Publications by authors named "Pengfei Zhang"

923 Publications

Review on the Application of Low-Field Nuclear Magnetic Resonance Technology in Coalbed Methane Production Simulation.

ACS Omega 2022 Aug 20;7(30):26298-26307. Epub 2022 Jul 20.

School of Resources and Earth Science, China University of Mining and Technology, Xuzhou 221116, China.

Low-field nuclear magnetic resonance has become one of the main methods to characterize static parameters and dynamic changes in unconventional reservoirs. The research focus of this paper is process simulation of coalbed methane (CBM) production. The dynamic variation of pore volume with different pore sizes during pressure drop, methane desorption-diffusion process, and methane-water interaction during migration is discussed. Moreover, the calculation principles of NMR single and multifractal models are systematically described, and the applicability of NMR fractal models within different research contexts is discussed. Four aspects need urgent attention in the application of this technology in CBM production: (1) overburden NMR technology has limitations in characterizing the stress sensitivity of shale and high-rank coal reservoirs with micropores developed, and we should aim to enable an accurate description of micropore pore stress sensitivity; (2) dynamic NMR physical simulation of reservoir gas and water production based on in-situ and actual geological development conditions should become one of the key aspects of follow-up research; (3) low-temperature freeze-thaw NMR technology, as a new pore-fracture characterization method, needs to be further applied in characterizing the distribution characteristics of pores and fractures; and (4) NMR fractal model should be used as the main theoretical method to expand the simulation results. The applicability of different fractal models in characterizing pore-fracture structure (static) and CBM production process (dynamic) needs to be clarified.
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http://dx.doi.org/10.1021/acsomega.2c02112DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352340PMC
August 2022

A multifaceted signal recorder of cellular experiences using Cas12a base-editing.

Trends Biotechnol 2022 Aug 3. Epub 2022 Aug 3.

Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA; Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address:

Technological advances have led to the emergence of lineage tracers, but signal recorders for mammalian systems have remained elusive. Kempton et al. have developed a Cas12a base-editing signal recorder capable of capturing diverse signals and operating in various experimental designs. The recorder enables new opportunities to chronicle cellular history.
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http://dx.doi.org/10.1016/j.tibtech.2022.07.009DOI Listing
August 2022

Myocardial work: the analytical methodology and clinical utilities.

Hellenic J Cardiol 2022 Aug 2. Epub 2022 Aug 2.

The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese National Health Commission and Chinese Academy of Medical Sciences, The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Department of Cardiology, Qala Hospital, CeeLo College of Medicine, Shandong University, Shandong, China. Electronic address:

The evaluation of left ventricular (LV) systolic function is an essential part of the clinical practice of cardiology. Although left ventricular ejection fraction (LVEF) is the most validated and widely used parameter, it has fundamental limitations. LV strain is more sensitive to detect subtle myocardial dysfunction when LVEF was preserved, but it is load-dependent. Invasive left ventricular pressure-volume loop (LV-PVL) is the reliable standard to evaluate cardiac function, but its wide clinical application is limited by the risk of invasive LV pressure detection. Until the advent of non-invasive LV pressure-strain loop (LV-PSL), things have changed. LV-PSL is in good agreement with regional myocardial oxygen consumption and metabolism. Compared with traditional echocardiographic parameters or LV strain, myocardial work (MW) derived from LV-PSL is a more advanced tool that combines deformation as well as hemodynamics through integration of global longitudinal strain and non-invasive LV systolic pressure. In recent years, researches on MW are going on in full swing and show many advantages of MW. This review described the method and discussed the applications, advantages, limitations, and prospects of MW in multiple cardiovascular diseases. The goal is to provide the readers new insights for evaluating LV systolic function and promote the incorporation of MW into daily practice.
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http://dx.doi.org/10.1016/j.hjc.2022.07.007DOI Listing
August 2022

Letter to the Editor regarding "Effect of Altmetric score on manuscript citations: A randomized-controlled trial".

Cephalalgia 2022 Aug 4:3331024221118925. Epub 2022 Aug 4.

Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

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http://dx.doi.org/10.1177/03331024221118925DOI Listing
August 2022

Heterogeneous Feature Selection Based on Neighborhood Combination Entropy.

IEEE Trans Neural Netw Learn Syst 2022 Aug 4;PP. Epub 2022 Aug 4.

Feature selection aims to remove irrelevant or redundant features and thereby remain relevant or informative features so that it is often preferred for alleviating the dimensionality curse, enhancing learning performance, providing better readability and interpretability, and so on. Data that contain numerical and categorical representations are called heterogeneous data, and they exist widely in many real-world applications. Neighborhood rough set (NRS) can effectively deal with heterogeneous data by using neighborhood binary relation, which has been successfully applied to heterogeneous feature selection. In this article, the NRS model as a unified framework is used to design a feature selection method to handle categorical, numerical, and heterogeneous data. First, the concept of neighborhood combination entropy (NCE) is presented. It can reflect the probability of pairs of the neighborhood granules that are probably distinguishable from each other. Then, the conditional neighborhood combination entropy (cNCE) based on NCE is proposed under the condition of considering decision attributes. Moreover, some properties and relationships between cNCE and NCE are derived. Finally, the functions of inner and outer significances are constructed to design a feature selection algorithm based on cNCE (FScNCE). The experimental results show the effectiveness and superiority of the proposed algorithm.
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http://dx.doi.org/10.1109/TNNLS.2022.3193929DOI Listing
August 2022

Facile and scalable tubing-free sample loading for droplet microfluidics.

Sci Rep 2022 Aug 3;12(1):13340. Epub 2022 Aug 3.

Department of Biomedical Engineering, Johns Hopkins University, 3400 N. Charles Street, Baltimore, MD, 21218, USA.

Droplet microfluidics has in recent years found a wide range of analytical and bioanalytical applications. In droplet microfluidics, the samples that are discretized into droplets within the devices are predominantly loaded through tubings, but such tubing-based sample loading has drawbacks such as limited scalability for processing many samples, difficulty for automation, and sample wastage. While advances in autosamplers have alleviated some of these drawbacks, sample loading that can instead obviate tubings offers a potentially promising alternative but has been underexplored. To fill the gap, we introduce herein a droplet device that features a new Tubing Eliminated Sample Loading Interface (TESLI). TESLI integrates a network of programmable pneumatic microvalves that regulate vacuum and pressure sources so that successive sub-microliter samples can be directly spotted onto the open-to-atmosphere TESLI inlet, vacuumed into the device, and pressurized into nanoliter droplets within the device with minimal wastage. The same vacuum and pressure regulation also endows TESLI with cleaning and sample switching capabilities, thus enabling scalable processing of many samples in succession. Moreover, we implement a pair of TESLIs in our device to parallelize and alternate their operation as means to minimizing idle time. For demonstration, we use our device to successively process 44 samples into droplets-a number that can further scale. Our results demonstrate the feasibility of tubing-free sample loading and a promising approach for advancing droplet microfluidics.
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http://dx.doi.org/10.1038/s41598-022-17352-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9349288PMC
August 2022

In Situ Analysis of Membrane-Protein Binding Kinetics and Cell-Surface Adhesion Using Plasmonic Scattering Microscopy.

Angew Chem Int Ed Engl 2022 Aug 3. Epub 2022 Aug 3.

Arizona State University Biodesign Institute, Center for Bioelectronics and Biosensors, 1001 S McAllister Avenue, PO BOX 875801, 85248, Tempe, UNITED STATES.

Surface plasmon resonance microscopy (SPRM) is an excellent platform for in situ studying cell-substrate interactions. However, SPRM suffers from poor spatial resolution and small field of view. Herein, we demonstrate plasmonic scattering microscopy (PSM) by adding a dry objective on a popular prism-coupled surface plasmon resonance (SPR) system. PSM not only retains SPRM's high sensitivity and real-time analysis capability, but also provides ~7 times higher spatial resolution and ~70 times larger field of view than the typical SPRM, thus providing more details about membrane protein response to ligand binding on over 100 cells simultaneously. In addition, PSM allows quantifying the target movements in the axial direction with a high spatial resolution, thus allowing mapping adhesion spring constants for quantitatively describing the mechanical properties of the cell-substrate contacts. This work may offer a powerful and cost-effective strategy for upgrading current SPR products.
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http://dx.doi.org/10.1002/anie.202209469DOI Listing
August 2022

Putting precision and elegance in enzyme immobilisation with bio-orthogonal chemistry.

Chem Soc Rev 2022 Aug 3. Epub 2022 Aug 3.

Molecular Sciences Institute, School of Chemistry, University of the Witwatersrand, PO Wits, 2050, Johannesburg, South Africa.

The covalent immobilisation of enzymes generally involves the use of highly reactive crosslinkers, such as glutaraldehyde, to couple enzyme molecules to each other or to carriers through, for example, the free amino groups of lysine residues, on the enzyme surface. Unfortunately, such methods suffer from a lack of precision. Random formation of covalent linkages with reactive functional groups in the enzyme leads to disruption of the three dimensional structure and accompanying activity losses. This review focuses on recent advances in the use of bio-orthogonal chemistry in conjunction with rec-DNA to affect highly precise immobilisation of enzymes. In this way, cost-effective combination of production, purification and immobilisation of an enzyme is achieved, in a single unit operation with a high degree of precision. Various bio-orthogonal techniques for putting this precision and elegance into enzyme immobilisation are elaborated. These include, for example, fusing (grafting) peptide or protein tags to the target enzyme that enable its immobilisation in cell lysate or incorporating non-standard amino acids that enable the application of bio-orthogonal chemistry.
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http://dx.doi.org/10.1039/d1cs01004bDOI Listing
August 2022

Controlled fabrication of functional liver spheroids with microfluidic flow cytometric printing.

Biofabrication 2022 Aug 2. Epub 2022 Aug 2.

Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, 1700 4th St, San Francisco, San Francisco, California, 94158, UNITED STATES.

Multicellular liver spheroids are 3D culture models useful in the development of therapies for liver fibrosis. While these models can recapitulate fibrotic disease, current methods for generating them via random aggregation are uncontrolled, yielding spheroids of variable size, function, and utility. Here, we report fabrication of precision liver spheroids with microfluidic flow cytometric printing. Our approach fabricates spheroids cell-by-cell, yielding structures with exact numbers of different cell types. Because spheroid function depends on composition, our precision spheroids have superior functional uniformity, allowing more accurate and statistically significant screens compared to randomly generated spheroids. The approach produces thousands of spheroids per hour, and thus affords a scalable platform by which to manufacture single-cell precision spheroids for disease modeling and high throughput drug testing.
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http://dx.doi.org/10.1088/1758-5090/ac8622DOI Listing
August 2022

Sliding Window Dynamic Time-series Warping Based Ultrasonic Guided Wave Temperature Compensation and Defect Monitoring Method for Turnout Rail Foot.

IEEE Trans Ultrason Ferroelectr Freq Control 2022 Aug 1;PP. Epub 2022 Aug 1.

Temperature changes are a major challenge in outdoor guided wave structural health monitoring of rails. Temperature variations greatly impact the waveform of guided wave signals, making it challenging to diagnose and characterize defects. Traditional temperature compensation methods, such as signal stretch and scale-transform, are restricted to use in regular structures, such as plates and pipes. To solve the temperature compensation problem in long rails with serious mode conversion and complex structure echo, we propose a temperature compensation and defect monitoring method, namely, sliding window dynamic time-series warping (SWDTW), which overcomes the challenges of mass computation and overcompensation of dynamic time-series warping (DTW). The basic idea of SWDTW is to utilize sliding windows to accelerate the computation and identify defects from subsequence scales. Then, an index, window subsequence Teager energy (WSTE), is used to indicate the local abnormality of guided wave signals, and a sliding window net (SWnet) is devised to monitor the occurrence of defects automatically. Outdoor monitoring of turnout rails showed that the proposed method can effectively reduce the temperature noise and recognize an artificial defect with 1.16% and 0.36% cross-sectional change rates(CSCR) on the switch and stock rails, respectively, at different temperatures; moreover, the defect signals processed by SWDTW showed better defect identification performance than those processed by scale-transform and DTW.
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http://dx.doi.org/10.1109/TUFFC.2022.3195933DOI Listing
August 2022

Synthesis of fluoroolefin derivatives by nickel(II)-catalyzed trifluorovinylation and 1,2,2-trifluoroethylation of cinnamyl alcohols.

Org Biomol Chem 2022 Jul 28. Epub 2022 Jul 28.

College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, China.

Nickel(II)-catalyzed regioselective trifluorovinylation and 1,2,2-trifluoroethylation of allyl alcohols with trifluorovinyl reagents were performed. The reaction of ()-3-phenylprop-2-en-1-ol and trifluorovinylzinc bromide (TFVZ) afforded 1,2,2-trifluorovinyl diene in moderate to high yields. The reaction of ()-3-phenylprop-2-en-1-ol and trifluorovinyl trimethylsilane (TFVTMS) resulted in the novel nucleophilic addition product 1,1,2-trifluoroethoxy aryl olefin.
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http://dx.doi.org/10.1039/d2ob01078jDOI Listing
July 2022

Influence of prazosin on systemic iron levels and the associated iron metabolic alterations in spontaneously hypertensive rats.

Pharmacol Res Perspect 2022 Aug;10(4):e00991

College of Life Science, Hebei Normal University, Shijiazhuang, Hebei, People's Republic of China.

The relationship between cardiovascular diseases and iron disorders has gained increasing attention; however, the effects of hypotensive drugs on iron metabolic alterations in hypertension are not well understood. The purpose of this study was to investigate iron metabolic changes after prazosin treatment of spontaneously hypertensive rats (SHRs) and Wistar-Kyoto (WKY) rats. Our second objective was to examine the effects of hypertension and anti-hypertensive drugs on bone formation and resorption. SHRs and WKY rats were randomized into either prazosin-treated groups (WKY + PZ and SHR + PZ) or untreated groups (WKY and SHR). After 7 days of intragastric prazosin administration, the rats were sacrificed for analysis; blood samples and organs (the duodenum, liver, kidneys, spleen, and femur) were collected. Both WKY + PZ and SHR groups exhibited iron deficiency in the serum and liver. Prazosin increased the iron levels in the bone tissue of SHRs. Prazosin stimulated the expression of hepcidin mRNA in the liver of SHRs and inhibited the expression of this iron-regulatory hormone in WKY rats. FPN1 expression in the duodenum was increased significantly in SHRs, however markedly decreased after prazosin treatment. The expression of TLR4 and Ctsk was enhanced in the bone tissue of SHRs, whereas CLC-7 expression was inhibited. Both hypotension and hypertension can lead to iron deficiency. Treatment with prazosin restored iron homeostasis in SHRs. The inverse impacts of prazosin on hepatic hepcidin expression in SHRs versus WKY rats indicates differing iron regulatory mechanisms between hypertensive and normal animals. The osteoclast activity was found to be enhanced in SHRs. Further study is needed to address whether the changes in osteoblast and osteoclast activity in SHRs correlates with the effects on iron metabolism.
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http://dx.doi.org/10.1002/prp2.991DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326454PMC
August 2022

Photothermal Regulated Nanozyme of CuFeS Nanoparticles for Efficiently Promoting Wound Healing Infected by Multidrug Resistant Bacteria.

Nanomaterials (Basel) 2022 Jul 19;12(14). Epub 2022 Jul 19.

Institute of Biomedical Engineering, College of Life Sciences, Qingdao University, 308 Ningxia Road, Qingdao 266071, China.

Peroxidase-mediated chemokinetic therapy (CDT) can effectively resist bacteria; however, factors such as the high dosage of drugs seriously limit the antibacterial effect. Herein, CuFeS nanoparticles (NPs) nanozyme antibacterial system with the photothermal effect and peroxidase-like catalytic activity are proposed as a combined antibacterial agent with biosafety, high-efficiency, and broad-spectrum antibacterial ability. In addition, the as-obtained CuFeS NPs with a low doses of Cu and Fe can change the permeability of bacterial cell membranes and break the antioxidant balance by consuming intracellular glutathione (GSH), which results in more conducive ROS production. Meanwhile, the photothermal heating can regulate the CuFeS NPs close to their optimal reaction temperature (60 °C) to release more hydroxyl radical in low concentrations of HO (100 µM). The proposed CuFeS NPs-based antibacterial system achieve more than 99% inactivation efficiency of methicillin-resistant Staphylococcus aureus (10 CFU mL MRSA), hyperspectral bacteria β-Escherichia coli (10 CFU mL ESBL) and Pseudomonas aeruginosa (10 CFU mL PA), even at low concentration (2 μg mL), which is superior to those of the conventional CuO NPs at 4 mg mL reported in the literature. In vivo experiments further confirm that CuFeS NPs can effectively treat wounds infected by MRSA and promote the wound healing. This study demonstrates that excellent antibacterial ability and good biocompatibility make CuFeS NPs a potential anti-infection nanozyme with broad application prospects.
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http://dx.doi.org/10.3390/nano12142469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9315979PMC
July 2022

Programmable Polyproteams of Tyrosine Ammonia Lyases as Cross-Linked Enzymes for Synthesizing -Coumaric Acid.

Biomolecules 2022 07 18;12(7). Epub 2022 Jul 18.

Key Laboratory of Organosilicon Chemistry and Material Technology, College of Material, Chemistry and Chemical Engineering, Ministry of Education, Hangzhou Normal University, No. 2318, Road Yuhangtang, Hangzhou 311121, China.

Ideal immobilization with enhanced biocatalyst activity and thermostability enables natural enzymes to serve as a powerful tool to yield synthetically useful chemicals in industry. Such an enzymatic method strategy becomes easier and more convenient with the use of genetic and protein engineering. Here, we developed a covalent programmable polyproteam of tyrosine ammonia lyases () by fusing SpyTag and SpyCatcher peptides into the -terminal and -terminal of the TAL, respectively. The resulting circular enzymes were clear after the spontaneous isopeptide bonds formed between the SpyTag and SpyCatcher. Furthermore, the catalytic performance of the was measured via a synthesis sample of -Coumaric acid. Our showed excellent catalytic efficiency, with 98.31 ± 1.14% yield of the target product-which is 4.15 ± 0.08 times higher than that of traditional glutaraldehyde-mediated enzyme aggregates. They also showed over four times as much enzyme-activity as wild-type TAL does and demonstrated good reusability, and so may become a good candidate for industrial enzymes.
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http://dx.doi.org/10.3390/biom12070997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313006PMC
July 2022

ATM-TCR: TCR-Epitope Binding Affinity Prediction Using a Multi-Head Self-Attention Model.

Front Immunol 2022 6;13:893247. Epub 2022 Jul 6.

School of Computing and Augmented Intelligence, Arizona State University, Tempe, AZ, United States.

TCR-epitope pair binding is the key component for T cell regulation. The ability to predict whether a given pair binds is fundamental to understanding the underlying biology of the binding mechanism as well as developing T-cell mediated immunotherapy approaches. The advent of large-scale public databases containing TCR-epitope binding pairs enabled the recent development of computational prediction methods for TCR-epitope binding. However, the number of epitopes reported along with binding TCRs is far too small, resulting in poor out-of-sample performance for unseen epitopes. In order to address this issue, we present our model ATM-TCR which uses a multi-head self-attention mechanism to capture biological contextual information and improve generalization performance. Additionally, we present a novel application of the attention map from our model to improve out-of-sample performance by demonstrating on recent SARS-CoV-2 data.
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http://dx.doi.org/10.3389/fimmu.2022.893247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299376PMC
July 2022

Comprehensive Analysis of Immune Cell Infiltration of m6a-Related lncRNA in Lung Squamous Cell Carcinoma and Construction of Relevant Prognostic Models.

Biomed Res Int 2022 14;2022:9139823. Epub 2022 Jul 14.

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150000, China.

Lung squamous cell carcinoma (LUSC) is the main cause of cancer-related mortality. Some studies demonstrate that m6a and long noncoding RNA (lncRNA) are vital in the pathogenesis of LUSC. In this study, we aimed to further understand the prognostic value of m6a-related lncRNAs in LUSC and their role in the immune microenvironment. For this, we obtained LUSC transcriptome and clinical data from the TCGA database. Further, the identified m6a-related and prognostically relevant lncRNAs were clustered into groups based on prognostic lncRNA expression. Further analysis of the differences between clusters was performed. Five m6A-related lncRNAs were used for model construction using the LASSO regression. The receiver-operating characteristic curve (ROC curves) and decision curve analysis (DCA) were used to assess the model accuracy. Finally, the model was validated using polymerase chain reaction (PCR). We identified 12 m6a-related lncRNAs that were associated with prognosis and were lowly expressed in tumors. Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) highly correlated with prognostic genes, and differential analysis indicated that it was highly expressed in the tumor group and cluster 1. In cluster 2 TIME, tumor cells were less pure and more immune, and stromal-associated cells were present. A prognostic model was constructed based on five m6a-lncRNAs. The area under the curve (AUC) was >0.5 in test group and train group. The PCR results showed that the genes in the prognostic model were lowly expressed in the tumor and were statistically significant ( < 0.05). We noted that m6a-lncRNAs were strongly associated with LUSC prognosis and the immune microenvironment. Thus, PRC1-AS1, AL132780.2, AC013731.1, SNHG30, and AL358472.2 can be considered as new targets for the treatment of patients with LUSC.
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http://dx.doi.org/10.1155/2022/9139823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303127PMC
July 2022

Corrigendum: Hinokiflavone Inhibits Growth of Esophageal Squamous Cancer By Inducing Apoptosis Regulation of the PI3K/AKT/mTOR Signaling Pathway.

Front Oncol 2022 5;12:970020. Epub 2022 Jul 5.

Department of Thoracic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.

[This corrects the article DOI: 10.3389/fonc.2022.833719.].
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http://dx.doi.org/10.3389/fonc.2022.970020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295615PMC
July 2022

Digital quantum simulation of Floquet symmetry-protected topological phases.

Nature 2022 07 20;607(7919):468-473. Epub 2022 Jul 20.

Department of Physics, ZJU-Hangzhou Global Scientific and Technological Innovation Center, Interdisciplinary Center for Quantum Information, and Zhejiang Province Key Laboratory of Quantum Technology and Device, Zhejiang University, Hangzhou, China.

Quantum many-body systems away from equilibrium host a rich variety of exotic phenomena that are forbidden by equilibrium thermodynamics. A prominent example is that of discrete time crystals, in which time-translational symmetry is spontaneously broken in periodically driven systems. Pioneering experiments have observed signatures of time crystalline phases with trapped ions, solid-state spin systems, ultracold atoms and superconducting qubits. Here we report the observation of a distinct type of non-equilibrium state of matter, Floquet symmetry-protected topological phases, which are implemented through digital quantum simulation with an array of programmable superconducting qubits. We observe robust long-lived temporal correlations and subharmonic temporal response for the edge spins over up to 40 driving cycles using a circuit of depth exceeding 240 and acting on 26 qubits. We demonstrate that the subharmonic response is independent of the initial state, and experimentally map out a phase boundary between the Floquet symmetry-protected topological and thermal phases. Our results establish a versatile digital simulation approach to exploring exotic non-equilibrium phases of matter with current noisy intermediate-scale quantum processors.
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http://dx.doi.org/10.1038/s41586-022-04854-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9300455PMC
July 2022

Hyperosmotic-stress-induced liquid-liquid phase separation of ALS-related proteins in the nucleus.

Cell Rep 2022 Jul;40(3):111086

Institute of Nano Biomedicine and Engineering, Department of Instrument Science and Engineering, School of Electronic Information and Electrical Engineering, Shanghai Jiao Tong University, Shanghai 200240, China; Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of Sciences, The Cancer Hospital of the University of Chinese Academy of Sciences, Hangzhou, Zhejiang 310022, China. Electronic address:

Hyperosmotic stress as physiologic dysfunction can reduce the cell volume and then redistribute both protein concentration and ionic strength, but its effect on liquid-liquid phase separation (LLPS) is not well understood. Here, we map the hyperosmotic-stress-induced nuclear LLPS of amyotrophic lateral sclerosis (ALS)-related proteins (fused in sarcoma [FUS], TAR DNA-binding protein 43 [TDP-43]). The dynamic and reversibility of FUS granules are continuable with the increase of hypertonic stimulation time, but those of TDP-43 granules decrease significantly. Strikingly, FUS granules, but not TDP-43 granules, contain essential chaperone Hsp40, which can protect amyloid protein from solid aggregation. Moreover, FUS nuclear granules can co-localize with paraspeckles, but not promyelocytic leukemia (PML) bodies or nuclear speckles, while TDP-43 nuclear granules cannot co-localize with the above nuclear bodies. Together, these results may broaden our understanding of the LLPS of ALS-related proteins in response to cellular stress.
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http://dx.doi.org/10.1016/j.celrep.2022.111086DOI Listing
July 2022

Label-Free Imaging of Single Proteins and Binding Kinetics Using Total Internal Reflection-Based Evanescent Scattering Microscopy.

Anal Chem 2022 08 19;94(30):10781-10787. Epub 2022 Jul 19.

Biodesign Center for Bioelectronics and Biosensors, Arizona State University, Tempe, Arizona 85287, United States.

Single-molecule detection can push beyond ensemble averages and reveal the statistical distributions of molecular properties. Measuring the binding kinetics of single proteins also represents one of the critical and challenging tasks in protein analysis. Here, we report total internal reflection-based evanescent scattering microscopy with label-free single-protein detection capability. Total internal reflection is employed to excite the evanescent field to enhance light-analyte interaction and reduce environmental noise. As a result, the system provides wide-field imaging capability and allows excitation and observation using one objective. In addition, this system quantifies protein binding kinetics by simultaneously counting the binding of individual molecules and recording their binding sites with nanometer precision, providing a digital method to measure binding kinetics with high spatiotemporal resolution. This approach does not employ specially designed microspheres or nanomaterials and may pave a way for label-free single-protein analysis in conventional microscopy.
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http://dx.doi.org/10.1021/acs.analchem.2c01510DOI Listing
August 2022

Genomic profiling and the impact of MUC19 mutation in hepatoid adenocarcinoma of the stomach.

Cancer Commun (Lond) 2022 Jul 19. Epub 2022 Jul 19.

Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, 20032, P. R. China.

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http://dx.doi.org/10.1002/cac2.12336DOI Listing
July 2022

Early Changes in the White Matter Microstructure and Connectome Underlie Cognitive Deficit and Depression Symptoms After Mild Traumatic Brain Injury.

Front Neurol 2022 30;13:880902. Epub 2022 Jun 30.

Department of Magnetic Resonance, Lanzhou University Second Hospital, Lanzhou, China.

Cognitive and emotional impairments are frequent among patients with mild traumatic brain injury (mTBI) and may reflect alterations in the brain structural properties. The relationship between microstructural changes and cognitive and emotional deficits remains unclear in patients with mTBI at the acute stage. The purpose of this study was to analyze the alterations in white matter microstructure and connectome of patients with mTBI within 7 days after injury and investigate whether they are related to the clinical questionnaires. A total of 79 subjects (42 mTBI and 37 healthy controls) underwent neuropsychological assessment and diffusion-tensor MRI scan. The microstructure and connectome of white matter were characterized by tract-based spatial statistics (TBSSs) and graph theory approaches, respectively. Mini-mental state examination (MMSE) and self-rating depression scale (SDS) were used to evaluate the cognitive function and depressive symptoms of all the subjects. Patients with mTBI revealed early increases of fractional anisotropy in most areas compared with the healthy controls. Graph theory analyses showed that patients with mTBI had increased nodal shortest path length, along with decreased nodal degree centrality and nodal efficiency, mainly located in the bilateral temporal lobe and right middle occipital gyrus. Moreover, lower nodal shortest path length and higher nodal efficiency of the right middle occipital gyrus were associated with higher SDS scores. Significantly, the strength of the rich club connection in the mTBI group decreased and was associated with the MMSE. Our study demonstrated that the neuroanatomical alterations of mTBI in the acute stage might be an initial step of damage leading to cognitive deficits and depression symptoms, and arguably, these occur due to distinct mechanisms.
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http://dx.doi.org/10.3389/fneur.2022.880902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9279564PMC
June 2022

A novel machine learning model based on sparse structure learning with adaptive graph regularization for predicting drug side effects.

J Biomed Inform 2022 Aug 14;132:104131. Epub 2022 Jul 14.

NHC Key Laboratory of Cancer Proteomics, Department of Oncology, PR China; National Clinical Research Center for Gerontology, Xiangya Hospital, Central South University, PR China.

Drug side effects are closely related to the success and failure of drug development. Here we present a novel machine learning method for side effect prediction. The proposed method treats side effect prediction as a multi-label learning problem and uses sparse structure learning to model the relationships between side effects. Additionally, the proposed method adopts the adaptive graph regularization strategy to explore the local structure in drug data and fuse multiple types of drug features. An alternating optimization algorithm is proposed to solve the optimization problem. We collected chemical structures and biological pathway features of drugs as the inputs of our method to predict drug side effects. The results of the cross-validation experiment showed that our method could significantly improve the prediction performance compared to the other state-of-the-art methods. Besides, our model is highly interpretable. It could learn the drug neighbourhood relationships, side effect relationships, and drug features related to side effects. We systematically validated the information extracted by the model with independent data. Some prediction results could also be supported by literature reports. The proposed method could be applied to integrate both chemical and biological data to predict side effects and helps improve drug safety.
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http://dx.doi.org/10.1016/j.jbi.2022.104131DOI Listing
August 2022

H O -Responsive NIR-II AIE Nanobomb for Carbon Monoxide Boosting Low-Temperature Photothermal Therapy.

Angew Chem Int Ed Engl 2022 Jul 15:e202207213. Epub 2022 Jul 15.

Guangdong Key Laboratory of Nanomedicine, Shenzhen Engineering Laboratory of Nanomedicine and Nanoformulations, CAS-HK Joint Lab for Biomaterials, Research Laboratory for Biomedical Optics and Molecular Imaging, Shenzhen Key Laboratory for Molecular Imaging, CAS Key Lab for Health Informatics, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.

Low-temperature photothermal therapy (PTT), which circumvents the limitations of conventional PTT (e.g., thermotolerance and adverse effects), is an emerging therapeutic strategy which shows great potential for future clinical applications. The expression of heat shock proteins (HSPs) can dramatically impair the therapeutic efficacy of PTT. Thus, inhibition of HSPs repair and reducing the damage of nearby normal cells is crucial for improving the efficiency of low-temperature PTT. Herein, we developed a nanobomb based on the self-assembly of NIRII AIE polymer PBPTV and carbon monoxide (CO) carrier polymer mPEG(CO). This smart nanobomb can be exploded in a tumor microenvironment in which hydrogen peroxide is overexpressed and release CO into cancer cells to significantly inhibit the expression of HSPs and hence improve the antitumor efficiency of the low-temperature PTT.
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http://dx.doi.org/10.1002/anie.202207213DOI Listing
July 2022

MVFStain: Multiple virtual functional stain histopathology images generation based on specific domain mapping.

Med Image Anal 2022 08 23;80:102520. Epub 2022 Jun 23.

School of Biomedical Engineering, Western University, London, ON, Canada. Electronic address:

To the best of our knowledge, artificial intelligence stain generation is an urgent requirement for histopathology images. Pathological examinations usually only utilize hematoxylin and eosin (H&E) regular staining to show histomorphological characteristics, but to accurately diagnose the disease, functional staining (such as oil red O and Ki67) are also required to provide important auxiliary information. However, the same tissue section is usually stained with one stain, and additional functional staining is not only time-consuming but also causes inevitable morphological misalignment due to manual manipulation. This brings difficulties to the development of artificial intelligence pathological image analysis tools. In this work, we propose a histopathology staining transfer framework to generate virtual functional staining images from H&E regular staining images. Compared with the framework that emphasizes generation diversity in the natural image field, we use KL loss and histo loss to align and separate style feature spaces in different domains to obtain domain-variant style features. The proposed multiple virtual functional stain (MVFStain) abstracts staining conversion to domain mapping and comprehensively utilizes multiple staining information. We evaluated the proposed method on four datasets (lung lesion, lung lobes, breast, and atherosclerotic lesion). The experiment involves the translation of H&E to nine other functional stains: CC10, Ki67, proSPC, HER2, PR, ER, oil red O, α-SMA, and macrophages. The major quantitative results are divided into image quality and positive signal prediction. MVFStain is close to or even surpasses one-to-one image translation on psnr and HTI image quality metrics. The best psnr reaches 26.1919, and HIT reaches 0.9430. We used mIOD to evaluate the optical density of positive signals, and CNR and gCNR to evaluate the lesion detectability. The results show that the mIOD of positive signals of virtual staining was slightly lower than the ground truth and close the lesion detectability of artificial staining. These results prove that the potential exists to develop a successful clinical alternative to artificial functional stains.
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http://dx.doi.org/10.1016/j.media.2022.102520DOI Listing
August 2022

Comparative Proteomic Analyses of Poorly Motile Swamp Buffalo Spermatozoa Reveal Low Energy Metabolism and Deficiencies in Motility-Related Proteins.

Animals (Basel) 2022 Jul 1;12(13). Epub 2022 Jul 1.

State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangxi University, Nanning 530004, China.

The acquisition of mammalian sperm motility is a main indicator of epididymal sperm maturation and helps ensure fertilization. Poor sperm motility will prevent sperm cells from reaching the fertilization site, resulting in fertilization failure. To investigate the proteomic profiling of normal and poorly motile buffalo spermatozoa, a strategy applying liquid chromatography tandem mass spectrometry combined with tandem mass targeting was used. As a result, 145 differentially expressed proteins (DEPs) were identified in poorly motile spermatozoa (fold change > 1.5), including 52 upregulated and 93 downregulated proteins. The upregulated DEPs were mainly involved in morphogenesis and regulation of cell differentiation. The downregulated DEPs were involved with transport, oxidation-reduction, sperm motility, regulation of cAMP metabolism and regulation of DNA methylation. The mRNA and protein levels of PRM1 and AKAP3 were lower in poorly motile spermatozoa, while the expressions of SDC2, TEKT3 and IDH1 were not correlated with motility, indicating that their protein changes were affected by transcription or translation. Such changes in the expression of these proteins suggest that the formation of poorly motile buffalo spermatozoa reflects a low efficiency of energy metabolism, decreases in sperm protamine proteins, deficiencies in motility-related proteins, and variations in tail structural proteins. Such proteins could be biomarkers of poorly motile spermatozoa. These results illustrate some of the molecular mechanisms associated with poorly motile spermatozoa and provide clues for finding molecular markers of these pathways.
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http://dx.doi.org/10.3390/ani12131706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9264820PMC
July 2022

Establishment of a Real-Time Quantitative PCR Assay for Porcine Circovirus-Like Virus and the First Evidence of Its Spread to Hainan and Jiangxi Provinces of China.

Front Vet Sci 2022 21;9:853761. Epub 2022 Jun 21.

National Pig Breeding Industry Engineering and Technical Research Center, College of Animal Science and National Engineering Center for Swine Breeding Industry, South China Agriculture University, Guangzhou, China.

Porcine Circovirus-like (PCL) virus, a new emerging virus, has been widely detected in Guangdong, Guangxi, and Anhui provinces in China, which may be a novel agent causing severe diarrhea in newborn piglets and tending to spread widely. Evidence suggests that the virus is related to hemorrhagic enteritis and diarrhea, and many newborn piglets were emaciated to death after infection. Therefore, a sensitive, quick, and accurate detection system for virus detection and epidemiological investigation is necessary. In this study, we developed a real-time quantitative PCR assay based on SYBR green for the detection of PCL virus. The ORF4 conserved region of PCL virus was found by the alignment of the uploaded genome sequences to design specific primers, and the primers were tested and showed good specificity, sensitivity, and reproducibility. Approximately, 138 fecal samples were obtained from diarrheal pigs in South China from June to December 2021. Approximately, 22.46% (31/138) of the samples and 40% (8/20) of the pig farms were positive for PCL virus, respectively, by using this method. Moreover, it is worth noting that the virus was first detected in Hainan and Jiangxi Provinces of China, which means that the virus may spread widely in China. Through evolutionary tree analysis and partial sequence comparison, there are some differences of virus genes in each province, suggesting that there is a risk of variation, and the four PCL virus strains showed a sequence similarity of 86.7%-87.8% for the rep gene and 92.2%-92.9% for the Rep protein, respectively, with Bo-Circo-like virus that is detected in bovine, which further demonstrates a close relationship between the two viruses that originated from different animals. In conclusion, our study provides a useful diagnostic approach to PCL virus detection and epidemiological inquiry. Meanwhile, the epidemic data using this real-time qPCR assay provide evidence for the widespread variations and epidemic of the virus in South China, and warn the appropriate measures for prevention, and control of porcine circovirus-like virus infection should be under consideration in pig production.
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http://dx.doi.org/10.3389/fvets.2022.853761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9253630PMC
June 2022

Mechanisms of the Chinese Government's Efforts to Fight COVID-19: Integration of Top-down Interventions and Local Governance.

Health Secur 2022 Jul 4. Epub 2022 Jul 4.

Pengfei Zhang, PhD, School of Labor and Human Resources, Renmin University of China, Beijing, China.

The experiences and lessons of China's response to COVID-19 have been described in several studies, but the mechanisms of the Chinese government's efforts to fight COVID-19 have not been well characterized. Despite strong policy directives and orders from the central government, the response and handling of the epidemic also reflected distinctive characteristics of local governments in terms of their governance systems and capacities. In this article, the authors analyze public health policies and mechanisms of the Chinese government's response to COVID-19 based on the integration of top-down and local governance. A compendium of key events and measures provides the foundation for our analysis. Mechanisms related to leadership, emergency response, centralized mobilization, and accountability fully reflect the decisive measures for top-down interventions in the face of emergencies. China's policies and mechanisms to address the COVID-19 pandemic are consistent with its party-state bureaucracy and socioeconomic context. However, lower levels of government have used "repeated increments" and "one-size-fits-all" practices in the implementation of antiepidemic policies. Conservative local officials are more averse to social innovation and favor strict controls to manage the pandemic. Moreover, even under a unified system, there are substantial differences in the capacity and level of crisis management among local governments, especially in the mobilization of nonprofit organizations and volunteers. In this case study, we aim to expand the existing understanding of the tension between top-down interventions and local governance innovations.
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http://dx.doi.org/10.1089/hs.2021.0161DOI Listing
July 2022

Cardiovascular Outcomes in the Patients With Colorectal Cancer: A Multi-Registry-Based Cohort Study of 197,699 Cases in the Real World.

Front Cardiovasc Med 2022 16;9:851833. Epub 2022 Jun 16.

Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.

Purpose: We aimed to investigate the mortality patterns and quantitatively assess the risks of cardiovascular death (CVD) in patients with colorectal cancer (CRC). We also established a competing-risk model to predict the probability of CVD for patients with CRC.

Patients And Methods: Patients with CRC who diagnosed between 2007 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database were included in the present study. The cumulative incidence function (CIF) was used for CVD and other causes of death, and Gray's test was used to determine the subgroup difference in CIF. The Fine-Gray proportional subdistribution hazards model was used for identifying independent risk factors for CVD. A novel competing-risk model was established to evaluate the probability of CVD for patients with CRC. The performance of the nomogram was measured by concordance index (C-index), calibration curve, decision curve analysis (DCA), and risk stratification.

Results: After a median follow-up of 37.00 months, 79,455 deaths occurred, of whom 56,185 (70.71%) succumbed to CRC and 23,270 (29.29%) patients died due to non-CRC, among which CVD accounted for 9,702 (41.69%), being the major cause of non-cancer deaths. The 1-, 3-, and 5-year cumulative rates for CVD were 12.20, 24.25, and 30.51%, respectively. In multivariate analysis, age, race, marital status, tumor size, tumor stage, advanced stage, surgery, and chemotherapy were independent risk factors of CVD among patients with CRC. The nomogram was well calibrated and had good discriminative ability, with a c-index of 0.719 (95% CI, 0.738-0.742) in the training cohort and 0.719 (95% CI, 0.622-0.668) in the validation cohort. DCA demonstrated that nomogram produced more benefit within wide ranges of threshold probabilities for 1-, 3-, and 5-year CVD, respectively.

Conclusion: This study was the first to analyze the CIF and risk factors for CVD among CRC based on a competing-risk model. We have also built the first 1-, 3-, and 5-year competing nomogram for predicting CVD. This nomogram had excellent performance and could help clinicians to provide individualized management in clinical practice.
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http://dx.doi.org/10.3389/fcvm.2022.851833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9243221PMC
June 2022

Practical chemoselective aromatic substitution: the synthesis of -(4-halo-2-nitrophenyl)benzenesulfonamide through the efficient nitration and halogenation of -phenylbenzenesulfonamide.

Org Biomol Chem 2022 07 13;20(27):5444-5451. Epub 2022 Jul 13.

Institute of Pharmacology, Pharmacy College, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an 271016, China.

A novel route involving the metal-promoted tandem nitration and halogenation of -phenylbenzenesulfonamide to synthesize -(4-halo-2-nitrophenyl)benzenesulfonamide derivatives has been developed. The method shows highly practical chemoselective and functional group compatibility. In addition, it employs insensitive and inexpensive Cu(NO)·3HO, Fe(NO)·9HO, and NHNO as the nitration reagents, and it provides a direct approach for the preparation of 4-halo-2-nitroaniline, which is a crucial intermediate for the synthesis of benzimidazoles and quinoxaline derivatives.
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http://dx.doi.org/10.1039/d2ob01028cDOI Listing
July 2022
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