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1.
Sci Adv ; 10(23): eadl2201, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38848371

RESUMO

La Niña climate anomalies have historically been associated with substantial reductions in the atmospheric CO2 growth rate. However, the 2021 La Niña exhibited a unique near-neutral impact on the CO2 growth rate. In this study, we investigate the underlying mechanisms by using an ensemble of net CO2 fluxes constrained by CO2 observations from the Orbiting Carbon Observatory-2 in conjunction with estimates of gross primary production and fire carbon emissions. Our analysis reveals that the close-to-normal atmospheric CO2 growth rate in 2021 was the result of the compensation between increased net carbon uptake over the tropics and reduced net carbon uptake over the Northern Hemisphere mid-latitudes. Specifically, we identify that the extreme drought and warm anomalies in Europe and Asia reduced the net carbon uptake and offset 72% of the increased net carbon uptake over the tropics in 2021. This study contributes to our broader understanding of how regional processes can shape the trajectory of atmospheric CO2 concentration under climate change.

2.
Anal Chem ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833718

RESUMO

Visualization of the mitochondrial state is crucial for tracking cell life processes and diagnosing disease, while fluorescent probes that can accurately assess mitochondrial status are currently scarce. Herein, a fluorescent probe named "SYN" was designed and prepared, which can target mitochondria via the mitochondrial membrane potential. Upon pathology or external stimulation, SYN can be released from the mitochondria and accumulate in the nucleolus to monitor the status of mitochondria. During this process, the brightness of the nucleolus can then serve as an indicator of mitochondrial damage. SYN has demonstrated excellent photostability in live cells as well as an extremely inert fluorescence response to bioactive molecules and the physiological pH environment of live cells. Spectroscopic titration and molecular docking studies have revealed that SYN can be lit up in nucleoli due to the high viscosity of the nucleus and the strong electrostatic interaction with the phosphate backbone of RNA. This probe is expected to be an exceptional tool based on its excellent imaging properties for tracking mitochondrial state in live cells.

3.
Mater Horiz ; 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38842407

RESUMO

Eukaryotic cells regulate various cellular processes through membrane-bound and membrane-less organelles, enabling active signal communication and material exchange. Lysosomes and lipid droplets are representative organelles, contributing to cell lipophagy when their interaction and metabolism are disrupted. Our limited understanding of the interacting behaviours and physicochemical properties of different organelles during lipophagy hinders accurate diagnosis and treatment of related diseases. In this contribution, we report a fluorescent probe, PTZ, engineered for dual-targeting of lipid droplets and lysosomes. PTZ can track liquid-liquid phase separation and respond to polarity shifts through ratiometric fluorescence emission, elucidating the lipophagy process from the perspective of organelle behavior and physicochemical properties. Leveraging on the multifunctionality of PTZ, we have successfully tracked the polarity and dynamic changes of lysosomes and lipid droplets during lipophagy. Furthermore, an unknown homogeneous transition of lipid droplets and lysosomes was discovered, which provided a new perspective for understanding lipophagy processes. And this work is expected to serve as a reference for diagnosis and treatment of lipophagy-related diseases.

4.
Adv Mater ; : e2405109, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38845131

RESUMO

Physically crosslinked microgels (PCMs) offer a biocompatible platform for various biomedical applications. However, current PCM fabrication methods suffer from their complexity and poor controllability, due to their reliance on altering physical conditions to initiate gelation and their dependence on specific materials. To address this issue, a novel PCM fabrication method was devised, which employs water transport-induced liquid-liquid phase separation (LLPS) to trigger the intermolecular interaction-supported sol-gel transition within aqueous emulsion droplets. This method enables the controllable and facile generation of PCMs through a single emulsification step, allowing for the facile production of PCMs with various materials and sizes, as well as controllable structures and mechanical properties. Moreover, this PCM fabrication method holds great promise for diverse biomedical applications. The interior of the PCM not only supports the encapsulation and proliferation of bacteria but also facilitates the encapsulation of eukaryotic cells after transforming the system into an all-aqueous emulsion. Furthermore, through appropriate surface functionalization, the PCMs effectively activate T cells in vitro upon co-culturing. This work represents an advancement in PCM fabrication and offers new insights and perspectives for microgel engineering. This article is protected by copyright. All rights reserved.

5.
Anal Bioanal Chem ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38853180

RESUMO

Radix ginseng and Schisandra chinensis have been extensively documented in traditional Chinese medicine (TCM) for their potential efficacy in treating dementia. However, the precise mechanism of their therapeutic effects remains to be fully elucidated. In this study, air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) and network pharmacology are used to investigate the pharmacodynamics and mechanism underlying the herbal combination consisting of Radix ginseng-Schisandra chinensis (RS) in a rodent model for Alzheimer's disease (AD). Brain histopathological findings suggested that RS attenuates hippocampal damage in AD mice, making this combination a potential AD treatment. Twenty-eight biomarkers were identified by spatial metabolomics analysis, which are intricately linked to neuroinflammation, neurotransmitter imbalance, energy deficiency, oxidative stress, and aberrant fatty acid metabolism in AD. The total extract of RS (TE) affected 22 of these biomarkers, with the small molecule components of RS (SN) significantly influencing 19 and the large molecule components of RS (PR) impacting 14. Nine small molecule components are likely to dominate the pharmacodynamics of RS. We constructed a target interaction network based on the corresponding bioactivities that revealed relationships amongst 11 key biomarkers, 8 active ingredients and 12 critical targets. This research illustrates the immense potential of spatial metabolomics and network pharmacology in the study of TCM, revealing the targets and mechanisms underlying herbal formulas.

6.
Adv Sci (Weinh) ; : e2404172, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874481

RESUMO

Smart drug platforms based on spatiotemporally controlled release and integration of tumor imaging are expected to overcome the inefficiency and uncertainty of traditional theranostic modes. In this study, a composite consisting of a thermosensitive hydrogel (polyvinyl alcohol-carboxylic acid hydrogel (PCF)) and a multifunctional nanoparticle (Fe3O4@Au/Mn(Zn)-4-carboxyphenyl porphyrin/polydopamine (FAMxP)) is developed to combine tumor immunogenic cell death (ICD)/immune checkpoint blockade (ICB) therapy under the guidance of magnetic resonance imaging (MRI) and fluorescence imaging (FI). It can not only further recognize the target cells through the folate receptor of tumor cells, but also produce thermal dissolution after exposure to near-infrared light to slowly release FAMxP in situ, thereby prolonging the treatment time and avoiding tumor recurrence. As FAMxP entered the tumor cells, it released FAMx in a pH-dependent manner. Chemodynamic, photothermal and photodynamic therapy can cause significant ICD in cancer cells. ICB can thus be further enhanced by injecting anti-programmed cell death ligand 1, improving the effectiveness of tumor treatment. The developed PCF-FAMxP composite hydrogel may represent an updated drug design approach with simple compositions for cooperative MRI/FI-guided targeted therapeutic pathways for tumors.

7.
Nano Lett ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860507

RESUMO

The majority of dislocations in nitride epilayers are edge threading dislocations (TDs), which diminish the performance of nitride devices. However, it is extremely difficult to reduce the edge TDs due to the lack of available slip systems. Here, we systematically investigate the formation mechanism of edge TDs and find that besides originating at the coalescence boundaries, these dislocations are also closely related to geometrical misfit dislocations at the interface. Based on this understanding, we propose a novel strategy to reduce the edge TD density of the GaN epilayer by nearly 1 order of magnitude via graphene-assisted remote heteroepitaxy. The first-principles calculations confirm that the insertion of graphene dramatically reduces the energy barrier required for interfacial sliding, which promotes a new strain release channel. This work provides a unique approach to directly suppress the formation of edge TDs at the source, thereby facilitating the enhanced performance of photoelectronic and electronic devices.

8.
BMC Cardiovasc Disord ; 24(1): 267, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773388

RESUMO

BACKGROUND: The effect of nonalcoholic fatty liver disease (NAFLD) on major adverse cardiovascular events (MACEs) can be influenced by the degree of coronary artery stenosis. However, the association between the severity of NAFLD and MACEs in patients who underwent coronary computed tomography angiography (CCTA) is unclear. METHODS: A total of 341 NAFLD patients who underwent CCTA were enrolled. The severity of NAFLD was divided into mild NAFLD and moderate-severe NAFLD by abdominal CT results. The degree of coronary artery stenosis was evaluated by using Coronary Artery Disease Reporting and Data System (CAD-RADS) category. Cox regression analysis and Kaplan-Meier analysis were used to assess poor prognosis. RESULTS: During the follow-up period, 45 of 341 NAFLD patients (13.20%) who underwent CCTA occurred MACEs. The severity of NAFLD (hazard ratio [HR] = 2.95[1.54-5.66]; p = 0.001) and CAD-RADS categories 3-5 (HR = 16.31[6.34-41.92]; p < 0.001) were independent risk factors for MACEs. The Kaplan-Meier analysis showed that moderate to severe NAFLD patients had a worsen prognosis than mild NAFLD patients (log-rank p < 0.001). Moreover, the combined receiver operating characteristic curve of the severity of NAFLD and CAD-RADS category showed a good predicting performance for the risk of MACEs, with an area under the curve of 0.849 (95% CI = 0.786-0.911). CONCLUSION: The severity of NAFLD was independent risk factor for MACEs in patients with obstructive CAD, having CAD-RADS 3-5 categories on CCTA.


Assuntos
Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Estenose Coronária , Hepatopatia Gordurosa não Alcoólica , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Humanos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Medição de Risco , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/complicações , Idoso , Prognóstico , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/mortalidade , Estudos Retrospectivos , Fatores de Tempo
9.
Nutrients ; 16(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794748

RESUMO

The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.


Assuntos
Constipação Intestinal , Fraturas Ósseas , Lacticaseibacillus rhamnosus , Complicações Pós-Operatórias , Probióticos , Humanos , Constipação Intestinal/terapia , Probióticos/uso terapêutico , Probióticos/administração & dosagem , Feminino , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Método Simples-Cego , Fraturas Ósseas/cirurgia , Fraturas Ósseas/complicações , Adulto , Microbioma Gastrointestinal , Fezes/microbiologia , Idoso , Resultado do Tratamento
10.
Mater Today Bio ; 26: 101089, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38779557

RESUMO

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

11.
Cir Cir ; 92(2): 211-218, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38782385

RESUMO

OBJECTIVES: The aim of the study was to investigate the clinical effect of stainless-steel wire fixation on the early mouth-opening movement of an intracapsular fracture involving the condylar process. MATERIALS AND METHODS: In this study, patients who underwent mandibular condylar intracapsular fracture surgery in our hospital from 2012 to 2020 were selected as research subjects. A total of 44 patients received steel wire internal fixation treatment, 32 patients received titanium plate-and-nail rigid internal fixation, and 28 patients underwent conservative non-surgical treatment. RESULTS: For the patients in the stainless-steel wire group, the degree of mouth opening reached normal levels of 3.7 cm approximately 10 days after surgery. The recovery time for the patients in the titanium plate-and-nail rigid internal-fixation group was 21 days, while the patients in the conservative treatment group needed 60 days to recover. CONCLUSION: The treatment of fixation with a stainless-steel wire for intracapsular condylar fracture reduced the time taken to perform mouth-opening exercises and improved the recovery rate of patients.


OBJETIVO: Explorar el efecto clínico de la fijación de alambre de acero inoxidable en el movimiento temprano de apertura de la boca en la fractura interna del cóndilo. MÉTODO: Este estudio seleccionó a pacientes que se sometieron a cirugía de fractura intracapsular de cóndilo en nuestro hospital de 2012 a 2020 como sujetos de investigación. Un total de 44 pacientes recibieron tratamiento de fijación interna de alambre de acero, 32 recibieron placa de titanio y fijación interna con clavos, y 28 recibieron tratamiento conservador no quirúrgico. RESULTADOS: En los pacientes del grupo de alambre de acero inoxidable, alrededor de 10 días después de la cirugía el grado de apertura de la boca alcanzó un valor normal de 3.7 cm. El tiempo de recuperación de los pacientes en el grupo de fijación interna con clavos y placa de titanio fue de 21 días, mientras que los pacientes en el grupo de tratamiento conservador tardaron 60 días en recuperarse. CONCLUSIONES: La fijación con alambre de acero inoxidable para el tratamiento de la fractura intracapsular del cóndilo acorta el tiempo hasta la apertura de la boca y mejora la tasa de recuperación de los pacientes.


Assuntos
Placas Ósseas , Fios Ortopédicos , Fixação Interna de Fraturas , Côndilo Mandibular , Fraturas Mandibulares , Aço Inoxidável , Humanos , Fixação Interna de Fraturas/métodos , Fixação Interna de Fraturas/instrumentação , Fraturas Mandibulares/cirurgia , Côndilo Mandibular/lesões , Côndilo Mandibular/cirurgia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Titânio , Amplitude de Movimento Articular , Pinos Ortopédicos , Adulto Jovem , Estudos Retrospectivos
12.
Br J Pharmacol ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38779864

RESUMO

BACKGROUND AND PURPOSE: Sevoflurane, a commonly used inhaled anaesthetic known for its favourable safety profile and rapid onset and offset, has not been thoroughly investigated as a potential treatment for depression. In this study, we reveal the mechanism through which sevoflurane delivers enduring antidepressant effects. EXPERIMENTAL APPROACH: To assess the antidepressant effects of sevoflurane, behavioural tests were conducted, along with in vitro and ex vivo whole-cell patch-clamp recordings, to examine the effects on GluN1-GluN2 incorporated N-methyl-d-aspartate (NMDA) receptors (NMDARs) and neuronal circuitry in the medial prefrontal cortex (mPFC). Multiple-channel electrophysiology in freely moving mice was performed to evaluate sevoflurane's effects on neuronal activity, and GluN2D knockout (grin2d-/-) mice were used to confirm the requirement of GluN2D for the antidepressant effects. KEY RESULTS: Repeated exposure to subanaesthetic doses of sevoflurane produced sustained antidepressant effects lasting up to 2 weeks. Sevoflurane preferentially inhibited GluN2C- and GluN2D-containing NMDARs, causing a reduction in interneuron activity. In contrast, sevoflurane increased action potentials (AP) firing and decreased spontaneous inhibitory postsynaptic current (sIPSC) in mPFC pyramidal neurons, demonstrating a disinhibitory effect. These effects were absent in grin2d-/- mice, and both pharmacological blockade and genetic knockout of GluN2D abolished sevoflurane's antidepressant actions, suggesting that GluN2D is essential for its antidepressant effect. CONCLUSION AND IMPLICATIONS: Sevoflurane directly targets GluN2D, leading to a specific decrease in interneuron activity and subsequent disinhibition of pyramidal neurons, which may underpin its antidepressant effects. Targeting the GluN2D subunit could hold promise as a potential therapeutic strategy for treating depression.

13.
Front Microbiol ; 15: 1329976, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38803377

RESUMO

Hemorrhoids are a common ailment that can cause significant disruptions to one's daily life. While some researchers have speculated about a potential link between hemorrhoid development and gut microbes, there is currently insufficient evidence to support this claim. In this study, we collected samples from 60 hemorrhoid patients and analyzed the composition and characteristics of microbiomes in hemorrhoids. PCoA results revealed distinct differences between the microbiomes of hemorrhoids, skin-originated microbiomes, and gut microbes, highlighting the complex nature of hemorrhoidal microbiomes. The distribution characteristics of Staphylococcus suggest that the skin microbiome influences the microbiome of hemorrhoids. Additionally, we observed higher levels of Prevotella in two cases of thrombosed hemorrhoids compared to non-thrombosed hemorrhoids. This finding suggests that Prevotella may play a crucial role in the development of thrombosed hemorrhoids.

14.
Sci Rep ; 14(1): 12135, 2024 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802446

RESUMO

To compare diffusion-kurtosis imaging (DKI) and diffusion-weighted imaging (DWI) parameters of single-shot echo-planar imaging (ss-EPI) and readout-segmented echo-planar imaging (rs-EPI) in the differentiation of luminal vs. non-luminal breast cancer using histogram analysis. One hundred and sixty women with 111 luminal and 49 non-luminal breast lesions were enrolled in this study. All patients underwent ss-EPI and rs-EPI sequences on a 3.0T scanner. Histogram metrics were derived from mean kurtosis (MK), mean diffusion (MD) and the apparent diffusion coefficient (ADC) maps of two DWI sequences respectively. Student's t test or Mann-Whitney U test was performed for differentiating luminal subtype from non-luminal subtype. The ROC curves were plotted for evaluating the diagnostic performances of significant histogram metrics in differentiating luminal from non-luminal BC. The histogram metrics MKmean, MK50th, MK75th of luminal BC were significantly higher than those of non-luminal BC for both two DWI sequences (all P<0.05). Histogram metrics from rs-EPI sequence had better diagnostic performance in differentiating luminal from non-Luminal breast cancer compared to those from ss-EPI sequence. MK75th derived from rs-EPI sequence was the most valuable single metric (AUC, 0.891; sensitivity, 78.4%; specificity, 87.8%) for differentiating luminal from non-luminal BC among all the histogram metrics. Histogram metrics of MK derived from rs-EPI yielded better diagnostic performance for distinguishing luminal from non-luminal BC than that from ss-EPI. MK75th was the most valuable metric among all the histogram metrics.


Assuntos
Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética , Imagem Ecoplanar , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Imagem Ecoplanar/métodos , Pessoa de Meia-Idade , Adulto , Imagem de Difusão por Ressonância Magnética/métodos , Idoso , Diagnóstico Diferencial , Curva ROC
15.
J Agric Food Chem ; 72(23): 13186-13195, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38814711

RESUMO

Ketopantoate hydroxymethyltransferase (KPHMT) plays a pivotal role in d-pantothenic acid biosynthesis. Most KPHMTs are homodecamers with low thermal stability, posing challenges for protein engineering and limiting output enhancement. Previously, a high-enzyme activity KPHMT mutant (K25A/E189S) from Corynebacterium glutamicum was screened as mother strain (M0). Building upon this strain, our study focused on interface engineering modifications, employing a multifaceted approach including integrating folding-free energy calculation, B-factor analysis, and conserved site analysis. Preliminary screening led to the selection of five mutants in the interface─E106S, E98T, E98N, S247I, and S247D─showing improved thermal stability, culminating in the double-site mutant M8 (M0-E98N/S247D). M8 exhibited a T1/2 value of 288.79 min at 50 °C, showing a 3.29-fold increase compared to M0. Meanwhile, the Tm value of M8 was elevated from 53.2 to 59.6 °C. Investigations of structural and molecular dynamics simulations revealed alterations in surface electrostatic charge distribution and the formation of increased hydrogen bonds between subunits, contributing to enhanced thermal stability. This investigation corroborates the efficacy of interface engineering modifications in bolstering KPHMT stability while showing its potential for positively impacting industrial d-pantothenic acid synthesis.


Assuntos
Proteínas de Bactérias , Corynebacterium glutamicum , Estabilidade Enzimática , Engenharia de Proteínas , Corynebacterium glutamicum/enzimologia , Corynebacterium glutamicum/genética , Corynebacterium glutamicum/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Simulação de Dinâmica Molecular , Cinética , Temperatura Alta
16.
Discov Oncol ; 15(1): 194, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806979

RESUMO

Accumulating evidence indicates that exosomal proteins are critical in diagnosing malignant tumors. To identify novel exosomal biomarkers for lung cancer diagnosis, we isolated plasma exosomes from 517 lung cancer patients and 168 healthy controls (NLs)-186 lung adenocarcinoma (LUAD) patients (screening (SN): 20, validation (VD): 166), 159 lung squamous carcinoma (LUSC) patients (SN: 20, VD: 139), 172 benign nodules (LUBN) patients (SN: 20, VD: 152) and 168 NLs (SN: 20, VD: 148)-and randomly assigned them to the SN or VD group. Proteomic analysis by LC-MS/MS and PRM were performed on all groups. The candidate humoral markers were evaluated and screened by a machine learning method. All selected biomarkers were identified in the VD groups. For LUAD, a 7-protein panel had AUCs of 97.9% and 87.6% in the training and test sets, respectively, and 89.5% for early LUAD. For LUSC, an 8-protein panel showed AUCs of 99.1% and 87.0% in the training and test sets and 92.3% for early LUSC. For LUAD + LUSC (LC), an 8-protein panel showed AUCs of 85.9% and 80.3% in the training and test sets and 87.1% for early LC diagnosis. The characteristics of the exosomal proteome make exosomes potential diagnostic tools.

17.
Cancer Med ; 13(11): e7155, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38808852

RESUMO

BACKGROUND: For medullary thyroid carcinoma (MTC) with no positive findings in the lateral neck before surgery, whether prophylactic lateral neck dissection (LND) is needed remains controversial. A better way to predict occult metastasis in the lateral neck is needed. METHODS: From January 2010 to January 2022, patients who were diagnosed with MTC and underwent primary surgery at our hospital were retrospectively reviewed. We collected the patients' baseline characteristics, surgical procedure, and rescored the ultrasound images of the primary lesions using American College of Radiology (ACR) Thyroid Imaging, Reporting and Data System (TI-RADS). Regularized logistic regression, 5-fold cross-validation and decision curve analysis was applied for lateral lymph node metastasis (LLNM) model's development and validation. Then, we tested the predictive ability of the LLNM model for occult LLNM in cN0-1a patients. RESULTS: A total of 218 patients were enrolled. Five baseline characteristics and two TI-RADS features were identified as high-risk factors for LLNM: gender, baseline calcitonin (Ctn), tumor size, multifocality, and central lymph node (CLN) status, as well as TI-RADS margin and level. A LLNM model was developed and showed a good discrimination with 5-fold cross-validation mean area under curve (AUC) = 0.92 ± 0.03 in the test dataset. Among cN0-1a patients, our LLNM model achieved an AUC of 0.91 (95% CI, 0.88-0.94) for predicting occult LLNM, which was significantly higher than the AUCs of baseline Ctn (0.83) and CLN status (0.64). CONCLUSIONS: We developed a LLNM prediction model for MTC using machine learning based on clinical baseline characteristics and TI-RADS. Our model can predict occult LLNM for cN0-1a patients more accurately, then benefit the decision of prophylactic LND.


Assuntos
Carcinoma Neuroendócrino , Metástase Linfática , Aprendizado de Máquina , Neoplasias da Glândula Tireoide , Humanos , Neoplasias da Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/cirurgia , Estudos Retrospectivos , Adulto , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Esvaziamento Cervical , Idoso , Tireoidectomia
18.
Technol Cancer Res Treat ; 23: 15330338241246653, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38773763

RESUMO

Purpose: Head and neck adenoid cystic carcinoma (HNACC) is a radioresistant tumor. Particle therapy, primarily proton beam therapy and carbon-ion radiation, is a potential radiotherapy treatment for radioresistant malignancies. This study aims to conduct a meta-analysis to evaluate the impact of charged particle radiation therapy on HNACC. Methods: A comprehensive search was conducted in Pubmed, Cochrane Library, Web of Science, Embase, and Medline until December 31, 2022. The primary endpoints were overall survival (OS), local control (LC), and progression-free survival (PFS), while secondary outcomes included treatment-related toxicity. Version 17.0 of STATA was used for all analyses. Results: A total of 14 studies, involving 1297 patients, were included in the analysis. The pooled 5-year OS and PFS rates for primary HNACC were 78% (95% confidence interval [CI] = 66-91%) and 62% (95% CI = 47-77%), respectively. For all patients included, the pooled 2-year and 5-year OS, LC, and PFS rates were as follows: 86.1% (95% CI = 95-100%) and 77% (95% CI = 73-82%), 92% (95% CI = 84-100%) and 73% (95% CI = 61-85%), and 76% (95% CI = 68-84%) and 55% (95% CI = 48-62%), respectively. The rates of grade 3 and above acute toxicity were 22% (95% CI = 13-32%), while late toxicity rates were 8% (95% CI = 3-13%). Conclusions: Particle therapy has the potential to improve treatment outcomes and raise the quality of life for HNACC patients. However, further research and optimization are needed due to the limited availability and cost considerations associated with this treatment modality.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma Adenoide Cístico/radioterapia , Carcinoma Adenoide Cístico/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Radioterapia com Íons Pesados/efeitos adversos , Radioterapia com Íons Pesados/métodos , Resultado do Tratamento
19.
J Affect Disord ; 359: 241-252, 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-38768820

RESUMO

BACKGROUND: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated. METHODS: We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Delta-subunit-deficient (Gabrd-/-) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice. RESULTS: We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo. LIMITATIONS: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types. CONCLUSION: Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice.


Assuntos
Astrócitos , Atrofia , Depressão Pós-Parto , Modelos Animais de Doenças , Prostaglandina D2 , Transdução de Sinais , Animais , Astrócitos/patologia , Astrócitos/metabolismo , Feminino , Depressão Pós-Parto/patologia , Depressão Pós-Parto/metabolismo , Camundongos , Transdução de Sinais/fisiologia , Prostaglandina D2/metabolismo , Núcleo Central da Amígdala/metabolismo , Oxirredutases Intramoleculares/genética , Oxirredutases Intramoleculares/metabolismo , Lipocalinas/genética , Lipocalinas/metabolismo , Quinases da Família src/metabolismo , Camundongos Knockout
20.
Biochem Biophys Res Commun ; 720: 150073, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38754161

RESUMO

Astrocytes in the central nervous system play a vital role in modulating synaptic transmission and neuronal activation by releasing gliotransmitters. The 5-HTergic neurons in the ventrolateral periaqueductal gray (vlPAG) are important in anxiety processing. However, it remains uncertain whether the regulation of astrocytic activity on vlPAG 5-HTergic neurons is involved in anxiety processing. Here, through chemogenetic manipulation, we explored the impact of astrocytic activity in the PAG on the regulation of anxiety. To determine the role of astrocytes in the control of anxiety, we induced anxiety-like behaviors in mice through foot shock and investigated their effects on synaptic transmission and neuronal excitability in vlPAG 5-HTergic neurons. Foot shock caused anxiety-like behaviors, which were accompanied with the increase of the amplitude and frequency of miniature excitatory postsynaptic currents (mEPSCs), the area of slow inward currents (SICs), and the spike frequency of action potentials (AP) in vlPAG 5-HTergic neurons. The chemogenetic inhibition of vlPAG astrocytes was found to attenuate stress-induced anxiety-like behaviors and decrease the heightened synaptic transmission and neuronal excitability of vlPAG 5-HTergic neurons. Conversely, chemogenetic activation of vlPAG astrocytes triggered anxiety-like behaviors, enhanced synaptic transmission, and increased the excitability of vlPAG 5-HTergic neurons in unstressed mice. In summary, this study has provided initial insights into the pathway by which astrocytes influence behavior through the rapid regulation of associated neurons. This offers a new perspective for the investigation of the biological mechanisms underlying anxiety.


Assuntos
Ansiedade , Astrócitos , Substância Cinzenta Periaquedutal , Animais , Substância Cinzenta Periaquedutal/fisiologia , Astrócitos/metabolismo , Ansiedade/fisiopatologia , Camundongos , Masculino , Transmissão Sináptica/fisiologia , Comportamento Animal/fisiologia , Camundongos Endogâmicos C57BL , Potenciais Pós-Sinápticos Excitadores/fisiologia , Estresse Psicológico/fisiopatologia , Neurônios/fisiologia
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