Publications by authors named "Ming Lei"

907 Publications

Development of Calcium Carbonate-Based Coatings by the Carbonation of Gamma-CS (γ-CS).

Materials (Basel) 2022 Jul 22;15(15). Epub 2022 Jul 22.

State Key Laboratory of Silicate Materials for Architectures, Wuhan University of Technology, Wuhan 430070, China.

A calcium carbonate (CaCO)-based coating with gamma-CS (γ-CS) as the main carbonatable binder is proposed to protect the metal substrate against corrosion in this paper. Here, the morphology and phase assemblage of the coatings are studied by scanning electron microscopy (SEM) and X-ray diffraction (XRD), and the corrosion resistance of the coating is evaluated by electrochemical impedance spectroscopy (EIS) and X-ray photoelectron spectroscopy (XPS). Results show that the carbonated coating has excellent properties in terms of ultraviolet (UV) aging resistance, salt fog resistance, and electrochemical corrosion resistance. The porosity of deposited coating on steel substrates decreases by 47.1% after carbonation due to the compacted calcium carbonate formation, which is recognized as a self-compacting process during carbonation. The coating also exhibits rapid strength development within the first 2 h of carbonation; both the CO uptake efficiency and degree of carbonation (DOC) can reach more than 95% of the total CO uptake efficiency and final DOC values. This study provides a novel insight to extend the category of inorganic coating with additional benefits of CO solidification.
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http://dx.doi.org/10.3390/ma15155088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331133PMC
July 2022

Divergent Synthesis of Fused Tetracyclic Heterocycles from Diarylalkynes Enabled by the Selective Insertion of Isocyanide.

Angew Chem Int Ed Engl 2022 Jul 22. Epub 2022 Jul 22.

South China University of Technology, School of Chemistry & Chemical Engineering, No. 381, Wushan Road, Tianhe Strict,, 510640, Guangzhou, CHINA.

Herein, we present a direct and efficient synthesis of diverse polysubstituted fused tetracyclic heterocycles with good functional group tolerance from diarylalkynes under different palladium catalytic systems. In this chemistry, an unprecedented intermolecular nucleopalladation of diarylalkynes through the highly selective sequential double insertion of isocyanide was achieved for the first time. The practicality of this method was further demonstrated by the construction of various bioactive molecules and important structural motifs, with potential applications in materials science and biochemistry. In addition, density functional theory calculations (DFT) elucidated an interesting "Pd walk" might occur during the cyclization process.
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http://dx.doi.org/10.1002/anie.202208203DOI Listing
July 2022

Transition-Metal-Free Synthesis of Functionalized Quinolines by Direct Conversion of β-O-4 Model Compounds.

Angew Chem Int Ed Engl 2022 Jul 22:e202206284. Epub 2022 Jul 22.

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Direct production of heterocyclic aromatic compounds from lignin β-O-4 models remains a huge challenge due to the incompatible catalysis for aryl ether bonds cleavage and heterocyclic ring formation. Herein, the first example of quinoline synthesis from β-O-4 model compounds by a one-pot cascade reaction is reported in yields up to 89 %. The reaction pathway involves selective cleavage of C-O bonds, dehydrogenation, aldol condensation, C-N bond formation along with heterocyclic aromatic ring construction. The control experiments suggest that both imine and chalcone were identified as the key intermediates, and the rate determining step as well as the preferred pathway were experimentally clarified and supported by density functional theory (DFT) calculations. Based on this protocol, the conversion of β-O-4 polymer delivered 56 wt % yield of quinoline derivative in three steps. This transformation provides a potential petroleum-independent choice for heterocyclic aromatic chemicals.
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http://dx.doi.org/10.1002/anie.202206284DOI Listing
July 2022

Fourier Optical Spin Splitting Microscopy.

Phys Rev Lett 2022 Jul;129(2):020801

Department of Electrical and Computer Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA.

In this Letter, we propose a new quantitative phase imaging methodology named Fourier optical spin splitting microscopy (FOSSM). FOSSM relies on a metasurface located at the Fourier plane of a polarized microscope to separate the object image into two replicas of opposite circularly polarized states. The bias retardation between the two replicas is tuned by translating the metasurface or rotating the analyzer. Combined with a polarized camera, FOSSM can easily achieve single-shot quantitative phase gradient imaging, which greatly reduces the complexity of current phase microscope setups, paving the way for the next generation high-speed real-time multifunctional microscopy.
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http://dx.doi.org/10.1103/PhysRevLett.129.020801DOI Listing
July 2022

Breathable and Waterproof Electronic Skin with Three-Dimensional Architecture for Pressure and Strain Sensing in Nonoverlapping Mode.

ACS Nano 2022 Jul 20. Epub 2022 Jul 20.

Joint Key Laboratory of the Ministry of Education, Institute of Applied Physics and Materials Engineering, University of Macau, Avenida da Universidade, Taipa, Macau 999078, China.

Wearable sensors have recently attracted extensive interest not only in the field of healthcare monitoring but also for convenient and intelligent human-machine interactions. However, challenges such as wearable comfort, multiple applicable conditions, and differentiation of mechanical stimuli are yet to be fully addressed. Herein, we developed a breathable and waterproof electronic skin (E-skin) that can perceive pressure/strain with nonoverlapping signals. The synergistic effect from magnetic attraction and nanoscaled aggregation renders the E-skin with microscaled pores for breathability and three-dimensional microcilia for superhydrophobicity. Upon applied pressure, the bending of conductive microcilia enables sufficient contacts for resistance decrease, while the stretching causes increased resistance due to the separation of conductive materials. The optimized E-skin exhibits a high gauge factor of 7.747 for small strain (0-80%) and a detection limit down to 0.04%. The three-dimensional microcilia also exhibit a sensitivity of -0.0198 kPa (0-3 kPa) and a broad detection range up to 200 kPa with robustness. The E-skin can reliably and precisely distinguish kinds of the human joint motions, covering a broad spectrum including bending, stretching, and pressure. With the nonoverlapping readouts, ternary inputs "1", "0", and "-1" could be produced with different stimuli, which expands the command capacity for logic outputs such as effective Morse code and intuitive robotic control. Owing to the rapid response, long-term stability (10 000 cycles), breathability, and superhydrophobicity, we believe that the E-skin can be widely applied as wearable devices from body motion monitoring to human-machine interactions toward a more convenient and intelligent future.
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http://dx.doi.org/10.1021/acsnano.2c04188DOI Listing
July 2022

Structural insights into Pot1-ssDNA, Pot1-Tpz1 and Tpz1-Ccq1 Interactions within fission yeast shelterin complex.

PLoS Genet 2022 Jul 18;18(7):e1010308. Epub 2022 Jul 18.

Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The conserved shelterin complex caps chromosome ends to protect telomeres and regulate telomere replication. In fission yeast Schizosaccharomyces pombe, shelterin consists of telomeric single- and double-stranded DNA-binding modules Pot1-Tpz1 and Taz1-Rap1 connected by Poz1, and a specific component Ccq1. While individual structures of the two DNA-binding OB folds of Pot1 (Pot1OB1-GGTTAC and Pot1OB2-GGTTACGGT) are available, structural insight into recognition of telomeric repeats with spacers by the complete DNA-binding domain (Pot1DBD) remains an open question. Moreover, structural information about the Tpz1-Ccq1 interaction requires to be revealed for understanding how the specific component Ccq1 of S. pombe shelterin is recruited to telomeres to function as an interacting hub. Here, we report the crystal structures of Pot1DBD-single-stranded-DNA, Pot1372-555-Tpz1185-212 and Tpz1425-470-Ccq1123-439 complexes and propose an integrated model depicting the assembly mechanism of the shelterin complex at telomeres. The structure of Pot1DBD-DNA unveils how Pot1 recognizes S. pombe degenerate telomeric sequences. Our analyses of Tpz1-Ccq1 reveal structural basis for the essential role of the Tpz1-Ccq1 interaction in telomere recruitment of Ccq1 that is required for telomere maintenance and telomeric heterochromatin formation. Overall, our findings provide valuable structural information regarding interactions within fission yeast shelterin complex at 3' ss telomeric overhang.
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http://dx.doi.org/10.1371/journal.pgen.1010308DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9333443PMC
July 2022

Highly sensitive Curcumin-conjugated nanotheranostic platform for detecting amyloid-beta plaques by magnetic resonance imaging and reversing cognitive deficits of Alzheimer's disease via NLRP3-inhibition.

J Nanobiotechnology 2022 Jul 14;20(1):322. Epub 2022 Jul 14.

Department of Neurology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder without effective therapy and lack diagnosis strategy for preclinical AD patients. There is an urgent need for development of both early diagnosis and therapeutic intervention of AD.

Results: Herein, we developed a nanotheranostics platform consisting of Curcumin (Cur), an anti-inflammatory molecule, and superparamagnetic iron oxide (SPIO) nanoparticles encapsulated by diblock 1,2-dio-leoyl-sn-glycero-3-phosphoethanolamine-n-[poly(ethylene glycol)] (DSPE-PEG) that are modified with CRT and QSH peptides on its surface. Furthermore, we demonstrated that this multifunctional nanomaterial efficiently reduced β-amyloid plaque burden specifically in APP/PS1 transgenic mice, with the process noninvasively detected by magnetic resonance imaging (MRI) and the two-dimensional MRI images were computed into three-dimension (3D) plot. Our data demonstrated highly sensitive in vivo detection of β-amyloid plaques which more closely revealed real deposition of Aβ than previously reported and we quantified the volumes of plaques for the first time based on 3D plot. In addition, memory deficits of the mice were significantly rescued, probably related to inhibition of NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasomes.

Conclusions: Gathered data demonstrated that this theranostic platform may have both early diagnostic and therapeutic potential in AD.
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http://dx.doi.org/10.1186/s12951-022-01524-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9281113PMC
July 2022

Advancing equity through strengthening research on health and well-being of Asian American, Native Hawaiian, and Pacific Islander.

Cell Biosci 2022 Jul 5;12(1):101. Epub 2022 Jul 5.

U.S. Department of Health and Human Services, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.

The National Institutes of Health's Asian American, Native Hawaiian and Pacific Islander Health Scientific Interest Group (NIH AANHPI-HSIG) provides a viewpoint on developing approaches to enhance research on health and wellbeing for Asian American, Native Hawaiian, and Pacific Islander ethnic populations, in order to advance racial equity amongst such populations.
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http://dx.doi.org/10.1186/s13578-022-00834-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9254580PMC
July 2022

The Correlation Between White Matter Hyperintensity Burden and Regional Brain Volumetry in Patients With Alzheimer's Disease.

Front Hum Neurosci 2022 14;16:760360. Epub 2022 Jun 14.

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background: White matter hyperintensities (WMHs) and regional brain lobe atrophy coexist in the brain of patients with Alzheimer's disease (AD), but the association between them in patients with AD still lacks comprehensive investigation and solid imaging data support.

Objective: We explored whether WMHs can promote the pathological process of AD by aggravating atrophy in specific brain regions and tried to explain the regional specificity of these relationships.

Methods: A sample of 240 adults including 180 normal controls (NCs) and 80 cases with AD were drawn from the ADNI database. T1-weighted magnetic resonance imaging (MRI) and T2-weighted fluid-attenuated MRI of the participants were downloaded and were analyzed using AccuBrain to generate the quantitative ratio of WMHs (WMHr, WMH volumes corrected by intracranial volume) and regional brain atrophy. We also divided WMHr into periventricular WMHr (PVWMHr) and deep WMHr (DWMHr) for the purpose of this study. The Cholinergic Pathways Hyperintensities Scale (CHIPS) scores were conducted by two evaluators. Independent -test, Mann-Whitney test, or χ test were used to compare the demographic characteristics, and Spearman correlation coefficient values were used to determine the association between WMHs and different regions of brain atrophy.

Results: Positive association between WMHr and quantitative medial temporal lobe atrophy (QMTA) ( = 0.281, = 0.011), temporal lobe atrophy ( = 0.285, = 0.011), and insular atrophy ( = 0.406, < 0.001) was found in the AD group before Bonferroni correction. PVWMHr contributed to these correlations. By separately analyzing the relationship between PVWMHr and brain atrophy, we found that there were still positive correlations after correction in QMTA ( = 0.325, = 0.003), temporal lobe atrophy ( = 0.298, = 0.007), and insular atrophy ( = 0.429, < 0.001) in AD group.

Conclusion: WMH severity tends to be associated with regional brain atrophy in patients with AD, especially with medial temporal lobe, temporal lobe, and insular lobe atrophy. PVWMHs were devoted to these correlations.
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http://dx.doi.org/10.3389/fnhum.2022.760360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237397PMC
June 2022

Elastic Image Pair Method for Finding Transition States on Potential Energy Surfaces Using Only First Derivatives.

J Chem Theory Comput 2022 Aug 30;18(8):5108-5115. Epub 2022 Jun 30.

State Key Laboratory of Chemical Resource Engineering, Institute of Computational Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.

Herein, an elastic image pair (EIP) method is proposed to search transition states between two potential-energy minima using only first derivatives. In this method, two images are generated, and the spring forces are added to the images to control the distance between the two images. Transition states are reached when the force and the distance of the image pair are both converged. A set of test molecules is optimized using the EIP method, which shows its efficiency in transition state searching compared to other methods. This new method is more stable and reliable in finding transition states with much less computations.
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http://dx.doi.org/10.1021/acs.jctc.2c00137DOI Listing
August 2022

Low-cost synthesis of small molecule acceptors makes polymer solar cells commercially viable.

Nat Commun 2022 Jun 27;13(1):3687. Epub 2022 Jun 27.

Beijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, 100190, Beijing, China.

The acceptor-donor-acceptor (A-D-A) or A-DA'D-A structured small molecule acceptors (SMAs) have triggered substantial progress for polymer solar cells (PSCs). However, the high-cost of the SMAs impedes the commercial viability of such renewable energy, as their synthesis via the classical pyridine-catalyzed Knoevenagel condensation usually suffers from low reaction efficiency and tedious purifying work-up. Herein, we developed a simple and cheap boron trifluoride etherate-catalyzed Knoevenagel condensation for addressing this challenge, and found that the coupling of the aldehyde-terminated D unit and the A-end groups could be quantitatively finished in the presence of acetic anhydride within 15 minutes at room temperature. Compared with the conventional method, the high reaction efficiency of our method is related to the germinal diacetate pathway that is thermodynamically favorable to give the final products. For those high performing SMAs (such as ITIC-4F and Y6), the cost could be reduced by 50% compared with conventional preparation. In addition to the application in PSCs, our synthetic approach provides a facile and low-cost access to a wide range of D-A organic semiconductors for emerging technologies.
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http://dx.doi.org/10.1038/s41467-022-31389-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9237043PMC
June 2022

Experiences in managing different consequences of forgotten ureteral stents.

Urol Ann 2022 Apr-Jun;14(2):141-146. Epub 2022 Feb 15.

Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.

Purpose: We reported the different consequences of forgotten stents and share our managing experiences.

Patients And Methods: From July 2011 to August 2019, eight patients (five men and three women) with forgotten encrusted ureteral stents were treated by different endoscopic procedures in our center. Plain-film radiography (kidney, ureter, and bladder [KUB]) and computed tomography were used to evaluate the position of stents, the site of encrustation, and the stone burden. Various sole or combined endoscopic techniques including percutaneous nephrolithotomy, retrograde ureteroscopic lithotripsy, and cystolitholapaxy were used to achieve stent removal.

Results: The average age of the patients was 50.9 years (range: 25-72 years). The mean indwelling time of the stents was 32.9 months (range: 12-83 months). Mean stent stone burden was 15 mm × 10 mm. Three patients had stent stone burden larger than 20 mm. Three patients had a preoperative positive urine culture before treatment. The stent was fragmented in two patients. The ureteral stents and related stones were successfully removed without any complications by a sole or combined endoscopic techniques with stone-free status achieved in all patients. There is no complications occurred.

Conclusion: Forgotten stents can lead to complicated urinary tract calculi, stent encrustation, urinary tract infection, vesicoureteric reflux, and even ureteral polyps. Various sole or combined endourological techniques can be used to manage the forgotten encrusted ureteral stents.
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http://dx.doi.org/10.4103/UA.UA_165_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9197003PMC
February 2022

A theoretical study on the hydrogenation of CO to methanol catalyzed by ruthenium pincer complexes.

Dalton Trans 2022 Jul 5;51(26):10020-10028. Epub 2022 Jul 5.

State Key Laboratory of Chemical Resource Engineering, Institute of Computational Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing, 100029, China.

Herein, a density functional theory (DFT) study was performed to investigate thoroughly the cascade reaction mechanism for the hydrogenation of carbon dioxide to methanol catalyzed by ruthenium pincer complex [RuH(MePCHSiMe)NH(CO)]. Three catalytic stages involving the hydrogenation of carbon dioxide (stage I), formic acid (stage II) and formaldehyde (stage III) were studied. The calculated results show that the dominant H activation strategy in the hydrogenation of CO to methanol may not be the methanol-assisted H activation, but the formate-assisted H activation. In this cascade reaction, all energy spans of stage I, II and III are 20.2 kcal mol of the formate-assisted H activation. This implies that it could occur under mild conditions. Meanwhile, the catalyst is proposed to be efficient for the transfer hydrogenation using isopropanol as the hydrogen resource, and the ruthenium pincer complexes [RuH(MePCHSiMe)NH(CO)], [RuH(PhPCHSiMe)NH(CO)] and [RuH(MePCHSiMe)NH(CO)] exhibit similar catalytic activities for the hydrogenation of CO to methanol.
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http://dx.doi.org/10.1039/d2dt01352eDOI Listing
July 2022

Transition-metal-free synthesis of pyrimidines from lignin β-O-4 segments via a one-pot multi-component reaction.

Nat Commun 2022 06 11;13(1):3365. Epub 2022 Jun 11.

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.

Heteroatom-participated lignin depolymerization for heterocyclic aromatic compounds production is of great importance to expanding the product portfolio and meeting value-added biorefinery demand, but it is also particularly challenging. In this work, the synthesis of pyrimidines from lignin β-O-4 model compounds, the most abundant segment in lignin, mediated by NaOH through a one-pot multi-component cascade reaction is reported. Mechanism study suggests that the transformation starts by NaOH-induced deprotonation of Cα-H bond in β-O-4 model compounds, and involves highly coupled sequential cleavage of C-O bonds, alcohol dehydrogenation, aldol condensation, and dehydrogenative aromatization. This strategy features transition-metal free catalysis, a sustainable universal approach, no need of external oxidant/reductant, and an efficient one-pot process, thus providing an unprecedented opportunity for N-containing aromatic heterocyclic compounds synthesis from biorenewable feedstock. With this protocol, an important marine alkaloid meridianin derivative can be synthesized, emphasizing the application feasibility in pharmaceutical synthesis.
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http://dx.doi.org/10.1038/s41467-022-30815-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188570PMC
June 2022

Investigation of the potential role of TGR5 in pancreatic cancer by a comprehensive molecular experiments and the liquid chromatography mass spectrometry (LC-MS) based metabolomics.

Discov Oncol 2022 Jun 11;13(1):46. Epub 2022 Jun 11.

Department of Interventional Radiology, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.

Background: Takeda G protein receptor 5 (TGR5) is widely recognized as a potential drug target for the treatment of metabolic diseases. TGR5 is not only a metabolic regulator, but also has a potential role that participating in developing and progressing of gastrointestinal cancer. We aimed to investigate the potential role of TGR5 in pancreatic cancer by utilizing molecular experiments and the liquid chromatography mass spectrometry (LC-MS) based metabolomics.

Methods: Herein, we assessed pancreatic cancer proliferation, migration and invasion in response to TGR5 antagonist SBI-115 in vitro experiments. Cell death was examined by using TUNEL assay on agarose-embedded sections. Then we investigated the effects of TGR5 on PANC-1 and BXPC3 cells via transmission electron microscopy (TEM). Moreover, LC-MS-based metabolomics was performed to explore the potential underlying mechanisms of TGR5 in pancreatic cancer. The correlations between TGR5 and the metabolism-related genes were further analysed by GEPIA 2 database.

Results: We found the proliferation capacities were decreased significantly in PANC-1 and BXPC3 cells after the treatment of SBI-115 for 48 h. The results of TUNEL assay showed that antagonism of TGR5 by SBI-115 had a remarkable effect on inducing cell death. Analysis of TEM demonstrated that SBI-115 treatment could impair the morphology of mitochondria in most PANC-1 and BXPC3 cells. The LC-MS-based analyses revealed that antagonism of TGR5 could alter the metabolic profiles of PANC-1 cells in vitro. Moreover, TGR5 was associated with some metabolism-related genes in pancreatic cancer.

Conclusion: Our data suggests that antagonism of TGR5 may suppress cell proliferation and induce apoptosis in pancreatic cancer cells. TGR5 may affect the metabolism of pancreatic cancer, and TGR5 would be an attractive target for pancreatic cancer treatment.
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http://dx.doi.org/10.1007/s12672-022-00504-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9188013PMC
June 2022

Metabolic and Transcriptomic Analyses Reveal the Effects of Ethephon on Rodin.

Molecules 2022 May 31;27(11). Epub 2022 May 31.

Guangxi Key Laboratory of Medicinal Resources Protection and Genetic Improvement, Guangxi Botanical Garden of Medicinal Plants, Nanning 530023, China.

The roots of Rodin (TKS) are well-known and valued for their rubber-producing ability. Therefore, research on the analysis and detection of metabolites from the roots of TKS have been reported in previous studies. However, all of these studies have the shortcoming of focusing on only the rubber of TKS, without profiling the other metabolites in a systematic and comprehensive way. Here, the primary and secondary metabolites from the leaves of TKS were investigated using UPLC-ESI-MS/MS, and a total of 229 metabolites were characterized. Carboxylic acid derivatives, fatty acyls, phenols, and organooxygen compounds were found to be the major metabolites of TKS. The transcriptome data indicated that ribosomal, glycolysis/gluconeogenesis, phenylpropanoid biosynthesis, and linoleic acid metabolism genes were significantly differentially expressed. This study is the first to report the differences in the metabolic and transcriptome profiles of TKS leaves under exogenous ethephon spray, which improves our understanding of the main metabolites and their molecular mechanisms in TKS leaves.
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http://dx.doi.org/10.3390/molecules27113548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9182187PMC
May 2022

High-Resolution 3D Heart Models of Cardiomyocyte Subpopulations in Cleared Murine Heart.

Front Physiol 2022 18;13:779514. Epub 2022 May 18.

Laboratory of Medical Electrophysiology, Ministry of Education, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease/Institute of Cardiovascular Research, Luzhou Medical College, Luzhou, China.

Biological tissues are naturally three-dimensional (3D) opaque structures, which poses a major challenge for the deep imaging of spatial distribution and localization of specific cell types in organs in biomedical research. Here we present a 3D heart imaging reconstruction approach by combining an improved heart tissue-clearing technique with high-resolution light-sheet fluorescence microscopy (LSFM). We have conducted a three-dimensional and multi-scale volumetric imaging of the ultra-thin planes of murine hearts for up to 2,000 images per heart in x-, y-, and z three directions. High-resolution 3D volume heart models were constructed in real-time by the Zeiss Zen program. By using such an approach, we investigated detailed three-dimensional spatial distributions of two specific cardiomyocyte populations including HCN4 expressing pacemaker cells and Pnmt cell-derived cardiomyocytes by using reporter mouse lines Hcn4 and Pnmt. HCN4 is distributed throughout right atrial nodal regions (i.e., sinoatrial and atrioventricular nodes) and the superior-inferior vena cava axis, while Pnmt cell-derived cardiomyocytes show distinct ventral, left heart, and dorsal side distribution pattern. Our further electrophysiological analysis indicates that Pnmt + cell-derived cardiomyocytes rich left ventricular (LV) base is more susceptible to ventricular arrhythmia under adrenergic stress than left ventricular apex or right ventricle regions. Thus, our 3D heart imaging reconstruction approach provides a new solution for studying the geometrical, topological, and physiological characteristics of specific cell types in organs.
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http://dx.doi.org/10.3389/fphys.2022.779514DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9158482PMC
May 2022

p53-Dependent Mitochondrial Compensation in Heart Failure With Preserved Ejection Fraction.

J Am Heart Assoc 2022 06 3;11(11):e024582. Epub 2022 Jun 3.

Department of Cardiology Ninth People's HospitalShanghai Jiao Tong University School of Medicine Shanghai China.

Background Heart failure with preserved ejection fraction (HFpEF) accounts for 50% of patients with heart failure. Clinically, HFpEF prevalence shows age and gender biases. Although the majority of patients with HFpEF are elderly, there is an emergence of young patients with HFpEF. A better understanding of the underlying pathogenic mechanism is urgently needed. Here, we aimed to determine the role of aging in the pathogenesis of HFpEF. Methods and Results HFpEF dietary regimen (high-fat diet + Nω-Nitro-L-arginine methyl ester hydrochloride) was used to induce HFpEF in wild type and telomerase RNA knockout mice (second-generation and third-generation telomerase RNA component knockout), an aging murine model. First, both male and female animals develop HFpEF equally. Second, cardiac wall thickening preceded diastolic dysfunction in all HFpEF animals. Third, accelerated HFpEF onset was observed in second-generation telomerase RNA component knockout (at 6 weeks) and third-generation telomerase RNA component knockout (at 4 weeks) compared with wild type (8 weeks). Fourth, we demonstrate that mitochondrial respiration transitioned from compensatory state (normal basal yet loss of maximal respiratory capacity) to dysfunction (loss of both basal and maximal respiratory capacity) in a p53 dosage dependent manner. Last, using myocardial-specific p53 knockout animals, we demonstrate that loss of p53 activation delays the development of HFpEF. Conclusions Here we demonstrate that p53 activation plays a role in the pathogenesis of HFpEF. We show that short telomere animals exhibit a basal level of p53 activation, mitochondria upregulate mtDNA encoded genes as a mean to compensate for blocked mitochondrial biogenesis, and loss of myocardial p53 delays HFpEF onset in high fat diet + Nω-Nitro-L-arginine methyl ester hydrochloride challenged murine model.
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http://dx.doi.org/10.1161/JAHA.121.024582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9238719PMC
June 2022

A theoretical study of asymmetric ketone hydrogenation catalyzed by Mn complexes: from the catalytic mechanism to the catalyst design.

Phys Chem Chem Phys 2022 Jun 1;24(21):13365-13375. Epub 2022 Jun 1.

State Key Laboratory of Chemical Resource Engineering, Institute of Computational Chemistry, College of Chemistry, Beijing University of Chemical Technology, Beijing, 100029, China.

Herein, a density functional theory (DFT) study was performed to investigate asymmetric ketone hydrogenation (AKH) catalyzed by Mn complexes, from the catalytic mechanism to the catalyst design. The calculated results indicated that the Mn(CO)-PSiNSiP (A1, PSiNSiP = P(Ph)Si(CH)NSi(CH)P(Ph)) pincer complex has potential high catalytic activity for ketone hydrogenation. The Mn(CO)-LYB (B, LYB = P(Ph)Si(CH)NSi(CH)P(Me)) pincer complex was then designed to catalyze AKH with good stereoselectivity. The hydrogen transfer (HT) step is the chirality-determining step. To avoid the enantiomer of Mn(CO)-LYB, which could eliminate the high stereoselectivity during AKH, novel Mn complexes with quadridentate ligands, such as Mn(CO)-LYC (C, LYC = P(CH)CHSi(CH)NSi(CH)(Si(CH)CHP(CH))CHP(Ph)) and Mn(CO)-LYD (D, LYD = P(CH)CHSi(CH)NSi(CH)(Si(CH)CHP(CH))CHP(Cy)), were designed to drive AKH with medium stereoselectivity. In order to increase the stereoselectivity of AKH, Mn(CO)-LYE (E, LYE = PHCHSi(CH)NSi(CH)(Si(CH)CHP(CH))CHP(Ph)) and Mn(CO)-LYF (F, LYF = PHCHSi(CH)NSi(CH)(Si(CH)CHP(CH))CHP(Cy)) were further designed and showed very good stereoselectivity, which is due to the lower deformation energy and stronger interactions between the ketone substrates and catalysts. This work may shed light on the design of cheap metal catalysts with a new ligand framework for the asymmetric hydrogenation (AH) of CX bonds (X = O, N).
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http://dx.doi.org/10.1039/d2cp00818aDOI Listing
June 2022

The diagnostic performance of ultra-low-dose 320-row detector CT with different reconstruction algorithms on limb joint fractures in the emergency department.

Jpn J Radiol 2022 May 19. Epub 2022 May 19.

Department of Radiology, Zhuhai Hospital, Guangdong Provincial Hospital of Traditional Chinese Medicine, 53 Jingle Road, Zhuhai, Guangdong, China.

Background: The aim of the study was to evaluate whether ultra-low-dose computed tomography (ULD-CT) could replace conventional-dose CT (CD-CT) for diagnosis of acute wrist, ankle, knee, and shoulder fractures in emergency departments (ED).

Methods: We developed CD-CT and ULD-CT scanning schemes for the various joints of the four limbs and scanned emergency patients prospectively. When performing CD-CT, a conventional bone reconstruction algorithm was used, while ULD-CT used both soft tissue and bone algorithms. A five-point scale was used to evaluate whether ULD-CT image quality affected surgical planning. The image quality and diagnostic performance of different types of scanned and reconstructed images for diagnosing fractures were evaluated and compared. Effective radiation dose of each group was calculated.

Results: Our study included 56 normal cases and 185 fracture cases. The combination of bone and soft tissue algorithms on ULD-CT can improve diagnostic performance, such that on ULD-CT, the sensitivity improved from 96.7% to 98.9%, specificity from 98.2% to 100%, positive predictive value from 99.4% to 100%, negative predictive value from 90.2% to 96.6% and diagnostic accuracy ranged from 97.5% to 99.1%. There were no statistically significant differences between ULD-CT and CD-CT on diagnostic performance (p values, 0.40-1.00). The radiation doses for ULD-CT protocols were only 3.0-7.7% of those for CD-CT protocols (all p < 0.01).

Conclusions: In the emergency department, the 320-row detector ULD-CT could replace CD-CT in the diagnosis of limb joint fractures. The combination of bone algorithm with soft tissue algorithm reconstruction can further improve the image quality and diagnostic performance.
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http://dx.doi.org/10.1007/s11604-022-01290-1DOI Listing
May 2022

Nivolumab in Esophageal Squamous-Cell Carcinoma. Reply.

Authors:
Ken Kato Ming Lei

N Engl J Med 2022 05;386(20):1961

Bristol Myers Squibb, Princeton, NJ.

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http://dx.doi.org/10.1056/NEJMc2202880DOI Listing
May 2022

AD Resemblance Atrophy Index of Brain Magnetic Resonance Imaging in Predicting the Progression of Mild Cognitive Impairment Carrying Apolipoprotein E-ε4 Allele.

Front Aging Neurosci 2022 28;14:859492. Epub 2022 Apr 28.

Department of Neurology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Background And Objective: Early identification is important for timely Alzheimer's disease (AD) treatment. Apolipoprotein E ε4 allele (APOE-ε4) is an important genetic risk factor for sporadic AD. The AD-Resemblance Atrophy Index (RAI)-a structural magnetic resonance imaging-derived composite index-was found to predict the risk of progression from mild cognitive impairment (MCI) to AD. Therefore, we investigated whether the AD-RAI can predict cognitive decline and progression to AD in patients with MCI carrying APOE ε4.

Methods: We included 733 participants with MCI from the Alzheimer's Disease Neuroimaging Initiative Database (ADNI). Their APOE genotypes, cognitive performance, and levels of AD-RAI were assessed at baseline and follow-up. Linear regression models were used to test the correlations between the AD-RAI and baseline cognitive measures, and linear mixed models with random intercepts and slopes were applied to investigate whether AD-RAI and APOE-ε4 can predict the level of cognitive decline. Cox proportional risk regression models were used to test the association of AD-RAI and APOE status with the progression from MCI to AD.

Results: The baseline AD-RAI was higher in the MCI converted to AD group than in the MCI stable group ( < 0.001). The AD-RAI was significantly correlated with cognition, and had a synergistic effect with APOE-ε4 to predict the rate of cognitive decline. The AD-RAI predicted the risk and timing of MCI progression to AD. Based on the MCI population carrying APOE-ε4, the median time to progression from MCI to AD was 24 months if the AD-RAI > 0.5, while the median time to progression from MCI to AD was 96 months for patients with an AD-RAI ≤ 0.5.

Conclusion: The AD-RAI can predict the risk of progression to AD in people with MCI carrying APOE ε4, is strongly correlated with cognition, and can predict cognitive decline.
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http://dx.doi.org/10.3389/fnagi.2022.859492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9097868PMC
April 2022

Anti-IL-8 antibody activates myeloid cells and potentiates the anti-tumor activity of anti-PD-1 antibody in the humanized pancreatic cancer murine model.

Cancer Lett 2022 Jul 7;539:215722. Epub 2022 May 7.

The Sidney Kimmel Comprehensive Cancer Center, Department of Oncology, Department of Surgery, and the Pancreatic Cancer Precision Medicine Center of Excellence Program, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address:

Pancreatic ductal adenocarcinoma(PDAC) does not respond to single-agent immune checkpoint inhibitor therapy, including anti-PD-1 antibody(aPD-1) therapy. Higher plasma levels of IL-8 are associated with poorer outcomes in patients who receive aPD-1 therapies, providing a rationale for combination immunotherapy with an anti-IL-8 antibody(aIL-8) and aPD-1. We thus investigated whether human aIL-8 therapy can potentiate the antitumor activity of aPD-1 and further investigated how the combination affects the immune response by regulating myeloid cells in the tumor microenvironment in a humanized murine model of PDAC with a reconstituted immune system consisting of human T cells and a combination of CD14 and CD16 myeloid cells. The results show that the combination of aIL-8 and aPD-1 treatment significantly enhanced antitumor activity following the infusion of myeloid cells. Our results further showed that the target of IL-8 is mainly present in CD16 myeloid cells and is likely to be granulocytes. FACS analysis showed that aIL-8 treatment increased granulocytic myeloid cells in tumors. Consistently, single-nuclear RNA-sequencing analysis of tumor tissue showed that the innate immune response and cytokine response pathways in the myeloid cell cluster were activated by aIL-8 treatment. This is the first preclinical study using a humanized mouse model for new combination immunotherapeutic development and supports the further clinical testing of aIL-8 in combination with aPD-1 for PDAC treatment. This study also suggests that peripherally derived myeloid cells can potentiate the antitumor response of T cells, likely through the innate immune response, and aIL-8 re-educates tumor-infiltrating myeloid cells by activating the innate immune response.
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http://dx.doi.org/10.1016/j.canlet.2022.215722DOI Listing
July 2022

Structure-based identification and pathway elucidation of flavonoids in .

Synth Syst Biotechnol 2022 Jun 18;7(2):824-836. Epub 2022 Apr 18.

College of Science, Sichuan Agricultural University, Ya'an, 625014, PR China.

Flavonoid metabolism in remained an untapped area for years. A tandem MS approach was used and focused on the mining and characterizing of flavonoids in mature . Fifteen new flavonoids and forty-three known flavonoids, including fifteen flavone analogs, sixteen flavonol analogs, seven flavanone analogs, six chalcone analogs, four xanthone analogs, ten flavane analogs were mined and identified based on their MS/MS fragments. Fifty-three of them were firstly characterized in Eight biosynthetic precursors for these flavonoids were also identified. We constructed a specific metabolic map for flavonoids according to their relative contents in the flowers, fruits, stems, and leaves of . Furthermore, the most probable genes involved in chalcone biosynthesis, flavonoid hydroxylation, methylation, and glycosylation were further mined and fished in the gene reservoir of according to their conserved domains and co-expression analysis. These findings enable us to acquire a better understanding of versatile flavonoid metabolism in .
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http://dx.doi.org/10.1016/j.synbio.2022.03.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9043410PMC
June 2022

Neuropilin-1 is a valuable biomarker for predicting response of advanced non-small cell lung cancer patients to hypofractionated radiotherapy and PD-1 blockade.

Int Immunopharmacol 2022 Aug 22;109:108732. Epub 2022 Apr 22.

Immune Mechanism and Therapy of Major Diseases of Luzhou Key Laboratory, Public Center of Experimental Technology, School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China. Electronic address:

Programmed death-1 (PD-1) blockade promoted the combination therapy of advanced non-small cell lung cancer (NSCLC), induces changes in peripheral memory T cell subsets. Neuropilin-1 (NRP1) is a new T cell memory checkpoint, its association with the clinical prognosis of NSCLC is less reported. Here, we detected the expression of NRP1 and the depletion-associated factor thymocyte selection-associated HMG box protein (TOX) in peripheral T cell subsets with responders treated with hypofractionated radiotherapy (HFRT) combined with PD-1 blockade and chemoimmunotherapy, aimed to explore their association with the prognosis of advanced NSCLC. NRP1 and TOX expression was localized on tissue-infiltrating T cells by immunofluorescence assay in nine patients who had undergone surgery. Flow cytometry was used to detect the expression of NRP1 and TOX in peripheral circulating T cells in patients with advanced NSCLC before and after HFRT combined with PD-1 blockade (HFRT+PD-1) and chemoimmunotherapy in thirty-nine patients. NSCLC patients showed an increase in NRP1 and TOX in peripheral T cells as compared to that in healthy controls. The expression of NRP1 and TOX in CD8 T cells was higher in tumor tissues than in uninvolved tissues. Patients who responded to HFRT+PD-1 blockade showed a reduction in NRP1CD8, TOXCD4, and TOXCD8 levels, chemoimmunotherapy responders showed decreased expression of NRP1 in the CD4 T cell subpopulation. In conclusion, lower expression levels of NRP1 and TOX in peripheral circulating CD8 T cells were associated with a better prognosis for advanced NSCLC patients treated with HFRT+PD-1 blockade.
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http://dx.doi.org/10.1016/j.intimp.2022.108732DOI Listing
August 2022

Endometrial cancer risk factors in Singapore Chinese: a prospective cohort study.

Ann Epidemiol 2022 07 21;71:9-14. Epub 2022 Apr 21.

University of Pittsburgh School of Medicine, Pittsburgh, PA; Magee-Womens Research Institute, Pittsburgh, PA; Duquesne University, Rangos School of Health Sciences, Department of Health Administration and Public Health, Pittsburgh, PA. Electronic address:

Purpose: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia.

Methods: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors.

Results: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort.

Conclusions: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities.
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http://dx.doi.org/10.1016/j.annepidem.2022.04.002DOI Listing
July 2022

Lignin-first biorefinery of corn stalk via zirconium(IV) chloride/sodium hydroxide-catalyzed aerobic oxidation to produce phenolic carbonyls.

Bioresour Technol 2022 Jun 16;354:127183. Epub 2022 Apr 16.

Key Laboratory of Energy Thermal Conversion and Control of Ministry of Education, School of Energy and Environment, Southeast University, Nanjing 210096, PR China.

Lignin-first biorefinery of corn stalk via ZrCl/NaOH-catalyzed aerobic oxidation for phenolic carbonyls production was reported. Under the co-catalysis of ZrCl and NaOH, lignin in corn stalk was oxidized into phenolic aldehydes (p-hydroxybenzaldehyde, vanillin, and syringaldehyde), ketones (p-hydroxyacetophenone, acetovanillone, and acetosyringone), acids (p-hydroxybenzoic acid and vanillic acid), and other derivatives. Reaction conditions, including time, temperature, ZrCl dosage, NaOH dosage, MeCN/HO ratio, and initial O pressure were comprehensively screened, and the optimal lignin-derived monomer yields of 13.2 wt% was obtained. Among these aromatic compounds, phenolic aldehydes were the main products, and the overall selectivity of phenolic carbonyls was as high as 93%. Cellulose-rich residues after lignin-first oxidation were further characterized by thermogravimetry and analytical pyrolysis with corn stalk as the control, proving the good fragmentation and dissolution of lignin streams. In general, ZrCl/NaOH-catalyzed lignin-first oxidation provided a novel approach for lignin valorization, and achieved the highest reported phenolic carbonyls selectivity.
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http://dx.doi.org/10.1016/j.biortech.2022.127183DOI Listing
June 2022

Homogeneous and Heterogeneous Pd-Catalyzed Selective C-P Activation and Transfer Hydrogenation for "Group-Substitution" Synthesis of Trivalent Phosphines.

Org Lett 2022 Apr 13;24(15):2868-2872. Epub 2022 Apr 13.

State Key Laboratory of Chemical Resource Engineering, College of Chemistry, Beijing University of Chemical Technology, Beijing 100029, China.

A "group-substitution" synthesis of trivalent phosphines via a C-P activation of phosphonium salts is reported. The alkyl groups were introduced by alkylation of phosphines to form phosphonium salts. The "de-arylation" of phosphonium salts was achieved by C-P activation and transfer hydrogenation with homogeneous or heterogeneous Pd (0) catalysts. With this method, a series of trivalent phosphines were prepared from commercially available triarylphosphines. A chiral monophosphine ligand could be prepared from BINAP in a "de-phosphination" process.
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http://dx.doi.org/10.1021/acs.orglett.2c00844DOI Listing
April 2022

Triage by PAX1 and ZNF582 Methylation in Women With Cervical Intraepithelial Neoplasia Grade 3: A Multicenter Case-Control Study.

Open Forum Infect Dis 2022 May 13;9(5):ofac013. Epub 2022 Jan 13.

Department of Gynecology, Xiangya Hospital, Central South University, Changsha, China.

Background: The colposcopy-conization inconsistency is common in women with cervical intraepithelial neoplasia grade 3 (CIN3). No adequate method has been reported to identify the final pathology of conization. In this study, we explored the ability of PAX1 and ZNF582 methylation to predict the pathological outcome of conization in advance.

Methods: This was a multicenter study and included 277 histologically confirmed CIN3 women who underwent cold knife conization (CKC) from January 2019 to December 2020. The methylation levels of PAX1 (PAX1) and ZNF582 (ZNF582) were determined by quantitative methylation-specific polymerase chain reaction (qMSP) and expressed in ΔCp. Receiver operating characteristic curves were used to evaluate predictive accuracy.

Results: The final pathological results in 48 (17.33%) patients were inflammation or low-grade squamous intraepithelial lesion (LSIL), 190 (68.59%) were high-grade squamous intraepithelial lesion (HSIL), and 39 (14.08%) were squamous cervical cancer (SCC). PAX1 and ZNF582 increased as lesions progressed from inflammation/LSIL, HSIL, to SCC. PAX1 and ZNF582 methylation yielded better prediction performance compared with common screening strategies, whether individually or combined. A 4.33-fold increase in the probability of inflammation/LSIL was observed in patients with lower ZNF582 methylation levels (ΔCp ≥ 19.18). A 6.53-fold increase in SCC risk was observed in patients with elevated ZNF582 methylation (ΔCp< 7.09).

Conclusions: DNA methylation would be an alternative screening method to triage and predict the final outcome of conization in CIN3 cases.
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http://dx.doi.org/10.1093/ofid/ofac013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8988013PMC
May 2022

Novel benzothiazole‒urea hybrids: Design, synthesis and biological activity as potent anti-bacterial agents against MRSA.

Eur J Med Chem 2022 Jun 31;236:114333. Epub 2022 Mar 31.

Anhui Prevention and Treatment Center for Occupational Disease, Anhui No. 2 Provincial People's Hospital, Hefei, 230022, China. Electronic address:

Novel benzothiazole‒urea hybrids were designed, synthesized and evaluated their anti-bacterial activity. They only exhibited anti-bacterial activity against Gram-positive bacteria, including clinical methicillin-resistant S. aureus (MRSA), compounds 5f, 5i, 8e, 8k and 8l exhibited potent activity (MIC = 0.39 and 0.39/0.78 μM against SA and MRSA, respectively). Crystal violet assay showed that compounds 5f, 8e and 8l not only inhibited the formation of biofilms but also eradicated preformed biofilms. Compound 8l had membrane disruption, little propensity to induce resistance, benign safety and in vivo anti-MRSA efficacy in a mouse model of abdominal infection. Therefore, our data demonstrated the potential to advance benzothiazole‒urea hybrids as a new class of antibiotics.
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http://dx.doi.org/10.1016/j.ejmech.2022.114333DOI Listing
June 2022
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