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1.
Front Chem ; 10: 899287, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35572110

RESUMO

Iron-chromium redox flow batteries (ICRFBs) have the advantages of high safety, long cycle life, flexible design, and low maintenance costs. Polyacrylonitrile-based graphite felt composite material has good temperature resistance, corrosion resistance, large surface area and excellent electrical conductivity, and is often used as the electrode material of ICRFB, but its chemical activity is poor. In order to improve the activity of the graphite felt electrode, In3+ was used for modification in this paper, and the modified graphite felt was used as the electrode material for iron-chromium batteries. The structure and surface morphology of the modified graphite felt were analyzed by the specific surface area analyzer and scanning electron microscope; the electrochemical impedance spectroscopy and cyclic voltammetry experiments were carried out on the electrochemical workstation to study the electro catalytic activity of In3+ modified graphite felt and its performance in ICRFBS. The results show that the graphite felt electrode modified with a concentration of 0.2 M In3+ was activated at 400°C for 2 h, and its surface showed a lot of grooves, and the specific surface area reached 3.889 m2/g, while the specific surface area of the untreated graphite felt was only 0.995 m2/g significantly improved. Electrochemical tests show that the electrochemical properties of graphite felt electrodes are improved after In3+ modification. Therefore, the In3+ modified graphite felt electrode can improve the performance of ICRFB battery, and also make it possible to realize the engineering application of ICRFB battery.

2.
Comput Biol Med ; 146: 105565, 2022 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-35594683

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is a subtype of non-Hodgkin lymphoma (NHL) with the highest incidence, accounting for approximately one-third of NHL cases. Given the accumulated scientific publications related to the DLBCL domain, this study aimed to provide a comprehensive review of DLBCL studies from this millennium using the bibliometric method. With a strict retrieval strategy applied in the Web of Science database, a total of 10,869 publications from 2001 to 2020 were obtained and exported. The temporal and geographical distribution of these publications and the performance of contributing countries, institutions, journals, and authors corresponding to these documents were investigated, as well as an in-depth content analysis through keyword co-occurrence. With regard to the most productive countries, the United States ranks first with 2344 (21.6%) publications and shows the most frequent collaborations with other countries. By contrast, China has demonstrated remarkable performance in the growth rate of publications over the years, and it ranks first in the number of publications in the last five years. The University of Texas System is the institution with the highest number of published articles (4.99%). Leukemia Lymphoma is the journal with the highest number of publications in this field which contributed 588 articles. Solid and close collaborations between scholars are becoming more frequent over the four five-year periods. Overall, the highest cooperation frequency in the last two decades happens to Gascoyne RD at the British Columbia Cancer Agency and British Columbia Cancer Research Center in Canada. By comparing the article citation and keyword co-occurrence in each five-year period, as well as the changes in keyword clusters over two decades, we conclude that the stage, evaluation, prognosis, and treatment of DLBCL have always been the research hotspots in this field. Meanwhile, the evolution of keyword co-occurrence over the years demonstrates that new clusters appear. For instance, the effect of ferroptosis mechanism in DLBCL, immunotherapy for DLBCL, and PDL-1, PDL-2, and CAR-T therapy have drawn increasing attention from academia. Our research highlights the key characteristics of DLBCL research and provides comprehensive insights into the research status and evolutions in this field.

3.
Nat Commun ; 13(1): 2855, 2022 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-35606397

RESUMO

Muscarinic acetylcholine receptors (mAChRs) respond to the neurotransmitter acetylcholine and play important roles in human nervous system. Muscarinic receptor 4 (M4R) is a promising drug target for treating neurological and mental disorders, such as Alzheimer's disease and schizophrenia. However, the lack of understanding on M4R's activation by subtype selective agonists hinders its therapeutic applications. Here, we report the structural characterization of M4R selective allosteric agonist, compound-110, as well as agonist iperoxo and positive allosteric modulator LY2119620. Our cryo-electron microscopy structures of compound-110, iperoxo or iperoxo-LY2119620 bound M4R-Gi complex reveal their different interaction modes and activation mechanisms of M4R, and the M4R-ip-LY-Gi structure validates the cooperativity between iperoxo and LY2119620 on M4R. Through the comparative structural and pharmacological analysis, compound-110 mostly occupies the allosteric binding pocket with vertical binding pose. Such a binding and activation mode facilitates its allostersic selectivity and agonist profile. In addition, in our schizophrenia-mimic mouse model study, compound-110 shows antipsychotic activity with low extrapyramidal side effects. Thus, this study provides structural insights to develop next-generation antipsychotic drugs selectively targeting on mAChRs subtypes.

4.
J Nurs Res ; 2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35608396

RESUMO

BACKGROUND: Differences in short-term cognitive function between mechanically ventilated patients treated with multicomponent interventions and those receiving routine nursing care have not been established because of the lack of follow-up in previous studies. PURPOSE: This study was designed to evaluate the effects of the pain, agitation, and delirium (PAD) care bundle on delirium occurrence and clinical outcomes, specifically in terms of short-term cognitive function, in mechanically ventilated patients. METHODS: Data on 243 patients with mechanical ventilation were analyzed from January 2017 to February 2019. The eligible patients were divided randomly into two groups. The control group (n = 120) received usual care, whereas the intervention group (n = 123) received the PAD bundle, including pain monitoring and management, light sedation and daily awakening, early mobility, sleep promotion, and delirium monitoring. The incidence and duration of delirium, ventilator time, and intensive care unit (ICU) length of stay were compared between the two groups. Upon discharge from the ICU and at 3 and 6 months after discharge, cognitive function was assessed using the Montreal Cognitive Assessment scale and compared between the two groups. RESULTS: The incidence of delirium was reduced significantly in the intervention group, and significant decreases in the duration of delirium, ventilator time, and ICU length of stay were found. Cognitive impairment in the intervention group was significantly lower at the 3-month follow-up assessment. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The PAD bundle was shown to be associated with a lower incidence of delirium and improved clinical outcomes. Short-term cognitive impairment occurred in fewer patients who were managed with the PAD bundle after ICU discharge. Our findings indicate that the PAD bundle has the potential to improve clinical outcomes. The administrative staff of ICUs should use strategies, such as interdisciplinary teamwork, to facilitate the buy-in and implementation of interventions.

5.
J Clin Lab Anal ; : e24479, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35527696

RESUMO

BACKGROUND: SARS-CoV-2 has spread worldwide causing more than 400 million people with virus infections since early 2020. Currently, the existing vaccines targeting the spike glycoprotein (S protein) of SARS-CoV-2 are facing great challenge from the infection of SARS-CoV-2 virus and its multiple S protein variants. Thus, we need to develop a new generation of vaccines to prevent infection of the SARS-CoV-2 variants. Compared with the S protein, the nucleocapsid protein (N protein) of SARS-CoV-2 is more conservative and less mutations, which also plays a vital role in viral infection. Therefore, the N protein may have the great potential for developing new vaccines. METHODS: The N protein of SARS-CoV-2 was recombinantly expressed and purified in Escherichia coli. Western Blot and ELISA assays were used to demonstrate the immunoreactivity of the recombinant N protein with the serum of 22 COVID-19 patients. We investigated further the response of the specific serum antibodies and cytokine production in BALB/c mice immunized with recombinant N protein by Western Blot and ELISA. RESULTS: The N protein had good immunoreactivity and the production of IgG antibody against N protein in COVID-19 patients was tightly correlated with disease severity. Furthermore, the N protein was used to immunize BALB/c mice to have elicited strong immune responses. Not only high levels of IgG antibody, but also cytokine-IFN-γ were produced in the N protein-immunized mice. Importantly, the N protein immunization induced a high level of IgM antibody produced in the mice. CONCLUSION: SARS-CoV-2 N protein shows a great big bundle of potentiality for developing a new generation of vaccines in fighting infection of SARS-CoV-2 and its variants.

6.
J Hazard Mater ; 436: 129049, 2022 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-35526344

RESUMO

Safe treatment of antibiotics requires efficient removal of both antibiotics and their degraded intermediates. In this study, we demonstrate that FeC2O4•2H2O enables the more sustainable conversion of H2O2 to •OH than commonly used FeSO4•7H2O, promoting the detoxification of a typical antibiotic sulfadimidine. It was found that the FeC2O4/H2O2 system could completely degrade 250 mg L-1 of sulfadimidine within 40 min at pH 3.0, along with decreasing the contents of chemical oxygen demand and total organic carbon by 295.0 and 33.5 mg L-1, respectively, more efficient than those in a classical Fenton system (FeSO4/H2O2). Analysis of sulfadimidine degraded intermediates and toxicity evaluation suggested that the FeC2O4/H2O2 treatment could more effectively decrease the overall toxicity of the sulfadimidine solution than the FeSO4/H2O2 counterpart. The sustainability of FeC2O4•2H2O in H2O2 conversion to •OH was attributed to its controlled release of Fe2+ into the solution to prevent the quenching of •OH by excessive Fe2+, as well as the simultaneous release of C2O42- to complex with Fe2+ and Fe3+, which could inhibit iron sludge formation and accelerate Fe3+/Fe2+ redox cycle. This study provides a promising Fenton system for the safe treatment of antibiotics and sheds light on the potential of FeC2O4•2H2O in environmental remediation.

7.
Oncol Rep ; 47(5)2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35362540

RESUMO

Glioma is the most common primary intracranial malignancy in the central nervous system. At present, the most important treatment option is surgical resection of the tumor combined with radiotherapy and chemotherapy. The principle of operation is to remove the tumor to the maximal extent on the basis of preserving brain function. However, prominent invasive and infiltrative proliferation of glioma tumor cells into the surrounding normal tissues frequently reduces the efficacy of treatment. This in turn worsens the prognosis, because the tumor cannot be completely removed, which can readily relapse. Chemotherapeutic agents when applied individually have demonstrated limited efficacy for the treatment of glioma. However, multiple different chemotherapeutic agents can be used in combination with other treatment modalities to improve the efficacy while circumventing systemic toxicity and drug resistance. Therefore, it is pivotal to unravel the inhibitory mechanism mediated by the different chemotherapeutic drugs on glioma cells in preclinical studies. The aim of the present review is to provide a summary for understanding the effects of different chemotherapeutic drugs in glioma, in addition to providing a reference for the preclinical research into novel chemotherapeutic agents for future clinical application.


Assuntos
Antineoplásicos , Neoplasias Encefálicas , Glioma , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/patologia , Glioma/patologia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico
8.
Viruses ; 14(4)2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35458455

RESUMO

The H9N2 subtype avian influenza viruses (AIVs) have been circulating in China for more than 20 years, attracting more and more attention due to the potential threat of them. At present, vaccination is a common prevention and control strategy in poultry farms, but as virus antigenicity evolves, the immune protection efficiency of vaccines has constantly been challenged. In this study, we downloaded the hemagglutinin (HA) protein sequences of the H9N2 subtype AIVs from 1994 to 2019 in China-with a total of 5138 sequences. The above sequences were analyzed in terms of time and space, and it was found that h9.4.2.5 was the most popular in various regions of China. Furthermore, the prevalence of H9N2 subtype AIVs in China around 2006 was different. The domestic epidemic branch was relatively diversified from 1994 to 2006. After 2006, the epidemic branch each year was h9.4.2.5. We compared the sequences around 2006 as a whole and screened out 15 different amino acid positions. Based on the HA protein of A/chicken/Guangxi/55/2005 (GX55), the abovementioned amino acid mutations were completed. According to the 12-plasmid reverse genetic system, the rescue of the mutant virus was completed using A/PuertoRico/8/1934 (H1N1) (PR8) as the backbone. The cross hemagglutination inhibition test showed that these mutant sites could transform the parental strain from the old to the new antigenic region. Animal experiments indicated that the mutant virus provided significant protection against the virus from the new antigenic region. This study revealed the antigenic evolution of H9N2 subtype AIVs in China. At the same time, it provided an experimental basis for the development of new vaccines.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H9N2 , Influenza Aviária , Aminoácidos/genética , Animais , Galinhas , China/epidemiologia , Evolução Molecular , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Hemaglutininas/genética , Vírus da Influenza A Subtipo H9N2/genética , Filogenia
9.
Emerg Microbes Infect ; 11(1): 1371-1389, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35476817

RESUMO

Currently, SARS-CoV-2, especially the Omicron strain, is ravaging the world and even co-infecting human beings with IAV, which is a serious threat to human public health. As of yet, no specific antiviral drug has been discovered for SARS-CoV-2. This requires deeper understandings of the molecular mechanisms of SARS-CoV-2-host interaction, to explore antiviral drug targets and provide theoretical basis for developing anti-SARS-CoV-2 drugs. This article discussed IAV, which has been comprehensively studied and is expected to provide the most important reference value for the SARS-CoV-2 study apart from members of the Coronaviridae family. We wish to establish a theoretical system for the studies on virus-host interaction. Previous studies have shown that host PRRs recognize RNAs of IAV or SARS-CoV-2 and then activate innate immune signaling pathways to induce the expression of host restriction factors, such as ISGs, to ultimately inhibit viral replication. Meanwhile, viruses have also evolved various regulatory mechanisms to antagonize host innate immunity at transcriptional, translational, post-translational modification, and epigenetic levels. Besides, viruses can hijack supportive host factors for their replication. Notably, the race between host antiviral innate immunity and viral antagonism of host innate immunity forms virus-host interaction networks. Additionally, the viral replication cycle is co-regulated by proteins, ncRNAs, sugars, lipids, hormones, and inorganic salts. Given this, we updated the mappings of antiviral drug targets based on virus-host interaction networks and proposed an innovative idea that virus-host interaction networks as new antiviral drug targets for IAV and SARS-CoV-2 from the perspectives of viral immunology and systems biology.

10.
Nat Commun ; 13(1): 2183, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35449135

RESUMO

Glass-to-glass transitions are useful for us to understand the glass nature, but it remains difficult to tune the metallic glass into significantly different glass states. Here, we have demonstrated that the high-entropy can enhance the degree of disorder in an equiatomic high-entropy metallic glass NbNiZrTiCo and elevate it to a high-energy glass state. An unusual glass-to-glass phase transition is discovered during heating with an enormous heat release even larger than that of the following crystallization at higher temperatures. Dramatic atomic rearrangement with a short- and medium-range ordering is revealed by in-situ synchrotron X-ray diffraction analyses. This glass-to-glass transition leads to a significant improvement in the modulus, hardness, and thermal stability, all of which could promote their applications. Based on the proposed high-entropy effect, two high-entropy metallic glasses are developed and they show similar glass-to-glass transitions. These findings uncover a high-entropy effect in metallic glasses and create a pathway for tuning the glass states and properties.

11.
Nano Lett ; 22(8): 3298-3306, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35385667

RESUMO

Aqueous Zn batteries are emerging as promising energy storage devices. However, severe dendrite growth and side reactions of Zn anodes restrict their further development. Herein, we develop a nucleophilic interfacial layer (NIL) on Zn to achieve a highly stable Zn anode for rechargeable Zn batteries. The NIL in a composition of zinc acetate acetamide is homogeneous, compact, and Zn2+-conductive, rendering dendrite-free Zn deposition, which is observed by in situ optical microscopy. Benefiting from the advantages of NIL, the Zn||Zn symmetric cells show a low overpotential of 0.12 V at a high current density of 40 mA/cm2, enhanced Coulombic efficiency up to 99.9%, and extended lifespan over 2600 cycles. The Zn||Ti asymmetric cells exhibit a high areal capacity of 5 mAh/cm2. Moreover, the NIL functionalized Zn anode enables stable cycling of both anode-free Zn||Cl2 cells and zinc-ion capacitors, providing opportunities for the development of high-performance energy storage devices.


Assuntos
Fontes de Energia Elétrica , Zinco , Eletrodos , Microscopia
12.
ACS Appl Mater Interfaces ; 14(14): 16846-16855, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35363489

RESUMO

The superior optical and electronic characteristics of quasi-two-dimensional ß-Ga2O3 make it suitable for solar-blind (200-280 nm) photodetectors (PDs). The metal-semiconductor-metal (MSM) PDs commonly suffer from low photoresponsivity, slow response speed, and a narrow detection wavelength range despite their simple fabrication process. Herein, we report a high-performance MSM PD by integrating exfoliated ß-Ga2O3 flakes with zero-dimensional graphene quantum dots (GQDs), which exhibits the advantages of enhancing the photoresponsivity, shortening the photoresponse time, and stimulating a broad range of photon detection. The hybrid GQDs/ß-Ga2O3 heterostructure PD is sensitive to deep-ultraviolet (DUV) light (250 nm) with an ultrahigh responsivity (R of ∼2.4 × 105 A/W), a large detectivity (D* of ∼4.3 × 1013 Jones), an excellent external quantum efficiency (EQE of ∼1.2 × 108%), and a fast photoresponse (150 ms), which is superior to the bare ß-Ga2O3 PD. These improvements result from effective charge transfer due to the introduction of GQDs, which enhance the light absorption and the generation of electron-hole pairs. In addition, the hybrid GQDs/ß-Ga2O3 PD also exhibits better photoelectric performance than the bare ß-Ga2O3 PD at a 1000 nm wavelength. As a conclusion, the hybrid GQDs/ß-Ga2O3 DUV photodetector shows potential applications in commercial optoelectronic products and provides an alternative solution for the design and preparation of high-performance photodetectors.

13.
Molecules ; 27(7)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35408750

RESUMO

Evaluation of the hydrophobic/hydrophilic interaction individually between the sorbent and target compounds in sample pretreatment is a big challenge. Herein, a smart titanium substrate with switchable surface wettability was fabricated and selected as the sorbent for the solution. The titanium wires and meshes were fabricated by simple hydrothermal etching and chemical modification so as to construct the superhydrophilic and superhydrophobic surfaces. The micro/nano hierarchical structures of the formed TiO2 nanoparticles in situ on the surface of Ti substrates exhibited the switchable surface wettability. After UV irradiation for about 15.5 h, the superhydrophobic substrates became superhydrophilic. The morphologies and element composition of the wires were observed by SEM, EDS, and XRD, and their surface wettabilities were measured using the Ti mesh by contact angle goniometer. The pristine hydrophilic wire, the resulting superhydrophilic wire, superhydrophobic wire, and the UV-irradiated superhydrophilic wire were filled into a stainless tube as the sorbent instead of the sample loop of a six-port valve for on-line in-tube solid-phase microextraction. When employed in conjunction with HPLC, four kinds of wires were comparatively applied to extract six estrogens in water samples. The optimal conditions for the preconcentration and separation of target compounds were obtained with a sample volume of 60 mL, an injection rate of 2 mL/min, a desorption time of 2 min, and a mobile phase of acetonile/water (47/53, v/v). The results showed that both the superhydrophilic wire and UV-irradiated wire had the highest extraction efficiency for the polar compounds of estrogens with the enrichment factors in the range of 20-177, while the superhydrophobic wire exhibited the highest extraction efficiency for the non-polar compounds of five polycyclic aromatic hydrocarbons (PAHs). They demonstrated that extraction efficiency was mainly dependent on the surface wettability of the sorbent and the polarity of the target compounds, which was in accordance with the molecular theory of like dissolves like.


Assuntos
Microextração em Fase Sólida , Titânio , Estrogênios , Interações Hidrofóbicas e Hidrofílicas , Microextração em Fase Sólida/métodos , Titânio/química , Água/química
14.
Opt Express ; 30(7): 10428-10442, 2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35473010

RESUMO

An all-photonic approach of microwave waveforms generation and transformation is proposed and experimentally demonstrated. From the perspective of envelope function operation in time domain, an initial triangular waveform is transformed into square waveform and sawtooth (or reversed-sawtooth) waveform via two types of differentiators, respectively. In addition, by using a SOA as a multiplier, both bright and dark parabolic pulses are achieved, which are further transformed into sawtooth (or reversed-sawtooth) waveform by taking the first derivative operation. The feasibility of the system is verified by theoretical analysis and simulation. In experiment, all of the expected results are successfully demonstrated and agree with the theoretical analysis well. This scheme provides a novel access to implement all-optical microwave waveforms generation, transformation, signal processing and computing.

15.
Front Endocrinol (Lausanne) ; 13: 832665, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370987

RESUMO

Objective: The purpose of this study was to clarify the influence of the vanishing twin (VT) on the perinatal outcomes in the surviving singleton and further identify the susceptible window. Study design: Retrospective cohort study. Methods: A total of 636 survivors of a vanished co-twin and 11,148 singleton controls were enrolled. The exposed group was further divided into early VT (EVT, VT ≤13 weeks, N = 593) and late VT subgroups (LVT, VT >13 weeks, N = 43) according to the gestational age of the twin vanishing. All participants were conceived through in vitro fertilization (IVF). Perinatal outcomes including gestational age, birthweight, and the incidence of preterm birth (PTB), low birthweight (LBW), small for gestational age (SGA), neonatal intensive care unit (NICU) admission, umbilical cord abnormality, jaundice of the newborn, and oligohydramnios were compared among the groups. Results: In our birth cohort, about 5.4% of all singleton deliveries originated from vanishing twin pregnancies. Compared with the singletons, both early and late VT pregnancy had a significantly lower birth weight (3337.57±532.24 g and 2916.05±526.07 g vs. 3446.15±526.07 g; p < 0.001 and p < 0.001), more frequent neonatal jaundice (47.0% and 60.5% vs. 40.6%; p = 0.002 and p = 0.008), and decreased incidence of umbilical cord abnormality (15.5% and 7.0% vs. 19.9%; p = 0.009 and p = 0.034). Newborns in the early VT group were more likely to manifest as SGA (5.4% vs. 3.6%, p = 0.002) and suffered oligohydramnios (5.4% vs. 3.4%; p = 0.008) than the primary singletons. In addition, the gestational age of late VT survivors was shorter than that of the controls (37.25 ± 3.25 vs. 39.04 ± 1.63, p = 0.001) and had a significantly higher risk of PTB (30.2% vs. 6.6%; p < 0.001) and NICU admission (27.9% vs. 9.4%, p < 0.001). All differences except for SGA maintain significance after adjusting for maternal age, BMI, and parity. Conclusions: Singletons with a vanished co-twin had worse perinatal outcomes compared with the original singletons, with LVT burden even much on the survival one. Therefore, close monitoring during the perinatal period was suggested in this type of neonates. Moreover, elective single embryo transfer should also be fully considered which could tackle the problem at its root.


Assuntos
Aborto Espontâneo , Nascimento Prematuro , Aborto Espontâneo/epidemiologia , Feminino , Fertilização In Vitro , Humanos , Recém-Nascido , Gravidez , Resultado da Gravidez/epidemiologia , Nascimento Prematuro/epidemiologia , Estudos Retrospectivos
16.
J Biochem Mol Toxicol ; : e23056, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35384129

RESUMO

Cadmium (Cd) is an environmental pollutant and pregnant women are especially susceptible to the effects of exposure to Cd. Our previous study found Cd can be accumulated in the placenta and causes fetal growth restriction (FGR) through damage the placental glucocorticoid barrier. Selenium (Se), as an essential micronutrient, can allivate Cd-induced toxicity. In this study, we aim to explore the protective mechanism of Se against Cd-induced the placental glucocorticoid barrier damage and FGR. Pregnant Sprague Dawley (SD) rats were exposed to CdCl2 (1 mg/kg/day) and Na2 SeO3 (0.1-0.2-0.3 mg/kg/day) by gavage from gestational day (GD) 0 to GD 19. The results showed that reduced fetal weight, increased corticosterone concentrations in the maternal and fetal serum, and impaired placental labyrinth layer blood vessel development, appeared in pregnant rats after Cd exposure and improved after treated with Se. In cell experiments, we confirmed that Se reduces Cd-induced apoptosis. Moreover, Se can abolish Cd-induced 11ß-HSD2 and specificity protein 1 (Sp1) decreasing in vivo and vitro. In human JEG-3 cells, the knockdown of Sp1 expression by small interfering RNA can suppressed the protective effect of Se on Cd-induced 11ß-HSD2 decreasing. In general, our results demonstrated that Se is resistant to Cd-induced FGR through upregulating the placenta barrier via activation of the transcription factor Sp1.

17.
EBioMedicine ; 78: 103969, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35349825

RESUMO

BACKGROUND: Some circulating proteins are linked to central adiposity. Gremlin 2 (GREM2) functions as a secreted factor involved in osteogenesis and adipogenesis. Here, we investigated the association of blood GREM2 levels and central adiposity, and the biological roles of GREM2 in the browning program of visceral preadipocytes. METHODS: Three independent cohorts were applied to detect circulating GREM2 levels. Recombinant Grem2 protein, Grem2 overexpression and knockout mouse models, and preadipocyte-specific Bmpr2 knockout mice were used to assess the roles of Grem2 in the browning program. FINDINGS: We detected the presence of GREM2 protein in human serum using an ELISA approach. We revealed elevated GREM2 levels in severely obese subjects and validated this finding in a large-scale community population involving 10,327 subjects. Notably, serum GREM2 was positively associated with visceral fat volume, as quantified by 3D reconstruction methods. In mice, Grem2 was highly expressed in visceral fat and liver tissues, while surgical removal of visceral fat lowered circulating Grem2 levels. Visceral fat secreted more Grem2 in obese mice. Grem2-overexpressed mice exhibited a reduced browning ability of visceral fat, whereas Grem2 ablation enhanced the browning capacity and reduced visceral fat content. Mechanistically, Grem2 attenuated the browning program of visceral preadipocytes partially by antagonizing BMP4/7-SMAD1/5/8 signaling pathway. Further, genetic deletion of Bmpr2 in Pdgfrα+ preadipocytes abolished the antagonistic effect of Grem2. INTERPRETATION: These findings indicate that GREM2 might function as a circulating protein factor associated with human visceral adiposity, and Grem2 inhibits the browning capacity of visceral preadipocytes partially by BMP4/7-BMPR2 signaling pathway. FUNDING: The complete list of funders can be found in the Acknowledgement section.


Assuntos
Citocinas , Obesidade Abdominal , Adipogenia/genética , Tecido Adiposo Marrom , Animais , Citocinas/genética , Humanos , Gordura Intra-Abdominal/metabolismo , Camundongos , Camundongos Obesos , Obesidade Abdominal/genética
18.
J Med Chem ; 65(7): 5334-5354, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35319895

RESUMO

Small-molecule irreversible tyrosine kinase inhibitors as high potent agents have led to improvements in disease-free and overall survival in patients with HER2-amplified cancer. The approved irreversible HER2 inhibitors, neratinib and pyrotinib, both lack HER2 selectivity, leading to off-target adverse events in patients. The development of HER2 mutation during treatment also hampers the progress of the treatment. We used a molecular hybridization strategy for structural optimizations, in conjunction with in vitro and in vivo drug-like property screening, to obtain a clinical candidate SPH5030. Overall, SPH5030 showed excellent activities against four frequent kinds of HER2 mutants and high relative HER2 selectivity compared with neratinib and pyrotinib, good pharmacokinetic characteristics with desirable bioavailabilities, and significant in vivo antitumor efficacy in xenograft mouse models, especially in a HER2 mutation A775_G776insYVMA xenograft mouse model with its potency much higher than those of neratinib and pyrotinib.


Assuntos
Neoplasias da Mama , Receptor ErbB-2 , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Feminino , Humanos , Camundongos , Inibidores de Proteínas Quinases/efeitos adversos
19.
Adv Mater ; : e2105590, 2022 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-35238092

RESUMO

Manipulation of the propagation and energy-transport characteristics of subwavelength infrared (IR) light fields is critical for the application of nanophotonic devices in photocatalysis, biosensing, and thermal management. In this context, metamaterials are useful composite materials, although traditional metal-based structures are constrained by their weak mid-IR response, while their associated capabilities for optical propagation and focusing are limited by the size of attainable artificial optical structures and the poor performance of the available active means of control. Herein, a tunable planar focusing device operating in the mid-IR region is reported by exploiting highly oriented in-plane hyperbolic phonon polaritons in α-MoO3 . Specifically, an unprecedented change of effective focal length of polariton waves from 0.7 to 7.4 µm is demonstrated by the following three different means of control: the dimension of the device, the employed light frequency, and engineering of phonon-plasmon hybridization. The high confinement characteristics of phonon polaritons in α-MoO3 permit the focal length and focal spot size to be reduced to 1/15 and 1/33 of the incident wavelength, respectively. In particular, the anisotropic phonon polaritons supported in α-MoO3 are combined with tunable surface-plasmon polaritons in graphene to realize in situ and dynamical control of the focusing performance, thus paving the way for phonon-polariton-based planar nanophotonic applications.

20.
Analyst ; 147(8): 1534-1539, 2022 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-35311862

RESUMO

Single base mutations are closely related to cancer diagnosis and treatment. The fluorescent probe method is one of the important methods to detect single-base mutations. We constructed a universal probe detection system based on endonuclease IV and the DNA strand displacement reaction. The system uses two toehold strand displacement reactions to relay the mutation information to the universal strand. There is no need to design the probe one-by-one for each mutation point during multi-site detection. It has the advantages of simple operation, rapid detection, and low cost. We used this method to detect common clinical mutation sites (PTEN R130Q/EGFR L858R/PTEN rs1473918395), and the detection limit can reach 0.1%-1%. The detection system can provide a new rapid and economical method for clinical single-base mutation detection, and has broad application prospects in diagnosis and prognostic evaluation.


Assuntos
Técnicas Biossensoriais , Mutação Puntual , Técnicas Biossensoriais/métodos , DNA/genética , Desoxirribonuclease IV (Fago T4-Induzido)/genética , Corantes Fluorescentes , Mutação
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