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1.
Planta Med ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838717

RESUMO

Thrombin is a crucial enzyme in the coagulation cascade, and inhibitors of thrombin have been extensively studied as potential antithrombotic agents. The objective of this study was to identify natural inhibitors of thrombin from Panax notoginseng and evaluate their biological activity in vitro and binding characteristics. A combined approach involving molecular docking, thrombin inhibition assay, surface plasmon resonance (SPR) and molecular dynamics simulation was utilized to identify natural thrombin inhibitors. The results demonstrated that that panaxatriol directly inhibits thrombin with an IC50 of 10.3 µM. Binding studies using SPR revealed that panaxatriol interacts with thrombin with a KD value of 7.8 µM. Molecular dynamics analysis indicated that the thrombin-panaxatriol system reached equilibrium rapidly with minimal fluctuations, and the calculated binding free energy was -23.8 kcal/mol. The interaction between panaxatriol and thrombin involves the amino acid residues Glu146, Glu192, Gly216, Gly219, Tyr60A, and Trp60D. This interaction provides a mechanistic basis for further optimizing panaxatriol as a thrombin inhibitor. Our study has shown that panaxatriol serves as a direct thrombin inhibitor, laying the groundwork for further research and development of novel thrombin inhibitor.

2.
Nature ; 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38838737

RESUMO

Synaptic vesicles are organelles with a precisely defined protein and lipid composition1,2, yet the molecular mechanisms for the biogenesis of synaptic vesicles are mainly unknown. Here, we discovered a well-defined interface between the synaptic vesicle V-ATPase and synaptophysin by in situ cryo-electron tomography and single particle cryo-electron microscopy of functional synaptic vesicles isolated from mouse brains3. The synaptic vesicle V-ATPase is an ATP-dependent proton pump that establishes the protein gradient across the synaptic vesicle, which in turn drives the uptake of neurotransmitters4,5. Synaptophysin6 and its paralogs synaptoporin7 and synaptogyrin8 belong to a family of abundant synaptic vesicle proteins whose function is still unclear. We performed structural and functional studies of synaptophysin knockout mice, confirming the identity of synaptophysin as an interaction partner with the V-ATPase. Although there is little change in the conformation of the V-ATPase upon interaction with synaptophysin, the presence of synaptophysin in synaptic vesicles profoundly affects the copy number of V-ATPases. This effect on the topography of synaptic vesicles suggests that synaptophysin assists in their biogenesis. In support of this model, we observed that synaptophysin knockout mice exhibit severe seizure susceptibility, suggesting an imbalance of neurotransmitter release as a physiological consequence of the absence of synaptophysin.

3.
Opt Express ; 32(11): 19042-19056, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38859048

RESUMO

Lidar using active light illumination is capable of capturing depth and reflectivity information of target scenes. Among various technologies, streak tube imaging lidar (STIL) has garnered significant attention due to its high resolution and excellent precision. The echo signals of a STIL system using single laser pulse are often overwhelmed by noise in complex environments, making it difficult to discern the range of the target. By combining high-frequency laser pulses with the repetitive sweep circuit, the STIL system enables efficient detection of few-photons signal in weak-light environments. Additionally, we have developed a robust algorithm for estimating the depth and reflectivity images of targets. The results demonstrate that this lidar system achieves a depth resolution better than 0.5 mm and a ranging accuracy of 95 um. Furthermore, the imaging of natural scenes also validates the exceptional 3D imaging capability of this system.

4.
Transl Stroke Res ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861152

RESUMO

Existing research indicates the potential for white matter injury repair during the subacute phase following subarachnoid hemorrhage (SAH). However, elucidating the role of brain cell subpopulations in the acute and subacute phases of SAH pathogenesis remains challenging due to the cellular heterogeneity of the central nervous system. In this study, single-cell RNA sequencing was conducted on SAH model mice to delineate distinct cell populations. Gene Set Enrichment Analysis was performed to identify involved pathways, and cellular interactions were explored using the CellChat package in R software. Validation of the findings involved a comprehensive approach, including magnetic resonance imaging, immunofluorescence double staining, and Western blot analyses. This study identified ten major brain clusters with cell type-specific gene expression patterns. Notably, we observed infiltration and clonal expansion of reparative microglia in white matter-enriched regions during the subacute stage after SAH. Additionally, microglia-associated pleiotrophin (PTN) was identified as having a role in mediating the regulation of oligodendrocyte precursor cells (OPCs) in SAH model mice, implicating the activation of the mTOR signaling pathway. These findings emphasize the vital role of microglia-OPC interactions might occur via the PTN pathway, potentially contributing to white matter repair during the subacute phase after SAH. Our analysis revealed precise transcriptional changes in the acute and subacute phases after SAH, offering insights into the mechanism of SAH and for the development of drugs that target-specific cell subtypes.

5.
J Environ Manage ; 362: 121313, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38824887

RESUMO

As global climate change progresses, soil will experience prolonged periods of both drought and heavy rainfall, leading to a more frequent drought-re-wetting process that may impact the ecosystem's carbon (C) cycle. However, understanding the extent to which different water conditions and wet-dry cycles alter the process of soil organic carbon (SOC) mineralization remains limited. Therefore, our study focused on the dammed land unique to the Loess Plateau, silted by check dams constructed for erosion control. We implemented three water gradients-drought (30% WHC), water stress (100% WHC), and wet-dry cycling (30-100%)-indoors to observe the SOC mineralization process five times. We identified a transient excitation effect of the wet-dry cycles on SOC mineralization. Soil mineralization decreased gradually with the alternation of wet-dry cycles. The wet-dry cycles not only significantly impacted the contents of SOC and TN but also stimulated the activities of enzymes related to C and N cycles. As the cycle frequency increased, the utilization of C sources by soil microorganisms gradually decreased, and the dominance of carbohydrates, amines, and acids evolved into a single acid, esters, or alcohols. Phosphatase and Chloroflexi were the main factors influencing SOC mineralization under drought stress, while TN and Ascomycota were the primary factors under water stress. SOC and Gemmatimonadetes were the main limiting factors for SOC mineralization under the wet-dry cycles. Additionally, we quantified the direct and interactive contributions of each factor to SOC mineralization. The direct contributions of drought stress, water stress, and the wet-dry cycles to SOC mineralization were 0.961, 0.736, and 0.942, respectively. This study contributes to a more comprehensive understanding of the mechanisms underlying SOC mineralization in the Loess Plateau under changing conditions.


Assuntos
Carbono , Solo , Solo/química , Secas , Ecossistema , Mudança Climática , Ciclo do Carbono , Água
6.
PLOS Glob Public Health ; 4(6): e0002661, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38857265

RESUMO

The COVID-19 pandemic had an unprecedented impact on global mental health and well-being, including across the Asia-Pacific. Efforts to mitigate virus spread led to far-reaching disruption in the delivery of health and social services. In response, there was a rapid shift to the use of digital mental health (DMH) approaches. Though these technologies helped to improve access to care for many, there was also substantial risk of access barriers leading to increased inequities in access to mental health care, particularly among at-risk and equity-deserving populations. The objective of this study was to conduct a needs assessment and identify priorities related to equitable DMH access among at-risk and equity-deserving populations in the Asia Pacific region during the first year of the COVID-19 pandemic. The study consisted of a modified Delphi consensus methodology including two rounds of online surveys and online consultations with stakeholders from across the region. Study participants included policy makers, clinicians and service providers, and people with lived experience of mental health conditions. Results demonstrate that vulnerabilities to negative mental health impacts and access barriers were compounded during the pandemic. Access barriers included a lack of linguistically and culturally appropriate DMH options, low mental health literacy and poor access to technological infrastructure and devices, low levels of awareness and trust of DMH options, and lack of policies and guidelines to support effective and equitable delivery of DMH. Recommendations to improve equitable access include ensuring that diverse people with lived experience are engaged in research, co-design and policy development, the development and implementation of evidence-based and equity-informed guidelines and frameworks, clear communication about DMH evidence and availability, and the integration of DMH into broader health systems. Study results can inform the development and implementation of equitable DMH as its use becomes more widespread across health systems.

7.
Sci Rep ; 14(1): 12647, 2024 06 02.
Artigo em Inglês | MEDLINE | ID: mdl-38825659

RESUMO

Variations in immune cell counts can trigger depressive symptoms, while physical activity effectively reduces the risk and severity of depressive symptoms. This study, based on the NHANES database, analyzes the relationship between neutrophil count and depressive symptoms and explores the moderating effect of physical activity on this relationship. Cross-sectional data from the NHANES database were extracted, including immune cell counts, PHQ-9 scores for self-assessment of depressive symptoms, and Global Physical Activity Questionnaire (GPAQ) scores (PA). The interrelations among physical activity, neutrophil count, and depressive symptoms were analyzed. After controlling for confounding factors, neutrophil count was found to have a significant role in identifying depressive symptoms with an odds ratio (OR) [95% Confidence Interval (CI)] = 1.13 [1.02, 1.251]; the moderating effect of physical activity on the impact of neutrophil count on depressive symptoms was statistically significant (coefficient = -0.0028, P < 0.05). Neutrophil count may be a significant factor in identifying depressive symptoms in adults. As an effective moderating factor, physical activity can mitigate the impact of neutrophil count on depressive symptoms to a certain extent.


Assuntos
Depressão , Exercício Físico , Neutrófilos , Humanos , Neutrófilos/imunologia , Depressão/imunologia , Depressão/sangue , Masculino , Feminino , Adulto , Contagem de Leucócitos , Pessoa de Meia-Idade , Estudos Transversais , Inquéritos e Questionários , Idoso
8.
Neurochem Res ; 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834846

RESUMO

Neuroinflammation and endothelial cell apoptosis are prominent features of blood-brain barrier (BBB) disruption, which have been described in Alzheimer's disease (AD) and can predict cognitive decline. Recent reports revealed vascular ß-amyloid (Aß) deposits, Muller cell degeneration and microglial dysfunction in the retina of AD patients. However, there has been no in-depth research on the roles of inflammation, retinal endothelial cell apoptosis, and blood-retinal barrier (BRB) damage in AD retinopathy. We found that Raddeanin A (RDA) could improve pathological and cognitive deficits in a mouse model of Alzheimer's disease by targeting ß-amyloidosis, However, the effects of RDA on AD retinal function require further study. To clarify whether RDA inhibits inflammation and apoptosis and thus improves BRB function in AD-related retinopathy. In vitro we used Aß-treated HRECs and MIO-M1 cells, and in vivo we used 3×Tg-AD mice to investigate the effect of RDA on BRB in AD-related retinopathy. We found that RDA could improve BRB function in AD-related retinopathy by inhibiting NLRP3-mediated inflammation and suppressing Wnt/ß-catenin pathway-mediated apoptosis, which is expected to improve the pathological changes in AD-related retinopathy and the quality of life of AD patients.

9.
Nanotechnology ; 35(33)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38829163

RESUMO

Dry eye disease (DED) is a major global eye disease leading to severe eye discomfort and even vision impairment. The incidence of DED has been gradually increasing with the high frequency of use of electronic devices. It has been demonstrated that celastrol (Cel) has excellent therapeutic efficacy in ocular disorders. However, the poor water solubility and short half-life of Cel limit its further therapeutic applications. In this work, a reactive oxygen species (ROS) sensitive polymeric micelle was fabricated for Cel delivery. The micelles improve the solubility of Cel, and the resulting Cel loaded micelles exhibit an enhanced intervention effect for DED. Thein vitroresults demonstrated that Cel-nanomedicine had a marked ROS responsive release behavior. The results ofin vitroandin vivoexperiments demonstrated that Cel has excellent biological activities to alleviate inflammation in DED by inhibiting TLR4 signaling activation and reducing pro-inflammatory cytokine expression. Therefore, the Cel nanomedicine can effectively eliminate ocular inflammation, promote corneal epithelial repair, and restore the number of goblet cells and tear secretion, providing a new option for the treatment of DED.


Assuntos
Síndromes do Olho Seco , Micelas , Nanomedicina , Triterpenos Pentacíclicos , Espécies Reativas de Oxigênio , Triterpenos , Síndromes do Olho Seco/tratamento farmacológico , Triterpenos Pentacíclicos/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Nanomedicina/métodos , Triterpenos/farmacologia , Triterpenos/química , Inflamação/tratamento farmacológico , Receptor 4 Toll-Like/metabolismo , Humanos , Lágrimas/metabolismo , Lágrimas/efeitos dos fármacos
10.
BMC Public Health ; 24(1): 1541, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849814

RESUMO

BACKGROUND: Dose-response and nonlinear relationships of cigarette exposure with sleep disturbances and depression are warranted, and the potential mechanism of sex hormones in such associations remains unclear. METHODS: Cigarette exposure, trouble sleeping, and depression were assessed by standard questionnaires, and the levels of cotinine and sex steroid hormones were determined among 9900 adults from the National Health and Nutrition Examination Survey (NHANES). Multiple linear regression, logistic regression, and mediation models were conducted to evaluate the associations between smoking, sex steroid hormones, trouble sleeping, and depression. RESULTS: With never smokers as a reference, current smokers had a higher prevalence of trouble sleeping (OR = 1.931, 95% CI: 1.680, 2.219) and depression (OR = 2.525, 95% CI: 1.936, 3.293) as well as testosterone level (ß = 0.083, 95% CI: 0.028, 0.140). Pack-years of smoking and cigarettes per day were positively associated with the prevalence of trouble sleeping and depression as well as testosterone level (Ptrend <0.05). The restricted cubic spline model showed linear relationships of cotinine with trouble sleeping, depression, and testosterone. The positive associations of cigarettes per day with trouble sleeping and depression were greater in females than that in males (Pmodification <0.05). However, the potential role of sex hormones was not observed in the association of cotinine with trouble sleeping or depression (Pmediation >0.05). CONCLUSION: Smoking may induce sex hormone disturbance and increase the risk of sleep problems and depression symptoms, and ceasing smoking may reduce the risk of such complications.


Assuntos
Cotinina , Depressão , Inquéritos Nutricionais , Humanos , Masculino , Feminino , Estudos Transversais , Adulto , Depressão/epidemiologia , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Cotinina/sangue , Cotinina/análise , Transtornos do Sono-Vigília/epidemiologia , Fumar/epidemiologia , Prevalência , Hormônios Esteroides Gonadais/sangue , Adulto Jovem , Testosterona/sangue , Idoso
11.
Appl Opt ; 63(14): 3973-3983, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38856361

RESUMO

In this work, a novel, to our knowledge, visible light communication (VLC) channel model is proposed for underground mining scenarios taking into account the impact of coal dust particles and obstacles. Specifically, the extinction effect of the coal dust particles is analyzed on the basis of the Mie theory, and the quantitative formula of the influence on channel direct current (DC) gain is derived. Meanwhile, the effect of a random shadowing phenomenon is investigated and quantified with the geometric and statistical model considering the position, size, and shape of the obstacles. The channel impulse response, path loss, root mean square delay spread, and bit error rate (BER) are further investigated in two different underground mining scenarios, namely, a mining roadway and coal mine working face. Simulation results show that the shadowing effect plays a major role in the influence of DC gain attenuation. Furthermore, the BER performance is noticeably degraded due to the presence of coal dust particles and obstacles, especially when the receiver is located far from the transmitter. This work will benefit the design of the VLC systems in underground mines.

12.
Sci Rep ; 14(1): 13864, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38879710

RESUMO

Despite of excellent thermal properties and high sputtering resistance, pure tungsten cannot fully satisfy the requirements for plasma facing materials in future high-duty cycle nuclear fusion reactions due to the coupled extreme environments, including the high thermal loads, plasma exposure, and radiation damage. Here, we demonstrated that tungsten-based composite materials fabricated using spark-plasma sintering (SPS) present promising solutions to these challenges. Through the examination of two model systems, i.e., tungsten-zirconium composite for producing porous tungsten near the surface and dispersoid-strengthened tungsten, we discussed both the strengths and limitations of the SPS-fabricated materials. Our findings point towards the need for future studies aimed at optimizing the SPS process to achieve desired microstructures and effective control of oxygen impurities in the tungsten-based composite materials.

13.
Adv Sci (Weinh) ; : e2400203, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38874532

RESUMO

Therapeutic benefits and underlying biomechanism(s) of antibody drug conjugates (ADC) in combination with other targeted therapeutics are largely unknown. Here, the synergy between ADC and epigenetic drug decitabine (DAC), a clinically approved DNA methylation inhibitor, in multiple preclinical models of melanoma specifically investigated. Mechanistically, the underlying biomechanisms of how DAC cooperatively worked with ICAM1 antibody conjugated DNA topoisomerase I inhibitor DXd (I1-DXd) is elucidated. DAC treatment significantly enhanced anti-tumor efficacy of I1-DXd by upregulating antigen expression, enhancing antibody internalization and potentiating tumor sensitivity by epigenetically reprogramming of melanoma. Meanwhile, I1-DXd/DAC combination also exerted regulatory effects on tumor microenvironment (TME) by enhancing tumor infiltration of innate and adaptive immune cells and improving penetration of ADCs with a boosted antitumor immunity. This study provides a rational ADC combination strategy for solid tumor treatment.

14.
Aging (Albany NY) ; 162024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38829771

RESUMO

Currently, the repair of large bone defects still faces numerous challenges, with the most crucial being the lack of large bone grafts with good osteogenic properties. In this study, a novel bone repair implant (degradable porous zinc scaffold/BF Exo composite implant) was developed by utilizing laser melting rapid prototyping 3D printing technology to fabricate a porous zinc scaffold, combining it under vacuum conditions with highly bioactive serum exosomes (BF EXO) and Poloxamer 407 thermosensitive hydrogel. The electron microscope revealed the presence of tea saucer-shaped exosomes with a double-layered membrane structure, ranging in diameter from 30-150 nm, with an average size of 86.3 nm and a concentration of 3.28E+09 particles/mL. In vitro experiments demonstrated that the zinc scaffold displayed no significant cytotoxicity, and loading exosomes enhanced the zinc scaffold's ability to promote osteogenic cell activity while inhibiting osteoclast activity. In vivo experiments on rabbits indicated that the hepatic and renal toxicity of the zinc scaffold decreased over time, and the loading of exosomes alleviated the hepatic and renal toxic effects of the zinc scaffold. Throughout various stages of repairing radial bone defects in rabbits, loading exosomes reinforced the zinc scaffold's capacity to enhance osteogenic cell activity, suppress osteoclast activity, and promote angiogenesis. This effect may be attributed to BF Exo's regulation of p38/STAT1 signaling. This study signifies that the combined treatment of degradable porous zinc scaffolds and BF Exo is an effective and biocompatible strategy for bone defect repair therapy.

16.
Anal Chim Acta ; 1315: 342797, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38879209

RESUMO

BACKGROUND: Harmful algal blooms (HABs), caused by the rapid proliferation or aggregation of microorganisms, are catastrophic for the environment. The Prymnesium parvum is a haptophyte algal species that is found worldwide and is responsible for extensive blooms and death of larval amphibians and bivalves, causing serious negative impacts on the ecological environment. For the prevention and management of environmental pollution, it is crucial to explore and develop early detection strategies for HABs on-site using simple methods. The major challenge related to early detection is the accurate and sensitive detection of algae present in low abundance. RESULTS: Herein, recombinase polymerase amplification (RPA) was combined with clustered regularly interspaced short palindromic repeats and Cas12a protein (CRISPR-LbaCas12a) systems, and the lateral flow dipstick (LFD) was used for the first time for early detection of P. parvum. The internal transcribed spacer (ITS) of P. parvum was selected as the target sequence, and the concentration of single-strand DNA reporters, buffer liquid system, reaction time, and amount of gold particles were optimized. The RPA-CRISPR-LbaCas12a-LFD approach demonstrated highly specificity during experimental testing, with no cross-reaction against different microalgae used as controls. In addition, the lowest detection limit was 10,000 times better than the lowest detection limit of the standalone RPA approach. The feasibility and robustness of this approach were further verified by using the different environmental samples. It also observed that P. parvum are widely distributed in Chinese Sea, but the cell density of P. parvum is relatively low (<0.1 cells/mL). SIGNIFICANCE: The developed approach has an excellent specificity and offers 10,000 times better sensitivity than the standalone RPA approach. These advantages make this approach suitable for early warning detection and prevention of HAB events in environmental water. Also, the outcomes of this study could promote a shift from traditional laboratory-based detection to on-site monitoring, facilitating early warning against HABs.


Assuntos
Sistemas CRISPR-Cas , Sistemas CRISPR-Cas/genética , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos , Recombinases/metabolismo , Proliferação Nociva de Algas , Ouro/química , Proteínas Associadas a CRISPR/genética , Endodesoxirribonucleases/genética , Proteínas de Bactérias/genética
17.
Int J Biol Macromol ; 273(Pt 2): 132961, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38848846

RESUMO

Zn-air batteries are a highly promising clean energy sustainable conversion technology, and the design of dual-function electrocatalysts with excellent activity and stability is crucial for their development. In this work, FeCo alloy loaded biomass-based N and S co-doped carbon aerogels (FeCo@NS-LCA) were fabricated from chitosan and lignosulfonate-metal chelates via liquid nitrogen pre-frozen synergistic high-temperature carbonization with application in electrocatalytic reactions. The abundant oxygen-containing functional groups on lignosulfonates have a chelating effect on metal ions, which can avoid the aggregation of metal nanoparticles during carbonation and catalysis, facilitating the construction of a nanoconfinement catalytic system with biomass carbon as the domain-limiting body and FeCo nanoparticles as the active sites. FeCo@NS-LCA exhibited catalytic activity (E1/2 = 0.87 V, JL = 5.7 mA cm-2) comparable to the commercial Pt/C in the oxygen reduction reaction (ORR), excellent resistance to methanol toxicity and stability. Meanwhile, the overpotential of oxygen evolution reaction (OER) was 324 mV, close to that of commercial RuO2 catalysts (351 mV). This study utilizes the coordination action of lignosulfonate to provide a novel and environmentally friendly method for the preparation of confined nano-catalysts and provides a new perspective for the high-value utilization of biomass resources.

18.
Transl Cancer Res ; 13(5): 2518-2534, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38881923

RESUMO

Background: Elevated expression of SLC7A11, in conjunction with glucose deprivation, has revealed disulfidptosis as an emerging cell death modality. However, the prevalence of disulfidptosis across tumor cell lines, irrespective of SLC7A11 levels, remains uncertain. Additionally, deletion of the ribophorin I (RPN1) gene imparts resistance to disulfidptosis, yet the precise mechanism linking RPN1 to disulfidptosis remains elusive. The aim of this study is to determine the mechanism of RPN1-induced disulfidptosis and to determine the possibility of RPN1 as a pan-cancer marker. Methods: We hypothesized the widespread occurrence of disulfidptosis in various tumor cells, and proposed that RPN1-mediated disulfidptosis may be executed through cell skeleton breakdown. Experimental validation was conducted via flow cytometry, immunofluorescence, and western blot techniques. Furthermore, given RPN1's status as an emerging cell death marker, we utilized bioinformatics to analyze its expression in tumor tissues, clinical relevance, mechanisms within the tumor microenvironment, and potential for immunotherapy. Results: Conducting experiments on breast cancer (MDA-MB-231) and lung cancer (A549) cell lines under glucose-starved conditions, we found that RPN1 primarily induces cell skeleton breakdown to facilitate disulfidptosis. RPN1 demonstrated robust messenger RNA (mRNA) expression across 16 solid tumors, validated by data from 12 tumor types in the Gene Expression Omnibus (GEO). Across 12 cancer types, RPN1 exhibited significant diagnostic potential, particularly excelling in accuracy for glioblastoma (GBM). Elevated RPN1 expression in tumor tissues was found to correlate with improved overall survival (OS) in certain cancers [diffuse large B-cell lymphoma (DLBC) and thymoma (THYM)] but poorer prognosis in others [adrenocortical carcinoma (ACC), kidney chromophobe (KICH), brain lower grade glioma (LGG), liver hepatocellular carcinoma (LIHC), and pancreatic adenocarcinoma (PAAD)]. RPN1 is enriched in immune-related pathways and correlates with immune scores in tumor tissues. In urothelial carcinoma (UCC), RPN1 demonstrates potential in predicting the efficacy of anti-programmed cell death ligand 1 (PD-L1) immune therapy. Conclusions: This study underscores RPN1's role in facilitating disulfidptosis, its broad relevance as a pan-cancer biomarker, and its association with the efficacy of anti-PD-L1 immune therapy.

19.
Acta Neurochir (Wien) ; 166(1): 202, 2024 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-38703244

RESUMO

BACKGROUND: There is a paucity of conclusive evidence regarding the impact of downward drift in hematocrit levels among patients who have undergone surgical clipping for aneurysmal subarachnoid hemorrhage (aSAH). This study endeavors to explore the potential association between hematocrit drift and mortality in this specific patient population. METHODS: A cohort study was conducted, encompassing adult patients diagnosed with aSAH at a university hospital. The primary endpoint was follow-up mortality. Propensity score matching was employed to align patients based on their baseline characteristics. Discrimination capacity across various models was assessed and compared using net reclassification improvement (NRI). RESULTS: Among the 671 patients with aSAH in the study period, 118 patients (17.6%) experienced an in-hospital hematocrit drift of more than 25%. Following adjustment with multivariate regression analysis, patients with elevated hematocrit drift demonstrated significantly increased odds of mortality (aOR: 2.12, 95% CI: 1.14 to 3.97; P = 0.019). Matching analysis yielded similar results (aOR: 2.07, 95% CI: 1.05 to 4.10; P = 0.036). The inclusion of hematocrit drift significantly improved the NRI (P < 0.0001) for mortality prediction. When in-hospital hematocrit drift was served as a continuous variable, each 10% increase in hematocrit drift corresponded to an adjusted odds ratio of 1.31 (95% CI 1.08-1.61; P = 0.008) for mortality. CONCLUSIONS: In conclusion, the findings from this comprehensive cohort study indicate that a downward hematocrit drift exceeding 25% independently predicts mortality in surgical patients with aSAH. These findings underscore the significance of monitoring hematocrit and managing anemia in this patient population.


Assuntos
Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/cirurgia , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/sangue , Hematócrito , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Idoso , Estudos de Coortes , Resultado do Tratamento , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos
20.
Int J Neurosci ; : 1-15, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738478

RESUMO

BACKGROUND: Sciatica is a phrase used to describe radiating leg discomfort. The most common cause is lumbar disc herniation (LDH), which is considered to start in the nucleus pulposus. Advancements in lipidomics and metabolomics have unveiled the complex role of fatty acid metabolism (FAM) in both healthy and pathological states. However, the specific roles of fatty acid metabolism-related genes (FAMGs) in shaping therapeutic approaches, especially in LDH, remain largely unexplored and are a subject of ongoing research. METHODS: The junction of the weighted correlation network analysis (WGCNA) test with 6 FAMGs enabled the finding of FAMGs. Gene set variation analysis (GSVA) was used to identify the possible biological activities and pathways of FAMGs. LASSO was used to determine diagnostic effectiveness of the four FAMGs in diagnosing LDH. GSE124272, GSE147383, GSE150408, and GSE153761 were utilized to confirm the levels of expression of four FAMGs. RESULTS: Four FAMGs were discovered [Acyl-CoA Thioesterase 4 (ACOT4), Cytochrome P450 Family 4 Subfamily A Member 11 (CYP4A11), Acyl-CoA Dehydrogenase Long Chain (ACADL), Enoyl-CoA Hydratase and 3-Hydroxyacyl CoA Dehydrogenase (EHHADH)] For biological function analysis, mhc class ib receptor activity, response to thyroxine, response to l phenylalanine derivative were emphasized. CONCLUSIONS: FAMGs can help with prognosis and immunology, and provide evidence for fatty acid metabolism-related targeted therapeutics. In LDH, FAMGs and their interactions with immune cells might be therapeutic targets.

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