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1.
BMC Cancer ; 23(1): 25, 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36611155

RESUMO

BACKGROUND: Hepatocellular carcinoma (HCC) is a common abdominal cancer with dissatisfactory therapeutic effects. The discovery of cuproptosis lights on new approach for cancer treatment and assessment. So far, there is extremely limited research investigating the roles of cuproptosis-related (CR) genes in cancers. METHODS: A novel CR risk signature was constructed using the Lasso regression analysis. Its prognostic value was assessed via a series of survival analyses and validated in three GEO cohorts. The effects of CR risk signature on tumor immune microenvironment (TIM) were explored through CIBERSORT, ESTIMATE, and ssGSEA algorithms. Using GESA, we investigated its impacts on various metabolism process. The somatic mutation features of CR signature genes were also explored via cBioPortal database. Using tumor mutation burden, expressions of immune checkpoints, TIDE score, IMvigor 210 cohort, and GSE109211 dataset, we explored the potential associations of CR risk score with the efficacy of immune checkpoint inhibitors (ICIs) and sorafenib. Finally, the biofunctions of DLAT in HCC cells were ascertained through qPCR, immunohistochemistry, colony formation, and Transwell assays. RESULTS: FDX1, DLAT, CDKN2A and GLS constituted the CR risk signature. CR risk signature possessed high prognostic value and was also applicable to three validation cohorts. Meanwhile, it could improve the accuracy and clinical making-decision benefit of traditional prognostic model. Moreover, high CR risk was indicative of unfavorable anti-tumor immune response and active metabolisms of glycolysis and nucleotide. As for therapeutic correlation, CR risk score was a potential biomarker for predicting the efficacy of ICIs and sorafenib. Through qPCR and immunohistochemistry detection in clinical samples, we reconfirmed DLAT was significantly upregulated in HCC samples. Overexpression of DLAT could promote the proliferation, migration, and invasion of HepG2 and HuH-7 cells. CONCLUSIONS: The novel CR risk signature greatly contributed to the clinical assessment of HCC. Cuproptosis regulatory gene DLAT possessed cancer-promoting capacities and was expected to be a promising therapeutic target for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Sorafenibe , Neoplasias Hepáticas/genética , Genes Reguladores , Fatores de Risco , Microambiente Tumoral/genética
2.
Chem Commun (Camb) ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36632696

RESUMO

Herein, a palladium-catalyzed general synthetic strategy to access an attractive and decorated set of chiral spiro derivatives of benzoxazine compounds is unveiled utilizing vinyl benzoxazinanones reacted with pyrazolone 4,5-diones, which extends the application of vinyl benzoxazinanones with ketones. This asymmetric catalytic [4+2] cycloaddition reaction demonstrates a broad substrate scope with functional group tolerance in yields of up to 76% and up to 96% ee. A facile scale-up and straightforward conversion to diversely substituted products verify the synthetic utility of this method.

3.
Phys Chem Chem Phys ; 2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36636943

RESUMO

Correction for 'Rich magnetic phase transitions and completely dual-spin polarization of zigzag PC3 nanoribbons under uniaxial strain' by Hui-Min Ni et al., Phys. Chem. Chem. Phys., 2023, https://doi.org/10.1039/d2cp05066h.

4.
Phys Chem Chem Phys ; 25(3): 2342-2348, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36597962

RESUMO

Among many modulation methods, strain engineering is often chosen for nanomaterials to produce tunable band gaps continuously. Inspired by the recently reported two-dimensional material PC3, we explore the tuning of strain on the spin-dependent transport properties of PC3 nanoribbons using the first-principle approach. Surprisingly, strain regulation achieves uninterrupted completely dual-spin polarization over a wide energy range near EF. Analysis reveals that the peculiar transmission spectra arise from the interesting evolution of the band structure, in which strain induces bands to shift and broaden/flatten. This results in triggering the transition of PC3NRs from bandgap-tunable bipolar magnetic semiconductors to spin-gapless semiconductors to ferromagnetic metals or half-metal magnets. Their unique performance demonstrates great potential in spintronics, and our study is expected to provide ideas and theoretical support for the design and application of novel PC3-based spintronic devices in the future.

5.
JAMA Netw Open ; 5(12): e2246538, 2022 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-36512354

RESUMO

Importance: Both tuina therapy and yijinjing exercise were beneficial to patients with nonspecific chronic neck pain, but the evidence for this combination is limited. Objective: To investigate the effectiveness of tuina therapy combined with yijinjing exercise compared with tuina therapy alone for patients with nonspecific chronic neck pain. Design, Setting, and Participants: A 12-week, open-label, analyst-blinded randomized clinical trial (8-week intervention plus 4-week observational follow-up) was conducted from September 7, 2020, to October 25, 2021. A total of 102 participants with nonspecific chronic neck pain were recruited, and data were analyzed from December 10, 2021, to March 26, 2022. Interventions: Participants in the tuina group or tuina combined with yijinjing group received 3 sessions of tuina therapy per week for 8 weeks, for a total of 24 sessions. Participants in the tuina combined with yijinjing group practiced yijinjing 3 times a week for 8 weeks, including an instructor-guided exercise at the hospital and 2 self-practice exercises at home. Main Outcomes and Measures: The primary outcome was change in visual analog scale (VAS) score from baseline to week 8. Secondary outcomes included Neck Disability Index scores, Self-rating Anxiety Scale scores, tissue hardness, and active range of motion. Results: This randomized clinical trial recruited 102 patients (mean [SD] age, 36.5 [4.9] years; 69 [67.6%] female) who were randomized to 2 groups. All 102 patients (100%) completed all the outcome measurements. The mean difference in VAS scores from baseline at week 8 for the tuina combined with yijinjing group was -5.4 (95% CI, -5.8 to -5.1). At week 8, the difference in VAS score was -1.2 (95% CI, -1.6 to -0.8; P < .001) between the tuina group and the tuina combined with yijinjing group. The effectiveness of tuina combined with yijinjing in treating nonspecific chronic neck pain remained at the 12-week follow-up. Conclusions and Relevance: In this randomized clinical trial, for patients with nonspecific chronic neck pain, tuina combined with yijinjing was more effective than tuina therapy alone in terms of pain, functional recovery, and anxiety at week 8, and effectiveness remained at week 12. A combination of tuina and yijinjing should be considered in the management of nonspecific chronic neck pain. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2000036805.


Assuntos
Dor Crônica , Terapia por Exercício , Cervicalgia , Adulto , Feminino , Humanos , Masculino , Dor Crônica/terapia , Cervicalgia/terapia , Medição da Dor , Resultado do Tratamento
6.
Can Respir J ; 2022: 1485719, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36582191

RESUMO

Asthma is a chronic inflammatory disturbance of the airways in which many cells and cellular elements are involved. Wheezing, breathlessness, chest tightness, and coughing, especially at night or in the early morning, are typical symptoms of asthma. At present, inhaled corticosteroid (ICS) and long-acting ß-agonists (LABAs) are standard treatments for regular management. Oral corticosteroids (OCSs) were recommended for controlling asthma exacerbation but only for a short-term treatment because of the side effects on organs. Biologic therapies have achieved exciting and notable effects in clinical treatment but are not applicable for all phenotypes of asthma. At present, some new approaches are under exploration to lessen side effects and improve curative effects. Studies have revealed that bone marrow mesenchymal stem cells (BMMSCs) hold various curative effects in asthma and may benefit in the long term with high safety. Extracellular vesicles (EVs) enriched in body fluid were characterized as subcomponents of extracellular vesicles and delivered carriers combined with genetic messages in vivo. The therapeutic potential of exosomes has become a research hotspot in many diseases. BMMSC-derived exosomes were considered as the dominant part of BMMSCs in cell-to-cell communications and playing curative effects. Points also hold that BMMSC-Exo could interfere with airway inflammation and airway remolding in asthma via modulating the immune response, regulating gene expression, adjusting the phenotype of macrophage, etc. However, BMMSC-Exo still lacked more clinical trials for evaluating the effects on asthma, and the technology of extraction and purification still needs to be improved for wide use. This review aims to draw the relationship among asthma, BMMSC, and exosome, which may provide innovate ideas for treatment of asthma, and arouse attention about the curative potential of BMMSC-Exo.


Assuntos
Asma , Exossomos , Células-Tronco Mesenquimais , Humanos , Asma/tratamento farmacológico , Asma/metabolismo , Corticosteroides/uso terapêutico , Quimioterapia Combinada , Células-Tronco Mesenquimais/metabolismo
7.
J Gastrointest Oncol ; 13(5): 2539-2552, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388652

RESUMO

Background: Sodium-glucose co-transporters-2 (SGLT-2) has been reported as overexpressed in tumors including pancreatic cancer (PC). The aim of this study was to investigate the clinicopathological and prognostic significance, as well as the potential role of SGLT-2 in PC development and progression. Methods: The expression of SGLT-2 was assessed using The Cancer Genome Atlas (TCGA) PC dataset (179 cases). The overall survival (OS) and disease-free survival (DFS) of PC patients with high and low SLC5A2 expression were compared using the online database Gene Expression Profiling Interactive Analysis (GEPIA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool. The genetic correlations of SLC5A2 genes in different subtypes of PC were analyzed by using cBioPortal and LinkedOmics online databases. Results: No relationship between SGLT-2 expression and PC risk factors, tumor location, histology grade, or tumor-node-metastasis (TNM) stage was identified. Further, SGLT-2 could not be used as prognosis predictor. The KEGG analyses demonstrated that high SGLT-2 expression is correlated with activation of pathways related with chemical carcinogenesis, energy metabolism and drug metabolism, and the suppression of nucleotide excision repair, messenger RNA (mRNA) surveillance, and cell cycle regulation. Specifically, high SGLT-2 level also coexisted with upregulation of gene symbols for pancreatic progenitor subtype for PC. Conclusions: There is potential for SGLT-2 as a potential target for PC treatment, and SGLT-2 inhibitors should be further evaluated as a novel therapy in PC.

8.
Anal Chim Acta ; 1235: 340537, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36368825

RESUMO

As the most aggressive reactive oxygen species (ROS), hydroxyl radical (•OH) can directly modulate the biological ion channel and interfere with the progression of diseases. Inspired by biological •OH-activated ion channel, we reported a novel •OH-regulated glass nanopore functionalized with protoporphyrin Ⅸ (PP) film. This system showed outstanding •OH selective response owing to the ultra-fast reaction between •OH and thiol derivatives. In this case, the PP film is responsible for the changing not only of wettability but also of the inner surface charge. The synergetic effect of the dual transitions can regulate the ion transportation within the nanochannels and enabled tremendous enhancement of responsive efficiency. The detection limit could be achieved down to 1.58 nM. Taking advantage of the excellent analytical performance and mechanical qualities of this glass nanopore, the changes of •OH in single living cells were in situ monitored. Together, this study is beneficial for exploring the role of •OH in pathological events and shows promising potential for biomedical research.


Assuntos
Radical Hidroxila , Nanoporos , Espécies Reativas de Oxigênio , Vidro
9.
Chem Commun (Camb) ; 58(98): 13632-13635, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36408907

RESUMO

In this work, we introduce trimethylbromosilane (C3H9SiBr), which can protect lithium metal anodes via an in situ formed SEI layer while catalyzing the decomposition of Li2O2. As a result, lithium-oxygen batteries with C3H9SiBr offer a long cycle life of 110 cycles with a significantly reduced charging/discharging overpotential.

10.
Yi Chuan ; 44(10): 937-949, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384729

RESUMO

Idiopathic hypogonadotropic hypogonadism (IHH) is a rare endocrine disease characterized by gonadal dysplasia. According to whether the sense of smell is affected, this disorder is classified into Kallmann syndrome (KS) and normosmic isolated hypogonadotropic hypogonadism (nIHH). In this study, we reported a case of nIHH patient and explored the pathogenic mechanism of FGFR1 in nIHH. A FGFR1 variant (c.2008G>A, p.E670K) and a CEP290 variant (c.964G>A, p.D322N) were detected by the whole exome sequencing in this nIHH patient. Bioinformatic analysis revealed that this FGFR1 variant (c.2008G>A) causes structural perturbations in TK2 domain demonstrating that this variant result in FGFR1 loss-of-function and abnormal signaling. The identification of an additional CEP290 variant (c.964G>A) indicated that CEP290 might play a potential role in developmental abnormalities and inhibition of GnRH neuron release. A protein interaction network analysis showed that CEP290 was predicted to interact with FGFR1. In summary, our study identified the potential pathogenic mechanism(s) of the novel FGFR1 variant and indicated that CEP290 might play a role in the GnRH neuron migration route. Our findings expand the mutation spectrum of FGFR1 and CEP290 and provide a reference for clinical diagnosis and treatment of IHH.


Assuntos
Hipogonadismo , Síndrome de Kallmann , Humanos , Hipogonadismo/genética , Hipogonadismo/diagnóstico , Síndrome de Kallmann/genética , Mutação , Hormônio Liberador de Gonadotropina/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Antígenos de Neoplasias , Proteínas do Citoesqueleto/genética , Proteínas de Ciclo Celular/genética
11.
RSC Adv ; 12(48): 31024-31031, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36349032

RESUMO

Ozonation process is a promising yet challenging method for the removal of refractory organic matter due to the sluggish reaction for generating hydroxyl radical (˙OH) at a neutral pH condition. Herein, an efficient heterogeneous catalytic ozonation system using CeO2/Al2O3 catalyst was developed to remove dimethyl phthalate (DMP) from wastewater. Under a neutral condition of pH = 6, this system achieved almost 100% DMP removal within 15 min at an optimized catalyst dosage of 30 g L-1 and the ozone flow rate of 22.5 mg min-1. Moreover, the catalytic ozonation system exhibited a stable degradation performance of DMP in a wider pH range (pH = 5-10). The results of electron paramagnetic resonance (EPR) and quantitative tests confirmed the ultrafast conversion of O3 to ˙OH (0.774 µM min-1) on the surface of CeO2 based ceramic catalyst. The quenching experiments further supported the predominant role of ˙OH in the mineralization of DMP. These results highlight the potential of using the heterogeneous catalytic ozonation system for the efficient removal of refractory organic matter from wastewater.

12.
Front Psychol ; 13: 1003536, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36324776

RESUMO

Objectives: This study aimed to identify the relationship among proactive personality, psychological safety, academic self-efficacy and critical thinking, and to further explore whether psychological safety and academic self-efficacy could be a moderator in the association between proactive personality and critical thinking among Chinese medical students. Materials and methods: The cross-sectional study was carried out from October to December 2020 in China. Totally, 5,920 valid responses were collected at four Chinese medical universities. Critical thinking, proactive personality, psychological safety, academic self-efficacy and demographic factors were assessed through questionnaires. Hierarchical multiple regression was used to identify interrelationship clusters among variables. Simple slope analyses were performed to explore the moderating effects of psychological safety and academic self-efficacy. Results: The mean score of critical thinking among medical students was 3.85 ± 0.61. Proactive personality, psychological safety, and academic self-efficacy were shown to be important factors for critical thinking. Psychological safety and academic self-efficacy moderated the association between proactive personality and critical thinking. A simple slope analysis showed that high psychological safety and academic self-efficacy weakened the impact of proactive personality on critical thinking. Conclusion: Most medical students surveyed in China might have relatively high levels of critical thinking. Psychological safety and academic self-efficacy moderated the association between proactive personality and critical thinking. More interventions related to psychological safety and academic self-efficacy will be helpful to improve critical thinking among Chinese medical students.

13.
Biomater Sci ; 10(24): 6893-6910, 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36317535

RESUMO

Smart nanomaterials with stimuli-responsive imaging enhancement have been widely developed to meet the requirements of accurate cancer diagnosis. However, these imaging nanoenhancers tend to be always on during circulation, which significantly increases the background signal when assessing the imaging performance. To improve unfavorable signal-to-noise ratios, an effective way is to shield the noise signal of these nanoprobes in non-targeted areas. Fortunately, there is a natural mutual shielding effect between some imaging nanomaterials, which provides the possibility of designing engineered nanomaterials with imaging quenching between two different components at the beginning. Once in the tumor microenvironment, the two components will present activated dual-mode imaging ability because of their separation, designated as two-way imaging tuning. This review highlights the design and mechanism of a series of engineered nanomaterials with two-way imaging tuning and their latest applications in the fields of cancer magnetic resonance imaging, fluorescence imaging, and their combination. The challenges and future directions for the improvement of these engineered nanomaterials towards clinical transformation are also discussed. This review aims to introduce the special constraint relationships of imaging components and provide scientists with simpler and more efficient nanoplatform construction ideas, promoting the development of engineered nanomaterials with two-way imaging tuning in cancer theranostics.

14.
Angew Chem Int Ed Engl ; : e202212939, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36310119

RESUMO

Magnetic molecules have shown great potential in quantum information processing due to the chemical tunablity of their quantum behaviors. Chemical derivatives of endohedral nitrogen fullerenes with long coherence time and rich energy levels were synthesized and studied to demonstrate the ability of multiprocessing in quantum information using electron magnetic resonance. After initialization of the 12-levelled spin system, subgroups of spin energy levels coursed by the hyperfine couplings can be selectively manipulated. The cooperatively combining of the parallel calculations enabled quantum error correction, increasing the correct rate by up to 17.82 %. Also, different subgroups of transitions divided by hyperfine coupling can be treated as independent qubits, and multi-task quantum computing were realized by performing Z-gate and X-gate simultaneously, which accelerates the overall gating speed.

15.
Am J Transl Res ; 14(9): 6303-6312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247276

RESUMO

BACKGROUND: HMO (Hereditary Multiple Osteochondroma), an uncommon autosomal dominant disorder, is characterized by the development of multiple osteochondromas, which are nonmalignant cartilage-capped bone tumors growing outwards from long bone metaphyses. METHODS: The present work retrospectively analyzed seven children with HMO who were enrolled for routine clinical diagnosis and treatment, including X-ray examination. Subsequent genetic detection was carried out using whole exome sequencing (WES). In addition, this work applied Sanger sequencing to be the validation approach. Moreover, this work also examined amino acid (AA) evolutionary conservatism under the influence of certain missense variants. RESULTS: The clinical indications of all seven patients and their family members were thoroughly indexed. WES identified diagnostic variants in the EXT1 or EXT2 gene in these patients. In these variants, four were reported for the first time, namely EXT1: c.1285-2A>T, EXT2: c.1139delT, EXT1: c.203G>A, and EXT1: c.1645_1673del. Familial validation revealed that three of the variants were hereditary, while the other four were de novo, which was consistent with the phenotype in each case. CONCLUSION: Our results expanded HMO variation spectrum, and laid certain foundations for the precise counseling of those affected families.

16.
Front Cardiovasc Med ; 9: 996467, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36247460

RESUMO

Aim: The study (PROSPERO: CRD42021240905) aims to reveal the relationships among red meat, serum lipids and inflammatory biomarkers. Methods and results: PubMed, EMBASE and the Cochrane databases were explored through December 2021 to identify 574 studies about red meat and serum lipids markers including total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP) or hypersensitive-CRP (hs-CRP). Finally, 20 randomized controlled trials (RCTs) involving 1001 people were included, red meat and serum lipid markers and their relevant information was extracted. The pooled standard mean difference (SMD) was obtained by applying a random-effects model, and subgroup analyses and meta-regression were employed to explain the heterogeneity. Compared with white meat or grain diets, the gross results showed that the consumption of red meat increased serum lipid concentrations like TG (0.29 mmol/L, 95% CI 0.14, 0.44,P<0.001), but did not significantly influence the TC (0.13 mmol/L, 95% CI -0.07, 0.33, P = 0.21), LDL-C (0.11 mmol/L, 95% CI -0.23, 0.45, P = 0.53), HDL-C (-0.07 mmol/L, 95% CI -0.31, 0.17, P = 0.57),CRP or hs-CRP (0.13 mmol/L, 95% CI -0.10, 0.37,P = 0.273). Conclusion: Our study provided evidence to the fact that red meat consumption affected serum lipids levels like TG, but almost had no effect on TC, LDL-C, HDL-C and CRP or hs-CRP. Such diets with red meat should be taken seriously to avoid the problem of high lipid profiles. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO], identifier [CRD42021240905].

17.
Adv Mater ; : e2207689, 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36259588

RESUMO

Toward the well-explored lithium-sulfur (Li-S) catalytic chemistry, the slow adsorption-migration-conversion kinetics of lithium polysulfides on catalytic materials and Li2 S deposition-induced passivation of active sites limit the rapid and complete conversion of sulfur. Conceptively, molecular architectures can provide atom-precise models to understand the underlying active sites responsible for selective adsorption and conversion of LiPSs and Li2 S2 /Li2 S species. Here, an octanuclear Zn(II) (Zn8 ) cluster is presented, which features a metallacalix[8]arene with double cavities up and down the Zn8 ring. The central Zn8 ring and the specific double cavities with organic ligands of different electronegativity and bonding environments render active sites with variable steric hindrance and interaction toward the sulfur-borne species. An intramolecular tandem transformation mechanism is realized exclusively by Zn8 cluster, which promotes the self-cleaning of active sites and continuous electrochemical reaction. Notably, the external azo groups and internal Zn/O sites of Zn8 cluster in sequence stimulate the adsorption and conversion of long chain Li2 Sx (x ≥ 4) and short chain Li2 S/Li2 S2 , contributing to remarkable rate performance and cycling stability. This work pioneers the application of metallacalix[n]arene clusters with atom-precise structure in Li-S batteries, and the proposed mechanism advances the molecule-level understanding of Li-S catalytic chemistry.

18.
Phys Chem Chem Phys ; 24(41): 25656-25662, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36255329

RESUMO

Compared with traditional magnetic approaches, electrical modulation of spin-polarized current can greatly reduce the energy consumption and scale of nanodevices and improve their operating speed, which has become a promising research field in spintronics. Motivated by the latest reported novel two-dimensional material ß-SiC7, we employ first-principles calculations to investigate its spin-dependent electron transport with diverse edge configurations. By introducing a gate voltage, the three-terminal device can not only switch between spin-unpolarized and fully spin-polarized states, but also easily change the polarization direction, behaving as an excellent electrically modulated reversible dual-spin filter. Surprisingly, an arbitrary proportion of spin-up and spin-down electron numbers is achieved, enabling precise control of spin polarization. Analysis reveals that it is attributed to the peculiar transmission spectrum, where two broad peaks with opposite spins are located around the Fermi level and respond differently to gate voltage. They belong to the spatially separated edge states originating from the p orbitals of the edge atoms. This feature is robust to different edge configurations of ß-SiC7 nanoribbons, indicating that this may be an intrinsic property of such systems, showing great potential for applications.

19.
Angew Chem Int Ed Engl ; : e202203553, 2022 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-36300875

RESUMO

RNA G-quadruplex (rG4) structures in the 5' untranslated region (5'UTR) play crucial roles in fundamental cellular processes. ADAR is an important enzyme that binds to double-strand RNA and accounts for the conversion of Adenosine to Inosine in RNA editing. However, so far there is no report on the formation and regulatory role of rG4 on ADAR expression. Here, we identify and characterize a thermostable rG4 structure within the 5'UTR of the ADAR1 mRNA and demonstrate its formation and inhibitory role on translation in reporter gene and native gene constructs. We reveal rG4-specific helicase DHX36 interacts with this rG4 in vitro and in cells under knockdown and knockout conditions by GTFH (G-quadruplex-triggered fluorogenic hybridization) probes and modulates translation in an rG4-dependent manner. Our results further substantiate the rG4 structure-DHX36 protein interaction in cells and highlight rG4 to be a key player in controlling ADAR1 translation.

20.
Front Psychol ; 13: 871322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36304878

RESUMO

Nowadays, the traditional production is unable to meet the new diverse needs of target customers. In the current customization era, more and more companies are required by customers to provide more desirable customized products. However, research on customization and standardization based on quantitative analysis has drawn little attention in the literature of dual channel supply chain. In this paper, we study the effect of adopting a dual channel supply chain on the performance of a two-level system (manufacturer-retailer) by using a novelty quantitative approach. We try to analyze the system to get optimal prices and maximize profits, where manufactures offer both standardized and customized products via their traditional and customized channels, respectively. We build a Stackelberg game mode to construct a centralized and a decentralized dual channel scenarios. Furthermore, we study the effects of the different channel structures on price, degree of customization, degree of standardization, and supply chain profitability. We also analyze the effects of both standardized and customized demand sensitivities on their prices and profits. Eventually, we introduce a cost-sharing coordinating contract to optimize the channel's performance. We find that the potential market demand for customization affects the price of customized products and the profits of customized channels. Compared with the decentralized dual channel case, the cost-sharing contract can achieve higher total channel profits. In the cost-coordination case, there is an optimal range for the proportion of standardized costs borne by manufacturers.

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