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1.
Carcinogenesis ; 45(8): 569-581, 2024 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-38470063

RESUMO

Previous studies have indicated that transmembrane protein 16A (TMEM16A) plays a crucial role in the pathogenesis and progression of various tumors by influencing multiple signaling pathways. However, the role of TMEM16A in regulating autophagy via the mammalian target of rapamycin (mTOR) pathway and its impact on the development of hypopharyngeal squamous cell carcinoma (HSCC) remain unclear. Immunohistochemistry and western blotting were used to assess the expression of TMEM16A in HSCC tissues and metastatic lymph nodes. Manipulation of TMEM16A expression levels was achieved in the FaDu cell line through overexpression or knockdown, followed by assessment of its biological effects using cell colony formation, wound healing, transwell and invasion assays. Additionally, apoptosis and autophagy-related proteins, as well as autophagosome formation, were evaluated through western blotting, transmission electron microscopy and immunofluorescence following TMEM16A knockdown or overexpression in FaDu cells. Our study revealed significantly elevated levels of TMEM16A in both HSCC tissues and metastatic lymph nodes compared with normal tissues. In vitro experiments demonstrated that silencing TMEM16A led to a notable suppression of HSCC cell proliferation, invasion and migration. Furthermore, TMEM16A silencing effectively inhibited tumor growth in xenografted mice. Subsequent investigations indicated that knockdown of TMEM16A in HSCC cells could suppress mTOR activation, thereby triggering autophagic cell death by upregulating sequestosome-1 (SQSTM1/P62) and microtubule-associated protein light chain 3 II (LC3II). This study highlights the crucial role of TMEM16A in modulating autophagy in HSCC, suggesting its potential as a therapeutic target for the treatment of this malignancy.


Assuntos
Anoctamina-1 , Autofagia , Movimento Celular , Proliferação de Células , Neoplasias Hipofaríngeas , Invasividade Neoplásica , Proteínas de Neoplasias , Transdução de Sinais , Serina-Treonina Quinases TOR , Humanos , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/genética , Neoplasias Hipofaríngeas/metabolismo , Animais , Camundongos , Anoctamina-1/metabolismo , Anoctamina-1/genética , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Linhagem Celular Tumoral , Masculino , Apoptose , Regulação Neoplásica da Expressão Gênica , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Feminino , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/genética
2.
J Org Chem ; 89(16): 11558-11566, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39082143

RESUMO

Efficient copper-catalyzed radical thiocyanosulfonylation of alkenes and alkynes with potassium thiocyanate and sodium phenylsulfinate is described. The reactions provide general and convenient methods toward the synthesis of ß-thiocyanoalkyl sulfones and ß-thiocyanoalkenyl sulfones, respectively, in satisfactory yields. Based on conducted mechanistic experiments, a mechanism involving oxidative generation of sulfonyl radicals and subsequent addition to alkenes followed by Cu-assisted thiocyanation is proposed. Moreover, the practicability of the reaction is successfully demonstrated by its successful application on a gram scale.

3.
Dig Dis Sci ; 69(4): 1200-1213, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38400886

RESUMO

BACKGROUND: Circular RNAs (CircRNAs) play essential roles in cancer occurrence as regulatory RNAs. However, circRNA-mediated regulation of gastric cancer (GC) remains poorly understood. AIM: The purpose of this study was to investigate the molecular mechanism of circSLC22A23 (hsa_circ_0075504) underlying GC occurrence. METHODS: CircSLC22A23 levels were first quantified by quantitative real-time reverse transcription-polymerase chain reaction in GC cell lines, 80 paired GC tissues and adjacent normal tissues, and 27 pairs of plasma samples from preoperative and postoperative patients with GC. Then circSLC22A23 was knocked-down with short hairpin RNA to analyze its oncogenic effects on the proliferation, migration, and invasion of GC cells. Finally, circRNA-binding proteins and their downstream target genes were identified by RNA pulldown, mass spectrometry, RNA immunoprecipitation, quantitative real-time reverse transcription-polymerase chain reaction, and Western blot assays. RESULTS: CircSLC22A23 was found to be highly expressed in GC cells, GC tissues, and plasma from GC patients. Knockdown of circSLC22A23 inhibited GC cell proliferation, migration and invasion. RNA pulldown and RNA immunoprecipitation assays verified the interaction between circSLC22A23 and heterogeneous nuclear ribonucleoprotein U (HNRNPU). Knockdown of circSLC22A23 decreased HNRNPU protein levels. Moreover, rescue assays showed that the tumor suppressive effect of circSLC22A23 knockdown was reversed by HNRNPU overexpression. Finally, epidermal growth factor receptor (EGFR) was found to be one of the downstream target genes of HNRNPU that was up regulated by circSLC22A23. CONCLUSION: CircSLC22A23 regulated the transcription of EGFR through activation of HNRNPU in GC cells, suggesting that circSLC22A23 may serve as a potential therapeutic target for the treatment of GC.


Assuntos
MicroRNAs , RNA Circular , Neoplasias Gástricas , Humanos , Linhagem Celular Tumoral , Proliferação de Células/genética , Receptores ErbB/metabolismo , Regulação Neoplásica da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo U/metabolismo , MicroRNAs/genética , RNA Circular/genética , RNA Circular/metabolismo , RNA Interferente Pequeno , Neoplasias Gástricas/patologia , Transportadores de Ânions Orgânicos/genética
4.
Inhal Toxicol ; 36(1): 1-12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38175690

RESUMO

Background: Paraquat (PQ) plays an important role in agricultural production due to its highly effective herbicidal effect. However, it has led to multiple organ failure in those who have been poisoned, with damage most notable in the lungs and ultimately leading to death. Because of little research has been performed at the genetic level, and therefore, the specific genetic changes caused by PQ exposure are unclear.Methods: Paraquat poisoning model was constructed in Sprague Dawley (SD) rats, and SD rats were randomly divided into Control group, paraquat (PQ) poisoning group and Anthrahydroquinone-2,6-disulfonate (AH2QDS) treatment group. Then, the data was screened and quality controlled, compared with reference genes, optimized gene structure, enriched at the gene expression level, and finally, signal pathways with significantly different gene enrichment were screened.Results: This review reports on lung tissues from paraquat-intoxicated Sprague Dawley (SD) rats that were subjected to RNA-seq, the differentially expressed genes were mainly enriched in PI3K-AKT, cGMP-PKG, MAPK, Focal adhesion and other signaling pathways.Conclusion: The signaling pathways enriched with these differentially expressed genes are summarized, and the important mechanisms mediated through these pathways in acute lung injury during paraquat poisoning are outlined to identify important targets for AH2QDS treatment of acute lung injury due to paraquat exposure, information that will be used to support a subsequent in-depth study on the mechanism of PQ action.


Assuntos
Lesão Pulmonar Aguda , Paraquat , Ratos , Animais , Ratos Sprague-Dawley , Paraquat/toxicidade , RNA-Seq , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/metabolismo , Pulmão , Transdução de Sinais , Tecnologia
5.
Angew Chem Int Ed Engl ; 63(26): e202406069, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38630112

RESUMO

The construction of C(sp3)-N bonds via direct N-centered radical addition with olefins under benign conditions is a desirable but challenging strategy. Herein, we describe an organo-photocatalytic approach to achieve anti-Markovnikov alkene hydroamidation with sulfonyl azides in a highly efficient manner under transition-metal-free and mild conditions. A broad range of substrates, including both activated and unactivated alkenes, are suitable for this protocol, providing a convenient and practical method to construct sulfonylamide derivatives. A synergistic experimental and computational mechanistic study suggests that the additive, Hantzsch ester (HE), might undergo a triplet-triplet energy transfer manner to achieve photosensitization by the organo-photocatalyst under visible light irradiation. Next, the resulted triplet excited state 3HE* could lead to a homolytic cleavage of C4-H bond, which triggers a straightforward H-atom transfer (HAT) style in converting sulfonyl azide to the corresponding key amidyl radical. Subsequently, the addition of the amidyl radical to alkene followed by HAT from p-toluenethiol could proceed to afford the desired anti-Markovnikov hydroamidation product. It is worth noting that mechanistic pathway bifurcation could be possible for this reaction. A feasible radical chain propagation mechanistic pathway is also proposed to rationalize the high efficiency of this reaction.

6.
J Stroke Cerebrovasc Dis ; 32(12): 107446, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38442074

RESUMO

OBJECTIVES: This study aimed to investigate the causal relationship between Atrial Fibrillation (AF) and the risk of Stroke using a Mendelian randomization (MR) approach. METHODS: A two-sample MR analysis was conducted using publicly available genome-wide association study (GWAS) summary statistics data. In this analysis, genetic variants associated with AF were used as instrumental variables to estimate the causal effect. The inverse-variance weighted (IVW) method, weighted median estimator, and MR-Egger regression were employed for estimation. Additionally, sensitivity analysis was performed using the leave-one-out method. RESULTS: The analysis included 87 single nucleotide polymorphisms (SNPs) associated with AF. The results from the IVW method indicated a positive association between genetic predisposition to AF and the risk of stroke (OR 1.002, 95 % CI 1.001-1.003, P < 0.001). The weighted median and MR-Egger methods showed consistent results (weighted median: OR 1.001, 95 % CI 1.000-1.002, P = 0.034; MR-Egger: OR 1.001, 95 % CI 1.000-1.003, P = 0.086). Sensitivity analysis demonstrated that no individual SNP significantly influenced the causal inference. CONCLUSIONS: This study provides evidence of a causal relationship between AF and an elevated risk of stroke. These findings emphasize the significance of managing AF in order to prevent and treat strokes. Additional research is required to better understand the underlying mechanisms of this causal association.


Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/genética , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Predisposição Genética para Doença , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética
7.
Zhongguo Zhong Yao Za Zhi ; 48(22): 5985-5992, 2023 Nov.
Artigo em Zh | MEDLINE | ID: mdl-38114204

RESUMO

Vaccination is an effective method for preventing influenza, and adjuvants can enhance the immune response intensity and persistence of influenza vaccines. However, there are currently shortcomings in clinical adjuvant approvals, ineffectiveness against weak antigens, and a tendency to cause headaches. Therefore, the development of safe and effective novel adjuvants for influenza vaccines is particularly important to enhance vaccine immunogenicity and safety. Given the wide range of sources, high safety, and biodegradability of traditional Chinese medicine(TCM), some studies have described it as a vaccine adjuvant. This article reviewed the current status and challenges of influenza vaccine adjuvants, summarized the types of TCM adjuvants, the safety and immunomodulatory effects of natural active ingredients from TCM combined with influenza vaccines, the role of TCM adjuvants in antigen storage, antigen presentation capability, immune cells and cytokines, and immune responses, and analyzed the advantages and disadvantages of TCM adjuvants compared with small molecule adjuvants, with the aim of promoting the clinical development and commercialization of TCM adjuvants for influenza vaccines.


Assuntos
Vacinas contra Influenza , Influenza Humana , Humanos , Adjuvantes Imunológicos/farmacologia , Medicina Tradicional Chinesa , Influenza Humana/prevenção & controle , Adjuvantes Farmacêuticos
8.
Exp Ther Med ; 27(5): 222, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38590579

RESUMO

Colorectal cancer (CRC) is a deadly and aggressive type of cancer that has a high fatality rate. The expression levels of replication factor C subunit 3 (RFC3) and kinesin family member 14 (KIF14) have been reported to be increased in CRC. The current study aimed to explore the effects of RFC3 on the malignant behaviors of CRC cells and its possible underlying mechanism involving KIF14. RFC3 and KIF14 expression levels in CRC tissues were analyzed using TNMplot database and Gene Expression Profiling Interactive Analysis database bioinformatics tools. RFC3 and KIF14 levels in CRC cells were examined using reverse transcription-quantitative PCR and western blotting. Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine assays were performed to assess cell proliferation. Cell apoptosis was determined using flow cytometric analysis. Wound healing and Transwell assays were adopted for the evaluation of cell migration and invasion. Tube formation assay in human umbilical vein endothelial cells was used to measure angiogenesis. Western blotting analysis was performed to determine the expression of apoptosis-, migration- and angiogenesis-associated proteins. Additionally, bioinformatics tools predicted the co-expression and interaction of RFC3 and KIF14, which was verified by a co-immunoprecipitation assay. RFC3 displayed elevated expression in CRC tissues and cells, and depletion of RFC3 halted the proliferation, migration, invasion and angiogenesis, while increasing the apoptosis of CRC cells; this was accompanied by changes in the expression levels of related proteins. In addition, RFC3 bound to KIF14 and interference with RFC3 reduced KIF14 expression. Moreover, KIF14 upregulation reversed the effects of RFC3 depletion on the aggressive cellular behaviors in CRC. In conclusion, RFC3 might interact with KIF14 to function as a contributor to the malignant development of CRC.

9.
Cell Transplant ; 33: 9636897241245796, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38629748

RESUMO

Immunoregulation and indoleamine 2,3-dioxygenase 1 (IDO1) play pivotal roles in the rejection of allogeneic organ transplantation. This study aims to elucidate the immune-related functional mechanisms of exosomes (Exos) derived from bone marrow-derived mesenchymal stem cells (BMSCs) overexpressing IDO1 in the context of allogeneic heart transplantation (HTx) rejection. A rat model of allogeneic HTx was established. Exos were extracted after transfection with oe-IDO1 and oe-NC from rat BMSCs. Exos were administered via the caudal vein for treatment. The survival of rats was analyzed, and reverse transcription qualitative PCR (RT-qPCR) and immunohistochemistry (IHC) were employed to detect the expression of related genes. Histopathological examination was conducted using hematoxylin and eosin (HE) staining, and flow cytometry was utilized to analyze T-cell apoptosis. Proteomics and RNA-seq analyses were performed on Exos. The data were subjected to functional enrichment analysis using the R language. A protein interaction network was constructed using the STRING database, and miRWalk, TargetScan, and miRDB databases predicted the target genes, differentially expressed miRNAs, and transcription factors (TFs). Exos from BMSCs overexpressing IDO1 prolonged the survival time of rats undergoing allogeneic HTx. These Exos reduced inflammatory cell infiltration, mitigated myocardial damage, induced CD4 T-cell apoptosis, and alleviated transplantation rejection. The correlation between Exos from BMSCs overexpressing IDO1 and immune regulation was profound. Notably, 13 immune-related differential proteins (Anxa1, Anxa2, C3, Ctsb, Hp, Il1rap, Ntn1, Ptx3, Thbs1, Hspa1b, Vegfc, Dcn, and Ptpn11) and 10 significantly different miRNAs were identified. Finally, six key immune proteins related to IDO1 were identified through common enrichment pathways, including Thbs1, Dcn, Ptpn11, Hspa1b, Il1rap, and Vegfc. Thirteen TFs of IDO1-related key miRNAs were obtained, and a TF-miRNA-mRNA-proteins regulatory network was constructed. Exosome miRNA derived from BMSCs overexpressing IDO1 may influence T-cell activation and regulate HTx rejection by interacting with mRNA.


Assuntos
Exossomos , Transplante de Células-Tronco Hematopoéticas , MicroRNAs , Ratos , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Exossomos/metabolismo , Rejeição de Enxerto/genética , RNA Mensageiro/metabolismo
10.
ACS Appl Mater Interfaces ; 16(14): 18184-18193, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38556720

RESUMO

We experimentally investigated the coalescence-induced droplet-particle jumping phenomenon on a submillimeter scale in symmetric and asymmetric particle arrangements with poly(methyl methacrylate) (PMMA) particles and stainless steel (SS) particles. Coalescence-induced droplet-particle jumping exhibited excellent capability and interesting behavior for both droplet jumping enhancement and particle transport. The particle increased the normalized droplet jumping velocity from 0.250 for no particle case to 0.315 and 0.320 for symmetric and asymmetric particle cases. Compared with similar-sized macrostructures fixed between droplets, better jumping performance with particles may be attributed to avoiding the work of adhesion during droplet-macrostructure separation. Besides, all particles always sunk at the bottom in the symmetric cases, while the stick mode for PMMA particles and sink, wander, and jet modes for SS particles appeared in the asymmetry cases. We revealed that the asymmetric particle arrangement induces an unbalanced surface tension force, which may provide a driving force in the vertical direction. Additionally, a small enough resistive force caused by hydrophobic particles is another necessary condition for the wonder and jet mode. Finally, we realized a significantly superior particle transport in the asymmetric SS particle cases with maximum particle height reaching ∼2.1 mm, ∼12.4 times the particle radius, the most significant vertical self-propelled transport distance currently.

11.
Chem Commun (Camb) ; 60(37): 4894-4897, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38623623

RESUMO

An efficient method for the radical difunctionalization of aromatic alkynes has been developed, resulting in the synthesis of a range of valuable triarylethenes. This approach utilizes strategically designed aryldiazonium salts with tertiary alcohol substitution as bifunctional reagents, along with cost-effective cuprous chloride as a catalyst. The method demonstrates remarkable Z-selectivity and is capable of gram-scale preparation. Additionally, a novel spin-trapping reagent has been developed based on the synthesized product.

12.
Environ Pollut ; 349: 123993, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38636838

RESUMO

Landfill is a huge pathogen reservoir and needs special attention. Herein, the distribution and spread risk of pathogen were assessed in excavated landfill scenario. The results show that landfill excavation will greatly increase the risk of environmental microbial contamination. The highest total concentration of culturable bacteria among landfill refuse, topsoil and plant leaves was found to be as high as 1010 CFU g-1. Total coliforms, Hemolytic bacteria, Staphylococcus aureus, Salmonella, Enterococci, and Fecal coliforms were detected in the landfill surrounding environment. Notably, pathogens were more likely to adhere to plant leaves, making it an important source of secondary pathogens. The culturable bacteria concentration in the air samples differed with the landfill zone with different operation status, and the highest culturable bacteria concentration was found in the excavated area of the landfill (3.3 × 104 CFU m-3), which was the main source of bioaerosol release. The distribution of bioaerosols in the downwind outside of the landfill showed a tendency of increasing and then decreasing, and the highest concentration of bioaerosols outside of the landfill (6.56 × 104 CFU m-3) was significantly higher than that in the excavated area of the landfill. The risk of respiratory inhalation was the main pathway leading to infection, whereas the HQin (population inhalation hazardous quotient) at 500 m downwind the excavation landfill was still higher than 1, indicating that the neighboring residents were exposed to airborne microbial pollutants. The results of the study provide evidence for bioaerosols control protective measures taken to reduce health risk from the excavated landfill.


Assuntos
Microbiologia do Ar , Monitoramento Ambiental , Instalações de Eliminação de Resíduos , Bactérias/isolamento & purificação , Eliminação de Resíduos , Aerossóis/análise , Microbiologia do Solo , Medição de Risco
13.
Chem Sci ; 15(5): 1879-1884, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38303955

RESUMO

Pyrroline derivatives are common in bioactive natural products and therapeutic agents. We report here a synthesis of pyrrolines and fused diaziridines by divergent radical cyclization of homoallylic diazirines, which can serve as an internal radical trap and a nitrogen source. This reaction proceeds by selective radical addition to C[double bond, length as m-dash]C or N[double bond, length as m-dash]N bonds followed by intramolecular cyclization. Frontier molecular orbital analysis provides a deep insight into the origin of the selectivity. The reaction demonstrates a new cyclization mode, broad functional group compatibility and high product diversity, and reveals a much broader chemical space for diazirine studies.

14.
Environ Sci Pollut Res Int ; 31(14): 21044-21056, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38381293

RESUMO

Proper composting treatment of poultry manure waste is recommended before its use as a fertilizer. This involves many bioprocesses driven by microorganisms. Therefore, it is important to understand microbial mechanisms behind these bioprocesses in manure composting systems. Many efforts have been made to study the microbial community structure and diversity in these systems using high-throughput sequencing techniques. However, the dynamics of microbial interaction and functionality, especially for key microbial functional guilds, are not yet fully understood. To address these knowledge gaps, we collected samples from a 150-day industrial chicken manure composting system and performed the microbial network analysis based on the sequencing data. We found that the family Bacillaceae and genus Bacillus might play important roles in organic matter biodegradation at the mesophilic/thermophilic phases. Genera Virgibacillus, Gracilibacillus, Nocardiopsis, Novibacillus, and Bacillaceae_BM62 were identified as the key ones for humic acid synthesis at the mature phases. These findings improve our understanding about the fundamental mechanisms behind manure composting and can aid the development of microbial agents to promote manure composting performance.


Assuntos
Bacillaceae , Compostagem , Animais , Solo , Esterco , Galinhas , Substâncias Húmicas
15.
DNA Cell Biol ; 43(5): 232-244, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513058

RESUMO

Numerous studies have shown that circular RNAs are associated with the occurrence and development of various cancers, but the biological functions and mechanisms of hsa_circ_0006847 (circASPHD1) in gastric cancer (GC) remain unclear. The expression of hsa_circ_0006847 in GC cell lines, tissue, and plasma from GC patients was assayed by quantitative real-time reverse transcription-polymerase chain reaction. Hsa_circ_0006847 expression in cells was downregulated or upregulated by transfected small interfering RNA (siRNA) or overexpression plasmid. The role of hsa_circ_0006847 in GC was investigated with Cell Counting Kit-8, EdU, Transwell, flow cytometry assays, and in a subcutaneous xenograft tumor model. In addition, the interaction of eukaryotic translation initiation factor 4A3 (EIF4A3) and hsa_circ_0006847 was determined with western blot, biotin-labeled RNA pull-down, and RNA immunoprecipitation assays. Co-immunoprecipitation and mass spectrometry were used to validate the combination of EIF4A3 and synaptopodin-2 (SYNPO2). The expression of hsa_circ_0006847 was decreased in GC tissues and cells and indicated poor survival and prognosis. Overexpression of hsa_circ_0006847 inhibited cell proliferation, migration, and invasion. Flow cytometry showed that upregulation of hsa_circ_0006847 resulted in promotion of apoptosis of GC cells and inhibited their progression through the G0/G1 phase. Downregulation of hsa_circ_0006847 expression had the opposite effects. Overexpression of hsa_circ_0006847 in subcutaneous tumor xenografts inhibited tumor growth. Mechanically, hsa_circ_0006847 promoted the binding of EIF4A3 to SYNPO2 by recruiting EIF4A3, which inhibited the growth of GC. The tumor suppressor activity of hsa_circ_0006847, inhibition of the occurrence and development of GC, was mediated by promotion of EIF4A3 and the binding of EIF4A3 to SYNPO2. The results support the study of hsa_circ_0006847 as a novel therapeutic target for the treatment of GC.


Assuntos
Proliferação de Células , Fator de Iniciação 4A em Eucariotos , Camundongos Nus , RNA Circular , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/metabolismo , Humanos , Fator de Iniciação 4A em Eucariotos/metabolismo , Fator de Iniciação 4A em Eucariotos/genética , RNA Circular/genética , RNA Circular/metabolismo , Animais , Proliferação de Células/genética , Linhagem Celular Tumoral , Camundongos , Regulação Neoplásica da Expressão Gênica , Movimento Celular/genética , Feminino , Masculino , Apoptose/genética , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , RNA Helicases DEAD-box
16.
Org Lett ; 26(22): 4705-4710, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38781570

RESUMO

Herein, visible-light-promoted [4π + 2σ] annulation of dienes and alkylamines was achieved via dual C(sp3)-H bond functionalization of alkylamines. The elusive enamine precursors are generated under mild conditions by photoredox catalysis, efficiently annulated by the diene, and simultaneously functionalized with two aliphatic C(sp3)-H bonds, resulting in the productive synthesis of new aromatic rings. The aromatic ring construction provides direct access to 2-hydroxybenzophenone derivatives in high yields (up to 90%). This [4π + 2σ] annulation reaction demonstrates mild reaction conditions, high reaction efficiency, and broad functional group tolerance, and this synthetic protocol has been made available for the late-stage transformation of natural products and commercial drugs.

17.
Transl Stroke Res ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602659

RESUMO

The objective of this study is to conduct a systematic review and meta-analysis aimed at evaluating the efficacy and safety of flow-diverting devices (FDs) treatment for intracranial vertebral artery (VA) aneurysms. We searched PubMed, Web of Science, OVID, and Embase for English-language studies up to February 2024 and included clinical studies on FD treatment of intracranial VA aneurysms. Sensitivity analysis evaluated outcome stability. Of 2273 articles, 29 studies involving 541 aneurysms treated with FDs were included. Based on the Methodological Index for Non-Randomized Studies (MINORS), six were high-quality and 23 moderate quality. FD treatment showed a 95% rate of favorable clinical outcomes (95% CI, 89-99%), 81% (95% CI, 74-88%) complete aneurysmal occlusion, 4% (95% CI, 2-7%) ischemic complication incidence, 1% (95% CI, 0-3%) hemorrhagic complication incidence, 95% (95% CI, 87-100%) posterior inferior cerebellar artery (PICA) preservation, and 6% (95% CI, 3-10%) in-stent stenosis or occlusion across clinical and angiographic follow-up periods of 13.62 months (95% CI, 10.72-16.52) and 11.85 months (95% CI, 9.36-14.33), respectively. Subgroup analyses, based on a 12-month angiographic follow-up threshold, indicated no statistically significant differences in rates of complete aneurysm occlusion, PICA preservation, or in-stent stenosis or occlusion incidence (p > 0.05) between subgroups. Moreover, significant differences were observed in clinical and angiographic outcomes between ruptured and unruptured aneurysms, particularly in hemorrhagic complications (p < 0.05), without significant disparity in ischemic complications (p > 0.05). The results' stability was confirmed via sensitivity analysis. FDs treatment for VA aneurysms is efficacious and safe, offering high rates of positive clinical and angiographic outcomes with minimal complications, underscoring FDs' viability as a treatment option for VA aneurysms. The study was registered with PROSPERO (registration number: CRD42024499894).

18.
Adv Sci (Weinh) ; 11(16): e2309022, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38348551

RESUMO

Radical difunctionalization of aliphatic alkynes provides direct access to valuable multi-substituted alkenes, but achieving a high level of chemo- and stereo-control remains a formidable challenge. Herein a novel photoredox neutral alkyne di-functionalization is reported through functional group migration followed by a radical-polar crossover and energy transfer-enabled stereoconvergent isomerization of alkenes. In this sequence, a hydroxyalkyl and an aryl group are incorporated concomitantly into an alkyne, leading to diversely functionalized E-allyl alcohols. The scope of alkynes is noteworthy, and the reaction tolerates aliphatic alkynes containing hydrogen donating C─H bonds that are prone to intramolecular hydrogen atom transfer. The protocol features broad functional group compatibility, high product diversity, and exclusive chemo- and stereoselectivity, thus providing a practical strategy for the elusive radical di-functionalization of unactivated alkynes.

19.
Bioresour Technol ; 406: 131048, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38945501

RESUMO

The nitrogen loss in composting is primarily driven by the transformation of organic nitrogen, yet the mechanisms underlying the degradation process remain incompletely understood. This study employed protein family domains (Pfams) analysis based on metagenomic sequencing to investigate the functional characteristics, key microorganisms, and environmental parameters influencing organic nitrogen degradation in chicken manure and pig manure composting. 154 Pfams associated with ammonification function were identified. Predominant Pfams: proteolytic peptidase, followed by chitin/cell wall degraders, least involved in nucleic acid degradation. Ammonifying microbial diversity was basically consistent among compost types, particularly in the thermophilic stage with the peak of abundance of dominant ammonifying microorganisms. Viruses played an important role in ammonification process, especially Uroviricota. 26 key ammonifying genera were identified by the microbial network. pH dominated the metabolic activity of ammonifying microorganisms in various manure compost types, primarily consisting of protein-degrading bacteria with stable community structures.


Assuntos
Galinhas , Compostagem , Esterco , Metagenômica , Nitrogênio , Animais , Nitrogênio/metabolismo , Metagenômica/métodos , Suínos , Domínios Proteicos , Bactérias/metabolismo , Bactérias/genética , Microbiologia do Solo
20.
ASAIO J ; 2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38587868

RESUMO

No previous studies have reported the use of a percutaneous suture technique performed by bedside intensivists for site closure during decannulation without direct artery repair in venoarterial extracorporeal membrane oxygenation (VA-ECMO) cases. Thus, the objective of this study was to evaluate the safety and effectiveness of this alternative approach. This retrospective study included 26 consecutive patients who underwent percutaneous VA-ECMO decannulation at Maoming People's Hospital. Bedside percutaneous suture technique performed by intensivists facilitated cannula site closure. Primary outcome was successful closure without additional interventions. Secondary outcomes included procedural time, surgical conversion rate, complications (bleeding, vascular/wound complications, neuropathy, lymphocele), procedure-related death. Follow-up ultrasound were conducted within 6 months after discharge. All patients achieved successful site hemostasis with a median procedural time of 28 minutes. Procedure-related complications included minor bleeding (7.7%), acute lower limb ischemia (15.4%), venous thrombus (11.5%), minor arterial stenosis (7.7%), wound infection (4.2%), delayed healing (15.4%), and wound secondary suturing (6.3%). No procedure-related deaths occurred. Follow-up vascular ultrasound revealed two cases (7.7%) of minor arterial stenosis. The perivascular suture technique may offer intensivists a safe and effective alternative method for access site closure without direct artery suture during ECMO decannulation.

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