ABSTRACT
Transition metal dichalcogenide (TMD) nanotubes offer a unique platform to explore the properties of TMD materials at the one-dimensional limit. Despite considerable efforts thus far, the direct growth of TMD nanotubes with controllable chirality remains challenging. Here we demonstrate the direct and facile growth of high-quality WS2 and WSe2 nanotubes on Si substrates using catalytic chemical vapour deposition with Au nanoparticles. The Au nanoparticles provide unique accommodation sites for the nucleation of WS2 or WSe2 shells on their surfaces and seed the subsequent growth of nanotubes. We find that the growth mode of nanotubes is sensitive to the temperature. With careful temperature control, we realize ~79% WS2 nanotubes with single chiral angles, with a preference of 30° (~37%) and 0° (~12%). Moreover, we demonstrate how the geometric, electronic and optical properties of the synthesized WS2 nanotubes can be modulated by the chirality. We anticipate that this approach using Au nanoparticles as catalysts will facilitate the growth of TMD nanotubes with controllable chirality and promote the study of their interesting properties and applications.
ABSTRACT
BACKGROUND: Vesicular stomatitis virus (VSV) is a typical non-segmented negative-sense RNA virus of the genus Vesiculovirus in the family Rhabdoviridae. VSV can infect a wide range of animals, including humans, with oral blister epithelial lesions. VSV is an excellent model virus with a wide range of applications as a molecular tool, a vaccine vector, and an oncolytic vector. To further understand the interaction between VSV and host cells and to provide a theoretical basis for the application prospects of VSV, we analyzed the expression of host differentially expressed genes (DEGs) during VSV infection using RNA-Seq. RESULTS: Our analyses found a total of 1015 differentially expressed mRNAs and 161 differentially expressed LncRNAs in BHK-21 cells infected with VSV for 24 h compared with controls. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment showed that the differentially expressed lncRNAs and their target genes were mainly concentrated in pathways related to apoptosis, cancer, disease, and immune system activation, including the TNF, P53, MAPK, and NF-kappaB signaling pathways. The differentially expressed lncRNA can modulate immune processes by regulating genes involved in these signaling transmissions. Ten randomly selected DEGs, namely, Il12rb2, F2, Masp2, Mcl1, FGF18, Ripk1, Fas, BMF, POLK, and JAG1, were validated using RT-qPCR. As predicted through RNA-Seq analysis, these DEGs underwent either up- or downregulation, suggesting that they may play key regulatory roles in the pathways mentioned previously. CONCLUSIONS: Our study showed that VSV infection alters the host metabolic network and activates immune-related pathways, such as MAPK and TNF. The above findings provide unique insights for further study of the mechanism of VSV-host interactions and, more importantly, provide a theoretical basis for VSV as an excellent vaccine carrier.
Subject(s)
RNA, Long Noncoding , Vaccines , Animals , Humans , RNA, Long Noncoding/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Gene Expression Profiling , RNA-Seq , TranscriptomeABSTRACT
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a condition that may cause persistent pulmonary damage. The transformation of pericytes into myofibroblasts has been recognized as a key player during IPF progression. This study aimed to investigate the functions of lncRNA growth arrest-specific transcript 5 (GAS5) in myofibroblast transformation during IPF progression. METHODS: We created a mouse model of pulmonary fibrosis (PF) via intratracheal administration of bleomycin. Pericytes were challenged with exogenous transforming growth factor-ß1 (TGF-ß1). To determine the expression of target molecules, we employed quantitative reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemical and immunofluorescence staining. The pathological changes in the lungs were evaluated via H&E and Masson staining. Furthermore, the subcellular distribution of GAS5 was examined using FISH. Dual-luciferase reporter assay, ChIP, RNA pull-down, and RIP experiments were conducted to determine the molecular interaction. RESULTS: GAS5 expression decreased whereas PDGFRα/ß expression increased in the lungs of IPF patients and mice with bleomycin-induced PF. The in vitro overexpression of GAS5 or silencing of PDGFRα/ß inhibited the TGF-ß1-induced differentiation of pericytes to myofibroblasts, as evidenced by the upregulation of pericyte markers NG2 and desmin as well as downregulation of myofibroblast markers α-SMA and collagen I. Further mechanistic analysis revealed that GAS5 recruited KDM5B to promote H3K4me2/3 demethylation, thereby suppressing PDGFRα/ß expression. In addition, KDM5B overexpression inhibited pericyte-myofibroblast transformation and counteracted the promotional effect of GAS5 knockdown on pericyte-myofibroblast transformation. Lung fibrosis in mice was attenuated by GAS5 overexpression but promoted by GAS5 deficiency. CONCLUSION: GAS5 represses pericyte-myofibroblast transformation by inhibiting PDGFRα/ß expression via KDM5B-mediated H3K4me2/3 demethylation in IPF, identifying GAS5 as an intervention target for IPF.
Subject(s)
Idiopathic Pulmonary Fibrosis , RNA, Long Noncoding , Animals , Mice , Bleomycin/adverse effects , Demethylation , DNA-Binding Proteins/metabolism , Fibroblasts/metabolism , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/genetics , Idiopathic Pulmonary Fibrosis/metabolism , Jumonji Domain-Containing Histone Demethylases/metabolism , Lung , Mice, Inbred C57BL , Myofibroblasts/metabolism , Pericytes/metabolism , Pericytes/pathology , Receptor, Platelet-Derived Growth Factor alpha/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
1,2-Unsaturated pyrrolizidine alkaloids (PAs) are carcinogenic phytochemicals. We previously determined that carcinogenic PAs and PA N-oxides commonly form a set of four (±)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP)-DNA adducts, namely, DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4. This set of DHP-DNA adducts has been implicated as a potential biomarker of PA-induced liver tumor initiation from metabolism of individual carcinogenic PAs. To date, it is not known whether this generality occurs from metabolism of PA-containing plant extracts. In this study, we investigate the rat liver microsomal metabolism of nine PA-containing plant extracts and two PA-containing dietary supplements in the presence of calf thymus DNA. The presence of carcinogenic PAs and PA N-oxides in plant extracts was first confirmed by LC-MS/MS analysis with selected reaction monitoring mode. Upon rat liver microsomal metabolism of these PA-containing plant extracts and dietary supplements, the formation of this set of DHP-DNA adducts was confirmed. Thus, these results indicate that metabolism of PA-containing plant extracts and dietary supplements can generate DHP-dG-3, DHP-dG-4, DHP-dA-3, and DHP-dA-4 adducts, thereby potentially initiating liver tumor formation.
Subject(s)
Liver Neoplasms , Pyrrolizidine Alkaloids , Rats , Animals , Pyrrolizidine Alkaloids/metabolism , DNA Adducts , Plant Extracts/metabolism , Chromatography, Liquid , Rats, Inbred F344 , Tandem Mass Spectrometry , Carcinogens/metabolism , Dietary Supplements/analysis , OxidesABSTRACT
Carbonaceous matter (CM) (such as water-insoluble organic carbon (WIOC), black carbon (BC), and water-soluble organic carbon (WSOC)) has a significant impact on the carbon cycle and radiative forcing (RF) of glacier. Precipitation samples and glacier's snow/ice samples (snowpit, surface snow, and granular ice) (Xiao dongkemadi Glacier) were collected at the Dongkemadi River Basin (DRB) in the central Tibetan Plateau (TP) between May and October 2016 to investigate the characteristics and roles of CM in the TP River Basin. WIOC, BC, and WSOC concentrations in precipitation were relatively higher than that in snowpit, but lower than that in surface snow/ice, with the wet deposition fluxes of 0.10 ± 0.002, 0.04 ± 0.001, and 0.12 ± 0.002 g C m-2 yr-1 at DRB, respectively. The positive matrix factorization model identified four major sources (biomass burning source, secondary precursors, secondary aerosol, and dust source) of CM in precipitation at DRB. Two source areas (South Asia and the interior of TP) contributing to the pollution at DRB were identified using a potential source contribution function model, a concentration-weighted trajectory method, and the back-trajectory model. Moreover, the light-absorption by WSOC in the ultraviolet region was 23.0%, 12.1%, and 3.4% relative to the estimated total light-absorption in precipitation, snowpit, and surface snow/ice, respectively. Optical indices analysis revealed that WSOC in snowpit samples presented higher molecular weight, while presented higher aromatic and higher molecule sizes in surface snow/ice and precipitation samples, respectively. RF by WSOC relative to that of BC was estimated to be 17.6 ± 17.6% for precipitation, 10.9 ± 5.8% for snowpit, and 10.7 ± 11.6% for surface snow/ice, respectively, during the melt season in the central TP River Basin. These results help us understand how CM affects glaciers, and they can be utilized to create policies and recommendations that efficiently reduce emissions.
Subject(s)
Environmental Monitoring , Rivers , Environmental Monitoring/methods , Tibet , Ice Cover , Soot/analysis , Carbon/analysis , Water/analysisABSTRACT
OBJECTIVE: Pregnant women experience enormous psychological pressure, particularly during the late trimester. Symptoms of depression in late pregnancy may persist postpartum, increasing the incidence of postpartum depression. This study is aimed to investigate the factors influencing depressive symptoms among pregnant women in their third trimester at a Chinese tertiary hospital and provide information for effective intervention. METHODS: Pregnant women in their third trimester who visited the Ningbo Women and Children's Hospital between January 1, 2020 and June 30, 2022 participated in this study. A score of ≥ 13 on the Edinburgh Postnatal Depression Scale (EPDS) was considered as positive for depressive symptom. Potential influencing factors were examined by using an online questionnaire and analyzed using multivariate logistic regression. RESULTS: A total of 1196 participants were recruited. The mean EPDS score was 7.12 ± 4.22. The positive screening rate for depressive symptom was 9.9%. Univariate analysis showed that living with partner, annual family income, planned pregnancy, sleep quality, and partner's drinking habits were related to positive screening for depression(P < 0.05). Furthermore, multivariate logistic regression analysis showed that living away from the partner (odds ratio [OR]: 2.054, 95% confidence interval [CI]: 1.094-3.696, P = 0.02), annual family income < 150,000 Chinese Yuan (CNY; OR: 1.762, 95% CI: 1.170-2.678, P = 0.007), poor sleep quality (OR: 4.123, 95% CI: 2.764-6.163, P < 0.001), and partner's frequent drinking habit (OR: 2.227, 95% CI: 1.129-4.323, P = 0.019) were independent influencing factors for positive depression screening (P < 0.05). CONCLUSION: Family's economic condition, sleep quality, living with partner, and partner's drinking habits were related to positive depression screening in late pregnancy. Pregnant women with these risk factors should be given more attention and supported to avoid developing depression.
Subject(s)
Depression, Postpartum , Depression , Female , Humans , Pregnancy , Cross-Sectional Studies , Depression/diagnosis , Depression/epidemiology , Depression/psychology , Depression, Postpartum/diagnosis , Depression, Postpartum/epidemiology , Depression, Postpartum/psychology , East Asian People , Pregnancy Trimester, Third , Risk Factors , Tertiary Care CentersABSTRACT
A low F-number and 100% cold stop efficiency are beneficial for improving the performance of optical systems and have a wide range of applications in various thermal imaging scenarios. The cooled infrared coaxial four-mirror system can meet these two requirements, improve system integration, and reduce adjustment costs and difficulties. However, the secondary obstruction caused by the central hole of the third mirror will generate potential stray light. A structure model is proposed in which the primary mirror and the quaternary mirror are processed on the same mirror blank. In this model, a method is given to calculate system parameters using the obstruction ratio and magnification of each mirror. To evaluate the performance of the method, two design examples with different F-numbers (1.4, 1.0) were constructed. The influence of initial structural constraints on the exit pupil position and secondary obstruction was analyzed based on the design objectives of the examples. The aberrations were optimized by targeting the spot. In the optimization process, the incident coordinates and directions of the restricted edge field rays in the tertiary mirror and the quaternary mirror were limited to achieve control of the obstruction caused by the holes in the center of the mirrors. In the results, the RMS spot radius of the two design examples is smaller than the Airy disk radius, and the axial beam wavefront deviation RMS values are 0.026λ and 0.024λ, respectively. Moreover, the obstruction caused by the central holes of the mirrors is controlled within the given field of view. The results show that the proposed model and method can be used to design a low F-number cooled infrared coaxial four-mirror system and have good application prospects.
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BACKGROUND: The greater omentum is derived from the foregut, and the right hemicolon is derived from the midgut based on developmental anatomy. This study aimed to investigate whether the greater omentum should be resected in laparoscopic complete mesocolic excision based on developmental anatomy for right-sided colon cancer. METHODS: A total of 183 consecutive patients with right-sided colon cancer were recruited in this study between February 2020 and July 2022. Ninety-eight patients underwent standard laparoscopic complete mesocolic excision surgery (CME group). The presence of isolated tumor cells and micrometastases was detected in resected greater omentum by the HE staining and immunohistochemistry analysis. Based on developmental anatomy, laparoscopic CME surgery with greater omentum preservation (DACME group) was proposed and performed on 85 right-sided colon cancer patients. To overcome selection bias, we performed a 1:1 match between two groups using four variables: age, sex, BMI, and ASA scores. RESULTS: No isolated tumor cells and micrometastases were found in the resected greater omentum specimen in the CME group. After the propensity score, 81 pairs were balanced and analyzed. Patients in the DACME group showed shorter operative time (194.9 ± 16.4 min vs.201.5 ± 11.5 min, p = 0.002), less blood loss (23.5 ± 24.7 ml vs.33.6 ± 26.3 ml, p = 0.013), and the shorter hospital stays (9.6 ± 1.7 days vs.10.3 ± 2.0 days, p = 0.010) compared with patients in the CME group. In addition, patients in the DACME group had a lower incidence of postoperative complications (4.9% vs.14.8%, p = 0.035) than patients in the CME group. CONCLUSION: The greater omentum should be preserved during right-sided colon cancer surgery, laparoscopic CME surgery based on developmental anatomy is technically safe and feasible for right-sided colon cancer.
Subject(s)
Colonic Neoplasms , Laparoscopy , Mesocolon , Humans , Colonic Neoplasms/surgery , Colonic Neoplasms/pathology , Treatment Outcome , Omentum/surgery , Omentum/pathology , Neoplasm Micrometastasis , Colectomy , Lymph Node Excision , Mesocolon/surgeryABSTRACT
On-chip nanoscale optical platforms capable of efficient second harmonic generation (SHG) are highly desired for optical sensing, subwavelength coherent sources, and quantum photonic devices. Here, we develop a remotely excited dual cavity resonance scheme to achieve significantly enhanced SHG in a CdSe nanobelt on Au film hybrid waveguide system. The SHG emission with superior efficiency originates from counter-propagating plasmonic modes interference in a horizontal Fabry-Pérot (FP) cavity enabled by remote excitation of propagating surface plasmons, which is further enhanced through a vertical FP cavity. With this effective cooperation of hybrid plasmon modes and FP cavity modes, 2 orders of magnitude enhancement of the conversion efficiency (3.5 × 10-4 W-1) is achieved compared to the off-resonance case. Our design provides new insight into the development of a multifunctional hybrid plasmonic device toward on-chip nonlinear nanophotonic applications.
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Baicalein is a plant-derived compound, it has widespread attention among biomedical researchers due to its biocompatibility and efficient biological activities. But it has non-solubility in physiological conditions and short bioavailability in the clinical process. The Discovery of a stimuli-based drug delivery system (DDS) is a perfect strategy to improve the bioactivity of baicalin in post-caesarean section wound care. We prepared a baicalein-encapsulated pH-responsive DDS with a zeolite imidazole framework-8 (ZIF-8) as a carrier. We investigated the material characteristics of DDS in terms of crystal structure, surface area morphology, particle size, FTIR, UV-vis, Powder XRD, and BET analysis techniques. The in vitro cytotoxicity, biocompatibility, and cell proliferation properties of BA@ZIF-8 were assessed against human fibroblast L929 cells. In vitro studies showed that BA@ZIF-8 nanocomposite significantly enhanced the biocompatibility against L929 cells after 72 h post-exposure. The pH-responsive drug release kinetics shows excellent baicalein release under acidic conditions and without unwanted drug release in physiological conditions. Wound scratch assay results revealed, that BA@ZIF-8 nanocomposite-treated cells exhibit the fastest cell proliferation and migration process in a very short period. In the antibacterial activity study, nanocomposite exposed dose depended on inhibition against wound infectious pathogens. The overall study signifies that BA@ZIF-8 nano-DDSs are effective and suitable DDS for stimuli-based post-caesarean section wound care.
Subject(s)
Zeolites , Female , Pregnancy , Humans , Zeolites/therapeutic use , Zeolites/chemistry , Cesarean Section , Imidazoles/therapeutic use , Imidazoles/chemistry , Hydrogen-Ion ConcentrationABSTRACT
Plasmonic demultiplexers hold promise for the realization of the subwavelength and high-splitting ratio dichroic splitter and have a wide range of applications from optical communication, and manipulation to ultrafast data treatment. However, this vision has not been realized for a long time due to lacking the suitable splitting structure design, which limits its further development of integrated photonic circuits. Here, we demonstrate a plasmonic demultiplexer with subwavelength feature size (0.54â µm) and broadband spectral (620-870â nm) range, and high-splitting ratio (17â dB in experiments and 20â dB in calculations). It consists of two adjacent Fabry-Perot cavities (covered by PMMA polymer) and coupling gratings, which are integrated with the Au waveguide. The relatively simple double cavities design of our device has a simple theoretical analysis and fabrication process. Our work has relevance for various optical applications, such as multiple wavelength photodetectors and optical multichannel interconnects.
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Enzymes of the matrixin family could be seen as a critical determinant in the breakdown of the extracellular matrix, cell membrane, and tissue regeneration and are interned in the process of brain bleeding. On the other hand, coagulation factor XIII deficiency is a sporadic hemorrhagic disease with an estimated prevalence of 1 in 1-2 million people. Cerebral hemorrhage is the leading cause of death in these patients. This study investigated the relationship between the expression of matrix metalloproteinase 9 and 2 genes with cerebral hemorrhage in these patients. For this purpose, in this case-control study, by examining the clinical and general findings of the studied patients, the Q-Real-time RT-PCR method was used to quantitatively examine the mRNA levels of matrix metalloproteinase 9 and 2 in 42 patients with hereditary deficiency of coagulation factor XIII, including two groups with and without a history of cerebral hemorrhage (case and control groups, respectively). A comparative method (2-ΔΔCT) was used to check the expression level of the target genes. The GAPDH gene expression levels were used to standardize the expression of the measured matrix metalloproteinase genes. The results showed that bleeding from the umbilical cord was the most common clinical symptom among all patients. High levels of MMP-9 gene expression were observed in 13 patients of the case group (69.99%) and three patients of the control group (11.9%). which showed a significant difference (CI: 2.77-95.3, P=0.001) Patients with coagulation factor XIII deficiency show a wide range of clinical symptoms crucial in screening and diagnosing this group of patients. Based on the results of this study, it seems that the increased expression of the MMP-9 gene is due to polymorphism or inflammation related to the pathogenesis of cerebral hemorrhage in this category of patients. It may be conceivable to diminish this impact by utilizing MMP-9 inhibitors and offering assistance to diminishes these patients' hospitalization and passing rates.
Subject(s)
Factor XIII Deficiency , Matrix Metalloproteinase 9 , Humans , Matrix Metalloproteinase 9/genetics , Factor XIII/genetics , Factor XIII/metabolism , Case-Control Studies , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/genetics , Factor XIII Deficiency/complications , Factor XIII Deficiency/genetics , Gene ExpressionABSTRACT
OBJECTIVE: To evaluate the outcomes and risk factors for trial of labor after cesarean delivery (TOLAC) failure in patients in China. METHODS: Consecutive patients who had a previous cesarean delivery (CD) and attempted TOLAC were included from 2014 to 2020. Patients who successfully delivered were classified into the TOLAC success group. Patients who attempted TOLAC but had a repeat CD due to medical issues were classified into the TOLAC failure group. Multiple logistic regression analyses were performed to examine the risk factors for TOLAC failure. RESULTS: In total, 720 women who had a previous CD and attempted TOLAC were identified and included. The success rate of TOLAC was 84.2%(606/720). Seven patients were diagnosed with uterine rupture, none of whom underwent hysterectomy. Multiple logistic regression analysis showed that the induction of labor (OR = 2.843, 95% CI: 1.571-5.145, P < 0.001) was positively associated with TOLAC failure, but the thickness of the lower uterine segment (LUS) (OR = 0.215, 95% CI: 0.103-0.448, P < 0.001) was negatively associated with TOLAC failure. CONCLUSIONS: This study suggested that TOLAC was effective in decreasing CD rates in the Chinese population. The induction of labor was positively associated with TOLAC failure, but the thickness of the LUS was negatively associated with TOLAC failure. Our findings need to be confirmed in larger samples with patients of different ethnicities.
Subject(s)
Trial of Labor , Vaginal Birth after Cesarean , Cesarean Section/adverse effects , Cesarean Section, Repeat/adverse effects , Female , Humans , Pregnancy , Retrospective Studies , Risk Factors , Vaginal Birth after Cesarean/adverse effectsABSTRACT
Many nitrosamines are recognized as mutagens and potent rodent carcinogens. Over the past few years, nitrosamine impurities have been detected in various drugs leading to drug recalls. Although nitrosamines are included in a 'cohort of concern' because of their potential human health risks, most of this concern is based on rodent cancer and bacterial mutagenicity data, and there are little data on their genotoxicity in human-based systems. In this study, we employed human lymphoblastoid TK6 cells transduced with human cytochrome P450 (CYP) 2A6 to evaluate the genotoxicity of six nitrosamines that have been identified as impurities in drug products: N-nitrosodiethylamine (NDEA), N-nitrosoethylisopropylamine (NEIPA), N-nitroso-N-methyl-4-aminobutanoic acid (NMBA), N-nitrosomethylphenylamine (NMPA), N-nitrosodiisopropylamine (NDIPA), and N-nitrosodibutylamine (NDBA). Using flow cytometry-based assays, we found that 24-h treatment with NDEA, NEIPA, NMBA, and NMPA caused concentration-dependent increases in the phosphorylation of histone H2A.X (γH2A.X) in CYP2A6-expressing TK6 cells. Metabolism of these four nitrosamines by CYP2A6 also caused significant increases in micronucleus frequency as well as G2/M phase cell-cycle arrest. In addition, nuclear P53 activation was found in CYP2A6-expressing TK6 cells exposed to NDEA, NEIPA, and NMPA. Overall, the genotoxic potency of the six nitrosamine impurities in our test system was NMPA > NDEA ≈ NEIPA > NMBA > NDBA ≈ NDIPA. This study provides new information on the genotoxic potential of nitrosamines in human cells, complementing test results generated from traditional assays and partially addressing the issue of the relevance of nitrosamine genotoxicity for humans. The metabolically competent human cell system reported here may be a useful model for risk assessment of nitrosamine impurities found in drugs.
Subject(s)
Histones , Nitrosamines , Amides , Carcinogens/metabolism , Carcinogens/toxicity , Cytochrome P-450 Enzyme System/metabolism , DNA Damage , Diethylnitrosamine/toxicity , Humans , Mutagens/toxicity , Nitrosamines/toxicity , Propionates , Tumor Suppressor Protein p53 , gamma-Aminobutyric AcidABSTRACT
A circular polarizer is proposed based on a single layered metasurface. This metasurface circular polarizer is composed of L-shaped nanoholes etched on the silver film. The L-shaped nanoholes are rotational symmetric, and the special symmetric structure determines the polarization selection transmission of the metasurface. The theoretical analysis elaborates the design process of the metasurface circular polarizer. The proposed metasurface circular polarizers have good polarization selective transmittance, and more interestingly, they take on the opposite circular dichroism at different wavebands. The numerical simulations and experiment measurement confirm the circular dichroism of the proposed circular polarizers. The compact design, ultrathin thickness and available performance can expand the applications of the metasurface circular polarizers in the integrated optics.
ABSTRACT
Phosphatidylethanolamines (PEs) are targets of non-enzymatic glycation, a chemical process that occurs between glucose and primary amine-containing biomolecules. As the early-stage non-enzymatic glycation products of PE, Amadori-PEs are implicated in the pathogenesis of various diseases. However, only a few Amadori-PE molecular species have been identified so far; a comprehensive profiling of these glycated PE species is needed to establish their roles in disease pathology. Herein, based on our previous work using liquid chromatography-coupled neutral loss scanning and product ion scanning tandem mass spectrometry (LC-NLS-MS and LC-PIS-MS) in tandem, we extend identification of Amadori-PE to the low-abundance species, which is facilitated by using plasma lipids glycated in vitro. The confidence of identification is improved by high-resolution tandem mass spectrometry and chromatographic retention time regression. A LC-coupled multiple reaction monitoring mass spectrometry (LC-MRM-MS) assay is further developed for more sensitive quantitation of the Amadori compound-modified lipids. Using synthesized stable isotope-labeled Amadori lipids as internal standards, levels of 142 Amadori-PEs and 33 Amadori-LysoPEs are determined in the NIST human plasma standard reference material. These values may serve as an important reference for future investigations of Amadori-modified lipids in human diseases.
Subject(s)
Chromatography, High Pressure Liquid/methods , Mass Spectrometry/methods , Phosphatidylethanolamines/analysis , Blood Chemical Analysis/methods , Fatty Acids/analysis , Glycosylation , Humans , Limit of Detection , Lipid Peroxidation , Lipids/analysis , Lipids/chemistry , Plasma/chemistry , Reference Standards , Reproducibility of ResultsABSTRACT
BACKGROUND: Pancreatic cancer (PAC) is one of the most devastating cancer types with an extremely poor prognosis, characterized by a hypoxic microenvironment and resistance to most therapeutic drugs. Hypoxia has been found to be one of the factors contributing to chemoresistance in PAC, but also a major driver of the formation of the tumor immunosuppressive microenvironment. However, the method to identify the degree of hypoxia in the tumor microenvironment (TME) is incompletely understood. METHODS: The mRNA expression profiles and corresponding clinicopathological information of PAC patients were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database, respectively. To further explore the effect of hypoxia on the prognosis of patients with PAC as well as the tumor immune microenvironment, we established a hypoxia risk model and divided it into high- and low-risk groups in line with the hypoxia risk score. RESULTS: We established a hypoxia risk model according to four hypoxia-related genes, which could be used to demonstrate the immune microenvironment in PAC and predict prognosis. Moreover, the hypoxia risk score can act as an independent prognostic factor in PAC, and a higher hypoxia risk score was correlated with poorer prognosis in patients as well as the immunosuppressive microenvironment of the tumor. CONCLUSIONS: In summary, we established and validated a hypoxia risk model that can be considered as an independent prognostic indicator and reflected the immune microenvironment of PAC, suggesting the feasibility of hypoxia-targeted therapy for PAC patients.
Subject(s)
Hypoxia/genetics , Pancreatic Neoplasms/genetics , Tumor Microenvironment , Biomarkers, Tumor/genetics , Databases, Genetic , Gene Expression Profiling/methods , Gene Expression Regulation, Neoplastic/genetics , Humans , Pancreatic Neoplasms/pathology , PrognosisABSTRACT
1-Formyl-7-hydroxy-6,7-dihydro-5H-pyrrolizine (1-CHO-DHP) is a potential proximate carcinogenic metabolite of pyrrolizidine alkaloids. In the present study, we determined that the reaction of 1-CHO-DHP with cysteine generated four identified products. By mass and 1H NMR spectral analyses, these products are cysteinyl-[2'-S-7]-1-CHO-DHP (P2), cysteinyl-[3'-N-7]-1-CHO-DHP (P3), 7-keto-DHP (P4), and 1-cysteinylimino-DHP (P5). These four compounds were also formed from the incubation of 1-CHO-DHP in HepG2 cells. Compounds P3 and P5 were interconvertible in acetonitrile and water. Incubation of P2 in HepG2 cells generated the four DHP-dG and -dA adducts that we propose to be potential common biomarkers of pyrrolizidine alkaloids exposure and pyrrolizidine alkaloids-induced liver tumor initiation. These four DHP-DNA adducts were also formed from the incubation of a mixture of P3 and P5 in HepG2 cells but not from the incubation with 7-keto-DHP. From the reaction of 1-CHO-DHP with glutathione, only trace amounts of the glutathione-1-CHO-DHP adduct were detected, with the structure unable to be characterized.
Subject(s)
Cysteine/metabolism , DNA/metabolism , Hepatocytes/metabolism , Pyrrolizidine Alkaloids/metabolism , Animals , Binding Sites , Cysteine/chemistry , DNA/chemistry , Hep G2 Cells , Hepatocytes/chemistry , Humans , Male , Molecular Structure , Pyrrolizidine Alkaloids/chemistry , RatsABSTRACT
Measurements of land-air mercury (Hg) exchanges over vegetated surfaces are needed to further constrain Hg fluxes over vegetated terrestrial surfaces. Yet, knowledge of land-air Hg dynamics in alpine grasslands remains poor. Hg fluxes over an alpine meadow were measured throughout a full vegetation period in the central Tibetan Plateau (TP). This TP grassland served as a small source of atmospheric total gaseous Hg (TGM) during vegetation period (0.92 µg m-2). Hg fluxes decreased logarithmically during plant growing season, resulting from the influence of vegetation by light shading and plant Hg uptake, although the latter might be minor due to low biomass at this site. Temporal patterns of TGM indicated the importance of land-air dynamics in regulating TGM levels. During the plant emergence, diel pattern of TGM covaried with Hg emission fluxes resulting in lower concentrations at night and higher concentrations in afternoon. During all other vegetation stages, TGM showed minima before dawn and "morning peak" shortly after sunrise, in conjunction with corresponding Hg fluxes showing sink before dawn and source after sunrise. Moreover, TGM concentrations showed a decreasing trend with plant growing, further indicating the role of vegetation in driving seasonal TGM variations by regulating land-air Hg dynamics.
Subject(s)
Air Pollutants/analysis , Mercury/analysis , Permafrost , Environmental Monitoring , Seasons , TibetABSTRACT
OBJECTIVE: Osteoporosis is diagnosed based on the results of BMD assessment and/or fragility fractures. Vertebral fracture is the most common fragility fracture. Many vertebral fractures are asymptomatic and are not clinically recognized. Early detection of vertebral fracture may increase diagnosis of osteoporosis. In this study, we performed BMD measurement combined with vertebral fracture assessment (VFA) by DXA for the postmenopausal women receiving the first bone densitometry and studied the impact of VFA on the diagnosis of osteoporosis. METHODS: A total of 502 postmenopausal women were enrolled in our study. Patients' age was 66.7 ± 9.5 years. All patients had BMD assessment and VFA by dual-energy X-ray absorptiometry. Genant's semiquantitative assessment was used. The impact of VFA on the diagnosis of osteoporosis was studied. All parameters of groups were compared using the Chi-squared test. RESULTS: There were 257 patients with T-score ≤-2.5, 202 patients with a T-score between -1 and - 2.5, and 43 patients with BMD within the normal range. There were 162 patients with 345 fractured vertebrae identified by VFA, among which 84% of patients were previously unknown. Osteoporosis or severe osteoporosis was presented in 51.2% patients diagnosed by BMD alone, in 55.2% patients diagnosed by BMD plus fracture history, and in 62.4% of patients diagnosed by BMD plus fracture history and VFA. Severe osteoporosis significantly increased by 17.2% in patients receiving VFA. CONCLUSIONS: VFA combined with BMD can detect previously unknown vertebral fractures and increase clinical diagnosis of osteoporosis. It is plausible to speculate that this method should be considered in postmenopausal women for the first BMD assessment.