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BACKGROUND: The global increase in the aging population has led to a higher incidence of osteoporosis among the elderly. OBJECTIVE: This study aimed to evaluate the protective properties of pinoresinol diglucoside (PDG), an active constituent of Eucommia ulmoides, against dexamethasone-induced osteoporosis and chondrodysplasia. METHODS: A zebrafish model of osteoporosis was established by exposing larval zebrafish to dexamethasone. The impact of PDG on bone mineralization was assessed through alizarin red and calcein staining. Alkaline phosphatase activity was quantified to evaluate osteoblast function. The influence of PDG on chondrogenesis was estimated using alcian blue staining. Fluorescence imaging and motor behavior analysis were employed to assess the protective effect of PDG on the structure and function of dexamethasone-induced skeletal teratogenesis. qPCR determined the expression of osteogenesis and Wnt signaling-related genes. Molecular docking was used to assess the potential interactions between PDG and Wnt receptors. RESULTS: PDG significantly increased bone mineralization and corrected spinal curvature and cartilage malformations in the zebrafish model. Furthermore, PDG enhanced swimming abilities compared to the model group. PDG mitigated dexamethasone-induced skeletal abnormalities in zebrafish by upregulating Wnt signaling, showing potential interaction with Wnt receptors FZD2 and FZD5. CONCLUSION: PDG mitigates dexamethasone-induced osteoporosis and chondrodysplasia by promoting bone formation and activating Wnt signaling.
Subject(s)
Lignans , Osteoporosis , Zebrafish , Humans , Animals , Aged , Molecular Docking Simulation , Osteogenesis , Dexamethasone/pharmacology , Osteoporosis/chemically induced , Osteoporosis/prevention & control , Receptors, Wnt , Cell DifferentiationABSTRACT
In this work, GeSn lateral p-i-n photodetectors (PDs) on insulator were fabricated with an active GeSn layer grown by the rapid melting growth (RMG) method. Taking advantages of the defect-free GeSn strips, GeSn PDs with 5.3% Sn content have low dark current and high responsivities, which are about 0.48, 0.47, and 0.24 A/W for wavelengths of 1550, 1630, and 2000 nm, respectively. The radio frequency of the lateral GeSn PDs was also studied and a 3 dB bandwidth of about 3.8 GHz was achieved. These results indicate that the GeSn grown by the rapid melting growth method is capable of fabricating high-performance Si-based optoelectronic devices.
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Benzalkonium chloride (BAC) is a broad-spectrum antibacterial agent that possesses cleaning and bactericidal properties, but impact of BAC on wellbeing of aquatic organisms remains uncertain. Consequently, in this current study, we have examined the immunotoxic potential of BAC in zebrafish embryos, thus marking it as the pioneering effort in this field. According to the findings, zebrafish embryos exposed to BAC exhibited a decline in yolk area that varied with the concentration, along with a significant decrease in the count of neutrophils, macrophages, red blood cells, and thymus T-cells. We observed significantly up-regulated expression of immune-related signaling genes such as cxcl-c1c, il-8, tir4 and inf-γ, but expression of nf-κb was downregulated. In addition, we observed a marked reduction in the number of hematopoietic stem cells in zebrafish larvae after BAC exposure, which could be the result of oxidative stress-mediated apoptosis. We found that compared with the control group, the number of red blood cells in juvenile zebrafish in BAC-exposure group was significantly down-regulated, which could be attributed to hematopoietic stem cell defect. Astaxanthin restored immune cells and hematopoietic stem cells after BAC exposure, whereas Inhibitor of Wnt Response-1(IWR-1) restored neutrophils after BAC exposure. The research findings demonstrated that exposure to BAC displayed harmful effects on the development and immune system of zebrafish embryos. These effects might be associated with alterations in reactive oxygen species(ROS) levels and activation of the Wnt signaling pathway caused by BAC.
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Metal halide perovskites have attracted considerable attention as novel optoelectronic materials for their excellent optical and electrical properties. Inorganic perovskites (CsPbX3, X = Cl, Br, I) are now viable alternative candidates for third-generation photovoltaic technology because of their high photoelectric conversion efficiency, high carrier mobility, good defect tolerance, simple preparation method and many other advantages. However, the toxicity of lead is problematic for practical implementation. Thus, the fabrication of lead-free perovskite materials and devices has been actively conducted. In this work, the energy band and photoelectric properties of inorganic perovskites CsBX3 (B = Pb, Sn, Ge, X = Cl, Br, I) have been investigated with the first principles calculation, and the possible defect energy levels and their formation energies in different components, in particular, have been systematically studied. The advantages and disadvantages of Sn and Ge as replacement elements for Pb have been demonstrated from the perspective of defects. This study provides an important basis for the study of the properties and applications of lead-free perovskites.
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In this work, high-performance GeSn photodetectors with a Sn content gradient GeSn layer were fabricated on SOI substrate by CMOS-compatible process for C and L band telecommunication. The active GeSn layer has a Sn component increased from 9 to 10.7% with the controlled relaxation degree up to 84%. The responsivities of GeSn detectors at 1550â nm and 1630â nm are 0.47â A/W and 0.32â A/W under -4â V bias, respectively. Over 50â GHz 3â dB bandwidth with the eye pattern about 70â Gb/s was also evidenced at 1630â nm. These results indicate that the GeSn photodetectors have a promising application for extending the silicon photonics from C band to L band.
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In this paper, a carrier-injection electro-absorption modulator (EAM) at 2 µm is demonstrated on Ge-on-Si platform. The EAM shows a compact size and high modulation efficiency due to the strong free-carrier electroabsorption (FCEA) effect in Ge. A modulation depth of 40 dB can be obtained under the injection current of only 420 mA. Small-signal frequency response measurement is performed and a small-signal equivalent circuit model is proposed. Based on reflection coefficients and equivalent circuit, the frequency response of carrier-injection EAM is discussed in detail. The 500 Mbps open eye diagram verifies the data-processing capacity of our EAM at 2 µm wavelength for its application in biological, chemical molecular detection, and infrared imaging systems.
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In this work, GeSn resonant cavity enhanced (RCE) p-i-n photodetectors (PDs) with 3.7% Sn content in a GeSn layer were fabricated on a silicon on insulator (SOI) substrate. The gold (Au) layer and the deposited SiO2 layer constitute the bottom reflector and top reflector of the RCE detectors, respectively. The GeSn RCE PD has three resonant peaks and its responsivity is improved about 4.5 times at 1630 nm, compared with GeSn PDs without a gold bottom mirror. The cutoff wavelength of GeSn RCE PDs is up to 1820 nm, while it is only 1730 nm for GeSn PDs without a gold reflector. The responsivity of RCE PDs at 1630 nm reaches 0.126 A/W and 3-dB bandwidth at about 36 GHz is achieved. These results indicate that the RCE structure is an effective approach for enhancing the GeSn PD performance operated at the L band.
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A high-performance waveguide-coupled lateral avalanche photodetector (APD) is experimentally demonstrated without silicon epitaxy and charge layer ion implantation. At the wavelength of 1550 nm, it shows a high responsivity of 48 A/W and a gain-bandwidth product (GBP) of 360 GHz. Wide-open eye diagrams at 25 Gbps can be observed at various avalanche gains. These outstanding performances indicate the proposed APD has great potential in high-speed optical transceivers for optical links.
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A compact high-power germanium photodetector (Ge PD) is experimentally demonstrated by re-engineering light distribution in the absorber. Compared with a conventional Ge PD, the proposed structure shows a DC saturation photocurrent improved by 28.9% and 3 dB bandwidth as high as 49.5 GHz at 0.1 mA. Under the same photocurrent of 10.5 mA, the proposed Ge PD shows a 3 dB bandwidth of 11.1 GHz, which is almost double the conventional Ge PD (5.6 GHz). The 25 Gb/s eye-diagram measurement verifies the improved power handling capability. The compact size and manufacturing simplicity of this structure will enable new applications for integrated silicon photonics.
ABSTRACT
A high-power germanium photodetector is designed and fabricated using a cold-wall ultrahigh vacuum chemical vapor deposition. A back-to-back dual-absorption structure improves high-power characteristics by reducing the space-charge effect. Compared to a typical p-i-n photodetector, the saturated photocurrent of the back-to-back dual-absorption photodetector is improved from 16.2 to 21.3 mA at $ - {3}\;{\rm V}$-3V. At a bias voltage of $ - {1}\;{\rm V}$-1V, the dark current is 1.31 µA. The optical responsivities are 0.31 and 0.52 A/W at 1550 and 1310 nm, respectively. The 3 dB bandwidth of 4.14 GHz is achieved at $ - {3}\;{\rm V}$-3V. Theoretically, the 3 dB bandwidth can be further optimized in future device fabrication.
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Ge0.998Pb0.002 photodetectors (PDs) with a GePb layer grown on n-type Ge (100) substrate by magnetron sputtering epitaxy were fabricated by complementary metal-oxide semiconductor (CMOS)-compatible technology. For Ge0.998Pb0.002 PDs, the room-temperature dark current density at -1 V was 3.3 A/cm2. At room temperature, the GePb PDs demonstrated a longwave cutoff of 2.5 µm and the optical responsivities of GePb PDs ranging from 1500 nm to 2000 nm were measured. A temperature dependence optical characterization of these detectors was conducted and temperature-dependent energy bandgaps of Ge0.998Pb0.002 were derived from the photocurrent spectra.
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A high-quality Ge0.88Si0.08Sn0.04/Ge0.94Sn0.06 multiple quantum well (MQW) structure was grown on a Ge (001) substrate by sputtering epitaxy. The MQW structure was characterized by high-resolution x-ray diffraction and transmission electron microscopy. Surface-illuminated Ge0.88Si0.08Sn0.04/Ge0.94Sn0.06 MQW pin photodetectors were fabricated with cutoff wavelengths of up to 2140 nm. The analysis of transitions from spectral response was fitted well with the theoretical calculations. Results suggest that sputtering epitaxy is a promising method for preparing high-quality low-dimensional Sn-based group IV materials and that Ge1-x-ySiySnx/Ge1-xSnx MQWs have potential applications in the development of efficient Si-based photonic devices.
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STUDY OBJECTIVES: To systemically describe the clinical features, polysomnography (PSG) finding, laboratory tests and single-nucleotide polymorphisms (SNPs) in a clinic based Chinese primary restless legs syndrome (RLS) population. METHODS: This observational study, conducted from January 2020 to October 2021 across 22 sleep labs in China, recruited 771 patients diagnosed with RLS following the 2014 RLSSG criteria. Clinical data, PSG testing, and laboratory examination and SNPs of patients with RLS were collected. A total of 32 SNPs in 24 loci were replicated using the Asian Screening Array chip, employing data from the Han Chinese Genomes Initiative as controls. RESULTS: In this study with 771 RLS patients, 645 had primary RLS, and 617 has DNA available for SNP study. Among the 645 primary RLS, 59.7% were women. 33% had a family history of RLS, with stronger familial influence in early-onset cases. Clinical evaluations showed 10.4% had discomfort in body parts other than legs. PSG showed that 57.1% of RLS patients had periodic leg movement index (PLMI) of >5/h and 39.1% had PLMI >15/h, respectively; 73.8% of RLS patients had an Apnea-Hypopnea Index (AHI) > 5/h, and 45.3% had an AHI >15/h. The laboratory examinations revealed serum ferritin levels <75 ng/ml in 31.6%, and transferrin saturation (TSAT) of <45% in 88.7% of RLS patients. Seven new SNPs in 5 genes showed a significant allelic association with Chinese primary RLS, with one previously reported (BTBD9) and four new findings (TOX3, PRMT6, DCDC2C, NOS1). CONCLUSIONS: Chinese RLS patients has specific characters in many aspects. A high family history with RLS not only indicates strong genetic influence, but also reminds us to consider the familial effect in the epidemiological study. Newly developed sequencing technique with large samples remains to be done.
Subject(s)
Restless Legs Syndrome , Humans , Female , Male , Polysomnography , Restless Legs Syndrome/epidemiology , Sleep , Leg , China , Nuclear Proteins , Protein-Arginine N-MethyltransferasesABSTRACT
Benzophenone (BP) is found in many popular consumer products, such as cosmetics. BP potential toxicity to humans and aquatic organisms has emerged as an increased concern. In current study, we utilized a zebrafish model to assess BP-induced developmental cardiotoxicity. Following BP exposure, zebrafish embryos exhibited developmental toxicity, including increased mortality, reduced hatchability, delayed yolk sac absorption, and shortened body length. Besides, BP exposure induced cardiac defects in zebrafish embryos, comprising pericardial edema, reduced myocardial contractility and rhythm disturbances, and altered expression levels of cardiac developmental marker genes. Mechanistically, BP exposure disturbed the redox state and increased the level of apoptosis in zebrafish cardiomyocytes. Transcriptional expression levels of Wnt signaling genes, involving lef1, axin2, and ß-catenin, were upregulated after BP treatment. Inhibition of Wnt signaling with IWR-1 could rescue the BP-induced cardiotoxicity in zebrafish. In summary, BP exposure causes cardiotoxicity via upregulation of the Wnt signaling pathway in zebrafish embryos.
Subject(s)
Wnt Signaling Pathway , Zebrafish , Animals , Humans , Zebrafish/metabolism , Cardiotoxicity , Embryo, Nonmammalian/metabolism , Myocytes, CardiacABSTRACT
Cysteamine, a sulfhydryl compound, is an intermediate in the metabolism of coenzyme A to taurine in living organisms. However, the potential side effects of cysteamine such as hepatotoxicity in pediatric patients have been reported in some studies. To evaluate the impact of cysteamine on infants and children, larval zebrafish (a vertebrate model) were exposed to 0.18, 0.36 and 0.54 mM cysteamine from 72 hpf to 144 hpf. Alterations in general and pathological evaluation, biochemical parameters, cell proliferation, lipid metabolism factors, inflammatory factors and Wnt signaling pathway levels were examined. Increased liver area and lipid accumulation were observed in liver morphology, staining and histopathology in a dose-dependent manner with cysteamine exposure. In addition, the experimental cysteamine group exhibited higher alanine aminotransferase, aspartate aminotransferase, total triglyceride and total cholesterol levels than the control group. Meanwhile, the levels of lipogenesis-related factors ascended whereas lipid transport-related factors descended. Oxidative stress indicators such as reactive oxygen species, MDA and SOD were upregulated after cysteamine exposure. Afterwards, transcription assays revealed that biotinidase and Wnt pathway-related genes were upregulated in the exposed group, and inhibition of Wnt signaling partially rescued the abnormal liver development. The current study found that cysteamine-induced hepatotoxicity in larval zebrafish is due to inflammation and abnormal lipid metabolism, which is mediated by biotinidase (a potential pantetheinase isoenzyme) and Wnt signaling. This provides a perspective on the safety of cysteamine administration in children and identifies potential targets for protection against adverse reactions.
Subject(s)
Chemical and Drug Induced Liver Injury , Lipid Metabolism Disorders , Animals , Zebrafish/metabolism , Cysteamine/toxicity , Cysteamine/metabolism , Lipid Metabolism , Biotinidase/metabolism , Liver , Lipid Metabolism Disorders/metabolism , Lipid Metabolism Disorders/pathology , Oxidative Stress , Triglycerides/metabolism , Chemical and Drug Induced Liver Injury/pathologyABSTRACT
The increasing use of cosmetics has raised widespread concerns regarding their ingredients. Cysteamine hydrochloride (CSH) is a newly identified allergenic component in cosmetics, and therefore its potential toxicity needs further elucidation. Here, we investigated the in vivo toxicity of CSH during ocular development utilizing a zebrafish model. CSH exposure was linked to smaller eyes, increased vasculature of the fundus and decreased vessel diameter in zebrafish larvae. Moreover, CSH exposure accelerated the process of vascular sprouting and enhanced the proliferation of ocular vascular endothelial cells. Diminished behavior in response to visual stimuli and ocular structural damage in zebrafish larvae after CSH treatment were confirmed by analysis of the photo-visual motor response and pathological examination, respectively. Through transcriptional assays, transgenic fluorescence photography and molecular docking analysis, we determined that CSH inhibited Notch receptor transcription, leading to an aberrant proliferation of ocular vascular endothelial cells mediated by Vegf signaling activation. This process disrupted ocular homeostasis, and induced an inflammatory response with neutrophil accumulation, in addition to the generation of high levels of reactive oxygen species, which in turn promoted the occurrence of apoptotic cells in the eye and ultimately impaired ocular structure and visual function during zebrafish development.
Subject(s)
Cysteamine , Zebrafish , Animals , Cysteamine/toxicity , Endothelial Cells , Molecular Docking Simulation , Inflammation/chemically inducedABSTRACT
Hexafluoropropylene oxide trimer acid (HFPO-TA), a novel alternative to perfluorooctanoic acid (PFOA), has emerged as a potential environmental pollutant. Here, to investigate the toxic effects of HFPO-TA on liver and biliary system development, zebrafish embryos were exposed to 0, 50, 100, or 200 mg/L HFPO-TA from 6 to 120 h post-fertilization (hpf). Results showed that the 50 % lethal concentration (LC50) of HFPO-TA was 231 mg/L at 120 hpf, lower than that of PFOA. HFPO-TA exposure decreased embryonic hatching, survival, and body length. Furthermore, HFPO-TA exerted higher toxicity at the specification stage than during the differentiation and maturation stages, leading to small-sized livers in Tg(fabp10a: DsRed) transgenic larvae and histopathological changes. Significant decreases in the mRNA expression of genes related to liver formation were observed. Alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), and direct bilirubin (DBIL) levels were significantly increased. HFPO-TA decreased total cholesterol (TCHO) and triglyceride (TG) activities, disturbed lipid metabolism through the peroxisome proliferator-activated receptor (PPAR) pathway, and induced an inflammatory response. Furthermore, HFPO-TA inhibited intrahepatic biliary development in Tg(Tp1:eGFP) transgenic larvae and interfered with transcription of genes associated with biliary duct development. HFPO-TA reduced bile acid synthesis but increased bile acid transport, resulting in disruption of bile acid metabolism. Therefore, HFPO-TA influenced embryonic liver and biliary system morphogenesis, caused liver injury, and may be an unsafe alternative for PFOA.
Subject(s)
Biliary Tract , Fluorocarbons , Animals , Zebrafish , Fluorocarbons/toxicity , Liver , Bile Acids and SaltsABSTRACT
Ge/Si heterojunction light emitting diodes with 20-bilayers undoped or phosphorus in situ doped GeSi islands were fabricated on n(+)(-)Si(001) substrates by ultrahigh vacuum chemical vapor deposition (UHV-CVD). Enhanced room temperature photoluminescence (PL) and electroluminescence (EL) around 1.5 µm were observed from the devices with phosphorus-doped GeSi islands. Theoretical calculations indicated that the emission is from the radiative recombination in GeSi islands. The intensity enhancement of PL and EL is attributed to the sufficient supply of electrons in active layer for radiative recombination.
Subject(s)
Germanium/chemistry , Lighting/instrumentation , Phosphorus/chemistry , Semiconductors , Silicon/chemistry , Equipment Design , Equipment Failure Analysis , LuminescenceABSTRACT
BACKGROUND: The prevalence of diabetic retinopathy is not well studied in the Chinese pre-diabetic population, also known as impaired glucose regulation. Hence, we investigated the prevalence of and risk factors associated with retinopathy in diabetic and pre-diabetic subjects from Chinese communities. METHODS: A total of 3736 Chinese subjects were recruited from urban communities in Shanghai. The participants were classified as normal glucose tolerance, impaired glucose regulation (IGR) and diabetes based on the 75 g oral glucose tolerance test. The levels of diabetic retinopathy (DR) were assessed with non-mydriatic retinal photographs according to the Diabetic Retinopathy Disease Severity Scale. RESULTS: The prevalence of diabetic retinopathy in patients with diabetes and impaired glucose regulation subjects was 9.4% and 2.5%, respectively. In subjects with IGR, hypertension (odds ratio: 3.54, p = 0.028), including elevated systolic and diastolic blood pressure and obesity (odds ratio: 3.53, p = 0.028) were significantly associated with diabetic retinopathy after age and sex adjustments. The factors associated with retinopathy in diabetes included diabetes duration, blood glucose levels, glycated hemoglobin levels, and the presence of albuminuria. Diabetic retinopathy was significantly associated with fasting plasma glucose in known diabetes, whereas in newly-diagnosed subjects, diabetic neuropathy was closely correlated to postprandial plasma glucose. CONCLUSIONS: Hyperglycemia was a strong risk factor for diabetic retinopathy. In pre-diabetic subjects, diabetic retinopathy was also associated with hypertension and obesity.
Subject(s)
Blood Glucose/metabolism , Diabetic Retinopathy/epidemiology , Glucose Intolerance/complications , Hyperglycemia/complications , Hypertension/complications , Obesity/complications , Prediabetic State/complications , Adolescent , Adult , Aged , Aged, 80 and over , Albuminuria/complications , Asian People , China/epidemiology , Diabetes Complications/epidemiology , Female , Glucose Intolerance/epidemiology , Glycated Hemoglobin/metabolism , Humans , Male , Middle Aged , Prediabetic State/epidemiology , Prevalence , Risk FactorsABSTRACT
STUDY OBJECTIVES: We assessed the yearly seasonal, environmental effects on birth pattern in Chinese patients later diagnosed with narcolepsy and cataplexy and explored if this effect persisted in patients with symptoms onset date before, following, and after the 2009 H1N1 pandemic. METHODS: A total of 1,942 patients with birth data information and diagnosed narcolepsy with cataplexy were included in this study. The birth month and seasonal effect of 1,064 patients born from 1970 to 2000 were compared to controls (n = 2,028,714) from the general population. Furthermore, birth season effect in 1,373 patients with definite disease onset month were compared among patients with onset date before (n = 595), following (from January 2010 to December 2010) (n = 325), and after (n = 453) the H1N1 pandemic. RESULTS: Patients with narcolepsy and cataplexy had a significantly different seasonality from the general population (P = .027). The monthly distribution of birth month yielded a peak in November (odds ratio = 1.23 [95% confidence interval, 1.01-1.49], P = .042) and a trough in April (odds ratio = 0.68 [95% confidence interval, 0.52-0.88], P = .004). No significant difference was observed in the birth month across patients with symptom onset dates before, following, and after the 2009 H1N1 pandemic (P = .603). CONCLUSIONS: This finding across many years of seasonal effect in Chinese narcolepsy cataplexy supports a role for early-life environmental influences on disease development. CITATION: Guo J, Xu L, Wang J, et al. The month of birth has a seasonal effect in Chinese patients with narcolepsy and cataplexy. J Clin Sleep Med. 2022;18(2):461-467.