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1.
Biotechnol Lett ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076042

RESUMO

OBJECTIVES: Polymyxins are antibacterial polypeptides used as "last resort" therapy option for multidrug-resistant Gram-negative bacteria. The expansion of polymyxin-resistant infections has inspired development of novel polymyxin derivatives, and deacylation is one of the critical steps in generating those antibiotics. Deacylase from Actinoplanes utahensis hydrolyze the acyl moieties of echinocandins, and also efficiently deacylates daptomycin, ramoplanin and other important antibiotics. Here, deacylase was studied considering its potential usefulness in deacylating polymyxin B1. RESULTS: All the six recombinant strains containing the deacylase gene catalyzed hydrolysis of polymyxin B1, yielding cyclic heptapeptides. The efficiency of recombinant S. albus (SAL701) was higher than that of the others, and deacylation was the most efficient at 40 °C in 0.2 M Tris buffer (pH 8.0) with 0.2 M Mg2+. The optimal substrate concentration of SAL701 was increased from 2.0 to 6.0 g/L. SAL701 was highly thermostable, showing no loss of activity at 50 °C for 12 h, and the mycelia could be recycled at least three times without loss of catalytic activity. SAL701 could not deacylate ß-lactam substrate such as penicillin G and cephalosporin C. Deacylase catalyzes the amide bond 1 closest to the nucleus of polymyxin B1 rather than the other bond, suggesting that it has high catalytic site specificity. Homology modeling and the docking results implied that Thr190 in deacylase could facilitate hydrolysis with high regioselectivity. CONCLUSIONS: These results show that SAL701 is effective in increasing the cyclic heptapeptide moiety of polymyxin B1. These properties of the biocatalyst may enable its development in the industrial production of polymyxins antibiotics.

2.
J Transl Med ; 20(1): 386, 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36058929

RESUMO

BACKGROUND: Although the anti-programmed death-1 (PD-1) inhibitor plus chemotherapy combination has been approved as the standard first-line treatment for advanced gastric cancer, a proportion of patients do not significantly benefit from this therapy. Who would respond poorly to this treatment and the underlying mechanisms of treatment failure are far from clear. METHODS: We retrospectively analyzed the associations between the peripheral basophils at baseline and clinical outcomes in 63 advanced gastric cancer patients treated with anti-PD-1 plus chemotherapy and 54 patients treated with chemotherapy alone. Immunohistochemistry and immunofluorescence staining in gastric cancer samples were utilized to investigate the basophil-related immunophenotype. RESULTS: The optimal cutoff of basophil count to distinguish responders to anti-PD-1 plus chemotherapy from non-responders was 20.0/µL. Compared with the low basophil group (≤ 20.0/µL, n = 40), the high basophil group (> 20.0/µL, n = 23) had a significantly lower objective response rate (ORR 17.4% vs. 67.5%, p = 0.0001), worse progression-free survival (median PFS 4.0 vs. 15.0 months, p = 0.0003), and worse overall survival (median OS not reached, p = 0.027). Multivariate analyses identified a basophil count of > 20.0/µL as an independent risk factor for a worse ORR (OR 0.040, 95% CI 0.007-0.241, p = 0.0004), worse PFS (HR 3.720, 95% CI 1.823-7.594, p = 0.0003) and worse OS (HR 3.427, 95% CI 1.698-6.917, p = 0.001). In contrast, there was no significant association between peripheral basophil counts and tumor response or survival in the chemotherapy-alone group (p > 0.05). In primary gastric cancer samples, we observed a correlation between higher peripheral basophil counts and the accumulation of tumor-infiltrating basophils (r = 0.6833, p = 0.005). Tumor-infiltrating basophils were found to be spatially proximate to M2 macrophages within TME and positively correlated with tumor M2 macrophage infiltration (r = 0.7234, p = 0.0023). The peripheral basophil counts also had a significant positive correlation with tumor-infiltrating M2 macrophage counts (r = 0.6584, p = 0.003). Further validation in tumor samples treated with the neoadjuvant anti-PD-1 inhibitor plus chemotherapy combination suggests that the peripheral basophils, tumor infiltration of basophils, and M2 macrophages were significantly more abundant in non-responders than in responders (p = 0.0333, p = 0.0007, and p = 0.0066, respectively). CONCLUSIONS: The peripheral basophil count was observed to be a potential biomarker of anti-PD-1 efficacy for advanced gastric cancer. Moreover, basophils may induce an immune-evasive tumor microenvironment by increasing M2 macrophage infiltration, which could be a potential immunotherapeutic target for advanced gastric cancer.


Assuntos
Neoplasias Pulmonares , Neoplasias Gástricas , Basófilos , Humanos , Contagem de Leucócitos , Macrófagos , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Microambiente Tumoral
3.
BMC Musculoskelet Disord ; 23(1): 843, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064666

RESUMO

BACKGROUND: This study aimed to analyze the efficacy of the simultaneous rectification of adjacent asymptomatic lumbar disc herniation (asLDH) of L5-S1 isthmic spondylolisthesis (IS). METHODS: One hundred and forty-eight patients with L5-S1 IS, and simultaneous L4-5 asLDH, were recruited between January 2012 and December 2017, for this study. Group A: seventy-two patients received PLIF at L5-S1. Group B: seventy-six patients received PLIF at L4-S1. The radiographic outcomes were assessed via the lumbar lordosis (LL), segmental lordosis (SL), sacral slope (SS), pelvic incidence (PI), pelvic tilt (PT), PI-LL and slip degree (SD). The functional outcomes were evaluated via the visual analog scale (VAS), Oswestry disability index (ODI), and reoperation rate. The potential risk hazards for reoperation were identified using both uni- and multivariate logistic regression analyses. RESULTS: The postoperative LL, SL, PT, SS, SD, VAS, and ODI exhibited vast improvements (P < 0.05). Relative to Group A, Group B exhibited markedly better LL, SL, PT, PI-LL,VAS and ODI scores at the final follow-up (P < 0.05). Group B also achieved better SD values post surgery than Group A (P < 0.05). The reoperation rate was remarkably elevated in Group A, compared to Group B (P < 0.05). The multivariate logistic regression analysis showed the L4-5 asLDH grade was a stand-alone risk hazard for reoperation, whereas, pre-SL and pre-LL offered protection against reoperation (P < 0.05). CONCLUSIONS: L4-S1 PLIF is recommended to correct asLDH in L5-S1 IS patients, with high-grade disc herniation and abnormal sagittal alignment.


Assuntos
Deslocamento do Disco Intervertebral , Lordose , Espondilolistese , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Sacro/diagnóstico por imagem , Sacro/cirurgia , Espondilolistese/diagnóstico por imagem , Espondilolistese/cirurgia
4.
J Nutr ; 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36055794

RESUMO

BACKGROUND: Deoxynivalenol (DON) is a major mycotoxin present in staple foods (particularly in cereal products), which induces intestinal inflammation and disrupts intestinal integrity. Lactoferrin (LF) is a multifunctional protein that contributes to maintaining intestinal homeostasis and improving host health. However, the protective effects of LF on DON-induced intestinal dysfunction remain unclear. OBJECTIVES: This study aimed to investigate the effects of LF on the DON-induced intestinal dysfunction in mice, and its underlying protective mechanism. METHODS: Male BALB/c mice (5 wk old) with similar body weights were divided into 4 groups (n = 6/group) and treated as follows for 5 wk: Veh (peroral vehicle daily, commercial (C) diet); LF (peroral 10 mg LF/d, C diet); DON (Veh, C diet containing 12 mg DON/kg); and LF + DON (peroral 10 mg LF/d, DON diet). Intestinal morphology, tight junction proteins, cytokines, and microbial community were determined. Data were analyzed by two-way ANOVA or Kruskal-Wallis test. RESULTS: The DON group exhibited lower final body weight (-12%), jejunal villi height (-41%), jejunal occludin expression (-36%), and higher plasma interleukin (IL)-1ß level (+85%) and jejunal Il1b mRNA expression (+98%) than the Veh group (P < 0.05). In contrast, final body weight (+19%), jejunal villi height (+49%), jejunal occludin (+53%), and intelectin 1 protein expression (+159%) were greater in LF + DON compared with DON (P < 0.05). Additionally, jejunal Il1b mRNA expression (-31%) and phosphorylation p38 and ERK1/2 (-40% and - 38%) were lower in LF + DON compared with DON (P < 0.05). Furthermore, relative abundance of Clostridium XIVa (+181%) and colonic butyrate levels (+53%) were greater in LF + DON compared with DON (P < 0.05). CONCLUSION: Our study highlights a promising antimycotoxin approach of LF to alleviate DON-induced intestinal dysfunction via modulating the mitogen-activated protein kinase (MAPK) pathway and gut microbial community in mice.

5.
Artigo em Inglês | MEDLINE | ID: mdl-36058783

RESUMO

BACKGROUND: Polydatin, a glucoside of resveratrol, has been shown to have protective effects against various diseases. However, little is known about its effect on hepatic ischemia-reperfusion (I/R) injury. This study aimed to elucidate whether polydatin protects liver against I/R-induced injury and to explore the underlying mechanism. METHODS: After gavage feeding polydatin once daily for a week, mice underwent a partial hepatic I/R procedure. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST), hematoxylin-eosin (H&E) and TdT-mediated dUTP nick-end labeling (TUNEL) staining were used to evaluate liver injury. The severity related to the inflammatory response and reactive oxygen species (ROS) production was also investigated. Furthermore, immunofluorescence and Western blotting were used to detect macrophage polarization and the NF-κB signaling pathway in macrophages. RESULTS: Compared with the I/R group, polydatin pretreatment significantly attenuated I/R-induced liver damage and apoptosis. The oxidative stress marker (dihydroethidium fluorescence, malondialdehyde, superoxide dismutase and glutathione peroxidase) and I/R related inflammatory cytokines (interleukin-1ß, interleukin-10 and tumor necrosis factor-α) were significantly suppressed after polydatin treatment. In addition, the result of immunofluorescence indicated that polydatin reduced the polarization of macrophages toward M1 macrophages both in vivo and in vitro. Western blotting showed that polydatin inhibited the pro-inflammatory function of RAW264.7 via down-regulating the NF-κB signaling pathway. CONCLUSIONS: Polydatin protects the liver from I/R injury by remodeling macrophage polarization via NF-κB signaling.

6.
Cereb Cortex ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36047921

RESUMO

Ventral adult hippocampal neurogenesis may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders. However, the underlying mechanism remains unclear. Here, we show that the expression of Tau and Tau isoforms is markedly increased in the ventral dentate gyrus (vDG) after social defeat stress in young adult mice. Furthermore, glycogen synthase kinase-3ß and calcium/calmodulin-dependent protein kinase II-α activity and calcium/calmodulin-dependent protein kinase II-ß upregulation substantially promote Tau phosphorylation, which disrupts the dendritic structural plasticity of granule cells in the vDG of the hippocampus, and this action is necessary and sufficient for the stress response. In addition, Tau substantially inhibits the proliferation of newborn neurons in the vDG by regulating the PI3K-AKT signaling pathway in a mouse model of social defeat stress. Taken together, our findings reveal a novel mechanism by which Tau exacerbates stress responses and anxiety-related behavior by inhibiting the proliferation and maturation of hippocampal vDG neurons, providing a potential molecular target for the treatment of anxiety-like behavior induced by stress.

7.
Pest Manag Sci ; 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36088646

RESUMO

BACKGROUND: Plants respond to attackers by triggering phytohormones signaling associated metabolites including herbivore-induced plant volatiles (HIPVs). HIPVs can indirectly act against herbivory by recruitment of natural enemies and priming of neighboring plants. Ostrinia furnacalis and Mythimna separata are important insect herbivores of maize plants, which have a devastating influence on yield. However, little is known about how maize temporally reconfigures its defense systems against these herbivores, and variation of neighboring plant resistance. RESULTS: This study investigated the effects of HIPVs on the behavior of the dominant predatory beetle Harmonia axyridis and priming in neighboring maize defense against O. furnacalis and M. separata over time. The results showed that maize damaged by either O. furnacalis or M. separata enhanced the release of volatiles including terpenes, aldehydes, alkanes and an ester, which elicited an increased attractive response to H. axyridis after 3 and 12 h, respectively. Ostrinia furnacalis damage resulted in accumulations of leaf jasmonic acid (JA) and salicylic acid (SA) in maize after 6 and 3 h, respectively, while M. separata damage only raised the JA level after 3 h. Furthermore, HIPVs were able to prime neighboring plants through the accumulation of JA after 24 h. Both larvae showed a significant decrease in weight accumulation after 48 h of feeding on the third leaves of the primed plant. CONCLUSION: Taken together, the findings provide a dynamic overview of how attacked maize reconfigures its volatiles and phytohormones to defend against herbivores, as well as priming of neighboring plants against oncoming attacks. This article is protected by copyright. All rights reserved.

8.
J Orthop Res ; 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36058620

RESUMO

To compare the differences among constructs with one-level cervical disc arthroplasty (CDA) and two-level anterior cervical discectomy and fusion (ACDF). A retrospective study was conducted involving patients who underwent one-level CDA and two-level ACDF between June 2012 and July 2020. According to the different locations of CDA and ACDF, we divided the constructs into three types: type Ⅰa: CDA-ACDF-ACDF; type Ⅰb: ACDF-CDA-ACDF; type Ⅰc: ACDF-ACDF-CDA. The differences of clinical and radiological outcomes were evaluated. Fifty-three patients were included with 29 in type Ⅰa group, 11 in type Ⅰb group, and 13 in type Ⅰc group. After surgery, all groups showed significant improvement in apanese Orthopedic Association, Neck Disability Index, and Visual Analog Scale scores (p < 0.001). Range of motion (ROM) of the total cervical spine in type Ⅰc group decreased significantly compared with those in type Ⅰa and type Ⅰb groups (p < 0.05). No significant differences in ROM of the arthroplasty segment and the variations in ROM of the superior adjacent segment were observed among the three groups. The fusion rates of the superior ACDF segments were significantly higher at 6 and 12 months postoperatively than those of the inferior ACDF segments (p < 0.05). The clinical outcomes were similar among constructs concerning different locations of CDA and ACDF in three-level hybrid surgery. ROM of the cervical spine in type Ⅰc group decreased significantly compared with that in type Ⅰa and type Ⅰb groups. The fusion rates of superior ACDF segments were higher at early time points after surgery than those of inferior ACDF segments.

9.
Foods ; 11(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36076866

RESUMO

Xinyang Maojian (XYMJ) is one of the premium green teas and originates from Xinyang, which is the northernmost green tea production area in China. The special geographic location, environmental conditions, and manufacturing process contribute to the unique flavor and rich nutrition of XYMJ green tea. Aroma is an important quality indicator in XYMJ green tea. In order to illustrate the aroma of XYMJ green tea, the key odorants in XYMJ green tea and their dynamic changes during the manufacturing processes were analyzed by headspace solid-phase microextraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS). A total of 73 volatile compounds of six different chemical classes were identified in the processed XYMJ green tea samples, and the manufacturing processes resulted in the losses of total volatile compounds. Among the identified volatile compounds, twenty-four aroma-active compounds, such as trans-nerolidol, geranylacetone, nonanal, (+)-δ-cadinene, linalool, (Z)-jasmone, cis-3-hexenyl butyrate, cis-3-hexenyl hexanoate, methyl jasmonate, and ß-ocimene, were identified as the key odorants of XYMJ green tea based on odor activity value (OAV). The key odorants are mainly volatile terpenes (VTs) and fatty acid-derived volatiles (FADVs). Except for (+)-δ-cadinene, copaene, cis-ß-farnesene, (Z,E)-α-farnesene and phytol acetate, the key odorants significantly decreased after fixing. The principal coordinate analysis (PCoA) and the hierarchical cluster analysis (HCA) analyses suggested that fixing was the most important manufacturing process for the aroma formation of XYMJ green tea. These findings of this study provide meaningful information for the manufacturing and quality control of XYMJ green tea.

10.
Sensors (Basel) ; 22(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36081001

RESUMO

Based on the analysis of the airborne bistatic synthetic aperture radar (SAR) imaging geometric mode, an extended nonlinear chirp scaling algorithm is employed to simulate and verify the imaging effect of the bistatic SARs. A gradient theory-based two-dimensional resolution bistatic SAR model is proposed, and the constraints of the multi-platform flight trajectory parameters meeting the imaging accuracy of the bistatic SAR are analyzed. Finally, through the bistatic SAR imaging simulation of cooperative flight trajectories under various situations, the spatial configuration constraint envelope between the flight vehicles to achieve the optimal resolution is revealed. The results of this paper will provide a theoretical reference for the SAR application in formation flight control.


Assuntos
Aumento da Imagem , Interpretação de Imagem Assistida por Computador , Algoritmos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Radar
11.
Geriatr Orthop Surg Rehabil ; 13: 21514593221119625, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36090795

RESUMO

Background: Osteoporotic vertebral compression fracture (OVCF) has become a health issue of worldwide concern. Percutaneous kyphoplasty (PKP) is one of the main surgical methods for OVCFs. This study aimed to evaluate and compare the clinical efficacy and safety of PKP with high- and low-viscosity bone cement for OVCFs. Methods: Totally 62 patients with single-level OVCF were enrolled in this study from December 2018 to April 2021. Among them, 32 cases underwent PKP with high-viscosity bone cement, while 30 cases underwent PKP with low-viscosity bone cement. Visual analog scale (VAS) scores and Oswestry disability index (ODI) scores were used in the pre- and post-operative period to assess patients' rehabilitation. Compression rates of anterior vertebra height (AVH) and posterior vertebra height (PVH) were analyzed to evaluate the restoration of vertebra height. Leakage rates and locations were recorded to show clinical safety. Results: VAS and ODI scores both significantly improved in 2 groups at 1 day, 1 month, and 3 months after surgery. Compression rates of AVH and PVH at 1 day and 3 months after PKP were lower than those before surgery. However, there was no significant difference in VAS scores, ODI scores, and compression rates between both groups. However, PKP with high-viscosity bone cement achieved a lower bone cement leakage rate significantly, which showed the safety of high-viscosity bone cement in PKP. Conclusions: PKP with high- and low-viscosity bone cement both improved the recovery of patients and restored vertebra heights. Notably, PKP with high-viscosity bone cement can achieve favorable clinical outcomes as well as lower bone cement leakage rate.

12.
Transbound Emerg Dis ; 2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36057957

RESUMO

A novel neurological disorder, shaking mink syndrome (SMS), emerged in Denmark and Sweden since 2000. SMS has seldom been reported in China, but the causative agent has not been detected in the country. SMS outbreaks occurred in multiple provinces in 2020. A total of 44 brain samples from minks associated with SMS were collected from Heilongjiang, Liaoning, and Shandong provinces, of which 28 samples (63.3%) were SMS-Astrovirus (SMS-AstV) positive by reverse transcription PCR. Histopathological examination revealed non-suppurative encephalitis in 3 minks. Moreover, the complete coding region sequences (CDS, 6559 bp) of a sample collected from a two-month-old mink (termed SMS-AstV-H1, GSA accession No. SAMC816786) were amplified by PCR and Sanger sequenced. The complete CDS and ORF2 sequences of SMS-AstV-H1 were 94.3% and 96.4% identical to a SMS-AstV strain (GenBank accession number: GU985458). Phylogenetically, SMS-AstV-H1 was closely related to an SMS-AstV strain (GU985458). Based on the above results, we describe SMS-AstV-associated encephalitis in farmed minks in China. Future studies need to focus on epidemiology, virus isolation, and potential interspecies transmission of SMS-AstV. This article is protected by copyright. All rights reserved.

13.
J Hepatocell Carcinoma ; 9: 901-912, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061234

RESUMO

Objective: To develop a nomogram for predicting post-hepatectomy liver failure (PHLF) in patients with resectable hepatocellular carcinoma (HCC) based on portal hypertension, the extent of resection, ALT, total bilirubin, and platelet count. Methods: Patients with HCC hospitalized from January 2015 to December 2020 were included in a retrospective cohort study. 595 HCC patients were divided into a training cohort (n=416) and a validation cohort (n=179) by random sampling. Univariate and multivariable analyses were performed to identify the independent variables to predict PHLF. The nomogram models for predicting the overall risk of PHLF and the risk of PHLF B+C were constructed based on the independent variables. Comparisons were made by using receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) with traditional models, such as FIB-4 score, APRI score, CP class (Child-Pugh), MELD score (model of end-stage liver disease), and ALBI score (albumin-bilirubin) to analyze the accuracy and superiority of the nomogram. Results: We discovered that portal hypertension (yes vs no) (OR=1.677,95% CI:1.817-4.083, p=0.002), the extent of liver resection (OR=1.872,95% CI:3.937-47.096, p=0.001), ALT (OR=1.003,95% CI:1.003-1.016, P=0.003), total bilirubin (OR=1.036,95% CI:1.031-1.184, p=0.005), and platelet count (OR= 1.004, 95% CI:0.982-0.998, p=0.020) were independent risk factors for PHLF using multifactorial analysis. The nomogram models were constructed using well-fit calibration curves for each of these five covariates. When compared to the FIB4, ALBI, MELD, and CP score, our nomogram models have a better predictive value for predicting the overall risk of PHLF or the risk of PHLF B+C. The validation cohort's results were consistent. DCA also confirmed the conclusion. Conclusion: Our models, in the form of static nomogram or web application, were developed to predict PHLF overall risk and PHLF B+C risk in patients with HCC, with a high prediction sensitivity and specificity performance than other commonly used scoring systems.

14.
Opt Lett ; 47(17): 4335-4338, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36048647

RESUMO

A novel, to the best of our knowledge, performance-enhanced laser heterodyne radiometer has been developed by utilizing a semiconductor optical amplifier to amplify the collected weak solar radiation in an optical fiber. High-spectral-resolution measurements of atmospheric carbon dioxide column absorption are used to validate the technique and performance of the developed instrument. The implementation of optical amplification led to a 9-times improvement in sensitivity according to the Allan variance analysis for noise fluctuations, and resulted in a 7.7-times enhancement in measurement precision for atmospheric carbon dioxide. The promising results showed the great potential of employing this type of compact fiber-optics-based spectral radiometer for applications such as atmospheric greenhouse gas sensing.

15.
Nat Commun ; 13(1): 5154, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36056014

RESUMO

Improving power efficiency (PE) and reducing roll-off are of significant importance for the commercialization of white organic light-emitting diodes (WOLEDs) in consideration of energy conservation. Herein, record-beating PE of 130.7 lm W-1 and outstanding external quantum efficiency (EQE) of 31.1% are achieved in all-fluorescence two-color WOLEDs based on a simple sandwich configuration of emitting layer consisting of sky-blue and orange delayed fluorescence materials. By introducing a red fluorescence dopant, all-fluorescence three-color WOLEDs with high color rendering index are constructed based on an interlayer sensitization configuration, furnishing ultrahigh PE of 110.7 lm W-1 and EQE of 30.8%. More importantly, both two-color and three-color WOLEDs maintain excellent PEs at operating luminance with smaller roll-offs than the reported state-of-the-art WOLEDs, and further device optimization realizes outstanding comprehensive performances of low driving voltages, large luminance, high PEs and long operational lifetimes. The underlying mechanisms of the impressive device performances are elucidated by host-tuning effect and electron-trapping effect, providing useful guidance for the development of energy-conserving all-fluorescence WOLEDs.

16.
J Med Chem ; 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36067356

RESUMO

Blockade of the interaction between programmed cell death ligand-1 (PD-L1) and its receptor PD-1 has shown great success in cancer immunotherapy. Peptides possess unique characteristics that give them significant advantages as immune checkpoint inhibitors. However, unfavorable physicochemical properties and proteolytic stability profiles limit the translation of bioactive peptides as therapeutic agents. Studies have revealed that cyclization improves the biological activity and stability of linear peptides. In this study, we report the use of macrocyclization scanning for the discovery of cyclic anti-PD-L1 peptides with improved bioactivity. The cyclic peptides demonstrated up to a 34-fold improvement in the PD-1/PD-L1 blocking activity and significant in vivo anti-tumor activity. Our results demonstrate that macrocyclization scanning is an effective way to improve the serum stability and bioactivity of the anti-PD-L1 linear peptide. This strategy can be employed in the optimization of other bioactive peptides, particularly those for protein-protein interaction modulation.

17.
Cancer Res ; 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36069931

RESUMO

Resistance to HER2-targeted therapy represents a significant challenge for the successful treatment of breast cancer patients with HER2-positive tumors. Through a global mass spectrometry-based proteomics approach, we discovered that the expression of the N6-methyladenosine (m6A) demethylase ALKBH5 was significantly upregulated in HER2-targeted therapy-resistant breast cancer cells. Elevated expression of ALKBH5 was sufficient to confer resistance to HER2-targeted therapy, and specific knockdown of ALKBH5 rescued the efficacy of trastuzumab and lapatinib in resistant breast cancer cells. Mechanistically, ALKBH5 promoted m6A demethylation of GLUT4 mRNA and increased GLUT4 mRNA stability in a YTHDF2-dependent manner, resulting in enhanced glycolysis in resistant breast cancer cells. In breast cancer tissues obtained from patients with poor response to HER2-targeted therapy, increased expression of ALKBH5 or GLUT4 was observed and was significantly associated with poor prognosis in the patients. Moreover, suppression of GLUT4 via genetic knockdown or pharmacological targeting with a specific inhibitor profoundly restored the response of resistant breast cancer cells to trastuzumab and lapatinib both in vitro and in vivo. In conclusion, ALKBH5-mediated m6A demethylation of GLUT4 mRNA promotes resistance to HER2-targeted therapy, and targeting the ALKBH5/GLUT4 axis has therapeutic potential for treating breast cancer patients refractory to HER2-targeted therapies.

18.
Int J Mol Sci ; 23(17)2022 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-36077153

RESUMO

Salinization seriously threatens the normal growth of maize, especially at the seedling stage. Recent studies have demonstrated that circular RNAs (circRNAs) play vital roles in the regulation of plant stress resistance. Here, we performed a genome-wide association study (GWAS) on the survival rate of 300 maize accessions under a salt stress treatment. A total of 5 trait-associated SNPs and 86 candidate genes were obtained by the GWAS. We performed RNA sequencing for 28 transcriptome libraries derived from 2 maize lines with contrasting salt tolerance under normal and salt treatment conditions. A total of 1217 highly expressed circRNAs were identified, of which 371 were responsive to a salt treatment. Using PCR and Sanger sequencing, we verified the reliability of these differentially expressed circRNAs. An integration of the GWAS and RNA-Seq analyses uncovered two differentially expressed hub genes (Zm00001eb013650 and Zm00001eb198930), which were regulated by four circRNAs. Based on these results, we constructed a regulation model of circRNA/miRNA/mRNA that mediated salt stress tolerance in maize. By conducting hub gene-based association analyses, we detected a favorable haplotype in Zm00001eb198930, which was responsible for high salt tolerance. These results help to clarify the regulatory relationship between circRNAs and their target genes as well as to develop salt-tolerant lines for maize breeding.


Assuntos
RNA Circular , Zea mays , Perfilação da Expressão Gênica , Estudo de Associação Genômica Ampla , Melhoramento Vegetal , RNA Circular/genética , Reprodutibilidade dos Testes , Tolerância ao Sal/genética , Transcriptoma , Zea mays/genética
19.
Environ Res ; 215(Pt 1): 114233, 2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36058268

RESUMO

A novel 3D α-FeOOH@MoS2/rGO nanocomposite was successfully fabricated by a simple in situ hydrothermal method. It is a highly efficient heterogeneous catalyst in activation of peroxymonosulfate (PMS) for rapid degradation of rhodamine B (RhB), with 99.9% of RhB removed within 20 min. The introduction of rGO contributes to uniform dispersion and sufficient contact of α-FeOOH and MoS2 nanosheets. Highly active Mo(IV) enhances the reduction of Fe(III), improves Fe(III)/Fe(II) conversion and promotes the generation of O21, which ensures an improved catalytic activity. MoS2/rGO hybrid can effectively solve the problem of material reunion and make α-FeOOH exhibit excellent catalytic performance. The α-FeOOH@MoS2-rGO/PMS system is a co-catalytic system based on the active components of α-FeOOH and MoS2. The main reactive oxygen species in the α-FeOOH@MoS2-rGO/PMS system are O21, SO4.- and ⋅O2-, which contribute to a high reactivity over a wide range of pH (5-9). Besides, this system is highly resistant to anions (Cl-, SO42-) and natural organic matter (humic acid), and can be widely used for degradation of common organic pollutants. The α-FeOOH@MoS2/rGO is a promising Fenton-like catalyst for refractory organic wastewater treatment.

20.
Neural Plast ; 2022: 6131696, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36061584

RESUMO

Background: Repetitive transcranial magnetic stimulation (rTMS) has been widely used in the treatment of neuropathic orofacial pain (NOP). The consistency of its therapeutic efficacy with the optimal protocol is highly debatable. Objective: To assess the effectiveness of rTMS on pain intensity, psychological conditions, and quality of life (QOL) in individuals with NOP based on randomized controlled trials (RCTs). Methods: We carefully screened and browsed 5 medical databases from inception to January 1, 2022. The study will be included that use of rTMS as the intervention for patients with NOP. Two researchers independently completed record retrieval, data processing, and evaluation of methodological quality. Quality and evidence were assessed using the PEDro scores and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Results: Six RCTs with 214 participants were included in this systematic review: 2 studies were considered level 1 evidence, and 4 were considered level 2 evidence. Six studies found that high-frequency rTMS had a pain-relieving effect, while 4 studies found no improvement in psychological conditions and QOL. Quality of evidence (GRADE system) ranged from moderate to high. No significant side effects were found. Conclusions: There is moderate-to-high evidence to prove that high-frequency rTMS is effective in reducing pain in individuals with NOP, but it has no significant positive effect on psychological conditions and QOL. High-frequency rTMS can be used as an alternative treatment for pain in individuals with NOP, but further studies will be conducted to unify treatment parameters, and the sample size will be expanded to explore its influence on psychological conditions and QOL.


Assuntos
Neuralgia , Estimulação Magnética Transcraniana , Dor Facial/etiologia , Dor Facial/terapia , Humanos , Neuralgia/etiologia , Neuralgia/terapia , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
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