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1.
Front Genet ; 13: 941389, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36046234

RESUMO

Background: Cellular senescence plays a critical role in the occurrence and development, and immune modulation of cancer. This research primarily investigated the role of senescence-associated genes (SAGs) in the survival and tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC). Methods: From the Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) database, the gene expression profiles and clinical data of PDAC samples were downloaded. SAGs in the TCGA cohort were used to build a novel prognostic model and validated in the ICGC cohort. The relationship of signature with the immune landscape, tumor mutational burden (TMB), as well as the sensitivity of different therapies, was explored. Moreover, a nomogram was developed to predict the overall survival of PDAC patients. Results: A prognostic signature was constructed on basis of three SAGs, and patients in the low-risk score group had a longer survival time. The accuracy of the signature to distinguish different score groups was confirmed through principal component analysis (PCA) and the Receiver operator curves curve. The mRNA expression of the three signature genes was also verified in normal pancreatic and PDAC cell lines by RT-qPCR. The signature could independently predict the prognosis of PDAC patients and had broad applicability. Meanwhile, the nomogram predicted that 1- and 3-years survival rates were in good agreement with the observed overall survival rates. Low-risk patients had lower tumor mutational burden, and low-TMB patients had a better prognosis. Low- and high-risk patients exhibit distinct immune cell infiltration and immune checkpoint changes. By further analyzing the risk score, patients in the low-risk group were more responsive to immunotherapy and a variety of commonly used chemotherapeutic drugs. Conclusion: The prognostic signature can well predict the prognosis and assess the possibility of immunotherapy in personalized PDAC treatment.

2.
Plant Dis ; 2022 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-36089683

RESUMO

Gaillardia pulchella Foug., belonging to the family Asteraceae, is an annual herb commonly seen in tropical America and China. It is often used as ornamental flowers because of its bright color, long flowering period and simple cultivation and management. In June 2021, leaf spot on G. pulchella with ∼40% disease incidence was observed in Laoshan scenic spot of Qingdao, Shandong Province, China. Initial symptoms on leaves appeared as light yellow to brown round or oval spots with dark brown borders, and the lesion area gradually expanded and the color deepened with the development of the disease. Small tissue samples collected from the infected lesions were surface-sterilized with 70% ethanol for 30 s, then rinsed with 2% sodium hypochlorite (NaClO) for 60 s, and finally rinsed with sterilized water three times. All the samples were transferred to potato dextrose agar (PDA) medium and incubated at 25℃ in the dark for 5 days (Zhu et al. 2013). A total of 9 isolates were obtained from the 11 selected tissues of symptomatic leaves. Afterward, all the single spore isolates were transferred onto potato carrot agar (PCA) plates (Mirkova 2003). After 7 to 10 days of incubation on PCA at 25℃ in the dark, colonies had a cottony mycelium with round margins, colored in white to gray. To test pathogenicity, six healthy G. pulchella plants were inoculated with mycelial plugs of the above pure cultures from a 7-day-old culture grown on PCA, while six germfree PCA plugs were served as negative controls. All the inoculated plants were set in greenhouse incubator at 25℃ and 80% relative humidity. Following 5 days incubation, brown spots began to appear on the sites of all inoculated leaves with mycelial plugs, while all the negative controls inoculated with sterile PCA plugs remained healthy. Infected lesions were separated and cultured as the same as those isolated in the field, and the same isolate was again microscopically identified, fulfilling Koch's postulates. 5 isolates were characterized, the colony margins of single spore isolate were round with gray or black aerial mycelia. Conidia were clustered and unbranched with 1 to 4 septa, colored in light or dark brown, shaped in obclavate or ellipsoid with short conical beak at the tip, dimensions varied from 14 to 51 µm (length) × 4.5 to 11 µm (width). The described morphological characteristics were consistent with Alternaria alternata (Simmons 2007). For further identification of molecular characterization, the genes of Chitin synthase (CHSD), RNA polymerase II second largest subunit (PRB2), Tsr1 ribosome biogenesis protein (Tsr1) and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) were obtained by PCR amplification with the primer pairs CHSDF1/CHSDR1, PRB2DF/PRB2DR, Tsr1F/Tsr1R and GAPDHF1/GAPDHR1 (Damn et al. 2019; Lawrence et al. 2013), respectively. The sequenced genes (GenBank accession nos. ON660874, ON660875, ON660876 and ON660877) had more than 99% nucleotide identity with the corresponding genes (GenBank accession nos. KY996470.1, MN304718.1, KY996472.1 and MN158133.1) of the reference strains of A. alternata in GenBank, and the re-inoculated and re-isolated strains have the same results which were repeated three times. The causal agent occurred on G. pulchella was identified as A. alternata based on the morphological and molecular characteristics. To our knowledge, this is the first record causing leaf spot on G. pulchella by A. alternata in China.

3.
ACS Omega ; 7(36): 32131-32152, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36120034

RESUMO

The pathogenesis of Alzheimer's disease (AD) is very complex, and there are many hypotheses. Therefore, the development of a multi-target-directed-ligand may be an effective therapeutic strategy. Our previous study showed that notopterol (a natural product from Notopterygium) is a dual BACE1/GSK3ß inhibitor. In this study, we designed and synthesized 48 notopterol derivatives with furacoumarin as a scaffold in order to enhance their balanced AChE/BACE1/GSK3ß inhibitory activity. Fortunately, 1c showed effective inhibitory activity against AChE (58.7% at 1.0 µM), BACE1 (48.3% at 20 µM), and GSK3ß (40.3% at 10 µM). Furthermore, 1c showed good blood-brain barrier penetrability, suitable bioavailability, and oral safety. More importantly, 1c could ameliorate the impaired learning and memory in Aß-induced AD mice. In conclusion, we reported the triple inhibitor of AChE/BACE1/GSK3ß lead compounds based on a furocoumarin scaffold of notopterol for the first time, which provides a potential new strategy for the treatment of AD.

4.
Int J Biol Macromol ; 221: 1041-1052, 2022 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-36113586

RESUMO

Lignin nanoparticles (LNPs), as a new type of green nanomaterial, initiate many promising applications in polymer composites. However, their heterogeneity, dissolution in organic solvents, and poor compatibility in the polymer matrix greatly limited the applications of LNPs fillers. Herein, we proposed an antisolvent precipitation of the fractionations by combining a hydrothermal treatment-assisted synthesis to fabricate self-crosslinked LNPs (ScLNPs), which have good stability in the organic solvent and controllable sizes. After surface grafting modification with d-lactide, ScLNPs-graft-poly(d-lactide) (ScLNPs-g-PDLA) exhibited excellent dispersion and compatibility in PLLA matrix. Using the rational design and addition of ScLNPs-g-PDLA fillers, the strength and toughness of the generated PLLA composite reached 31.6 MPa and 396 % (the highest value among the PLLA materials), respectively. Furthermore, the mechanical performance can also be well-tuned by the sizes and amounts of LNPs fillers. This strategy involving only green and recyclable materials provides an effective route to producing sustainable polymeric plastics with integrated strength and super-toughness.

5.
Front Med (Lausanne) ; 9: 977586, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091674

RESUMO

Purpose: This research aims to study the corneal morphological changes in adult patients with myopic anisometropia after small incision lenticule extraction (SMILE) and the safety, efficacy, and predictability of clinical outcomes. Methods: This was a prospective cohort study. Patients with myopic anisometropia [refractive difference >2.0 diopters (D)] were included in this study who underwent SMILE at our hospital from September 2019 to March 2021. For the two eyes of each patient, the one with higher myopia was defined as group A, and the fellow eye was group B. The follow-up time points were set as 1 week, 1 month, 3 months, and 6 months after the surgery. The data collected were uncorrected and best-corrected distance visual acuity (UDVA and CDVA), spherical equivalent (SE), efficacy and safety indexes, posterior corneal elevation (PCE), anterior and posterior corneal radius of curvature in the 3 mm area at the center of the thinnest point of the cornea (ARC and PRC), and higher-order aberrations (HOAs). Results: The study included 36 patients (72 eyes), and the mean age was 25.2 ± 6.4 years. The preoperative SEs were -6.45 ± 1.25 D in group A and -3.76 ± 1.29 D in group B. Six months after surgery, the SEs in groups A and B were -0.09 ± 0.50 D and 0.07 ± 0.47 (P = 0.059), respectively. The efficacy indexes were 1.06 ± 0.16 in group A and 1.07 ± 0.14 in group B (P = 0.750). The safety indexes were 1.08 ± 0.14 in group A and 1.12 ± 0.15 in group B (P = 0.173). The PCE was significantly reduced at 6 months after surgery in pagebreak both groups (P < 0.05). The ARC was significantly higher than before the surgery (P < 0.05) in the two groups. The two groups showed significant increases in total HOAs, coma 90°, and spherical aberrations (P < 0.05). Conclusion: SMILE is predictable, effective, and safe in correcting myopic anisometropia. The postoperative changes in HOAs are characteristic.

6.
Front Pharmacol ; 13: 893244, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091836

RESUMO

Yuan-Zhi Decoction (YZD) is a traditional Chinese medical formulation with demonstrated clinical benefits in Alzheimer's disease (AD). We used liquid chromatography coupled with mass spectrometry to identify 27 unique chemical components of YZD. Analyzing these using network pharmacology and molecular docking models identified 34 potential interacting molecular targets involved in 26 biochemical pathways. When tested in an animal model of AD, the APP/PS1 transgenic mice showed measurable improvements in spatial orientation and memory after the administration of YZD. These improvements coincided with significantly reduced deposition of Aß plaques and tau protein in the hippocampi in the treated animals. In addition, a decreased BACE1 and beta-amyloid levels, a downregulation of the p-GSK-3ß/GSK-3ß, and an upregulation of the PI3K and p-AKT/AKT pathway was seen in YZD treated animals. These in vivo changes validated the involvement of molecular targets and pathways predicted in silico analysis of the chemical components of YZD. This study provides scientific support for the clinical use of YZD and justifies further investigations into its effects in AD. Furthermore, it demonstrates the utility of network pharmacology in elucidating the biochemical mechanisms underlying the beneficial effects of traditional Chinese medicines (TCM).

7.
J Gastrointest Oncol ; 13(4): 2020-2032, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092326

RESUMO

Background and Objective: Colorectal cancer (CRC) is the third most common cancer worldwide, and the incidence and mortality rates continue to increase annually. Many factors, including genetic, immune, and environmental factors, influence the occurrence and development of CRC. Along with the economic development, changes in lifestyle, especially dietary factors, have been shown to greatly affect the progression of CRC. Increasing evidence showed that dietary patterns influence the risk of CRC and affect CRC treatment. The present review describes the role of diet in the prevention and treatment of CRC with the hope that doctors attach importance to dietary patterns in educating patients with CRC or at risk of CRC and that diet may be regarded as an auxiliary treatment strategy to improve patients' outcomes. Methods: English language articles published from 2000 to December 2021 in PubMed and Embase were identified by searching titles for keywords including "diet", "colorectal cancer", "dietary pattern", and "dietary factor"; 101 articles were selected for review. Key Content and Findings: The present review describes the role of different dietary patterns and factors in the prevention and treatment of CRC. We found that dietary intervention is closely related to the occurrence, development, and prognosis of CRC. Adherence to the Mediterranean diet (MD), the Dietary Approaches to Stop Hypertension (DASH) diet, fasting, vegetarian diets and the ketogenic diet (KD) were found to reduce the risk of CRC, prolong patient survival, and delay disease progression. Moderate intake of dietary fiber (DF), omega-3 fatty acids, micronutrients (e.g., calcium, iron, and selenium), and vitamins have been shown to be beneficial in the prevention and treatment of CRC. Conversely, diets high in fat or sugar and those rich in red meat or processed meat promote CRC. Conclusions: People at high risk of CRC and those with CRC are recommended to eat a plant-based diet rich in fruits, vegetables, and whole grains with appropriate DF intake and to avoid high levels of processed meat, red meat, and highly refined grains.

8.
Biomed Pharmacother ; 155: 113681, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-36108392

RESUMO

The modern rise in type 2 diabetes mellitus (T2DM) and its correlation to commensal microbiota have elicited global concern about the patterns of microbial action in the host. With the exception of that linked to gut, microbiota were also colonized in pancreas, oral, and lung, contributing to the physiopathology of T2DM. In this study, we aimed to explore the protective effects of Ganoderma atrum polysaccharide (PSG) and White Hyacinth Bean polysaccharide (WHBP) on the intestine, pancreas, oral, and lung microbiota in T2DM rats. Here we showed that, despite capacities of polysaccharides that exerted similar protective effects on hyperglycemia, dyslipidemia, insulin resistance and dysbacteriosis in T2DM rats, PSG and WHBP were able to be characterized by their own "target" bacteria, which could be proposed for activity-fingerprinting of polysaccharide species. Furthermore, we found a mutual bacteria spectrum in the pancreas and lung, and most bacteria could be tracked to oral or gut samples. Notably, the overlapping areas of the microbiota profile between organs (pancreas, lung) and saliva were more than in the gut, suggesting that a saliva sample was also of interest to serve as a "telltale sign" for judging pancreatic injury. Together, these microbiota interactions provided a new potential to harvest alternative samples for disease surveillance. Meanwhile, polysaccharides had anti-T2DM abilities, which could be distinguished by their own characteristic bacteria.

9.
J Zhejiang Univ Sci B ; 23(9): 778-783, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36111574

RESUMO

To increase the efficiency and accuracy of clinical tumor detection, we explored multiple imaging by preparing carbon quantum dot (CQD)-loaded nanobubbles for ultrasonic fluorescence dual detection. In this experiment, we prepared 1,2-dioleoyl3-trimethylammonium-propane chloride (DOTAP) cationic liposomes using the film dispersion method and chose perfluoropentane as the core gas material of the nanobubbles. The nanobubbles were coupled with the negatively charged CQDs through the charge effect to prepare the testing agent for two-way diagnosis with ultrasound contrast and fluorescence detection. The formulation and preparation of the loaded CQD liposome nanobubbles were screened. In vivo experiments showed that nanobubbles can be enriched to the tumor site within 5 min, which enables clearer ultrasound imaging and is conducive to tumor detection. We expect CQD-loaded liposome (Lip-CQD) nanobubbles to become a new ultrasonic contrast agent for clinical applications that can provide a basis for early tumor diagnosis and thus earlier treatment.


Assuntos
Neoplasias , Pontos Quânticos , Carbono , Cloretos , Meios de Contraste , Fluorescência , Humanos , Lipossomos , Neoplasias/diagnóstico , Propano , Ultrassom
10.
Adv Healthc Mater ; : e2201441, 2022 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-36125400

RESUMO

Thermotherapy can directly kill tumor cells while accompanied by immune-enhancing effects. However, this immune-enhancing effect suffers from insufficient expression of immune response factors (e.g., heat shock protein 70, HSP70), resulting in no patient benefiting due to the recurrence of tumor cells after thermotherapy. Herein, we  explore the nanoengineered strategy of programmed upregulating the immune response factors for amplifying synergistic therapy. The as-prepared metal-organic frameworks nanoamplifier (teprenone/nitrocysteine@ZrMOF-NH2 @L-menthol@triphenylphosphine, GGA/CSNO@ZrMOF-NH2 -LM-TPP nanoamplifier, GCZMT nanoamplifier) achieve excellent microwave (MW) thermal-immunotherapy by programmed induction of HSP70 expression. After intravenous administration, GCZMT nanoamplifiers target to the mitochondrial, and then release nitric oxide (NO) under MW irradiation. NO inhibits the growth of tumor cells by interfering with the energy supply of cells. Subsequently, under the combination of MW, NO and GGA, HSP70 expression can be programmed upregulated, which can induce the response of cytotoxic CD4+ T cells and CD8+ T cells, and effectively activate antitumor immunotherapy. Hence, GCZMT nanoamplifier-mediated MW therapy can achieve satisfactory therapeutic effect with the tumor inhibition of 97%. This research offers a distinctive insight into the exploitation of metal-organic frameworks nanoamplifier for enhanced tumor therapy, which provides a new approach for highly effective cancer treatment. This article is protected by copyright. All rights reserved.

11.
Eur J Med Chem ; 242: 114701, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36054949

RESUMO

CDK2/9 are members of the CDKs family, which play key roles in the occurrence and development of many cancers by regulating cell cycle and transcriptional prolongation, respectively. To further optimize and discuss the structure-activity relationships (SARs), a series of tacrine-based compounds were designed and synthesized from the compound ZLWT-37, which was studied by our group previously but no detailed SARs study was conducted on CDK2/9. Among this series, compounds ZLMT-12 (35) exhibited the most potent antiproliferative activity (GI50 = 0.006 µM for HCT116) and superior CDK2/9 inhibitory properties (CDK2: IC50 = 0.011 µM, CDK9: IC50 = 0.002 µM). Meanwhile, ZLMT-12 showed a weak inhibitory effect on acetylcholinesterase (AChE, IC50 = 19.023 µM) and butyrylcholinesterase (BuChE, IC50 = 2.768 µM). In addition, ZLMT-12 can suppress colony formation and migration in HCT116 cells, as well as induce the apoptosis and arrest the cell cycle in the S phase and G2/M phase. In vivo investigations revealed that ZLMT-12 inhibits tumor growth in the HCT116 xenograft tumor model at a low dose of 10 mg/kg without causing hepatotoxicity. The acute toxicity test showed low toxicity with a median lethal dosage (LD50) of 104.417 mg/kg. These findings showed that ZLMT-12 might be used as a drug candidate by targeting CDK2/9.


Assuntos
Neoplasias , Tacrina , Acetilcolinesterase/metabolismo , Butirilcolinesterase/metabolismo , Inibidores da Colinesterase/metabolismo , Inibidores da Colinesterase/farmacologia , Quinase 2 Dependente de Ciclina/metabolismo , Humanos , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade , Tacrina/farmacologia
12.
Front Pharmacol ; 13: 915161, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105188

RESUMO

Background: Inadequate lymphangiogenesis is closely related to the occurrence of many kinds of diseases, and one of the important treatments is to promote lymphangiogenesis. Kuoxin Decoction (KXF) is an herbal formula from traditional Chinese medicine used to treat dilated cardiomyopathy (DCM), which is associated with lymphangiogenesis deficiency. In this study, we comprehensively verified whether KXF promotes lymphangiogenesis in zebrafish and in vitro based on network analysis. Methods: We performed virtual screening of the active compounds of KXF and potential targets regarding DCM based on network analysis. Tg (Flila: EGFP; Gata1: DsRed) transgenic zebrafish embryos were treated with different concentrations of KXF for 48 h with or without the pretreatment of MAZ51 for 6 h, followed by morphological observation of the lymphatic vessels and an assessment of lymphopoiesis. RT-qPCR was employed to identify VEGF-C, VEGF-A, PROX1, and LYVE-1 mRNA expression levels in different groups. After the treatment of lymphatic endothelial cells (LECs) with different concentrations of salvianolic acid B (SAB, the active ingredient of KXF), their proliferation, migration, and protein expression of VEGF-C and VEGFR-3 were compared by CCK-8 assay, wound healing assay, and western blot. Results: A total of 106 active compounds were identified constituting KXF, and 58 target genes of KXF for DCM were identified. There were 132 pathways generated from KEGG enrichment, including 5 signaling pathways related to lymphangiogenesis. Zebrafish experiments confirmed that KXF promoted lymphangiogenesis and increased VEGF-C and VEGF-A mRNA expression levels in zebrafish with or without MAZ51-induced thoracic duct injury. In LECs, SAB promoted proliferation and migration, and it could upregulate the protein expression of VEGF-C and VEGFR-3 in LECs after injury. Conclusion: The results of network analysis showed that KXF could regulate lymphangiogenesis through VEGF-C and VEGF-A, and experiments with zebrafish confirmed that KXF could promote lymphangiogenesis. Cell experiments confirmed that SAB could promote the proliferation and migration of LECs and upregulate the protein expression of VEGF-C and VEGFR-3. These results suggest that KXF promotes lymphangiogenesis by a mechanism related to the upregulation of VEGF-C/VEGFR-3, and the main component exerting this effect may be SAB.

13.
Oncogene ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109629

RESUMO

Abnormal translation of the MYC proto-oncogene is a hallmark of the initiation and maintenance of tumorigenesis. However, the molecular mechanism underlying increased MYC protein levels in certain cancer types without a corresponding increase in MYC mRNA levels is unclear. Here, we identified a novel lncRNA, MTAR1, which is critical for post-transcriptional regulation of MYC-induced tumorigenesis. MTAR1 is essential for recruiting IGF2BPs into PABP1-mediated liquid-liquid phase separation (LLPS) complexes and facilitates IGF2BPs-mediated MYC mRNA translation. MTAR1 enhanced binding between IGF2BPs and PABP1, thereby promoting MYC mRNA stability and increased MYC mRNA translation. In summary, MTAR1 is a novel MYC-related lncRNA that contributes to tumor progression by enhancing MYC translation through mediating PABP1/IGF2BPs liquid-liquid phase separation.

14.
Expert Opin Investig Drugs ; : 1-8, 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36112084

RESUMO

OBJECTIVE: HS-20090 is a proposed biosimilar candidate of Denosumab (Xgeva®). The study aimed to evaluate the similarity of pharmacokinetics (PK), pharmacodynamics (PD), safety, and immunogenicity between HS-20090 and Xgeva® in healthy Chinese subjects. METHODS: A single-center, randomized, double-blinded, active-controlled study was conducted in healthy Chinese adult male subjects. A total of 154 subjects were planned to be randomly assigned (1:1) to receive 120 mg of either HS-20090 or Xgeva® in a single subcutaneous injection, with a follow-up period of 155 days. The primary objective was to evaluate the bioequivalence of PK. The primary endpoints were Cmax and AUC0-∞. The secondary objectives were to evaluate the similarity of PD, safety, and immunogenicity. RESULTS: All 154 subjects were included in the PK, PD, and safety analyses. The 90% CIs of GMRs of HS-20090/Xgeva® for Cmax, AUC0-t, and AUC0-∞ were 90.49 ~ 100.23%, 94.45 ~ 104.61%, and 94.08 ~ 105.23%, respectively, achieving the bioequivalence criteria of 80 ~ 125%. The PD parameters and incidence of adverse events between HS-20090 and denosumab were also similar, with no detection of ADA in both the groups. CONCLUSION: HS-20090 was highly similar to Xgeva®, with regard to PK, PD, safety profiles, and immunogenicity in healthy Chinese subjects. These data support subsequently comparative clinical study for bone metastases in solid tumors. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT04494373.

15.
Front Genet ; 13: 970907, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081995

RESUMO

Hepatocellular carcinoma (HCC) is a primary malignancy with increasing incidence and poor prognosis. Heterogeneity originating from genomic instability is one of the critical reasons of poor outcomes. However, the studies of underlying mechanisms and pathways affected by mutations are still not intelligible. Currently, integrative molecular-level studies using multiomics approaches enable comprehensive analysis for cancers, which is pivotal for personalized therapy and mortality reduction. In this study, genomic and transcriptomic data of HCC are obtained from The Cancer Genome Atlas (TCGA) to investigate the affected coding and non-coding RNAs, as well as their regulatory network due to certain mutational signatures of HCC. Different types of RNAs have their specific enriched biological functions in mutational signature-specific HCCs, upregulated coding RNAs are predominantly associated with lipid metabolism-related pathways, and downregulated coding RNAs are enriched in axonogenesis for tumor microenvironment generation. Additionally, differentially expressed miRNAs are inclined to concentrate in cancer-related signaling pathways. Some of these RNAs also serve as prognostic factors that help predict the survival outcome of HCCs with certain mutational signatures. Furthermore, deregulation of competing endogenous RNA (ceRNA) regulatory network is identified, which suggests a potential therapy via interference of miRNA activity for mutational signature-specific HCC. This study proposes a projection approach to reduce therapeutic complexity from genomic mutations to transcriptomic alterations. Through this method, we identify genes and pathways critical for mutational signature-specific HCC and further discover a series of prognostic markers indicating patient survival outcome.

16.
Nanomaterials (Basel) ; 12(16)2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-36014629

RESUMO

The magnetic interactions between neighboring magnetic nanoparticles make the synthesis of nanocomposites made of two kinds of magnetic nanoparticles extremely difficult. In this paper, to achieve an effective nanocomposite of Co and Fe3O4 nanoparticles, a special urchin-like Co nanomatrix was used to prepare the Co/Fe3O4 nanocomposites. The Fe3O4 nanoparticles are evenly embedded into the branches of the CO clusters, bringing the two types of particles into close contact and ensuring the optimal magnetic and microwave properties. The electromagnetic (EM) parameters at 1-18 GHz and the magnetic loss tangents can be effectively modulated, and the absorption frequency bands of the EM waves are shifted to the X-Ku bands (8-18 GHz) from the S-C bands (2-8 GHz) after the Fe3O4 nanoparticles are compounded.

17.
Front Med (Lausanne) ; 9: 911807, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36017002

RESUMO

Introduction: As the presence of hepatic metastases is very important to cancer patients' clinical stage which would directly affect the selection and application of anti-cancer treatments. Although conventional ultrasound is commonly performed as a screening tool, most of the examinations have relatively poor sensitivity and specificity for detecting liver metastases. Contrast-enhanced ultrasound (CEUS) with Sonazoid has been reported to have the advantage of the diagnosis and therapeutic support of focal hepatic lesions and its specific Kupffer phase whole liver scan (KPWLS) is believed to be sensitive to detect liver metastases. And the purpose of this study is to determine the number, size, location and diagnosis of metastatic lesions, and to compare the results with conventional ultrasound and contrast-enhanced computed tomography (CECT), thus to clarify the application value, indications of Sonazoid-CEUS in screening liver metastasis. Methods and analysis: Kupffer phase whole liver scan for metastases (KPWLSM) is a self-control, blind map-reading, single-center, prospective superiority trial. Approved by the institutional review committee, the study period is planned to be from 1 January 2022 to 31 December 2025. Our study will include 330 patients with history of malignant tumors that cling to metastasize to liver. All patients will undergo the examinations of conventional ultrasound, Sonazoid-CEUS, and contrast-enhanced magnetic resonance imaging (CEMRI), and 65 of them should have additional CECT scans. The primary endpoint is the comparative analysis of the numbers of detected liver metastatic lesions among Sonazoid-CEUS, conventional ultrasound and CECT in screening liver metastases. Subjective conditions of patient after injection of Sonazoid will be followed up 3 and 30 days after KPWLSM, and any short-term and long-term adverse events are to be recorded with telephone interviews. Ethics and dissemination: This study has been granted by the Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (Approval No: 2021-197). When the KPWLSM is completed, we will publish it in an appropriate journal to promote further widespread use. Registration: Trial Registration Number and Date of Registration: Chinese Clinical Trial Registry, ChiCTR2100054385, December 16, 2021.

18.
PLoS One ; 17(8): e0271960, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35925902

RESUMO

This study explores the influence of organizational learning and external cooperation configuration on enterprise technological innovation and constructs a comprehensive theoretical framework of "organizational learning-external cooperation-technological innovation" based on the fuzzy set qualitative comparative analysis (fsQCA) method. The results show the following. (1) A single episode of organizational learning or external cooperation cannot affect the enterprise's technological innovation, which requires the mutual linkage of the two to improve enterprise technological innovation performance. (2) The technological innovation model in which organizational learning and external cooperation interact is an effective way for enterprises to improve technological innovation performance. There are four technological innovation models that produce high technological innovation performance, namely consciousness-system synergy, consciousness-led, quasi-full, and all-around drive. (3) There are four models of non-high-tech innovation performance, which are not opposed to the technological innovation model of high-tech innovation performance. This research expands the technological innovation perspective of organizational learning and external cooperation matching, provides enterprises with effective technological innovation activities, and provides a theoretical reference and practical guidance for improving technological innovation performance.


Assuntos
Invenções , Tecnologia
19.
Sci Rep ; 12(1): 13219, 2022 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-35918449

RESUMO

Recent research has begun to identify the neural mechanisms underlying the beneficial impact of mindfulness meditation training (MMT) on health and cognition. However, little is known about the effects of MMT on the global interplay of large-scale networks (LSNs) in the brain. In the present study, healthy, meditation-naïve adults (N = 46) underwent resting state fMRI prior to and upon completing 31 days of MMT or an active control intervention. Independent component analysis, sliding time window, and seed-based correlation analyses were performed to assess training-related changes in functional connectivity (FC) within and between networks with relevance to mindfulness meditation. Across sliding time window analyses and seed-based correlation analyses, we found increased FC between nodes of the default mode network (DMN) and nodes of the salience network (SN) in participants of the MMT. Seed-based correlation analyses revealed further connectivity increases between the SN and key regions of the central executive network (CEN). These results indicate, that, among multiple LSNs, one month of mindfulness meditation effectively increases interconnectivity between networks of the triple network model (DMN, SN, CEN), hereby introducing a potential mechanistic concept underlying the beneficial impact of MMT.Clinical trial registration: This study is listed as a clinical trial on the ISRCTN registry with trial ID ISRCTN95197731 (date of first registration: 15/02/2022).


Assuntos
Meditação , Atenção Plena , Adulto , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico/métodos , Humanos , Imageamento por Ressonância Magnética/métodos , Meditação/métodos , Atenção Plena/métodos , Rede Nervosa/diagnóstico por imagem
20.
Zhongguo Dang Dai Er Ke Za Zhi ; 24(8): 928-935, 2022 Aug 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-36036133

RESUMO

OBJECTIVES: To study the mechanism of retinoic acid receptor α (RARα) signal change to regulate neurexin 1 (NRXN1) in the visual cortex and participate in the autistic-like behavior in rats with vitamin A deficiency (VAD). METHODS: The models of vitamin A normal (VAN) and VAD pregnant rats were established, and some VAD maternal and offspring rats were given vitamin A supplement (VAS) in the early postnatal period. Behavioral tests were performed on 20 offspring rats in each group at the age of 6 weeks. The three-chamber test and the open-field test were used to observe social behavior and repetitive stereotyped behavior. High-performance liquid chromatography was used to measure the serum level of retinol in the offspring rats in each group. Electrophysiological experiments were used to measure the long-term potentiation (LTP) level of the visual cortex in the offspring rats. Quantitative real-time PCR and Western blot were used to measure the expression levels of RARα, NRXN1, and N-methyl-D-aspartate receptor 1 (NMDAR1). Chromatin co-immunoprecipitation was used to measure the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene. RESULTS: The offspring rats in the VAD group had autistic-like behaviors such as impaired social interactions and repetitive stereotypical behaviors, and VAS started immediately after birth improved most of the behavioral deficits in offspring rats. The offspring rats in the VAD group had a significantly lower serum level of retinol than those in the VAN and VAS groups (P<0.05). Compared with the offspring rats in the VAN and VAS groups, the offspring rats in the VAD group had significant reductions in the mRNA and protein expression levels of NMDAR1, RARα, and NRXN1 and the LTP level of the visual cortex (P<0.05). The offspring rats in the VAD group had a significant reduction in the enrichment of RARα transcription factor in the promoter region of the NRXN1 gene in the visual cortex compared with those in the VAN and VAS groups (P<0.05). CONCLUSIONS: RARα affects the synaptic plasticity of the visual cortex in VAD rats by regulating NRXN1, thereby participating in the formation of autistic-like behaviors in VAD rats.


Assuntos
Transtorno Autístico , Córtex Visual , Deficiência de Vitamina A , Animais , Feminino , Gravidez , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , Receptor alfa de Ácido Retinoico , Vitamina A
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