Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.612
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-36700528

RESUMO

Flexible synaptic devices with information sensing, processing, and storage functions are indispensable in the development of wearable artificial intelligence electronic systems. Here, a semiconductor/dielectric bilayer structure was prepared by a one-step deposition method and used for the first time in a flexible biomimetic photonic synaptic transistor device. Specifically, poly(3-hexylthiophene)-block-poly(phenyl isocyanide) with pentafluorophenyl ester (P3HT-b-PPI(5F)) was prepared as the device active layer, where the P3HT segment served as a carrier transport channel and optical gate and the PPI(5F) segment was used for charge trapping. Various biomimetic synaptic behaviors, such as excitatory postsynaptic currents, paired-pulse facilitation, and short-term/long-term memory, were successfully simulated under green light stimulation. An ultra-low energy consumption of 1.82 fJ was achieved with a greatly reduced operating voltage. Further, the "Morse-code" optical decoding was simulated using the excellent synaptic plasticity of the device. In addition, flexible synaptic devices were prepared by a one-step deposition method and can be well-affixed to arbitrary substrates. This has promising applications in the field of wearable bionic electronics.

2.
Int J Antimicrob Agents ; : 106717, 2023 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-36640850

RESUMO

Ceftolozane/tazobactam is approved in several countries to treat complicated urinary tract and complicated intra-abdominal infections and nosocomial pneumonia. There is a paucity of pharmacokinetics and safety data for ceftolozane/tazobactam in Chinese participants. This study evaluated pharmacokinetics, safety, and tolerability of ceftolozane/tazobactam in 12 healthy Chinese participants after three single administrations of increasing doses (0.75 g, 1.5 g, and 3 g) and multiple administrations of 1.5 g ceftolozane/tazobactam every 8 hours for 3 days. After single doses, maximum concentrations of ceftolozane and tazobactam were reached by the end of the 1-hour infusion and declined in a biphasic manner thereafter, with mean half-lives of 1.9-2.2 h and 0.74-0.95 h, respectively. Volume of distribution (Vd) and renal clearance (CL) were consistent across the three single-dose levels for ceftolozane (Vd, 15.8-19.5 L; CL, 5.68-6.09 L/h) and tazobactam (Vd, 23.3-28.6 L; CL, 20.8-23.5 L/h). Area under the concentration-time curve (AUC) extrapolated to infinity (ceftolozane, 88.1-328 h∙µg/mL; tazobactam, 10.7-48.0 h∙µg/mL) increased in a dose-dependent manner. After multiple doses over 3 days, AUC from time 0 to 8 hours, and concentration at the end of infusion were similar to single-dose measurements (geometric mean ratios, 0.87-1.01 for both drugs). Ceftolozane/tazobactam was well tolerated, with no serious adverse events or discontinuations reported; all adverse events were mild. The pharmacokinetics and safety/tolerability of ceftolozane/tazobactam in healthy Chinese participants was comparable to previous studies, which did not include Chinese participants, supporting the use of ceftolozane/tazobactam for the treatment of Chinese patients.

3.
Clin Cancer Res ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36693175

RESUMO

PURPOSE: Clinical biomarkers to identify patients unlikely to benefit from CDK4/6 inhibition (CDK4/6i) in combination with endocrine therapy (ET) are lacking. We implemented a comprehensive circulating tumor DNA (ctDNA) analysis to identify genomic features for predicting and monitoring treatment resistance. EXPERIMENTAL DESIGN: ctDNA was isolated from 216 plasma samples collected from 51 patients with hormone receptor-positive (HR+)/HER2-negative (HER2-) metastatic breast cancer (MBC) on a phase II trial of palbociclib combined with letrozole or fulvestrant (NCT03007979). Boosted whole exome sequencing (WES) was performed at baseline and clinical progression to evaluate genomic alterations, mutational signatures, and blood tumor mutational burden (bTMB). Low-pass whole-genome sequencing was performed at baseline and serial timepoints to assess blood copy number burden (bCNB). RESULTS: High bTMB and bCNB were associated with lack of clinical benefit and significantly shorter progression-free survival (PFS) compared to patients with low bTMB or low bCNB (all P<0.05). Dominant APOBEC signatures were detected at baseline exclusively in cases with high bTMB (5/13, 38.5%) vs. low bTMB (0/37, 0%) (P=0.0006). Alterations in ESR1 were enriched in samples with high bTMB (P=0.0005). There was a high correlation between bTMB determined by WES and bTMB determined using a 600-gene panel (R=0.98). During serial monitoring, an increase in bCNB scores preceded radiographic progression in 12/18 (66.7%) patients. CONCLUSIONS: Genomic complexity detected by non-invasive profiling of bTMB and bCNB predicted poor outcomes in patients treated with ET and CDK4/6i and identified early disease progression before imaging. Novel treatment strategies including immunotherapy-based combinations should be investigated in this population.

4.
JCI Insight ; 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36692953

RESUMO

Loss of function mutations in CCM genes and gain of function mutation in the MAP3K3 gene encoding MEKK3 cause cerebral cavernous malformation (CCM). Deficiency of CCM proteins leads to the activation of MEKK3-KLF2/4 signaling, but it is not clear how this occurs. Here we demonstrate that deletion of the CCM3 interacting kinases STK24/25 in endothelial cells cause defects in vascular patterning during development as well as CCM lesion formation during postnatal life. While permanent deletion of STK24/25 in endothelial cells caused developmental defects of the vascular system, inducible postnatal deletion of STK24/25 impaired angiogenesis in the retina and brain. More importantly, deletion of STK24/25 in neonatal mice led to the development of severe CCM lesions. At the molecular level, a hybrid protein consisting of the STK kinase domain and the MEKK3 interacting domain of CCM2 rescued the vascular phenotype caused by the loss of ccm gene function in zebrafish. Our study suggests that CCM2/3 proteins act as adapters to allow recruitment of STK24/25 to limit the constitutive MEKK3 activity that contributes to vessel stability. Loss of STK24/25 causes MEKK3 activation leading to CCM lesion formation.

5.
Food Res Int ; 163: 112212, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36596140

RESUMO

Rapid and sensitive quantitative detection methods are required to monitor and detect Salmonella throughout the food supply chain and early prevention of foodborne disease outbreaks. In this study, a magnetic microbead enzyme-linked immunoassay (MELISA) based on phage receptor binding protein was developed for rapid enrichment and detection of Salmonella in complex food matrices. RBP 41 from phage T102 acted as a species-specific recognition element for Salmonella by exploiting its strong binding capacity to Salmonella surface receptors. RBP 41-MBs were prepared by coupling recombinant RBP 41 with MBs and used to separate and enrich Salmonella cells from spiked food samples. The captured complexes were further integrated with ELISA procedures by HRP-labeled anti-Salmonella antibody for rapid and accurate detection of Salmonella. The whole method took <1.5 h and the detection limit was 10 CFU/mL. Therefore, MELISA was successfully developed for the detection of Salmonella in various spiked food samples (skim milk, lettuce, and chicken breast). The ELISA reaction process of this method was carried out on magnetic beads. It simplified the process of the traditional ELISA method and reduces the reaction time. This study expanded the use of phage-associated proteins and demonstrated the promising prospects for practical applications in the detection of foodborne pathogens.


Assuntos
Bacteriófagos , Microesferas , Imunoensaio/métodos , Salmonella , Fenômenos Magnéticos
6.
Br J Ophthalmol ; 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596662

RESUMO

BACKGROUND: The visual outcome of open globe injury (OGI)-no light perception (NLP) eyes is unpredictable traditionally. This study aimed to develop a model to predict the visual outcomes of vitrectomy surgery in OGI-NLP eyes using a machine learning algorithm and to provide an interpretable system for the prediction results. METHODS: Clinical data of 459 OGI-NLP eyes were retrospectively collected from 19 medical centres across China to establish a training data set for developing a model, called 'VisionGo', which can predict the visual outcome of the patients involved and compare with the Ocular Trauma Score (OTS). Another 72 cases were retrospectively collected and used for human-machine comparison, and an additional 27 cases were prospectively collected for real-world validation of the model. The SHapley Additive exPlanations method was applied to analyse feature contribution to the model. An online platform was built for real-world application. RESULTS: The area under the receiver operating characteristic curve (AUC) of VisionGo was 0.75 and 0.90 in previtrectomy and intravitrectomy application scenarios, which was much higher than the OTS (AUC=0.49). VisionGo showed better performance than ophthalmologists in both previtrectomy and intravitrectomy application scenarios (AUC=0.73 vs 0.57 and 0.87 vs 0.64). In real-world validation, VisionGo achieved an AUC of 0.60 and 0.91 in previtrectomy and intravitrectomy application scenarios. Feature contribution analysis indicated that wound length-related indicators, vitreous status and retina-related indicators contributed highly to visual outcomes. CONCLUSIONS: VisionGo has achieved an accurate and reliable prediction in visual outcome after vitrectomy for OGI-NLP eyes.

7.
Cardiovasc Res ; 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36651911

RESUMO

AIMS: Trastuzumab, the first humanized monoclonal antibody that targets human epidermal growth factor receptor 2 (ERBB2/HER2), is currently used as a first-line treatment for HER2 (+) tumours. However, trastuzumab increases the risk of cardiac complications without affecting myocardial structure, suggesting a distinct mechanism of cardiotoxicity. METHODS AND RESULTS: We used medium from trastuzumab-treated human umbilical vein endothelial cells (HUVECs) to treat CCC-HEH-2 cells, the human embryonic cardiac tissue-derived cell lines, and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) to assess the crosstalk between vascular endothelial cells (VECs) and cardiomyocytes. Protein mass spectrometry analysis was used to identify the key factors from VECs that regulate the function of cardiomyocytes. We applied RNA-sequencing to clarify the mechanism, by which PTX3 causes cardiac dysfunction. We used an anti-human/rat HER2 (neu) monoclonal antibody to generate a rat model that was used to evaluate the effects of trastuzumab on cardiac structure and function and the rescue effects of lapatinib on trastuzumab-induced cardiac side effects. Medium from trastuzumab-treated HUVECs apparently impaired the contractility of CCC-HEH-2 cells and iPSC-CMs. PTX3 from VECs caused defective cardiomyocyte contractility and cardiac dysfunction in mice, phenocopying trastuzumab treatment. PTX3 affected calcium homeostasis in cardiomyocytes, which led to defective contractile properties. EGFR/STAT3 signalling in VECs contributed to the increased expression and release of PTX3. Notably, lapatinib, a dual inhibitor of EGFR/HER2, could rescue the cardiac complications caused by trastuzumab by blocking the release of PTX3. CONCLUSIONS: We identified a distinct mode of cardiotoxicity, wherein the activation of EGFR/STAT3 signalling by trastuzumab in VECs promotes PTX3 excretion, which contributes to the impaired contractility of cardiomyocytes by inhibiting cellular calcium signalling. We confirmed that lapatinib could be a feasible preventive agent against trastuzumab-induced cardiac complications and provided the rationale for the combined application of lapatinib and trastuzumab in cancer-therapy. TRANSLATIONAL PERSPECTIVE: We identified PTX3 as a potential biomarker and target for the treatment of trastuzumab-induced cardiac complications and demonstrated that lapatinib can prevent cardiac dysfunction caused by trastuzumab by blocking EFGR/STAT3-mediated PTX3 release from VECs, which provided a mechanistic rationale for the combined application of lapatinib and trastuzumab in cancer.

8.
Int J Mol Sci ; 24(1)2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36614332

RESUMO

Clinically, large diameter artery defects (diameter larger than 6 mm) can be substituted by unbiodegradable polymers, such as polytetrafluoroethylene. There are many problems in the construction of small diameter blood vessels (diameter between 1 and 3 mm) and microvessels (diameter less than 1 mm), especially in the establishment of complex vascular models with multi-scale branched networks. Throughout history, the vascularization strategies have been divided into three major groups, including self-generated capillaries from implantation, pre-constructed vascular channels, and three-dimensional (3D) printed cell-laden hydrogels. The first group is based on the spontaneous angiogenesis behaviour of cells in the host tissues, which also lays the foundation of capillary angiogenesis in tissue engineering scaffolds. The second group is to vascularize the polymeric vessels (or scaffolds) with endothelial cells. It is hoped that the pre-constructed vessels can be connected with the vascular networks of host tissues with rapid blood perfusion. With the development of bioprinting technologies, various fabrication methods have been achieved to build hierarchical vascular networks with high-precision 3D control. In this review, the latest advances in 3D bioprinting of vascularized tissues/organs are discussed, including new printing techniques and researches on bioinks for promoting angiogenesis, especially coaxial printing, freeform reversible embedded in suspended hydrogel printing, and acoustic assisted printing technologies, and freeform reversible embedded in suspended hydrogel (flash) technology.


Assuntos
Bioimpressão , Células Endoteliais , Bioimpressão/métodos , Impressão Tridimensional , Engenharia Tecidual/métodos , Tecidos Suporte , Tecnologia , Hidrogéis , Polímeros
9.
J Oral Sci ; 65(1): 53-56, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36631127

RESUMO

PURPOSE: The purpose of this study was to investigate the reaction products formed by application of three tooth etchants to hydroxyapatite. METHODS: Tooth etchants with three different compositions, designed for application to teeth before dental adhesive - " K-etchant GEL" (containing phosphoric acid), "Enamel Conditioner" (containing organic acids), and "Multi Etchant" (containing acidic monomer) - were applied to hydroxyapatite plates. RESULTS: Atomic force microscopy measurements revealed that Multi Etchant formed nano-sized particles on the hydroxyapatite. X-ray diffraction and Fourier transform infrared spectrometer analyses of the powdered hydroxyapatite indicated that Enamel Conditioner produced calcium tartrate whereas K-etchant GEL generated monetite. These results indicated that each etchant reacted with hydroxyapatite in a different way. CONCLUSION: Not only differences among the etching ability of etchants, but also differences in the reaction compounds they produce may influence bonding performance in clinical practice.


Assuntos
Colagem Dentária , Durapatita , Ácidos Fosfóricos , Esmalte Dentário , Difração de Raios X , Colagem Dentária/métodos , Teste de Materiais , Microscopia Eletrônica de Varredura , Cimentos de Resina
10.
Circ Res ; 132(1): 87-105, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36475898

RESUMO

BACKGROUND: The Hippo-YAP (yes-associated protein) signaling pathway is modulated in response to various environmental cues. Activation of YAP in vascular smooth muscle cells conveys the extracellular matrix stiffness-induced changes in vascular smooth muscle cells phenotype and behavior. Recent studies have established a mechanoreceptive role of receptor tyrosine kinase DDR1 (discoidin domain receptor 1) in vascular smooth muscle cells. METHODS: We conduced 5/6 nephrectomy in vascular smooth muscle cells-specific Ddr1-knockout mice, accompanied by pharmacological inhibition of the Hippo pathway kinase LATS1 (large tumor suppressor 1), to investigate DDR1 in YAP activation. We utilized polyacrylamide gels of varying stiffness or the DDR1 ligand, type I collagen, to stimulate the cells. We employed multiple molecular biological techniques to explore the role of DDR1 in controlling the Hippo pathway and to determine the mechanistic basis by which DDR1 exerts this effect. RESULTS: We identified the requirement for DDR1 in stiffness/collagen-induced YAP activation. We uncovered that DDR1 underwent stiffness/collagen binding-stimulated liquid-liquid phase separation and co-condensed with LATS1 to inactivate LATS1. Mutagenesis experiments revealed that the transmembrane domain is responsible for DDR1 droplet formation. Purified DDR1 N-terminal and transmembrane domain was sufficient to drive its reversible condensation. Depletion of the DDR1 C-terminus led to failure in co-condensation with LATS1. Interaction between the DDR1 C-terminus and LATS1 competitively inhibited binding of MOB1 (Mps one binder 1) to LATS1 and thus the subsequent phosphorylation of LATS1. Introduction of the single-point mutants, histidine-745-proline and histidine-902-proline, to DDR1 on the C-terminus abolished the co-condensation. In mouse models, YAP activity was positively correlated with collagen I expression and arterial stiffness. LATS1 inhibition reactivated the YAP signaling in Ddr1-deficient vessels and abrogated the arterial softening effect of Ddr1 deficiency. CONCLUSIONS: These findings identify DDR1 as a mediator of YAP activation by mechanical and chemical stimuli and demonstrate that DDR1 regulates LATS1 phosphorylation in an liquid-liquid phase separation-dependent manner.


Assuntos
Via de Sinalização Hippo , Histidina , Camundongos , Animais , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Colágeno , Colágeno Tipo I
11.
EMBO Mol Med ; 15(1): e16373, 2023 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-36511116

RESUMO

The pathological retinal angiogenesis often causes blindness. Current anti-angiogenic therapy for proliferative retinopathy targets the vascular endothelial growth factor (VEGF), but many patients do not radically benefit from this therapy. Herein, we report that circulating prostaglandin (PG) F2α metabolites were increased in type 2 diabetic patients with proliferative retinopathy, and the PGF2α receptor (Ptgfr) was upregulated in retinal endothelial cells (ECs) from a mouse model of oxygen-induced retinopathy (OIR). Further, disruption of the PTGFR receptor in ECs attenuated OIR in mice. PGF2α promoted the proliferation and tube formation of human retinal microvascular endothelial cells (HRMECs) via the release of ELR+ CXC chemokines, such as CXCL8 and CXCL2. Mechanistically, the PGF2α /PTGFR axis potentiated ELR+ CXC chemokine expression in HRMECs through the Gq /CAMK2G/p38/ELK-1/FOS pathway. Upregulated FOS-mediated ELR+ CXC chemokine expression was observed in retinal ECs from PDR patients. Moreover, treatment with PTGFR inhibitor lessened the development of OIR in mice in a CXCR2-dependent manner. Therefore, inhibition of PTGFR may represent a new avenue for the treatment of retinal neovascularization, particularly in PDR.


Assuntos
Quimiocinas CXC , Doenças Retinianas , Humanos , Camundongos , Animais , Quimiocinas CXC/fisiologia , Células Endoteliais/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Neovascularização Patológica/patologia , Doenças Retinianas/patologia , Oxigênio , Camundongos Endogâmicos C57BL , Fator de Crescimento Placentário
12.
Int J Nanomedicine ; 17: 5825-5850, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36474526

RESUMO

Inorganic polyphosphates (polyP) are long-chain polymers of orthophosphate residues, which, depending on the external conditions, can be present both physiologically and synthetically in either soluble, nanoparticulate or coacervate form. In recent years, these polymers have received increasing attention due to their unprecedented ability to exhibit both morphogenetic and metabolic energy delivering properties. There are no other physiological molecules that contain as many metabolically utilizable, high-energy bonds as polyP, making these polymers of particular medical interest as components of advanced hydrogel scaffold materials for potential applications in ATP-dependent tissue regeneration and repair. However, these polymers show physiological activity only in soluble form and in the coacervate phase, but not as stable metal-polyP nanoparticles. Therefore, understanding the mechanisms of formation of polyP coacervates and nanoparticles as well as their transformations is important for the design of novel materials for tissue implants, wound healing, and drug delivery and is discussed here.

14.
medRxiv ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36482978

RESUMO

Purpose: Enhanced understanding of the dynamic changes in the dysregulated inflammatory response in COVID-19 may help improve patient selection and timing for immunomodulatory therapies. Methods: We enrolled 323 COVID-19 inpatients on different levels of baseline respiratory support: i) Low Flow Oxygen (37%), ii) Non-Invasive Ventilation or High Flow Oxygen (NIV_HFO, 29%), iii) Invasive Mechanical Ventilation (IMV, 27%), and iv) Extracorporeal Membrane Oxygenation (ECMO, 7%). We collected plasma samples upon enrollment and days 5 and 10 to measure host-response biomarkers. We classified subjects into inflammatory subphenotypes using two validated predictive models. We examined clinical, biomarker and subphenotype trajectories and outcomes during hospitalization. Results: IL-6, procalcitonin, and Angiopoietin-2 were persistently elevated in patients at higher levels of respiratory support, whereas sRAGE displayed the inverse pattern. Patients on NIV_HFO at baseline had the most dynamic clinical trajectory, with 26% eventually requiring intubation and exhibiting worse 60-day mortality than IMV patients at baseline (67% vs. 35%, p<0.0001). sRAGE levels predicted NIV failure and worse 60-day mortality for NIV_HFO patients, whereas IL-6 levels were predictive in IMV or ECMO patients. Hyper-inflammatory subjects at baseline (<10% by both models) had worse 60-day survival (p<0.0001) and 50% of them remained classified as hyper-inflammatory on follow-up sampling at 5 days post-enrollment. Receipt of combined immunomodulatory therapies (steroids and anti-IL6 agents) was associated with markedly increased IL-6 and lower Angiopoietin-2 levels (p<0.05). Conclusions: Longitudinal study of systemic host responses in COVID-19 revealed substantial and predictive inter-individual variability, influenced by baseline levels of respiratory support and concurrent immunomodulatory therapies.

15.
Polymers (Basel) ; 14(23)2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36501537

RESUMO

Diabetes is the most common chronic disease in the world, and it brings a heavy burden to people's health. Against this background, diabetic research, including islet functionalization has become a hot topic in medical institutions all over the world. Especially with the rapid development of microencapsulation and three-dimensional (3D) bioprinting technologies, organ engineering and manufacturing have become the main trends for disease modeling and drug screening. Especially the advanced 3D models of pancreatic islets have shown better physiological functions than monolayer cultures, suggesting their potential in elucidating the behaviors of cells under different growth environments. This review mainly summarizes the latest progress of islet capsules and 3D printed pancreatic organs and introduces the activities of islet cells in the constructs with different encapsulation technologies and polymeric materials, as well as the vascularization and blood glucose control capabilities of these constructs after implantation. The challenges and perspectives of the pancreatic organ engineering/manufacturing technologies have also been demonstrated.

16.
Plant Cell ; 2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36512471

RESUMO

Tight control of lateral root (LR) initiation is vital for root system architecture and function. Regulation of cortical microtubule reorganization is involved in the asymmetric radial expansion of founder cells during LR initiation in Arabidopsis (Arabidopsis thaliana). However, critical genetic evidence on the role of microtubules in LR initiation is lacking and the mechanisms underlying this regulation are poorly understood. Here, we found that the previously uncharacterized microtubule-stabilizing protein TPX2-LIKE5 (TPXL5) participates in LR initiation, which is finely regulated by the transcription factor ELONGATED HYPOCOTYL5 (HY5). In tpxl5 mutants, LR density was decreased and more LR primordia (LRPs) remained in stage I, indicating delayed LR initiation. In particular, the cell width in the peripheral domain of LR founder cells after the first asymmetric cell division was larger in tpxl5 mutants than in the wild type. Consistently, ordered transverse cortical microtubule arrays were not well generated in tpxl5 mutants. In addition, HY5 directly targeted the promoter of TPXL5 and downregulated TPXL5 expression. The hy5 mutant exhibited higher LR density and fewer stage I LRPs, indicating accelerated LR initiation. Such phenotypes were partially suppressed by TPXL5 knockout. Taken together, our data provide genetic evidence supporting the notion that cortical microtubules are essential for LR initiation and unravel a molecular mechanism underlying HY5 regulation of TPXL5-mediated microtubule reorganization and cell remodeling during LR initiation.

17.
J Clin Med ; 11(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36498761

RESUMO

We investigated the prevalence of human papillomavirus (HPV) infection in the female partner of infertile couples and the reproductive outcomes after in vitro fertilization/intracytoplasmic sperm injection-embryo transfer (IVF/ICSI-ET). We conducted a retrospective analysis on 8117 women from infertile couples who underwent IVF/ICSI treatment and evaluated the prevalence of HPV infection in these women. The prevalence of HPV infection in the female partner of infertile couples was 9.2% (747/8117). These HPV-infected female patients undergoing ART were divided into high-risk HPV (hrHPV) (n = 130) and low-risk HPV (lrHPV) groups (n = 94), and non-infected women patients formed the negative group (n = 126). Of the 747 cases infected with HPV, 529 showed hrHPV infection (70.82%; primarily genotypes 16, 52, 53, 58, and 59); 175 exhibited lrHPV infection (23.43%; primarily genotypes 6, 43, 44, 55, 61, and 81); and 43 cases were co-infected with hrHPV and lrHPV (5.76%). Except for the Day-3 high-quality embryo rate, there were no differences in ovum maturation, fertilization, implantation, clinical pregnancy, live birth, or miscarriage rates between women infected with HPV and non-infected women (p > 0.05); however, we noted an increased miscarriage rate after logistic regression analyses (OR, 0.16; 95% CI, 0.03-0.84; p = 0.041). For single-male-factor-induced infertility in couples (smHPV), although we likewise observed no differences in ovum maturation, fertilization, or implantation rates (p > 0.05) between the smHPV group and the negative group, we discerned diminutions in the Day-3 high-quality embryo rate (46.01% vs. 70.04%, p = 0.013), clinical pregnancy rate (46.67% vs. 57.94%, p = 0.003), and live birth rate (33.33% vs. 46.83%, p = 0.027) as well as an augmented miscarriage rate (11.11% vs. 4.76%, p = 0.003), respectively. Logistic regression analyses indicated that smHPV was a risk factor for decreased clinical pregnancy rate (OR, 4.17; 95% CI, 2.31-7.53; p < 0.001) and live birth rate (OR, 1.83; 95% CI, 0.81-2.14; p = 0.045) and elevated miscarriage rate (OR, 6.83; 95% CI, 2.22-21.00; p = 0.001). HPV infection in women was associated with increased miscarriage rate, and single-male-factor infertility influenced reproductive outcomes in couples undergoing IVF/ICSI treatment. Both were potentially due to HPV infection in the couple.

18.
Front Psychol ; 13: 1071986, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36571030

RESUMO

Introduction: Corporates need to break through the dilemma of system and efficiency with the help of digital transformation in the digital economy era. This paper aims to examine the influence of digital transformation on corporate total factor productivity by investigating whether and how corporate technical cooperation and ESG performance mediate and moderate the relationship between them. Methods: This study choose Chinese A-share listed manufacturing firms from 2016-2020 as the research sample and use the FGLS regression model to test the proposed hypotheses. Results: Results show that digital transformation has a positive effect on corporate total factor productivity, and this positive impact is more pronounced when corporates have higher ESG performance. Corporate technical cooperation plays a mediating role between digital transformation and total factor productivity. ESG performance also plays a positive moderating role in the relationship between digital transformation and corporate technical cooperation. Discussion: Our results contribute to the literature on digital transformation and corporate total factor productivity at the micro-corporate level. Further, our findings offer insights to decision-makers and regulatory bodies regarding the current practices of digital transformation and its potential economic impact.

19.
Toxicol Sci ; 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36583546

RESUMO

The purpose of this study was to use chemical similarity evaluations, transcriptional profiling, in vitro toxicokinetic data and physiologically based pharmacokinetic (PBPK) models to support read across for a series of branched carboxylic acids using valproic acid (VPA), a known developmental toxicant, as a comparator. The chemicals included 2-propylpentanoic acid (VPA), 2-ethylbutanoic acid (EBA), 2-ethylhexanoic acid (EHA), 2-methylnonanoic acid (MNA), 2-hexyldecanoic acid (HDA), 2-propylnonanoic acid (PNA), dipentyl acetic acid (DPA) or 2-pentylheptanoic acid (PHA), octanoic acid (OA, a straight chain alkyl acid) and 2-ethylhexanol. Transcriptomics was evaluated in four cell types (A549, HepG2, MCF7 and iCell cardiomyocytes) 6 hours after exposure to 3 concentrations of the compounds, using the L1000 platform. The transcriptional profiling data indicate that two- or three-carbon alkyl substituents at the alpha position of the carboxylic acid (EHA and PNA) elicit a transcriptional profile similar to the one elicited by VPA. The transcriptional profile is different for the other chemicals tested, which provides support for limiting read across from VPA to much shorter and longer acids. Molecular docking models for histone deacetylases, the putative target of VPA, provides a possible mechanistic explanation for the activity cliff elucidated by transcriptomics. In vitro toxicokinetic data was utilized in a PBPK model to estimate internal dosimetry. The PBPK modeling data show that as the branched chain increases, predicted plasma Cmax decreases. This work demonstrates how transcriptomics and other mode of action-based methods can improve read across.

20.
Aquat Toxicol ; 253: 106333, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36368229

RESUMO

Zinc oxide nanoparticles (ZnONPs) are widespread pollutants that are present in diverse environmental samples. Here, we determined metabolomic and bioenergetic responses in the liver of female and male zebrafish exposed to a prolonged environmentally relevant concentration of ZnONPs. Metabolome analysis revealed that exposure to 500 µg/L ZnONPs reduced the abundance of metabolites in the tricarboxylic acid (TCA) cycle by modulating the activities of rate-limiting enzymes α-ketoglutarate dehydrogenase and isocitrate dehydrogenase. Moreover, oxidative phosphorylation (OXPHOS) was negatively impacted in the liver based upon decreased activities of mitochondrial Complex I and V in both female and male livers. Our results revealed that bioenergetic responses were not attributed to dissolved Zn2+ and were not sex-specific. However, the metabolic responses in liver following exposure to ZnONPs did show sex-specific responses. Females exposed to ZnONPs compensated for the energetic stress via increasing fatty acids and amino acids metabolism, while males compensated to ZnONPs exposure by adjusting amino acids metabolism, based upon transcript profiles. This study demonstrates that zebrafish adjust the transcription of metabolic enzymes in the liver to compensate for metabolic disruption following ZnONPs exposure. Taken together, this study contributes to a comprehensive understanding of risks related to ZnONPs exposure in relation to metabolic activity in the liver. Environmental implication Zinc oxide nanoparticles (ZnONPs) are widely used in industry and are subsequently released into environments. However, biological responses between female and male following ZnONPs exposure has never been compared. Our data revealed for the first time that female and male zebrafish showed comparable bioenergetic responses, but different metabolic responses to ZnONPs at an environmentally relevant dose. Females compensated for the energetic stress via increasing fatty acids and amino acids metabolism, while males compensated to ZnONPs exposure by adjusting amino acids metabolism in livers. This study reveals that sex may be an important variable to consider in risk assessments of nanoparticles released into environments.


Assuntos
Nanopartículas , Poluentes Químicos da Água , Óxido de Zinco , Animais , Masculino , Feminino , Óxido de Zinco/química , Peixe-Zebra/metabolismo , Poluentes Químicos da Água/toxicidade , Fígado/metabolismo , Ácidos Graxos/metabolismo , Aminoácidos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...