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1.
Nat Mater ; 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36717665

RESUMO

The ideal vaccine against viruses such as influenza and SARS-CoV-2 must provide a robust, durable and broad immune protection against multiple viral variants. However, antibody responses to current vaccines often lack robust cross-reactivity. Here we describe a polymeric Toll-like receptor 7 agonist nanoparticle (TLR7-NP) adjuvant, which enhances lymph node targeting, and leads to persistent activation of immune cells and broad immune responses. When mixed with alum-adsorbed antigens, this TLR7-NP adjuvant elicits cross-reactive antibodies for both dominant and subdominant epitopes and antigen-specific CD8+ T-cell responses in mice. This TLR7-NP-adjuvanted influenza subunit vaccine successfully protects mice against viral challenge of a different strain. This strategy also enhances the antibody response to a SARS-CoV-2 subunit vaccine against multiple viral variants that have emerged. Moreover, this TLR7-NP augments antigen-specific responses in human tonsil organoids. Overall, we describe a nanoparticle adjuvant to improve immune responses to viral antigens, with promising implications for developing broadly protective vaccines.

2.
Signal Transduct Target Ther ; 8(1): 39, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650130

RESUMO

Nucleic acid drugs have the advantages of rich target selection, simple in design, good and enduring effect. They have been demonstrated to have irreplaceable superiority in brain disease treatment, while vectors are a decisive factor in therapeutic efficacy. Strict physiological barriers, such as degradation and clearance in circulation, blood-brain barrier, cellular uptake, endosome/lysosome barriers, release, obstruct the delivery of nucleic acid drugs to the brain by the vectors. Nucleic acid drugs against a single target are inefficient in treating brain diseases of complex pathogenesis. Differences between individual patients lead to severe uncertainties in brain disease treatment with nucleic acid drugs. In this Review, we briefly summarize the classification of nucleic acid drugs. Next, we discuss physiological barriers during drug delivery and universal coping strategies and introduce the application methods of these universal strategies to nucleic acid drug vectors. Subsequently, we explore nucleic acid drug-based multidrug regimens for the combination treatment of brain diseases and the construction of the corresponding vectors. In the following, we address the feasibility of patient stratification and personalized therapy through diagnostic information from medical imaging and the manner of introducing contrast agents into vectors. Finally, we take a perspective on the future feasibility and remaining challenges of vector-based integrated diagnosis and gene therapy for brain diseases.


Assuntos
Encefalopatias , Ácidos Nucleicos , Humanos , Preparações Farmacêuticas , Ácidos Nucleicos/genética , Ácidos Nucleicos/uso terapêutico , Terapia Genética , Encefalopatias/diagnóstico , Encefalopatias/tratamento farmacológico , Encefalopatias/genética , Sistemas de Liberação de Medicamentos/métodos
3.
iScience ; : 105995, 2023 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-36687314

RESUMO

The coronavirus nucleocapsid (N) protein is known to bind to nucleic acids and facilitate viral genome encapsulation. Here we report that N protein can mediate RNA or DNA entering neighboring cells through ACE2-independent, receptor (STEAP2)-mediated endocytosis, and achieve gene expression. The effect is more pronounced for the N protein of wild-type SARS-CoV-2 than that of Omicron variant and other human coronaviruses. This effect is enhanced by RANTES (CCL5), a chemokine induced by N protein, and lactate, a metabolite produced in hypoxia, to cause more damage. These findings might explain the clinical observations in SARS-CoV-2-infected cases. Moreover, the N protein-mediated function can be inhibited by N protein-specific monoclonal antibodies or p38 mitogen-activated protein kinases inhibitors. Since the N-protein-mediated nucleic acid endocytosis involves a receptor commonly expressed in many types of cells, our findings suggest N protein may have an additional role in SARS-CoV-2 pathogenesis.

4.
Br J Pharmacol ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36702458

RESUMO

BACKGROUND AND PURPOSE: Currently, chemotherapy-induced neuropathic pain (CINP) has limited effective treatment. The roles of Oxytocin (OXT) and the oxytocin receptor (OXTR) in central analgesia have been well documented. However, the expression and function of OXTR in the peripheral nervous system remain unclear. Here, we evaluated the peripheral antinociceptive profiles of OXTR in CINP. EXPERIMENTAL APPROACH: Paclitaxel (PTX) was used to establish CINP. qRT-PCR, in-situ hybridization, and immunohistochemistry were used to observe the properties of OXTR expression in the dorsal root ganglion (DRG). The antinociceptive effects were assessed by the hot-plate and Von-Frey tests. The whole-cell patch-clamp was performed to record the sodium currents, the excitability of DRG neurons, and the excitatory synapse transmissions. KEY RESULTS: The expression of OXTR in DRG neurons was boosted significantly after PTX treatment. The activation of OXTR exhibited antinociceptive effects and decreased the hyperexcitability of DRG neurons in PTX-treated mice. Additionally, the OXTR activation upregulated the phosphorylation of protein kinase C (pPKC), and in turn impaired the voltage-gated sodium current, especially Nav 1.7 current which performs an indispensable role in PTX-induced neuropathic pain. Oxytocin also suppressed the excitatory transmission in the spinal dorsal horn and the excitatory inputs from the primary afferents in PTX-treated mice. CONCLUSION AND IMPLICATIONS: The OXTR in small-sized DRG neurons is upregulated in CINP and the activation of OXTR relieved CINP by inhibiting the neural excitability by an impairment in NaV 1.7 currents via pPKC. Our results suggested that OXTR on peripheral sensory neurons can be a potential target to relieve CINP.

5.
Adv Sci (Weinh) ; : e2300133, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703612

RESUMO

Transparent field-effect transistors (FETs) are attacking intensive interest for constructing fancy "invisible" electronic products. Presently, the main technology for realizing transparent FETs is based on metal oxide semiconductors, which have wide-bandgap but generally demand sputtering technique or high-temperature (>350 °C) solution process for fabrication. Herein, a general device fabrication strategy for metal halide perovskite (MHP) FETs is shown, by which transparent perovskite FETs are successfully obtained using low-temperature (<150 °C) solution process. This strategy involves the employment of ferroelectric copolymer poly(vinylidene fluoride-co-trifluoroethylene) (PVDF-TrFE) as the dielectric, which conquers the challenging issue of gate-electric-field screening effect in MHP FETs. Additionally, an ultra-thin SnO2 is inserted between the source/drain electrodes and MHPs to facilitate electron injection. Consequently, n-type semi-transparent MAPbBr3 FETs and fully transparent MAPbCl3 FETs which can operate well at room temperature with mobility over 10-3  cm2  V-1  s-1 and on/off ratio >103 are achieved for the first time. The low-temperature solution processability of these FETs makes them particularly attractive for applications in low-cost, large-area transparent electronics.

6.
Heliyon ; 9(1): e12690, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685392

RESUMO

Dengue infection is one of the most prevalent arthropod-borne viral diseases, which can result in severe complications. Identification of genes and long non-coding RNAs (lncRNAs) involved in dengue infection would help in deciphering potential mechanisms responsible for the disease progression. We comprehensively analyzed the dynamic transcriptome during dengue disease progression and identified critical genes and lncRNAs with expression perturbations. Our findings revealed that the expression of genes (i.e., CCR10 and GNG7) and lncRNAs (i.e., CTBP1-AS and MAFG-AS1) were potentially regulated by m6A RNA methylation. Interestingly, dengue viral proteins prevalently interact with genes or lncRNAs with expression perturbations, which are involved in cell cycle, inflammation signaling pathways and immune response. Dynamically expressed genes and lncRNAs were likely to locate in the central regions of human protein-protein network, which play crucial roles in mediating signaling spread and helping viral replication. Immune microenvironments analysis revealed that plasma cells levels were increased and T cells infiltrations were decreased during dengue disease progression. Dynamically expressed genes and lncRNAs were correlated with immune cell infiltrations. Moreover, network analysis reveals the associations between dengue viral infections and human complex diseases (i.e., digestive diseases and neoplasms). Our comprehensive transcriptome analysis of dengue disease progression identified potential gene and lncRNA biomarkers, providing novel insights for understanding the pathogenesis of and developing effective therapeutic strategies for dengue infection.

7.
Adv Mater ; : e2211296, 2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36689736

RESUMO

High-performance all-polymer solar cells (all-PSCs) deeply rely on the joint contributions of desirable optical absorption, adaptive energy level and appropriate morphology. Herein, two structural analogous polymerized small molecule acceptors (PSMAs), PYFCl-T and PYF&PYCl-T, were synthesized, and then incorporated into the PM6:PY-IT binary blends to construct ternary all-PSCs. Due to the superior compatibility of PY-IT and PYFCl-T, the ternary all-PSC based on PM6:PY-IT:PYFCl-T with 10 wt% PYFCl-T, presented higher and more balanced charge mobilities, suppressed charge recombination, and faster charge transfer kinetics, resulting in an outstanding power conversion efficiency (PCE) of 18.12% with the enhanced Jsc and FF, which is much higher than that (PCE of 16.09%) of the binary all-PSCs based on PM6:PY-IT. Besides, the ternary all-PSCs also exhibited improved photostability. The conspicuous performance enhancement principally should give the credit to the miscibility-driven phase optimization of the donor and acceptor. These findings highlight the significance of polymer backbone configuration modulation of PSMAs in morphology optimization toward boosting the device properties of all-PSCs. This article is protected by copyright. All rights reserved.

8.
J Med Chem ; 2023 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-36695404

RESUMO

AXL kinase is heavily involved in tumorigenesis, metastasis, and drug resistance of many cancers, and several AXL inhibitors are in clinical investigations. Recent studies demonstrated that the N-terminal distal region of AXL plays more important roles in cell invasiveness than its C-terminal kinase domain. Therefore, degradation of AXL may present a novel superior therapeutic approach than the kinase inhibitor therapy. Herein, we report the discovery of a series of new AXL PROTAC degraders. One representative compound 6n potently depletes AXL with a DC50 value of 5 nM in MDA-MB-231 TNBC cells. It also demonstrates significantly improved potencies against the AXL signaling activation, cell proliferation, migration and invasion of TNBC cells comparing with the corresponding kinase inhibitor. Moreover, the compound exhibits promising therapeutic potential both in patient-derived organoids and a xenograft mouse model of MDA-MB-231 cells.

9.
Glob Chang Biol ; 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36700364

RESUMO

No tillage (NT) has been proposed as a practice to reduce the adverse effects of tillage on contaminant (e.g., sediment and nutrient) losses to waterways. Nonetheless, previous reports on impacts of NT on nitrate (NO3 - ) leaching are inconsistent. A global meta-analysis was conducted to test the hypothesis that the response of NO3 - leaching under NT, relative to tillage, is associated with tillage type (inversion vs non-inversion tillage), soil properties (e.g., soil organic carbon [SOC]), climate factors (i.e., water input), and management practices (e.g., NT duration and nitrogen fertilizer inputs). Overall, compared with all forms of tillage combined, NT had 4% and 14% greater area-scaled and yield-scaled NO3 - leaching losses, respectively. The NO3 - leaching under NT tended to be 7% greater than that of inversion tillage but comparable to non-inversion tillage. Greater NO3 - leaching under NT, compared with inversion tillage, was most evident under short-duration NT (<5 years), where water inputs were low (<2 mm day-1 ), in medium texture and low SOC (<1%) soils, and at both higher (>200 kg ha-1 ) and lower (0-100 kg ha-1 ) rates of nitrogen addition. Of these, SOC was the most important factor affecting the risk of NO3 - leaching under NT compared with inversion tillage. Globally, on average, the greater amount of NO3 - leached under NT, compared with inversion tillage, was mainly attributed to corresponding increases in drainage. The percentage of global cropping land with lower risk of NO3 - leaching under NT, relative to inversion tillage, increased with NT duration from 3 years (31%) to 15 years (54%). This study highlighted that the benefits of NT adoption for mitigating NO3 - leaching are most likely in long-term NT cropping systems on high-SOC soils.

10.
Artigo em Inglês | MEDLINE | ID: mdl-36674278

RESUMO

Improving teacher well-being at work is a great challenge worldwide. Understanding the stressors of Chinese university teachers in teaching activities is critical for shedding light on well-being in the midst of the rapid expansion of the higher education system and the quest to rise in world rankings. This study integrates the well-being perspective and the transactional model of stress and coping to investigate the mechanisms underlying the effect of challenge-hindrance stressors on teacher engagement. Data were collected through the online platform SoJump in mainland China (N = 7743), and structural equation modeling was used to test the relationship between challenge-hindrance stressors and teaching engagement. The statistical results revealed the following: (1) challenge stressors had a significant positive effect on teaching engagement, while hindrance stressors were negatively related to teaching engagement; (2) challenge and hindrance stressors were significant negative predictors of teacher job satisfaction; (3) teacher job satisfaction suppressed the impact of challenge stressors on teaching engagement and partially mediated the process by which hindrance stressors impact teaching engagement. The findings suggest that the theoretically opposing effects of the two stressors are not absolute and that special consideration should be given to teachers' job satisfaction in relation to stress management for university teachers.


Assuntos
Pessoal de Educação , Satisfação no Emprego , Humanos , Universidades , Adaptação Psicológica , Professores Escolares
11.
Nutrients ; 15(2)2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36678238

RESUMO

Drinking alcohol during adolescence has short-term and long-term effects on physical and mental health. At this stage, teenagers are greatly influenced by their schoolmates and friends. We conducted a multicenter cross-sectional study to investigate the association between school environment factors and adolescents' drinking behavior in China. Using multistage stratified cluster sampling, the study investigated 27,762 middle school students from six cities in China. The logistic regression model was used to explore the association between the school environment and adolescent alcohol drinking behaviors after adjusting for confounders, including gender, age, city, location, and smoking status. Compared with students with none of their close friends drinking, students with more than half of their close friends drinking were more likely to drink in a year (OR = 20.148, 95% CI: 17.722-22.905, p < 0.001) and in a month (OR = 13.433, 95% CI: 11.779-15.319, p < 0.001). In addition, classmates' drinking behaviors, friends' persuasion, and attending parties were risk factors for adolescents' drinking behavior, while the propaganda and regulations of banning drinking in school were protective factors. The school environment, especially friends drinking, is associated with students' drinking behavior. It is necessary to mobilize the strength of schools and peers to strengthen the prevention and control of adolescent drinking.


Assuntos
Comportamento do Adolescente , Consumo de Álcool por Menores , Adolescente , Humanos , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Cidades , Estudos Transversais , Fatores de Risco , Comportamento do Adolescente/psicologia
12.
Environ Pollut ; 319: 121021, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36621718

RESUMO

China fully implemented the new emission standards in 2016 to further reduce the emissions of air pollutants from the municipal solid waste (MSW) incineration industry; however, the implementation effect of the new standards remains unknown. This study developed the first nationwide air pollutant emission inventory of MSW incineration plants in China based on the measured concentration data from China's continuous emissions monitoring systems (CEMS) network, and activity level data from the China Urban Construction Statistical Yearbook, to evaluate the effectiveness of implementing the new emission standards and estimate the future reduction potentials. Our results demonstrated that the overall standard-reaching proportions of particulate matter (PM), sulfur dioxide (SO2), nitrogen oxide (NOX), hydrogen chloride (HCl) and carbon monoxide (CO) were 98.8%, 99.3%, 99.4%, 99.4% and 97.6%, respectively, by comparing with the corresponding concentration limits of new emission standards. The total emissions of PM, SO2, NOX, HCl and CO from 412 MSW incineration plants in 2019 were 1.9, 6.2, 50.8, 4.3 and 6.6 kt yr-1, respectively, which is 33.6-75.8% lower than those in 2015, mainly due to the sharp decrease in emission factors. Pollutant emission hotspots were mainly concentrated in eastern and central and southern regions with large populations and well-developed economies. The analysis of future scenario results shows that despite the continuous increase of MSW incineration amount in the future, if the government strengthens pollutant emission standards and comprehensively implements waste sorting, total emissions and emission factors of air pollutants could be further reduced by 25.8-72.7% and 59.8-81.2%, respectively, by 2050. These findings provide helpful insights into future policymaking and technology selection for China and other countries seeking to reduce pollutant emissions from the MSW incineration industry.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Resíduos Sólidos/análise , Incineração/métodos , China , Dióxido de Enxofre/análise , Material Particulado/análise , Óxido Nítrico/análise , Poluição do Ar/prevenção & controle , Poluição do Ar/análise
13.
Hortic Res ; 10(1): uhac241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643737

RESUMO

The genus Rhododendron (Ericaceae), with more than 1000 species highly diverse in flower color, is providing distinct ornamental values and a model system for flower color studies. Here, we investigated the divergence between two parental species with different flower color widely used for azalea breeding. Gapless genome assembly was generated for the yellow-flowered azalea, Rhododendron molle. Comparative genomics found recent proliferation of long terminal repeat retrotransposons (LTR-RTs), especially Gypsy, has resulted in a 125 Mb (19%) genome size increase in species-specific regions, and a significant amount of dispersed gene duplicates (13 402) and pseudogenes (17 437). Metabolomic assessment revealed that yellow flower coloration is attributed to the dynamic changes of carotenoids/flavonols biosynthesis and chlorophyll degradation. Time-ordered gene co-expression networks (TO-GCNs) and the comparison confirmed the metabolome and uncovered the specific gene regulatory changes underpinning the distinct flower pigmentation. B3 and ERF TFs were found dominating the gene regulation of carotenoids/flavonols characterized pigmentation in R. molle, while WRKY, ERF, WD40, C2H2, and NAC TFs collectively regulated the anthocyanins characterized pigmentation in the red-flowered R simsii. This study employed a multi-omics strategy in disentangling the complex divergence between two important azaleas and provided references for further functional genetics and molecular breeding.

14.
Hortic Res ; 10(1): uhac228, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36643758

RESUMO

Momordica charantia L. var. abbreviata Ser. (Mca), known as bitter gourd or bitter melon, is a Momordica variety with medicinal value and belongs to the Cucurbitaceae family. In view of the lack of genomic information on bitter gourd and other Momordica species and to promote Mca genomic research, we assembled a 295.6-Mb telomere-to-telomere (T2T) high-quality Mca genome with six gap-free chromosomes after Hi-C correction. This genome is anchored to 11 chromosomes, which is consistent with the karyotype information, and comprises 98 contigs (N50 of 25.4 Mb) and 95 scaffolds (N50 of 25.4 Mb). The Mca genome harbors 19 895 protein-coding genes, of which 45.59% constitute predicted repeat sequences. Synteny analysis revealed variations involved in fruit quality during the divergence of bitter gourd. In addition, assay for transposase-accessible chromatin by high-throughput sequencing and metabolic analysis showed that momordicosides and other substances are characteristic of Mca fruit pulp. A combined transcriptomic and metabolomic analysis revealed the mechanisms of pigment accumulation and cucurbitacin biosynthesis in Mca fruit peels, providing fundamental molecular information for further research on Mca fruit ripening. This report provides a new genetic resource for Momordica genomic studies and contributes additional insights into Cucurbitaceae phylogeny.

15.
Biomater Sci ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36648453

RESUMO

Porphyrinic covalent organic frameworks (COFs) have emerged as prospective materials in photodynamic and photothermal sterilization. However, it is still a great challenge to construct an efficient COF-based sterilizing agent with good photothermal and photodynamic properties and bacterial targeting ability. Herein, we report a multifunctional porphyrin-COF for bacterial-targeted and reaction-enhanced synergistic phototherapy/chemotherapy for sterilization and wound healing. The ordered crystal structure of the porphyrin-COF not only effectively avoids the self-aggregation-induced quenching of the porphyrin monomer, but also facilitates the storage and transport of singlet oxygen. The acrylate substituent in the other monomer serves as a bacterial targeting moiety and the in situ reaction site with the sulfhydryl group of the bacterial surface protein via a Michael addition reaction, thus fixing the bacteria on the surface of COF and making them lose the colonization ability. Furthermore, the bonding of COF and bacteria further amplifies the therapeutic efficiency of phototherapy. Therefore, the developed multifunctional sterilization platform not only provides a new strategy for the design of novel bactericidal materials but also broadens the biological applications of COF-based materials.

16.
Mol Ther ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36638800

RESUMO

Blindness caused by advanced stages of inherited retinal diseases and age-related macular degeneration are characterized by photoreceptor loss. Cell therapy involving replacement with functional photoreceptor-like cells generated from human pluripotent stem cells holds great promise. Here, we generated a human recombinant retina-specific laminin isoform, LN523, and demonstrated the role in promoting the differentiation of human embryonic stem cells into photoreceptor progenitors. This chemically defined and xenogen-free method enables reproducible production of photoreceptor progenitors within 32 days. We observed that the transplantation into rd10 mice were able to protect the host photoreceptor outer nuclear layer (ONL) up to 2 weeks post transplantation as measured by full-field electroretinogram. At 4 weeks post transplantation, the engrafted cells were found to survive, mature, and associate with the host's rod bipolar cells. Visual behavioral assessment using the water maze swimming test demonstrated visual improvement in the cell-transplanted rodents. At 20 weeks post transplantation, the maturing engrafted cells were able to replace the loss of host ONL by extensive association with host bipolar cells and synapses. Post-transplanted rabbit model also provided congruent evidence for synaptic connectivity with the degenerated host retina. The results may pave the way for the development of stem cell-based therapeutics for retina degeneration.

17.
Adv Mater ; : e2210735, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36652589

RESUMO

Nanoscale electronic devices that can work in harsh environments are in high demand for wearable, automotive, and aerospace electronics. Clean and defect-free interfaces are of vital importance for building nanoscale harsh-environment-resistant devices. However, current nanoscale devices are subject to failure in these environments, especially at defective electrode-channel interfaces. Here, we develop harsh-environment-resistant MoS2 transistors by engineering electrode-channel interfaces with an all-transfer of van der Waals electrodes. The delivered defect-free, graphene-buffered electrodes keep the electrode-channel interfaces intact and robust. As a result, the as-fabricated MoS2 devices have reduced Schottky barrier heights, leading to a very large on-state current and high carrier mobility. More importantly, the defect-free, hydrophobic graphene buffer layer prevents metal diffusion from the electrodes to MoS2 and the intercalation of water molecules at the electrode-MoS2 interfaces. This enables high resistances of MoS2 devices with all-transfer electrodes to various harsh environments, including humid, oxidizing, and high-temperature environments, surpassing the devices with other kinds of electrodes. Our work deepens the understanding of the roles of electrode-channel interfaces in nanoscale devices and provides a promising interface engineering strategy to build nanoscale harsh-environment-resistant devices. This article is protected by copyright. All rights reserved.

18.
Scand J Clin Lab Invest ; : 1-6, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650947

RESUMO

Cell division control 42 (CDC42) regulates blood lipids, atherosclerosis, T cell differentiation and inflammation, which is involved in the process of coronary heart disease (CHD). This study aimed to evaluate the CDC42 level and its correlation with clinical features, the T-helper 17 (Th17)/regulatory-T (Treg) cell ratio and prognosis in CHD patients. In total, 210 CHD patients, 20 healthy controls and 20 disease controls were enrolled. Serum CDC42 levels of all participants were measured by enzyme-linked immunosorbent assay. In CHD patients, Th17 and Treg cells were discovered by flow cytometry; CHD patients were followed-up for a median of 16.9 months (range of 2.5-38.2 months). CDC42 level was lowest in CHD patients (median (interquartile range (IQR)): 402.5 (287.3-599.0) pg/mL), moderate in disease controls (median (IQR): 543.5 (413.0-676.3) pg/mL) and highest in healthy controls (median (IQR): 668.0 (506.5-841.3) pg/mL) (p < .001). Moreover, in CHD patients, lower CDC42 level was related to more prevalent diabetes mellitus (p = .021), and higher levels of C-reactive protein (p = .001), Gensini score (p = .006), Th17 cells (p = .001) and Th17/Treg ratio (p < .001) but was associated with lower Treg cells (p = .018). Furthermore, CDC42 low level [below the median level (402.5 pg/mL) of CDC42 in CHD patients] was correlated with higher accumulating major adverse cardiovascular event (MACE) risk (p = .029), while no correlation was found between the quartile of CDC42 level and accumulating MACE risk in CHD patients (p = .102). The serum CDC42 level is decreased and its low level is related to higher Th17/Treg ratio and increased accumulating MACE risk in CHD patients.

19.
Cancer Imaging ; 23(1): 6, 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36647150

RESUMO

BACKGROUND: Deep-learning-based computer-aided diagnosis (DL-CAD) systems using MRI for prostate cancer (PCa) detection have demonstrated good performance. Nevertheless, DL-CAD systems are vulnerable to high heterogeneities in DWI, which can interfere with DL-CAD assessments and impair performance. This study aims to compare PCa detection of DL-CAD between zoomed-field-of-view echo-planar DWI (z-DWI) and full-field-of-view DWI (f-DWI) and find the risk factors affecting DL-CAD diagnostic efficiency. METHODS: This retrospective study enrolled 354 consecutive participants who underwent MRI including T2WI, f-DWI, and z-DWI because of clinically suspected PCa. A DL-CAD was used to compare the performance of f-DWI and z-DWI both on a patient level and lesion level. We used the area under the curve (AUC) of receiver operating characteristics analysis and alternative free-response receiver operating characteristics analysis to compare the performances of DL-CAD using f- DWI and z-DWI. The risk factors affecting the DL-CAD were analyzed using logistic regression analyses. P values less than 0.05 were considered statistically significant. RESULTS: DL-CAD with z-DWI had a significantly better overall accuracy than that with f-DWI both on patient level and lesion level (AUCpatient: 0.89 vs. 0.86; AUClesion: 0.86 vs. 0.76; P < .001). The contrast-to-noise ratio (CNR) of lesions in DWI was an independent risk factor of false positives (odds ratio [OR] = 1.12; P < .001). Rectal susceptibility artifacts, lesion diameter, and apparent diffusion coefficients (ADC) were independent risk factors of both false positives (ORrectal susceptibility artifact = 5.46; ORdiameter, = 1.12; ORADC = 0.998; all P < .001) and false negatives (ORrectal susceptibility artifact = 3.31; ORdiameter = 0.82; ORADC = 1.007; all P ≤ .03) of DL-CAD. CONCLUSIONS: Z-DWI has potential to improve the detection performance of a prostate MRI based DL-CAD. TRIAL REGISTRATION: ChiCTR, NO. ChiCTR2100041834 . Registered 7 January 2021.


Assuntos
Aprendizado Profundo , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Imageamento por Ressonância Magnética/métodos , Imagem de Difusão por Ressonância Magnética/métodos
20.
J Appl Toxicol ; 2023 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-36617218

RESUMO

Cadmium (Cd) is a toxic heavy metal pollutant and serves as an important environmental endocrine-disrupting chemical. Cd exposure is believed to can enhance the risks of age-related disorders including benign prostatic hyperplasia (BPH). This study was to investigate the harms of Cd exposure on mice prostate and human nonmalignant prostate epithelial RWPE-1 cells. Mice prostate fibrosis was evaluated by visualizing the prostatic collagen deposition via Masson and Sirius red staining, and detecting the content of hydroxyproline. Additionally, the epithelial-mesenchymal transition (EMT), primary ciliogenesis and SHH signaling pathways in both mice prostate and RWPE-1 cells were evaluated. It was found that Cd exposure stimulated prostatic collagen deposition, EMT and primary ciliogenesis, as well as enhanced the circ_0027470 level and reduced the miRNA-1236-3p level. Circ_0027470 functioned as a sponge of miRNA-1236-3p, which had the inhibiting target of SHH. The whole results showed that circ_0027470 promoted Cd exposure-induced prostatic fibrosis via sponging miRNA-1236-3p and subsequently stimulating SHH signaling pathway. This study shed a light on a novel molecular mechanism involved in circRNA for Cd exposure-induced prostate deficits.

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