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1.
Int J Biol Macromol ; : 133908, 2024 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-39019362

RESUMO

Developing bifunctional innovative food packaging for maintaining and monitoring food freshness is crucial for food safety. Here, we prepared tannic acid cinnamaldehyde nanoemulsions through self-assembly and ionic cross-linking between the natural emulsifiers tannic acid and cinnamaldehyde, and were incorporated into chitosan as a protective outer layer. Sodium alginate anchored with alizarin was employed as the sensing inner layer. A pH-sensitive bilayer film integrating real-time monitoring and maintenance of food fresh food freshness was designed using layer-by-layer assembly (LBL) technology. The prepared bilayer film exhibited 100 % UV protection, >99 % antimicrobial effect, and 94.86 % and 97.91 % clearance rates for DPPH and ABTS free radicals, respectively. In addition, the bilayer film exhibited high biosafety and sensitive, reversible, and rapid response to pH/NH3. Shrimp preservation experiments showed that the smart bilayer film could effectively slow down the growth of microorganisms on the surface of shrimp, extend the freshness period of shrimp, and could monitor the freshness of shrimp in real-time through color changes. In conclusion, the prepared SL-CCT bilayer film has excellent potential for food preservation and freshness monitoring, providing a new perspective for design and development of multifunctional smart food packaging films.

2.
Int J Biol Macromol ; 276(Pt 1): 133807, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996887

RESUMO

To fulfill the current need for intelligent active food packaging. This study incorporated the curcumin inclusion complexes (CUR-CD) into chitosan/polyvinyl alcohol polymer to develop a new intelligent active film. The structures of films were analyzed by Fourier-transform infrared (FT-IR), scanning electron microscope (SEM), and so on. The CP-Cur150 film displays exceptional mechanical properties, water vapor barrier, and UV blocking capabilities as demonstrated by physical analysis. The CP-Cur150 film exhibited free radical scavenging rates on 2,2-diazo-di-3-ethylbenzothiazolin-6-sulfonic (ABTS) (98 %) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (87 %). Additionally, it showed inhibitory effects on Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), reducing live colony counts by approximately 2.7 and 1.3 Log10 CFU/mL, respectively. The films were used to monitor the shrimp's freshness in real time. With the spoilage of shrimp, the film exhibited clear color fluctuations, from light yellow to red. In addition, the evaluation of the impact of films on pork pH, total volatile basic nitrogen, and total bacterial counts demonstrated that the CP-Cur150 film displayed the most significant effectiveness in preserving freshness, thereby extending the shelf life of pork.

3.
Bioorg Chem ; 150: 107596, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38941699

RESUMO

A novel series of 1,8-naphthalimide piperazinamide based benzenesulfonamides derivatives were designed and synthesized as carbonic anhydrase IX (CA IX) inhibitors and ferroptosis inducers for the treatment of triple-negative breast cancer (TNBC). The representative compound 9o exhibited more potent inhibitory activity and selective against CA IX over off-target CA II, compared with positive control SLC-0111. Molecular docking study was also performed to gain insights into the binding interactions of 9o in the binding pocket of CAIX. Moreover, compound 9o exhibited superior antitumor activities against breast cancer cells under hypoxia than that of normoxia conditions. Mechanism studies revealed that compound 9o could act as DNA intercalator and effectively suppressed cell migration, arrested the cell cycle at G1/S phase and induced apoptosis in MDA-MB-231 cells, while inducing ferroptosis accompanied by the dissipation of MMP and the elevation intracellular levels of ROS. Notably, in vivo studies demonstrated that 9o effectively inhibited tumor growth and metastasis in a highly metastatic murine breast cancer 4 T1 xenograft model. Taken together, this study suggests that compound 9o represents a potent and selective CA IX inhibitor and ferroptosis inducer for the treatment of TNBC.


Assuntos
Antineoplásicos , Benzenossulfonamidas , Anidrase Carbônica IX , Inibidores da Anidrase Carbônica , Proliferação de Células , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Ferroptose , Naftalimidas , Sulfonamidas , Neoplasias de Mama Triplo Negativas , Humanos , Anidrase Carbônica IX/antagonistas & inibidores , Anidrase Carbônica IX/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Inibidores da Anidrase Carbônica/farmacologia , Inibidores da Anidrase Carbônica/química , Inibidores da Anidrase Carbônica/síntese química , Ferroptose/efeitos dos fármacos , Sulfonamidas/farmacologia , Sulfonamidas/química , Sulfonamidas/síntese química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Animais , Estrutura Molecular , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Camundongos , Feminino , Naftalimidas/química , Naftalimidas/farmacologia , Naftalimidas/síntese química , Descoberta de Drogas , Apoptose/efeitos dos fármacos , Simulação de Acoplamento Molecular , Piperazinas/farmacologia , Piperazinas/química , Piperazinas/síntese química , Linhagem Celular Tumoral , Antígenos de Neoplasias
4.
Planta ; 260(1): 23, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38850310

RESUMO

MAIN CONCLUSION: In this study, we assembled the first complete mitochondrial genome of Setaria italica and confirmed the multi-branched architecture. The foxtail millet (Setaria italica) holds significant agricultural importance, particularly in arid and semi-arid regions. It plays a pivotal role in diversifying dietary patterns and shaping planting strategies. Although the chloroplast genome of S. italica has been elucidated in recent studies, the complete mitochondrial genome remains largely unexplored. In this study, we employed PacBio HiFi sequencing platforms to sequence and assemble the complete mitochondrial genome. The mitochondrial genome spans a total length of 446,614 base pairs and harbors a comprehensive set of genetic elements, including 33 unique protein-coding genes (PCGs), encompassing 24 unique mitochondrial core genes and 9 variable genes, along with 20 transfer RNA (tRNA) genes and 3 ribosomal RNA (rRNA) genes. Our analysis of mitochondrial PCGs revealed a pronounced codon usage preference. For instance, the termination codon exhibits a marked preference for UAA, while alanine (Ala) exhibits a preference for GCU, and glutamine (Gln) favors CAA. Notably, the maximum Relative Synonymous Codon Usage (RSCU) values for cysteine (Cys) and phenylalanine (Phe) are both below 1.2, indicating a lack of strong codon usage preference for these amino acids. Phylogenetic analyses consistently place S. italica in close evolutionary proximity to Chrysopogon zizanioides, relative to other Panicoideae plants. Collinearity analysis showed that a total of 39 fragments were identified to display homology with both the mitochondrial and chloroplast genomes. A total of 417 potential RNA-editing sites were discovered across the 33 mitochondrial PCGs. Notably, all these editing events involved the conversion of cytosine (C) to uracil (U). Through the employment of PCR validation coupled with Sanger sequencing for the anticipated editing sites of these codons, RNA-editing events were conclusively identified at two specific loci: nad4L-2 and atp6-1030. The results of this study provide a pivotal foundation for advanced genomic breeding research in foxtail millet. Furthermore, they impart essential insights that will be instrumental for forthcoming investigations into the evolutionary and molecular dynamics of Panicoideae species.


Assuntos
Genoma Mitocondrial , Setaria (Planta) , Setaria (Planta)/genética , Genoma Mitocondrial/genética , Filogenia , RNA de Transferência/genética , Genoma de Planta/genética , Uso do Códon , RNA Ribossômico/genética , Códon/genética
5.
Adv Sci (Weinh) ; 11(28): e2400790, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38741381

RESUMO

Heterotopic ossification (HO), the pathological formation of bone within soft tissues such as tendon and muscle, is a notable complication resulting from severe injury. While soft tissue injury is necessary for HO development, the specific molecular pathology responsible for trauma-induced HO remains a mystery. The previous study detected abnormal autophagy function in the early stages of tendon HO. Nevertheless, it remains to be determined whether autophagy governs the process of HO generation. Here, trauma-induced tendon HO model is used to investigate the relationship between autophagy and tendon calcification. In the early stages of tenotomy, it is observed that autophagic flux is significantly impaired and that blocking autophagic flux promoted the development of more rampant calcification. Moreover, Gt(ROSA)26sor transgenic mouse model experiments disclosed lysosomal acid dysfunction as chief reason behind impaired autophagic flux. Stimulating V-ATPase activity reinstated both lysosomal acid functioning and autophagic flux, thereby reversing tendon HO. This present study demonstrates that autophagy-lysosomal dysfunction triggers HO in the stages of tendon injury, with potential therapeutic targeting implications for HO.


Assuntos
Autofagia , Modelos Animais de Doenças , Lisossomos , Camundongos Transgênicos , Ossificação Heterotópica , Tendões , Ossificação Heterotópica/metabolismo , Ossificação Heterotópica/genética , Ossificação Heterotópica/patologia , Animais , Autofagia/fisiologia , Camundongos , Lisossomos/metabolismo , Tendões/metabolismo , Tendões/patologia , Tendões/fisiopatologia , Tenotomia/métodos , Masculino , Traumatismos dos Tendões/fisiopatologia , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/patologia , Camundongos Endogâmicos C57BL
6.
RSC Med Chem ; 15(5): 1640-1651, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38784471

RESUMO

A set of biotin-polyethylene glycol (PEG)-naphthalimide derivatives 4a-4h with dual targeting of ferroptosis and DNA were designed and optimized using docking simulation as antitumor agents. Docking simulation optimization results indicated that biotin-PEG4-piperazine-1,8-naphthalimide 4d should be the best candidate among these designed compounds 4a-4h, and therefore, we synthesized and evaluated it as a novel antitumor agent. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and MGC-803 and U251 xenograft models identified 4d as a good candidate antitumor agent with potent efficacy and safety profiles, compared with amonafide and temozolomide. The findings of the docking simulations, fluorescence intercalator displacement (FID), western blot, comet, 5-ethynyl-2'-deoxyuridine (EdU), flow cytometry, transmission electron microscopy, and BODIPY-581/591-C11, FerroOrange, and dihydroethidium (DHE) fluorescent probe assays revealed that 4d could induce DNA damage, affect DNA synthesis, and cause cell cycle arrest in the S phase in MGC-803 cells. Also, it could induce lipid peroxidation and thus lead to ferroptosis in MGC-803 cells, indicating that it mainly exerted antitumor effects through dual targeting of ferroptosis and DNA. These results suggested that it was feasible to design, optimize using docking simulation, and evaluate the potency and safety of biotin-PEG-1,8-naphthalimide as a antitumor agent with dual targeting of ferroptosis and DNA, based on a multi-target drug strategy.

7.
Ecotoxicol Environ Saf ; 274: 116191, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38460408

RESUMO

The reproduction toxicity of pubertal exposure to Microcystin-LR (MC-LR) and the underlying mechanism needs to be further investigated. In the current study, pubertal male ICR mice were intraperitoneally injected with 2 µg/kg MC-LR for four weeks. Pubertal exposure to MC-LR decreased epididymal sperm concentration and blocked spermatogonia proliferation. In-vitro studies found MC-LR inhibited cell proliferation of GC-1 cells and arrested cell cycle in G2/M phase. Mechanistically, MC-LR exposure evoked excessive reactive oxygen species (ROS) and induced DNA double-strand break in GC-1 cells. Besides, MC-LR inhibited DNA repair by reducing PolyADP-ribosylation (PARylation) activity of PARP1. Further study found MC-LR caused proteasomal degradation of SIRT6, a monoADP-ribosylation enzyme which is essential for PARP1 PARylation activity, due to destruction of SIRT6-USP10 interaction. Additionally, MG132 pretreatment alleviated MC-LR-induced SIRT6 degradation and promoted DNA repair, leading to the restoration of cell proliferation inhibition. Correspondingly, N-Acetylcysteine (NAC) pre-treatment mitigated the disturbed SIRT6-USP10 interaction and SIRT6 degradation, causing recovered DNA repair and subsequently restoration of cell proliferation inhibition in MC-LR treated GC-1 cells. Together, pubertal exposure to MC-LR induced spermatogonia cell cycle arrest and sperm count reduction by oxidative DNA damage and simultaneous SIRT6-mediated DNA repair failing. This study reports the effect of pubertal exposure to MC-LR on spermatogenesis and complex mechanism how MC-LR induces spermatogonia cell proliferation inhibition.


Assuntos
Toxinas Marinhas , Microcistinas , Sirtuínas , Espermatogônias , Animais , Masculino , Camundongos , Apoptose , Proliferação de Células , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Reparo do DNA , Toxinas Marinhas/metabolismo , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos ICR , Microcistinas/metabolismo , Microcistinas/toxicidade , Sêmen , Sirtuínas/efeitos dos fármacos , Sirtuínas/metabolismo , Espermatogônias/efeitos dos fármacos , Espermatogônias/metabolismo
8.
Curr Radiopharm ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532606

RESUMO

BACKGROUND: Head and Neck Squamous Cell Carcinoma (HNSCC) is a malignant tumor with a high degree of malignancy, invasiveness, and metastasis rate. Radiotherapy, as an important adjuvant therapy for HNSCC, can reduce the postoperative recurrence rate and improve the survival rate. Identifying the genes related to HNSCC radiotherapy resistance (HNSCC-RR) is helpful in the search for potential therapeutic targets. However, identifying radiotherapy resistance-related genes from tens of thousands of genes is a challenging task. While interactions between genes are important for elucidating complex biological processes, the large number of genes makes the computation of gene interactions infeasible. METHODS: We propose a gene selection algorithm, RGIE, which is based on ReliefF, Gene Network Inference with Ensemble of Trees (GENIE3) and Feature Elimination. ReliefF was used to select a feature subset that is discriminative for HNSCC-RR, GENIE3 constructed a gene regulatory network based on this subset to analyze the regulatory relationship among genes, and feature elimination was used to remove redundant and noisy features. RESULTS: Nine genes (SPAG1, FIGN, NUBPL, CHMP5, TCF7L2, COQ10B, BSDC1, ZFPM1, GRPEL1) were identified and used to identify HNSCC-RR, which achieved performances of 0.9730, 0.9679, 0.9767, and 0.9885 in terms of accuracy, precision, recall, and AUC, respectively. Finally, qRT-PCR validated the differential expression of the nine signature genes in cell lines (SCC9, SCC9-RR). CONCLUSION: RGIE is effective in screening genes related to HNSCC-RR. This approach may help guide clinical treatment modalities for patients and develop potential treatments.

9.
PeerJ Comput Sci ; 10: e1880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435594

RESUMO

This article presents a hybrid recommender framework for smart medical systems by introducing two methods to improve service level evaluations and doctor recommendations for patients. The first method uses big data techniques and deep learning algorithms to develop a registration review system in medical institutions. This system outperforms conventional evaluation methods, thus achieving higher accuracy. The second method implements the term frequency and inverse document frequency (TF-IDF) algorithm to construct a model based on the patient's symptom vector space, incorporating score weighting, modified cosine similarity, and K-means clustering. Then, the alternating least squares (ALS) matrix decomposition and user collaborative filtering algorithm are applied to calculate patients' predicted scores for doctors and recommend top-performing doctors. Experimental results show significant improvements in metrics called precision and recall rates compared to conventional methods, making the proposed approach a practical solution for department triage and doctor recommendation in medical appointment platforms.

10.
Cell Death Dis ; 15(2): 139, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355684

RESUMO

Radioresistance imposes a great challenge in reducing tumor recurrence and improving the clinical prognosis of individuals having oral squamous cell carcinoma (OSCC). OSCC harbors a subpopulation of CD44(+) cells that exhibit cancer stem-like cell (CSC) characteristics are involved in malignant tumor phenotype and radioresistance. Nevertheless, the underlying molecular mechanisms in CD44( + )-OSCC remain unclear. The current investigation demonstrated that methyltransferase-like 3 (METTL3) is highly expressed in CD44(+) cells and promotes CSCs phenotype. Using RNA-sequencing analysis, we further showed that Spalt-like transcription factor 4 (SALL4) is involved in the maintenance of CSCs properties. Furthermore, the overexpression of SALL4 in CD44( + )-OSCC cells caused radioresistance in vitro and in vivo. In contrast, silencing SALL4 sensitized OSCC cells to radiation therapy (RT). Mechanistically, we illustrated that SALL4 is a direct downstream transcriptional regulation target of METTL3, the transcription activation of SALL4 promotes the nuclear transport of ß-catenin and the expression of downstream target genes after radiation therapy, there by activates the Wnt/ß-catenin pathway, effectively enhancing the CSCs phenotype and causing radioresistance. Herein, this study indicates that the METTL3/SALL4 axis promotes the CSCs phenotype and resistance to radiation in OSCC via the Wnt/ß-catenin signaling pathway, and provides a potential therapeutic target to eliminate radioresistant OSCC.


Assuntos
Adenina/análogos & derivados , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/radioterapia , Neoplasias Bucais/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Linhagem Celular Tumoral , Recidiva Local de Neoplasia/patologia , Neoplasias de Cabeça e Pescoço/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Proliferação de Células/genética , Células-Tronco Neoplásicas/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
11.
Appl Spectrosc ; 78(2): 217-226, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38190986

RESUMO

The generation and presence of excessive hypochlorous acid derivative ionic form (ClO-) could cause various diseases, such as arteriosclerosis, DNA damage, and cardiovascular illness. It is a critical need to develop a highly sensitive sensor for reliable detection of ClO- in cells and water-soluble systems. In this work, a hydroxyl group has been introduced into the compound 2-amino-3-(((E)-4-(2-(2-(2-hydroxyethoxy)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)benzylidene)amino)maleonitrile (NDC) to increase its solubility in water, at the same time, the hydrazone unit was designed as a specific recognition group for the "off-on" fluorescence probe of ClO-. The probe NDC presents high selectivity, sensitivity, anti-interference, and low detection limit (67 nM) for ClO-. The recognition mechanism that ClO- breaks the C=N bond and forms the fluorescent compound 4-(2-(2-(2-hydroxyethoxy)ethyl)-1,3-dioxo-2,3-dihydro-1H-benzo[de]isoquinolin-6-yl)benzaldehyde (ND-3) has been confirmed by time-of-flight mass spectrometry. The probe NDC presents a good performance in the actual test of water samples and can be designed as the test papers for the quick and convenient detection of ClO- range from 0 to 1 µM. Moreover, the practical application was demonstrated by the successful imaging of endogenous and exogenous ClO- in HeLa cells. Our fluorescent biomass-based platform opens vast possibilities for repeatability, sensitivity, and selectivity detection of ClO- in cells and water-soluble systems.


Assuntos
Imagem Óptica , Água , Humanos , Células HeLa , Biomassa , Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Ácido Hipocloroso/química
12.
ISA Trans ; 145: 399-411, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38142174

RESUMO

This paper proposes a method for high-performance motion control of the dual-valve hydraulic system subject to parameter and model uncertainties, unknown proportional valve dead-zone, and servo valve fault. By constructing a detailed dual-valve fault system model (DFSM), a disturbance observer-based adaptive robust fault-tolerant controller is proposed via the backstepping method. This controller integrates a model-based fault detection algorithm for real-time fault monitoring and subsequent controller reconfiguration. Additionally, the DFSM-based adaptive robust control (ARC) technique is applied to handle the unknown dead-zone problem and other nonlinearities, ensuring precise control. Once the servo valve fault occurs, a nonlinear observer estimates the fault and collaborates with the ARC to establish a reconfigured controller, thereby maintaining motion control. The effectiveness of the proposed method has been experimentally verified.

13.
Int J Psychiatry Med ; : 912174231219041, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38047438

RESUMO

OBJECTIVE: This survey aimed to explore the relationships between burnout, moral injury, and suicidal/self-harm ideation among Chinese health professionals to provide a reference for protecting their mental health. METHOD: Health professionals were surveyed online using the Maslach Burnout Inventory-Human Services Survey for Medical Personnel, Patient Health Questionnaire-9, and the Moral Injury Symptoms Scale-Health Professional. RESULTS: In the analysis, 6146 eligible respondents were included in the study. The average participant age was 34.9 ± 8.5 years, and suicidal/self-harm ideation was detected in 2338 participants (38.0%). The prevalence of suicidal/self-harm ideation among those with severe burnout in the dimensions of emotional exhaustion, depersonalisation, and decreased personal accomplishment was significantly higher than those with mild burnout. The prevalence of suicidal/self-harm ideation among those with significant moral injury symptoms was higher than those without moral injury. Unconditional logistic regression analysis showed that those with moderate or severe emotional exhaustion, moderate or severe reduced sense of professional accomplishment and moderate or severe depersonalisation had increased risks of suicidal/self-harm ideation. CONCLUSIONS: Structural equation modelling demonstrated that burnout significantly mediated the relationship between moral injury and suicidal/self-harm ideation. The proportion of mediation (PM) by burnout was 43.0%. Burnout and moral injury were potential predictors of suicidal/self-harm ideation among health professionals. Both moral injury and burnout had positive and direct effects on suicidal/self-harm ideation, and burnout was a mediator in this relationship among Chinese health professionals. Therefore, to alleviate the moral injury and subsequent burnout of healthcare workers and enhance their mental qualities, active interventions should be developed in the future.

14.
J Med Virol ; 95(11): e29182, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37909805

RESUMO

INTRODUCTION: Human adenovirus 7 (HAdV-7) is an important viral pathogen of severe pneumonia in children and a serious threat to health. METHODS: A cohort of 45 pediatric patients diagnosed with HAdV-7-associated severe pneumonia and admitted to the Pediatric Intensive Care Unit at the Children's Hospital of Chongqing Medical University from May 2018 to January 2020 were included. Risk factors of death were analyzed by the Cox proportional risk mode with Clinical data, serum, and nasopharyngeal aspirate adenovirus load, Genome analysis, Olink proteomics, and cytokine profile between dead and surviving patients were also analyzed. RESULTS: A total of 45 children with a median age of 12.0 months (interquartile range [IQR]: 6.5, 22.0) were included (female 14), including 14 (31.1%) who died. High serum viral load was an independent risk factor for mortality (hazard ratio [HR] = 2.16, 95% confidence interval [CI], 1.04-4.49, p = 0.039). BTB and CNC homology 1 (BACH1), interleukin-5 (IL-5), and IL-9 levels were significantly correlated with serum viral load (p = 0.0400, 0.0499, and 0.0290; r = 0.4663, 0.3339, and -0.3700, respectively), with significant differences between the dead and survival groups (p = 0.021, 0.001, and 0.021). CONCLUSIONS: Severe cytokine storm-associated high serum viral load after HAdV-7 infection may be the main mechanism responsible for poor prognosis in children.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções Comunitárias Adquiridas , Pneumonia Viral , Pneumonia , Criança , Humanos , Feminino , Lactente , Adenovírus Humanos/genética , Proteômica , Fatores de Risco
15.
Artigo em Inglês | MEDLINE | ID: mdl-37917890

RESUMO

Background: Aortic dissection is a critical cardiovascular disease, with Stanford Type A aortic dissection (TAAD) posing significant concern due to its high mortality rate, especially in obese patients. Acute respiratory distress syndrome (ARDS) is among the most common postoperative complications. Therefore, preventing ARDS is critically important for TAAD patients. Objective: This study aims to investigate the impact of enhanced prone mechanical ventilation on oxygenation levels, early extubation rates, and length of stay in the intensive care unit (ICU) among obese TAAD patients. The goal is to assess its potential to improve patient clinical outcomes and provide a scientific foundation for clinical practice. Case Presentation: Following evaluation by the attending physician, two hypoxemic patients underwent prone mechanical ventilation on postoperative day 3 for 12 hours daily, consecutively for 3-5 days. Patients' oxygenation significantly improved, and mechanical ventilation was discontinued after respiratory exercises. Successful removal of oral intubation was achieved, followed by individualized nursing care. No complications arose during intensive care, and both patients were transferred out of the ICU and subsequently discharged. Conclusions: The early implementation of modified prone position ventilation effectively mitigates postoperative hypoxemia in obese patients with aortic dissection. It increases the rate of early postoperative oral extubation and reduces the length of stay in the ICU.

16.
Molecules ; 28(16)2023 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-37630387

RESUMO

Indoleamine-2,3-dioxygenase 1 (IDO1) and signal transducer and activator of transcription 3 (STAT3) have emerged as significant targets in the tumor microenvironment for cancer therapy. In this study, we synthesized three novel 2-amino-1,4-naphthoquinone amide-oxime derivatives and identified them as dual inhibitors of IDO1 and STAT3. The representative compound NK3 demonstrated effective binding to IDO1 and exhibited good inhibitory activity (hIDO1 IC50 = 0.06 µM), leading to its selection for further investigation. The direct interactions between compound NK3 and IDO1 and STAT3 proteins were confirmed through surface plasmon resonance analysis. A molecular docking study of compound NK3 revealed key interactions between NK3 and IDO1, with the naphthoquinone-oxime moiety coordinating with the heme iron. In the in vitro anticancer assay, compound NK3 displayed potent antitumor activity against selected cancer cell lines and effectively suppressed nuclear translocation of STAT3. Moreover, in vivo assays conducted on CT26 tumor-bearing Balb/c mice and an athymic HepG2 xenograft model revealed that compound NK3 exhibited potent antitumor activity with low toxicity relative to 1-methyl-L-tryptophan (1-MT) and doxorubicin (DOX). Overall, these findings provided evidence that the dual inhibitors of IDO1 and STAT3 may offer a promising avenue for the development of highly effective drug candidates for cancer therapy.


Assuntos
Naftoquinonas , Fator de Transcrição STAT3 , Humanos , Animais , Camundongos , Simulação de Acoplamento Molecular , Estudos Prospectivos , Amidas/farmacologia , Camundongos Endogâmicos BALB C , Naftoquinonas/farmacologia , Oximas/farmacologia
17.
Nat Commun ; 14(1): 4334, 2023 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474573

RESUMO

The Asteraceae (daisy family) is one of the largest families of plants. The genetic basis for its high biodiversity and excellent adaptability has not been elucidated. Here, we compare the genomes of 29 terrestrial plant species, including two de novo chromosome-scale genome assemblies for stem lettuce, a member of Asteraceae, and Scaevola taccada, a member of Goodeniaceae that is one of the closest outgroups of Asteraceae. We show that Asteraceae originated ~80 million years ago and experienced repeated paleopolyploidization. PII, the universal regulator of nitrogen-carbon (N-C) assimilation present in almost all domains of life, has conspicuously lost across Asteraceae. Meanwhile, Asteraceae has stepwise upgraded the N-C balance system via paleopolyploidization and tandem duplications of key metabolic genes, resulting in enhanced nitrogen uptake and fatty acid biosynthesis. In addition to suggesting a molecular basis for their ecological success, the unique N-C balance system reported for Asteraceae offers a potential crop improvement strategy.


Assuntos
Asteraceae , Asteraceae/genética , Filogenia , Genômica/métodos , Lactuca/genética , Biodiversidade
18.
Plant Cell ; 35(10): 3757-3781, 2023 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-37437118

RESUMO

The mechanical properties of guard cells have major effects on stomatal functioning. Reinforced stiffness in the stomatal polar regions was recently proposed to play an important role in stomatal function, but the underlying molecular mechanisms remain elusive. Here, we used genetic and biochemical approaches in poplar (Populus spp.) to show that the transcription factor MYB156 controls pectic homogalacturonan-based polar stiffening through the downregulation of the gene encoding pectin methylesterase 6 (PME6). Loss of MYB156 increased the polar stiffness of stomata, thereby enhancing stomatal dynamics and response speed to various stimuli. In contrast, overexpression of MYB156 resulted in decreased polar stiffness and impaired stomatal dynamics, accompanied by smaller leaves. Polar stiffening functions in guard cell dynamics in response to changing environmental conditions by maintaining normal stomatal morphology during stomatal movement. Our study revealed the structure-function relationship of the cell wall of guard cells in stomatal dynamics, providing an important means for improving the stomatal performance and drought tolerance of plants.


Assuntos
Estômatos de Plantas , Populus , Estômatos de Plantas/fisiologia , Fatores de Transcrição/genética , Populus/genética , Regulação da Expressão Gênica de Plantas/genética , Parede Celular/fisiologia
19.
Immunotherapy ; 15(12): 897-903, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37337737

RESUMO

Herein, we report a case of an elderly male patient who underwent extended radical resection of cardiac carcinoma after regular chemotherapy combined with sintilimab (PD-1 monoclonal antibody) immunotherapy complicated with severe pneumonitis postoperatively. We performed several treatments for aspiration pneumonitis; however, the patient's pulmonary infection and oxygenation were not efficiently improved. The multidisciplinary team considered it an immune checkpoint inhibitor-associated pneumonitis after diagnosis and treatment and then modified the treatment regimen. The pulmonary inflammation was effectively controlled with improved oxygenation; the patient was gradually weaned from the ventilator and finally discharged. The possibility of immune checkpoint inhibitor-associated pneumonitis should be fully considered particularly for patients with a history of immunosuppressive therapy with clinical symptoms of severe pneumonitis.


Pneumonia is well known. Immune pneumonia may be a new problem. It occurs in 2­5% of patients with immune therapy. It is a bad reaction with low incidence. If this disease is not treated in time, it will cause a relatively terrible result. The fatality rate can reach 12.8­22.7%. The most severe cases can be life threatening. At present, the reason for immune pneumonia is not clear. Some experts believe that it is related to immune change. Dyspnea, cough, fever and chest pain are symptoms of this disease. Although the incidence of immune pneumonia is very low, it should be noted. If you are on immunotherapy, consult your doctor when you feel unwell.


Assuntos
Neoplasias Pulmonares , Pneumonia , Humanos , Masculino , Idoso , Inibidores de Checkpoint Imunológico/efeitos adversos , Pneumonia/diagnóstico , Pneumonia/etiologia , Pulmão/patologia , Anticorpos Monoclonais/efeitos adversos , Imunoterapia/efeitos adversos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/tratamento farmacológico
20.
Nat Genet ; 55(7): 1232-1242, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37291196

RESUMO

Setaria italica (foxtail millet), a founder crop of East Asian agriculture, is a model plant for C4 photosynthesis and developing approaches to adaptive breeding across multiple climates. Here we established the Setaria pan-genome by assembling 110 representative genomes from a worldwide collection. The pan-genome is composed of 73,528 gene families, of which 23.8%, 42.9%, 29.4% and 3.9% are core, soft core, dispensable and private genes, respectively; 202,884 nonredundant structural variants were also detected. The characterization of pan-genomic variants suggests their importance during foxtail millet domestication and improvement, as exemplified by the identification of the yield gene SiGW3, where a 366-bp presence/absence promoter variant accompanies gene expression variation. We developed a graph-based genome and performed large-scale genetic studies for 68 traits across 13 environments, identifying potential genes for millet improvement at different geographic sites. These can be used in marker-assisted breeding, genomic selection and genome editing to accelerate crop improvement under different climatic conditions.


Assuntos
Setaria (Planta) , Mapeamento Cromossômico , Setaria (Planta)/genética , Setaria (Planta)/metabolismo , Melhoramento Vegetal , Fenótipo , Locos de Características Quantitativas , Genoma de Planta/genética , Filogenia , Proteínas de Plantas/genética
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