Publications by authors named "Ping Hu"

828 Publications

Site-Selective C-C Cleavage of Benzocyclobutenones Enabled by a Blocking Strategy Using Nickel Catalysis.

Angew Chem Int Ed Engl 2021 Jun 29. Epub 2021 Jun 29.

Department of Chemistry, Fudan University, Shanghai, 200433, China.

Controlling the chemo- and regioselectivity of transition-metal-catalyzed C-C activation remains a great challenge. The transformations of benzocyclobutenones (BCBs) usually involve the cleavage of C1-C2 bond. In this work, an unprecedented highly selective cleavage of C1-C8 bond with the insertion of alkynes is achieved by using blocking strategy via Ni catalysis, providing an efficient method for synthesis of 1,8-disubstituted naphthalenes. Notably, the blocking group could be readily removed after the transformation.
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http://dx.doi.org/10.1002/anie.202106709DOI Listing
June 2021

Tumor chemical suffocation therapy by dual respiratory inhibitions.

Chem Sci 2021 Apr 28;12(22):7763-7769. Epub 2021 Apr 28.

The State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences 1295 Ding-xi Road Shanghai 200050 P. R. China.

The extraordinarily rapid growth of malignant tumors depends heavily on the glucose metabolism by the pathways of glycolysis and mitochondrial oxidative phosphorylation to generate adenosine 5'-triphosphate (ATP) for maintaining cell proliferation and tumor growth. This study reports a tumor chemical suffocation therapeutic strategy by concurrently suppressing both glycolysis and mitochondrial oxidative phosphorylation (OXPHOS) the co-deliveries of EDTA and rotenone into a glutathione (GSH)-overexpressed tumor microenvironment. EDTA is to block the glycolytic pathway through inhibiting the activity of glycolytic enzymes the chelation of magnesium ion, a co-worker of glycolytic enzymes, despite the presence of Ca. Meanwhile rotenone is to inhibit the mitochondrial OXPHOS. This work provides a novel tumor suffocation strategy by the co-deliveries of glucose metabolism inhibitors, especially by de-functioning glycolytic enzymes eliminating their co-worker magnesium.
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http://dx.doi.org/10.1039/d1sc00929jDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188586PMC
April 2021

Analysis of Biomarkers for Congenital Heart Disease Based on Maternal Amniotic Fluid Metabolomics.

Front Cardiovasc Med 2021 7;8:671191. Epub 2021 Jun 7.

Center of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.

Congenital heart disease (CHD) is the most common birth defect. The prenatal diagnosis of fetal CHD is completely dependent on ultrasound testing, but only ~40% of CHD can be detected. The purpose of this study is to find good biomarkers in amniotic fluid (AF) to detect CHD in the second trimester, so as to better manage this group of people and reduce the harm of CHD to the fetus. Metabolites analysis were performed in two separate sets. The discovery set consisted of 18 CHD fetal maternal AF samples and 35 control samples, and the validation set consisted of 53 CHD fetal maternal AF samples and 114 control samples. Untargeted metabolite profiles were analyzed by gas chromatography/time-of-flight-mass spectrometry (GC-TOF/MS). Orthogonal partial least square discrimination analysis (OPLS-DA) demonstrated that CHD and control samples had significantly different metabolic profiles. Two metabolites, uric acid and proline, were significantly elevated in CHD and verified in two data sets. Uric acid was associated with CHD [odds ratio (OR): 7.69 (95% CI: 1.18-50.13) in the discovery set and 3.24 (95% CI:1.62-6.48) in the validation set]. Additionally, uric acid showed moderate predictive power; the area under curve (AUC) was 0.890 in the discovery set and 0.741 in the validation set. The sensitivity and specificity of uric acid to detect CHD was, respectively, 94.4 and 74.3% in the discovery set and 67.9 and 71.9% in the validation set. The identification of uric acid as a biomarker for CHD has the potential to stimulate research on the pathological mechanism of CHD and the development of a diagnostic test for clinical applications.
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http://dx.doi.org/10.3389/fcvm.2021.671191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215886PMC
June 2021

ID-MAM: A Validated Identity and Multi-Attribute Monitoring Method for Commercial Release and Stability Testing of a Bispecific Antibody.

Anal Chem 2021 07 23;93(26):9166-9173. Epub 2021 Jun 23.

BioTherapeutics Development & Supply-Analytical Development, Janssen Research and Development, LLC, Malvern, Pennsylvania 19355, United States.

Post-translational modifications (PTMs) that impact the safety or efficacy of protein therapeutics are critical quality attributes (CQAs) that need to be controlled to ensure product quality. Peptide mapping with online mass spectrometry (MS) is a powerful tool that has been used for many years to monitor PTM CQAs during product development. However, operating peptide mapping methods with high-resolution mass spectrometers in GMP compliant, commercial quality control (QC) labs can be difficult. Peptide mapping is also required as an identity test in several countries. To address these two different needs, we utilized high-resolution peptide mapping for comprehensive characterization during development and then developed and validated a targeted multi-attribute monitoring (MAM) method using the low-resolution Waters QDa MS system with a fully automated data processing workflow that is suitable for identity (ID) testing, sequence variant control, and CQA quantitation in commercial QC labs. The ID-MAM method was validated for the quantitation of three selected PTM CQAs (CDR isomerization, Fc Met oxidation, and CDR Met oxidation) to ensure control of the oxidation and isomerization degradation pathways of a bispecific antibody (BsAb). This ID-MAM method was successfully validated in six labs (three analytical development and three QC labs) across four countries for commercial release and stability testing of a BsAb. CQA results obtained with the ID-MAM method were similar to results obtained using high-resolution peptide mapping, and the method was robust and reproducible. To our knowledge, this ID-MAM method is the first MS-based peptide mapping method implemented in GMP compliant QC labs for commercial release and stability testing of a biotherapeutic.
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http://dx.doi.org/10.1021/acs.analchem.1c01029DOI Listing
July 2021

Reply to: "Leukocytes, platelets and cardiovascular diseases".

Atherosclerosis 2021 Jul 13;329:52-54. Epub 2021 Jun 13.

Key Laboratory of Environment and Health (HUST), Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. Electronic address:

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http://dx.doi.org/10.1016/j.atherosclerosis.2021.06.007DOI Listing
July 2021

Impact of Scoring First on Match Outcome in the Chinese Football Super League.

Front Psychol 2021 28;12:662708. Epub 2021 May 28.

National School of Development, Peking University, Beijing, China.

The aim of this study was to explore the effect of scoring first on match outcomes in the Chinese Football Super League (CSL). A total of 1,116 matches in which at least one goal was scored from the 2014 to 2018 seasons were collected. Match outcomes, absolute goal differences, the minute of the first goal, match locations, and teams' budgets were analyzed. A team's budget was measured in terms of a team's value at the beginning of the season, and teams were clustered into two groups (high and low budget with means of 50.77 and 13.77 million dollars, respectively). A descriptive analysis was conducted, and two generalized linear models (a multinomial logit model and a Poisson model; < 0.05) were applied. The results showed a favorable outcome for the team that scored first both in match outcome and goal difference. Regarding the teams that scored first, 66.31% won their matches, 20.70% achieved a draw, and 12.99% lost. Specifically, home teams were more likely to win (13.42%) and less likely to lose (9.52%) or draw (3.90%) than away teams. Home teams also had a higher likelihood of obtaining a larger goal difference. Higher budget teams were more likely to win (14.90%) and less likely to lose (9.75%) or draw (5.14%) than low-budget teams. Additionally, for each minute, the team scores closer to the end of the match, and the average probability of winning increased by 0.0028. These findings can guide the strategies of coaches in different match scenarios according to the match location and the opponent's quality.
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http://dx.doi.org/10.3389/fpsyg.2021.662708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194256PMC
May 2021

Endothelial nitric oxide synthase polymorphism and venous thromboembolism: A meta-analysis of 9 studies involving 3993 subjects.

Phlebology 2021 Jun 9:2683555211016626. Epub 2021 Jun 9.

Department of Trauma Surgery, Emergency Medical Cental of Chongqing, The Affiliated Central Hospital of Chongqin University, Chongqing, China.

Background: Endothelial nitric oxide synthase (eNOS) polymorphism may influence the risk of venous thromboembolism (VTE). However, data from published studies with low statistical power are inconclusive. The present meta-analysis aimed to assess the relationship between eNOS polymorphism and the risk of VTE.

Method: Case-control studies evaluating the association between the eNOS polymorphism and VTE were searched in PubMed, Embase, Web of Science, Google Scholar, Wanfang, Chinese National Knowledge Infrastructure (CNKI), the Chongqing VIP Chinese Science and Technology Periodical Database (VIP), and Chinese Biomedical Literature Database (CBM).

Results: A total of 1588 cases and 2405 controls from 9 studies were included in the analysis. The results showed that eNOS G894T polymorphism was related to VTE susceptibility and the difference was statistically significant [T vs G: OR = 1.41, 95% CI (1.13, 1.75),  = 0.002; TT + GG vs TG: OR = 0.71, 95% CI (0.60, 0.84),  = 0.000; TT + TG vs GG: OR = 1.45, 95% CI (1.23, 1.70),  = 0.000]. Additionally, eNOS Intron 4 VNTR polymorphism was related to VTE susceptibility and the difference was statistically significant [4b4b vs 4a4a + 4a4b: OR = 2.77, 95% CI (1.01, 7.61),  = 0.048].

Conclusion: ENOS G894T and eNOS Intron 4 VNTR polymorphisms were associated with VTE susceptibility, especially in Asian populations. However, multicenter studies with larger samples should be conducted to further clarify this association and verify our findings.
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http://dx.doi.org/10.1177/02683555211016626DOI Listing
June 2021

Identification of anti-Parkinson's Disease Lead Compounds from Aspergillus ochraceus Targeting Adenosin Receptors A.

ChemistryOpen 2021 Jun;10(6):630-638

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, China.

Two novel alkaloids compounds together with fifteen know metabolites were identified from Aspergillus ochraceus. The stereochemistry features of the new molecules were determined via HRESIMS, NMR, ECD, and XRD analyses. Amongst these, compounds two compounds exhibited potential efficacy as anti-Parkinson's disease with the EC values of 2.30 and 2.45 μM, respectively. ADMET prediction showed that these compounds owned favorable drug-like characteristics and safe toxicity scores towards CNS drugs. Virtual screening analyses manifested that the compounds exhibited not only robust and reliable interactions to adenosine receptors A , but also higher binding selectivity to A receptors than to A and A receptors. Molecular dynamics simulation demonstrated the reliability of molecular docking results and the stability of the complexes obtained with the novel compounds and A receptors in natural environments. It is the first time that anti-PD lead compounds have been identified from Aspergillus ochraceus and targeting adenosine A receptors.
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http://dx.doi.org/10.1002/open.202100022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186885PMC
June 2021

Relating self-other overlap to ingroup bias in emotional mimicry.

Soc Neurosci 2021 Jun 13:1-9. Epub 2021 Jun 13.

Department of Psychology, Renmin University of China, Beijing, P.R. China.

Humans tend to show congruent facial expressions automatically in reaction to their partners which is defined as emotional mimicry. Although occurring unconsciously, this tendency has been proven to be modulated by social contextual factors such as group membership. Ingroup bias in emotional mimicryhas been well-documented in previous research; however, few studies have investigated the underlying mechanism. Based on the mimicry-as-social-regulator model, this study explored whether the ingroup bias in emotional mimicry arises from the greater self-ingroup overlap. By recording participants' facial electromyographic responses while passively viewing dynamic emotional clips performed by either racial ingroup or outgroup actors, Study 1 validated the presence of ingroup bias in the mimicry of happiness, but not anger. Using asimilar procedure in Study 2, anew sample was employed ( = 37), and a measurement of self-other overlaps via the Inclusion of the Other in the Self Scale was added. The results of Study 2 reproduced the ingroup bias in happy mimicry, and further demonstrated that the effect of group membership on emotional mimicry was mediated by the self-other overlap. In summary, this study provides evidence that the level of interpersonal closeness predicts emotional mimicry.
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http://dx.doi.org/10.1080/17470919.2021.1940273DOI Listing
June 2021

Associations of serum apolipoprotein A1, B levels and their ratio with blood pressure in Chinese adults with coronary artery disease.

Blood Press Monit 2021 Jun 1. Epub 2021 Jun 1.

Scientific Education Section and Department of Child Healthcare, Affiliated Maternity & Child Health Care Hospital of Nantong University, Nantong Department of Geriatric Medicine, Qingdao Municipal Hospital, Qingdao Department of Finance section, Affiliated Traditional Chinese Medicine Hospital of Nantong University, Nantong Image Center, Wuhan Asia Heart Hospital, Wuhan Department of Pharmacy, Nantong Health College of Jiangsu Province, Nantong Department of Health care, Linyi People's Hospital, Linyi, China.

Objective: We examined the relationships of apolipoprotein A1 (ApoA1), ApoB levels and ApoB/A1 ratio with blood pressure (BP) in Chinese adults with coronary artery disease (CAD).

Methods: This cross-sectional study included 4921 adults with CAD. SBP, DBP, serum ApoA1 and ApoB levels were measured. The associations between Apo and BP were assessed by analyses of covariance.

Results: Serum ApoA1 was inversely associated with BP, whereas ApoB and the ApoB/A1 ratio exhibited positive associations with BP. For all subjects, a higher ApoA1 level was associated with lower SBP. Subjects in the fourth quartile for ApoA1 exhibited - 2.85 and - 2.63% lower DBP and mean arterial pressure (MAP), respectively than those in the third quartile. In contrast, higher ApoB and ApoB/A1 ratios were associated with higher SBP, DBP and MAP. The mean differences between ApoB quartiles 4 and 1 were 1.54% for SBP, 2.92% for DBP and 2.29% for MAP. The mean differences between the ApoB/A1 ratio quartiles 4 and 1 were 1.94% for SBP, 3.53% for DBP and 2.80% for MAP. In analyses stratified by gender, graded and inverse associations of ApoA1 with SBP, DBP and MAP were observed in both men and women, but positive associations were observed for ApoB and the ApoB/A1 ratio. Path analysis showed that BMI mediated the associations between ApoB and the ApoB/A1 ratio and SBP.

Conclusions: In general, serum ApoA1 was inversely associated with BP in persons with CAD. In contrast, serum ApoB and the ApoB/A1 ratio were positively associated with BP, and these associations were mediated by BMI.
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http://dx.doi.org/10.1097/MBP.0000000000000549DOI Listing
June 2021

A Ricin B-like lectin protein physically interacts with TaPFT and is involved in resistance to Fusarium head blight in wheat.

Phytopathology 2021 May 31. Epub 2021 May 31.

College of Life Science and Technology, Henan Engineering Research Center of Crop Genome Editing, Henan Institute of Science and Technology, Xinxiang, China;

Fusarium head blight (FHB), mainly caused by , has become one of the most serious diseases that damage wheat. The () and () genes at the quantitative trait locus (QTL) were identified to confer resistance to FHB in the wheat cultivar Sumai 3. Here, a wheat ricin B-like lectin gene (designated ) that interacted with TaPFT was isolated by a yeast two-hybrid screen of a wheat cDNA library. A yeast two-hybrid and bimolecular fluorescence complementation study further verified that TaRBL interacted with TaPFT but not with TaHRC. Gene expression studies showed upon infection, expression was upregulated in resistant cultivars but downregulated in susceptible cultivars. Furthermore, knockdown of TaRBL expression by barley stripe mosaic virus-induced gene silencing significantly reduced the resistance of wheat to FHB in both the resistant cultivar Sumai 3 and the susceptible cultivar Jimai 22. Thus, we conclude that encodes a Ricin B-like lectin protein that interacts with TaPFT and is involved in resistance to FHB in wheat.
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http://dx.doi.org/10.1094/PHYTO-11-20-0506-RDOI Listing
May 2021

Muscle regeneration controlled by a designated DNA dioxygenase.

Cell Death Dis 2021 May 25;12(6):535. Epub 2021 May 25.

Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 20023, China.

Tet dioxygenases are responsible for the active DNA demethylation. The functions of Tet proteins in muscle regeneration have not been well characterized. Here we find that Tet2, but not Tet1 and Tet3, is specifically required for muscle regeneration in vivo. Loss of Tet2 leads to severe muscle regeneration defects. Further analysis indicates that Tet2 regulates myoblast differentiation and fusion. Tet2 activates transcription of the key differentiation modulator Myogenin (MyoG) by actively demethylating its enhancer region. Re-expressing of MyoG in Tet2 KO myoblasts rescues the differentiation and fusion defects. Further mechanistic analysis reveals that Tet2 enhances MyoD binding by demethylating the flanking CpG sites of E boxes to facilitate the recruitment of active histone modifications and increase chromatin accessibility and activate its transcription. These findings shed new lights on DNA methylation and pioneer transcription factor activity regulation.
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http://dx.doi.org/10.1038/s41419-021-03817-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149877PMC
May 2021

Decellularized Extracellular Matrix (ECM) as a Model to Study Fibrotic ECM Mechanobiology.

Methods Mol Biol 2021 ;2299:237-261

Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA.

Aberrant deposition of the extracellular matrix (ECM) causes fibrosis and leads to ECM stiffening. This fibrotic ECM provides biological and biophysical stimulations to alter cell activity and drive progression of fibrosis. As an emerging discipline, mechanobiology aims to access the impact of both these cues on cell behavior and relates the reciprocity of mechanical and biological interactions; it incorporates concepts from different fields, like biology and physics, to help study the mechanical and biological facets of fibrosis extensively. A useful experimental platform in mechanobiology is decellularized ECM (dECM), which mimics the native microenvironment more accurately than standard 2D culture techniques as its composition includes similar ECM protein components and stiffness. dECM, therefore, generates more reliable results that better recapitulate in vivo fibrosis.
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http://dx.doi.org/10.1007/978-1-0716-1382-5_18DOI Listing
January 2021

Association of Gut Microbiota during Early Pregnancy with Risk of Incident Gestational Diabetes Mellitus.

J Clin Endocrinol Metab 2021 May 20. Epub 2021 May 20.

Key Laboratory of Environment & Health ( Huazhong University of Science and Technology), Ministry of Education.

Aims: We aimed to assess the association between gut bacterial biomarkers during early pregnancy and subsequent risk of gestational diabetes mellitus (GDM) in Chinese pregnant women.

Methods: Within the Tongji-Shuangliu Birth Cohort study, we conducted a nested case-control study among 201 incident GDM cases and 201 matched controls. Fecal samples were collected during early pregnancy (at 6-15 weeks), and GDM was diagnosed at 24-28 weeks of pregnancy. Community DNA isolated from fecal samples and V3-V4 region of 16S rRNA gene amplicon libraries were sequenced.

Results: In GDM cases versus controls, Rothia, Actinomyces, Bifidobacterium, Adlercreutzia, and Coriobacteriaceae, and Lachnospiraceae spp. were significantly reduced, while Enterobacteriaceae, Ruminococcaceae spp. and Veillonellaceae were over-represented. In addition, the abundance of Staphylococcus relative to Clostridium, Roseburia and Coriobacteriaceae as reference microorganisms were positively correlated with fasting blood glucose, 1-h and 2-h postprandial glucose levels. Adding microbial taxa to the base GDM prediction model with conventional risk factors increased the C-statistic significantly (P<0.001) from 0.69 to 0.75.

Conclusions: Gut microbiota during early pregnancy was associated with subsequent risk of GDM. Several beneficial and commensal gut microorganisms showed inverse relations with incident GDM, while opportunistic pathogenic members were related to higher risk of incident GDM and positively correlated with glucose levels on OGTT.
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http://dx.doi.org/10.1210/clinem/dgab346DOI Listing
May 2021

Two factors affecting the success rate of the second non-invasive prenatal screening after initial no-call result: experience from a single tertiary center in China.

Chin Med J (Engl) 2021 May 13;134(12):1416-1421. Epub 2021 May 13.

Department of Prenatal Diagnosis, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, China.

Background: One inevitable shortcoming of non-invasive prenatal screening (NIPS)/cell-free DNA (cfDNA) sequencing is the uninterpretable ("no-call") result, which is mainly caused by an insufficient fetal fraction. This study was performed to investigate the factors associated with a successful second NIPS in these cases and determine the optimal management for women with initial no-call results.

Methods: We retrospectively analyzed the data of women who underwent NIPS with initial no-call results due to an insufficient fetal fraction from 2017 to 2019 in our center. We compared these women's maternal and pregnancy information with the data of women who had attained a successful second NIPS result and women who had received no-call results for a second time.

Results: Among the 33,684 women who underwent NIPS, 137 with a no-call result underwent a retest. Comparison between the 87 (63.50%) women with a successful retest and the other 50 (36.50%) women showed a significant difference in both the initial fetal fraction and maternal body mass index (BMI), whereas the other factors showed no significant differences. In addition, with an initial fetal fraction of < 2.00%, the retest success rate was very limited.

Conclusions: We identified two major factors associated with a successful NIPS retest: the initial fetal fraction and the maternal BMI. These findings suggest the need for specialized management for this subset of women and would be instructional for the counseling for these women.
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http://dx.doi.org/10.1097/CM9.0000000000001531DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213247PMC
May 2021

Effect of vitamin D deficiency on spontaneous peritonitis in cirrhosis: a meta-analysis.

Prz Gastroenterol 2021 8;16(1):10-14. Epub 2020 Dec 8.

Department of Gastroenterology, The First People's Hospital of Wenling, Taizhou, China.

Introduction: Few studies have reported the relationship between spontaneous peritonitis in cirrhosis and vitamin D, and the result is not very convincing.

Aim: To conduct a meta-analysis to clarify the relationship between vitamin D and spontaneous peritonitis.

Material And Methods: Articles published up to 1 October 2019 in the PubMed, Medline, and Embase databases were searched. According to the inclusion and exclusion criteria, relevant statistical data were extracted and analysed by STATA.

Results: Six articles met the inclusion criteria. It was demonstrated that the average 25(OH)D level in spontaneous peritonitis patients was 2.36 less than that in control individuals (SMD = -2.36, 95% CI: -3.92, -0.8, = 97.2%, < 0.01). Moreover, it found that spontaneous peritonitis patients were 4.33 times more likely to be vitamin D deficient than controls (OR = 4.33, 95% CI: 1.57, 11.93, = 50.1%, = 0.111). Sensitivity analysis showed that the meta-analysis results were stable and reliable.

Conclusions: Vitamin D may be an importantly protective factor in spontaneous peritonitis.
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http://dx.doi.org/10.5114/pg.2020.101632DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112263PMC
December 2020

Rapid determination of folic acid and riboflavin in urine by polypyrrole magnetic solid-phase extractant combined ultra-performance liquid chromatography.

J Chromatogr A 2021 Jul 27;1648:462192. Epub 2021 Apr 27.

Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, Shanghai 200237, China. Electronic address:

Determination of folic acid and riboflavin in biological samples is difficult due to their high polarity, low concentration, chemical instability, and complex matrix. In this study, the polypyrrole-coated magnetic nanocomposite ([email protected]) was synthesized innovatively with the assistance of hexadecyltrimethylammonium bromide. To evaluate the adsorption mechanism and the feasibility of synthesized [email protected] as an adsorbent, the adsorption capacities, kinetics and thermodynamics of folic acid and riboflavin were investigated systemically. Furthermore, in light of the chemical instability of folic acid and riboflavin a method for rapid extraction and detection of them from human urine within 10 min was developed successfully by combining magnetic solid phase extraction with ultra-performance liquid chromatography (MSPE/UPLC). The adsorption parameters including sorbent amount, pH value, extraction time, desorption solvent and desorption time were studied. Under optimum conditions, the performance of the established determination method was validated with the linearly dependent coefficients (>0.9995), the limits of detection (0.02-0.05 µg/mL), the limits of quantification (0.07-0.18 µg/mL), and the recoveries (92.2-105.1%, with relative standard deviation < 3.3%). The rapid extraction and detection of folic acid and riboflavin from real urine samples were achieved subsequently. The present study suggests that the developed method exhibits a promising application in the analysis of free folic acid and riboflavin in human urine samples, which can provide a reference for the clinical drug monitoring and treatment.
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http://dx.doi.org/10.1016/j.chroma.2021.462192DOI Listing
July 2021

Remote Regioselective Radical C-H Functionalization of Unactivated C-H Bonds in Amides: The Synthesis of -Difluoroalkenes.

Org Lett 2021 Jun 13;23(11):4457-4462. Epub 2021 May 13.

College of Chemistry and Materials Science, Sichuan Normal University, Chengdu 610068, China.

The site-selective functionalization of unactivated aliphatic amines is an attractive and challenging synthetic approach. We herein report a general strategy for the remote site-selective functionalization of unactivated C(sp)-H bonds in amides by photogenerated amidyl radicals to form -difluoroalkenes with trifluoromethyl-substituted alkenes. The site selectivity is controlled by a 1,5-hydrogen atom transfer (HAT) process of the amide. This photocatalyzed transformation shows both chemo- and site-selectivity, facilitating the formation of a secondary, tertiary, or quaternary carbon center.
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http://dx.doi.org/10.1021/acs.orglett.1c01385DOI Listing
June 2021

Discovery of myricetin as an inhibitor against Streptococcus mutans and an anti-adhesion approach to biofilm formation.

Int J Med Microbiol 2021 May 5;311(4):151512. Epub 2021 May 5.

Center of Stomatology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, No. 1095, Jiefang Road, Wuhan, Hubei, People's Republic of China; School of Stomatology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China. Electronic address:

Streptococcus mutans (S. mutans) are cariogenic microorganisms. Sortase A (SrtA) is a transpeptidase that attaches Pac to the cell surface. The biofilm formation of S. mutans is promoted by SrtA regulated Pac. Myricetin (Myr) has a variety of pharmacological properties, including inhibiting SrtA activity of Staphylococcus aureus. The purpose of this research was to investigate the inhibitory effect of Myr on SrtA of S. mutans and its subsequent influence on the biofilm formation. Here, Myr was discovered as a potent inhibitor of S. mutans SrtA, with an IC of 48.66 ± 1.48 μM, which was lower than the minimum inhibitory concentration (MIC) of 512 ug/mL. Additionally, immunoblot and biofilm assays demonstrated that Myr at a sub-MIC level could reduce adhesion and biofilm formation of S. mutans. The reduction of biofilm was possibly caused by the decreased amount of Pac on the cells' surface by releasing Pac into the medium via inhibiting SrtA activity. Molecular dynamics simulations and mutagenesis assays suggested that Met123, Ile191, and Arg213 of SrtA were pivotal for the interaction of SrtA and Myr. Our findings indicate that Myr is a promising candidate for the control of dental caries by modulating Pac-involved adhesive mechanisms without developing drug resistance to S.mutans.
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http://dx.doi.org/10.1016/j.ijmm.2021.151512DOI Listing
May 2021

Combined Analysis of RNA Sequence and Microarray Data Reveals a Competing Endogenous RNA Network as Novel Prognostic Markers in Malignant Pleural Mesothelioma.

Front Oncol 2021 23;11:615234. Epub 2021 Apr 23.

Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Malignant pleural mesothelioma (MPM) is a highly aggressive cancer with short survival time. Unbalanced competing endogenous RNAs (ceRNAs) have been shown to participate in the tumor pathogenesis and served as biomarkers for the clinical prognosis. However, the comprehensive analyses of the ceRNA network in the prognosis of MPM are still rarely reported. In this study, we obtained the transcriptome data of the MPM and the normal samples from TCGA, EGA, and GEO databases and identified the differentially expressed (DE) mRNAs, lncRNAs, and miRNAs. The functions of the prognostic genes and the overlapped DEmRNAs were further annotated by the multiple enrichment analyses. Then, the targeting relationships among lncRNA-miRNA and miRNA-mRNA were predicted and calculated, and a prognostic ceRNA regulatory network was established. We included the prognostic 73 mRNAs and 13 miRNAs and 26 lncRNAs into the ceRNA network. Moreover, 33 mRNAs, three miRNAs, and seven lncRNAs were finally associated with prognosis, and a model including seven mRNAs, two lincRNAs, and some clinical factors was finally established and validated by two independent cohorts, where CDK6 and SGMS1-AS1 were significant to be independent prognostic factors. In addition, the identified co-expressed modules associated with the prognosis were overrepresented in the ceRNA network. Multiple enrichment analyses showed the important roles of the extracellular matrix components and cell division dysfunction in the invasion of MPM potentially. In summary, the prognostic ceRNA network of MPM was established and analyzed for the first time and these findings shed light on the function of ceRNAs and revealed the potential prognostic and therapeutic biomarkers of MPM.
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http://dx.doi.org/10.3389/fonc.2021.615234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104912PMC
April 2021

Mild Magnetic Hyperthermia-Activated Innate Immunity for Liver Cancer Therapy.

J Am Chem Soc 2021 Jun 30;143(21):8116-8128. Epub 2021 Apr 30.

State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, PR China.

Magnetic hyperthermia therapy (MHT) is noninvasive and features excellent tissue penetration for deep-seated tumors, but unfortunately, it suffers the low therapeutic efficacy due to the limited magneto-thermal efficiency and insufficient intratumor accumulation of conventional intravenous-injected magnetic nanoparticles, which are actually mostly sequestered by the mononuclear phagocyte system, especially the liver. Such a disadvantageous characteristic of preferential liver uptake is here exploited, for the first time as far as we know, to treat orthotopic liver cancer by mild MHT using specially designed composite magnetic nanoparticles. A kind of core-shell-structured and Zn-doped [email protected] superparamagnetic nanoparticles (ZCMF) has been synthesized which exhibits excellent and highly controllable magnetic hyperthermia performance owing to an exchange-coupled magnetism between the core and shell, and Zn doping. The controllable mild MHT at 43-44 °C based on ZCMF demonstrates almost complete inhibition of liver cancer cell proliferation and tumor growth, which is associated with the suppression of heat shock protein 70 (HSP70) expression. More importantly, the mild MHT-treated liver cancer cells are capable of activating natural killer (NK) cells by dramatically upregulating the expression of UL16-binding proteins (ULBPs), ligands of natural killer group 2 member D (NKG2D). As a result, the growth of both xenograft tumors and orthotopic liver tumors were almost completely suppressed under mild MHT via induced NK-cell-related antitumor immunity . This work not only evidences the great potential of mild MHT but also reveals the underlying immunity activation mechanism in liver cancer treatment by mild MHT.
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http://dx.doi.org/10.1021/jacs.1c02537DOI Listing
June 2021

A Ferroptosis-Related Signature Robustly Predicts Clinical Outcomes and Associates With Immune Microenvironment for Thyroid Cancer.

Front Med (Lausanne) 2021 13;8:637743. Epub 2021 Apr 13.

Department of Endocrinology, Linyi Central Hospital, Linyi, China.

This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment. Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR. A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score ( = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis ( = 0.015, HR: 1.870, 95%CI: 1.132-3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues. Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.
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http://dx.doi.org/10.3389/fmed.2021.637743DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076739PMC
April 2021

Isolation, Identification and Function of AR and Its Effects on the Growth and Health of Weaned Pigs.

Animals (Basel) 2021 Apr 20;11(4). Epub 2021 Apr 20.

Fermentation Engineering Department, Hunan Institute of Microbiology, Changsha 410009, China.

This study isolates and identifies () AR, and studies its effect on the growth and health of weaned pigs. A strain from solid wine koji is isolated and identified using 26S rDNA analysis, and its culture conditions are optimized. Heat tolerance, bile salt tolerance, artificial gastric, and intestinal juice tolerance are evaluated. In our methodology, thirty 28 d Large White × Landrace × Rongchang weaned pigs were randomly divided into three groups with 10 barrows in each, and fed a maize-soybean meal diet and orally administered 0.85% saline (CK), 1 mL 1 × 10 cfu/mL (), and 1 mL 1 × 10 cfu/mL once daily for 28 days. A strain was identified and named AR. AR grew best in yeast extract peptone dextrose medium with pH 5.0 at 28 °C, 180 r/min and could tolerate 45 °C for 0.5 h, 0.2% pig bile salts, simulated gastric fluid, and 1.0% simulated intestinal fluid. Our results show that compared with the CK group, orally administered AR increases average daily gain, the ileal villus height, the ileal mucosal concentrations of occludin and zonula occluens-1, the serum glucose and total protein concentration, total superoxide dismutase, glutathione peroxidase, and total antioxidative capacity activity, the trypsin and lipase activity in jejunal and ileal contents, the jejunal and ileal mucosa mRNA levels of ALP, TNF-α, and TLR-2, and the relative abundance of Bacteroidetes, Actinobacteria, Succinivibrionaceae, Lachnospiraceae, and Prevotellaceae ( < 0.05). Compared with the CK group, oral administration of AR decreased the incidence of diarrhea, aspartate aminotransferase activity, alanine amino-transferase-activity, malondialdehyde, D-lactic acid and endotoxin content in serum, the mRNA level of aminopeptidase N of ileum mucosa, and the relative abundance of Proteobacteria, Clostridiaceae, Campylobacteraceae, Vibrionaceae, , and Pseudon ( < 0.05). Collectively, the study indicates that AR can tolerate high acidity and high bile salts, and has high survivability in the artificial gastric intestinal juice environment. Oral administration of AR improves the growth performance, reduces the incidence of diarrhea, enhances intestinal barrier function, and improves microflora in weaned pigs.
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http://dx.doi.org/10.3390/ani11041179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074749PMC
April 2021

Metabolomic profiling reveals the effects of early-life lactoferrin intervention on protein synthesis, energy production and antioxidative capacity in the liver of suckling piglets.

Food Funct 2021 Apr 22;12(8):3405-3419. Epub 2021 Mar 22.

National Center for International Research on Animal Gut Nutrition, Jiangsu Key Laboratory of Gastrointestinal Nutrition and Animal Health, Laboratory of Gastrointestinal Microbiology, National Experimental Teaching Demonstration Center of Animal Science, College of Animal Science and Technology, Nanjing Agricultural University, Jiangsu Province 210095, P. R. China.

This study aimed to determine the effects of an early-life lactoferrin (LF) intervention on liver metabolism in suckling piglets. Sixty newborn piglets with an average initial body weight (BW) of 1.51 ± 0.05 kg were assigned to a control (CON) group and an LF group. At age 1 to 7 days, the piglets in the LF group were orally administered LF solution (0.5 g per kg BW daily), whereas the piglets in the CON group were orally administered the same dose of physiological saline. Plasma, jejunum and liver samples were collected on days 8 and 21. The LF piglets showed a decreased plasma urea nitrogen level on day 8 and an increased plasma albumin level on day 21. Pathway analysis of the metabolomic profiles showed that the LF treatment affected amino acid metabolism in the liver. In addition, the LF treatment upregulated the gene expression levels of proteolytic enzymes and amino acid transporters (APA, APN, EAAC1, Pept1, CAT1, B0AT1 and ASCT2) in the jejunum, and it enhanced the phosphorylation levels of mTOR and p70S6K in the liver. The LF treatment also upregulated the expression of a β-oxidation-related gene (CPT1) and affected the tricarboxylic acid cycle in the liver on day 21. Furthermore, the LF piglets showed a decreased level of malondialdehyde and increased levels of GSH, GSH-Px and GCLC in the liver mitochondria. Overall, the early-life LF intervention affected the protein synthesis, energy production and antioxidative capacity in the liver of the neonatal piglets.
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http://dx.doi.org/10.1039/d0fo01747gDOI Listing
April 2021

Propionic Acid-Based PET Imaging of Prostate Cancer.

Mol Imaging Biol 2021 Apr 19. Epub 2021 Apr 19.

Department of Nuclear Medicine and Medical Imaging, Guangdong Engineering Research Center for Translational Application of Medical Radiopharmaceuticals, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.

Purpose: This study aimed to evaluate the potential value of 2-[F]fluoropropionic acid ([F]FPA) for PET imaging of prostate cancer (PCa) and to explore the relationship between [F]FPA accumulation and fatty acid synthase (FASN) levels in PCa models. The results of the first [F]FPA PET study of a PCa patient are reported.

Procedures: The LNCaP, PC-3 cell lines with high FASN expression, and DU145 cell lines with low FASN expression were selected for cell culture. A PET imaging comparison of [F]FDG and [F]FPA was performed in LNCaP, PC-3, and DU145 tumors. Additionally, in vivo inhibition experiments in those models were conducted with orlistat. In a human PET study, a patient with PCa before surgery was examined with [F]FPA PET and [F]FDG PET.

Results: The uptake of [F]FPA in the LNCaP and PC-3 tumors was higher than that of [F]FDG (P<0.05 and P<0.05), but was lower in DU145 tumors (P<0.05). The accumulation (% ID/g) of [F]FPA in the LNCaP, PC-3, and DU145 tumors decreased by 27.6, 40.5, and 11.7 %, respectively, after treatment with orlistat. The [F]FPA showed higher radioactive uptake than [F]FDG in the first PCa patient.

Conclusions: The [F]FPA uptake in PCa models may be varies with fatty acid synthase activity and could be reduced after administration of a single FASN inhibitor, albeit the activity that is not measured directly. The [F]FPA seems to be a potential broad-spectrum PET imaging agent and may serve as a valuable tool in the diagnosis of PCa in humans.
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http://dx.doi.org/10.1007/s11307-021-01608-xDOI Listing
April 2021

Factor structure and construct validity of the short form of managing the emotions of others (MEOS-SF) scale in the Chinese sample.

PLoS One 2021 15;16(4):e0249774. Epub 2021 Apr 15.

The Department of Psychology, Renmin University of China, Beijing, China.

Objectives: Emotional manipulation is an important strategy in social interaction. The English version of MEOS-SF has been developed to make the measurement of such manipulation ability more efficient. The purpose of the current study was to assess the psychometric properties of the Chinese version of MEOS-SF.

Methods: Explore factor analysis and Confirmatory factor analysis were adopted to examine the Chinese version of the MEOS-SF factor structure in 645 Chinese participants (mean age = 24.68 ± 6.01 years) recruited online.

Results: Factor analysis supported a new three-factor model that included Conceal, Prosocial, and Non-prosocial, different from the original English MEOS-SF. Enhance and Divert merged to Prosocial factor while Worsen and Inauthentic merged to Non-prosocial factor because both prosocial and non-prosocial pairs had similar objectives, which would be perceived as the same thing by people in Eastern culture. As expected, MEOS-SF factors were found to be correlated with the Big Five, psychopathy, narcissism, Machiavellianism, and trait EI.

Conclusions: Our results suggested that the Chinese version of MEOS-SF had acceptable psychometric properties and could be used to assess emotional manipulation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249774PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049282PMC
April 2021

Letter to the Editor: Non-selective bilateral internal iliac artery embolization is a safe and effective way in hemorrhage control for hemodynamically unstable pelvic fractures.

Authors:
Hui Li Ping Hu

BMC Musculoskelet Disord 2021 Apr 14;22(1):355. Epub 2021 Apr 14.

Department of Traumatology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, 1 Jiankang Road, 400014, Yuzhong District, Chongqing, China.

A recently published article by Lai et al. in BMC Musculoskeletal Disorders trying to show that patients with pelvic fractures undergoing non-selective internal iliac artery embolization may lead to a higher rate of surgical site infection. The authors also noted that only a small percentage of patients with contrast extravasation detected by emergency contrast-enhanced CT were subsequently confirmed by angiography, thus, considered that the value of enhanced CT in predicting arterial injury was limited. The authors also believe that embolization of the main stem may cause incomplete hemostasis due to the abundant collateral circulations in the pelvic cavity. Although the author's findings are mentioned in other studies, the article's data and pictures only partially supported its inferences, and the conclusions cannot be drawn directly. In this Correspondence, we tried to reinterpret the additional findings in the article from our perspective. Through this discussion, we hope that more colleagues can re-understand the safety and effectiveness of non-selective internal iliac artery embolization in treating hemodynamically unstable pelvic fractures during the early resuscitation stage.
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http://dx.doi.org/10.1186/s12891-021-04212-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048307PMC
April 2021

Overexpression of miR-365a-3p relieves sepsis-induced acute myocardial injury by targeting MyD88/NF-κB pathway.

Can J Physiol Pharmacol 2021 Apr 14. Epub 2021 Apr 14.

Eastern District of the Hospital Jining No.1 People's Hospital, Neonatal Ward, No. 6 Health Road, Jining City, Shandong Province 272000,China., Jining, Shandong, China, 272000;

Background: Sepsis often leads to systemic multiple organ dysfunction, with the majority of deaths attributable to acute myocardial injury (AMI). In this study, we aimed to explore the functional role of miR-365a-3p in sepsis induced AMI.

Materials And Methods: The sepsis myocardial injury model was constructed using lipopolysaccharide (LPS) both in vitro and in vivo with selective regulation of miR-365a-3p expression. RT-PCR or western blot was employed to detect the expressions of miR-365a-3p, inflammatory cytokines (TNF-α, IL6, IL-1β), and inflammation-related proteins (NF-κB, I-κB, MyD88) in myocardial tissues and cells. Also, cell counting kit-8 (CCK8) and flow cytometry assays were used measuring cardiomyocyte proliferation and apoptosis, respectively. Furthermore, the targeting relationship between miR-365a-3p and MyD88 was verified with the dual luciferase activity assay.

Results: MiR-365a-3p was down-regulated in LPS-induced myocardial injury model. MiR-365a-3p overexpression attenuated cardiomyocyte apoptosis, and suppressed the expressions of inflammatory cytokines and proteins. Inhibiting miR-365a-3p, however, produced the opposite effects. Mechanistically, miR-365a-3p targeted the 3'-untranslated region (3'UTR) of MyD88, thereby inactivating MyD88 mediated NF-κB pathway.

Conclusion: MiR-365a-3p overexpression mitigated sepsis-mediated myocardial injury by inhibiting MyD88-mediated NF-κB activation.
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http://dx.doi.org/10.1139/cjpp-2020-0646DOI Listing
April 2021
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