RESUMO
Studies have identified genes and molecular pathways regulating cancer metastasis. However, it remains largely unknown whether metastatic potentials of cancer cells from different lineage types are driven by the same or different gene networks. Here, we aim to address this question through integrative analyses of 493 human cancer cells' transcriptomic profiles and their metastatic potentials in vivo. Using an unsupervised approach and considering both gene coexpression and protein-protein interaction networks, we identify different gene networks associated with various biological pathways (i.e. inflammation, cell cycle, and RNA translation), the expression of which are correlated with metastatic potentials across subsets of lineage types. By developing a regularized random forest regression model, we show that the combination of the gene module features expressed in the native cancer cells can predict their metastatic potentials with an overall Pearson correlation coefficient of 0.90. By analyzing transcriptomic profile data from cancer patients, we show that these networks are conserved in vivo and contribute to cancer aggressiveness. The intrinsic expression levels of these networks are correlated with drug sensitivity. Altogether, our study provides novel comparative insights into cancer cells' intrinsic gene networks mediating metastatic potentials across different lineage types, and our results can potentially be useful for designing personalized treatments for metastatic cancers.
Assuntos
Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Metástase Neoplásica , Neoplasias , Humanos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/metabolismo , Mapas de Interação de Proteínas/genética , Transcriptoma , Perfilação da Expressão Gênica , Linhagem da Célula/genéticaRESUMO
Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.
Assuntos
Antifúngicos , Candida albicans , Chalconas , Glicólise , Fosfopiruvato Hidratase , Candida albicans/efeitos dos fármacos , Fosfopiruvato Hidratase/metabolismo , Fosfopiruvato Hidratase/antagonistas & inibidores , Fosfopiruvato Hidratase/genética , Antifúngicos/farmacologia , Antifúngicos/química , Chalconas/farmacologia , Chalconas/química , Glicólise/efeitos dos fármacos , Camundongos , Animais , Humanos , Candidíase/tratamento farmacológico , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/antagonistas & inibidores , Testes de Sensibilidade Microbiana , Proteínas de Ligação a DNA , Biomarcadores Tumorais , Proteínas Supressoras de TumorRESUMO
An approach for continuous tuning of on-chip optical delay with a microring resonator is proposed and demonstrated. By introducing an electro-optically tunable waveguide coupler, the bus waveguide to the resonance coupling can be effectively tuned from the under-coupling regime to the over-coupling regime. The optical delay is experimentally characterized by measuring the relative phase shift between lasers and shows a large dynamic range of delay from -600 to 600 ps and an efficient tuning of delay from -430 to -180 ps and from 40 to 240 ps by only a 5 V voltage.
RESUMO
3'-end cleavage and polyadenylation is an essential process for eukaryotic mRNA maturation. In yeast species, the polyadenylation signals that recruit the processing machinery are degenerate and remain poorly characterized compared with the well-defined regulatory elements in mammals. Here we address this issue by developing deep learning models to deconvolute degenerate cis-regulatory elements and quantify their positional importance in mediating yeast poly(A) site formation, cleavage heterogeneity, and strength. In S. cerevisiae, cleavage heterogeneity is promoted by the depletion of U-rich elements around poly(A) sites as well as multiple occurrences of upstream UA-rich elements. Sites with high cleavage heterogeneity show overall lower strength. The site strength and tandem site distances modulate alternative polyadenylation (APA) under the diauxic stress. Finally, we develop a deep learning model to reveal the distinct motif configuration of S. pombe poly(A) sites, which show more precise cleavage than S. cerevisiae Altogether, our deep learning models provide unprecedented insights into poly(A) site formation of yeast species, and our results highlight divergent poly(A) signals across distantly related species.
RESUMO
BACKGROUND: Volumetric modulated arc therapy (VMAT) is a novel form of IMRT, which can deliver more accurate dose distribution and shorten treatment time. Compared to MRI-guided adaptive brachytherapy, which is recommended as gold standard imaging for cervical cancer contours, CT-guided adaptive brachytherapy (CTGAB) is more available, more widespread, and more affordable in many centers. This study aims to retrospectively analyze the efficacy and the safety of VMAT combined with CTGAB for patients with locally advanced cervical cancer. METHODS AND MATERIALS: This study retrospectively analyzed 102 patients with locally advanced cervical cancer who underwent VMAT and CTGAB. Clinical outcomes including local control (LC), overall survival (OS) and progression-free survival (PFS), tumor response to treatment evaluated by the Response Evaluation Criteria in Solid Tumors (RECIST) (version 1.1), and toxicities including gastrointestinal toxicity, urinary toxicity and hematologic toxicity evaluated by the Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) were analyzed. The Kaplan-Meier method was used to calculate LC, OS, and PFS. RESULTS: Median follow-up time was 19 months. Complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) occurred in 68 (66.7%), 24 (23.5%), 4 (3.92%), and 6 (5.88%), respectively. The 2-year and 3-year OS were 89.6% and 83%, respectively. The 2-year and 3-year PFS were 84.2% and 74.3%, respectively. The 2-year and 3-year LC were 90.1% and 79.3%, respectively. The average cumulative D2cm3 in the rectum, the bladder, the colon, and the small intestine were 78.07 (SD: 0.46) Gy, 93.20 (SD: 0.63) Gy, 63.55 (SD: 1.03) Gy and 61.07 (SD: 0.75) Gy, respectively. The average cumulative D90% of the high-risk clinical target volume (HR-CTV) was 92.26 (SD: 0.35) Gy. Grade ≥ 3 gastrointestinal and urinary toxicities occurred in 4.9% and 0.98%, respectively. 1.96% of patients were observed grade ≥ 4 gastrointestinal toxicities and none of the patients observed grade ≥ 4 urinary toxicities. CONCLUSION: VMAT combined with CTGAB for locally advanced cervical cancer was an effective and safe treatment method, which showed satisfactory LC, OS, PFS, and acceptable toxicities.
Assuntos
Braquiterapia , Radioterapia Guiada por Imagem , Radioterapia de Intensidade Modulada , Tomografia Computadorizada por Raios X , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/diagnóstico por imagem , Neoplasias do Colo do Útero/mortalidade , Radioterapia de Intensidade Modulada/métodos , Radioterapia de Intensidade Modulada/efeitos adversos , Braquiterapia/métodos , Braquiterapia/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Idoso , Radioterapia Guiada por Imagem/métodos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Idoso de 80 Anos ou mais , Taxa de SobrevidaRESUMO
Adaptation to hypoxia is a major challenge for the survival of Mycobacterium tuberculosis (Mtb) in vivo. Interferon (IFN)-γ-producing CD8+ T cells contribute to control of Mtb infection, in part by promoting antimicrobial activities of macrophages. Whether Mtb counters these responses, particularly during hypoxic conditions, remains unknown. Using metabolomic, proteomic and genetic approaches, here we show that Mtb induced Rv0884c (SerC), an Mtb phosphoserine aminotransferase, to produce D-serine. This activity increased Mtb pathogenesis in mice but did not directly affect intramacrophage Mtb survival. Instead, D-serine inhibited IFN-γ production by CD8+ T cells, which indirectly reduced the ability of macrophages to restrict Mtb upon co-culture. Mechanistically, D-serine interacted with WDR24 and inhibited mTORC1 activation in CD8+ T cells. This decreased T-bet expression and reduced IFN-γ production by CD8+ T cells. Our findings suggest an Mtb evasion mechanism where pathogen metabolic adaptation to hypoxia leads to amino acid-dependent suppression of adaptive anti-TB immunity.
Assuntos
Linfócitos T CD8-Positivos , Interferon gama , Macrófagos , Mycobacterium tuberculosis , Serina , Tuberculose , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Mycobacterium tuberculosis/imunologia , Camundongos , Serina/metabolismo , Interferon gama/metabolismo , Interferon gama/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/microbiologia , Tuberculose/imunologia , Tuberculose/microbiologia , Camundongos Endogâmicos C57BL , Transaminases/metabolismo , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Hipóxia/imunologia , Hipóxia/metabolismo , Feminino , Interações Hospedeiro-Patógeno/imunologiaRESUMO
An experimental validation of a robotic system for radioactive iodine-125 seed implantation (RISI) in tumor treatment was conducted using customized phantom models and animal models simulating liver and lung lesions. The robotic system, consisting of planning, navigation, and implantation modules, was employed to implant dummy radioactive seeds into the models. Fiducial markers were used for target localization. In phantom experiments across 40 cases, the mean errors between planned and actual seed positions were 0.98 ± 1.05 mm, 1.14 ± 0.62 mm, and 0.90 ± 1.05 mm in the x, y, and z directions, respectively. The x, y, and z directions correspond to the left-right, anterior-posterior, and superior-inferior anatomical planes. Silicone phantoms exhibiting significantly smaller x-axis errors compared to liver and lung phantoms (p < 0.05). Template assistance significantly reduced errors in all axes (p < 0.05). No significant dosimetric deviations were observed in parameters such as D90, V100, and V150 between plans and post-implant doses (p > 0.05). In animal experiments across 23 liver and lung cases, the mean implantation errors were 1.28 ± 0.77 mm, 1.66 ± 0.69 mm, and 1.86 ± 0.93 mm in the x, y, and z directions, slightly higher than in phantoms (p < 0.05), with no significant differences between liver and lung models. The dosimetric results closely matched planned values, confirming the accuracy of the robotic system for RISI, offering new possibilities in clinical tumor treatment.
Assuntos
Radioisótopos do Iodo , Neoplasias Pulmonares , Imagens de Fantasmas , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Robóticos/métodos , Procedimentos Cirúrgicos Robóticos/instrumentação , Radioisótopos do Iodo/uso terapêutico , Animais , Neoplasias Pulmonares/radioterapia , Braquiterapia/métodos , Braquiterapia/instrumentação , Neoplasias Hepáticas/radioterapia , Humanos , Marcadores FiduciaisRESUMO
Background: This study assessed clinical outcomes of three-dimensional-printed template (3DPT)-guided radioactive seed brachytherapy (RSBT) via a submental approach for recurrent base of tongue and floor of mouth cancer. Methods: Thirty-one patients with recurrent lingual and floor of mouth squamous cell carcinoma after surgery and radiotherapy were treated with 3DPT-guided RSBT from 2015 to 2022. Seeds were implanted through a submental approach guided by 3DPTs. Local control (LC), overall survival (OS), disease control (DC) and quality of life (QOL) were evaluated. Results: The median follow-up was 13.7 months. The 1-, 3- and 5-year LC rates were 66.1%, 66.1%, and 55.1% respectively. The 1-, 3- and 5-year OS rates were 63.4%, 33.4%, and 8.3%. The 1-, 3- and 5-year DC rates were 37.8%, 26.5%, and 21.2%. Univariate analysis showed tumor size significantly affected LC (P = 0.031). The presence of extraterritorial lesions affected DC and OS on multivariate analysis (P < 0.01). QOL improved significantly in domains of pain, swallowing, chewing, taste, and emotion after treatment compared to baseline. Four patients (13%) developed necrosis and osteoradionecrosis. Conclusions: 3DPT-guided submental RSBT provided favorable LC and QOL for recurrent tongue/floor of mouth cancer with minimal toxicity; moreover, severe toxicity should be noted.
RESUMO
Antimicrobial peptides (AMPs), ancient scavengers of bacteria, are very poorly induced in macrophages infected by Mycobacterium tuberculosis (M. tuberculosis), but the underlying mechanism remains unknown. Here, we report that L-alanine interacts with PRSS1 and unfreezes the inhibitory effect of PRSS1 on the activation of NF-κB pathway to induce the expression of AMPs, but mycobacterial alanine dehydrogenase (Ald) Rv2780 hydrolyzes L-alanine and reduces the level of L-alanine in macrophages, thereby suppressing the expression of AMPs to facilitate survival of mycobacteria. Mechanistically, PRSS1 associates with TAK1 and disruptes the formation of TAK1/TAB1 complex to inhibit TAK1-mediated activation of NF-κB pathway, but interaction of L-alanine with PRSS1, disables PRSS1-mediated impairment on TAK1/TAB1 complex formation, thereby triggering the activation of NF-κB pathway to induce expression of AMPs. Moreover, deletion of antimicrobial peptide gene ß-defensin 4 (Defb4) impairs the virulence by Rv2780 during infection in mice. Both L-alanine and the Rv2780 inhibitor, GWP-042, exhibits excellent inhibitory activity against M. tuberculosis infection in vivo. Our findings identify a previously unrecognized mechanism that M. tuberculosis uses its own alanine dehydrogenase to suppress host immunity, and provide insights relevant to the development of effective immunomodulators that target M. tuberculosis.
Assuntos
Alanina , Peptídeos Antimicrobianos , Macrófagos , Mycobacterium tuberculosis , NF-kappa B , Tuberculose , Mycobacterium tuberculosis/patogenicidade , Mycobacterium tuberculosis/metabolismo , Animais , Camundongos , NF-kappa B/metabolismo , Humanos , Macrófagos/microbiologia , Macrófagos/metabolismo , Macrófagos/imunologia , Alanina/metabolismo , Peptídeos Antimicrobianos/metabolismo , Peptídeos Antimicrobianos/genética , Tuberculose/microbiologia , Tuberculose/imunologia , Alanina Desidrogenase/metabolismo , Alanina Desidrogenase/genética , MAP Quinase Quinase Quinases/metabolismo , MAP Quinase Quinase Quinases/genética , Proteínas de Bactérias/metabolismo , Proteínas de Bactérias/genética , Transdução de Sinais , Camundongos Endogâmicos C57BL , Células RAW 264.7 , FemininoRESUMO
PURPOSE: This study aimed to investigate the impact of tumor size on survival in early-onset colon and rectal cancer. METHODS: Early-onset colon and rectal cancer patients were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. Tumor size was analyzed as both continuous and categorical variables. Several statistical techniques, including restricted cubic spline (RCS), Cox proportional hazard model, subgroup analysis, propensity score matching (PSM), and Kaplan-Meier survival analysis, were employed to demonstrate the association between tumor size and overall survival (OS) and cancer-specific survival (CSS) of early-onset colon and rectal cancer. RESULTS: Seventeen thousand five hundred fifty-one (76.7%) early-onset colon and 5323 (23.3%) rectal cancer patients were included. RCS analysis confirmed a linear association between tumor size and survival. Patients with a tumor size > 5 cm had worse OS and CSS, compared to those with a tumor size ≤ 5 cm for both early-onset colon and rectal cancer. Notably, subgroup analysis showed that a smaller tumor size (≤ 50 mm) was associated with worse survival in stage II early-onset colon cancer, although not statistically significant. After PSM, Kaplan-Meier survival curves showed that the survival of patients with tumor size ≤ 50 mm was better than that of patients with tumor size > 50 mm. CONCLUSION: Patients with tumors larger than 5 cm were associated with worse survival in early-onset colon and rectal cancer. However, smaller tumor size may indicate a more biologically aggressive phenotype, correlating with poorer survival in stage II early-onset colon cancer.
Assuntos
Idade de Início , Neoplasias do Colo , Neoplasias Retais , Carga Tumoral , Humanos , Masculino , Feminino , Neoplasias Retais/patologia , Neoplasias Retais/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto , Estimativa de Kaplan-Meier , Programa de SEER , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , IdosoRESUMO
Lignocellulose biorefinery depended on effective pretreatment strategies is of great significance for solving the current global crisis of ecosystem and energy security. This study proposes a novel approach combining seawater hydrothermal pretreatment (SHP) and microwave-assisted deep eutectic solvent (MD) pretreatment to achieve an effective fractionation of Pinus massoniana into high value-added products. The results indicated that complex ions (Mg2+, Ca2+, and Cl-) in natural seawater served as Lewis acids and dramatically promoted the depolymerization of mannose and xylan into oligosaccharides with 40.17 % and 75.43 % yields, respectively. Subsequent MD treatment realized a rapid and effective lignin fractionation (~90 %) while retaining cellulose. As a result, the integrated pretreatment yielded ~85 % of enzymatic glucose, indicating an eightfold increase compared with untreated pine. Because of the increased hydrophobicity induced by the formation of acyl groups during MD treatment, uniform lignin nanospheres were successfully recovered from the DES. It exhibited low dispersibility (PDI = 2.23), small molecular weight (1889 g/mol), and excellent oxidation resistance (RSI = 5.94), demonstrating promising applications in functional materials. The mechanism of lignin depolymerization was comprehensively elucidated via FTIR, 2D-HSQC NMR, and GPC analyses. Overall, this study provides a novel and environmentally friendly strategy for lignocellulose biorefinery and lignin valorization.
Assuntos
Solventes Eutéticos Profundos , Lignina , Nanosferas , Pinus , Água do Mar , Lignina/química , Pinus/química , Solventes Eutéticos Profundos/química , Água do Mar/química , Nanosferas/química , Açúcares/química , Fermentação , Micro-OndasRESUMO
Studies have revealed dozens of functional peptides in putative 'noncoding' regions and raised the question of how many proteins are encoded by noncanonical open reading frames (ORFs). Here, we comprehensively annotate genome-wide translated ORFs across five eukaryotes (human, mouse, zebrafish, worm, and yeast) by analyzing ribosome profiling data. We develop a logistic regression model named PepScore based on ORF features (expected length, encoded domain, and conservation) to calculate the probability that the encoded peptide is stable in humans. Systematic ectopic expression validates PepScore and shows that stable complex-associating microproteins can be encoded in 5'/3' untranslated regions and overlapping coding regions of mRNAs besides annotated noncoding RNAs. Stable noncanonical proteins follow conventional rules and localize to different subcellular compartments. Inhibition of proteasomal/lysosomal degradation pathways can stabilize some peptides especially those with moderate PepScores, but cannot rescue the expression of short ones with low PepScores suggesting they are directly degraded by cellular proteases. The majority of human noncanonical peptides with high PepScores show longer lengths but low conservation across species/mammals, and hundreds contain trait-associated genetic variants. Our study presents a statistical framework to identify stable noncanonical peptides in the genome and provides a valuable resource for functional characterization of noncanonical translation during development and disease.
Assuntos
Perfil de Ribossomos , Ribossomos , Humanos , Animais , Camundongos , Ribossomos/genética , Ribossomos/metabolismo , Fases de Leitura Aberta/genética , Peixe-Zebra/genética , Peptídeos/genética , Peptídeos/metabolismo , Mamíferos/genéticaRESUMO
On-chip acousto-optic modulators that operate at an optical wavelength of 780 nm and a microwave frequency of 6.835 GHz are proposed. The modulators are based on a lithium-niobate-on-sapphire platform and efficiently excite surface acoustic waves and exhibit strong interactions with tightly confined optical modes in waveguides. In particular, a high-efficiency phase modulator and single-sideband mode converter are designed. We found that for both microwave and optical wavelengths below 1 µm, the interactions at the cross-sections of photonic waveguides are sensitive to the waveguide width and are significantly different from those in previous studies. Our designed devices have small footprints and high efficiencies, making them suitable for controlling rubidium atoms and realizing hybrid photonic-atomic chips. Furthermore, our devices have the potential to extend the acousto-optic modulators to other visible wavelengths for other atom transitions and for visible light applications, including imaging and sensing.
RESUMO
This study presents a novel approach using polyol-based proliposome to produce marine phospholipids nanoliposomes. Proliposomes were formulated by blending glycerol with phospholipids across varying mass ratios (2:1 to 1:10) at room temperature. Analysis employing polarized light microscopy, FTIR, and DSC revealed that glycerol disrupted the stacked acyl groups within phospholipids, lowering the phase transition temperature (Tm). Krill oil phospholipids (KOP) proliposomes exhibited superior performance in nanoliposomes formation, with a mean diameter of 125.60 ± 3.97 nm, attributed to the decreased Tm (-7.64 and 7.00 °C) compared to soybean phospholipids, along with a correspondingly higher absolute zeta potential (-39.77 ± 1.18 mV). The resulting KOP proliposomes demonstrated liposomes formation stability over six months and under various environmental stresses (dilution, thermal, ionic strength, pH), coupled with in vitro absorption exceeding 90 %. This investigation elucidates the mechanism behind glycerol-formulated proliposomes and proposes innovative strategies for scalable, solvent-free nanoliposome production with implications for functional foods and pharmaceutical applications.
Assuntos
Glicerol , Lipossomos , Nanopartículas , Fosfolipídeos , Lipossomos/química , Glicerol/química , Fosfolipídeos/química , Animais , Nanopartículas/química , Tamanho da Partícula , Euphausiacea/químicaRESUMO
Nitrogen (N) is one of the most important nutrients for crop plant performance, however, the excessive application of nitrogenous fertilizers in agriculture significantly increases production costs and causes severe environmental problems. Therefore, comprehensively understanding the molecular mechanisms of N-use efficiency (NUE) with the aim of developing new crop varieties that combine high yields with improved NUE is an urgent goal for achieving more sustainable agriculture. Plant NUE is a complex trait that is affected by multiple factors, of which hormones are known to play pivotal roles. In this review, we focus on the interaction between the biosynthesis and signaling pathways of plant hormones with N metabolism, and summarize recent studies on the interplay between hormones and N, including how N regulates multiple hormone biosynthesis, transport and signaling and how hormones modulate root system architecture (RSA) in response to external N sources. Finally, we explore potential strategies for promoting crop NUE by modulating hormone synthesis, transport and signaling. This provides insights for future breeding of N-efficient crop varieties and the advancement of sustainable agriculture.
Assuntos
Nitrogênio , Plantas , Nitrogênio/metabolismo , Plantas/metabolismo , Agricultura , Transdução de Sinais , Fertilizantes , Hormônios/metabolismoRESUMO
Regardless of the underlying etiology, renal fibrosis is the final histological outcome of progressive kidney disease. Unilateral ureteral obstruction (UUO) is an ideal and reproducible experimental rodent model of renal fibrosis, which is characterized by tubulointerstitial inflammatory responses, accumulation of extracellular matrix, tubular dilatation and atrophy, and fibrosis. The magnitude of UUO-induced renal fibrosis is experimentally manipulated by the species chosen, animal age, and the severity and duration of the obstruction, while relief of the obstruction allows the animal to recover from fibrosis. The pathogenesis of renal fibrosis is complex and multifactorial and is orchestrated by activation of renin-angiotensin system (RAS), oxidative stress, inflammatory response, transforming growth factor beta 1-Smad pathway, activated myofibroblasts, cell death (apoptosis, autophagy, ferroptosis, and necroptosis), destruction of intracellular organelles, and signaling pathway. The current therapeutic approaches have limited efficacy. Inhibition of RAS and use of antioxidants and antidiabetic drugs, such as inhibitors of sodium-glucose cotransporter 2 and dipeptidyl peptidase-4, have recently gained attention as therapeutic strategies to prevent renal scarring. This literature review highlights the state of the art regarding the molecular mechanisms relevant to the management of renal fibrosis caused by UUO.
RESUMO
BACKGROUND AND PURPOSE: Vertebrobasilar dolichoectasia aneurysm is a rare type of cerebrovascular disorder with a poor natural history, and endovascular treatment is widely accepted. Whether a high-profile braided stent (flow diverter) could promote occlusion of vertebrobasilar dolichoectasia aneurysm without increasing the complications rather than a low-profile braided stent remains uncertain. The aim of the study was to present a single-center experience of the safety and efficacy of a low-profile braided stent versus a flow diverter in treating patients with vertebrobasilar dolichoectasia aneurysms. MATERIALS AND METHODS: The retrospective review was conducted on a total of 432 consecutive patients diagnosed with posterior circulation aneurysms who underwent endovascular treatment in our center from August 2013 to December 2021. Among these patients, 47 individuals with vertebrobasilar dolichoectasia aneurysms who were treated with low-profile braided stents or flow diverters were included. Vertebrobasilar dolichoectasia aneurysms involving only the vertebral artery were excluded. Patients were divided into 2 groups: the low-profile braided stent group and the flow diverter group based on the device used. Safety and efficacy outcomes were subsequently analyzed. RESULTS: There were 25 total patients enrolled in low-profile braided stent group and 22 patients in flow diverter group. The safety of low-profile braided stents and flow diverters in the treatment of vertebrobasilar dolichoectasia aneurysms was evaluated by clinical outcome, a new neurologic deficit due to procedural complications, and neurologic death. The rates of good clinical outcome were similar between the 2 groups (low-profile braided stent, 56%, versus flow diverter, 59.1%; P = .831), and the rates of neurologic death were also similar (low-profile braided stent, 12%, versus flow diverter, 9.1%; P = .747). Higher rates of new neurologic deficits due to procedural complications were observed in the flow diverter group, but the difference was not significant (low-profile braided stent, 24%, versus flow diverter, 40.9%; P = .215). The efficacy was evaluated by angiographic occlusion of vertebrobasilar dolichoectasia aneurysms and progression of mass effect resulting from these aneurysms. Significantly higher rates of complete occlusion of vertebrobasilar dolichoectasia aneurysms were shown in the flow diverter group (41.2%; P = .028) than in the low-profile braided stent group (10%). CONCLUSIONS: Both low-profile braided stents and flow diverters have similar high risks in reconstructive techniques in the treatment of vertebrobasilar dolichoectasia aneurysms, while a flow diverter is more effective in promoting complete occlusion of vertebrobasilar dolichoectasia aneurysm than a low-profile braided stent. A flow diverter may be a better alternative for carefully selected patients with vertebrobasilar dolichoectasia aneurysms.
Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Insuficiência Vertebrobasilar , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Seguimentos , Resultado do Tratamento , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Stents , Insuficiência Vertebrobasilar/complicações , Insuficiência Vertebrobasilar/diagnóstico por imagem , Insuficiência Vertebrobasilar/cirurgia , Estudos RetrospectivosRESUMO
Soil microbes play vital roles in estuarine wetlands. Understanding the soil bacterial community structure and function profiles is essential to reveal the ecological functions of microbes in estuarine wetlands. Herein, soil samples were collected from Liao River estuarine wetland, Northeast China, along the river to the estuarine mouth, and soil bacterial communities were explored. Results showed that soil physiochemical properties, bacterial community structure and functions exhibited distinct variations influenced by geographical location. Bacterial phyla in soils were dominated by Proteobacteria and Bacteroidetes, while Gillisia and Woeseia were the predominant genera. Soil pH, electrical conductivity and nitrogen-related nutrients were the important factors affecting bacterial community structure. Based on PICRUSt prediction, the genes related to metabolism of nitrogen, sulfur and methane showed spatial distribution patterns, and the abundances of most biomarker genes increased as the distance from estuarine mouth extended. These findings could enrich the understanding of soil microbiome in estuarine wetlands.
Assuntos
Solo , Áreas Alagadas , Solo/química , Rios , Bactérias/genética , China , Nitrogênio , Microbiologia do SoloRESUMO
Botulinum toxin type A (BTXA) has the potential to treat androgenetic alopecia (AGA); however, its impact on the apoptosis of dermal papillary cells (DPCs) is not yet fully understood. Noncoding RNAs play a crucial role in AGA. In this study, we investigated the potential mechanism by which BTXA alleviates apoptosis induced by dihydrotestosterone (DHT) in DPCs. We assessed the mRNA levels of circ_0135062, miR-506-3p, and Bax using qRT-PCR. Binding interactions were analyzed using RNA pulldown and dual-luciferase assays. Cell viability was determined using a cell counting kit-8 assay, and cell apoptosis was assessed using flow cytometry, TUNEL assays, and western blotting. Our findings revealed that BTXA inhibited the apoptosis of DPCs treated with DHT. Moreover, circ_0135062 overexpression counteracted the protective effect of BTXA on DHT-treated DPCs. MiR-506-3p was found to interact with Bax and inhibit apoptosis in DPCs by suppressing Bax expression in response to DHT-induced damage. Furthermore, circ_0135062 acted as a sponge for miR-506-3p, thereby inhibiting the targeting of Bax expression by miR-506-3p. In conclusion, BTXA exhibited an antiapoptotic effect on DHT-induced DPC injury via the circ_0135062/miR-506-3p/Bax axis.Level of Evidence II This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
RESUMO
In this study, a combination of microcosmic and chemical analysis methods was used to investigate deep eutectic solvent (DES) pretreatment effects on cell wall's micromorphology and lignin's dissolution regular, in order to achieve high-performance biorefinery. The atomic force microscope observed that DES pretreatment peeled off non-cellulose components to reduced "anti-degradation barrier", resulting to improve the enzymatic saccharification from 12.36 % to 90.56 %. In addition, DES pretreatment can break the ß-O-4 bond between the lignin units resulting in a decline in molecular weight from 3187 g/mol to 1112 g/mol (0-6 h). However, long pretreatment time resulted regenerated lignin samples repolymerization. Finally, DES has good recoverability which showed saccharification still can reach 51.51 % at 6 h following four recycling rounds and regenerated lignin also had a typical and well-preserved structure. In general, this work offers important information for industrial biorefinery technologies and lignin valorization.