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"Qian, Christopher"
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Transferrin receptors
The transferrin receptor (TfR) is one of the key proteins involved in cellular iron uptake. TfR-mediated endocytosis of transferrin-bound iron is the major pathway for iron acquisition by most cells in the body. Over the past three decades, the studies on TfR have made significant progress, and also, our knowledge on cell iron uptake has greatly been improved. Here we focus on recent advances in the studies on TfR and a brief discussion of the structures and functions of four different types of TfR, namely TfR1 (transferrin receptor 1), TfR2 (transferrin receptor 2), TfR3 (glyceraldehyde-3-phosphate dehydrogenase) and TfR4 (cubilin). These proteins work in different cells or organs and at different times, ensuring that cells and tissues get the iron they need. Their normal expression and function are fundamental to the body’s iron homeostasis.
Exploring the role of transferrin receptors in cellular iron homeostasis
Iron metabolism disorders affect many people worldwide, making it crucial to understand how the body manages iron. Here the authors review research on transferrin receptors (TfRs), which are proteins that help cells take in iron. The study focuses on four types of TfR: TfR1, TfR2, TfR3 and TfR4. TfR1 is the main receptor for iron uptake in most cells, especially red blood cells. It binds to transferrin and helps transport iron into cells. TfR2 is similar to TfR1 but plays a role in regulating hepcidin, a hormone that controls iron levels in the body. TfR3 and TfR4 are less understood but involved in rapid iron uptake during stress and in kidney function. The research highlights the importance of these receptors in maintaining iron balance. Future research could lead to new treatments for disorders caused by abnormal iron metabolism.
This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.
Journal Article
Indoor PV Modeling Based on the One-Diode Model
The use of photovoltaic (PV) panels in interior spaces is expected to increase due to the proliferation of low-power sensor devices in the IoT domain. PV models are critical for estimating the I–V curves that define their performance at various light intensities. These models and the extraction of their parameters have been extensively studied under outdoor conditions, but their indoor illumination performance is less studied. With respect to the latter, several studies have used the parameter-scaling technique. However, the model’s accuracy degrades when the light level decreases. In this study, we propose a simple PV modeling technique that can be applied at various illuminance levels by only using characteristic points (short-circuit current, open-circuit voltage, and maximum-power voltage points) at a reference illumination level. The model uses the characteristic point translation technique to translate the reference characteristic points to other operating conditions. Then, parameter extraction technique is used to extract the model’s parameters. The proposed model’s accuracy is verified using two commercial PV panels and different indoor lighting technologies. The results indicate that the proposed model outperforms the other examined works in terms of accuracy, with an average improvement of 15.75%.
Journal Article
The Multifocal Pathway: A Pilot Study of a Trainee-Led Multifocal Intraocular Lens Protocol in a Tertiary Referral Hospital in Australia
To develop a selection pathway to facilitate the use of multifocal intraocular lenses (mfIOLs) in cataract surgery in a public hospital setting.
A single-surgeon prospective cohort study in an Australian tertiary referral public hospital was conducted. A mfIOL selection pathway was designed and assessed. Outcomes measured included unaided distance (UDVA), intermediate (UIVA) and near visual acuity (UNVA), dysphotopsia, spectacle dependence and satisfaction. Patient-reported outcome measures (PROMs) were assessed using Catquest-9SF (CQ) and Near Visual Acuity Questionnaire (NAVQ). A cost-analysis was performed.
Fifty-four eyes from 27 patients underwent cataract surgery with mfIOL implantation. The monocular UDVA (mean ± standard deviation) was 0.05 ± 0.12 logMAR; UIVA 0.19 ± 0.05 logMAR; UNVA 0.28 ± 0.14 logMAR; 87% and 98% of eyes achieved within 0.5D and 1.0D of target refraction respectively. Spectacle independence was 85% at distance, 81% at intermediate, 59% at near vision. High satisfaction was reported with CQ (>85%) and NAVQ (100%). The cost difference between bilateral monofocal and mfIOLs is comparable to a pair of spectacles. Projected annual cost to the health system for a 5%-10% eligibility rate is 1.1-2.3 million Australian dollars.
The selection pathway presented overcomes the challenges in patient selection inherent to a public hospital setting and was implemented by a senior trainee with excellent vision and PROMs. The pathway ensures the cost-effectiveness of mfOL implantation. There are several funding models that can be applied to support equitable access and improved visual outcomes with mfIOLs within the government funded health system.
Journal Article
A combination of serum iron, ferritin and transferrin predicts outcome in patients with intracerebral hemorrhage
Association of a high-serum ferritin with poor outcome showed that iron might play a detrimental role in the brain after intracerebral hemorrhage (ICH). Here, we investigated changes in serum iron, ferritin, transferrin (Tf) and ceruloplasmin (CP) in patients with ICH (n = 100) at day 1 (admission), 3, 7, 14 and 21 and those in control subjects (n = 75). The hematoma and edema volumes were also determined in ICH-patients on admission and at day 3. The Modified Rankin Scale (mRS) of 59 patients was ≥3 (poor outcome) and 41 < 3 (good outcome) at day 90. Serum ferritin was significantly higher and serum iron and Tf markedly lower in patients with poor-outcome than the corresponding values in patients with good-outcome at day 1 to 7 and those in the controls. There was a significant positive correlation between serum ferritin and relative edema volume or ratio at day 1 and 3 and hematoma volume at day 1 (n = 28), and a negative correlation between serum iron or Tf and hematoma volume at day 1 (n = 100). We concluded that not only increased serum ferritin but also reduced serum iron and Tf are associated with outcome as well as hematoma volume.
Journal Article
HMGB1 Mediates Inflammation-Induced DMT1 Increase and Dopaminergic Neurodegeneration in the Early Stage of Parkinsonism
Both neuroinflammation and iron accumulation play roles in the pathogenesis of Parkinson’s disease (PD). However, whether inflammation induces iron dyshomeostasis in dopaminergic neurons at an early stage of PD, at which no quantifiable dopaminergic neuron loss can be observed, is still unknown. As for the inflammation mediators, although several cytokines have been reported to increase in PD, the functions of these cytokines in the SN are double-edged and controversial. In this study, whether inflammation could induce iron dyshomeostasis in dopaminergic neurons through high mobility group protein B1 (HMGB1) in the early stage of PD is explored. Lipopolysaccharide (LPS), a toxin that primarily activates glia cells, and 6-hydroxydopamine (6-OHDA), the neurotoxin that firstly impacts dopaminergic neurons, were utilized to mimic PD in rats. We found a common and exceedingly early over-production of HMGB1, followed by an increase of divalent metal transporter 1 with iron responsive element (DMT1+) in the dopaminergic neurons before quantifiable neuronal loss. HMGB1 neutralizing antibody suppressed inflammation in the SN, DMT1+ elevation in dopaminergic neurons, and dopaminergic neuronal loss in both LPS and 6-OHDA administration- induced PD models. On the contrary, interleukin-1β inhibitor diacerein failed to suppress these outcomes induced by 6-OHDA. Our findings not only demonstrate that inflammation could be one of the causes of DMT1+ increase in dopaminergic neurons, but also highlight HMGB1 as a pivotal early mediator of inflammation-induced iron increase and subsequent neurodegeneration, thereby HMGB1 could serve as a potential target for early-stage PD treatment.
Journal Article
Cystathionine β-synthase (CBS) deficiency suppresses erythropoiesis by disrupting expression of heme biosynthetic enzymes and transporter
The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS
−/−
) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, including; two key enzymes involved in the heme biosynthetic pathway, ALAS2 (delta-aminolevulinate synthase 2) and FECH (ferrochelatase), a heme exporter from the cytosol and mitochondria, FLVCR (feline leukemia virus subgroup C cellular receptor) as well as EPO (erythropoietin), EPOR (erythropoietin receptor) and HIF-2α (hypoxia inducible factor-2 subunit α), in the blood, bone marrow or liver of CBS
−/−
(homozygous), CBS
+/−
(heterozygous) and CBS
+/+
(Wild Type) mice. Our findings demonstrate that CBS deficiency can induce a significant reduction in the expression of ALAS2, FECH, FLVCR, HIF-2α, EPO, and EPOR as well as an increase in interleukin-6 (IL-6), hepcidin and iron content in the blood, bone marrow or liver of mice. We conclude that the suppression of erythropoiesis is mainly due to the CBS deficiency-induced disruption in the expression of heme biosynthetic enzymes and heme-transporter.
Journal Article
Chromatoprobe as a sample-sparing technique for residual solvent analysis of drug discovery candidates by gas chromatography
In drug discovery research, residual solvent measurement is an integral part of purity analysis for synthesis of a drug candidate before it is used for toxicity testing. This is usually carried out using gas chromatography (GC)with direct injection sample introduction. This method requires testing compounds to be soluble at high concentrations ( > 50 mg/mL, usually in DMSO) to achieve acceptable sensitivity, a hurdle which is not always achievable for some samples such as cyclic peptides and oligonucleotides. To overcome the limitation associated with the direct injection approach, a new method using the Chromatoprobe thermal extraction device was developed for quantifying residual solvents of drug discovery compounds. This method not only consumes significantly less material (less than 1 mg), but also shows higher sensitivity than the direct injection approach.In addition, because no diluent is required with the Chromatoprobe thermal extraction, all residual solvents can be detected and measured without further method optimization. In our study, we compared data from GC residual solvent analysis using the Chromatoprobe solid sample introduction to those of the direct injection method for seven in-house samples. Our results showed a good agreement between the data from these two sample introduction methods. Thus, the Chromatoprobe sample introduction method provided a samplesparing alternative to the direct injection method for the measurement of residual solvents in drug discovery.This method can be particularly useful for residual solvent analysis in samples that are available only in limited amounts, poorly soluble, and/or unstable in the diluents used for the direct injection method.
Journal Article
Three-dimensional human facial morphologies as robust aging markers
Aging is associated with many complex diseases. Reliable prediction of the aging process is important for assessing the risks of aging-associated diseases. However, despite intense research, so far there is no reliable aging marker. Here we addressed this problem by examining whether human 3D facial imaging features could be used as reliable aging markers. We collected 〉 300 3D human facial images and blood profiles well-distributed across ages of 17 to 77 years. By analyzing the morphological profiles, we generated the first comprehensive map of the aging human facial phenome. We identified quantitative facial features, such as eye slopes, highly associated with age. We constructed a robust age predictor and found that on average people of the same chronological age differ by ~ 6 years in facial age, with the deviations increasing after age 40. Using this predictor, we identified slow and fast agers that are significantly supported by levels of health indicators. Despite a close relationship between facial morphological features and health indicators in the blood, facial features are more reliable aging biomarkers than blood profiles and can better reflect the general health status than chronological age.
Journal Article
The U.S. and China: curbing missile and nuclear weapons proliferation
On October 4, 1994, the United States and The People's Republic of China met to discuss nuclear non-proliferation. The two main topics of conversation were the export of missiles and the production of fissile material. Measures which will be taken by both countries to further non-proliferation are explained.
Journal Article