels. Compared with dimethyl sulfoxide (DMSO), L-Pro and GelMA demonstrated excellent biocompatibility when co-culturing with cells. Cryopreservation procedures were optimized using 3T3 as model cells. The results showed that rapid cooling was the most suitable cooling procedure for L-Pro and GelMA among the three cooling procedures. Co-culturing with cells for 3 h before cryopreservation, 6 % L-Pro +7 % GelMA had the highest survival rate, reaching up to 80 %. Differential Scanning Calorimetry (DSC) analysis showed that 6 % L-Pro + 7 % GelMA lowered the freezing point of the solution to -4.2 °C and increased the unfrozen water content to 20 %. To the best of our knowledge, this is the first report of cell cryopreservation using a combination of L-Pro and GelMA hydrogels, which provides a new strategy for improving cell cryopreservation.


Asunto(s)
Supervivencia Celular , Criopreservación , Crioprotectores , Dimetilsulfóxido , Gelatina , Hidrogeles , Prolina , Criopreservación/métodos , Crioprotectores/química , Crioprotectores/farmacología , Ratones , Animales , Prolina/química , Supervivencia Celular/efectos de los fármacos , Gelatina/química , Hidrogeles/química , Dimetilsulfóxido/química , Dimetilsulfóxido/farmacología , Congelación , Células 3T3 , Rastreo Diferencial de Calorimetría , Técnicas de Cocultivo
20.
J Investig Med ; : 10815589241262003, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38869155

RESUMEN

Non-Hodgkin lymphoma (NHL) is one of the most common hematological cancers in the United States. The mortality rate of NHL in the United States is the sixth highest among all cancers. Our cross-sectional study aims to examine the trends and disparity in NHL mortality. We analyzed death certificate data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research (CDC WONDER) United States to determine the NHL mortality trends among the U.S. population aged ≥15 years. NHL (ICD-10 C82-85) was listed as the underlying cause of death. Age-adjusted mortality rates (AAMRs) per 100,000 individuals and joinpoint trend analysis were performed to determine the average annual percent change (AAPC) in AAMR trends. From 1999 to 2020, NHL accounted for 457,143 deaths in the United States, of which 54% are men and 46% are women. The NHL AAMR decreased significantly from 10.59 to 6.21 per 100,000 individuals with an AAPC of -2.55. Men had a higher AAMR than women (10.10 vs 6.29 per 100,000 individuals). Whites recorded the highest AAMR (8.43 per 100,000 individuals), followed by Hispanics (6.32 per 100,000 individuals), Blacks (5.71 per 100,000 individuals), American Indians (5.31 per 100,000 individuals), and Asians (5.10 per 100,000 individuals). Those who lived in the Midwest and the rural areas had the highest AAMR at 8.60 and 8.35 per 100,000 individuals respectively. Despite the declining NHL mortality rate, this study calls for targeted intervention to improve outcomes for susceptible individuals affected by NHL.

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