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1.
Transl Psychiatry ; 14(1): 255, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866779

RESUMO

Differences in clinical manifestations and biological underpinnings between Major Depressive Disorder (MDD) onset during adolescence and adulthood have been posited in previous studies, implying an influential role of age of onset (AOO) in the clinical subtyping and therapeutic approaches to MDD. However, direct comparisons between the two cohorts and their age-matched controls have been lacking in extant investigations. In this investigation, 156 volunteers participated, comprising 46 adolescents with MDD (adolescent-onset group), 35 adults with MDD (adult-onset group), 19 healthy adolescents, and 56 healthy adults. Resting-state functional MRI scans were undergone by all participants. Large-scale network analyses were applied. Subsequently, a 2 × 2 ANOVA was employed to analyze the main effects of diagnosis, age, and their interaction effect on functional connectivity (FC). Furthermore, regression analysis was employed to scrutinize the association between anomalous FC and HAMD sub-scores. Increased FC in visual network (VN), limbic network (LN), VN-dorsal attention network (DAN), VN-LN, and LN-Default Mode (DMN) was found in both adolescent-onset and adult-onset MDD; however, the increased FC in DAN and LN were only found in adult-onset MDD and the decreased FC in DAN was only found in adolescent-onset MDD. Additionally, the relationship between HAMD factor 1 anxiety somatization and altered FC of DAN, VN, and VN-DAN was moderated by AOO. In conclusion, shared and distinctive large-scale network alterations in adolescent-onset and adult-onset MDD patients were suggested by our findings, providing valuable contributions towards refining clinical subtyping and treatment approaches for MDD.


Assuntos
Idade de Início , Transtorno Depressivo Maior , Imageamento por Ressonância Magnética , Humanos , Transtorno Depressivo Maior/fisiopatologia , Transtorno Depressivo Maior/diagnóstico por imagem , Adolescente , Masculino , Feminino , Adulto , Adulto Jovem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiopatologia , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Conectoma , Estudos de Casos e Controles
2.
Eur J Radiol ; 177: 111556, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38875748

RESUMO

PURPOSE: To conduct the fusion of radiomics and deep transfer learning features from the intratumoral and peritumoral areas in breast DCE-MRI images to differentiate between benign and malignant breast tumors, and to compare the diagnostic accuracy of this fusion model against the assessments made by experienced radiologists. MATERIALS AND METHODS: This multi-center study conducted a retrospective analysis of DCE-MRI images from 330 women diagnosed with breast cancer, with 138 cases categorized as benign and 192 as malignant. The training and internal testing sets comprised 270 patients from center 1, while the external testing cohort consisted of 60 patients from center 2. A fusion feature set consisting of radiomics features and deep transfer learning features was constructed from both intratumoral (ITR) and peritumoral (PTR) areas. The Least absolute shrinkage and selection operator (LASSO) based support vector machine was chosen as the classifier by comparing its performance with five other machine learning models. The diagnostic performance and clinical usefulness of fusion model were verified and assessed through the area under the receiver operating characteristics (ROC) and decision curve analysis. Additionally, the performance of the fusion model was compared with the diagnostic assessments of two experienced radiologists to evaluate its relative accuracy. The study strictly adhered to CLEAR and METRICS guidelines for standardization to ensure rigorous and reproducible methods. RESULTS: The findings show that the fusion model, utilizing radiomics and deep transfer learning features from the ITR and PTR, exhibited exceptional performance in classifying breast tumors, achieving AUCs of 0.950 in the internal testing set and 0.921 in the external testing set. This performance significantly surpasses that of models relying on singular regional radiomics or deep transfer learning features alone. Moreover, the fusion model demonstrated superior diagnostic accuracy compared to the evaluations conducted by two experienced radiologists, thereby highlighting its potential to support and enhance clinical decision-making in the differentiation of benign and malignant breast tumors. CONCLUSION: The fusion model, combining multi-regional radiomics with deep transfer learning features, not only accurately differentiates between benign and malignant breast tumors but also outperforms the diagnostic assessments made by experienced radiologists. This underscores the model's potential as a valuable tool for improving the accuracy and reliability of breast tumor diagnosis.

3.
Int Dent J ; 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38866671

RESUMO

OBJECTIVES: With rising rates of maxillofacial fracture, postoperative infection following rigid internal fixation is an important issue that requires immediate resolution. It is important to explore an alternative antibacterial method apart from conventional antibiotics. A controlled experiment was conducted to evaluate the effectiveness of a caerin 1.9 peptide-coated titanium plate in reducing mandibular infection in New Zealand (NZ) rabbits, aiming to minimise the risk of post-metallic implantation infection. METHODS: Twenty-two NZ rabbits were randomly divided into 3 groups. The experiment group received caerin 1.9 peptide-coated titanium plates and mixed oral bacteria exposure. The control group received normal titanium plates with mixed oral bacteria exposure. The untreated group served as a control to prove that bacteria in the mouth can cause infection. Weight, temperature, hepatic function, and C-reactive protein levels were measured. Wound and bone conditions were evaluated. Further analysis included local infection, anatomic conditions, histology, and bacterial load. RESULTS: No significant differences were found in temperature, weight, blood alanine aminotransferase, and C-reactive protein levels amongst the 3 groups. The experiment group showed the lowest amount of bacterial RNA in wounds. Additionally, the experiment group had higher peripheral lymphocyte counts compared to the control group and lower neutrophil counts on the third and seventh day postoperatively. Histologic analysis revealed lower levels of inflammatory cell infiltration, bleeding, and areas of necrosis in the experimental group compared with the controls. CONCLUSIONS: A caerin 1.9-coated titanium plate is able to inhibit bacterial growth in a NZ rabbit mandibular mixed bacteria infection model and is worth further investigation.

4.
Theriogenology ; 225: 152-161, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38805997

RESUMO

Oocytes and embryos are highly sensitive to environmental stress in vivo and in vitro. During in vitro culture, many stressful conditions can affect embryo quality and viability, leading to adverse clinical outcomes such as abortion and congenital abnormalities. In this study, we found that valeric acid (VA) increased the mitochondrial membrane potential and ATP content, decreased the level of reactive oxygen species that the mitochondria generate, and thus improved mitochondrial function during early embryonic development in pigs. VA decreased expression of the autophagy-related factors LC3B and BECLIN1. Interestingly, VA inhibited expression of autophagy-associated phosphorylation-adenosine monophosphate-activated protein kinase (p-AMPK), phosphorylation-UNC-51-like autophagy-activated kinase 1 (p-ULK1, Ser555), and ATG13, which reduced apoptosis. Short-chain fatty acids (SCFAs) can signal through G-protein-coupled receptors on the cell membrane or enter the cell directly through transporters. We further show that the monocarboxylate transporter 1 (MCT1) was necessary for the effects of VA on embryo quality, which provides a new molecular perspective of the pathway by which SCFAs affect embryos. Importantly, VA significantly inhibited the AMPK-ULK1 autophagic signaling pathway through MCT1, decreased apoptosis, increased expression of embryonic pluripotency genes, and improved embryo quality.


Assuntos
Proteínas Quinases Ativadas por AMP , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Autofagia , Desenvolvimento Embrionário , Mitocôndrias , Transportadores de Ácidos Monocarboxílicos , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/genética , Suínos/embriologia , Desenvolvimento Embrionário/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/genética , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Transportadores de Ácidos Monocarboxílicos/genética , Transdução de Sinais/efeitos dos fármacos , Blastocisto/efeitos dos fármacos , Blastocisto/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Técnicas de Cultura Embrionária/veterinária , Simportadores
5.
Adv Sci (Weinh) ; : e2401263, 2024 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-38767182

RESUMO

Single-cell multiomic and exosome analyses are potent tools in various fields, such as cancer research, immunology, neuroscience, microbiology, and drug development. They facilitate the in-depth exploration of biological systems, providing insights into disease mechanisms and aiding in treatment. Single-cell isolation, which is crucial for single-cell analysis, ensures reliable cell isolation and quality control for further downstream analyses. Microfluidic chips are small lightweight systems that facilitate efficient and high-throughput single-cell isolation and real-time single-cell analysis on- or off-chip. Therefore, most current single-cell isolation and analysis technologies are based on the single-cell microfluidic technology. This review offers comprehensive guidance to researchers across different fields on the selection of appropriate microfluidic chip technologies for single-cell isolation and analysis. This review describes the design principles, separation mechanisms, chip characteristics, and cellular effects of various microfluidic chips available for single-cell isolation. Moreover, this review highlights the implications of using this technology for subsequent analyses, including single-cell multiomic and exosome analyses. Finally, the current challenges and future prospects of microfluidic chip technology are outlined for multiplex single-cell isolation and multiomic and exosome analyses.

6.
Nutrients ; 16(10)2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38794751

RESUMO

Unhealthy lifestyles (high-fat diet, smoking, alcohol consumption, too little exercise, etc.) in the current society are prone to cause lipid metabolism disorders affecting the health of the organism and inducing the occurrence of diseases. Saponins, as biologically active substances present in plants, have lipid-lowering, inflammation-reducing, and anti-atherosclerotic effects. Saponins are thought to be involved in the regulation of lipid metabolism in the body; it suppresses the appetite and, thus, reduces energy intake by modulating pro-opiomelanocortin/Cocaine amphetamine regulated transcript (POMC/CART) neurons and neuropeptide Y/agouti-related peptide (NPY/AGRP) neurons in the hypothalamus, the appetite control center. Saponins directly activate the AMP-activated protein kinase (AMPK) signaling pathway and related transcriptional regulators such as peroxisome-proliferator-activated-receptors (PPAR), CCAAT/enhancer-binding proteins (C/EBP), and sterol-regulatory element binding proteins (SREBP) increase fatty acid oxidation and inhibit lipid synthesis. It also modulates gut-liver interactions to improve lipid metabolism by regulating gut microbes and their metabolites and derivatives-short-chain fatty acids (SCFAs), bile acids (BAs), trimethylamine (TMA), lipopolysaccharide (LPS), et al. This paper reviews the positive effects of different saponins on lipid metabolism disorders, suggesting that the gut-liver axis plays a crucial role in improving lipid metabolism processes and may be used as a therapeutic target to provide new strategies for treating lipid metabolism disorders.


Assuntos
Microbioma Gastrointestinal , Metabolismo dos Lipídeos , Fígado , Saponinas , Saponinas/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Humanos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Transdução de Sinais/efeitos dos fármacos , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/efeitos dos fármacos
7.
BMC Psychiatry ; 24(1): 381, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773555

RESUMO

BACKGROUND: Nowadays, moderate gaming behaviors can be a pleasant and relaxing experiences among adolescents. However, excessive gaming behavior may lead to gaming disorder (GD) that disruption of normal daily life. Understanding the possible risk factors of this emerging problem would help to suggest effective at preventing and intervening. This study aimed to investigate the prevalence of GD and analyze its possible risk factors that adolescents with GD. METHODS: Data were collected between October 2020 and January 2021. In total, a sample of 7901 students (4080 (52%) boys, 3742 (48%) girls; aged 12-18 years) completed questionnaires regarding the Gaming-Related Behaviors Survey, Gaming Disorder Symptom Questionnaire-21 (GDSQ-21); Behavioral Inhibition System and Behavioral Activation System Scale (BIS/BAS Scale); Emotion Regulation Questionnaire (ERQ); Short-form Egna Minnenav Barndoms Uppfostran for Chinese (s-EMBU-C); and Adolescent Self-Rating Life Events Checklist (ASLEC). RESULTS: The prevalence of GD was 2.27% in this adolescent sample. The GD gamers were a little bit older (i.e., a higher proportion of senior grades), more boys, with more gaming hours per week in the last 12 months, with more reward responsiveness, maternal rejecting and occurrence of negative life events (e.g., interpersonal relationships, being punished and bereavement factors). CONCLUSION: These possible risk factors may influence the onset of GD. Future research in clinical, public health, education and other fields should focus on these aspects for provide target prevention and early intervention strategies.


Assuntos
Transtorno de Adição à Internet , Humanos , Adolescente , Masculino , Feminino , China/epidemiologia , Fatores de Risco , Prevalência , Criança , Transtorno de Adição à Internet/epidemiologia , Transtorno de Adição à Internet/psicologia , Jogos de Vídeo/psicologia , Comportamento do Adolescente/psicologia , Inquéritos e Questionários , Comportamento Aditivo/epidemiologia , Comportamento Aditivo/psicologia
8.
Chemistry ; 30(32): e202400899, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38576216

RESUMO

An amphiphilic aza-BODIPY dye (S)-1 bearing two chiral hydrophilic side chains with S-stereogenic centers was synthesized. This dye exhibited kinetic-controlled self-assembly pathways and supramolecular chiral polymorphism properties in MeOH/H2O (9/1, v/v) mixed solvent. The (S)-1 monomers first aggregated into a kinetic controlled, off-pathway species Agg. A, which was spontaneously transformed into an on-pathway metastable aggregate (Agg. B) and subsequently into the thermodynamic Agg. C. The three aggregate polymorphs of dye (S)-1 displayed distinct optical properties and nanomorphologies. In particular, chiral J-aggregation characteristics were observed for both Agg. B and Agg. C, such as Davydov-split absorption bands (Agg. B), extremely sharp and intense J-band with large bathochromic shift (Agg. C), non-diminished fluorescence upon aggregation, as well as strong bisignated Cotton effects. Moreover, the AFM and TEM studies revealed that Agg. A had the morphology of nanoparticle while fibril or rod-like helical nanostructures with left-handedness were observed respectively for Agg. B and Agg. C. By controlling the kinetic transformation process from Agg. B to Agg. C, thin films consisting of Agg. B and Agg. C with different ratios were prepared, which displayed tunable CPL with emission maxima at 788-805 nm and g-factors between -4.2×10-2 and -5.1×10-2.

9.
J Mol Biol ; 436(11): 168590, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38663547

RESUMO

Redß is a protein from bacteriophage λ that binds to single-stranded DNA (ssDNA) to promote the annealing of complementary strands. Together with λ-exonuclease (λ-exo), Redß is part of a two-component DNA recombination system involved in multiple aspects of genome maintenance. The proteins have been exploited in powerful methods for bacterial genome engineering in which Redß can anneal an electroporated oligonucleotide to a complementary target site at the lagging strand of a replication fork. Successful annealing in vivo requires the interaction of Redß with E. coli single-stranded DNA-binding protein (SSB), which coats the ssDNA at the lagging strand to coordinate access of numerous replication proteins. Previous mutational analysis revealed that the interaction between Redß and SSB involves the C-terminal domain (CTD) of Redß and the C-terminal tail of SSB (SSB-Ct), the site for binding of numerous host proteins. Here, we have determined the x-ray crystal structure of Redß CTD in complex with a peptide corresponding to the last nine residues of SSB (MDFDDDIPF). Formation of the complex is predominantly mediated by hydrophobic interactions between two phenylalanine side chains of SSB (Phe-171 and Phe-177) and an apolar groove on the CTD, combined with electrostatic interactions between the C-terminal carboxylate of SSB and Lys-214 of the CTD. Mutation of any of these residues to alanine significantly disrupts the interaction of full-length Redß and SSB proteins. Structural knowledge of this interaction will help to expand the utility of Redß-mediated recombination to a wider range of bacterial hosts for applications in synthetic biology.


Assuntos
Bacteriófago lambda , DNA de Cadeia Simples , Proteínas de Ligação a DNA , Proteínas de Escherichia coli , Escherichia coli , Proteínas Virais , Bacteriófago lambda/genética , Bacteriófago lambda/metabolismo , Sítios de Ligação , Cristalografia por Raios X , DNA de Cadeia Simples/metabolismo , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Escherichia coli/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Proteínas Virais/metabolismo , Proteínas Virais/química , Proteínas Virais/genética
10.
Eye Vis (Lond) ; 11(1): 12, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38561862

RESUMO

BACKGROUND: Near work is generally considered as a risk factor for myopia onset and progression. This study aimed to investigate the choroidal responses to a brief-period of near work in children and young adults. METHODS: Thirty myopic medical students (aged 18-28 years) and 30 myopic children (aged 8-12 years) participated in this study. The submacular total choroidal area (TCA), luminal area (LA), stromal area (SA), choroidal vascularity index (CVI) and choriocapillaris flow deficit (CcFD), as well as subfoveal choroidal thickness (SFCT) were measured with swept-source optical coherence tomography/optical coherence tomography angiography (SS-OCT/OCTA) before and immediately after 20 min, 40 min, 60 min of near work at a distance of 33 cm. RESULTS: In adults, 20 min of near work induced a significant reduction in SFCT (- 5.1 ± 6.5 µm), LA [(- 19.2 ± 18.6) × 103 µm2], SA [(- 8.2 ± 12.6) × 103 µm2] and TCA [(- 27.4 ± 24.9) × 103 µm2] (all P < 0.01). After 40 min of near work, LA was still reduced [(- 9.4 ± 18.3) × 103 µm2], accompanied with a decreased CVI (- 0.39% ± 0.70%) and an increased CcFD (0.30% ± 0.78%) (all P < 0.05). After 60 min of near work, CVI was still reduced (- 0.28% ± 0.59%), and CcFD was still increased (0.37% ± 0.75%) (all P < 0.05). In children, 20 min of near work induced a significant increase in CcFD (0.55% ± 0.64%), while 60 min of near work induced increases in SA [(7.2 ± 13.0) × 103 µm2] and TCA [(9.7 ± 25.3) × 103 µm2] and a reduction in CVI (- 0.28% ± 0.72%) (all P < 0.05). Children exhibited lower near work-induced LA and TCA reduction than adults, with a mean difference of - 0.86% and - 0.82%, respectively (all P < 0.05). CONCLUSIONS: The temporal characteristics and magnitude of changes of choroidal vascularity and choriocapillaris perfusion during near work was not identical between children and adults. The initial response to near work was observed in choriocapillaris in children, whereas it was observed in the medium- and large-sized vessels in adults. TRIAL REGISTRATION: Clinical Trial Registry (ChiCTR), ChiCTR2000040205. Registered on 25 November 2020, https://www.chictr.org.cn/bin/project/edit?pid=64501 .

11.
Brain Behav ; 14(4): e3473, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38594225

RESUMO

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping (QSM) technique was a new quantitative magnetic resonance imaging technique to evaluate the cerebral iron deposition in clinical practice. The current study was aimed to investigate the reproducibility of the volumetric susceptibility value of the subcortical gray nuclei at two different MR vendor with the same magnetic strength. METHODS: Cerebral magnitude and phase images of 21 normal subjects were acquired from a 3D multiecho enhanced gradient recalled echo sequence at two different 3.0T MR scanner, and then the magnetic susceptibility images were generated by STI software. The brain structural images were coregistered with magnitude images and generated the normalized parameters, and then generated the normalized susceptibility images. The subcortical gray nuclei template was applied to extract the volumetric susceptibility value of the target nuclei. RESULTS: ICC value (95% CI) of the caudate, putamen and GP were 0.847 (0.660-0.935), 0.848 (0.663-0.935) and 0.838 (0.643-0.931), respectively. The ICC value of the thalamus was 0.474 (0.064-0.747). Ninety-five point two percent (20/21) of the difference points of the susceptibility located between the 95% LA for the caudate at the two different 3.0T MR scanner, while the less than 95% of the difference points of the susceptibility value located between the 95% LA for the putamen, globus pallidus and thalamus. CONCLUSION: The current study identified that the caudate had the stable reproducibility of the magnetic susceptibility value, and the other basal ganglion nuclei should be cautious for the quantitative evaluation of the magnetic susceptibility value at different 3.0T MR scanner.


Assuntos
Encéfalo , Substância Cinzenta , Humanos , Substância Cinzenta/diagnóstico por imagem , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Putamen
12.
Langmuir ; 40(17): 9082-9096, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38619979

RESUMO

Great efforts have been devoted to the development of novel and multifunctional wound dressing materials to meet the different needs of wound healing. Herein, we covalently grafted quaternary ammonium groups (QAGs) containing 12-carbon straight-chain alkanes to the dextran polymer skeleton. We then oxidized the resulting product into oxidized quaternized dextran (OQD). The obtained OQD polymer is rich in antibacterial QAGs and aldehyde groups. It can react with glycol chitosan (GC) via the Schiff-base reaction to form a multifunctional GC@OQD hydrogel with good self-healing behavior, hemostasis, injectability, inherent superior antibacterial activity, biocompatibility, and excellent promotion of healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. The biosafe and nontoxic GC@OQD hydrogel with a three-dimensional porous network structure possesses an excellent swelling rate and water retention capacity. It can be used for hemostasis and treating irregular wounds. The designed GC@OQD hydrogel with inherent antibacterial activity possesses good antibacterial efficacy on both S. aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria), as well as MRSA bacteria, with antibacterial activity greater than 99%. It can be used for the treatment of wounds infected by MRSA and significantly promotes the healing of wounds. Thus, the multifunctional antibacterial GC@OQD hydrogel has the potential to be applied in clinical practice as a wound dressing.


Assuntos
Antibacterianos , Quitosana , Escherichia coli , Hidrogéis , Staphylococcus aureus Resistente à Meticilina , Cicatrização , Hidrogéis/química , Hidrogéis/farmacologia , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Animais , Quitosana/química , Quitosana/farmacologia , Dextranos/química , Dextranos/farmacologia , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos , Camundongos , Polissacarídeos/química , Polissacarídeos/farmacologia
13.
Res Sq ; 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38645058

RESUMO

Genome wide association studies (GWASs) have identified numerous risk loci associated with prostate cancer, yet unraveling their functional significance remains elusive. Leveraging our high-throughput SNPs-seq method, we pinpointed rs4519489 within the multi-ancestry GWAS-discovered 2p25 locus as a potential functional SNP due to its significant allelic differences in protein binding. Here, we conduct a comprehensive analysis of rs4519489 and its associated gene, NOL10, employing diverse cohort data and experimental models. Clinical findings reveal a synergistic effect between rs4519489 genotype and NOL10 expression on prostate cancer prognosis and severity. Through unbiased proteomics screening, we reveal that the risk allele A of rs4519489 exhibits enhanced binding to USF1, a novel oncogenic transcription factor (TF) implicated in prostate cancer progression and prognosis, resulting in elevated NOL10 expression. Furthermore, we elucidate that NOL10 regulates cell cycle pathways, fostering prostate cancer progression. The concurrent expression of NOL10 and USF1 correlates with aggressive prostate cancer characteristics and poorer prognosis. Collectively, our study offers a robust strategy for functional SNP screening and TF identification through high-throughput SNPs-seq and unbiased proteomics, highlighting the rs4519489-USF1-NOL10 regulatory axis as a promising biomarker or therapeutic target for clinical diagnosis and treatment of prostate cancer.

14.
Front Immunol ; 15: 1389993, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38665917

RESUMO

Kikuchi-Fujimoto disease (KFD) is a benign, self-limiting illness that can progress to systemic lupus erythematosus (SLE) in approximately 30% of cases. Neurological injuries can occur in both diseases, albeit with distinct presentations. Venous sinus thrombosis is a serious cerebrovascular complication in patients with neuropsychiatric SLE but is rarely observed in patients with KFD. The involvement of various antibodies, particularly antiphospholipid antibodies, can cause vascular endothelial cell injury, resulting in focal cerebral ischemia and intracranial vascular embolism in SLE. However, there are cases in which thrombotic pathology occurs without antiphospholipid antibody positivity, attributed to vascular lesions. In this report, we present a case of KFD and lupus encephalopathy featuring cerebral venous sinus thrombosis, despite the patient being negative for antiphospholipid antibody. We also conducted a comparative analysis of C3 and C4 levels in cerebrospinal fluid (CSF) and peripheral blood, along with the protein ratio in CSF and serum, to elucidate the pathological changes and characteristics of lupus encephalopathy.


Assuntos
Linfadenite Histiocítica Necrosante , Lúpus Eritematoso Sistêmico , Trombose dos Seios Intracranianos , Humanos , Linfadenite Histiocítica Necrosante/diagnóstico , Linfadenite Histiocítica Necrosante/complicações , Linfadenite Histiocítica Necrosante/patologia , Trombose dos Seios Intracranianos/etiologia , Trombose dos Seios Intracranianos/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Feminino , Adulto
15.
Int J Biol Macromol ; 268(Pt 2): 131642, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38641283

RESUMO

To better treat bacteria-infected wounds and promote healing, new wound dressings must be developed. In this study, we obtained PA@Fe by chelating iron trivalent ions (Fe3+) with protocatechualdehyde (PA), which has a catechol structure. Subsequently, we reacted it with ethylene glycol chitosan (GC) via a Schiff base reaction and loaded vancomycin to obtain an antibacterial Gel@Van hydrogel with a photothermal response. The as-prepared Gel@Van hydrogel exhibited good injectability, self-healing, hemostasis, photothermal stability, biocompatibility, and antioxidant and antibacterial properties. Moreover, Gel@Van hydrogel achieved highly synergistic antibacterial efficacy through photothermal and antibiotic sterilization. In a mouse skin-damaged infection model, Gel@Van hydrogel had a strong ability to promote the healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds, indicating the great potential application value of Gel@Van hydrogel in the field of treating and promoting the healing of infected wounds.


Assuntos
Benzaldeídos , Catecóis , Hidrogéis , Ferro , Polissacarídeos , Infecção dos Ferimentos , Antioxidantes/síntese química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antibacterianos/síntese química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Hidrogéis/síntese química , Hidrogéis/farmacologia , Hidrogéis/uso terapêutico , Ferro/química , Polissacarídeos/química , Catecóis/química , Benzaldeídos/química , Infecção dos Ferimentos/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Vancomicina/uso terapêutico , Terapia Fototérmica , Modelos Animais , Animais , Camundongos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico
16.
Curr Med Imaging ; 20: e15734056219963, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38660947

RESUMO

BACKGROUND: A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. METHODS: We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. RESULTS: Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). CONCLUSION: The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.


Assuntos
Circulação Cerebrovascular , Transtornos de Enxaqueca , Marcadores de Spin , Humanos , Circulação Cerebrovascular/fisiologia , Transtornos de Enxaqueca/diagnóstico por imagem , Transtornos de Enxaqueca/fisiopatologia , Feminino , Adulto , Masculino , Imageamento Tridimensional/métodos , Doença Crônica , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Encéfalo/fisiopatologia , Estudos de Casos e Controles , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/irrigação sanguínea
17.
Appl Microbiol Biotechnol ; 108(1): 314, 2024 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-38683435

RESUMO

The importance of dietary fiber (DF) in animal diets is increasing with the advancement of nutritional research. DF is fermented by gut microbiota to produce metabolites, which are important in improving intestinal health. This review is a systematic review of DF in pig nutrition using in vitro and in vivo models. The fermentation characteristics of DF and the metabolic mechanisms of its metabolites were summarized in an in vitro model, and it was pointed out that SCFAs and gases are the important metabolites connecting DF, gut microbiota, and intestinal health, and they play a key role in intestinal health. At the same time, some information about host-microbe interactions could have been improved through traditional animal in vivo models, and the most direct feedback on nutrients was generated, confirming the beneficial effects of DF on sow reproductive performance, piglet intestinal health, and growing pork quality. Finally, the advantages and disadvantages of different fermentation models were compared. In future studies, it is necessary to flexibly combine in vivo and in vitro fermentation models to profoundly investigate the mechanism of DF on the organism in order to promote the development of precision nutrition tools and to provide a scientific basis for the in-depth and rational utilization of DF in animal husbandry. KEY POINTS: • The fermentation characteristics of dietary fiber in vitro models were reviewed. • Metabolic pathways of metabolites and their roles in the intestine were reviewed. • The role of dietary fiber in pigs at different stages was reviewed.


Assuntos
Ração Animal , Fibras na Dieta , Fermentação , Microbioma Gastrointestinal , Animais , Fibras na Dieta/metabolismo , Suínos , Microbioma Gastrointestinal/fisiologia , Ração Animal/análise , Fenômenos Fisiológicos da Nutrição Animal , Ácidos Graxos Voláteis/metabolismo
18.
Insect Sci ; 31(3): 748-758, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38445520

RESUMO

Lipid homeostasis is crucial for growth and development of organisms. Several cytochrome P450 monooxygenases (CYPs) are involved in lipid metabolism. The function of Cyp311a1 in the anterior midgut as a regulator of phosphatidylethanolamine (PE) metabolism in Drosophila melanogaster has been demonstrated, as depletion of Cyp311a1 caused larval growth arrest that was partially rescued by supplying PE. In this study, we investigated the role of CYP311A1 in wing morphogenesis in Drosophila. Using the GAL4-UAS system, Cyp311a1 was selectively knocked down in the wing disc. A deformed wing phenotype was observed in flies with reduced Cyp311a1 transcripts. BODIPY and oil red O staining revealed a reduction of neutral lipids in the wing disc after the depletion of Cyp311a1. In addition, we observed an enhanced sensitivity to Eosin Y penetration in the wings of Cyp311a1 knocked-down flies. Moreover, the reduction of CYP311A1 function in developing wings does not affect cell proliferation and apoptosis, but entails disordered Phalloidin or Cadherin distribution, suggesting an abnormal cell morphology and cell cortex structure in wing epithelial cells. Taken together, our results suggest that Cyp311a1 is needed for wing morphogenesis by participating in lipid assembly and cell homeostasis.


Assuntos
Sistema Enzimático do Citocromo P-450 , Proteínas de Drosophila , Drosophila melanogaster , Asas de Animais , Animais , Drosophila melanogaster/crescimento & desenvolvimento , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Asas de Animais/crescimento & desenvolvimento , Asas de Animais/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Morfogênese , Larva/crescimento & desenvolvimento , Larva/genética , Larva/metabolismo , Metabolismo dos Lipídeos
19.
Curr Med Imaging ; 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38485680

RESUMO

BACKGROUND: Although the amygdala has structural and functional abnormalities in Chronic Migraine (CM), less is known about the altered perfusion of the amygdala in CM. OBJECTIVE: The current study aimed to assess amygdala perfusion in CM using a contrast agent-free and quantitative approach. METHODS: 15 Normal Controls (NC) and 13 patients with CM during the migraine interval were assessed for brain structure and subjected to 3D Pseudo- Continuous Arterial Spin Labeling (3D-PCASL) MR imaging. The Cerebral Blood Flow (CBF) value of the amygdala was automatically extracted based on the individual amygdala mask for all participants. The independent sample t-test, Receiver Operating Characteristic (ROC) curve, and correlation analysis were used to evaluate the perfusion changes in CM. RESULTS: Bilateral amygdala cerebral perfusion was lower in CM (left amygdala, 42.21±4.49 ml/100mg/min; right amygdala, 42.38±4.41 ml/100mg/min) than in NC (left amygdala, 48.31±6.92 ml/100mg/min; right amygdala, 47.88±6.53 ml/100mg/min) (left, p = 0.01; right, p = 0.02). There was no significant correlation between the perfusion of bilateral amygdalas and the clinical variables. Also, there was no significant difference in the volume of bilateral amygdalas between the two groups. The Area Under the Curve (AUC) of the CBF values of the left and right amygdala was 0.78 (95%CI: 0.58-0.91) and 0.75 (95%CI: 0.55-0.89), respectively. The cut-off value was 44.24 ml/100mg/min (left amygdala, with sensitivity 76.90% and specificity 78.70%) and 46.75 ml/100mg/min (right amygdala, with sensitivity 92.3% and specificity 58.80%), respectively. CONCLUSION: CM presented bilateral hypoperfusion in the amygdala, offering potential diagnostic value in distinguishing CM from NC. The 3D-PCASL could be regarded as a simple and efficient neuroimaging tool to assess the perfusion status in CM patients.

20.
Microbiol Res ; 283: 127705, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38554650

RESUMO

There is still a lack of longitudinal dynamic studies on the taxonomic features, functional reserves, and metabolites of the rabbit gut microbiome. An experiment was conducted to characterize the bacterial community of rabbits. By combining metagenomics and metabolomics, we have comprehensively analyzed the longitudinal dynamics of the rabbit gut microbiota and its effect on host adaptability. Our data reveal an overall increasing trend in microbial community and functional gene diversity and richness during the pre-harvest lifespan of rabbits. The introduction of solid feed is an important driving factor affecting rabbit gut microbiological compositions. Clostridium and Ruminococcus had significantly higher relative abundances in the solid feed stage. Further, the starch and fiber in solid feed promote the secretion of carbohydrate-degrading enzymes, which helps the host adapt to dietary changes. The rabbit gut microbiota can synthesize lysine, and the synthase is gradually enriched during the diet transformation. The gut microbiota of newborn rabbits has a higher abundance of lipid metabolism, which helps the host obtain more energy from breast milk lipids. The rabbit gut microbiota can also synthesize a variety of secondary bile acids after the introduction of solid feed. These findings provide a novel understanding of how the gut microbiota mediates adaptability to environment and diet in rabbits and provide multiple potential strategies for regulating intestinal health and promoting higher feed efficiency.


Assuntos
Microbioma Gastrointestinal , Microbiota , Humanos , Animais , Feminino , Coelhos , Microbioma Gastrointestinal/genética , Metabolômica , Dieta , Intestinos , Metagenômica
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