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1.
Mol Cell ; 84(10): 1917-1931.e15, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38723633

RESUMO

Many multi-spanning membrane proteins contain poorly hydrophobic transmembrane domains (pTMDs) protected from phospholipid in mature structure. Nascent pTMDs are difficult for translocon to recognize and insert. How pTMDs are discerned and packed into mature, muti-spanning configuration remains unclear. Here, we report that pTMD elicits a post-translational topogenesis pathway for its recognition and integration. Using six-spanning protein adenosine triphosphate-binding cassette transporter G2 (ABCG2) and cultured human cells as models, we show that ABCG2's pTMD2 can pass through translocon into the endoplasmic reticulum (ER) lumen, yielding an intermediate with inserted yet mis-oriented downstream TMDs. After translation, the intermediate recruits P5A-ATPase ATP13A1, which facilitates TMD re-orientation, allowing further folding and the integration of the remaining lumen-exposed pTMD2. Depleting ATP13A1 or disrupting pTMD-characteristic residues arrests intermediates with mis-oriented and exposed TMDs. Our results explain how a "difficult" pTMD is co-translationally skipped for insertion and post-translationally buried into the final correct structure at the late folding stage to avoid excessive lipid exposure.


Assuntos
Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP , Retículo Endoplasmático , Proteínas de Membrana , ATPases do Tipo-P , Dobramento de Proteína , Humanos , Transportadores de Cassetes de Ligação de ATP/metabolismo , Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/química , Retículo Endoplasmático/metabolismo , Células HEK293 , Interações Hidrofóbicas e Hidrofílicas , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/química , Domínios Proteicos , Processamento de Proteína Pós-Traducional , ATPases Translocadoras de Prótons/metabolismo , ATPases Translocadoras de Prótons/genética , ATPases Translocadoras de Prótons/química , ATPases do Tipo-P/metabolismo , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/química , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/genética , Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo
2.
Mol Cell ; 82(18): 3453-3467.e14, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35961308

RESUMO

Membrane protein clients of endoplasmic reticulum (ER)-associated degradation must be retrotranslocated from the ER membrane by the AAA-ATPase p97 for proteasomal degradation. Before direct engagement with p97, client transmembrane domains (TMDs) that have partially or fully crossed the membrane must be constantly shielded to avoid non-native interactions. How client TMDs are seamlessly escorted from the membrane to p97 is unknown. Here, we identified ER-anchored TMUB1 as a TMD-specific escortase. TMUB1 interacts with the TMD of clients within the membrane and holds ∼10-14 residues of a hydrophobic sequence that is exposed out of membrane, using its transmembrane and cytosolic regions, respectively. The ubiquitin-like domain of TMUB1 recruits p97, which can pull client TMDs from bound TMUB1 into the cytosol. The disruption of TMUB1 escortase activity impairs retrotranslocation and stabilizes retrotranslocating intermediates of client proteins within the ER membrane. Thus, TMUB1 promotes TMD segregation by safeguarding the TMD movement from the membrane to p97.


Assuntos
Retículo Endoplasmático , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas de Membrana , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , Proteínas de Ciclo Celular/metabolismo , Retículo Endoplasmático/metabolismo , Degradação Associada com o Retículo Endoplasmático , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Ubiquitina/metabolismo , Proteína com Valosina/genética , Proteína com Valosina/metabolismo
3.
Mol Cell ; 79(2): 320-331.e9, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32645369

RESUMO

Valosin-containing protein (VCP)/p97 is an AAA-ATPase that extracts polyubiquitinated substrates from multimeric macromolecular complexes and biological membranes for proteasomal degradation. During p97-mediated extraction, the substrate is largely deubiquitinated as it is threaded through the p97 central pore. How p97-extracted substrates are targeted to the proteasome with few or no ubiquitins is unknown. Here, we report that p97-extracted membrane proteins undergo a second round of ubiquitination catalyzed by the cytosolic ubiquitin ligase RNF126. RNF126 interacts with transmembrane-domain-specific chaperone BAG6, which captures p97-liberated substrates. RNF126 depletion in cells diminishes the ubiquitination of extracted membrane proteins, slows down their turnover, and dramatically stabilizes otherwise transient intermediates in the cytosol. We reconstitute the reubiquitination of a p97-extracted, misfolded multispanning membrane protein with purified factors. Our results demonstrate that p97-extracted substrates need to rapidly engage ubiquitin ligase-chaperone pairs that rebuild the ubiquitin signal for proteasome targeting to prevent harmful accumulation of unfolded intermediates.


Assuntos
Proteínas de Membrana/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Proteína com Valosina/metabolismo , Catálise , Citosol/metabolismo , Células HEK293 , Humanos , Chaperonas Moleculares/metabolismo , Dobramento de Proteína , Proteólise , Solubilidade , Ubiquitinação
4.
J Immunol ; 210(11): 1771-1789, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37017564

RESUMO

The type IV IFN (IFN-υ) is reported in vertebrates from fish to primary mammals with IFN-υR1 and IL-10R2 as receptor subunits. In this study, the proximal promoter of IFN-υ was identified in the amphibian model, Xenopus laevis, with functional IFN-sensitive responsive element and NF-κB sites, which can be transcriptionally activated by transcription factors, such as IFN regulatory factor (IRF)1, IRF3, IRF7, and p65. It was further found that IFN-υ signals through the classical IFN-stimulated gene (ISG) factor 3 (ISGF3) to induce the expression of ISGs. It seems likely that the promoter elements of the IFN-υ gene in amphibians is similar to type III IFN genes, and that the mechanism involved in IFN-υ induction is very much similar to type I and III IFNs. Using recombinant IFN-υ protein and the X. laevis A6 cell line, >400 ISGs were identified in the transcriptome, including ISGs homologous to humans. However, as many as 268 genes were unrelated to human or zebrafish ISGs, and some of these ISGs were expanded families such as the amphibian novel TRIM protein (AMNTR) family. AMNTR50, a member in the family, was found to be induced by type I, III, and IV IFNs through IFN-sensitive responsive element sites of the proximal promoter, and this molecule has a negative role in regulating the expression of type I, III, and IV IFNs. It is considered that the current study contributes to the understanding of transcription, signaling, and functional aspects of type IV IFN at least in amphibians.


Assuntos
Interferon Tipo I , Interferons , Animais , Humanos , Xenopus laevis , Interferons/genética , Interferons/metabolismo , Peixe-Zebra/metabolismo , Regulação da Expressão Gênica , Transdução de Sinais , Interferon Tipo I/metabolismo , Mamíferos/metabolismo
5.
Fish Shellfish Immunol ; 149: 109614, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38710342

RESUMO

Chemokines are critical molecules involved in immune reaction and immune system homeostasis, and some chemokines play a role in antiviral immunity. It is not known if the C-C motif chemokine ligand 3 (CCL3), a member of the CC chemokine family, possesses antiviral properties in fish. In this study, a ccl3 was cloned from the mandarin fish (Siniperca chuatsi), and it has an open reading frame (ORF) of 276 base pairs, which are predicted to encode a 91-amino acid peptide. Mandarin fish CCL3 revealed conserved sequence features with four cysteine residues and closely relationships with the CCL3s from other vertebrates based on the sequence alignment and phylogenetic analysis. The transcripts of ccl3 were notably enriched in immune-related organs, such as spleen and gills in healthy mandarin fish, and the ccl3 was induced in the isolated mandarin fish brain (MFB) cells following infection with infectious spleen and kidney necrosis virus (ISKNV). Moreover, in MFB cells, overexpression of CCL3 induced immune factors, such as IL1ß, TNFα, MX, IRF1 and IFNh, and exhibited antiviral activity against ISKNV. This study sheds light on the immune role of CCL3 in immune response of mandarin fish, and its antiviral defense mechanism is of interest for further investigation.


Assuntos
Sequência de Aminoácidos , Infecções por Vírus de DNA , Doenças dos Peixes , Proteínas de Peixes , Imunidade Inata , Iridoviridae , Perciformes , Filogenia , Alinhamento de Sequência , Animais , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Proteínas de Peixes/química , Doenças dos Peixes/imunologia , Doenças dos Peixes/virologia , Perciformes/imunologia , Perciformes/genética , Infecções por Vírus de DNA/imunologia , Infecções por Vírus de DNA/veterinária , Iridoviridae/fisiologia , Alinhamento de Sequência/veterinária , Imunidade Inata/genética , Regulação da Expressão Gênica/imunologia , Quimiocina CCL3/genética , Quimiocina CCL3/imunologia , Clonagem Molecular , Perfilação da Expressão Gênica/veterinária , Sequência de Bases
6.
Acta Pharmacol Sin ; 45(5): 1032-1043, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38286833

RESUMO

It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.


Assuntos
Nefropatias Diabéticas , Matriz Extracelular , Ferroptose , Animais , Ferroptose/efeitos dos fármacos , Ferroptose/fisiologia , Nefropatias Diabéticas/metabolismo , Matriz Extracelular/metabolismo , Camundongos , Masculino , Camundongos Endogâmicos C57BL , Humanos , Células Mesangiais/metabolismo
7.
J Opt Soc Am A Opt Image Sci Vis ; 41(3): A47-A54, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38437429

RESUMO

In this study, we proposed a holographic identity verification encryption system that integrates face recognition, air-writing, and the multiple point cloud gridding encryption (M-PCGE) method to ensure multi-level security for objects. The experimental results show that the M-PCGE algorithm proposed in this paper achieves image encryption and decryption quickly with a high degree of restoration, and the security is verified.

8.
Cell Mol Life Sci ; 80(12): 347, 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37943391

RESUMO

Tubulointerstitial fibrosis (TIF) plays a crucial role in the progression of diabetic kidney disease (DKD). However, the underlying molecular mechanisms remain obscure. The present study aimed to examine whether transmembrane member 16A (TMEM16A), a Ca2+-activated chloride channel, contributes to the development of TIF in DKD. Interestingly, we found that TMEM16A expression was significantly up-regulated in tubule of murine model of DKD, which was associated with development of TIF. In vivo inhibition of TMEM16A channel activity with specific inhibitors Ani9 effectively protects against TIF. Then, we found that TMEM16A activation induces tubular mitochondrial dysfunction in in vivo and in vitro models, with the evidence of the TMEM16A inhibition with specific inhibitor. Mechanically, TMEM16A mediated tubular mitochondrial dysfunction through inhibiting PGC-1α, whereas overexpression of PGC-1α could rescue the changes. In addition, TMEM16A-induced fibrogenesis was dependent on increased intracellular Cl-, and reducing intracellular Cl- significantly blunted high glucose-induced PGC-1α and profibrotic factors expression. Taken together, our studies demonstrated that tubular TMEM16A promotes TIF by suppressing PGC-1α-mediated mitochondrial homeostasis in DKD. Blockade of TMEM16A may serve as a novel therapeutic approach to ameliorate TIF.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Animais , Camundongos , Nefropatias Diabéticas/genética , Homeostase , Mitocôndrias , Fibrose
9.
Ann Vasc Surg ; 100: 39-46, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38104925

RESUMO

BACKGROUND: To evaluate the safety and efficacy of endovascular denervation (EDN) as an adjunct to percutaneous vascular intervention (PVI) for peripheral artery disease (PAD). METHODS: From August 2019 to April 2021, 38 eligible patients with PAD enrolled in this study were randomly and equally assigned into 2 groups: the PVI group and the PVI + EDN group treated with EDN at the iliac and femoral arteries before PVI. The primary endpoint was the improvement in the ankle brachial index at 6 months after the procedure. The secondary endpoints were transcutaneous oxygen pressure (TcPO2), Rutherford category, numerical rating scale score, and safety. RESULTS: The technical success rates of PVI and EDN were 100%, and no device-related or procedure-related major adverse events occurred in either group. Compared with PVI alone, PVI + EDN demonstrated a significant improvement in limb hemodynamics at 6 months (Δ ankle brachial index 0.44 ± 0.31 vs. 0.24 ± 0.15, P = 0.018). Microcirculatory perfusion of PAD was significantly better at 6 months in the PVI + EDN group (ΔTcPO2, 15.68 ± 16.72 vs. 4.95 ± 13.43, P = 0.036). The Rutherford category was significantly improved in the PVI + EDN group in comparison with the PVI group at the 3-month follow-up (100.00% vs. 68.42%, P = 0.02). The decrease in the numerical rating scale score in the PVI + EDN group was greater than that in the PVI group at 1 week following the procedure (3 [2-5] vs. 4 [4-6], P = 0.022). CONCLUSIONS: In this single-center pilot analysis of a heterogeneous cohort of patients with PAD, PVI with EDN demonstrated a significant improvement in limb ischemia at 6 months compared with PVI alone.


Assuntos
Procedimentos Endovasculares , Doença Arterial Periférica , Humanos , Microcirculação , Resultado do Tratamento , Doença Arterial Periférica/diagnóstico por imagem , Doença Arterial Periférica/cirurgia , Isquemia/diagnóstico por imagem , Isquemia/cirurgia , Denervação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Fatores de Risco
10.
Biotechnol Lett ; 46(1): 37-46, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38064043

RESUMO

Metabolic Engineering of yeast is a critical approach to improving the production capacity of cell factories. To obtain genetically stable recombinant strains, the exogenous DNA is preferred to be integrated into the genome. Previously, we developed a Golden Gate toolkit YALIcloneNHEJ, which could be used as an efficient modular cloning toolkit for the random integration of multigene pathways through the innate non-homologous end-joining repair mechanisms of Yarrowia lipolytica. We expanded the toolkit by designing additional building blocks of homologous arms and using CRISPR technology. The reconstructed toolkit was thus entitled YALIcloneHR and designed for gene-specific knockout and integration. To verify the effectiveness of the system, the gene PEX10 was selected as the target for the knockout. This system was subsequently applied for the arachidonic acid production, and the reconstructed strain can accumulate 4.8% of arachidonic acid. The toolkit will expand gene editing technology in Y. lipolytica, which would help produce other chemicals derived from acetyl-CoA in the future.


Assuntos
Sistemas CRISPR-Cas , Yarrowia , Sistemas CRISPR-Cas/genética , Yarrowia/genética , Yarrowia/metabolismo , Ácido Araquidônico/metabolismo , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Edição de Genes , Engenharia Metabólica
11.
J Neurochem ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38115597

RESUMO

Diosgenin, a natural steroid saponin, holds promise as a multitarget therapeutic for various diseases, including neurodegenerative conditions. Its efficacy in slowing Alzheimer's disease, Parkinson's disease, multiple sclerosis, and stroke progression has been demonstrated. However, the role of diosgenin in anti-epilepsy and its potential connection to the modulation of the intestinal microbiota remain poorly understood. In this study, exogenous diosgenin significantly mitigated pentylenetetrazole (PTZ)-induced seizures, learning and memory deficits, and hippocampal neuronal injury. 16S ribosomal RNA (16S rRNA) sequencing revealed a reversal in the decrease of Bacteroides and Parabacteroides genera in the PTZ-induced mouse epileptic model following diosgenin treatment. Fecal microbiota transplantation (FMT) experiments illustrated the involvement of diosgenin in modulating gut microbiota and providing neuroprotection against epilepsy. Our results further indicated the repression of enteric glial cells (EGCs) activation and the TLR4-MyD88 pathway, coupled with reduced production of inflammatory cytokines in the colonic lumen, and improved intestinal barrier function in epilepsy mice treated with diosgenin or FMT. This study suggests that diosgenin plays a role in modifying gut microbiota, contributing to the alleviation of intestinal inflammation and neuroinflammation, ultimately inhibiting epilepsy progression in a PTZ-induced mouse model. Diosgenin emerges as a potential therapeutic option for managing epilepsy and its associated comorbidities.

12.
J Med Virol ; 95(1): e28139, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36089764

RESUMO

The coronavirus disease 2019 (COVID-19) pandemic caused extensive loss of life worldwide. Further, the COVID-19 and influenza mix-infection had caused great distress to the diagnosis of the disease. To control illness progression and limit viral spread within the population, a real-time reverse-transcription PCR (RT-PCR) assay for early diagnosis of COVID-19 was developed, but detection was time-consuming (4-6 h). To improve the diagnosis of COVID-19 and influenza, we herein developed a recombinase polymerase amplification (RPA) method for simple and rapid amplification of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19 and Influenza A (H1N1, H3N2) and B (influenza B). Genes encoding the matrix protein (M) for H1N1, and the hemagglutinin (HA) for H3N2, and the polymerase A (PA) for Influenza B, and the nucleocapsid protein (N), the RNA-dependent-RNA polymerase (RdRP) in the open reading frame 1ab (ORF1ab) region, and the envelope protein (E) for SARS-CoV-2 were selected, and specific primers were designed. We validated our method using SARS-CoV-2, H1N1, H3N2 and influenza B plasmid standards and RNA samples extracted from COVID-19 and Influenza A/B (RT-PCR-verified) positive patients. The method could detect SARS-CoV-2 plasmid standard DNA quantitatively between 102 and 105 copies/ml with a log linearity of 0.99 in 22 min. And this method also be very effective in simultaneous detection of H1N1, H3N2 and influenza B. Clinical validation of 100 cases revealed a sensitivity of 100% for differentiating COVID-19 patients from healthy controls when the specificity was set at 90%. These results demonstrate that this nucleic acid testing method is advantageous compared with traditional PCR and other isothermal nucleic acid amplification methods in terms of time and portability. This method could potentially be used for detection of SARS-CoV-2, H1N1, H3N2 and influenza B, and adapted for point-of-care (POC) detection of a broad range of infectious pathogens in resource-limited settings.


Assuntos
COVID-19 , Vírus da Influenza A Subtipo H1N1 , Influenza Humana , Ácidos Nucleicos , Humanos , COVID-19/diagnóstico , Influenza Humana/diagnóstico , SARS-CoV-2/genética , Recombinases , Vírus da Influenza A Subtipo H1N1/genética , Vírus da Influenza A Subtipo H3N2/genética , Sensibilidade e Especificidade , Nucleotidiltransferases , RNA , Técnicas de Amplificação de Ácido Nucleico/métodos , RNA Viral/genética
13.
Opt Express ; 31(2): 1641-1655, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36785195

RESUMO

At present, a real objects-based full-color holographic system usually uses a digital single-lens reflex (DSLR) camera array or depth camera to collect data. It then relies on a spatial light modulator to modulate the input light source for the reconstruction of the 3-D scene of the real objects. However, the main challenges the high-quality holographic 3-D display faced were the limitation of generation speed and the low accuracy of the computer-generated holograms. This research generates more effective and accurate point cloud data by developing an RGB-D salient object detection model in the acquisition unit. In addition, a divided point cloud gridding method is proposed to enhance the computing speed of hologram generation. In the RGB channels, we categorized each object point into depth grids with identical depth values. The depth girds are divided into M × N parts, and only the effective parts will be calculated. Compared with traditional methods, the calculation time is dramatically reduced. The feasibility of our proposed approach is established through experiments.

14.
Phys Rev Lett ; 130(25): 253202, 2023 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-37418708

RESUMO

We report the experimental observation of quantum interference in the nuclear wave-packet dynamics driving ultrafast excitation-energy transfer in argon dimers below the threshold of interatomic Coulombic decay (ICD). Using time-resolved photoion-photoion coincidence spectroscopy and quantum dynamics simulations, we reveal that the electronic relaxation dynamics of the inner-valence 3s hole on one atom leading to a 4s or 4p excitation on the other one is influenced by nuclear quantum dynamics in the initial state, giving rise to a deep, periodic modulation on the kinetic-energy-release (KER) spectra of the coincident Ar^{+}-Ar^{+} ion pairs. Moreover, the time-resolved KER spectra show characteristic fingerprints of quantum interference effects during the energy-transfer process. Our findings pave the way to elucidating quantum-interference effects in ultrafast charge- and energy-transfer dynamics in more complex systems, such as molecular clusters and solvated molecules.


Assuntos
Polímeros , Transferência de Energia
15.
J Vasc Interv Radiol ; 34(7): 1135-1142, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36906134

RESUMO

PURPOSE: To analyze the risk factors for access-related adverse events (AEs) of the preclose technique in thoracic endovascular aortic repair (TEVAR). MATERIALS AND METHODS: Ninety-one patients with Stanford type B aortic dissection who underwent the preclose technique in TEVAR between January 2013 and December 2021 were included. According to the occurrence of access-related AEs, the patients were divided into 2 groups: those with AE and those without AE. Age, sex, combined diseases, body mass index, skin depth, femoral artery diameter, access calcification, iliofemoral artery tortuosity, and sheath size were recorded for risk factor analysis. The sheath-to-femoral artery ratio (SFAR), the ratio of the femoral artery inner diameter (in millimeters) to the sheath's outer diameter (in millimeters), was also included in the analysis. RESULTS: SFAR was identified as an independent risk factor for AEs using multivariable logistic analysis (odds ratio, 251.748; 95% CI, 7.004-9,048.534; P = .002). The cutoff value of SFAR was 0.85 and was related to a higher incidence of access-related AEs (5.2% vs 33.3%, P = .001), especially to a higher stenosis rate (0.0% vs 21.2%, P = .001). CONCLUSIONS: SFAR is an independent risk factor for access-related AEs of preclose in TEVAR with a cutoff value of 0.85. SFAR could be a new criterion for preoperative access evaluation in high-risk patients that may allow the detection and treatment of access-related AEs at the early stage.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Correção Endovascular de Aneurisma , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Fatores de Risco , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/métodos , Estudos Retrospectivos , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/etiologia , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/métodos
16.
Fish Shellfish Immunol ; 137: 108732, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37044186

RESUMO

Polymeric immunoglobulin receptor (pIgR) can bind and transport immunoglobulins (Igs), thus playing a role in mucosal immunity. In this study, pIgR gene was cloned in mandarin fish, Siniperca chuatsi, with the open reading frame (ORF) of 1011 bp, encoding 336 amino acids. The pIgR protein consists of a signal peptide, an extracellular domain, a transmembrane domain and an intracellular region, with the presence of two Ig-like domains (ILDs) in the extracellular domain, as reported in other species of fish. The pIgR gene was expressed in all organs/tissues of healthy mandarin fish, with higher level observed in liver and spleen. Following the immersion infection of Flavobacterium columnare, pIgR transcripts were detected in immune related, especially mucosal tissues, with significantly increased transcription during the first two days of infection. Through transfection of plasmids expressing pIgR, IgT and IgM, pIgR was found to be interacted with IgT and IgM as revealed by co-immunoprecipitation and immunofluorescence.


Assuntos
Doenças dos Peixes , Perciformes , Receptores de Imunoglobulina Polimérica , Animais , Sequência de Aminoácidos , Alinhamento de Sequência , Receptores de Imunoglobulina Polimérica/genética , Peixes , Clonagem Molecular , Imunoglobulina M/genética , Proteínas de Peixes
17.
Acta Pharmacol Sin ; 44(12): 2455-2468, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37596398

RESUMO

Renal tubulointerstitial fibrosis (TIF) is considered as the final convergent pathway of diabetic nephropathy (DN) without effective therapies currently. MiRNAs play a key role in fibrotic diseases and become promising therapeutic targets for kidney diseases, while miRNA clusters, formed by the cluster arrangement of miRNAs on chromosomes, can regulate diverse biological functions alone or synergistically. In this study, we developed clustered miR-23a/27a/26a-loaded skeletal muscle satellite cells-derived exosomes (Exos) engineered with RVG peptide, and investigated their therapeutic efficacy in a murine model of DN. Firstly, we showed that miR-23a-3p, miR-26a-5p and miR-27a-3p were markedly decreased in serum samples of DN patients using miRNA sequencing. Meanwhile, we confirmed that miR-23a-3p, miR-26a-5p and miR-27a-3p were primarily located in proximal renal tubules and highly negatively correlated with TIF in db/db mice at 20 weeks of age. We then engineered RVG-miR-23a/27a/26a cluster loaded Exos derived from muscle satellite cells, which not only enhanced the stability of miR-23a/27a/26a cluster, but also efficiently delivered more miR-23a/27a/26a cluster homing to the injured kidney. More importantly, administration of RVG-miR-23a/27a/26a-Exos (100 µg, i.v., once a week for 8 weeks) significantly ameliorated tubular injury and TIF in db/db mice at 20 weeks of age. We revealed that miR-23a/27a/26a-Exos enhanced antifibrotic effects by repressing miRNA cluster-targeting Lpp simultaneously, as well as miR-27a-3p-targeting Zbtb20 and miR-26a-5p-targeting Klhl42, respectively. Knockdown of Lpp by injection of AAV-Lpp-RNAi effectively ameliorated the progression of TIF in DN mice. Taken together, we established a novel kidney-targeting Exo-based delivery system by manipulating the miRNA-23a/27a/26a cluster to ameliorate TIF in DN, thus providing a promising therapeutic strategy for DN.


Assuntos
Nefropatias Diabéticas , Exossomos , MicroRNAs , Células Satélites de Músculo Esquelético , Animais , Humanos , Camundongos , Diabetes Mellitus/terapia , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/terapia , Exossomos/metabolismo , Fibrose , MicroRNAs/metabolismo , MicroRNAs/farmacologia , MicroRNAs/uso terapêutico , Células Satélites de Músculo Esquelético/metabolismo , Complicações do Diabetes/terapia
18.
J Opt Soc Am A Opt Image Sci Vis ; 40(4): B1-B7, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37132944

RESUMO

In this study, a 3D salient object detection model is built at the acquisition step in the full-color holographic system, and a deep network architecture U 2-reverse attention and residual learning (RAS) algorithm is proposed for salient object detection to obtain more efficient and accurate point cloud information. In addition, we also use the point cloud gridding method to improve the hologram generation speed. Compared with the traditional region of interest method, RAS algorithm, and U 2-Net algorithm, the computational complexity is significantly reduced. Finally, the feasibility of this method is proved by experiments.

19.
Nano Lett ; 22(18): 7336-7342, 2022 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-36122383

RESUMO

Lithium intercalation has become a versatile tool for realizing emergent quantum phenomena in two-dimensional (2D) materials. However, the insertion of lithium ions may be accompanied by the creation of wrinkles and cracks, which prevents the material from manifesting its intrinsic properties under substantial charge injection. By using the recently developed ion backgating technique, we successfully realize lateral intercalation in 1T-TiSe2 and 2H-NbSe2, which shows substantially improved sample homogeneity. The homogeneity at high lithium doping is not only demonstrated via low-temperature transport measurements but also directly visualized by topographical imaging through in situ atomic force microscopy (AFM). The application of lateral intercalation to a broad spectrum of 2D materials can greatly facilitate the search for exotic quantum phenomena.

20.
Beijing Da Xue Xue Bao Yi Xue Ban ; 55(5): 857-864, 2023 Oct 18.
Artigo em Chinês | MEDLINE | ID: mdl-37807740

RESUMO

OBJECTIVE: To explore the impacts of delayed ureteral stent removal on the quality of life (QoL) and mental health of urinary calculi postoperative patients due to the corona virus disease 2019(COVID-19) pandemic. METHODS: The demographic and clinical data of patients with ureteral stent placement after urinary endoscopic lithotripsy and returned to Peking University People's Hospital for stent removal from December 2019 to June 2020 were collected. Ureteral stent symptoms questionnaire (USSQ) score and the outcome 20-item self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were collected to estimate the QoL and mental status. The USSQ consisted of 44 questions in 6 domains (including urinary symptom, physical pain, general health, work performance, sexual function, and ureteral stent related infection). For most questions in each domain, its score was a five-point Likert-type scale from 1 to 5, and a small proportion of questions was quantified by 1 to 4 or 1 to 7 scale. SAS and SDS both contained 20 questions used to assess a patient's level of anxiety and depression. Its scoring for each item was on a four-point Likert-type scale from 1 to 4. A total score (ranging from 20 to 80) was the main statistical indicator. The level of clinical anxiety and depression was quantified by using standard scores (total score multiplied by 1.25 to produce integers). And the multi-group structural equation model was constructed by analysis of moment structure (AMOS) analysis. RESULTS: Overall, 71 patients were enrolled for analysis. It was found that the median duration of ureteral stent time differed significantly between the control and delayed groups for 32 (30, 33) d and 94.5 (88, 103) d, respectively. The delayed group resulted in higher scores in the USSQ multidimensional, which included urinary symptoms, general health, work performance and ureteral stent related infections. Anxiety and depression were also significantly serious in the delayed group than in the control group. A longer indwelling time of a ureteral stent could exacerbate the effects of urinary symptoms and physical pain on work performance (P=0.029 < 0.05). Among them, the patients with severe urinary symptoms leading to poor work performance were most significantly affected by prolonged ureteral stent duration time (CR=2.619>1.96). CONCLUSION: Patients with delayed ureteral stent removal due to the COVID-19 had resulted in worse QoL and mental status. Stents related symptoms are more severe in patients with higher anxiety and depression degree during COVID-19. To improve the QoL and mental health of patients after urinary calculi surgery during COVID-19, it is still not recommended to prolong the stent duration time or corresponding intervention measures should be taken.


Assuntos
COVID-19 , Ureter , Cálculos Ureterais , Doenças Ureterais , Cálculos Urinários , Humanos , Qualidade de Vida , Pandemias , COVID-19/epidemiologia , Ureter/cirurgia , Dor , Stents , Inquéritos e Questionários
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