Publications by authors named "Xiang Huang"

280 Publications

Changes in volatile flavor of yak meat during oxidation based on multi-omics.

Food Chem 2021 Sep 8;371:131103. Epub 2021 Sep 8.

School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang 550000, China. Electronic address:

Hydroxyl radical system combined with GC-IMS and metabolomics were used to assess the effect of oxidation on the formation of volatile flavor emitted from yak meat. The formation of volatile compounds, including heptanal, octanal, nonanal, 2,3-glutaraldehyde, 3-hydroxy-2-butanone, etc. were promoted by oxidation. Among them, 2,3-pentanedione and 3-hydroxy-2-butanone, etc. maybe contributed most to the overall aroma of yak meat, while octanal, nonanal and benzaldehyde maybe related to the formation of off-odor or acidification. Meanwhile, the content of metabolites such as oleic acid, linoleic acid, etc. fatty acids and 3-dehydromangiferic acid, tyrosine were increased or decreased with the time of oxidation. More importantly, the formation of most flavor components in yak meat during the course of oxidation were related to stearidonic acid, acetylleucine, dehydroshikimate, 6-phosphate-glucose etc. differential metabolic components. Moreover, starch and sucrose metabolism (prediction), and amino acid metabolism (enrichment) etc. pathways maybe related with the process of oxidation.
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http://dx.doi.org/10.1016/j.foodchem.2021.131103DOI Listing
September 2021

Anterior spinal artery syndrome, intravenous alteplase or not.

Acta Neurol Belg 2021 Sep 17. Epub 2021 Sep 17.

Department of Neurology, Yueyang Central Hospital , Yueyang, China.

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http://dx.doi.org/10.1007/s13760-021-01802-2DOI Listing
September 2021

Safety profile of poly (ADP-ribose) polymerase (PARP) inhibitors in cancer: a network meta-analysis of randomized controlled trials.

Ann Transl Med 2021 Aug;9(15):1229

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

Background: Poly (ADP-ribose) polymerase (PARP) inhibitors, which are among the most important breakthroughs in precision medicine, have played a crucial role in cancer treatment. Understanding the toxicity profiles of the different PARP inhibitors will improve strategic treatment in clinical practice.

Methods: PubMed, Cochrane Library, and Web of Science were systematically searched to include related studies published in English between January 2009 and February 2020. Only prospective, phase II and III randomized controlled trials were included. The following treatment groups were analyzed: niraparib, talazoparib, olaparib, rucaparib, conventional therapy (chemotherapy), one PARP inhibitor with one angiogenesis inhibitor, and placebo. Baseline data and adverse event data were extracted from the Bayesian random-effects network meta-analysis.

Results: Fourteen phase II and III randomized controlled trials (4,336 patients) were included. When considering grade 3-5 adverse events, olaparib may be a better choice (probability =57%), followed by conventional therapy (50%), talazoparib (45%), rucaparib (75%), niraparib (77%), and a PARP inhibitor with one angiogenesis inhibitor (94%). Niraparib and rucaparib had higher risks for hematological and gastrointestinal toxicities, respectively. Talazoparib was safer for gastrointestinal function. Constipation and neutropenia were less observed in olaparib, but the risks for anorexia increased. The combination of PARP inhibitor and angiogenesis inhibitor increased the risk of general, metabolic, and gastrointestinal disorders.

Conclusions: This network meta-analysis suggested that the toxicity spectrum of each PARP inhibitor is different. Olaparib had the best safety profile among all PARP inhibitors because of its mild toxicity and narrow spectrum. This study may guide clinicians and support further research.
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http://dx.doi.org/10.21037/atm-21-1883DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421942PMC
August 2021

Developing Proton-Conductive Metal Coordination Polymer as Highly Efficient Electrocatalyst toward Oxygen Reduction.

J Phys Chem Lett 2021 Sep 16:9197-9204. Epub 2021 Sep 16.

Department of Physics, Southern University of Science and Technology, Shenzhen 518055, China.

Developing earth-abundant transition metal (TM)-based electrocatalysts toward oxygen reduction reaction (ORR) is significant in overcoming the high cost of fuel cells. Herein, using an as-synthesized proton-conductive coordination polymer (termed TM-DHBQ) as a template, we investigate the ORR performance of a series of such TM-DHBQs via screening 3d, 4d, and 5d TMs. We find that most 3d TM-DHBQs exhibit distinguished durability under ORR turnover conditions. The formation energies of these TM-DHBQs and adsorption free energies of ORR intermediates show a good correlation with the number of outer electrons of TM ions in TM-DHBQs, enabling the formation energy as a robust ORR activity descriptor. The Sabatier-type volcano plot and microkinetic modeling coidentify Fe- and Co-DHBQs as two promising alternatives to Pt-based ORR electrocatalysts. For those TM-DHBQs showing strong bonding to oxygen species, the ORR intermediate is found to combine with the TM ion serving as the active center.
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http://dx.doi.org/10.1021/acs.jpclett.1c02665DOI Listing
September 2021

Differential Effect of Anaerobic Digestion on Gaseous Products from Sequential Pyrolysis of Three Organic Solid Wastes.

ACS Omega 2021 Aug 19;6(34):22103-22113. Epub 2021 Aug 19.

School of Environmental and Chemical Engineering, Key Laboratory of Organic Compound Pollution Control, Ministry of Education, Shanghai University, Shanghai 200444, China.

Studies have shown that anaerobic digestion (AD) has an effect on the liquid and solid product property of sequential pyrolysis, but its influence on the gaseous products is lacking. In this study, syngas produced by pyrolysis from three raw organic solid wastes and the corresponding digestates, i.e., food waste, vinasse, and cow manure were investigated. AD causes a decrease in the contents of volatile solid, fixed carbon, C, H, and N and an increase in the S content. The weight loss of the wastes mainly occurs at 200-550 °C during the pyrolysis and the loss of the food waste and vinasse is higher than that of cow manure. In the carbon (C)-containing gas, AD leads to a decrease in the CH content of the syngas, implying that the heat values of the digestates are lower than that of the raw substrates. After AD, the total amount of nitrogen (N)-containing gas from the vinasse increases by 40.1%, while that from cow manure decreases by 14.1%. On the contrary, the total amount of sulfur (S)-containing groups in the syngas from vinasse drop by 22.0%, while that from cow manure increases by 9.1%. In addition, slight changes in the C-, N-, and S-containing gases are found from food waste. The results indicate that AD has a different effect on the N- and S- containing gaseous groups from different organic solid wastes, and the mechanisms deserve further investigation. The findings supply a theoretical foundation for environmental-friendly application of syngas from the digestates.
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http://dx.doi.org/10.1021/acsomega.1c02678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412929PMC
August 2021

Mechanism of differences in characteristics of thick/thin egg whites during storage: Physicochemical, functional and molecular structure characteristics analysis.

Food Chem 2021 Aug 11;369:130828. Epub 2021 Aug 11.

School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, China. Electronic address:

This study systematically analyzed and compared thechanges of physicochemical, functional and molecular structural characteristics between thick egg white (KEW) and thin egg white (NEW) during storage. Analysis of physicochemical properties showed that moisture content decreased significantly with the increase of pH during storage. KEW was gradually thinning, while NEW was closer to Newtonian fluid. Functional properties indicated that KEW thermal gel was gradually hard and brittle with the properties of NEW. KEW had better emulsifying property than NEW, and NEW had superior foaming ability. The α-helix and β-sheet in the FT-IR spectrum showed a downward trend, revealing secondary structure changed from order to disorder. Enhancement of fluorescence intensity indicated the structural unfolding and exposure of tryptophan residues. SDS-PAGE proved that OVO might be related to the difference between KEW and NEW characteristics. This study provided new idea and reference value for egg storage and diversified utilization of egg white.
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http://dx.doi.org/10.1016/j.foodchem.2021.130828DOI Listing
August 2021

Single Iridium Atom Doped NiP Catalyst for Optimal Oxygen Evolution.

J Am Chem Soc 2021 Sep 16;143(34):13605-13615. Epub 2021 Aug 16.

Department of Materials Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China.

Single-atom catalysts (SACs) with 100% active sites have excellent prospects for application in the oxygen evolution reaction (OER). However, further enhancement of the catalytic activity for OER is quite challenging, particularly for the development of stable SACs with overpotentials <180 mV. Here, we report an iridium single atom on NiP catalyst (Ir-NiP) with a record low overpotential of 149 mV at a current density of 10 mA·cm in 1.0 M KOH. The Ir-NiP catalyst delivers a current density up to ∼28-fold higher than that of the widely used IrO at 1.53 V vs RHE. Both the experimental results and computational simulations indicate that Ir single atoms preferentially occupy Ni sites on the top surface. The reconstructed Ir-O-P/Ni-O-P bonding environment plays a vital role for optimal adsorption and desorption of the OER intermediate species, which leads to marked enhancement of the OER activity. Additionally, the dynamic "top-down" evolution of the specific structure of the [email protected] particles is responsible for the robust single-atom structure and, thus, the stability property. This Ir-NiP catalyst offers novel prospects for simplifying decoration strategies and further enhancing OER performance.
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http://dx.doi.org/10.1021/jacs.1c04682DOI Listing
September 2021

Anchoring an Fe Dimer on Nitrogen-Doped Graphene toward Highly Efficient Electrocatalytic Ammonia Synthesis.

ACS Appl Mater Interfaces 2021 Sep 30;13(36):43632-43640. Epub 2021 Aug 30.

Department of Physics, Southern University of Science and Technology, Shenzhen 518055, China.

Electrochemical reduction of N to NH based on sustainable energy is a green technique to produce decentralized and on-demand ammonia. In this work, taking graphene as a design platform, we explore the dual-atom catalysts (DACs) via embedding two homonuclear transition metal (TM) atoms into graphene decorated with four neighboring pyrrolic nitrogen atoms ([email protected]) to computationally screen the qualified nitrogen reduction reaction (NRR) catalysts. On the basis of the activity, selectivity, and stability of 15 homonuclear DACs of [email protected], [email protected] is identified as the most efficient NRR catalyst with a limiting potential of only -0.32 V. Electronic structure analysis demonstrates that the low oxidation state of Fe (+1) remarkably activates the molecular N, which contributes to its excellent NRR catalytic activity. Moreover, the kinetic studies reveal all of the NRR elementary steps exhibiting barriers smaller than that of the hydrogen evolution reaction (HER), showing that HER is effectively suppressed. In addition, we find that the integral crystal orbital Hamilton population (ICOHP) can be used as a descriptor to describe the Gibbs free energy of each step for its NRR performance. This work not only provides theoretical guidance for designing DACs for NRR but also promotes the understanding of DACs for N fixation.
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http://dx.doi.org/10.1021/acsami.1c11585DOI Listing
September 2021

Dexmedetomidine Protects Human Renal Tubular Epithelial HK-2 Cells against Hypoxia/Reoxygenation Injury by Inactivating Endoplasmic Reticulum Stress Pathway.

Cell J 2021 Sep 29;23(4):457-464. Epub 2021 Aug 29.

Department of Anesthesiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.Email:

Objective: The study was aimed to investigate the effects and potential mechanisms of Dexmedetomidine (Dex) on hypoxia/reoxygenation (H/R) injury in human renal tubular epithelial HK-2 cells.

Materials And Methods: In this experimental study, HK-2 cells were divided into four groups: control group, Dex group, H/R group, and Dex+H/R group. The cells in control group received no treatment, and cells in Dex group were only treated with 0.1 nmol/L Dex. The cells in H/R group and Dex+H/R group were all treated with H/R (hypoxia for 24 hours and normoxia for 4 hours), and only the cells in Dex+H/R group were pre-administrated with 0.1 nmol/L Dex. Following treatments at 37˚C for 28 hours, cell viability and apoptosis were measured by MTT assay and flow cytometry, respectively. Also, the expressions of hypoxia-inducible factor 1 (HIF-1α), glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), caspase-12 and cleaved caspase-3 were determined by western blot.

Results: The cell viability was significant decreased in H/R group compared with control group (P<0.05), while was significantly increased in Dex+H/R group compared with that in H/R group (P<0.05). However, the change tendency of the cell apoptosis was opposite to that of cell viability. Compared with H/R group, the expression of HIF-1α was evidently up-regulated, while GRP78, CHOP, capase-12 and cleaved caspase-3 expressions were all obviously downregulated in Dex+H/R group (P<0.05). In addition, the concentrations of malondialdehyde (MDA) in H/R group and Dex+H/R group were 1.68 ± 0.22 nmol/mgprot and 0.85 ± 0.16 nmol/mgprot, respectively. The superoxide dismutase (SOD) activity was higher in Dex+H/R group (121 ± 11 U/L), which which was more than twice larger than that in H/R group (57 ± 10 U/L).

Conclusion: Dex could promote cell viability and inhibit apoptosis through up-regulating HIF-1α, reducing endoplasmic reticulum (ER) stress and mediating oxidative stress, thus ameliorating the H/R injury.
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http://dx.doi.org/10.22074/cellj.2021.7220DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8405080PMC
September 2021

Visible-Light-Catalyzed in Situ Denitrogenative Sulfonylation of Sulfonylhydrazones.

Org Lett 2021 Sep 18;23(17):6784-6788. Epub 2021 Aug 18.

Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510641, China.

A photocatalyzed denitrogenative sulfonylation of -arylsulfonyl hydrazones has been developed. This transformation provides a low-carbon strategy to assemble arylalkyl sulfones in a stepwise denitrogenation/sulfonylation manner.
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http://dx.doi.org/10.1021/acs.orglett.1c02369DOI Listing
September 2021

Risk Signature of Cancer-Associated Fibroblast-Secreted Cytokines Associates With Clinical Outcomes of Breast Cancer.

Front Oncol 2021 28;11:628677. Epub 2021 Jul 28.

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

Cancer-associated fibroblasts (CAFs) are key components in tumor microenvironment (TME). The secreted products of CAFs play important roles in regulating tumor cells and further impacting clinical prognosis. This study aims to reveal the relationship between CAF-secreted cytokines and breast cancer (BC) by constructing the risk signature. We performed three algorithms to reveal CAF-related cytokines in the TCGA BC dataset and identified five prognosis-related cytokines. Then we used single-cell RNA sequencing (ScRNA-Seq) datasets of BC to confirm the expression level of these five cytokines in CAFs. METABRIC and other independent datasets were utilized to validate the findings in further analyses. Based on the identified five-cytokine signature derived from CAFs, BC patients with high-risk score (RS) had shorter overall survival than low-RS cases. Further analysis suggested that the high-RS level correlated with cell proliferation and mast cell infiltration in BCs of the Basal-like subtype. The results also indicated that the level of RS could discriminate the high-risk BC cases harboring driver mutations (i.e., PI3KCA, CDH1, and TP53). Additionally, the status of five-cytokine signature was associated with the frequency and molecular timing of whole genome duplication (WGD) events. Intratumor heterogeneity (ITH) analysis among BC samples indicated that the high-RS level was associated with the increase of tumor subclones. This work demonstrated that the prognostic signature based on CAF-secreted cytokines was associated with clinical outcome, tumor progression, and genetic alteration. Our findings may provide insights to develop novel strategies for early intervention and prognostic prediction of BC.
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http://dx.doi.org/10.3389/fonc.2021.628677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8356635PMC
July 2021

Unmasking antibiotic-associated neurological disorders: The underminer in Intensive Care Unit.

J Clin Neurosci 2021 Sep 7;91:131-135. Epub 2021 Jul 7.

Department of Neurology, The First People's Hospital of Yueyang, Yueyang, China. Electronic address:

Psychosis is a common and intractable disorder of hospitalization, especially in patients hospitalized in Intensive Care Unit (ICU). Along with the widely use of multiple antibiotics in community-acquired infection and hospital-acquired infection, the occurrence of antibiotic-associated neurological disorders has become more frequently. However, antibiotic neurotoxicity is often overlooked or misinterpreted. In this review, we summarized the neurological disorders caused by antibacterial agent usage and firstly systematically formulated the pathogenesis of antibiotic-associated neurotoxic reactions. Precautions of the complications are critical in preventing serious clinical outcome as the inducement is curable. Regular neurological physical examination, electroencephalogram (EEG) examination, lumbar puncture and therapeutic drug monitoring closely are essential for early diagnosis and differential diagnosis.
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http://dx.doi.org/10.1016/j.jocn.2021.06.040DOI Listing
September 2021

How Entrepreneurship Education at Universities Influences Entrepreneurial Intention: Mediating Effect Based on Entrepreneurial Competence.

Front Psychol 2021 6;12:655868. Epub 2021 Jul 6.

Institute of China Innovation and Entrepreneurship Education, Wenzhou Medical University, Wenzhou, China.

Research shows that entrepreneurial activities significantly promote economic development, which enhances the importance of the innovative entrepreneurial potential of college students. This study analyzes the effect of entrepreneurship education on entrepreneurial intention from the perspective of planned behavior theory. By examining the significant role of entrepreneurship education at colleges and universities on economic and social development, we established a conceptual model. To understand the relationship between entrepreneurship education and entrepreneurial intention, the hypotheses propose the intermediary role of entrepreneurial ability, and the study provides evidence from China the relationship between entrepreneurship education and entrepreneurial intention. Improving entrepreneurial intention and encouraging college students to establish businesses through entrepreneurship education in universities is crucial. This study proposes a hypothetical model of the relationship between entrepreneurial competence and entrepreneurial intention in entrepreneurship education at universities. Using a questionnaire survey of college students with practical experience in the Yangtze River Delta of China, the bootstrap method in the SPSS macro program process software verifies the hypotheses. The results show that entrepreneurial teaching, business plan competition, and entrepreneurial practice support positively affect entrepreneurial competence. In addition, entrepreneurial competence plays an intermediary role in the relationship between entrepreneurial teaching, business plan competition, entrepreneurship practice support, and entrepreneurial intention. Entrepreneurship education improves the ability to establish a business in the present and in entrepreneurial activities in the future. Entrepreneurial competence obtained through entrepreneurship education continuously affects entrepreneurial intention.
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http://dx.doi.org/10.3389/fpsyg.2021.655868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289882PMC
July 2021

On the robustness of inference of association with the gut microbiota in stool, rectal swab and mucosal tissue samples.

Sci Rep 2021 Jul 21;11(1):14828. Epub 2021 Jul 21.

Department of Bioinformatics and Genomics, University of North Carolina at Charlotte, 9331 Robert D. Snyder Rd, Room 361, Charlotte, NC, 28223, USA.

The gut microbiota plays an important role in human health and disease. Stool, rectal swab and rectal mucosal tissue samples have been used in individual studies to survey the microbial community but the consequences of using these different sample types are not completely understood. In this study, we report differences in stool, rectal swab and rectal mucosal tissue microbial communities with shotgun metagenome sequencing of 1397 stool, swab and mucosal tissue samples from 240 participants. The taxonomic composition of stool and swab samples was distinct, but less different to each other than mucosal tissue samples. Functional profile differences between stool and swab samples are smaller, but mucosal tissue samples remained distinct from the other two types. When the taxonomic and functional profiles were used for inference in association with host phenotypes of age, sex, body mass index (BMI), antibiotics or non-steroidal anti-inflammatory drugs (NSAIDs) use, hypothesis testing using either stool or rectal swab gave broadly significantly correlated results, but inference performed on mucosal tissue samples gave results that were generally less consistent with either stool or swab. Our study represents an important resource for determination of how inference can change for taxa and pathways depending on the choice of where to sample within the human gut.
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http://dx.doi.org/10.1038/s41598-021-94205-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295290PMC
July 2021

Identification of electronic descriptors for catalytic activity of transition-metal and non-metal doped MoS.

Phys Chem Chem Phys 2021 Jul;23(28):15101-15106

Department of Physics & Shenzhen Institute for Quantum Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China. and Guangdong Provincial Key Laboratory of Computational Science and Material Design, Southern University of Science and Technology, Shenzhen, 518055, China and Guangdong-Hong Kong-Macao Joint Laboratory for Photonic-Thermal-Electrical Energy Materials and Devices, Southern University of Science and Technology, Shenzhen 518055, China.

While the d-band theory offers successful electronic descriptors for catalytic activity of transition metals, transition metal compounds still need substantial theoretical input for the identification of reactivity descriptors for fast screening of earth-abundant catalysts. We study transition metal (TM) and non-metal doped MoS2, a promising substitute for noble metals as catalysts for multiple reactions, to clarify how doping modifies the reactivity by regulating the electronic structure of the host. We find that doping can significantly change the density of states (DOS) at band edges and the position of the Fermi level, which renders the S p-band center εp a good descriptor for H adsorption on both TM and non-metal doped MoS2. Dopants to the left of the host elements in the periodic table that have fewer electrons pin the Fermi level into the valence band, and those to the right that have more electrons pin the Fermi level into the conduction band, resulting in separated linear relationships between H binding energy and S p-band center. Moreover, by a close examination of the electronic structure of late TM doped systems, we identify the position of the late TM dopant induced DOS peak near the conduction band minimum (CBM), εTM, as a refined descriptor which shows a linear relationship for H as well as C, N, O adsorption. Finally, we generalize our descriptor to MoSe2 and MoTe2 to include all three anions in transition metal dichalcogenides (TMDs) and show a universal scaling relationship between the H binding energy and anion p-band center. Together we further enhance our understanding on identifying electronic descriptors for TM compounds.
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http://dx.doi.org/10.1039/d1cp01458gDOI Listing
July 2021

Lung abscess secondary to lung cancer with a coinfection of Granulicatellaadiacens and other bacteria: a case report.

BMC Infect Dis 2021 Jul 8;21(1):662. Epub 2021 Jul 8.

The first Clinical College of Xinjiang Medical University, Urumqi city, China.

Background: Granulicatella adiacens is facultative anaerobic Gram-positive bacteria, which mainly involve bacterial endocarditis and bacteremia, but there are few reports of local suppurative infection. A case of lung abscess with a coinfection of Granulicatella adiacens and other bacteria in a lung cancer patient will be reported in this paper. To our knowledge, this is the first case report describing lung abscess due to G.adiacens.

Case Presentation: A 52-year-old Chinese woman was admitted to the hospital, She complained of coughing and expectoration for 1 month, shortness of breath for half a month, and dyspnea for 1 day. After a series of examinations, she was diagnosed with lung abscess, pleural effusion, and bronchogenic carcinoma. Draining pus culture demonstrated Granulicatella adiacens. After more than 5 weeks of antibiotic therapies in total, she gradually recovered to fight against lung cancer.

Conclusion: This is the first reported lung abscess caused by G.adiacens. In immunosuppressed hosts, G.adiacens is a virulent pathogen associated with a spectrum of intrathoracic suppurative. Earlier diagnosis and proper drainage surgery with effective antibiotics treatment are very important, and antimicrobial treatment should be more than 5 weeks. When complex pulmonary infection interferes with the CT diagnosis, clinical suspicion of lung cancer should be increased if G.adiacens or Eikenella corrodens is detected from a pulmonary infection.
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http://dx.doi.org/10.1186/s12879-021-06191-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265077PMC
July 2021

Deficiency of CXXC finger protein 1 leads to small changes in heart rate but moderate epigenetic alterations and significant protein downregulation of hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) ion channels in mice.

Heart Rhythm 2021 Jun 25. Epub 2021 Jun 25.

Department of Pharmacology (The Key Laboratory of Cardiovascular Research, Ministry of Education) at College of Pharmacy, Harbin Medical University, Harbin, China; Key Laboratory of Cell Transplantation, The First Affiliated Hospital, Harbin Medical University, Harbin, China. Electronic address:

Background: The normal cardiac rhythm is generated in the sinoatrial node (SAN). Changes in ionic currents of the SAN may cause sinus arrhythmia. CXXC finger protein 1 (Cfp1) is an epigenetic regulator that is involved in transcriptional regulation of multiple genes.

Objective: The purpose of this study was to explore whether Cfp1 controls SAN function through regulation of ion channel-related genes.

Methods: Electrophysiological study, patch clamp recording, reverse transcriptase polymerase chain reaction, optical mapping, chromatin immunoprecipitation, and immunofluorescence staining were performed to evaluate the function of SAN and underlying mechanism on Cfp1 heterozygous knockout (Cfp1) mice.

Results: Heart rate was slower slightly and SAN recovery time was longer in Cfp1 mice than controls. Whole-cell patch-clamp recording showed that the firing rate of action potentials was reduced in Cfp1 mice. The density of I current was reduced by 66% in SAN cells of Cfp1 mice but the densities of I, I, and I were not changed. The hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) mRNA level in SAN tissue of Cfp1 mice was reduced. The HCN4 protein was significantly decreased in SAN cells and tissues after heterozygous deletion of Cfp1. Chromatin immunoprecipitation assay on cultured HL-1 cells demonstrated that Cfp1 was enriched in the promoter regions of HCN4. Knockdown of Cfp1 reduced H3K4 trimethylation, H3K9 acetylation, and H3K27 acetylation of HCN4 promoter region.

Conclusion: Deficiency of Cfp1 leads to small changes in heart rate by moderate epigenetic modification alterations and significant protein downregulation of HCN4 ion channels in mice.
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http://dx.doi.org/10.1016/j.hrthm.2021.06.1190DOI Listing
June 2021

Thermochromic Polyvinyl Alcohol-Iodine Hydrogels with Safe Threshold Temperature for Infectious Wound Healing.

Adv Healthc Mater 2021 Jun 24:e2100722. Epub 2021 Jun 24.

School of Food and Biological Engineering, Hefei University of Technology, Hefei, 230009, China.

Iodophor (povidone-iodine) has been widely used for antibacterial applications in the clinic. Yet, limited progress in the field of iodine-based bactericides has been achieved since the invention of iodophor. Herein, a blue polyvinyl alcohol-iodine (PAI) complex-based antibacterial hydrogel is explored as a new generation of biocompatible iodine-based bactericides. The obtained PAI hydrogel maintains laser triggered liquefaction, thermochromic, and photothermal features for highly efficient elimination of bacteria. In vitro antibacterial test reveals that the relative bacteria viabilities of Escherichia coli (E.coli) and methicillin-resistant Staphylococcus aureus (MRSA) incubated with PAI hydrogel are only 8% and 3.8%, respectively. Upon single injection of the PAI hydrogel, MRSA-infected open wounds can be efficiently healed in only 5 days, and the healing speed is further accelerated by laser irradiation due to the dynamic interaction between iodine and polyvinyl alcohol, causing up to ∼29% of wound area being closed on day 1. In addition, a safe threshold temperature of skin scald (∼45 °C) emerges for PAI hydrogels because of thermochromic properties, avoiding thermal injuries during irradiation. In addition, no observed toxicity or skin irritation is observed for the PAI hydrogel. This work expands the category of iodine-based bactericides for safe and controllable management of infected wounds.
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http://dx.doi.org/10.1002/adhm.202100722DOI Listing
June 2021

Nature-inspired dimerization as a strategy to modulate neuropeptide pharmacology exemplified with vasopressin and oxytocin.

Chem Sci 2021 Feb 4;12(11):4057-4062. Epub 2021 Feb 4.

Institute for Molecular Bioscience, The University of Queensland Brisbane 4072 Australia

Vasopressin (VP) and oxytocin (OT) are cyclic neuropeptides that regulate fundamental physiological functions four G protein-coupled receptors, VR, VR, VR, and OTR. Ligand development remains challenging for these receptors due to complex structure-activity relationships. Here, we investigated dimerization as a strategy for developing ligands with novel pharmacology. We regioselectively synthesised and systematically studied parallel, antiparallel and N- to C-terminal cyclized homo- and heterodimer constructs of VP, OT and dVDAVP (1-deamino-4-valine-8-d-arginine-VP). All disulfide-linked dimers, except for the head-to-tail cyclized constructs, retained nanomolar potency despite the structural implications of dimerization. Our results support a single chain interaction for receptor activation. Dimer orientation had little impact on activity, except for the dVDAVP homodimers, where an antagonist to agonist switch was observed at the VR. This study provides novel insights into the structural requirements of VP/OT receptor activation and spotlights dimerization as a strategy to modulate pharmacology, a concept also frequently observed in nature.
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http://dx.doi.org/10.1039/d0sc05501hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8179488PMC
February 2021

Landscape of IDH1/2 mutations in Chinese patients with solid tumors: A pan-cancer analysis.

Mol Genet Genomic Med 2021 Aug 18;9(8):e1697. Epub 2021 Jun 18.

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

Background: Isocitrate dehydrogenase (IDH) is an enzyme family involved in cell aerobic metabolism of tricarboxylic acid cycle. However, the landscape of IDH mutations in pan-cancer has not been fully characterized.

Methods: Tissue or blood samples were subjected to next-generation sequencing (NGS) for detection the IDH mutation.

Results: A total of 28.868 patients from more than 20 solid tumor species were analyzed. A total of 374 cases (1.30%) with IDH mutations were identified. Among all the IDH mutations cases, 80 (21.4%) were biliary tract cancer (BTC), 80 (21.4%) were lung cancer, 57 (15.2%) were liver cancer, and 42 (11.2%) were colorectal cancer. The most common IDH variant were IDH1 and IDH2 which were discovered in 0.81% cases and 0.47% cases, respectively. However, there were significant differences in IDH1 and IDH2 mutation frequency among different tumor species (p = 0.0003). Of the patients with IDH1 mutations, about 53.0% of these mutations occur in codons 132. Codons 172 (25.4%) was high-frequency mutation subtypes in IDH2 mutation. TP53, PBRM1, and BAP1 were the most significantly mutated genes in BTC which were different from others cancer. Moreover, TMB were significantly higher in lung cancer, colorectal cancer, and gastric cancer than BTC (p = 0.0164, p < 0.0001, p = 0.0067, respectively) and BTC patients with IDH mutation had lower TMB compared with wild-type IDH.

Conclusion: Somatic IDH mutation was found in multiple solid tumors and IDH would be a driver gene in BTC.
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http://dx.doi.org/10.1002/mgg3.1697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404228PMC
August 2021

Magnesium treatment on methylation changes of transmembrane serine protease 2 (TMPRSS2).

Nutrition 2021 09 7;89:111340. Epub 2021 May 7.

Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Electronic address:

Objectives: The viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike protein priming. This study aims to test the hypothesis that magnesium (Mg) treatment leads to DNA methylation changes in TMPRSS2.

Methods: This study is nested within the Personalized Prevention of Colorectal Cancer Trial, a double-blind 2 × 2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center.

Results: We found that 12 wk of personalized Mg treatment significantly increased 5-methylcytosine methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to the placebo arm (decreased by 0.1%) in those ages < 65 y. The difference remained statistically significant after adjusting for age, sex, and baseline methylation as well as correction for false discovery rate (adjusted P = 0.014). Additionally, Mg treatment significantly reduced 5-hydroxymethylcytosine levels at cg26337277 (close proximity to TSS200 and the 5' untranslated region, promoter) by 2.3% compared to an increase of 7.1% in the placebo arm after adjusting for covariates in those ages < 65 y (P = 0.003). The effect remained significant at a false discovery rate of 0.10 (adjusted P = 0.088).

Conclusions: Among individuals ages < 65 y with calcium-to-magnesium intake ratios equal to or over 2.6, reducing the ratio to around 2.3 increased 5-methylcytosine modifications (i.e., cg16371860) and reduced 5-hydroxymethylcytosine modifications (i.e., cg26337277) in the TMPRSS2 gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention in the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the TMPRSS2 genotype.
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http://dx.doi.org/10.1016/j.nut.2021.111340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8102075PMC
September 2021

Early Prediction Model of Gestational Hypertension by Multi-Biomarkers Before 20 Weeks Gestation.

Diabetes Metab Syndr Obes 2021 31;14:2441-2451. Epub 2021 May 31.

Department of Laboratory, Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangzhou, 510623, People's Republic of China.

Background: Gestational hypertension (GH), a hypertensive disorder of pregnancy (HDP), is a leading cause of maternal and fetal mortality due to the lack of clarity on its exact etiology and clinically feasible prediction models. This study was performed to discover novel biomarkers before 20 weeks gestation and thereby construct an early GH prediction model.

Methods: This study was designed based on differentially expressed protein screening followed by clinical validation. In the screening phase, a nested case-controlled study was conducted by plasma proteomic analyses using label-free LC-MS/MS and plasma samples from seven pre-GH cases before 20-week gestation and seven age- and gestational week-matched controls. In the validation phase, 10 proteins with differential expression in the screening phase were validated by ELISA or electrochemiluminescence in an independent study consisting of 29 pre-GH cases before 20-week gestation and 29 matched controls.

Results: In the screening phase, 149 proteins were found to be differentially expressed between the two groups and were predominantly involved in complement and coagulation cascades, platelet degranulation and positive regulation of cell motility. Further validation showed that serpin family C member 1 (SERPINC1), serpin family A member 5 (SERPINA5), complement factor H-related protein 5 (CFHR5), clusterin, cytokeratin 18 (CK18) and histidine-rich glycoprotein (HRG) levels were significantly higher in women who later developed GH compared to women with uncomplicated pregnancies (<0.05). Binary logistic regression analysis was used to determine the combination efficacy of models for early prediction of GH. The model with a combination of SERPINC1, CK18 and HRG had a significantly better discriminatory power (AUC = 0.91, 95% CI 0.83-0.98) compared to the models with those proteins alone as independent predictors of GH.

Conclusion: Plasma levels of SERPINC1, SERPINA5, CFHR5, clusterin, CK18 and HRG are potential novel predictive biomarkers of GH, and a prediction model using a combination of SERPINC1, CK18 and HRG has good discriminatory performance for GH before 20 weeks gestation.
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http://dx.doi.org/10.2147/DMSO.S309725DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8178612PMC
May 2021

Triangular boron carbon nitrides: an unexplored family of chromophores with unique properties for photocatalysis and optoelectronics.

Phys Chem Chem Phys 2021 Jun;23(23):12968-12975

Department of Chemistry, Technical University of Munich, 85747 Garching, Germany.

It has recently been shown that cycl[3.3.3]azine and heptazine (1,3,4,6,7,9,9b-heptaazaphenalene) as well as related azaphenalenes exhibit inverted singlet and triplet states, that is, the energy of the lowest singlet excited state (S1) is below the energy of the lowest triplet excited state (T1). This feature is unique among all known aromatic chromophores and is of outstanding relevance for applications in photocatalysis and organic optoelectronics. Heptazine is the building block of the polymeric material graphitic carbon nitride which is an extensively explored photocatalyst in hydrogen evolution photocatalysis. Derivatives of heptazine have also been identified as efficient emitters in organic light emitting diodes (OLEDs). In both areas, the inverted singlet-triplet gap of heptazine is a highly beneficial feature. In photocatalysis, the absence of a long-lived triplet state eliminates the activation of atmospheric oxygen, which is favourable for long-term operational stability. In optoelectronics, singlet-triplet inversion implies the possibility of 100% fluorescence efficiency of electron-hole recombination. However, the absorption and luminescence wavelengths of heptazine and the S1-S0 transition dipole moment are difficult to tune for optimal functionality. In this work, we employed high-level ab initio electronic structure theory to devise and characterize a large family of novel heteroaromatic chromophores, the triangular boron carbon nitrides. These novel heterocycles inherit essential spectroscopic features from heptazine, in particular the inverted singlet-triplet gap, while their absorption and luminescence spectra and transition dipole moments are widely tuneable. For applications in photocatalysis, the wavelength of the absorption maximum can be tuned to improve the overlap with the solar spectrum at the surface of earth. For applications in OLEDs, the colour of emission can be adjusted and the fluorescence yield can be enhanced.
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http://dx.doi.org/10.1039/d1cp02026aDOI Listing
June 2021

NF-YCs modulate histone variant H2A.Z deposition to regulate photomorphogenic growth in Arabidopsis.

J Integr Plant Biol 2021 Jun 3;63(6):1120-1132. Epub 2021 Jun 3.

Key Laboratory of South China Agricultural Plant Molecular Analysis and Genetic Improvement & Guangdong Provincial Key Laboratory of Applied Botany, South China Botanical Garden, The Chinese Academy of Sciences, Guangzhou, 510650, China.

In plants, light signals trigger a photomorphogenic program involving transcriptome changes, epigenetic regulation, and inhibited hypocotyl elongation. The evolutionarily conserved histone variant H2A.Z, which functions in transcriptional regulation, is deposited in chromatin by the SWI2/SNF2-RELATED 1 complex (SWR1c). However, the role of H2A.Z in photomorphogenesis and its deposition mechanism remain unclear. Here, we show that in Arabidopsis thaliana, H2A.Z deposition at its target loci is induced by light irradiation via NUCLEAR FACTOR-Y, subunit C (NF-YC) proteins, thereby inhibiting photomorphogenic growth. NF-YCs physically interact with ACTIN-RELATED PROTEIN6 (ARP6), a key component of the SWR1c that is essential for depositing H2A.Z, in a light-dependent manner. NF-YCs and ARP6 function together as negative regulators of hypocotyl growth by depositing H2A.Z at their target genes during photomorphogenesis. Our findings reveal an important role for the histone variant H2A.Z in photomorphogenic growth and provide insights into a novel transcription regulatory node that mediates H2A.Z deposition to control plant growth in response to changing light conditions.
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http://dx.doi.org/10.1111/jipb.13109DOI Listing
June 2021

Comprehensive description of the current breast cancer microenvironment advancements via single-cell analysis.

J Exp Clin Cancer Res 2021 Apr 27;40(1):142. Epub 2021 Apr 27.

Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Breast cancer is a heterogeneous disease with a complex microenvironment consisting of tumor cells, immune cells, fibroblasts and vascular cells. These cancer-associated cells shape the tumor microenvironment (TME) and influence the progression of breast cancer and the therapeutic responses in patients. The exact composition of the intra-tumoral cells is mixed as the highly heterogeneous and dynamic nature of the TME. Recent advances in single-cell technologies such as single-cell DNA sequencing (scDNA-seq), single-cell RNA sequencing (scRNA-seq) and mass cytometry have provided new insights into the phenotypic and functional diversity of tumor-infiltrating cells in breast cancer. In this review, we have outlined the recent progress in single-cell characterization of breast tumor ecosystems, and summarized the phenotypic diversity of intra-tumoral cells and their potential prognostic relevance.
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http://dx.doi.org/10.1186/s13046-021-01949-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077685PMC
April 2021

An Emerging Energy Storage System: Advanced Na-Se Batteries.

ACS Nano 2021 Apr 31;15(4):5876-5903. Epub 2021 Mar 31.

Institute for Superconducting and Electronic Materials, Australian Institute for Innovative Materials, University of Wollongong, North Wollongong 2500, Australia.

Sodium-selenium (Na-Se) batteries have aroused enormous attention due to the large abundance of the element sodium as well as the high electronic conductivity and volumetric capacity of selenium. In this battery system, some primary advances in electrode materials have been achieved, mainly involving the design of Se-based cathode materials. In this Review, the electrochemical mechanism is discussed, thus revealing the main challenges in Na-Se batteries. Then, the advances in the design of Se-based cathode materials for Na-ion storage are systemically summarized, classified, and discussed, including Se/carbon composite, Se/polar material/carbon composites, and hybrid SeS alloys. Some potential strategies enabling the improvement of crucial challenges and enhancement of electrochemical performance are also proposed to provide guidelines for the enhancements of Na-ion storage. An outlook for future valuable research directions is proposed to understand more deeply the electrochemical mechanism of Na-Se batteries and promote their further developments in full cell performance and commercialization.
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http://dx.doi.org/10.1021/acsnano.0c10078DOI Listing
April 2021

Structural Evolution and Underlying Mechanism of Single-Atom Centers on MoC(100) Support during Oxygen Reduction Reaction.

ACS Appl Mater Interfaces 2021 Apr 31;13(14):17075-17084. Epub 2021 Mar 31.

Department of Physics, Southern University of Science and Technology, Shenzhen 518055, China.

The single-metal atoms coordinating with the surface atoms of the support constitute the active centers of as-prepared single-atom catalysts (SACs). However, under hash electrochemical conditions, (1) supports' surfaces may experience structural change, which turn to be distinct from those at ambient conditions; (2) during catalysis, the dynamic responses of a single atom to the attack of reaction intermediates likely change the coordination environment of a single atom. These factors could alter the performance of SACs. Herein, we investigate these issues using MoC(100)-supported single transition-metal (TM) atoms as model SACs toward catalyzing the oxygen reduction reaction (ORR). It is found that the MoC(100) surface is oxidized under ORR turnover conditions, resulting in significantly weakened bonding between single TM atoms and the MoC(100) surface ([email protected](100)_O* term for SAC). While the intermediate in 2 e ORR does not change the local structures of the active centers in these SACs, the O* intermediate emerging in 4 e ORR can damage [email protected] and [email protected](100)_O*. Furthermore, on the basis of these findings, we propose [email protected](100)_O* as a qualified ORR catalyst, which exhibits extraordinary 4 e ORR activity with an overpotential of only 0.33 V, surpassing the state-of-the-art Pt(111), and thus being identified as a promising alternative to the commercial Pt/C catalyst.
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http://dx.doi.org/10.1021/acsami.1c01477DOI Listing
April 2021

Magnesium Treatment on Methylation Changes of Transmembrane Serine Protease 2 (TMPRSS2).

medRxiv 2021 Mar 12. Epub 2021 Mar 12.

Background: The viral entry of SARS-CoV-2 requires host-expressed TMPRSS2 to facilitate the viral spike (S) protein priming.

Objectives: To test the hypothesis that Mg treatment leads to DNA methylation changes in .

Methods: This study is nested within the Personalized Prevention of Colorectal Cancer Trial (PPCCT), a double-blind 2×2 factorial randomized controlled trial, which enrolled 250 participants from Vanderbilt University Medical Center. Target doses for both Mg and placebo arms were personalized.

Results: We found that 12-week of personalized Mg treatment significantly increased 5-mC methylation at cg16371860 (TSS1500, promoter) by 7.2% compared to placebo arm (decreased by 0.1%) in those aged < 65 years old. The difference remained statistically significant after adjusting for age, sex and baseline methylation as well as FDR correction (FDR-adjusted =0.014). Additionally, Mg treatment significantly reduced 5-hmC level at cg26337277 (close proximity to TSS200 and 5'UTR, promoter) by 2.3% compared to increases by 7.1% in the placebo arm after adjusting for covariates in those aged < 65 years old ( =0.003). The effect remained significant at FDR of 0.10 (adjusted value=0.088).

Conclusion: Among individuals aged younger than 65 years with the Ca:Mg intake ratios equal to or over 2.6, reducing Ca:Mg ratios to around 2.3 increased 5-mC modifications (i.e. cg16371860) and reduced 5-hmC modifications (i.e. cg26337277) in the gene. These findings, if confirmed, provide another mechanism for the role of Mg intervention for the prevention of COVID-19 and treatment of early and mild disease by modifying the phenotype of the genotype.
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http://dx.doi.org/10.1101/2021.03.11.21253287DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987044PMC
March 2021

Ab Initio Surface-Hopping Simulation of Femtosecond Transient-Absorption Pump-Probe Signals of Nonadiabatic Excited-State Dynamics Using the Doorway-Window Representation.

J Chem Theory Comput 2021 Apr 23;17(4):2394-2408. Epub 2021 Mar 23.

Department of Chemistry, Technical University of Munich, D-85747 Garching, Germany.

An ab initio theoretical framework for the simulation of femtosecond time-resolved transient absorption (TA) pump-probe (PP) spectra with quasi-classical trajectories is presented. The simulations are based on the classical approximation to the doorway-window (DW) representation of third-order four-wave-mixing signals. The DW formula accounts for the finite duration and spectral shape of the pump and probe pulses. In the classical DW formalism, classical trajectories are stochastically sampled from a positive definite doorway distribution, and the signals are evaluated by averaging over a positive definite window distribution. Nonadiabatic excited-state dynamics is described by a stochastic surface-hopping algorithm. The method has been implemented for the pyrazine molecule with the second-order algebraic-diagrammatic construction (ADC(2)) ab initio electronic-structure method. The methodology is illustrated by ab initio simulations of the ground-state bleach, stimulated emission, and excited-state absorption contributions to the TA PP spectrum of gas-phase pyrazine.
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http://dx.doi.org/10.1021/acs.jctc.1c00109DOI Listing
April 2021

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis.

Bone Res 2021 Mar 22;9(1):21. Epub 2021 Mar 22.

Department of Orthopedics, Chinese PLA General Hospital, Beijing, China.

Angiogenesis and osteogenesis are coupled. However, the cellular and molecular regulation of these processes remains to be further investigated. Both tissues have recently been recognized as endocrine organs, which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues. This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature. In addition, research progress related to the bone vasculature, vessel-related skeletal diseases, pathological conditions, and angiogenesis-targeted therapeutic strategies are also summarized. With respect to future perspectives, new techniques such as single-cell sequencing, which can be used to show the cellular diversity and plasticity of both tissues, are facilitating progress in this field. Moreover, extracellular vesicle-mediated nuclear acid communication deserves further investigation. In conclusion, a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.
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http://dx.doi.org/10.1038/s41413-021-00138-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7985324PMC
March 2021
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