Publications by authors named "Hua-Chang Chen"

Photocatalytic hydrogen peroxide (HO) generation is largely subject to the sluggish conversion kinetics of the superoxide radical (O) intermediate, which has relatively low reactivity and requires high energy. Here, we present a lattice-strain strategy to accelerate the conversion of O to highly active singlet oxygen(O) by optimizing the distance between two adjacent active sites, thereby stimulating HO generation via low-barrier oxygen-oxygen coupling. As the initial demonstration, the defect-induced strain in ZnInS nanosheet optimizes the distance of two adjacent Zn sites from 3.

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Tenascin-C (TNC) is a secreted extracellular matrix protein that is highly expressed during embryonic development and re-expressed during wound healing, inflammation, and neoplasia. Studies in developmental models suggest that TNC may regulate the Wnt signaling pathway. Our lab has shown high levels of Wnt signaling and TNC expression in anaplastic thyroid cancer (ATC), a highly lethal cancer with an abysmal ~3-5 month median survival.

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  • This study examines how glucagon-like peptide 1 receptor agonists (GLP-1RAs) may help protect kidneys, in addition to aiding in weight loss and blood sugar control.
  • Researchers analyzed data from over 353,000 veterans to see if genetic variations related to GLP-1R gene expression were linked to kidney disease progression.
  • The findings indicated that higher levels of genetic GLP-1R expression were associated with a reduced risk of kidney disease progression, suggesting potential nephroprotective benefits of GLP-1RAs.
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Importance: Nicotinamide metabolites have recently been implicated in increased risk of major cardiovascular events (MACE). Supportive data about clinical risk of MACE for nicotinamide users is lacking.

Objective: To determine whether nicotinamide use results in an increase of MACE.

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Extracellular vesicles and particles (EVPs) play a crucial role in mediating cell-to-cell communication by transporting various molecular cargos, with small non-coding RNAs (ncRNAs) holding particular significance. A thorough investigation into the abundance and sorting mechanisms of ncRNA within EVPs is imperative for advancing their clinical applications. We have developed EVPsort, which not only provides an extensive overview of ncRNA profiling in 3,162 samples across various biofluids, cell lines, and disease contexts but also seamlessly integrates 19 external databases and tools.

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Adapter trimming is an essential step for analyzing small RNA sequencing data, where reads are generally longer than target RNAs ranging from 18 to 30 bp. Most adapter trimming tools require adapter information as input. However, adapter information is hard to access, specified incorrectly, or not provided with publicly available datasets, hampering their reproducibility and reusability.

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Importance: Clinical trial data have called into question the efficacy of thiazide diuretics for the prevention of kidney stones.

Objective: To identify whether there is an association between genetic proxies of thiazide diuretics and the risk of kidney stones.

Design, Setting, And Participants: This genetic association study undertook a mendelian randomization analysis of derived exposures and outcomes from genome-wide association study summary statistics.

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  • - A 26-year-old woman diagnosed with Diamond-Blackfan anemia (DBA) was referred to the Undiagnosed Diseases Network due to the lack of a specific genetic cause found for her condition.
  • - Her case was uniquely identified as being influenced by digenic interactions, specifically involving variations in two different genes (RPS19 and RPL27), rather than the typical single-gene mutations usually associated with DBA.
  • - The findings were supported by advanced techniques including machine learning models, co-segregation analysis, and RNA sequencing, highlighting that atypical presentations of DBA may arise from multiple gene interactions and not just single-gene effects.
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  • African Americans are more susceptible to chronic kidney disease (CKD) partly due to high-risk variants in the APOL1 gene, specifically G1/G2 variants, but a different variant, p.N264K, appears to lower this risk significantly.
  • A study of over 121,000 participants showed that those with the p.N264K variant had CKD and end-stage kidney disease (ESKD) risks comparable to individuals with low-risk APOL1 variants.
  • Research indicates that p.N264K blocks harmful pore-forming functions of APOL1 high-risk variants, suggesting that drugs mimicking this protective mutation could potentially prevent or treat kidney disease related to APOL1.
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Single-cell sequencing have been widely used to characterize cellular heterogeneity. Sample multiplexing where multiple samples are pooled together for single-cell experiments, attracts wide attention due to its benefits of increasing capacity, reducing costs, and minimizing batch effects. To analyze multiplexed data, the first crucial step is to demultiplex, the process of assigning cells to individual samples.

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  • Extracellular vesicles (EVs) are important for cell communication, carrying molecular cargo like proteins and small RNAs, but there's a lack of systematic analysis regarding their small RNA profiles across different conditions and cell types.
  • A study reanalyzed 2,756 small RNA sequencing samples from various studies to assess quality metrics, RNA composition, and the presence of different RNA biotypes in EVs versus donor cells.
  • Findings revealed variability in EV extraction methods affecting RNA composition, with certain RNA types (like rRNA and tRNA) being enriched while others (like miRNAs) were less abundant in EVs, suggesting that the methods used should be carefully selected for accurate analysis.
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  • Genetically predicted levels of IL-6 are linked to an increased risk of end-stage kidney disease (ESKD).
  • Modifying IL-6 levels through therapy may help lower this risk.
  • Understanding the relationship between IL-6 and ESKD could lead to new treatments for kidney disease.
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Introduction: Common variants in the gene are considered an evolutionary adaptation against urinary tract infections (UTIs) and have been implicated in kidney stone formation, chronic kidney disease (CKD), and hypertension. However, differences in variant-phenotype associations across population groups are unclear.

Methods: We tested associations between variants and up to 1528 clinical diagnosis codes mapped to phenotype groups in the Million Veteran Program (MVP), using published phenome-wide association study (PheWAS) methodology.

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Remdesivir is the first US Food and Drug Administration (FDA)-approved drug for the treatment of coronavirus disease 2019 (COVID-19). We conducted a retrospective pharmacogenetic study to examine remdesivir-associated liver enzyme elevation among Million Veteran Program participants hospitalized with COVID-19 between March 15, 2020, and June 30, 2021. Pharmacogene phenotypes were assigned using Stargazer.

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  • * Researchers identified significant associations between specific genetic variants near the RGS14 and CASR genes and levels of phosphate, calcium, and FGF23, with the variant rs4074995 showing the strongest effects.
  • * Findings indicate that the minor allele of rs4074995 correlates with lower phosphorus, lower FGF23 levels, and reduced hyperparathyroidism prevalence, along with decreased RGS14 gene expression in the kidneys; further research is needed to understand its role in CKD mineral metabolism.
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Importance: Coronavirus disease 2019 (COVID-19) confers significant risk of acute kidney injury (AKI). Patients with COVID-19 with AKI have high mortality rates.

Objective: Individuals with African ancestry with 2 copies of apolipoprotein L1 (APOL1) variants G1 or G2 (high-risk group) have significantly increased rates of kidney disease.

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The incidence and severity of sepsis is higher among individuals of African versus European ancestry. We found that genetic risk variants (RVs) in the trypanolytic factor apolipoprotein L1 (APOL1), present only in individuals of African ancestry, were associated with increased sepsis incidence and severity. Serum APOL1 levels correlated with sepsis and COVID-19 severity, and single-cell sequencing in human kidneys revealed high expression of APOL1 in endothelial cells.

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Prioritizing causal variants is one major challenge for the clinical application of sequencing data. Prompted by the observation that 74.3% of missense pathogenic variants locate in protein domains, we developed an approach named domain damage index (DDI).

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Introduction: The programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors, atezolizumab and durvalumab, have received regulatory approval for the first-line treatment of patients with extensive-stage SCLC. Nevertheless, when used in combination with platinum-based chemotherapy, these PD-L1 inhibitors only improve overall survival by 2 to 3 months. This may be due to the observation that less than 20% of SCLC tumors express PD-L1 at greater than 1%.

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Phosphoinositides (PIs) as regulatory membrane lipids play essential roles in multiple cellular processes. Although the exact molecular targets of PI-dependent modulation remain largely elusive, the effects of disturbed PI metabolism could be employed to identify regulatory modules associated with particular downstream targets of PIs. Here, we identified the role of (), which encodes a suppressor of actin (SAC) domain-containing phosphatase with unknown function in rice ().

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  • Global warming is reducing crop yields, making it urgent to develop heat-tolerant crops to combat this issue.
  • Researchers identified a significant genetic trait (TT1) in African rice that helps plants tolerate heat by degrading harmful proteins more effectively.
  • Enhancing the expression of this gene has shown promising results in improving thermotolerance in various plant species, potentially increasing crop security amid climate change challenges.
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