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1.
J Diabetes Investig ; 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38989799

RESUMO

INTRODUCTION: The fasting blood glucose test is widely used for diabetes screening. However, it may fail to detect early-stage diabetes characterized by elevated postprandial glucose levels. Hence, we developed and internally validated a nomogram to predict the diabetes risk in older adults with normal fasting glucose levels. MATERIALS AND METHODS: This study enrolled 2,235 older adults, dividing them into a Training Set (n = 1,564) and a Validation Set (n = 671) based on a 7:3 ratio. We employed the least absolute shrinkage and selection operator regression to identify predictors for constructing the nomogram. Calibration and discrimination were employed to assess the nomogram's performance, while its clinical utility was evaluated through decision curve analysis. RESULTS: Nine key variables were identified as significant factors: age, gender, body mass index, fasting blood glucose, triglycerides, alanine aminotransferase, the ratio of alanine aminotransferase to aspartate aminotransferase, blood urea nitrogen, and hemoglobin. The nomogram demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.824 in the Training Set and 0.809 in the Validation Set. Calibration curves for both sets confirmed the model's accuracy in estimating the actual diabetes risk. Decision curve analysis highlighted the model's clinical utility. CONCLUSIONS: We provided a dynamic nomogram for identifying older adults at risk of diabetes, potentially enhancing the efficiency of diabetes screening in primary healthcare units.

2.
Arch Virol ; 169(8): 164, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990242

RESUMO

Upregulation of ADAMTS-4 has been reported to have an important role in lung injury, and ADAMTS-4 expression is regulated by miR-126a-5p in abdominal aortic aneurysms. The aim of this study was to investigate whether miR-126a-5p/ADAMTS-4 plays a role in influenza-virus-induced lung injury. Lung fibroblasts were infected with H1N1 influenza virus to detect changes in miR-126a-5p and ADAMTS-4 expression, and cell viability was measured by CCK-8 assay. Inflammatory factors and matrix protease levels were examined using ELISA kits, and cell apoptosis was assessed by measuring the levels of apoptosis-related proteins. A dual luciferase assay was used to verify the regulatory relationship between miR-126a-5p and ADAMTS-4. H1N1 influenza virus reduced fibroblast viability, inhibited miR-126a-5p expression, and promoted ADAMTS-4 expression. Overexpression of miR-126a-5p attenuated the cellular inflammatory response, apoptosis, matrix protease secretion, and virus replication. Luciferase reporter assays revealed that miR-126a-5p inhibited ADAMTS-4 expression by targeting ADAMTS-4 mRNA. Further experiments showed that overexpression of ADAMTS-4 significantly reversed the inhibitory effects of miR-126a-5p on fibroblast inflammation, apoptosis, matrix protease secretion, and virus replication. Upregulation of miR-126a-5p inhibits H1N1-induced apoptosis, inflammatory factors, and matrix protease secretion, as well as virus replication in lung fibroblasts.


Assuntos
Proteína ADAMTS4 , Apoptose , Fibroblastos , Inflamação , Vírus da Influenza A Subtipo H1N1 , Pulmão , MicroRNAs , MicroRNAs/genética , MicroRNAs/metabolismo , Fibroblastos/virologia , Fibroblastos/metabolismo , Humanos , Pulmão/virologia , Pulmão/patologia , Proteína ADAMTS4/genética , Proteína ADAMTS4/metabolismo , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H1N1/fisiologia , Inflamação/genética , Sobrevivência Celular , Replicação Viral , Influenza Humana/virologia , Influenza Humana/genética , Influenza Humana/metabolismo , Linhagem Celular
3.
Heart Lung ; 68: 107-115, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38943717

RESUMO

BACKGROUND: Heart failure (HF) imposes a substantial burden on older adults, and healthy diets and lifestyles may bring with benefits. However, quantifiable studies on the dietary and lifestyle risk factors for HF are scant. The Oxidative Balance Score (OBS) reflects the oxidative stress status of dietary components and lifestyle factors, but its relationship with HF risk is unclear. OBJECTIVE: We aims to explore the association between OBS and the prevalence of HF. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018, the association between OBS and the HF prevalence was analyzed by weighted logistic regression and restricted cubic splines (RCS). Subgroup and sensitivity analyses assessed the stability of the results. RESULTS: The prevalence of HF in the cohort of 6238 older adults was 5.55 %. Compared to the lowest quintile, the adjusted ORs for HF in the highest quintile of OBS and lifestyle OBS were 0.57 (95 % CI: 0.33,0.97) and 0.21 (95 %CI: 0.09,0.50), respectively. The association between OBS and HF prevalence remained stable across different models and subgroups. RCS revealed a potential inflection point. Sensitivity analysis validated the negative association between OBS and HF prevalence, and the correlation analysis between OBS and serum γ-glutamyltransferase (γ-GGT) confirmed the reliability of the study design. CONCLUSION: The OBS is negatively associated with HF prevalence in older adults, and may help prevent HF in this population.

5.
Microbiol Spectr ; 12(7): e0080224, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38860816

RESUMO

The diversity of birds in most parts of the world is very high, and thus, they may carry different types of highly differentiated and unknown viruses. Thanks to advanced sequencing technologies, studies on the diversity of bird-associated viruses have increased over the past few years. In this study, a large-scale viral metagenomics survey was performed on cloacal swabs of 2,990 birds from nine provinces of the Chinese mainland. To detect undescribed RNA viruses in birds, more than 1,800 sequences sharing relatively low (<60%) amino acid sequence identity with the best match in the GenBank database were screened. Potentially novel viruses related to vertebrates have been identified, and several potential recombination signals were found. Additionally, hundreds of RNA viral sequences related to plants, fungi, and insects were detected, including previously unknown viruses. Furthermore, we investigated the novelty, functionality, and classification of the phages examined in this study. These viruses occupied topological positions on the evolutionary trees to a certain extent and might form novel putative families, genera, or species, thus providing information to fill the phylogenetic gaps of related viruses. These findings provided new insights into bird-associated viruses, but the interactions among these viruses remain unknown and require further investigation.IMPORTANCEStudying the diversity of RNA viruses in birds and mammals is crucial due to their potential impact on human health and the global ecosystem. Many RNA viruses, such as influenza and coronaviruses, have been shown to cross the species barrier and cause zoonotic diseases. In this metagenomics study involving 2,990 birds from at least 82 species, we identified over 1,800 RNA sequences with distant relationships to known viruses, some of which are rare in birds. The study highlights the scope and diversity of RNA viruses in birds, providing data to predict disease risks and monitor potential viral threats to wildlife, livestock, and human health. This information can aid in the development of strategies for disease prevention and control.


Assuntos
Bacteriófagos , Aves , Metagenômica , Filogenia , Vírus de RNA , Animais , Vírus de RNA/genética , Vírus de RNA/classificação , Vírus de RNA/isolamento & purificação , Aves/virologia , Bacteriófagos/genética , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , China , Genoma Viral/genética , Cloaca/virologia
6.
Transl Androl Urol ; 13(5): 802-811, 2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38855586

RESUMO

Background: Benign prostatic hyperplasia (BPH) is the most common benign disease causing voiding dysfunction in middle-aged and elderly men. the current "gold standard" for surgical treatment is transurethral resection of the prostate (TURP). Continuous bladder irrigation (CBI) is routinely given for 3 to 5 days after operation. However, this may induce bladder spasm. Bladder spasm not only brings physical and mental pain to patients, delaying the postoperative recovery process, but it also increases the medical economic burden. Therefore, it is important to take active measures to effectively warn and deal with bladder spasm. The color of the drainage fluid is an important indicator and requires close observation during CBI, as it can reflect real-time postoperative bleeding. When the color of drainage fluid is abnormal, effective measures should be undertaken. Grading nursing intervention divides patients into different conditions according to their possible changes, and then recommends targeted nursing intervention. Existing studies have formulated CBI programs from the perspective of quantifying the relationship between drainage fluid color and irrigation speed, but have yet to incorporate bladder spasm prevention and control levels or design corresponding grading nursing intervention programs according to different drainage fluid colors. This study aimed to construct the risk warning classification and intervention plan of bladder spasm under the guidance of CBI speed adjusting card after TURP. Methods: Based on the rate adjustment card of CBI after TURP, we formulated the first draft of an early warning classification of risk in bladder spasm and its intervention plans by combining methods suggested from a literature search with semi-structured interviews and results from 2 rounds of correspondence inquiries with 28 experts by the Delphi method. We further screened and revised grading standards and measures. Results: The positive coefficients of experts in 2 rounds of correspondence inquiries were both 100%, the authority coefficients were both 0.952, and the Kendall harmony coefficients were 0.238 and 0.326, respectively (P<0.01). In the second round of correspondence inquiries, the coefficient of variation of expert opinions was 0.000-0.154, and the coefficient of variation of all items was <0.25. Finally, a 3-level risk warning classification standard and 23 nursing measures for CBI complicated by bladder spasm was constructed. Conclusions: The early warning classification of risk in bladder spasm and its intervention plans guided by rate adjustment card of CBI after TURP are scientific and feasible, and can provide a basis and guidance for effective and standardized CBI in patients after TURP.

7.
BMJ Open ; 14(6): e077267, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38925703

RESUMO

INTRODUCTION: Inflammatory bowel disease (IBD) is a chronic idiopathic inflammatory disorder that arises from complex interactions between genetics, environment and gut microbiota. It encompasses Crohn's disease, ulcerative colitis and IBD-unclassified. The protracted course of IBD imposes a significant burden on patients' quality of life, economic productivity, social functioning, as well as treatment, hospitalisation and surgery. This study aims to conduct an umbrella review of meta-analyses to systematically evaluate the methodology's quality, potential biases and validity of all epidemiological evidence focused on risk factors for IBD while providing an overview of the evidence concerning IBD risk factors. METHODS AND ANALYSIS: We will systematically search, extract and analyse data from reported systematic reviews and meta-analyses that specifically focus on the risk factors of IBD, following the guidelines outlined in Preferred Reporting Items for Overviews of Reviews. Our search will encompass PubMed, Embase, Web of Science and the Cochrane Database of Systematic Reviews from the initial period up until April 2023 (last update), targeting systematic reviews and meta-analyses based on non-interventional studies. Inclusion criteria allow for systematic reviews and meta-analyses evaluating IBD risk factors across all countries and settings, regardless of ethnicity or sex. The identified risk factors will be categorised according to the health ecological model into innate personal traits, behavioural lifestyles, interpersonal networks, socioeconomic status and macroenvironments. To assess methodological quality for each meta-analysis included in our study, two authors will employ a measurement tool to assess the methodological quality of systematic reviews (AMSTAR)-2, Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria along with evidence classification criteria. ETHICS AND DISSEMINATION: Ethical approval is not required for this umbrella review. We will seek to submit the results for publication in a peer-reviewed journal or present it at conferences. PROSPERO REGISTRATION NUMBER: CRD42023417175.


Assuntos
Doenças Inflamatórias Intestinais , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Humanos , Fatores de Risco
8.
Phytopathology ; 114(5): 1050-1056, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38709298

RESUMO

Auxin is an important phytohormone that regulates diverse biologic processes, including plant growth and immunity. Indole-3-acetic acid (IAA), known as one of the main forms of auxin, is able to activate plant immunity. However, it is unknown whether IAA enhances plant resistance and/or suppresses the growth of the fungal pathogen Magnaporthe oryzae. Here, we found that IAA could induce expression levels of pathogenesis-related genes to enhance disease resistance and could control the development of blast disease through inhibiting M. oryzae infection. Exogenous IAA suppressed mycelial growth and delayed spore germination by inhibiting fungal endogenous IAA biosynthesis and impairing redox homeostasis, respectively. When applied to a field test, two IAA analogues, 1-naphthaleneacetic acid and 2,4-dichlorophenoxy acetic acid, can effectively control rice blast disease. Our study advances the understanding of IAA in controlling rice blast disease through suppressing pathogen growth and enhancing plant resistance.


Assuntos
Resistência à Doença , Ácidos Indolacéticos , Oryza , Doenças das Plantas , Ácidos Indolacéticos/metabolismo , Oryza/microbiologia , Oryza/crescimento & desenvolvimento , Oryza/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Doenças das Plantas/prevenção & controle , Resistência à Doença/genética , Resistência à Doença/efeitos dos fármacos , Reguladores de Crescimento de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Ascomicetos/efeitos dos fármacos , Ascomicetos/fisiologia , Ácidos Naftalenoacéticos/farmacologia , Esporos Fúngicos/efeitos dos fármacos , Esporos Fúngicos/crescimento & desenvolvimento
9.
Biomed Mater ; 19(4)2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38697149

RESUMO

To effectively address underlying issues and enhance the healing process of hard-to-treat soft tissue defects, innovative therapeutic approaches are required. One promising strategy involves the incorporation of bioactive substances into biodegradable scaffolds to facilitate synergistic tissue regeneration, particularly in vascular regeneration. In this study, we introduce a composite hydrogel design that mimics the extracellular matrix by covalently combining gelatin and hyaluronic acid (HA), with the encapsulation of deferoxamine nanoparticles (DFO NPs) for potential tissue regeneration applications. Crosslinked hydrogels were fabricated by controlling the ratio of HA in the gelatin-based hydrogels, resulting in improved mechanical properties, enhanced degradation ability, and optimised porosity, compared with hydrogel formed by gelatin alone. The DFO NPs, synthesized using a double emulsion method with poly (D,L-lactide-co-glycolide acid), exhibited a sustained release of DFO over 12 d. Encapsulating the DFO NPs in the hydrogel enabled controlled release over 15 d. The DFO NPs, composite hydrogel, and the DFO NPs loaded hydrogel exhibited excellent cytocompatibility and promoted cell proliferationin vitro. Subcutaneous implantation of the composite hydrogel and the DFO NPs loaded hydrogel demonstrated biodegradability, tissue integration, and no obvious adverse effects, evidenced by histological analysis. Furthermore, the DFO NPs loaded composite hydrogel exhibited accelerated wound closure and promoted neovascularisation and granular formation when tested in an excisional skin wound model in mice. These findings highlight the potential of our composite hydrogel system for promoting the faster healing of diabetes-induced skin wounds and oral lesions through its ability to modulate tissue regeneration processes.


Assuntos
Materiais Biomiméticos , Desferroxamina , Gelatina , Ácido Hialurônico , Hidrogéis , Nanopartículas , Gelatina/química , Desferroxamina/química , Desferroxamina/farmacologia , Animais , Hidrogéis/química , Ácido Hialurônico/química , Nanopartículas/química , Camundongos , Materiais Biomiméticos/química , Proliferação de Células/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Humanos , Porosidade , Regeneração , Biomimética
10.
BMC Genomics ; 25(1): 517, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38797853

RESUMO

BACKGROUND: Like all other species, fungi are susceptible to infection by viruses. The diversity of fungal viruses has been rapidly expanding in recent years due to the availability of advanced sequencing technologies. However, compared to other virome studies, the research on fungi-associated viruses remains limited. RESULTS: In this study, we downloaded and analyzed over 200 public datasets from approximately 40 different Bioprojects to explore potential fungal-associated viral dark matter. A total of 12 novel viral sequences were identified, all of which are RNA viruses, with lengths ranging from 1,769 to 9,516 nucleotides. The amino acid sequence identity of all these viruses with any known virus is below 70%. Through phylogenetic analysis, these RNA viruses were classified into different orders or families, such as Mitoviridae, Benyviridae, Botourmiaviridae, Deltaflexiviridae, Mymonaviridae, Bunyavirales, and Partitiviridae. It is possible that these sequences represent new taxa at the level of family, genus, or species. Furthermore, a co-evolution analysis indicated that the evolutionary history of these viruses within their groups is largely driven by cross-species transmission events. CONCLUSIONS: These findings are of significant importance for understanding the diversity, evolution, and relationships between genome structure and function of fungal viruses. However, further investigation is needed to study their interactions.


Assuntos
Micovírus , Fungos , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Vírus de RNA , Vírus de RNA/genética , Vírus de RNA/classificação , Fungos/genética , Micovírus/genética , Micovírus/classificação , Evolução Molecular
12.
BMJ Open ; 14(5): e081018, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38719320

RESUMO

INTRODUCTION: In recent years, the use of frozen embryo transfers (FET) has rapidly increased following the freeze-all strategy due to the advantages of increased maternal safety, improved pregnancy rates, lower ectopic pregnancy rates and better obstetric and neonatal outcomes. Currently, there is still no good scientific evidence to support when to perform FET following a stimulated in vitro fertilisation (IVF) cycle in the freeze-all strategy. METHODS/ANALYSIS: This will be a randomised controlled trial. A total of 828 women undergoing their first FET following their first stimulated IVF cycle in the freeze-all strategy will be enrolled and randomised into one of the following groups according to a computer-generated randomisation list: (1) the immediate group, in which FET will be performed in the first menstrual cycle following the stimulated IVF cycle; or (2) the delayed group, in which FET will be performed at least in the second menstrual cycle following the stimulated IVF cycle. The primary outcome will be live birth, which is defined as the delivery of any infants at ≥22 gestational weeks with heartbeat and breath. ETHICS/DISSEMINATION: Ethical approval was granted by the Ethics Committee of Assisted Reproductive Medicine at the Shanghai JiAi Genetics & IVF Institute (JIAI E2019-15). Written informed consent will be obtained from each woman before any study procedure is performed, according to good clinical practice. The results of this trial will be disseminated in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT04371783.


Assuntos
Criopreservação , Fertilização in vitro , Taxa de Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Adulto , Feminino , Humanos , Gravidez , China , Criopreservação/métodos , Transferência Embrionária/métodos , Fertilização in vitro/métodos , Nascido Vivo , Transferência de Embrião Único/métodos , Fatores de Tempo
13.
ACS Appl Mater Interfaces ; 16(23): 30284-30295, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38812067

RESUMO

As the power core of an electric vehicle, the performance of lithium-ion batteries (LIBs) is directly related to the vehicle quality and driving range. However, the charge-discharge performance and cycling performance are affected by the temperature. Excessive temperature can cause internal short circuits and even lead to safety issues, such as thermal runaway. The separator plays a crucial role in protecting the battery from regular operation, preventing direct touch between the cathode and the anode while allowing the transport of lithium ions. In this study, we have designed a thermoregulating separator in the shape of calabash, which uses melamine-encapsulated paraffin phase change material (PCM) with a wide enthalpy (0-168.52 J g-1) to dissipate the heat generated inside the battery promptly. Under extra-long-use conditions, the heat emitted by the battery is absorbed by the PCM without causing a significant temperature rise that triggers thermal runaway. The PCM separator can effectively suppress the temperature increase caused by battery penetration. Due to the unique structure of the PCM, the battery is short-circuited; it can significantly delay the internal temperature rise of the battery and quickly dissipate the heat, which is consistent with the characteristics of natural calabash in nutrient absorption and water diffusion, improving the melting and heat storage efficiency of the PCM. The design of the phase change separator provides an effective reference for overheat protection and improved safety in lithium-ion batteries.

14.
Heliyon ; 10(8): e29603, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38655348

RESUMO

Background: Predicting the severity of acute pancreatitis (AP) early poses a challenge in clinical practice. While there are well-established clinical scoring tools, their actual predictive performance remains uncertain. Various studies have explored the application of machine-learning methods for early AP prediction. However, a more comprehensive evidence-based assessment is needed to determine their predictive accuracy. Hence, this systematic review and meta-analysis aimed to evaluate the predictive accuracy of machine learning in assessing the severity of AP. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were systematically searched until December 5, 2023. The risk of bias in eligible studies was assessed using the Prediction Model Risk of Bias Assessment Tool (PROBAST). Subgroup analyses, based on different machine learning types, were performed. Additionally, the predictive accuracy of mainstream scoring tools was summarized. Results: This systematic review ultimately included 33 original studies. The pooled c-index in both the training and validation sets was 0.87 (95 % CI: 0.84-0.89) and 0.88 (95 % CI: 0.86-0.90), respectively. The sensitivity in the training set was 0.81 (95 % CI: 0.77-0.84), and in the validation set, it was 0.79 (95 % CI: 0.71-0.85). The specificity in the training set was 0.84 (95 % CI: 0.78-0.89), and in the validation set, it was 0.90 (95 % CI: 0.86-0.93). The primary model incorporated was logistic regression; however, its predictive accuracy was found to be inferior to that of neural networks, random forests, and xgboost. The pooled c-index of the APACHE II, BISAP, and Ranson were 0.74 (95 % CI: 0.68-0.80), 0.77 (95 % CI: 0.70-0.85), and 0.74 (95 % CI: 0.68-0.79), respectively. Conclusions: Machine learning demonstrates excellent accuracy in predicting the severity of AP, providing a reference for updating or developing a straightforward clinical prediction tool.

15.
Anal Sci ; 40(7): 1289-1299, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38582804

RESUMO

Liquid chromatography‒mass spectrometry employing porous graphite carbon columns and an n-octane-isopropanol mobile phase was utilized for the separation of triacylglycerols (TAGs) in various edible oils, aiming to identify lard adulteration in soybean, corn, and sunflower seed oils. Experiments were conducted using a Hypercarb column (2.1 mm × 100 mm, 5 µm) and an n-octane-isopropanol (70:30, V/V) mobile phase at a flow rate of 0.25 mL· min-1 and a column temperature of 60 °C. Detection was achieved through atmospheric pressure chemical ionization-mass spectrometry. Analysis of diverse edible oil samples revealed that oils of the same type shared similar TAG compositions, while different types exhibited distinct TAG profiles. Distinct variations in triglyceride composition were observed across different edible oils. Based on liquid chromatography‒mass spectrometry analysis, the characteristic component 1-stearic acid-2-palmitic acid-3-oleic acid glyceride (SPO), which may also include PSO, was identified in lard through principal component analysis and orthogonal partial least squares discriminant analysis. This component served as a marker for detecting as low as 0.1% lard adulteration in soybean, corn, and sunflower seed oils. The technique offers a precise and effective approach for the identification of lard adulteration in these edible oils.


Assuntos
Grafite , Espectrometria de Massas , Óleos de Plantas , Óleos de Plantas/química , Óleos de Plantas/análise , Grafite/química , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Porosidade , Contaminação de Alimentos/análise , Carbono/química , Espectrometria de Massa com Cromatografia Líquida
16.
Heliyon ; 10(7): e28218, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560106

RESUMO

Host-virus interactions can significantly impact the viral life cycle and pathogenesis; however, our understanding of the specific host factors involved in highly pathogenic avian influenza A virus H7N9 (HPAI H7N9) infection is currently restricted. Herein, we designed and synthesized 65 small interfering RNAs targeting host genes potentially associated with various aspects of RNA virus life cycles. Afterward, HPAI H7N9 viruses were isolated and RNA interference was used to screen for host factors likely to be involved in the life cycle of HPAI H7N9. Moreover, the research entailed assessing the associations between host proteins and HPAI H7N9 proteins. Twelve key host proteins were identified: Annexin A (ANXA)2, ANXA5, adaptor related protein complex 2 subunit sigma 1 (AP2S1), adaptor related protein complex 3 subunit sigma 1 (AP3S1), ATP synthase F1 subunit alpha (ATP5A1), COPI coat complex subunit alpha (COP)A, COPG1, heat shock protein family A (Hsp70) member 1A (HSPA)1A, HSPA8, heat shock protein 90 alpha family class A member 1 (HSP90AA1), RAB11B, and RAB18. Co-immunoprecipitation revealed intricate interactions between viral proteins (hemagglutinin, matrix 1 protein, neuraminidase, nucleoprotein, polymerase basic 1, and polymerase basic 2) and these host proteins, presumably playing a crucial role in modulating the life cycle of HPAI H7N9. Notably, ANXA5, AP2S1, AP3S1, ATP5A1, HSP90A1, and RAB18, were identified as novel interactors with HPAI H7N9 proteins rather than other influenza A viruses (IAVs). These findings underscore the significance of host-viral protein interactions in shaping the dynamics of HPAI H7N9 infection, while highlighting subtle variations compared with other IAVs. Deeper understanding of these interactions holds promise to advance disease treatment and prevention strategies.

17.
Cell Cycle ; 23(5): 537-554, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38662954

RESUMO

Cholesteatoma is a common disease of the middle ear. Currently, surgical removal is the only treatment option and patients face a high risk of relapse. The molecular basis of cholesteatoma remains largely unknown. Here, we show that Osteopontin (OPN), a predominantly secreted protein, plays a crucial role in the development of middle ear cholesteatoma. Global transcriptome analysis revealed the loss of epithelial features and an enhanced immune response in human cholesteatoma tissues. Quantitative RT-PCR and immunohistochemical staining of middle ear cholesteatoma validated the reduced expression of epithelial markers, as well as the elevated expression of mesenchymal markers including Vimentin and Fibronectin, but not N-Cadherin, α-smooth muscle actin (α-SMA) or ferroptosis suppressor protein 1 (FSP1), indicating a partial epithelial-mesenchymal transition (EMT) state. Besides, the expression of OPN was significantly elevated in human cholesteatoma tissues. Treatment with OPN promoted cell proliferation, survival and migration and led to a partial EMT in immortalized human keratinocyte cells. Importantly, blockade of OPN signaling could remarkably improve the cholesteatoma-like symptoms in SD rats. Our mechanistic study demonstrated that the AKT-zinc finger E-box binding homeobox 2 (ZEB2) axis mediated the effects of OPN. Overall, these findings suggest that targeting the OPN signaling represents a promising strategy for the treatment of middle ear cholesteatoma.


Assuntos
Proliferação de Células , Colesteatoma da Orelha Média , Transição Epitelial-Mesenquimal , Osteopontina , Ratos Sprague-Dawley , Transição Epitelial-Mesenquimal/genética , Humanos , Osteopontina/metabolismo , Osteopontina/genética , Animais , Colesteatoma da Orelha Média/metabolismo , Colesteatoma da Orelha Média/patologia , Colesteatoma da Orelha Média/genética , Ratos , Proliferação de Células/genética , Movimento Celular/genética , Transdução de Sinais , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética , Queratinócitos/metabolismo , Queratinócitos/patologia , Feminino
18.
J Cachexia Sarcopenia Muscle ; 15(3): 1209-1217, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38641928

RESUMO

BACKGROUND: Sarcopenia is characterized by progressive loss of muscle mass and function due to aging. DNA methylation has been identified to play important roles in the dysfunction of skeletal muscle. The aim of our present study was to explore the whole blood sample-based methylation changes of skeletal muscle function-related factors in patients with sarcopenia. METHODS: The overall DNA methylation levels were analysed by using MethlTarget™ DNA Methylation Analysis platform in a discovery set consistent of 50 sarcopenic older adults (aged ≥65 years) and 50 age- and sex-matched non-sarcopenic individuals. The candidate differentially methylated regions (DMRs) were further validated by Methylation-specific PCR (MSP) in another two independent larger sets and confirmed by pyrosequencing. Receiver operating characteristic (ROC) curve analysis was used to determine the optimum cut-off levels of fibroblast growth factor 2 (FGF2)_30 methylation best predicting sarcopenia and area under the ROC curve (AUC) was measured. The correlation between candidate DMRs and the risk of sarcopenia was investigated by univariate analysis and multivariate logistic regression analysis. RESULTS: Among 1149 cytosine-phosphate-guanine (CpG) sites of 27 skeletal muscle function-related secretary factors, 17 differentially methylated CpG sites and 7 differentially methylated regions (DMRs) were detected between patients with sarcopenia and control subjects in the discovery set. Further methylation-specific PCR identified that methylation of fibroblast growth factor 2 (FGF2)_30 was lower in patients with sarcopenia and the level was decreased as the severity of sarcopenia increased, which was confirmed by pyrosequencing. Correlation analysis demonstrated that the methylation level of FGF2_30 was positively correlated to ASMI (r = 0.372, P < 0.001), grip strength (r = 0.334, P < 0.001), and gait speed (r = 0.411, P < 0.001). ROC curve analysis indicated that the optimal cut-off value of FGF2_30 methylation level that predicted sarcopenia was 0.15 with a sensitivity of 84.6% and a specificity of 70.1% (AUC = 0.807, 95% CI = 0.756-0.858, P < 0.001). Multivariate logistic regression analyses showed that lower FGF2_30 methylation level (<0.15) was significantly associated with increased risk of sarcopenia even after adjustment for potential confounders including age, sex, and BMI (adjusted OR = 9.223, 95% CI: 6.614-12.861, P < 0.001). CONCLUSIONS: Our results suggest that lower FGF2_30 methylation is correlated with the risk and severity of sarcopenia in the older adults, indicating that FGF2 methylation serve as a surrogate biomarker for the screening and evaluation of sarcopenia.


Assuntos
Biomarcadores , Metilação de DNA , Fator 2 de Crescimento de Fibroblastos , Músculo Esquelético , Curva ROC , Sarcopenia , Idoso , Feminino , Humanos , Masculino , Biomarcadores/sangue , Ilhas de CpG , Fator 2 de Crescimento de Fibroblastos/sangue , Fator 2 de Crescimento de Fibroblastos/genética , Músculo Esquelético/metabolismo , Sarcopenia/diagnóstico , Sarcopenia/genética
19.
Brief Bioinform ; 25(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38426324

RESUMO

Emerging clinical evidence suggests that sophisticated associations with circular ribonucleic acids (RNAs) (circRNAs) and microRNAs (miRNAs) are a critical regulatory factor of various pathological processes and play a critical role in most intricate human diseases. Nonetheless, the above correlations via wet experiments are error-prone and labor-intensive, and the underlying novel circRNA-miRNA association (CMA) has been validated by numerous existing computational methods that rely only on single correlation data. Considering the inadequacy of existing machine learning models, we propose a new model named BGF-CMAP, which combines the gradient boosting decision tree with natural language processing and graph embedding methods to infer associations between circRNAs and miRNAs. Specifically, BGF-CMAP extracts sequence attribute features and interaction behavior features by Word2vec and two homogeneous graph embedding algorithms, large-scale information network embedding and graph factorization, respectively. Multitudinous comprehensive experimental analysis revealed that BGF-CMAP successfully predicted the complex relationship between circRNAs and miRNAs with an accuracy of 82.90% and an area under receiver operating characteristic of 0.9075. Furthermore, 23 of the top 30 miRNA-associated circRNAs of the studies on data were confirmed in relevant experiences, showing that the BGF-CMAP model is superior to others. BGF-CMAP can serve as a helpful model to provide a scientific theoretical basis for the study of CMA prediction.


Assuntos
MicroRNAs , Humanos , MicroRNAs/genética , RNA Circular/genética , Curva ROC , Aprendizado de Máquina , Algoritmos , Biologia Computacional/métodos
20.
Math Biosci Eng ; 21(2): 1765-1790, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38454659

RESUMO

Detecting abnormal surface features is an important method for identifying abnormal fish. However, existing methods face challenges in excessive subjectivity, limited accuracy, and poor real-time performance. To solve these challenges, a real-time and accurate detection model of abnormal surface features of in-water fish is proposed, based on improved YOLOv5s. The specific enhancements include: 1) We optimize the complete intersection over union and non-maximum suppression through the normalized Gaussian Wasserstein distance metric to improve the model's ability to detect tiny targets. 2) We design the DenseOne module to enhance the reusability of abnormal surface features, and introduce MobileViTv2 to improve detection speed, which are integrated into the feature extraction network. 3) According to the ACmix principle, we fuse the omni-dimensional dynamic convolution and convolutional block attention module to solve the challenge of extracting deep features within complex backgrounds. We carried out comparative experiments on 160 validation sets of in-water abnormal fish, achieving precision, recall, mAP50, mAP50:95 and frames per second (FPS) of 99.5, 99.1, 99.1, 73.9% and 88 FPS, respectively. The results of our model surpass the baseline by 1.4, 1.2, 3.2, 8.2% and 1 FPS. Moreover, the improved model outperforms other state-of-the-art models regarding comprehensive evaluation indexes.


Assuntos
Peixes , Água , Animais , Distribuição Normal
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