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1.
Abdom Radiol (NY) ; 2024 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-39302444

RESUMO

OBJECTIVE: To construct a nomogram model based on multi-slice spiral CT imaging features to predict and differentiate between duodenal gastrointestinal stromal tumors (GISTs) and pancreatic head neuroendocrine tumors (NENs), providing imaging evidence for clinical treatment decisions. METHODS: A retrospective collection of clinical information, pathological results, and imaging data was conducted on 115 cases of duodenal GISTs and 76 cases of pancreatic head NENs confirmed by surgical pathology at Zhongshan Hospital Fudan University from November 2013 to November 2022. Comparative analysis was performed on the tumor's maximum diameter, shortest diameter, long diameter/short diameter ratio, tumor morphology, tumor border, central position of the lesion, lesion long-axis direction, the relationship between tumor and common bile duct (CBD), duodenal side ulceration of the lesion, calcification, cystic and solid proportion within the tumor, thickened feeding arteries, tumor neovascularization, distant metastasis, and CT values during plain and enhanced scans in arterial and venous phases. Statistical analysis was conducted using t-tests, Mann-Whitney U tests, and χ2 tests. Univariate and multivariate logistic regression analyses were used to identify independent predictors for differentiating duodenal GISTs from pancreatic head NENs. Based on these independent predictors, a nomogram model was constructed, and the receiver operating characteristic (ROC) curve was used to evaluate the diagnostic performance of the model. The nomogram was validated using a calibration curve, and decision curve analysis was applied to assess the clinical application value of the nomogram. RESULTS: There were significant differences in the duodenal GISTs group and the pancreatic head NENs group in terms of longest diameter (P < 0.001), shortest diameter (P < 0.001), plain CT value (P < 0.001), arterial phase CT value (P < 0.001), venous phase CT value (P = 0.002), lesion long-axis direction (P < 0.001), central position of the lesion (P < 0.001), the relationship between tumor and CBD(< 0.001), border (P = 0.004), calcification (P = 0.017), and distant metastasis (P = 0.018). Multivariate logistic regression analysis identified uncertain location (OR 0.040, 95% CI 0.003-0.549), near the duodenum (OR 0, 95% CI 0-0.009), with the lesion long-axis direction along the pancreas as a reference, along the duodenum (OR 0.106, 95% CI 0.010-1.156) or no significant difference (OR 4.946, 95% CI 0.453-54.017), and the relationship between tumor and CBD (OR 0.013, 95% CI 0.001-0.180), shortest diameter (OR 0.705, 95% CI 0.546-0.909), and calcification (OR 18.638, 95% CI 1.316-263.878) as independent risk factors for differentiating between duodenal GISTs and pancreatic head NENs (all P values < 0.05). The combined diagnostic model's AUC values based on central position of the lesion, calcification, lesion long axis orientation, the relationship between tumor and CBD, shortest diameter, and the joint diagnostic model were 0.937 (0.902-0.972), 0.700(0.624-0.776), 0.717(0.631-0.802), 0.559 (0.473-0.644), 0.680 (0.603-0.758), and 0.991(0.982-0.999), respectively, with a sensitivity of 97.3% and a specificity of 93.0% for the joint diagnostic model. The nomogram model's AUC value was 0.985(0.973-0.996), with a sensitivity and specificity of 94.7% and 93.9%, respectively. The calibration curve indicated good agreement between predicted and actual risks. Decision curve analysis verified the clinical application value of the nomogram. CONCLUSION: The nomogram model based on CT imaging features effectively differentiates between duodenal GISTs and pancreatic head NENs, aiding in more precise clinical treatment decisions.

2.
Proc Natl Acad Sci U S A ; 121(39): e2403222121, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39302967

RESUMO

Algae mostly occur either as unicellular (microalgae) or multicellular (macroalgae) species, both being uninucleate. There are important exceptions, however, as some unicellular algae are multinucleate and macroscopic, some of which inhabit tropical seas and contribute to biocalcification and coral reef robustness. The evolutionary mechanisms and ecological significance of multinucleation and associated traits (e.g., rapid wound healing) are poorly understood. Here, we report the genome of Halimeda opuntia, a giant multinucleate unicellular chlorophyte characterized by interutricular calcification. We achieve a high-quality genome assembly that shows segregation into four subgenomes, with evidence for polyploidization concomitant with historical sea level and climate changes. We further find myosin VIII missing in H. opuntia and three other unicellular multinucleate chlorophytes, suggesting a potential mechanism that may underpin multinucleation. Genome analysis provides clues about how the unicellular alga could survive fragmentation and regenerate, as well as potential signatures for extracellular calcification and the coupling of calcification with photosynthesis. In addition, proteomic alkalinity shifts were found to potentially confer plasticity of H. opuntia to ocean acidification (OA). Our study provides crucial genetic information necessary for understanding multinucleation, cell regeneration, plasticity to OA, and different modes of calcification in algae and other organisms, which has important implications in reef conservation and bioengineering.


Assuntos
Calcificação Fisiológica , Calcificação Fisiológica/genética , Clorófitas/genética , Clorófitas/metabolismo , Filogenia , Genoma de Planta , Fotossíntese/genética
3.
Drug Des Devel Ther ; 18: 4017-4027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39258273

RESUMO

Objective: Ciprofol is a novel anesthetic agent, its efficacy and safety had been verified and its clinical implementation has been expanded. However, the knowledge about ciprofol in children is meager. The aim of study is to evaluate the safety and effectiveness of ciprofol in general anesthesia in children undergoing adenoidectomy and adenotonsillectomy, compared with propofol. Materials: We retrospectively analyzed data of children who underwent adenoidectomy or adenotonsillectomy with general anesthesia from June to August 2023 to evaluate the safety and effectiveness of ciprofol. The primary outcomes included hemodynamic changes during induction and postoperative complications in post-anesthesia care unit. The secondary outcomes were extubation time, pediatric anesthesia emergence delirium (PAED) score. Meanwhile, subgroup analysis was performed based on age. Results: 301 children met the inclusion criteria, 157 received ciprofol induction and 144 received propofol. Patient demographics and operation-related information were similar in the two groups. However, the dosage of dexmedetomidine in the propofol group was significantly higher than that of the ciprofol group (p=0.001). The trends of hemodynamic shift during induction and intubation were the same in the two groups. The PAED scores on post-extubation 10min and 20min were significantly reduced in the ciprofol group (p<0.001 and p=0.046). Moreover, in the ≤72 months and the >72 months subgroups, the scores were also significantly lower in the ciprofol group on post-extubation 10min. With the score of >10, the incidence of emergence delirium of the ciprofol group was significantly lower on post-extubation 10min and 20min in the population and the ≤72 months subgroups (p=0.03 and p=0.02). There were no obvious postoperative complications in both groups. Conclusion: Ciprofol exhibited advantageous characteristics in the induction of children, such as stable hemodynamics, a relatively lower incidence of postoperative delirium without apparent post-anesthesia complications. Ciprofol may emerge as a novel option for general anesthesia in pediatric patients.


Assuntos
Adenoidectomia , Anestesia Geral , Tonsilectomia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pré-Escolar , Criança , Adenoidectomia/efeitos adversos , Anestesia Geral/efeitos adversos , Tonsilectomia/efeitos adversos , Propofol/administração & dosagem , Propofol/efeitos adversos , Complicações Pós-Operatórias , Lactente , Estudos de Coortes
4.
J Vis Exp ; (210)2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39248530

RESUMO

Membranous nephropathy (MN) is a common pathological type of adult nephrotic syndrome. Up to 20% of patients with MN develop end-stage renal disease (ESRD). Podocytes have an important function in maintaining the glomerular filtration barrier and play a crucial role in the occurrence and development of proteinuria and MN. PI3K/AKT signaling pathway is involved in the entire process of podocyte growth, differentiation, and apoptosis. Kemeng Fang (KMF) is a traditional Chinese medicine formula that has been used to delay kidney injury. However, the therapeutic mechanism of KMF in MN is unclear. Here, the MN rat model was established by axillary, inguinal, and tail vein injections of cationized bovine serum albumin (C-BSA), and then KMF and PI3K inhibitor (LY294002) were administered. The data of liver function, kidney function, blood lipid, renal pathology, podocyte function, expression level of PI3K/AKT signaling pathway, and transcriptomics of rats demonstrated that KMF has a protective effect on the podocytes of MN rats by activating the PI3K/AKT signaling pathway, and it can effectively prevent the progression of MN.


Assuntos
Apoptose , Medicamentos de Ervas Chinesas , Glomerulonefrite Membranosa , Fosfatidilinositol 3-Quinases , Podócitos , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Animais , Glomerulonefrite Membranosa/patologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/metabolismo , Podócitos/efeitos dos fármacos , Podócitos/metabolismo , Podócitos/patologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Masculino , Ratos Sprague-Dawley , Morfolinas/farmacologia , Morfolinas/uso terapêutico , Cromonas/farmacologia , Modelos Animais de Doenças
5.
J Cancer ; 15(15): 5072-5084, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39132153

RESUMO

Mitochondrial oxidative phosphorylation (OXPHOS) has long been considered the primary energy source in breast cancer cells. Cytochrome c oxidase assembly factor 6 (COA6), which functions as a metal chaperone to transport copper to complex Ⅳ during the OXPHOS process, plays a crucial role in the carcinogenesis of lung adenocarcinoma. Nevertheless, its specific function in breast cancer is undefined. The present investigation aimed to clarify COA6's expression profile and regulatory functions in breast cancer, as well as to unveil its underlying mechanisms. Initially, our findings revealed a significant upregulation of COA6 in breast cancer, as evidenced by an analysis of the TCGA database and tissue microarrays. This upregulation correlated with tumor size and histological grade. Additionally, survival analysis revealed that elevated COA6 amounts were correlated with decreased overall survival (OS) in breast cancer. To delve deeper into the functions of COA6, both COA6-overexpressing and COA6-knockdown breast cancer cell models were established. These experiments demonstrated COA6 is pivotal in regulating cell proliferation, apoptosis, migration, and invasion, thereby promoting cancer progression in vitro. Notably, functional enrichment analysis indicated COA6 might be involved in breast cancer progression by modulating oxidative phosphorylation (OXPHOS). Collectively, this study reveals an overt tumorigenic role for COA6 in breast cancer and sheds light on its potential mechanisms, offering valuable therapeutic targets for breast cancer therapy.

6.
Nat Commun ; 15(1): 5936, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009560

RESUMO

Jellyfish exhibit innovative swimming patterns that contribute to exploring the origins of animal locomotion. However, the genetic and cellular basis of these patterns remains unclear. Herein, we generated chromosome-level genome assemblies of two jellyfish species, Turritopsis rubra and Aurelia coerulea, which exhibit straight and free-swimming patterns, respectively. We observe positive selection of numerous genes involved in statolith formation, hair cell ciliogenesis, ciliary motility, and motor neuron function. The lineage-specific absence of otolith morphogenesis- and ciliary movement-related genes in T. rubra may be associated with homeostatic structural statocyst loss and straight swimming pattern. Notably, single-cell transcriptomic analyses covering key developmental stages reveal the enrichment of diapause-related genes in the cyst during reverse development, suggesting that the sustained diapause state favours the development of new polyps under favourable conditions. This study highlights the complex relationship between genetics, locomotion patterns and survival strategies in jellyfish, thereby providing valuable insights into the evolutionary lineages of movement and adaptation in the animal kingdom.


Assuntos
Cifozoários , Análise de Célula Única , Natação , Animais , Cifozoários/genética , Cifozoários/fisiologia , Diapausa/genética , Genômica/métodos , Genoma/genética , Transcriptoma , Perfilação da Expressão Gênica
7.
Sci Adv ; 10(25): eadn8709, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38905345

RESUMO

Androgen deprivation therapy (ADT) for prostate cancer is associated with an increased risk of dementia, including Alzheimer's disease (AD). The mechanistic connection between ADT and AD-related cognitive impairment in patients with prostate cancer remains elusive. We established a clinically relevant prostate cancer-bearing AD mouse model to explore this. Both tumor-bearing and ADT induce complex changes in immune and inflammatory responses in peripheral blood and in the brain. ADT disrupts the integrity of the blood-brain barrier (BBB) and promotes immune cell infiltration into the brain, enhancing neuroinflammation and gliosis without affecting the amyloid plaque load. Moreover, treatment with natalizumab, an FDA-approved drug targeting peripheral immune cell infiltration, reduces neuroinflammation and improves cognitive function in this model. Our study uncovers an inflammatory mechanism, extending beyond amyloid pathology, that underlies ADT-exacerbated cognitive deficits, and suggests natalizumab as a potentially effective treatment in alleviating the detrimental effects of ADT on cognition.


Assuntos
Doença de Alzheimer , Antagonistas de Androgênios , Barreira Hematoencefálica , Encéfalo , Disfunção Cognitiva , Modelos Animais de Doenças , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Doença de Alzheimer/metabolismo , Masculino , Disfunção Cognitiva/tratamento farmacológico , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/patologia , Disfunção Cognitiva/etiologia , Camundongos , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/metabolismo , Humanos , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Antagonistas de Androgênios/efeitos adversos , Antagonistas de Androgênios/farmacologia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Natalizumab/efeitos adversos , Natalizumab/farmacologia , Natalizumab/uso terapêutico , Placa Amiloide/patologia , Placa Amiloide/tratamento farmacológico
8.
Orphanet J Rare Dis ; 19(1): 123, 2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38486238

RESUMO

BACKGROUND: Pathogenic missense variants in the dystrophin (DMD) gene are rarely reported in dystrophinopathies. Most DMD missense variants are of uncertain significance and their pathogenicity interpretation remains complicated. We aimed to investigate whether DMD missense variants would cause aberrant splicing and re-interpret their pathogenicity based on mRNA and protein studies. METHODS: Nine unrelated patients who had an elevated serum creatine kinase level with or without muscle weakness were enrolled. They underwent a detailed clinical, imaging, and pathological assessment. Routine genetic testing and muscle-derived mRNA and protein studies of dystrophin and sarcoglycan genes were performed in them. RESULTS: Three of the 9 patients presented with a Duchenne muscular dystrophy (DMD) phenotype and the remaining 6 patients had a suspected diagnosis of Becker muscular dystrophy (BMD) or sarcoglycanopathy based on their clinical and pathological characteristics. Routine genetic testing detected only 9 predicted DMD missense variants in them, of which 6 were novel and interpreted as uncertain significance. Muscle-derived mRNA studies of sarcoglycan genes didn't reveal any aberrant transcripts in them. Dystrophin mRNA studies confirmed that 3 predicted DMD missense variants (c.2380G > C, c.4977C > G, and c.5444A > G) were in fact splicing and frameshift variants due to aberrant splicing. The 9 DMD variants were re-interpreted as pathogenic or likely pathogenic based on mRNA and protein studies. Therefore, 3 patients with DMD splicing variants and 6 patients with confirmed DMD missense variants were diagnosed with DMD and BMD, respectively. CONCLUSION: Our study highlights the importance of muscle biopsy and aberrant splicing for clinical and genetic interpretation of uncertain DMD missense variants.


Assuntos
Distrofina , Distrofia Muscular de Duchenne , Humanos , Distrofina/genética , Distrofia Muscular de Duchenne/genética , Mutação de Sentido Incorreto/genética , RNA Mensageiro/genética , Sarcoglicanas/genética
9.
Appl Radiat Isot ; 208: 111303, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38531243

RESUMO

Boron neutron capture therapy (BNCT) is an effective binary radiation therapy that depends on nuclear capture reactions. In recent years, BNCT can be performed without a reactor owing to the development of accelerator-based neutron sources. A new BNCT irradiation facility is proposed, which is based on a 15 mA 2.5 MeV proton accelerator with a 100 µm thickness natural lithium target as a neutron converter. A great quantity of studies has shown that neutron beams with different spectra have unique therapeutic effects on tumors. An appropriate neutron beam for BNCT is obtained by Beam Shaping Assembly (BSA) and the moderator plays a main role in determining the BSA outlet beam spectrum. To figure out the dose distribution in phantom with various kinds of neutron spectrum modes during BNCT, a series of cases are calculated by MCNPX code. The results give a database for treatment of brain tumors with BNCT by using different moderators.


Assuntos
Terapia por Captura de Nêutron de Boro , Neoplasias Encefálicas , Humanos , Terapia por Captura de Nêutron de Boro/métodos , Neoplasias Encefálicas/radioterapia , Lítio , Dosagem Radioterapêutica , Prótons , Nêutrons , Método de Monte Carlo
10.
J Multidiscip Healthc ; 17: 573-583, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38343756

RESUMO

Purpose: This study aims to explore the factors linked to the occurrence of acute pulmonary thromboembolism (PE) within a cohort of patients exhibiting hypoxic saturation (oxygen saturation levels falling below 93%), subsequent to undergoing off-pump coronary artery bypass grafting (OPCABG). Methods: A retrospective case-control study was conducted. A total of 296 patients met the inclusion and exclusion criteria, divided into PE group (100 cases) and non-PE group (196 cases) according to whether they had PE or not. The preoperative and postoperative information of patients were collected and statistically analyzed. Results: The results from a multivariate logistic regression analysis indicated the following factors were independently linked to PE following OPCABG: history of smoking (OR = 3.019, 95% CI, 1.437-6.634, P = 0.004), preoperative arterial oxygen partial pressure ≤78.9 mmHg (OR = 3.686, 95% CI, 1.708-8.220, P = 0.001), presence of postoperative lower extremity deep venous thrombosis (OR = 4.125, 95% CI, 1.886-9.310, P < 0.001), elevated postoperative D-dimer levels >6.76 mg/l (OR = 8.078, 95% CI, 3.749-18.217, P<0.001), postoperative NT-BNP levels (OR = 1.001, 95% CI: 1.000-1.001, P = 0.011), and elevated postoperative pulmonary arterial pressure >33.0 mmHg (OR = 10.743, 95% CI: 3.422-37.203, P < 0.001). The developed nomogram exhibited a high predictive accuracy with an area under the curve of 0.913 (95% CI: 0.878-0.948). Conclusion: When patients have a history of preoperative smoking, decreased preoperative arterial oxygen pressure, postoperative lower limb DVT, increased postoperative pulmonary artery pressure, and elevated postoperative D-Dimer and NT pro-BNP levels, it is recommended to take perioperative preventive measures, timely diagnostic evaluation, and if necessary, anticoagulant treatment. In addition, the results of this study may improve the diagnostic sensitivity of medical staff for postoperative PE in OPCABG, thereby increasing the detection rate and potentially reducing the need for excessive medical imaging procedures.

11.
Front Med (Lausanne) ; 10: 1239351, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38034540

RESUMO

Objective: Over the past few decades, the development of anti-cancer drugs in China has made outstanding achievements based on the support of national policies. To assess the progress of non-small cell lung cancer (NSCLC) drugs, we conducted a statistical analysis of clinical trials of drugs targeting NSCLC in China from 2005 to 2023. Methods: We downloaded, screened and analysed the data from three official websites, the Centre for Drug Evaluation of China National Medical Products Administration website (NMPA), ClinicalTrials.gov and the Chinese Clinical Trial Registry (ChiCTR). Results: From January 1, 2005 to April 15, 2023, a total of 1,357 drug clinical trials that met the standards were included, and the number of registered drug clinical trials has been increasing year by year, reaching the maximum of 199 in 2021. Among them, the maximum of 462 items (34.05%) in phase II clinical trials, followed by 333 (24.54%) in phase III clinical trials, and 139 (10.24%) in phase IV clinical trials. In all drug clinical trials, industry sponsored trials (ISTs) have 722 items (53.21%), which are higher than investigator-initiated trials (IITs). The clinical trials of chemical drugs have a maximum of 723 items (53.28%), while biopharmaceuticals have grown rapidly in the past 10 years, with a total of 374 (27.56%), and 48.19% of the drug clinical trials of combined medication. In addition, the geographical distribution of the leading units and participating units of Chinese drug clinical trials are uneven, and economic regions such as Beijing, Shanghai, Jiangsu are obviously ahead of other regions. Conclusion: From 2005 to 2023, the clinical trials of registered drugs for the treatment of NSCLC increased rapidly. Among them, due to the development of immunotherapy, the clinical trials of biopharmaceuticals and drugs for combined medication are growing most rapidly, while the exploration of the original drugs is a little far from enough. Our research provides a direction for the future drug clinical trials of NSCLC, laying foundation for further extending the survival rate of patients with NSCLC.

12.
Int J Womens Health ; 15: 1771-1778, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38020936

RESUMO

Introduction: Lymphatic malformation (LM), most commonly present in the neck area, is benign vascular malformations of the lymphatic system. In an infant, however, LM poses a high risk of adverse outcomes. Case Presentation: We present a case with a giant fetal LM. Through ultrasonography, at 23+ weeks of gestation, a septate cystic mass 7.2×6.5×6.3 cm in size was found on the right side of the fetus's neck. After extensive counseling by the multidisciplinary team, the parents chose to continue the pregnancy. Severe fetal tracheal compression was observed at 29 weeks by magnetic resonance imaging (MRI). At 31 weeks and 5 days, owing to suspected fetal distress, an emergency cesarean section was performed and a male baby weighing 1720 g was delivered. The mass was 10×16×8 cm in size and ex utero intrapartum treatment (EXIT) was implemented. Due to progressive growth of the mass secondary to intralesional bleeding, an intralesional injection of bleomycin was administered three days later. This injection was repeated at the age of 1 month and 8 days. The baby was followed up and, by a year after his birth, LM had disappeared. The baby has since been in good health. Conclusion: Accurate prenatal diagnosis and regular monitoring of a fetus with LM may improve prognosis. It is essential to have a trained multidisciplinary team to evaluate the condition of the fetus and the neonate and to provide treatment based on the evaluation. Our experience with intralesional bleomycin injection for the treatment of a giant fetal neck LM in a preterm infant had a favorable outcome. Long-term follow-up by a multidisciplinary team is needed in such cases.

13.
Front Physiol ; 14: 1164287, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37650111

RESUMO

Introduction: Mitochondrial disease is a spectrum of debilitating disorders caused by mutations in the mitochondrial DNA (mtDNA) or nuclear DNA that compromises the respiratory chain. Mitochondrial 3243A>G (m.3243 A>G) is the most common mutation showing great heterogeneity in phenotype. Previous studies have indicated that NADH: ubiquinone oxidoreductase (complex I) deficiency accompanied by a decreased nicotinamide adenine dinucleotide (NAD+)/reduced NAD+ (NADH) ratio may play a pivotal role in the pathogenesis of m.3243A>G mutation. Methods: To evaluate the potential effects of strategies targeting the imbalanced NAD+/NADH ratio in m.3243A>G mutation, we treated fibroblasts derived from patients with the m.3243 A>G mutation using nicotinamide riboside (NR) or mitochondria-targeted H2O-forming NADH oxidase (mitoLbNOX). Results: M.3243 A>G fibroblasts showed a significant reduction in complex I core subunit 6, complex I enzymatic activity, complex I-dependent oxygen consumption rate (OCR), and adenosine triphosphate (ATP) production compared to the controls. The NAD+/NADH ratio was also significantly reduced in m.3243 A>G fibroblasts, and, using fluorescence lifetime imaging microscopy, we also found that the NADH level was elevated in m.3243 A>G fibroblasts. After NR treatment, the NAD+/NADH ratio, complex I-dependent OCR, and ATP levels increased, whereas NADH levels remained unchanged. More excitingly, after treatment with mitoLbNOX, the NAD+/NADH ratio, complex I-independent OCR, and ATP levels increased more pronouncedly compared with the NR treatment group, accompanied by significantly reduced NADH levels. Discussion: The present study suggests that compared with repletion of NAD+ alone, the combination of this therapeutic modality with alleviation of NADH overload may amplify the treatment effect of restoring NAD+/NADH balance in m.3243A>G fibroblasts.

14.
Int J Womens Health ; 15: 1327-1332, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37583490

RESUMO

Introduction: Umbilical artery thrombosis is a rare complication associated with poor perinatal outcomes. The incidence of umbilical artery thrombosis in pregnancy is estimated from 0.0025% to 0.045%. Prenatal screening and diagnosis of umbilical artery thrombosis is usually performed by ultrasonography. Up to now, no treatment consensus has been achieved. Case Presentation: We present a case of dichorionic diamniotic twin pregnancy complicated with selective termination of one twin with lymphoid cystic tumor at 14 weeks and 2 days of gestation and the alive twin occurred single umbilical artery thrombosis at 35 weeks and 6 days of gestation. The emergency cesarean section was performed after emergency admission. A healthy male baby was delivered weighing 2690g with Apgar scores of 10 and 10 at 1 and 5 minutes, respectively, whereas the dead fetus weighed 10 g. Thrombosis was observed throughout one of the umbilical artery of the alive fetus. The woman and the infant are followed up closely and both in good condition. Conclusion: The number and morphology of umbilical arteries should be carefully observed during pregnancy. Individualized management of umbilical artery thrombosis should be based on clinical conditions. Timely termination of pregnancy if necessary could be suitable to improve adverse pregnancy outcomes.

15.
Front Nutr ; 10: 1160954, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37426180

RESUMO

To investigate the specific differences in flavor characteristics of Huangjiu fermented with different rice varieties, dynamic sensory evaluation, comprehensive two-dimensional gas chromatography-quadrupole mass spectrometry (GC × GC-qMS) and multivariate statistical analysis were employed. Dynamic sensory evaluation methods including temporal dominance of sensations (TDS) and temporal check all that apply (TCATA) were applied to explore the differences and variations in sensory attributes. The sensory results showed that the intensity of astringency and post-bitterness in the Huangjiu fermented with glutinous rice was weaker while ester and alcoholic aroma were more prominent than the one fermented with japonica rice. The results of free amino acids and aroma compounds analysis indicated that the amino acids were mainly sweet and bitter amino acids, and some key aroma compounds were predominant in the Huangjiu fermented with glutinous rice, such as ethyl butyrate (OAV: 38-59), 3-methylthiopropionaldehyde (OAV: 47-96), ethyl caprylate (OAV: 30-38), while nonanal, phenyl acetaldehyde and vanillin contributed significantly to the Huangjiu fermented with japonica rice. The multivariate statistical analysis further confirmed that 17 compounds (VIP > 1 and p < 0.05) could be supposed to be the key compouns that cause significant flavor differences in Huangjiu samples fermented with different brewing rice. Moreover, partial least-squares analysis revealed that most compounds (ethyl butyrate, 3-penten-2-one, isoamyl acetate, and so on) correlated with ester and alcoholic aroma. The results could provide basic data and theoretical basis for the selection of raw materials in Huangjiu.

17.
Food Chem X ; 18: 100696, 2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37187488

RESUMO

The adulteration of soymilk (SM) into raw bovine milk (RM) to gain profit without declaration could cause a health risk. In this study, electronic nose (E-nose) and headspace-gas chromatography ion-mobility spectrometry (HS-GC-IMS) were applied to establish a rapid and effective method to identify adulteration in RM with SM. The obtained data from HS-GC-IMS and E-nose can distinguish the adulterated samples with SM by principal component analysis. Furthermore, a quantitative model of partial least squares was established. The detection limits of E-nose and HS-GC-IMS quantitative models were 1.53% and 1.43%, the root mean square errors of prediction were 0.7390 and 0.5621, the determination coefficients of prediction were 0.9940 and 0.9958, and the relative percentage difference were 10.02 and 13.27, respectively, indicating quantitative regression and good prediction performances of SM adulteration levels in RM were achieved. This research can provide scientific information on the rapid, non-destructive and effective adulteration detection for RM.

18.
Environ Toxicol ; 38(9): 2100-2110, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37209385

RESUMO

Diallyl sulfide (DAS), as a major component of garlic extracts, has been shown to inhibit growth of hepatocellular carcinoma cells (HCC), but the underlying mechanism is still elusive. In this study, we aimed to explore the involvement of autophagy in DAS-induced growth inhibition of HepG2 and Huh7 hepatocellular carcinoma cells. We studied growth of DAS-treated HepG2 and Huh7 cells using the MTS and clonogenic assays. Autophagic flux was examined by immunofluorescence and confocal microscopy. The expression levels of autophagy-related proteins AMPK, mTOR, p62, LC3-II, LAMP1, and cathepsin D in the HepG2 and Huh7 cells treated with DAS as well as the tumors formed by HepG2 cells in the nude mice in the presence or absence of DAS were examined using western blotting and immunohistochemistry analysis. We found that DAS treatment induced activation of AMPK/mTOR, and accumulation of LC3-II and p62 both in vivo and in vitro. DAS inhibited autophagic flux through blocking the fusion of autophagosomes with lysosomes. Furthermore, DAS induced an increase in lysosomal pH and inhibition of Cathepsin D maturation. Co-treatment with an autophagy inhibitor (Chloroquine, CQ) further enhanced the growth inhibitory activity of DAS in HCC cells. Thus, our findings indicate that autophagy is involved in DAS-mediated growth inhibition of HCC cells both in vitro and in vivo.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Catepsina D/metabolismo , Camundongos Nus , Proteínas Quinases Ativadas por AMP/metabolismo , Autofagia , Serina-Treonina Quinases TOR/metabolismo , Lisossomos/metabolismo
19.
Int J Mol Sci ; 24(10)2023 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-37240101

RESUMO

Lampriform fishes (Lampriformes), which primarily inhabit deep-sea environments, are large marine fishes varying from the whole-body endothermic opah to the world's longest bony fish-giant oarfish, with species morphologies varying from long and thin to deep and compressed, making them an ideal model for studying the adaptive radiation of teleost fishes. Moreover, this group is important from a phylogenetic perspective owing to their ancient origins among teleosts. However, knowledge about the group is limited, which is, at least partially, due to the dearth of recorded molecular data. This study is the first to analyze the mitochondrial genomes of three lampriform species (Lampris incognitus, Trachipterus ishikawae, and Regalecus russelii) and infer a time-calibrated phylogeny, including 68 species among 29 orders. Our phylomitogenomic analyses support the classification of Lampriformes as monophyletic and sister to Acanthopterygii; hence, addressing the longstanding controversy regarding the phylogenetic status of Lampriformes among teleosts. Comparative mitogenomic analyses indicate that tRNA losses existed in at least five Lampriformes species, which may reveal the mitogenomic structure variation associated with adaptive radiation. However, codon usage in Lampriformes did not change significantly, and it is hypothesized that the nucleus transported the corresponding tRNA, which led to function substitutions. The positive selection analysis revealed that atp8 and cox3 were positively selected in opah, which might have co-evolved with the endothermic trait. This study provides important insights into the systematic taxonomy and adaptive evolution studies of Lampriformes species.


Assuntos
Genoma Mitocondrial , Animais , Filogenia , Peixes/genética , RNA de Transferência/genética
20.
Sci China Life Sci ; 66(6): 1213-1230, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37204606

RESUMO

The leafy seadragon certainly is among evolution's most "beautiful and wonderful" species aptly named for its extraordinary camouflage mimicking its coastal seaweed habitat. However, limited information is known about the genetic basis of its phenotypes and conspicuous camouflage. Here, we revealed genomic signatures of rapid evolution and positive selection in core genes related to its camouflage, which allowed us to predict population dynamics for this species. Comparative genomic analysis revealed that seadragons have the smallest olfactory repertoires among all ray-finned fishes, suggesting adaptations to the highly specialized habitat. Other positively selected and rapidly evolving genes that serve in bone development and coloration are highly expressed in the leaf-like appendages, supporting a recent adaptive shift in camouflage appendage formation. Knock-out of bmp6 results in dysplastic intermuscular bones with a significantly reduced number in zebrafish, implying its important function in bone formation. Global climate change-induced loss of seagrass beds now severely threatens the continued existence of this enigmatic species. The leafy seadragon has a historically small population size likely due to its specific habitat requirements that further exacerbate its vulnerability to climate change. Therefore, taking climate change-induced range shifts into account while developing future protection strategies.


Assuntos
Ecossistema , Peixe-Zebra , Animais , Mudança Climática , Fenótipo
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