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1.
Comput Biol Med ; 179: 108813, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38955127

RESUMO

BACKGROUND: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. METHOD: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-scale variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. RESULTS: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R2-scores > 0.01 for 71.55 % of metabolites. CONCLUSION: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research.

2.
Chin J Integr Med ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958885

RESUMO

Coronavirus disease 2019 (COVID-19) is an acute infectious respiratory disease that has been prevalent since December 2019. Chinese medicine (CM) has demonstrated its unique advantages in the fight against COVID-19 in the areas of disease prevention, improvement of clinical symptoms, and control of disease progression. This review summarized the relevant material components of CM in the treatment of COVID-19 by searching the relevant literature and reports on CM in the treatment of COVID-19 and combining with the physiological and pathological characteristics of the novel coronavirus. On the basis of sorting out experimental methods in vivo and in vitro, the mechanism of herb action was further clarified in terms of inhibiting virus invasion and replication and improving related complications. The aim of the article is to explore the strengths and characteristics of CM in the treatment of COVID-19, and to provide a basis for the research and scientific, standardized treatment of COVID-19 with CM.

3.
Front Endocrinol (Lausanne) ; 15: 1417007, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952389

RESUMO

Ovarian aging is a complex process characterized by a decline in oocyte quantity and quality, directly impacting fertility and overall well-being. Recent researches have identified mitochondria as pivotal players in the aging of ovaries, influencing various hallmarks and pathways governing this intricate process. In this review, we discuss the multifaceted role of mitochondria in determining ovarian fate, and outline the pivotal mechanisms through which mitochondria contribute to ovarian aging. Specifically, we emphasize the potential of targeting mitochondrial dysfunction through innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, mitochondrial transfer, and traditional Chinese medicine. These strategies hold promise as effective means to mitigate age-related fertility decline and preserve ovarian health. Drawing insights from advanced researches in the field, this review provides a deeper understanding of the intricate interplay between mitochondrial function and ovarian aging, offering valuable perspectives for the development of novel therapeutic interventions aimed at preserving fertility and enhancing overall reproductive health.


Assuntos
Envelhecimento , Mitocôndrias , Ovário , Humanos , Feminino , Mitocôndrias/metabolismo , Envelhecimento/fisiologia , Envelhecimento/metabolismo , Ovário/metabolismo , Ovário/fisiologia , Animais , Antioxidantes/uso terapêutico , Oócitos/metabolismo , Oócitos/fisiologia , Mitofagia/fisiologia
4.
J Asian Nat Prod Res ; : 1-7, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38949198

RESUMO

One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.

5.
J Vis Exp ; (208)2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38949315

RESUMO

Extensive studies have proven the promise of chimeric antigen receptor T (CAR-T) cell therapy in treating hematological malignancies. However, treating solid tumors remains challenging, as exemplified by the safety concerns that arise when CAR-T cells attack normal cells expressing the target antigens. Researchers have explored various approaches to enhance the tumor selectivity of CAR-T cell therapy. One representative strategy along this line is the construction of hypoxia-sensitive CAR-T cells, which are designed by fusing an oxygen-dependent degradation domain to the CAR moiety and are strategized to attain high CAR expression only in a hypoxic environment-the tumor microenvironment (TME). This paper presents a protocol for the generation of such CAR-T cells and their functional characterization, including methods to analyze the changes in CAR expression and killing capacity in response to different oxygen levels established by a mobile incubator chamber. The constructed CAR-T cells are anticipated to demonstrate CAR expression and cytotoxicity in an oxygen-sensitive manner, thus supporting their capability to distinguish between hypoxic TME and normoxic normal tissues for selective activation.


Assuntos
Receptores de Antígenos Quiméricos , Linfócitos T , Receptores de Antígenos Quiméricos/imunologia , Receptores de Antígenos Quiméricos/genética , Humanos , Linfócitos T/imunologia , Imunoterapia Adotiva/métodos , Hipóxia Celular/fisiologia , Microambiente Tumoral/imunologia
6.
Front Immunol ; 15: 1421012, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38979414

RESUMO

Objective: This study revealed a core regulator and common upstream mechanisms for the multifaceted pathological processes of age-related macular degeneration (AMD) and provided proof-of-concept for this new therapeutic target. Methods: Comprehensive gene expression analysis was performed using RNA sequencing of eye cup from old mice as well as laser-induced choroidal neovascularization (CNV) mouse model. Through integrative analysis and protein-protein interaction (PPI) analysis, common pathways and key transcription factor was identified simultaneously engaged in age-related retinal degeneration and CNV, the two typical pathological process of AMD. Subsequently, the expression changes of Spi1, the key regulator, as well as the alternation of the downstream mechanisms were validated in both models through qRT-PCR, Elisa, flow cytometry and immunofluorescence. Further, we assessed the impact of Spi1 knockdown in vitro and in vivo using gene intervention vectors carried by adeno-associated virus or lentivirus to test its potential as a therapeutic target. Results: Compared to corresponding controls, we found 1,939 and 1,319 genes differentially expressed in eye cups of old and CNV mice respectively. The integrative analysis identified a total of 275 overlapping DEGs, of which 150 genes were co-upregulated. PPI analysis verified a central transcription factor, SPI1. The significant upregulation of Spi1 expression was then validated in both models, accompanied by macrophage polarization towards the M1 phenotype. Finally, SPI1 suppression significantly inhibited M1 polarization of BMDMs and attenuated neovascularization in CNV mice. Conclusion: This study demonstrates that SPI1 exerts a pivotal role in AMD by regulation of macrophage polarization and innate immune response, offering promise as an innovative target for treating AMD.


Assuntos
Neovascularização de Coroide , Modelos Animais de Doenças , Macrófagos , Degeneração Macular , Transativadores , Animais , Degeneração Macular/imunologia , Degeneração Macular/metabolismo , Degeneração Macular/genética , Degeneração Macular/patologia , Camundongos , Macrófagos/imunologia , Macrófagos/metabolismo , Neovascularização de Coroide/imunologia , Neovascularização de Coroide/genética , Neovascularização de Coroide/metabolismo , Transativadores/genética , Transativadores/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Camundongos Endogâmicos C57BL , Ativação de Macrófagos/genética , Humanos , Perfilação da Expressão Gênica , Masculino
7.
Heliyon ; 10(12): e32688, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975145

RESUMO

The persistence of neuronal degeneration and damage is a major obstacle in ageing medicine. Nucleotide-binding oligomerization domain (NOD)-like receptors detect environmental stressors and trigger the maturation and secretion of pro-inflammatory cytokines that can cause neuronal damage and accelerate cell death. NLR (NOD-like receptors) inflammasomes are protein complexes that contain NOD-like receptors. Studying the role of NLR inflammasomes in ageing-related neurological disorders can provide valuable insights into the mechanisms of neurodegeneration. This includes investigating their activation of inflammasomes, transcription, and capacity to promote or inhibit inflammatory signaling, as well as exploring strategies to regulate NLR inflammasomes levels. This review summarizes the use of NLR inflammasomes in guiding neuronal degeneration and injury during the ageing process, covering several neurological disorders such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, stroke, and peripheral neuropathies. To improve the quality of life and slow the progression of neurological damage, NLR-based treatment strategies, including inhibitor-related therapies and physical therapy, are presented. Additionally, important connections between age-related neurological disorders and NLR inflammasomes are highlighted to guide future research and facilitate the development of new treatment options.

8.
Angew Chem Int Ed Engl ; : e202407075, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990170

RESUMO

Sodium metal batteries (SMBs) have received increasing attention due to the abundant sodium resources and high energy density, but suffered from the sluggish interfacial kinetic and unstable plating/stripping of sodium anode at low temperature, especially when matched with ester electrolytes. Here, we develop a stable ultra-low-temperature SMBs with high-capacity retention at -50°C in a weak solvated carbonate ester-based electrolyte, combined with an electrodeposited Na (Cu/Na) anode. The Cu/Na anode with electrochemically activated "deposited sodium" and stable inorganic-rich solid electrolyte interphase (SEI) was favor for the fast Na+ migration, therefore accelerating the interfacial kinetic process. As a result, the Cu/Na || NaCrO2 battery exhibited the highest capacity retention (compared to room-temperature capacity) in carbonate ester-based SMBs (98.05% at -25°C, 91.3% at -40°C, 87.9% at -50°C, respectively). The cyclic stability of 350 cycles at -25°C with a high energy efficiency of 96.15% and 70 cycles at -50°C can be achieved. Even in chill atmospheric environment with the fluctuant temperature, the battery can still operate over one month. This work provides a new opportunity for the development of low-temperature carbonate ester-based SMBs.

9.
Cell Rep ; 43(7): 114460, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38996068

RESUMO

Natural silks are renewable proteins with impressive mechanical properties and biocompatibility that are useful in various fields. However, the cellular and spatial organization of silk-secreting organs remains unclear. Here, we combined single-nucleus and spatially resolved transcriptomics to systematically map the cellular and spatial composition of the silk glands (SGs) of mulberry silkworms late in larval development. This approach allowed us to profile SG cell types and cell state dynamics and identify regulatory networks and cell-cell communication related to efficient silk protein synthesis; key markers were validated via transgenic approaches. Notably, we demonstrated the indispensable role of the ecdysone receptor (ultraspiracle) in regulating endoreplication in SG cells. Our atlas presents the results of spatiotemporal analysis of silk-secreting organ architecture late in larval development; this atlas provides a valuable reference for elucidating the mechanism of efficient silk protein synthesis and developing sustainable products made from natural silk.

10.
Shanghai Kou Qiang Yi Xue ; 33(2): 141-147, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-39005089

RESUMO

PURPOSE: To study the stability of physicochemical properties and sterilizing effect about two commercially available hypochlorous acid (HClO) products under simulated clinical conditions, and to evaluate the compatibility of HClO on soft and hard tissues and cells in oral cavity. METHODS: Samples of HClO solution with different production processes were prepared, to detect the changes of physicochemical indexes of each sample over time under simulated clinical conditions (shielded from light at 20-25 ℃, open the cover for 5 minutes every day), including free available chlorine, oxidation-reduction potential and pH. Through suspension quantitative germicidal test, the antibiosis-concentration curve of HClO solution was made, so as to calibrate the change of antibacterial ability of disinfectant with the decrease of available chlorine content during storage. Pulp, tongue and dentine were immersed in PBS, 100 ppm HClO, 200 ppm HClO and 3% NaClO. The influence on soft and hard tissues was evaluated by weighing method and microhardness test. The toxic effects of HClO, NaClO and their 10-fold diluent on human gingival fibroblasts were determined by CCK-8 cytotoxicity assay. GraphPad PRIS 8.0 software was used to analyze the data. RESULTS: Under simulated conditions, the free available chlorine (FAC) of HClO solution decayed with time, and the attenuation degree was less than 20 ppm within 1 month. The bactericidal effect of each HClO sample was still higher than 5log after concentration decay. There was no obvious dissolution and destruction to soft and hard tissues for HClO(P>0.05). The cell viability of HClO to human gingival fibroblast cells (HGFC) was greater than 80%, which was much higher than 3% NaClO (P<0.001). CONCLUSIONS: The bactericidal effect and stability of HClO solution can meet clinical needs, which has low cytotoxicity and good histocompatibility. It is expected to become a safe and efficient disinfection product in the field of living pulp preservation and dental pulp regeneration.


Assuntos
Fibroblastos , Ácido Hipocloroso , Boca , Ácido Hipocloroso/química , Humanos , Boca/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Gengiva/citologia , Gengiva/efeitos dos fármacos , Irritantes , Desinfetantes/farmacologia , Desinfetantes/química , Antibacterianos/farmacologia , Antibacterianos/química
11.
Sci Total Environ ; 947: 174565, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38986715

RESUMO

Long-term waste accumulation (LTWA) in soil not only alters its physical and chemical properties but also affects heavy metals and microorganisms in polluted soil through the dissolved organic matter (DOM) it produces. However, research on the impact of DOM from LTWA on heavy metals and microorganisms in polluted soil is limited, which has resulted in an incomplete understanding of the mechanisms involved in LTWA soils remediation. This study focuses on the DOM generated by waste accumulation and analyses the physicochemical properties, microbial community structure, and vertical distribution of heavy metals in four types of LTWA soils at different depths (0-100 cm). A causal analysis is conducted using structural equation modelling. The results indicate that due to the retention effect of the soil and microorganisms, heavy metal pollution is concentrated on the soil surface layer (>30 cm). With increasing depth, there is a decrease in heavy metal concentration and an increase in microbial diversity and abundance. DOM plays a significant role in regulating the concentration of soil heavy metals and the diversity and abundance of microorganisms. The DOM from different soils gradually transforms into substances dominated by tyrosine, tryptophan, and fulvic acid, which sustain the normal life activities and gene expression of microorganisms. Bacteria such as Pseudarthrobacter, Desulfurivibrio, Thiobacillus, and Sulfurimonas, which are involved in energy transformation, along with genes such as water channel protein and YDIF, which enhance heavy metal metabolism, ensure that microbial communities can maintain basic life processes in polluted environments and gradually select for dominant species that are adapted to heavy metal pollution. These novel discoveries illuminate the potential for modulating the composition of DOM to amplify microbial activity, while concurrently offering insights into the migration patterns of various long-term exogenous pollutants. This foundational knowledge provides a foundation for the development of efficacious remediation strategies.

12.
J Neuroeng Rehabil ; 21(1): 116, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38997727

RESUMO

OBJECTIVE: This study explored the impact of one session of low-pressure leg blood flow restriction (BFR) during treadmill walking on dual-task performance in older adults using the neurovisceral integration model framework. METHODS: Twenty-seven older adults participated in 20-min treadmill sessions, either with BFR (100 mmHg cuff pressure on both thighs) or without it (NBFR). Dual-task performance, measured through light-pod tapping while standing on foam, and heart rate variability during treadmill walking were compared. RESULTS: Following BFR treadmill walking, the reaction time (p = 0.002) and sway area (p = 0.012) of the posture dual-task were significantly reduced. Participants exhibited a lower mean heart rate (p < 0.001) and higher heart rate variability (p = 0.038) during BFR treadmill walking. Notably, BFR also led to band-specific reductions in regional brain activities (theta, alpha, and beta bands, p < 0.05). The topology of the EEG network in the theta and alpha bands became more star-like in the post-test after BFR treadmill walking (p < 0.005). CONCLUSION: BFR treadmill walking improves dual-task performance in older adults via vagally-mediated network integration with superior neural economy. This approach has the potential to prevent age-related falls by promoting cognitive reserves.


Assuntos
Frequência Cardíaca , Caminhada , Humanos , Idoso , Masculino , Feminino , Caminhada/fisiologia , Frequência Cardíaca/fisiologia , Teste de Esforço , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Fluxo Sanguíneo Regional/fisiologia , Desempenho Psicomotor/fisiologia , Perna (Membro)/fisiologia
13.
Sci Total Environ ; 947: 174519, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38972410

RESUMO

The health effects of ultrafine particles (UFPs) are of growing global concern, but the epidemiological evidence remains limited. Sleep-disordered breathing (SDB) characterized by hypoxemia is a prevalent condition linked to many debilitating chronic diseases. However, the role of UFPs in the development of SDB is lacking. Therefore, this prospective panel study was performed to specifically investigate the association of short-term exposure to UFPs with SDB parameters in patients with chronic obstructive pulmonary disease (COPD). Ninety-one COPD patients completed 226 clinical visits in Beijing, China. Personal exposure to ambient UFPs of 0-7 days was estimated based on infiltration factor and time-activity pattern. Real-time monitoring of sleep oxygen saturation, spirometry, respiratory questionnaires and airway inflammation detection were performed at each clinical visit. Generalized estimating equation was used to estimate the effects of UFPs. Exposure to UFPs was significantly associated with increased oxygen desaturation index (ODI) and percent of the time with oxygen saturation below 90 % (T90), with estimates of 21.50 % (95%CI: 6.38 %, 38.76 %) and 18.75 % (95%CI: 2.83 %, 37.14 %), respectively, per 3442 particles/cm3 increment of UFPs at lag 0-3 h. Particularly, UFPs' exposure within 0-7 days was positively associated with the concentration of alveolar nitric oxide (CaNO), and alveolar eosinophilic inflammation measured by CaNO exceeding 5 ppb was associated with 29.63 % and 33.48 % increases in ODI and T90, respectively. In addition, amplified effects on oxygen desaturation were observed in current smokers. Notably, individuals with better lung function and activity tolerance were more affected by ambient UFPs due to longer time spent outdoors. To our knowledge, this is the first study to link UFPs to hypoxemia during sleep and uncover the key role of alveolar eosinophilic inflammation. Our findings provide new insights into the effect spectrum of UFPs and potential environmental and behavioral intervention strategies to protect susceptible populations.

14.
Int Ophthalmol ; 44(1): 315, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967725

RESUMO

Acute acquired comitant esotropia (AACE) is mainly characterized by sudden onset, accompanied by diplopia, without extraocular muscles paralysis or ocular motility disorders. In recent years, the incidence of AACE has been increasing, researchers have found that this phenomenon may be related to the widespread use of electronic devices and the increase in the number of people working from home during the COVID-19 pandemic. However, its neural mechanisms have not been fully elucidated. This article primarily reviews the latest developments in the diagnosis and treatment of AACE from the perspectives of etiology and treatment methods, aiming to provide direction for future in-depth exploration of the pathogenesis and treatment approaches of this disease.


Assuntos
COVID-19 , Esotropia , Humanos , Esotropia/diagnóstico , Esotropia/terapia , Esotropia/fisiopatologia , Esotropia/etiologia , COVID-19/complicações , COVID-19/diagnóstico , COVID-19/epidemiologia , Doença Aguda , Músculos Oculomotores/fisiopatologia , SARS-CoV-2
15.
Artigo em Inglês | MEDLINE | ID: mdl-38985654

RESUMO

Background: Intersection of gender and race and/or ethnicity in academic medicine is understudied; we aim to understand these factors in relation to scholarly achievements for neurology faculty. Methods: Faculty from 19 US neurology departments completed a survey (2021-2022) to report rank, leadership positions, publications, funded projects, awards, and speaker invitations. Regression analyses examined effects of gender, race, and their intersectionality on these achievements. Women, Black/Indigenous/People of Color (BIPOC), and BIPOC women were comparator groups. Results: Four hundred sixty-two faculty responded: 55% women, 43% men; 31% BIPOC, 63% White; 21% BIPOC women, 12% BIPOC men, 36% White women, 31% White men. Men and White faculty are more likely to be full professors than women and BIPOC faculty. The number of leadership positions, funded projects, awards, and speaker invitations are significantly greater in White compared to BIPOC faculty. Relative to BIPOC women, the number of leadership positions is significantly higher among BIPOC men, White women, and White men. Publication numbers for BIPOC men are lower, number of funded projects and speaker invitations for White women are higher, and number of awards among White men and White women is higher compared to BIPOC women. Discussion: Our study highlights that inequities in academic rank, award number, funded projects, speakership invitations, and leadership roles disproportionately impacted BIPOC women. More studies are needed to evaluate gender and race and/or ethnicity intersectionality effects on faculty achievements, reasons for inequities, recognition, and potential solutions.

16.
Langmuir ; 40(29): 15232-15243, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38995620

RESUMO

Three long alkyl chain-bearing dibenzotriazole ionic liquids (BTA-R-BTA, R = 8, 12, and 16) were synthesized with high yield (>98%) through a simple and eco-friendly process. Their anticorrosion performance for Q235 carbon steel in 6 M hydrochloride acid was comprehensively evaluated by weight loss tests, electrochemical methods (potentiodynamic polarization and electrochemical impedance spectroscopy), and surface analysis techniques. As the length of the alkyl chain increased, the maximum corrosion inhibition efficiency enhanced from 55.02% (for BTA-8-BTA at 1.2 mM) to 97.10% (for BTA-12-BTA at 0.3 mM) and 98.84% (for BTA-16-BTA at 0.3 mM). Density functional theory calculation indicated that the alkyl chain length had little influence on the inhibitors' electronic structures, while molecular dynamics simulations revealed that the thickness, surface coverage, and compactness of adsorption films formed at the metal-electrolyte interface increased with the elongated alkyl chain. Corrosion inhibition efficiency is strongly correlated with the structures of the adsorption film.

17.
Food Chem Toxicol ; : 114875, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39033872

RESUMO

Our previous study identified that nuclear factor-erythroid-2 p45-related factor 2 (NRF2) was activated in arsenite-induced tumorigenesis. However, the underlying mechanisms of NRF2 mediating apoptosis in arsenic-induced skin carcinogenesis remain unknown. This study explored the dynamic changes in apoptosis rate and the expression of apoptosis proteins in immortalized human keratinocytes (HaCaT) malignant transformation caused by 1.0 µM NaAsO2 at passages 0, 1, 7, 14, 21, 28, and 35. The result showed that the apoptosis rate decreased. The apoptosis-related proteins cleaved-caspase-3/caspase-3 ratio decreased in the later stages (passages 21, 28, and 35). Moreover, the expression of intrinsic ER stress pathway-related CHOP, ATF4, ATF6, and the intrinsic mitochondrial pathway-related Bax protein decreased in the later stages, while Bcl-2 and Mcl-1 increased, and NRF2 protein levels also increased. The apoptosis rate increased by silencing NRF2 expression in arsenite-transformed HaCaT (T-HaCaT) cells. Meanwhile, the expression of pro-apoptotic proteins (cleaved-caspase-3/caspase-3, CHOP, Bax) and ATF4, ATF6 increased. On the contrary, antiapoptotic protein levels (Bcl-2 and Mcl-1) decreased. The ability of colony formation and migration of T-HaCaT cells decreased. In conclusion, arsenite activated NRF2 in the later stages, decreasing apoptosis characterized by inhibiting endoplasmic reticulum stress-depended and mitochondria-depended apoptosis pathway, and further promoting NaAsO2-induced HaCaT cellular malignant transformation.

18.
Front Physiol ; 15: 1394740, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39015225

RESUMO

Ischemic stroke, a significant threat to human life and health, refers to a class of conditions where brain tissue damage is induced following decreased cerebral blood flow. The incidence of ischemic stroke has been steadily increasing globally, and its disease mechanisms are highly complex and involve a multitude of biological mechanisms at various scales from genes all the way to the human body system that can affect the stroke onset, progression, treatment, and prognosis. To complement conventional experimental research methods, computational systems biology modeling can integrate and describe the pathogenic mechanisms of ischemic stroke across multiple biological scales and help identify emergent modulatory principles that drive disease progression and recovery. In addition, by running virtual experiments and trials in computers, these models can efficiently predict and evaluate outcomes of different treatment methods and thereby assist clinical decision-making. In this review, we summarize the current research and application of systems-level computational modeling in the field of ischemic stroke from the multiscale mechanism-based, physics-based and omics-based perspectives and discuss how modeling-driven research frameworks can deliver insights for future stroke research and drug development.

19.
Eur J Surg Oncol ; 50(9): 108541, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-39029208

RESUMO

OBJECTIVES: Subsegmentectomy has been adopted for non-small cell lung cancer (NSCLC) for decades. This study aimed to compare the features between subsegmentectomy, segmentectomy and wedge resection for NSCLC. MATERIALS AND METHODS: NSCLC patients who underwent subsegmentectomy, segmentectomy, or wedge resection between 2014 and 2019 were retrospectively screened. Demographic, radiomic, and perioperative characteristics between patients were compared. Further, log-rank test, univariate and multivariate Cox regression were used for prognostic evaluation. RESULTS: There were 276, 670, and 494 patients undergoing subsegmentectomy, segmentectomy, and wedge resection, respectively. Patients with segmentectomy and subsegmentectomy had larger tumor sizes and greater distances to the pleura than those with wedge resection. Subsegmentectomy and segmentectomy were more likely to achieve adequate surgical margins than wedge resection (82.0 % vs. 79.5 % vs. 64.7 %, P < 0.001), which was especially true for nodules away from the pleura (80.2 % vs. 81.4 % vs. 55.8 %, P < 0.001). In addition, anatomic resection allowed for more lymph node dissection and required less preoperative localization than wedge reception. Subsegmentectomy preserved about two subsegments than segmentectomy (P < 0.001). The incidence of prolonged air leakage after subsegmentectomy (3.3 %) and wedge (1.8 %) was similar (P = 0.308). Notably, 66.8 % of patients who underwent segmentectomy or subsegmentectomy were considered unsuitable for wedge. During the follow-up (55.1 months), no tumor recurrence or death occurred in patients undergoing subsegmentectomy. No significant recurrence-free survival (P = 0.140) or overall survival (P = 0.370) difference existed between these groups. CONCLUSIONS: Subsegmentectomy could achieve more adequate surgical margins than wedge resection and showed superiority for deep nodules. Compared to segmentectomy, subsegmentectomy could preserve more lung parenchyma.

20.
Environ Pollut ; : 124572, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39029859

RESUMO

Arsenic (As) can accumulate in edible plant parts and thus pose a serious threat to human health. Identifying the contributions of various factors to soil available As is crucial for evaluating environmental risks. However, research quantitatively assessing the importance of soil properties on available As is scarce. In this study, we utilized 442 datasets covering total As, available As, and properties of farmland soils. The five machine learning models were employed to predict soil available As content, and the model with the best predictive performance was selected to calculate the importance of soil properties on available As and interpret the model results. The Random Forest model exhibited the best predictive performance, with R2 for the test set of dryland and paddy fields being 0.83 and 0.82 respectively, while also outperforming other machine learning models in terms of accuracy. Concurrently, evaluating the contribution of soil properties to soil available As revealed that increases in soil total arsenic, pH, organic matter (OM), and cation exchange capacity (CEC) led to higher soil available As content. Among these factors, soil total As had the greatest impact, followed by CEC. The influence of pH on soil available As was greater in dryland compared to OM, while in paddy fields, it was smaller than OM (p<0.01). Sensitivity analysis results indicated that reducing soil total As content had the greatest effect on available As. In both dryland and paddy field soils, reducing soil total As had the most pronounced effect on available As, leading to reductions of 10.09% and 8.48%, respectively. Therefore, prioritizing the regulation of soil total As and CEC is crucial in As contamination management practices to alter As availability in farmland soils.

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