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1.
Nature ; 628(8007): 313-319, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38570689

RESUMO

Transition metal tellurides (TMTs) have been ideal materials for exploring exotic properties in condensed-matter physics, chemistry and materials science1-3. Although TMT nanosheets have been produced by top-down exfoliation, their scale is below the gram level and requires a long processing time, restricting their effective application from laboratory to market4-8. We report the fast and scalable synthesis of a wide variety of MTe2 (M = Nb, Mo, W, Ta, Ti) nanosheets by the solid lithiation of bulk MTe2 within 10 min and their subsequent hydrolysis within seconds. Using NbTe2 as a representative, we produced more than a hundred grams (108 g) of NbTe2 nanosheets with 3.2 nm mean thickness, 6.2 µm mean lateral size and a high yield (>80%). Several interesting quantum phenomena, such as quantum oscillations and giant magnetoresistance, were observed that are generally restricted to highly crystalline MTe2 nanosheets. The TMT nanosheets also perform well as electrocatalysts for lithium-oxygen batteries and electrodes for microsupercapacitors (MSCs). Moreover, this synthesis method is efficient for preparing alloyed telluride, selenide and sulfide nanosheets. Our work opens new opportunities for the universal and scalable synthesis of TMT nanosheets for exploring new quantum phenomena, potential applications and commercialization.

2.
Genes Dev ; 36(1-2): 38-52, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969824

RESUMO

Barrett's esophagus (BE) and gastric intestinal metaplasia are related premalignant conditions in which areas of human stomach epithelium express mixed gastric and intestinal features. Intestinal transcription factors (TFs) are expressed in both conditions, with unclear causal roles and cis-regulatory mechanisms. Ectopic CDX2 reprogrammed isogenic mouse stomach organoid lines to a hybrid stomach-intestinal state transcriptionally similar to clinical metaplasia; squamous esophageal organoids resisted this CDX2-mediated effect. Reprogramming was associated with induced activity at thousands of previously inaccessible intestine-restricted enhancers, where CDX2 occupied DNA directly. HNF4A, a TF recently implicated in BE pathogenesis, induced weaker intestinalization by binding a novel shadow Cdx2 enhancer and hence activating Cdx2 expression. CRISPR/Cas9-mediated germline deletion of that cis-element demonstrated its requirement in Cdx2 induction and in the resulting activation of intestinal genes in stomach cells. dCas9-conjugated KRAB repression mapped this activity to the shadow enhancer's HNF4A binding site. Altogether, we show extensive but selective recruitment of intestinal enhancers by CDX2 in gastric cells and that HNF4A-mediated ectopic CDX2 expression in the stomach occurs through a conserved shadow cis-element. These findings identify mechanisms for TF-driven intestinal metaplasia and a likely pathogenic TF hierarchy.


Assuntos
Esôfago de Barrett , Fatores de Transcrição , Animais , Esôfago de Barrett/genética , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Fator de Transcrição CDX2/genética , Proteínas de Homeodomínio/genética , Metaplasia/genética , Camundongos , Fatores de Transcrição/genética
3.
Small ; : e2401384, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38940385

RESUMO

Understanding the reconstruction mechanism to rationally design cost-effective electrocatalysts for oxygen evolution reaction (OER) is still challenging. Herein, a defect-rich NiMoO4 precatalyst is used to explore its OER activity and reconstruction mechanism. In situ generated oxygen vacancies, distorted lattices, and edge dislocations expedite the deep reconstruction of NiMoO4 to form polycrystalline Ni (oxy)hydroxides for alkaline oxygen evolution. It only needs ≈230 and ≈285 mV to reach 10 and 100 mA cm-2, respectively. The reconstruction boosted by the redox of Ni is confirmed experimentally by sectionalized cyclic voltammetry activations at different specified potential ranges combined with ex situ characterization techniques. Subsequently, the reconstruction route is presented based on the acid-base electronic theory. Accordingly, the dominant contribution of the adsorbate evolution mechanism to reconstruction during oxygen evolution is revealed. This work develops a novel route to synthesize defect-rich materials and provides new tactics to investigate the reconstruction.

4.
New Phytol ; 242(6): 2604-2619, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38563391

RESUMO

Soil contamination with arsenic (As) can cause phytotoxicity and reduce crop yield. The mechanisms of As toxicity and tolerance are not fully understood. In this study, we used a forward genetics approach to isolate a rice mutant, ahs1, that exhibits hypersensitivity to both arsenate and arsenite. Through genomic resequencing and complementation tests, we identified OsLPD1 as the causal gene, which encodes a putative lipoamide dehydrogenase. OsLPD1 was expressed in the outer cell layer of roots, root meristem cells, and in the mesophyll and vascular tissues of leaves. Subcellular localization and immunoblot analysis demonstrated that OsLPD1 is localized in the stroma of plastids. In vitro assays showed that OsLPD1 exhibited lipoamide dehydrogenase (LPD) activity, which was strongly inhibited by arsenite, but not by arsenate. The ahs1 and OsLPD1 knockout mutants exhibited significantly reduced NADH/NAD+ and GSH/GSSG ratios, along with increased levels of reactive oxygen species and greater oxidative stress in the roots compared with wild-type (WT) plants under As treatment. Additionally, loss-of-function of OsLPD1 also resulted in decreased fatty acid concentrations in rice grain. Taken together, our finding reveals that OsLPD1 plays an important role for maintaining redox homeostasis, conferring tolerance to arsenic stress, and regulating fatty acid biosynthesis in rice.


Assuntos
Arsênio , Ácidos Graxos , Regulação da Expressão Gênica de Plantas , Homeostase , Oryza , Oxirredução , Proteínas de Plantas , Plastídeos , Estresse Fisiológico , Oryza/genética , Oryza/efeitos dos fármacos , Oryza/metabolismo , Homeostase/efeitos dos fármacos , Arsênio/toxicidade , Oxirredução/efeitos dos fármacos , Ácidos Graxos/metabolismo , Ácidos Graxos/biossíntese , Plastídeos/metabolismo , Plastídeos/efeitos dos fármacos , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Mutação/genética , Di-Hidrolipoamida Desidrogenase/metabolismo , Di-Hidrolipoamida Desidrogenase/genética , Espécies Reativas de Oxigênio/metabolismo , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/metabolismo , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Estresse Oxidativo/efeitos dos fármacos , Arsenitos/toxicidade
5.
Thromb J ; 22(1): 4, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178144

RESUMO

BACKGROUND: Primary pulmonary artery sarcoma (PAS) is an extremely rare malignant tumor with a poor prognosis. The clinical manifestations of PAS are diverse, including dyspnea, chest pain, cough, and hemoptysis. The poor prognosis is often due to delayed diagnosis caused by similarity in imaging findings with pulmonary thromboembolism (PTE). These cues of diagnosis include the "wall eclipsing sign", lobulated bulging margins, gadolinium enhancement during MRI imaging, and FDG uptake during PET/CT imaging. However, there are still many misdiagnoses. CASE PRESENTATION: This article reports a woman of reproductive age presenting with a pulmonary artery mass. The computed tomographic pulmonary angiography and positron emission tomography/computed tomography did not show obvious signs of pulmonary artery sarcoma, however, contrast-enhanced echocardiography showed moderate perfusion, which helped differentiate between pulmonary artery sarcoma and pulmonary artery thrombosis, leading to timely surgical treatment. CONCLUSIONS: PAS is a rare form of cancer that can occasionally be visually similar to PTE on radiographic images. Early diagnosis of PAS is of vital importance to the prognosis of the patients. There are several visual cues that can help differentiate between the two conditions. Additionally, contrast-enhanced echocardiography provides additional information on tumor perfusion, offering another effective approach for a prompt and accurate diagnosis.

6.
BMC Cardiovasc Disord ; 24(1): 239, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714966

RESUMO

OBJECTIVE: Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes. METHODS: The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated. RESULTS: A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h. CONCLUSION: This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications. TRIAL REGISTRATION: The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023.


Assuntos
Aneurisma Aórtico , Dissecção Aórtica , Circulação Cerebrovascular , Humanos , Dissecção Aórtica/cirurgia , Dissecção Aórtica/mortalidade , Dissecção Aórtica/complicações , Dissecção Aórtica/fisiopatologia , Dissecção Aórtica/diagnóstico por imagem , Resultado do Tratamento , Fatores de Risco , Fatores de Tempo , Aneurisma Aórtico/cirurgia , Aneurisma Aórtico/mortalidade , Aneurisma Aórtico/complicações , Aneurisma Aórtico/fisiopatologia , Aneurisma Aórtico/diagnóstico por imagem , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Doença Aguda , Transtornos Cerebrovasculares/cirurgia , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/mortalidade , Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/fisiopatologia , Adulto , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Medição de Risco , Reperfusão , Tempo para o Tratamento
7.
Langenbecks Arch Surg ; 409(1): 81, 2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38430305

RESUMO

PURPOSE: This study aims to compare the efficiency and clinical outcomes between the suctioning ureteral access sheath (UAS) group and the traditional UAS group during retrograde intrarenal surgery (RIRS) for kidney stones and explore the impact of suctioning UAS on postoperative infectious complications. METHODS: We retrospectively reviewed the clinical data of 162 patients with kidney stones who underwent RIRS with a traditional UAS (n = 74) or a suctioning UAS (n = 71) between March 2021 and May 2023. RESULTS: The mean operative time in suctioning UAS group (39.03 ± 18.01 s) was significantly shorter than that (49.73 ± 20.77 s) in the traditional UAS group (P = 0.037). The mean postoperative hospital stay was significantly shorter in the suctioning UAS group (1.57 ± 0.82d) compared with the traditional UAS group (2.30 ± 1.6 2 d) (P = 0.032). The instant SFRs were significantly higher in the suctioning UAS group (88.73%) than in the traditional UAS group (75.68%) (P = 0.040). The overall SFR in suctioning UAS group (92.96%) was slightly higher than the traditional UAS group (85.14%). The incidence of overall complications was significantly higher in the traditional UAS group (35.14%) than in the suctioning UAS group (16.90%) (P = 0.013). In multivariate analysis, female patients (OR 0.053, P = 0.018), positive urine WBC (OR 10.382, P = 0.034), operative time > 60 min (OR 20.231, P = 0.032), and the application of traditional UAS (OR 0.042, P = 0.017) were independent risk factors associated with infectious complications. CONCLUSION: We demonstrated that suctioning UAS provided a higher instant SFR and fewer postoperative infectious complications during RIRS, and patients with predictable risk factors for infectious complications could potentially benefit from the use of the suctioning UAS.


Assuntos
Cálculos Renais , Ureter , Humanos , Feminino , Estudos Retrospectivos , Cálculos Renais/cirurgia , Tempo de Internação , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia
8.
BMC Surg ; 24(1): 145, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734631

RESUMO

BACKGROUND: Delayed gastric emptying (DGE) commonly occurs after pancreaticoduodenectomy (PD). Risk factors for DGE have been reported in open PD but are rarely reported in laparoscopic PD (LPD). This study was designed to evaluate the perioperative risk factors for DGE and secondary DGE after LPD in a single center. METHODS: This retrospective cohort study included patients who underwent LPD between October 2014 and April 2023. Demographic data, preoperative, intraoperative, and postoperative data were collected. The risk factors for DGE and secondary DGE were analyzed. RESULTS: A total of 827 consecutive patients underwent LPD. One hundred and forty-two patients (17.2%) developed DGE of any type. Sixty-five patients (7.9%) had type A, 62 (7.5%) had type B, and the remaining 15 (1.8%) had type C DGE. Preoperative biliary drainage (p = 0.032), blood loss (p = 0.014), and 90-day any major complication with Dindo-Clavien score ≥ III (p < 0.001) were independent significant risk factors for DGE. Seventy-six (53.5%) patients were diagnosed with primary DGE, whereas 66 (46.5%) patients had DGE secondary to concomitant complications. Higher body mass index, soft pancreatic texture, and perioperative transfusion were independent risk factors for secondary DGE. Hospital stay and drainage tube removal time were significantly longer in the DGE and secondary DGE groups. CONCLUSION: Identifying patients at an increased risk of DGE and secondary DGE can be used to intervene earlier, avoid potential risk factors, and make more informed clinical decisions to shorten the duration of perioperative management.


Assuntos
Esvaziamento Gástrico , Laparoscopia , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Humanos , Pancreaticoduodenectomia/efeitos adversos , Masculino , Feminino , Estudos Retrospectivos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Idoso , Fatores de Risco , Esvaziamento Gástrico/fisiologia , Gastroparesia/etiologia , Gastroparesia/epidemiologia , Adulto
9.
Int J Mol Sci ; 25(10)2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38791411

RESUMO

Melon (Cucumis melo L.) is a global commercial crop that is sensitive to seed-borne wilt infections caused by Fusarium oxysporum f. sp. melonis (Fom). To address the challenge of detecting Fom contamination, we designed a probe-based real-time PCR method, TDCP2, in combination with rapid or column-based DNA extraction protocols to develop reliable molecular detection methods. Utilizing TDCP2, the detection rate reached 100% for both artificially Fom-inoculated (0.25-25%) and pod-inoculated melon seeds in conjunction with DNA samples from either the rapid or column-based extraction protocol. We performed analyses of precision, recall, and F1 scores, achieving a maximum F1 score of 1 with TDCP2, which highlights the robustness of the method. Additionally, intraday and interday assays were performed, which revealed the high reproducibility and stability of column-based DNA extraction protocols combined with TDCP2. These metrics confirm the reliability of our developed protocols, setting a foundation for future enhancements in seed pathology diagnostics and potentially broadening their applicability across various Fom infection levels. In the future, we hope that these methods will reduce food loss by improving the control and management of melon diseases.


Assuntos
Fusarium , Doenças das Plantas , Reação em Cadeia da Polimerase em Tempo Real , Sementes , Fusarium/genética , Fusarium/isolamento & purificação , Sementes/microbiologia , Doenças das Plantas/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos , Cucurbitaceae/microbiologia , DNA Fúngico/genética , DNA Fúngico/isolamento & purificação , Cucumis melo/microbiologia , Reprodutibilidade dos Testes
10.
Int Wound J ; 21(3): e14761, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38420690

RESUMO

Following heart operation, a severe life-threatening complication has been identified by investigators who have recently discovered that local application of platelet-rich plasma (PRP) can lower the rate of wound infection in heart surgery. Nevertheless, due to the low quality of these trials, we have tried to perform high-quality meta-analyses to prove the efficacy of PRP in heart surgery for post-operative wound infections. In this study, five randomised controlled trials (RCTs) were chosen from three databases, and there were 1005 studies to analyse the data. Among 181 cases, PRP was applied to the surgical site, and 205 in the control group. Both the CI and the OR or the average difference (MD) were computed with either a fixed or random-effect model. A meta-analysis of the data was carried out with RevMan 5.3. The results showed that there were no statistically significant differences in the incidence of post-operative surgical site infection (SSI) in control group compared to those treated with PRP gel (OR, 0.97; 95% CI, 0.38, 2.47; p = 0.95); In the heart operation, the local application of PRP gel decreased the rate of drainage after operation (MD, -217.82; 95% CI, -335.38, -100.26; p = 0.0003); The operation time of the PRP gel was not significantly different from that of the control group (MD, 12.65; 95% CI, -2.95, 28.24; p = 0.11). Contrary to earlier research, the application of autoplatelet gel in heart surgery did not seem to decrease operative site infections after the operation, but it did decrease the amount of postoperative drainage. Nevertheless, because of the limited number of RCTs in this meta-analysis, caution should be exercised in their treatment. More high-quality randomised, large-sample trials are required to further confirm the findings.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Plasma Rico em Plaquetas , Humanos , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Drenagem , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Angew Chem Int Ed Engl ; 63(3): e202316903, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-37997556

RESUMO

Proton exchange membrane water electrolysis is a highly promising hydrogen production technique for sustainable energy supply, however, achieving a highly active and durable catalyst for acidic water oxidation still remains a formidable challenge. Herein, we propose a local microenvironment regulation strategy for precisely tuning In-RuO2 /graphene (In-RuO2 /G) catalyst with intrinsic electrochemical activity and stability to boost acidic water oxidation. The In-RuO2 /G displays robust acid oxygen evolution reaction performance with a mass activity of 671 A gcat -1 at 1.5 V, an overpotential of 187 mV at 10 mA cm-2 , and long-lasting stability of 350 h at 100 mA cm-2 , which arises from the asymmetric Ru-O-In local structure interactions. Further, it is unraveled theoretically that the asymmetric Ru-O-In structure breaks the thermodynamic activity limit of the traditional adsorption evolution mechanism which significantly weakens the formation energy barrier of OOH*, thus inducing a new rate-determining step of OH* absorption. Therefore, this strategy showcases the immense potential for constructing high-performance acidic catalysts for water electrolyzers.

12.
Am J Transplant ; 23(3): 336-352, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36695693

RESUMO

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.


Assuntos
Transplante de Fígado , MicroRNAs , Animais , Humanos , Ratos , Leucócitos Mononucleares/metabolismo , Macrófagos/metabolismo , MicroRNAs/genética , NF-kappa B/metabolismo , Pró-Colágeno/metabolismo , Pró-Colágeno/farmacologia
13.
Bioorg Chem ; 130: 106236, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371817

RESUMO

Cannabinoid receptor 1 (CB1) is a G protein-coupled receptor and a therapeutic target for metabolic disorders. Numerous CB1 antagonists have been developed, but their functional selectivities and bias towards G protein or ß-arrestin signaling have not been systemically characterized. In this study, we analyzed the binding affinities and downstream signaling of two series of pyrazole derivatives bearing 1-aminopiperidine (Series I) or 4-aminothiomorpholine 1,1-dioxide (Series II) moieties, as well as the well-known CB1 antagonists rimonabant and taranabant. Analyses of the results for the Series I and II derivatives showed that minor structure modifications to their functional groups and especially the incorporation of 1-aminopiperidine or 4-aminothiomorpholine 1,1-dioxide motifs can profoundly affect their bias toward G protein or ß-arrestin signaling, and that their binding affinity and functional activity can be disassociated. Docking and molecular dynamics simulations revealed that the binding modes of Series I and II antagonists differed primarily in that Series I antagonists formed an additional hydrogen bond with the receptor, whereas those in Series II formed a water bridge.


Assuntos
Antagonistas de Receptores de Canabinoides , Proteínas de Ligação ao GTP , Antagonistas de Receptores de Canabinoides/farmacologia , Antagonistas de Receptores de Canabinoides/metabolismo , Rimonabanto , beta-Arrestinas/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Receptores de Canabinoides/metabolismo
14.
Acta Pharmacol Sin ; 44(9): 1777-1789, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37186122

RESUMO

Histone modification plays an important role in pathological cardiac hypertrophy and heart failure. In this study we investigated the role of a histone arginine demethylase, Jumonji C domain-containing protein 6 (JMJD6) in pathological cardiac hypertrophy. Cardiac hypertrophy was induced in rats by subcutaneous injection of isoproterenol (ISO, 1.2 mg·kg-1·d-1) for a week. At the end of the experiment, the rats underwent echocardiography, followed by euthanasia and heart collection. We found that JMJD6 levels were compensatorily increased in ISO-induced hypertrophic cardiac tissues, but reduced in patients with heart failure with reduced ejection fraction (HFrEF). Furthermore, we demonstrated that JMJD6 overexpression significantly attenuated ISO-induced hypertrophy in neonatal rat cardiomyocytes (NRCMs) evidenced by the decreased cardiomyocyte surface area and hypertrophic genes expression. Cardiac-specific JMJD6 overexpression in rats protected the hearts against ISO-induced cardiac hypertrophy and fibrosis, and rescued cardiac function. Conversely, depletion of JMJD6 by single-guide RNA (sgRNA) exacerbated ISO-induced hypertrophic responses in NRCMs. We revealed that JMJD6 interacted with NF-κB p65 in cytoplasm and reduced nuclear levels of p65 under hypertrophic stimulation in vivo and in vitro. Mechanistically, JMJD6 bound to p65 and demethylated p65 at the R149 residue to inhibit the nuclear translocation of p65, thus inactivating NF-κB signaling and protecting against pathological cardiac hypertrophy. In addition, we found that JMJD6 demethylated histone H3R8, which might be a new histone substrate of JMJD6. These results suggest that JMJD6 may be a potential target for therapeutic interventions in cardiac hypertrophy and heart failure.


Assuntos
Insuficiência Cardíaca , NF-kappa B , Animais , Ratos , Cardiomegalia/induzido quimicamente , Cardiomegalia/prevenção & controle , Cardiomegalia/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Histonas/metabolismo , Isoproterenol/toxicidade , Miócitos Cardíacos/metabolismo , NF-kappa B/metabolismo , Ratos Sprague-Dawley , RNA Guia de Sistemas CRISPR-Cas , Volume Sistólico
15.
Tohoku J Exp Med ; 260(1): 35-45, 2023 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-36858511

RESUMO

Renal interstitial fibrosis, a pathological feature of diabetic nephropathy, is closely related to endothelial-to-mesenchymal transition (EMT). This study aimed to explore the effect of H-1-2, a polysaccharide of Pseudostellaria heterophylla, on high glucose (HG) induced-podocyte EMT in vivo and ex vivo. DBA/2 mice were given five consecutive days of streptozotocin injection to induce the diabetic nephropathy model. H-1-2 treatment effectively attenuated general states (bodyweight and blood glucose level) and reduced oral glucose tolerance, insulin tolerance, kidney index, as well as the level of serum urine nitrogen, serum creatinine, and urinary albumin excretion rate in diabetic nephropathy mice. The injury and EMT of podocytes in diabetic nephropathy mice were restrained by H-1-2. After exposing podocytes to HG, the impaired cell viability, apoptosis, the downregulation of nephrin, synaptopodin, sirtuin 1 (SIRT1) and P-cadherin, and the upregulation of N-cadherin were observed in podocytes. H-1-2 treatment could reverse these effects induced by HG. To uncover the mechanism underlying H-1-2 suppressing EMT, small interference RNA for SIRT1 was transfected into podocytes. Mechanically, silencing SIRT1 largely restrained the protective effect of H-1-2 on HG-induced podocytes. In conclusion, H-1-2 exerts a potential role in alleviating HG-induced dysfunction and EMT of podocytes in vivo and ex vivo via SIRT1.


Assuntos
Nefropatias Diabéticas , Podócitos , Camundongos , Animais , Podócitos/patologia , Nefropatias Diabéticas/tratamento farmacológico , Sirtuína 1/farmacologia , Camundongos Endogâmicos DBA , Glucose/toxicidade , Transição Epitelial-Mesenquimal
16.
Vascular ; 31(2): 250-256, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34875933

RESUMO

OBJECTIVE: This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. METHODS: The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru - T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. RESULTS: After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference (p < 0.05). CONCLUSION: Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.


Assuntos
Doenças da Aorta , Arteriopatias Oclusivas , Isquemia do Cordão Espinal , Ratos , Animais , Isquemia do Cordão Espinal/etiologia , Isquemia , Medula Espinal/irrigação sanguínea , Medula Espinal/patologia , Medula Espinal/fisiologia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Aorta Torácica/patologia , Doenças da Aorta/patologia , Necrose/patologia
17.
Artigo em Inglês | MEDLINE | ID: mdl-37648554

RESUMO

BACKGROUND: Ischemia-reperfusion injury (IRI) poses a significant challenge to liver transplantation (LT). The underlying mechanism primarily involves overactivation of the immune system. Heat shock protein 110 (HSP110) functions as a molecular chaperone that helps stabilize protein structures. METHODS: An IRI model was established by performing LT on Sprague-Dawley rats, and HSP110 was silenced using siRNA. Hematoxylin-eosin staining, TUNEL, immunohistochemistry, ELISA and liver enzyme analysis were performed to assess IRI following LT. Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes. RESULTS: Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT (P < 0.05). However, when rats were injected with siRNA-HSP110, IRI subsequent to LT was notably reduced (P < 0.05). Additionally, the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced (P < 0.05). Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver (P < 0.05). CONCLUSIONS: HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells. Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

18.
J Craniofac Surg ; 34(2): e190-e195, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36745135

RESUMO

BACKGROUND: This study aimed to explore the changes in hard tissue after applying invisible orthodontic-orthognathic treatment and the digital design, and to explore the accuracy of the treatment effect of maxillofacial tissue after invisible orthodontic treatment and orthognathic treatment. METHODS: From September 2020 to January 2022, 25 patients with class III skeletal malocclusion and 7 patients with class II skeletal malocclusion, were treated with invisible orthodontic treatment and orthognathic combined treatment. Orthodontic treatment with preoperative invisible orthodontic treatment followed by orthodontic surgery. All patients had cephalometric lateral films after surgery to analyze orthognathic surgery's goals and surgical effects of orthognathic surgery and the digital design. Measure the angle of the sella-nasion-A point angle, angle of sella-nasion-B point, ANB angle, maxillary convex angle, mandibular plane (MP) angle, 1-SN angle, 1-MP angle, etc, and compare surgery outcome with digital design. RESULT: All patients were satisfied with the effect and no complications occurred. Angle of sella-nasion-A point, angle of sella-nasion-B point, ANB angle, maxillary convex angle, MP angle, 1-SN angle, and 1-MP angle had no significant difference between the postoperative effect and the purpose of digital design ( P >0.05), there was no apparent deviation between the upper and lower jaw and the chin ( P >0.05). CONCLUSION: The combined invisible orthodontic treatment and orthognathic treatment are accurate and effective, and are worthy of promotion. It supplements traditional orthognathic therapy and is suitable for corresponding patients.


Assuntos
Má Oclusão Classe III de Angle , Má Oclusão Classe II de Angle , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Mandíbula/cirurgia , Má Oclusão Classe III de Angle/cirurgia , Maxila/cirurgia , Queixo , Cefalometria
19.
Int J Environ Health Res ; : 1-11, 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37669754

RESUMO

Few studies have been conducted that use biomarkers as early warning signals for noise-associated health hazards. To explore potentially effective biomarkers for noise-exposed populations, we recruited 218 noise-exposed male workers in China. We calculated cumulative noise exposure (CNE) through noise intensity and noise-exposed duration. When the model was fully adjusted, ln-transformed relative mitochondrial DNA copy number (mtDNAcn) decreased by 0.014 (95% confidence interval (CI): -0.026, -0.003) units with each 1 dB(A)∙year increase in CNE levels. CNE was further included in the model as a grouping variable, and the results showed a negative dose-effect relationship between relative mtDNAcn and CNE (P-trend = 0.045). However, we did not find a correlation between CNE and micronucleus (MN) frequencies. Our findings suggest that CNE in workers was associated with a decrease in relative mtDNAcn which may provide a potential biomarker for noise and for certain health risk but not with MN frequencies.

20.
Yi Chuan ; 45(2): 165-175, 2023 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-36927663

RESUMO

The currently widely used CRISPR-Cas9 genome editing technology enables the editing of target genes (knock-out or knock-in) with high accuracy and efficiency. Guided by the small guide RNA, the Cas9 nuclease induces a DNA double-strand break at the targeted genomic locus. The DNA double-strand break can be repaired by the homology-directed repair pathway in the presence of a repair template. With the repair template containing the coding sequence of a fluorescent tag, the targeted gene can be inserted with the sequence of a fluorescent tag at the designed position. The genome editing mediated labeling of endogenous proteins with fluorescent tags avoids the potential artifacts caused by gene overexpression and substantially improves the reproductivity of imaging experiments. This protocol focuses on creating mammalian cell lines with endogenous proteins tagged with fluorescent proteins or self-labeling protein tags using CRISPR-Cas9 genome editing.


Assuntos
Sistemas CRISPR-Cas , Edição de Genes , Animais , Edição de Genes/métodos , Proteína 9 Associada à CRISPR/genética , Reparo de DNA por Recombinação , DNA , Mamíferos/genética
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