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1.
Mol Cell ; 83(22): 4000-4016.e6, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37935198

RESUMO

While 19S proteasome regulatory particle (RP) inhibition is a promising new avenue for treating bortezomib-resistant myeloma, the anti-tumor impact of inhibiting 19S RP component PSMD14 could not be explained by a selective inhibition of proteasomal activity. Here, we report that PSMD14 interacts with NSD2 on chromatin, independent of 19S RP. Functionally, PSMD14 acts as a histone H2AK119 deubiquitinase, facilitating NSD2-directed H3K36 dimethylation. Integrative genomic and epigenomic analyses revealed the functional coordination of PSMD14 and NSD2 in transcriptional activation of target genes (e.g., RELA) linked to myelomagenesis. Reciprocally, RELA transactivates PSMD14, forming a PSMD14/NSD2-RELA positive feedback loop. Remarkably, PSMD14 inhibitors enhance bortezomib sensitivity and fosters anti-myeloma synergy. PSMD14 expression is elevated in myeloma and inversely correlated with overall survival. Our study uncovers an unappreciated function of PSMD14 as an epigenetic regulator and a myeloma driver, supporting the pursuit of PSMD14 as a therapeutic target to overcome the treatment limitation of myeloma.


Assuntos
Histonas , Mieloma Múltiplo , Humanos , Histonas/genética , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , Bortezomib/farmacologia , Bortezomib/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Mieloma Múltiplo/patologia , Linhagem Celular Tumoral , Enzimas Desubiquitinantes/metabolismo , Inibidores de Proteassoma/farmacologia , Transativadores/metabolismo
2.
Nano Lett ; 24(25): 7809-7818, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38874576

RESUMO

Noncontact sensing technology serves as a pivotal medium for seamless data acquisition and intelligent perception in the era of the Internet of Things (IoT), bringing innovative interactive experiences to wearable human-machine interaction perception networks. However, the pervasive limitations of current noncontact sensing devices posed by harsh environmental conditions hinder the precision and stability of signals. In this study, the triboelectric nanopaper prepared by a phase-directed assembly strategy is presented, which possesses low charge transfer mobility (1618 cm2 V-1 s-1) and exceptional high-temperature stability. Wearable self-powered noncontact sensors constructed from triboelectric nanopaper operate stably under high temperatures (200 °C). Furthermore, a temperature warning system for workers in hazardous environments is demonstrated, capable of nonintrusively identifying harmful thermal stimuli and detecting motion status. This research not only establishes a technological foundation for accurate and stable noncontact sensing under high temperatures but also promotes the sustainable intelligent development of wearable IoT devices under extreme environments.

3.
Nano Lett ; 24(23): 7125-7133, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38808683

RESUMO

Wearable sensors are experiencing vibrant growth in the fields of health monitoring systems and human motion detection, with comfort becoming a significant research direction for wearable sensing devices. However, the weak moisture-wicking capability of sensor materials leads to liquid retention, severely restricting the comfort of the wearable sensors. This study employs a pattern-guided alignment strategy to construct microhill arrays, endowing triboelectric materials with directional moisture-wicking capability. Within 2.25 s, triboelectric materials can quickly and directionally remove the droplets, driven by the Laplace pressure differences and the wettability gradient. The directional moisture-wicking triboelectric materials exhibit excellent pressure sensing performance, enabling rapid response/recovery (29.1/37.0 ms), thereby achieving real-time online monitoring of human respiration and movement states. This work addresses the long-standing challenge of insufficient moisture-wicking driving force in flexible electronic sensing materials, holding significant implications for enhancing the comfort and application potential of electronic skin and wearable electronic devices.


Assuntos
Pressão , Dispositivos Eletrônicos Vestíveis , Molhabilidade , Humanos , Desenho de Equipamento
4.
Nano Lett ; 24(12): 3826-3834, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38498923

RESUMO

Lightweight, easily processed, and durable polymeric materials play a crucial role in wearable sensor devices. However, achieving simultaneously high strength and toughness remains a challenge. This study addresses this by utilizing an ion-specific effect to control crystalline domains, enabling the fabrication of a polymeric triboelectric material with tunable mechanical properties. The dense crystal-domain cross-linking enhances energy dissipation, resulting in a material boasting both high tensile strength (58.0 MPa) and toughness (198.8 MJ m-3), alongside a remarkable 416.7% fracture elongation and 545.0 MPa modulus. Leveraging these properties, the material is successfully integrated into wearable self-powered devices, enabling real-time feedback on human joint movement. This work presents a valuable strategy for overcoming the strength-toughness trade-off in polymeric materials, paving the way for their enhanced applicability and broader use in diverse sensing applications.

5.
Nano Lett ; 24(10): 3273-3281, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38427598

RESUMO

As intelligent technology surges forward, wearable electronics have emerged as versatile tools for monitoring health and sensing our surroundings. Among these advancements, porous triboelectric materials have garnered significant attention for their lightness. However, these materials face the challenge of improving structural stability to further enhance the sensing accuracy of triboelectric sensors. In this study, a lightweight and strong porous cellulosic triboelectric material is designed by cell wall nanoengineering. By tailoring of the cell wall structure, the material shows a high mechanical strength of 51.8 MPa. The self-powered sensor constructed by this material has a high sensitivity of 33.61 kPa-1, a fast response time of 36 ms, and excellent pressure detection durability. Notably, the sensor still enables a high sensing performance after the porous cellulosic triboelectric material exposure to 200 °C and achieves real-time feedback of human motion, thereby demonstrating great potential in the field of wearable electronic devices.


Assuntos
Parede Celular , Dispositivos Eletrônicos Vestíveis , Humanos , Eletrônica , Movimento (Física) , Porosidade
6.
Small ; : e2310622, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377299

RESUMO

As the global population ages, bone diseases have become increasingly prevalent in clinical settings. These conditions often involve detrimental factors such as infection, inflammation, and oxidative stress that disrupt bone homeostasis. Addressing these disorders requires exogenous strategies to regulate the osteogenic microenvironment (OME). The exogenous regulation of OME can be divided into four processes: induction, modulation, protection, and support, each serving a specific purpose. To this end, metal-organic frameworks (MOFs) are an emerging focus in nanomedicine, which show tremendous potential due to their superior delivery capability. MOFs play numerous roles in OME regulation such as metal ion donors, drug carriers, nanozymes, and photosensitizers, which have been extensively explored in recent studies. This review presents a comprehensive introduction to the exogenous regulation of OME by MOF-based nanomaterials. By discussing various functional MOF composites, this work aims to inspire and guide the creation of sophisticated and efficient nanomaterials for bone disease management.

7.
Small ; 20(16): e2307504, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38018269

RESUMO

Triboelectric materials present great potential for harvesting huge amounts of dispersed energy, and converting them directly into useful electricity, a process that generates power more sustainably. Triboelectric nanogenerators (TENGs) have emerged as a technology to power electronics and sensors, and it is expected to solve the problem of energy harvesting and self-powered sensing from extreme environments. In this paper, a high-temperature-resistant triboelectric material is designed based on multilevel non-covalent bonding interactions, which achieves an ultra-high surface charge density of 192 µC m-2 at high temperatures. TENGs based on the triboelectric material exhibit more than an order of magnitude higher power output (2750 mW m-2 at 200 °C) than the existing devices at high temperatures. These remarkable properties are achieved based on enthalpy-driven molecular assembly in highly unbonded states. Thus, the material maintains bond strength and ultra-high surface charge density in entropy-dominated high-temperature environments. This molecular design concept points out a promising direction for the preparation of polymers with excellent triboelectric properties.

8.
Exp Dermatol ; 33(1): e14890, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37474877

RESUMO

A number of randomized controlled trials and real-world studies have demonstrated the effectiveness and safety of secukinumab in the treatment of moderate to severe psoriasis, whereas data on a large cohort of Chinese patients in long-term real-world practice are limited. This was a single-centre, uncontrolled, single-arm, prospective, observational cohort study that included 254 psoriatic patients treated with secukinumab between September 2019 and December 2022. Demographic and clinical characteristics of patients, clinical response and adverse events were evaluated. The 75% improvement in Psoriasis Area and Severity Index score (PASI 75), PASI 90, and PASI 100 in the 300 mg secukinumab group at 12 weeks were 91.7%, 74.0% and 39.7% respectively, increasing to 94.5%, 74.5% and 47.6% at 52 weeks. High body mass index (BMI), previous exposure to biologic therapies and history of previous conventional systemic therapies were associated with lower rates of PASI response. During the study period, 68 patients reported 83 adverse events (AEs) and the most frequent AEs were eczematous lesions. Up to 14.5% patients withdrew treatment due to disease remission combined with inconvenient transportation during the COVID-19 pandemic at 52 weeks. The rate of psoriasis exacerbation after COVID-19 infection in patients treated with secukinumab was 24.3% (17/70). This real-world study confirmed the high effectiveness of secukinumab in Chinese patients with moderate to severe plaque psoriasis, with an acceptable safety profile.


Assuntos
Anticorpos Monoclonais Humanizados , Anticorpos Monoclonais , Psoríase , Humanos , Anticorpos Monoclonais/efeitos adversos , Estudos Prospectivos , Pandemias , Resultado do Tratamento , Índice de Gravidade de Doença , Psoríase/patologia , China
9.
Exp Dermatol ; 33(1): e14891, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37493071

RESUMO

Generalized pustular psoriasis (GPP) is a rare and potentially life-threatening skin disease and the clinical heterogeneity of which is largely unknown. Retrospective cohort analysis was conducted on hospitalized GPP patients between January 2010 and November 2022. A total of 416 patients with GPP and psoriasis vulgaris (PV) respectively were included, matched 1:1 by sex and age. The heterogeneity of GPP was stratified by PV history and age. Compared with PV, GPP was significantly associated with prolonged hospitalization (11.7 vs. 10.3 day, p < 0.001), elevated neutrophil lymphocyte ratio (NLR) (5.93 vs. 2.44, p < 0.001) and anemia (13.9% vs. 1.2%, p < 0.001). Moreover, GPP alone (without PV history) was a relatively severer subtype with higher temperature (37.6°C vs. 38.0°C, p = 0.002) and skin infections (5.2% vs. 11.4%, p = 0.019) than GPP with PV. For patients across different age, compared with juvenile patients, clinical features support a severer phenotype in middle-aged, including higher incidence of anaemia (7.5% vs. 16.0%, p = 0.023) and NLR score (3.83 vs. 6.88, p < 0.001). Interleukin-6 (r = 0.59), high density lipoprotein cholesterol (r = -0.56), albumin (r = -0.53) and C-reactive protein-to-albumin ratio (r = 0.49) were the most relevant markers of severity in GPP alone, GPP with PV, juvenile and middle-aged GPP, respectively. This retrospective cohort suggests that GPP is highly heterogeneous and GPP alone and middle-aged GPP exhibit severe disease phenotypes. More attention on the heterogeneity of this severe disease is warranted to meet the unmet needs and promote the individualized management of GPP.


Assuntos
Exantema , Psoríase , Dermatopatias Vesiculobolhosas , Pessoa de Meia-Idade , Humanos , Estudos Retrospectivos , Psoríase/genética , Doença Aguda , Doença Crônica , Proteína C-Reativa
10.
BMC Cancer ; 24(1): 110, 2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38254159

RESUMO

BACKGROUNDS: Lymphoplasmacyte-rich meningioma(LPM) is a rare subtype of meningioma with a low degree of malignancy and an overall preferable prognosis. The purpose of this article is to increase the understanding of the disease, reduce misdiagnosis, and improve prognosis. METHODS: A search was conducted in the PubMed database for English articles published from 1993 to 2023. The keywords were "lymphoplasmacyte-rich (all fields) and meningioma (all fields) and English (lang)" and "lymphoplasmacyte-rich meningioma (title/abstract) and English (lang)".We further analyzed the clinical manifestations, imaging manifestations, pathological features, treatment strategies, and prognosis of LPM.The possible prognostic indicators were analyzed by the log-rank test and Pearson's chi-squared test. RESULTS: Fourteen reports with 95 LPM patients were included in this report, including 47 males and 48 females who were diagnosed between the ages of 9 and 79, with an average age of 45 years. The most common clinical manifestations are headache and limb movement disorders. In most cases, the tumor occurred on the convex portion of the brain. All tumors showed significant enhancement, with homogeneous enhancement being more common, and most patients showed peritumoral edema. Postoperative pathological EMA, LCA, and vimentin positivity were helpful for the final diagnosis of the patient. Log-rank tests showed a correlation between complete resection and better prognosis and recurrence. CONCLUSION: There is a lack of significant differences in the clinical symptoms and imaging manifestations of LPM compared to other diseases that need to be differentiated, and a clear diagnosis requires pathological examination. After standardized surgical treatment, the recurrence rate and mortality rate of LPM are both low. Complete surgical resection of tumors is associated with a better prognosis and lower recurrence rate.


Assuntos
Neoplasias Meníngeas , Meningioma , Feminino , Masculino , Humanos , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Meningioma/diagnóstico , Meningioma/epidemiologia , Prognóstico , Encéfalo , Bases de Dados Factuais , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/epidemiologia
11.
Endocr Pract ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38876178

RESUMO

OBJECTIVE: Continuous glucose monitoring (CGM) may have benefits in achieving glycemic control in critically ill patients. The aim of this study was to assess the accuracy of the Freestyle Libre H (professional version of the Libre Pro). in patients with acute respiratory failure (ARF) in the intensive care unit (ICU). METHODS: 52 adult patients with ARF were selected. The performance of CGM was evaluated using arterial blood glucose (aBG) and point-of-care (POC) glucose as reference values. Numerical accuracy was evaluated by the mean absolute relative difference (MARD), Bland-Altman analysis, and %15/15(the percentage of CGM values within 15 mg/dL or 15% of reference values <100 mg/dL or >100mg/dL, respectively), %20/20 and %30/30; Clinical accuracy was assessed by Clarke error grid analysis. RESULTS: 519 and 1504 pairs of aBG/CGM and POC/CGM glucose values were analyzed. The MARD values were 13.8% and 14.7%, respectively. The mean deviation of the Bland‒Altman analysis was 0.82 mmol/L and 0.81 mmol/L. %15/15, %20/20 and %30/30 of aBG values were 62.6%, 75.5%, and 92.4%, respectively; %15/15, %20/20 and %30/30 of POC values were 57.1%, 72.9%, and 88.7%, respectively. The Clarke error grid analysis showed that 97.8% and 99.3% of the values located in the (A+B) zone. Additionally, accuracy of CGM is not affected by general patient factors. CONCLUSION: This study demonstrated that the accuracy of CGM in patients with ARF is lower than that in most outpatients, and it is not affected by general patient factors. Whether CGM is beneficial to glucose management in ICU needs further evaluation.

12.
J Nanobiotechnology ; 22(1): 319, 2024 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-38849938

RESUMO

Myeloid-derived suppressor cells (MDSCs) have played a significant role in facilitating tumor immune escape and inducing an immunosuppressive tumor microenvironment. Eliminating MDSCs and tumor cells remains a major challenge in cancer immunotherapy. A novel approach has been developed using gemcitabine-celecoxib twin drug-based nano-assembled carrier-free nanoparticles (GEM-CXB NPs) for dual depletion of MDSCs and tumor cells in breast cancer chemoimmunotherapy. The GEM-CXB NPs exhibit prolonged blood circulation, leading to the preferential accumulation and co-release of GEM and CXB in tumors. This promotes synergistic chemotherapeutic activity by the proliferation inhibition and apoptosis induction against 4T1 tumor cells. In addition, it enhances tumor immunogenicity by immunogenic cell death induction and MDSC-induced immunosuppression alleviation through the depletion of MDSCs. These mechanisms synergistically activate the antitumor immune function of cytotoxic T cells and natural killer cells, inhibit the proliferation of regulatory T cells, and promote the M2 to M1 phenotype repolarization of tumor-associated macrophages, considerably enhancing the overall antitumor and anti-metastasis efficacy in BALB/c mice bearing 4T1 tumors. The simplified engineering of GEM-CXB NPs, with their dual depletion strategy targeting immunosuppressive cells and tumor cells, represents an advanced concept in cancer chemoimmunotherapy.


Assuntos
Desoxicitidina , Gencitabina , Imunoterapia , Camundongos Endogâmicos BALB C , Células Supressoras Mieloides , Nanopartículas , Animais , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Desoxicitidina/uso terapêutico , Células Supressoras Mieloides/efeitos dos fármacos , Camundongos , Imunoterapia/métodos , Feminino , Nanopartículas/química , Linhagem Celular Tumoral , Microambiente Tumoral/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Proliferação de Células/efeitos dos fármacos
13.
Neoplasma ; 71(3): 209-218, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38764295

RESUMO

WNK lysine deficient protein kinase 4 (WNK4) has been shown to be significantly associated with cancer progression. Nevertheless, its involvement in gastric cancer (GC) is unclear. The objective of this work was to investigate the WNK4's regulatory mechanism in GC. Quantitative RT-PCR and immunoblots revealed that WNK4 expression was downregulated in GC and that low expression of WNK4 was strongly linked to poor prognosis. Functional assays including cell counting kit-8 assay and colony formation assay demonstrated that overexpression of WNK4 led to limited tumor proliferation both in vitro and in vivo, while the WNK4 reduction yielded to the opposite results. Gene Set Enrichment Analysis (GSEA) indicated a potential association between WNK4 and the signal transducer and activator of transcription (STAT3). WNK4 suppressed the phosphorylation of signal transducer and activator of transcription 3 (p-STAT3) in GC cells. The inhibition of the STAT3 pathway with Stattic reversed growth and proliferation induced by WNK4 knockdown in GC cells. These findings provide new insights for identifying key therapeutic targets for GC in the future.


Assuntos
Proliferação de Células , Regulação para Baixo , Proteínas Serina-Treonina Quinases , Fator de Transcrição STAT3 , Transdução de Sinais , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Linhagem Celular Tumoral , Animais , Camundongos , Masculino , Feminino , Regulação Neoplásica da Expressão Gênica , Prognóstico , Fosforilação
14.
Neurosurg Rev ; 47(1): 35, 2024 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-38183517

RESUMO

Clear cell meningiomas are a rare histological subtype of World Health Organization (WHO) grade II meningioma. Despite its relatively low frequency, clear cell meningioma has attracted considerable attention because of its unique pathological characteristics, clinical behavior, and challenging management considerations. The purpose of our systematic review is to provide clinicians with a better understanding of this rare disease. PubMed was searched for articles in the English language published from 1988 to 2023 June. The keywords were as follows: "clear cell meningioma," "clear cell" and "meningioma." We analyzed clinical manifestations, radiological manifestations, pathological features, comprehensive treatment strategies, and prognosis to determine the factors influencing recurrence-free survival (RFS). Recurrence-free survival curves of related factors were calculated by the Kaplan‒Meier method. The log-rank test and Cox univariate analysis were adopted to assess the intergroup differences and seek significant factors influencing prognosis and recurrence. Fifty-seven papers met the eligibility criteria, including 207 cases of clear cell meningioma (CCM), which were confirmed by postoperative pathology. The fifty-seven articles involved 84 (40.6%) males and 123 (59.4%) females. The average age at diagnosis was 27.9 years (range, 14 months to 84 years). Among the symptoms observed, headache, neurologic deficit, and hearing loss were the most commonly reported clinical manifestations. Most tumors (47.8%) were located in the skull base region. Most tumors showed significant enhancement, and homogeneous enhancement was more common. A total of 152 (74.1%) patients underwent gross total resection (GTR), and 53 (25.9%) patients underwent subtotal resection (STR). During the follow-up, the tumor recurred in 80 (39.4%) patients. The log-rank test and the Cox univariate analysis revealed that tumor resection range (GTR vs. STR) and adjuvant treatment (YES vs. NO) were significant predictors of recurrence-free survival (RFS). Clear cell meningioma is a rare type of meningioma with challenging diagnosis and therapy. The prognosis of this disease is different from that of regular meningiomas. Recurrence remains a possibility even after total tumor resection. We found that the surgical resection range and adjuvant treatment affected the recurrence period. This finding provides significant guidance for the treatment of clear cell meningioma.


Assuntos
Neoplasias Meníngeas , Meningioma , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Sistema Nervoso Central , Cefaleia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia
15.
BMC Med Educ ; 24(1): 315, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38509488

RESUMO

BACKGROUND: Given the importance of perceptions of decent work for nursing students' future career choices, we attempted to determine potential classifications and characteristics of nursing students' perceptions of decent work so that targeted interventions could be developed. METHODS: A convenience sample of 1004 s- to fourth-year nursing students completed the General Information Questionnaire, Self-Regulatory Fatigue Scale, Occupational Identity Questionnaire, and Decent Work Perceptions Scale in a cross-sectional survey in Heilongjiang Province, China, resulting in 630 valid questionnaires with a valid return rate of 62.75%. Nursing students' perceptions of decent work were defined using descriptive and regression analysis. RESULTS: Latent profile analysis (LPA) identified three subgroups: low perceived decent work group, medium perceived decent work group, and high perceived decent work group, accounting for 4.76%, 69.37%, and 25.87% of the sample, respectively. The results of unordered multiclass logistic regression show that nursing students with relatively low levels of perceived decent work are more likely to have a low professional identity, a lack of respect for nursing seniors, an involuntary choice of nursing major, and a low family income. CONCLUSION: Different types of nursing students have different perceptions of decent work, and these universities and related departments can use different educational guidance strategies.


Assuntos
Bacharelado em Enfermagem , Estudantes de Enfermagem , Humanos , Estudos Transversais , Inquéritos e Questionários , China , Percepção
16.
Inflammopharmacology ; 32(2): 965-974, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38347300

RESUMO

OBJECTIVE: It was to systematically evaluate the effect of corticosteroids on 28d all-cause mortality (ACM), in-hospital death rate, and ICU death rate in critically ill sepsis patients. METHODS: PubMed, Embase, and Medline databases were used to screen the published literatures on the therapeutic effect of corticosteroids in the treatment of critically ill sepsis patients. After evaluating the quality of the included literatures, RevMan 5.3 software was used for meta-analysis. 4524 literatures regarding the application of corticosteroids to treat critically ill sepsis patients were preliminarily searched. After screening was carried out, 9 literatures were finally included. 2,850 patients were treated with corticosteroids and 2867 patients were treated with placebo. RESULTS: The meta-analysis of the effect of corticosteroids versus placebo on 28dACM showed [OR = 0.87, 95% CI 0.78-0.98, Z = 2.22, P = 0.03], P < 0.05; the meta-analysis of the outcome of corticosteroids versus placebo on ICU death rate showed [OR = 0.77, 95% CI 0.63-0.94, Z = 2.60, P = 0.009], P < 0.05; and the meta-analysis of the effect of corticosteroids versus placebo on in-hospital death rate showed [OR = 0.80, 95% CI 0.66-0.96, Z = 2.34, P = 0.002], P < 0.05. CONCLUSION: In summary, corticosteroids can reduce the death rate of critically ill sepsis patients to a certain extent and have good clinical application value.


Assuntos
Estado Terminal , Sepse , Humanos , Mortalidade Hospitalar , Sepse/tratamento farmacológico , Corticosteroides/uso terapêutico
17.
J Proteome Res ; 22(1): 36-46, 2023 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-36564034

RESUMO

Fatty aldehydes (FALs) are involved in various biological processes, and their abnormal metabolism is related to the occurrence and development of neurological diseases. Because of their low ionization efficiency, methods for in situ detection and mass spectrometry imaging (MSI) analysis of FALs remain underreported. On-tissue chemical tagging of hardly ionizable target analytes with easily ionized moieties can improve ionization efficiency and detection sensitivity in MSI experiments. In this study, an on-tissue chemical derivatization-air-flow-assisted desorption electrospray ionization-MSI method was developed to visualize FALs in the rat brain. The method showed high sensitivity and specificity, allowing the use of in situ high-resolution MS3 to identify FALs. The methodology was applied to investigate the region-specific distribution of FALs in the brains of control and diabetic encephalopathy (DE) rats. In DE rats, FALs were found to be significantly enriched in various brain regions, especially in the cerebral cortex, hippocampus, and amygdala. Thus, increased FAL levels and oxidative stress occurred in a region-dependent manner, which may contribute to cognitive function deficits in DE. In summary, we provide a novel method for the in situ detection of FALs in biological tissues as well as new insights into the potential pathogenesis of DE.


Assuntos
Diabetes Mellitus , Espectrometria de Massas por Ionização por Electrospray , Ratos , Animais , Espectrometria de Massas por Ionização por Electrospray/métodos , Aldeídos , Encéfalo/diagnóstico por imagem , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
18.
Clin Immunol ; 248: 109266, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36796469

RESUMO

To identify T cell subsets associated with control of tuberculosis, single-cell transcriptome and T cell receptor sequencing were performed on total T cells from patients with tuberculosis and healthy controls. Fourteen distinct subsets of T cells were identified by unbiased UMAP clustering. A GZMK-expressing CD8+ cytotoxic T cell cluster and a SOX4-expressing CD4+ central memory T cell cluster were depleted, while a MKI67-expressing proliferating CD3+ T cell cluster was expanded in patients with tuberculosis compared with healthy controls. The ratio of Granzyme K-expressing CD8+CD161-Ki-67- and CD8+Ki-67+ T cell subsets was significantly reduced and inversely correlated with the extent of TB lesions in patients with TB. In contrast, ratio of Granzyme B-expressing CD8+Ki-67+ and CD4+CD161+Ki-67- T cells and Granzyme A-expressing CD4+CD161+Ki-67- T cells were correlated with the extent of TB lesions. It is concluded that granzyme K-expressing CD8+ T cell subsets might contribute to protection against tuberculosis dissemination.


Assuntos
Linfócitos T CD8-Positivos , Tuberculose , Humanos , Granzimas , Antígeno Ki-67 , Linfócitos T CD8-Positivos/patologia , Subpopulações de Linfócitos T , Linfócitos T CD4-Positivos , Fatores de Transcrição SOXC
19.
Plant Physiol ; 188(1): 151-166, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-34601578

RESUMO

MYB transcription factors play essential roles in regulating plant secondary metabolism and jasmonate (JA) signaling. Putrescine N-methyltransferase is a key JA-regulated step in the biosynthesis of nicotine, an alkaloidal compound highly accumulated in Nicotiana spp. Here we report the identification of NtMYB305a in tobacco (Nicotiana tabacum) as a regulatory component of nicotine biosynthesis and demonstrate that it binds to the JA-responsive GAG region, which comprises a G-box, an AT-rich motif, and a GCC-box-like element, in the NtPMT1a promoter. Yeast one-hybrid analysis, electrophoretic mobility shift assay and chromatin immunoprecipitation assays showed that NtMYB305a binds to the GAG region in vitro and in vivo. Binding specifically occurs at the ∼30-bp AT-rich motif in a G/C-base-independent manner, thus defining the AT-rich motif as previously unknown MYB-binding element. NtMYB305a localized in the nucleus of tobacco cells where it is capable of activating the expression of a 4×GAG-driven GUS reporter in an AT-rich motif-dependent manner. NtMYB305a positively regulates nicotine biosynthesis and the expression of NtPMT and other nicotine pathway genes. NtMYB305a acts synergistically with NtMYC2a to regulate nicotine biosynthesis, but no interaction between these two proteins was detected. This identification of NtMYB305a provides insights into the regulation of nicotine biosynthesis and extends the roles played by MYB transcription factors in plant secondary metabolism.


Assuntos
Metiltransferases/genética , Metiltransferases/metabolismo , Nicotiana/genética , Nicotiana/metabolismo , Nicotina/biossíntese , Nicotina/genética , Oxilipinas/metabolismo , Ciclopentanos/metabolismo , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Reguladores de Crescimento de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Regiões Promotoras Genéticas , Fatores de Transcrição/metabolismo
20.
Crit Rev Food Sci Nutr ; 63(19): 3430-3451, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34666569

RESUMO

This study aimed to summarize the evidence regarding the effects of dietary intake before conception on pregnancy outcomes by performing a systematic review and meta-analysis of prospective studies. Electronic databases were searched from inception up to August 2021. Overall, 65 studies involving 831 798 participants were included and 38 studies were quantitatively pooled. With regard to maternal outcomes, pre-pregnancy intake of fried food, fast food, red and processed meat, heme iron and a low-carbohydrate dietary pattern was positively associated with the risk of gestational diabetes mellitus (GDM) (all P < 0.05). However, a high dietary fiber intake and folic acid supplementation were negatively associated with GDM risk (both P < 0.05). With regard to neonatal outcomes, maternal caffeine intake before pregnancy significantly increased the risk of spontaneous abortion, while folic acid supplementation had protective effects on total adverse neonatal outcomes, preterm birth, and small-for-gestational age (SGA, all P < 0.05). However, no significant associations were found between adverse pregnancy outcomes (i.e., GDM and SGA) and the pre-pregnancy dietary intake of sugar-sweetened beverages, potato, fish, and carbohydrates and the Healthy Eating Index. Our study suggests that maintaining a healthy diet before conception has significant beneficial effects on pregnancy outcomes.Supplemental data for this article is available online at https://doi.org/10.1080/10408398.2021.1989658.


Assuntos
Diabetes Gestacional , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Estudos Prospectivos , Resultado da Gravidez , Ingestão de Alimentos , Ácido Fólico
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