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1.
Br J Cancer ; 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36635499

RESUMO

BACKGROUND: GRP78 has been implicated in hepatocarcinogenesis. However, the clinical relevance, biological functions and related regulatory mechanisms of GRP78 in hepatitis B virus (HBV)-associated hepatoma carcinoma (HCC) remain elusive. METHODS: The association between GRP78 expression and HBV-related HCC was investigated. The effects of HBV X protein (HBX) on GRP78 and MAN1B1 expression, biological functions of GRP78 and MAN1B1 in HBX-mediated HCC cells and mechanisms related to TRIM25 on GRP78 upregulation to induce MAN1B1 expression in HBX-related HCC cells were examined. RESULTS: GRP78 expression was correlated with poor prognosis in HBV-positive HCC. HBX increased MAN1B1 protein expression depending on GRP78, and HBX enhanced the levels of MAN1B1 to promote proliferation, migration and PI3-K/mTOR signalling pathway activation in HCC cells. GRP78 activates Smad4 via its interaction with Smad4 to increase MAN1B1 expression in HBX-expressing HCC cells. TRIM25 enhanced the stability of GRP78 by inhibiting its ubiquitination. HBX binds to GRP78 and TRIM25 and accelerates their interaction of GRP78 and TRIM25, leading to an increase in GRP78 expression. CONCLUSIONS: HBX enhances the stability of GRP78 through TRIM25 to increase the expression of MAN1B1 to facilitate tumorigenesis, and we provide new insights into the molecular mechanisms underlying HBV-induced malignancy.

2.
Plant Physiol Biochem ; 195: 170-181, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36640684

RESUMO

Cottonseed is the main coproduct of cotton production. The carbohydrate metabolism provides carbon substrate for the accumulation of cottonseed kernel biomass which was the basis of cottonseed kernel development. However, the responses of drought stress on carbohydrate metabolism in kernels are still unclear. To address this, two cotton cultivars (Dexiamian 1 and Yuzaomian 9110) were cultivated under three water treatments including soil relative water content (SRWC) at (75 ± 5)% (control), (60 ± 5)% (mild drought) and (45 ± 5)% (severe drought) to investigate the effects of soil drought on cottonseed kernel carbohydrate metabolism and kernel biomass accumulation. Results suggested that drought restrained the accumulation of cottonseed kernel biomass which eventually decreased cottonseed kernel biomass at maturity. In detail, the down-regulation of sucrose phosphate synthase (SPS) activity led to the inhibition of sucrose synthesis, while the up-regulation of invertase (INV) promoted the sucrose decomposite, which reduced the sucrose content eventually under drought. Though hexose content was increased, phosphoenolpyruvic acid (PEP) content was decreased under drought by downregulating 6-phosphofructokinase (PFK) and pyruvate kinase (PK) activities, which hindered the conversion of hexose to PEP. The large decrease of sucrose and PEP contents hindered the accumulation of kernel biomass. The related substances contents and enzyme activities in carbohydrate metabolism of Yuzaomian 9110 were more susceptible to drought stress than Dexiamian 1.

3.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614304

RESUMO

Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinß6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.


Assuntos
Carcinoma , Neoplasias do Colo do Útero , Humanos , Feminino , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Cisplatino , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Neoplasias do Colo do Útero/patologia , Proliferação de Células/genética , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Ubiquitina-Proteína Ligases/metabolismo
4.
J Chem Theory Comput ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693136

RESUMO

Low-rank approximations have long been considered an efficient way to accelerate electronic structure calculations associated with the evaluation of electron repulsion integrals (ERIs). As an accurate and efficient algorithm for compressing the ERI tensor, the interpolative separable density fitting (ISDF) decomposition has recently attracted great attention in this context. In this perspective, we introduce the ISDF decomposition from the theoretical aspects and technique details. The ISDF decomposition can construct a fully separable low-rank approximation (tensor hypercontraction factorization) of ERIs in real space with a cubic cost, offering great flexibility for accelerating high-scaling electronic structure calculations. We review the typical applications of ISDF in hybrid functionals, time-dependent density functional theory, and GW approximation. Finally, we discuss the promising directions for future development of ISDF.

5.
ACS Omega ; 8(2): 2586-2595, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36687056

RESUMO

PURPOSE: As a traditional herb product, the root of Caragana sinica (Buc'hoz) Rehder (Chinese name: Jin Quegen [JQG]) has been widely used in folk medicines for rheumatoid arthritis (RA) treatment. However, which herbal constituents exert a core pharmacological role in RA treatment remains a great challenge due to the multiple phytochemical constituents, targets, and pathways. In this work, we aimed to use a new strategy to explore the core herbal constituents and potential mechanisms of JQG against RA for the first time. METHODS: A successively partitioned extract of JQG, bioactive partition screening in vitro and in vivo, qualitative analysis, bioinformatic analysis, molecular docking, and mechanism validation were used in this study. The partitioned extract was used to obtain the bioactive partition, while in vitro anti-inflammatory effects and in vivo anti-arthritis effects in adjuvant-induced arthritis (AIA) rats were applied to screen the bioactive partition with the best efficacy. Qualitative analysis was used to identify bioactive constituents. Bioinformatic analysis was used to explore the potential mechanism for RA treatment. Molecular docking and immunofluorescence were used to validate the underlying mechanism. RESULTS: After successively partitioning extract and bioactive partition screening, ethyl acetate extract (EAE) yielded the best anti-inflammatory effects in vitro and in vivo among JQG extracts. By ultra-performance liquid chromatography (UPLC) coupled with Orbitrap mass spectrometry, a total of 58 constituents were identified in EAE, and 17 constituents were regarded as the core constituents based on their oral bioavailability and drug-like properties. The nuclear factor kappa B (NF-κB) signal pathway was screened as the core pathway of core constituents for RA treatment based on bioinformatic analysis, and the core constituents showed good ligand-receptor binding activity to NF-κB P65. In vitro study demonstrated that EAE could significantly reduce NF-κB P65 transfer from the cytoplasm to the nucleus. CONCLUSION: Our study suggested that the therapeutic efficacy of JQG for RA treatment could be derived from negative regulation of the NF-κB pathway, and EAE of JQG could represent a promising herb product for RA treatment that deserves further development.

6.
Diagnostics (Basel) ; 13(2)2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36673134

RESUMO

BACKGROUND: Metagenomic Next Generation Sequencing (mNGS) has the potential to detect pathogens rapidly. We aimed to assess the diagnostic performance of mNGS in hospitalized patients with suspected sepsis and evaluate its role in guiding antimicrobial therapy. METHODS: A multicenter, prospective cohort study was performed. We enrolled patients with suspected sepsis, collected clinical characteristics and blood samples, and recorded the 30-day survival. Diagnostic efficacy of mNGS test and blood culture was compared, and the clinical impact of mNGS on antibiotic regimen modification was analyzed. RESULTS: A total of 277 patients were enrolled, and 162 were diagnosed with sepsis. The mortality was 44.8% (121/270). The mNGS test exhibited shorter turn-out time (27.0 (26.0, 29.0) vs. 96.0 (72.0, 140.3) hours, p < 0.001) and higher sensitivity (90.5% vs. 36.0%, p < 0.001) compared with blood culture, especially for fungal infections. The mNGS test showed better performance for patients with mild symptoms, prior antibiotic use, and early stage of infection than blood culture, and was capable of guiding antibiotic regimen modification and improving prognosis. Higher reads of pathogens detected by mNGS were related to 30-day mortality (p = 0.002). CONCLUSIONS: Blood mNGS testing might be helpful for early etiological diagnosis of patients with suspected sepsis, guiding the antibiotic regimen modification and improving prognosis.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36674375

RESUMO

As a great practice of building a community of shared future for mankind, the Belt and Road Initiative is facing geopolitical risk brought by great power games, regional conflicts and terrorism. It is an important mission of geopolitical research to scientifically deal with the geopolitical risk along the Belt and Road. This study systematically constructs the geopolitical risk assessment index system and analyzes the spatiotemporal evolution, obstacle factors and risk types of geopolitical risk of countries along the Belt and Road by using the entropy weight TOPSIS model, obstacle degree model and minimum variance method. The research results showed that: (1) From 2005 to 2020, the polarization of geopolitical risk in countries along the Belt and Road was very significant, and the overall trend of geopolitical risk tended to deteriorate. (2) The Middle East and Eastern Europe were the most important geopolitical risk zones along the Belt and Road, and Afghanistan, Iraq, Russia and Ukraine were the main high geopolitical risk centers, with significant risk spillover effects from these centers. (3) Terrorism and close relations with the United States were the most important obstacle factors for geopolitical risk in countries along the Belt and Road, and military intervention politics, trade dependence degree and foreign debt burden were important obstacle factors for geopolitical risk in countries along the Belt and Road. (4) Geopolitical risk along the Belt and Road can be divided into sovereign risk dominant type, sovereign and military risk dominant type, sovereign and major power intervention risk dominant type, and sovereign and military and major power intervention risk jointly dominated type, among which sovereign and military and major power intervention risk jointly dominated type was the most important geopolitical risk type. In order to scientifically deal with geopolitical risk in countries along the Belt and Road, it is necessary to strengthen geopolitical risk awareness, pay attention to the dominant geopolitical risk factors, strengthen the control of regional geopolitical risk spillover and formulate reasonable risk prevention and control scheme based on geopolitical risk types.


Assuntos
Oriente Médio , Europa Oriental , Iraque , Afeganistão , Ucrânia , China
8.
BMC Plant Biol ; 23(1): 5, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36597026

RESUMO

BACKGROUND: Fruit flesh colour is not only an important commodity attribute of eggplant but is also closely related to maturity. However, very little is known about its formation mechanism in eggplant. RESULTS: Two inbred lines of eggplant, green 'NC7' and white 'BL', were used in this study to explain the differences in flesh colour. Transcriptome sequencing results revealed a total of 3304 differentially expressed genes (DEGs) in NC7 vs. BL. Of the DEGs obtained, 2050 were higher and 1254 were lower in BL. These DEGs were annotated to 126 pathways, where porphyrin and chlorophyll metabolism, flavonoid biosynthesis, and photosynthesis-antenna proteins play vital roles in the colour formation of eggplant flesh. At the same time, Gene Ontology (GO) enrichment significance analysis showed that a large number of unigenes involved in the formation of chloroplast structure were lower in BL, which indicated that the formation of chloroplasts in white-fleshed eggplant was blocked. This was confirmed by transmission electron microscopy (TEM), which found only leucoplasts but no chloroplasts in the flesh cells of white-fleshed eggplant. Several genes encoding ERF and bHLH transcription factors were predicted to participate in the regulation of chlorophyll biosynthetic genes. CONCLUSIONS: The results of this study indicated that differences in the gene expression of the chlorophyll metabolic pathway were the main cause of the different flesh colour formations. These findings will increase our understanding of the genetic basis in eggplant flesh colors formation mechanism.


Assuntos
Solanum melongena , Solanum melongena/genética , Solanum melongena/metabolismo , Transcriptoma , Cor , Perfilação da Expressão Gênica , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
9.
J Phys Chem Lett ; 14(2): 347-353, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36606717

RESUMO

Herein, we report an environmentally stable and friendly halide perovskite based resistive random access memory device with an Ag/PMMA/(PMA)2CuBr4/FTO (PMMA = poly(methyl methacrylate); PMA = C6H5CH2NH3) architecture. The device exhibits the coexistence of two bipolar resistive switching modes, including counterclockwise and clockwise switching characteristics. The devices with both switching modes show stable endurance (>100 cycles) and long retention performance (>104 s). By applying a suitable electrical stimulation, the counterclockwise and clockwise switching behaviors are interconvertible. Furthermore, the Au/PMMA/(PMA)2CuBr4/FTO and Ag/(PMA)2CuBr4/FTO devices were fabricated to verify the origin of dual resistive switching behaviors. The similar dual resistive switching behaviors after electroforming processes of three types of memory devices suggest that the interconvertible dual resistive switching characteristics could be attributed to the ionic migration in the (PMA)2CuBr4 perovskite layer.

10.
Free Radic Biol Med ; 195: 359-370, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36610560

RESUMO

Cigarette smoking (CS) exposure-induced airway inflammatory responses drive the occurrence and development of emphysema and chronic obstructive pulmonary disease (COPD). However, its precise mechanisms have not been fully elucidated. In this study, we explore the role of Rab26 in CS exposure modulating the inflammatory response of airway epithelium and the novel mechanism of CS exposure regulation Rab26. These data showed that CS exposure and H2O2 (a type of ROS) suppressed the expression of Rab26 and increased the expression of DNMT3b in vivo and in vitro. GEO data analysis found the level of Rab26 was decreased in the lung tissue of COPD patients. CSE-induced ROS promoted DNA methylation of the Rab26 promoter and inhibited its promoter activity by elevating the DNMT3b level. Antioxidants N-Acetyl-l-cysteine (NAC), 5-Aza-2'-deoxycytidine (5-AZA) (DNA methylation inhibitor) and DNMT3B siRNA alleviated CSE's inhibitory effect on Rab26 expression in vitro. Importantly, NAC alleviated the improved expression of Rab26 and reduced DNMT3B expression, in the airway of smoking exposure as well as attenuated the inflammatory response in vivo. Overexpression of Rab26 attenuated CSE-induced production of inflammatory mediators through part inactivation of p38 and JNK MAPK. On the contrary, silencing Rab26 enhanced p38 and JNK activation and aggravated inflammatory response. These findings suggest that ROS-mediated Rab26 promoter hypermethylation is a critical step in cigarette smoking-induced airway epithelial inflammatory response. Restoring Rab26 in the airway epithelium might be a potential strategy for treating airway inflammation and COPD.


Assuntos
Fumar Cigarros , Doença Pulmonar Obstrutiva Crônica , Espécies Reativas de Oxigênio , Proteínas rab de Ligação ao GTP , Humanos , Fumar Cigarros/efeitos adversos , Metilação de DNA , Células Epiteliais/metabolismo , Peróxido de Hidrogênio/metabolismo , Inflamação/induzido quimicamente , Inflamação/genética , Inflamação/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/metabolismo , Proteínas rab de Ligação ao GTP/genética , Proteínas rab de Ligação ao GTP/metabolismo , Espécies Reativas de Oxigênio/metabolismo
11.
Am J Cardiovasc Drugs ; 23(1): 101-112, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36622539

RESUMO

BACKGROUND: Tecarfarin (ATI-5923), a structural analog of warfarin, was designed to provide more uniform and stable anticoagulation. OBJECTIVE: We aimed to evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profile of tecarfarin when administered in multiple ascending doses (MADs) to healthy Chinese volunteers. METHODS: Forty healthy Chinese volunteers were enrolled into four sequential cohorts (10, 20, 30, and 40 mg), with 10 subjects in each cohort. Participants in the MAD study for each sequential cohort were dose-titrated to achieve the target international normalized ratio (INR 1.7-2.0) for 14 days. Safety and tolerability were assessed throughout the study. RESULTS: The pharmacokinetic and pharmacodynamic profile of tecarfarin was investigated in a healthy Chinese population. Dose titration of tecarfarin was necessary to keep the INR in the target range in all subjects in the 20, 30 and 40 mg cohorts and a few subjects (n = 3) in the 10 mg cohort. Tecarfarin was well tolerated without serious adverse events. Only one treatment-related adverse event (hematochezia) resulted in early withdrawal from the MAD 40 mg cohort. CONCLUSION: Tecarfarin was well-tolerated by Chinese volunteers. Dose titration was needed for tecarfarin doses larger than 20 mg to keep the INR in the target range. REGISTRATION: ClinicalTrials.gov identifier: NCT04627116.


Assuntos
Varfarina , Humanos , Varfarina/efeitos adversos , Benzoatos/efeitos adversos , Benzoatos/farmacocinética , Cumarínicos/efeitos adversos , Cumarínicos/farmacocinética , Voluntários Saudáveis , Método Duplo-Cego , Relação Dose-Resposta a Droga
12.
Genetica ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652142

RESUMO

Plant hormone abscisic acid (ABA) plays an important role in plant growth, development and response to biotic / abiotic stressors. Thus, it is necessary to investigate the crucial genes associated with ABA synthesis. Currently, the carotenoid cleavage oxygenases (CCOs) family that function as the key step for ABA synthesis are not well understood in banana. In this study, 13 MaCCO genes and 12 MbCCO genes, divided into NCED subgroup and CCD subgroup, were identified from the banana genome, and their evolutionary relationship, protein motifs, and gene structures were also determined. Transcriptomic analysis suggested the involvement of CCO genes in banana development, ripening, and response to abiotic and biotic stressors, and homologous gene pairs showed homoeologue expression bias in the A or B subgenome. Our results identified MaNCED3A, MaCCD1, and MbNCED3B as the genes with the highest expression during fruit development and ripening. MaNCED5 / MbNCED5 and MaNCED9A might respond to abiotic stress, and MaNCED3A, 3B, 6 A, 9 A, and MbNCED9A showed transcriptional changes that could be a response to Foc4 infection. These findings may contribute to the characterization of key enzymes involved in ABA biosynthesis, as well as to identify potential targets for the genetic improvement of banana.

13.
J Gastrointest Surg ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652180

RESUMO

BACKGROUND: Laparoscopic transcystic common bile duct exploration (LTCBDE) is used to treat cholecystolithiasis and choledocholithiasis. This study aimed to investigate the safety, effectiveness and generalisability of LTCBDE in patients with cholecystolithiasis and choledocholithiasis based on our LTCBDE experience within 8 years. METHODS: Four hundred patients with cholecystolithiasis and choledocholithiasis (including 62 of cholecystolithiasis and choledocholithiasis with common bile duct no-dilatation) treated with LTCBDE at a single centre from January 2014 to February 2022 were retrospectively evaluated. They were divided into the first 200 and last 200 LTCBDE cases. The disease characteristics, cystic duct incision methods, surgical outcomes and follow-up data were analysed retrospectively. Each patient was followed up for > 3 months. RESULTS: Four hundred patients underwent LTCBDE, including 188 males and 212 females aged from 15 to 91 years (average age: 56 years). LTCBDE was successful in 377 (94.3%) patients, while treatment was converted to laparoscopic choledocholithotomy with T-tube drainage in 23 (5.8%), owing to intraoperative choledochoscope insertion failure. The CBD diameter (10.89 ± 1.76 vs 9.97 ± 2.39, P < 0.05), cystic duct diameter (4.62 ± 1.03 vs 5.03 ± 1.29, P < 0.05), and operation time (164.60 ± 24.30 vs 135.34 ± 30.00, P < 0.05). Residual stones were found in six (1.5%) patients and removed during the second operation; post-operative bile leakage was found in one (0.3%) patient, who was discharged safely after the second operation. CONCLUSIONS: Phase I LTCBDE is safe and effective in treating cholecystolithiasis and choledocholithiasis. With continuous technological advances, LTCBDE has been effectively promoted and applied.

14.
Anal Chim Acta ; 1240: 340775, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36641145

RESUMO

Development of high-throughput and rapid screening analytical method is in high demand for anti-doping and clinical point-of-care (POC) analysis. Solid-phase microextraction and mass spectrometry direct coupling (SPME-MS) has been proved as a rapid and effective way for target analysis in complex sample matrixes. An online direct coupling of in-tube SPME (IT-SPME) with MS using polymer coated open-tubular column has been developed in this work. A sharp stainless-steel needle was attached at the end of the SPME column, which enables the direct ionization of the analytes after elution from the IT-SPME column. Itaconic acid-benzene co-polymer was in-situ grown on the inner surface of the fused silica capillary and used as extraction phase. This column has low backpressure and provides both hydrophobic and weak cationic exchange interaction with the target analytes due to the chemical properties. The developed online IT-SPME-MS method showed good extraction performance towards various target analytes and good reusability at least for 60 times. As a proof-of-concept application, the above method was applied for the analysis of antiepileptic drugs (AEDs) in both plasma and urine samples with linear range (1 ng/mL-200 ng/mL), good linearity (R2 ≥ 0.99), and good reproducibility (intra-day RSDs less than 4.36%, inter-day RSDs less than 6.55%). The method exhibited high enrichment factors between 187 and 204 for the two AEDs and high sensitivity for the analysis of human plasma samples and urine samples.


Assuntos
Anticonvulsivantes , Polímeros , Humanos , Polímeros/química , Microextração em Fase Sólida/métodos , Reprodutibilidade dos Testes , Espectrometria de Massas/métodos
16.
Free Radic Biol Med ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36681202

RESUMO

Ferroptosis is a form of non-apoptotic cell death caused by iron-dependent peroxidation of lipids. It contributes to ischemic stroke-induced neuronal damage. Elabela (ELA), a novel endogenous ligand for Apelin receptor (APJ), regulates oxidative stress and exerts a protective role in cardiovascular disease. However, the effect of ELA-APJ axis on cellular ferroptosis in cerebral ischemia/reperfusion (I/R) remains elusive. The present study showed that ELA and APJ were expressed on neurons and increased after cerebral I/R injury. The I/R insult triggered typical molecular and morphological features of neuronal ferroptosis, including iron and MDA accumulation, mitochondrial shrink and membrane rupture, upregulation of positive ferroptosis regulators and downregulation of negative regulators. ELA-32 treatment reduced brain infarction and improved neurobehavioral deficits and cognitive dysfunction. Moreover, ELA-32 administration alleviated neuronal ferroptosis, accompanied by reduced iron deposition, decreased mitochondrial damage, relived lipid peroxidation and glutathione reduction. Such effects of ELA-32 were abolished by AAV-APJ-RNAi or nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor ML385. Mechanistically, ELA was shown to bind to APJ and activate NRF2/ARE anti-oxidative signaling pathway via Gα13. Together, these findings suggested that ELA-APJ axis mitigates neuronal ferroptosis after ischemic stroke and that the ELA-32 peptide may be a putative therapeutic avenue for ischemic stroke.

17.
Environ Pollut ; 319: 121016, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36610651

RESUMO

The land-sea breeze circulation significantly impacts the atmospheric transport of organic aerosols in coastal regions. However, the links between organic aerosols and land-sea breezes remain poorly understood. In this study, organic marker compounds for biomass burning, primary biological aerosols, biogenic and anthropogenic secondary organic aerosols (SOA) in fine particles from a coastal city in East China were analysed using gas chromatography-mass spectrometry. Land-sea breeze circulations were identified to explore their potential influence on organic molecular compositions. Organic marker compounds showed obvious diurnal/seasonal patterns. Surprisingly, due to the combined influence of weakened East Asian monsoons and land-sea breezes, all detected organic markers decreased except α/ß-pinene SOA markers during land-sea breeze periods in early autumn; whereas, all the organic markers increased except α/ß-pinene SOA markers, pollen and plant debris markers during land-sea breeze periods in early spring. Furthermore, the reaction pathway and aging of biogenic SOA were also related to land-sea breezes. During the land-sea breeze periods, the ratios of 2-methylglyceric acid (2-MGA) to 2-methyltetrols increased in early autumn, indicating that more isoprene-derived SOA generated from the high-NOx (nitrogen oxides) pathway when the land-sea breezes occurred; while the ratios decreased in early spring, this may be related to the chemical transformation of 2-MGA to 2-MGA sulfates. Changes in the ratio of monoterpene SOA markers demonstrate that monoterpene SOA was relatively aged during sea breeze periods, while it was fresher when the land breeze occurred. Although boundary layer height, emissions, gas/particle partitioning, etc. are important reasons for the diurnal variations of organic aerosols, night/day ratios of molecular markers increased obviously when land-sea breezes occurred in both early autumn and early spring. Our results provide new insights into the shift in the chemical composition of organic aerosols over coastal areas that are influenced by land-sea breezes.


Assuntos
Poluentes Atmosféricos , Compostos Orgânicos , Monoterpenos Bicíclicos/análise , Compostos Orgânicos/análise , Aerossóis/análise , China , Poluentes Atmosféricos/análise
18.
Aging (Albany NY) ; 15(1): 92-107, 2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36622275

RESUMO

BACKGROUND: Forkhead box proteins (FOXs) play important roles in multiple biological processes; while little is known regarding the role of FOX members in pancreatic adenocarcinoma (PAAD). This study aimed to comprehensively investigate the function of FOX family members in PAAD. METHODS: Expression and prognostic value of FOXs were analyzed by R language and GEPIA. Genetic alteration and promoter methylation level were analyzed using CBioPortal and UALCAN. Protein-protein interactions and gene functions were analyzed using STRING and DAVID. TIMER and SENESCopedia were utilized to analyze the correlation of FOXs with immune cell infiltration or tumor senescence. Protein levels of FOXs were detected by immunohistochemistry. RESULTS: Expression of 15 of 50 FOXs were significantly elevated in PAAD. Among these 15 differentially expressed FOXs (DE-FOXs), 4 were significantly associated with the clinical cancer stage and 4 were negatively associated with overall survival. Functions of DE-FOXs were related to epithelial tube morphogenesis, nuclear chromatin, and DNA-binding. Promoter methylation and genomic alterations were not major causes of FOX dysregulation. Most DE-FOX was correlated with diverse immune infiltration cells. Seven of the DE-FOXs were positively related to tumor senescence. The protein levels of FOXM1, FOXP1, and FOXN3 were negatively correlated with OS in the collected PAAD patients. CONCLUSIONS: FOXM1, FOXP1, and FOXN3 have prognostic value. Seven FOXs were related senescence, whereas most DE-FOXs were related to immune infiltration in PAAD. Our findings are instructive for future research on FOX family and provide novel insights into the selection of FOXs with potential prognostic or therapeutic target value.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Adenocarcinoma/genética , Neoplasias Pancreáticas/genética , Biologia Computacional , Genômica , Prognóstico , Proteínas Repressoras , Fatores de Transcrição Forkhead/genética
19.
Diagnostics (Basel) ; 13(2)2023 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-36672980

RESUMO

Using a deep learning algorithm in the development of a computer-aided system for colon polyp detection is effective in reducing the miss rate. This study aimed to develop a system for colon polyp detection and classification. We used a data augmentation technique and conditional GAN to generate polyp images for YOLO training to improve the polyp detection ability. After testing the model five times, a model with 300 GANs (GAN 300) achieved the highest average precision (AP) of 54.60% for SSA and 75.41% for TA. These results were better than those of the data augmentation method, which showed AP of 53.56% for SSA and 72.55% for TA. The AP, mAP, and IoU for the 300 GAN model for the HP were 80.97%, 70.07%, and 57.24%, and the data increased in comparison with the data augmentation technique by 76.98%, 67.70%, and 55.26%, respectively. We also used Gaussian blurring to simulate the blurred images during colonoscopy and then applied DeblurGAN-v2 to deblur the images. Further, we trained the dataset using YOLO to classify polyps. After using DeblurGAN-v2, the mAP increased from 25.64% to 30.74%. This method effectively improved the accuracy of polyp detection and classification.

20.
J Hazard Mater ; 446: 130702, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36587597

RESUMO

Secondary mineralization is a promising method for remediating cadmium (Cd) pollution in sediments, but the poor stability of Cd-containing secondary minerals is a bottleneck that limits the development of this approach. The existence of phosphate can enhance the formation of stable secondary minerals and points a new direction for Cd immobilization. In this research, a novel syntrophic system composed of phosphate solubilizing bacteria (PSB) and dissimilatory iron reducing bacteria (DIRB) was established and the effect and mechanism of Cd immobilization in the system were also explored. The results showed that under the conditions of DIRB:PSB (V:V)= 3:1, syntrophic bacteria dosage of 5% and glucose dosage of 5 g/L, Cd incorporated in the secondary minerals could account for about 60% of the total Cd. In the pH range of 5-9, alkaline environment was conducive to the immobilization of Cd and the percentage of combined Cd was up to 58%, while the combined Cd in secondary minerals decreased from 62% to 56% with the increase of initial Cd concentration from 0.1 to 0.3 mmol/L. In addition, XRD, XPS, Mössbauer and other characterization results showed that secondary minerals, such as Cd exchange hydroxyapatite (Cd-HAP) and kryzhanovskite (Fe3(PO4)2(OH)3) were formed in this new system. The established syntrophic system of PSB and DIRB is thus a prospective bioremediation technology for Cd immobilization in sediments and can avoid the potential risk might be caused by the addition of phosphorus-containing materials.

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