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1.
Nat Immunol ; 25(6): 969-980, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38831104

RESUMO

Rare genetic variants in toll-like receptor 7 (TLR7) are known to cause lupus in humans and mice. UNC93B1 is a transmembrane protein that regulates TLR7 localization into endosomes. In the present study, we identify two new variants in UNC93B1 (T314A, located proximally to the TLR7 transmembrane domain, and V117L) in a cohort of east Asian patients with childhood-onset systemic lupus erythematosus. The V117L variant was associated with increased expression of type I interferons and NF-κB-dependent cytokines in patient plasma and immortalized B cells. THP-1 cells expressing the variant UNC93B1 alleles exhibited exaggerated responses to stimulation of TLR7/-8, but not TLR3 or TLR9, which could be inhibited by targeting the downstream signaling molecules, IRAK1/-4. Heterozygous mice expressing the orthologous Unc93b1V117L variant developed a spontaneous lupus-like disease that was more severe in homozygotes and again hyperresponsive to TLR7 stimulation. Together, this work formally identifies genetic variants in UNC93B1 that can predispose to childhood-onset systemic lupus erythematosus.


Assuntos
Predisposição Genética para Doença , Lúpus Eritematoso Sistêmico , Receptor 7 Toll-Like , Lúpus Eritematoso Sistêmico/genética , Humanos , Animais , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Camundongos , Criança , Feminino , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Masculino , Idade de Início , Variação Genética , NF-kappa B/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Adolescente , Células THP-1 , Interferon Tipo I/metabolismo
3.
Trends Genet ; 38(6): 524-528, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35115176

RESUMO

The etiology and heterogeneity of idiopathic scoliosis (IS) are poorly understood. Studies using scoliotic zebrafish models have indicated a potential link between ciliary defects and scoliosis. They may further explain the onset of IS partially. However, it is necessary to further interpret the link between this progress and clinical medicine.


Assuntos
Escoliose , Peixe-Zebra , Animais , Modelos Animais de Doenças , Escoliose/genética , Coluna Vertebral , Peixe-Zebra/genética , Proteínas de Peixe-Zebra
4.
Nat Mater ; 23(1): 131-138, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37884671

RESUMO

Consecutive mechanical loading cycles cause irreversible fatigue damage and residual strain in gels, affecting their service life and application scope. Hysteresis-free hydrogels within a limited deformation range have been created by various strategies. However, large deformation and high elasticity are inherently contradictory attributes. Here we present a nanoconfined polymerization strategy for producing tough and near-zero-hysteresis gels under a large range of deformations. Gels are prepared through in situ polymerization within nanochannels of covalent organic frameworks or molecular sieves. The nanochannel confinement and strong hydrogen bonding interactions with polymer segments are crucial for achieving rapid self-reinforcement. The rigid nanostructures relieve the stress concentration at the crack tips and prevent crack propagation, enhancing the ultimate fracture strain (17,580 ± 308%), toughness (87.7 ± 2.3 MJ m-3) and crack propagation strain (5,800%) of the gels. This approach provides a general strategy for synthesizing gels that overcome the traditional trade-offs of large deformation and high elasticity.

5.
BMC Biotechnol ; 24(1): 36, 2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38796454

RESUMO

BACKGROUND: To establish a strategy for stem cell-related tissue regeneration therapy, human gingival mesenchymal stem cells (hGMSCs) were loaded with three-dimensional (3D) bioengineered Matrigel matrix scaffolds in high-cell density microtissues to promote local tissue restoration. METHODS: The biological performance and stemness of hGMSCs under 3D culture conditions were investigated by viability and multidirectional differentiation analyses. A Sprague‒Dawley (SD) rat full-thickness buccal mucosa wound model was established, and hGMSCs/Matrigel were injected into the submucosa of the wound. Autologous stem cell proliferation and wound repair in local tissue were assessed by histomorphometry and immunohistochemical staining. RESULTS: Three-dimensional suspension culture can provide a more natural environment for extensions and contacts between hGMSCs, and the viability and adipogenic differentiation capacity of hGMSCs were significantly enhanced. An animal study showed that hGMSCs/Matrigel significantly accelerated soft tissue repair by promoting autologous stem cell proliferation and enhancing the generation of collagen fibers in local tissue. CONCLUSION: Three-dimensional cell culture with hydrogel scaffolds, such as Matrigel, can effectively improve the biological function and maintain the stemness of stem cells. The therapeutic efficacy of hGMSCs/Matrigel was confirmed, as these cells could effectively stimulate soft tissue repair to promote the healing process by activating the host microenvironment and autologous stem cells.


Assuntos
Colágeno , Combinação de Medicamentos , Laminina , Células-Tronco Mesenquimais , Proteoglicanas , Ratos Sprague-Dawley , Alicerces Teciduais , Cicatrização , Animais , Laminina/química , Proteoglicanas/química , Colágeno/química , Humanos , Ratos , Células-Tronco Mesenquimais/citologia , Alicerces Teciduais/química , Diferenciação Celular , Proliferação de Células , Gengiva/citologia , Técnicas de Cultura de Células em Três Dimensões/métodos , Células Cultivadas , Engenharia Tecidual/métodos , Masculino , Mucosa Bucal/citologia
6.
Am J Physiol Regul Integr Comp Physiol ; 326(6): R567-R577, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38646812

RESUMO

Postexercise reduction in blood pressure, termed postexercise hypotension (PEH), is relevant for both acute and chronic health reasons and potentially for peripheral cardiovascular adaptations. We investigated the interactive effects of exercise intensity and recovery postures (seated, supine, and standing) on PEH. Thirteen normotensive men underwent a V̇o2max test on a cycle ergometer and five exhaustive constant load trials to determine critical power (CP) and the gas exchange threshold (GET). Subsequently, work-matched exercise trials were performed at two discrete exercise intensities (10% > CP and 10% < GET), with 1 h of recovery in each of the three postures. For both exercise intensities, standing posture resulted in a more substantial PEH (all P < 0.01). For both standing and seated recovery postures, the higher exercise intensity led to larger reductions in systolic [standing: -33 (11) vs. -21 (8) mmHg; seated: -34 (32) vs. -17 (37) mmHg, P < 0.01], diastolic [standing: -18 (7) vs. -8 (5) mmHg; seated: -10 (10) vs. -1 (4) mmHg, P < 0.01], and mean arterial pressures [-13 (8) vs. -2 (4) mmHg, P < 0.01], whereas in the supine recovery posture, the reduction in diastolic [-9 (9) vs. -4 (3) mmHg, P = 0.08) and mean arterial pressures [-7 (5) vs. -3 (4) mmHg, P = 0.06] was not consistently affected by prior exercise intensity. PEH is more pronounced during recovery from exercise performed above CP versus below GET. However, the effect of exercise intensity on PEH is largely abolished when recovery is performed in the supine posture.NEW & NOTEWORTHY The magnitude of postexercise hypotension is greater following the intensity above the critical power in a standing position.


Assuntos
Pressão Sanguínea , Exercício Físico , Hipotensão Pós-Exercício , Postura , Humanos , Masculino , Exercício Físico/fisiologia , Adulto , Pressão Sanguínea/fisiologia , Postura/fisiologia , Hipotensão Pós-Exercício/fisiopatologia , Adulto Jovem , Decúbito Dorsal , Recuperação de Função Fisiológica , Posição Ortostática , Postura Sentada , Hipotensão/fisiopatologia , Consumo de Oxigênio
7.
Ann Surg Oncol ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39164605

RESUMO

BACKGROUND: The risk of cardiac disease mortality has recently become a focal point of concern within the medical community for patients with prostate cancer (PCa). Given that radical prostatectomy (RP) and external beam radiation therapy (EBRT) are the main treatment modalities for localized PCa, their specific impact on cardiovascular-specific mortality (CSM) remains unclear. This study explored the specific effects of RP and EBRT on CSM risk to guide clinical treatment decisions. METHODS: Data from patients aged 45-74 years, who were diagnosed with T1-2N0M0 stage PCa from the SEER database (2010-2015), were used. Multivariate statistical methods, including propensity score matching (PSM), competing risk regression, COX regression analysis, and Fine-Gray testing, were applied to assess the impact of RP and EBRT on CSM risk. RESULTS: Among 146,082 T1-2 stage PCa patients, cardiac disease emerged as the primary cause of death, surpassing PCa itself. Multifactorial COX regression and competing risk regression analyses indicated that local treatments do not increase CSM risk. Further analysis revealed a significant increase in CSM risk for patients undergoing only EBRT compared with those undergoing only RP (hazard ratio [HR] = 2.71, 95% confidence interval [CI] 1.96-3.74, P < 0.001), with subsequent PSM adjustment, further confirming a significantly reduced risk in the RP treatment group (HR 0.23, 95% CI 0.13-0.40, P < 0.001). CONCLUSIONS: T1-2 stage PCa patients face a significant risk of CSM, with RP offering a potential advantage over EBRT in reducing this risk. These findings encourage clinicians to comprehensively consider the potential impact on cardiac health when formulating treatment plans, providing crucial guidance for optimizing treatment strategies.

8.
Conserv Biol ; 38(4): e14264, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38563105

RESUMO

Antarctica terrestrial ecosystems are facing the most threats from global climate change, which is altering plant composition greatly. These transformations may cause major reshuffling of soil community composition, including functional traits and diversity, and therefore affect ecosystem processes in Antarctica. We used high-throughput sequencing analysis to investigate soil nematodes under 3 dominant plant functional groups (lichens, mosses, and vascular plants) and bare ground in the Antarctic region. We calculated functional diversity of nematodes based on their diet, life histories, and body mass with kernel density n-dimensional hypervolumes. We also calculated taxonomic and functional beta diversity of the nematode communities based on Jaccard dissimilarity. The presence of plants had no significant effect on the taxonomic richness of nematodes but significantly increased nematode functional richness. The presence of plants also significantly decreased taxonomic beta diversity (homogenization). Only mosses and vascular plants decreased nematode functional beta diversity, which was mostly due to a decreased effect of the richness difference component. The presence of plants also increased the effect of deterministic processes potentially because environmental filtering created conditions favorable to nematodes at low trophic levels with short life histories and small body size. Increasing plant cover in the Antarctic due to climate change may lead to increased diversity of nematode species that can use the scarce resources and nematode taxonomic and functional homogenization. In a future under climate change, community restructuring in the region is possible.


Efectos de la posición taxonómica de las plantas sobre las comunidades de nemátodos del suelo en la Antártida Resumen Los ecosistemas terrestres de la Antártida enfrentan las mayores amenazas del cambio climático global, que está alterando gravemente la composición de plantas. Estas transformaciones pueden provocar una reorganización importante de la composición de la comunidad del suelo, incluyendo atributos y diversidad funcionales, y por lo tanto afectar los procesos ecosistémicos en la Antártida. Utilizamos análisis de secuenciación de alto rendimiento para investigar nemátodos del suelo debajo de tres grupos funcionales de plantas dominantes (líquenes, musgos y plantas vasculares) y de suelo desnudo en la región de la Antártida. Calculamos la diversidad funcional de nemátodos con base en su dieta, historia de vida y masa corporal mediante hipervolúmenes n­dimensionales de densidad del núcleo. También calculamos la diversidad beta taxonómica y funcional de las comunidades de nemátodos con base en la disimilitud de Jacard. La presencia de plantas no tuvo efecto significativo sobre la riqueza taxonómica de nemátodos, pero incrementó su riqueza funcional significativamente. La presencia de plantas también disminuyó la diversidad beta taxonómica (homogenización) significativamente. Solo musgos y plantas vasculares disminuyeron la diversidad beta funcional de nemátodos, lo cual se debió principalmente a un menor efecto del componente de diferencia de riqueza. La presencia de plantas también incrementó el efecto de los procesos determinísticos posiblemente porque el filtrado ambiental creó condiciones favorables para los nemátodos de niveles tróficos inferiores con historias de vida corta y tamaño corporal pequeño. El incremento de la cobertura de plantas en la Antártida debido al cambio climático puede conducir a una mayor diversidad de especies de nemátodos que pueden utilizar los escasos recursos y a la homogenización taxonómica y funcional de los nemátodos. En un futuro bajo el cambio climático, es posible la reestructuración comunitaria en la región.


Assuntos
Biodiversidade , Nematoides , Plantas , Solo , Animais , Regiões Antárticas , Nematoides/fisiologia , Plantas/classificação
9.
Acta Pharmacol Sin ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39198663

RESUMO

The transcription factor STAT3 is a promising target for the treatment of non-small cell lung cancer (NSCLC). STAT3 activity is mainly dependent on phosphorylation at tyrosine 705 (pSTAT3-Y705), but the modulation on pSTAT3-Y705 is elusive. By screening a library of deubiquitinases (Dubs), we found that the Otub1 increases STAT3 transcriptional activity. As a Dub, Otub1 binds to pSTAT3-Y705 and specifically abolishes its K48-linked ubiquitination, therefore preventing its degradation and promoting NSCLC cell survival. The Otub1/pSTAT3-Y705 axis could be a potential target for the treatment of NSCLC. To explore this concept, we screen libraries of FDA-approved drugs and natural products based on STAT3-recognition element-driven luciferase assay, from which crizotinib is found to block pSTAT3-Y705 deubiquitination and promotes its degradation. Different from its known action to induce ALK positive NSCLC cell apoptosis, crizotinib suppresses ALK-intact NSCLC cell proliferation and colony formation but not apoptosis. Furthermore, crizotinib also suppresses NSCLC xenograft growth in mice. Taken together, these findings identify Otub1 as the first deubiquitinase of pSTAT3-Y705 and provide that the Otub1/pSTAT3-Y705 axis is a promising target for the treatment of NSCLC.

10.
J Craniofac Surg ; 35(5): 1438-1443, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38838360

RESUMO

There is a current lack of bibliometric analysis in facial bone aging and relevant fields. By providing clear and intuitive references, predictions, and guidance for future research, this study aims to fill the gap in the current field, summarize the related research, and guide the researchers' future work. Literature data were retrieved from the Web of Science Core Collection database. Results Analysis and Citation Report of Web of Science, and CiteSpace software were used to optimize the visualization results, including publication characteristics, disciplines, journals, literature, countries/regions, institutions, authors, research focuses, etc. A total of 277 publications were included after manual screening, and the overall trend of annual publications and citations was increasing. On the basis of the analysis, the characteristics of facial bone aging, aging of facial soft tissue, and facial rejuvenation have been the focuses of research in this field. As stem cell research advances and researchers, deepen their comprehension of facial bone aging, basic scientific research on facial bones has witnessed a growing trend.


Assuntos
Envelhecimento , Bibliometria , Ossos Faciais , Rejuvenescimento , Humanos , Envelhecimento/fisiologia
11.
J Craniofac Surg ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830018

RESUMO

There is currently a lack of scientific bibliometric analyses in the field of Pierre Robin sequence (PRS). Pierre Robin sequence is known for its clinical triad of micrognathia, glossoptosis, airway obstruction, and possible secondary cleft palate. These defects can lead to upper airway obstruction, sleep apnea, feeding difficulties, affect an individual's growth and development, education level, and in severe cases can be life-threatening. Through analysis of literature retrieved from the Web of Science Core Collection (WoSCC) database using Results Analysis and Citation Report and Citespace software, 933 original articles and reviews were included after manual screening. The overall trend for the number of annual publications and citations was increasing. On the basis of the analysis, airway evaluation and treatment, mandibular distraction osteogenesis (MDO), as well as descriptions of PRS characteristics have been the focus of research in this field. In addition, with advances in new technologies such as gene sequencing and expanding understanding of diseases among researchers, research on genetics and etiology related to PRS has become a growing trend.

12.
Molecules ; 29(13)2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38998974

RESUMO

Considering the high evolutionary rate and great harmfulness of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is imperative to develop new pharmacological antagonists. Human angiotensin-converting enzyme-2 (ACE2) functions as a primary receptor for the spike protein (S protein) of SARS-CoV-2. Thus, a novel functional peptide, KYPAY (K5), with a boomerang structure, was developed to inhibit the interaction between ACE2 and the S protein by attaching to the ACE2 ligand-binding domain (LBD). The inhibition property of K5 was evaluated via molecular simulations, cell experiments, and adsorption kinetics analysis. The molecular simulations showed that K5 had a high affinity for ACE2 but a low affinity for the cell membrane. The umbrella sampling (US) simulations revealed a significant enhancement in the binding potential of this functional peptide to ACE2. The fluorescence microscopy and cytotoxicity experiments showed that K5 effectively prevented the interaction between ACE2 and the S protein without causing any noticeable harm to cells. Further flow cytometry research indicated that K5 successfully hindered the interaction between ACE2 and the S protein, resulting in 78% inhibition at a concentration of 100 µM. This work offers an innovative perspective on the development of functional peptides for the prevention and therapy of SARS-CoV-2.


Assuntos
Enzima de Conversão de Angiotensina 2 , Peptídeos , Ligação Proteica , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , Humanos , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/metabolismo , Peptídeos/química , Peptídeos/farmacologia , Simulação de Dinâmica Molecular , COVID-19/virologia , COVID-19/metabolismo , Tratamento Farmacológico da COVID-19 , Antivirais/química , Antivirais/farmacologia , Cinética
13.
Angew Chem Int Ed Engl ; 63(1): e202316375, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-37997003

RESUMO

Service life and range of polymer materials is heavily reliant on their elasticity and mechanical stability under long-term loading. Slippage of chain segments under load leads to significant hysteresis of the hydrogels, limiting its repeatability and mechanical stability. Achieving the desired elasticity exceeding that of rubber is a great challenge for hydrogels, particularly when subjected to large deformations. Here, low-hysteresis and high-toughness hydrogels were developed through controllable interactions of porous cationic polymers (PCPs) with adjustable counteranions, including reversible bonding of PCP frameworks/polymer segments (polyacrylamide, PAAm) and counteranions/PAAm. This strategy reduces chain segment slippage under load, endowing the PCP-based hydrogels (PCP-gels) with good elasticity under large deformations (7 % hysteresis at a strain ratio of 40). Furthermore, due to the enlarged chain segments entanglement by PCP, the PCP-gels exhibit large strain (13000 %), significantly enhanced toughness (68 MJ m-3 ), high fracture energy (43.1 kJ m-2 ), and fatigue resistance. The unique properties of these elastic PCP-gels have promising applications in the field of flexible sensors.

14.
J Neurosci ; 42(4): 532-551, 2022 01 26.
Artigo em Inglês | MEDLINE | ID: mdl-34848499

RESUMO

Mutations in some cell adhesion molecules (CAMs) cause abnormal synapse formation and maturation, and serve as one of the potential mechanisms of autism spectrum disorders (ASDs). Recently, DSCAM (Down syndrome cell adhesion molecule) was found to be a high-risk gene for autism. However, it is still unclear how DSCAM contributes to ASD. Here, we show that DSCAM expression was downregulated following synapse maturation, and that DSCAM deficiency caused accelerated dendritic spine maturation during early postnatal development. Mechanistically, the extracellular domain of DSCAM interacts with neuroligin1 (NLGN1) to block the NLGN1-neurexin1ß (NRXN1ß) interaction. DSCAM extracellular domain was able to rescue spine overmaturation in DSCAM knockdown neurons. Precocious spines in DSCAM-deficient mice showed increased glutamatergic transmission in the developing cortex and induced autism-like behaviors, such as social novelty deficits and repetitive behaviors. Thus, DSCAM might be a repressor that prevents premature spine maturation and excessive glutamatergic transmission, and its deficiency could lead to autism-like behaviors. Our study provides new insight into the potential pathophysiological mechanisms of ASDs.SIGNIFICANCE STATEMENTDSCAM is not only associated with Down syndrome but is also a strong autism risk gene based on large-scale sequencing analysis. However, it remains unknown exactly how DSCAM contributes to autism. In mice, either neuron- and astrocyte-specific or pyramidal neuron-specific DSCAM deficiencies resulted in autism-like behaviors and enhanced spatial memory. In addition, DSCAM knockout or knockdown in pyramidal neurons led to increased dendritic spine maturation. Mechanistically, the extracellular domain of DSCAM binds to NLGN1 and inhibits NLGN1-NRXN1ß interaction, which can rescue abnormal spine maturation induced by DSCAM deficiency. Our research demonstrates that DSCAM negatively modulates spine maturation, and that DSCAM deficiency leads to excessive spine maturation and autism-like behaviors, thus providing new insight into a potential pathophysiological mechanism of autism.


Assuntos
Transtorno do Espectro Autista/metabolismo , Moléculas de Adesão Celular/deficiência , Espinhas Dendríticas/metabolismo , Neurogênese/fisiologia , Córtex Somatossensorial/metabolismo , Animais , Transtorno do Espectro Autista/genética , Transtorno do Espectro Autista/patologia , Células COS , Moléculas de Adesão Celular/genética , Células Cultivadas , Chlorocebus aethiops , Espinhas Dendríticas/patologia , Células HEK293 , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Córtex Somatossensorial/patologia
15.
Hum Mol Genet ; 30(17): 1579-1590, 2021 08 12.
Artigo em Inglês | MEDLINE | ID: mdl-33987657

RESUMO

Duchenne muscular dystrophy (DMD) is an X-linked neuromuscular disease characterized by progressive wasting of skeletal muscles. The neuromuscular junction (NMJ) is a synapse between motor neurons and skeletal muscle fibers, critical for the control of muscle contraction. The NMJ decline is observed in DMD patients, but the mechanism is unclear. LRP4 serves as a receptor for agrin, a proteoglycan secreted by motor neurons to induce NMJ, and plays a critical role in NMJ formation and maintenance. Interestingly, we found that protein levels of LRP4 were reduced both in muscles of the DMD patients and DMD model mdx mice. We explored whether increasing LRP4 is beneficial for DMD and crossed muscle-specific LRP4 transgenic mice with mdx mice (mdx; HSA-LRP4). The LRP4 transgene increased muscle strength, together with improved neuromuscular transmission in mdx mice. Furthermore, we found the LRP4 expression mitigated NMJ fragments and denervation in mdx mice. Mechanically, we showed that overexpression of LRP4 increased the activity of MuSK and expression of dystrophin-associated glycoprotein complex proteins in the mdx mice. Overall, our findings suggest that increasing LRP4 improves both function and structure of NMJ in the mdx mice and Agrin signaling might serve as a new therapeutic strategy in DMD.


Assuntos
Proteínas Relacionadas a Receptor de LDL/metabolismo , Distrofia Muscular de Duchenne/genética , Animais , Autoanticorpos/genética , Autoanticorpos/metabolismo , China , Modelos Animais de Doenças , Distrofina/metabolismo , Humanos , Proteínas Relacionadas a Receptor de LDL/genética , Camundongos , Camundongos Endogâmicos mdx , Camundongos Transgênicos , Contração Muscular , Fibras Musculares Esqueléticas/metabolismo , Força Muscular , Músculo Esquelético/metabolismo , Distrofia Muscular de Duchenne/metabolismo , Junção Neuromuscular/metabolismo , Regeneração , Transmissão Sináptica
16.
J Transl Med ; 21(1): 80, 2023 02 04.
Artigo em Inglês | MEDLINE | ID: mdl-36739412

RESUMO

BACKGROUND: The treatment of gastric cancer remains a challenge. METHODS: We divided gastric cancer into three subtypes based on 14 cancer functional states. We investigated differences between subtypes through multi-omics data, especially at the single-cell level, which allowed us to analyze differences from the perspective of each type of cell rather than the whole. RESULTS: The cluster 1 is characterized by high levels of tumor progression-related cancer functional status, worst survival outcomes, low metabolic level, high infiltration of immunosuppressive cells, high copy number variations (CNV), and low tumor mutational burden (TMB). The cluster 2 is characterized by low levels of tumor progression-related cancer functional status, favorable prognosis, moderate metabolic level, low immune cell infiltration, high CNV, and moderate TMB. Then, the cluster 3 is characterized by the high level of all cancer functional status, high metabolic level, low CNV, high TMB, high infiltration of immune cells with high cytotoxicity, and better response to immunotherapy. We also established a prognostic model based on cancer functional status and validated its robustness. CONCLUSIONS: Collectively, our study identified gastric cancer subtypes and provided new insights into the clinical treatment of gastric cancer.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Variações do Número de Cópias de DNA/genética , Imunossupressores , Imunoterapia , Multiômica , Prognóstico , Microambiente Tumoral
17.
BMC Microbiol ; 23(1): 8, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-36627563

RESUMO

BACKGROUND: Verticillium wilt, caused by the fungus Verticillium dahliae, leads to significant losses in cotton yield worldwide. Biocontrol management is a promising means of suppressing verticillium wilt. The purpose of the study was to obtain and analyze endophytic bacteria with Verticillium wilt-resistant activities from the roots of Gossypium barbadense 'Xinhai15' and to explore the interactions between the soil and plants. RESULTS: An endophytic bacterium Bacillus sp. T6 was obtained from the Verticillium wilt-resistant cotton G. barbadense 'Xinhai15', which showed significant antagonistic abilities against cotton Verticillium wilt. The bioassay results indicated that the strain possessed strong antagonistic abilities that inhibited V. dahliae spore germination and mycelial growth without contact, and thus it was speculated that the active factor of the bacteria might be volatile compounds. A total of 46 volatile substances were detected via headspace solid-phase microextraction and gas chromatography-mass spectrometry analysis. The pure product verification experiment confirmed that the styrene produced by the T6 strain was the main virulence factor. Transcriptome analysis showed that following styrene induction, 247 genes in V. dahliae, including four hydrolase genes, eight dehydrogenase genes, 11 reductase genes, 17 genes related to transport and transfer were upregulated. Additionally, 72 genes, including two chitinase genes, two protease genes, five transport-related genes, and 33 hypothetical protein genes, were downregulated. The quantitative real-time PCR results confirmed that the expression of the four genes VDAG_02838, VDAG_09554, VDAG_045572, and VDAG_08251 was increased by 3.18, 78.83, 2.71, and 2.92 times, respectively, compared with the uninduced control group. CONCLUSIONS: The research provides a new reference for the development and application of the volatile compounds of endophytic bacteria as new biocontrol agents for the control of Verticillium wilt and as biological preservatives for agricultural products.


Assuntos
Bacillus , Verticillium , Verticillium/metabolismo , Gossypium/microbiologia , Bacillus/genética , Bactérias , Estirenos/metabolismo , Doenças das Plantas/microbiologia
18.
Environ Res ; 235: 116694, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37467939

RESUMO

Climate projections foresee intense precipitation and long-term drought events is increasing with consequent rapid changes in surface water bodies in a short period. In areas with drastic hydrological changes, achieving accurate and rapid mapping of these phenomena in combination with hydrologic variability characteristics is a key of effective emergency management and disaster risk reduction plans. This study presents an automatic method for mapping drought and flood hazards, particularly in regions with significant hydrological changes. We use Sentinel-1/2 and Landsat data to extract surface water and classify permanent and seasonal water bodies in historical periods, which serve as the basis for identifying flood or drought areas. The water extraction method combines index-based analysis for optical data and the region-Otsu method for radar data, ensuring accurate identification of water. The effectiveness of this approach is demonstrated through comparisons with existing products in Poyang Lake (China), the Po River Plain (Italy), and the Indus River Plain (Pakistan). Findings show a high similarity between the two, and our results can provide more specific details. Our method is particularly well-suited for areas with fluctuating hydrological conditions, can also map quickly without optical data. By effectively identifying areas affected by drought and flood hazards while mitigating errors from natural hydrological dynamics, this methodology contributes valuable insights to enhance emergency management and disaster risk reduction plans.


Assuntos
Inundações , Água , Rios , Lagos , China
19.
Clin Oral Investig ; 27(9): 4973-4985, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37417986

RESUMO

OBJECTIVE: The purpose of this study was to analyze three-dimensional dental compensation in patients with different types of skeletal Class III malocclusion with mandibular asymmetry, using cone-beam computed tomography (CBCT) and three-dimensional reconstruction measurement technology, thereby providing clinical guidance and reference for combined orthodontic and orthognathic treatment. METHODS: 81 patients with skeletal Class III malocclusion with mandibular asymmetry were selected in accordance with the inclusion criteria. According to a new classification method based on the direction and amount of menton deviation relative to ramus deviation, patients were divided into three groups called Type 1, Type 2, and Type 3. In Type 1, the direction of menton deviation was consistent with that of ramus deviation and the amount of menton deviation was greater than that of ramus deviation. In Type 2, the direction of menton deviation was consistent with that of ramus deviation and the amount of menton deviation was smaller than that of ramus deviation. In Type 3, the direction of menton deviation was inconsistent with that of ramus deviation. The maxillary occlusal plane (OP), anterior occlusal plane (AOP), and posterior occlusal plane (POP) were measured on reconstructed CBCT images. The vertical, transverse, and anteroposterior distances from maxillary teeth to reference planes and the 3D angles between the long axis of these teeth and reference planes were measured. These dental variables measured from the deviated and non-deviated sides were compared within each group, as well as among each other. RESULTS: Of the 81 patients with asymmetrical Class III malocclusion, 52 patients were categorized in Type 1, 12 patients in Type 2, and 17 patients in Type 3. There were significant differences between deviated and non-deviated sides in Type 1 and Type 3 (p < 0.05). In Type 1, the vertical distances of maxillary teeth on the deviated side were lower than those on the non-deviated side, and AOP, OP, and POP on the deviated side were larger than those on the non-deviated side (p < 0.05). In Type 3, the vertical distances of the maxillary teeth on the deviated side were lower (p < 0.05), and the AOP and OP on the deviated side were larger than those on the non-deviated side. In all three groups, the transverse distances of the maxillary teeth from the mid-sagittal plane on the deviated side were larger than those on the non-deviated side (p < 0.05), and the angles between the long axis of maxillary teeth and the mid-sagittal plane on the deviated side were larger, respectively (p < 0.05). CONCLUSIONS: The maxillary teeth on the deviated side were observed to have smaller eruption heights in Type 1 and Type 3. In Type 1, AOP, POP, and OP were greater on the deviated side, while in Type 3, only AOP and OP were greater on the deviated side. The maxillary teeth of patients in all three groups on the deviated side were buccal and buccally inclined. Larger sample observations are still needed to further verify these findings.


Assuntos
Má Oclusão Classe III de Angle , Má Oclusão , Humanos , Estudos Transversais , Assimetria Facial/diagnóstico por imagem , Cefalometria/métodos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Mandíbula/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Imageamento Tridimensional/métodos
20.
J Craniofac Surg ; 34(8): 2291-2296, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37477192

RESUMO

There is a current lack of scientific bibliometric analyses in craniofacial microsomia (CFM) and relevant fields. Craniofacial microsomia is a congenital disease resulting from a series of structural malformations involving the first and second branchial arches. Craniofacial microsomia and related fields have attracted the attention of clinicians and interested researchers worldwide. This study summarizes the research status and focuses to help researchers fully grasp the current research situation of CFM and relevant fields in the past three decades and drive future research into new publications. Literature data were retrieved from the Web of Science Core Collection database. Results Analysis and Citation Report of Web of Science, and CiteSpace software were used to evaluate and visualize the results, including publication characteristics, disciplines, journals, literature, countries/regions, institutions, authors, research focuses, etc. A total of 949 original articles and reviews were included after manual screening, and the overall trend of the number of annual publications and citations was increasing. According to the analysis, the description of the clinical characteristics of CFM, the classification of CFM, and mandibular distraction osteogenesis have always been the focus of research in this field. Besides, with the continuous progress of new technologies such as gene sequencing and the expansion of researchers' understanding of diseases, research on genetics and etiology related to CFM has been a developing trend.


Assuntos
Síndrome de Goldenhar , Humanos , Mandíbula , Bibliometria , Região Branquial , Bases de Dados Factuais
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