Publications by authors named "Yun Huang"

742 Publications

CaMKII inhibition protects against hyperthyroid arrhythmias and adverse myocardial remodeling.

Biochem Biophys Res Commun 2022 Apr 20;615:136-142. Epub 2022 Apr 20.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

Hyperthyroidism can potentiate arrhythmias and cardiac hypertrophy, whereas Ca/calmodulin-dependent kinase II (CaMKII) promotes maladaptive myocardial remodeling. However, it remains unclear whether CaMKII contributes to the progression of hyperthyroid heart disease (HHD). This study demonstrated that CaMKII inhibition can relieve adverse myocardial remodeling and reduce sinus tachycardia, isoproterenol-induced atrial fibrillation, and ventricular arrhythmias in hyperthyroid mice with preserved heart function. Hyperthyroid cardiac hypertrophy was promoted by CaMKII upregulation-induced HDAC4/MEF2a activation. Briefly, CaMKII inhibition benefits HHD management greatly in mice by preventing arrhythmias and maladaptive remodeling.
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http://dx.doi.org/10.1016/j.bbrc.2022.04.082DOI Listing
April 2022

Biobased carbon dots production via hydrothermal conversion of microalgae Chlorella pyrenoidosa.

Sci Total Environ 2022 May 21:156144. Epub 2022 May 21.

Key Laboratory of Low-grade Energy Utilization Technologies and Systems, Chongqing University, Ministry of Education, Chongqing 400044, China; Institute of Engineering Thermophysics, School of Energy and Power Engineering, Chongqing University, Chongqing 400044, China. Electronic address:

A promising green hydrothermal process was used to produce biobased nanomaterials carbon dots (CDs) by using microalgae Chlorella pyrenoidosa (CP) and its main model compounds (i.e., glucose, glycine, and octadecanoic acid). The possible reaction pathway including hydrolysis, Amadori rearrangement, cyclization/aromatization, and polymerization was first proposed for the hydrothermal process to produce microalgae-based CDs. Interactions among carbohydrates and proteins in microalgae were vital intermediate reactions in the generation of CDs. The mass yield of CDs reached 7.2% when the CP was hydrothermally treated with 20:1 of liquid-to-solid ratio at 230 °C for 6 h. It was confirmed that nitrogen, sulfur, phosphorous, and potassium were doped onto CP-based CDs (CD-CP) successfully without additional reagents or treatments. The CD-CP yield was 4.0-24.3 times higher than that of model compound-based CDs. Regarding morphology, CD-CP was constituted by many spherical nanoparticles smaller than 20 nm. These CDs emitted blue fluorescence under ultraviolet light, and the fluorescence quantum yield of CD-CP was 4.7-9.4 times higher than that of CP model compound-based CDs. Last, CD-CP displayed broad application prospects as a sensor for Fe detection in wastewater with high sensitivity.
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http://dx.doi.org/10.1016/j.scitotenv.2022.156144DOI Listing
May 2022

A novel magnet-driven rotary mixing aerator for carbon dioxide fixation and microalgae cultivation: focusing on bubble behavior and cultivation performance.

J Biotechnol 2022 May 20. Epub 2022 May 20.

Key Laboratory of Low-grade Energy Utilization Technologies and Systems, Chongqing University, Ministry of Education, Chongqing 400044, China; Institute of Engineering Thermophysics, School of Energy and Power Engineering, Chongqing University, Chongqing 400044, China.

A novel magnet-driven rotary mixing aerator (MDRMA) was proposed to reduce the diameter and rising rate of bubbles while improving CO mass transfer during microalgae growth in a column photobioreactor. Visualization results showed that the bubble number density increased significantly with the increasing rotation rate of MDRMA. As the rotation rate increased from 0 to 300 r min, the average bubble diameter decreased from 3.8mm to 2.0mm (47.4% reduction), while the corresponding average bubble rising rate decreased from 0.32ms to 0.22ms (31.3% reduction). Notably, when the rotation rate of MDRMA exceeded 300 r min, a significant number of microbubbles with diameters below 0.5mm were generated. When synthetic flue gas containing 12% CO (v/v) was supplied for microalgae cultivation, a maximum biomass concentration of 1.75gL was obtained with rotating MDRMA at 200 r min, showing a 57.7% increase compared to the control aerated with a silicone tube aerator. Meanwhile, the pigment content reached 14.48mgL, 22.7% higher than that of the control.
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http://dx.doi.org/10.1016/j.jbiotec.2022.05.007DOI Listing
May 2022

Effect of lncRNA MALAT1 on the Granulosa Cell Proliferation and Pregnancy Outcome in Patients With PCOS.

Front Endocrinol (Lausanne) 2022 27;13:825431. Epub 2022 Apr 27.

Key Laboratory of Reproductive Genetics, Ministry of Education, Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Follicle arrest is one of the main characteristics of polycystic ovary syndrome (PCOS), the most common endocrinological disorder in reproductive-aged women. Increasing evidence proves that high anti-Mullerian hormone (AMH) levels may play an important role in follicular development. Long noncoding RNA (lncRNA) with a length of more than 200 nt is widely involved in the directional differentiation, growth, and development of cells, whereas whether lncRNA is involved in AMH's role in follicular development is unknown. In this study, we analyzed lncRNA expression in ovarian granulosa cells (GCs) collected from women with and without PCOS high-throughput sequencing. The results showed that a total of 79 noncoding transcripts were differently expressed in GCs of PCOS patients, including upregulated lncRNA MALAT1. The upregulation of MALAT1 was further confirmed by RT-qPCR in GCs from a larger cohort of PCOS patients. Furthermore, knockdown MALAT1 can promote the proliferation of KGN cell . These data suggested a role for MALAT1 in the development of PCOS. Meanwhile, MALAT1 and phosphorylated SMAD 1/5 (Ser463/465) protein were upregulated in KGN cells after exogenous AMH stimulation, which identified AMH perhaps as a regulator for the expression of MALAT1. We also found that MALAT1 can predict clinical pregnancy outcome to a certain extent by ROC curve analysis (area: 0.771,  = 0.007, 95% CI: 0.617-0.925, sensitivity: 57.1%, specificity: 91.7%). Thus, our findings revealed a role of lncRNA MALAT1 in inhibiting granulosa cell proliferation and may be correlated with pregnancy outcome in PCOS.
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http://dx.doi.org/10.3389/fendo.2022.825431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9094420PMC
May 2022

The disordered N-terminal domain of DNMT3A recognizes H2AK119ub and is required for postnatal development.

Nat Genet 2022 May 9;54(5):625-636. Epub 2022 May 9.

Molecular and Cellular Biology Department, Stem Cells and Regenerative Medicine Center, Baylor College of Medicine, Houston, TX, USA.

DNA methyltransferase 3a (DNMT3A) plays a crucial role during mammalian development. Two isoforms of DNMT3A are differentially expressed from stem cells to somatic tissues, but their individual functions remain largely uncharacterized. Here we report that the long isoform DNMT3A1, but not the short DNMT3A2, is essential for mouse postnatal development. DNMT3A1 binds to and regulates bivalent neurodevelopmental genes in the brain. Strikingly, Dnmt3a1 knockout perinatal lethality could be partially rescued by DNMT3A1 restoration in the nervous system. We further show that the intrinsically disordered N terminus of DNMT3A1 is required for normal development and DNA methylation at DNMT3A1-enriched regions. Mechanistically, a ubiquitin-interacting motif embedded in a putative α-helix within the N terminus binds to mono-ubiquitinated histone H2AK119, probably mediating recruitment of DNMT3A1 to Polycomb-regulated regions. These data demonstrate an isoform-specific role for DNMT3A1 in mouse postnatal development and reveal the N terminus as a necessary regulatory domain for DNMT3A1 chromatin occupancy and functions in the nervous system.
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http://dx.doi.org/10.1038/s41588-022-01063-6DOI Listing
May 2022

Nomogram to predict the risk of endoscopic removal failure with forceps/baskets for treating submandibular stones.

World J Clin Cases 2022 Mar;10(9):2710-2720

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-Sen University, Guangzhou 510055, Guangdong Province, China.

Background: Endoscopic removal with forceps/baskets is favored in treating submandibular stones due to its minimal invasiveness. However, recent studies have found that endoscopic removal failure (ERF) is not unusual, and stones in such cases still need to be removed with other surgical methods. If the risk of ERF can be predicted preoperatively, it could be helpful for surgeons when choosing the appropriate therapy.

Aim: To develop a predictive nomogram for the risk of ERF when treating submandibular stones based on their preoperative clinical features.

Methods: A total of 180 patients with 211 submandibular stones treated from January 2012 to December 2020 were included in the current study. Based on the preoperative clinical features of the stones, independent risk factors for ERF were identified by logistic regression analysis. The stones were then randomly divided into training and testing sets. A nomogram was constructed to predict the risk of ERF using the training set and then validated using both sets. The predictive performance of the nomogram was assessed by calibration curves and the concordance index (C-index).

Results: Three independent predictors, location ( = 0.040), transverse diameter ( < 0.001) and longitudinal diameter ( < 0.001) measured on the cone beam computed tomography (CBCT) images of the submandibular stones, were identified and included in the predictive nomogram. Calibration curves of the nomogram showed good agreement between the predicted and observed probabilities in both sets. The C-index in the training set was 0.917 (95%CI, 0.875-0.959) and that in the testing set was 0.925 (95%CI, 0.862-0.989).

Conclusion: A nomogram based on the location, transverse and longitudinal diameters on CBCT images of submandibular stones showed satisfactory efficacy in predicting the risk of ERF preoperatively when treating submandibular stones.
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http://dx.doi.org/10.12998/wjcc.v10.i9.2710DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8968823PMC
March 2022

Identification of cis-acting elements in response to fenvalerate in the CYP6B7 promoter of Helicoverpa armigera.

Pestic Biochem Physiol 2022 May 23;183:105060. Epub 2022 Feb 23.

Innovation Center of Pesticide Research, Department of Applied Chemistry, College of Science, China Agricultural University, Beijing 100193, China. Electronic address:

Cytochrome P450-mediated detoxification plays an important role in the development of insecticide resistance. Previous studies have shown that cytochrome P450 CYP6B7 was induced by fenvalerate and involved in fenvalerate detoxification in Helicoverpa armigera. However, the transcriptional regulation of CYP6B7 induced by fenvalerate remains unclear. Here, a series of progressive 5' deletions of CYP6B7 promoter reporter genes were constructed, and the relative luciferase activities were detected. The results revealed that the relative luciferase activity of plasmid p (-655/-1) was significantly induced by fenvalerate. Further deletion of the region between -655 and -486 bp showed that the highest luciferase activity induced by fenvalerate was observed in plasmid p (-528/-1), while p (-485/-1) had the lowest fenvalerate-induced luciferase activity. Moreover, internal deletion and mutation in the region between -508 and -486 bp resulted in a significant reduction in fenvalerate-induced CYP6B7 promoter activity, suggesting that the cis-acting element responsible for fenvalerate in the CYP6B7 promoter was located between -508 and -486 bp. These results promote an understanding of the expression regulation mechanism of P450 genes that conferring resistance to insecticides.
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http://dx.doi.org/10.1016/j.pestbp.2022.105060DOI Listing
May 2022

ENKUR expression induced by chemically synthesized cinobufotalin suppresses malignant activities of hepatocellular carcinoma by modulating β-catenin/c-Jun/MYH9/USP7/c-Myc axis.

Int J Biol Sci 2022 21;18(6):2553-2567. Epub 2022 Mar 21.

Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510315, China.

ENKUR plays a crucial role in lung and colorectal cancers. Chemically synthesized cinobufotalin (CB) showed its significant anti-cancer effect in nasopharyngeal carcinoma. However, the roles of ENKUR and CB along with their correlation are still unknown in hepatocellular carcinoma (HCC). In this study, ENKUR expression in HCC tissue and cells were detected. The relationship between ENKUR expression and clinical pathology was also assessed. and experiments were conducted to explore the effects and molecular basis of ENKUR and CB in HCC. ENKUR expression was correlated with HCC progression and patient prognosis. Furthermore, ENKUR could inhibit tumor proliferation, metastasis, and sorafenib resistance in HCC. Mechanistic studies showed that ENKUR or its Enkurin domain could bind to MYH9 and decrease its expression by binding to β-catenin and inhibiting its nuclear transfer, thus decreasing c-Jun level. Low expression of MYH9 suppressed recruitment of deubiquitination enzyme USP7, promoting degradation of the c-Myc. Therefore, cell cycle and EMT signals were suppressed. CB as a safe and effective anti-cancer compound up-regulates the expression of ENKUR via inhibiting PI3K/AKT/c-Jun-mediated transcription suppression. These findings show that ENKUR induced by CB antagonizes β-catenin/c-Jun/MYH9/USP7 pathway, thus increasing c-Myc ubiquitin degradation and finally suppressing cell cycle and EMT signals.
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http://dx.doi.org/10.7150/ijbs.67476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990461PMC
April 2022

α-Synuclein arginylation in the human brain.

Transl Neurodegener 2022 04 8;11(1):20. Epub 2022 Apr 8.

Department of Biomedical Sciences, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, 19104, USA.

Background: Alpha-synuclein (α-syn) exhibits pathological misfolding in many human neurodegenerative disorders. We previously showed that α-syn is arginylated in the mouse brain and that lack of arginylation leads to neurodegeneration in mice.

Methods: Here, we tested α-syn arginylation in human brain pathology using newly derived antibodies in combination with Western blotting, biochemical assays, and experiments in live neurons.

Results: We found that α-syn was arginylated in the human brain on E46 and E83, two sites previously implicated in α-syn pathology and familial cases of Parkinson's disease. The levels of arginylation in different brain samples ranged between ~ 3% and ~ 50% of the total α-syn pool, and this arginylation nearly exclusively concentrated in the subcellular α-syn fraction that sedimented at low centrifugation speeds and appeared to be simultaneously targeted by multiple posttranslational modifications. Arginylated α-syn was less susceptible to S129 phosphorylation and pathological aggregation in neurons. The arginylation level inversely correlated with the overall α-syn levels and with patient age, suggesting a possible causal relationship between arginylation decline and α-syn-dependent neuropathology.

Conclusion: We propose that α-syn arginylation constitutes a potential neuroprotective mechanism that prevents its abnormal accumulation during neurodegeneration and aging in the human brain.
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http://dx.doi.org/10.1186/s40035-022-00295-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8991655PMC
April 2022

Acute respiratory infections in children, before and after the COVID-19 pandemic, a sentinel study.

J Infect 2022 Apr 5. Epub 2022 Apr 5.

Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China; Shanghai public health clinical center, Fudan University, Shanghai, 201508, China. Electronic address:

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http://dx.doi.org/10.1016/j.jinf.2022.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8979835PMC
April 2022

Red-shifted optogenetics comes to the spotlight.

Clin Transl Med 2022 04;12(4):e807

Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, Texas, USA.

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http://dx.doi.org/10.1002/ctm2.807DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8989019PMC
April 2022

Investigation on the Thermal Characteristics of Enhancement-Mode p-GaN HEMT Device on Si Substrate Using Thermoreflectance Microscopy.

Micromachines (Basel) 2022 Mar 18;13(3). Epub 2022 Mar 18.

Science and Technology on Reliability Physics and Application of Electronic Component Laboratory, China Electronic Product Reliability and Environmental Testing Research Institute, Guangzhou 510610, China.

In this paper, thermoreflectance microscopy was used to measure the high spatial resolution temperature distribution of the p-GaN HEMT under high power density. The maximum temperature along the GaN channel was located at the drain-side gate edge region. It was found that the thermal resistance () of the p-GaN HEMT device increased with the increase of channel temperature. The dependence on the temperature was well approximated by a function of ~ (a = 0.2). The three phonon Umklapp scattering, point mass defects and dislocations scattering mechanisms are suggested contributors to the heat transfer process for the p-GaN HEMT. The impact of bias conditions and gate length on the thermal characteristics of the device was investigated. The behaviour of temperature increasing in the time domain with 50 µs pulse width and different drain bias voltage was analysed. Finally, a field plate structure was demonstrated for improving the device thermal performance.
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http://dx.doi.org/10.3390/mi13030466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8952125PMC
March 2022

A Bayesian Network to Predict the Risk of Post Influenza Vaccination Guillain-Barré Syndrome: Development and Validation Study.

JMIR Public Health Surveill 2022 Mar 25;8(3):e25658. Epub 2022 Mar 25.

Department of Medical Statistics, Sun Yat-Sen University, Guangzhou, China.

Background: Identifying the key factors of Guillain-Barré syndrome (GBS) and predicting its occurrence are vital for improving the prognosis of patients with GBS. However, there are scarcely any publications on a forewarning model of GBS. A Bayesian network (BN) model, which is known to be an accurate, interpretable, and interaction-sensitive graph model in many similar domains, is worth trying in GBS risk prediction.

Objective: The aim of this study is to determine the most significant factors of GBS and further develop and validate a BN model for predicting GBS risk.

Methods: Large-scale influenza vaccine postmarketing surveillance data, including 79,165 US (obtained from the Vaccine Adverse Event Reporting System between 1990 and 2017) and 12,495 European (obtained from the EudraVigilance system between 2003 and 2016) adverse events (AEs) reports, were extracted for model development and validation. GBS, age, gender, and the top 50 prevalent AEs were included for initial BN construction using the R package bnlearn.

Results: Age, gender, and 10 AEs were identified as the most significant factors of GBS. The posttest probability of GBS suggested that male vaccinees aged 50-64 years and without erythema should be on the alert or be warned by clinicians about an increased risk of GBS, especially when they also experience symptoms of asthenia, hypesthesia, muscular weakness, or paresthesia. The established BN model achieved an area under the receiver operating characteristic curve of 0.866 (95% CI 0.865-0.867), sensitivity of 0.752 (95% CI 0.749-0.756), specificity of 0.882 (95% CI 0.879-0.885), and accuracy of 0.882 (95% CI 0.879-0.884) for predicting GBS risk during the internal validation and obtained values of 0.829, 0.673, 0.854, and 0.843 for area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy, respectively, during the external validation.

Conclusions: The findings of this study illustrated that a BN model can effectively identify the most significant factors of GBS, improve understanding of the complex interactions among different postvaccination symptoms through its graphical representation, and accurately predict the risk of GBS. The established BN model could further assist clinical decision-making by providing an estimated risk of GBS for a specific vaccinee or be developed into an open-access platform for vaccinees' self-monitoring.
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http://dx.doi.org/10.2196/25658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8994148PMC
March 2022

VPS28 regulates brain vasculature by controlling neuronal VEGF trafficking through extracellular vesicle secretion.

iScience 2022 Apr 9;25(4):104042. Epub 2022 Mar 9.

Department of Neurosurgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, 1111 XianXia Road, Shanghai 20033, China.

Extracellular vesicles (EVs) participate in intercellular communication and contribute to the angiogenesis. However, the understanding of the mechanisms underlying EVs secretion by neurons and their action on the vascular system of the central nervous system (CNS) remain rudimentary. Here, we show that vacuolar protein sorting 28 (Vps28) is essential for the sprouting of brain central arteries (CtAs) and for the integrity of blood-brain barrier (BBB) in zebrafish. Disruption of neuron-enriched Vps28 significantly decreased EVs secretion by regulating the formation of intracellular multivesicular bodies (MVBs). EVs derived from zebrafish embryos or mouse cortical neurons partially rescued the brain vasculature defect and brain leakage. Further investigations revealed that neuronal EVs containing vascular endothelial growth factor A (VEGF-A) are key regulators in neurovascular communication. Our results indicate that Vps28 acts as an intercellular endosomal regulator mediating the secretion of neuronal EVs, which in turn communicate with endothelial cells to mediate angiogenesis through VEGF-A trafficking.
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http://dx.doi.org/10.1016/j.isci.2022.104042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8938284PMC
April 2022

Optical control of protein delivery and partitioning in the nucleolus.

Nucleic Acids Res 2022 Mar 23. Epub 2022 Mar 23.

Center for Translational Cancer Research, Institute of Biosciences and Technology, Texas A&M University, Houston, TX 77030, USA.

The nucleolus is a subnuclear membraneless compartment intimately involved in ribosomal RNA synthesis, ribosome biogenesis and stress response. Multiple optogenetic devices have been developed to manipulate nuclear protein import and export, but molecular tools tailored for remote control over selective targeting or partitioning of cargo proteins into subnuclear compartments capable of phase separation are still limited. Here, we report a set of single-component photoinducible nucleolus-targeting tools, designated pNUTs, to enable rapid and reversible nucleoplasm-to-nucleolus shuttling, with the half-lives ranging from milliseconds to minutes. pNUTs allow both global protein infiltration into nucleoli and local delivery of cargoes into the outermost layer of the nucleolus, the granular component. When coupled with the amyotrophic lateral sclerosis (ALS)-associated C9ORF72 proline/arginine-rich dipeptide repeats, pNUTs allow us to photomanipulate poly-proline-arginine nucleolar localization, perturb nucleolar protein nucleophosmin 1 and suppress nascent protein synthesis. pNUTs thus expand the optogenetic toolbox by permitting light-controllable interrogation of nucleolar functions and precise induction of ALS-associated toxicity in cellular models.
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http://dx.doi.org/10.1093/nar/gkac191DOI Listing
March 2022

Ten-Eleven Translocation Ablation Impairs Cardiac Differentiation of Mouse Embryonic Stem Cells.

Stem Cells 2022 Mar;40(3):260-272

Center for Epigenetics & Disease Prevention, Institute of Biosciences and Technology, Texas A&M University, Houston, TX, USA.

Ten-eleven Translocation (TET) dioxygenases mediated DNA methylation oxidation plays an important role in regulating the embryonic stem cells (ESCs) differentiation. Herein, we utilized a CRISPR/Cas9 based genome editing method to generate single, double, and triple Tet-deficient mouse ESCs (mESCs) and differentiated these cells toward cardiac progenitors. By using emerald green fluorescent protein (GFP; emGFP) expression under the control of Nkx2.5 promoter as marker for cardiac progenitor cells, we discovered that Tet1 and Tet2 depletion significantly impaired mESC-to-cardiac progenitor differentiation. Single-cell RNA-seq analysis further revealed that Tet deletion resulted in the accumulation of mesoderm progenitors to hamper cardiac differentiation. Re-expression of the Tet1 catalytic domain (Tet1CD) rescued the differentiation defect in Tet-triple knockout mESCs. Dead Cas9 (dCas9)-Tet1CD mediated loci-specific epigenome editing at the Hand1 loci validated the direct involvement of Tet-mediated epigenetic modifications in transcriptional regulation during cardiac differentiation. Our study establishes that Tet-mediated epigenetic remodeling is essential for maintaining proper transcriptional outputs to safeguard mESC-to-cardiac progenitor differentiation.
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http://dx.doi.org/10.1093/stmcls/sxab017DOI Listing
March 2022

Mn Ions Capture and Uniform Composite Electrodes with PEI Aqueous Binder for Advanced LiMnO-Based Battery.

ACS Appl Mater Interfaces 2022 Mar 16;14(12):14226-14234. Epub 2022 Mar 16.

School of New Energy and Materials, Southwest Petroleum University, Chengdu, 610500, China.

The electrode deterioration and capacity decay caused by the dissolution of transition metal ions have been criticized for a long time. The branched polyethyleneimine (PEI) was employed as a functional binder for spinel lithium manganese oxide (LiMnO, LMO) and layer structure lithium cobalt oxide (LiCoO, LCO) to resolve the problem. Due to the chelation reaction of amine groups, PEI polymer binder can effectively absorb soluble transition metal ions, which is beneficial to reduce the loss of active materials. For PEI-based cathode, the uniform distribution of key components is achieved by the rapid curing process of water, which endow PEI-based cathode with a higher Li diffusion coefficient and improved electrochemical reaction kinetics. In addition, the fixed binder coating is favorable to protecting the active materials from parasitic reaction with the lithium hexafluorophosphate (LiPF)-based electrolyte. Therefore, the PEI-based cell shows superior rate capability and long-term cycle performance. Functional binders of this study provide a simple and effective strategy to achieve higher capacity and longer cycle stability for transition metal oxide electrodes.
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http://dx.doi.org/10.1021/acsami.2c00392DOI Listing
March 2022

Age-Dependent Metabolomic Profile of the Follicular Fluids From Women Undergoing Assisted Reproductive Technology Treatment.

Front Endocrinol (Lausanne) 2022 16;13:818888. Epub 2022 Feb 16.

Key Laboratory of Reproductive Genetics (Ministry of Education) and Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Female fertility declines with age, and this natural variation culminates in reproductive senescence. Human follicular fluids are rich in low-molecular weight metabolites which are responsible for the maturation of oocytes. The metabolomic approaches are powerful tools to study biochemical markers of oocyte quality in the follicular fluids. It is necessary to identify and quantify the reliable metabolites in follicular fluids reflecting oocyte developmental potential. The goal of this study is to conduct a metabolomic analysis of the follicular fluids in women of different ages and study the metabolomic profile of the follicular fluids in relationship with oocyte quality in assisted reproductive technology (ART) treatment. A total of 30 women seeking for ART treatment at the Women's Hospital, Zhejiang University School of Medicine from October 2014 to April 2015 were recruited for the present study. Fifteen women aged from 39 to 47 were grouped as advanced maternal age, and the other 15 women aged from 27 to 34, as young controls. Ovarian stimulation and oocyte retrieval were conducted using a regular protocol involving mid-luteal pituitary down-regulation and controlled ovarian stimulation. Follicular fluids from mature follicles were collected and centrifuged for analyses. Liquid Chromatography-Mass Spectrometry (LC-MS) and Gas Chromatography-Mass Spectroscopy (GC-MS) were used to perform the quantitative metabolomic analysis. The follicular fluid levels of 311 metabolites and the metabolic significance were assessed. 70 metabolites showed significant differences between women with young and advanced ages. Follicular fluids from women with advanced age showed significantly higher levels of creatine, histidine, methionine, trans-4-hydroxyproline, choline, mevalonate, N2,N2-dimethylguanosine and gamma-glutamylvaline, as compared to those from the young age group. 8 metabolites were found significantly correlated with maternal age positively. Moreover, 3 metabolites were correlated with the number of oocytes retrieved, and 5 metabolites were correlated with cleaved embryo numbers, both negatively. The follicular fluids from women undergoing ART treatment exhibited age-dependent metabolomic profile. Metabolites associated with oocyte quality were identified, suggesting them as potential biomarkers for oocyte maturation and ART outcomes.
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http://dx.doi.org/10.3389/fendo.2022.818888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888916PMC
April 2022

[Preparation of modified rosin bonded silica high performance liquid chromatographic stationary phase and separation of Panax notoginseng saponins].

Se Pu 2022 Mar;40(3):234-241

Key Laboratory of Chemistry and Engineering of Forest Products, State Ethnic Affairs Commission, Guangxi Key Laboratory of Chemistry and Engineering of Forest Products, Guangxi Collaborative Innovation Center for Chemistry and Engineering of Forest Products, College of Chemistry and Chemical Engineering, Guangxi University for Nationalities, Nanning 530006, China.

The sanqi is the dried root of Panax notoginseng (Burk.) F. H. Chen. The main components responsible for the drug actions of sanqi are notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1, and ginsenoside Rd, which account for about 80% of the saponin content in sanqi. It is widely used in the treatment of anemia, coronary heart disease, hypertension, stroke sequelae, and other diseases. However, sanqi has many chemical components with complex and similar structures, which are difficult to separate. In this study, alkylated silica gel bonded with hydrogenated rosin hydroxyethyl acrylate (HRHA) was prepared via mercapto-ene click chemistry. A new type of modified rosin-bonded silica stationary phase ([email protected]) for high performance liquid chromatography was prepared for the separation of five saponins (R1, Rg1, Re, Rb1, and Rd). It was characterized by thermogravimetric analysis, Fourier-transform infrared spectroscopy, specific surface area and microporous physical adsorption and elemental analysis. The results showed that [email protected] had a regular spherical shape with porous surfaces, along with a specific surface area of 308.55 m/g and an average pore diameter of 6.78 nm. Performance evaluation of the column revealed that the [email protected] column showed typical reversed-phase chromatographic behavior with better flowability and reproducibility. Results of the Tanaka test showed that [email protected] column had good stereoselectivity and hydrogen bond capacity. Compared to other stationary phases, e. g. silica modified with acrylopimaric acid (16-hydroxyethyl-34-hydroxyethyl acrylate) ester (AAE) and dihydroterpineol (DTP), which were prepared in our laboratory at the same time, the [email protected] column demonstrated better resolution (R) for the separation of the five saponins under optimal chromatographic conditions. The R values for R1, Rg1, Re, Rb1, and Rd were 3.33, 3.54, 20.17 and 9.72, respectively on the [email protected] column. R between Rg1 and Re was also better than that obtained on a C18 column. Panax notoginseng saponins were separated on the [email protected] column using acetonitrile and water as the mobile phases at the flow rate of 1.0 mL/min at 25 ℃. The optimal UV detection wavelength was 203 nm. It was found that the five saponins could be separated better using the [email protected] column than the [email protected] and [email protected] columns. Because the ternary phenanthrene skeleton of the rosin group in [email protected] had structural similarity and good stereoselectivity to the polycyclic compounds (Panax notoginseng saponins). In addition, according to the hydrophobicity evaluation, the [email protected] column showed the best hydrophobicity among the three columns, which may be conducive to the separation of the five saponins. Thus, this study can provide a new avenue for the separation and purification of Panax notoginseng saponins from actual samples.
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http://dx.doi.org/10.3724/SP.J.1123.2021.07008DOI Listing
March 2022

Exploring the Potential Pharmacological Mechanism of Hesperidin and Glucosyl Hesperidin against COVID-19 Based on Bioinformatics Analyses and Antiviral Assays.

Am J Chin Med 2022 2;50(2):351-369. Epub 2022 Mar 2.

Department of Respirology & Allergy, Third Affiliated Hospital of Shenzhen University, Shenzhen 518020, P. R. China.

The development of anti-COVID-19 drugs has become the top priority since the outbreak of the epidemic, and Traditional Chinese medicine plays an important role in reducing mortality. Here, hesperidin and its glycosylation product, glucosyl hesperidin were selected to determine their antiviral activity against SARS-CoV-2 due to their structural specificity as reported. To be specific, their binding ability with ACE2, M, S, RBD and N proteins were verified with both and wet lab methods, i.e., molecular docking and binding affinity tests, including biolayer interferometry assay (BLI) and isothermal titration calorimetry assay (ITC). Moreover, systematic pharmacological analysis was conducted to reveal their pharmacological mechanism in treating COVID-19. Finally, their antiviral activity against SARS-CoV-2 was determined in a biosafety level 3 (BSL3) laboratory. The results demonstrated their outstanding binding affinity with ACE2, M, S and RBD proteins, while showed barely unobserved binding with N protein, indicating their key roles in influencing the invasion and early replication phase of SARS-CoV-2. In addition, both hesperidin and glucosyl hesperidin were shown to have a great impact on immune, inflammation and virus infection induced by COVID-19 according to the systematic pharmacological analysis. Moreover, the IC50s of hesperidin and glucosyl hesperidin against SARS-CoV-2 were further determined (51.5 [Formula: see text]M and 5.5 mM, respectively) with cell-based assay, suggesting their great anti-SARS-CoV-2 activity. All in all, present research was the first to verify the binding ability of hesperidin and glucosyl hesperidin with SARS-CoV-2 proteins with both and wet-lab methods and proposed the possibility of applying hesperidin and glucosyl hesperidin to treat COVID-19.
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http://dx.doi.org/10.1142/S0192415X22500148DOI Listing
March 2022

Ca/calmodulin-dependent protein kinase II inhibition reduces myocardial fatty acid uptake and oxidation after myocardial infarction.

Biochim Biophys Acta Mol Cell Biol Lipids 2022 06 26;1867(6):159120. Epub 2022 Feb 26.

Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022,China. Electronic address:

An AMP-activated kinase (AMPK) signaling pathway is activated during myocardial ischemia and promotes cardiac fatty acid (FA) uptake and oxidation. Similarly, the multifunctional Ca/calmodulin-dependent protein kinase II (CaMKII) is also triggered by myocardial ischemia, but its function in FA metabolism remains unclear. Here, we explored the role of CaMKII in FA metabolism during myocardial ischemia by investigating the effects of cardiac CaMKII on AMPK-acetyl-CoA carboxylase (ACC), malonyl CoA decarboxylase (MCD), and FA translocase cluster of differentiation 36 (FAT/CD36), as well as cardiac FA uptake and oxidation. Moreover, we tested whether CaMKII and AMPK are binding partners. We demonstrated that diseased hearts from patients with terminal ischemic heart disease displayed increased phosphorylation of CaMKII, AMPK, and ACC and increased expression of MCD and FAT/CD36. AC3-I mice, which have a genetic myocardial inhibition of CaMKII, had reduced gene expression of cardiac AMPK. In post-MI (myocardial infarction) AC3-I hearts, AMPK-ACC phosphorylation, MCD and FAT/CD36 levels, cardiac FA uptake, and FA oxidation were significantly decreased. Notably, we demonstrated that CaMKII interacted with AMPK α1 and α2 subunits in the heart. Additionally, AC3-I mice displayed significantly less cardiac hypertrophy and apoptosis 2 weeks post-MI. Overall, these findings reveal a unique role for CaMKII inhibition in repressing FA metabolism by interacting with AMPK signaling pathways, which may represent a novel mechanism in ischemic heart disease.
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http://dx.doi.org/10.1016/j.bbalip.2022.159120DOI Listing
June 2022

How Interfacial Properties Affect Adhesion: An Analysis from the Interactions between Microalgal Cells and Solid Substrates.

Langmuir 2022 03 1;38(10):3284-3296. Epub 2022 Mar 1.

Key Laboratory of Low-Grade Energy Utilization Technologies and Systems, Chongqing University, Ministry of Education, Chongqing 400044, China.

Microalgal biofilm, a stable community of many algal cells attached to a solid substrate, plays a significant role in the efficient accumulation of renewable energy feedstocks, wastewater treatment, and carbon reduction. The adhesion tendency of microalgal cells on solid substrates is the basis for controlling the formation and development of microalgal biofilm. To promote the adhesion of microalgal cells on solid substrates, it is necessary to clarify which surface properties have to be changed in the most critical factors affecting the adhesion. However, there have been few systematic discussions on what surface properties influence the adhesion tendency of algal cells on solid substrates. In this study, the essential principle of microalgal cell adhesion onto solid substrates was explored from the perspective of the interaction energy between microalgal cells and solid substrates. The influence of surface properties between microalgal cells and solid substrates on interaction energies was discussed via extended Derjaguin-Landau-Verwey-Overbeek (eDLVO) theory and a sensitivity analysis. The results showed that surface properties, including surface potential (ξ) and surface free energy components, significantly affect the adhesion tendency of microalgal cells on different solid substrates. When the solid surface possesses positive charges (ξ > 0), reducing ξ or the electron donor components of the solid substrate (γ) is an effective measure to promote microalgal cell adhesion onto the solid substrate. When the solid surface possesses negative charges (ξ < 0), an increase in either γ or the absolute value of ξ should be avoided in the process of microalgae adhesion. Overall, this research provides a direction for the selection of solid substrates and a direction for surface modification to facilitate the adhesion tendency of microalgal cells on solid substrates under different scenarios.
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http://dx.doi.org/10.1021/acs.langmuir.2c00042DOI Listing
March 2022

Photo-Reduction with NIR Light of Nucleus-Targeting Pt Nanoparticles for Combined Tumor-Targeted Chemotherapy and Photodynamic Immunotherapy.

Angew Chem Int Ed Engl 2022 May 16;61(20):e202201486. Epub 2022 Mar 16.

Beijing National Laboratory for Molecular Science, State Key Laboratory of Polymer Physical and Chemistry, Institute of Chemistry Chinese Academy of Science, Beijing, 100190, China.

The development of Pt prodrugs which are selectively reduced within cancerous cells into their Pt therapeutically active species has received increasing attention within the last decade. Despite recent research progress, the majority of investigated compounds are excited using ultraviolet or blue light. As the light penetration depth is low at these wavelengths, the treatment of deep-seated or large tumors is limited. To overcome this limitation, herein, the example of Pt -functionalized nanoparticles that could be excited within the NIR region at 808 nm is reported. The polymer backbone which can self-assemble into nanoparticles was functionalized with Pt complexes for chemotherapy, photosensitizers for photodynamic immunotherapy, and nucleus/cancer-targeting peptides. Upon irradiation, the Pt center is reduced to Pt and the axially coordinated ligands are released, presenting a multimodal treatment. While selectively accumulating in tumorous tissue, the nanoparticles demonstrated the ability to eradicate a triple-negative breast cancer tumor inside a mouse model.
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http://dx.doi.org/10.1002/anie.202201486DOI Listing
May 2022

A Novel AlGaN/GaN Transient Voltage Suppression Diode with Bidirectional Clamp Capability.

Micromachines (Basel) 2022 Feb 14;13(2). Epub 2022 Feb 14.

The Science and Technology on Reliability Physics and Application of Electronic Component Laboratory, China Electronic, Product Reliability and Environmental Testing Research Institute, Guangzhou 510610, China.

This work proposes a novel AlGaN/GaN transient voltage suppression (TVS) diode (B-TVS-D) with bidirectional clamp capability, which consists of a small-size AlGaN/GaN monolithic bidirectional switch, two 2DEG-based current-limiting resistors (/, in parallel connection between the gate electrodes and the neighboring ohmic-contact electrodes (anode/cathode)), and a 2DEG-based proportional amplification resistor (, in parallel connection between two gate electrodes). It is demonstrated that the proposed B-TVS-D possesses a symmetrical triggering voltage () and a high secondary breakdown current (, over 8 A, corresponding to 12 kV human body model failure voltage) in different directional electrostatic discharge (ESD) events. The proposed diode can effectively enhance the electrostatic discharge robustness for the GaN-based power system. It is also verified that / and have an important impact on of the proposed B-TVS-D. Both the decrease in and increase in / can lead to the decrease of . In addition, the proposed B-TVS-D can be fabricated on the conventional p-GaN HEMT platform, making the ESD design of the GaN-based power system more convenient.
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http://dx.doi.org/10.3390/mi13020299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875646PMC
February 2022

Improving Breakdown Voltage and Threshold Voltage Stability by Clamping Channel Potential for Short-Channel Power p-GaN HEMTs.

Micromachines (Basel) 2022 Jan 25;13(2). Epub 2022 Jan 25.

Science and Technology on Reliability Physics and Application of Electronic Component Laboratory, China Electronic Product Reliability and Environmental Testing Research Institute, Guangzhou 510610, China.

This paper proposes a novel p-GaN HEMT (P-HEMT) by clamping channel potential to improve breakdown voltage (BV) and threshold voltage () stability. The clamping channel potential for P-HEMT is achieved by a partially-recessed p-GaN layer (PR p-GaN layer). At high drain bias, the two-dimensional electron gas (2DEG) channel under the PR p-GaN layer is depleted to withstand the drain bias. Therefore, the channel potential at the drain-side of the p-GaN layer is clamped to improve BV and stability. Compared with the conventional p-GaN HEMT (C-HEMT), simulation results show that the BV is improved by 120%, and the stability induced by high drain bias is increased by 490% for the same on-resistance. In addition, the influence of the PR p-GaN layers' length, thickness, doping density on BV and stability is analyzed. The proposed device can be a good reference to improve breakdown voltage and threshold voltage stability for short-channel power p-GaN HEMTs.
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http://dx.doi.org/10.3390/mi13020176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8875532PMC
January 2022

PTPN6-EGFR Protein Complex: A Novel Target for Colon Cancer Metastasis.

J Oncol 2022 11;2022:7391069. Epub 2022 Feb 11.

General Surgery Department, No. 6 Medical Center, General Hospital of Chinese PLA, Beijing 100048, China.

This study investigates the expression of nonreceptor protein tyrosine phosphatase 6 (PTPN6) gene in different colon cancer cells and its effect on malignant biological behavior. The expression level of PTPN6 mRNA in different colon cancer cell lines was detected by qPCR. CCK-8, clone formation assay, scratch assay, and transwell assay were used to detect the effect of knockdown or overexpression of the PTPN6 gene on the malignant biological behavior of colon cancer cells. CO-IP assay was used to detect the interaction protein of PTPN6. PTPN6 was highly expressed in colorectal cancer tissues. High expression of PTPN6 is associated with poor prognosis in patients with colon cancer. PtPN6 knockdown inhibited the proliferation, invasion, migration, and clonogenesis of colorectal cancer LOVO and SW480 cells. At the same time, the knockdown of PTPN6 inhibited the EMT process in colorectal cancer. CO-IP results showed that PTPN6 had a protein-protein interaction with EGFR. Overexpression of EGFR increased the carcinogenic effect of PTPN6. The high expression of the PTPN6 gene can promote the proliferation, migration, and invasion of colon cancer cells. PTPN6 can interact with EGFR. PTPN6-EGFR complex may be an important factor affecting the biological characteristics of colon cancer cells and a potential therapeutic target.
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http://dx.doi.org/10.1155/2022/7391069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8856819PMC
February 2022

Erratum: Promotes Metastasis in Colorectal Cancer by Activating Autophagy Signaling via the Upregulation of CARD3 Expression: Erratum.

Theranostics 2022 1;12(3):1333-1334. Epub 2022 Jan 1.

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, China.

[This corrects the article DOI: 10.7150/thno.38870.].
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http://dx.doi.org/10.7150/thno.69114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8771555PMC
January 2022

Narciclasine targets STAT3 via distinct mechanisms in tamoxifen-resistant breast cancer cells.

Mol Ther Oncolytics 2022 Mar 3;24:340-354. Epub 2022 Jan 3.

Shanghai Frontiers Science Center of TCM Chemical Biology, Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

STAT3 is constitutively activated in multiple malignant tumors. Compared with regular estrogen receptor (ER)-positive breast cancers, the patients with tamoxifen-resistant breast cancers often exhibit higher levels of STAT3 phosphorylation. Narciclasine (Nar) possesses strong inhibiting effects against a variety of cancer cells; however, the underlying antitumor target(s)/mechanism(s) remains barely understood. In this study, we successfully identified the STAT3 was the direct target of Nar through the combination strategies of connectivity map and drug affinity responsive target stability. In MCF7 cells, Nar could suppress phosphorylation, activation, dimerization, and nuclear translocation of STAT3 by directly binding with the STAT3 SH2 domain. In addition, Nar could specifically degrade total STAT3 via the proteasome pathway in MCF-7/TR (tamoxifen-resistant MCF-7) cells. This distinct mechanism of Nar-targeting STAT3 was mainly attributed to the various levels of reactive oxygen species in regular and tamoxifen-resistant ER-positive breast cancer cells. Meanwhile, Nar-loaded nanoparticles could markedly decrease the protein levels of STAT3 in tumors, resulting in significantly increased MCF-7/TR xenograft tumor regression without obvious toxicity. Our findings successfully highlight the STAT3 as the direct therapeutic target of Nar in ER-positive breast cancer cells, especially, Nar leaded STAT3 degradation as a promising strategy for the tamoxifen-resistant breast cancer treatment.
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http://dx.doi.org/10.1016/j.omto.2021.12.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8783118PMC
March 2022

Revealing the synergistic effects of cells, pigments, and light spectra on light transfer during microalgae growth: A comprehensive light attenuation model.

Bioresour Technol 2022 Mar 29;348:126777. Epub 2022 Jan 29.

Key Laboratory of Low-grade Energy Utilization Technologies and Systems, Chongqing University, Ministry of Education, Chongqing 400044, China; Institute of Engineering Thermophysics, School of Energy and Power Engineering, Chongqing University, Chongqing 400044, China.

As the sole energy for photosynthesis, light decrease rapidly with path due to absorption by pigments and scattering by cells in microalgal suspensions. By comprehensively considering cell concentrations, pigment components, and light spectra, a modified Cornet model for light transmission in microalgal suspensions is established. The developed model better fits experimental data with a higher adjusted R, which is 5% higher than the model that is based only on cell concentration. The attenuation of blue light is the most severe, followed by red and green light. Among the three main pigments, total carotenoids contribute the most to the absorption of blue and green light (with contribution coefficients of 89.26 ± 4.53% and 46.04 ± 3.77%, respectively), and chlorophyll a contributes the most to the absorption of red light (with a contribution coefficient of 75.33 ± 5.08%). This study provides a better understanding and prediction of light transmission during microalgal cultivation.
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http://dx.doi.org/10.1016/j.biortech.2022.126777DOI Listing
March 2022

Identification of a STIM1 Splicing Variant that Promotes Glioblastoma Growth.

Adv Sci (Weinh) 2022 04 25;9(11):e2103940. Epub 2022 Jan 25.

Department of Medical Oncology, Laboratory of Cancer Biology, Institute of Clinical Science, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, P. R. China.

Deregulated store-operated calcium entry (SOCE) mediated by aberrant STIM1-ORAI1 signaling is closely implicated in cancer initiation and progression. Here the authors report the identification of an alternatively spliced variant of STIM1, designated STIM1β, that harbors an extra exon to encode 31 additional amino acids in the cytoplasmic domain. STIM1β, highly conserved in mammals, is aberrantly upregulated in glioma tissues to perturb Ca signaling. At the molecular level, the 31-residue insertion destabilizes STIM1β by perturbing its cytosolic inhibitory domain and accelerating its activation kinetics to efficiently engage and gate ORAI calcium channels. Functionally, STIM1β depletion affects SOCE in glioblastoma cells, suppresses tumor cell proliferation and growth both in vitro and in vivo. Collectively, their study establishes a splicing variant-specific tumor-promoting role of STIM1β that can be potentially targeted for glioblastoma intervention.
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http://dx.doi.org/10.1002/advs.202103940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008427PMC
April 2022
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