Publications by authors named "Peng Zhou"

1,311 Publications

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Clinical features and development of Sepsis in Klebsiella pneumoniae infected liver abscess patients: a retrospective analysis of 135 cases.

BMC Infect Dis 2021 Jun 23;21(1):597. Epub 2021 Jun 23.

Department of Pharmacy, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University, No. 150, Ximen Road of Linhai, Taizhou, 317000, Zhejiang Province, China.

Background: Klebsiella pneumoniae is a primary pathogen of pyogenic liver abscess (PLA). However, little data are available on combination with sepsis. In this study, we aimed to evaluate the clinical characteristics and prognostic differences of PLA patients with sepsis.

Methods: This retrospective cohort study was conducted to investigate 135 patients with confirmed Klebsiella pneumoniae-caused liver abscesses (KPLA) from a tertiary teaching hospital, from 2013 to 2019. The patients were divided into two groups, KPLA with sepsis and KPLA without sepsis. The demographic characteristics, clinical features as well as laboratory and microbiologic findings were analyzed.

Results: A total of 135 patients with KPLA were analyzed. The mean age of patients was 60.9 ± 12.7 years, and the percentage of men was 59.3%. Among them, 37/135 (27.4%) of patients had sepsis and the mortality rate was 1.5%. The most common symptom was fever (91.1%). KPLA patients with sepsis had a significantly higher proportion of frailty, diarrhea, fatty liver, chronic renal insufficiency, and hepatic dysfunction compared to KPLA patients without sepsis (p < 0.05). Antibiotic therapy and percutaneous drainage were most frequently therapeutic strategy. Furthermore, the incidences of sepsis shock and acute respiratory distress syndrome were higher in the sepsis group compared to the non-sepsis group. As for metastatic infections, the lung was the most common site. In addition, KPLA patients with sepsis showed respiratory symptoms in 11 patients, endophthalmitis in 4 patients, and meningitis in 1 patient.

Conclusion: Our findings emphasize that KPLA patients combined with or without sepsis have different clinical features, but KPLA patients with sepsis have higher rates of complications and metastatic infections. Taken together, further surveillance and control of septic spread is essential for KPLA patients.
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http://dx.doi.org/10.1186/s12879-021-06325-yDOI Listing
June 2021

Design and Methodology of a Multicenter Randomized Clinical Trial to Evaluate the Efficacy of Tongmai Jiangtang Capsules in Type 2 Diabetic Coronary Heart Disease Patients.

Front Pharmacol 2021 3;12:625785. Epub 2021 Jun 3.

School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China.

Population-based studies have consistently showed an increased incidence of coronary heart disease and cardiac mortality in patients with type 2 diabetes mellitus (T2DM). Tongmai Jiangtang capsules (TJC) are Chinese patent medicines that have been approved in China for the treatment of diabetic vascular complications. However, the evidence supporting the efficacy of Tongmai Jiangtang capsules in type 2 diabetic coronary heart disease (T2DM-CHD) remains unclear. Herein, we designed a randomized, parallel-controlled clinical trial to investigate a new complementary therapy for T2DM-CHD patients. A total of 360 T2DM-CHD subjects (aged 18-75 years) will be randomly assigned to the TJC group or the placebo group at a 2:1 ratio. On the basis of western medicine therapy, all the participants will receive TJC or placebo, orally, three capsules/treatment, three per day for 12 weeks. The primary outcomes will be assessed according to the Canadian Cardiovascular Society (CCS) classification. All statistical analyses will be performed setting a two-sided 0.05 significance level, using SAS 9.4 statistical software. The efficacy of TJC for the treatment of T2DM-CHD patients will be evaluated. The study will provide reliable clinical research evidence for application of TJC in treating T2DM-CHD patients. https://www.chictr.org.cn/enIndex.aspx, Chinese Clinical Trial Registry ChiCTR2000037491.
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http://dx.doi.org/10.3389/fphar.2021.625785DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209367PMC
June 2021

Synthetic Route to Enaminones via Metal-Free Four-Component Sequential Reactions of Aryl Olefins with CHCl, EtN, and TBHP.

J Org Chem 2021 Jun 14. Epub 2021 Jun 14.

College of Chemistry, Guangdong University of Petrochemical Technology, Guandu Road, Maoming 525000, P. R. China.

An efficient and modular strategy was used to obtain enaminones with a wide range of functional groups a four-component sequential reaction. This reaction proceeded under mild conditions without a catalyst in one pot. Furthermore, the products could be transformed into thiadiazoles.
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http://dx.doi.org/10.1021/acs.joc.1c00823DOI Listing
June 2021

An in-memory computing architecture based on two-dimensional semiconductors for multiply-accumulate operations.

Nat Commun 2021 06 7;12(1):3347. Epub 2021 Jun 7.

State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai, China.

In-memory computing may enable multiply-accumulate (MAC) operations, which are the primary calculations used in artificial intelligence (AI). Performing MAC operations with high capacity in a small area with high energy efficiency remains a challenge. In this work, we propose a circuit architecture that integrates monolayer MoS transistors in a two-transistor-one-capacitor (2T-1C) configuration. In this structure, the memory portion is similar to a 1T-1C Dynamic Random Access Memory (DRAM) so that theoretically the cycling endurance and erase/write speed inherit the merits of DRAM. Besides, the ultralow leakage current of the MoS transistor enables the storage of multi-level voltages on the capacitor with a long retention time. The electrical characteristics of a single MoS transistor also allow analog computation by multiplying the drain voltage by the stored voltage on the capacitor. The sum-of-product is then obtained by converging the currents from multiple 2T-1C units. Based on our experiment results, a neural network is ex-situ trained for image recognition with 90.3% accuracy. In the future, such 2T-1C units can potentially be integrated into three-dimensional (3D) circuits with dense logic and memory layers for low power in-situ training of neural networks in hardware.
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http://dx.doi.org/10.1038/s41467-021-23719-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184885PMC
June 2021

Melt-processed poly (vinyl alcohol)/corn starch/nanocellulose composites with improved mechanical properties.

Int J Biol Macromol 2021 Jun 6;183:1903-1910. Epub 2021 Jun 6.

State Key Laboratory of Polymer Materials Engineering, Polymer Research Institute of Sichuan University, Chengdu 610065, China. Electronic address:

Corn starch (CS) and cellulose nanofibrils (CNFs) were incorporated into biodegradable poly (vinyl alcohol) (PVA) to prepare mechanically robust and sustainable composites through melt-processing. Based on the regulation and control of hydrogen bonding network, CS and CNFs can extend the processing window and improve the thermoplasticity of PVA composites. Fourier transform infrared spectroscopy and Raman spectra analysis indicate that the intra- and inter-molecular hydrogen bonds of PVA are broken, accompanied by the formation of new hydrogen bonds among PVA, CS and CNFs during the melt-processing treatment. Thermal analysis shows that the processing window of PVA composite is significantly broadened to 131.46 °C. The tensile strength, modulus and elongation at break of the composites reach to 28.19 MPa, 1572.54 MPa and 10.72% by the incorporation of 10 wt% CS and 10 wt% CNFs. This strategy is not only expected to provide a direction for preparing complex three-dimensional products of PVA by melt-processing, but also provide a method to enhance the mechanical properties of other biodegradable plastics.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.011DOI Listing
June 2021

Identification of Tumor Necrosis Factor-Alpha (TNF-α) Inhibitor in Rheumatoid Arthritis Using Network Pharmacology and Molecular Docking.

Front Pharmacol 2021 21;12:690118. Epub 2021 May 21.

The Fourth Affiliated Hospital, Anhui Medical University, Hefei, China.

This study aimed to investigate the molecular mechanism of Paeoniae Alba (white peony, WP) in treating immune inflammatory diseases of rheumatoid arthritis (RA) and tumor necrosis factor-alpha (TNF-α) inhibitors (TNFis) by using network pharmacology and molecular docking. In this study, the ingredient of WP and the potential inflammatory targets of RA were obtained from the Traditional Chinese Medicine Systematic Pharmacology Database, GeneCard, and OMIM databases, respectively. The establishment of the RA-WP-potential inflammatory target gene interaction network was accomplished using the STRING database. Network maps of the WP-RA-potential inflammatory target gene network were constructed using Cytoscape software. Gene ontology (GO) and the biological pathway (KEGG) enrichment analyses were used to further explore the RA mechanism and therapeutic effects of WP. Molecular docking technology was used to analyze the optimal effective components from WP for docking with TNF-α. Thirteen active ingredients and 71 target genes were screened from WP, and 49 of the target genes intersected with RA target inflammatory genes and were considered potential therapeutic targets. Network pharmacological analysis showed that the WP active ingredients such as mairin, DPHCD, (+)-catechin, beta-sitosterol, paeoniflorin, sitosterol, and kaempferol showed better correlation with RA inflammatory target genes such as PGR, PTGS1, PTGS2, NR3C2, TNFSF15, and CHRM2, respectively. The immune-inflammatory signaling pathways of the active ingredients for the treatment of RA are the TNF-α signaling pathway, Toll-like receptor signaling pathway, cell apoptosis, interleukin-17 signaling pathway, C-type lectin receptor signaling pathway, mitogen-associated protein kinase, . Molecular docking results suggested that mairin was the most appropriate natural TNFis. Our findings provide an essential role and basis for further immune-inflammatory studies into the molecular mechanisms of WP and TNFis development in RA.
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http://dx.doi.org/10.3389/fphar.2021.690118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175775PMC
May 2021

Molecular characterization of pleomorphic liposarcomatous differentiation in malignant phyllodes tumor of the breast: A case report.

Pathol Res Pract 2021 May 24;224:153489. Epub 2021 May 24.

Department of Pathology, The 960th Hospital of PLA, Jinan, 250031, China. Electronic address:

Phyllodes tumors of the breast are rare fibroepithelial tumors, and malignant phyllodes tumors occasionally exhibit heterogeneous differentiation. Here, we report a case of malignant phyllodes tumor with pleomorphic liposarcomatous differentiation, and examined the genomic features of both components using capture-based next-generation sequencing of 425 cancer-related genes. A 56-year-old woman presented with a palpable, asymptomatic nodule in the right breast measuring 4.0 cm × 3.0 cm. Based on the findings from microscopic examination, the lesions were identified as malignant phyllodes tumor and pleomorphic liposarcoma. The liposarcomatous differentiation component was positive for S-100, but had no MDM2 and CDK4 amplifications according to the results of fluorescence in situ hybridization. The malignant phyllodes tumor and liposarcomatous differentiation component had similar genetic mutations, such as TP53, TERT, EGFR, RARA, RB1, and MED12 mutations, all of which are common mutations in phyllodes tumors. These results indicate that the pathogenesis of the pleomorphic liposarcomatous differentiation was similar with that of phyllodes tumor, but was different from the pleomorphic liposarcoma in extramammary sites. Thus, the intratumoral heterogeneity may have independently evolved after tumorigenesis.
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http://dx.doi.org/10.1016/j.prp.2021.153489DOI Listing
May 2021

Ultrafast non-volatile flash memory based on van der Waals heterostructures.

Nat Nanotechnol 2021 Jun 3. Epub 2021 Jun 3.

State Key Laboratory of ASIC and System, School of Microelectronics, Fudan University, Shanghai, China.

Flash memory has become a ubiquitous solid-state memory device widely used in portable digital devices, computers and enterprise applications. The development of the information age has demanded improvements in memory speed and retention performance. Here we demonstrate an ultrafast non-volatile flash memory based on MoS/hBN/multilayer graphene van der Waals heterostructures, which achieves an ultrafast writing/erasing speed of 20 ns through two-triangle-barrier modified Fowler-Nordheim tunnelling. Using detailed theoretical analysis and experimental verification, we postulate that a suitable barrier height, gate coupling ratio and clean interface are the main reasons for the breakthrough writing/erasing speed of our flash memory devices. Because of its non-volatility this ultrafast flash memory could provide the foundation for the next generation of high-speed non-volatile memory.
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http://dx.doi.org/10.1038/s41565-021-00921-4DOI Listing
June 2021

Construction and Characterization of an Multi-Gene Deletion Strain and Evaluation of Its Potential as a Live-Attenuated Vaccine in Grass Carp.

Vaccines (Basel) 2021 May 3;9(5). Epub 2021 May 3.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.

is an important pathogen that causes motile septicemia (MAS) in the aquaculture industry. Aerolysin, hemolysin, serine protease and enterotoxins are considered to be the major virulence factors of . In this study, we constructed a five-gene (A, , , and ) deletion mutant strain (named five-gene deletion strain, AHFGDS) to observe the biological characteristics and detect its potential as a live-attenuated vaccine candidate. AHFGDS displayed highly attenuated and showed increased susceptibility to fish blood and skin mucus killing, while the wild-type strain ZYAH72 was highly virulent. In zebrafish (), AHFGDS showed a 240-fold higher 50% lethal dose (LD50) than that of the wild-type strain. Immunization with AHFGDS by intracelomic injection or immersion routes both provided grass carp () significant protection against the challenge of the strain ZYAH72 or J-1 and protected the fish organs from serious injury. Further agglutinating antibody titer test supported that AHFGDS could elicit a host-adaptive immune response. These results suggested the potential of AHFGDS to serve as a live-attenuated vaccine to control infection in aquaculture.
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http://dx.doi.org/10.3390/vaccines9050451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147641PMC
May 2021

Study on Omentin-1 and miR-502-3p in osteoporotic fracture.

J Musculoskelet Neuronal Interact 2021 Jun;21(2):308-316

Huangdao District Central Hospital, Shandong Province, China.

Objectives: To explore the expression and correlation of Omentin-1 and miR-502-3p in serum of patients with osteoporotic fracture (OPF).

Methods: Sixty OPF patients diagnosed and treated in our hospital from June 2018 to December 2019 were included in group A. Fifty-six osteoporosis patients without fractures were included in group B. Omentin-1 and miR-502-3p levels were detected by enzyme-linked immunosorbent assay (ELISA) and real-time quantitative PCR (qRT-PCR). Their predictive value for diagnostic efficiency was assessed by ROC curve. Spearman's rank correlation test was used for correlation analysis. The risk factors related to the prognosis of OPF were analyzed by Logistic univariate and multivariate analysis.

Results: The expression of Omentin-1 and miR-502-3p in group A was markedly lower than in group B (P<0.001). Spearman correlation analysis showed that in OPF, there was a negative correlation between serum Omentin-1 and TNF-α (r=0.8579, P<0.001), a negative correlation between serum miR-502-3p and TNF-α (r= 0.8653, P<0.001), and a positive correlation between serum Omentin-1 and miR-502-3p (r= 0.8764, P<0.001).

Conclusions: Omentin-1 and miR-502-3p were down-regulated in serum of patients with OPF, both of which could be used as potential biomarkers for the diagnosis and disease evaluation of OPF.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185270PMC
June 2021

Transvesical versus extravesical approach to laparoscopic posthysterectomy vesicovaginal fistula repair: A retrospective study from two medical centers.

Neurourol Urodyn 2021 May 31. Epub 2021 May 31.

Department of Urology, Nanchang University, Nanchang, Jiangxi, China.

Background: The controversy on the best surgical approach for vesicovaginal fistula (VVF) repair remains due to the scarcity of high-level evidences. We aim to analyze the efficacy and safety of the laparoscopic transvesical (LT) and laparoscopic extravesical (LE) approaches to posthysterectomy VVF (PH-VVF).

Methods: Data of 64 patients with PH-VVFs who were laparoscopicly treated in the First Affiliated Hospital of Nanchang University and the Hangzhou Third Hospital from January 2011 to November 2019 were retrospectively collected. The operative time (OT), estimated bleeding volume (EBV), postoperative bladder function and complications, hospital stay length (HSL), surgery success rate, and recurrence were compared between the two groups.

Results: In all, there were no significant differences in baseline characteristics between those two arms. Both approaches were successfully performed without open conversion in either group. The LT group was significantly corrected with a shorter mean OT than the LE group (p < 0.001), regardless of the fistula's position. No significant differences existed in the mean EBV and HSL between the two interventions (p = 0.136 and p = 0.210, respectively). The tendency of postoperative complications and success rates of surgery were also comparable in both groups. The patients in the LT group had similar bladder functions to those in LE group. The recurrence occurred in one patient in each arm during the follow-up periods of 12-36 months.

Conclusions: The LT approach is significantly related to a shorter OT than the LE approach without compromising the safety and success rates in repairing PH-VVF.
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http://dx.doi.org/10.1002/nau.24724DOI Listing
May 2021

Ubiquitin Modification Patterns of Clear Cell Renal Cell Carcinoma and the Ubiquitin Score to Aid Immunotherapy and Targeted Therapy.

Front Cell Dev Biol 2021 13;9:659294. Epub 2021 May 13.

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Ubiquitin modification is the most common protein post-translational modification (PTM) process in organisms, and 1332 ubiquitin regulators have been identified in humans. Ubiquitin regulators, especially E3 ligases and deubiquitinases, are widely involved in immune processes. This study aims to explore the ubiquitin modification features of clear cell renal cell carcinoma (ccRCC) and to elucidate the role of such ubiquitin modifications in shaping anti-tumor immunity and individual benefits from immune checkpoint blockade (ICB). A comprehensive analysis was performed in the TCGA cohort ( = 530) and GEO cohort ( = 682). RNA sequencing data of 758 differentially expressed regulators, which was validated by the proteomics data, was used for k-means unsupervised consensus clustering and three ubiquitin patterns of ccRCC were identified. Then, we focused on the ubiquitin modification and tumor progression signatures, immune infiltration characteristics, and prognostic value. The three patterns with different ubiquitin modification signatures correspond to "immune desert phenotype," "immune resistance phenotype," and "immune-inflammatory phenotype," respectively. To facilitate clinical application, we constructed a ubiquitin score to evaluate individual patients' ubiquitination outcome, and it was demonstrated to be an independent risk factor for overall survival (OS) in multivariate Cox analysis. It was found that the high score group was correlated to higher immune cells infiltrating level and PD-1/PD-L1/CTLA-4 expression. More importantly, we found that the high score group was predicted to be sensitive to anti-PD-1 treatment, while the low-score group showed lower predicted IC50 values in treatment with Pazopanib and Axitinib. In summary, this study elucidated the potential link between ubiquitin modification and immune infiltration landscape of ccRCC for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced ccRCC.
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http://dx.doi.org/10.3389/fcell.2021.659294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158301PMC
May 2021

Low-Power Memristive Logic Device Enabled by Controllable Oxidation of 2D HfSe for In-Memory Computing.

Adv Sci (Weinh) 2021 May 29:e2005038. Epub 2021 May 29.

Wuhan National Laboratory for Optoelectronics, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan, 430074, China.

Memristive logic device is a promising unit for beyond von Neumann computing systems and 2D materials are widely used because of their controllable interfacial properties. Most of these 2D memristive devices, however, are made from semiconducting chalcogenides which fail to gate the off-state current. To this end, a crossbar device using 2D HfSe is fabricated, and then the top layers are oxidized into "high-k" dielectric HfSe O via oxygen plasma treatment, so that the cell resistance can be remarkably increased. This two-terminal Ti/HfSe O /HfSe /Au device exhibits excellent forming-free resistive switching performance with high switching speed (<50 ns), low operation voltage (<3 V), large switching window (10 ), and good data retention. Most importantly, the operation current and the power consumption reach 100 pA and 0.1 fJ to 0.1 pJ, much lower than other HfO based memristors. A functionally complete low-power Boolean logic is experimentally demonstrated using the memristive device, allowing it in the application of energy-efficient in-memory computing.
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http://dx.doi.org/10.1002/advs.202005038DOI Listing
May 2021

Insights into the Electron-Transfer Mechanism of Permanganate Activation by Graphite for Enhanced Oxidation of Sulfamethoxazole.

Environ Sci Technol 2021 May 28. Epub 2021 May 28.

State Key Laboratory of Hydraulics and Mountain River Engineering, College of Architecture and Environment, Sichuan University, Chengdu 610065, China.

Many reagents as electron sacrificers have been recently investigated to induce decomposition of permanganate (KMnO) to produce highly reactive intermediate Mn species toward oxidation of organic contaminants; however, this strategy meanwhile causes low KMnO utilization efficiency. This study surprisingly found that graphite can mediate direct electron transfer from organics (e.g., sulfamethoxazole (SMX)) to KMnO, resulting in high KMnO utilization efficiency, rather than reductive sites of graphite-induced conversion of KMnO to highly reactive intermediate Mn species. The galvanic oxidation process (GOP) and comparative experiments of different organic contaminants prove that the KMnO/graphite system mainly extracts electrons from organic contaminants via a one-electron pathway instead of a two-electron pathway. More importantly, the KMnO/graphite system has superior reusability, graphite can keep a long-lasting reactivity, and the KMnO utilization efficiency elevates significantly after each cycle of graphite. The transformation of SMX in the KMnO/graphite system mainly includes self-coupling, hydroxylation, oxidation, and hydrolytic reaction. The work will improve insights into the electron-transfer mechanism and unveil the advantages of efficient KMnO utilization in the KMnO-based technologies in environmental remediation.
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http://dx.doi.org/10.1021/acs.est.1c00020DOI Listing
May 2021

Unexpected Role of Achiral Glycine in Determining the Suprastructural Handedness of Peptide Nanofibrils.

ACS Nano 2021 Jun 28;15(6):10328-10341. Epub 2021 May 28.

State Key Laboratory of Heavy Oil Processing and School of Materials Science and Engineering, China University of Petroleum (East China), 66 Changjiang West Road, Qingdao 266580, China.

Helical supramolecular architectures play important structural and functional roles in biological systems. Although their occurrence is widely perceived to correlate to fundamental chiral units including l-amino acids and d-sugars, the detailed relationship between molecular and supramolecular handedness is still unclear. At the same time, although achiral units are practically always in close proximity to chiral ones by covalent linkage along a polymeric chain, their effect on supramolecular handedness has received relatively less attention. Here, we designed a set of short amphiphilic peptides, in which an achiral glycine residue was incorporated at the interface between the hydrophobic and hydrophilic segments. We observed that glycine incorporation caused dramatic variations in suprastructural handedness in self-assembled peptide nanofibrils, and the effect of the hydrophilic charged residue at the C-terminus on supramolecular handedness was demolished, leading to chiral truncation. Furthermore, molecular dynamics simulations and quantum chemistry calculations revealed that the unanticipated role of the glycine residue in regulating supramolecular handedness originated from its effect on the conformational preference of single β-strands. Importantly, reduced density gradient analyses on single β-strands indicated that, due to the lack of a side chain in glycine, intricate noncovalent interactions were produced among the neighboring amino acid side chains of the incorporated glycine and its local backbone, resulting in diverse β-strand conformations.
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http://dx.doi.org/10.1021/acsnano.1c02547DOI Listing
June 2021

Huang-Pu-Tong-Qiao Formula Ameliorates Tau Phosphorylation by Inhibiting the CaM-CaMKIV Pathway.

Evid Based Complement Alternat Med 2020 11;2020:8956071. Epub 2020 May 11.

School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei 230012, Anhui, China.

Alzheimer's disease (AD) is a complex neurodegenerative disease. It is a chronic, lethal disease in which brain function is severely impaired and neuronal damage is irreversible. Huang-Pu-Tong-Qiao (HPTQ), a formula from traditional Chinese medicine, has been used in the clinical treatment of AD for many years, with remarkable effects. However, the neuroprotective mechanisms of HPTQ in AD have not yet been investigated. In the present study, we used AD models and , to investigate both the neuroprotective effect of HPTQ water extracts (HPTQ-W) and the potential mechanisms of this action. For the study, after HPTQ intervention, the Morris water maze test was used to examine learning and memory in rats. Transmission electron microscopy and immunofluorescence methods were then used to investigate neuronal damage. For the experiments, rat primary hippocampal neurons were cultured and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. Additionally, mRNA levels of CaM, CaMKK, CaMKIV, and tau were examined using qRT-PCR, and protein expression of CaM, CaMKK, p-CaMKIV, and p-tau were examined using western blot. , we revealed that HPTQ significantly improved learning and memory deficits and attenuated neuronal damage in the AD rat model. Furthermore, results showed that HPTQ significantly increased cell viability in the AD cell model. We also demonstrated that HPTQ significantly decreased the mRNA levels of CaM, CaMKK, CaMKIV, and tau and significantly decreased the protein expressions of CaM, CaMKK, p-CaMKIV, and p-tau. In conclusion, our results indicated that HPTQ improved cognition and ameliorated neuronal damage in AD models and implicated a reduction in tau phosphorylation caused by inhibition of the CaM-CaMKIV pathway as a possible mechanism.
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http://dx.doi.org/10.1155/2020/8956071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8128057PMC
May 2020

Rat plasma protein binding of kaempferol-3-O-rutinoside from Lu'an GuaPian tea and its anti-inflammatory mechanism for cardiovascular protection.

J Food Biochem 2021 May 26:e13749. Epub 2021 May 26.

Natural Products Laboratory, State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, Hefei, China.

Previous study found a high content of kaempferol-3-O-rutinoside (KR) in Lu'an GuaPian tea, however, the rat plasma protein binding and mechanism of KR for cardiovascular protection are unclear. Thus, we studied plasma protein binding using ultrafiltration followed by UPLC, and screened its inhibition against LPS-induced inflammation injury in vitro as well as the underlying mechanism by molecular docking and western blot. KR showed over 74% plasma protein binding ratio. Furthermore, KR may act on the toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). In vitro experiments showed that KR decreases the overexpression of TLR4, MyD88, and nuclear factor-κB (NF-κB), which further validates the molecular docking results, suggesting that KR could block TLR4/MyD88/NF-κB signaling. These results indicate that KR could be a potential active agent in the protection of myocardial injury. PRACTICAL APPLICATIONS: Health benefits of tea are largely dependent on the intake of flavonoids. Flavonoids are a group of compounds beneficial to cardiovascular disease and an important part of "functional foods." Lu'an GuaPian tea is mainly produced in Lu'an City, Anhui Province and is one of the top 10 famous teas in China. Kaempferol-3-O-rutinoside in Lu'an GuaPian has good hypoglycemic effect, mainly manifested in a strong inhibition of α-glucosidase and α-amylase activities. Present study showed that kaempferol-3-O-rutinoside could block TLR4/MyD88/NF-κB signaling, suggesting that it could be a potential active agent in the protection of myocardial injury.
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http://dx.doi.org/10.1111/jfbc.13749DOI Listing
May 2021

Astragaloside IV prevents acute myocardial infarction by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

J Food Biochem 2021 May 25:e13757. Epub 2021 May 25.

School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, P.R. China.

Although astragaloside IV protects from acute myocardial infarction (AMI)-induced chronic heart failure (CHF), the underlying mechanism of action is unclear. We determined the potential therapeutic effect of astragaloside IV using molecular docking approaches and validated the findings by the ligation of the left anterior descending (LAD) coronary artery-induced AMI rat model. The interaction between astragaloside IV and myeloid differentiation factor 88 (MyD88) was evaluated by SwissDock. To explore the mechanisms underlying the beneficial effects of astragaloside IV in the LAD coronary artery ligation-induced AMI model, we administered the rats with astragaloside IV for 4 weeks. Hemodynamic indexes were used to evaluate the degree of myocardial injury in model rats. The histopathological changes in myocardium were detected by hematoxylin & eosin (H&E) staining and Masson's staining. Myocardium homogenate contents of collagen I and collagen III were evaluated by ELISA. The level of myocardial hydroxyproline (HYP) was determined by alkaline hydrolysis. Immunohistochemistry was used to examine collagen I. Western blotting was used to examine relevant proteins. As per the molecular docking study results, astragaloside IV may act on MyD88. Furthermore, astragaloside IV improved hemodynamic disorders, alleviated pathological changes, and reduced abnormal collagen deposition and myocardial HYP in vivo. Astragaloside IV significantly reduced the overexpression of TLR4, MyD88, NF-Κb, and TGF-β, which further validated the molecular docking findings. Hence, astragaloside IV ameliorates AMI by reducing inflammation and blocking TLR4/MyD88/NF-κB signaling. These results indicate that astragaloside IV may alleviate AMI. PRACTICAL APPLICATIONS: Astragaloside IV, a small active substance extracted from Astragalus membranaceus, has demonstrated potent protective effects against cardiovascular ischemia/reperfusion, diabetic nephropathy, and other diseases. Molecular docking experiments showed that astragaloside IV might act on the myeloid differentiation factor 88 (MyD88). Astragaloside IV can effectively reduce the overexpression of TLR4, MyD88, and NF-κB p65, indicating that astragaloside IV inhibits inflammation via TLR4/MyD88/NF-κB signaling pathway. These results indicate that astragaloside IV may alleviate acute myocardial infarction.
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http://dx.doi.org/10.1111/jfbc.13757DOI Listing
May 2021

Oxygen functionalized g-CN strengthen Fe(III)/HO system by accelerating Fe(III)/Fe(II) cycles under natural solar light: A mutual-promoting configuration.

Sci Total Environ 2021 Jul 8;778:146280. Epub 2021 Mar 8.

College of Architecture and Environment, Sichuan University, Chengdu, Sichuan 610065, PR China. Electronic address:

In response to the inherent restriction of low Fe(II) regeneration in the Fenton process, this study demonstrated a mutual-promoting configuration, where oxygen functionalized g-CN (OCN) was applied in Fe(III)/HO system to utilize mild natural solar light (SL) for persistent Fe(II) generation. The constructed OCN/Fe(III)/HO/SL system exhibited strong adaptability to various pollutants, and it well outperformed the g-CN (GCN) modified system and the traditional Fenton system in pollutants degradation efficiency. Compared with GCN, OCN could significantly promote the Fe(II) generation under solar light (SL), leading to more efficient HO activation. The characterization analyses revealed the larger surface area and enhanced charge separation of OCN, which were considered to take main responsibility for its enhanced photoactivity. The complexation of Fe(III) with the carboxyl groups of OCN also benefited the Fe(II) generation. ·OH was detected as the dominant radical responsible for metronidazole (MNZ) degradation, and its production in the OCN modified system was about twice that in the GCN modified system and the Fenton system. Moreover, the precipitation of FeO on the OCN surface benefited the charge separation of the OCN, so that the improved OCN enabled a slight enhancement of MNZ degradation in the reuse experiments. The intermediates of MNZ degradation were analyzed based on the results of LC-MS, which provided insight into MNZ degradation pathways. This work highlighted the concept of self-improving photocatalyst, the ingenious combination of photocatalysis and Fenton-like system formed a mutual-promoting situation where the OCN and the Fenton-like system could both be improved, which endowed the configuration great potential for green and economical oxidation in environmental remediation.
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http://dx.doi.org/10.1016/j.scitotenv.2021.146280DOI Listing
July 2021

Impact of Postprocedural High-Sensitivity C-Reactive Protein on Lipoprotein(a)-Associated Cardiovascular Risk with ST-Segment Elevation Myocardial Infarction With Percutaneous Coronary Intervention.

Am J Cardiol 2021 Jul 15;150:8-14. Epub 2021 May 15.

Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China; Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

This study aimed to investigate the impact of high-sensitivity C-reactive protein (hsCRP) on Lipoprotein(a) [Lp(a)] associated cardiovascular risk in patients with ST-segment elevation myocardial infarction (STEMI) underwent percutaneous coronary intervention (PCI). A total of 2318 STEMI-PCI patients were retrospectively recruited, and further stratified based on postprocedural hsCRP levels (≥ 2 vs < 2 mg/L). Major adverse cardiac events (MACE) were defined as all-cause death, myocardial infarction and stroke. During a mean follow-up of 2.5 years, MACE occurred in 159 (6.9%) patients. In the setting of hsCRP ≥ 2mg/L, per unit increase of Lp(a) was associated with a 28% increase of MACE risk (HR: 1.28, 95% CI: 1.09 to 1.49, p = 0.002; p = 0.031 for interaction); increasing tertiles of Lp(a) were significantly related to greater rates of MACE (p = 0.011 for interaction; p = 0.005 for trend across tertiles). Patients with upper tertile of Lp(a) had a significant lower event-free survival (p = 0.034) when hsCRP ≥ 2mg/L. No similar association between Lp(a) and MACE was noted when hsCRP < 2mg/L. In conclusion, high Lp(a) levels were associated with poor prognosis when hsCRP ≥ 2mg/L, implying systemic inflammation can modulate Lp(a)-associated MACE risk in STEMI-PCI patients. Measurement of Lp(a) in patients with high inflammation risk may identify individuals at high cardiovascular risk.
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http://dx.doi.org/10.1016/j.amjcard.2021.03.038DOI Listing
July 2021

Primitive neuroectodermal tumor of the cervix diagnosed during pregnancy: a rare case report with discussion.

BMC Pregnancy Childbirth 2021 May 18;21(1):382. Epub 2021 May 18.

Department of Gynaecology and Obstetrics, The First College of Clinical Medical Science, Three Gorges University, YiChang, 443000, China.

Background: Primitive neuroectodermal tumor (PNET) is a relatively rare malignant small round cell tumor, and the occurrence of cervical PNET during pregnancy is extremely rare.

Case Presentation: A case of pregnancy complicated by PNET at our hospital was reported. A 19-year-old pregnant woman presented to the hospital due to multiple instances of vaginal bleeding during the first and second trimesters. She was initially considered for threatened abortion but was ultimately diagnosed with cervical PNET. No standard treatment plan has been developed for pregnant women with this tumor. After completing the necessary examinations, doctors cooperated with the patient and her family to develop a surgical treatment plan. The patient recovered well after surgery, but she refused radiotherapy and chemotherapy. After nearly 3 years of follow-up visits, the patient is alive with no signs of recurrence.

Conclusions: PNET during pregnancy is a rare but complex condition. It is necessary to devise an individualized treatment plan according to gestational age. Timely surgical treatment can significantly prolong the survival time of patients but may also lead to fetal loss and the inability to carry a pregnancy.
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http://dx.doi.org/10.1186/s12884-021-03859-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132392PMC
May 2021

The clinical significance of spondin 2 eccentric expression in peripheral blood mononuclear cells in bronchial asthma.

J Clin Lab Anal 2021 Jun 16;35(6):e23764. Epub 2021 May 16.

Department of Respiratory, Hangzhou Children's Hospital, Hangzhou, China.

Background: Bronchial asthma (BA) was a heterogeneous disease characterized by chronic airway inflammation. Spondin 2 (SPON2) was reported to be implicated in the integrin pathway, protein metabolism, and drug-induced lupus erythematosus. The purpose of this study was to evaluate the significance of SPON2 in BA diagnosis and treatment.

Methods: Peripheral blood samples were obtained from 137 BA pediatric patients (61 mild-to-moderate BA and 76 severe BA) and 59 healthy children. Subject's information, clinical indexes, pulmonary ventilation functions were recorded in the two groups. Peripheral blood mononuclear cells (PBMCs) were isolated from patients' samples. qRT-PCR and ELISA assays were employed to examine the levels of SPON2 and inflammatory cytokines, respectively. Pearson's correlation analysis confirmed the association between SPON2 and inflammatory cytokines. Receiver operating characteristic (ROC) analysis was used to evaluate the potentials of SPON2 in terms of BA detection and discriminating against the severity of BA.

Results: Bioinformatics analysis showed that SPON2, OLFM4, XIST, and TSIX were significantly upregulated, while KDM5D and RPS4Y1 were reduced in BA. GO analysis verified that these six genes were mainly involved in neutrophil degranulation, neutrophil activation involved in immune response, neutrophil activation, and neutrophil-mediated immunity. After isolating PBMCs, we found that SPON2 was remarkably increased in BA pediatric group compared with healthy children, and the relative levels of SPON2 were related to the severity of BA. The receiver operating characteristic (ROC) analysis revealed the high potentials of SPON2 in BA diagnosis (AUC was 0.8080) and severity distinctions (AUCs were 0.7341 and 0.8541, respectively). Also, we found that there were significant differences in fractional exhaled nitric oxide (FeNO), forced expiratory volume in 1 s (FEV1)%, FEV1/ forced vital capacity (FVC)%, immunoglobulin E (IgE), serum eosinophils, and serum neutrophils between mild-to-moderate BA group and severe BA group. Finally, SPON2 was negatively correlated with IL-12 while positively associated with IL-4, IL-13, and IL-17A.

Conclusions: SPON2 was a viable biomarker for diagnosing and degree of severity in BA, providing more insight into exploring BA and treatment's pathogenesis.
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http://dx.doi.org/10.1002/jcla.23764DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183911PMC
June 2021

Phosphatidylserine-exposing tumor-derived microparticles exacerbate coagulation and cancer cell transendothelial migration in triple-negative breast cancer.

Theranostics 2021 19;11(13):6445-6460. Epub 2021 Apr 19.

Department of Ultrasound, The First Hospital, Harbin Medical University, Harbin, China.

Neoadjuvant chemotherapy is relevant to the formation of thromboembolism and secondary neoplasms in triple-negative breast cancer (TNBC). Chemotherapy-induced breast cancer cell-derived microparticles (BCMPs) may have important thrombogenic and pro-metastatic effects on platelets and endothelium, which may be related to the expression and distribution of phosphatidylserine (PS). However, investigating these interactions is challenging due to technical limitations. A study was conducted in 20 healthy individuals and 18 patients who had been recently diagnosed with TNBC and were undergoing neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. BCMPs were isolated from patient blood samples and doxorubicin-treated breast cancer cell lines. Their structure and morphology were studied by electron microscopy and antigen levels were measured by fluorescence-activated cell sorting. In an inhibition assay, isolated BCMPs were pretreated with lactadherin or tissue factor antibodies. Platelets isolated from healthy subjects were treated with BCMPs and coagulation time, fibrin formation, and expression of intrinsic/extrinsic factor Xase (FXa) and thrombin were evaluated. The effects of BCMPs on endothelial thrombogenicity and integrity were assessed by confocal microscopy, electron microscopy, measurement of intrinsic/extrinsic FXa, prothrombinase assay, and transwell permeability assay. Neoadjuvant chemotherapy significantly increased the expression of PS+ BCMPs in patient plasma. Its expression was associated with a rapid increase in procoagulant activity. Treatment with lactadherin, a PS-binding scavenging molecule, markedly reduced the adhesion of BCMPs and abolished their procoagulant activity, but this was not observed with tissue factor antibody treatment. Intravenous injection of BCMPs in mice induced a significant hypercoagulable state, reducing the extent of plasma fibrinogen and promoting the appearance of new thrombus. Cancer cells incubated with doxorubicin released large numbers of PS+ BCMPs, which stimulated and transformed endothelial cells into a procoagulant phenotype and increased the aggregation and activation of platelets. Moreover, cancer cells exploited this BCMP-induced endothelial leakiness and showed promoted metastasis. Pretreatment with lactadherin increased uptake of both PS+ BCMPs and cancer cells by endothelial cells and limited the transendothelial migration of cancer cells. Lactadherin, a biosensor that we developed, was used to study the extracellular vesicle distribution of PS, which revealed a novel PS+ BCMPs administrative axis that initiated a local coagulation cascade and facilitated metastatic colonization of circulating cancer cells.
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http://dx.doi.org/10.7150/thno.53637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120203PMC
April 2021

Linking melem with conjugated Schiff-base bonds to boost photocatalytic efficiency of carbon nitride for overall water splitting.

Nanoscale 2021 May;13(20):9315-9321

Department of Chemistry, Brown University, Providence, Rhode Island 02912, USA.

Developing an efficient single component photocatalyst for overall water splitting under visible-light irradiation is extremely challenging. Herein, we report a metal-free graphitic carbon nitride (g-CxN4)-based nanosheet photocatalyst (x = 3.2, 3.6, or 3.8) with melem rings conjugated by Schiff-base bonds (N[double bond, length as m-dash]C-C[double bond, length as m-dash]N). The presence of the conjugated Schiff-base bond tunes the band gap of g-CxN4 and, more importantly, serves as an electron sink to suppress electron-hole pair recombination. The projected density of states (PDOS) calculations suggest that the melem ring and Schiff-base bond act as oxidizing and reducing centers, respectively, for photocatalytic water splitting. As a result, g-CxN4, in particular g-C3.6N4, can catalyze overall water splitting without the need for any co-catalyst or sacrificial donor. Under visible light (>420 nm wavelength) irradiation, g-C3.6N4 catalyzes the overall water splitting with H2 and O2 generation rates of 75.0 and 36.3 μmol h-1 g-1, respectively. g-C3.6N4 is the most efficient single-component photocatalyst ever reported for overall water splitting. Our studies demonstrate a new approach for tuning the bandgap and the electronic structure of graphitic carbon nitride for maximizing its photocatalytic performance for water splitting, which will be important for hydrogen generation and for energy applications.
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http://dx.doi.org/10.1039/d1nr01940fDOI Listing
May 2021

Long-term effect of bilateral anterior elevation of occlusion on the temporomandibular joints.

Oral Dis 2021 May 12. Epub 2021 May 12.

Department of Oral Anatomy and Physiology and Clinic of temporomandibular Joint Disorders and Oral and Maxillofacial Pain, The Key Laboratory of Military Stomatology of State and the National Clinical Research Center for Oral Diseases, School of Stomatology, The Fourth Military Medical University, Xi'an, China.

Objective: Incisors tubed prosthesis with bilateral anterior elevation (BAE) relation had been reported to stimulate the proliferative response in the mandibular condylar cartilage of mice, thus the prosthetic occlusion elevation had been proposed to treat cartilage degeneration. Currently, we aimed to detect the long-term effect of BAE on temporomandibular joints (TMJs).

Materials And Methods: Twelve 6-week-old female mice were assigned to age-matched control and BAE groups (n = 6). Micro-CT images and the macro- and micro-morphology of the mandibular condyles were analyzed at 29 weeks.

Results: Compared with the age-matched controls, in BAE group, there were loss of subchondral cortical bone and heavy loss of the subchondral trabecular bone at the superior sites of the TMJ condyles, but hyperostosis at the inferior sites as revealed by micro-CT images and histological slices. In BAE group, cartilage thickness and matrix area were increased with upregulated expression of type II, type X collagen, and Ki67, but the expression of cleaved caspase-3 was downregulated (all, p < 0.05).

Conclusion: In addition to cartilage thickening, long-term BAE induces loss of the subchondral cortical bone and heavy loss of the underneath subchondral trabecular bone, but hyperostosis further underneath. Using BAE as a treatment remains double-edged.
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http://dx.doi.org/10.1111/odi.13914DOI Listing
May 2021

A Bubble-Assisted Approach for Patterning Nanoscale Molecular Aggregates.

Angew Chem Int Ed Engl 2021 May 11. Epub 2021 May 11.

Key Laboratory of Green Printing, Institute of Chemistry, Chinese Academy of Sciences (ICCAS), Beijing National Laboratory for Molecular Sciences (BNLMS), University of the Chinese Academy of Sciences, Beijing, 100190, P. R. China.

We demonstrate a new approach to pattern functional organic molecules with a template of foams, and achieve a resolution of sub 100 nm. The bubble-assisted assembly (BAA) process is consisted of two periods, including bubble evolution and molecular assembly, which are dominated by the Laplace pressure and molecular interactions, respectively. Using TPPS (meso-tetra(4-sulfonatophenyl) porphyrin), we systematically investigate the patterns and assembly behaviour in the bubble system with a series of characterizations, which show good uniformity in nanoscale resolution. Theoretical simulations reveal that TPPS's J-aggregates contribute to the ordered construction of molecular patterns. Finally, we propose an empirical rule for molecular patterning approach, that the surfactant and functional molecules should have the same type of charge in a two-component system. This approach exhibits promising feasibility to assemble molecular patterns at nanoscale resolution for micro/nano functional devices.
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http://dx.doi.org/10.1002/anie.202103765DOI Listing
May 2021

Prognostic Value of D-dimer in patients with acute coronary syndrome treated by percutaneous coronary intervention: a retrospective cohort study.

Thromb J 2021 May 7;19(1):30. Epub 2021 May 7.

Fuwai Hospital, Chinese Academy of Medical Sciences, Shenzhen, China.

Background: Associations between D-dimer and outcomes of patients with acute coronary syndromes (ACS) remain controversial. This study aimed to investigate the prognostic value of D-dimer in ACS patients treated by percutaneous coronary intervention (PCI).

Methods: In this observational study, 3972 consecutive patients with ACS treated by PCI were retrospectively recruited. The X-tile program was used to determine the optimal D-dimer thresholds for risk stratifications. Cox regression with multiple adjustments was used for outcome analysis. Restricted cubic spline (RCS) analysis was performed to assess the dose-response association between D-dimer and outcomes. The C-index was calculated to evaluate the additional prognostic value of D-dimer when added to clinical risk factors and commonly used clinical risk scores, with internal validations using bootstrapping methods. The primary outcome was all-cause death.

Results: During a median follow-up of 720 days, 225 deaths occurred. Based on the thresholds generated by X-tile, ACS-PCI patients with median (420-1150 ng/mL, hazard ratio [HR]: 1.58, 95 % confidence interval [CI]: 1.14-2.20, P = 0.007) and high (≥ 1150 ng/mL, HR: 1.98, 95 % CI: 1.36-2.89, P < 0.001) levels of D-dimer showed substantially higher risk of death compared to those with low D-dimer (< 420 ng/mL). RCS analysis depicted a constant relation between D-dimer and various outcomes. The addition of D-dimer levels significantly improved risk predictions for all-cause death when combined with the fully adjusted models (C-index: 0.853 vs. 0.845, P = 0.021), the GRACE score (C-index: 0.826 vs. 0.814, P = 0.027), and the TIMI score (C-index: 0.804 vs. 0.776, P < 0.001). The predicted mortality at the median follow-up (two years) was 1.7 %, 5.2 %, and 10.9 % for patients with low, median, and high D-dimer, respectively, which was well matched with the observed mortality (low D-dimer group: 1.2 %, median D-dimer group: 5.2 %, and high D-dimer group: 12.6 %).

Conclusions: For ACS patients treated by PCI, D-dimer level was an independent predictor for adverse outcomes, and provided additional prognostic value when combined with clinical risk factors and risk scores. Risk stratifications based on D-dimer was plausible to differentiate ACS-PCI patients with higher risk of death.
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http://dx.doi.org/10.1186/s12959-021-00281-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106213PMC
May 2021

A Unique Gas-Migration, Trapping, and Emitting Strategy for High-Loading Single Atomic Cd Sites for Carbon Dioxide Electroreduction.

Nano Lett 2021 May 7;21(10):4262-4269. Epub 2021 May 7.

School of Materials Science and Engineering, Peking University, Beijing 100871, China.

Single-atom catalysts (SACs) exhibit great potential in heterogeneous catalysis. However, the achievement of obtaining high-loading SACs remains a bottleneck. Herein, we first demonstrate a unique gas-migration, trapping, and emitting strategy for building a kind of Cd-based SAC for CO reduction (CORR). The gas-migration and trapping processes (≤750 °C) endows the material with an ultrahigh Cd loading amount of 30.3 wt %, while the emitting process can facilely modulate the loading amount from 30.3 to 1.4 wt %. For the CORR, the Cd-NC SACs with a loading amount of 18.4 wt % exhibits the maximum Faraday efficiency of 91.4% for CO at -0.728 V. The operando infrared spectroscopy studies prove the presence of main intermediates *COO, *COOH, and *CO on Cd-NC-5M SACs during the catalytic process, indicating that the CORR follows the proton-decoupled electron-transfer mechanism. Density functional theory simulations reveal that the Cd-N structure reduces the Gibbs free energy of the rate-determining step (the hydrogenation step of *COOH).
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http://dx.doi.org/10.1021/acs.nanolett.1c00432DOI Listing
May 2021

Thermostable, Dissolvable Buccal Film Rotavirus Vaccine Is Highly Effective in Neonatal Gnotobiotic Pig Challenge Model.

Vaccines (Basel) 2021 Apr 30;9(5). Epub 2021 Apr 30.

Universal Stabilization Technologies, Inc., San Diego, CA 92121, USA.

Difficulties related to storage and transport of currently available live oral rotavirus vaccines can have detrimental consequences on the efficacy of the vaccines. Thus, there is a great need for thermostable vaccines that can eliminate the necessity for cold chain storage or reconstitution before administration. In this study, we developed a dissolvable oral polymeric film comprised of a live attenuated thermostable tetravalent rhesus-human reassortant rotavirus vaccine (RRV-TV) powder and antacid (CaCO). Immunogenicity and protective efficacy of the vaccine after buccal delivery was evaluated in the gnotobiotic pig model of human rotavirus (HRV) infection and diarrhea. Two doses of the vaccine were highly immunogenic and conferred strong protection against virus shedding and diarrhea upon challenge with a high dose of a virulent G1 HRV in gnotobiotic pigs. Those pigs vaccinated with the preserved film vaccine had significantly delayed onset of diarrhea; reduced duration and area under the curve of diarrhea; delayed onset of fecal virus shedding; and reduced duration and peak of fecal virus shedding titers compared to pigs in both the placebo and the reconstituted liquid oral RRV-TV vaccine groups. Associated with the strong protection, high titers of serum virus neutralization antibodies against each of the four RRV-TV mono-reassortants and G1 HRV-specific serum IgA and IgG antibodies, as well as intestinal IgA antibodies, were induced by the preserved film vaccine. These results demonstrated the effectiveness of our thermostable buccal film rotavirus vaccine and warrant further investigation into the promise of the novel technology in addressing drawbacks of the current live oral HRV vaccines.
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http://dx.doi.org/10.3390/vaccines9050437DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8147248PMC
April 2021

CYLD deficiency causes auditory neuropathy due to reduced neurite outgrowth.

J Clin Lab Anal 2021 Jun 2;35(6):e23783. Epub 2021 May 2.

State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin, China.

Background: Auditory neuropathy is a cause of hearing loss that has been studied in a number of animal models. Signal transmission from hair cells to spiral ganglion neurons plays an important role in normal hearing. CYLD is a microtubule-binding protein, and deubiquitinase involved in the regulation of various cellular processes. In this study, we used Cyld knockout (KO) mice and nerve cell lines to examine whether CYLD is associated with auditory neuropathy.

Methods: Hearing of Cyld KO mice was studied using the TDT RZ6 auditory physiology workstation. The expression and localization of CYLD in mouse cochlea and cell lines were examined by RT-PCR, immunoblotting, and immunofluorescence. CYLD expression was knocked down in SH-SY5Y cells by shRNAs and in PC12 and N2A cells by siRNAs. Nerve growth factor and retinoic acid were used to induce neurite outgrowth, and the occurrence and length of neurites were statistically analyzed between knockdown and control groups.

Results: Cyld KO mice had mild hearing impairment. Moreover, CYLD was widely expressed in mouse cochlear tissues and different nerve cell lines. Knocking down CYLD significantly reduced the length and proportion of neurites growing from nerve cells.

Conclusions: The abnormal hearing of Cyld KO mice might be caused by a decrease in the length and number of neurites growing from auditory nerve cells in the cochlea, suggesting that CYLD is a key protein affecting hearing.
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http://dx.doi.org/10.1002/jcla.23783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8183908PMC
June 2021