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1.
PLoS Pathog ; 20(1): e1011934, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38206974

RESUMO

Epstein-Barr virus (EBV) is associated with several types of human cancer including nasopharyngeal carcinoma (NPC). The activation of EBV to the lytic cycle has been observed in advanced NPC and is believed to contribute to late-stage NPC development. However, how EBV lytic cycle promotes NPC progression remains elusive. Analysis of clinical NPC samples indicated that EBV reactivation and immunosuppression were found in advanced NPC samples, as well as abnormal angiogenesis and invasiveness. To investigate the role of the EBV lytic cycle in tumor development, we established a system that consists of two NPC cell lines, respectively, in EBV abortive lytic cycle and latency. In a comparative analysis using this system, we found that the NPC cell line in EBV abortive lytic cycle exhibited the superior chemotactic capacity to recruit monocytes and polarized their differentiation toward tumor-associated macrophage (TAM)-like phenotype and away from DCs, compared to EBV-negative or EBV-latency NPC cells. EBV-encoded transcription activator ZTA is responsible for regulating monocyte chemotaxis and TAM phenotype by up-regulating the expression of GM-CSF, IL-8, and GRO-α. As a result, TAM induced by EBV abortive lytic cycle promotes NPC angiogenesis, invasion, and migration. Overall, this study elucidated the role of the EBV lytic life cycle in the late development of NPC and revealed a mechanism underlying the ZTA-mediated establishment of the tumor microenvironment (TME) that promotes NPC late-stage progression.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/genética , Monócitos/metabolismo , Neoplasias Nasofaríngeas/genética , Microambiente Tumoral
2.
Eur J Neurosci ; 60(2): 4078-4094, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38777332

RESUMO

Although the attractiveness of voices plays an important role in social interactions, it is unclear how voice attractiveness and social interest influence social decision-making. Here, we combined the ultimatum game with recording event-related brain potentials (ERPs) and examined the effect of attractive versus unattractive voices of the proposers, expressing positive versus negative social interest ("I like you" vs. "I don't like you"), on the acceptance of the proposal. Overall, fair offers were accepted at significantly higher rates than unfair offers, and high voice attractiveness increased acceptance rates for all proposals. In ERPs in response to the voices, their attractiveness and expressed social interests yielded early additive effects in the N1 component, followed by interactions in the subsequent P2, P3 and N400 components. More importantly, unfair offers elicited a larger Medial Frontal Negativity (MFN) than fair offers but only when the proposer's voice was unattractive or when the voice carried positive social interest. These results suggest that both voice attractiveness and social interest moderate social decision-making and there is a similar "beauty premium" for voices as for faces.


Assuntos
Tomada de Decisões , Potenciais Evocados , Voz , Humanos , Masculino , Feminino , Potenciais Evocados/fisiologia , Voz/fisiologia , Tomada de Decisões/fisiologia , Adulto Jovem , Adulto , Eletroencefalografia/métodos , Encéfalo/fisiologia , Adolescente
3.
Planta ; 260(1): 33, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896325

RESUMO

MAIN CONCLUSION: γ-Aminobutyric acid alleviates acid-aluminum toxicity to roots associated with enhanced antioxidant metabolism as well as accumulation and transportation of citric and malic acids. Aluminum (Al) toxicity has become the main limiting factor for crop growth and development in acidic soils and is further being aggravated worldwide due to continuous industrial pollution. The current study was designed to examine effects of GABA priming on alleviating acid-Al toxicity in terms of root growth, antioxidant defense, citrate and malate metabolisms, and extensive metabolites remodeling in roots under acidic conditions. Thirty-seven-day-old creeping bentgrass (Agrostis stolonifera) plants were used as test materials. Roots priming with or without 0.5 mM GABA for 3 days were cultivated in standard nutrient solution for 15 days as control or subjected to nutrient solution containing 5 mM AlCl3·6H2O for 15 days as acid-Al stress treatment. Roots were sampled for determinations of root characteristics, physiological and biochemical parameters, and metabolomics. GABA priming significantly alleviated acid-Al-induced root growth inhibition and oxidative damage, despite it promoted the accumulation of Al in roots. Analysis of metabolomics showed that GABA priming significantly increased accumulations of organic acids, amino acids, carbohydrates, and other metabolites in roots under acid-Al stress. In addition, GABA priming also significantly up-regulated key genes related to accumulation and transportation of malic and citric acids in roots under acid-Al stress. GABA-regulated metabolites participated in tricarboxylic acid cycle, GABA shunt, antioxidant defense system, and lipid metabolism, which played positive roles in reactive oxygen species scavenging, energy conversion, osmotic adjustment, and Al ion chelation in roots.


Assuntos
Agrostis , Alumínio , Antioxidantes , Malatos , Raízes de Plantas , Ácido gama-Aminobutírico , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Antioxidantes/metabolismo , Ácido gama-Aminobutírico/metabolismo , Alumínio/toxicidade , Agrostis/efeitos dos fármacos , Agrostis/metabolismo , Agrostis/fisiologia , Malatos/metabolismo , Ácido Cítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos
4.
Opt Express ; 32(4): 5362-5379, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439265

RESUMO

The light field (LF) imaging systems face a trade-off between the spatial and angular resolution in a limited sensor resolution. Various networks have been proposed to enhance the spatial resolution of the sub-aperture image (SAI). However, the spatial shift-variant characteristics of the LF are not considered, and few efforts have been made to recover a full-resolution (FR) image. In this paper, we propose an FR image restoration method by embedding LF degradation kernels into the network. An explicit convolution model based on the scalar diffraction theory is first derived to calculate the system response and imaging matrix. Based on the analysis of LF image formation, we establish the mapping from an FR image to the SAI through the SAI kernel, which is a spatial shift-variant degradation (SSVD) kernel. Then, the SSVD kernels are embedded into the proposed network as prior knowledge. An SSVD convolution layer is specially designed to handle the view-wise degradation feature and speed up the training process. A refinement block is designed to preserve the entire image details. Moreover, our network is evaluated on extensive simulated and real-world LF images to demonstrate its superior performance compared with other methods. Experiments on a multi-focus scene further prove that our network is suitable for any in-focus or defocused conditions.

5.
Muscle Nerve ; 70(2): 210-216, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38828855

RESUMO

INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.


Assuntos
Técnicas de Imagem por Elasticidade , Cotovelo , Nervo Ulnar , Neuropatias Ulnares , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Técnicas de Imagem por Elasticidade/métodos , Neuropatias Ulnares/diagnóstico por imagem , Neuropatias Ulnares/fisiopatologia , Cotovelo/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/fisiopatologia , Microvasos/diagnóstico por imagem , Eletrodiagnóstico/métodos
6.
Physiol Plant ; 176(4): e14433, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38994561

RESUMO

Cadmium (Cd) is a leading environmental issue worldwide. The current study was conducted to investigate Cd tolerance of 10 commercial white clover (Trifolium repens) cultivars during seed germination and to further explore differences in lipid remodelling, glycometabolism, and the conversion of lipids into sugars contributing to Cd tolerance in the early phase of seedling establishment as well as the accumulation of Cd in seedlings and mature plants. The results show that Cd stress significantly reduced seed germination of 10 cultivars. Compared to Cd-sensitive Sulky, Cd-tolerant Pixie accelerated amylolysis to produce more glucose, fructose, and sucrose by maintaining higher amylase and sucrase activities under Cd stress. Pixie maintained higher contents of various lipids, higher DGDG/MGDG ratio, and lower unsaturation levels of lipids, which could be beneficial to membrane stability and integrity as well as signal transduction in cells after being subjected to Cd stress. In addition, Pixie upregulated expression levels of key genes (TrACX1, TrACX4, TrSDP6, and TrPCK1) involved in the conversion of lipids into sugars for early seedling establishment under Cd stress. These findings indicate that lipid remodelling, enhanced glycometabolism, and accelerated conversion of lipids into sugars are important adaptive strategies for white clover seed germination and subsequent seedling establishment under Cd stress. In addition, Pixie not only accumulated more Cd in seedlings and mature plants than Sulky but also had significantly better growth and phytoremediation efficiency under Cd stress. Pixie could be used as a suitable and critical germplasm for the rehabilitation and re-establishment of Cd-contaminated areas.


Assuntos
Cádmio , Germinação , Sementes , Trifolium , Cádmio/toxicidade , Germinação/efeitos dos fármacos , Trifolium/efeitos dos fármacos , Trifolium/metabolismo , Trifolium/genética , Trifolium/crescimento & desenvolvimento , Trifolium/fisiologia , Sementes/efeitos dos fármacos , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Plântula/efeitos dos fármacos , Plântula/genética , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Açúcares/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos
7.
Org Biomol Chem ; 22(30): 6135-6140, 2024 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-39011846

RESUMO

A new chemodosimeter SWJT-31 with an aggregation-induced emission (AIE) effect was designed and constructed. Upon increasing the water fraction in the solution, it exhibited typical AIE, which showed bright red fluorescence at 610 nm. SWJT-31 could sensitively and specifically recognize hydrazine by the TICT effect with an LOD of 33.8 nM, which was much lower than the standard of the USEPA. A portable test strip prepared using SWJT-31 was also developed for the visual detection of hydrazine. Eventually, it was successfully used for the detection of hydrazine in water samples and HeLa cells.


Assuntos
Corantes Fluorescentes , Hidrazinas , Imidazóis , Hidrazinas/química , Humanos , Células HeLa , Imidazóis/química , Imidazóis/síntese química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Imagem Óptica , Estrutura Molecular
8.
J Chem Inf Model ; 64(15): 5853-5866, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-39052623

RESUMO

Machine learning plays a role in accelerating drug discovery, and the design of effective machine learning models is crucial for accurately predicting molecular properties. Characterizing molecules typically involves the use of molecular fingerprints and molecular graphs. These are input into a multilayer perceptron (MLP) and variants of graph neural networks, such as graph attention networks (GATs). Due to the diverse types and large dimension of fingerprints, models may contain many features that are relatively irrelevant or redundant; meanwhile, although the GAT excels in handling heterogeneous graph tasks, it lacks the ability to extract collaborative information from neighboring nodes, which is crucial in scenarios where it cannot capture the joint influence of adjacent groups on atoms. To overcome these challenges, we introduce a hybrid model, combining improved GAT and MLP. In GAT, the recurrent neural network is employed to capture collaborative information. To address the dimensionality issue, we propose a feature selection algorithm, which is based on the principle of maximizing relevance while minimizing redundancy. Through experiments on 13 public data sets and 14 breast cell lines, our model demonstrates superior performance compared to state-of-the-art deep learning and traditional machine learning algorithms. Additionally, a series of ablation experiments were conducted to demonstrate the advantages of our improved version, as well as its antinoise capability and interpretability. These results indicate that our model holds promising prospects for practical applications.


Assuntos
Redes Neurais de Computação , Humanos , Aprendizado de Máquina , Algoritmos , Linhagem Celular Tumoral , Descoberta de Drogas/métodos
9.
BMC Infect Dis ; 24(1): 972, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271984

RESUMO

BACKGROUND: X-linked agammaglobulinemia (XLA), also referred to as Bruton's tyrosine kinase deficiency, is a rare genetic disorder that affects the immune system. We conducted genetic analysis on patients suffering from immunodeficiency by utilizing Next-Generation Sequencing techniques, as well as their closest relatives, to facilitate accurate diagnosis, offer genetic counseling services, and enhance our comprehension of XLA.


Assuntos
Agamaglobulinemia , Doenças Genéticas Ligadas ao Cromossomo X , Pneumonia por Mycoplasma , Humanos , Agamaglobulinemia/complicações , Agamaglobulinemia/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Masculino , Pneumonia por Mycoplasma/complicações , Pneumonia por Mycoplasma/microbiologia , Tirosina Quinase da Agamaglobulinemia/genética , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/isolamento & purificação , Adulto , Sequenciamento de Nucleotídeos em Larga Escala
10.
Mol Biol Rep ; 51(1): 720, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38824268

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) exert a significant influence on the progression and heterogeneity of various subtypes of breast cancer (BRCA). However, the roles of heterogeneous TAM within BRCA subtypes remain unclear. Therefore, this study sought to elucidate the role of TAM across the following three BRCA subtypes: triple-negative breast cancer, luminal, and HER2. MATERIALS AND METHODS: This investigation aimed to delineate the variations in marker genes, drug sensitivity, and cellular communication among TAM across the three BRCA subtypes. We identified specific ligand-receptor (L-R) pairs and downstream mechanisms regulated by VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Experimental verification of these pairs was conducted by co-culturing macrophages with three subtypes of BRCA cells. RESULTS: Our findings reveal the heterogeneity of macrophages within the three BRCA subtypes, evidenced by variations in marker gene expression, composition, and functional characteristics. Notably, heterogeneous TAM were found to promote invasive migration and epithelial-mesenchymal transition (EMT) in MDA-MB-231, MCF-7, and SKBR3 cells, activating NF-κB pathway via P38 MAPK, TGF-ß1, and AKT, respectively, through distinct VEGFA-VEGFR1, SPP1-CD44, and SPP1-ITGB1 L-R pairs. Inhibition of these specific L-R pairs effectively reversed EMT, migration, and invasion of each cancer cells. Furthermore, we observed a correlation between ligand gene expression and TAM sensitivity to anticancer drugs, suggesting a potential strategy for optimizing personalized treatment guidance. CONCLUSION: Our study highlights the capacity of heterogeneous TAM to modulate biological functions via distinct pathways mediated by specific L-R pairs within diverse BRCA subtypes. This study might provide insights into precision immunotherapy of different subtypes of BRCA.


Assuntos
Neoplasias da Mama , Transição Epitelial-Mesenquimal , Macrófagos Associados a Tumor , Humanos , Feminino , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/imunologia , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Célula Única/métodos , Células MCF-7 , Movimento Celular/genética , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Análise de Sequência de RNA/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Transdução de Sinais/genética , Microambiente Tumoral/genética
11.
Bioorg Chem ; 149: 107507, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38850778

RESUMO

Opioids are currently the most effective and widely used painkillers in the world. Unfortunately, the clinical use of opioid analgesics is limited by serious adverse effects. Many researchers have been working on designing and optimizing structures in search of novel µ opioid receptor(MOR) agonists with improved analgesic activity and reduced incidence of adverse effects. There are many strategies to develop MOR drugs, mainly focusing on new low efficacy agonists (potentially G protein biased agonists), MOR agonists acting on different Gα subtype, targeting opioid receptors in the periphery, acting on multiple opioid receptor, and targeting allosteric sites of opioid receptors, and others. This review summarizes the design methods, clinical applications, and structure-activity relationships of small-molecule agonists for MOR based on these different design strategies, providing ideas for the development of safer novel opioid ligands with therapeutic potential.


Assuntos
Analgésicos Opioides , Receptores Opioides mu , Receptores Opioides mu/agonistas , Receptores Opioides mu/metabolismo , Humanos , Relação Estrutura-Atividade , Analgésicos Opioides/farmacologia , Analgésicos Opioides/química , Animais , Estrutura Molecular
12.
Pain Med ; 25(7): 468-477, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38374234

RESUMO

OBJECTIVES: Pain catastrophizing (PC) is a cognitive/emotional response to and in anticipation of pain that can be maladaptive, further exacerbating pain and difficulty in emotion regulation (ER). There is a lack of research on the interplay between PC and ER and its impact on pain. Our aim was to investigate whether ER exacerbated the pain experience through PC. METHODS: Adults with chronic non-cancer pain of >3 months' duration (n = 150) who were taking opioid medication were recruited from a large medical center in Pennsylvania. A battery of questionnaires was conducted to gather data on demographics, substance use, mental health histories, and health and pain outcomes. Measures used included the 18-Item Difficulties in Emotion Regulation Scale, the Pain Catastrophizing Scale, the Brief Pain Inventory-Short Form, and the Hospital Anxiety and Depression Scale. A structural equation model with latent variables was conducted to examine our aim. RESULTS: Both pain interference and severity were significantly positively associated with several psychosocial variables, such as anxiety, depression, ER constructs, PC, and distress intolerance. The associations between subscales and pain interference were larger than the associations between subscales and pain severity. PC fully mediated the paths from ER to pain experiences. DISCUSSION: Our results highlight the importance of several cognitive and emotional constructs: nonacceptance of negative emotions, lack of emotional awareness, magnification of the pain experience, and a sense of helplessness. Furthermore, by showing the indirect effects of PC in affecting ER and pain, we posit that ER, mediated by PC, might serve a critical role in influencing the pain experience in patients with chronic pain.


Assuntos
Catastrofização , Dor Crônica , Regulação Emocional , Humanos , Catastrofização/psicologia , Dor Crônica/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Medição da Dor , Inquéritos e Questionários , Depressão/psicologia , Analgésicos Opioides/uso terapêutico , Ansiedade/psicologia
13.
BMC Psychiatry ; 24(1): 510, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39020309

RESUMO

BACKGROUND: Parent-child separation poses a significant challenge for left-behind children (LBC). However, limited empirical evidence exists regarding the correlation between left-behind characteristics and the psychological symptoms of LBC. This study investigated psychological symptoms among LBC and explored associations between left-behind characteristics and those symptoms. METHODS: Using stratified cluster sampling, 1,832 LBC aged 13-18 years from three cities in East China were selected for analysis. Participants' depression and anxiety symptoms were assessed with the Patient Health Questionnaire 9 and the General Anxiety Disorder 7, respectively. Chi-square tests were used to compare differences in detection rates of psychological symptoms among LBC in different groups. Binary logistic regression analysis was used to infer associations between left-behind characteristics and psychological symptoms. RESULTS: Depression and anxiety symptoms were detected in 32.86% and 33.24%, respectively, of participating LBC. Univariate analysis showed statistically significant differences in detection rates of depression symptoms by sex, grade, and timing of parent-child separation. Statistically significant differences were observed in anxiety symptom rates by sex, grade, type of caregiver, and timing of mother-child separation. Multivariate analysis indicated a positive association between LBC's anxiety symptoms and mother-child separation that occurred during post-primary school, and type of caregiver (father only or mother only). Our findings confirm a positive association between left-behind characteristics and anxiety symptoms among LBC. CONCLUSION: The timing of mother-child separation and type of caregiver are potential risk factors for the development of anxiety symptoms in this population.


Assuntos
Ansiedade , Depressão , Humanos , Feminino , Masculino , Adolescente , China/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Depressão/diagnóstico , Ansiedade/psicologia , Ansiedade/epidemiologia , Separação da Família
14.
Clin Neuropathol ; 43(1): 29-35, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38050756

RESUMO

The Brain Tumor Epidemiology Consortium (BTEC) is an international organization with membership of individuals from the scientific community with interests related to brain tumor epidemiology including surveillance, classification, methodology, etiology, and factors associated with morbidity and mortality. The 2023 annual BTEC meeting entitled "Impact of Environment on Pediatric and Adult Brain Tumors" was held in Lexington, KY, USA on May 22 - 24, 2023. The meeting gathered scientists from the United States, Canada, Australia, and Europe and included four keynote sessions covering genomic, epigenomic, and metabolomic considerations in brain tumor epidemiology, cancer clusters, environmental risk factors, and new approaches to cancer investigation. The meeting also included three abstract sessions and a brainstorming session. A summary of the meeting content is included in this report.


Assuntos
Neoplasias Encefálicas , Humanos , Neoplasias Encefálicas/epidemiologia , Neoplasias Encefálicas/etiologia
15.
Am J Respir Crit Care Med ; 207(10): 1376-1382, 2023 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-36790881

RESUMO

Rationale: We developed a standardized method, possible poor treatment response (PPTR), to help ascertain efficacy endpoints in Study S31/A5349 (NCT02410772), an open-label trial comparing two 4-month rifapentine-based regimens with a standard 6-month regimen for the treatment of pulmonary tuberculosis (TB). Objectives: We describe the use of the PPTR process and evaluate whether the goals of minimizing bias in efficacy endpoint assessment and attainment of relevant data to determine outcomes for all participants were achieved. Methods: A PPTR event was defined as the occurrence of one or more prespecified triggers. Each PPTR required initiation of a standardized evaluation process that included obtaining multiple sputum samples for microbiology. Measurements and Main Results: Among 2,343 participants with culture-confirmed drug-susceptible TB, 454 individuals (19.4%) had a total of 534 individual PPTR events, of which 76.6% were microbiological (positive smear or culture at or after 17 wk). At least one PPTR event was experienced by 92.4% (133 of 144) of participants with TB-related unfavorable outcome and between 13.8% and 14.7% of participants with favorable and not-assessable outcomes. A total of 75% of participants with TB-related unfavorable outcomes had microbiological confirmation of failure to achieve a disease-free cure. Conclusions: Standardized methodologies, such as our PPTR approach, could facilitate unbiased efficacy outcome determinations, improve discrimination between outcomes that are related and unrelated to regimen efficacy, and enhance the ability to conduct pooled analyses of contemporary trials.


Assuntos
Tuberculose Pulmonar , Tuberculose , Humanos , Antituberculosos/uso terapêutico , Tuberculose/tratamento farmacológico , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/microbiologia
16.
Proc Natl Acad Sci U S A ; 118(10)2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33674386

RESUMO

Osteosarcoma is the most common malignant tumor of bone predominately affecting adolescents and young adults. Based on animal studies, a viral etiology of osteosarcoma was proposed more than a half-century ago, but no viral association with human osteosarcoma has been found. The Uyghur ethnic population in Xinjiang, China, has an unusually high prevalence of Kaposi's sarcoma-associated herpesvirus (KSHV) infection and elevated incidence of osteosarcoma. In the current study, we explored the possible association of KSHV infection and osteosarcoma occurrence. Our seroepidemiological study revealed that KSHV prevalence was significantly elevated in Uyghur osteosarcoma patients versus the general Uyghur population (OR, 10.23; 95%CI, 4.25, 18.89). The KSHV DNA genome and viral latent nuclear antigen LANA were detected in most osteosarcoma tumor cells. Gene expression profiling analysis showed that KSHV-positive osteosarcoma represents a distinct subtype of osteosarcomas with viral gene-activated signaling pathways important for osteosarcoma development. We conclude that KSHV infection is a risk factor for osteosarcoma, and KSHV is associated with some osteosarcomas, representing a newly identified viral-associated endemic cancer.


Assuntos
Infecções por Herpesviridae , Herpesvirus Humano 8/metabolismo , Osteossarcoma , Adolescente , Adulto , Antígenos Virais/metabolismo , Criança , Pré-Escolar , China/epidemiologia , China/etnologia , DNA Viral/metabolismo , Feminino , Genoma Viral , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/etnologia , Infecções por Herpesviridae/metabolismo , Infecções por Herpesviridae/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Osteossarcoma/epidemiologia , Osteossarcoma/etnologia , Osteossarcoma/metabolismo , Osteossarcoma/virologia , Prevalência , Proteínas Virais/metabolismo
17.
BMC Biol ; 21(1): 94, 2023 04 24.
Artigo em Inglês | MEDLINE | ID: mdl-37095490

RESUMO

BACKGROUND: Circular RNAs (circRNAs) are a large class of mammalian RNAs. Several protein products translated by circRNAs have been reported to be involved in the development of various tissues and systems; however, their physiological functions in male reproduction have yet not been explored. RESULTS: Here, we report an endogenous circRNA (circRsrc1) that encodes a novel 161-amino-acid protein which we named Rsrc1-161aa through circRNA sequencing coupled with mass spectrometry analysis on mouse testicular tissues. Deletion of Rsrc1-161aa in mice impaired male fertility with a significant decrease in sperm count and motility due to dysfunctions of mitochondrial energy metabolism. A series of in vitro rescue experiments revealed that circRsrc1 regulates mitochondrial functions via its encoded protein Rsrc1-161aa. Mechanistically, Rsrc1-161aa directly interacts with mitochondrial protein C1qbp and enhances its binding activity to mitochondrial mRNAs, thereby regulating the assembly of mitochondrial ribosomes and affecting the translation of oxidative phosphorylation (OXPHOS) proteins and mitochondrial energy metabolism. CONCLUSIONS: Our studies reveal that Rsrc1-161aa protein encoded by circRsrc1 regulates mitochondrial ribosome assembly and translation during spermatogenesis, thereby affecting male fertility.


Assuntos
Ribossomos Mitocondriais , RNA Circular , Masculino , Animais , Camundongos , Ribossomos Mitocondriais/metabolismo , RNA Circular/metabolismo , Sêmen/metabolismo , Espermatogênese , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Mamíferos/genética , Biossíntese de Proteínas
18.
Int J Mol Sci ; 25(9)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38732221

RESUMO

Abdominal aortic aneurysm (AAA) has been recognized as a serious chronic inflammatory degenerative aortic disease in recent years. At present, there is no other effective intervention except surgical treatment for AAA. With the aging of the human population, its incidence is increasing year by year, posing a serious threat to human health. Modern studies suggest that vascular chronic inflammatory response is the core process in AAA occurrence and development. Inflammasome, a multiprotein complex located in the cytoplasm, mediates the expression of various inflammatory cytokines like interleukin (IL)-1ß and IL-18, and thus plays a pivotal role in inflammation regulation. Therefore, inflammasome may exert a crucial influence on the progression of AAA. This article reviews some mechanism studies to investigate the role of inflammasome in AAA and then summarizes several potential drugs targeting inflammasome for the treatment of AAA, aiming to provide new ideas for the clinical prevention and treatment of AAA beyond surgical methods.


Assuntos
Aneurisma da Aorta Abdominal , Inflamassomos , Aneurisma da Aorta Abdominal/metabolismo , Humanos , Inflamassomos/metabolismo , Animais , Inflamação/metabolismo
19.
J Environ Sci (China) ; 144: 148-158, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38802226

RESUMO

Humic acid (HA) is a typical refractory organic matter, so it is of great significance to investigate its effect on the performance of Anammox granular sludge. When the dosage of HA ≤ 50 mg/L, HA promotes the total nitrogen removal rate (NRR) to 1.45 kg/(m3·day). When HA was between 50 and 100 mg/L, the NRR of Anammox was stable. At this time, the adsorption of HA causes the sludge to gradually turn from red to brown, but the activities of heme and enzymes showed that its capacity was not affected. When HA levels reached 250 mg/L, the NRR dropped to 0.11 kg/(m3·day). Moderate HA levels promoted the release of extracellular polymeric substance (EPS), but excessive HA levels lead to a decrease in EPS concentrations. HA inhibited Anammox activity, which indirectly hindered the transmission of substrate and accumulated substrate toxicity. Although HA promoted the increase of heterotrophic microbial abundance in Anammox system, the microbial diversity decreased gradually. With the increase of HA concentration, the abundance of Candidatus_Brocadia, the main functional microorganism of Anammox system, decreased gradually, while the abundance of Candidatus_Kuenenia increased gradually.


Assuntos
Substâncias Húmicas , Nitrogênio , Esgotos , Eliminação de Resíduos Líquidos , Esgotos/microbiologia , Eliminação de Resíduos Líquidos/métodos , Reatores Biológicos/microbiologia , Microbiota , Anaerobiose
20.
Lancet Oncol ; 24(12): 1434-1442, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37972608

RESUMO

BACKGROUND: Female survivors of childhood cancer are at risk for primary ovarian insufficiency (POI), defined as the cessation of gonadal function before the age of 40 years. We aimed to develop and validate models to predict age-specific POI risk among long-term survivors of childhood cancer. METHODS: To develop models to predict age-specific POI risk for the ages of 21-40 years, we used data from the Childhood Cancer Survivor Study (CCSS). Female survivors aged 18 years or older at their latest follow-up, with self-reported menstrual history information and free of subsequent malignant neoplasms within 5 years of diagnosis, were included. We evaluated models that used algorithms based on statistical or machine learning to consider all predictors, including cancer treatments. Cross-validated prediction performance metrics (eg, area under the receiver operating characteristic curve [AUROC]) were compared to select the best-performing models. For external validation of the models, we used data from 5-year survivors in the St Jude Lifetime Cohort (SJLIFE) with ovarian status clinically ascertained using hormone measurements (menopause defined by follicle stimulating hormone >30 mIU/mL and oestradiol <17 pg/mL) and medical chart or questionnaire review. We also evaluated an SJLIFE-based polygenic risk score for POI among 1985 CCSS survivors with genotype data available. FINDINGS: 7891 female CCSS survivors (922 with POI) were included in the development of the POI risk prediction model, and 1349 female SJLIFE survivors (101 with POI) were included in the validation study. Median follow-up from cancer diagnosis was 23·7 years (IQR 18·3-30·0) in CCSS and 15·1 years (10·4-22·9) in SJLIFE. Between the ages of 21 and 40 years, POI prevalence increased from 7·9% (95% CI 7·3-8·5) to 18·6% (17·3-20·0) in CCSS and 7·3% (5·8-8·9) to 14·9% (11·6-19·1) in SJLIFE. Age-specific logistic regression models considering ovarian radiation dosimetry or prescribed pelvic and abdominal radiation dose, along with individual chemotherapy predictors, performed well in CCSS. In the SJLIFE validation, the prescribed radiation dose model performed well (AUROC 0·88-0·95), as did a simpler model that considered any exposures to pelvic or abdominal radiotherapy or alkylators (0·82-0·90). Addition of the polygenic risk predictor significantly improved the average positive predictive value (from 0·76 [95% CI 0·63-0·89] to 0·87 [0·80-0·94]; p=0·029) among CCSS survivors treated with ovarian radiation and chemotherapy. INTERPRETATION: POI risk prediction models using treatment information showed robust prediction performance in adult survivors of childhood cancer. FUNDING: Canadian Institutes of Health Research, US National Cancer Institute.


Assuntos
Sobreviventes de Câncer , Neoplasias , Insuficiência Ovariana Primária , Adulto , Humanos , Criança , Feminino , Adulto Jovem , Neoplasias/terapia , Neoplasias/tratamento farmacológico , Insuficiência Ovariana Primária/diagnóstico , Insuficiência Ovariana Primária/epidemiologia , Insuficiência Ovariana Primária/etiologia , Canadá , Sobreviventes , Fatores de Risco , Fatores Etários
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