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1.
Cell ; 185(10): 1646-1660.e18, 2022 05 12.
Artigo em Inglês | MEDLINE | ID: mdl-35447073

RESUMO

Incomplete lineage sorting (ILS) makes ancestral genetic polymorphisms persist during rapid speciation events, inducing incongruences between gene trees and species trees. ILS has complicated phylogenetic inference in many lineages, including hominids. However, we lack empirical evidence that ILS leads to incongruent phenotypic variation. Here, we performed phylogenomic analyses to show that the South American monito del monte is the sister lineage of all Australian marsupials, although over 31% of its genome is closer to the Diprotodontia than to other Australian groups due to ILS during ancient radiation. Pervasive conflicting phylogenetic signals across the whole genome are consistent with some of the morphological variation among extant marsupials. We detected hundreds of genes that experienced stochastic fixation during ILS, encoding the same amino acids in non-sister species. Using functional experiments, we confirm how ILS may have directly contributed to hemiplasy in morphological traits that were established during rapid marsupial speciation ca. 60 mya.


Assuntos
Marsupiais , Animais , Austrália , Evolução Molecular , Especiação Genética , Genoma , Marsupiais/genética , Fenótipo , Filogenia
2.
Nat Rev Mol Cell Biol ; 25(5): 359-378, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38182846

RESUMO

A growing class of small RNAs, known as tRNA-derived RNAs (tdRs), tRNA-derived small RNAs or tRNA-derived fragments, have long been considered mere intermediates of tRNA degradation. These small RNAs have recently been implicated in an evolutionarily conserved repertoire of biological processes. In this Review, we discuss the biogenesis and molecular functions of tdRs in mammals, including tdR-mediated gene regulation in cell metabolism, immune responses, transgenerational inheritance, development and cancer. We also discuss the accumulation of tRNA-derived stress-induced RNAs as a distinct adaptive cellular response to pathophysiological conditions. Furthermore, we highlight new conceptual advances linking RNA modifications with tdR activities and discuss challenges in studying tdR biology in health and disease.


Assuntos
RNA de Transferência , Animais , RNA de Transferência/metabolismo , RNA de Transferência/genética , Humanos , Neoplasias/genética , Neoplasias/metabolismo , Regulação da Expressão Gênica , Pequeno RNA não Traduzido/genética , Pequeno RNA não Traduzido/metabolismo
3.
Genome Res ; 34(1): 20-33, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38190638

RESUMO

As an essential part of the central nervous system, white matter coordinates communications between different brain regions and is related to a wide range of neurodegenerative and neuropsychiatric disorders. Previous genome-wide association studies (GWASs) have uncovered loci associated with white matter microstructure. However, GWASs suffer from limited reproducibility and difficulties in detecting multi-single-nucleotide polymorphism (multi-SNP) and epistatic effects. In this study, we adopt the concept of supervariants, a combination of alleles in multiple loci, to account for potential multi-SNP effects. We perform supervariant identification and validation to identify loci associated with 22 white matter fractional anisotropy phenotypes derived from diffusion tensor imaging. To increase reproducibility, we use United Kingdom (UK) Biobank White British (n = 30,842) data for discovery and internal validation, and UK Biobank White but non-British (n = 1927) data, Europeans from the Adolescent Brain Cognitive Development study (n = 4399) data, and Europeans from the Human Connectome Project (n = 319) data for external validation. We identify 23 novel loci on the discovery set that have not been reported in the previous GWASs on white matter microstructure. Among them, three supervariants on genomic regions 5q35.1, 8p21.2, and 19q13.32 have P-values lower than 0.05 in the meta-analysis of the three independent validation data sets. These supervariants contain genetic variants located in genes that have been related to brain structures, cognitive functions, and neuropsychiatric diseases. Our findings provide a better understanding of the genetic architecture underlying white matter microstructure.


Assuntos
Substância Branca , Humanos , Adolescente , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão , Estudo de Associação Genômica Ampla , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem
4.
EMBO J ; 41(6): e108544, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-34850409

RESUMO

Since numerous RNAs and RBPs prevalently localize to active chromatin regions, many RNA-binding proteins (RBPs) may be potential transcriptional regulators. RBPs are generally thought to regulate transcription via noncoding RNAs. Here, we describe a distinct, dual mechanism of transcriptional regulation by the previously uncharacterized tRNA-modifying enzyme, hTrmt13. On one hand, hTrmt13 acts in the cytoplasm to catalyze 2'-O-methylation of tRNAs, thus regulating translation in a manner depending on its tRNA-modification activity. On the other hand, nucleus-localized hTrmt13 directly binds DNA as a transcriptional co-activator of key epithelial-mesenchymal transition factors, thereby promoting cell migration independent of tRNA-modification activity. These dual functions of hTrmt13 are mutually exclusive, as it can bind either DNA or tRNA through its CHHC zinc finger domain. Finally, we find that hTrmt13 expression is tightly associated with poor prognosis and survival in diverse cancer patients. Our discovery of the noncatalytic roles of an RNA-modifying enzyme provides a new perspective for understanding epitranscriptomic regulation.


Assuntos
RNA de Transferência , tRNA Metiltransferases , Humanos , Metilação , RNA/metabolismo , Processamento Pós-Transcricional do RNA , RNA de Transferência/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , tRNA Metiltransferases/genética , tRNA Metiltransferases/metabolismo
5.
Small ; 20(26): e2310970, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38243848

RESUMO

Hypergolicity is a highly desired characteristic for hybrid rocket engine-based fuels because it eliminates the need for a separate ignition system. Introducing hypergolic additives into conventional fuels through physical mixing is a feasible approach, but achieving highly reliable hypergolic ignition and energy release remains a major challenge. Here, the construction of core-shell Al@metal organic framework (MOF) heterostructures is reported as high-performance solid hypergolic propellants. Upon contact with the liquid oxidizer the uniformly distributed hypergolic MOF (Ag-MOF) shell can induce the ignition of hypergolic-inert fuel Al, resulting in Al combustion. Such a synthetic strategy is demonstrated to be favorable in hotspot generation and heat transfer relative to a simple physical mixture of Al/Ag-MOF, thus producing shorter ignition delay times and more efficient combustion. Thermal reactivity study indicated that the functionalization of the Ag-MOF shell changes the energy release process of the inner Al, which is accompanied by a thermite reaction. The synergistic effect of implantation of hypergolic MOF and high energy Al contributes to high specific impulses of 230-270 s over a wide range of oxidizer-to-fuel ratios.

6.
Small ; 20(5): e2304452, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37752683

RESUMO

Carbon-based hole transport layer-free perovskite solar cells (PSCs) based on methylammonium lead triiodide (MAPbI3 ) have become one of the research focus due to low cost, easy preparation, and good optoelectronic properties. However, instability of perovskite under vacancy defects and stress-strain makes it difficult to achieve high-efficiency and stable power output. Here, a soft-structured long-chain 2D pentanamine iodide (abbreviated as "PI") is used to improve perovskite quality and interfacial mechanical compatibility. PI containing CH3 (CH2 )4 NH3 + and I- ions not only passivate defects at grain boundaries, but also effectively alleviate residual stress during high temperature annealing via decreasing Young's modulus of perovskite film. Most importantly, PI effectively increases matching degree of Young's modulus between MAPbI3 (47.1 GPa) and carbon (6.7 GPa), and strengthens adhesive fracture energy (Gc ) between perovskite and carbon, which is helpful for outward release of nascent interfacial stress generated under service conditions. Consequently, photoelectric conversion efficiency (PCE) of optimal device is enhanced from 10.85% to 13.76% and operational stability is also significantly improved. 83.1% output is maintained after aging for 720 h at room temperature and 25-60% relative humidity (RH). This strategy of regulation from chemistry and physics provides a strategy for efficient and stable carbon-based PSCs.

7.
Plant Biotechnol J ; 22(4): 1017-1032, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38012865

RESUMO

Maize is one of the most important crops for food, cattle feed and energy production. However, maize is frequently attacked by various pathogens and pests, which pose a significant threat to maize yield and quality. Identification of quantitative trait loci and genes for resistance to pests will provide the basis for resistance breeding in maize. Here, a ß-glucosidase ZmBGLU17 was identified as a resistance gene against Pythium aphanidermatum, one of the causal agents of corn stalk rot, by genome-wide association analysis. Genetic analysis showed that both structural variations at the promoter and a single nucleotide polymorphism at the fifth intron distinguish the two ZmBGLU17 alleles. The causative polymorphism near the GT-AG splice site activates cryptic alternative splicing and intron retention of ZmBGLU17 mRNA, leading to the downregulation of functional ZmBGLU17 transcripts. ZmBGLU17 localizes in both the extracellular matrix and vacuole and contribute to the accumulation of two defence metabolites lignin and DIMBOA. Silencing of ZmBGLU17 reduces maize resistance against P. aphanidermatum, while overexpression significantly enhances resistance of maize against both the oomycete pathogen P. aphanidermatum and the Asian corn borer Ostrinia furnacalis. Notably, ZmBGLU17 overexpression lines exhibited normal growth and yield phenotype in the field. Taken together, our findings reveal that the apoplastic and vacuolar localized ZmBGLU17 confers resistance to both pathogens and insect pests in maize without a yield penalty, by fine-tuning the accumulation of lignin and DIMBOA.


Assuntos
Zea mays , beta-Glucosidase , Animais , Bovinos , Zea mays/genética , Zea mays/química , beta-Glucosidase/genética , Estudo de Associação Genômica Ampla , Lignina , Melhoramento Vegetal , Insetos
8.
J Transl Med ; 22(1): 316, 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38549133

RESUMO

BACKGROUND: Propofol is a widely used anesthetic and sedative, which has been reported to exert an anti-inflammatory effect. TLR4 plays a critical role in coordinating the immuno-inflammatory response during sepsis. Whether propofol can act as an immunomodulator through regulating TLR4 is still unclear. Given its potential as a sepsis therapy, we investigated the mechanisms underlying the immunomodulatory activity of propofol. METHODS: The effects of propofol on TLR4 and Rab5a (a master regulator involved in intracellular trafficking of immune factors) were investigated in macrophage (from Rab5a-/- and WT mice) following treatment with lipopolysaccharide (LPS) or cecal ligation and puncture (CLP) in vitro and in vivo, and peripheral blood monocyte from sepsis patients and healthy volunteers. RESULTS: We showed that propofol reduced membrane TLR4 expression on macrophages in vitro and in vivo. Rab5a participated in TLR4 intracellular trafficking and both Rab5a expression and the interaction between Rab5a and TLR4 were inhibited by propofol. We also showed Rab5a upregulation in peripheral blood monocytes of septic patients, accompanied by increased TLR4 expression on the cell surface. Propofol downregulated the expression of Rab5a and TLR4 in these cells. CONCLUSIONS: We demonstrated that Rab5a regulates intracellular trafficking of TLR4 and that propofol reduces membrane TLR4 expression on macrophages by targeting Rab5a. Our study not only reveals a novel mechanism for the immunomodulatory effect of propofol but also indicates that Rab5a may be a potential therapeutic target against sepsis.


Assuntos
Propofol , Sepse , Camundongos , Humanos , Animais , Propofol/farmacologia , Propofol/uso terapêutico , Propofol/metabolismo , Receptor 4 Toll-Like/metabolismo , Modelos Animais de Doenças , Macrófagos/metabolismo , Sepse/complicações , Lipopolissacarídeos/farmacologia , Lipopolissacarídeos/metabolismo
9.
Opt Express ; 32(3): 2959-2971, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38297531

RESUMO

The diffuse attenuation coefficient (Kd) is known to be closely related to the light transmittance of sea ice, which plays a critical role in the energy balance and biological processes of the upper ocean. However, the commercial instruments cannot easily measure Kd in sea ice because sea ice is a solid. The authors of this study are developing an instrument with a high spectral solution to measure the irradiance profile of sea ice and the irradiance in the atmosphere. Three Kd experiments were carried out, including two in-situ experiments in the Liaodong Bay and one in the laboratory. The results showed that the Kd of the sea ice varied with depth, and the values in adjacent sea ice layers differed by up to 2 times. In addition, due to changes in the climate environment, the Kd of sea ice showed temporal variations. For example, there was a 1.38-fold difference in the Kd values of the surface layer of sea ice at different times in 2022. The values in different sea ice layers also showed different trends over time, and the coefficient of determination (R2) of Kd between adjacent layers over time was as low as 0.008. To explain the driving mechanism of spatio-temporal variability of Kd, an additional experiment focusing on the physical microstructure of sea ice was conducted in Liaodong Bay in 2022. The result shows that the change in air bubbles in the sea ice may be the main the reason for the change in Kd. For example, when the sea ice was exchanging brine and bubbles with the atmosphere above and the seawater below, the highly absorbent particles in it tend to remain in their original position. Considering that the total absorption coefficient changed slightly, the bubbles with the characteristic of intense scattering were found to be the main factor influencing the Kd changes. This conclusion is supported by the fact that the value of R2 between the bubbles and Kd was 0.52. If climatic changes have led to an increase in the volume of bubbles, the more bubbles will increase the scattering properties of sea ice and lead to an increase in Kd. Conversely, the reduced bubble volume would reduce the scattering properties of sea ice, which in turn would reduce Kd.

10.
BMC Med Res Methodol ; 24(1): 69, 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38494505

RESUMO

BACKGROUND: Intensive longitudinal data (ILD) collected in near real time by mobile health devices provide a new opportunity for monitoring chronic diseases, early disease risk prediction, and disease prevention in health research. Functional data analysis, specifically functional principal component analysis, has great potential to abstract trends in ILD but has not been used extensively in mobile health research. OBJECTIVE: To introduce functional principal component analysis (fPCA) and demonstrate its potential applicability in estimating trends in ILD collected by mobile heath devices, assessing longitudinal association between ILD and health outcomes, and predicting health outcomes. METHODS: fPCA and scalar-to-function regression models were reviewed. A case study was used to illustrate the process of abstracting trends in intensively self-measured blood glucose using functional principal component analysis and then predicting future HbA1c values in patients with type 2 diabetes using a scalar-to-function regression model. RESULTS: Based on the scalar-to-function regression model results, there was a slightly increasing trend between daily blood glucose measures and HbA1c. 61% of variation in HbA1c could be predicted by the three preceding months' blood glucose values measured before breakfast (P < 0.0001, [Formula: see text]). CONCLUSIONS: Functional data analysis, specifically fPCA, offers a unique tool to capture patterns in ILD collected by mobile health devices. It is particularly useful in assessing longitudinal dynamic association between repeated measures and outcomes, and can be easily integrated in prediction models to improve prediction precision.


Assuntos
Diabetes Mellitus Tipo 2 , Telemedicina , p-Cloroanfetamina/análogos & derivados , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Glicemia , Hemoglobinas Glicadas , Análise de Componente Principal , Avaliação de Resultados em Cuidados de Saúde
11.
Pediatr Blood Cancer ; 71(5): e30928, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38418934

RESUMO

OBJECTIVES: This study aims to analyze the behavior and treatment of adenoid cystic carcinoma (AdCC) in the pediatric and young adult population and to identify factors affecting overall survival (OS). MATERIALS AND METHODS: The study analyzed salivary gland malignancies in patients aged 0-21 with AdCC histology using the National Cancer Database from 2004 to 2018. RESULTS: A total of 72 patients (59.7% parotid, 36.1% submandibular, 1.4% sublingual, 2.8% unspecified) met criteria. Median age was 18 years [range: 0-21]. High-grade dysplasia was present in 67% of cases. Therapy consisted of primary surgery for all cases, regional lymph node dissection (LND) (74%), radiotherapy (71%), chemotherapy (8%), and chemoradiation (7%). The 5-year OS rate was 93.2% [95% confidence interval (CI): 86.9%-99.9%], respectively. Patients who underwent associated LND had improved OS (p = .0083, log-rank test) with a 5-year OS at 82.4% [95% CI: 66.1%-100%] versus 97.6% [95% CI: 93.0%-100%]. A significant difference in OS was found with unfavorable outcomes after positive marginal status: 5-year OS 84.1% [95% CI: 71.0%-99.7%] versus 100% [95% CI: 100%]; p < .001. Adjuvant therapy did not seem to impact the outcome. CONCLUSION: This study confirms that AdCC in children and young adults has an overall good prognosis despite frequent high grade. It suggests that cervical LND may be of importance, but the value of systematic adjuvant therapy is not confirmed. These findings emphasize the importance and relevance of population-based studies in shaping clinical practice and informing the design of future prospective investigations.


Assuntos
Carcinoma Adenoide Cístico , Neoplasias das Glândulas Salivares , Humanos , Adulto Jovem , Criança , Adolescente , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/radioterapia , Glândula Submandibular/patologia , Esvaziamento Cervical , Estudos Retrospectivos , Prognóstico
12.
Mol Breed ; 44(3): 20, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38404720

RESUMO

Nonapomictic citrus tetraploids are desirable in citrus breeding for the production of triploid, seedless varieties, and polyploid rootstocks. However, only a few lines have been reported, and they were all generated using chemical methods. A 2x + 4 × cytochimera of the nonapomictic citrus variety 'Orah' mandarin, which developed from a bud mutant, was found due to its morphology differing from that of diploid plants and characterised via ploidy analysis combining flow cytometry and chromosome observation. The chimaera was stable, and there were 1.86-1.90 times as tetraploid cells as diploid cells. Anatomical structure observation revealed that the 'Orah' chimaera may be a periclinal chimaera with diploid cells in the L1 layer and tetraploid cells in the L2 and L3 layers. The chimaera showed some typical traits of polyploid plants, including thicker shoots, wider and thicker leaves, larger flowers and fruits, and fewer but larger seeds in fruits than in diploid plants. Almost all the seeds of the chimaera were monoembryonic. Most of the self-pollinated progenies of the chimaera were identified as tetraploids, and some triploid, pentaploid, and hexaploid plants were found. As a female, the chimaera produced allotriploids when crossed with Australian finger lime. In addition, 6 plants developed from polyembryonic seeds of the chimaera were identified as sexual tetraploid progenies with low-level recombinant genomes. Therefore, the 'Orah' 2x + 4 × chimaera can be used as a female parent to produce hybrid triploid and tetraploid citrus plants with high efficiency. Identification of the chimaera demonstrated that tetraploid citrus plants, especially nonapomictic varieties, can be generated from shoot bud mutants. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01456-x.

13.
J Phys Chem A ; 128(17): 3273-3284, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38635947

RESUMO

Herein, we report a computation study based on the density functional theory calculations to understand the mechanism and ligand effect of the base-stabilized dialumenes toward dihydrogen activation. Among all of the examined modes of dihydrogen activation using the base-stabilized dialumene, we found that the concerted 1,2-hydrogenation of the Al═Al double bond is kinetically more preferable. The concerted 1,2-hydrogenation of the Al═Al double bond adopts an electron-transfer model with certain asynchrony. That is, the initial electron donation from the H-H σ bonding orbital to the empty 3p orbital of the Al1 center is followed by the backdonation from the lone pair electron of the Al2 center to the H-H σ antibonding orbital. Combined with the energy decomposition analysis on the transition states of the concerted 1,2-hydrogenation of the Al═Al double bond and the topographic steric mapping analysis on the free dialumenes, we ascribe the higher reactivity of the aryl-substituted dialumene over the silyl-substituted analogue in dihydrogen activation to the stronger electron-withdrawing effect of the aryl group, which not only increases the flexibility of the Al═Al double bond but also enhances the Lewis acidity of the Al═Al core. Consequently, the aryl-substituted dialumene fragment suffers less geometric deformation, and the orbital interactions between the dialumene and dihydrogen moieties are more attractive during the 1,2-hydrogenation process. Moreover, our calculations also predict that the Al═Al double bond has a good tolerance with the stronger electron-withdrawing group (-CF3) and the weaker σ-donating N-heterocyclic carbene (NHC) analogue (e.g., triazol carbene and NHSi). The reactivity of the dialumene in dihydrogen activation can be further improved by introducing these groups as the supporting ligand and the stabilizing base on the Al═Al core, respectively.

14.
Bioorg Chem ; 148: 107427, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38728911

RESUMO

Histone acetyltransferase CREB-binding protein (CBP) and its homologous protein p300 are key transcriptional activators that can activate oncogene transcription, which present promising targets for cancer therapy. Here, we designed and synthesized a series of p300/CBP targeted low molecular weight PROTACs by assembling the covalent ligand of RNF126 E3 ubiquitin ligase and the bromodomain ligand of the p300/CBP. The optimal molecule A8 could effectively degrade p300 and CBP through the ubiquitin-proteasome system in time- and concentration-dependent manners, with half-maximal degradation (DC50) concentrations of 208.35/454.35 nM and 82.24/79.45 nM for p300/CBP in MV4-11 and Molm13 cell lines after 72 h of treatment. And the degradation of p300/CBP by A8 is dependent on the ubiquitin-proteasome pathway and its simultaneous interactions with the target proteins and RNF126. A8 exhibits good antiproliferative activity in a series of p300/CBP-dependent cancer cells. It could transcriptionally inhibit the expression of c-Myc, induce cell cycle arrest in the G0/G1 phase and apoptosis in MV4-11 cells. This study thus provided us a new chemotype for the development of drug-like PROTACs targeting p300/CBP, which is expected to be applied in cancer therapy.


Assuntos
Antineoplásicos , Proliferação de Células , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Ubiquitina-Proteína Ligases , Fatores de Transcrição de p300-CBP , Humanos , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Fatores de Transcrição de p300-CBP/metabolismo , Fatores de Transcrição de p300-CBP/antagonistas & inibidores , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Relação Estrutura-Atividade , Estrutura Molecular , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral
15.
Environ Res ; 251(Pt 2): 118734, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38493854

RESUMO

Mercury (Hg), especially in the form of methylmercury (MeHg), poses a significant threat to both organisms and the environment due to its extreme toxicity. While methylation process of Hg in sediments has been extensively studied, recognition of its associated risks and mechanisms during cyanobacterial blooms remains limited. This study investigated the distribution characteristics of Hg and MeHg in sediments of Taihu Lake, China. The concentration of Hg and MeHg varied within the range of 96.0-212.0 ng g-1 and 0.1-0.5 ng g-1, respectively. Higher ecological risks of Hg were found in algal-dominated regions compared to macrophyte areas. The significant correlations observed between Hg, MeHg, and algal-derived dissolved organic matter (ADOM) components C1 and C2 in algal-dominated regions indicate a close association between ADOM components and the Hg methylation process. These components are involved in the absorption or complexation of Hg, participate in redox reactions, and modulate microbial activity. The dsrB gene in sulfate-reducing bacteria (SRB) was found to accelerate the metabolic pathways of Hg methylation. These findings indicate that ADOM could enhance the methylation process of Hg during cyanobacterial blooms, which warrants attention.


Assuntos
Cianobactérias , Eutrofização , Sedimentos Geológicos , Lagos , Mercúrio , Compostos de Metilmercúrio , Poluentes Químicos da Água , Lagos/microbiologia , Lagos/química , Mercúrio/análise , Sedimentos Geológicos/microbiologia , Sedimentos Geológicos/química , Metilação , China , Poluentes Químicos da Água/análise , Compostos de Metilmercúrio/análise , Monitoramento Ambiental
16.
BMC Anesthesiol ; 24(1): 7, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38166634

RESUMO

BACKGROUND: Stellate ganglion block (SGB) has been shown to reduce perioperative complications in various surgeries. Because laparoscopic techniques and instruments have advanced during the past two decades, laparoscopic liver resection is being increasingly adopted worldwide. Lesser blood loss, fewer postoperative complications, and shorter postoperative hospital stays are the advantages of laparoscopic liver resection, as compared to conventional open surgery. There is an urgent need for an effective intervention to reduce perioperative complications and accelerate postoperative recovery. This study investigated the effect of ultrasound-guided SGB on enhanced recovery after laparoscopic partial hepatectomy. METHODS: We compared patients who received SGB with 0.5% ropivacaine (group S) with those who received SGB with 0.9% saline (group N). A total of 58 patients with partial hepatectomy were enrolled (30 S) and (28 N). Before induction of anesthesia, SGB was performed with 0.5% ropivacaine in group S and 0.9% saline in group N. MAIN OUTCOME: Comparison of serum inflammatory cytokines concentration at each time point. RESULTS: Main outcome: When comparing IL-6 and IL-10 concentrations among groups, group S showed less variation over time compared to group N. For comparison between groups, the serum IL-6 concentration in group S was lower than that in group N at 6 and 24 h after operation (P < 0.01), and there was a significant linear relationship between serum IL-6 concentration at 24 h after operation and hospitalization situation. CONCLUSIONS: Ultrasound-guided SGB can stabilize perioperative inflammatory cytokines plays a positive role in the enhanced recovery of patients after laparoscopic partial hepatectomy. The serum IL-6 level within 24 h after surgery may be used as a predictor of hospitalization. TRIAL REGISTRATION: The study was registered at the ClinicalTrials.gov (Registration date: 13/09/2021; Trial ID: NCT05042583).


Assuntos
Citocinas , Hepatectomia , Humanos , Ropivacaina/farmacologia , Hepatectomia/métodos , Gânglio Estrelado , Interleucina-6 , Solução Salina/farmacologia , Ultrassonografia de Intervenção
17.
Ecotoxicol Environ Saf ; 270: 115778, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38147774

RESUMO

BACKGROUND: Studies have shown that fine particulate matter (PM2.5) remains a significant problem in developing countries and plays a critical role in the onset and progression of respiratory illnesses. Circular RNAs (circRNAs) are involved in many pathophysiological processes,but their relationship to PM2.5 pollution is largely unexplored. OBJECTIVES: To elucidate the functional role of hsa_circ_0000992 in PM2.5-induced inflammation in a human bronchial epithelial cell line (16HBE) and to clarify whether the competing endogenous RNA (ceRNA) mechanism is involved in the interrelationships between hsa_circ_0000992 and hsa-miR-936 and the inflammatory signaling pathways. METHODS: Detection of inflammatory factors in 16HBE cells exposed to PM2.5 by RT-qPCR and ELISA.High throughput sequencing and bioinformatics analysis methods were used to screen circRNA.The bioinformatics analysis method western blotting and dual-luciferase reporter gene system were used to verify mechanisms associated with circRNA. RESULTS: PM2.5 cause inflammation in the 16HBE cells. High throughput sequencing and RT-qPCR result revealed that the expression of hsa_circ_0000992 was markedly up-regulated in 16HBE exposed to PM2.5. The binding sites between hsa_circ_0000992 and hsa-miR-936 was confirmed by dual-luciferase reporter gene system.Western blotting and RT-qPCR showed that hsa_circ_0000992 can interact with hsa-miR-936 to regulate AKT serine/threonine kinase 3(AKT3),thereby activating the PI3K/AKT pathway and ultimately promoting the expression of interleukin (IL)- 1ß and IL-8. CONCLUSION: PM2.5 can induce the inflammatory response in 16HBE cells by activating the PI3K/AKT pathway. The expression of hsa_circ_0000992 increased when PM2.5 stimulated 16HBE cells,and the circRNA could then regulate the inflammatory response.Hsa_circ_0000992 regulates the hsa-miR-936/AKT3 axis through the ceRNA mechanism,thereby activating the PI3K/AKT signaling pathway,increasing the expression of cellular inflammatory factors,and promoting PM2.5-induced respiratory inflammation.


Assuntos
MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Células Epiteliais/metabolismo , Material Particulado/toxicidade , Inflamação/induzido quimicamente , Inflamação/genética , Luciferases
18.
J Stroke Cerebrovasc Dis ; 33(1): 107471, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37966095

RESUMO

INTRODUCTION: The best anesthetic choice for patients with acute posterior circulation stroke during endovascular treatment (EVT) remains uncertain. METHOD: We searched five databases to identify studies that met the inclusion criteria. Our primary outcome measure was functional independence (FI). Secondary outcomes were 3-month mortality, any intracranial hemorrhage (ICH), symptomatic ICH (sICH), successful reperfusion, and procedure- and ventilator-associated complications. RESULTS: A total of 10 studies were included in our meta-analysis. No significant differences were detected between the general anesthesia (GA) and conscious sedation and local anesthesia (CS/LA) groups in 3-month FI (nine studies; OR=0.69; 95% CI 0.45-1.06; P=0.083; I2=66%;), 3-month mortality (nine studies; OR=1.41; 95% CI 0.94-2.11; P=0.096; I2=61.2%;), any ICH (three studies; OR=0.75; 95% CI 0.44-1.25; P=0.269; I2=0%;), or sICH (six studies; OR=0.64; 95% CI 0.40-1.04; P=0.073; I2=0%;). No significant differences were observed for successful reperfusion (10 studies; OR=1.17; 95% CI 0.91-1.49; P=0.219; I2=0%;), procedure-related complications (four studies; OR=1.14; 95% CI 0.70-1.87; P=0.603; I2=7.9%;), or respiratory complications (four studies; OR=1.19; 95% CI 0.61-2.32; P=0.616; I2=64.9%;) between the two groups. CONCLUSIONS: Our study showed no differences in 3-month FI, 3-month mortality, and successful reperfusion between patients treated with GA and those treated with CS/LA. Additionally, no increased risk of hemorrhagic transformation or pulmonary infection was observed in the CS/LA group. These results indicate that CS/LA may be an EVT option for acute posterior circulation stroke patients.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Anestesia Local/efeitos adversos , AVC Isquêmico/etiologia , Sedação Consciente/efeitos adversos , Sedação Consciente/métodos , Resultado do Tratamento , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Anestesia Geral/efeitos adversos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/etiologia , Hemorragias Intracranianas/etiologia , Trombectomia/efeitos adversos
19.
Molecules ; 29(11)2024 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-38893390

RESUMO

This study details the rational design and synthesis of Cu2ZnSnS4 (CZTS)-doped anatase (A) heterostructures, utilizing earth-abundant elements to enhance the efficiency of solar-driven water splitting. A one-step hydrothermal method was employed to fabricate a series of CZTS-A heterojunctions. As the concentration of titanium dioxide (TiO2) varied, the morphology of CZTS shifted from floral patterns to sheet-like structures. The resulting CZTS-A heterostructures underwent comprehensive characterization through photoelectrochemical response assessments, optical measurements, and electrochemical impedance spectroscopy analyses. Detailed photoelectrochemical (PEC) investigations demonstrated notable enhancements in photocurrent density and incident photon-to-electron conversion efficiency (IPCE). Compared to pure anatase electrodes, the optimized CZTS-A heterostructures exhibited a seven-fold increase in photocurrent density and reached a hydrogen production efficiency of 1.1%. Additionally, the maximum H2 production rate from these heterostructures was 11-times greater than that of pure anatase and 250-times higher than the original CZTS after 2 h of irradiation. These results underscore the enhanced PEC performance of CZTS-A heterostructures, highlighting their potential as highly efficient materials for solar water splitting. Integrating Cu2ZnSnS4 nanoparticles (NPs) within TiO2 (anatase) heterostructures implied new avenues for developing earth-abundant and cost-effective photocatalytic systems for renewable energy applications.

20.
J Gene Med ; 25(10): e3516, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37118998

RESUMO

BACKGROUND: Liver hepatocellular carcinoma (LIHC) remains a malignant malignancy with a low cure rate. Anoikis is a newly recognized cancer hallmark. However, an Anoikis-related model has not been clarified in LIHC. METHODS: The Anoikis-related score in the present study was created using Survival Random Forest and least absolute shrinkage and selection operator (LASSO) machine learning algorithms. Anoikis-related scores with respect to mutation analysis, immunological analysis, function annotation, and medication prediction were all thoroughly investigated. RESULTS: The Anoikis-related score accurately predicted the patients' immunological activity, altered genes, and medication sensitivity. SPP1 immunological analysis, function annotation, medication prediction, and immunotherapy prediction were systematically investigated. SPP1 may effectively predict the outcomes of immunotherapy. SPP1 was revealed to be a mediator of LIHC cell proliferation and migration. A putative axis in LIHC was YBX1/SPP1. CONCLUSIONS: Clinical care and the treatment plan for patients with LIHC were anticipated to benefit significantly from the established Anoikis-related score.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Anoikis/genética , Neoplasias Hepáticas/genética , Aprendizado de Máquina , Proteína 1 de Ligação a Y-Box/genética , Osteopontina
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