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1.
Nanomaterials (Basel) ; 11(3)2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33803677

RESUMO

Photothermal therapy (PTT) has received constant attention as an efficient cancer therapy method due to locally selective treatment, which is not affected by the tumor microenvironment. In this study, a novel 880 nm near-infrared (NIR) laser-triggered photothermal agent (PTA), 3TT-IC-4Cl, was used for PTT of a tumor in deep tissue. Folic acid (FA) conjugated amphiphilic block copolymer (folic acid-polyethylene glycol-poly (ß-benzyl-L-aspartate)10, FA-PEG-PBLA10) was employed to encapsulate 3TT-IC-4Cl by nano-precipitation to form stable nanoparticles (TNPs), and TNPs exhibit excellent photothermal stability and photothermal conversion efficiency. Furthermore, the in vitro results showed TNPs display excellent biocompatibility and significant phototoxicity. These results suggest that 880 nm triggered TNPs have great potential as effective PTAs for photothermal therapy of tumors in deep tissue.

2.
J Hazard Mater ; 416: 125795, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33836324

RESUMO

We reported the discovery and identification of emerging sulfur-containing polycyclic aromatic hydrocarbons, namely polycyclic aromatic sulfur heterocycles (PASHs), in PM2.5 collected from two typical regions of China, Taiyuan and Guangzhou. Until now, there is no research on contamination status, sources and potential health risks of this unexpected group of organic contaminants in PM2.5. High atmospheric concentrations (ngm-3) and significant time-dependent variations were determined in PM2.5 of Taiyuan from 2017 to 2018. Coal combustion/secondary formation and traffic emission/secondary formation were apportioned as possible pollution sources for the PM2.5-bound PASHs in Taiyuan and Guangzhou, respectively. Dithiothreitol and cell viability assays were applied for evaluations of PASH-induced reactive oxygen species (ROS) production and cell toxicity based on the determined real exposure levels for adults. The results illustrated that PASHs in PM2.5 possibly caused oxidative stress and inhibition of human bronchial epithelial cells in seriously polluted regions such as Taiyuan, suggesting that the pollutant-induced health concerns may need more investigations. This study provides new insights into PM2.5 pollution, and is beneficial for the development of effective contamination control strategies and reduction of risks on public health.

3.
Neural Regen Res ; 16(11): 2316-2323, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33818518

RESUMO

Although the transcriptional alterations inside the facial nucleus after facial nerve injury have been well studied, the gene expression changes in the facial nerve trunk after injury are still unknown. In this study, we established an adult rat model of facial nerve crush injury by compressing the right lateral extracranial nerve trunk. Transcriptome sequencing, differential gene expression analysis, and cluster analysis of the injured facial nerve trunk were performed, and 39 intersecting genes with significant variance in expression were identified. Gene Ontology annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the 39 intersecting genes revealed that these genes are mostly involved in leukocyte cell-cell adhesion and phagocytosis and have essential roles in regulating nerve repair. Quantitative real-time polymerase chain reaction assays were used to validate the expression of pivotal genes. Finally, nine pivotal genes that contribute to facial nerve recovery were identified, including Arhgap30, Akr1b8, C5ar1, Csf2ra, Dock2, Hcls1, Inpp5d, Sla, and Spi1. Primary Schwann cells were isolated from the sciatic nerve of neonatal rats. After knocking down Akr1b8 in Schwann cells with an Akr1b8-specific small interfering RNA plasmid, expression levels of monocyte chemoattractant protein-1 and interleukin-6 were decreased, while cell proliferation and migration were not obviously altered. These findings suggest that Akr1b8 likely regulates the interaction between Schwann cells and macrophages through regulation of cytokine expression to promote facial nerve regeneration. This study is the first to reveal a transcriptome change in the facial nerve trunk after facial nerve injury, thereby revealing the potential mechanism underlying repair of facial nerve injury. This study was approved by the Animal Ethics Committee of Nantong University, China in 2018 (approval No. S20180923-007).

4.
Nano Lett ; 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33645230

RESUMO

Generating and controlling spin current (SC) are of central interest in spin physics and applications. To date, the spin-orbit interaction (SOI) is an established pathway to generate SC through the spin-charge current conversion. We predict an efficient spin-light conversion via the Rashba and higher-order cubic Dresselhaus SOIs in ferroelectrics. Different from the known Edelstein effect, where SC is created by the nonequilibrium spin density, our predicted spin-polarized current is from direct interactions between light and unique spin textures generated by SOI in ferroelectrics. Using first-principles simulations, we demonstrate these concepts by calculating the DC spin photocurrent in a prototypical Rashba ferroelectric, α-GeTe. The photoinduced SC is about 2 orders of magnitude larger than the charge photocurrent. More importantly, we can conveniently switch the direction of SC by an applied electric field via inverting the spin textures. These predictions give hope to generating and controlling light-driven SC via a nonvolatile electric field.

5.
BMC Public Health ; 21(1): 517, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726720

RESUMO

BACKGROUND: The effect of high levels of physical activity and relationship between daily total physical activity and the risk of cardiovascular disease (CVD) among hypertensive people were not clear. This study aimed to explore the optimum level of physical activity for CVD prevention. METHODS: Data used in the present study was derived from the sub-study of China Kadoorie Biobank study (CKB) in Jiangsu province of China. The CKB was a prospective cohort study established during 2004-2008. At baseline, 53,259 participants aged 35-74 years were recruited for the CKB Jiangsu sub-study conducted in Wuzhong district of Suzhou City. Among those 53,259 participants, the 20,179 hypertensive individuals were our study population. The outcome events were cardiovascular diseases (CVDs), while the independent variable was total daily physical activity. The Cox proportional hazard models were introduced to investigate the association between total physical activity and CVDs, reporting as hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: During a 10.1-year follow-up, 2419 CVD cases were identified. After adjustment for potential confounding factors, compared with participants at the lowest level of daily total physical activity, the hazard ratios for CVDs were 0.87 (95%CI: 0.79-0.97), 0.73 (95%CI: 0.65-0.83) and 0.75 (95%CI: 0.65-0.85) for participants within 2, 3 and 4 quartiles of physical activity. Such a negative association between total physical activity and CVDs were also observed among participants by gender and age-group, but within patients with stage 1 hypertension only. Moreover, the association of physical activity with CVDs was U-shape and the lowest HR (0.63, 95%CI: 0.54-0.74) was observed at 35.4 MET-h/d of total physical activity. CONCLUSIONS: Total daily physical activity was negatively associated with CVDs among hypertensive adults in China, and this association was U-shape. It has some public health implications that community-based total physical activity intervention campaigns can be of help for CVDs prevention among hypertensive people in China.

6.
Trials ; 22(1): 218, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736696

RESUMO

BACKGROUND: Cytomegalovirus retinitis (CMVR) is an important opportunistic infection (OI) occurring mainly in patients with acquired immunodeficiency syndrome (AIDS) and has the potential to cause severe visual impairment and blindness among AIDS patients. Subsequent to the adoption and implementation of widespread antiretroviral therapy (ART), the prognosis of AIDS-associated CMVR has been substantially improved. Nevertheless, the equivocal clinical evidence as regards the optimal timing for ART initiation in patients with an established CMVR diagnosis is required. We therefore designed the present study in order to investigate the optimal timing for ART initiation in AIDS/CMVR patients. METHODS: This will be a prospective, randomized controlled trial to be performed at 17 hospitals in mainland China. A total of 300 participants with CMVR will be randomly assigned to an early ART initiation group (ART initiation within 2 weeks after anti-CMV therapy), or a deferred ART initiation group (initiation of ART more than 2 weeks after anti-CMV therapy) at a 1:1 ratio. All participants will receive 48 weeks of follow-up after anti-CMV therapy initiation. Our primary outcome will be the incidence of visual loss (to a visual acuity worse than 20/40 or 20/200) in the two groups during the 48-week follow-up period. Secondary outcomes will include changes in HIV virological suppression and serum CD4+ T-cell counts, the incidence of mortality, retinitis progression (movement of the peripheral border of a CMV lesion ≥ ½ disc diameter, or occurrence of a new CMV lesion), retinal detachment, immune recovery uveitis (IRU), and other OIs and adverse events between the two study groups during the 48 weeks of follow-up. DISCUSSION: The study aims to investigate the optimal timing for ART initiation in AIDS/CMVR patients. We hope to be able to extract robust clinical evidence for use in optimal AIDS/CMVR management should our trial be successful. TRIAL REGISTRATION: This research was registered as one of the twelve clinical trials under the name of a general project "A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections", ChiCTR1900021195. Registered on 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362 .

7.
Iran J Kidney Dis ; 1(2): 109-115, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33764321

RESUMO

INTRODUCTION: Steroid-dependent (SD)/frequently relapsing (FR) nephrotic syndrome (NS) follows a relapsing and remitting course. It is also characterized by proteinuria and edema, which can significantly affect health-related quality of life (HRQOL) in children. This study evaluated the effectiveness and safety of a single dose of rituximab (RTX) as well as the impact of RTX on HRQOL in children with SDFRNS. METHODS: Sixteen children with SDFRNS were enrolled in the study. Each patient was administered a single intravenous dose of RTX (375 mg/m2). Effectiveness was defined as remission of proteinuria. The side effects of RTX were monitored. HRQOL was assessed using PedsQL™ 4.0 Generic Core Scales. RESULTS: All the patients completed the study. Three SDNS patients and three FRNS patients discontinued treatment over 1 to 3.25 years of follow-up. Additionally, three SDNS patients and three FRNS patients experienced 1 to 2 relapses. The mean relapse-free period was 79.0 ± 77.6 days. The mean dosages of prednisolone and other immunosuppressants required were significantly lower (P < .05, < .001) six months after treatment with RTX compared with six months before treatment. Relapse rate was significantly reduced (P < .001) after treatment with RTX. Skin rash, hypotension, and fever were observed in one child. Total health score and physical, emotional, and school functioning were significantly higher six months after treatment with RTX (P < .001). CONCLUSION: A single dose of RTX is effective and safe for children with SDFRNS and can improve HRQOL, especially physical, emotional, and school functioning.

8.
Front Immunol ; 12: 616343, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717108

RESUMO

Babesia microti is a protozoan that infects red blood cells. Babesiosis is becoming a new global threat impacting human health. Rhoptry neck proteins (RONs) are proteins located at the neck of the rhoptry and studies indicate that these proteins play an important role in the process of red blood cell invasion. In the present study, we report on the bioinformatic analysis, cloning, and recombinant gene expression of two truncated rhoptry neck proteins 2 (BmRON2), as well as their potential for incorporation in a candidate vaccine for babesiosis. Western blot and immunofluorescence antibody (IFA) assays were performed to detect the presence of specific antibodies against BmRON2 in infected mice and the localization of N-BmRON2 in B. microti parasites. In vitro experiments were carried out to investigate the role of BmRON2 proteins during the B. microti invasion process and in vivo experiments to investigate immunoprotection. Homologous sequence alignment and molecular phylogenetic analysis indicated that BmRON2 showed similarities with RON2 proteins of other Babesia species. We expressed the truncated N-terminal (33-336 aa, designated rN-BmRON2) and C-terminal (915-1171 aa, designated rC-BmRON2) fragments of the BmRON2 protein, with molecular weights of 70 and 29 kDa, respectively. Western blot assays showed that the native BmRON2 protein is approximately 170 kDa, and that rN-BmRON2 was recognized by serum of mice experimentally infected with B. microti. Immunofluorescence analysis indicated that the BmRON2 protein was located at the apical end of merozoites, at the opposite end of the nucleus. In vitro red blood cell invasion inhibition studies with B. microti rBmRON2 proteins showed that relative invasion rate of rN-BmRON2 and rC-BmRON2 group is 45 and 56%, respectively. Analysis of the host immune response after immunization and B. microti infection showed that both rN-BmRON2 and rC-BmRON2 enhanced the immune response, but that rN-BmRON2 conferred better protection than rC-BmRON2. In conclusion, our results indicate that truncated rhoptry neck protein 2, especially its N-terminal fragment (rN-BmRON2), plays an important role in the invasion of host red blood cells, confers immune protection, and shows good potential as a candidate vaccine against babesiosis.

9.
J Ultrasound Med ; 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33724514

RESUMO

PURPOSE: To investigate whether phase-shift perfluoropetane (PFP) nanoemulsions can enhance pulsed high-intensity focused ultrasound (HIFU) ablation. METHODS: PFP was encapsulated by poly(lactic-co-glycolic acid) (PLGA) to form a nanometer-sized droplet (PLGA-PFP), which was added to an isolated perfused liver system. Meanwhile, phosphate-buffered saline (PBS) was used as a control. The perfused liver was exposed to HIFU (150 W, t = 3/5/10 s) at various duty cycles (DCs). The ultrasound images, cavitation emissions, and temperature were recorded. Rabbits with subcutaneous VX2 tumors were exposed to HIFU (150 W) at various DCs with or without PLGA-PFP. After ablation, necrosis volume and energy efficiency factor were calculated. Pathologic characteristics were observed. RESULTS: Compared to the PBS control, PLGA-PFP nanoemulsions markedly enhanced HIFU-induced necrosis volume in both perfused livers and subcutaneous VX2 tumor-bearing rabbits (P <.05). Inertial cavitation was much stronger in the pulsed-HIFU exposure at 10% than that in the continuous-wave HIFU exposure (P <.01). Peak temperature at 100% DC was significantly higher than that at 10% (P <.05). Compared to 100% DC HIFU exposure, the mean necrosis volume induced by 10 s exposure at 50% DC was significantly larger (P <.005) but lower at 10% DC in the isolated perfused livers (P <.05). In addition, the mean necrosis volume in subcutaneous VX2 tumor-bearing rabbits was significantly increased after HIFU exposure at 10% DC when compared to those at 100% DC (P <.05). Histopathologic analysis showed liquefaction necrosis in pulsed HIFU. CONCLUSION: PLGA-PFP nanoemulsions can enhance HIFU ablation in the isolated perfused livers and promote tumor ablation in the subcutaneous xenograft rabbit model. Appropriate pulsed HIFU exposure may increase the necrosis volume and reduce total ultrasound energy required for HIFU ablation.

10.
J Exp Med ; 218(5)2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33688917

RESUMO

Although widely used for their potent anti-inflammatory and immunosuppressive properties, the prescription of glucocorticoid analogues (e.g., dexamethasone) has been associated with deleterious glucose metabolism, compromising their long-term therapeutic use. However, the molecular mechanism remains poorly understood. In the present study, through transcriptomic and epigenomic analysis of two mouse models, we identified a growth arrest and DNA damage-inducible ß (Gadd45ß)-dependent pathway that stimulates hepatic glucose production (HGP). Functional studies showed that overexpression of Gadd45ß in vivo or in cultured hepatocytes activates gluconeogenesis and increases HGP. In contrast, liver-specific Gadd45ß-knockout mice were resistant to high-fat diet- or steroid-induced hyperglycemia. Of pathophysiological significance, hepatic Gadd45ß expression is up-regulated in several mouse models of obesity and diabetic patients. Mechanistically, Gadd45ß promotes DNA demethylation of PGC-1α promoter in conjunction with TET1, thereby stimulating PGC-1α expression to promote gluconeogenesis and hyperglycemia. Collectively, these findings unveil an epigenomic signature involving Gadd45ß/TET1/DNA demethylation in hepatic glucose metabolism, enabling the identification of pathogenic factors in diabetes.

11.
J Comp Neurol ; 2021 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-33719053

RESUMO

In mammalian cochlea, sound-induced vibration is amplified by a three-row lattice of Y-shaped microstructures consisting of electromotile outer hair cell and supporting Deiters cell. This highly organized structure is thought to be essential for hearing of low-level sounds. Prior studies reported differences in geometry and synaptic innervation of the outer hair cells between rows, but how these fine features are achieved at subcellular level still remains unclear. Using serial block-face electron microscopy, we acquired few-hundred-micron-sized cytoarchitecture of mouse organ of Corti at nanometer resolution. Structural quantifications were performed on the Y-shapes as well as afferent and efferent projections to outer hair cells (OHCs). Several new features, which support the previously observed inter-row heterogeneity, are described. Our result provides structural bases for the gradient of mechanical properties and diverse centrifugal regulation of OHC rows.

13.
ACS Chem Neurosci ; 12(6): 1018-1030, 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33650843

RESUMO

κ opioid receptor (κOR) is a subtype of opioid receptors, and there are two major κOR agonists currently available, morphinans and arylacetamides, which are structurally distinct from each other. Numerous efforts had been made to correlate these series of compounds in order to establish a consensus binding pattern for κOR agonists. Unfortunately, no morphinan-based agent with an arylacetamidyl substituent has been identified as a κOR agonist with a pharmacological profile similar to arylacetamides. Since the recently described morphinan-based compound SLL-039 was identified as a selective and potent κOR agonist that contains a unique benzamidyl substituent in structure similar to arylacetamides, numerous arylacetamidyl substituents were introduced to this scaffold to examine whether the structure-activity relationships (SARs) of arylacetamides in conferring κOR agonistic activities could be reproduced by these analogues. Thus, a series of N-cyclopropylmethyl-7α-arylacetamidylphenyl-6,14-endoethanotetrahydronorthebaine analogues were designed, synthesized, and assayed for biological activities. Among these compounds, compound 4j with a 3',4'-dimethylphenylacetamidyl substituent showed a single digit low nanomolar affinity to the κOR and relatively high subtype selectivity in binding assays, but this profile was not reproduced in functional assays. In contrast, compound 4i displayed moderately selective κOR agonistic activities in functional assays, which was inconsistent with its nonselective nature in binding assays. Overall, introduction of an arylacetamidyl substituent to the morphinan-based scaffold was associated with pharmacological diversity in both binding and functional activities on opioid receptors in vitro. The resultant SARs were inconsistent with that of classical arylacetamides as κOR agonists, despite bearing a similar arylacetamidyl substituent in the structure. Therefore, the arylacetamidyl substituent of the morphinan-based scaffold was found to be disconnected from that of arylacetamides in conferring κOR activities.

14.
J Biol Chem ; : 100512, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33676893

RESUMO

Smad2 and Smad3 (Smad2/3) are structurally similar proteins that primarily mediate the transforming growth factor-ß (TGF-ß) signaling responsible for driving cell proliferation, differentiation and migration. The dynamics of the Smad2/3 phosphorylation provides the key mechanism for regulating the TGF-ß signaling pathway, but the details surrounding this phosphorylation remain unclear. Here, using in vitro kinase assay coupled with mass spectrometry we identified for the first time that nemo-like kinase (NLK) regulates TGF-ß signaling via modulation of Smad2/3 phosphorylation in the linker region. TGF-ß-mediated transcriptional and cellular responses are suppressed by NLK overexpression, whereas NLK depletion exerts opposite effects. Specifically, we discovered that NLK associates with Smad3 and phosphorylates the designated serine residues located in the linker region of Smad2 and Smad3, which inhibits phosphorylation at the C-terminus, thereby decreasing the duration of TGF-ß signaling. Overall, this work demonstrates that phosphorylation on the linker region of Smad2/3 by NLK counteracts the canonical phosphorylation in response to TGF-ß signals, thus providing new insight into the mechanisms governing TGF-ß signaling transduction.

15.
Cardiovasc Res ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33757126

RESUMO

AIMS: Aortic valve calcification is more prevalent in chronic kidney disease accompanied by hypercalcemia. SPARC (Secreted Protein Acidic and Rich in Cysteine)-related modular calcium binding 1 (SMOC1) is a regulator of BMP2 signalling, but the role of SMOC1 in aortic valve calcification under different conditions has not been studied. This study aimed to investigate the roles of SMOC1 in aortic valve calcification under normal and high calcium conditions, focusing on the effects on aortic valve interstitial cells (AVICs). METHODS AND RESULTS: SMOC1 was expressed by aortic valve endothelial cells and secreted into the extracellular matrix in non-calcific valves and downregulated in calcific aortic valves. In vitro studies demonstrated that HUVEC secreted SMOC1 could enter the cytoplasm of AVICs. Overexpression of SMOC1 attenuated warfarin-induced AVIC calcification but promoted high calcium/phosphate or vitamin D-induced AVIC and aortic valve calcification by regulating BMP2 signalling both in vitro and in vivo. Co-immunoprecipitation revealed that SMOC1 binds to BMP receptor II (BMPR-II) and inhibits BMP2-induced phosphorylation of p38 (p-p38) via amino acids 372-383 of its EF-hand calcium-binding domain. Inhibition of p-p38 by the p38 inhibitor SB203580 blocked the effects of SMOC1 on BMP2 signalling and AVIC calcification induced by high calcium/phosphate medium. In high-calcium-treated AVICs, SMOC1 lost its ability to bind to BMPR-II, but not to caveolin-1, promoting p-p38 and cell apoptosis due to increased expression of BMPR-II and enhanced endocytosis. CONCLUSIONS: These observations support that SMOC1 works as a dual-directional modulator of AVIC calcification by regulating p38-dependent BMP2 signalling transduction according to different extracellular calcium concentrations.

16.
Sci Rep ; 11(1): 5411, 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33686159

RESUMO

Cataracts are a common cause of visual impairment and blindness in mammals. They are usually associated with aging, but approximately one third of cases have a significant genetic component. Cataracts are increasingly prevalent among aging populations of captive giant pandas (Ailuropoda melanoleuca) and it is therefore important to identify genetic determinants that influence the likelihood of cataract development in order to distinguish between congenital and age-related disease. Here we screened for cataract-related genetic effects using a functional candidate gene approach combined with bioinformatics to identify the underlying genetic defect in a giant panda with congenital cataracts. We identified a missense mutation in exon 10 of the HSF4 gene encoding heat shock transcription factor 4. The mutation causes the amino acid substitution R377W in a highly conserved segment of the protein between the isoform-specific and downstream hydrophobic regions. Predictive modeling revealed that the substitution is likely to increase the hydrophobicity of the protein and disrupt interactions with spatially adjacent amino acid side chains. The mutation was not found in 13 unaffected unrelated animals but was found in an unrelated animal also diagnosed with senile congenital cataract. The novel missense mutation in the HSF4 gene therefore provides a potential new genetic determinant that could help to predict the risk of cataracts in giant pandas.

17.
J Immunol Res ; 2021: 6686284, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33688507

RESUMO

Background: Cutaneous melanoma is defined as one of the most aggressive skin tumors in the world. An increasing body of evidence suggested an indispensable association between immune-associated gene (IAG) signature and melanoma. This article is aimed at formulating an IAG signature to estimate prognosis of melanoma. Methods: 434 melanoma patients were extracted from The Cancer Genome Atlas (TCGA) database, and 1811 IAGs were downloaded from the ImmPort database in our retrospective study. The Cox regression analysis and LASSO regression analysis were utilized to establish a prognostic IAG signature. The Kaplan-Meier (KM) survival analysis was performed, and the time-dependent receiver operating characteristic curve (ROC) analysis was further applied to assess the predictive value. Besides, the propensity score algorithm was utilized to balance the confounding clinical factors between the high- and low-risk groups. Results: A total of six prognostic IAGs comprising of INHA, NDRG1, IFITM1, LHB, GBP2, and CCL8 were eventually filtered out. According to the KM survival analysis, the results displayed a shorter overall survival (OS) in the high-risk group compared to the low-risk group. In the multivariate Cox model, the gene signature was testified as a remarkable prognostic factor (HR = 45.423, P < 0.001). Additionally, the ROC curve analyses were performed which demonstrated our IAG signature was superior to four known biomarkers mentioned in the study. Moreover, the IAG signature was significantly related to immunotherapy-related biomarkers. Conclusion: Our study demonstrated that the six IAG signature played a critical role in the prognosis and immunotherapy of melanoma, which might help clinicians predict patients' survival and provide individualized treatment.

18.
Langmuir ; 37(12): 3761-3765, 2021 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-33724026

RESUMO

A series of nucleobases guanine (G) and cytosine (C) pairing configurations have been fabricated on highly oriented pyrolytic graphite (HOPG) surface by controlling the molar ratio of G and C in water solution. Watson-Crick (WC) base pairing governs the association of C and G nucleobases when the molar ratio of C/G is adjusted to 1:1. Nucleobase-rich is preferentially hydrogen-bonded to the sites exposed around WC motifs with the adjustment of the C/G molar ratio. At a higher C/G molar ratio imbalance, the pairing configurations depend on the combination of interspace and sites of hydrogen binding between G and C bases. The systematic analysis of the high-resolution STM images and DFT calculations reveal that hydrogen bonding plays a dominant role in the formation of these pairing configurations and that the competition between the priority and diversity of hydrogen-bonded configurations bonding between G and C is the key for the pairing structural polymorphism.

19.
Expert Rev Respir Med ; : 1-6, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33787428

RESUMO

OBJECTIVE: This study explored the change in mortality rates of respiratory disease during the corona virus disease 2019 (COVID-19) pandemic. METHODS: Death data of registered residents of Suzhou from 2014 to 2020 were collected and the weekly mortality rates due to respiratory disease and all deaths were analyzed. The differences in mortality rates during the pandemic and the same period in previous years were compared. RESULTS: Before the pandemic, the crude mortality rate (CMR) and standardized mortality rate (SMR) of Suzhou residents including respiratory disease, were not much different from those in previous years. During the emergency period, the CMR of Suzhou residents was 180.2/100,000 and the SMR was 85.5/100,000, decreasing by 9.1% and 14.6%, respectively; the CMR of respiratory disease was 16.4/100,000 and the SMR was 6.8/100,000, down 41.4% and 44.9%, respectively. Regardless of the mortality rates of all deaths or respiratory disease, the rates were higher in males than in females, although males had aslightly greater decrease in all deaths during the emergency period compared with females, and the opposite was true for respiratory disease. CONCLUSION: During the pandemic, the death rate of residents decreased, especially that due to respiratory disease.

20.
J Ethnopharmacol ; 273: 113996, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-33684516

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bu Shen Huo Xue Tang (BSHXT) is a traditional Chinese medicine formula that is clinically used in the treatment of premature ovarian insufficiency (POI). However, its therapeutic mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the underlying molecular mechanism of pharmacological activity of BSHXT, via the Nrf2/Keap1 signaling pathway, in the treatment of autoimmune POI. MATERIALS AND METHODS: The chemical composition of BSHXT was analyzed using ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The autoimmune POI mouse model was induced by immunizing mice twice, with zona pellucida (ZP) glycoprotein 3 antigen. The autoimmune POI mice were continuously administered BSHXT for 28 days. Body weight and organ indices were recorded. The pathological morphology of the ovaries was observed. The estrous cycle of each mouse was recorded. Immunofluorescence assay was used to detect the levels of ZP antibodies in the mouse ovaries. The levels of ZP antibodies, follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH), estradiol (E2), luteinizing hormone (LH), superoxide dismutase (SOD), and malondialdehyde (MDA) were measured. The expression of genes and proteins involved in the Nrf2/Keap1 signaling pathway were measured by Q-PCR and IHC, respectively. RESULTS: Twenty-one compounds were identified in the BSHXT water extract. BSHXT was found to increase the body weight and ovarian index, improve ovarian function, and reduce disorders in the estrus cycle. It also reduced the expression of ZP antibodies in the ovaries and serum of POI mice. BSHXT significantly increased E2 and AMH levels and decreased FSH and LH levels. It also increased the levels of SOD, and reduced MDA levels. The levels of Nrf2 and Keap1 were also increased, and the expression of Nrf2, HO-1 and NQO1 genes was upregulated. CONCLUSIONS: BSHXT has a therapeutic effect on autoimmune POI in mice, which may be a result of the enhanced antioxidant capacity and activation of the Nrf2/Keap1 signaling pathway. BSHXT is a good drug candidate for use as a protective agent for POI and may be used in clinical practice.

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