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1.
Talanta ; 237: 122912, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34736649

RESUMO

Quinones are important components participating in various biological processes as well as hazardous substances to human health. Rapid determination of quinones in environmental samples and biofluids is the basis for assessing their health effect. Here, we presented a rapid, straightforward, highly sensitive and environmental-friendly wooden-tip electrospray ionization mass spectrometry (ESI-MS) method for the determination of quinones in PM2.5, urine and serum. An amine group "tag" was introduced to the quinone structure through in situ derivatization with cysteamine to improve ionization efficiency of quinones in wooden-tip ESI-MS. The toothpicks were treated by sharpening and acidification with HNO3. Experimental parameters, including sample volume, spray voltage, and spray solvent composition were optimized to be 1 µL, 3.5 kV, and ACN/CH3COOC2H5 (v/v, 9:1), respectively. The limits of detection for the determination of 1,4-benzoquinone, methyl-p-benzoquinone, 1,4-naphthoquinone and 1,4-anthraquinone in ACN under the optimal conditions were 1.00, 0.96, 0.13, 0.16 ng (1.00, 0.96, 0.13, 0.16 µg/mL, sample volume, 1 µL), respectively. This approach was successfully applied to the determination of 1,4-naphthoquinone and 1,4-anthraquinone in complex matrices, including PM2.5, urine and serum without or with minimal sample preparation (LOD range: 0.22-1.48 ng).


Assuntos
Quinonas , Espectrometria de Massas por Ionização por Electrospray , Humanos
2.
Front Vet Sci ; 8: 759252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722713

RESUMO

Background: Sarcocystosis is a parasitic disease caused by intracellular protozoan parasite of the genus Sarcocystis. Tissue samples of alpacas (n = 4) from Henan province (China) were screened for Sarcocystis spp. infection by histological examination, pepsin digestion, and molecular assays. Results: Sarcocystis spp. was detected in heart, liver, spleen, lung, and kidney of an alpaca by molecular assays. Many sarcocysts with inflammation responses were observed in this alpaca myocardium, and they showed a high similarity to Sarcocystis masoni by sequence analysis. Conclusion: This study is the first to demonstrate Sarcocystis spp. infection in alpaca from China. The higher parasite load in the alpaca myocardium indicated that it had contact with an environment contaminated with sporocysts, and that the alpaca was susceptible to Sarcocystis spp.

3.
J Thorac Dis ; 13(10): 5942-5953, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34795942

RESUMO

Background: Surgical intervention is generally not considered as a treatment option in patients with advanced non-small cell lung cancer (NSCLC). Accumulating data suggest that surgery may have beneficial effects for these advanced patients. However, no evidence supports the significance of primary tumor resection (PTR) and metastatic tumor resection (MTR) in patients with stage IV lung adenocarcinoma (LUAD). Methods: A total of 32,497 patients diagnosed with primary stage IV LUAD were selected through the Surveillance, Epidemiology, and End Results (SEER) database. Possible confounders were eliminated by propensity score matching (PSM). The overall survival (OS) and lung cancer-specific survival (LCSS) were estimated as the primary endpoints. Furthermore, the independent prognostic factors of patients with the surgical intervention were retrospectively analyzed. Results: Patients underwent surgical intervention had better OS and LCSS than those who did not (P=0.001 for OS; P<0.001 for LCSS). Meanwhile, patients who underwent surgery combined with lymph node dissection had better survival outcomes (P<0.001 for OS and LCSS) in the K-M analysis. For different metastatic sites, PTR was beneficial to the survival of patients with isolated lung metastases (LUM) and multiple organ metastases (MOM) (LUM: P=0.041; MOM: P=0.003). As for metastatic surgery, no patients were found to benefit from resection of metastatic tumor [bone metastasis (BOM): P=0.696; brain metastasis (BRM): P=0.951; LUM: P=0.402; MOM: P=0.365]. Conclusions: Surgical intervention strategies can prolong survival to some extent, depending on different sites of metastasis and highly selected patients.

4.
Front Neurol ; 12: 744017, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764930

RESUMO

Objective: Epilepsy is a chronic disease that places a heavy burden on caregivers. Previous studies have shown that caregivers of epilepsy patients often experience anxiety and depression; however, few comprehensive studies have assessed their sleep quality and family function. Based on the current understanding of the anxiety and depression state of caregivers in children with epilepsy, we further explored the caregivers' sleep and family function and evaluated the predictors of the depression state of caregivers. Methods: In this cross-sectional online anonymous survey, we sent an online questionnaire to the caregivers of children with epilepsy who visited our hospital. The QR code of the questionnaire was scanned at the follow-up course to conduct an online survey. The questionnaire contained questions about sociodemographic and clinical information, the Self-rating Anxiety Scale, Self-rating Depression Scale, Pittsburgh Sleep Quality Index, and the Family Assessment Device. Results: A total of 308 caregivers of children with epilepsy aged 0-12 years were included in this study. The mean age of children with epilepsy was 4.8 ± 3.18 years, and the average illness duration was 34.2 ± 29.18 months. Further, 47.1% of the children took three or more anti-seizure medications, and 43.2% were on ketogenic diet therapy. We found that in 77.9% of the cases, the subjects were the mothers, in 89% there was more than one co-caregiver, and in 51.9%, financial help was required. Further, 63.6% of the caregivers thought they could not get enough access to disease knowledge education, and 83.7% perceived epilepsy was a terrible disease. Our results also showed that 65.6% of the caregivers were in depression status, 41.9% were in anxiety status, and 49.0% had poor sleep quality. The proportion of unhealthy family functioning in each subscale was 45.1-96.1%, and the unhealthy behavior control function accounted for 96.1%. Binary logistic regression analysis of the data showed that without co-caregivers [odds ratio (OR), 5.193], free of anxiety status (OR, 0.063), good sleep quality (OR, 0.446), healthy family role dimension (OR, 0.344), and healthy family general functional dimension (OR, 0.259) were predictors of depression status in caregivers of children with epilepsy. Conclusion: Anxiety and depression status are common in caregivers of children with epilepsy, with depression status being more prominent. Moreover, a considerable proportion of caregivers had poor sleep quality and unhealthy family function. The caregivers' anxiety status, sleep quality, family role dimension, family general function dimension, and the number of co-caregivers were predictors of depression status in caregivers. In clinical practice, caregivers' anxiety and depression status, poor sleep quality, and unhealthy family functioning should be addressed along with the treatment of children with epilepsy.

5.
Front Cell Dev Biol ; 9: 688873, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34765599

RESUMO

Background: Increasing circular RNAs (circRNAs) are reported to participate in cancer progression. Nonetheless, the role of circRNAs in nasopharyngeal carcinoma (NPC) has not been fully clarified. This work is aimed to probe the role of circ_0000215 in NPC. Methods: Circ_0000215 expression in NPC tissues and cell lines was examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell counting kit-8 (CCK-8) assay, 5-bromo-2'-deoxyuridine (BrdU) assay, scratch healing assay and Transwell experiment were executed to investigate the regulatory function of circ_0000215 on the proliferation, migration and invasion of NPC cells. RNA immunoprecipitation (RIP), pull-down and dual-luciferase reporter experiments were utilized to determine the binding relationship between circ_0000215 and miR-512-5p, and between miR-512-5p and phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) 3'UTR. The effects of circ_0000215 on NPC growth and metastasis in vivo were examined with nude mice model. Western blot was applied to detect the regulatory effects of circ_0000215 and miR-512-5p on PIK3R1 expression. Results: Circ_0000215 was overexpressed in NPC tissues and cell lines. The functional experiments confirmed that knockdown of circ_0000215 impeded the growth and metastasis of NPC cells in vitro and in vivo. Additionally, circ_0000215 could also work as a molecular sponge to repress miR-512-5p expression. PIK3R1 was validated as a target gene of miR-512-5p, and circ_0000215 could increase the expression level of PIK3R1 in NPC cells via suppressing miR-512-5p. Conclusion: Circ_0000215 is overexpressed in NPC and exerts oncogenic effects in NPC through regulating miR-512-5p/PIK3R1 axis.

6.
Front Mol Biosci ; 8: 751506, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34746234

RESUMO

Background: Recently, many studies have suggested that bilirubin is associated with the prognosis of colorectal cancer (CRC). Conversely, there is substantial evidence that lactate dehydrogenase (LDH) levels are associated with the prognosis of cancer. Therefore, we sought to find a novel marker based on the above to predict prognosis in patients with resectable CRC. Methods: A total of 702 patients from Hubei Cancer Hospital were included. The whole population was randomly divided into training (n = 491) and testing (n = 211) cohorts. Next, we established a new index based on direct bilirubin, indirect bilirubin and LDH levels. Chi-square tests, Kaplan-Meier survival analyses, and Cox regression analyses were used to evaluate prognosis. The prediction accuracies of models for overall survival (OS) and disease-free survival (DFS) were estimated through Harrell's concordance index (C-index) and the Brier score. Results: The median DFS duration was 32 months (range: 0-72.6 months), whereas the median OS duration was 35 months (range: 0 months-73.8 months). In addition, a new indicator, (DIR.LDH) (HR: 1.433; 95% CI, 1.069-1.920) could independently predict outcomes in CRC patients. Moreover, the module based on DIR. LDH was found to have exceptional performance for predicting OS and DFS. The C-index of the nomogram for OS was 0.802 (95% CI, 0.76-0.85) in the training cohort and 0.829 (95% CI, 0.77-0.89) in the testing cohort. The C-index of the nomogram for DFS was 0.774 (95% CI, 0.74-0.81) in the training cohort and 0.775 (95% CI, 0.71-0.84) in the testing cohort. Conclusion: We successfully established a novel module to guide clinical decision-making for CRC.

7.
Natl Sci Rev ; 8(3): nwaa297, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34676096

RESUMO

Receptor recognition and subsequent membrane fusion are essential for the establishment of successful infection by SARS-CoV-2. Halting these steps can cure COVID-19. Here we have identified and characterized a potent human monoclonal antibody, HB27, that blocks SARS-CoV-2 attachment to its cellular receptor at sub-nM concentrations. Remarkably, HB27 can also prevent SARS-CoV-2 membrane fusion. Consequently, a single dose of HB27 conferred effective protection against SARS-CoV-2 in two established mouse models. Rhesus macaques showed no obvious adverse events when administrated with 10 times the effective dose of HB27. Cryo-EM studies on complex of SARS-CoV-2 trimeric S with HB27 Fab reveal that three Fab fragments work synergistically to occlude SARS-CoV-2 from binding to the ACE2 receptor. Binding of the antibody also restrains any further conformational changes of the receptor binding domain, possibly interfering with progression from the prefusion to the postfusion stage. These results suggest that HB27 is a promising candidate for immuno-therapies against COVID-19.

8.
Dalton Trans ; 50(43): 15473-15487, 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34668916

RESUMO

Molecular magnetorefrigerant materials for low-temperature magnetic refrigeration and single-molecule magnets for high-density information storage and quantum computing have received extensive attention from chemists and magnetic experts. Lanthanide ions with unique magnetic properties have always been considered as ideal candidates for the construction of such materials. This frontier article focuses on GdIII-based molecular magnetorefrigerants and lanthanide-based single-molecule magnets and highlights the most significant advances.

9.
Front Immunol ; 12: 719807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691027

RESUMO

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson's disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.

10.
Parasit Vectors ; 14(1): 502, 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34579769

RESUMO

BACKGROUND: Eimeria necatrix is one of the most pathogenic parasites, causing high mortality in chickens. Although its genome sequence has been published, the sequences and complete structures of its mRNA transcripts remain unclear, limiting exploration of novel biomarkers, drug targets and genetic functions in E. necatrix. METHODS: Second-generation merozoites (MZ-2) of E. necatrix were collected using Percoll density gradients, and high-quality RNA was extracted from them. Single-molecule real-time (SMRT) sequencing and Illumina sequencing were combined to generate the transcripts of MZ-2. Combined with the SMRT sequencing data of sporozoites (SZ) collected in our previous study, the transcriptome and transcript structures of E. necatrix were studied. RESULTS: SMRT sequencing yielded 21,923 consensus isoforms in MZ-2. A total of 17,151 novel isoforms of known genes and 3918 isoforms of novel genes were successfully identified. We also identified 2752 (SZ) and 3255 (MZ-2) alternative splicing (AS) events, 1705 (SZ) and 1874 (MZ-2) genes with alternative polyadenylation (APA) sites, 4019 (SZ) and 2588 (MZ-2) fusion transcripts, 159 (SZ) and 84 (MZ-2) putative transcription factors (TFs) and 3581 (SZ) and 2039 (MZ-2) long non-coding RNAs (lncRNAs). To validate fusion transcripts, reverse transcription-PCR was performed on 16 candidates, with an accuracy reaching up to 87.5%. Sanger sequencing of the PCR products further confirmed the authenticity of chimeric transcripts. Comparative analysis of transcript structures revealed a total of 3710 consensus isoforms, 815 AS events, 1139 genes with APA sites, 20 putative TFs and 352 lncRNAs in both SZ and MZ-2. CONCLUSIONS: We obtained many long-read isoforms in E. necatrix SZ and MZ-2, from which a series of lncRNAs, AS events, APA events and fusion transcripts were identified. Information on TFs will improve understanding of transcriptional regulation, and fusion event data will greatly improve draft versions of gene models in E. necatrix. This information offers insights into the mechanisms governing the development of E. necatrix and will aid in the development of novel strategies for coccidiosis control.

11.
Dalton Trans ; 50(41): 14714-14723, 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34586106

RESUMO

The reaction of the redox-active tetrathiafulvalene ligand and lanthanide ions is an important approach to prepare photo-electro-magnetic multifunctional metal-organic framework materials. A series of isostructural lanthanide metal-organic frameworks (Ln-MOFs) based on the in situ generated tetrathiafulvalene dicarboxylate (TTF-DC) ligand, {[Ln4(TTF-DC)6(DMF)4(H2O)2]·4DMF}n (Ln = Gd (1-Gd), Tb (1-Tb), Dy (1-Dy) and Er (1-Er)), was synthesized and characterized. These Ln-MOFs display tunable redox-active properties and semiconductor performance, and their electronic conductivities have been significantly improved after oxidation. All MOFs except 2-Tb exhibit slow magnetic relaxation under an applied dc field. 1-Dy and 2-Dy show field-induced single-molecule magnet (SMM) behaviour with energy barriers (Ueff) of 30.77 K (τ0 = 5.23 × 10-8) and 26.41 K (1.04 × 10-8 s), respectively.

12.
J Gastrointest Oncol ; 12(4): 1568-1576, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532111

RESUMO

Background: The use of surgery in patients with colorectal cancer (CRC) aged ≥90 years remains controversial. This study aimed to evaluate the short-term postoperative and long-term oncologic outcomes of CRC surgery in patients within this age group. Methods: A total of 151 consecutive nonagenarian patients who underwent CRC surgery were included from 3 different hospitals. The Comprehensive Complication Index (CCI) was used to grade postoperative complications. Univariate and multivariate analyses were conducted to identify factors associated with CCI and overall survival (OS). Results: The patients had a mean age of 92.8 years (standard deviation ±1.9 years). Forty-six patients (30.5%) underwent emergency surgery, and 105 patients (69.5%) underwent elective surgery. The postoperative complications rate was 66.2% (100/151), and the mean CCI was 26.3 (±30.8). Twenty-three patients (15.2%) died postoperatively, and the perioperative mortality rates for elective surgery and emergency surgery were 7.6% (8/105) and 32.6% (15/46), respectively (P<0.001). The 1-, 3-, and 5-year survival rates were 77.5%, 53.9%, and 38.6%, respectively. Multivariate analysis revealed emergency surgery and American Society of Anesthesiologists (ASA) score to be predictors of postoperative complications. Advanced tumor stage, palliative surgery, ASA score ≥4, and CCI >17 were associated with poor OS. Conclusions: CRC surgery should not be denied to nonagenarian patients. Surgical treatment can be performed with acceptable morbidity and mortality, and achieves long-term survival in a select group.

13.
J Biomed Nanotechnol ; 17(8): 1535-1544, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34544531

RESUMO

This study aimed to detect miR-455-5p and S1PR1 proteins using nanoparticle-assisted polymerase chain reaction (nano-PCR) to determine their correlation with cervical carcinoma prognosis. To achieve this study's goals, we selected 48 cervical carcinoma patients between January 2014 to January 2016 and subjected them to the miR-455-5p test by nano-PCR. The collected samples were then divided into two groups based on miR-455-5p levels. We had four HeLa cell groups, one group as the control, and one group overexpressed the miR-455-5p protein. A third group was miR-455-5p silent, and a separate group overexpressed both the miR-455-5p and S1PR1 proteins. Results also proved that the nano-PCR had a higher sensitivity than RT-PCR, and patients with poor prognosis had lesser miR-455-5p levels. Similarly, high levels of miR-455-5 contributed to cancer cell apoptosis and migration inhibition by targeting S1PR1 expression negatively. These two biomarkers are therefore significantly related to the prognosis of cervical carcinoma patients.


Assuntos
Carcinoma , Nanopartículas Metálicas , MicroRNAs , Neoplasias do Colo do Útero , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Ouro , Células HeLa , Humanos , Fosfatos , Reação em Cadeia da Polimerase , Esfingosina , Neoplasias do Colo do Útero/genética
14.
Laser Photon Rev ; 15(8)2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34539926

RESUMO

Imaging systems with miniaturized device footprint, real-time processing speed and high resolution three-dimensional (3D) visualization are critical to broad biomedical applications such as endoscopy. Most of existing imaging systems rely on bulky lenses and mechanically refocusing to perform 3D imaging. Here, we demonstrate GEOMScope, a lensless single-shot 3D microscope that forms image through a single layer of thin microlens array and reconstructs objects through an innovative algorithm combining geometrical-optics-based pixel back projection and background suppressions. We verify the effectiveness of GEOMScope on resolution target, fluorescent particles and volumetric objects. Comparing to other widefield lensless imaging devices, we significantly reduce the required computational resource and increase the reconstruction speed by orders of magnitude. This enables us to image and recover large volume 3D object in high resolution with near real-time processing speed. Such a low computational complexity is attributed to the joint design of imaging optics and reconstruction algorithms, and a joint application of geometrical optics and machine learning in the 3D reconstruction. More broadly, the excellent performance of GEOMScope in imaging resolution, volume, and reconstruction speed implicates that geometrical optics could greatly benefit and play an important role in computational imaging.

15.
Photonics Res ; 9(3): B57-B70, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34532505

RESUMO

The need for high-speed imaging in applications such as biomedicine, surveillance and consumer electronics has called for new developments of imaging systems. While the industrial effort continuously pushes the advance of silicon focal plane array image sensors, imaging through a single-pixel detector has gained significant interests thanks to the development of computational algorithms. Here, we present a new imaging modality, Deep Compressed Imaging via Optimized-Pattern Scanning (DeCIOPS), which can significantly increase the acquisition speed for a single-detector-based imaging system. We project and scan an illumination pattern across the object and collect the sampling signal with a single-pixel detector. We develop an innovative end-to-end optimized auto-encoder, using a deep neural network and compressed sensing algorithm, to optimize the illumination pattern, which allows us to reconstruct faithfully the image from a small number of samples, and with a high frame rate. Compared with the conventional switching-mask based single-pixel camera and point scanning imaging systems, our method achieves a much higher imaging speed, while retaining a similar imaging quality. We experimentally validated this imaging modality in the settings of both continuous-wave (CW) illumination and pulsed light illumination and showed high-quality image reconstructions with a high compressed sampling rate. This new compressed sensing modality could be widely applied in different imaging systems, enabling new applications which require high imaging speed.

17.
ACS Sens ; 6(10): 3517-3535, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34529414

RESUMO

Rapid and sensitive detection of clinical biomolecules in a multiplexed fashion is of great importance for accurate diagnosis of diseases. Mass spectrometric (MS) approaches are exceptionally suitable for clinical analysis due to its high throughput, high sensitivity, and reliable qualitative and quantitative capabilities. To break through the bottleneck of MS technique for detecting high-molecular-weight substances with low ionization efficiency, the concept of mass spectrometric biosensing has been put forward by adopting mass spectrometric chips to recognize the targets and mass spectrometry to detect the signals switched by the recognition. In this review, the principle of mass spectrometric sensing, the construction of different mass tags used for biosensing, and the typical combination mode of mass spectrometric imaging (MSI) technique are summarized. Future perspectives including the design of portable matching platforms, exploitation of novel mass tags, development of effective signal amplification strategies, and standardization of MSI methodologies are proposed to promote the advancements and practical applications of mass spectrometric biosensing.


Assuntos
Espectrometria de Massas , Padrões de Referência
18.
Mol Carcinog ; 60(12): 813-825, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34499772

RESUMO

Cancer multidrug resistance (MDR) is existence in stem cell-like cancer cells characterized by stemness including high-proliferation and self-renewal. Programmed cell death 4 (PDCD4), as a proapoptotic gene, whether it engaged in cancer stemness and cisplatin resistance is still unknown. Here we showed that PDCD4 expressions in Hela/DDP (cisplatin resistance) cells were lower than in parental Hela cells. Moreover, the levels of drug resistance genes and typical stemness markers were markedly elevated in Hela/DDP cells. In vivo, xenograft tumor assay confirmed that knockdown of PDCD4 accelerated the grafted tumor growth. In vitro, colony formation and MTT assay demonstrated that PDCD4 overexpression inhibited cells proliferation in conditions with or without cisplatin. By contrast, PDCD4 deficiency provoked cell proliferation and cisplatin resistance. On mechanism, PDCD4 decreased the protein levels of pAKT and pYB1, accompanied by reduced MDR1 expression. Correspondingly, luciferase reporter assay showed PDCD4 regulated MDR1 promoter activity entirely relied on YB1. Furthermore, Ch-IP, GST-pulldown, and Co-IP assays provided novel evidence that PDCD4 could directly bind with YB1 by the nucleolar localization signal (NOLS) segment, causing the reduced YB1 binding into the MDR1 promoter region through blocking YB1 nucleus translocation, triggering the decreased MDR1 transcription. Taken together, PDCD4-pAKT-pYB1 forms the integrated molecular network to regulate MDR1 transcription during the process of stemness-associated cisplatin resistance.

19.
Proc Natl Acad Sci U S A ; 118(36)2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34462354

RESUMO

The molecular events that determine the recycling versus degradation fates of internalized membrane proteins remain poorly understood. Two of the three members of the SNX-FERM family, SNX17 and SNX31, utilize their FERM domain to mediate endocytic trafficking of cargo proteins harboring the NPxY/NxxY motif. In contrast, SNX27 does not recycle NPxY/NxxY-containing cargo but instead recycles cargo containing PDZ-binding motifs via its PDZ domain. The underlying mechanism governing this divergence in FERM domain binding is poorly understood. Here, we report that the FERM domain of SNX27 is functionally distinct from SNX17 and interacts with a novel DLF motif localized within the N terminus of SNX1/2 instead of the NPxY/NxxY motif in cargo proteins. The SNX27-FERM-SNX1 complex structure reveals that the DLF motif of SNX1 binds to a hydrophobic cave surrounded by positively charged residues on the surface of SNX27. The interaction between SNX27 and SNX1/2 is critical for efficient SNX27 recruitment to endosomes and endocytic recycling of multiple cargoes. Finally, we show that the interaction between SNX27 and SNX1/2 is critical for brain development in zebrafish. Altogether, our study solves a long-standing puzzle in the field and suggests that SNX27 and SNX17 mediate endocytic recycling through fundamentally distinct mechanisms.

20.
Mol Biochem Parasitol ; 245: 111408, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34343548

RESUMO

Thioredoxin peroxidase (TPx) plays an important role in protecting parasites against oxidative damage. However, studies on the role of TPxs in Echinococcus multilocularis are limited. In this study, one tpx gene of E. multilocularis, named as emtpx-1, was identified. EmTPx-1 shares two positionally conserved cysteine residues (Cys48 and Cys169) with orthologs from other platyhelminths. EmTPx-1 is highly expressed in the germinal layer and present in exosome-like vesicles secreted by E. multilocularis metacestodes. EmTPx-1 displays peroxidase activity, which removes hydrogen peroxide in the presence of dithiothreitol. Furthermore, EmTPx-1 could protect DNA from oxidative damages, and EmTPx-1-expressing E. coli cells had an enhanced resistance to oxidative stress. In addition, EmTPx-1 enhanced the expression of arg1, ym1, and il-10, but suppressed inos, tnf-α, and il-1ß expression in LPS-stimulated macrophages. Our data suggest a critical role for EmTPx-1 in oxidative stresses and M2 macrophage polarization.

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