Publications by authors named "Yi Tang"

907 Publications

How Bayesian statistics may help answer some of the controversial questions in clinical research on Alzheimer's disease.

Alzheimers Dement 2021 Jun;17(6):917-919

Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany.

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http://dx.doi.org/10.1002/alz.12374DOI Listing
June 2021

Fungal siderophore biosynthesis catalysed by an iterative nonribosomal peptide synthetase.

Chem Sci 2020 Sep 28;11(42):11525-11530. Epub 2020 Sep 28.

Department of Chemical and Biomolecular Engineering, University of California Los Angeles California 90095 USA

Siderophores play a vital role in the viability of fungi and are essential for the virulence of many pathogenic fungal species. Despite their importance in fungal physiology and pathogenesis, the programming rule of siderophore assembly by fungal nonribosomal peptide synthetases (NRPSs) remains unresolved. Here, we report the characterization of the bimodular fungal NRPS, SidD, responsible for construction of the extracellular siderophore fusarinine C. The use of intact protein mass spectrometry, together with biochemical assays of native and dissected enzymes, provided snapshots of individual biosynthetic steps during NPRS catalysis. The adenylation and condensation domain of SidD can iteratively load and condense the amino acid building block -AMHO, respectively, to synthesize fusarinine C. Our study showcases the iterative programming features of fungal siderophore-producing NRPSs.
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http://dx.doi.org/10.1039/d0sc03627gDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162485PMC
September 2020

Biosynthesis of the fungal glyceraldehyde-3-phosphate dehydrogenase inhibitor heptelidic acid and mechanism of self-resistance.

Chem Sci 2020 Aug 19;11(35):9554-9562. Epub 2020 Aug 19.

Department of Chemical and Biomolecular Engineering, University of California Los Angeles CA 90095 USA

Overcoming resistance to bioactive small molecules is a significant challenge for health care and agriculture. As a result, efforts to uncover the mechanisms of resistance are essential to the development of new antibiotics, anticancer drugs and pesticides. To study how nature evolves resistance to highly potent natural products, we examined the biosynthesis and mechanism of self-resistance of the fungal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) inhibitor heptelidic acid (HA). HA is a nanomolar inhibitor of GADPH through the covalent modification of the active site cysteine thiol. The biosynthetic pathway of HA was elucidated, which uncovered the enzymatic basis of formation of the epoxide warhead. Structure-activity relationship study using biosynthetic intermediates established the importance of the fused lactone ring system in HA. The molecular basis of HA inhibiting human GAPDH was illustrated through the crystal structure of -GAPDH covalently bound with HA. A GAPDH isozyme HepG encoded in the HA cluster was characterized to be less sensitive to HA, and therefore contribute to self-resistance for the producing host. Comparison of the crystal structures of human GAPDH and HepG showed mutations both within and remote to the active site can contribute to resistance of inactivation, which was confirmed through mutagenesis. Due to the critical role GAPDH plays in aerobic glycolysis and other cellular functions, knowledge of HA mode of action and self-resistance mechanism could accelerate the development of improved inhibitors.
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http://dx.doi.org/10.1039/d0sc03805aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162069PMC
August 2020

CircHECTD1 Regulates Cell Proliferation and Migration by the miR-320-5p/SLC2A1 Axis in Glioblastoma Multiform.

Front Oncol 2021 17;11:666391. Epub 2021 May 17.

Department of Anatomy and Neurobiology, Jiangsu Key Laboratory of Neuroregeneration, Collaborative Innovation Center of Neuroregeneration, Nantong University, Nantong, China.

Glioblastoma multiform (GBM) is the most common and malignant primary brain cancer in adults, and thus, novel potential therapeutic targets for diagnosis and treatment are urgently needed. Circular RNAs (circRNAs) are a class of widespread and diverse endogenous RNAs that have been suggested as potential critical mediators during progression of various tumors. In this study, we investigated the involvement of circHECTD1 in GBM progression. CircHECTD1 Lentivirus, miR-320-5p mimic, and SLC2A1 Lentivirus were transduced into cancer cells independently or together. circHECTD1, miR-320-5p, and SLC2A1 level were detected by qRT-PCR. Western blot and qRT-PCR were applied to measure the expression of SLC2A1, CyclinD1, CDK2, and PCNA. Flow cytometry, EdU, colony formation, Transwell and wound-healing assays were conducted to assess cell proliferation and migration. Luciferase reporter assays were performed to determine the effect of miR-320-5p on circHECTD1 or SLC2A1. Xenograft experiments were implemented to evaluate tumor growth . CircHECTD1 expression led to the promotion of proliferation and migration of GBM cells. In addition, circHECTD1 acted as a ceRNA to interact with miR-320-5p, which targeted the solute carrier family 2 member 1 (SLC2A1). In vivo experiments also revealed that circHECTD1 promoted tumor growth. Collectively, our findings showed that the circHECTD1-miR-320-5p-SLC2A1 regulatory pathway promoted the progression of GBM, suggesting that circHECTD1 may be a therapeutic target for GBM.
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http://dx.doi.org/10.3389/fonc.2021.666391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166227PMC
May 2021

Association of Urinary Strontium Levels with Pregnancy-induced Hypertension.

Curr Med Sci 2021 May 28. Epub 2021 May 28.

Key Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Pregnancy-induced hypertension (PIH), including gestational hypertension and preeclampsia, accounts for the majority of maternal and perinatal morbidity and mortality. Strontium (Sr) has been recently associated with preeclampsia in a small group of women; however, the role of Sr in PIH is not fully understood and warrants further investigation. In this study, we examined the association between urinary Sr levels and PIH, and assessed the effect of maternal age on the association. Urinary Sr concentrations were measured in 5423 pregnant women before delivery by inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression analysis adjusting for potential confounders was applied to explore the association between Sr and PIH, and to evaluate the Sr-PIH relationship stratified by maternal age. Among the participants, 200 (3.83%) women were diagnosed with PIH. Compared with non-PIH women, women who developed PIH had lower urinary Sr concentrations (131.26 vs. 174.98 µg/L creatinine, P<0.01). With the natural log-transformed urinary creatinine-standardized Sr concentrations increasing, the risk of PIH decreased significantly [adjusted OR=0.60 (95%CI: 0.51, 0.72)]. Furthermore, the significant association of Sr with PIH was found among women under 35 years (P<0.01). Our finding suggested that Sr may play a potential protective role in the pathogenesis of PIH, especially among young pregnant women under 35 years old.
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http://dx.doi.org/10.1007/s11596-021-2366-6DOI Listing
May 2021

White Matter Fractional Anisotropy Is a Superior Predictor for Cognitive Impairment Than Brain Volumes in Older Adults With Confluent White Matter Hyperintensities.

Front Psychiatry 2021 5;12:633811. Epub 2021 May 5.

Department of Neurology, Innovation Center for Neurological Disorders, National Clinical Research Center for Geriatric Disorders, Xuanwu Hospital, Capital Medical University, Beijing, China.

Older patients with confluent white matter hyperintensities (WMHs) on magnetic resonance imaging have an increased risk for the onset of vascular cognitive impairment (VCI). This study investigates the predictive effects of the white matter (WM) fractional anisotropy (FA) and brain volumes on cognitive impairment for those with confluent WMHs. This study enrolled 77 participants with confluent WMHs (Fazekas grade 2 or 3), including 44 with VCI-no dementia (VCIND) and 33 with normal cognition (NC). The mean FA of 20 WM tracts was calculated to evaluate the global WM microstructural integrity, and major WM tracts were reconstructed using probabilistic tractography. Voxel-based morphometry was used to calculate brain volumes for the total gray matter (GM), the hippocampus, and the nucleus basalis of Meynert (NbM). All volumetric assays were corrected for total intracranial volume. All regression analyses were adjusted for age, gender, education, and apolipoprotein E (ApoE) gene ε4 status. Logistic regression analysis revealed that the mean FA value for global WM was the only independent risk factor for VCI (z score of FA: OR = 4.649, 95%CI 1.576-13.712, = 0.005). The tract-specific FAs were not associated with the risk of cognitive impairment after controlling the mean FA for global WM. The mean FA value was significantly associated with scores of Mini-Mental State Examination (MMSE) and Auditory Verbal Learning Test. A lower FA was also associated with smaller volumes of total GM, hippocampus, and NbM. However, brain volumes were not found to be directly related to cognitive performances, except for an association between the hippocampal volume and MMSE. In conclusion, the mean FA for global WM microstructural integrity is a superior predictor for cognitive impairment than tract-specific FA and brain volumes in people with confluent WMHs.
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http://dx.doi.org/10.3389/fpsyt.2021.633811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131652PMC
May 2021

The R2R3-MYB transcription factor GhMYB1a regulates flavonol and anthocyanin accumulation in Gerbera hybrida.

Hortic Res 2020 May 20;7(1):78. Epub 2020 May 20.

Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Sciences, South China Normal University, Guangzhou, 510631, China.

Anthocyanins and flavonols have vital roles in flower coloration, plant development, and defense. Because anthocyanins and flavonols share the same subcellular localization and common biosynthetic substrates, these pathways may compete for substrates. However, the mechanism regulating this potential competition remains unclear. Here, we identified GhMYB1a, an R2R3-MYB transcription factor involved in the regulation of anthocyanin and flavonol accumulation in gerbera (Gerbera hybrida). GhMYB1a shares high sequence similarity with that of other characterized regulators of flavonol biosynthesis. In addition, GhMYB1a is also phylogenetically grouped with these proteins. The overexpression of GhMYB1a in gerbera and tobacco (Nicotiana tabacum) resulted in decreased anthocyanin accumulation and increased accumulation of flavonols by upregulating the structural genes involved in flavonol biosynthesis. We further found that GhMYB1a functions as a homodimer instead of interacting with basic helix-loop-helix cofactors. These results suggest that GhMYB1a is involved in regulating the anthocyanin and flavonol metabolic pathways through precise regulation of gene expression. The functional characterization of GhMYB1a provides insight into the biosynthesis and regulation of flavonols and anthocyanins.
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http://dx.doi.org/10.1038/s41438-020-0296-2DOI Listing
May 2020

Urinary involvement in Erdheim-Chester disease: computed tomography imaging findings.

Abdom Radiol (NY) 2021 May 10. Epub 2021 May 10.

Department of Radiology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100730, China.

Purpose: To describe the urological manifestations of Erdheim-Chester disease (ECD) and their computed tomography (CT) findings.

Methods: We retrospectively reviewed 48 patients diagnosed with ECD at Peking Union Medical College Hospital from January 2014 to January 2020. Twenty-four patients exhibited urological manifestations. Their CT findings, including appearances of the involved area (e.g., perirenal space, renal sinus, ureters, renal arteries, and adrenal glands), occurrence rate of ECD involvement in each area, signal enhancement pattern after CT contrast agent administration, disease progression, and causes of hydronephrosis were discussed.

Results: In 24 patients with evidence of ECD urological involvement, the most common manifestation was perirenal infiltration, appearing as "hairy kidney" on unenhanced CT scans and moderate signal enhancement on enhanced CT scans (17/24, 70.8%). Other manifestations included renal sinus infiltration (16/24, 66.7%), proximal ureter involvement (14, 58.3%), renal artery sheath (10, 41.7%), hydronephrosis (14, 58.3%), and adrenal glands involvement (8, 33.3%). The histiocytic infiltrate was mostly bilateral, starting from the perirenal space and spreading to the renal sinus and ureters. Hydronephrosis was usually associated with infiltration of ureters.

Conclusion: Kidneys are the most common visceral organs affected by ECD. CT scanning is not only advantageous in early diagnosis, but also critical for designing the treatment regime for patients with ECD.
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http://dx.doi.org/10.1007/s00261-021-03106-8DOI Listing
May 2021

A transcriptional hub integrating gibberellin-brassinosteroid signals to promote seed germination in Arabidopsis.

J Exp Bot 2021 May 8. Epub 2021 May 8.

Guangdong Provincial Key Laboratory of Biotechnology for Plant Development, School of Life Science, South China Normal University, Guangzhou 510631, China.

Seed germination is regulated by multiple phytohormones, including Gibberellins (GAs) and Brassinosteroids (BRs); however, the molecular mechanism underlying GA and BR co-induced seed germination is not well elucidated. We demonstrated that BRs induce seed germination through promoting testa and endosperm rupture in Arabidopsis. BRs promote cell elongation, rather than cell division, at the hypocotyl-radicle transition region of embryonic axis during endosperm rupture. Two key basic helix-loop-helix transcription factors (TFs) in the BR signaling pathway, HBI1 and BEE2, are involved in the regulation of endosperm rupture. Expression of HBI1 and BEE2 was induced in response to BR and GA treatment. In addition, HBI1 or BEE2 overexpressing Arabidopsis plants are less sensitive to the BR biosynthesis inhibitor, brassinazole, and the GA biosynthesis inhibitor, paclobutrazol. HBI1 and BEE2 promote endosperm rupture and seed germination by directly regulating the GA-Stimulated Arabidopsis 6 (GASA6) gene. Expression of GASA6 was altered in Arabidopsis overexpressing HBI1, BEE2, or SRDX-repressor forms of the two TFs. In addition, HBI1 interacts with BEE2 to synergistically activate GASA6 expression. Our findings define a new role for GASA6 in GA and BR signaling and reveal a regulatory module that controls GA and BR co-induced seed germination in Arabidopsis.
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http://dx.doi.org/10.1093/jxb/erab192DOI Listing
May 2021

AoiQ Catalyzes Geminal Dichlorination of 1,3-Diketone Natural Products.

J Am Chem Soc 2021 May 6;143(19):7267-7271. Epub 2021 May 6.

Leibniz Institute for Natural Product Research and Infection Biology - HKI, 07745 Jena, Germany.

Enzymes that can perform halogenation of aliphatic carbons are of significant interest to the synthetic and biocatalysis communities. Here we describe the characterization of AoiQ, a single-component flavin-dependent halogenase (FDH) that catalyzes dichlorination of 1,3-diketone substrates in the biosynthesis of dichlorodiaporthin. AoiQ represents the first biochemically reconstituted FDH that can halogenate an enolizable sp-hybridized carbon atom.
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http://dx.doi.org/10.1021/jacs.1c02868DOI Listing
May 2021

Total Synthesis of (-)-Strictosidine and Interception of Aryne Natural Product Derivatives "Strictosidyne" and "Strictosamidyne".

J Am Chem Soc 2021 May 6;143(19):7471-7479. Epub 2021 May 6.

Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095, United States.

Monoterpene indole alkaloids are a large class of natural products derived from a single biosynthetic precursor, strictosidine. We describe a synthetic approach to strictosidine that relies on a key facially selective Diels-Alder reaction between a glucosyl-modified alkene and an enal to set the C15-C20-C21 stereotriad. DFT calculations were used to examine the origin of stereoselectivity in this key step, wherein two of 16 possible isomers are predominantly formed. These calculations suggest the presence of a glucosyl unit, also inherent in the strictosidine structure, guides diastereoselectivity, with the reactive conformation of the vinyl glycoside dienophile being controlled by an -anomeric effect. (-)-Strictosidine was subsequently accessed using late-stage synthetic manipulations and an enzymatic Pictet-Spengler reaction. Several new natural product analogs were also accessed, including precursors to two unusual aryne natural product derivatives termed "strictosidyne" and "strictosamidyne". These studies provide a strategy for accessing glycosylic natural products and a new platform to access monoterpene indole alkaloids and their derivatives.
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http://dx.doi.org/10.1021/jacs.1c02004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162926PMC
May 2021

Product Control and Insight into Conversion of C6 Aldose Toward C2, C4 and C6 Alditols in One-Pot Retro-Aldol Condensation and Hydrogenation Processes.

ChemistryOpen 2021 May;10(5):560-566

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Laboratory of Advanced Materials, Collaborative Innovation Centre of Chemistry for Energy Materials, Fudan University, 200433 postcode is missing, Shanghai city is missing, P. R. China.

Alcohols have a wide range of applicability, and their functions vary with the carbon numbers. C6 and C4 alditols are alternative of sweetener, as well as significant pharmaceutical and chemical intermediates, which are mainly obtained through the fermentation of microorganism currently. Similarly, as a bulk chemical, C2 alditol plays a decisive role in chemical synthesis. However, among them, few works have been focused on the chemical production of C4 alditol yet due to its difficult accumulation. In this paper, under a static and semi-flowing procedure, we have achieved the product control during the conversion of C6 aldose toward C6 alditol, C4 alditol and C2 alditol, respectively. About C4 alditol yield of 20 % and C4 plus C6 alditols yield of 60 % are acquired in the one-pot conversion via a cascade retro-aldol condensation and hydrogenation process. Furthermore, in the semi-flowing condition, the yield of ethylene glycol is up to 73 % thanks to its low instantaneous concentration.
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http://dx.doi.org/10.1002/open.202100023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095293PMC
May 2021

Biosynthesis and synthetic biology of psychoactive natural products.

Chem Soc Rev 2021 Jun;50(12):6950-7008

Department of Chemical and Biomolecular Engineering, University of California, Los Angeles, Los Angeles, CA, USA. and Invizyne Technologies, Inc., Monrovia, CA, USA.

Psychoactive natural products play an integral role in the modern world. The tremendous structural complexity displayed by such molecules confers diverse biological activities of significant medicinal value and sociocultural impact. Accordingly, in the last two centuries, immense effort has been devoted towards establishing how plants, animals, and fungi synthesize complex natural products from simple metabolic precursors. The recent explosion of genomics data and molecular biology tools has enabled the identification of genes encoding proteins that catalyze individual biosynthetic steps. Once fully elucidated, the "biosynthetic pathways" are often comparable to organic syntheses in elegance and yield. Additionally, the discovery of biosynthetic enzymes provides powerful catalysts which may be repurposed for synthetic biology applications, or implemented with chemoenzymatic synthetic approaches. In this review, we discuss the progress that has been made toward biosynthetic pathway elucidation amongst four classes of psychoactive natural products: hallucinogens, stimulants, cannabinoids, and opioids. Compounds of diverse biosynthetic origin - terpene, amino acid, polyketide - are identified, and notable mechanisms of key scaffold transforming steps are highlighted. We also provide a description of subsequent applications of the biosynthetic machinery, with an emphasis placed on the synthetic biology and metabolic engineering strategies enabling heterologous production.
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http://dx.doi.org/10.1039/d1cs00065aDOI Listing
June 2021

Nitrogen-Doped Multiwalled Carbon Nanotubes Enhance Bone Remodeling through Immunomodulatory Functions.

ACS Appl Mater Interfaces 2021 Jun 28;13(21):25290-25305. Epub 2021 Apr 28.

College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Tai'an 271018, China.

It has been reported that multiwalled carbon nanotubes (MWCNTs) can reportedly positively affect growth and differentiation of bone-related cells and therefore offer great potential in biomedical applications. To overcome negative immune responses that limit their application, specific doping and functionalization can improve their biocompatibility. Here, we demonstrated that nitrogen-doped carboxylate-functionalized MWCNTs (N-MWCNTs) enhance bone remodeling both and with excellent biocompatibility, via stimulation of both bone resorption and formation. We revealed that 0.2 μg/mL N-MWCNTs not only increase the transcription of osteoblastogenic and osteoclastogenic genes but also up-regulate the activities of both TRAP and AKP in the differentiation of bone marrow stromal cells (BMSCs). Additionally, intramuscular administration of N-MWCNTs at a dosage of 1.0 mg/kg body weight enhances bone mineral density and bone mass content in mice, as well as induces potentiated degree of TRAP- and ARS-positive staining in the femur. The positive regulation of N-MWCNTs on bone remodeling is initiated by macrophage phagocytosis, which induces altered production of inflammatory cytokines by immune response pathways, and consequently up-regulates IL1α, IL10, and IL16. These cytokines collectively regulate the central osteoclastogenic transcription factor NFATc1 and osteoblastogenic BMP signaling, the suppression of which confirmed that these factors respectively participate in N-MWCNT-mediated regulation of osteoclastic and osteoblastic bone marrow stem cell activities. These results suggest that N-MWCNTs can be readily generalized for use as biomaterials in bone tissue engineering for metabolic bone disorders.
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http://dx.doi.org/10.1021/acsami.1c05437DOI Listing
June 2021

Introduction to the special issue: "Natural Product Discovery and Development in the Genomic Era: 2021".

J Ind Microbiol Biotechnol 2021 06;48(3-4)

Department of Chemical, Biological, and Materials Engineering, University of South Florida, Tampa, FL 33620, USA.

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http://dx.doi.org/10.1093/jimb/kuab030DOI Listing
June 2021

Effect of Long-Term Frozen Storage on Health-Promoting Compounds and Antioxidant Capacity in Baby Mustard.

Front Nutr 2021 6;8:665482. Epub 2021 Apr 6.

College of Horticulture, Sichuan Agricultural University, Chengdu, China.

This study investigated the effects of blanching and subsequent long-term frozen storage on the retention of health-promoting compounds and antioxidant capacity in frozen lateral buds of baby mustard. Results showed that all glucosinolates were well preserved during frozen storage, and 72.48% of total glucosinolate content was retained in the unblanched treatment group after 8 months, as were chlorophylls, carotenoids, ascorbic acid, total phenolics, soluble sugars, soluble proteins, and antioxidant capacity. The loss of nutritional qualities mainly occurred in the 1st month of frozen storage, and nutritional qualities in the unblanched treatment group were significantly better than those in the blanched treatment group during frozen storage. Blanching before freezing reduced contents of high-content glucosinolates and ascorbic acid, as well as antioxidant capacity levels. Therefore, we recommend using long-term frozen storage to preserve the quality of baby mustard to achieve annual supply, and freezing without blanching.
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http://dx.doi.org/10.3389/fnut.2021.665482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055821PMC
April 2021

Targeted Genome Mining Reveals the Biosynthetic Gene Clusters of Natural Product CYP51 Inhibitors.

J Am Chem Soc 2021 Apr 15;143(16):6043-6047. Epub 2021 Apr 15.

Texas Therapeutics Institute, The Brown Foundation Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, Houston, Texas 77054, United States.

Lanosterol 14α-demethylase (CYP51) is an important target in the development of antifungal drugs. The fungal-derived restricticin and related molecules are the only examples of natural products that inhibit CYP51. Here, using colocalizations of genes encoding self-resistant CYP51 as the query, we identified and validated the biosynthetic gene cluster (BGC) of . Additional genome mining of related BGCs with CYP51 led to production of the related lanomycin . The pathways for both and were identified from fungi not known to produce these compounds, highlighting the promise of the self-resistance enzyme (SRE) guided approach to bioactive natural product discovery.
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http://dx.doi.org/10.1021/jacs.1c01516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8119659PMC
April 2021

Objective Findings on the K-Doped -CN Photocatalysts: The Presence and Influence of Organic Byproducts on K-Doped -CN Photocatalysis.

Langmuir 2021 Apr 14;37(16):4859-4868. Epub 2021 Apr 14.

Chongqing Research Academy of Environmental Sciences, Chongqing 401147, China.

The thermal-condensation method is widely used for the synthesis of K-doped -CN photocatalysts, but the presence of organic byproducts in the resultant products is often overlooked in previous reports. Here, we demonstrated the universal presence of organic byproducts in K-doped -CN synthesized by typical thermal condensation of KOH/melamine, KOH/dicyandiamide, or KOH/urea. Taking the K-doped -CN photocatalysis for the degradation of dimethyl phthalate as an example, the negative influence of the organic byproducts on K-doped -CN photocatalysis was confirmed. Specifically, the organic byproducts can be gradually dissolved into the photocatalytic system of K-doped -CN as new and stable pollutants. Based on the solubility investigations on the byproducts in several solvents, hot-water washing was demonstrated to be a relatively effective approach to remove the organic byproducts from K-doped -CN. The formation of organic byproducts during the synthesis of K-doped -CN could be ascribed to the fact that the presence of K salts in melamine, dicyandiamide, or urea molecules results in their insufficient thermal condensation into expected -CN. The present work provides objective information about the K-doped -CN photocatalysts and reminds researchers about the influence of the organic byproducts on the applications of the other impurity-doped -CN photocatalysts.
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http://dx.doi.org/10.1021/acs.langmuir.1c00044DOI Listing
April 2021

Role of mono-ADP-ribosylation histone modification (Review).

Exp Ther Med 2021 Jun 31;21(6):577. Epub 2021 Mar 31.

Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing 400016, P.R. China.

The current knowledge regarding ADP-ribosylation modifications of histones, particularly mono-ADP-ribosylation modifications, is limited. However, recent studies have identified an increasing number of mono-ADP-ribosyltransferases and the role of mono-ADP-ribosylation has become a hot research topic. In particular, histones that are substrates of several mono-ADP-ribosyltransferases and mono-ADP-ribosylated histones were indicated to be involved in numerous physiological or pathological processes. Compared to poly-ADP-ribosylation histone modification, the use of mono-ADP-ribosylation histone modification is restricted by the limited methods for research into its function in physiological or pathological processes. The aim of the present review was to discuss the details regarding mono-ADP-ribosylation modification of histones and the currently known functions thereof, such as cell physiological and pathological processes, including tumorigenesis.
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http://dx.doi.org/10.3892/etm.2021.10009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027728PMC
June 2021

Novel Predictors and Risk Score of Treatment Failure in Peritoneal Dialysis-Related Peritonitis.

Front Med (Lausanne) 2021 19;8:639744. Epub 2021 Mar 19.

Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, China.

Peritonitis is a severe complication in peritoneal dialysis (PD). This study was performed to identify predictors and establish a risk score for treatment failure in peritonitis patients. A single-center, retrospective observational study was conducted. The basic demographic characteristics, clinical and laboratory data of all patients with peritonitis during the study period were documented and analyzed. Multivariate logistic regression was applied to examine independent predictors of treatment failure, and a risk prediction score was established. Three hundred fourteen episodes experienced by 241 patients were included in the final analysis. Logistic regression analysis indicated that PD duration (OR 1.017; P 0.005), fibrinogen (OR 1.327; P 0.021), high-density lipoprotein (OR 0.443; P 0.032), fungal infection (OR 63.413; < 0.001), intestinal obstruction (OR 5.186, P 0.007), and diabetes mellitus (OR 2.451; P 0.018), hemodialysis history (OR 2.804, P 0.006) were independent predictors of treatment failure. The risk prediction score system showed a good calibration ( > 0.05) and discrimination (AUROC 0.80, < 0.001). Fibrinogen, PD duration, fungal infection, hemodialysis history, concurrent intestinal obstruction, or diabetes mellitus were independent risk factors for a poor peritonitis outcome, while the high-density lipoprotein was a protective factor. This novel risk prediction score system may be used to predict a high risk of treatment failure effectively.
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http://dx.doi.org/10.3389/fmed.2021.639744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033636PMC
March 2021

Mesangial IgM deposition predicts renal outcome in patients with IgA nephropathy: a multicenter, observational study.

Clin Exp Med 2021 Apr 10. Epub 2021 Apr 10.

Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

Mesangial IgM deposition is found in patients with immunoglobulin A nephropathy (IgAN). This study aims to investigate the relationships between mesangial IgM deposition and disease progression in IgAN patients. A total of 1239 patients with biopsy-proven primary IgAN were enrolled in this multicenter, observational study between January 2013 and August 2017. According to the degree of IgM deposition, 1239 patients were divided into three groups: Grade 0 (no or trace; n = 713, 57.55%), Grade 1 (mild; n = 414, 33.41%), Grades 2 + 3 (moderate and marked; n = 112, 9.04%). Using a 1:1 propensity score matching (PSM) method identifying age, gender and treatment modality to minimize confounding factors, 1042 matched patients (out of 1239) with different degrees of IgM deposition were enrolled to evaluate the severity of baseline clinicopathological features and renal outcome: Grade 0 (n = 521, 50.00%), Grade 1 (n = 409, 39.25%), Grades 2 + 3 (n = 112, 10.75%). Kaplan-Meier and Cox proportional hazards analyses were performed to determine whether different degrees of mesangial IgM deposition are associated with varying renal outcomes in IgAN. During a mean follow-up of 48.90 ± 23.86 and 49.01 ± 23.73 months, before and after adjusting for propensity scores, respectively, the rate of complete remission (CR) was progressively lower with increased IgM deposition in both unmatched (63.39%, 46.14%, 45.54%) and matched cohort (61.80%, 46.45%, 45.54%), whereas the proportion of patients progressing to end-stage renal disease (ESRD) showed reverse correlation (P < 0.001). Kaplan-Meier analysis indicated negative correlation between the intensity of mesangial IgM deposits and cumulative renal survival (all P < 0.05). Moreover, Cox regression analysis revealed that the degree of mesangial IgM deposition predicted renal outcome independent of MESTC score and clinical variables in the unmatched (Grade 1, HR, 1.59; 95% CI, 1.11-2.29; P = 0.01; Grades 2 + 3, HR, 1.69; 95% CI, 1.02-2.08; P = 0.04) and matched cohort (Grade 1, HR, 1.84; 95% CI, 1.19-2.85; P = 0.01; Grades 2 + 3, HR, 1.91; 95% CI, 1.01-3.24; P = 0.04). Mesangial IgM deposition is associated with histological activity, clinical severity and renal outcome and is an independent risk factor for poor renal prognosis in IgAN. TRIAL REGISTRATION: TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074 .
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http://dx.doi.org/10.1007/s10238-021-00703-1DOI Listing
April 2021

Observing a Zeolite Nucleus (Subcrystal) with a Uniform Framework Structure and Its Oriented Attachment without Single-Molecule Addition.

Angew Chem Int Ed Engl 2021 Jun;60(24):13444-13451

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Centre of Chemistry for Energy Materials (iChEM), Fudan University, Shanghai, 200433, P. R. China.

Multiple and complex crystallization process of zeolite including complementary single-molecule condensation and particle assembly, and alternately dominant nucleation and growth behavior, plays the critical role in zeolite crystallization but meanwhile makes us hard to study the respective effects. Herein, we strip nuclei from the synthetic solution and find that high-ordered nucleus (subcrystal) is the premise to ignite high-speed growth of zeolite crystal. The high-ordered subcrystals with the size of only 6-10 nm possess regular aperture structure and microporous area similar to zeolite nanocrystal. Interestingly, a unitary oriented aggregation process of the subcrystals towards nanosheets is well observed and characterized where single-molecule addition process is greatly repressed. If a wider range of zeotype nuclei can be expanded, a new synthetic strategy of zeotype materials with heterogeneous framework and active sites may be expected, which may novelize zeolite catalytic properties.
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http://dx.doi.org/10.1002/anie.202102621DOI Listing
June 2021

Biosynthesis of Cyclophane-Containing Hirsutellone Family of Fungal Natural Products.

J Am Chem Soc 2021 Apr 9;143(15):5605-5609. Epub 2021 Apr 9.

State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, MOE-LSB and MOE-LSC, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.

Hirsutellones are fungal natural products containing a macrocyclic cyclophane connected to a decahydrofluorene ring system. We have elucidated the biosynthetic pathway for pyrrocidine B () and GKK1032 A (). Two small hypothetical proteins, an oxidoreductase and a lipocalin-like protein, function cooperatively in the oxidative cyclization of the cyclophane, while an additional hypothetical protein in the pyrrocidine pathway catalyzes the specific cycloaddition to form the fused decahydrofluorene.
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http://dx.doi.org/10.1021/jacs.1c00098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094548PMC
April 2021

Critical role of SMG7 in activation of the ATR-CHK1 axis in response to genotoxic stress.

Sci Rep 2021 Apr 5;11(1):7502. Epub 2021 Apr 5.

Department of Regenerative and Cancer Cell Biology, Albany Medical College, 47 New Scotland Ave, Albany, NY, 12208, USA.

CHK1 is a crucial DNA damage checkpoint kinase and its activation, which requires ATR and RAD17, leads to inhibition of DNA replication and cell cycle progression. Recently, we reported that SMG7 stabilizes and activates p53 to induce G arrest upon DNA damage; here we show that SMG7 plays a critical role in the activation of the ATR-CHK1 axis. Following genotoxic stress, SMG7-null cells exhibit deficient ATR signaling, indicated by the attenuated phosphorylation of CHK1 and RPA32, and importantly, unhindered DNA replication and fork progression. Through its 14-3-3 domain, SMG7 interacts directly with the Ser635-phosphorylated RAD17 and promotes chromatin retention of the 9-1-1 complex by the RAD17-RFC, an essential step to CHK1 activation. Furthermore, through maintenance of CHK1 activity, SMG7 controls G-M transition and facilitates orderly cell cycle progression during recovery from replication stress. Taken together, our data reveals SMG7 as an indispensable signaling component in the ATR-CHK1 pathway during genotoxic stress response.
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http://dx.doi.org/10.1038/s41598-021-86957-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021557PMC
April 2021

F-FDG PET Combined With MR Spectroscopy Elucidates the Progressive Metabolic Cerebral Alterations After Blast-Induced Mild Traumatic Brain Injury in Rats.

Front Neurosci 2021 18;15:593723. Epub 2021 Mar 18.

Department of Nuclear Medicine, Daping Hospital, Army Medical University, Chongqing, China.

A majority of blast-induced mild traumatic brain injury (mTBI) patients experience persistent neurological dysfunction with no findings on conventional structural MR imaging. It is urgent to develop advanced imaging modalities to detect and understand the pathophysiology of blast-induced mTBI. Fluorine-18 fluorodeoxyglucose positron emission tomography (F-FDG PET) could detect neuronal function and activity of the injured brain, while MR spectroscopy provides complementary information and assesses metabolic irregularities following injury. This study aims to investigate the effectiveness of combining F-FDG PET with MR spectroscopy to evaluate acute and subacute metabolic cerebral alterations caused by blast-induced mTBI. Thirty-two adult male Sprague-Dawley rats were exposed to a single blast (mTBI group) and 32 rats were not exposed to the blast (sham group), followed by F-FDG PET, MRI, and histological evaluation at baseline, 1-3 h, 1 day, and 7 days post-injury in three separate cohorts. F-FDG uptake showed a transient increase in the amygdala and somatosensory cortex, followed by a gradual return to baseline from day 1 to 7 days post-injury and a continuous rise in the motor cortex. In contrast, decreased F-FDG uptake was seen in the midbrain structures (inferior and superior colliculus). Analysis of MR spectroscopy showed that inflammation marker myo-inositol (Ins), oxidative stress marker glutamine + glutamate (Glx), and hypoxia marker lactate (Lac) levels markedly elevated over time in the somatosensory cortex, while the major osmolyte taurine (Tau) level immediately increased at 1-3 h and 1 day, and then returned to sham level on 7 days post-injury, which could be due to the disruption of the blood-brain barrier. Increased F-FDG uptake and elevated Ins and Glx levels over time were confirmed by histology analysis which showed increased microglial activation and gliosis in the frontal cortex. These results suggest that F-FDG PET and MR spectroscopy can be used together to reflect more comprehensive neuropathological alterations , which could improve our understanding of the complex alterations in the brain after blast-induced mTBI.
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http://dx.doi.org/10.3389/fnins.2021.593723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012735PMC
March 2021

A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy.

Sci Rep 2021 Mar 9;11(1):5467. Epub 2021 Mar 9.

Division of Nephrology, Department of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.

It was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan-Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074 .
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http://dx.doi.org/10.1038/s41598-021-84715-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943768PMC
March 2021

More than meets the eye: a missed traumatic laser in situ keratomileusis flap dislocation.

Med J Aust 2021 04 21;214(7):305-305.e1. Epub 2021 Mar 21.

Canberra Hospital, Canberra, ACT.

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http://dx.doi.org/10.5694/mja2.50985DOI Listing
April 2021

Efficacy of NB-UVB as Add-on Therapy to Antihistamine in the Treatment of Chronic Urticaria: A Systematic Review and Meta-analysis.

Dermatol Ther (Heidelb) 2021 Jun 18;11(3):681-694. Epub 2021 Mar 18.

Institute of Dermatology, Guangzhou Medical University, Guangzhou, 510095, Guangdong, China.

Introduction: Narrow-band ultraviolet B (NB-UVB) phototherapy has been used for the treatment of chronic urticaria (CU), but the clinical efficacy of this treatment modality requires further evidence. A systematic review and meta-analysis of randomized clinical trials were conducted to evaluate the efficacy and safety of NB-UVB as add-on therapy in the treatment of CU.

Methods: A literature search was conducted in the Cochrane, Embase, PubMed, Web of Science, CNKI, CBM, VIP and WanFang databases up to October 2020. A total of nine studies involving 713 participants met the inclusion criteria.

Results: Two trials showed a significant difference in the Urticaria Activity Score between therapy with NB-UVB + antihistamines and that with antihistamines alone (mean difference 8.23, 95% confidence interval [CI] 5.78-10.68, p < 0.00001). Six trials (563 participants) showed a significant benefit of NB-UVB as add-on therapy to antihistamines in the total effective rate (risk ratio [RR] 1.56, 95% CI 1.39-1.75, p < 0.00001). In terms of adverse events, no statistically significant differences were found for NB-UVB + antihistamines versus antihistamines alone (RR 1.10, 95% CI 0.67-1.79, p = 0.71). Combination therapy of NB-UVB + antihistamines yielded a significantly lower risk of recurrence (RR 0.25, 95% CI 0.14-0.44, p < 0.00001).

Conclusion: Our meta-analysis suggests that combination therapy of NB-UVB + antihistamines is significantly more effective in treating CU than antihistamines alone.
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http://dx.doi.org/10.1007/s13555-021-00510-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8163931PMC
June 2021

Analysis of Mono-ADP-Ribosylation Levels in Human Colorectal Cancer.

Cancer Manag Res 2021 12;13:2401-2409. Epub 2021 Mar 12.

Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, 400016, People's Republic of China.

Background: Colorectal cancer remains a major public health problem with high morbidity and mortality rates. In the search for the mechanisms of colorectal cancer occurrence and development, increasing attention has been focused on epigenetics. The overall level of Mono-ADP-ribosylation, an epigenetic, has not been investigated now. The aim of our study was to analysis of the overall level of mono-ADP-ribosylation in colorectal cancer.

Methods: Immunohistochemistry was used to investigate the level of mono-ADP-ribosylation in colorectal cancer and normal colorectal adjacent tissue from 64 CRC patients. The data of patient demographic, clinical and pathological characteristics were acquired and analyzed.

Results: Mono-ADP-ribosylation was present in both colorectal adenocarcinoma and normal colorectal tissue. The overall level of mono-ADP-ribosylation in colorectal cancer was significantly higher than that in normal colorectal adjacent tissue. In the nucleus, the majority of samples in the high-level group were colorectal adenocarcinoma (55/64), but the opposite was true for normal colorectal tissues (7/32). In particular, increases in the level of mono-ADP-ribosylation in the cytoplasm of colorectal cancer cells was associated with a greater invasion depth of the tumor.

Conclusion: The increased level of mono-ADP-ribosylation in colorectal cancer enhances tumor invasion, which suggests that mono-ADP-ribosylation is involved in the development of colorectal cancer and may become a new direction to solve the problem of colorectal cancer.
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http://dx.doi.org/10.2147/CMAR.S303064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965690PMC
March 2021

Effect of TMUV on immune organs of TMUV infected ducklings.

Vet Microbiol 2021 Apr 5;255:109033. Epub 2021 Mar 5.

College of Animal Science and Technology, Shandong Agricultural University, Tai'an, Shandong, China; Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Tai'an, Shandong, China; Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, Tai'an, Shandong, China. Electronic address:

Tembusu Virus (TMUV), a pathogenic member of Flavivirus family, acts as the causative agent of egg-laying and has severely threatened the duck industry over the past few years. Thus far, the pathogenicity of such virus has been extensively studied, whereas TMUV on immune system has been less comprehensively assessed, especially on ducklings that exhibit more susceptible to TMUV attack. Accordingly, in the present study, 5-day-old ducklings were infected with TMUV-TC2B (10 TCID) via intravenous injection, and mock ones were inoculated with phosphate-buffered saline (PBS) in identical manner as control. At 1 day-post inoculation (dpi), the innate immunity was strongly activated, and reacted rapidly to TMUV invasion, which was reflected as the significantly up-regulated IFN-stimulated genes (ISGs), especially in immune organs (e.g., thymus, bursa of Fabricius (BF) and spleen). Subsequently, under the continuous monitoring, the levels of IgA, IgM and IgG acting as the representative immunoglobulins (Igs) were constantly higher than those of mock ducklings, demonstrating that humoral immunity also played a major role in anti-virus infection. Despite the immune system activated positively, TMUV still caused systemic infection, and in particular, the immune organs were subject to severe damage in the early infection. With our constant observation, the injury of spleen and BF turned out to be getting more serious, and at 6 dpi, TMUV antigen was widely detected in both of two immune organs by immunohistochemistry (IHC) and main histopathological lesion presented as lymphocytopenia. Moreover, the elevated apoptosis rate of splenic lymphocytes and the alteration of immune organ index also revealed the damage of lymphoid organs and similarly, it is worth noting that severe damages were detected in thymus of TMUV-infected ducklings as well. In brief, the present study systematically described the dynamic damage of immune system after being attacked by TMUV and presented insights into the research of pathogenicity.
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http://dx.doi.org/10.1016/j.vetmic.2021.109033DOI Listing
April 2021