Publications by authors named "Liqiang Wang"

200 Publications

Rapid assessments of light-duty gasoline vehicle emissions using on-road remote sensing and machine learning.

Sci Total Environ 2022 Jan 4;815:152771. Epub 2022 Jan 4.

Research Center for Air Pollution and Health, Key Laboratory of Environmental Remediation and Ecological Health, Ministry of Education, College of Environment and Resource Sciences, Zhejiang University, Hangzhou, Zhejiang 310058, PR China; Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address:

In-time and accurate assessments of on-road vehicle emissions play a central role in urban air quality and health policymaking. However, official insight is hampered by the Inspection/Maintenance (I/M) procedure conducted in the laboratory annually. It not only has a large gap to real-world situations (e.g., meteorological conditions) but also is incapable of regular supervision. Here we build a unique dataset including 103,831 light-duty gasoline vehicles, in which on-road remote sensing (ORRS) measurements are linked to the I/M records based on the vehicle identification numbers and license plates. On this basis, we develop an ensemble model framework that integrates three machining learning algorithms, including neural network (NN), extreme gradient boosting (XGBoost), and random forest (RF). We demonstrate that this ensemble model could rapidly assess the vehicle-specific emissions (i.e., CO, HC, and NO). In particular, the model performs quite well for the passing vehicles under normal conditions (i.e., lower VSP (<18 kw/t), temperature (6-32 °C), relative humidity (<80%), and wind speed (<5 m/s)). Together with the current emission standard, we identify a large number of the 'dirty' (2.33%) or 'clean' (74.92%) vehicles in the real world. Our results show that the ORRS measurements, assisted by the machine-learning-based ensemble model developed here, can realize day-to-day supervision of on-road vehicle-specific emissions. This approach framework provides a valuable opportunity to reform the I/M procedures globally and mitigate urban air pollution deeply.
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http://dx.doi.org/10.1016/j.scitotenv.2021.152771DOI Listing
January 2022

In situ metabolic profile and spatial distribution of ocular tissues: New insights into dry eye disease.

Ocul Surf 2022 Jan 3. Epub 2022 Jan 3.

State Key Laboratory of Kidney Diseases, Chinese PLA General Hospital, Beijing, China; Senior Department of Ophthalmology, Chinese PLA General Hospital, Beijing, China. Electronic address:

Purpose: Dry eye disease (DED) is a chronic multifactorial disorder affecting millions of people, yet the pathogenesis mechanisms still remain unclear. Matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) is a novel in situ visualization approach combined high-throughput mass spectrometry and molecular imaging. We aimed to explore the in situ ocular metabolic changes via MALDI-MSI to accelerate the recognition of DED pathogenesis.

Methods: Experimental dry eye was established in Wistar rats by subcutaneous injection of scopolamine. The induction of DED was assessed by tear film breakup time, sodium fluorescein, histopathological staining and cell apoptosis. MALDI-MSI was applied to explore in situ ocular metabolomic in DED rats, and histopathological staining from same sections were used for side-by-side comparison with MALDI to annotate different tissue structures in the eye.

Results: Considering the complexity of ocular tissue, we visualized the metabolites in specific ocular regions (central cornea, peripheral cornea, fornix conjunctiva, eyelid conjunctiva and aqueous humor), and identified metabolites related to DED, with information of relative abundance and spatial signatures. In addition, integrative pathway analysis illustrated that, several metabolic pathways such as glycerophospholipid, sphingolipid phenylalanine, and metabolism of glycine, serine and threonine were significantly altered in certain regions in the dry eye tissue. Moreover, we discussed how the metabolic pathways with spatiotemporal signatures might be involved in the DED process.

Conclusions: Our data exploit the advantages of in situ analysis of MALDI-MSI to accurately analyze the region-specific metabolic behaviors in DED, and provide new clues to uncover DED pathogenesis.
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http://dx.doi.org/10.1016/j.jtos.2021.12.013DOI Listing
January 2022

Complete chloroplast genome of the rare medicinal vegetable .

Mitochondrial DNA B Resour 2022 9;7(1):6-7. Epub 2021 Dec 9.

College of Applied Technology, Lijiang Teachers College, Lijiang, China.

is a rare medicinal plant with unique flavor. In this study, the first complete chloroplast (cp) genome of was sequenced and assembled based on the next generation sequencing. The cp genome is 153,592 bp in length, including a large single-copy (LSC) region of 82,609 bp, a small single-copy (SSC) region of 17,487 bp, and a pair of inverted repeat (IR) regions of 26,748 bp each. The genome encodes 131 genes, including 86 protein-coding genes, 39 tRNA genes, and six rRNA genes. The GC content of whole genome is 36.99%. The phylogenetic analysis based on 24 complete cp sequences revealed that was at the base of the phylogenetic tree, indicating an older species in the genus.
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http://dx.doi.org/10.1080/23802359.2021.2003262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8667927PMC
December 2021

Topical retinoic acid induces corneal strengthening by upregulating transglutaminase 2 in murine cornea.

Exp Eye Res 2021 Dec 1;214:108850. Epub 2021 Dec 1.

Department of Ophthalmology, The Third Medical Center, Chinese PLA General Hospital, Beijing, 100089, China. Electronic address:

Transglutaminase 2 (TG2) is the most abundant crosslinking enzyme in murine and human cornea, while retinoids are well-known inducers of TG2 expression. This study aims to determine if the retinoic acid supplementation can increase corneal stiffness by crosslinking through upregulating the corneal TG2 expression. The right eyes of C57BL/6 mice were treated with 2 × 10M retinol palmitate (VApal) eyedrops or control eyedrops and hold for 30 min, once a day for 28 consecutive days. The WB and qPCR results showed increased expression of TG2 in murine cornea with the prolongation of VApal eyedrop application. After 28 days of VApal eyedrop treatment, the increased TG2 were found catalytically active and distributed in corneal epithelium and stroma as detected by 5-(biotinamido) pentylamine (5-BP) incorporation method and immunofluorescence staining. The transmission electron microscope image revealed that VApal treated cornea manifested with increased collagen density in anterior and middle layer of stroma. The higher elastic module was found among VApal treated cornea by nano-indentation test. In cultured corneal epithelial cells and keratocytes, all-trans retinoid acid (ATRA) treatment increased the content of TG2 in cell lysis and in culture medium. These results indicate that retinoic acid induce the reinforcement of the cornea by TG2 mediated crosslinking via increasing the TG2 expression in corneal epithelium and keratocyte. As TG2 was found to be less in the cornea of keratoconus patients in several RNA-sequencing studies, retinoic acid could serve as a non-invasive prevention method for keratoconus progression.
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http://dx.doi.org/10.1016/j.exer.2021.108850DOI Listing
December 2021

Carfilzomib alleviated osteoporosis by targeting PSME1/2 to activate Wnt/β-catenin signaling.

Mol Cell Endocrinol 2022 01 24;540:111520. Epub 2021 Nov 24.

Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Key Laboratory of basic and translational research of Bone and Joint Degenerative Diseases, Guangxi Biomedical Materials Engineering Research Center for Bone and Joint Degenerative Diseases, Baise, 533000, Guangxi, China; Youjiang Medical University for Nationalities, Baise, 533000, Guangxi, China. Electronic address:

Osteoporosis (OP) is characterized by decreased bone mineral density and impaired bone strength. Carfilzomib (CFZ) is a new-generation proteasome inhibitor and has been found to affect bone metabolism. However, the effect and mechanism of CFZ on OP has not been investigated systematically. In this study, we found that protein levels of proteasome activator subunit 1/2 (PSME1/2) increased in OP, and accumulated mostly in osteoblasts and osteoclasts. Treatment with PSME1/2 recombinant protein inhibited osteogenesis and promoted osteoclast formation in vitro. Also, PSME1/2 inhibited the expression of β-catenin protein, resulting in limitation of Wnt/β-catenin signaling. CFZ inhibited PSME1 and PSME2 proteasome activities and increased β-catenin protein level, resulting in the translocation of β-catenin to the nucleus and activation of canonical Wnt/β-catenin signaling, further promoting osteogenesis and inhibiting osteoclastic differentiation. In vivo, we conducted ovariectomy (OVX) to create a model of OVX-induced postmenopausal OP in mice. When analyzed by micro-CT scanning, enhancement of bone mineral density, bone volume, trabecular number, and thickness was seen in the CFZ-treated mice. Also, we noticed increased osteogenesis and decreased osteoclastogenesis, diminished expression of PSME1 and PSME2 and activated Wnt/β-catenin signaling in bone sections from OP mice treated with CFZ. Overall, our data indicated that PSME1/2 may serve as new targets for the treatment of OP, and targeting PSME1/2 with CFZ provides a candidate therapeutic molecule for postmenopausal OP.
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http://dx.doi.org/10.1016/j.mce.2021.111520DOI Listing
January 2022

3D Printing of Tricalcium Phosphate/Poly Lactic-co-glycolic Acid Scaffolds Loaded with Carfilzomib for Treating Critical-sized Rabbit Radial Bone Defects.

Int J Bioprint 2021 14;7(4):405. Epub 2021 Sep 14.

State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

The rapid development of scaffold-based bone tissue engineering strongly relies on the fabrication of advanced scaffolds and the use of newly discovered functional drugs. As the creation of new drugs and their clinical approval often cost a long time and billions of U.S. dollars, producing scaffolds loaded with repositioned conventional drugs whose biosafety has been verified clinically to treat critical-sized bone defect has gained increasing attention. Carfilzomib (CFZ), an approved clinical proteasome inhibitor with a much fewer side effects, is used to replace bortezomib to treat multiple myeloma. It is also reported that CFZ could enhance the activity of alkaline phosphatase and increase the expression of osteogenic transcription factors. With the above consideration, in this study, a porous CFZ/β-tricalcium phosphate/poly lactic-co-glycolic acid scaffold (designated as "cytidine triphosphate [CTP]") was produced through cryogenic three-dimensional (3D) printing. The hierarchically porous CTP scaffolds were mechanically similar to human cancellous bone and can provide a sustained CFZ release. The implantation of CTP scaffolds into critical-sized rabbit radius bone defects improved the growth of new blood vessels and significantly promoted new bone formation. To the best of our knowledge, this is the first work that shows that CFZ-loaded scaffolds could treat nonunion of bone defect by promoting osteogenesis and angiogenesis while inhibiting osteoclastogenesis, through the activation of the Wnt/β-catenin signaling. Our results suggest that the loading of repositioned drugs with effective osteogenesis capability in advanced bone tissue engineering scaffold is a promising way to treat critical-sized defects of a long bone.
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http://dx.doi.org/10.18063/ijb.v7i4.405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8600297PMC
September 2021

Genome-Wide Identification of Circular RNAs Potentially Involved in the Biosynthesis of Secondary Metabolites in .

Front Genet 2021 5;12:645115. Epub 2021 Nov 5.

Key Laboratory of Bioactive Substances and Resource Utilization of Chinese Herbal Medicine from Ministry of Education, Engineering Research Center of Chinese Medicine Resources from Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

Circular RNAs (circRNAs) play various roles in cellular functions. However, no studies have been reported on the potential involvement of circRNAs in the biosynthesis of secondary metabolites in plants. Here, we performed a genome-wide discovery of circRNAs from root, stem and leaf samples of using RNA-Seq. We predicted a total of 2,476 circRNAs with at least two junction reads using circRNA_finder and CIRI, of which 2,096, 151 and 229 were exonic, intronic and intergenic circRNAs, respectively. Sequence similarity analysis showed that 294 out of 2,476 circRNAs were conserved amongst multiple plants. Of the 55 predicted circRNAs, 31 (56%) were validated successfully by PCR and Sanger sequencing using convergent and divergent primer pairs. Alternative circularisation analysis showed that most parental genes produced two circRNAs. Functional enrichment analyses of the parental genes showed that the primary metabolism pathways were significantly enriched, particularly the carbon metabolism. Differential expression analysis showed that the expression profiles of circRNAs were tissue-specific. Co-expression analysis showed 275 circRNAs, and their parental genes had significantly positive correlations. However, 14 had significantly negative correlations. Weighted gene co-expression network analysis showed that nine circRNAs were co-expressed with four modules of protein-coding genes. Next, we found 416 exonic circRNAs with miRNA-binding sites, suggesting possible interactions between circRNAs and miRNAs. Lastly, we found six validated circRNAs, namely, SMscf2473-46693-46978, SMscf3091-29256-29724, SMscf16-111773-112193, SMscf432-13232-13866, SMscf7007-10563-10888 and SMscf1730-1749-2013, which were originated from the genes involved in the biosynthesis of secondary metabolites. Their parental genes were acetyl-CoA C-acetyltransferase 1 (SmAACT1), 1-deoxy-d-xylulose-5-phosphate synthase 2 (SmDXS2), 4-hydroxy-3-methylbut-2-enyl diphosphate reductase 1 (SmHDR1), kaurene synthase-like 2 (SmKSL2), DWF4 and CYP88A3, respectively. In particular, the correlation coefficient of SMscf2473-46693-46978 and SmDXS2 gene was 0.86 ( = 0.003), indicating a potential interaction between this pair of circRNA and its parent gene. Our results provided the first comprehensive catalogue of circRNAs in and identified one circRNA that might play important roles in the biosynthesis of secondary metabolites.
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http://dx.doi.org/10.3389/fgene.2021.645115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8602197PMC
November 2021

FSH inhibits autophagy and lysosomal biogenesis to regulate protein degradation in cultured goat Sertoli cells.

Mol Cell Endocrinol 2022 01 10;540:111505. Epub 2021 Nov 10.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest Agriculture and Forestry University, Yangling, Shaanxi, 712100, People's Republic of China. Electronic address:

Although the follicle-stimulating hormone (FSH) plays a vital role in male reproduction, the molecular relationships among FSH, autophagy, and the secretory function of Sertoli cells remain largely undetermined. In this study, we sought to investigate the effects of FSH on dairy goat Sertoli cell autophagy and the role of autophagy in protein clearance. FSH treatment of primary Sertoli cells was found to enhance the expression level of LC3-II, reduce p62 degradation and the number of lysosomes, and downregulate the levels of LAMP2 protein and lysosomal gene mRNAs. Further analyses revealed that starvation-induced autophagy promotes the translocation of transcription factor EB (TFEB) from the cytoplasm to nucleus and its binding to the promoter region of LAMP2, whereas FSH suppresses the nuclear translocation of TFEB. Moreover, we found that the FSH-mediated inhibition of autophagy extends the biological half-lives of androgen-binding protein (ABP), glial-derived neurotrophic factor (GDNF), and stem cell factor (SCF) and promotes the secretion of these proteins. Collectively, these observations indicate that FSH inhibits autophagy by reducing lysosomal biogenesis, which is associated with the suppression of TFEB nuclear translocation via activation of the PI3K/Akt/mTOR pathway, thereby extending the biological half-lives and enhancing the expression of ABP, GDNF, and SCF in dairy goat Sertoli cells.
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http://dx.doi.org/10.1016/j.mce.2021.111505DOI Listing
January 2022

MOF Encapsulating N-Heterocyclic Carbene-Ligated Copper Single-Atom Site Catalyst towards Efficient Methane Electrosynthesis.

Angew Chem Int Ed Engl 2022 Jan 13;61(4):e202114450. Epub 2021 Dec 13.

Department of Chemistry, Tsinghua University, Beijing, 100084, P. R. China.

The exploitation of highly efficient carbon dioxide reduction (CO RR) electrocatalyst for methane (CH ) electrosynthesis has attracted great attention for the intermittent renewable electricity storage but remains challenging. Here, N-heterocyclic carbene (NHC)-ligated copper single atom site (Cu SAS) embedded in metal-organic framework is reported ([email protected]), which can achieve an outstanding Faradaic efficiency (FE) of 81 % for the CO reduction to CH at -1.5 V vs. RHE with a current density of 420 mA cm . The CH FE of our catalyst remains above 70 % within a wide potential range and achieves an unprecedented turnover frequency (TOF) of 16.3 s . The σ donation of NHC enriches the surface electron density of Cu SAS and promotes the preferential adsorption of CHO* intermediates. The porosity of the catalyst facilitates the diffusion of CO to 2Bn-Cu, significantly increasing the availability of each catalytic center.
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http://dx.doi.org/10.1002/anie.202114450DOI Listing
January 2022

Outcomes from the Use of Perioperative Extracorporeal Membrane Oxygenation in Patients Undergoing Thoracic Surgery: An 8-Year Single-Center Experience.

Med Sci Monit 2021 Nov 2;27:e931842. Epub 2021 Nov 2.

Department of Cardiothoracic Surgery, Zhongshan Hospital of Sun Yat-Sen University (Zhongshan People's Hospital), Zhongshan, Guangdong, China (mainland).

BACKGROUND Extracorporeal membrane oxygenation (ECMO) plays an important role in thoracic surgery. This retrospective study from a single center aimed to evaluate patient outcomes from the use of perioperative ECMO in 22 patients undergoing thoracic surgery during an 8-year period. MATERIAL AND METHODS Data were collected retrospectively from 22 patients who received ECMO (veno-arterial and veno-venous ECMO) as perioperative treatment during general thoracic surgery from January 2012 to October 2020. Patients required ECMO due to perioperative cardiopulmonary resuscitation (CPR) (2 cases), perioperative pulmonary embolism (PE) (2 cases), lung transplant (4 cases), undergoing complicated thoracic surgery (5 cases), postoperative acute respiratory distress syndrome (ARDS) (6 cases), and thoracic trauma (3 cases). RESULTS Veno-arterial ECMO was used for circulatory support in 13 cases and veno-venous ECMO was used for respiratory support in 9 cases. The average ECMO support time was 71.6±42.4 h. Twenty patients (90.9%) were successfully decannulated and 17 (77.2%) survived to discharge. Complications included severe hemorrhage (3/22 patients, 13.6%), sepsis (3/22, 13.6%), and destruction of blood cells (1/22, 4.5%). There were no significant differences in survival rates between patients receiving pre- or postoperative ECMO (P=0.135) or between veno-venous ECMO (V-V ECMO) and veno-arterial ECMO (V-A ECMO) (P=0.550). CONCLUSIONS The findings from this small retrospective study from a single center showed that perioperative ECMO improved cardiac and respiratory function in patients undergoing thoracic surgery. Optimal results require surgeons to have an understanding of the indications and ability to control the complications of ECMO.
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http://dx.doi.org/10.12659/MSM.931842DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570047PMC
November 2021

Immune Checkpoint Inhibitors Plus Single-Agent Chemotherapy for Advanced Non-Small-Cell Lung Cancer After Resistance to EGFR-TKI.

Front Oncol 2021 20;11:700023. Epub 2021 Sep 20.

State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.

Purpose: Platinum-based chemotherapy remains the classic treatment option for patients with advanced non-small-cell lung cancer (NSCLC) who progress while receiving treatment with epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). In this study, we analyzed real-world outcomes of treatment with immune checkpoint inhibitors (ICIs) combined with platinum-free chemotherapy in patients with NSCLC after developing resistance to EGFR-TKIs.

Methods: This retrospective study included patients with mutation-positive NSCLC after developing resistance to EGFR-TKIs. Patients who received chemotherapy alone plus ICIs with or without anti-angiogenic drugs (cohort A) or platinum-based chemotherapy (cohort B) between February 2019 and August 2020 were enrolled. Clinical characteristics, EGFR mutation status, response to therapy, and adverse events (AEs) were retrospectively analyzed.

Results: Seventeen patients were eligible and included in the analysis, including 8 in cohort A and 9 in cohort B. After a median follow-up of 7.6 months, the median progression-free survival was 6.5 months [95% confidence interval (CI), 6.1 to 7.0] in cohort A and 3.6 months (95% CI, 1.3-5.8) in cohort B (hazard ratios, 0.22; 95% CI, 0.05-0.93; P = 0.039). The overall response and disease control rates were 50% and 100% in cohort A, and 22% and 89% in cohort B, respectively. Adverse events of grade 3 or higher occurred in 25% of the patients in cohort A and in 33.3% of the patients in cohort B.

Conclusion: ICIs plus platinum-free, single-agent chemotherapy provides promising progression-free survival and overall response rate benefit, along with a low rate of severe AEs in patients with EGFR-TKI-resistant advanced NSCLC.
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http://dx.doi.org/10.3389/fonc.2021.700023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488293PMC
September 2021

A scalable open-source MATLAB toolbox for reconstruction and analysis of multispectral optoacoustic tomography data.

Sci Rep 2021 10 6;11(1):19872. Epub 2021 Oct 6.

Department of Radiology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX, 75390-9058, USA.

Multispectral photoacoustic tomography enables the resolution of spectral components of a tissue or sample at high spatiotemporal resolution. With the availability of commercial instruments, the acquisition of data using this modality has become consistent and standardized. However, the analysis of such data is often hampered by opaque processing algorithms, which are challenging to verify and validate from a user perspective. Furthermore, such tools are inflexible, often locking users into a restricted set of processing motifs, which may not be able to accommodate the demands of diverse experiments. To address these needs, we have developed a Reconstruction, Analysis, and Filtering Toolbox to support the analysis of photoacoustic imaging data. The toolbox includes several algorithms to improve the overall quantification of photoacoustic imaging, including non-negative constraints and multispectral filters. We demonstrate various use cases, including dynamic imaging challenges and quantification of drug effect, and describe the ability of the toolbox to be parallelized on a high performance computing cluster.
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http://dx.doi.org/10.1038/s41598-021-97726-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8494751PMC
October 2021

Characterization and comparative analysis of the plastome sequence from (Lamiales: Acanthaceae).

Mitochondrial DNA B Resour 2021 14;6(10):2896-2902. Epub 2021 Sep 14.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.

is a characteristic ethnic herb commonly used to treat Orthopedic pains. Here, to confirm its phylogenetic position and to develop molecular markers that can distinguish different species, we obtained and analyzed the plastome of The plastome was sequenced using the Illumina HiSeq sequencing platform, assembled with NOVOPlasty, and annotated with CPGAVAS2. The genome has a circular structure of 149,700 bp, containing a large single-copy region of 82,324 bp, a small single-copy region of 17,260 bp, and two reverse repeat regions of 25,058 bp each. It encodes 112 unique genes, including 76 protein-coding genes, eight ribosomal RNA genes, and 28 transfer RNA genes. Twenty cis-splicing genes were found. In total, we predicted 19 microsatellite repeats and 13 tandem repeat sequences. For distributed repeats, four were palindrome repeats and five were direct repeats. To find the highly variable intergenic spacer (IGS) regions, we calculated the K2P distances for IGS regions from four species. The K2P values ranged from 6.11 to 57.82. The largest K2P distances were found for AD, BD, KI, and 4A. Phylogenetic analysis results showed that was most closely related to . To determine how species adapt to the environment, we performed selection pressure analysis. Nine genes were found to have undergone positive selection. Lastly, we performed a genome-wise DNA barcode prediction, seven pairs of primers were found. The results provide valuable information that can be used for molecular marker development and bioprospecting in species.
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http://dx.doi.org/10.1080/23802359.2021.1922099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480419PMC
September 2021

First complete chloroplast genome of the rare medicinal plant .

Mitochondrial DNA B Resour 2021 20;6(10):2993-2994. Epub 2021 Sep 20.

Chinese Herbal Medicine Industry Center of Xiushan Tujia and Miao Autonomous County, Chongqing, China.

is a medicinal plant used in traditional Chinese medicine. However, the molecular biology data of the species was too scarce to bioprospect the medicinal species. In this study, the first complete chloroplast genome (cp) of was sequenced and assembled based on the next generation sequencing. The cp genome is 157,004 bp in length, including a large single-copy (LSC) region of 83,605 bp, a small single-copy (SSC) region of 36,899 bp, and a pair of inverted repeat (IR) regions of 18,250 bp each. The genome encodes 134 genes, including 90 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The GC content of whole genome is 37.80%. The phylogenetic analysis based on 20 complete cp sequences (19 genome sequences from the Teucrioideae of Lamiaceae and an outgroup of ) revealed that was closely related to
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http://dx.doi.org/10.1080/23802359.2021.1975507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462896PMC
September 2021

Characterization of the first chloroplast genome of and its phylogenetic analysis.

Mitochondrial DNA B Resour 2021 20;6(10):2991-2992. Epub 2021 Sep 20.

Research and Utilization on Characteristic Biological Resources of Sichuan and Chongqing Co-construction Lab, Chongqing Institute of Medicinal Plant Cultivation, Chongqing, China.

, seen as a medicinal plant, has a long history in traditional Chinese medicine. In this study, we adopted Illumina Hiseq sequencing technology in order to determine the first complete chloroplast (cp) genome of The cp genome was 157,647 bp in length, including a large single-copy (LSC) region of 86,728 bp, a small single-copy (SSC) region of 18,675 bp, and a pair of inverted repeat (IR) regions of 26,122 bp. The genome encoded 128 genes, including 84 protein-coding genes, 36 tRNA genes, and 8 rRNA genes. The phylogenetic analysis based on 20 complete cp genome sequences revealed that was the sister of the ancestor of the reported Hydrangeeae species. The findings of the study will serve as a stepping stone for follow-up researches regarding the development of the species.
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http://dx.doi.org/10.1080/23802359.2021.1975506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8462831PMC
September 2021

Phylogenetic analysis and development of molecular markers for five medicinal Alpinia species based on complete plastome sequences.

BMC Plant Biol 2021 Sep 22;21(1):431. Epub 2021 Sep 22.

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, 100193, Beijing, People's Republic of China.

Background: Alpinia species are widely used as medicinal herbs. To understand the taxonomic classification and plastome evolution of the medicinal Alpinia species and correctly identify medicinal products derived from Alpinia species, we systematically analyzed the plastome sequences from five Alpinia species. Four of the Alpinia species: Alpinia galanga (L.) Willd., Alpinia hainanensis K.Schum., Alpinia officinarum Hance, and Alpinia oxyphylla Miq., are listed in the Chinese pharmacopeia. The other one, Alpinia nigra (Gaertn.) Burtt, is well known for its medicinal values.

Results: The four Alpinia species: A. galanga, A. nigra, A. officinarum, and A. oxyphylla, were sequenced using the Next-generation sequencing technology. The plastomes were assembled using Novoplasty and annotated using CPGAVAS2. The sizes of the four plastomes range from 160,590 bp for A. galanga to 164,294 bp for A. nigra, and display a conserved quadripartite structure. Each of the plastomes encodes a total of 111 unique genes, including 79 protein-coding, 28 tRNA, and four rRNA genes. In addition, 293-296 SSRs were detected in the four plastomes, of which the majority are mononucleotides Adenine/Thymine and are found in the noncoding regions. The long repeat analysis shows all types of repeats are contained in the plastomes, of which palindromic repeats occur most frequently. The comparative genomic analyses revealed that the pair of the inverted repeats were less divergent than the single-copy region. Analysis of sequence divergence on protein-coding genes showed that two genes (accD and ycf1) had undergone positive selection. Phylogenetic analysis based on coding sequence of 77 shared plastome genes resolves the molecular phylogeny of 20 species from Zingiberaceae. In particular, molecular phylogeny of four sequenced Alpinia species (A. galanga, A. nigra, A. officinarum, and A. oxyphylla) based on the plastome and nuclear sequences showed congruency. Furthermore, a comparison of the four newly sequenced Alpinia plastomes and one previously reported Alpinia plastomes (accession number: NC_048461) reveals 59 highly divergent intergenic spacer regions. We developed and validated two molecular markers Alpp and Alpr, based on two regions: petN-psbM and psaJ-rpl33, respectively. The discrimination success rate was 100 % in validation experiments.

Conclusions: The results from this study will be invaluable for ensuring the effective and safe uses of Alpinia medicinal products and for the exploration of novel Alpinia species to improve human health.
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http://dx.doi.org/10.1186/s12870-021-03204-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8456601PMC
September 2021

Characterization of the first chloroplast genome of Dunn and its phylogenetic analysis.

Mitochondrial DNA B Resour 2021 9;6(10):2884-2885. Epub 2021 Sep 9.

Chongqing Key Laboratory of Industrial Fermentation Microorganism, Department of Chemistry and Chemical Engineering, Chongqing University of Science and Technology, Chongqing, China.

Dunn not only is a national second-level protected wild plant in China, but also has a long history as a source plant in traditional Chinese medicine. The chloroplast (cp) genome of was 154,102 bp, consisting of a large single-copy region (LSC: 92,877 bp), a small single-copy region (SSC: 36,645 bp), and a pair of inverted repeat regions (IRb and Ira: 12,290 bp, respectively). These sequences encoded 123 genes, including 78 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The phylogenetic analysis showed that is close to species.
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http://dx.doi.org/10.1080/23802359.2021.1972866DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439238PMC
September 2021

Metabolic nuclear receptors coordinate energy metabolism to regulate Sox9 hepatocyte fate.

iScience 2021 Sep 19;24(9):103003. Epub 2021 Aug 19.

College of Veterinary Medicine/Bio-medical Center, Huazhong Agricultural University, Wuhan, Hu Bei 430070, China.

Recent research has indicated the adult liver Sox9 cells located in the portal triads contribute to the physiological maintenance of liver mass and injury repair. However, the physiology and pathology regulation mechanisms of adult liver Sox9 cells remain unknown. Here, PPARα and FXR bound to the shared site in Sox9 promoter with opposite transcriptional outputs. PPARα activation enhanced the fatty acid β-oxidation, oxidative phosphorylation (OXPHOS), and adenosine triphosphate (ATP) production, thus promoting proliferation and differentiation of Sox9 hepatocytes along periportal (PP)-perivenous (PV) axis. However, FXR activation increased glycolysis but decreased OXPHOS and ATP production, therefore preventing proliferation of Sox9 hepatocytes along PP-PV axis by promoting Sox9 hepatocyte self-renewal. Our research indicates that metabolic nuclear receptors play critical roles in liver progenitor Sox9 hepatocyte homeostasis to initiate or terminate liver injury-induced cell proliferation and differentiation, suggesting that PPARα and FXR are potential therapeutic targets for modulating liver regeneration.
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http://dx.doi.org/10.1016/j.isci.2021.103003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417399PMC
September 2021

Lewis Acid Site-Promoted Single-Atomic Cu Catalyzes Electrochemical CO Methanation.

Nano Lett 2021 Sep 17;21(17):7325-7331. Epub 2021 Aug 17.

Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China.

Developing an efficient catalyst for the electrocatalytic CO reduction reaction (CORR) is highly desired because of environmental and energy issues. Herein, we report a single-atomic-site Cu catalyst supported by a Lewis acid for electrocatalytic CO reduction to CH. Theoretical calculations suggested that Lewis acid sites in metal oxides (e.g., AlO, CrO) can regulate the electronic structure of Cu atoms by optimizing intermediate absorption to promote CO methanation. Based on these theoretical results, ultrathin porous AlO with enriched Lewis acid sites was explored as an anchor for Cu single atoms; this modification achieved a faradaic efficiency (FE) of 62% at -1.2 V (vs RHE) with a corresponding current density of 153.0 mA cm for CH formation. This work demonstrates an effective strategy for tailoring the electronic structure of Cu single atoms for the highly efficient reduction of CO into CH.
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http://dx.doi.org/10.1021/acs.nanolett.1c02502DOI Listing
September 2021

The first complete plastome of (Fenzl) Makino: assembly, annotation and phylogenetic analysis.

Mitochondrial DNA B Resour 2021 25;6(9):2762-2763. Epub 2021 Aug 25.

Chongqing Shangyao Huiyuan Pharmaceutical Co. Ltd, Chongqing, China.

(Fenzl) Makino is one of the 'Square Bamboo' due to its square-shaped culm. However, as an edible bamboo, there is no genomic information reported so far. In this study, we reported and characterized the first plastome of based on Illumina Hiseq sequencing. The plastome exhibited a typical angiosperm circular structure, containing four regions: large single-copy region (LSC: 83,125 bp), small single-copy region (SSC: 12,811 bp), and a pair of inverted repeat regions (IR: 21,802 bp). The plastome consisted of 139,540 bp in size, with 82 protein-coding genes, 39 tRNA genes, and eight rRNA genes. The total nucleotide composition consisted of 30.16% A, 30.97% T, 19.25% C, and 19.63% G. The G + C content of the whole plastome was 38.88%. Phylogenetic analysis based on the complete plastomes of six species indicated that was closed to . The plastome is helpful for studying the evolution of beneficial adaptations and developing bioremediation and biomedical science.
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http://dx.doi.org/10.1080/23802359.2021.1967808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405115PMC
August 2021

Changes in histology, protein expression, and autophagy in dairy goat testes during nonbreeding season†.

Biol Reprod 2021 11;105(5):1344-1354

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest Agriculture and Forestry University, Yangling, Shaanxi, China.

Seasonal reproduction contributes to increased chances of offspring survival in some animals. Dairy goats are seasonal breeding mammals. In this study, adult male Guanzhong dairy goats (10-12 months old) were used. Testis size, semen quality, hormone level, apoptosis of germ cells, and autophagy of Sertoli cells were analyzed in dairy goats during the breeding (October) and nonbreeding (April) seasons. We found that, during the nonbreeding season for dairy goats, semen quality, follicle-stimulating hormone (FSH) levels, and testosterone levels were reduced, and the number of apoptotic germ cells increased. The proliferation with decrease activity of germ cells in dairy goat during the nonbreeding season was significantly affected. However, the testis size did not change seasonally. Interestingly, Sertoli cell autophagy was more active during the nonbreeding season. The expression levels of FSH receptor, wilms tumor 1, androgen binding protein, glial cell derived neurotrophic factor, and stem cell factor decreased in dairy goats during the nonbreeding season. In summary, our results indicate that spermatogenesis in dairy goats during the nonbreeding season was not completely arrested. In addition, germ cell apoptosis and the morphology of Sertoli cells considerably changed in dairy goats during the nonbreeding season. Sertoli cell autophagy is involved in the seasonal regulation of spermatogenesis in dairy goats. These findings provide key insights into the fertility and spermatogenesis of seasonal breeding animals.
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http://dx.doi.org/10.1093/biolre/ioab164DOI Listing
November 2021

HA15 alleviates bone loss in ovariectomy-induced osteoporosis by targeting HSPA5.

Exp Cell Res 2021 09 13;406(2):112781. Epub 2021 Aug 13.

State Key Laboratory of Metal Matrix Composites, School of Material Science and Engineering, Shanghai Jiao Tong University, Shanghai, 200240, China.

The imbalance between osteogenesis and adipogenesis in the bone marrow is the main characteristic of osteoporosis (OP). Thus, exploring regulation of the differentiation of bone marrow stromal cells (BMSCs) into osteoblasts and adipocytes is important to identify novel targets for the treatment of OP. In the present study, the master regulator of endoplasmic reticulum (ER) stress, heat shock protein family A (Hsp70) member 5 (HSPA5) was shown to significantly accumulate in osteoblasts and adipocytes, but not in osteoclasts in bone sections from aged and postmenopausal OP mice. In vitro study revealed that HSPA5 negatively modulated osteogenic differentiation and positively promoted adipogenic differentiation, and that targeting HSPA5 with its inhibitor HA15 enhanced osteogenic differentiation and inhibited adipogenic differentiation. Also, HA15 treatment induces ER stress and autophagy, and decreases apoptosis in cells. We constructed a postmenopausal OP model in mice with ovariectomy surgery, and treated the mice with HA15. The results showed that HA15 treatment induced appropriate ER stress, activated autophagy and decreased apoptosis in osteoblasts, thereby alleviating bone loss in vivo. Our results indicated that HSPA5 participated in OP pathogenesis by regulating the differentiation of BMSCs. HSPA5 may serve as a new target for the treatment of OP, and targeting HSPA5 with HA15 prevents the progression of OP and provides a candidate therapeutic molecule for postmenopausal OP.
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http://dx.doi.org/10.1016/j.yexcr.2021.112781DOI Listing
September 2021

Postpartum extracorporeal membrane oxygenation of a woman with COVID-19-related acute respiratory distress syndrome: A case report.

Medicine (Baltimore) 2021 Jul;100(30):e26798

Department of Anesthesiology, Zhongshan People's Hospital (Zhongshan Hospital of Sun Yat-Sen University) China.

Introduction: Patients with coronavirus disease (COVID-19) may develop acute respiratory distress syndrome (ARDS). There have been few reports of postpartum woman with ARDS secondary to COVID-19 who required respiratory support using veno-venous extracorporeal membrane oxygenation (ECMO). We present the case of a 31-year-old woman who was admitted to hospital at 35 weeks gestation with ARDS secondary to COVID-19 and required ECMO during the postpartum period.

Patient Concerns: The patient had obvious dyspnea, accompanied by chills and fever. Her dyspnea worsened and her arterial oxygen saturation decreased rapidly.

Diagnosis: ARDS secondary to COVID-19.

Interventions: Emergency bedside cesarean section. Medications included immunotherapy (thymosin α 1), antivirals (lopinavir/ritonavir and ribavirin), antibiotics (imipenem-cilastatin sodium and vancomycin), and methylprednisolone. Ventilatory support was provided using invasive mechanical ventilation. This was replaced by venous-venous ECMO 5 days postpartum. ECMO management focused on blood volume control, coagulation function adjustment, and airway management.

Outcomes: The patient was successfully weaned for ECMO and the ventilator and made a good recovery.

Conclusion: Special care, including blood volume control, coagulation function adjustment, and airway management, should be provided to postpartum patients with ARDS secondary to COVID-19 who require ECMO support.
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http://dx.doi.org/10.1097/MD.0000000000026798DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322481PMC
July 2021

Black Carbon Induces Complement Activation via NLRP3 Inflammasome in Human Corneal Epithelial Cells.

Curr Eye Res 2021 Sep 27:1-6. Epub 2021 Sep 27.

Department of Ophthalmology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Purpose: To investigate the effect of black carbon (BC) particles on complement activation in human corneal epithelial cells (HCECs) and determine whether this effect can be attenuated by inhibiting the NLPR3 inflammasome pathway.

Materials And Methods: HCECs were treated with fresh BC (FBC) or ozone-oxidized BC (OBC) particles at a concentration of 200 μg/ml for 72 hours. Complement activation was observed by detecting C5b-9 protein level in cell culture supernatant using ELISA. HCECs were transfected with duplexes of siRNA targeting NLRP3 (NLRP3-siRNA) at 0.1 pmol/µl for 24 hours to inhibit the NLPR3 inflammasome pathway. RT-qPCR was performed to examine the efficacy of NLRP3-siRNA for inhibition; a random siRNA duplex was used for control siRNA.

Results: Both FBC exposure and OBC exposure for 72 hours significantly increased the C5b-9 protein level compared to negative control cells (all < .05). However, the difference in C5b-9 level after FBC exposure and OBC exposure was not statistically significant ( > .05). NLRP3-siRNA transfection reduced C5b-9 protein levels in FBC-treated and OBC-treated HCECs compared to control (lowered by 27% in the FBC-treated group and by 23% in the OBC-treated group, all < .05).

Conclusions: BC particles, including FBC and OBC, triggered complement activation, increasing the protein level of C5b-9 in cultured HCECs. siRNA targeting NLRP3 to inhibit NLRP3 generation reduced C5b-9 protein level in HCECs treated with FBC or OBC particles, indicating that BC induces complement activation potentially through the NLRP3 inflammasome in HCECs.
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http://dx.doi.org/10.1080/02713683.2021.1967404DOI Listing
September 2021

Nanomessenger-Mediated Signaling Cascade for Antitumor Immunotherapy.

ACS Nano 2021 Aug 3. Epub 2021 Aug 3.

Hunan Provincial Key Laboratory of Micro & Nano Materials Interface Science, College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, People's Republic of China.

Chemical messengers have been recognized as signaling molecules involved in regulating various physiological and metabolic activities. Nevertheless, they usually show limited regulatory efficiency due to the complexity of biological processes. Especially for tumor cells, antideath pathways and tumor metastasis are readily activated to resist chemical messenger regulation, further impairing antitumor outcomes. Therefore, it is imperative to develop strategies for tumor eradication with chemical messengers. Herein, a nanomessenger was prepared with signaling transduction cascades to amplify the regulatory activity of chemical messengers and mediate antitumor immunotherapy. Ca and HS as two chemical messengers were released from nanomessengers to synergistically elevate intracellular Ca stress and mediate subsequent cell death. Meanwhile, zinc protoporphyrin (ZnPP) as a messenger amplifier suppressed the antideath effect of tumor cells. As a result, tumor cells underwent Ca-dependent cell death signaling transduction cascades to release tumor-associated antigens, which further served as an tumor vaccine to activate antitumor immunity. studies revealed that both primary tumors and distant metastases were markedly eradicated. Furthermore, immunological memory was fabricated to arrest tumor metastasis and recurrence. This work introduces cascade engineering into chemical messengers and thus offers a strategy for amplifying chemical messenger-mediated cellular regulation, which would promote the future development of chemical messenger-mediated immunotherapy.̀.
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http://dx.doi.org/10.1021/acsnano.1c02765DOI Listing
August 2021

TLR7/8 signalling affects X-sperm motility via the GSK3 α/β-hexokinase pathway for the efficient production of sexed dairy goat embryos.

J Anim Sci Biotechnol 2021 Aug 3;12(1):89. Epub 2021 Aug 3.

Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, No. 22 Xinong Road, Yangling, Shaanxi, 712100, People's Republic of China.

Background: Goat milk is very similar to human milk in terms of its abundant nutrients and ease of digestion. To derive greater economic benefit, farmers require more female offspring (does); however, the buck-to-doe offspring sex ratio is approximately 50%. At present, artificial insemination after the separation of X/Y sperm using flow cytometry is the primary means of controlling the sex of livestock offspring. However, flow cytometry has not been successfully utilised for the separation of X/Y sperm aimed at sexing control in dairy goats.

Results: In this study, a novel, simple goat sperm sexing technology that activates the toll-like receptor 7/8 (TLR7/8), thereby inhibiting X-sperm motility, was investigated. Our results showed that the TLR7/8 coding goat X-chromosome was expressed in approximately 50% of round spermatids in the testis and sperm, as measured from cross-sections of the epididymis and ejaculate, respectively. Importantly, TLR7/8 was located at the tail of the X-sperm. Upon TLR7/8 activation, phosphorylated forms of glycogen synthase kinase α/β (GSK3 α/β) and nuclear factor kappa-B (NF-κB) were detected in the X-sperm, causing reduced mitochondrial activity, ATP levels, and sperm motility. High-motility Y-sperm segregated to the upper layer and the low-motility X-sperm, to the lower layer. Following in vitro fertilisation using the TLR7/8-activated sperm from the lower layer, 80.52 ± 6.75% of the embryos were XX females. The TLR7/8-activated sperm were subsequently used for in vivo embryo production via the superovulatory response; nine embryos were collected from the uterus of two does that conceived. Eight of these were XX embryos, and one was an XY embryo.

Conclusions: Our study reveals a novel TLR7/8 signalling mechanism that affects X-sperm motility via the GSK3 α/β-hexokinase pathway; this technique could be used to facilitate the efficient production of sexed dairy goat embryos.
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http://dx.doi.org/10.1186/s40104-021-00613-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8330071PMC
August 2021

Lineage Contribution of PDGFR-Expressing Cells in the Developing Mouse Eye.

Biomed Res Int 2021 2;2021:4982227. Epub 2021 Jul 2.

Department of Ophthalmology, The Third Medical Center of Chinese PLA General Hospital, Beijing 100853, China.

PDGFR signaling is critically important in ocular development. Previous data on PDGFR lacks an expression map with high spatial and temporal resolution and lineage information. In this study, we aim to present a detailed PDGFR expression and lineage map from early embryogenesis to adulthood. PDGFR-CreER; mT/mG reporter mice were analyzed. mEGFP-positive cells contributed to multiple ocular lineages in a spatiotemporally regulated manner. A dynamic PDGFR expression was identified in corneal stromal cells, lens epithelial cells, lens fiber cells, and retinal astrocytes during the entire period of eye development, while PDGFR expression in retinal astrocytes from E17.5 onwards and in Müller glial cells was identified within two weeks after birth. By revealing detailed characterization of gene expression and function, we present a comprehensive map of PDGFR-expressing cells in the eye for a better understanding of PDGFR signaling's role during eye development.
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http://dx.doi.org/10.1155/2021/4982227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275403PMC
September 2021

Low-dose repeated exposure to chemical surfactant impairs corneal epithelium: When personal cleaning products entering the eye.

Exp Eye Res 2021 09 3;210:108696. Epub 2021 Jul 3.

Department of Ophthalmology, The Third Medical Center, Chinese PLA General Hospital, Beijing, 100089, China. Electronic address:

Studies have reported that the incidence of ocular discomfort in people who often wear makeup is higher than that in the normal population. The incidence of ocular discomfort of these people may be also related to the daily ocular exposure to chemical surfactants during cleaning. The objectives of this study were to explore morphological and pathological changes in the murine ocular surface after low-dose repeated exposure to disodium cocoamphodiacetate (DC), a kind of chemical surfactant widely used in personal cleaning products, and to investigate the possible mechanisms. DC was administered in low dose (0.1%) to the ocular surface of C56BL/6 once daily for two weeks. We found that there were an increase of sodium fluorescein staining on the cornea, a significant thinning of corneal epithelial thickness, and increased TUNEL-positive cells in corneal epithelium in vivo. DC treatment also modulated the distribution of K14 and P63 epithelia from the limbal to the center on the cornea. In cultured murine corneal epithelial progenitor cell line (TKE2), DC treatment induced cell detachment and decreased the activation of Ak strain transforming protein (AKT), and extracellular signal-regulated kinase (ERK). And DC increased TUNEL-positive cells in vitro with increased expression of cleaved Caspase3 and B-cell lymphoma-2 associated X protein (Bax). Our results indicated that repeated low-dose DC exposure on ocular surface caused significant impairment on the structure and viability of the corneal epithelium by inhibiting epithelial proliferation and inducing apoptosis. It provides the foundations to understand the harmful effects of cleaning products daily exposure on the ocular surface.
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http://dx.doi.org/10.1016/j.exer.2021.108696DOI Listing
September 2021

The Functional Characterization of Epigenetically Related lncRNAs Involved in Dysregulated CeRNA-CeRNA Networks Across Eight Cancer Types.

Front Cell Dev Biol 2021 17;9:649755. Epub 2021 Jun 17.

Key Laboratory of Tropical Translational Medicine of Ministry of Education, College of Biomedical Information and Engineering, Hainan Medical University, Haikou, China.

Numerous studies have demonstrated that lncRNAs could compete with other RNAs to bind miRNAs, as competing endogenous RNAs (ceRNAs), to regulate each other. On the other hand, ceRNAs were found to be recurrently dysregulated in cancer status. However, limited studies considered the upstream epigenetic regulatory factors that disrupted the normal competing mechanism. In the present study, we constructed the lncRNA-associated dysregulated ceRNA networks across eight cancer types. lncRNAs in the individual dysregulated network and pan-cancer core dysregulated ceRNA subnetwork were found to play more important roles than mRNAs. Integrating lncRNA methylation profiles, we identified 49 epigenetically related (ER) lncRNAs involved in the dysregulated ceRNA networks, including 18 epigenetically activated (EA) lncRNAs, 18 epigenetically silenced (ES) lncRNAs, and 13 rewired ER lncRNAs across eight cancer types. Furthermore, we evaluated the epigenetic regulating patterns of these lncRNAs and screened nine pan-cancer ER lncRNAs (six EA and three ES lncRNAs). The nine lncRNAs were found to regulate the cancer hallmarks by competing with mRNAs. Moreover, we found that integrating the expression and methylation profiles of the nine lncRNAs could predict cancer incidence in eight cancer types robustly and the cancer outcome of several cancer types. These results provide an improved understanding of methylation regulation to ceRNA and offer novel potential molecular therapeutic targets for the diagnosis and prognosis across different cancer types.
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http://dx.doi.org/10.3389/fcell.2021.649755DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247484PMC
June 2021

Molecular Hydrogen Attenuated N-methyl-N-Nitrosourea Induced Corneal Endothelial Injury by Upregulating Anti-Apoptotic Pathway.

Invest Ophthalmol Vis Sci 2021 07;62(9)

Department of Ophthalmology, The Third Medical Center, Chinese PLA General Hospital, Beijing, China.

Purpose: Previous work by our group has demonstrated the value of N-methyl-N-nitrosourea (MNU)-induced corneal endothelial decompensation in animal models. The aim of this study was to investigate the effect of molecular hydrogen (H2) on MNU-induced corneal endothelial cell (CEC) injury and the underlying mechanism.

Methods: MNU-induced animal models of CEC injury were washed with hydrogen-rich saline (HRS) for 14 days. Immunofluorescence staining, immunohistochemical staining, and corneal endothelial assessment were applied to determine architectural and cellular changes on the corneal endothelium following HRS treatment. MNU-induced cell models of CEC injury were co-cultured with H2. The effect of H2 was examined using morphological and functional assays.

Results: It was shown that MNU could inhibit the proliferation and specific physiological functions of CECs by increasing apoptosis and decreasing the expression of ZO-1 and Na+/K+-ATPase, whereas H2 improved the proliferation and physiological function of CECs by anti-apoptosis. Cell experiments further confirmed that H2 could reverse MNU damage to CECs by decreasing oxidative stress injury, interfering with the NF-κB/NLRP3 pathway and the FOXO3a/p53/p21 pathway.

Conclusions: This study suggests that topical application of H2 could protect CECs against corneal damage factors through anti-apoptotic effect, reduce the incidence and severity of corneal endothelial decompensation, and maintain corneal transparency.
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http://dx.doi.org/10.1167/iovs.62.9.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267183PMC
July 2021
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