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1.
J Environ Sci (China) ; 148: 375-386, 2025 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-39095172

RESUMO

Tuojiang River Basin is a first-class tributary of the upper reaches of the Yangtze River-which is the longest river in China. As phytoplankton are sensitive indicators of trophic changes in water bodies, characterizing phytoplankton communities and their growth influencing factors in polluted urban rivers can provide new ideas for pollution control. Here, we used direct microscopic count and environmental DNA (eDNA) metabarcoding methods to investigate phytoplankton community structure in Tuojiang River Basin (Chengdu, Sichuan Province, China). The association between phytoplankton community structure and water environmental factors was evaluated by Mantel analysis. Additional environmental monitoring data were used to pinpoint major factors that influenced phytoplankton growth based on structural equation modeling. At the phylum level, the dominant phytoplankton taxa identified by the conventional microscopic method mainly belonged to Bacillariophyta, Chlorophyta, and Cyanophyta, in contrast with Chlorophyta, Dinophyceae, and Bacillariophyta identified by eDNA metabarcoding. In α-diversity analysis, eDNA metabarcoding detected greater species diversity and achieved higher precision than the microscopic method. Phytoplankton growth was largely limited by phosphorus based on the nitrogen-to-phosphorus ratios > 16:1 in all water samples. Redundancy analysis and structural equation modeling also confirmed that the nitrogen-to-phosphorus ratio was the principal factor influencing phytoplankton growth. The results could be useful for implementing comprehensive management of the river basin environment. It is recommended to control the discharge of point- and surface-source pollutants and the concentration of dissolved oxygen in areas with excessive nutrients (e.g., Jianyang-Ziyang). Algae monitoring techniques and removal strategies should be improved in 201 Hospital, Hongrihe Bridge and Colmar Town areas.


Assuntos
Monitoramento Ambiental , Fitoplâncton , Rios , Rios/química , China , Poluentes Químicos da Água/análise , Fósforo/análise
2.
Heliyon ; 10(15): e34416, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39144959

RESUMO

This study investigates the dynamic characteristics of the dual-mode resonant non-linear Schrodinger equation with a Bhom potential. Hydrodynamics, nonlinear optical fibre communication, elastic media, and plasma physics are just a few of the mathematical physics and engineering applications for this model. The study aims to achieve two main objectives: first, to discuss bifurcation analysis, and second, to extract optical soliton solutions using the extended hyperbolic function method. The study successfully derives various wave solutions, including bright, singular, periodic singular and dark solitons, based on the governing model. The findings conferred in this article show a crucial advancement in understanding the propagation of waves in non-linear media. Additionally, bifurcation of phase portraits of ordinary differential equation consistent with the partial differential equation under consideration is conducted. We also highlight specific constraint conditions that ensure the presence of these obtained solutions. The existing literature shows that these methods are first time applied on this model.

3.
Orthop Surg ; 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39142661

RESUMO

OBJECTIVE: Although several reconstructive methods have been developed to manage large segmental tibial bone defects including bone transport (distraction osteogenesis), contralateral fibular graft, allograft, tibiofibular synostosis, Masquelet technique, and 3D printed scaffold, neglected large tibial defects in adults remain challenging problems. This study describes gradual transverse transport of naturally tibialized fibula using hexapod frames in management of adult patients with neglected large tibial defects. METHODS: We retrospectively reviewed four cases of transverse transport of naturally tibialized fibula from November 2018 to February 2022. We measured the length of the tibial defect and the transported fibular segment, the mid-diaphyseal diameter and cortical thickness of the affected fibula, contralateral fibula, and tibia. The parameters measured both preoperatively and postoperatively were leg length discrepancy, hip-knee-ankle angle, medial proximal tibial angle, posterior proximal tibial angle, lateral distal tibial angle, range of motion of the knee and ankle joints, and Lower Extremity Functional Scores (LEFS). Patients' satisfaction rates using Likert scale were also recorded. RESULTS: Among four female patients, three suffered from tibial osteomyelitis, and one was due to congenital pseudarthrosis of the tibia. The average follow-up time was 2.7 ± 1.4 years. The average length of tibial defect was 14.0 ± 0.8 cm. The average preoperative shortening of the affected leg was 9.0 ± 2.5 cm, which changed to 0.6 ± 0.8 cm postoperatively. The median length of the transported fibular segment was 15.2 cm. Two patients had varus deformity, two had recurvatum, and one had procurvatum preoperatively. Postoperative radiological measurement showed all deformities corrected and no ankle valgus deformity developed during follow-up. All patients achieved union and can fully weight bear on the affected extremity. The average fixator time was 12.9 ± 2.9 months. The average preoperative and postoperative LEFS, respectively, were 53.5 ± 5.0, 70.5 ± 1.3, with a significant difference (p = 0.003). Three patients reported very satisfied with the outcome, and one patient reported satisfied. Three patients had pin tract infections, and one patient had skin necrosis which healed after additional surgery. One patient had surgical release of the hamstring tendons due to flexion contracture of the knee. Two patients had 15° of reduction in ankle range of motion. One patient had transient common peroneal nerve palsy which spontaneously recovered within 6 weeks. CONCLUSION: The transverse transport of naturally tibialized fibula was both a safe and effective method to treat the long-standing type V tibial segmental defect.

4.
J Multidiscip Healthc ; 17: 3743-3751, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39104383

RESUMO

Objective: Sarcopenia is more common in maintenance hemodialysis (MHD) patients, and the aim of this study is to analyze the risk factors associated with sarcopenia in MHD patients, along with its correlation to emotional status and quality of life. Methods: This is a cross-sectional cohort study. A total of 111 MHD patients who were treated in the Department of Nephrology of our hospital were selected as the study subjects by convenience sampling. The quality of life and emotional status were evaluated by health survey scale (SF-36), self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Regression analysis was used to explore the influencing factors of sarcopenia. Correlation analysis was used to investigate the correlation between sarcopenia and quality of life and emotional status. Results: The prevalence of sarcopenia was 59.8%. The results showed that age, gender, body mass index (BMI), dialysis time, economic status, marital status and pre-dialysis creatinine were significant factors affecting the development of sarcopenia in hemodialysis patients (p<0.05). The SF-36 total score was significantly lower in the sarcopenia group (72.05±12.28 vs 78.03±10.55) than in the non-sarcopenia group, but the anxiety scale score (52.97±4.67 vs 36.2±3.36) and depression scale score (57.67±4.58 vs 38.71±3.77) were significantly higher than those in the non-sarcopenia group (p< 0.001). Correlation analysis showed that sarcopenia was positively correlated with SAS and SDS scores and negatively correlated with SF-36 total score (p < 0.05). Conclusion: The risk of sarcopenia was higher among MHD patients who were older, male, single, with a longer MHD duration, lower economic status, lower BMI, comorbid diabetes and lower levels of creatinine.

5.
J Agric Food Chem ; 72(32): 17771-17781, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39087686

RESUMO

As the demand for lactoferrin increases, the search for cost-effective alternative proteins becomes increasingly important. Attention naturally turns to other members of the transferrin family such as ovotransferrin. The iron-binding abilities of these proteins influence their characteristics, although the underlying mechanisms remain unclear. This overview systematically summarizes the effects of the iron-binding ability on the fate of food-derived transferrins (lactoferrin and ovotransferrin) and their potential applications. The findings indicate that iron-binding ability significantly influences the structure of food-derived transferrins, particularly their tertiary structure. Changes in structure influence their physicochemical properties, which, in turn, lead to different behaviors in response to environmental variations. Thus, these proteins exhibit distinct digestive characteristics by the time they reach the small intestine, ultimately performing varied physiological functions in vivo. Consequently, food-derived transferrins with different iron-binding states may find diverse applications. Understanding this capability is essential for developing food-derived transferrins and driving innovation in lactoferrin-related industries.


Assuntos
Ferro , Lactoferrina , Ferro/metabolismo , Ferro/química , Animais , Humanos , Lactoferrina/metabolismo , Lactoferrina/química , Ligação Proteica , Transferrinas/metabolismo , Transferrinas/química , Conalbumina/química , Conalbumina/metabolismo
6.
Environ Sci Ecotechnol ; 22: 100450, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39161573

RESUMO

Rainfall data with high spatial and temporal resolutions are essential for urban hydrological modeling. Ubiquitous surveillance cameras can continuously record rainfall events through video and audio, so they have been recognized as potential rain gauges to supplement professional rainfall observation networks. Since video-based rainfall estimation methods can be affected by variable backgrounds and lighting conditions, audio-based approaches could be a supplement without suffering from these conditions. However, most audio-based approaches focus on rainfall-level classification rather than rainfall intensity estimation. Here, we introduce a dataset named Surveillance Audio Rainfall Intensity Dataset (SARID) and a deep learning model for estimating rainfall intensity. First, we created the dataset through audio of six real-world rainfall events. This dataset's audio recordings are segmented into 12,066 pieces and annotated with rainfall intensity and environmental information, such as underlying surfaces, temperature, humidity, and wind. Then, we developed a deep learning-based baseline using Mel-Frequency Cepstral Coefficients (MFCC) and Transformer architecture to estimate rainfall intensity from surveillance audio. Validated from ground truth data, our baseline achieves a root mean absolute error of 0.88 mm h-1 and a coefficient of correlation of 0.765. Our findings demonstrate the potential of surveillance audio-based models as practical and effective tools for rainfall observation systems, initiating a new chapter in rainfall intensity estimation. It offers a novel data source for high-resolution hydrological sensing and contributes to the broader landscape of urban sensing, emergency response, and resilience.

7.
Eur J Oncol Nurs ; 72: 102684, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39163755

RESUMO

PURPOSE: To explore and understand the conflict in decision-making of hematopoietic stem cell transplantation in patients with hematological neoplasms. METHODS: A descriptive qualitative study of 16 patients with hematologic neoplasms in the hematology department was conducted between February 2022 and May 2022. Purposive sampling was used to select participants. Face-to-face in-depth personal interviews were performed. Interviews were recorded, transcribed, and coded. This descriptive qualitative study adhered to the COREQ checklist. RESULTS: All patients indicated difficulties in making decisions regarding hematopoietic stem cell transplantation. Five themes were identified: (1) weighing the pros and cons of HSCT, (2) financial burden versus desire for rebirth, (3) treatment urgency versus being unprepared, (4) saving oneself versus damaging loved ones, and (5) family companionship versus emotional isolation. These themes reflect the contradictions, entanglements, and realistic conflicts in decision-making regarding hematopoietic stem cell transplantation for patients with hematological neoplasms. CONCLUSIONS: This study identified multiple conflicts of decision-making in patients with hematologic neoplasms regarding decisions on hematopoietic stem cell transplantations. Healthcare workers should provide patients with disease knowledge, doctor-patient and intra-family communication, and access to financial support in order to resolve their conflicts and ultimately help them make the decision that is most optimum for them.

8.
Eur J Oncol Nurs ; 72: 102666, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39163757

RESUMO

PURPOSE: To explore the symptom experience and self-management strategies of adults undergoing hematopoietic stem cell transplantation after hospital discharge. METHODS: A longitudinal qualitative study was employed. A heterogeneous sample of 22 patients who underwent hematopoietic stem cell transplantation from August 2022 to April 2023 were included. Semi-structured interviews were conducted at three time points post-discharge and provided a dataset of 56 interviews. The content analysis method was used for manual analysis. This study followed the COREQ checklist. RESULTS: The data from this study were categorized into four themes and 14 subthemes: (1) complexity and multidimensionality of symptom experience: diversity, dynamism, continuity, relatedness, and functional loading; (2) multiple variations in symptom self-management; (3) barriers to symptom self-management: limited access to information resources, insufficient awareness and skills in symptom self-management, lack of economic and social support, and difficulties in medical visits and reviews; and (4) facilitators of symptom self-management: perceived benefits, experience-driven, and peer experiences. CONCLUSION: Patients undergoing hematopoietic stem cell transplantation experience multiple and complex symptom experiences after hospital discharge, and their symptom self-management remains challenging. The findings underscore the necessity for healthcare professionals to regularly and consistently evaluate the symptoms and self-management practices of patients undergoing hematopoietic stem cell transplantation and execute focused interventions to alleviate their symptom load and enhance their long-term well-being.

9.
Diabetes Metab J ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39165112

RESUMO

Background: Endothelin-1 (ET-1) is an endogenous vasoconstrictor implicated in coronary artery disease (CAD) and diabetes. This study aimed to determine the prognostic value of ET-1 in the patients with stable CAD under different glucose metabolism states. Methods: In this prospective, large-cohort study, we consecutively enrolled 7,947 participants with angiography-diagnosed stable CAD from April 2011 to April 2017. Patients were categorized by baseline glycemic status into three groups (normoglycemia, prediabetes, and diabetes) and further divided into nine groups by circulating ET-1 levels. Patients were followed for the occurrence of cardiovascular events (CVEs), including nonfatal myocardial infarction, stroke, and cardiovascular mortality. Results: Of the 7,947 subjects, 3,352, 1,653, and 2,942 had normoglycemia, prediabetes, and diabetes, respectively. Over a median follow-up of 37.5 months, 381 (5.1%) CVEs occurred. The risk for CVEs was significantly higher in patients with elevated ET-1 levels after adjustment for potential confounders. When patients were categorized by both status of glucose metabolism and plasma ET-1 levels, the high ET-1 levels were associated with higher risk of CVEs in prediabetes (adjusted hazard ratio [HR], 2.089; 95% confidence interval [CI], 1.151 to 3.793) and diabetes (adjusted HR, 2.729; 95% CI, 1.623 to 4.588; both P<0.05). Conclusion: The present study indicated that baseline plasma ET-1 levels were associated with the prognosis in prediabetic and diabetic patients with stable CAD, suggesting that ET-1 may be a valuable predictor in CAD patients with impaired glucose metabolism.

10.
Cell Rep Med ; : 101666, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39094578

RESUMO

Epithelial ovarian cancer (EOC) is the deadliest women's cancer and has a poor prognosis. Early detection is the key for improving survival (a 5-year survival rate in stage I/II is over 70% compared to that of 25% in stage III/IV) and can be achieved through methylation markers from circulating cell-free DNA (cfDNA) using a liquid biopsy. In this study, we first identify top 500 EOC markers differentiating EOC from healthy female controls from 3.3 million methylome-wide CpG sites and validated them in 1,800 independent cfDNA samples. We then utilize a pretrained AI transformer system called MethylBERT to develop an EOC diagnostic model which achieves 80% sensitivity and 95% specificity in early-stage EOC diagnosis. We next develop a simple digital droplet PCR (ddPCR) assay which archives good performance, facilitating early EOC detection.

11.
Orthop Surg ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39161056

RESUMO

OBJECTIVE: Distal tibial deformities can significantly impact patients if left uncorrected, often leading to pain, alterations in gait, and the eventual development of post-traumatic arthritis. The criteria for surgical correction in these patients continues to be a subject of debate, while supramalleolar osteotomy (SMO) is an effective method for correcting distal tibial deformities. The purpose of this study was to evaluate and compare the clinical results of SMO using internal fixation or using computer-assisted hexapod external fixator in the treatment of distal tibial deformity. METHODS: A retrospective study was conducted on 290 patients who underwent SMO between June 2015 and January 2023. Forty-four patients met the inclusion and exclusion criteria. Among the participants, 19 underwent SMO combined with a computer-assisted hexapod external fixator, while 25 received SMO with plate and screw internal fixation. The tibial anterior surface (TAS) angle, tibial lateral surface (TLS) angle, the tibiotalar (TT) angle and the talocrural (TC) angle were assessed on weight-bearing X-ray films. Functional assessments were performed according to the American Orthopedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: The study followed patients for an average duration of 31.7 ± 15.3 months, with a range from 12 to 67 months. Successful bone union was achieved in all cases. For patients treated with the computer-assisted hexapod external fixator, significant improvements were observed: the mean deviation in sagittal plane deformity parameters decreased from 14.3 ± 10.4 degrees preoperatively to 2.8 ± 3.8 degrees postoperatively (p < 0.05). Similarly, coronal plane deformity parameters showed a reduction from 25.9 ± 22.5 degrees preoperatively to 5.9 ± 11.0 degrees postoperatively (p < 0.05). The AOFAS ankle-hindfoot score improved markedly from 66.0 ± 14.9 to 86.1 ± 11.7 points (p < 0.05). For patients undergoing internal fixation, the absolute difference in coronal plane parameters improved from 15.4 ± 12.6 degrees preoperatively to 3.7 ± 3.4 degrees postoperatively (p < 0.05). A significant enhancement in AOFAS ankle-hindfoot score was also noted, increasing from 68.3 ± 14.3 points to 79.4 ± 13.5 points (p < 0.05). There were no significant differences in gender, side, follow-up time, postoperative deviation of deformity, pre- or postoperative AOFAS between the two groups. CONCLUSION: In conclusion, comprehensive preoperative planning of SMO combined with either internal fixation or a hexapod external fixator for treating distal tibial deformities can achieve satisfactory outcomes. The utilization of a computer-assisted hexapod external fixator facilitates a gradual and precise correction process, which proved to be an effective and relatively safe method.

12.
Cell Commun Signal ; 22(1): 398, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39143495

RESUMO

Ovarian granulosa cells are essential to gonadotrophin-regulated estrogen production, female cycle maintenance and fertility. The epithelial Na+ channel (ENaC) is associated with female fertility; however, whether and how it plays a role in ovarian cell function(s) remained unexplored. Here, we report patch-clamp and Na+ imaging detection of ENaC expression and channel activity in both human and mouse ovarian granulosa cells, which are promoted by pituitary gonadotrophins, follicle stimulating hormone (FSH) or luteinizing hormone (LH). Cre-recombinase- and CRISPR-Cas9-based granulosa-specific knockout of ENaC α subunit (Scnn1a) in mice resulted in failed estrogen elevation at early estrus, reduced number of corpus luteum, abnormally extended estrus phase, reduced litter size and subfertility in adult female mice. Further analysis using technologies including RNA sequencing and Ca2+ imaging revealed that pharmacological inhibition, shRNA-based knockdown or the knockout of ENaC diminished spontaneous or stimulated Ca2+ oscillations, lowered the capacity of intracellular Ca2+ stores and impaired FSH/LH-stimulated transcriptome changes for estrogen production in mouse and/or human granulosa cells. Together, these results have revealed a previously undefined role of ENaC in modulating gonadotrophin signaling in granulosa cells for estrogen homeostasis and thus female fertility.


Assuntos
Cálcio , Canais Epiteliais de Sódio , Estrogênios , Fertilidade , Células da Granulosa , Homeostase , Feminino , Animais , Células da Granulosa/metabolismo , Canais Epiteliais de Sódio/metabolismo , Canais Epiteliais de Sódio/genética , Humanos , Estrogênios/metabolismo , Camundongos , Fertilidade/genética , Cálcio/metabolismo , Gonadotropinas/metabolismo , Transdução de Sinais , Camundongos Knockout , Sinalização do Cálcio
13.
Org Lett ; 26(32): 6847-6852, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39110700

RESUMO

We reported the visible-light-mediated photoredox-catalyzed oxidative radical-polar crossover and 1,5-hydrogen atom transfer combined site-selective remote C(sp3)-N cross-coupling alkylamination of alkenes. Various anilines and hydroxamides (1,5-hydrogen atom transfer reagents) could be tolerated. The mechanistic studies indicated the radical nature of the reaction and the indispensability of light and photocatalyst. Stern-Volmer fluorescence quenching and cyclic voltammetry experiments have been used to outline the proposed reaction pathway.

14.
Int J Cardiol ; 414: 132384, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032578

RESUMO

BACKGROUND: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study. METHODS: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR). RESULTS: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003). CONCLUSION: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up.

15.
Cell Rep Med ; 5(7): 101645, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39019012

RESUMO

Fms-like tyrosine kinase 3 (FLT3) mutations, present in over 30% of acute myeloid leukemia (AML) cases and dominated by FLT3-internal tandem duplication (FLT3-ITD), are associated with poor outcomes in patients with AML. While tyrosine kinase inhibitors (TKIs; e.g., gilteritinib) are effective, they face challenges such as drug resistance, relapse, and high costs. Here, we report that metformin, a cheap, safe, and widely used anti-diabetic agent, exhibits a striking synergistic effect with gilteritinib in treating FLT3-ITD AML. Metformin significantly sensitizes FLT3-ITD AML cells (including TKI-resistant ones) to gilteritinib. Metformin plus gilteritinib (low dose) dramatically suppresses leukemia progression and prolongs survival in FLT3-ITD AML mouse models. Mechanistically, the combinational treatment cooperatively suppresses polo-like kinase 1 (PLK1) expression and phosphorylation of FLT3/STAT5/ERK/mTOR. Clinical analysis also shows improved survival rates in patients with FLT3-ITD AML taking metformin. Thus, the metformin/gilteritinib combination represents a promising and cost-effective treatment for patients with FLT3-mutated AML, particularly for those with low income/affordability.


Assuntos
Compostos de Anilina , Proteínas de Ciclo Celular , Sinergismo Farmacológico , Leucemia Mieloide Aguda , Metformina , Mutação , Quinase 1 Polo-Like , Proteínas Serina-Treonina Quinases , Proteínas Proto-Oncogênicas , Pirazinas , Transdução de Sinais , Tirosina Quinase 3 Semelhante a fms , Metformina/farmacologia , Metformina/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/metabolismo , Tirosina Quinase 3 Semelhante a fms/antagonistas & inibidores , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Humanos , Animais , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Transdução de Sinais/efeitos dos fármacos , Pirazinas/farmacologia , Pirazinas/uso terapêutico , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Camundongos , Mutação/genética , Linhagem Celular Tumoral , Tiofenos/farmacologia , Tiofenos/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Fator de Transcrição STAT5/metabolismo , Fator de Transcrição STAT5/genética , Feminino , Ensaios Antitumorais Modelo de Xenoenxerto , Masculino , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Serina-Treonina Quinases TOR/metabolismo
16.
Org Biomol Chem ; 22(29): 6016-6021, 2024 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-39007287

RESUMO

Simple and practical strategies for visible-light-induced C-H alkylation of 2-amino-1,4-naphthoquinones with cyclobutanone oxime esters and hydroxamic acid derivatives have been developed under mild and redox-neutral conditions. These two reactions can be carried out at room temperature and obtain a variety of 2-amino-1,4-naphthoquinone derivatives with cyano and amide groups. Moreover, the cyanoalkylation reaction of 2-amino-1,4-naphthoquinones can proceed smoothly in the absence of photocatalysts.

17.
Nat Commun ; 15(1): 6043, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39025845

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is a devastating cancer with dismal prognosis due to distant metastasis, even in the early stage. Using RNA sequencing and multiplex immunofluorescence, here we find elevated expression of mixed lineage kinase domain-like pseudo-kinase (MLKL) and enhanced necroptosis pathway in PDAC from early liver metastasis T-stage (T1M1) patients comparing with non-metastatic (T1M0) patients. Mechanistically, MLKL-driven necroptosis recruits macrophages, enhances the tumor CD47 'don't eat me' signal, and induces macrophage extracellular traps (MET) formation for CXCL8 activation. CXCL8 further initiates epithelial-mesenchymal transition (EMT) and upregulates ICAM-1 expression to promote endothelial adhesion. METs also degrades extracellular matrix, that eventually supports PDAC liver metastasis. Meanwhile, targeting necroptosis and CD47 reduces liver metastasis in vivo. Our study thus reveals that necroptosis facilitates PDAC metastasis by evading immune surveillance, and also suggest that CD47 blockade, combined with MLKL inhibitor GW806742X, may be a promising neoadjuvant immunotherapy for overcoming the T1M1 dilemma and reviving the opportunity for radical surgery.


Assuntos
Antígeno CD47 , Carcinoma Ductal Pancreático , Transição Epitelial-Mesenquimal , Armadilhas Extracelulares , Neoplasias Hepáticas , Macrófagos , Necroptose , Neoplasias Pancreáticas , Proteínas Quinases , Humanos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/metabolismo , Animais , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/genética , Camundongos , Macrófagos/metabolismo , Macrófagos/imunologia , Linhagem Celular Tumoral , Antígeno CD47/metabolismo , Antígeno CD47/genética , Proteínas Quinases/metabolismo , Armadilhas Extracelulares/metabolismo , Molécula 1 de Adesão Intercelular/metabolismo , Molécula 1 de Adesão Intercelular/genética , Masculino , Transdução de Sinais , Feminino , Acrilamidas , Sulfonamidas
18.
Zhonghua Nan Ke Xue ; 30(1): 9-17, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-39046408

RESUMO

OBJECTIVE: To investigate the expression pattern of the D930020B18Rik gene in the testis of the mouse in different stages of development and its possible role in spermatogenesis. METHODS: Using gene expression profile microarray, we identified highly expressed D930020B18Rik in the mouse testis and analyzed the expression pattern of the gene by qPCR, immunohistochemistry, Western blot and immunofluorescence staining, and verified its function and molecular mechanism using bioinformatics analysis, dual-luciferase reporter assay and cell cycle synchronization. RESULTS: The expression of the D930020B18Rik gene remained low in the testis of the mouse and mainly localized in the cytoplasm of spermatogonia during the first 2 postnatal weeks (PNW), increased from the 3rd PNW to sexual maturity, localized in the cytoplasm of spermatogonia and the nuclei of round and elongated spermatids, but was absent in the nuclei of mature sperm. Phylogenetic analysis showed that the D930020B18Rik protein sequence was highly conserved in mammals. Gene set enrichment analysis indicated that D930020B18Rik and its homologous protein might be involved in regulating spermatogenesis of mammals by participating in nucleoplasmic condensation (normalized enrichment score ï¼»NESï¼½ = 1.652, P < 0.01, false discovery rate ï¼»FDRï¼½ = 0.153), meiosis (NES = 1.960, P < 0.01, FDR = 0.001) and formation of microtubule cytoskeleton during mitosis (NES = 1.903, P < 0.01, FDR = 0.009). Dual-luciferase reporter assay revealed that the transcription factors klf5 and foxo1 could identify and bind D930020B18Rik promoters and perform the function of positive or negative transcriptional regulation. CONCLUSION: The D930020B18Rik gene is expressed in the mouse testis in a time- and location-specific manner, highly associated with spermiogenesis, mainly localized in the nuclei of germ cells, and may be involved in the meiosis of spermatocytes and spermiogenesis.


Assuntos
Espermatogênese , Testículo , Animais , Masculino , Espermatogênese/genética , Camundongos , Testículo/metabolismo , Espermatogônias/metabolismo , Espermatogônias/citologia , Filogenia , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Perfilação da Expressão Gênica
19.
J Med Virol ; 96(8): e29838, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39081166

RESUMO

Enteroviruses are important human pathogens with diverse serotypes, posing a major challenge to develop vaccines for individual serotypes, the success of polio vaccines in controlling and eradicating polio, along with the recent emergence and high prevalence of enterovirus-caused infectious diseases, highlights the importance of enterovirus vaccine development. Given our previous report on enteroviruses weakened by the 2 A S/T125A mutation, we assessed the potential of the EV-A71 2A-125A mutant as a vaccine candidate to address this challenge. We found that the 2A-125A mutant caused transient mild symptoms, low viral loads, and no significant pathological changes mild pathological changes in hSCARB2-KI mice, producing long-lasting cross-neutralizing antibodies against two EV-A71 wild strains. Pre-exposure to the 2A-125A mutant substantially protected against the EV-A71 Isehara wild-type strain, causing minor pathologies, significantly reducing muscle and lung inflammation, and preventing neurological damage, with reduced viral loads in vivo. Pre-exposure also distinctly suppressed the expression of pro-inflammatory cytokines, correlating to the severity of clinical symptoms. Collectively, the EV-A71 2A-125A mutant was attenuated and could generate a robust and protective immune response, suggesting its potential as a vaccine candidate and global solution for specific enterovirus vaccine development.


Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Enterovirus Humano A , Infecções por Enterovirus , Vacinas Atenuadas , Carga Viral , Vacinas Virais , Animais , Enterovirus Humano A/imunologia , Enterovirus Humano A/genética , Infecções por Enterovirus/prevenção & controle , Infecções por Enterovirus/imunologia , Infecções por Enterovirus/virologia , Camundongos , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Vacinas Virais/imunologia , Vacinas Virais/genética , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/genética , Humanos , Desenvolvimento de Vacinas , Feminino , Mutação , Citocinas
20.
Environ Monit Assess ; 196(7): 675, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951302

RESUMO

Vegetation is an important link between land, atmosphere, and water, making its changes of great significance. However, existing research has predominantly focused on long-term vegetation changes, neglecting the intra-annual variations of vegetation. Hence, this study is based on the Enhanced Vegetation Index (EVI) data from 2000 to 2022, with a time step of 16 days, to analyze the intra-annual patterns of vegetation changes in China. The average intra-annual EVI values for each municipal-level administrative region were calculated, and the time-series k-means clustering algorithm was employed to divide these regions, exploring the spatial variations in China's intra-annual vegetation changes. Finally, the ridge regression and random forest methods were utilized to assess the drivers of intra-annual vegetation changes. The results showed that: (1) China's vegetation status exhibits a notable intra-annual variation pattern of "high in summer and low in winter," and the changes are more pronounced in the northern regions than in the southern regions; (2) the intra-annual vegetation changes exhibit remarkable regional disparities, and China can be optimally clustered into four distinct clusters, which align well with China's temperature and precipitation zones; and (3) the intra-annual vegetation changes demonstrate significant correlations with meteorological factors such as dew point temperature, precipitation, maximum temperature, and sea-level pressure. In conclusion, our study reveals the characteristics, spatial patterns and driving forces of intra-annual vegetation changes in China, which contribute to explaining ecosystem response mechanisms, providing valuable insights for ecological research and the formulation of ecological conservation and management strategies.


Assuntos
Monitoramento Ambiental , Tecnologia de Sensoriamento Remoto , China , Estações do Ano , Plantas , Análise por Conglomerados , Ecossistema
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