Publications by authors named "Zhen Zhao"

670 Publications

Protection of ischemic white matter and oligodendrocytes in mice by 3K3A-activated protein C.

J Exp Med 2022 Jan 30;219(1). Epub 2021 Nov 30.

The Zilkha Neurogenetic Institute, Keck School of Medicine of the University of Southern California, Los Angeles, CA.

Subcortical white matter (WM) stroke accounts for 25% of all strokes and is the second leading cause of dementia. Despite such clinical importance, we still do not have an effective treatment for ischemic WM stroke, and the mechanisms of WM postischemic neuroprotection remain elusive. 3K3A-activated protein C (APC) is a signaling-selective analogue of endogenous blood protease APC that is currently in development as a neuroprotectant for ischemic stroke patients. Here, we show that 3K3A-APC protects WM tracts and oligodendrocytes from ischemic injury in the corpus callosum in middle-aged mice by activating protease-activated receptor 1 (PAR1) and PAR3. We show that PAR1 and PAR3 were also required for 3K3A-APC's suppression of post-WM stroke microglia and astrocyte responses and overall improvement in neuropathologic and functional outcomes. Our data provide new insights into the neuroprotective APC pathway in the WM and illustrate 3K3A-APC's potential for treating WM stroke in humans, possibly including multiple WM strokes that result in vascular dementia.
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http://dx.doi.org/10.1084/jem.20211372DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635278PMC
January 2022

miR122-controlled all-in-one nanoplatform for theranostic of drug-induced liver injury by visualization imaging guided on-demand drug release.

Mater Today Bio 2021 Sep 12;12:100157. Epub 2021 Nov 12.

State Key Laboratory of Natural Medicines, China Pharmaceutical University, No. 24 Tongjia Lane, Nanjing, 210009, China.

Drug-induced liver injury (DILI) is a challenging clinical problem with respect to both diagnosis and management. As a newly emerging biomarker of liver injury, miR122 shows great potential in early and sensitive detection of DILI. Glycyrrhetinic acid (GA) possesses desirable therapeutic effect on DILI, but its certain dose-dependent side effects after long-term and/or high-dose administration limit its clinical application. In this study, in order to improve the precise diagnosis and effective treatment of DILI, GA loaded all-in-one theranostic nanoplatform was designed by assembling of upconversion nanoparticles and gold nanocages. As a proof of concept, we demonstrated the applicability of this single-wavelength laser-triggered theranostic nanoplatform for the spatiotemporally controllable imaging of DILI and miR122-controlled on-demand drug release and . This novel nanoplatform opens a promising avenue for the clinical diagnosis and treatment of DILI.
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http://dx.doi.org/10.1016/j.mtbio.2021.100157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8604687PMC
September 2021

Automatic differentiation of thyroid scintigram by deep convolutional neural network: a dual center study.

BMC Med Imaging 2021 11 25;21(1):179. Epub 2021 Nov 25.

Laboratory of Clinical Nuclear Medicine, Department of Nuclear Medicine, West China Hospital, Sichuan University, No.37 Guo Xue Alley, Chengdu, 610041, People's Republic of China.

Background: Tc-pertechnetate thyroid scintigraphy is a valid complementary avenue for evaluating thyroid disease in the clinic, the image feature of thyroid scintigram is relatively simple but the interpretation still has a moderate consistency among physicians. Thus, we aimed to develop an artificial intelligence (AI) system to automatically classify the four patterns of thyroid scintigram.

Methods: We collected 3087 thyroid scintigrams from center 1 to construct the training dataset (n = 2468) and internal validating dataset (n = 619), and another 302 cases from center 2 as external validating datasets. Four pre-trained neural networks that included ResNet50, DenseNet169, InceptionV3, and InceptionResNetV2 were implemented to construct AI models. The models were trained separately with transfer learning. We evaluated each model's performance with metrics as following: accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), recall, precision, and F1-score.

Results: The overall accuracy of four pre-trained neural networks in classifying four common uptake patterns of thyroid scintigrams all exceeded 90%, and the InceptionV3 stands out from others. It reached the highest performance with an overall accuracy of 92.73% for internal validation and 87.75% for external validation, respectively. As for each category of thyroid scintigrams, the area under the receiver operator characteristic curve (AUC) was 0.986 for 'diffusely increased,' 0.997 for 'diffusely decreased,' 0.998 for 'focal increased,' and 0.945 for 'heterogeneous uptake' in internal validation, respectively. Accordingly, the corresponding performances also obtained an ideal result of 0.939, 1.000, 0.974, and 0.915 in external validation, respectively.

Conclusions: Deep convolutional neural network-based AI model represented considerable performance in the classification of thyroid scintigrams, which may help physicians improve the interpretation of thyroid scintigrams more consistently and efficiently.
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http://dx.doi.org/10.1186/s12880-021-00710-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8620916PMC
November 2021

Facilitating Catalytic Purification of Auto-Exhaust Carbon Particles via the FeO{113} Facet-dependent Effect in Pt/FeO Catalysts.

Environ Sci Technol 2021 Nov 19. Epub 2021 Nov 19.

Key Laboratory of Beijing on Regional Air Pollution Control, Beijing Key Laboratory for Green Catalysis and Separation, Beijing University of Technology, Beijing 100124, China.

The purification efficiency of auto-exhaust carbon particles in the catalytic aftertreatment system of vehicle exhaust is strongly dependent on the interface nanostructure between the noble metal component and oxide supports. Herein, we have elaborately synthesized the catalysts (Pt/FeO-R) of Pt nanoparticles decorated on the hexagonal bipyramid α-FeO nanocrystals with co-exposed twelve {113} and six {104} facets. The area ratios () of co-exposed {113} to {104} facets in α-FeO nanocrystals were adjusted by the fluoride ion concentration in the hydrothermal method. The strong Pt-FeO{113} facet interaction boosts the formation of coordination unsaturated ferric sites for enhancing adsorption/activation of O and NO. Pt/FeO-R catalysts exhibited the FeO{113} facet-dependent performance during catalytic purification of soot particles in the presence of HO. Among the catalysts, the Pt/FeO-19 catalyst exhibits the highest catalytic activities ( = 365 °C, TOF = 0.13 h), the lowest apparent activation energy (69 kJ mol), and excellent catalytic stability during soot purification. Combined with the results of characterizations and density functional theory calculations, the catalytic mechanism is proposed: the active sites located at the Pt-FeO{113} interface can boost the key step of NO oxidation to NO. The crystal facet engineering is an effective strategy to obtain efficient catalysts for soot purification in practical applications.
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http://dx.doi.org/10.1021/acs.est.1c05908DOI Listing
November 2021

A Meta-Analysis of Randomized Controlled Trials on Therapeutic Efficacy and Safety of Autologous Cell Therapy for Atherosclerosis Obliterans.

J Vasc Surg 2021 Nov 14. Epub 2021 Nov 14.

Department of Vascular Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai 200000, China. Electronic address:

Background: Atherosclerosis obliterans (ASO) is a chronic occlusive arterial disease and the most common type of peripheral arterial disease. Current treatment options like medication and vascularization have limited effects for "no-option" patients, and stem cell therapy is considered a viable option although its application and efficacy have not been standardized. The objective of this review was to assess the safety and efficacy of autologous stem cell therapy in patients with ASO.

Methods: We performed a literature search of published RCTs for ASO patients receiving stem cell therapy without a revascularization option. PubMed, Embase, and the Cochrane Library were searched. This study was conducted by a pair of authors independently and audited by a third author. Data were synthesized with a random-effect model.

Results: 630 patients in 12 RCTs were included. The results showed that cell therapy significantly improved total amputation (RR: 0.64, p = 0.004, 95% CI: [0.47, 0.87]), major amputation (RR: 0.69, p = 0.02, 95% CI: [0.50, 0.94]), ankle-brachial index (ABI) (MD = 0.08, p = 0.004, 95% CI: [0.02, 0.13]), transcutaneous oxygen tension (TcO) (MD = 11.52, p = 0.004, 95% CI: [3.60, 19.43]) and rest pain score (MD = -0.64, p = 0.007, 95% CI: [-1.10, -0.17]) compared to placebo or standard care. However, current studies showed cell therapy was not superior to placebo or standard care in all-cause death (RR: 0.75, p = 0.34, 95% CI: [0.41, 1.36]) and ulcer size (MD = -8.85, p = 0.39, CI: [-29.05,11.36]).

Limitation: The number of trials included was limited. Moreover, most trials were designed for "no-option" patients and thus the results should be applied with caution to other PAD patients.

Conclusion: ASO patients can benefit from autologous cell therapy in limb salvage, limb blood perfusion, and rest pain alleviation.
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http://dx.doi.org/10.1016/j.jvs.2021.10.051DOI Listing
November 2021

Glutamine Synthetases Play a Vital Role in High Accumulation of Theanine in Tender Shoots of Albino Tea Germplasm "Huabai 1".

J Agric Food Chem 2021 Nov 14;69(46):13904-13915. Epub 2021 Nov 14.

College of Horticulture, Nanjing Agricultural University, Weigang No.1, Nanjing 210095, China.

Theanine (N-ethyl-γ-l-glutamine) is a special nonprotein amino acid that contributes to the umami taste and health function of tea. Although recent studies on tea breeding have focused on albino tea because of its umami taste, a factor of higher theanine concentration, the mechanism of biosynthesis of l-theanine is still unclear. In this study, four glutamine synthetase genes () were obtained and functionally characterized by overexpressing them in . The enzyme activities of the purified CsGS proteins from were detected. The results showed that CsGSs have a dual function in the synthesis of glutamine and theanine in vivo and in vitro. Interestingly, l-theanine was abundantly synthesized in the tender shoots of "Huabai 1". In the white tender shoots, the cytosol might exhibit increased expression to compensate for decreasing levels of chloroplast , which plays a vital role in high accumulation of theanine in "Huabai 1". In addition, was most likely the key l-theanine synthases in green tissues of tea. The present findings will provide basis for and considerably broaden the scope of understanding the function of and the mechanism of l-theanine accumulation in the tender shoots of "Huabai 1", and will be useful for breeding and screening tea with high l-theanine content.
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http://dx.doi.org/10.1021/acs.jafc.1c04567DOI Listing
November 2021

Single-cell analysis of human non-small cell lung cancer lesions refines tumor classification and patient stratification.

Cancer Cell 2021 Nov 2. Epub 2021 Nov 2.

The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

Immunotherapy is a mainstay of non-small cell lung cancer (NSCLC) management. While tumor mutational burden (TMB) correlates with response to immunotherapy, little is known about the relationship between the baseline immune response and tumor genotype. Using single-cell RNA sequencing, we profiled 361,929 cells from 35 early-stage NSCLC lesions. We identified a cellular module consisting of PDCD1CXCL13 activated T cells, IgG plasma cells, and SPP1 macrophages, referred to as the lung cancer activation module (LCAM). We confirmed LCAM enrichment in multiple NSCLC cohorts, and paired CITE-seq established an antibody panel to identify LCAM lesions. LCAM presence was found to be independent of overall immune cell content and correlated with TMB, cancer testis antigens, and TP53 mutations. High baseline LCAM scores correlated with enhanced NSCLC response to immunotherapy even in patients with above median TMB, suggesting that immune cell composition, while correlated with TMB, may be a nonredundant biomarker of response to immunotherapy.
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http://dx.doi.org/10.1016/j.ccell.2021.10.009DOI Listing
November 2021

Analysis of NH -TPD Profiles for CuSSZ-13 SCR Catalyst of Controlled Al Distribution - Complexity Resolved by First Principles Thermodynamics of NH Desorption, IR and EPR Insight into Cu Speciation*.

Chemistry 2021 Nov 9. Epub 2021 Nov 9.

Faculty of Chemistry, Jagiellonian University, ul. Gronostajowa 2, 30-387, Krakow, Poland.

NH temperature-programmed desorption (NH -TPD) is frequently used for probing the nature of the active sites in CuSSZ-13 zeolite for selective catalytic reduction (SCR) of NO . Herein, we propose an interpretation of NH -TPD results, which takes into account the temperature-induced dynamics of NH interaction with the active centers. It is based on a comprehensive DFT/GGA+D and first-principles thermodynamic (FPT) modeling of NH adsorption on single Cu , Cu , [CuOH] centers, dimeric [Cu-O-Cu] , [Cu-O -Cu] species, segregated CuO nanocrystals and Brønsted acid sites (BAS). Theoretical TPD profiles are compared with the experimental data measured for samples of various Si/Al ratios and distribution of Al within the zeolite framework. Copper reduction, its relocation, followed by the intrazeolite olation/oxolation processes, which are concomitant with NH desorption, were revealed by electron paramagnetic resonance (EPR) and IR. DFT/FPT results show that the peaks in the desorption profiles cannot be assigned univocally to the particular Cu and BAS centers, since the observed low-, medium- and high-temperature desorption bands have contributions coming from several species, which dynamically change their speciation and redox states during NH -TPD experiment. Thus, a rigorous interpretation of the NH -TPD profiles of CuSSZ-13 in terms of the strength and concentration of the active centers of a particular type is problematic. Nonetheless, useful connections for molecular interpretation of TPD profiles can be established between the individual component peaks and the corresponding ensembles of the adsorption centers.
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http://dx.doi.org/10.1002/chem.202102790DOI Listing
November 2021

Microglia and its genetics in Alzheimer's Disease.

Curr Alzheimer Res 2021 Nov 5. Epub 2021 Nov 5.

Center for Neurodegeneration and Regeneration, Zilkha Neurogenetic Institute and Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, California. United States.

Alzheimer's Disease (AD) is the most prevalent form of dementia across the world. While its discovery and pathological manifestations are centered on protein aggregations of amyloid-beta (Aβ) and hyperphosphorylated tau protein, neuroinflammation has emerged in the last decade as a main component of the disease in both pathogenesis and progression. As the main innate immune cell type in central nervous system (CNS), microglia play a very important role in regulating neuroinflammation, which occurs commonly in neurodegenerative conditions including AD. Under inflammatory response, microglia undergo morphological changes and status transition from homeostatic to activated forms. Different microglia subtypes displaying distinct genetic profiles have been identified in AD, and these signatures often link to AD risk genes identified from the genome-wide association studies (GWAS), such as APOE and TREM2. Furthermore, many of AD risk genes are highly enriched in microglia and specifically influence the functions of microglia in pathogenesis, e.g. releasing inflammatory cytokines and clearing Aβ. Therefore, building up a landscape of these risk genes in microglia, based on current preclinical studies and in the context of their pathogenic or protective effects, would largely help us to understand the complexed etiology of AD and provide new insight for the unmet need of effective treatment.
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http://dx.doi.org/10.2174/1567205018666211105140732DOI Listing
November 2021

Impaired granzyme B-producing regulatory B cells in systemic lupus erythematosus.

Mol Immunol 2021 Dec 5;140:217-224. Epub 2021 Nov 5.

Department of Rheumatology and Immunology, Peking University People's Hospital, Beijing, China; Beijing Key Laboratory for Rheumatism Mechanism and Immune Diagnosis (BZ0135), Beijing, China. Electronic address:

Granzyme B (GrB)-producing B cells are proposed to be a kind of regulatory B cells (Bregs) and have been revealed to be implicated in the pathogenesis of autoimmune diseases. Nevertheless, their role in SLE remains elusive. In this study, the frequencies of GrB-producing Bregs in peripheral blood of heathy control (HC) and systemic lupus erythematosus (SLE) were evaluated by flow cytometry, and their correlation with SLE patient clinical and immunological features were analyzed. The expression of GrB in HC and SLE B cells were also further detected by RT-qPCR analysis and ELISpot. The function of GrB-producing Bregs in HC and SLE patients was further investigated by in vitro CD4 effector T cells-B cells co-culture assays with GrB blockade. We found that GrB-producing Bregs were significantly decreased in SLE patients and correlated with the clinical and immunological features. Moreover, these cells were functionally impaired under SLE circumstance. The negative correlation between GrB-producing Bregs and CD4 T cells observed in healthy individuals disappeared in SLE patients. In vitro cell co-culture assay further showed that GrB-producing Bregs from SLE patients failed to suppress the Th1, Th2 and Th17 cell inflammatory responses, partially due to the dampened capacity of down-regulating TCR zeta and inducing T cell apoptosis. Taken together, these results revealed the disturbance of GrB-producing Bregs in SLE that might contribute to the disease initiation and progression.
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http://dx.doi.org/10.1016/j.molimm.2021.09.012DOI Listing
December 2021

Metal-free catalysis for the reaction of nitrogen dioxide dimer with phenol: An unexpected favorable source of nitrate and aerosol precursors in vehicle exhaust.

Chemosphere 2021 Oct 25:132705. Epub 2021 Oct 25.

Institute of Functional Material Chemistry, National & Local United Engineering Lab for Power Battery, Faculty of Chemistry, Northeast Normal University, Changchun, 130024, People's Republic of China. Electronic address:

Atmospheric reaction mechanism and dynamics of phenol with nitrogen dioxide dimer were explored by the density functional theory and high-level quantum chemistry combined with statistical kinetic calculations within 220-800 K. The nitric acid and phenyl nitrite, the typical aerosol precursors, are the preponderant products because of the low formation free energy barrier (∼8.7 kcal/mol) and fast rate constants (∼10 cm molecule s at 298 K). Phenyl nitrate is the minor product and it would be also formed from the transformation of phenyl nitrite in NO-rich environment. More importantly, kinetic effects and catalytic mechanism of a series of metal-free catalysts (HO, NH, CHNH, CHNHCH, HCOOH, and CHCOOH) on the title reaction were investigated at the same level. The results indicate that CHNH and CHNHCH can not only catalyze the title reaction by lowering the free energy barrier (about 1.4-6.5 kcal/mol) but also facilitate the production of organic ammonium nitrate via acting as a donor-acceptor of hydrogen. Conversely, the other species are non-catalytic upon the title reaction. The stabilization energies and donor-acceptor interactions in alkali-catalyzed product complexes were explored, which can provide new insights to the properties of aerosol precursors. Moreover, the lifetime of phenol determined by nitrogen dioxide dimer in the presence of dimethylamine may compete with that of determined by OH radicals, indicating that nitrogen dioxide dimer is responsible for the elimination of phenol in the polluted atmosphere. This work could help us thoroughly understand the removal of nitrogen oxides and phenol as well as new aerosol precursor aggregation in vehicle exhaust.
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http://dx.doi.org/10.1016/j.chemosphere.2021.132705DOI Listing
October 2021

Perfluoroalkyl acids in dust on residential indoor/outdoor window glass in Chinese cities: occurrence, composition, and toddler exposure.

Environ Sci Pollut Res Int 2021 Oct 1. Epub 2021 Oct 1.

MOE Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin, 300071, China.

The dust on indoor and outdoor surfaces of the window glasses were collected using sterile cotton balls in 11 cities from China. Two sampling campaigns were conducted with the time interval of 7 days to investigate the accumulation especially during the Spring festival holidays. Twenty-nine perfluoroalkyl acids (PFAA) were quantified to investigate concentration, composition, and toddlers' exposure. The concentrations of ∑PFAA ranged from no detection (nd) to 43 ng/m (mean 8.9 ± 10 ng/m). Perfluorobutanoic acid (PFBA) was detected in 78% samples and accounted for 55 ± 21% of ∑PFAA concentrations. 6:2 fluorotelomer sulfonic acid (6:2 FTSA) and hexafluoropropylene oxide dimer acid (HFPO-DA) were detected in more than 50% samples indicating the use of alternatives. Fluorotelomer carboxylic acid (FTCA) and fluorotelomer unsaturated acid (FTUCA) were found in the dust, implying the degradation of fluorotelomer alcohols (FTOH). The highest concentration of ∑PFAA (43 ng/m) was found in outdoor dust from Xinzhou, Shanxi Province. Higher ∑PFAA concentrations were found in indoor dust than outdoor in 6 paired samples (3 from Feb. 14 and 3 from Feb. 21). In Tianjin and Handan, the concentrations of ∑PFAA from outdoor surfaces were higher in sampling campaign I (SC I, Feb. 21) than in sampling campaign II (SC II, Feb. 14), implying intensive outdoor release. The exposure of 2-year-old toddlers to PFAA via hand-to-mouth ingestion and dermal absorption was estimated; the mean values of intake were 2.1 and 1.5 pg/kg body weight, respectively, assuming an exposure time of 1 h.
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http://dx.doi.org/10.1007/s11356-021-16653-wDOI Listing
October 2021

circRPS16 Promotes Proliferation and Invasion of Hepatocellular Carcinoma by Sponging miR-876-5p to Upregulate SPINK1.

Front Oncol 2021 14;11:724415. Epub 2021 Sep 14.

The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.

The roles of serine protease inhibitor Kazal type 1 (SPINK1) in multiple types of cancers have been significantly documented. However, its specific roles in hepatocellular carcinoma (HCC) remain to be investigated. This study found that SPINK1 is upregulated in HCC and its upregulation correlates with poor prognosis. Besides, functional assays revealed that SPINK1 promotes cell proliferation, cell cycle, and invasion . Through bioinformatics analysis, we speculate that circRPS16 regulates SPINK1 expression by sponging miR-876-5p. This was further verified by the dual-luciferase reporter and fluorescent hybridization (FISH) assays. Subsequently, rescue assays verified that circRPS16 promotes cell proliferation, cell cycle, and invasion through miR-876-5p. Importantly, silencing circRPS16 inhibited tumor growth by downregulating SPINK1 expression . Collectively, our results confirm that SPINK1 is a downstream target of circRPS16. Besides, circRPS16 and SPINK1 are oncogenic factors in HCC progression; they provide novel diagnostic and therapeutic targets for HCC patients.
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http://dx.doi.org/10.3389/fonc.2021.724415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8476860PMC
September 2021

Roton pair density wave in a strong-coupling kagome superconductor.

Nature 2021 11 29;599(7884):222-228. Epub 2021 Sep 29.

Beijing National Center for Condensed Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing, People's Republic of China.

The transition metal kagome lattice materials host frustrated, correlated and topological quantum states of matter. Recently, a new family of vanadium-based kagome metals, AVSb (A = K, Rb or Cs), with topological band structures has been discovered. These layered compounds are nonmagnetic and undergo charge density wave transitions before developing superconductivity at low temperatures. Here we report the observation of unconventional superconductivity and a pair density wave (PDW) in CsVSb using scanning tunnelling microscope/spectroscopy and Josephson scanning tunnelling spectroscopy. We find that CsVSb exhibits a V-shaped pairing gap Δ ~ 0.5 meV and is a strong-coupling superconductor (2Δ/kT ~ 5) that coexists with 4a unidirectional and 2a × 2a charge order. Remarkably, we discover a 3Q PDW accompanied by bidirectional 4a/3 spatial modulations of the superconducting gap, coherence peak and gap depth in the tunnelling conductance. We term this novel quantum state a roton PDW associated with an underlying vortex-antivortex lattice that can account for the observed conductance modulations. Probing the electronic states in the vortex halo in an applied magnetic field, in strong field that suppresses superconductivity and in zero field above T, reveals that the PDW is a primary state responsible for an emergent pseudogap and intertwined electronic order. Our findings show striking analogies and distinctions to the phenomenology of high-T cuprate superconductors, and provide groundwork for understanding the microscopic origin of correlated electronic states and superconductivity in vanadium-based kagome metals.
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http://dx.doi.org/10.1038/s41586-021-03983-5DOI Listing
November 2021

HPV Sequencing Facilitates Ultrasensitive Detection of HPV Circulating Tumor DNA.

Clin Cancer Res 2021 Nov 27;27(21):5857-5868. Epub 2021 Sep 27.

Department of Radiation Oncology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.

Purpose: Human papillomavirus (HPV) DNA offers a convenient circulating tumor DNA (ctDNA) marker for HPV-associated malignancies, but current methods, such as digital PCR (dPCR), provide insufficient accuracy for clinical applications in patients with low disease burden. We asked whether a next-generation sequencing approach, HPV sequencing (HPV-seq), could provide quantitative and qualitative assessment of HPV ctDNA in low disease burden settings.

Experimental Design: We conducted preclinical technical validation studies on HPV-seq and applied it retrospectively to a prospective multicenter cohort of patients with locally advanced cervix cancer (NCT02388698) and a cohort of patients with oropharynx cancer. HPV-seq results were compared with dPCR. The primary outcome was progression-free survival (PFS) according to end-of-treatment HPV ctDNA detectability.

Results: HPV-seq achieved reproducible detection of HPV DNA at levels less than 0.6 copies in cell line data. HPV-seq and dPCR results for patients were highly correlated ( = 0.95, = 1.9 × 10) with HPV-seq detecting ctDNA at levels down to 0.03 copies/mL plasma in dPCR-negative posttreatment samples. Detectable HPV ctDNA at end-of-treatment was associated with inferior PFS with 100% sensitivity and 67% specificity for recurrence. Accurate HPV genotyping was successful from 100% of pretreatment samples. HPV ctDNA fragment sizes were consistently shorter than non-cancer-derived cell-free DNA (cfDNA) fragments, and stereotyped cfDNA fragmentomic patterns were observed across HPV genomes.

Conclusions: HPV-seq is a quantitative method for ctDNA detection that outperforms dPCR and reveals qualitative information about ctDNA. Our findings in this proof-of-principle study could have implications for treatment monitoring of disease burden in HPV-related cancers. Future prospective studies are needed to confirm that patients with undetectable HPV ctDNA following chemoradiotherapy have exceptionally high cure rates.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-2384DOI Listing
November 2021

Regular Nanowire Formation on Fe-Based Metal Glass by Manipulation of Surface Waves.

Nanomaterials (Basel) 2021 Sep 14;11(9). Epub 2021 Sep 14.

GPL Photonics Laboratory, State Key Laboratory of Applied Optics, Changchun Institute of Optics, Fine Mechanics and Physics, Chinese Academy of Sciences, Changchun 130033, China.

We report the formation of a sole long nanowire structure and the regular nanowire arrays inside a groove on the surface of Fe-based metallic glass upon irradiation of two temporally delayed femtosecond lasers with the identical linear polarization parallel and perpendicular to the groove, respectively. The regular structure formation can be well observed within the delay time of 20 ps for a given total laser fluence of = 30 mJ/cm and within a total laser fluence range of = 30-42 mJ/cm for a given delay time of 5 ps. The structural features, including the unit width and distribution period, are measured on a one-hundred nanometer scale, much less than the incident laser wavelength of 800 nm. The degree of structure regularity sharply contrasts with traditional observations. To comprehensively understand such phenomena, we propose a new physical model by considering the spin angular momentum of surface plasmon and its enhanced inhomogeneous magnetization for the ferromagnetic metal. Therefore, an intensive TE polarized magnetic surface wave is excited to result in the nanometer-scaled energy fringes and the ablative troughs. The theory is further verified by the observation of nanowire structure disappearance at the larger time delays of two laser pulses.
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http://dx.doi.org/10.3390/nano11092389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464996PMC
September 2021

Tumor Cell-Derived Exosomal Circ-0072088 Suppresses Migration and Invasion of Hepatic Carcinoma Cells Through Regulating MMP-16.

Front Cell Dev Biol 2021 9;9:726323. Epub 2021 Sep 9.

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Tumor-derived exosomes (EXOs), commonly differentially expressed in circular RNAs, have been shown to be crucial determinants of tumor progression and may regulate the development and metastasis of hepatic carcinoma (HCC). Possibly differentially expressed circRNAs in patients with HCC were screened out from the Gene Expression Omnibus (GEO). EXOs were isolated from the culture medium of HCC cells and plasma of patients with HCC, followed by characterization by transmission electron microscope, NanHCCight, and western blotting. Additionally, RNA immunoprecipitation and luciferase reporter gene assays were carried out to explore the molecular mechanism of hsa_circRNA_103809 (circ-0072088) in HCC cells. The screening results showed that circ-0072088 was highly expressed in patients with HCC, and its increase indicated unfavorable prognosis of patients according to quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Additionally, circ-0072088 was mainly secreted by HCC cells via EXOs in plasma of such patients, and its high level in plasma EXOs was closely associated with tumor node metastasis (TNM) staging and tumor size. Moreover, HCC-secreted EXOs mediated the degradation of miR-375 via circ-0072088 and upregulated MMP-16, thus suppressing the metastasis of HCC. Upregulated in patients with HCC, circ-0072088 may be an index for diagnosis and prognosis of HCC. In addition, HCC-derived EXOs coated with circ-0072088 might be a treatment for HCC, with the ability to inhibit the metastasis of HCC cells.
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http://dx.doi.org/10.3389/fcell.2021.726323DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8458752PMC
September 2021

Vascular Dementia and Underlying Sex Differences.

Front Aging Neurosci 2021 8;13:720715. Epub 2021 Sep 8.

Department of Biomedical Engineering, Stony Brook University, Stony Brook, NY, United States.

Vascular dementia (VaD) is the second most common form of dementia after Alzheimer's disease (AD); where Alzheimer's accounts for 60-70% of cases of dementia and VaD accounts for 20% of all dementia cases. VaD is defined as a reduced or lack of blood flow to the brain that causes dementia. VaD is also known occasionally as vascular contributions to cognitive impairment and dementia (VCID) or multi-infarct dementia (MID). VCID is the condition arising from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior, and VaD is the most severe stage while MID is produced by the synergistic effects caused by multiple mini strokes in the brain irrespective of specific location or volume. There are also subtle differences in the presentation of VaD in males and females, but they are often overlooked. Since 1672 when the first case of VaD was reported until now, sex and gender differences have had little to no research done when it comes to the umbrella term of dementia in general. This review summarizes the fundamentals of VaD followed by a focus on the differences between sex and gender when an individual is diagnosed. In addition, we provide critical evidence concerning sex and gender differences with a few of the main risk factors of VaD including pre-existing health conditions and family history, gene variants, aging, hormone fluctuations, and environmental risk factors. Additionally, the pharmaceutical treatments and possible mitigation of risk factors is explored.
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http://dx.doi.org/10.3389/fnagi.2021.720715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457333PMC
September 2021

Coordination of consolidated bioprocessing technology and carbon dioxide fixation to produce malic acid directly from plant biomass in Myceliophthora thermophila.

Biotechnol Biofuels 2021 Sep 23;14(1):186. Epub 2021 Sep 23.

Key Laboratory of Systems Microbial Biotechnology, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin, 300308, China.

Background: Consolidated bioprocessing (CBP) technique is a promising strategy for biorefinery construction, producing bulk chemicals directly from plant biomass without extra hydrolysis steps. Fixing and channeling CO into carbon metabolism for increased carbon efficiency in producing value-added compounds is another strategy for cost-effective bio-manufacturing. It has not been reported whether these two strategies can be combined in one microbial platform.

Results: In this study, using the cellulolytic thermophilic fungus Myceliophthora thermophila, we designed and constructed a novel biorefinery system DMCC (Direct microbial conversion of biomass with CO fixation) through incorporating two CO fixation modules, PYC module and Calvin-Benson-Bassham (CBB) pathway. Harboring the both modules, the average rate of fixing and channeling CO into malic acid in strain CP51 achieved 44.4, 90.7, and 80.7 mg/L/h, on xylose, glucose, and cellulose, respectively. The corresponding titers of malic acid were up to 42.1, 70.4, and 70.1 g/L, respectively, representing the increases of 40%, 10%, and 7%, respectively, compared to the parental strain possessing only PYC module. The DMCC system was further improved by enhancing the pentose uptake ability. Using raw plant biomass as the feedstock, yield of malic acid produced by the DMCC system was up to 0.53 g/g, with C content of 0.44 mol/mol malic acid, suggesting DMCC system can produce 1 t of malic acid from 1.89 t of biomass and fix 0.14 t CO accordingly.

Conclusions: This study designed and constructed a novel biorefinery system named DMCC, which can convert raw plant biomass and CO into organic acid efficiently, presenting a promising strategy for cost-effective production of value-added compounds in biorefinery. The DMCC system is one of great options for realization of carbon neutral economy.
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http://dx.doi.org/10.1186/s13068-021-02042-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461902PMC
September 2021

Comparison of Microvascular Decompression and Two Isocenters Gamma Knife for the Treatment of Trigeminal Neuralgia Caused by Vertebrobasilar Dolichoectasia.

Front Neurol 2021 30;12:707985. Epub 2021 Aug 30.

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

Vertebrobasilar dolichoectasia (VBD) is one of the rare causes of trigeminal neuralgia (TN). The common surgical treatments for patients with TN caused by VBD (VBD-TN) are microvascular decompression (MVD) and Gamma Knife radiosurgery (GKRS). However, the therapeutic effects of the two methods have not been clinically compared, so this study was performed to evaluate the treatment outcomes of MVD and GKRS for patients with VBD-TN. The retrospective study was performed from March 2011 to March 2019 in Wuhan Union Hospital. A total of 80 patients diagnosed with VBD-TN were included in this study, and they were divided into the MVD group ( = 46) and GKRS group ( = 34) according to the surgical methods. The imaging data, intraoperative findings, treatment outcomes, and complications of the two groups were analyzed and compared. Meanwhile, the influencing factors of the treatment effect are also explored on the two groups. Patients who underwent MVD were younger than patients who underwent GKRS (median ages were 61.1 and 65.4 years old, respectively, = 0.03). The median follow-up was 61.1 months for the MVD group and 56.8 months for the GKRS group. The favorable outcomes [Barrow Neurological Institute (BNI) pain score, BNI scores I-II] occurred in 97.8% of patients treated with MVD and in 78.9% of patients treated with GKRS ( = 0.009). The favorable outcomes in the percentage of patients after MVD 1, 3, 5, and 7 years were 95.7, 85.1, 74.2, and 74.2%, respectively, whereas the corresponding percentages after GKRS were 76.5, 66.2, 56.6, and 47.2%, respectively ( = 0.031). The postoperative complications (except facial numbness) in the MVD group were higher than those in the GKRS group ( = 0.036), but the incidence of new and worsening facial numbness was lower in the GKRS group ( < 0.001). MVD is superior to GKRS in obtaining and maintaining favorable outcomes for patients with VBD-TN, but it also comes with more complications other than facial numbness. Thus, the treatment program can be tailored to a patient's unique condition and wishes.
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http://dx.doi.org/10.3389/fneur.2021.707985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8437393PMC
August 2021

LncRNA HOXA-AS2 Promotes Oral Squamous Cell Proliferation, Migration, and Invasion via Upregulating EZH2 as an Oncogene.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211039109

117878The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China.

Oral squamous cell carcinoma (OSCC) is one of the most common types of cancer worldwide. Accumulating evidence has shown that long noncoding RNAs (lncRNAs) serve important roles in the development of OSCC. The purpose of this study was to investigate the biological function and underlying regulatory mechanism of lncRNA homeobox A cluster antisense RNA2 (HOXA-AS2) in OSCC. RT-qPCR was performed to analyze the HOXA-AS2 expressions in human immortalized oral epithelial cell (HIOEC) line, human OSCC cell lines, and plasma. The expression of HOXA-AS2 and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) in Tca-8113 cells were knocked down or overexpressed by transfection with shRNA-HOXA-AS2 or pcDNA-EZH2, respectively. The interaction between HOXA-AS2 and EZH2 was validated by RNA immunoprecipitation assay. In addition, cell proliferation was assessed by CCK-8 and EdU assays. Cell cycle distribution was analyzed by flow cytometry. Cell migration and invasion were detected using wound healing and Transwell assays, respectively. Apoptosis was detected by TUNEL staining. The protein expression levels of cell cycle and apoptosis-related proteins were measured by western blot analysis. Compared with HIOEC cells, HOXA-AS2 expression in OSCC cells was upregulated. HOXA-AS2 knockdown significantly inhibited Tca-8113 cell proliferation, blocked the cell cycle by arresting cells in the G0/G1 phase, promoted apoptosis, and suppressed migration and invasion. In addition, HOXA-AS2 was predicted to directly target EZH2 and positively regulate EZH2 expression. EZH2 overexpression could reverse the inhibitory effect of HOXA-AS2 knockdown on the proliferation, migration, and invasion of Tca-8113 cells. In summary, the findings suggested that HOXA-AS2 may inhibit cell proliferation, invasion, and migration, induce cell cycle arrest in the G0/G1 phase, and increase cell apoptosis by targeting EZH2. The research indicated that HOXA-AS2/EZH2 axis may play a key role in the development of OSCC.
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http://dx.doi.org/10.1177/15330338211039109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8445530PMC
September 2021

Diagnosis of Invasive Meningioma Based on Brain-Tumor Interface Radiomics Features on Brain MR Images: A Multicenter Study.

Front Oncol 2021 20;11:708040. Epub 2021 Aug 20.

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

Background: Meningioma invasion can be preoperatively recognized by radiomics features, which significantly contributes to treatment decision-making. Here, we aimed to evaluate the comparative performance of radiomics signatures derived from varying regions of interests (ROIs) in predicting BI and ascertaining the optimal width of the peritumoral regions needed for accurate analysis.

Methods: Five hundred and five patients from Wuhan Union Hospital (internal cohort) and 214 cases from Taihe Hospital (external validation cohort) pathologically diagnosed as meningioma were included in our study. Feature selection was performed from 1,015 radiomics features respectively obtained from nine different ROIs (brain-tumor interface (BTI)2-5mm; whole tumor; the amalgamation of the two regions) on contrast-enhanced T1-weighted imaging using least-absolute shrinkage and selection operator and random forest. Principal component analysis with varimax rotation was employed for feature reduction. Receiver operator curve was utilized for assessing discrimination of the classifier. Furthermore, clinical index was used to detect the predictive power.

Results: Model obtained from BTI4mm ROI has the maximum AUC in the training set (0.891 (0.85, 0.932)), internal validation set (0.851 (0.743, 0.96)), and external validation set (0.881 (0.833, 0.928)) and displayed statistically significant results between nine radiomics models. The most predictive radiomics features are almost entirely generated from GLCM and GLDM statistics. The addition of PEV to radiomics features (BTI4mm) enhanced model discrimination of invasive meningiomas.

Conclusions: The combined model (radiomics classifier with BTI4mm ROI + PEV) had greater diagnostic performance than other models and its clinical application may positively contribute to the management of meningioma patients.
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http://dx.doi.org/10.3389/fonc.2021.708040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422846PMC
August 2021

Rapid, robust, and sustainable antibody responses to mRNA COVID-19 vaccine in convalescent COVID-19 individuals.

JCI Insight 2021 10 22;6(20). Epub 2021 Oct 22.

Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York, USA.

Longitudinal studies are needed to evaluate the SARS-CoV-2 mRNA vaccine antibody response under real-world conditions. This longitudinal study investigated the quantity and quality of SARS-CoV-2 antibody response in 846 specimens from 350 patients, comparing BNT162b2-vaccinated individuals (19 previously diagnosed with COVID-19, termed RecoVax; and 49 never diagnosed, termed NaiveVax) with 122 hospitalized unvaccinated (HospNoVax) and 160 outpatient unvaccinated (OutPtNoVax) COVID-19 patients. NaiveVax experienced delay in generating SARS-CoV-2 total antibodies (TAb) and surrogate neutralizing antibodies (SNAb) after the first vaccine dose (D1) but rapid increase in antibody levels after the second dose (D2). However, these never reached RecoVax's robust levels. In fact, NaiveVax TAb and SNAb levels decreased 4 weeks after D2. For the most part, RecoVax TAb persisted, after reaching maximal levels 2 weeks after D2, but SNAb decreased significantly about 6 months after D1. Although NaiveVax avidity lagged behind that of RecoVax for most of the follow-up periods, NaiveVax did reach similar avidity by about 6 months after D1. These data suggest that 1 vaccine dose elicits maximal antibody response in RecoVax and may be sufficient. Also, despite decreasing levels in TAb and SNAb over time, long-term avidity may be a measure worth evaluating and possibly correlating to vaccine efficacy.
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http://dx.doi.org/10.1172/jci.insight.151477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8564891PMC
October 2021

Alteration of Bone Density, Microarchitecture, and Strength in Patients with Camurati-Engelmann Disease: Assessed by HR-pQCT.

J Bone Miner Res 2021 Sep 7. Epub 2021 Sep 7.

Department of Endocrinology, Key Laboratory of Endocrinology, NHC, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

Camurati-Engelmann disease (CED) is a rare autosomal-dominant skeletal dysplasia caused by mutations in the transforming growth factor-β1 (TGFB1) gene. In this study, a retrospective review of patients with CED evaluated at Peking Union Medical College Hospital in Beijing, China, between November 30, 2000 and November 30, 2020 was conducted. Data including demographic data, manifestations, and examination results were characterized. Furthermore, bone geometry, density, and microarchitecture were assessed and bone strength was estimated by HR-pQCT. Results showed the median age at onset was 2.5 years. Common manifestations included pain in the lower limbs (94%, 17/18), abnormal gait (89%, 16/18), genu valgum (89%, 16/18), reduced subcutaneous fat (78%, 14/18), delayed puberty (73%, 8/11), muscle weakness (67%, 12/18), hearing loss (39%, 7/18), hepatosplenomegaly (39%, 7/18), exophthalmos or impaired vision or visual field defect (33%, 6/18), and anemia (33%, 7/18). Twenty-five percent (4/16) of patients had short stature. Serum level of alkaline phosphatase was elevated in 41% (7/17) of patients whereas beta-C-terminal telopeptide was elevated in 91% of patients (10/11). Among 12 patients, the Z-scores of two patients were greater than 2.5 at the femur neck and the Z-scores of five patients were lower than -2.5 at the femur neck and/or lumbar spine. HR-pQCT results showed lower volumetric BMD (vBMD), altered bone microstructure and lower estimated bone strength at the distal radius and tibia in patients with CED compared with controls. In addition, total volume bone mineral density and cortical volumetric bone mineral density at the radius were negatively correlated with age in patients with CED, but positively correlated with age in controls. In conclusion, the largest case series of CED with characterized clinical features in a Chinese population was reported here. In addition, HR-pQCT was used to investigate bone microstructure at the distal radius and tibia in nine patients with CED, and the alteration of bone density, microstructure, and strength was shown for the first time. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4436DOI Listing
September 2021

Automatic identification of suspicious bone metastatic lesions in bone scintigraphy using convolutional neural network.

BMC Med Imaging 2021 09 4;21(1):131. Epub 2021 Sep 4.

Laboratory of Clinical Nuclear Medicine, Department of Nuclear Medicine, West China Hospital, Sichuan University, No. 37 Guo Xue Alley, Chengdu, 610041, China.

Background: We aimed to construct an artificial intelligence (AI) guided identification of suspicious bone metastatic lesions from the whole-body bone scintigraphy (WBS) images by convolutional neural networks (CNNs).

Methods: We retrospectively collected the Tc-MDP WBS images with confirmed bone lesions from 3352 patients with malignancy. 14,972 bone lesions were delineated manually by physicians and annotated as benign and malignant. The lesion-based differentiating performance of the proposed network was evaluated by fivefold cross validation, and compared with the other three popular CNN architectures for medical imaging. The average sensitivity, specificity, accuracy and the area under receiver operating characteristic curve (AUC) were calculated. To delve the outcomes of this study, we conducted subgroup analyses, including lesion burden number and tumor type for the classifying ability of the CNN.

Results: In the fivefold cross validation, our proposed network reached the best average accuracy (81.23%) in identifying suspicious bone lesions compared with InceptionV3 (80.61%), VGG16 (81.13%) and DenseNet169 (76.71%). Additionally, the CNN model's lesion-based average sensitivity and specificity were 81.30% and 81.14%, respectively. Based on the lesion burden numbers of each image, the area under the receiver operating characteristic curve (AUC) was 0.847 in the few group (lesion number n ≤ 3), 0.838 in the medium group (n = 4-6), and 0.862 in the extensive group (n > 6). For the three major primary tumor types, the CNN-based lesion identifying AUC value was 0.870 for lung cancer, 0.900 for prostate cancer, and 0.899 for breast cancer.

Conclusion: The CNN model suggests potential in identifying suspicious benign and malignant bone lesions from whole-body bone scintigraphic images.
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http://dx.doi.org/10.1186/s12880-021-00662-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417997PMC
September 2021

C-Type Natriuretic Peptide Ameliorates Vascular Injury and Improves Neurological Outcomes in Neonatal Hypoxic-Ischemic Brain Injury in Mice.

Int J Mol Sci 2021 Aug 20;22(16). Epub 2021 Aug 20.

The Lawrence D. Longo, MD Center for Perinatal Biology, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA 92350, USA.

C-type natriuretic peptide (CNP) is an important vascular regulator that is present in the brain. Our previous study demonstrated the innate neuroprotectant role of CNP in the neonatal brain after hypoxic-ischemic (HI) insults. In this study, we further explored the role of CNP in cerebrovascular pathology using both in vivo and in vitro models. In a neonatal mouse HI brain injury model, we found that intracerebroventricular administration of recombinant CNP dose-dependently reduces brain infarct size. CNP significantly decreases brain edema and immunoglobulin G (IgG) extravasation into the brain tissue, suggesting a vasculoprotective effect of CNP. Moreover, in primary brain microvascular endothelial cells (BMECs), CNP dose-dependently protects BMEC survival and monolayer integrity against oxygen-glucose deprivation (OGD). The vasculoprotective effect of CNP is mediated by its innate receptors NPR2 and NPR3, in that inhibition of either NPR2 or NPR3 counteracts the protective effect of CNP on IgG leakage after HI insult and BMEC survival under OGD. Of importance, CNP significantly ameliorates brain atrophy and improves neurological deficits after HI insults. Altogether, the present study indicates that recombinant CNP exerts vascular protection in neonatal HI brain injury via its innate receptors, suggesting a potential therapeutic target for the treatment of neonatal HI brain injury.
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http://dx.doi.org/10.3390/ijms22168966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396645PMC
August 2021

Droplet digital PCR (ddPCR) for the detection and quantification of Ureaplasma spp.

BMC Infect Dis 2021 Aug 11;21(1):804. Epub 2021 Aug 11.

Clinical Laboratory, Minhang Hospital, Fudan University, No. 170, Xinsong Road, Shanghai, China.

Background: Ureaplasma spp. are associated with various infectious diseases in females, but there is still limited evidence regarding whether they are related to nonspecific cervicitis. The aim of this study was to develop and evaluate a digital droplet PCR (ddPCR) assay for the detection and quantification of Ureaplasma spp. in cervical swabs.

Methods: A total of 267 non-specific cervicitis (NSC) patients and 195 asymptomatic females were included in this study. We produced standard curves for Ureaplasma spp. to evaluate the analytical performance of the ddPCR assay. Then, we detected and quantified the bacterial load of Ureaplasma spp. in cervical swabs.

Results: The prevalences of U. parvum were 37.8% (101/267) and 29.7% (58/195),  U. urealyticum were 9.0% (24/267) and 8.7% (17/195) in the NSC group and control group, respectively. In addition, the median copy number of U. parvum was 2.5 × 10 copies/ml (n = 101) in the NSC group and 9.2 × 10 copies/ml (n = 58) in the control group. The U. parvum load in the NSC group was significantly higher than that in the asymptomatic individuals (P < 0.001). whereas the median load of U. urealyticum was 8.4 × 10 copies/ml (n = 24) and 1.4 × 10 (n = 17) copies/ml in the two groups, respectively, , the difference was not statistically significant (P = 0.450).

Conclusions: Our study is the first to develop a droplet digital PCR (ddPCR) method for the detection and quantification of Ureaplasma spp. in clinical samples, and the method has excellent analytical performance and a wide range of clinical application prospects.
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http://dx.doi.org/10.1186/s12879-021-06355-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359095PMC
August 2021

Microscopic versus endoscopic microvascular decompression for the treatment of hemifacial spasm in China: A meta-analysis and systematic review.

J Clin Neurosci 2021 Sep 28;91:23-31. Epub 2021 Jun 28.

Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan 430022, China. Electronic address:

Objective: To date, microvascular decompression has become the standard surgical treatment for hemifacial spasm. Microscopic microvascular decompression (MI-MVD) and endoscopic microvascular decompression (E-MVD) are both popular with surgeons. The present study aims to investigate whether MI-MVD and E-MVD show better results as surgical treatments for hemifacial spasm in the Chinese population.

Methods: Electronic retrieval of articles on PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wanfang Database was performed to identify comparative studies on Chinese patients who underwent MI-MVD and E-MVD from January 2000 to December 2020. After data extraction and quality assessment of the included studies, a meta-analysis was performed using the Review Manager 5.4 software. The pooled incidence of patient effective rate, detection rate of offensive blood vessels, total complication rate, and recurrence rate were calculated.

Results: A total of 12 studies with 1122 patients (MI-MVD: 562, E-MVD: 560) were identified. The patient effective rate (MI-MVD: 89% vs E-MVD:97%, OR = 0.22, P < 0.00001) and detection rate of offensive blood vessels (MI-MVD:91% vs E-MVD:98%, OR = 0.17, P = 0.0002) showed patients with E-MVD were significantly higher than patients who underwent MI-MVD. However, the total complication rate (MI-MVD: 27% vs E-MVD:12%, OR = 2.92, P = 0.0002) and recurrence rates (MI-MVD:5.7% vs E-MVD:0.3%, OR = 8.8, P = 0.0005) showed patients with E-MVD were significantly lower than patients who underwent MI-MVD. In addition, the incidence of facial paralysis or weakness and hearing loss in E-MVD group was lower than that of in MI-MVD group, whereas no statistical difference was found between the two groups in terms of the incidence of cerebrospinal fluid leakage and intracranial infection.

Conclusions: While the operation of MI-MVD is relatively simple and the learning curve is short, E-MVD is better than MI-MVD in terms of treatment effect, overall complications, and recurrence rate. Therefore, E-MVD can be used as an alternative to MI-MVD in the treatment of hemifacial spasm in the Chinese population.
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http://dx.doi.org/10.1016/j.jocn.2021.06.034DOI Listing
September 2021

Telmisartan ameliorates cardiac fibrosis and diastolic function in cardiorenal heart failure with preserved ejection fraction.

Exp Biol Med (Maywood) 2021 Dec 3;246(23):2511-2521. Epub 2021 Aug 3.

Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, China.

Chronic kidney disease (CKD) is a major contributor to the development of heart failure with preserved ejection fraction (HFpEF), whereas the underlying mechanism of cardiorenal HFpEF is still elusive. The aim of this study was to investigate the role of cardiac fibrosis in a rat model of cardiorenal HFpEF and explore whether treatment with Telmisartan, an inhibitor of renin-angiotensin-aldosterone system (RAAS), can ameliorate cardiac fibrosis and preserve diastolic function in cardiorenal HFpEF. Male rats were subjected to 5/6 subtotal nephrectomy (SNX) or sham operation (Sham), and rats were allowed four weeks to recover and form a stable condition of CKD. Telmisartan or vehicle was then administered p.o. (8 mg/kg/d) for 12 weeks. Blood pressure, brain natriuretic peptide (BNP), echocardiography, and cardiac magnetic resonance imaging were acquired to evaluate cardiac structural and functional alterations. Histopathological staining, real-time polymerase chain reaction (PCR) and western blot were performed to evaluate cardiac remodeling. SNX rats showed an HFpEF phenotype with increased BNP, decreased early to late diastolic transmitral flow velocity (E/A) ratio, increased left ventricular (LV) hypertrophy and preserved ejection fraction (EF). Pathology revealed increased cardiac fibrosis in cardiorenal HFpEF rats compared with the Sham group, while chronic treatment with Telmisartan significantly decreased cardiac fibrosis, accompanied by reduced markers of fibrosis (collagen I and collagen III) and profibrotic cytokines (α-smooth muscle actin, transforming growth factor-β1, and connective tissue growth factor). In addition, myocardial inflammation was decreased after Telmisartan treatment, which was in a linear correlation with cardiac fibrosis. Telmisartan also reversed LV hypertrophy and E/A ratio, indicating that Telmisartan can improve LV remodeling and diastolic function in cardiorenal HFpEF. In conclusion, cardiac fibrosis is central to the pathology of cardiorenal HFpEF, and RAAS modulation with Telmisartan is capable of alleviating cardiac fibrosis and preserving diastolic dysfunction in this rat model.
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http://dx.doi.org/10.1177/15353702211035058DOI Listing
December 2021
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