Publications by authors named "Xiang Zhou"

1,569 Publications

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BASS: multi-scale and multi-sample analysis enables accurate cell type clustering and spatial domain detection in spatial transcriptomic studies.

Authors:
Zheng Li Xiang Zhou

Genome Biol 2022 Aug 4;23(1):168. Epub 2022 Aug 4.

Department of Biostatistics, University of Michigan, Ann Arbor, MI, 48109, USA.

Spatial transcriptomic studies are reaching single-cell spatial resolution, with data often collected from multiple tissue sections. Here, we present a computational method, BASS, that enables multi-scale and multi-sample analysis for single-cell resolution spatial transcriptomics. BASS performs cell type clustering at the single-cell scale and spatial domain detection at the tissue regional scale, with the two tasks carried out simultaneously within a Bayesian hierarchical modeling framework. We illustrate the benefits of BASS through comprehensive simulations and applications to three datasets. The substantial power gain brought by BASS allows us to reveal accurate transcriptomic and cellular landscape in both cortex and hypothalamus.
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http://dx.doi.org/10.1186/s13059-022-02734-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351148PMC
August 2022

Protective anti-gB neutralizing antibodies targeting two vulnerable sites for EBV-cell membrane fusion.

Proc Natl Acad Sci U S A 2022 Aug 2;119(32):e2202371119. Epub 2022 Aug 2.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361005, China.

Epstein-Barr virus (EBV) infects more than 90% of the world's adult population and accounts for a significant cancer burden of epithelial and B cell origins. Glycoprotein B (gB) is the primary fusogen essential for EBV entry into host cells. Here, we isolated two EBV gB-specific neutralizing antibodies, 3A3 and 3A5; both effectively neutralized the dual-tropic EBV infection of B and epithelial cells. In humanized mice, both antibodies showed effective protection from EBV-induced lymphoproliferative disorders. Cryoelectron microscopy analyses identified that 3A3 and 3A5 bind to nonoverlapping sites on domains D-II and D-IV, respectively. Structure-based mutagenesis revealed that 3A3 and 3A5 inhibit membrane fusion through different mechanisms involving the interference with gB-cell interaction and gB activation. Importantly, the 3A3 and 3A5 epitopes are major targets of protective gB-specific neutralizing antibodies elicited by natural EBV infection in humans, providing potential targets for antiviral therapies and vaccines.
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http://dx.doi.org/10.1073/pnas.2202371119DOI Listing
August 2022

Ascending aortic prosthetic graft mucormycosis.

Eur Heart J 2022 Aug 1. Epub 2022 Aug 1.

Department of Cardiac Surgery, Wuhan Asia Heart Hospital, No.753 Jinghan Road, Hankou District, Wuhan 430000, P.R.  China.

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http://dx.doi.org/10.1093/eurheartj/ehac422DOI Listing
August 2022

Copper-catalyzed direct decarboxylative fluorosulfonylation of aliphatic carboxylic acids.

Chem Commun (Camb) 2022 Aug 1. Epub 2022 Aug 1.

Guangdong Provincial Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, 510006, People's Republic of China.

Sulfonyl fluorides are emerging as key structural motifs in organic synthesis, medicinal chemistry, and materials science. Herein we report two efficient and complementary methods for direct decarboxylative fluorosulfonylation of carboxylic acids by the merging of copper catalysis with different -centered HAT regents. A wide range of structurally diverse sulfonyl fluorides was readily accessed from primary, secondary, and tertiary carboxylic acids in a single step under mild conditions.
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http://dx.doi.org/10.1039/d2cc03221jDOI Listing
August 2022

Subtype-specific pattern of white blood cell differential in endogenous hypercortisolism.

Eur J Endocrinol 2022 Sep 29;187(3):439-449. Epub 2022 Jul 29.

Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Hospital, University of Würzburg, Würzburg, Germany.

Objective: Endogenous hypercortisolism predisposes to impaired immune function and infections. To date, however, it is unknown whether there is a subtype-specific pattern in white blood cell (WBC) and WBC differential (WBCD) count.

Methods: A retrospective monocentric cohort study was carried out in patients with overt endogenous Cushing's syndrome (CS) or adrenal incidentalomas and autonomous cortisol secretion (ACS), with WBC/WBCD analysis at initial diagnosis and after biochemical remission. Cut-offs were obtained by receiver-operating characteristics analysis.

Results: In total, 253 patients were analyzed (Cushing's disease (CD); n = 88; ectopic CS (ECS), n = 31; cortisol-producing adrenal adenomas (CPA), n = 40; ACS, n = 45; adrenocortical carcinomas (ACC), n = 49). Total leukocytes and neutrophils correlated positively with serum cortisol after 1-mg dexamethasone (r = 0.314 and r = 0.428), while a negative correlation was observed for lymphocytes and eosinophils (r = -0.374 and r= -0.380) (each P < 0.0001). Similar observations were made for 24 h-urinary free cortisol. CD and ECS differed in numbers of neutrophils and lymphocytes (P < 0.0001) and were well differentiated at a cut-off of 6.1 for the neutrophil/lymphocyte ratio (sensitivity 90.0%, specificity 89.4%, and areas under the curve (AUC) 0.918). For adrenocorticotropic hormone (ACTH)-independent CS, the best diagnostic outcome was obtained for the discrimination of CPA and ACC at a cut-off of 187.9 for the platelet/lymphocyte ratio (sensitivity 59.6%, specificity 80.6%, and AUC 0.713). For ECS, CPA, and CD, neutrophils decreased (delta -47.0, -29.7, and -26.2%) and lymphocytes increased (+123.2, +78.1, and +17.7%) already 3 months after remission.

Conclusion: Most immune cells correlate with the degree of hypercortisolism and differ among CS subtypes. WBCD changes are already identified 3 months after remission from endogenous hypercortisolism.
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http://dx.doi.org/10.1530/EJE-22-0211DOI Listing
September 2022

Integrated Full-Length Transcriptome and MicroRNA Sequencing Approaches Provide Insights Into Salt Tolerance in Mangrove ( Buch.-Ham.).

Front Genet 2022 11;13:932832. Epub 2022 Jul 11.

College of Coastal Agricultural Science, Guangdong Ocean University, Zhanjiang, China.

MicroRNAs (miRNAs) are small RNA molecules that serve as key players in plant stress responses. Although stress-regulated miRNAs have been explored in various plants, they are not well studied in mangroves. Herein, we combined PacBio isoform sequencing (Iso-Seq) with BGISEQ short-read RNA-seq to probe the role of miRNAs in the salt stress response of the mangrove plant, Buch.-Ham. A total of 1,702,463 circular consensus sequencing reads were generated that produced 295,501 nonredundant full-length transcripts from the leaves of a 1-year-old . After sequencing nine small RNA libraries constructed from control and 1- and 28-day 300 mM NaCl treatments, we identified 143 miRNAs (114 known and 29 novel) from a total of >261 million short reads. With the criteria of |logFC| ≥ 1 and q-value < 0.05, 42 and 70 miRNAs were differentially accumulated after 1- and 28-day salt treatments, respectively. These differential accumulated miRNAs potentially targeted salt-responsive genes encoding transcription factors, ion homeostasis, osmotic protection, and detoxificant-related proteins, reminiscent of their responsibility for salinity adaptation in . Particularly, 62 miRNAs were specific under salt stress, of which 34 were co-expressed with their 131 predicted targets, thus producing 140 miRNA-target interactions. Of these, 82 miRNA-target pairs exhibited negative correlations. Eighteen miRNA targets were categorized for the 'environmental information processing' during KEGG analysis and were related to plant hormone signal transduction (ko04075), MAPK signaling pathway-plant (ko04016), and ABC transporters (ko02010). These results underscored miRNAs as possible contributors to mangrove success in severe environments and offer insights into an miRNA-mediated regulatory mechanism of salt response in .
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http://dx.doi.org/10.3389/fgene.2022.932832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310009PMC
July 2022

Comparative Transcriptome Analyses of Geriatric Rats Associate Age-Related Erectile Dysfunction With a lncRNA-miRNA-mRNA Regulatory Network.

Front Endocrinol (Lausanne) 2022 11;13:887486. Epub 2022 Jul 11.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: The key regulatory roles of long non-coding RNAs (lncRNAs) in age-related erectile dysfunction (A-ED) are unknown.

Aim: This study aimed to identify putative lncRNAs that regulate age-related erectile dysfunction transcriptome analyses, and to predict their specific regulatory routes bioinformatics methods.

Methods: 22 geriatric male SD rats were divided into age-related erectile dysfunction (A-ED) and negative control (NC) groups after evaluations of intracavernous pressure (ICP). By comparative analysis of transcriptomes of cavernosal tissues from both groups, we identified differentially expressed lncRNAs, miRNAs, and mRNAs. Seven differentially expressed lncRNAs were selected and further verified by quantitative real-time polymerase chain reactions (RT-qPCR). The construction of the lncRNA-miRNA-mRNA network, the Gene Ontology (GO) term enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed in Cytoscape.

Results: From comparative transcriptome analyses of A-ED and NC groups, 69, 29, and 364 differentially expressed lncRNAs, miRNAs, and mRNAs were identified respectively. Differentially expressed lncRNAs were culled to seven, which were all verified by qPCR. Three of these lncRNAs (ENSRNOT00000090050, ENSRNOT00000076482, and ENSRNOT00000029245) were used to build regulatory networks, of which only ENSRNOT00000029245 was successful. Moreover, GO and KEGG analyses demonstrated that these lncRNAs possibly regulated muscle myosin complex, muscle cell cellular homeostasis, and ultimately erectile function in rats through PI3K-Akt, fluid shear stress, and atherosclerosis pathways.

Conclusion: Our study identified differentially expressed lncRNAs, miRNAs, and mRNAs through comparisons of transcriptomes of geriatric rats. An identified lncRNA verified by qPCR, was used to construct a lncRNA-miRNA-mRNA regulatory network. LncRNA ENSRNOT00000029245 possibly regulated downstream mRNAs through this regulatory network, leading to apoptosis in the cavernous tissue, fibrosis, and endothelial dysfunction, which ultimately caused ED. These findings provide seminal insights into the molecular biology of aging-related ED, which could spur the development of effective therapeutics.
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http://dx.doi.org/10.3389/fendo.2022.887486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9309694PMC
July 2022

Nanotopographical 3D-Printed Poly(ε-caprolactone) Scaffolds Enhance Proliferation and Osteogenic Differentiation of Urine-Derived Stem Cells for Bone Regeneration.

Pharmaceutics 2022 Jul 8;14(7). Epub 2022 Jul 8.

College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu 610065, China.

3D-printing technology can be used to construct personalized bone substitutes with customized shapes, but it cannot regulate the topological morphology of the scaffold surface, which plays a vital role in regulating the biological behaviors of stem cells. In addition, stem cells are able to sense the topographical and mechanical cues of surface of scaffolds by mechanosensing and mechanotransduction. In our study, we fabricated a 3D-printed poly(ε-caprolactone) (PCL) scaffold with a nanotopographical surface and loaded it with urine-derived stem cells (USCs) for application of bone regeneration. The topological 3D-printed PCL scaffolds (TPS) fabricated by surface epiphytic crystallization, possessed uniformly patterned nanoridges, of which the element composition and functional groups of nanoridges were the same as PCL. Compared with bare 3D-printed PCL scaffolds (BPS), TPS have a higher ability for protein adsorption and mineralization in vitro. The proliferation, cell length, and osteogenic gene expression of USCs on the surface of TPS were significantly higher than that of BPS. In addition, the TPS loaded with USCs exhibited a good ability for bone regeneration in cranial bone defects. Our study demonstrated that nanotopographical 3D-printed scaffolds loaded with USCs are a safe and effective therapeutic strategy for bone regeneration.
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http://dx.doi.org/10.3390/pharmaceutics14071437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9317219PMC
July 2022

Extracellular Vesicles Derived From Hypoxia-Conditioned Adipose-Derived Mesenchymal Stem Cells Enhance Lymphangiogenesis.

Cell Transplant 2022 Jan-Dec;31:9636897221107536

Department of Orthopedic, Huiya Hospital, The First Affiliated Hospital of Sun Yat-sen University, Huizhou, China.

Extracellular vesicles from adipose-derived mesenchymal stem cells (ADSCs) play an important role in lymphangiogenesis; however, the underlying mechanisms are not fully understood. In this study, we aimed to investigate the function of extracellular vesicles secreted by hypoxia-conditioned ADSCs in lymphangiogenesis and explore the potential molecular mechanisms. Extracellular vesicles were extracted from ADSCs cultured under hypoxia or normoxia conditions. The uptake of extracellular vesicles by lymphatic endothelial cells (LECs) was detected by immunofluorescence staining. The effects of extracellular vesicles on the viability, migration, and tube formation of LECs were determined by CCK-8 assay, migration assay, and tube formation assay, respectively. Molecules and pathway involved in lymphangiogenesis mediated by ADSC-derived extracellular vesicles were analyzed by luciferase reporter assay, qRT-polymerase chain reaction (PCR), and Western blot. Hypoxia ADSC-derived extracellular vesicles (H-ADSC/evs) significantly enhanced the proliferation, migration, and tube formation of LECs. Hypoxia decreased the expression of miR-129 in ADSC-derived extracellular vesicles. Overexpression of miR-129 counteracted the promoting effect of H-ADSC/evs on lymphangiogenesis. In addition, decreased exosomal miR-129 expression resulted in upregulation of HMGB1 in LECs, which led to AKT activation and lymphangiogenesis enhancement. Our data reveal that extracellular vesicles derived from hypoxia-conditioned ADSCs induce lymphangiogenesis, and this effect is mediated by miR-129/HMGB1/AKT signaling. Our findings imply that hypoxia ADSC-isolated extracellular vesicles may represent as a valuable target for the treatment of diseases associated with lymphatic remodeling.
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http://dx.doi.org/10.1177/09636897221107536DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310282PMC
July 2022

Pyroptosis-Related lncRNA Prognostic Model for Renal Cancer Contributes to Immunodiagnosis and Immunotherapy.

Front Oncol 2022 4;12:837155. Epub 2022 Jul 4.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Renal clear cell cancer (ccRCC) is one of the most common cancers in humans. Thus, we aimed to construct a risk model to predict the prognosis of ccRCC effectively.

Methods: We downloaded RNA sequencing (RNA-seq) data and clinical information of 539 kidney renal clear cell carcinoma (KIRC) patients and 72 normal humans from The Cancer Genome Atlas (TCGA) database and divided the data into training and testing groups randomly. Pyroptosis-related lncRNAs (PRLs) were obtained through Pearson correlation between pyroptosis genes and all lncRNAs ( < 0.05, coeff > 0.3). Univariate and multivariate Cox regression analyses were then performed to select suitable lncRNAs. Next, a novel signature was constructed and evaluated by survival analysis and ROC analysis. The same observation applies to the testing group to validate the value of the signature. By gene set enrichment analysis (GSEA), we predicted the underlying signaling pathway. Furthermore, we calculated immune cell infiltration, immune checkpoint, the T-cell receptor/B-cell receptor (TCR/BCR), SNV, and Tumor Immune Dysfunction and Exclusion (TIDE) scores in TCGA database. We also validated our model with an immunotherapy cohort. Finally, the expression of PRLs was validated by quantitative PCR (qPCR).

Results: We constructed a prognostic signature composed of six key lncRNAs (U62317.1, MIR193BHG, LINC02027, AC121338.2, AC005785.1, AC156455.1), which significantly predict different overall survival (OS) rates. The efficiency was demonstrated using the receiver operating characteristic (ROC) curve. The signature was observed to be an independent prognostic factor in cohorts. In addition, we found the PRLs promote the tumor progression immune-related pathways revealed in GSEA. Furthermore, the TCR, BCR, and SNV data were retrieved to screen immune features, and immune cell scores were calculated to measure the effect of the immune microenvironment on the risk model, indicating that high- and low-risk scores have different immune statuses. The TIDE algorithm was then used to predict the immune checkpoint blockade (ICB) response of our model, and subclass mapping was used to verify our model in another immunotherapy cohort data. Finally, qPCR validates the PRLs in cell lines.

Conclusion: This study provided a new risk model to evaluate ccRCC and may be pyroptosis-related therapeutic targets in the clinic.
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http://dx.doi.org/10.3389/fonc.2022.837155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9291251PMC
July 2022

The miR-590-3p/CFHR3/STAT3 signaling pathway promotes cell proliferation and metastasis in hepatocellular carcinoma.

Aging (Albany NY) 2022 Jul 18;14(14):5783-5799. Epub 2022 Jul 18.

Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan 430081, Hubei Province, People's Republic of China.

Accumulating evidence has indicated that Complement factor H-related 3 (CFHR3) plays an essential role in various diseases. However, the biological functions of CFHR3 in hepatocellular carcinoma (HCC) remain largely unclear. Therefore, we perform a further study on CFHR3 in HCC. In this article, we report the suppressive role of CFHR3 in the proliferation and metastasis of HCC cells. CFHR3 downregulation is closely associated with large (T3-T4) HCC, tumor recurrence, and advanced (stage III-IV) clinical stage, functioning as an independent factor for the prognoses of HCC patients. Knockdown of CFHR3 promotes proliferation, migration, and invasion of HCC cells. Mechanistically, downregulation of CFHR3 is induced by miR-590-3p binding to the 3' untranslated region (UTR) of CFHR3. CFHR3 downregulation promotes the phosphorylation of STAT3 protein, thereby suppressing p53 expression. The promotional effect upon downregulation of CFHR3 induced by CFHR3 stable knockdown or miR-590-3p on HCC cell malignant phenotypes is attenuated by STAT3 inhibitor, S3I-201. In conclusion, our results reveal that CFHR3 is a protective biomarker for HCC patients, and targeting the miR-590-3p/CFHR3/p-STAT3/p53 signaling axis provides a promising strategy for HCC therapeutics.
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http://dx.doi.org/10.18632/aging.204178DOI Listing
July 2022

Determination of 5-Formyluracil via Oxime-Based Nucleotide-Metal Coordination.

Chembiochem 2022 Jul 18:e202200355. Epub 2022 Jul 18.

College of Chemistry and Molecular Sciences, Key Laboratory of Biomedical Polymers of Ministry of Education, The Institute for Advanced Studies, Hubei Province Key Laboratory of Allergy and Immunology, Wuhan University, Wuhan, 430072, China.

2-(Aminooxy)-N-(quinolin-8-yl)acetamide was synthesized, and its ability to regulate activities of DNA polymerase was tested. In addition, we used the isothermal amplification technology to detect the content of 5-formyluracil sites in irradiated genomic DNA, which confirmed its capability for the detection of 5-formyluracil content in general samples. This study presents the first example of the determination of 5fU based on coordination chemistry.
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http://dx.doi.org/10.1002/cbic.202200355DOI Listing
July 2022

N-methyladenosine and Its Implications in Viruses.

Genomics Proteomics Bioinformatics 2022 Jul 11. Epub 2022 Jul 11.

College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.

N-methyladenine (mA) is the most abundant RNA modification in mammalian messenger RNA (mRNA) and participates in and regulates many important biological activities, such as tissue development and stem cell differentiation. Due to an improved understanding of mA, researchers have discovered that the biological function of mA can be linked to many stages of mRNA metabolism and that mA can regulate a variety of complex biological processes. In addition to its location on mammalian mRNAs, mA has been identified on viral transcripts. mA also plays important roles in the life cycle of many viruses and in viral replication in host cells. In this review, we briefly introduce the detection methods of mA, mA-related proteins, and the functions of mA. We also summarize the effects of mA-related proteins on viral replication and infection. We hope that this review provides researchers with some insights for elucidating the complex mechanisms of the epitranscriptome related to viruses, and provides information for further study of the mechanisms of other modified nucleobases acting on processes such as viral replication. We also anticipate the review can stimulate collaborative research from different fields, such as chemistry, biology, and medicine, and promote the development of antiviral drugs and vaccines.
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http://dx.doi.org/10.1016/j.gpb.2022.04.009DOI Listing
July 2022

COVID-Related Posttraumatic Stress and Adjustment Disorder Symptoms in a Sample of Nepali Adults.

Asia Pac J Public Health 2022 Jul 14:10105395221112833. Epub 2022 Jul 14.

Department of Psychological Sciences, University of Missouri-St. Louis, St. Louis, MO, USA.

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http://dx.doi.org/10.1177/10105395221112833DOI Listing
July 2022

MiR-142-5p/FAM134B Axis Manipulates ER-Phagy to Control PRRSV Replication.

Front Immunol 2022 20;13:842077. Epub 2022 Jun 20.

Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education & Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, Huazhong Agricultural University, Wuhan, China.

Porcine reproductive and respiratory syndrome virus (PRRSV) can replicate its RNA genome in endoplasmic reticulum (ER) and utilize ER to facilitate its assembly and maturation. To maintain ER homeostasis, host cells initiate reticulophagy (known as ER-phagy) to effectively digest the stressed ER. In this study, we found that PRRSV infection subverted ER-phagy by downregulating ER-phagy receptor FAM134B. PRRSV-induced miR-142-5p directly targeted FAM134B and significantly promoted PRRSV replication. Meanwhile, siRNA-mediated depletion of FAM134B protein and overexpression of FAM134B mutant protein significantly disrupted ER-phagy and facilitated PRRSV replication. Furthermore, our results showed that FAM134B-mediated ER-phagy activated type I interferon signaling to inhibit PRRSV replication. Overall, this study reveals the important role of ER-phagy in PRRSV replication in a FAM134B-dependent manner. Our findings provide an insight into the pathogenesis of PRRSV and offer a theoretical basis for further development of antiviral therapeutic targets.
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http://dx.doi.org/10.3389/fimmu.2022.842077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251429PMC
June 2022

AT2 Receptor Stimulation Inhibits Vascular Smooth Muscle Cell Senescence Induced by Angiotensin II and Hyperglycemia.

Am J Hypertens 2022 Jul 6. Epub 2022 Jul 6.

Department of Neurology, The Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou, China.

Background: Hyperglycemia has been widely reported to induce vascular senescence. We have previously demonstrated that angiotensin II (Ang II) could promote brain vascular smooth muscle cell (VSMC) senescence, and its type 2 (AT2) receptor deletion could enhance VSMC senescence. Therefore, we examined the possible cross-talk between Ang II and hyperglycemia on VSMC senescence, and the roles of AT2 receptor agonist, compound 21 (C21) on it.

Methods: Aortic VSMC were prepared from adult male mice and stimulated with Ang II and/or high glucose (Glu) and/or C21 and/or an autophagy inhibitor, 3-methyladenine (3-MA) and/or an autophagy agonist, rapamycin (RAP) for the indicated times. Cellular senescence,oxidative stress and protein expressions were evaluated.

Results: Combination treatment with Ang II and Glu synergistically increased the proportion of VSMC senescent area compared with control group and each treatment alone, which was almost completely attenuated by C21 treatment. Moreover, combination treatment induced significant changes in the levels of superoxide anion, the expressions of p21 and pRb, and the ratio of LC3B II/I expression, which were also significantly attenuated by C21 treatment. The proportion of VSMC senescent area and the levels of superoxide anion by combination treatment were increased after 3-MA treatment, the proportion of senescent area and the expressions of p21 and pRb were decreased after RAP treatment, both of which were further attenuated by C21 treatment.

Conclusions: Ang II and hyperglycemia synergistically promoted VSMC senescence, at least partly through the participation by autophagy, oxidative stress and p21-pRb pathway, which could be inhibited by C21.
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http://dx.doi.org/10.1093/ajh/hpac083DOI Listing
July 2022

Programmable Transcriptional Modulation with a Structured RNA-Mediated CRISPR-dCas9 Complex.

J Am Chem Soc 2022 Jul 6;144(28):12690-12697. Epub 2022 Jul 6.

School of Chemistry and Materials Science, Department of Polymer Science and Engineering, iChEM (Collaborative Innovation Center of Chemistry for Energy Materials), University of Science and Technology of China, Hefei, Anhui 230026, China.

Multi-module dCas9 engineering systems have been developed for controllable transcriptional manipulation such as chemical- or light-induced systems. However, there is still a need for a separate module that can be used for internal control over the CRISPR-dCas9 system. Here, we describe a multi-module CRISPR-dCas9 system in which a separate structured RNA was applied as a programmable component that could control dCas9-based gene regulation and achieved a higher activation efficiency than dCas9-VPR that is traditionally used. By introducing a microRNA sensor, we generated a dCas9-based transcriptional regulation platform that responded to endogenous microRNAs and allowed controllable activation of endogenous genes. Moreover, we applied the platform to selectively identify HCT116 cells in a cell mixture. This work provides a flexible platform for efficient and controllable gene regulation based on CRISPR-dCas9.
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http://dx.doi.org/10.1021/jacs.2c02271DOI Listing
July 2022

Study on the antipruritic mechanism of Zanthoxylum bungeanum and Zanthoxylum schinifolium volatile oil on chronic eczema based on H1R and PAR-2 mediated GRPR pathway.

Allergol Immunopathol (Madr) 2022 1;50(4):83-96. Epub 2022 Jul 1.

Institute of traditional Chinese medicine, Shandong Traditional Chinese Medicine University, Jinan, China;

Objective: To observe the antipruritic effect and mechanism of the volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium on chronic eczema to provide data support for clinical application and new drug development of Zanthoxylum bungeanum and Zanthoxylum schinifolium.

Methods: The model of chronic eczema was established by using 2-dinitrochlorobenzene (DNCB), and the composition and content of volatile oil in Zanthoxylum schinifolium and Zanthoxylum bungeanum was determined by gas chromatography-mass spectrometry (GC-MS). The antipruritic effect by (EASI) score of eczema area and severity index and scratching times was then evaluated. Then, the contents of histamine, gastrin-releasing peptide (GRP), interleukin-4 (IL-4), and immunoglobulin E (IgE) in serum of rats was determined by enzyme-linked immunosorbent assay (ELISA). The tissue morphology was observed by HE staining. The expressions of H1R, PAR-2, TRPV1, TRPA1, and GRPR was then detected by immunohistochemistry, Western blot, and QRT-PCR.

Results: The results revealed that there were differences in the composition of volatile oil between Zanthoxylum bungeanum and Zanthoxylum schinifolium. Compared to the model group, the medium-dose group of Zanthoxylum bungeanum and Zanthoxylum schinifolium group significantly increased the difference of EASI score and scratching times, significantly decreased the concentrations of IL-4, IgE, GRP, and histamine, and significantly decreased the expression levels of H1R, PAR-2, TRPV1, and GRPR. The degree of inhibition on the pathological manifestations of chronic eczema was evident. There was no significant difference in antipruritic effect between the two groups. The expression of TRPA1 was inconsistent at the protein and gene level, which needs to be further researched.

Conclusion: The volatile oil of Zanthoxylum bungeanum and Zanthoxylum schinifolium can reduce the expression of H1R, PAR-2, TRPV1, and GRPR. The mechanism may be through the H1R and PAR-2-mediated GRPR pathway intervention to achieve the effect, both of which have the same antipruritic effect.
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http://dx.doi.org/10.15586/aei.v50i4.486DOI Listing
July 2022

Measurements of Rayleigh ratios in linear alkylbenzene.

Rev Sci Instrum 2022 Jun;93(6):063106

Hubei Nuclear Solid Physics Key Laboratory, School of Physics and Technology, Wuhan University, Wuhan, Hubei 430072, China.

This paper describes a new experimental setup designed for the direct measurement of the Rayleigh ratio and Rayleigh scattering length for linear alkylbenzene, a solvent commonly used in liquid scintillator detectors for neutrino experiments. Using the new approach, the perpendicularly polarized Rayleigh ratio was determined to be (4.52 ± 0.28) × 10 m sr at 405 nm and (3.82 ± 0.24) × 10 m sr at 432 nm, and the corresponding Rayleigh scattering length was L = 22.9 ± 0.3(stat.) ± 1.7(sys.) m at 405 nm and L = 27.0 ± 0.9(stat.) ± 1.8(sys.) m at 432 nm. These results are consistent with both previous results determined using other experimental strategies and theoretical predictions.
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http://dx.doi.org/10.1063/5.0091847DOI Listing
June 2022

Quality metrics and outcomes among critically ill patients in China: results of the national clinical quality control indicators for critical care medicine survey 2015-2019.

Chin Med J (Engl) 2022 May 5;135(9):1064-1075. Epub 2022 May 5.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100029, China.

Background: It is crucial to improve the quality of care provided to ICU patient, therefore a national survey of the medical quality of intensive care units (ICUs) was conducted to analyze adherence to quality metrics and outcomes among critically ill patients in China from 2015 to 2019.

Methods: This was an ICU-level study based on a 15-indicator online survey conducted in China. Considering that ICU care quality may vary between secondary and tertiary hospitals, direct standardization was adopted to compare the rates of ICU quality indicators among provinces/regions. Multivariate analysis was performed to identify potential factors for in-hospital mortality and factors related to ventilator-associated pneumonia (VAP), catheter-related bloodstream infections (CRBSIs), and catheter-associated urinary tract infections (CAUTIs).

Results: From the survey, the proportions of structural indicators were 1.83% for the number of ICU inpatients relative to the total number of inpatients, 1.44% for ICU bed occupancy relative to the total inpatient bed occupancy, and 51.08% for inpatients with Acute Physiology and Chronic Health Evaluation II scores ≥15. The proportions of procedural indicators were 74.37% and 76.60% for 3-hour and 6-hour surviving sepsis campaign bundle compliance, respectively, 62.93% for microbiology detection, 58.24% for deep vein thrombosis prophylaxis, 1.49% for unplanned endotracheal extubations, 1.99% for extubated inpatients reintubated within 48 hours, 6.38% for unplanned transfer to the ICU, and 1.20% for 48-hour ICU readmission. The proportions of outcome indicators were 1.28‰ for VAP, 3.06‰ for CRBSI, 3.65‰ for CAUTI, and 10.19% for in-hospital mortality. Although the indicators varied greatly across provinces and regions, the treatment level of ICUs in China has been stable and improved based on various quality control indicators in the past 5 years. The overall mortality rate has dropped from 10.19% to approximately 8%.

Conclusions: The quality indicators of medical care in China's ICUs are heterogeneous, which is reflected in geographic disparities and grades of hospitals. This study is of great significance for improving the homogeneity of ICUs in China.
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http://dx.doi.org/10.1097/CM9.0000000000001933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276455PMC
May 2022

A Global Building Occupant Behavior Database.

Sci Data 2022 06 28;9(1):369. Epub 2022 Jun 28.

Department of Heating, Ventilation and Dust Removal Technology, Faculty of Energy and Environmental Engineering, Silesian University of Technology, 44-100, Gliwice, Poland.

This paper introduces a database of 34 field-measured building occupant behavior datasets collected from 15 countries and 39 institutions across 10 climatic zones covering various building types in both commercial and residential sectors. This is a comprehensive global database about building occupant behavior. The database includes occupancy patterns (i.e., presence and people count) and occupant behaviors (i.e., interactions with devices, equipment, and technical systems in buildings). Brick schema models were developed to represent sensor and room metadata information. The database is publicly available, and a website was created for the public to access, query, and download specific datasets or the whole database interactively. The database can help to advance the knowledge and understanding of realistic occupancy patterns and human-building interactions with building systems (e.g., light switching, set-point changes on thermostats, fans on/off, etc.) and envelopes (e.g., window opening/closing). With these more realistic inputs of occupants' schedules and their interactions with buildings and systems, building designers, energy modelers, and consultants can improve the accuracy of building energy simulation and building load forecasting.
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http://dx.doi.org/10.1038/s41597-022-01475-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9240009PMC
June 2022

Organophosphate flame retardant TDCPP: A risk factor for renal cancer?

Chemosphere 2022 Oct 25;305:135485. Epub 2022 Jun 25.

Department of Urology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China; Department of Urology, The Affiliated Kizilsu Kirghiz Autonomous Prefecture People's Hospital of Nanjing Medical University, Artux, 845350, China. Electronic address:

Tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a chlorinated organophosphate flame retardants(OPFRs), is widely used in a range of plastic foams, resins, and latexes. It can be detected in human tissues, including urine, and milk. Recent research has suggested that TDCPP has neurotoxic, reproductive, and potentially carcinogenic. In our study, we proposed a novel method for predicting the gene associated with tumor-compound interactions. We firstly used The Comparative Toxicogenomics Database (CTD) and downloaded potentially interactive genes about TDCPP in renal carcinoma. Gene expression data and the corresponding clinical information of the Kidney renal clear cell cancer (KIRC) patients were obtained from The Cancer Genome Atlas database (TCGA). Data from normal people in The Genotype-Tissue Expression (GTEx) databases was used to supplement the calculations. After being predicted by PharmMapper database, and validated by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, 25 genes were selected to construct protein-protein interaction network analysis. The prognostic value of these genes was evaluated with Kaplan-Meier analysis, and four interactive genes were selected. Gene set variation analysis and drug-target binding prediction proved the hub gene has a potential relationship with renal clear cell carcinoma. We then used the ChEA3 (Chip-X Enrichment Analysis, Version 3) database to predict the upstream of these interactive genes. Molecular docking was used to predict the binding of these transcription factors to TDCPP and interactive genes to TDCPP. Moreover, in cell lines and in vivo experiments demonstrated the cancer-promoting effect of TDCPP. The expression of the interactive genes was verified by qPCR and Western blot. Combining binding energy and qPCR results, we choose EPAS1 to verify its function in renal carcinoma cell lines. Our study provides a novel method to predict the potential interactive genes between TDCPP and renal cancer, which may reveal potential targets for the treatment and prevention of diseases.
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http://dx.doi.org/10.1016/j.chemosphere.2022.135485DOI Listing
October 2022

Increased Water-Soluble Yellow Pigment Productivity Dual Mutagenesis and Submerged Repeated-Batch Fermentation of .

Front Microbiol 2022 9;13:914828. Epub 2022 Jun 9.

National Engineering Research Center of Rice and Byproduct Deep Processing, Central South University of Forestry and Technology, Changsha, China.

pigments (MPs) have been used in the food industry for more than 2,000 years and are known for their safety, bold coloring, and physiological activity. MPs are mainly yellow (YMPs), orange (OMPs), and red (RMPs). In this study, a mutant strain H14 with high production of water-soluble YMPs (WSYMPs, at 370 nm) was generated instead of primary YMPs ( at 420 nm), OMPs ( at 470 nm), and RMPs ( at 510 nm) produced by the parent strain LQ-6 through dual mutagenesis of atmospheric and room-temperature plasma and heavy ion beam irradiation (HIBI), producing 22.68 U/ml extracellular YMPs and 10.67 U/ml intracellular YMPs. WSYMP production was increased by 289.51% in optimal conditions after response surface methodology was applied in submerged fermentation. Application of combined immobilized fermentation and extractive fermentation improved productivity to 16.89 U/ml/day, 6.70 times greater than with conservative submerged fermentation. The produced WSYMPs exhibited good tone stability to environmental factors, but their pigment values were unstable to pH, light, and high concentrations of Ca, Zn, Fe, Cu, and Mg. Furtherly, the produced exYMPs were identified as two yellow monascus pigment components (monascusone B and CHNOS) by UHPLC-ESI-MS. This strategy may be extended to industrial production of premium WSYMPs using .
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http://dx.doi.org/10.3389/fmicb.2022.914828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9218666PMC
June 2022

Mitigation of honokiol on fluoride-induced mitochondrial oxidative stress, mitochondrial dysfunction, and cognitive deficits through activating AMPK/PGC-1α/Sirt3.

J Hazard Mater 2022 09 16;437:129381. Epub 2022 Jun 16.

Department of Neurology, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China. Electronic address:

Oxidative stress and mitochondrial dysfunction contribute greatly to fluoride-induced cognitive impairment and behavioural disorders. Honokiol, a natural biphenolic compound, possesses antioxidant and mitochondrial protective properties. The present study investigated the protective actions of honokiol on NaF-elicited cognitive deficits and elucidated the possible mechanism of honokiol-mediated protection. The results demonstrated that honokiol administration markedly attenuated fluoride-induced cognitive impairments and neural/synaptic injury in mice. Moreover, honokiol elevated the activity and expression of SOD2 and promoted mtROS scavenging through Sirt3 activation in NaF-treated mice and SH-SY5Y cell lines. Meanwhile, honokiol substantially lowered mtROS production by enhancing Sirt3-mediated mitochondrial DNA (mtDNA) transcription, thereby leading to significant increases in ATP synthesis and complex I activity. Further studies revealed that honokiol activated AMPK and upregulated the PGC-1α and Sirt3 protein expression in vivo and in vitro. Intriguingly, the protective actions of honokiol on oxidative stress and mitochondrial dysfunction were abolished by AMPK shRNA or Sirt3 shRNA. Notably, AMPK knockdown prevented the increase in PGC-1α and Sirt3 expression induced by honokiol, while Sirt3 shRNA suppressed Sirt3 signaling without significant effects on p-AMPK and PGC-1α expression. In conclusion, our findings indicate that honokiol mitigates NaF-induced oxidative stress and mitochondrial dysfunction by regulating mtROS homeostasis, partly via the AMPK/PGC-1α/Sirt3 pathway, which ultimately contributes to neuronal/synaptic injury and cognitive deficits.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129381DOI Listing
September 2022

LiDAR Echo Gaussian Decomposition Algorithm for FPGA Implementation.

Sensors (Basel) 2022 Jun 19;22(12). Epub 2022 Jun 19.

Guangxi Key Laboratory of Spatial Information and Geomatics, Guilin University of Technology, Guilin 541004, China.

As the existing processing algorithms for LiDAR echo decomposition are time-consuming, this paper proposes an FPGA-based improved Gaussian full-waveform decomposition method. The proposed FPGA architecture consists of three modules: (i) a pre-processing module, which is used to pipeline data reading and Gaussian filtering, (ii) the inflection point coordinate solution module, applied to the second-order differential operation and to calculate inflection point coordinates, and (iii) the Gaussian component parameter solution and echo component positioning module, which is utilized to calculate the Gaussian component and echo time parameters. Finally, two LiDAR datasets, covering the Congo and Antarctic regions, are used to verify the accuracy and speed of the proposed method. The experimental results show that (i) the accuracy of the FPGA-based processing is equivalent to that of PC-based processing, and (ii) the processing speed of the FPGA-based processing is 292 times faster than that of PC-based processing.
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http://dx.doi.org/10.3390/s22124628DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9230592PMC
June 2022

Change of Gut Microbiota in PRRSV-Resistant Pigs and PRRSV-Susceptible Pigs from Tongcheng Pigs and Large White Pigs Crossed Population upon PRRSV Infection.

Animals (Basel) 2022 Jun 9;12(12). Epub 2022 Jun 9.

Key Laboratory of Agricultural Animal Genetics, Breeding, and Reproduction of Ministry of Education, Huazhong Agricultural University, Wuhan 430070, China.

Porcine Reproductive and Respiratory Syndrome (PRRS) is one of the serious infectious diseases that threatens the swine industry. Increasing evidence shows that gut microbiota plays an important role in regulating host immune responses to PRRS virus (PRRSV). The aim of this study was to investigate gut microbiota difference between PRRSV-resistant pigs and PRRSV-suspectable pigs derived from a Tongcheng pigs and Large White pigs crossed population. PRRSV infection induces an increase in the abundance and diversity of gut microbiota. Correlation analysis showed that 36 genera were correlated with viral loads or weight gain after PRRSV infection. , , and were highly correlated with both viral load and weight gain. Notably, the diversity and abundance of beneficial bacteria such as was high in resistant pigs, and the diversity and abundance of pathogenic bacteria such as and were high in susceptible pigs. Gut microbiota were significantly associated with immune function and growth performance, suggesting that these genera might be related to viremia, clinical symptoms, and disease resistance. Altogether, this study revealed the correlation of gut microbiota with PRRSV infection and gut microbiota interventions may provide an effective prevention against PRRSV infection.
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http://dx.doi.org/10.3390/ani12121504DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9219425PMC
June 2022

1,3,4-Oxadiazole Derivatives as Plant Activators for Controlling Plant Viral Diseases: Preparation and Assessment of the Effect of Auxiliaries.

J Agric Food Chem 2022 Jul 22;70(26):7929-7940. Epub 2022 Jun 22.

State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Center for R&D of Fine Chemicals of Guizhou University, Guiyang 550025, China.

Plant viral diseases cause the loss of millions of dollars to agriculture around the world annually. Therefore, the development of highly efficient, ultra-low-dosage agrochemicals is desirable for protecting the health of crops and ensuring food security. Herein, a series of 1,3,4-oxadiazole derivatives bearing an isopropanol amine moiety was prepared, and the inhibitory activity against tobacco mosaic virus (TMV) was assessed. Notably, compound exhibited excellent anti-TMV protective activity with an EC value of 137.7 mg L, which was superior to that of ribavirin (590.0 mg L) and ningnanmycin (248.2 mg L). Moreover, the anti-TMV activity of some compounds could be further enhanced (by up to 5-30%) through supplementation with 0.1% auxiliaries. Biochemical assays suggested that compound could suppress the biosynthesis of TMV and induce the plant's defense response. Given these merits, designed compounds had outstanding bioactivities and unusual action mechanisms and were promising candidates for controlling plant viral diseases.
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http://dx.doi.org/10.1021/acs.jafc.2c01988DOI Listing
July 2022

Preventive effects of arctigenin from Arctium lappa L against LPS-induced neuroinflammation and cognitive impairments in mice.

Metab Brain Dis 2022 08 22;37(6):2039-2052. Epub 2022 Jun 22.

School of Basic Medical Sciences, Henan University of Science and Technology, No. 263, Kaiyuan Avenue, Luolong District, Luoyang, 471023, China.

Arctigenin (Arc) is a phenylpropanoid dibenzylbutyrolactone lignan in Arctium lappa L, which has been widely applied as a traditional Chinese herbal medicine for treating inflammation. In the present study, we explored the neuroprotective effect and the potential mechanisms of arctigenin against LPS-evoked neuroinflammation, neurodegeneration, and memory impairments in the mice hippocampus. Daily administration of arctigenin (50 mg/kg per day, i.g.) for 28 days revealed noticeable improvements in spatial learning and memory deficits after exposure to LPS treatment. Arctigenin prevented LPS-induced neuronal/synaptic injury and inhibited the increases in Abeta (Aβ) generation and the levels of amyloid precursor protein (APP) and β-site amyloid precursor protein cleavage enzyme 1 (BACE1). Moreover, arctigenin treatment also suppressed glial activation and reduced the production of proinflammatory cytokines. In LPS-treated BV-2 microglial cells and mice, activation of the TLR4 mediated NF-κB signaling pathway was significantly suppressed by arctigenin administration. Mechanistically, arctigenin reduced the LPS-induced interaction of adiponectin receptor 1 (AdipoR1) with TLR4 and its coreceptor CD14 and inhibited the TLR4-mediated downstream inflammatory response. The outcomes of the current study indicate that arctigenin mitigates LPS-induced apoptotic neurodegeneration, amyloidogenesis and neuroinflammation as well as cognitive impairments, and suggest that arctigenin may be a potential therapeutic candidate for neuroinflammation/neurodegeneration-related diseases.
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http://dx.doi.org/10.1007/s11011-022-01031-3DOI Listing
August 2022

Statistical analysis of spatially resolved transcriptomic data by incorporating multiomics auxiliary information.

Genetics 2022 Jul;221(4)

School of Mathematics, Jilin University, Changchun, Jilin 130012, China.

Effective control of false discovery rate is key for multiplicity problems. Here, we consider incorporating informative covariates from external datasets in the multiple testing procedure to boost statistical power while maintaining false discovery rate control. In particular, we focus on the statistical analysis of innovative high-dimensional spatial transcriptomic data while incorporating external multiomics data that provide distinct but complementary information to the detection of spatial expression patterns. We extend OrderShapeEM, an efficient covariate-assisted multiple testing procedure that incorporates one auxiliary study, to make it permissible to incorporate multiple external omics studies, to boost statistical power of spatial expression pattern detection. Specifically, we first use a recently proposed computationally efficient statistical analysis method, spatial pattern recognition via kernels, to produce the primary test statistics for spatial transcriptomic data. Afterwards, we construct the auxiliary covariate by combining information from multiple external omics studies, such as bulk and single-cell RNA-seq data using the Cauchy combination rule. Finally, we extend and implement the integrative analysis method OrderShapeEM on the primary P-values along with auxiliary data incorporating multiomics information for efficient covariate-assisted spatial expression analysis. We conduct a series of realistic simulations to evaluate the performance of our method with known ground truth. Four case studies in mouse olfactory bulb, mouse cerebellum, human breast cancer, and human heart tissues further demonstrate the substantial power gain of our method in detecting genes with spatial expression patterns compared to existing classic approaches that do not utilize any external information.
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http://dx.doi.org/10.1093/genetics/iyac095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9339334PMC
July 2022

Unusual case of a right atrial inflammatory myofibroblastic tumor presenting with an episodic cyanosis in an infant.

J Card Surg 2022 Sep 21;37(9):2859-2861. Epub 2022 Jun 21.

Department of Cardiac Surgery, Wuhan Asia Heart Hospital, Wuhan, China.

Cardiac inflammatory myofibroblastic tumor (IMT) is a rare benign tumor that occurs mainly in infants and children. We report a case of right atrial IMT in a 1-month-old girl with episodic cyanosis. Both echocardiography and cardiac computed tomography revealed a right atrial mass. The patient underwent a complete surgical resection of the mass and the postoperative histological examination confirmed the diagnosis of cardiac IMT. The patient recovered well after the operation and further follow-up evaluation was uneventful.
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http://dx.doi.org/10.1111/jocs.16698DOI Listing
September 2022
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