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1.
Magn Reson Med ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860542

RESUMO

PURPOSE: Tractography of the facial nerve based on diffusion MRI is instrumental before surgery for the resection of vestibular schwannoma, but no excellent methods usable for the suppression of motion and image noise have been proposed. The aim of this study was to effectively suppress noise and provide accurate facial nerve reconstruction by extend a fiber trajectory distribution function based on the fourth-order streamline differential equations. METHODS: Preoperative MRI from 33 patients with vestibular schwannoma who underwent surgical resection were utilized in this study. First, T1WI and T2WI were used to obtain mask images and regions of interest. Second, probabilistic tractography was employed to obtain the fibers representing the approximate facial nerve pathway, and these fibers were subsequently translated into orientation information for each voxel. Last, the voxel orientation information and the peaks of the fiber orientation distribution were combined to generate a fiber trajectory distribution function, which was used to parameterize the anatomical information. The parameters were determined by minimizing the cost between the trajectory of fibers and the estimated directions. RESULTS: Qualitative and visual analyses were used to compare facial nerve reconstruction with intraoperative recordings. Compared with other methods (SD_Stream, iFOD1, iFOD2, unscented Kalman filter, parallel transport tractography), the fiber-trajectory-distribution-based tractography provided the most accurate facial nerve reconstructions. CONCLUSION: The fiber-trajectory-distribution-based tractography can effectively suppress the effect of noise. It is a more valuable aid for surgeons before vestibular schwannoma resection, which may ultimately improve the postsurgical patient's outcome.

2.
Fam Pract ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38706165

RESUMO

BACKGROUND: In primary care, health professionals use blood tests to investigate nonspecific presentations to inform referral decisions. Reference ranges for the commonly used blood tests in western countries were developed in predominately White populations, and so may perform differently when applied to non-White populations. Knowledge of ethnic variation in blood test results in healthy/general populations could help address ethnic inequalities in cancer referral for diagnosis and outcomes. OBJECTIVE: This systematic review explored evidence of ethnic differences in the distribution of selected blood test results among healthy/general populations to inform future research aimed at addressing inequalities in cancer diagnosis. METHODS: We searched PubMed and EMBASE to identify studies reporting measures of haemoglobin, MCV, calcium, albumin, platelet count, and CRP in nondiseased adults from at least 2 different ethnic groups. Two reviewers independently screened studies, completed data extraction and quality assessment using an adapted Newcastle-Ottawa scale. Participants were stratified into White, Black, Asian, Mixed, and Other groups. Data were synthesised narratively and meta-analyses were conducted where possible. RESULTS: A total of 47 papers were included. Black men and women have lower average values of haemoglobin, MCV, and albumin, and higher average values of CRP relative to their White counterparts. Additionally, Black men have lower average haemoglobin than Asian men, whereas Asian women have lower average CRP values when compared with White women. CONCLUSIONS: There is evidence of ethnic differences in average values of haemoglobin, MCV, CRP, and albumin in healthy/general populations. Further research is needed to explore the reasons for these differences. Systematic review registration: CRD42021274580.

3.
BMJ Med ; 3(1): e000451, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38800667

RESUMO

Objective: To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design: Prospective cohort study. Setting: UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants: 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study. Main outcome measures: Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Results: Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99). Conclusions: Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

4.
Adv Mater ; : e2402143, 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38609159

RESUMO

Perovskite/organic tandem solar cells (PO-TSCs) demonstrate exceptional suitability for emerging applications such as building-integrated photovoltaics, wearable devices, and greenhouse farming. By leveraging the distinctive attributes of perovskite and organic materials, which encompass expanded solar spectrum utilization, chemically benign solubility, and soft nature, PO-TSCs position themselves as ideal candidates for high-performance semi-transparent photovoltaics (ST-PVs). Despite these advantages, their development significantly lags behind other perovskite-based counterparts, such as perovskite/perovskite, perovskite/silicon, and perovskite/Cu(In, Ga)Se2. To address existing challenges and unlock the full potential of PO-TSCs, an exploration of the fundamental mechanisms governing tandem photovoltaic devices is embarked. Delving into critical aspects such as charge generation/separation, energy level alignment, and material choices becomes pivotal for optimizing PO-TSC performance. The investigation of monolithic two-terminal PO-TSCs offers insights into achievements and barriers, recognizing the competitive landscape with other TSC counterparts. Further scrutiny of perovskite absorbers and organic absorbers in TSCs reveals strategies aimed at enhancing stability and efficiency. The discussion extends to interconnection layers, elucidating their role in optimizing light transmission and balancing carrier recombination. In conclusion, a compelling outlook on the dynamic landscape of PO-TSCs is presented, highlighting the remarkable efficiency progression and signaling their potential to revolutionize solar energy harvesting technologies.

5.
Huan Jing Ke Xue ; 45(5): 3037-3046, 2024 May 08.
Artigo em Chinês | MEDLINE | ID: mdl-38629564

RESUMO

Through lettuce potting experiments, the effects of different types of biochar (apple branch, corn straw, and modified sorghum straw biochar with phosphoric acid modification) on lettuce growth under tetracycline (TC) and copper (Cu) co-pollution were investigated. The results showed that compared with those under CK, the addition of biochar treatment significantly increased the plant height, root length, shoot fresh weight, and root fresh weight of lettuce (P < 0.05). The addition of different biochars significantly increased the nitrate nitrogen, chlorophyll, and soluble protein content in lettuce physiological indicators to varying degrees, while also significantly decreasing the levels of malondialdehyde, proline content, and catalase activity. The effects of biochar on lettuce physiological indicators were consistent during both the seedling and mature stages. Compared with those in CK, the addition of biochar resulted in varying degrees of reduction in the TC and Cu contents of both the aboveground and underground parts of lettuce. The aboveground TC and Cu levels decreased by 2.49%-92.32% and 12.79%-36.47%, respectively. The underground TC and Cu levels decreased by 12.53%-55.64% and 22.41%-42.29%, respectively. Correlation analysis showed that nitrate nitrogen, chlorophyll, and soluble protein content of lettuce were negatively correlated with TC content, whereas malondialdehyde, proline content, and catalase activity were positively correlated with TC content. The resistance genes of lettuce were positively correlated with TC content (P < 0.05). In general, modified biochar was found to be more effective in improving lettuce growth quality and reducing pollutant accumulation compared to unmodified biochar, with modified sorghum straw biochar showing the best remediation effect.


Assuntos
Poluentes Ambientais , Poluentes do Solo , Cobre , Lactuca , Poluentes Ambientais/análise , Solo , Catalase , Nitratos/análise , Antibacterianos , Tetraciclina/análise , Carvão Vegetal , Poluentes do Solo/análise , Clorofila/análise , Malondialdeído , Nitrogênio/análise , Prolina
6.
World J Gastroenterol ; 30(14): 1968-1981, 2024 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-38681120

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is the most prevalent type of chronic liver disease. However, the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies. Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoetiology and suggest functional therapeutic and diagnostic options. Pyroptosis, ferroptosis, and necroptosis are the main subtypes of non-apoptotic regulated cell deaths (RCDs), each of which represents particular characteristics. Considering the complexity of the findings, the present study aimed to review these types of RCDs and their contribution to NAFLD progression, and subsequently discuss in detail the role of necroptosis in the pathoetiology, diagnosis, and treatment of the disease. The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer, hence it has potential in diagnostic and therapeutic approaches. Nevertheless, further studies are necessary.


Assuntos
Progressão da Doença , Hepatócitos , Necroptose , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/terapia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Humanos , Hepatócitos/patologia , Fígado/patologia , Ferroptose , Piroptose , Animais , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico
7.
Environ Res ; 252(Pt 2): 118962, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38642637

RESUMO

BACKGROUND: The association between long-term exposure to ozone (O3) and adult-onset asthma (AOA) remains inconclusive, and analysis of causality is lacking. OBJECTIVES: To examine the causal association between long-term O3 exposure and AOA. METHODS: A prospective cohort study of 362,098 participants was conducted using the UK Biobank study. Incident cases of AOA were identified using health administrative data of the National Health Services. O3 exposure at participants' residential addresses was estimated by a spatio-temporal model. Instrumental variable (IV) modelling was used to analyze the causal association between O3 exposure and AOA, by incorporating wind speed and planetary boundary layer height as IVs into time-dependent Cox model. Negative control outcome (accidental injury) was also used to additionally evaluate unmeasured confounding. RESULTS: During a mean follow-up of 11.38 years, a total of 10,973 incident AOA cases were identified. A U-shaped concentration-response relationship was observed between O3 exposure and AOA in the traditional Cox models with HR of 0.916 (95% CI: 0.888, 0.945) for O3 at low levels (<38.17 ppb), and 1.204 (95% CI: 1.168, 1.242) for O3 at high levels (≥38.17 ppb). However, in the IV analysis we only found a statistically significant association between high-level O3 exposure and AOA risk, but not for low-level O3 exposure. No significant associations between O3 exposure and accidental injury were observed. CONCLUSION: Our findings suggest a potential causal relationship between long-term exposure to high-level ambient O3 and increased risks of AOA.


Assuntos
Poluentes Atmosféricos , Asma , Exposição Ambiental , Ozônio , Humanos , Ozônio/análise , Ozônio/efeitos adversos , Asma/epidemiologia , Asma/induzido quimicamente , Estudos Prospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Adulto , Exposição Ambiental/efeitos adversos , Idoso , Reino Unido/epidemiologia , Incidência
8.
Ann Hematol ; 103(6): 1967-1977, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38676765

RESUMO

Acute myeloid leukemia (AML) is a highly heterogeneous hematological malignancy. Cytarabine (Ara-C)-based chemotherapy is the primary treatment for AML, but currently known prognostic risk stratification factors cannot fully explain the individual differences in outcome of patients. In this article, we reported that patients with homozygous GLI1 rs2228224 mutation (AA genotype) had a significantly lower complete remission rate than those with GG wild type (54.17% vs.76.02%, OR = 1.993, 95% CI: 1.062-3.504, P = 0.031). GLI1 rs2229300 T allele carriers had remarkably shorter overall survival (513 vs. 645 days, P = 0.004) and disease-free survival (342 vs. 456 days, P = 0.033) than rs2229300 GG carriers. Rs2229300 G > T variation increased the transcriptional activity of GLI1. CCND1, CD44 and PROM1 were potential target genes differentially regulated by GLI1 rs2229300. Our results demonstrated for the first time that GLI1 polymorphisms influence chemosensitivity and prognosis of young de novo AML patients treated with Ara-C.


Assuntos
Citarabina , Leucemia Mieloide Aguda , Indução de Remissão , Proteína GLI1 em Dedos de Zinco , Humanos , Proteína GLI1 em Dedos de Zinco/genética , Citarabina/uso terapêutico , Citarabina/administração & dosagem , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Feminino , Masculino , Adulto , Adolescente , Adulto Jovem , Prognóstico , Polimorfismo de Nucleotídeo Único , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Intervalo Livre de Doença
9.
Cancer Lett ; 592: 216905, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38677641

RESUMO

Craniopharyngiomas (CPs), particularly Adamantinomatous Craniopharyngiomas (ACPs), often exhibit a heightened risk of postoperative recurrence and severe complications of the endocrine and hypothalamic function. The primary objective of this study is to investigate potential novel targeted therapies within the microenvironment of ACP tumors. Cancer-Associated Fibroblasts (CAFs) were identified in the craniopharyngioma microenvironment, notably in regions characterized by cholesterol clefts, wet keratin, ghost cells, and fibrous stroma in ACPs. CAFs, alongside ghost cells, basaloid-like epithelium cells and calcifications, were found to secrete PROS1 and GAS6, which can activate AXL receptors on the surface of tumor epithelium cells, promoting immune suppression and tumor progression in ACPs. Additionally, the AXL inhibitor Bemcentinib effectively inhibited the proliferation organoids and enhanced the immunotherapeutic efficacy of Atezolizumab. Furthermore, neural crest-like cells were observed in the glial reactive tissue surrounding finger-like protrusions. Overall, our results revealed that the AXL might be a potentially effective therapeutic target for ACPs.


Assuntos
Receptor Tirosina Quinase Axl , Craniofaringioma , Neoplasias Hipofisárias , Proteínas Proto-Oncogênicas , Receptores Proteína Tirosina Quinases , Microambiente Tumoral , Humanos , Craniofaringioma/genética , Craniofaringioma/tratamento farmacológico , Craniofaringioma/patologia , Craniofaringioma/metabolismo , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/patologia , Neoplasias Hipofisárias/tratamento farmacológico , Neoplasias Hipofisárias/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Feminino , Masculino , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Perfilação da Expressão Gênica/métodos , RNA-Seq , Benzocicloeptenos/farmacologia , Animais , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Adulto , Terapia de Alvo Molecular , Pessoa de Meia-Idade , Triazóis
10.
Ultrasonics ; 140: 107301, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38522167

RESUMO

In this paper, a damage spatial imaging approach based on novel signal extraction is suggested to reconstruct the Lamb wave response signal under strong noise and realize the spatial localization of damage. First, the Variable Mode Decomposition (VMD) parameters are optimized by the improved Grey Wolf optimization method (IGWO) to decompose the response signal. To rebuild the response signal, the correlation coefficient is used to choose the optimal modal component and the residual. To give the best wavelet function and transform level for adaptive denoising of the reconstructed signal without a reference signal, an enhanced Discrete Wavelet Transform (DWT) based on Shannon entropy is proposed. To achieve damage localization imaging, a damage spatial localization model is built utilizing a reconstruction algorithm for probabilistic inspection of damage (RAPID) approach and a convolutional neural network (CNN). The suggested method may successfully increase the signal-to-noise ratio (SNR) of the reconstructed response signal and lower the error of spatial localization under strong noise through experiments. The spatial localization of composite damage using Lamb wave under strong noise is expanded in this paper.

11.
Chin J Cancer Res ; 36(1): 25-35, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38455372

RESUMO

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied. Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel (ThyroLead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification (MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS. Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIR-DTC. Genetic alterations were identified in 90% of all the patients, with BRAF (59.7% vs. 17.3%), TERT promoter (43.9% vs. 7.4%), and TP53 mutations (11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions (15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness (P<0.001), with an odds ratio (OR) of high to low MRS of 7.52 [95% confidence interval (95% CI), 3.96-14.28; P<0.001] and an OR of intermediate to low MRS of 3.20 (95% CI, 1.01-10.14; P=0.041). Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

12.
Nutr Rev ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38452296

RESUMO

CONTEXT: Increased adherence to a traditional Chinese diet (TCD) could reduce the increasing prevalence of noncommunicable diseases. Currently, there is no consistent definition of the TCD in the literature, and its associations with health outcomes have not yet been identified. OBJECTIVE: This systematic review aimed to assess the definition of the TCD, in the literature, and to evaluate whether the TCD, as described, is associated with health outcomes. DATA SOURCES: Fourteen databases were searched up to April 25, 2022. DATA EXTRACTION: Three reviewers (in pairs) independently screened and extracted data. A modified risk-of-bias tool was used to assess the quality of the studies assessing the TCD definition; the Newcastle-Ottawa Scale and the Cochrane Risk-of-Bias tool were used to assess the quality of the observational studies and randomized controlled trials assessing associations between the TCD and health outcomes. DATA ANALYSIS: Ninety-nine studies were identified that assessed the TCD definition. In at least 75% of the studies, rice and leafy vegetables were consistently reported as food groups that characterize the TCD; the most frequently cited food items were white rice, spinach, bokchoy, and cabbage. Fish and seafood, pork, and pork products were consistently reported in studies exclusively referring to the TCD consumed in southern China (n = 21 studies), whereas wheat and wheat products were commonly reported in studies focusing on northern China (n = 14 studies). Fifteen studies reported on the quantities of food groups that are characteristic of the TCD, but their findings were inconsistent. Of the 99 studies, 54 assessed associations with health outcomes. The TCD was overall inversely associated with obesity risk and weight gain, while relationships between the TCD and other health outcomes were inconsistent. CONCLUSION: Further studies are needed to determine the quantities of foods consumed in the TCD and to establish a consistent definition for further exploration of the TCD's potential role in preventing non-communicable diseases.

13.
Nutrients ; 16(5)2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38474722

RESUMO

Some studies suggest an association between iron overload and cardiovascular diseases (CVDs). However, the relationship between dietary iron intake and atrial fibrillation (AF) remains uncertain, as does the role of genetic loci on this association. The study involved 179,565 participants from UK Biobank, tracking incident atrial fibrillation (AF) cases. Iron intake was categorized into low, moderate, and high groups based on dietary surveys conducted from 2009 to 2012. The Cox regression model was used to estimate the risk of AF in relation to iron intake, assessing the hazard ratio (HR) and 95% confidence interval (95% CI). It also examined the impact of 165 AF-related and 20 iron-related genetic variants on this association. Pathway enrichment analyses were performed using Metascape and FUMA. During a median follow-up period of 11.6 years, 6693 (3.97%) incident AF cases were recorded. A total of 35,874 (20.0%) participants had high iron intake. High iron intake was associated with increased risk of AF [HR: 1.13 (95% CI: 1.05, 1.22)] in a fully adjusted model. Importantly, there were 83 SNPs (11 iron-related SNPs) that could enhance the observed associations. These genes are mainly involved in cardiac development and cell signal transduction pathways. High dietary iron intake increases the risk of atrial fibrillation, especially when iron intake exceeds 16.95 mg. The association was particularly significant among the 83 SNPs associated with AF and iron, the individuals with these risk genes. Gene enrichment analysis revealed that these genes are significantly involved in cardiac development and cell signal transduction processes.


Assuntos
Fibrilação Atrial , Humanos , Fibrilação Atrial/genética , Estudos Prospectivos , Ferro , Ferro da Dieta , Fatores de Risco , Ingestão de Alimentos , Variação Genética , Incidência
14.
J Hazard Mater ; 469: 133944, 2024 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-38457975

RESUMO

Epidemiological evidence for long-term air pollution exposure and Parkinson's disease (PD) is controversial, and analysis of causality is limited. We identified 293,888 participants who were free of PD at baseline in the UK Biobank (2006-2010). Time-varying air pollution [fine particulate (PM2.5) and ozone (O3)] exposures were estimated using spatio-temporal models. Incident cases of PD were identified using validated algorithms. Four methods were used to investigate the associations between air pollution and PD, including (1) standard time-varying Cox proportional-hazard model; (2) Cox models weighted by generalized propensity score (GPS) and inverse-probability weights (IPW); (3) instrumental variable (IV) analysis; and (4) negative control outcome analysis. During a median of 11.6 years of follow-up, 1822 incident PD cases were identified. Based on standard Cox regression, the hazard ratios (95% confidence interval) for a 1 µg/m3 or ppb increase in PM2.5 and O3 were 1.23 (1.17, 1.30) and 1.02 (0.98, 1.05), respectively. Consistent results were found in models weighted by GPS and IPW, and in IV analysis. There were no significant associations between air pollution and negative control outcomes. This study provides evidence to support a causal association between PM2.5 exposure and PD. Mitigation of air pollution could be a protective measure against PD.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Doença de Parkinson , Humanos , Poluentes Atmosféricos/toxicidade , Poluentes Atmosféricos/análise , Material Particulado/análise , Doença de Parkinson/epidemiologia , Doença de Parkinson/etiologia , Exposição Ambiental/análise , Poluição do Ar/análise , Dióxido de Nitrogênio
15.
Dev Cell ; 59(7): 882-897.e6, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38387460

RESUMO

Attenuated inflammatory response is a property of embryonic stem cells (ESCs). However, the underlying mechanisms are unclear. Moreover, whether the attenuated inflammatory status is involved in ESC differentiation is also unknown. Here, we found that autophagy-related protein ATG5 is essential for both attenuated inflammatory response and differentiation of mouse ESCs and that attenuation of inflammatory signaling is required for mouse ESC differentiation. Mechanistically, ATG5 recruits FBXW7 to promote ubiquitination and proteasome-mediated degradation of ß-TrCP1, resulting in the inhibition of nuclear factor κB (NF-κB) signaling and inflammatory response. Moreover, differentiation defects observed in ATG5-depleted mouse ESCs are due to ß-TrCP1 accumulation and hyperactivation of NF-κB signaling, as loss of ß-TrCP1 and inhibition of NF-κB signaling rescued the differentiation defects. Therefore, this study reveals a previously uncharacterized mechanism maintaining the attenuated inflammatory response in mouse ESCs and further expands the understanding of the biological roles of ATG5.


Assuntos
Proteína 5 Relacionada à Autofagia , Células-Tronco Embrionárias Murinas , Animais , Camundongos , Diferenciação Celular/fisiologia , Células-Tronco Embrionárias , Células-Tronco Embrionárias Murinas/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais/fisiologia , Proteína 5 Relacionada à Autofagia/metabolismo
16.
Mol Cell ; 84(7): 1257-1270.e6, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38377993

RESUMO

Current base editors (BEs) use DNA deaminases, including cytidine deaminase in cytidine BE (CBE) or adenine deaminase in adenine BE (ABE), to facilitate transition nucleotide substitutions. Combining CBE or ABE with glycosylase enzymes can induce limited transversion mutations. Nonetheless, a critical demand remains for BEs capable of generating alternative mutation types, such as T>G corrections. In this study, we leveraged pre-trained protein language models to optimize a uracil-N-glycosylase (UNG) variant with altered specificity for thymines (eTDG). Notably, after two rounds of testing fewer than 50 top-ranking variants, more than 50% exhibited over 1.5-fold enhancement in enzymatic activities. When eTDG was fused with nCas9, it induced programmable T-to-S (G/C) substitutions and corrected db/db diabetic mutation in mice (up to 55%). Our findings not only establish orthogonal strategies for developing novel BEs but also demonstrate the capacities of protein language models for optimizing enzymes without extensive task-specific training data.


Assuntos
Ácidos Alcanossulfônicos , Edição de Genes , Uracila-DNA Glicosidase , Animais , Camundongos , Mutação , Uracila-DNA Glicosidase/genética , Uracila-DNA Glicosidase/metabolismo
17.
Plant Dis ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386300

RESUMO

The genus Passiflora, commonly known as passion fruit, originated in South America, is an economically important horticulture crop and widely distributed in the tropics and subtropics. Yellow passion fruit (Passiflora edulis f. flavicarpa) and purple passion fruit (Passiflora edulis f. edulis) are the two most planted species (Santos-Jiménez et al., 2022), which have been largely cultivated in southern China. The average annual production reaches 600,000 tons, of which yellow fruit accounts for more than 70% (Zhou et al., 2022). In 2022 to 2023, a disease caused flower rot severely in passion fruit plantations. The incidence rate was generally 10% in purple passion fruit, with an incidence up to 60% in yellow passion fruit 'Qinmi No. 9'. Flower rot occurs mainly in the rainy season, especially during periods of prolonged rain. Infected flowers had black patches that were water-soaked on the interior of the flower bud. The patches covered the entire flower bud, and fluffy mycelium and sporangia developed, which caused the flower bud rotten and abscised easily. Five symptomatic flowers from Wuhua, Guangdong (23°23'N, 115°18'E) and 8 symptomatic flowers from Shangsi, Guangxi (21°15'N, 107°98'E) of 'Qinmi No. 9' were collected during flowering period in 2022 and 2023. Diseased flower pieces were surface-sterilized with 70% ethanol for 2 to 3 min, rinsed with sterile distilled water 3 times, and placed on PDA medium at 25℃ in darkness. Four and 6 fungal isolates with similar morphology were isolated from the infected samples of Wuhua and Shangsi, respectively. Two isolates, PRFJ01 from Wuhua and PRGX02 from Shangsi, were randomly selected for further study. Purified fungal colonies at the age of 3 days accompany with diffuse cottony mycelia, turned white to gray later. The mycelia were hyaline and aseptate. Sporangiophores with 0.56 (0.22~1.10) mm in length and 6.1 (3.18~10.87) µm in width (n=100) were erect, light brown, and had rhizoids and stolons at their bases. Sporangia with 48.0 (23.45~92.85) µm in diameter (n=100) were dark-colored, near spherical and having dark ovoid sporangiospores with 3.56 (2.34~6.39) µm × 2.82 (1.73~4.70) µm (n=100). The morphology of the fungus were identical to Rhizopus stolonifer (Ehrenb.) Vuill (Haque et al. 2023). The two isolates were molecularly identified using genomic regions of 28S large ribosomal subunit (LSU) with NL1 and LR3 primers (Cruz-Lachica et al., 2018). The phylogenetic trees revealed the sequences of PRFJ01 (OR801560.1) and PRGX02 (OR801561.1) were 100% and 99% identical to R. stolonifer (MK705761.1 and KC412868.1), respectively. Pathogenicity tests were conducted on healthy flowers and leaves of 5-month-old grafted 'Qinmi No. 9' plants. Mycelial plugs with 5-mm diameter were placed on the flowers and leaves. Three plants were performed for each of the isolates, and the test was repeated twice. The inoculated plants were moisturized with plastic bags. Healthy flowers and leaves inoculated with sterile PDA plugs were used as control. Typical symptoms were observed on inoculated plants after 2 days. The dark grey mycelia and sporangia covered the entire flower after 4 days inoculation. The flower bud became putrid and the flower stalk split off. Lesions on leaves expanded accompany with numerous aerial mycelium. However, the controls were symptomless. R. stolonifer was reisolated from inoculated tissues. Previously, flower rot on passion fruit caused by R. stolonifer has only been recorded in Brazil (Ploetz, 2003). To our knowledge, this is the first report of R. stolonifer causing flower rot on passion fruit in China.

18.
Phys Med Biol ; 69(7)2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38422543

RESUMO

Objective.Automated segmentation of vestibular schwannoma (VS) using magnetic resonance imaging (MRI) can enhance clinical efficiency. Though many advanced methods exist for automated VS segmentation, the accuracy is hindered by ambivalent tumor borders and cystic regions in some patients. In addition, these methods provide results that do not indicate segmentation uncertainty, making their translation into clinical workflows difficult due to potential errors. Providing a definitive segmentation result along with segmentation uncertainty or self-confidence is crucial for the conversion of automated segmentation programs to clinical aid diagnostic tools.Approach.To address these issues, we propose a U-shaped cascade transformer structure with a sliding window that utilizes multiple sliding samples, a segmentation head, and an uncertainty head to obtain both the segmentation mask and uncertainty map. We collected multimodal MRI data from 60 clinical patients with VS from Xuanwu Hospital. Each patient case includes T1-weighted images, contrast-enhanced T1-weighted images, T2-weighted images, and a tumor mask. The images exhibit an in-plane resolution ranging from 0.70 × 0.70 to 0.76 × 0.76 mm, an in-plane matrix spanning from 216 × 256 to 284 × 256, a slice thickness varying between 0.50 and 0.80 mm, and a range of slice numbers from 72 to 120.Main results.Extensive experimental results show that our method achieves comparable or higher results than previous state-of-the-art brain tumor segmentation methods. On our collected multimodal MRI dataset of clinical VS, our method achieved the dice similarity coefficient (DSC) of 96.08% ± 1.30. On a publicly available VS dataset, our method achieved the mean DSC of 94.23% ± 2.53.Significance.The method efficiently solves the VS segmentation task while providing an uncertainty map of the segmentation results, which helps clinical experts review the segmentation results more efficiently and helps to transform the automated segmentation program into a clinical aid diagnostic tool.


Assuntos
Processamento de Imagem Assistida por Computador , Neuroma Acústico , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neuroma Acústico/diagnóstico por imagem , Incerteza , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal
19.
J Nanobiotechnology ; 22(1): 79, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38419097

RESUMO

Osteoarthritis (OA) is a degenerative disease that significantly impairs quality of life. There is a pressing need for innovative OA therapies. While small extracellular vesicles (sEVs) show promising therapeutic effects against OA, their limited yield restricts clinical translation. Here, we devised a novel production system for sEVs that enhances both their yield and therapeutic properties. By stimulating mesenchymal stem cells (MSCs) using electromagnetic field (EMF) combined with ultrasmall superparamagnetic iron oxide (USPIO) particles, we procured an augmented yield of EMF-USPIO-sEVs. These vesicles not only activate anabolic pathways but also inhibit catabolic activities, and crucially, they promote M2 macrophage polarization, aiding cartilage regeneration. In an OA mouse model triggered by anterior cruciate ligament transection surgery, EMF-USPIO-sEVs reduced OA severity, and augmented matrix synthesis. Moreover, they decelerated OA progression through the microRNA-99b/MFG-E8/NF-κB signaling axis. Consequently, EMF-USPIO-sEVs present a potential therapeutic option for OA, acting by modulating matrix homeostasis and macrophage polarization.


Assuntos
Vesículas Extracelulares , Osteoartrite , Animais , Camundongos , Qualidade de Vida , Osteoartrite/metabolismo , Homeostase , Macrófagos/metabolismo , Vesículas Extracelulares/metabolismo
20.
Heliyon ; 10(4): e25660, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390093

RESUMO

Objective: This study explored the potential association between the Prognostic Nutritional Index (PNI) and the incidence of non-alcoholic fatty liver disease (NAFLD) and advanced liver fibrosis (AF) in the adult population of the United States. Methods: Information on 6409 participants ≥18 years old was downloaded from the U.S. National Health and Nutrition Examination Survey (NHANES) from 2017 to 2020. Multivariate analysis was combined with demographic factors to assess the relationships between PNI, NAFLD, and AF. A restricted cubic spline (RCS) was used to characterise the nonlinear association between the PNI and NAFLD and AF. Results: Patients without NAFLD had substantially lower mean values for parameters such as age, lymphocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammatory index (SII), total cholesterol, triglycerides, HbA1c, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) than patients with NAFLD. Interestingly, non-NAFLD patients showed a pronounced increase in serum albumin levels compared to their NAFLD counterparts. In the subset without AF, there were discernibly lower measures of NLR, age, AST, ALT, γ-glutamyl transferase, triglycerides, neutrophil count, and body mass index (BMI) than in patients with AF. It was evident that those without AF had markedly elevated mean albumin and PNI levels in comparison to AF-affected individuals. In the comprehensive multivariable framework, a direct correlation was observed between PNI and NAFLD (adjusted odds ratio[aOR] = 1.07, 95% confidence interval [CI]: 1.05-1.09; p < 0.001), whereas PNI and AF were inversely correlated (aOR = 0.92; 95% CI: 0.88-0.96; p < 0.001). Within the RCS model, a swift ascendancy was noted in the relationship between the PNI and NAFLD, peaking at approximately 52. Conversely, a non-linear inverse association was observed between PNI and AF. Conclusion: Our analytical results indicate that elevated PNI levels are positively associated with an increased risk of NAFLD, but inversely related to the risk of AF. For robust validation of these observations, further research is required.

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