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1.
Immunity ; 57(8): 1769-1779.e4, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-38901428

RESUMO

Many infections, including malaria, are associated with an increase in autoantibodies (AAbs). Prior studies have reported an association between genetic markers of susceptibility to autoimmune disease and resistance to malaria, but the underlying mechanisms are unclear. Here, we performed a longitudinal study of children and adults (n = 602) in Mali and found that high levels of plasma AAbs before the malaria season independently predicted a reduced risk of clinical malaria in children during the ensuing malaria season. Baseline AAb seroprevalence increased with age and asymptomatic Plasmodium falciparum infection. We found that AAbs purified from the plasma of protected individuals inhibit the growth of blood-stage parasites and bind P. falciparum proteins that mediate parasite invasion. Protected individuals had higher plasma immunoglobulin G (IgG) reactivity against 33 of the 123 antigens assessed in an autoantigen microarray. This study provides evidence in support of the hypothesis that a propensity toward autoimmunity offers a survival advantage against malaria.


Assuntos
Autoanticorpos , Imunoglobulina G , Malária Falciparum , Plasmodium falciparum , Humanos , Plasmodium falciparum/imunologia , Autoanticorpos/imunologia , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Criança , Pré-Escolar , Adulto , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Feminino , Mali , Masculino , Adolescente , Anticorpos Antiprotozoários/imunologia , Estudos Longitudinais , Lactente , Antígenos de Protozoários/imunologia , Adulto Jovem , Autoantígenos/imunologia , Estudos Soroepidemiológicos , Pessoa de Meia-Idade
2.
Nano Lett ; 24(18): 5474-5480, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38652833

RESUMO

Grain boundaries (GBs) and twin boundaries (TBs) in copper (Cu) are two major planar defects that influence electrical conductivity due to their complex electron transport characteristics, involving electron scattering and electron concentration. Understanding their local electronic states is crucial for the design of future conductor materials. In this study, we characterized electron behaviors at TBs and GBs within one Cu grain using atomic force microscopy. Our findings revealed that, compared with GBs, TBs exhibit better current transport capability (direct-current mode) and larger electromagnetic loss (high-frequency microwave mode). Both kelvin probe force microscopy and theoretical analysis suggested that TBs with smaller lattice disorder possess lower density of states at the Fermi level. The reduced density of states may result in decreased electron scattering and a lower electron concentration at TBs. The latter can be highlighted by the high-frequency skinning effect, manifested as larger electromagnetic loss and weaker high-frequency conductivity.

3.
Oncologist ; 29(8): e976-e983, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38943540

RESUMO

BACKGROUND: PREDICT is a web-based tool for forecasting breast cancer outcomes. PREDICT version 3.0 was recently released. This study aimed to validate this tool for a large population in mainland China and compare v3.0 with v2.2. METHODS: Women who underwent surgery for nonmetastatic primary invasive breast cancer between 2010 and 2020 from the First Affiliated Hospital of Wenzhou Medical University were selected. Predicted and observed 5-year overall survival (OS) for both v3.0 and v2.2 were compared. Discrimination was compared using receiver-operator curves and DeLong test. Calibration was evaluated using calibration plots and chi-squared test. A difference greater than 5% was deemed clinically relevant. RESULTS: A total of 5424 patients were included, with median follow-up time of 58 months (IQR 38-89 months). Compared to v2.2, v3.0 did not show improved discriminatory accuracy for 5-year OS (AUC: 0.756 vs 0.771), same as ER-positive and ER-negative patients. However, calibration was significantly improved in v3.0, with predicted 5-year OS deviated from observed by -2.0% for the entire cohort, -2.9% for ER-positive and -0.0% for ER-negative patients, compared to -7.3%, -4.7% and -13.7% in v2.2. In v3.0, 5-year OS was underestimated by 9.0% for patients older than 75 years, and 5.8% for patients with micrometastases. Patients with distant metastases postdiagnosis was overestimated by 10.6%. CONCLUSIONS: PREDICT v3.0 reliably predicts 5-year OS for the majority of Chinese patients with breast cancer. PREDICT v3.0 significantly improved the predictive accuracy for ER-negative groups. Furthermore, caution is advised when interpreting 5-year OS for patients aged over 70, those with micrometastases or metastases postdiagnosis.


Assuntos
Neoplasias da Mama , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/mortalidade , Feminino , Pessoa de Meia-Idade , China/epidemiologia , Adulto , Prognóstico , Idoso , Estudos de Coortes , População do Leste Asiático
4.
Anal Chem ; 96(22): 9285-9293, 2024 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-38768388

RESUMO

DNA biosynthesis, a focus of fundamental and applied research, typically involves DNA polymerases by using templates, primers, and dNTPs. Some polymerases can polymerize dNTPs for DNA de novo synthesis, although this is generally to occur randomly. This novel synthesis method has garnered our attention and practical use. Herein, we observed that the addition of endonuclease significantly enhances the efficiency of the de novo synthesis reaction catalyzed by the DNA polymerase. We further investigated the reaction conditions that influence this efficiency. Building on the optimal reaction conditions, we developed a rapid and efficient strategy for preparing DNA hydrogel. Further, coupled with the CRISPR-Cas system, we developed a nucleic acid signal amplification system characterized by versatility, sensitivity, specificity, and no risk of aerosol contamination. We successfully detected viral nucleic acids in clinical samples. In summary, our study demonstrates the significant potential of DNA polymerase- and endonuclease-catalyzed DNA de novo synthesis in diverse applications.


Assuntos
DNA Polimerase Dirigida por DNA , DNA , Técnicas de Amplificação de Ácido Nucleico , DNA Polimerase Dirigida por DNA/metabolismo , DNA/química , Técnicas de Amplificação de Ácido Nucleico/métodos , Sistemas CRISPR-Cas , Endonucleases/metabolismo , Humanos , Hidrogéis/química
5.
Biochem Biophys Res Commun ; 709: 149830, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38547606

RESUMO

HIV envelope protein gp120 is considered a primary molecular determinant of viral neutralization phenotype due to its critical role in viral entry and immune evasion. The intrinsically disordered regions (IDRs) in gp120 are responsible for their extensive sequence variations and significant structural rearrangements. Despite HIV neutralization phenotype and sequence/structural information of gp120 have been experimentally characterized, there remains a gap in our understanding of the correlation between the viral phenotype and IDRs in gp120. Here, we combined machine learning (ML) techniques and molecular dynamics (MD) simulations to gain data-driven and molecule-mechanism insights into relationships between viral sequence, structure, and phenotypes from the perspective of IDRs in gp120. ML models, trained only on the length and disorder score of IDRs, achieved equivalent performance to the best baseline model using amino acid sequences to discriminate HIV neutralization phenotype, indicating that the lengths or disorder of specific IDRs are strongly related to HIV neutralization phenotypes. Comparative MD analysis reveals that gp120 with extreme neutralization phenotypes in multiple conformational states, especially some IDRs, exhibit significantly distinct structural dynamics, conformational flexibility, and thermodynamic distributions. Taken together, our study provided insights into the role of IDRs in gp120 responding to HIV neutralization phenotypes, which will advance the understanding of molecular mechanisms underlying viral function associated with HIV neutralization phenotype and help develop antiviral vaccines or drugs.


Assuntos
Proteína gp120 do Envelope de HIV , Infecções por HIV , Humanos , Proteína gp120 do Envelope de HIV/genética , Conformação Proteica , Sequência de Aminoácidos , Fenótipo , Testes de Neutralização
6.
Small ; 20(24): e2308276, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38161263

RESUMO

Dielectric polymer composites exhibit great application prospects in advanced pulse power systems and electric systems. However, the decline of breakdown strength by loading of single high dielectric constant nanofiller hinders the sustained increase in energy density of the composites. Here, a sandwich-structured nanocomposite prepared with mica nanosheets as the second filler exhibits decoupled modulation of dielectric constant and breakdown strength. The traditional layered clay mineral mica is exfoliated into nanosheets and filled into polyvinylidene difluoride (PVDF), which shows a special depolarization effect in the polymer matrix. In Kelvin probe microscopy characterization and thermally stimulated depolarization current indicates that the mica nanosheets provided space charge traps for the polymer matrix and effectively suppressed the carrier motion. A sandwich structure composite material with mica nanosheets as the central layer has achieved a high energy density of 11.48 J cm-3, 2.4 times higher than the pure PVDF film. This is due to the fact that randomly oriented distribution of nanosheets in a polymer matrix provide better current blocking. This work provides an effective method to improve the energy density of dielectric polymer composites by synergistically introducing insulating nanosheets and high dielectric constant nanofillers.

7.
Small ; : e2402785, 2024 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-39109945

RESUMO

Aggregation-induced emission (AIE)allows tunable photoluminescence via the simple regulation of molecular aggregation. The research spurt along this vein has also offered tremendous opportunities for light-responsive artificial molecular machines that are to be fully explored for performing versatile functions. Herein, the study reports a light-driven Feringa-type motor, when in the appropriate aggregation state, not only demonstrates the light-activated rotary motion but emits photons with good quantum yield. A semi-quantitative TD-DFT calculation is also conducted to aid the understanding of the competitive photoluminescence and photoisomerization processes of the motor. Cytotoxicity test shows this motor possesses good biocompatibility, laying a solid foundation for applying it in the bio-environment. The results demonstrated that the engagement of the aggregation-induced emission concept and light-driven Feringa-motor can lead to the discovery of the novel motorized AIEgen, which will further stimulate the rise of more advanced molecular motors capable of executing multi-functionalities.

8.
Plant Cell Environ ; 47(9): 3654-3667, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38752443

RESUMO

Bamboo cultivation, particularly Moso bamboo (Phyllostachys edulis), holds significant economic importance in various regions worldwide. Bamboo shoot degradation (BSD) severely affects productivity and economic viability. However, despite its agricultural consequences, the molecular mechanisms underlying BSD remain unclear. Consequently, we explored the dynamic changes of BSD through anatomy, physiology and the transcriptome. Our findings reveal ruptured protoxylem cells, reduced cell wall thickness and the accumulation of sucrose and reactive oxygen species (ROS) during BSD. Transcriptomic analysis underscored the importance of genes related to plant hormone signal transduction, sugar metabolism and ROS homoeostasis in this process. Furthermore, BSD appears to be driven by the coexpression regulatory network of senescence-associated gene transcription factors (SAG-TFs), specifically PeSAG39, PeWRKY22 and PeWRKY75, primarily located in the protoxylem of vascular bundles. Yeast one-hybrid and dual-luciferase assays demonstrated that PeWRKY22 and PeWRKY75 activate PeSAG39 expression by binding to its promoter. This study advanced our understanding of the molecular regulatory mechanisms governing BSD, offering a valuable reference for enhancing Moso bamboo forest productivity.


Assuntos
Regulação da Expressão Gênica de Plantas , Redes Reguladoras de Genes , Proteínas de Plantas , Brotos de Planta , Fatores de Transcrição , Brotos de Planta/metabolismo , Brotos de Planta/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Poaceae/genética , Poaceae/fisiologia , Poaceae/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Senescência Vegetal/genética , Transcriptoma , Parede Celular/metabolismo
9.
Haematologica ; 109(8): 2639-2652, 2024 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-38450513

RESUMO

Mitapivat, a pyruvate kinase activator, shows great potential as a sickle cell disease (SCD)-modifying therapy. The safety and efficacy of mitapivat as a long-term maintenance therapy are currently being evaluated in two open-label studies. Here we applied a comprehensive multi-omics approach to investigate the impact of activating pyruvate kinase on red blood cells (RBC) from 15 SCD patients. HbSS patients were enrolled in one of the open-label, extended studies (NCT04610866). Leukodepleted RBC obtained from fresh whole blood at baseline, prior to drug initiation, and at longitudinal timepoints over the course of the study were processed for multi-omics through a stepwise extraction of metabolites, lipids and proteins. Mitapivat therapy had significant effects on the metabolome, lipidome and proteome of SCD RBC. Mitapivat decreased 2,3-diphosphoglycerate levels, increased adenosine triphosphate levels, and improved hematologic and sickling parameters in patients with SCD. Agreement between omics measurements and clinical measurements confirmed the specificity of mitapivat on targeting late glycolysis, with glycolytic metabolites ranking as the top correlates to parameters of hemoglobin S oxygen affinity (p50) and sickling kinetics (t50) during treatment. Mitapivat markedly reduced levels of proteins of mitochondrial origin within 2 weeks of initiation of treatment, with minimal changes in reticulocyte counts. In the first 6 months of treatment there were also transient elevations of lysophosphatidylcholines and oxylipins with depletion of free fatty acids, suggestive of an effect on membrane lipid remodeling. Multi-omics analysis of RBC identified benefits for glycolysis, as well as activation of the Lands cycle.


Assuntos
Anemia Falciforme , Eritrócitos , Piruvato Quinase , Humanos , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/sangue , Eritrócitos/metabolismo , Piruvato Quinase/metabolismo , Masculino , Feminino , Adulto , Metaboloma , Metabolômica/métodos , Proteoma , Proteômica/métodos , Adolescente , Adulto Jovem , Ativação Enzimática , Glicólise/efeitos dos fármacos , Ativadores de Enzimas/uso terapêutico , Ativadores de Enzimas/farmacologia , Resultado do Tratamento , Multiômica
10.
Chemistry ; 30(42): e202400741, 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-38745544

RESUMO

To address key concerns on solid-state pyrene-based luminescent materials, we propose a novel and efficient mechanical bond strategy. This strategy results in a transformation from ACQ to AIE effect and a remarkable enhancement of pyrene emission in the solid state. Moreover, an unusual purification of emission is also achieved. Through computational calculation and experimental characterisation, finally determined by X-ray diffraction analysis, we prove that the excellent emissions result from mechanical bond induced refinement of molecular arrangements, including reduced π-π stacking, well-ordered packing and enhanced structural stability. This work demonstrates the potential of mechanical bond in the field of organic luminescent molecules, providing a new avenue for developing high-performance organic luminescent materials.

11.
BMC Cancer ; 24(1): 292, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38439022

RESUMO

PANoptosis is a specific type of inflammatory programmed cell death (PCD) modality that can be involved in three key modes of cellular programmed cell death-pyroptosis, apoptosis and necroptosis. We analyzed PANoptosis activity in three common renal cell carcinoma subtypes (Clear cell renal cell carcinoma, Papillary renal cell carcinoma, and Chromophobe renal cell carcinoma) separately and constructed a new PANoptosis immunity index (PANII). In three renal cell carcinomas, we found that PANII was an effective predictor of immunotherapy efficacy in KIRC, KIRP and KICH, and the high PANII group was characterized by high immune infiltration and sensitivity to immunotherapy, while the low PANII group was prone to immune escape and immunotherapy resistance. We performed molecular docking prediction of each core protein comprising PANII and identified natural small molecule compounds with the highest affinity to target proteins. In addition, we found that down-regulation of PYCARD inhibited the proliferation and migration of renal clear cell carcinoma cells by in vitro functional assays, suggesting that PYCARD could be a novel target for renal clear cell carcinoma therapy. Our findings that the PANoptosis characterization-based index (PANII) helps to elucidate the tumor microenvironmental features of three common renal cell carcinoma subtypes and identify patient populations that will benefit from immunotherapy, providing a new tool for the clinical diagnosis and treatment of patients with intermediate- and advanced-stage renal cell carcinoma.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/terapia , Simulação de Acoplamento Molecular , Imunoterapia , Apoptose , Neoplasias Renais/terapia
12.
Gastrointest Endosc ; 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38431107

RESUMO

BACKGROUND & AIMS: Nonampullary duodenal neuroendocrine tumors (NAD-NETs) are rare with limited evidence regarding endoscopic treatment. The study aimed to investigate the efficacy and safety of endoscopic resection of well-differentiated NAD-NETs and evaluate long-term outcomes, including local recurrence and metastasis. METHODS: A total of 78 patients with NAD-NETs who underwent endoscopic resection between January 2011 and August 2022 were included. The clinicopathologic characteristics and treatment outcomes were collected and analyzed. RESULTS: En bloc resection was achieved for 74 of the tumors (94.9%) and R0 resection was obtained in 68 of the tumors (87.2%). Univariate analysis identified tumors in the second part of the duodenum, tumor size ≥ 10 mm and muscularis propria invasion as risk factors for non-curative resection. Two patients with R1 resection (vertical margin involvement) and two patients with lymphovascular invasion underwent additional surgery. Four patients experienced adverse events (5.1%), including two cases of delayed bleeding and two cases of perforation, all successfully managed conservatively. During a median follow-up period of 62.6 months, recurrence and lymph node metastasis were only detected in one patient with R1 resection 3 months after the original procedure. CONCLUSION: Endoscopic resection is safe and effective and provides a favorable long-term outcome for patients with well-differentiated NAD-NETs without regional lymph node or distant metastasis.

13.
Mol Pharm ; 21(7): 3623-3633, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38819959

RESUMO

Inflammation induced by activated macrophages within vulnerable atherosclerotic plaques (VAPs) constitutes a significant risk factor for plaque rupture. Translocator protein (TSPO) is highly expressed in activated macrophages. This study investigated the effectiveness of TSPO radiotracers, 18F-FDPA, in detecting VAPs and quantifying plaque inflammation in rabbits. 18 New Zealand rabbits were divided into 3 groups: sham group A, VAP model group B, and evolocumab treatment group C. 18F-FDPA PET/CTA imaging was performed at 12, 16, and 24 weeks in all groups. Optical coherence tomography (OCT) was performed on the abdominal aorta at 24 weeks. The VAP was defined through OCT images, and ex vivo aorta PET imaging was also performed at 24 weeks. The SUVmax and SUVmean of 18F-FDPA were measured on the target organ, and the target-to-background ratio (TBRmax) was calculated as SUVmax/SUVblood pool. The arterial sections of the isolated abdominal aorta were analyzed by HE staining, CD68 and TSPO immunofluorescence staining, and TSPO Western blot. The results showed that at 24 weeks, the plaque TBRmax of 18F-FDPA in group B was significantly higher than in groups A and C. Immunofluorescence staining of CD68 and TSPO, as well as Western blot, confirmed the increased expression of macrophages and TSPO in the corresponding regions of group B. HE staining revealed an increased presence of the lipid core, multiple foam cells, and inflammatory cell infiltration in the area with high 18F-FDPA uptake. This indicates a correlation between 18F-FDPA uptake, inflammation severity, and VAPs. The TSPO-targeted tracer 18F-FDPA shows specific uptake in macrophage-rich regions of atherosclerotic plaques, making it a valuable tool for assessing inflammation in VAPs.


Assuntos
Inflamação , Placa Aterosclerótica , Tomografia por Emissão de Pósitrons , Animais , Coelhos , Placa Aterosclerótica/diagnóstico por imagem , Placa Aterosclerótica/metabolismo , Inflamação/metabolismo , Inflamação/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Masculino , Macrófagos/metabolismo , Receptores de GABA/metabolismo , Compostos Radiofarmacêuticos/farmacocinética , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/metabolismo , Aorta Abdominal/patologia , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Acetanilidas
14.
J Cardiovasc Pharmacol ; 84(2): 175-187, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547523

RESUMO

ABSTRACT: Sepsis-induced myocardial dysfunction commonly occurs in individuals with sepsis and is a severe complication with high morbidity and mortality rates. This study aimed to investigate the effects and potential mechanisms of the natural steroidal sapogenin ruscogenin (RUS) against lipopolysaccharide (LPS)-induced myocardial injury in septic mice. We found that RUS effectively alleviated myocardial pathological damage, normalized cardiac function, and increased survival in septic mice. RNA sequencing demonstrated that RUS administration significantly inhibited the activation of the NOD-like receptor signaling pathway in the myocardial tissues of septic mice. Subsequent experiments further confirmed that RUS suppressed myocardial inflammation and pyroptosis during sepsis. In addition, cultured HL-1 cardiomyocytes were challenged with LPS, and we observed that RUS could protect these cells against LPS-induced cytotoxicity by suppressing inflammation and pyroptosis. Notably, both the in vivo and in vitro findings indicated that RUS inhibited NOD-like receptor protein-3 (NLRP3) upregulation in cardiomyocytes stimulated with LPS. As expected, knockdown of NLRP3 blocked the LPS-induced activation of inflammation and pyroptosis in HL-1 cells. Furthermore, the cardioprotective effects of RUS on HL-1 cells under LPS stimulation were abolished by the novel NLRP3 agonist BMS-986299. Taken together, our results suggest that RUS can alleviate myocardial injury during sepsis, at least in part by suppressing NLRP3-mediated inflammation and pyroptosis, highlighting the potential of this molecule as a promising candidate for sepsis-induced myocardial dysfunction therapy.


Assuntos
Anti-Inflamatórios , Modelos Animais de Doenças , Lipopolissacarídeos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Sepse , Transdução de Sinais , Espirostanos , Animais , Lipopolissacarídeos/toxicidade , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Espirostanos/farmacologia , Sepse/tratamento farmacológico , Sepse/complicações , Sepse/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Piroptose/efeitos dos fármacos , Masculino , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular , Anti-Inflamatórios/farmacologia , Camundongos , Cardiomiopatias/prevenção & controle , Cardiomiopatias/patologia , Cardiomiopatias/metabolismo , Cardiomiopatias/tratamento farmacológico , Cardiomiopatias/induzido quimicamente , Mediadores da Inflamação/metabolismo
15.
Scand J Gastroenterol ; 59(4): 411-418, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38149430

RESUMO

OBJECTIVES: The presence of intestinal flora in the gut has been linked to migraines in recent studies, but whether the association is causal or due to bias remains to be clarified. We aimed to explore whether there is a potential causal relationship between gut microbiota and migraine risk with this study. MATERIALS AND METHODS: We conducted a two-sample Mendelian randomized analysis study to explore whether gut microbiota has a causal relationship with migraine using publicly available data from large-scale genome-wide association studies. The inverse variance weighting was used as the main method, and weighted median and MR-Egger were used as supplementary methods for causal inference. Sensitivity analyses, including leave-one-out analysis, Cochran Q test, and MR-Egger intercept test, were used to verify the robustness of the results. RESULTS: After rigorous quality control of the results, we identified that genetic predisposition towards a higher abundance of genus.Lactobacillus was causally associated with higher of migraine (IVW OR = 1.10, 95% CI = 1.03 - 1.18, p = .004), whereas the higher abundance of family.Prvotellaceae predicted a decreased risk of migraine (IVW OR = 0.89, 95% CI = 0.80 - 0.98, p = .02). Sensitivity analyses indicated the results were not biased by pleiotropy. CONCLUSION: According to our research, there is evidence showing that gut microbiota may be involved in migraine development, which suggested that a stool examination might be helpful to recognize those with a higher risk of migraine. Further mechanisms remained to be elucidated in future studies.


Assuntos
Microbioma Gastrointestinal , Transtornos de Enxaqueca , Humanos , Microbioma Gastrointestinal/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Predisposição Genética para Doença , Transtornos de Enxaqueca/genética
16.
BMC Gastroenterol ; 24(1): 45, 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38262980

RESUMO

BACKGROUND: Alterations in the intestinal microbiota may play a role in the pathogenesis of functional bowel disorders (FBDs). Probiotics are widely used to improve intestinal dysbacteriosis in FBDs. In the context of FBDs, washed microbiota transplantation (WMT) appear to be a promising therapeutic option. We aimed to compare probiotics with WMT by using a propensity-score matching analysis (PSMA). METHODS: We conducted a retrospective investigation of 103 patients with FBDs, including irritable bowel syndrome (IBS), functional constipation (FC), functional diarrhea (FDr), functional abdominal bloating (FAB). Patients were divided into the WMT group or probiotics group (taking probiotics capsules). Data on the following parameters were matched for PSMA: age; sex; disease course; body mass index; anxiety; insomnia; tobacco smoking; alcohol consumption; and levels of D-lactate, diamine oxidase, and lipopolysaccharide. Intestinal barrier function (IBF) and symptoms were evaluated both before and after treatment initiation. Prognostic factors were assessed by Cox proportional hazards regression analysis. RESULTS: PSMA identified in 34 matched pairs (11 IBS, 12 FC, 7 FDr, and 4 FAB in the probiotics group and 14 IBS, 13 FC, 5 FDr, and 2 FAB in the WMT group. Improvement of FBD symptoms was greater with WMT than probiotics (P = 0.002). The WMT group had significantly fewer patients with intestinal barrier damage than the probiotics group (38.2% vs. 67.6%, P = 0.041). This improvement of FBD with WMT was further reflected as a reduction in D-lactate levels (P = 0.031). Increased D-lactate levels which were identified as a prognostic factor for FBDs (HR = 0.248, 95%CI 0.093-0.666, P = 0.006) in multivariate Cox regression analysis. CONCLUSION: WMT could improve symptoms and IBF in patients with FBDs. Increased D-lactate levels in patients with FBDs may predict a favorable response to WMT treatment.


Assuntos
Gastroenteropatias , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Humanos , Função da Barreira Intestinal , Estudos Retrospectivos , Flatulência , Lactatos
17.
Macromol Rapid Commun ; 45(15): e2400167, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38847293

RESUMO

Structurally well-defined small molecules with lower critical solution temperature (LCST) behavior offer enormous prospects for fine-tuning their phase transition properties to be "on-demand" applied in the specific scene but are still underexplored. Herein, a novel amphiphilic small LCST molecule is rationally designed and synthesized. The molecule, namely TG, features a conjugation of multiple short ethylene glycol (EG) chains with the functional coordinating terpyridine (Tpy) moiety. The molecule TG demonstrates excellent LCST behavior down to 0.05 × 10-3 m in a water solution. And a cloud point Tcp = 30.9 °C with a very short thermal hysteresis ΔT = 0.2 °C and good reversibility can be achieved when c = 0.1 × 10-3 m. The excellent LCST properties of TG have enabled its successful performance as the smart window for solar radiation management with the ∆Tlum, ∆TIR, and ∆Tsol being 83.6%, 49.1%, and 67.2%, respectively. Moreover, the presence of Tpy moiety in TG enables its coordination with Ru3+ and the resulting complex also exhibits modulated LCST behavior with different concentration-dependent Tcp. These studies would provide novel small-molecule-based scaffolds for constructing better solar radiation management systems as well as other thermal-responsive smart materials.


Assuntos
Temperatura , Soluções , Estrutura Molecular , Energia Solar , Luz Solar , Piridinas/química , Rutênio/química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/síntese química , Etilenoglicol/química , Transição de Fase
18.
J Gastroenterol Hepatol ; 39(7): 1352-1357, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38561861

RESUMO

BACKGROUND AND AIM: Endoscopic resection has been successfully used for the removal of digestive submucosal tumors (SMTs). However, the cardia has been considered a challenging location for endoscopic resection due to its narrow lumen and sharp angle. The objective of this study was to establish a clinical scoring model to grade the technical difficulty of endoscopic resection for cardial SMTs. METHODS: A total of 246 patients who suffered cardial SMTs and received endoscopic resection were included in this retrospective study. All of them were randomized into the training cohort (n = 123) or internal validation cohort (n = 123). Potential predictors were analyzed using univariate analysis. Then, covariates with P < 0.05 were selected for the multivariate logistic regression model. The ß coefficients from the logistic regression model were used to create a scoring system for technical difficulty prediction by rounding the score to the nearest integer of the absolute ß coefficient value. RESULTS: The clinical score consisted of the following factors: male gender (2 points), extraluminal growth (3 points), and maximum diameter ≥3 cm (3 points). The scoring model demonstrated good discriminatory power, with an area under the receiver operating characteristic curve of 0.860 and a 95% confidence interval of 0.763-0.958. The model also showed a good goodness of fit in the Hosmer-Lemeshow test (P = 0.979). In the training cohort, the probability of encountering technical difficulty in the easy (score = 0), intermediate (score = 1-3), difficult (score = 4-6), and very difficult (score >6) categories was 0, 6.8%, 33.3%, and 100.0%, respectively; similarly, in the validation cohort, it was 0, 5.6%, 22.2%, and 50.0%, respectively. CONCLUSIONS: This scoring system could serve as a valuable tool for clinicians in predicting the technical difficulty of endoscopic resection for cardial SMTs.


Assuntos
Cárdia , Neoplasias Gástricas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cárdia/cirurgia , Idoso , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Modelos Logísticos , Ressecção Endoscópica de Mucosa/métodos , Fatores Sexuais , Adulto , Valor Preditivo dos Testes
19.
Phys Chem Chem Phys ; 26(13): 10289-10300, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38497927

RESUMO

Constructing Z-scheme heterojunction photocatalysts with high solar-to-hydrogen (STH) efficiency is a practical alternative to produce clean and recyclable hydrogen energy on a large scale. This paper presents the design of stable Z-scheme blue phosphorene (BlueP)/γ-SnS heterostructures with excellent photocatalytic activities by applying strains. The first-principles calculations show that the BlueP/γ-SnS heterobilayer is a type-I heterojunction with an indirect bandgap of 1.41 eV and strong visible-light absorption up to 105 cm-1. Interestingly, biaxial strains (ε) can effectively regulate its bandgap width (semiconductor-metal) and induce the band alignment transition (type-I-type-II). Compressive and tensile strains can significantly enhance the interfacial interaction and visible-light absorption, respectively. More intriguingly, compressive strains can not only modulate the heterojunction types but also make the band edges meet the requirements for overall water splitting. In particular, the Z-scheme (type-I) BlueP/γ-SnS bilayer at -8% (-2%) strain exhibits a relatively high STH efficiency of 18% (17%), and the strained Z-scheme system (-8% ≤ ε ≤ -6%) also exhibits high and anisotropic carrier mobilities (158-2327 cm2 V-1 s-1). These strain-induced outstanding properties make BlueP/γ-SnS heterostructures promising candidates for constructing economically feasible photocatalysts and flexible nanodevices.

20.
Surg Endosc ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39174707

RESUMO

BACKGROUND: Transcolonic endoscopic appendectomy (TEA) is rapidly evolving and has been reported as a minimally invasive alternative to appendectomy. We aimed to characterize the feasibility and safety of a novel unassisted single-channel TEA. METHOD: We retrospectively investigated 23 patients with appendicitis or appendiceal lesions who underwent TEA from February 2016 to December 2022. We collected clinicopathological characteristics, procedure­related parameters, and follow­up data and analyzed the impact of previous abdominal surgery and traction technique. RESULTS: The mean age was 56.0 years. Of the 23 patients with appendiceal lesions, fourteen patients underwent TEA and nine underwent traction-assisted TEA (T-TEA). Eight patients (34.8%) had previous abdominal surgery. The En bloc resection rate was 95.7%. The mean procedure duration was 91.1 ± 45.5 min, and the mean wound closure time was 29.4 ± 18.6 min. The wounds after endoscopic appendectomy were closed with clips (21.7%) or a combination of clip closure and endoloop reinforcement (78.3%), and the median number of clips was 7 (range, 3-15). Three patients (13.0%) experienced major adverse events, including two delayed perforations (laparoscopic surgery) and one infection (salvage endoscopic suture). During a median follow-up of 23 months, no residual or recurrent lesions were observed, and no recurrence of abdominal pain occurred. There were no significant differences between TEA and T-TEA groups and between patients with and without abdominal surgery groups in each factor. CONCLUSION: Unassisted single-channel TEA for patients with appendiceal lesions has favorable short- and long-term outcomes. TEA can safely and effectively treat appendiceal disease in appropriately selected cases.

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