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2.
Sci Rep ; 14(1): 16033, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992112

RESUMO

The association between the triglyceride-glucose (TyG) index and impaired fasting glucose (IFG) in elderly individuals remains uncertain. Our study aimed to explore the association between the TyG index and the risk of future IFG in this population. This retrospective cohort study included 17,746 elderly individuals over 60. In this population, Cox regression models proportional to hazards, along with smooth curve fitting and cubic spline functions, were employed to examine the association between the baseline TyG index and the risk of IFG. Subgroup analyses and sensitivity were also performed to ensure the robustness of the study findings. After adjusting for covariates, a positive association between the TyG index and the risk of IFG was found (HR = 1.43, 95% CI 1.27-1.60, P < 0.0001). The likelihood of IFG rose steadily as the TyG index quartiles (from Q1 to Q4) increased, with Q4 demonstrating a 62% elevated risk compared to Q1 (adjusted HR = 1.62, 95% CI 1.37-1.90). Additionally, we found the association between TyG index and risk of IFG was a linear. Sensitivity and subgroup analyses confirmed the stability of the results. Our study observed a linear association between the TyG index and the development of IFG in elderly Chinese individuals. Recognizing this association can help clinicians identify high-risk individuals and implement targeted interventions to reduce their risk of progressing to diabetes.


Assuntos
Glicemia , Jejum , Triglicerídeos , Humanos , Idoso , Masculino , Feminino , Triglicerídeos/sangue , Glicemia/análise , Jejum/sangue , Estudos Retrospectivos , China/epidemiologia , Fatores de Risco , Pessoa de Meia-Idade , Povo Asiático , Modelos de Riscos Proporcionais , Intolerância à Glucose/sangue , Intolerância à Glucose/epidemiologia , Idoso de 80 Anos ou mais , População do Leste Asiático
3.
Heliyon ; 10(12): e32490, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38994096

RESUMO

Purpose: To investigate the factors influencing hypothermia during pancreaticoduodenectomy and establish and verify a prediction model. Method: The clinical data of patients undergoing pancreaticoduodenectomy in Hunan People's Hospital between January 1, 2022 and October 15, 2022 were analysed. The patients were divided into a hypothermia group (n = 302) and a non-hypothermia group (n = 164) according to whether hypothermia occurred during surgery. A binary logistic regression model was used to analyse the independent risk factors for hypothermia in patients undergoing pancreaticoduodenectomy. A risk prediction model was established, and R software was used to plot a column graph. The predictive value of the model was evaluated using the receiver operating characteristic (ROC) curve. Results: Among the 466 patients undergoing pancreaticoduodenectomy, 302 (64.81 %) had hypothermia, including 154 men and 148 women, with a median age of 58.6 (38-86) years. The binary logistic regression analysis showed that low body mass index (BMI), room temperature at the time of entry, intraoperative flushing fluid volume and peritoneal flushing fluid temperature were independent risk factors for intraoperative hypothermia in patients undergoing pancreaticoduodenal surgery (P < 0.05). A multivariate logistic regression analysis (backward logistic regression) was used to establish the prediction model. The area under the ROC curve was 0.927, P ≤ 0.001, the sensitivity was 0.921 and the specificity was 0.848, indicating good differentiation by the prediction model. Conclusion: The nomogram constructed using four independent risk factors: BMI, room temperature at the time of entry, intraoperative peritoneal flushing fluid volume and intraoperative peritoneal flushing fluid temperature, has good predictive efficacy and good clinical application value for predicting intraoperative hypothermia in patients undergoing pancreaticoduodenectomy.

4.
Poult Sci ; 103(9): 104023, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-39002366

RESUMO

Over 10,000 metric-ton broiler livers are produced annually in Taiwan. Concerning unpleasant odor and healthy issue, broiler livers are not attractive to consumers. Although the patented chicken-liver hydrolysates (CLHs) through pepsin digestion possess several biofunctionalities, there is no study on hepatoprotection of CLH-based formula capsule (GBHP01) against binge drinking (Whiskey, 50% Alc./Vol.). GBHP01 led to an accelerated blood-alcohol clearance in rats, as evidenced by lowering blood-alcohol increment within 0 to 4 h, increasing blood-alcohol decrement within 4 to 8 h, and smaller blood alcohol concentration areas under the curve (BAC AUC) in the 8-h period (p < 0.05). The ameliorative effects of GBHP01 against binge drinking in rats over 6 wk were attributed to accelerated alcohol metabolism by further increasing alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities while downregulating cytochrome P450 2E1 (CYP2E1) protein expression, elevating antioxidant capacity, decreasing zonula occludens-1 (ZO-1) protein decrement and serum endotoxin, and reducing inflammation related protein levels, that is, toll-like receptor 4 (TLR4) and mitogen-activated protein kinase (MAPK), and proinflammatory cytokines. The development of CLH supplements could not only enhance the added value of broiler livers through nutraceutical development but also offer a strategy to maximize the utilization of poultry processing residues, as shown in this study.

5.
Angew Chem Int Ed Engl ; : e202411845, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39031481

RESUMO

Chemically self-recharging zinc ion batteries (ZIBs), which are capable of auto-recharging in ambient air, are promising in self-powered battery systems. Nevertheless, the exclusive reliance on chemical energy from oxygen for ZIBs charging often would bring some obstacles in charging efficiency. Herein, we develop photo-assisted chemically self-recharging aqueous ZIBs with a heterojunction of MoS2/SnO2 cathode, which are favorable to enhancing both the charging and discharging efficiency as well as the chemical self-charging capabilities under illumination. The photo-assisted process promotes the electron transfer from MoS2/SnO2 to oxygen, accelerating the occurrence of the oxidation reaction during chemical self-charging. Furthermore, the electrons within the MoS2/SnO2 cathode exhibit a low transfer impedance under illumination, which is beneficial to reducing the migration barrier of Zn2+ within the cathode and thereby facilitating the uniform inserting of Zn2+ into MoS2/SnO2 cathode during discharging. This photo-assisted chemical self-recharging mechanism enables ZIBs to attain a maximum self-charging potential of 0.95 V within 3 hours, a considerable self-charging capacity of 202.5 mAh g-1 and excellent cycling performance in a self-charging mode. This work not only provides a route for optimizing chemical self-charging energy storage, but also broadens the potential application of aqueous ZIBs.

6.
Angew Chem Int Ed Engl ; : e202401910, 2024 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-39034290

RESUMO

The lack of stable solid-state electrolytes (SSEs) with high-ionic conductivity and rational design of electrode/electrolyte interfaces remains challenging for solid-state lithium batteries. Here, for the first time, a high-performance solid-state lithium-oxygen battery is developed based on the Li-ion-conducted hydrogen-bonded organic framework (LHOF) electrolyte and the core-shell HOF-DAT@CNT cathode with a few layers of HOF-DAT on surface of carbon nanotubes. Benefiting from the abundant dynamic hydrogen bonding network in LHOF-DAT SSEs, fast Li+ ion transport (2.2 × 10-4 S cm-1), a high Li+ transfer number (0.88), and a wide electrochemical window of 5.05 V are achieved. Symmetric batteries constructed with LHOF-DAT SSEs exhibit a stably cycled duration of over 1400 h, which mainly stems from the jumping sites that promote a uniformly high rate of Li+ flux and the hydrogen-bonding network structure that can relieve the structural changes during Li+ transport. LHOF-DAT SSEs-based Li-O2 batteries exhibit high specific capacity (10335 mAh g-1), and stable cycling life up to 150 cycles. Moreover, the solid-state lithium metal battery with LHOF-DAT SSEs endow good rate capability (128.8 mAh g-1 at 1 C), long-term discharge/charge stability (210 cycles). The design of LHOF-DAT SSEs opens an avenue for the development of novel SSEs-based solid-state lithium batteries.

7.
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
8.
J Agric Food Chem ; 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016055

RESUMO

Butachlor is widely used in agriculture around the world and therefore poses environmental and public health hazards due to persistent and poor biodegradability. Ferroptosis is a type of iron-mediated cell death controlled by glutathione (GSH) and GPX4 inhibition. P62 is an essential autophagy adaptor that regulates Keap1 to activate nuclear factor erythroid 2-related factor 2 (Nrf2), which effectively suppresses lipid peroxidation, thereby relieving ferroptosis. Here, we found that butachlor caused changes in splenic macrophage structure, especially impaired mitochondrial morphology with disordered structure, which is suggestive of the occurrence of ferroptosis. This was further confirmed by the detection of iron metabolism, the GSH system, and lipid peroxidation. Mechanistically, butachlor suppressed the protein level of p62 and promoted Keap1-mediated degradation of Nrf2, which results in decreased GPX4 expression and accelerated splenic macrophage ferroptosis. These findings suggest that targeting the p62-Nrf2-GPX4 signaling axis may be a promising strategy for treating inflammatory diseases.

9.
Org Biomol Chem ; 2024 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-39037724

RESUMO

Organic synthesis methods initiated by visible light have received increasing attention from synthetic chemists. Reactions initiated by EDA complexes do not require the use of toxic or expensive photoredox catalysts, unlike traditional photoreaction processes. However, this kind of reaction requires a particular structure for the substrate, so it is important to study the detailed and systematic reaction mechanism for its design. EDA complexes of substituted 1H-indole and substituted benzyl bromide derivatives were studied by density functional theory (DFT). The difference between EDA complexes with substituents of different kinds and locations were compared by theoretical study and a new EDA complex was predicted.

10.
J Anat ; 2024 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-38922713

RESUMO

Current studies on facial growth and development have been largely based on European populations. Less studied are African populations, who because of their distinct genetic makeup and environmental conditions, provide deeper insights into patterns of facial development. Patterns of facial shape development in African populations remain largely uncharacterised. Our study aimed to establish facial growth and development trajectories based on a cohort of 2874 Bantu Africans from Tanzania aged 6-18 years, with particular focus on identifying morphogenetic processes that lead to observed developmental shape changes. Procrustes ANCOVA suggested sexually dimorphic patterns of facial shape development (p = 0.0036). The forehead was relatively contracted during development in both sexes. The glabella region was more anteriorly displaced in females due to expansion in the region laterosuperior to the eyes. Nasal protrusion increased with development, which was found to arise from local expansion in the nasal alae and columella. Local expansion in the upper and lower labial regions resulted in forward displaced lips in both sexes, with the effect more pronounced in males. The mentum was displaced more anteriorly in females due to comparatively more expanded mental regions with development. The lateral facial region corresponding to the underlying body of the mandible were developmentally expanded but were posteriorly positioned due to protrusive growth of surrounding structures. Generalised additive modelling of Procrustes variance suggested that facial variation decreased non-linearly with age (p < 0.05). Relative principal component analysis suggested that variations in facial outline shape were developmentally constrained, whereas nasolabial and mental regions, where developmental changes were significant, became morphologically diversified with development. In contrast to simple descriptive illustration of facial shape development, we gained transformative insights into patterns of facial shape development by analysing morphogenetic processes and variational properties. Our analytical framework is broadly applicable to morphometric studies on ontogenetic shape changes.

11.
Chem Commun (Camb) ; 60(51): 6496-6499, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38836703

RESUMO

Cobalt substitution for manganese sites in Na0.44MnO2 initiates a dynamic structural evolution process, yielding a composite cathode material comprising intergrown P2 and P3 phases. The novel P2/P3 composite cathode exhibits a reversible phase transition process during Na+ extraction/insertion, showcasing its attractive battery performance in sodium-ion batteries.

12.
Mil Med Res ; 11(1): 39, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902798

RESUMO

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.


Assuntos
Etanol , Malformações Vasculares , Animais , Coelhos , Etanol/uso terapêutico , Etanol/farmacologia , Masculino , Malformações Vasculares/terapia , Malformações Vasculares/tratamento farmacológico , Humanos , Meios de Contraste/farmacocinética , Meios de Contraste/farmacologia , Meios de Contraste/uso terapêutico , Iohexol/análogos & derivados
13.
Int J Biol Macromol ; 273(Pt 2): 133095, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38866265

RESUMO

Mussel byssal proteins are of biomimetic importance for the development of novel underwater bio-adhesive agents. It is important to maintain a reduced state during the process of byssus adhesion. There are 19 mussel foot proteins (MFPs) have been reported in previous studies, among which only MFP-6 had been confirmed as an antioxidant protein in mussel byssus due to the function of cysteines, and playing an essential role in the redox balance of mussel byssus during adhesion process. Although the other four MFPs (MFP-16 ~ MFP-19) also have abundant cysteines, their function is still unknown. In this study, a novel mussel foot protein, named MFP-20, was identified from Mytilus coruscus foot. The sequential features, expression profile, and function of recombinant MFP-20 were verified. The results showed that MFP-20 has more abundant cysteines than other MFPs, the relative expression of mfp-20 was upregulated in Fe3+ stress and low pH seawater. In addition, different adhesive substrates induced significant changes of expression level of mfp-20. Furthermore, rMFP-20 showed strong antioxidant capacity in the DPPH assay, and the abundant cysteines in its sequence may play vital roles in the antioxidation activity. Our findings revealed the possible function of MFP-20 with a totally different sequence from the reported MFP-6 and provided new clues for exploring the redox balance of mussel byssus during the adhesion process.


Assuntos
Antioxidantes , Mytilus , Proteínas , Animais , Mytilus/metabolismo , Mytilus/química , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Proteínas/química , Proteínas/metabolismo , Sequência de Aminoácidos , Oxirredução , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo
14.
Viruses ; 16(6)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38932254

RESUMO

The human immunodeficiency virus type-1 epidemic in Pakistan has significantly increased over the last two decades. In Karachi, Pakistan, there is a lack of updated information on the complexity of HIV-1 genetic diversity and the burden of drug resistance mutations (DRMs) that can contribute to ART failure and poor treatment outcomes. This study aimed to determine HIV-1 genetic diversity and identify drug-resistance mutations among people living with HIV in Karachi. A total of 364 HIV-positive individuals, with a median age of 36 years, were enrolled in the study. The HIV-1 partial pol gene was successfully sequenced from 268 individuals. The sequences were used to generate phylogenetic trees to determine clade diversity and also to assess the burden of DRMs. Based on the partial pol sequences, 13 distinct HIV-1 subtypes and recombinant forms were identified. Subtype A1 was the most common clade (40%), followed by CRF02_AG (33.2%). Acquired DRMs were found in 30.6% of the ART-experienced patients, of whom 70.7%, 20.7%, and 8.5% were associated with resistance to NNRTIs, NRTIs, and PIs, respectively. Transmitted DRMs were found in 5.6% of the ART-naïve patients, of whom 93% were associated with resistance against NNRTIs and 7% to PIs. The high prevalence of DRMs in ART-experienced patients poses significant challenges to the long-term benefits and sustainability of the ART program. This study emphasizes the importance of continuous HIV molecular epidemiology and drug resistance surveillance to support evidence-based HIV prevention, precise ART, and targeted AIDS care.


Assuntos
Fármacos Anti-HIV , Farmacorresistência Viral , Variação Genética , Infecções por HIV , HIV-1 , Mutação , Filogenia , Humanos , HIV-1/genética , HIV-1/efeitos dos fármacos , HIV-1/classificação , Paquistão/epidemiologia , Infecções por HIV/virologia , Infecções por HIV/epidemiologia , Farmacorresistência Viral/genética , Adulto , Masculino , Feminino , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Pessoa de Meia-Idade , Adulto Jovem , Genótipo , Adolescente
15.
ACS Nano ; 18(27): 17622-17629, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38922204

RESUMO

Engineering atomic-scale defects has become an important strategy for the future application of transition metal dichalcogenide (TMD) materials in next-generation electronic technologies. Thus, providing an atomic understanding of the electron-defect interactions and supporting defect engineering development to improve carrier transport is crucial to future TMDs technologies. In this work, we utilize low-temperature scanning tunneling microscopy/spectroscopy (LT-STM/S) to elicit how distinct types of defects bring forth scattering potential engineering based on intervalley quantum quasiparticle interference (QPI) in TMDs. Furthermore, quantifying the energy-dependent phase variation of the QPI standing wave reveals the detailed electron-defect interaction between the substitution-induced scattering potential and the carrier transport mechanism. By exploring the intrinsic electronic behavior of atomic-level defects to further understand how defects affect carrier transport in low-dimensional semiconductors, we offer potential technological applications that may contribute to the future expansion of TMDs.

16.
Front Immunol ; 15: 1415246, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38911859

RESUMO

Purpose: To investigate the treatment response and toxicity of the combination of induction chemotherapy (IC) and PD-1 inhibitor in locally advanced nasopharyngeal carcinoma (LANPC). Methods: Patients with stage III-IVA NPC who received IC or IC + PD-1 inhibitor were included. The chi-square test and multivariate logistic regression analysis were used for statistical analysis. Results: A total of 225 patients were identified, including 193 (85.8%) and 32 (14.2%) who received IC alone and IC + PD-1 inhibitor, respectively. The addition of PD-1 inhibitor to IC significantly improved the tumor response than those treated with IC alone. The complete response (CR), partial response, stable disease, and progressive disease rates of 4.7% vs. 31.3%, 69.4% vs. 62.5%, 24.9% vs. 6.3%, and 1.0% vs. 0% in patients receiving IC alone and IC + PD-1 inhibitor, respectively (P<0.001). The results of the multivariate logistic regression showed that receiving PD-1 inhibitor was an independent predictor influencing the CR rate of patients (odds ratio 9.814, P<0.001). The most common toxicity by using IC and PD-1 inhibitor was hematological toxicity. In terms of non-hematological toxicity, 7 (21.9%) patients experienced thyroid dysfunction and all of them were hyperthyroidism. No grade 5 toxicities were found. In those who received IC and PD-1 inhibitor, the one-year locoregional recurrence-free survival, distant metastasis-free survival, disease-free survival, and overall survival were 100%, 96.9%, 96.9%, and 100%, respectively. Conclusion: The addition of PD-1 inhibitor to IC has promise as an effective treatment approach for LANPC. More studies are expected to provide further insights into the optimal use of this treatment strategy, paving the way for more personalized and effective treatment options for patients with LANPC.


Assuntos
Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Masculino , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Pessoa de Meia-Idade , Adulto , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Idoso , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Resultado do Tratamento , Estadiamento de Neoplasias , Adulto Jovem , Estudos Retrospectivos
17.
Mol Cell ; 84(12): 2304-2319.e8, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38838666

RESUMO

Circular RNAs (circRNAs) are upregulated during neurogenesis. Where and how circRNAs are localized and what roles they play during this process have remained elusive. Comparing the nuclear and cytoplasmic circRNAs between H9 cells and H9-derived forebrain (FB) neurons, we identify that a subset of adenosine (A)-rich circRNAs are restricted in H9 nuclei but exported to cytosols upon differentiation. Such a subcellular relocation of circRNAs is modulated by the poly(A)-binding protein PABPC1. In the H9 nucleus, newly produced (A)-rich circRNAs are bound by PABPC1 and trapped by the nuclear basket protein TPR to prevent their export. Modulating (A)-rich motifs in circRNAs alters their subcellular localization, and introducing (A)-rich circRNAs in H9 cytosols results in mRNA translation suppression. Moreover, decreased nuclear PABPC1 upon neuronal differentiation enables the export of (A)-rich circRNAs, including circRTN4(2,3), which is required for neurite outgrowth. These findings uncover subcellular localization features of circRNAs, linking their processing and function during neurogenesis.


Assuntos
Transporte Ativo do Núcleo Celular , Adenosina , Núcleo Celular , Neurogênese , Neurônios , Proteína I de Ligação a Poli(A) , RNA Circular , RNA , RNA Circular/metabolismo , RNA Circular/genética , Neurônios/metabolismo , Adenosina/metabolismo , Núcleo Celular/metabolismo , Humanos , Proteína I de Ligação a Poli(A)/metabolismo , Proteína I de Ligação a Poli(A)/genética , Animais , RNA/metabolismo , RNA/genética , Linhagem Celular , Diferenciação Celular , Citoplasma/metabolismo , Prosencéfalo/metabolismo
18.
J Am Soc Mass Spectrom ; 35(7): 1507-1515, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38905484

RESUMO

Over the past decades, proteomics has become increasingly important and a heavily discussed topic. The identification of intact proteins remains a major focus in this field. While most intact proteins are analyzed using high-resolution mass spectrometry, identifying them through low-resolution mass spectrometry continues to pose challenges. In our study, we investigated the capability of identifying various intact proteins using collision-induced dissociation (CID) and electron transfer without dissociation (ETnoD). Using myoglobin as our test protein, stable product ions were generated with CID, and the identities of the product ions were identified with ETnoD. ETnoD uses a short activation time (AcT, 5 ms) to create sequential charge-reduced precursor ion (CRI). The charges of the fragments and their sequences were determined with corresponding CRI. The product ions can be selected for subsequent CID (termed CIDn) combined with ETnoD for further sequence identification and validation. We refer to this method as CIDn/ETnoD. The use of a multistage CID activation (CIDn) and ETnoD protocol has been applied to several intact proteins to obtain multiple sequence identifications.


Assuntos
Mioglobina , Proteômica , Mioglobina/química , Mioglobina/análise , Proteômica/métodos , Animais , Proteínas/química , Proteínas/análise , Sequência de Aminoácidos , Cavalos , Espectrometria de Massas/métodos , Dados de Sequência Molecular , Espectrometria de Massas em Tandem/métodos
19.
J Agric Food Chem ; 72(27): 15334-15344, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38916549

RESUMO

Di-2-ethylhexyl phthalate (DEHP) is frequently used as a plasticizer to enhance the plasticity and durability of agricultural products, which pose adverse effects to human health and the environment. Aquaporin 1 (AQP1) is a main water transport channel protein and is involved in the maintenance of intestinal integrity. However, the impact of DEHP exposure on gut health and its potential mechanisms remain elusive. Here, we determined that DEHP exposure induced a compromised duodenum structure, which was concomitant with mitochondrial structural injury of epithelial cells. Importantly, DEHP exposure caused duodenum inflammatory epithelial cell damage and strong inflammatory response accompanied by activating the TLR4/MyD88/NF-κB signaling pathway. Mechanistically, DEHP exposure directly inhibits the expression of AQP1 and thus leads to an inflammatory response, ultimately disrupting duodenum integrity and barrier function. Collectively, our findings uncover the role of AQP1 in phthalate-induced intestinal disorders, and AQP1 could be a promising therapeutic approach for treating patients with intestinal disorders or inflammatory diseases.


Assuntos
Aquaporina 1 , Mucosa Intestinal , Animais , Aquaporina 1/genética , Aquaporina 1/metabolismo , Camundongos , Humanos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Inflamação/metabolismo , Inflamação/genética , Inflamação/induzido quimicamente , Masculino , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , NF-kappa B/metabolismo , NF-kappa B/genética , Dietilexilftalato/toxicidade , Ácidos Ftálicos , Transdução de Sinais/efeitos dos fármacos
20.
J Integr Plant Biol ; 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38888227

RESUMO

Anther dehiscence is a crucial event in plant reproduction, tightly regulated and dependent on the lignification of the anther endothecium. In this study, we investigated the rapid lignification process that ensures timely anther dehiscence in Arabidopsis. Our findings reveal that endothecium lignification can be divided into two distinct phases. During Phase I, lignin precursors are synthesized without polymerization, while Phase II involves simultaneous synthesis of lignin precursors and polymerization. The transcription factors MYB26, NST1/2, and ARF17 specifically regulate the pathway responsible for the synthesis and polymerization of lignin monomers in Phase II. MYB26-NST1/2 is the key regulatory pathway responsible for endothecium lignification, while ARF17 facilitates this process by interacting with MYB26. Interestingly, our results demonstrate that the lignification of the endothecium, which occurs within approximately 26 h, is much faster than that of the vascular tissue. These findings provide valuable insights into the regulation mechanism of rapid lignification in the endothecium, which enables timely anther dehiscence and successful pollen release during plant reproduction.

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