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1.
Transl Lung Cancer Res ; 13(5): 965-985, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38854934

RESUMO

Background: Tumor metastasis commonly affects pleura in advanced lung cancer and results in malignant pleural effusion (MPE). MPE is related to poor prognosis, but without systematic investigation on different cell types and their crosstalk at single cell resolution. Methods: We conducted single-cell RNA-sequencing (scRNA-seq) of lung cancer patients with pleural effusion. Next, our data were integrated with 5 datasets derived from individuals under normal, non-malignant disease and lung carcinomatous conditions. Mesothelial cells were re-clustered and their interactions with epithelial cells were comprehensively analyzed. Taking advantage of inferred ligand-receptor pairs, a prediction model of prognosis was constructed. The co-culture of mesothelial cells and malignant epithelial cells in vitro and RNA-seq was performed. Epidermal growth factor receptor (EGFR) antagonist cetuximab was utilized to prevent the lung cancer cells' invasiveness. Spatial distribution of cells in lung adenocarcinoma patients' samples were also analyzed to validate our findings. Results: The most distinctive transcriptome profiles between tumor and control were revealed in mesothelial cells, which is the predominate cell type of pleura. Five subtypes were divided, including one predominately identified in MPE which was characterized by enriched cancer-related pathways (e.g., cell migration) along evolutionary trajectory from normal mesothelial cells. Cancer-associated mesothelial cells (CAMCs) exhibited varied interactions with different subtypes of malignant epithelial cells, and multiple ligands/receptors exhibited significant correlation with poor prognosis. Experimentally, mesothelial cells can increase the migration ability of lung cancer cells through co-culturing. EGFR was the only affected gene in cancer cells that exhibited interaction with mesothelial cells and was associated with poor prognosis. Using EGFR antagonist cetuximab prevented the lung cancer cells' increased invasiveness caused by mesothelial cells. Moreover, epithelial mitogen (EPGN)-EGFR interaction was supported through spatial distribution analysis, revealing the significant proximity between EPGN+ mesothelial cells and EGFR+ epithelial cells. Conclusions: Our findings highlighted the important role of mesothelial cells and their interactions with cancer cells in pleural metastasis of lung cancer, providing potential targets for treatment.

2.
Endocrine ; 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38822895

RESUMO

PURPOSE: To investigate the implications of Lobectomy (LT) or total thyroidectomy (TT) on psychological distress and sleep quality in PTC patients with a low to intermediate risk of recurrence and tumors measuring 1 to 4 cm. METHODS: Patients who were admitted to our hospital between July 2021 and July 2022 were prospectively enrolled in this survey. Psychological distress and sleep quality were assessed at hospitalization, discharge, and 1, 3, and 6 months post-treatment using validated scales. Participants were divided into LT and TT groups, with propensity score matching (PSM) applied for analyses. RESULTS: Among 525 eligible PTC patients, 440 patients completed all the questionnaires throughout the follow-up. After PSM, 166 patients underwent LT, and 166 patients underwent TT were enrolled. The psychological distress and sleep quality of patients in the LT group remained relatively stable during the 6-month follow-up, but patients in the TT group may have faced greater sleep quality concerns in the longitudinal assessment. Additionally, the sleep quality of the TT group was also worse than that of the LT group postoperatively. CONCLUSIONS: The sleep quality rather than other psychological distress of patients with PTC with a low to intermediate risk of recurrence is associated with the extent of surgery.

3.
Plants (Basel) ; 13(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38891345

RESUMO

The investigation of taxonomic diversity within island plant communities stands as a central focus in the field of island biogeography. Phylogenetic diversity is crucial for unraveling the evolutionary history, ecological functions, and species combinations within island plant communities. Island effects (area and isolation effect) may shape species distribution patterns, habitat heterogeneity affects habitat diversity, and anthropogenic disturbances can lead to species extinction and habitat destruction, thus impacting both species diversity and phylogenetic diversity. To investigate how taxonomic and phylogenetic diversity in island natural plant communities respond to island effects, habitat heterogeneity, and anthropogenic disturbances, we took the main island of Haitan (a land-bridge island) and nine surrounding islands (oceanic islands) of varying sizes as the subjects of our study on the Pingtan islands. We aim to elucidate the influence of island effects, habitat heterogeneity, and anthropogenic disturbances on taxonomic and phylogenetic diversity. The results showed that, (1) Both the taxonomic and phylogenetic diversity of plants on the Pingtan islands followed the island area effect, indicating that as the island area increases, both taxonomic and phylogenetic diversity also increase. (2) Island effects and habitat heterogeneity were found to enhance taxonomic and phylogenetic diversity, whereas anthropogenic disturbances were associated with a decrease in both taxonomic and phylogenetic diversity. Furthermore, the synergistic influence of island effects, habitat heterogeneity, and anthropogenic disturbances collectively exerted a negative impact on both taxonomic and phylogenetic diversity. (3) The contribution of explanatory variables of anthropogenic disturbances for taxonomic and phylogenetic diversity was higher than that of island effects and habitat heterogeneity. Additionally, the contribution of the explanatory variables under the combined influence of island effects, habitat heterogeneity, and anthropogenic disturbances is higher than that of the individual variables for island effects and habitat heterogeneity. These findings suggest that anthropogenic disturbances emerged as the dominant factors influencing both taxonomic and phylogenetic diversity. These findings demonstrate the intricate interplay between island effects, habitat heterogeneity, and anthropogenic disturbances, highlighting their combined influence on both taxonomic and phylogenetic diversity on island.

4.
Adv Sci (Weinh) ; : e2403551, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38868953

RESUMO

With the onset of the 5G era, wearable flexible electronic devices have developed rapidly and gradually entered the daily life of people. However, the vast majority of research focuses on the integration of functions and performance improvement, while ignoring electromagnetic hazards caused by devices. Herein, the 3D double conductive networks are constructed through a repetitive vacuum-assisted dip-coating technique to decorate the 2D MXene and 1D silver nanowires on the melamine foam. Benefiting from the unique porous structure and multi-scale interconnected frame, the resultant composite foam exhibited high electrical conductivity, low density, superb electromagnetic interference shielding (48.32 dB), and Joule heating performance (up to 90.8 °C under 0.8 V). Furthermore, a single-electrode triboelectric nanogenerator (TENG) with powerful energy harvesting capability is assembled by combining the composite foam with an ultra-thin Ecoflex film and a polyvinylidene fluoride film. Simultaneously, the foam-based TENG can also be considered a reliable wearable sensor for monitoring activity patterns in different parts of the human body. The versatility and scalable manufacturing of high-performance composite foams will provide new design ideas for the development of next-generation flexible wearable devices.

5.
Artigo em Inglês | MEDLINE | ID: mdl-38878281

RESUMO

PURPOSE: Teprotumumab is the only drug approval by The US Food and Drug Administration (FDA) for the treatment of thyroid eye disease (TED), which targets the insulin-like growth factor-1 receptor. This study aimed to identify potential safety signals of teprotumumab by analyzing post-marketing safety data from the FDA Adverse Event Reporting System (FAERS) database in 2023. METHODS: The case/non-case approach was used to estimate the reporting odds ratio (ROR) and information component (IC) with relevant confidence intervals (95% CI) for adverse events (AEs) that numbered three or more. RESULTS: Total of 2158 cases were included in the analysis. Main safety signals identified were ear and labyrinth disorders, reproductive system and breast disorders, metabolism and nutrition disorders and gastrointestinal disorders. Specifically, autophony (ROR [95% CI] = 4188.34 [1403.29-12500.8]), eyelid retraction (ROR [95% CI] = 2094.17 [850.69-5155.29]), deafness permanent (ROR [95% CI] = 1552.35 [789.07-3053.98]), deafness bilateral (ROR [95% CI] = 73.12 [41.14-129.97]), inflammatory bowel disease (ROR [95% CI] = 23.26 [13.46-40.19]), hyperglycaemic hyperosmolar nonketotic syndrome (ROR [95% CI] = 17.75 [5.70-55.28]) and amenorrhoea (ROR [95% CI] = 47.98 [36.22-63.54]) showed significant safety signals of teprotumumab. CONCLUSIONS: This study identified ear and labyrinth disorders, reproductive system and breast disorders, as specific safety signals of teprotumumab. Clinicians and pharmacists should be vigilant regarding these AEs. However, available data are currently insufficient, and further pharmacovigilance and surveillance are needed to fully understand this issue.

6.
JAMA Pediatr ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856986

RESUMO

Importance: Overweight and obesity in childhood and adolescence is a global health issue associated with adverse outcomes throughout the life course. Objective: To estimate worldwide prevalence of overweight and obesity in children and adolescents from 2000 to 2023 and to assess potential risk factors for and comorbidities of obesity. Data Sources: MEDLINE, Web of Science, Embase, and Cochrane. Study Selection: The inclusion criteria were: (1) studies provided adequate information, (2) diagnosis based on body mass index cutoffs proposed by accepted references, (3) studies performed on general population between January 2000 and March 2023, (4) participants were younger than 18 years. Data Extraction and Synthesis: The current study was performed in accordance with the Meta-analysis of Observational Studies in Epidemiology guidelines. DerSimonian-Laird random-effects model with Free-Tukey double arcsine transformation was used for data analysis. Sensitivity analysis, meta-regression, and subgroup analysis of obesity among children and adolescents were conducted. Main Outcomes and Measures: Prevalence of overweight and obesity among children and adolescents assessed by World Health Organization, International Obesity Task Force, the US Centers for Disease Control and Prevention, or other national references. Results: A total of 2033 studies from 154 different countries or regions involving 45 890 555 individuals were included. The overall prevalence of obesity in children and adolescents was 8.5% (95% CI 8.2-8.8). We found that the prevalence varied across countries, ranging from 0.4% (Vanuatu) to 28.4% (Puerto Rico). Higher prevalence of obesity among children and adolescents was reported in countries with Human Development Index scores of 0.8 or greater and high-income countries or regions. Compared to 2000 to 2011, a 1.5-fold increase in the prevalence of obesity was observed in 2012 to 2023. Substantial differences in rates of obesity were noted when stratified by 11 risk factors. Children and adolescents with obesity had a high risk of depression and hypertension. The pooled estimates of overweight and excess weight in children and adolescents were 14.8% (95% CI 14.5-15.1) and 22.2% (95% CI 21.6-22.8), respectively. Conclusions and Relevance: This study's findings indicated 1 of 5 children or adolescents experienced excess weight and that rates of excess weight varied by regional income and Human Development Index. Excess weight among children and adolescents was associated with a mix of inherent, behavioral, environmental, and sociocultural influences that need the attention and committed intervention of primary care professionals, clinicians, health authorities, and the general public.

7.
Int J Nanomedicine ; 19: 4377-4409, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774029

RESUMO

Angiogenesis, or the formation of new blood vessels, is a natural defensive mechanism that aids in the restoration of oxygen and nutrition delivery to injured brain tissue after an ischemic stroke. Angiogenesis, by increasing vessel development, may maintain brain perfusion, enabling neuronal survival, brain plasticity, and neurologic recovery. Induction of angiogenesis and the formation of new vessels aid in neurorepair processes such as neurogenesis and synaptogenesis. Advanced nano drug delivery systems hold promise for treatment stroke by facilitating efficient transportation across the the blood-brain barrier and maintaining optimal drug concentrations. Nanoparticle has recently been shown to greatly boost angiogenesis and decrease vascular permeability, as well as improve neuroplasticity and neurological recovery after ischemic stroke. We describe current breakthroughs in the development of nanoparticle-based treatments for better angiogenesis therapy for ischemic stroke employing polymeric nanoparticles, liposomes, inorganic nanoparticles, and biomimetic nanoparticles in this study. We outline new nanoparticles in detail, review the hurdles and strategies for conveying nanoparticle to lesions, and demonstrate the most recent advances in nanoparticle in angiogenesis for stroke treatment.


Assuntos
AVC Isquêmico , Nanopartículas , Neovascularização Fisiológica , Humanos , AVC Isquêmico/tratamento farmacológico , Animais , Nanopartículas/química , Neovascularização Fisiológica/efeitos dos fármacos , Barreira Hematoencefálica/efeitos dos fármacos , Lipossomos/química , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Fármacos por Nanopartículas/química , Angiogênese
9.
J Chem Inf Model ; 64(10): 4002-4008, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38798191

RESUMO

Transcription factors (TFs) are important regulatory elements for vital cellular activities, and the identification of transcription factor binding sites (TFBS) can help to explore gene regulatory mechanisms. Research studies have proved that cfDNA (cell-free DNA) shows relatively higher coverage at TFBS due to the protection by TF from degradation by nucleases and short fragments of cfDNA are enriched in TFBS. However, there are still great difficulties in the noninvasive identification of TFBSs from experimental techniques. In this study, we propose a deep learning-based approach that can noninvasively predict TFBSs of cfDNA by learning sequence information from known TFBSs through convolutional neural networks. Under the addition of long short-term memory, our model achieved an area under the curve of 84%. Based on this model to predict cfDNA, we found consistent motifs in cfDNA fragments and lower coverage occurred upstream and downstream of these cfDNA fragments, which is consistent with a previous study. We also found that the binding sites of the same TF differ in different cell lines. TF-specific target genes were detected from cfDNA and were enriched in cancer-related pathways. In summary, our method of locating TFBSs from plasma has the potential to reflect the intrinsic regulatory mechanism from a noninvasive perspective and provide technical guidance for dynamic monitoring of disease in clinical practice.


Assuntos
Ácidos Nucleicos Livres , Aprendizado Profundo , Fatores de Transcrição , Fatores de Transcrição/metabolismo , Fatores de Transcrição/química , Sítios de Ligação , Humanos , Ácidos Nucleicos Livres/metabolismo , Ácidos Nucleicos Livres/química , DNA/metabolismo , DNA/química
10.
Biomed Res Int ; 2024: 5526942, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38726293

RESUMO

Background: Although inappropriate gestational weight gain is considered closely related to adverse maternal and birth outcomes globally, little evidence was found in low- and middle-income countries. Study Objectives. This study is aimed at identifying the determinants of gestational weight gain and examine the association between gestational weight gain and maternal and birth outcomes in the Northern Region of Ghana. Study Methods. The study used a facility-based cross-sectional study design involving 611 antenatal and delivery records in Tatale district, Tamale west, and Gushegu municipal hospitals. A two-stage sampling method involving cluster and simple random sampling was employed. Descriptive statistical analysis and measures of central tendency were used to describe the sample. The multinomial logistic regression model was used to determine the determinants of gestational weight gain and its association with maternal and birth outcomes. Results: Among the 611 women included in the study, 516 (84.45%) had inadequate gestational weight gain, and 19 (3.11%) had excessive gestational weight gain. The gestational weight gain ranged from 2 kg to 25 kg with a mean of 7.26 ± 3.70 kg. The risk factor for inadequate gestational weight gain was low prepregnancy BMI (adjusted odds ratio (AOR) = 1.33, 95% CI = 1.18 - 2.57, P = 0.002). Pregnant women who had inadequate gestational weight gain were significantly less likely to deliver through caesarean section (AOR = 0.27, 95% CI = 0.12 - 0.61, P = 0.002), and those who had excessive weight gain were more likely to undergo caesarean section (AOR = 19.81, 95% CI = 5.38 - 72.91, P = 0.001). The odds of premature delivery (birth < 37 weeks) among pregnant women with inadequate weight gain were 2.88 (95% CI = 1.27 - 6.50, P = 0.011). Furthermore, subjects who had excessive weight gain were 43.80 times more likely to give birth to babies with macrosomia (95% CI = 7.07 - 271.23, P = 0.001). Conclusion: Inappropriate gestational weight gain is prevalent in Ghana, which is associated with caesarean section, preterm delivery, delivery complications, and macrosomia. Urgent policy interventions are needed to improve on the frequent monitoring and management of gestational weight gain of pregnant women till term.


Assuntos
Ganho de Peso na Gestação , Resultado da Gravidez , Humanos , Feminino , Gravidez , Gana/epidemiologia , Adulto , Resultado da Gravidez/epidemiologia , Fatores de Risco , Estudos Transversais , Cesárea/estatística & dados numéricos , Recém-Nascido , Índice de Massa Corporal , Adulto Jovem , Peso ao Nascer , Aumento de Peso/fisiologia
11.
Phytomedicine ; 129: 155670, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38704915

RESUMO

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is recognized as the most aggressive and malignant form of thyroid cancer, underscoring the critical need for effective therapeutic strategies to curb its progression and improve patient prognosis. Halofuginone (HF), a derivative of febrifugine, has displayed antitumor properties across various cancer types. However, there is a paucity of published research focused on the potential of HF to enhance the clinical efficacy of treating ATC. OBJECTIVE: In this study, we thoroughly investigated the antitumor effects and mechanisms of HF in ATC, aiming to discover lead compounds for treating ATC and reveal novel therapeutic targets for ATC tumors. METHODS: A series of assays, including CCK8, colony formation, tumor xenograft models, and ATC tumor organoid experiments, were conducted to evaluate the anticancer properties of HF both in vitro and in vivo. Techniques such as drug affinity responsive target stability (DARTS), western blot, immunofluorescence, and immunohistochemistry were employed to pinpoint HF target proteins within ATC. Furthermore, we harnessed the GEPIA and GEO databases and performed immunohistochemistry to validate the therapeutic potential of the glutamyl-prolyl-tRNA-synthetase (EPRS)- activating transcription factor 4 (ATF4)- type I collagen (COLI) pathway axis in the context of ATC. The study also incorporated RNA sequencing analysis, confocal imaging, and flow cytometry to delve into the molecular mechanisms of HF in ATC. RESULTS: HF exhibited a substantial inhibitory impact on cell proliferation in vitro and on tumor growth in vivo. The DARTS results highlighted HF's influence on EPRS within ATC cells, triggering an amino acid starvation response (AASR) by suppressing EPRS expression, consequently leading to a reduction in COLI expression in ATC cells. The introduction of proline mitigated the effect of HF on ATF4 and COLI expression, indicating that the EPRS-ATF4-COLI pathway axis was a focal target of HF in ATC. Analysis of the expression levels of the EPRS, ATF4, and COLI proteins in thyroid tumors, along with an examination of the relationship between COLI expression and thyroid tumor stage, revealed that HF significantly inhibited the growth of ATC tumor organoids, demonstrating the therapeutic potential of targeting the EPRS-ATF4-COLI pathway axis in ATC. RNA sequencing analysis revealed significant differences in the pathways associated with metastasis and apoptosis between control and HF-treated cells. Transwell assays and flow cytometry experiments provided evidence of the capacity of HF to impede cell migration and induce apoptosis in ATC cells. Furthermore, HF hindered cell metastasis by suppressing the epithelial-mesenchymal transition (EMT) pathway, acting through the inhibition of FAK-AKT-NF-κB/Wnt-ß-catenin signaling and restraining angiogenesis via the VEGF pathway. HF also promoted apoptosis through the mitochondrial apoptotic pathway. CONCLUSION: This study provided inaugural evidence suggesting that HF could emerge as a promising therapeutic agent for the treatment of ATC. The EPRS-ATF4-COLI pathway axis stood out as a prospective biomarker and therapeutic target for ATC.


Assuntos
Fator 4 Ativador da Transcrição , Piperidinas , Quinazolinonas , Carcinoma Anaplásico da Tireoide , Neoplasias da Glândula Tireoide , Carcinoma Anaplásico da Tireoide/tratamento farmacológico , Fator 4 Ativador da Transcrição/metabolismo , Humanos , Animais , Linhagem Celular Tumoral , Neoplasias da Glândula Tireoide/tratamento farmacológico , Piperidinas/farmacologia , Quinazolinonas/farmacologia , Camundongos , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Transdução de Sinais/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C
12.
Biosens Bioelectron ; 259: 116365, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38759309

RESUMO

Effective wound management has the potential to reduce both the duration and cost of wound healing. However, traditional methods often rely on direct observation or complex and expensive biological testing to monitor and evaluate the invasive damage caused by wound healing, which can be time-consuming. Biosensors offer the advantage of precise and real-time monitoring, but existing devices are not suitable for integration with sensitive wound tissue due to their external dimensions. Here, we have designed a self-powered biosensing suture (SPBS) based on biofuel cells to accurately monitor glucose concentration at the wound site and promote wound healing. The anode of the SPBS consists of carbon nanotubes-modified carbon fibers, tetrathiafulvalene (TTF), and glucose oxidase (GOx), while the cathode is composed of Ag2O and carbon nanotubes modified nanotubes modified carbon fibers. It was observed that SPBS exhibited excellent physical and chemical stability in vitro. Regardless of different bending degrees or pH values, the maximum power density of SPBS remained above 92%, which is conducive to long-term dynamic evaluation. Furthermore, the voltage generated by SPBS reflects blood glucose concentration, and measurements at wound sites are consistent with those obtained using a commercially available blood glucose meter. SPBS achieves the healing effect of traditional medical sutures after complete healing within 14 days. It offers valuable insights for intelligent devices dedicated to real-time wound monitoring.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Suturas , Cicatrização , Técnicas Biossensoriais/instrumentação , Nanotubos de Carbono/química , Humanos , Glucose Oxidase/química , Desenho de Equipamento , Fontes de Energia Bioelétrica , Glicemia/análise , Animais , Glucose/análise , Glucose/isolamento & purificação , Fibra de Carbono/química
13.
Artigo em Inglês | MEDLINE | ID: mdl-38810928

RESUMO

OBJECTIVES: Tuberculous pleurisy is one of the most common types of extra-pulmonary tuberculosis, but the sensitivity of conventional mycobacterial culture (Culture) or Xpert MTB/RIF assay (Xpert) is not satisfying. This multicentre cohort study evaluated the accuracy of a new cell-free DNA droplet digital PCR assay (cf-ddPCR) for diagnosing tuberculous pleurisy. METHODS: Patients with suspected tuberculosis (≥5 years of age) with pleural effusion were consecutively recruited from nine research sites across six provinces in China between September 2020 to May 2022. Culture, Xpert, Xpert MTB/RIF Ultra assay (Ultra), real-time PCR, and cf-ddPCR were performed simultaneously for all specimens. RESULTS: A total of 321 participants were enrolled, and data from 281 (87.5%) participants were available, including 105 definite tuberculous pleurisy, 113 possible tuberculous pleurisy and 63 non-tuberculous pleurisy according to the composite reference standard. The sensitivity of cf-ddPCR was 90.5% (95/105, 95% CI, 82.8-95.1%) in the definite tuberculous pleurisy group, which was significantly higher than those of Culture (57.1%, 60/105, 95% CI, 47.1-66.6%, p < 0.001), Xpert (46.7%, 49/105, 95% CI, 37.0-56.6%, p < 0.001), Ultra (69.5%, 73/105, 95% CI, 59.7-77.9%, p < 0.001) and real-time PCR (75.2%, 79/105, 95% CI, 65.7-82.9%, p < 0.001). In possible tuberculous pleurisy, whose results of Culture and Xpert were both negative, the sensitivity of cf-ddPCR was 61.1% (69/113, 95% CI, 51.4-70.0%), which was still significantly higher than that of Ultra (27.4%, 31/113, 95% CI, 19.7-36.8%, p < 0.001) and real-time PCR (38.9%, 44/113, 95% CI, 30.0-48.6%, p < 0.001). DISCUSSION: The performance of cf-ddPCR is superior to Culture, Xpert, Ultra, and real-time PCR, indicating that improved diagnostic accuracy can be anticipated by incorporating this new assay.

14.
ACS Chem Neurosci ; 15(11): 2243-2252, 2024 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-38779816

RESUMO

Staining frozen sections is often required to distinguish cell types for spatial transcriptomic studies of the brain. The impact of the staining methods on the RNA integrity of the cells becomes one of the limitations of spatial transcriptome technology with microdissection. However, there is a lack of systematic comparisons of different staining modalities for the pretreatment of frozen sections of brain tissue as well as their effects on transcriptome sequencing results. In this study, four different staining methods were analyzed for their effect on RNA integrity in frozen sections of brain tissue. Subsequently, differences in RNA quality in frozen sections under different staining conditions and their impact on transcriptome sequencing results were assessed by RNA-seq. As one of the most commonly used methods for staining pathological sections, HE staining seriously affects the RNA quality of frozen sections of brain tissue. In contrast, the homemade cresyl violet staining method developed in this study has the advantages of short staining time, low cost, and less RNA degradation. The homemade cresyl violet staining proposed in this study can be applied instead of HE staining as an advance staining step for transcriptome studies in frozen sections of brain tissue. In the future, this staining method may be suitable for wide application in brain-related studies of frozen tissue sections. Moreover, it is expected to become a routine step for staining cells before sampling in brain science.


Assuntos
Encéfalo , Secções Congeladas , Coloração e Rotulagem , Animais , Encéfalo/metabolismo , Coloração e Rotulagem/métodos , Secções Congeladas/métodos , Crioultramicrotomia/métodos , Camundongos , Transcriptoma , Masculino , RNA/análise , Benzoxazinas , Camundongos Endogâmicos C57BL , Oxazinas
15.
Mol Pharmacol ; 106(1): 71-82, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38769019

RESUMO

Remdesivir (RDV), a broad-spectrum antiviral agent, is often used together with dexamethasone (DEX) for hospitalized COVID-19 patients requiring respiratory support. Potential hepatic adverse drug reaction is a safety concern associated with the use of RDV. We previously reported that DEX cotreatment effectively mitigates RDV-induced hepatotoxicity and reduces elevated serum alanine aminotransferase and aspartate aminotransferase levels in cultured human primary hepatocytes (HPH) and hospitalized COVID-19 patients, respectively. Yet, the precise mechanism behind this protective drug-drug interaction remains largely unknown. Here, we show that through the activation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling, RDV induces apoptosis (cleavage of caspases 8, 9, and 3), autophagy (increased autophagosome and LC3-II), and mitochondrial damages (decreased membrane potential, respiration, ATP levels, and increased expression of Bax and the released cytosolic cytochrome C) in HPH. Importantly, cotreatment with DEX partially reversed RDV-induced apoptosis, autophagy, and cell death. Mechanistically, DEX deactivates/dephosphorylates p38, JNK, and ERK1/2 signaling by enhancing the expression of dual specificity protein phosphatase 1 (DUSP1), a mitogen-activated protein kinase (MAPK) phosphatase, in a glucocorticoid receptor (GR)-dependent manner. Knockdown of GR in HPH attenuates DEX-mediated DUSP1 induction, MAPK dephosphorylation, as well as protection against RDV-induced hepatotoxicity. Collectively, our findings suggest a molecular mechanism by which DEX modulates the GR-DUSP1-MAPK regulatory axis to alleviate the adverse actions of RDV in the liver. SIGNIFICANCE STATEMENT: The research uncovers the molecular mechanisms by which dexamethasone safeguards against remdesivir-associated liver damage in the context of COVID-19 treatment.


Assuntos
Monofosfato de Adenosina , Alanina , Antivirais , Apoptose , Autofagia , Tratamento Farmacológico da COVID-19 , Doença Hepática Induzida por Substâncias e Drogas , Dexametasona , Fosfatase 1 de Especificidade Dupla , Hepatócitos , Dexametasona/farmacologia , Humanos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Alanina/análogos & derivados , Alanina/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Antivirais/farmacologia , Antivirais/efeitos adversos , Fosfatase 1 de Especificidade Dupla/metabolismo , Fosfatase 1 de Especificidade Dupla/genética , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Células Cultivadas , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
16.
Gland Surg ; 13(4): 500-511, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38720673

RESUMO

Background: Surgery is the only curative treatment strategy for parathyroid carcinoma (PC). However, the optimal extent of surgery remains uncertain, particularly regarding whether routine central lymph node dissection (LND) confers a survival advantage to patients with PC. This study aimed to evaluate the prognostic value of LND in PC patients. Methods: Patients diagnosed with PC between 2004 and 2018 were identified in the Surveillance, Epidemiology, and End Results (SEER)-18 registries. With inclusion and exclusion criteria, a total of 338 patients were included as cohort 1 to describe the characteristics of PC, while 215 patients were selected as cohort 2 to assess the effect of LND on cancer-specific survival (CSS). Univariate and multivariate Cox proportional hazards regression models were used to identify independent risk factors associated with CSS. Propensity score matching (PSM) was performed to adjust for potential confounding variables. The prognostic value of LND was further analyzed in subgroups stratified by predictors associated with CSS. Results: The 5- and 10-year CSS were 94.4% and 87.9% respectively in cohort 1. LND failed to significantly improve CSS in the entire cohort 2 and the PSM cohort 2. Large tumor size (>40 mm) and distant metastasis were independently associated with poor CSS. Subgroup analyses revealed that LND was not significantly associated with improved CSS in patients with aggressive PC, such as those with a tumor size greater than 40 mm. Unexpectedly, LND may compromise CSS in patients with distant disease (P=0.03). Conclusions: PC is a rare and indolent endocrine malignancy. The presence of large tumors and distant metastases are independent predictors of poor CSS. Routine central LND as part of initial surgery does not significantly improve CSS in PC patients, even for those with large tumors, lymph node metastasis, or distant disease.

17.
Rev Sci Instrum ; 95(4)2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38557878

RESUMO

With the rapid popularization of wireless electronic devices, there has been an increasing concern about the impacts of the electromagnetic environment on health. However, most research reports on the biological effects of microwaves have focused on a single frequency point. In reality, people are exposed to complex electromagnetic environments that consist of multiple frequency microwave signals in their daily lives. It is important to investigate whether multi-frequency combined microwave energies have different biological effects compared with single frequency microwave energy. Unfortunately, there are limited reports on this topic due to the lack of suitable platforms for research on multi-frequency microwave energy combined with biological exposure. To address this issue, this study presents a setup that has a very wide working frequency bandwidth and can be compatible with single frequency and multi-frequency microwave combined exposure. Moreover, it can achieve relatively equal exposure to multiple biological samples at any frequency point in the working frequency range, which is crucial for electromagnetic biology research. The experimental results are in good agreement with the simulation results, confirming its capability to facilitate the study of complex electromagnetic environment effects on organisms.


Assuntos
Micro-Ondas
18.
Head Neck ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38572629

RESUMO

BACKGROUND: Oncocytic carcinoma of the thyroid (OCA) is an independent type of thyroid cancer. Radioactive iodine (RAI) therapy was frequently administered to OCA patients, but its contribution to improving survival is indefinite. METHODS: 4641 OCA patients from 2000 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. Cox proportional hazard regression and competing risk analysis were applied. RESULTS: Tumor size, SEER stage, primary surgery, and neck dissection were prognostic factors for cancer-specific survival. The results of competing risk analysis demonstrated that age over 55 years dramatically increased non-OCA death risks. Treatments that improve non-OCA survival (including total thyroidectomy, RAI therapy, and systemic therapy) should be recommended in OCA patients older than 55 years of age. Neck lymphadenectomy should not be recommended for OCA, since the metastatic lymph node ratio was low (about 3%). CONCLUSIONS: RAI therapy can improve survival in OCA by reducing noncancer death risks.

19.
ACS Sens ; 9(5): 2499-2508, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38683974

RESUMO

Carbon nanotubes (CNTs) hold great promise in next-generation sensors because of their remarkable physical properties. Yet, maintaining precise stacking configurations of CNTs to make full use of their remarkable properties is challenging because of their susceptibility to spontaneous reconstruction. Inspired by the weaving technology, we propose a CNT-graphene nanoribbon hybrid woven model that can maintain the specific structure of CNTs to achieve their elaborately designed function. In this study, comprehensive molecular dynamics simulations are carried out to investigate the thermal stability of the CNT-graphene hybrid woven model, as well as their potential for pressure sensing applications by utilizing the unique response of thermal transport to mechanical deformation at heterojunctions. The thermal stability is sensitive to the size of the graphene nanoribbon, and the woven structure remains stable from 200-500 K when its width is greater than 2.0 nm. Moreover, it is exciting that the sensors are effective at predicting the shapes of externally loaded objects through the analysis of the thermal conductivity distribution, which can be derived from the relationship between the thermal conduction and the pressure. Our findings shed light on the bottom-up functional design of nanomaterials and expand wider applications of high-performance nanosensors in other related fields.


Assuntos
Grafite , Simulação de Dinâmica Molecular , Nanotubos de Carbono , Pressão , Nanotubos de Carbono/química , Grafite/química , Condutividade Térmica
20.
Materials (Basel) ; 17(7)2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38612077

RESUMO

In the present work, the effect of Zn on the aging precipitates and mechanical properties of Al-Cu-Li alloys was investigated by Vickers hardness, tensile tests, transmission electron microscopy (TEM) and differential scanning calorimetry (DSC). The results indicated that the addition of Zn reduced the activation energy of the T1 phase and makes it easier to precipitate. The activation energy of the T1 phase, which was 107.02 ± 1.8 KJ/mol, 94.33 ± 1.7 KJ/mol, 90.33 ± 1.7 KJ/mol and 90.28 ± 1.6 KJ/mol for 0Zn, 0.4Zn, 0.8Zn and 1.2Zn alloy, respectively. The area number density of the T1 precipitate ranged from 97.0 ± 4.4 pcs/µm2 to 118.2 ± 2.8 pcs/µm2 as the Zn content increased from 0 to 1.2 wt.%. Consequently, the addition of Zn promoted the precipitation of the T1 phase. Therefore, the peak hardness and tensile strength of the alloy also increased with the increase in the Zn content, and the hardness of the alloy with Zn content of 1.2 wt.% increased by 16.5 ± 1.4 HV; meanwhile, the ultimate tensile strength increased by 46.5 ± 2.5 MPa. Therefore, the area number density of precipitates increased and improved the strength of the Zn-containing alloy.

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