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1.
Cell ; 171(4): 849-864.e25, 2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29100074

RESUMO

Angiogenin (ANG) is a secreted ribonuclease (RNase) with cell-type- and context-specific roles in growth, survival, and regeneration. Although these functions require receptor-mediated endocytosis and appropriate subcellular localization, the identity of the cell surface receptor remains undefined. Here, we show that plexin-B2 (PLXNB2) is the functional receptor for ANG in endothelial, cancer, neuronal, and normal hematopoietic and leukemic stem and progenitor cells. Mechanistically, PLXNB2 mediates intracellular RNA processing that contribute to cell growth, survival, and regenerative capabilities of ANG. Antibodies generated against the ANG-binding site on PLXNB2 restricts ANG activity in vitro and in vivo, resulting in inhibition of established xenograft tumors, ANG-induced neurogenesis and neuroprotection, levels of pro-self-renewal transcripts in hematopoietic and patient-derived leukemic stem and progenitor cells, and reduced progression of leukemia in vivo. PLXNB2 is therefore required for the physiological and pathological functions of ANG and has significant therapeutic potential in solid and hematopoietic cancers and neurodegenerative diseases.


Assuntos
Proteínas do Tecido Nervoso/metabolismo , Ribonuclease Pancreático/metabolismo , Animais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Feminino , Glioblastoma/metabolismo , Glioblastoma/patologia , Células-Tronco Hematopoéticas/metabolismo , Xenoenxertos , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Transplante de Neoplasias , Proteínas do Tecido Nervoso/antagonistas & inibidores , Neurogênese , Ribonuclease Pancreático/química
2.
Cell ; 166(4): 894-906, 2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27518564

RESUMO

Regulation of stem and progenitor cell populations is critical in the development, maintenance, and regeneration of tissues. Here, we define a novel mechanism by which a niche-secreted RNase, angiogenin (ANG), distinctively alters the functional characteristics of primitive hematopoietic stem/progenitor cells (HSPCs) compared with lineage-committed myeloid-restricted progenitor (MyePro) cells. Specifically, ANG reduces the proliferative capacity of HSPC while simultaneously increasing proliferation of MyePro cells. Mechanistically, ANG induces cell-type-specific RNA-processing events: tRNA-derived stress-induced small RNA (tiRNA) generation in HSPCs and rRNA induction in MyePro cells, leading to respective reduction and increase in protein synthesis. Recombinant ANG protein improves survival of irradiated animals and enhances hematopoietic regeneration of mouse and human HSPCs in transplantation. Thus, ANG plays a non-cell-autonomous role in regulation of hematopoiesis by simultaneously preserving HSPC stemness and promoting MyePro proliferation. These cell-type-specific functions of ANG suggest considerable therapeutic potential.


Assuntos
Células-Tronco Hematopoéticas/metabolismo , Ribonuclease Pancreático/metabolismo , Animais , Proliferação de Células , Hematopoese , Células-Tronco Hematopoéticas/citologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Células Mieloides/metabolismo , RNA de Transferência/metabolismo , RNA não Traduzido/metabolismo
3.
Plant Cell ; 36(4): 919-940, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38180963

RESUMO

Soil salinity results in oxidative stress and heavy losses to crop production. The S-acylated protein SALT TOLERANCE RECEPTOR-LIKE CYTOPLASMIC KINASE 1 (STRK1) phosphorylates and activates CATALASE C (CatC) to improve rice (Oryza sativa L.) salt tolerance, but the molecular mechanism underlying its S-acylation involved in salt signal transduction awaits elucidation. Here, we show that the DHHC-type zinc finger protein DHHC09 S-acylates STRK1 at Cys5, Cys10, and Cys14 and promotes salt and oxidative stress tolerance by enhancing rice H2O2-scavenging capacity. This modification determines STRK1 targeting to the plasma membrane or lipid nanodomains and is required for its function. DHHC09 promotes salt signaling from STRK1 to CatC via transphosphorylation, and its deficiency impairs salt signal transduction. Our findings demonstrate that DHHC09 S-acylates and anchors STRK1 to the plasma membrane to promote salt signaling from STRK1 to CatC, thereby regulating H2O2 homeostasis and improving salt stress tolerance in rice. Moreover, overexpression of DHHC09 in rice mitigates grain yield loss under salt stress. Together, these results shed light on the mechanism underlying the role of S-acylation in RLK/RLCK-mediated salt signal transduction and provide a strategy for breeding highly salt-tolerant rice.


Assuntos
Oryza , Tolerância ao Sal , Tolerância ao Sal/genética , Oryza/metabolismo , Peróxido de Hidrogênio/metabolismo , Homeostase , Dedos de Zinco , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
4.
Plant J ; 120(2): 769-787, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39265046

RESUMO

Mature embryos are the main explants of tissue culture used in rice transgenic technology. However, the mechanism of mature embryo callus formation remains unclear. In this study, a microRNA-mediated gene regulatory network of rice calli was established using degradome sequencing. We identified a microRNA, OsmiR408, that regulates the formation of the callus derived from the mature rice embryo. OsUCLACYANIN 30 (OsUCL 30), a target gene of OsmiR408, was the most abundant cleavage mRNA in rice callus. OsUCL17 was verified as a target gene of OsmiR408 using RNA ligase-mediated 5'-RACE. In analysis of the OsmiR408 promoter reporter line and pri-miR408 transcript level, the promoter activity and transcript level of MIR408 were increased dramatically during callus formation. In phenotypic observations, OsmiR408 knockout caused severe defects in mature embryo callus formation, whereas OsmiR408 overexpression promoted callus formation. Transcriptome analysis demonstrated that OsUCLs and certain genes related to the plant hormone signal transduction and phenylpropanoid-flavonoid biosynthesis pathway had different differential expression patterns between OsmiR408 knockout and overexpression calli. Thus, OsmiR408 may regulate callus formation mainly by affecting plant hormone signal transduction and phenylpropanoid-flavonoid biosynthesis pathway. Our findings provide insight into OsmiR408/UCLs module function in callus formation.


Assuntos
Regulação da Expressão Gênica de Plantas , MicroRNAs , Oryza , Sementes , Oryza/genética , Oryza/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Sementes/genética , Sementes/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , RNA de Plantas/genética , Reguladores de Crescimento de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Perfilação da Expressão Gênica
5.
J Am Chem Soc ; 146(1): 84-88, 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38157411

RESUMO

Alkali metal-based metal-organic frameworks (MOFs) with permanent porosity are scarce because of their high tendency to coordinate with solvents such as water. However, these MOFs are lightweight and bear gravimetric benefits for gas adsorption related applications. In this study, we present the successful construction of a microporous MOF, designated as HIAM-111, built solely on sodium ions by using an octacarboxylate linker. The structure of HIAM-111 is based on 8-connected Na4 clusters and exhibits a novel topology with an underlying 32,42,8-c net. Remarkably, HAM-111 possesses a robust and highly porous framework with a BET surface area of 1561 m2/g, significantly surpassing that of the previously reported Na-MOFs. Further investigations demonstrate that HIAM-111 is capable of separating C2H2/CO2 and purifying C2H4 directly from C2H4/C2H2/C2H6 with high adsorption capacities. The current work may shed light on the rational design of robust and porous MOFs based on alkali metals.

6.
EMBO J ; 39(13): e103325, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32510170

RESUMO

Communication between myeloid cells and epithelium plays critical role in maintaining intestinal epithelial barrier integrity. Myeloid cells interact with intestinal epithelial cells (IECs) by producing various mediators; however, the molecules mediating their crosstalk remain incompletely understood. Here, we report that deficiency of angiogenin (Ang) in mouse myeloid cells caused impairment of epithelial barrier integrity, leading to high susceptibility to DSS-induced colitis. Mechanistically, myeloid cell-derived angiogenin promoted IEC survival and proliferation through plexin-B2-mediated production of tRNA-derived stress-induced small RNA (tiRNA) and transcription of ribosomal RNA (rRNA), respectively. Moreover, treatment with recombinant angiogenin significantly attenuated the severity of experimental colitis. In human samples, the expression of angiogenin was significantly down-regulated in patients with inflammatory bowel disease (IBD). Collectively, we identified, for the first time to our knowledge, a novel mediator of myeloid cell-IEC crosstalk in maintaining epithelial barrier integrity, suggesting that angiogenin may serve as a new preventive agent and therapeutic target for IBD.


Assuntos
Mucosa Intestinal/metabolismo , Células Mieloides/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Ribonuclease Pancreático/metabolismo , Transdução de Sinais , Animais , Comunicação Celular/genética , Colite/induzido quimicamente , Colite/genética , Colite/metabolismo , Sulfato de Dextrana/toxicidade , Humanos , Mucosa Intestinal/patologia , Camundongos , Camundongos Knockout , Células Mieloides/patologia , Proteínas do Tecido Nervoso/genética , RNA Ribossômico/genética , RNA Ribossômico/metabolismo , Ribonuclease Pancreático/genética
7.
Planta ; 260(1): 30, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38879830

RESUMO

MAIN CONCLUSION: Ectopic expression of OsWOX9A induces narrow adaxially rolled rice leaves with larger bulliform cells and fewer large veins, probably through regulating the expression of auxin-related and expansin genes. The WUSCHEL-related homeobox (WOX) family plays a pivotal role in plant development by regulating genes involved in various aspects of growth and differentiation. OsWOX9A (DWT1) has been linked to tiller growth, uniform plant growth, and flower meristem activity. However, its impact on leaf growth and development in rice has not been studied. In this study, we investigated the biological role of OsWOX9A in rice growth and development using transgenic plants. Overexpression of OsWOX9A conferred narrow adaxially rolled rice leaves and altered plant architecture. These plants exhibited larger bulliform cells and fewer larger veins compared to wild-type plants. OsWOX9A overexpression also reduced plant height, tiller number, and seed-setting rate. Comparative transcriptome analysis revealed several differentially expressed auxin-related and expansin genes in OsWOX9A overexpressing plants, consistent with their roles in leaf and plant development. These results indicate that the ectopic expression of OsWOX9A may have multiple effects on the development and growth of rice, providing a more comprehensive picture of how the WOX9 subfamily contributes to leaf development and plant architecture.


Assuntos
Expressão Ectópica do Gene , Regulação da Expressão Gênica de Plantas , Oryza , Folhas de Planta , Proteínas de Plantas , Plantas Geneticamente Modificadas , Oryza/genética , Oryza/crescimento & desenvolvimento , Oryza/anatomia & histologia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/anatomia & histologia , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Perfilação da Expressão Gênica
8.
J Magn Reson Imaging ; 59(4): 1394-1406, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37392060

RESUMO

BACKGROUND: Deep stromal invasion (DSI) is one of the predominant risk factors that determined the types of radical hysterectomy (RH). Thus, the accurate assessment of DSI in cervical adenocarcinoma (AC)/adenosquamous carcinoma (ASC) can facilitate optimal therapy decision. PURPOSE: To develop a nomogram to identify DSI in cervical AC/ASC. STUDY TYPE: Retrospective. POPULATION: Six hundred and fifty patients (mean age of 48.2 years) were collected from center 1 (primary cohort, 536), centers 2 and 3 (external validation cohorts 1 and 2, 62 and 52). FIELD STRENGTH/SEQUENCE: 5-T, T2-weighted imaging (T2WI, SE/FSE), diffusion-weighted imaging (DWI, EPI), and contrast-enhanced T1-weighted imaging (CE-T1WI, VIBE/LAVA). ASSESSMENT: The DSI was defined as the outer 1/3 stromal invasion on pathology. The region of interest (ROI) contained the tumor and 3 mm peritumoral area. The ROIs of T2WI, DWI, and CE-T1WI were separately imported into Resnet18 to calculate the DL scores (TDS, DDS, and CDS). The clinical characteristics were retrieved from medical records or MRI data assessment. The clinical model and nomogram were constructed by integrating clinical independent risk factors only and further combining DL scores based on primary cohort and were validated in two external validation cohorts. STATISTICAL TESTS: Student's t-test, Mann-Whitney U test, or Chi-squared test were used to compare differences in continuous or categorical variables between DSI-positive and DSI-negative groups. DeLong test was used to compare AU-ROC values of DL scores, clinical model, and nomogram. RESULTS: The nomogram integrating menopause, disruption of cervical stromal ring (DCSRMR), DDS, and TDS achieved AU-ROCs of 0.933, 0.807, and 0.817 in evaluating DSI in primary and external validation cohorts. The nomogram had superior diagnostic ability to clinical model and DL scores in primary cohort (all P < 0.0125 [0.05/4]) and CDS (P = 0.009) in external validation cohort 2. DATA CONCLUSION: The nomogram achieved good performance for evaluating DSI in cervical AC/ASC. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Aprendizado Profundo , Neoplasias do Colo do Útero , Feminino , Humanos , Pessoa de Meia-Idade , Nomogramas , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/terapia , Estudos Retrospectivos , Neoplasias do Colo do Útero/patologia , Imageamento por Ressonância Magnética/métodos , Adenocarcinoma/patologia
9.
Eur Radiol ; 34(2): 852-862, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37610442

RESUMO

OBJECTIVE: To develop a comprehensive nomogram based on MRI intra- and peritumoral radiomics signatures and independent risk factors for predicting parametrial invasion (PMI) in patients with early-stage cervical adenocarcinoma (AC) and adenosquamous carcinoma (ASC). METHODS: A total of 460 patients with IB to IIB cervical AC and ASC who underwent preoperative MRI examination and radical trachelectomy/hysterectomy were retrospectively enrolled and divided into primary, internal validation, and external validation cohorts. The original (Ori) and wavelet (Wav)-transform features were extracted from the volumetric region of interest of the tumour (ROI-T) and 3mm- and 5mm-peritumoral rings (ROI-3 and ROI-5), respectively. Then the Ori and Ori-Wav feature-based radiomics signatures from the tumour (RST) and 3 mm- and 5 mm-peritumoral regions (RS3 and RS5) were independently built and their diagnostic performances were compared to select the optimal ones. Finally, the nomogram was developed by integrating optimal intra- and peritumoral signatures and clinical independent risk factors based on multivariable logistic regression analysis. RESULTS: FIGO stage, disruption of the cervical stromal ring on MRI (DCSRMR), parametrial invasion on MRI (PMIMR), and serum CA-125 were identified as independent risk factors. The nomogram constructed by integrating independent risk factors, Ori-Wav feature-based RST, and RS5 yielded AUCs of 0.874 (0.810-0.922), 0.885 (0.834-0.924), and 0.966 (0.887-0.995) for predicting PMI in the primary, internal and external validation cohorts, respectively. Furthermore, the nomogram was superior to radiomics signatures and clinical model for predicting PMI in three cohorts. CONCLUSION: The nomogram can preoperatively, accurately, and noninvasively predict PMI in patients with early-stage cervical AC and ASC. CLINICAL RELEVANCE STATEMENT: The nomogram can preoperatively, accurately, and noninvasively predict PMI and facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy in patients with early-stage cervical AC and ASC. KEY POINTS: The accurate preoperative prediction of PMI in early-stage cervical AC and ASC can facilitate precise treatment decisions regarding chemoradiotherapy or radical hysterectomy. The nomogram integrating independent risk factors, Ori-Wav feature-based RST, and RS5 can preoperatively, accurately, and noninvasively predict PMI in early-stage cervical AC and ASC. The nomogram was superior to radiomics signatures and clinical model for predicting PMI in early-stage cervical AC and ASC.


Assuntos
Adenocarcinoma , Carcinoma Adenoescamoso , Neoplasias do Colo do Útero , Humanos , Feminino , Nomogramas , Carcinoma Adenoescamoso/diagnóstico por imagem , Carcinoma Adenoescamoso/patologia , Carcinoma Adenoescamoso/cirurgia , Estudos Retrospectivos , Radiômica , Imageamento por Ressonância Magnética , Neoplasias do Colo do Útero/patologia , Adenocarcinoma/patologia
10.
Bioorg Med Chem ; 110: 117793, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38917622

RESUMO

The pathogenic role of anti-phospholipase A2 receptor (PLA2R) antibodies in primary membranous nephropathy (MN) has been well-established. This study aimed to identify potential small-molecule inhibitors against the PLA2R-antibody interaction, offering potential therapeutic benefits. A comprehensive screening of over 4000 small-molecule compounds was conducted by ELISA to assess their inhibitory effects on the binding between the immobilized full-length extracellular PLA2R and its antibodies. The affinity of anti-PLA2R IgG from MN patients and the inhibitory efficacy of each compound were evaluated via surface plasmon resonance (SPR). Human podocyte injuries were analyzed using CCK-8 assay, wound healing assay, western blot analysis, and immunofluorescence, after exposure to MN plasma +/- blocking compound. Fifteen compounds were identified as potential inhibitors, demonstrating inhibition rates >20 % for the PLA2R-antibody interaction. Anti-PLA2R IgG exhibited a consistent affinity among patients (KD = 10-8 M). Macrocarpal B emerged as the most potent inhibitor, reducing the antigen-antibody interaction by nearly 30 % in a dose-dependent manner, comparable to the performance of the 31-mer peptide from the CysR domain. Macrocarpal B bound to the immobilized PLA2R with an affinity of 1.47 × 10-6 M, while showing no binding to anti-PLA2R IgG. Human podocytes exposed to MN plasma showed decreased podocin expression, impaired migration function, and reduced cell viability. Macrocarpal B inhibited the binding of anti-PLA2R IgG to podocytes and reduced the cellular injuries.


Assuntos
Receptores da Fosfolipase A2 , Humanos , Receptores da Fosfolipase A2/imunologia , Receptores da Fosfolipase A2/antagonistas & inibidores , Receptores da Fosfolipase A2/metabolismo , Receptores da Fosfolipase A2/química , Podócitos/metabolismo , Podócitos/efeitos dos fármacos , Relação Dose-Resposta a Droga , Estrutura Molecular , Relação Estrutura-Atividade , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/metabolismo , Imunoglobulina G/metabolismo , Imunoglobulina G/imunologia , Imunoglobulina G/química , Ligação Proteica , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia
11.
Hepatobiliary Pancreat Dis Int ; 23(1): 77-82, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37087368

RESUMO

BACKGROUND: Early systemic anticoagulation (SAC) is a common practice in acute necrotizing pancreatitis (ANP), and its impact on in-hospital clinical outcomes had been assessed. However, whether it affects long-term outcomes is unknown. This study aimed to evaluate the effect of SAC on 90-day readmission and other long-term outcomes in ANP patients. METHODS: During January 2013 and December 2018, ANP patients admitted within 7 days from the onset of abdominal pain were screened. The primary outcome was 90-day readmission after discharge. Cox proportional-hazards regression model and mediation analysis were used to define the relationship between early SAC and 90-day readmission. RESULTS: A total of 241 ANP patients were enrolled, of whom 143 received early SAC during their hospitalization and 98 did not. Patients who received early SAC experienced a lower incidence of splanchnic venous thrombosis (SVT) [risk ratio (RR) = 0.40, 95% CI: 0.26-0.60, P < 0.01] and lower 90-day readmission with an RR of 0.61 (95% CI: 0.41-0.91, P = 0.02) than those who did not. For the quality of life, patients who received early SAC had a significantly higher score in the subscale of vitality (P = 0.03) while the other subscales were all comparable between the two groups. Multivariable Cox regression model showed that early SAC was an independent protective factor for 90-day readmission after adjusting for potential confounders with a hazard ratio of 0.57 (95% CI: 0.34-0.96, P = 0.04). Mediation analysis showed that SVT mediated 37.0% of the early SAC-90-day readmission causality. CONCLUSIONS: The application of early SAC may reduce the risk of 90-day readmission in the survivors of ANP patients, and reduced SVT incidence might be the primary contributor.


Assuntos
Pancreatite Necrosante Aguda , Trombose Venosa , Humanos , Readmissão do Paciente , Estudos Retrospectivos , Pancreatite Necrosante Aguda/diagnóstico , Pancreatite Necrosante Aguda/tratamento farmacológico , Qualidade de Vida , Fatores de Risco , Trombose Venosa/tratamento farmacológico , Anticoagulantes/efeitos adversos
12.
Ergonomics ; : 1-21, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38635303

RESUMO

Although trust plays a vital role in human-robot interaction, there is currently a dearth of literature examining the effect of users' openness personality on trust in actual interaction. This study aims to investigate the interaction effects of users' openness and robot reliability on trust. We designed a voice-based walking task and collected subjective trust ratings, task metrics, eye-tracking data, and fNIRS signals from users with different openness to unravel the psychological intentions, task performance, visual behaviours, and cerebral activations underlying trust. The results showed significant interaction effects. Users with low openness exhibited lower subjective trust, more fixations, and higher activation of rTPJ in the highly reliable condition than those with high openness. The results suggested that users with low openness might be more cautious and suspicious about the highly reliable robot and allocate more visual attention and neural processing to monitor and infer robot status than users with high openness.


The study could deepen practitioners' understanding of the effect of openness on trust in robots by examining the psychological intention, task performance, visual behaviours, and physiological activations. Moreover, the interaction effect could provide guidelines for designing robots adaptive to users' personalities, and the multimodal method would be practical for measuring trust in interaction.

13.
J Neurochem ; 166(2): 328-345, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37300304

RESUMO

Ischemic stroke (IS) is a detrimental neurological disease with limited treatment options. Astragaloside IV (As-IV) was a promising bioactive constituent in the treatment of IS. However, the functional mechanism remains unclear. Here, IS cell and mouse models were established by oxygen glucose deprivation/re-oxygenation (OGD/R) and middle cerebral artery occlusion (MCAO). Quantitative reverse transcription PCR (RT-qPCR), Western blotting, or Immunofluorescence staining measured related gene and protein expression of cells or mice brain tissues, and the results revealed altered expression of acyl-CoA synthetase long-chain family member 4 (Acsl4), fat mass and obesity-associated (Fto), and activation transcription factor 3 (Atf3) after treatment with As-IV. Then, increased N6 -methyladenosine (m6 A) levels caused OGD/R or MCAO were reduced by As-IV according to the data from methylated RNA immunoprecipitation (MeRIP)-qPCR and dot blot assays. Moreover, through a series of functional experiments such as observing mitochondrial changes under transmission electron microscopy (TEM), evaluating cell viability by cell counting kit-8 (CCK-8), analyzing infract area of brain tissues by 2,3,5-triphenyltetrazolium chloride (TTC) staining, measuring levels of malondialdehyde (MDA), lactate dehydrogenase (LDH), Fe2+ , solute carrier family 7 member 11 (Slc7a11) and glutathione peroxidase 4 (Gpx4) and concentration of glutathione (GSH), we found that Fto knockdown, Acsl4 overexpression or Atf3 knockdown promoted the viability of OGD/R cells, inhibited cell ferroptosis, reduced infract size, while As-IV treatment or Fto overexpression reversed these changes. In mechanism, the interplays of YTH N6 -methyladenosine RNA-binding protein 3 (Ythdf3)/Acsl4 and Atf3/Fto were analyzed by RNA-pull down, RNA immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. Fto regulated the m6 A levels of Acsl4. Ythdf3 bound to Acsl4, and modulated its levels through m6 A modification. Atf3 bound to Fto and positively regulated its levels. Overall, As-IV promoted the transcription of Fto by upregulating Atf3, resulting in decreased m6 A levels of Acsl4, thus, improving neuronal injury in IS by inhibiting ferroptosis.


Assuntos
Ferroptose , AVC Isquêmico , Animais , Camundongos , Adenosina , Imunoprecipitação da Cromatina , Glutationa , Ligases
14.
BMC Plant Biol ; 23(1): 256, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37189032

RESUMO

BACKGROUND: Heat stress threatens rice yield and quality at flowering stage. In this study, average relative seed setting rate under heat stress (RHSR) and genotypes of 284 varieties were used for a genome-wide association study. RESULTS: We identified eight and six QTLs distributed on chromosomes 1, 3, 4, 5, 7 and 12 in the full population and indica, respectively. qHTT4.2 was detected in both the full population and indica as an overlapping QTL. RHSR was positively correlated with the accumulation of heat-tolerant superior alleles (SA), and indica accession contained at least two heat-tolerant SA with average RHSR greater than 43%, meeting the needs of stable production and heat-tolerant QTLs were offer yield basic for chalkiness degree, amylose content, gel consistency and gelatinization temperature. Chalkiness degree, amylose content, and gelatinization temperature under heat stress increased with accumulation of heat-tolerant SA. Gel consistency under heat stress decreased with polymerization of heat-tolerant SA. The study revealed qHTT4.2 as a stable heat-tolerant QTL that can be used for breeding that was detected in the full population and indica. And the grain quality of qHTT4.2-haplotype1 (Hap1) with chalk5, wx, and alk was better than that of qHTT4.2-Hap1 with CHALK5, WX, and ALK. Twelve putative candidate genes were identified for qHTT4.2 that enhance RHSR based on gene expression data and these genes were validated in two groups. Candidate genes LOC_Os04g52830 and LOC_Os04g52870 were induced by high temperature. CONCLUSIONS: Our findings identify strong heat-tolerant cultivars and heat-tolerant QTLs with great potential value to improve rice tolerance to heat stress, and suggest a strategy for the breeding of yield-balance-quality heat-tolerant crop varieties.


Assuntos
Oryza , Oryza/genética , Oryza/metabolismo , Estudo de Associação Genômica Ampla , Alelos , Amilose/metabolismo , Melhoramento Vegetal , Receptores Proteína Tirosina Quinases/genética
15.
Small ; 19(17): e2207876, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36703526

RESUMO

Covalent organic frameworks (COFs) are a unique new class of porous materials that arrange building units into periodic ordered frameworks through strong covalent bonds. Accompanied with structural rigidity and well-defined geometry, heteroacene-based COFs have natural advantages in constructing COFs with high stability and crystallinity. Heteroacene-based COFs usually have high physical and chemical properties, and their extended π-conjugation also leads to relatively low energy gap, effectively promoting π-electron delocalization between network units. Owing to excellent electron-withdrawing or -donating ability, heteroacene units have incomparable advantages in the preparation of donor-acceptor type COFs. Therefore, the physicochemical robust and fully conjugated heteroacene-based COFs solve the problem of traditional COFs lacking π-π interaction and chemical stability. In recent years, significant breakthroughs are made in this field, the choice of various linking modes and building blocks has fundamentally ensured the final applications of COFs. It is of great significance to summarize the heteroacene-based COFs for improving its complexity and controllability. This review first introduces the linkages in heteroacene-based COFs, including reversible and irreversible linkages. Subsequently, some representative building blocks are summarized, and their related applications are especially emphasized. Finally, conclusion and perspectives for future research on heteroacene-based COFs are presented.

16.
Opt Express ; 31(19): 30171-30183, 2023 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-37710565

RESUMO

The spectral features of high-order harmonic spectra can provide rich information for probing the structure and dynamics of molecules in intense laser fields. We theoretically study the high harmonic spectrum with the laser polarization direction perpendicular to the N2O molecule and find a minimum structure in the plateau region of the harmonic spectrum. Through analyzing the time-dependent survival probability of different electronic orbitals and the time-dependent wave packet evolution, it is found that this minimum position is caused by the harmonic interference of HOMO a, HOMO-1, and HOMO-3 a orbitals. Moreover, this interference minimum is discovered over a wide frequency range of 0.087 a.u. to 0.093 a.u., as well as a range of driving laser intensities with peak amplitudes between 0.056 a.u. and 0.059 a.u.. This study sheds light on the multi-electron effects and ultrafast dynamics of inner-shell electrons in intense laser pulses, which are crucial for understanding and controlling chemical reactions in molecules.

17.
J Org Chem ; 88(18): 13142-13148, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37654092

RESUMO

With the increasing relevance of organophosphorus fluorine compounds in the pharmaceutical industry, their synthesis has attracted great attention. Herein, we report an efficient fluorination strategy for P(O)-H and P(O)-OH compounds using sulfuryl fluoride as the fluorination reagent. Avoiding the use of expensive or complex prepreparation reagents for fluoridation, this strategy could conveniently construct a variety of fluorophosphonates and phosphonofluoridates under mild conditions and without additional oxidants.

18.
J Vasc Interv Radiol ; 34(11): 1875-1881.e3, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37460059

RESUMO

PURPOSE: To evaluate the physical and cognitive functions of patients with stroke who underwent either direct or bridging thrombectomy within 6 hours of stroke onset. MATERIALS AND METHODS: Patients with large vessel occlusion in anterior circulation treated with direct (direct group) or bridging thrombectomy (bridging group) were prospectively analyzed between June 2020 and February 2022. The efficacy outcome was the 3-month modified Rankin Scale (mRS) score, the safety outcome was symptomatic intracranial hemorrhage (sICH), and cognitive function was assessed using the Clinical Dementia Rating (CDR) scale at 6 months after stroke. RESULTS: A total of 125 patients (direct group, n = 75; bridging group, n = 50) who had completed follow-up at 3 months by telephone call were included. No significant differences were observed between the direct and bridging groups in terms of an mRS score of 0-2 (25.3% vs 22.0%, respectively; P = .83), an mRS score of 0-3 (37.3% vs 44.0%, respectively; P = .58), sICH (17.3% vs 14.0%, respectively; P = .80), or 3-month all-cause mortality (36.3% vs 30.0%, respectively; P = .34). Sixty-nine patients (direct group, n = 38; bridging group, n = 31) completed the CDR assessment at 6 months after stroke. There was no significant difference in poststroke dementia, defined as a CDR score of ≥1 point between the direct group (42.1%) and bridging group (22.6%) (P = .12). Ordinal regression analyses showed that the CDR score at 6 months was not associated with treatment type (direct thrombectomy vs bridging thrombectomy). CONCLUSIONS: With regard to physical and cognitive functions at 3 and 6 months, direct thrombectomy was comparable with bridging thrombectomy in patients who were treated within 6 hours of stroke onset.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Humanos , Estudos Prospectivos , Resultado do Tratamento , Trombectomia/efeitos adversos , Hemorragias Intracranianas/etiologia , Isquemia Encefálica/tratamento farmacológico , Fibrinolíticos/uso terapêutico , Terapia Trombolítica/efeitos adversos
19.
Inorg Chem ; 62(34): 13698-13701, 2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37573579

RESUMO

The purification of industrially valuable C2H2 and C2H4 from multicomponent mixtures represents a crucial process in the chemical industry. In this study, we present a copper-based metal-organic framework (L-py-Cu) built on a nitrogen-rich organic linker that is capable of separating C2H2/C2H4/C2H6 and C2H2/CO2 mixtures, therefore producing highly pure C2H4 and C2H2, respectively. L-py-Cu exhibits favorable adsorption of C2H2 and C2H6 over C2H4 and thus achieves one-step C2H4 purification from C2H2/C2H4/C2H6 ternary mixtures, as verified by multicomponent breakthrough measurements. In addition, it can also extract C2H2 from C2H2/CO2 binary mixtures.

20.
Environ Res ; 237(Pt 2): 116999, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37634690

RESUMO

To understand the dynamics of planktonic microbial community and its metabolism processes in subtropical drinking water river-reservoir system with lower man-made pollution loading, this study selected Dongzhen river-reservoir system in Mulan Creek as object to investigate spatial-temporal characteristics of community profile and functional genes involved in biological metabolism, and to analyze the influence of environmental factors. The results indicated that Proteobacteria and Actinobacteria were the most diverse phyla with proportion ranges of 9%-80% in target system, and carbohydrate metabolism (5.76-7.12 × 10-2), amino acid metabolism (5.78-7.21 × 10-2) and energy metabolism (4.07-5.17 × 10-2) were found to be the dominant pathways of biological metabolism. Although there were variations in biological properties both spatially and temporally, seasonal variation had a greater influence on microbial community and biological metabolism, than locational differences. Regarding the role of environmental factors, this study revealed that microbial diversity could be affected by multiple abiotic factors, with total organic carbon, total phosphorus and temperature being more influential (absolute value of standardized regression weights >2.13). Stochastic processes dominated the microbial community assembly (R2 of neutral community model = 0.645), while niche-based processes differences represented by nutrients, temperature and pH level played secondary roles (R > 0.388, P < 0.01). Notably, the synergistic influences among the environmental factors accounted for the higher percentages of community variation (maximum proportion up to 17.6%). Additionally, pH level, temperature, and concentrations of dissolved oxygen, carbon and nitrogen were found to be the significant factors affecting carbon metabolism pathways (P < 0.05), yet only total organic carbon significantly affected on nitrogen transformation (P < 0.05). In summary, the microbial profile in reservoir is not completely dominated by that in feeding river, and planktonic microbial community and its metabolism in subtropical drinking water river-reservoir system are shaped by multiple abiotic and biotic factors with underlying interactions.

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