Publications by authors named "Huan Zhao"

332 Publications

Network meta-analysis on efficacy and safety of different anti-CGRP monoclonal antibody regimens for prophylaxis and treatment of episodic migraine.

Neurol Res 2021 Jul 19:1-18. Epub 2021 Jul 19.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, PR China.

Background: Currently, studies have shown that anti-CGRP monoclonal antibodies are effective drugs for the prophylaxis and treatment of episodic migraine. Therefore, for the first time, we classified and concluded 10 treatment regimens according to the different doses, drugs, routes of administration, and courses of treatment, so as to provide a reference for further clinical studies.

Methods: We studied relevant randomized controlled trials (RCTs) published before August 2020 on PubMed, Embase, Ovid MEDLINE, Web of Science, and the Cochrane Central Register of Controlled Trials.

Results: Eleven RCTs involving 6397 patients were included in our analysis. Network meta-analysis results suggested that in the comparison of the average migraine days per month, Erenumab  (140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) were superior to placebo, Erenumab(7 mg), and the difference was statistically significant; Fremanezumab (225 mg, 675 mg) was superior to Erenumab (21 mg, 70 mg), and the difference was statistically significant; in the comparison of average medication days of acute migraine-specific drug per month, Erenumab (70 mg, 140 mg), Galcanezumab (120 mg, 240 mg), Fremanezumab (225 mg, 675 mg) was superior to placebo, and Erenumab (140 mg) and Galcanezumab (120 mg, 240 mg) were superior to Erenumab (70 mg), and the difference was statistically significant; there was no statistically significant difference in the average migraine days in the last month or in the medication days of acute migraine-specific drug.

Conclusion: Fremanezumab (225 mg) and Galcanezumab (120 mg) may be the best clinical protocol after a comprehensive assessment.
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http://dx.doi.org/10.1080/01616412.2021.1940672DOI Listing
July 2021

Decreased Physiological Serum Total Bile Acid Concentrations in Patients with Type 2 Diabetic Peripheral Neuropathy.

Diabetes Metab Syndr Obes 2021 28;14:2883-2892. Epub 2021 Jun 28.

Southwest Medical University, Luzhou, Sichuan, 646000, People's Republic of China.

Purpose: Bile acids, amphipathic cholesterol metabolites, have been reported to have cytoprotective and neuroprotective effects in humans and animal models. The relationship of physiological serum total bile acid (TBA) levels with diabetic peripheral neuropathy (DPN), however, has not been determined. The purpose of this study was to investigate the relationship between physiological serum TBA and DPN.

Patients And Methods: In total, 856 patients with type 2 diabetes mellitus (T2DM) aged 20-89 years were enrolled in this cross-sectional study. Serum TBA was measured, and its relationship with DPN and other parameters was analyzed.

Results: T2DM patients with DPN had significantly lower serum TBA compared with those without (<0.01). Serum TBA was negatively associated with glycated hemoglobin A1C, plateletcrit, fibrinogen, urine albumin-to-creatinine ratio, vibration perception thresholds, and prevalence of DPN, peripheral arterial disease, and diabetic foot ulceration after adjustment for age, sex, and body mass index (<0.01 or <0.05). A graded association with prevalence of DPN and increase in serum TBA quartiles was observed ( for trend <0.01), and there was an 48.2% decreased risk of DPN in the highest quartile of serum TBA versus the lowest quartile (95% CI 0.299-0.617; =0.000) after multivariate adjustment. Receiver-operating characteristic analysis revealed that the optimal cutoff point of serum TBA to indicate DPN was 2.85 μmol/L (sensitivity 77.6% and specificity 45.6%).

Conclusion: These findings suggest that lower physiological serum TBA level may be associated with the prevalence of DPN in T2DM patients and may be a potential biomarker for DPN.
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http://dx.doi.org/10.2147/DMSO.S313488DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254093PMC
June 2021

The effect of infertile semen on the mRNA-based body fluid identification.

Electrophoresis 2021 Jul 7. Epub 2021 Jul 7.

Department of Forensic Genetics, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu, Sichuan, P. R. China.

In the past decade, mRNA markers have been well demonstrated as promising molecular markers in forensic body fluid identification (BFI), and successfully used in wide applications. Several studies have assessed the performance of semen-specific mRNA markers in distinguishing semen from other common body fluids at the crime scene. Infertility has been reported as a global health problem that is affecting approximately 15% of couples worldwide. Therefore, it is important for forensic researchers to consider the impact of infertility on semen identification. This study aimed to explore the effect of semen from infertile men (hereinafter "infertile semen") on BFI and to identify semen-specific mRNAs that can efficiently and accurately distinguish normal and infertile semen samples from other body fluids. Results showed that the selected five mRNAs (KLK3, TGM4, SEMG1, PRM1, and PRM2) performed a significantly high semen specificity in normal semen. Moreover, KLK3 was slightly influenced by infertile semen samples with over 98% positive results in all semen samples. The accuracy to predict normal semen reached up to 96.6% using the discrimination function Y1 with KLK3 and PRM1. However, when the infertile semen samples were included in discrimination function (function Y2 with KLK3), the accuracy rate of semen identification (including the normal and infertile semen) was down to 89.5%. Besides, the sensitivity of multiplex assay could reach down to 50pg. Our results suggest that it is important to consider the presence of infertile semen when using mRNAs to identify semen samples, which would have a far-reaching impact in forensic identification.
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http://dx.doi.org/10.1002/elps.202000238DOI Listing
July 2021

Surface-Enhanced Infrared Absorption Spectroscopic Chalcogenide Waveguide Sensor Using a Silver Island Film.

ACS Appl Mater Interfaces 2021 Jul 29;13(27):32555-32563. Epub 2021 Jun 29.

Department of Electrical and Computer Engineering, Rice University, 6100 Main Street, Houston, Texas 77005, United States.

A surface-enhanced infrared absorption spectroscopic chalcogenide waveguide sensor based on the silver island film was proposed for the first time to enhance the sensing performance in both liquid and gas phases. The chalcogenide waveguide sensor was fabricated by the lift-off and oblique angle deposition methods. The surface morphology of the silver island film with different thicknesses was characterized. The absorption of ethanol (liquid) at a wavelength of 1654 nm and that of methane (gas) at 3291 nm were measured using the fabricated chalcogenide waveguide sensor. The chalcogenide waveguide sensor integrated with the 1.8 nm-thick silver island film revealed the best sensing performance. With an acceptable increased waveguide loss resulting from the fabrication of the film, the absorbance enhancement factors for ethanol and methane were experimentally obtained to be >1.5 and >2.3, respectively. The 1σ limit of detection of methane for the sensor integrated with the 1.8 nm-thick silver island film was ∼4.11% for an averaging time of 0.2 s. The mathematic relation between the absorbance enhancement factor and the waveguide loss was derived for sensing performance improvement. Also, the proposed rectangular waveguide sensor provides an idea for the design of a sensor-on-a-chip instead of other waveguide sensors with a high requirement of fabrication accuracy, for example, a slot waveguide or a photonic crystal waveguide.
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http://dx.doi.org/10.1021/acsami.1c08177DOI Listing
July 2021

Clinical application value of Inhibin B alone or in combination with other hormone indicators in subfertile men with different spermatogenesis status: A study of 324 Chinese men.

J Clin Lab Anal 2021 Jun 28:e23882. Epub 2021 Jun 28.

Department of Andrology, Jinghua Hospital of Shenyang, Shenyang, Liaoning, China.

Background: In this study, we investigated the clinical value of serum Inhibin B alone or in combination with other hormone indicators in subfertile men.

Methods: This is a multicenter study involving 324 men from different cities in China. Testicular volume, routine semen analysis, serum Inhibin B, anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, estradiol, and prolactin were measured. Testicular tissue samples were also analyzed in 78 of 129 patients with azoospermia to distinguish impaired spermatogenesis from obstructive azoospermia.

Results: The concentration of Inhibin B, FSH, and AMH is related to spermatogenesis. For men with impaired spermatogenesis, including mild-to-moderate oligozoospermia (IMO) and severe oligozoospermia (ISO), serum levels of Inhibin B and FSH are highly correlated with sperm counting. However, in patients with idiopathic moderate oligozoospermia or severe oligozoospermia, there was no significant correlation between Inhibin B (or FSH) and sperm concentration. The upper cutoff value of Inhibin B to diagnose ISO is 58.25 pg/ml with a predictive accuracy of 80.65%. To distinguish between nonobstructive azoospermia (NOA) and obstructive azoospermia (OA), the area under the curve (AUC) for AMH + Inhibin B + FSH is very similar to Inhibin B (0.943 vs. 0.941). The cutoff level of Inhibin B to diagnose nonobstructive azoospermia is 45.9 pg/ml with a positive and negative prediction accuracy of 97.70% and 85.71%, respectively.

Conclusion: In summary, Inhibin B is a promising biomarker alone or in combination with other hormone indicators for the diagnosis of testicular spermatogenesis status, helping clinical doctors to distinguish NOA from OA.
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http://dx.doi.org/10.1002/jcla.23882DOI Listing
June 2021

Subclassification of the Bethesda Category III (AUS/FLUS): A Study of thyroid FNA cytology based on ThinPrep slides from the National Cancer Center in China.

Cancer Cytopathol 2021 Jun 17. Epub 2021 Jun 17.

Department of Pathology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Background: The atypia of an undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a heterogeneous category, which includes various cell patterns. The subclassification of AUS/FLUS was suggested in the 2017 TBSRTC. However, the risk of malignancy (ROM) associated with different subgroups remains unresolved. Herein, AUS/FLUS aspirates were subclassified, from which the ROM of each subgroup was determined.

Methods: All cases undergoing fine-needle aspiration (FNA) from July 2013 to December 2018 were reviewed. Of 12,913 thyroid FNAs, 1053 (8.2%) were AUS/FLUS. The slides of 222 patients with AUS/FLUS with surgical follow-up were reviewed and subclassified according to the recommendations of the 2017 TBSRTC. There were 195 aspirates consistently diagnosed as AUS/FLUS and subclassified as cytologic atypia 1 (AUS-C1); cytologic atypia 2 (AUS-C2); architectural atypia (AUS-A); cytologic and architectural atypia (AUS-C&A); Hürthle cell aspirates (AUS-H); atypia, not otherwise specified (AUS-NOS); and atypical lymphoid cells, rule out lymphoma (AUS-L).

Results: Malignancy was identified in 83.3% (185 of 222) of the AUS/FLUS nodules. The AUS-C1 group was the most common (62.1%), followed by the AUS-C&A (12.8%), AUS-C2 (10.8%), AUS-H (6.7%), AUS-NOS (5.6%), AUS-L (1.5%), and AUS-A (0.5%) groups. AUS-C1 had the highest ROM (92.6%) among the groups and varied significantly from that of the AUS-C&A (P = .171), AUS-C2 (P = .001), AUS-H (P = .001), and AUS-NOS (P < .001) groups.

Conclusions: As a heterogeneous category of TBSRTC, the ROM for AUS/FLUS varies greatly among medical centers. Subclassification of AUS/FLUS might be helpful in identifying nodules with a high ROM in this category and improving the management of such nodules.
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http://dx.doi.org/10.1002/cncy.22417DOI Listing
June 2021

Inhibition of desmoglein-1 by aspirin leads to synthetic lethality of keratinocytes in Shuanghuanglian-induced cutaneous eruption response.

Toxicol Lett 2021 Oct 11;349:145-154. Epub 2021 Jun 11.

Chinese Materia Medica College, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China; Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China. Electronic address:

Cutaneous eruptions caused by the combination of Chinese and Western medicine have attracted widespread attention; however, the underlying mechanism remains unclear. This study aimed to evaluate the potential mechanism of cutaneous eruptions in vivo and in vitro using the combination of Shuanghuanglian injection powder (SHL) and aspirin (ASA) as an example. ASA and SHL co-administration induced inflammatory responses in HaCat cells, as evidenced by marked increases in the expression of IL-4 and TNF-α, and the level of apoptosis. Additionally, histopathological investigation of mice skin tissues showed local inflammatory cell infiltration. Western boltting was used to detect the effects of ASA on desmoglein-1 (DSG1) expression; we found that DSG1 expression was down-regulated in vivo and in vitro. Finally, the key components of SHL were administered to HaCat cells with down-regulated DSG1; it was seen that neochlorogenic acid and rutin have a significant effect on HaCat cell apoptosis. These results demonstrate that DSG1 deficiency is a potential cause of cutaneous eruptions caused by the combination of SHL and ASA, and neochlorogenic acid and rutin are the main allergenic components. This study provides a new research strategy for the safety evaluation of integrated traditional Chinese and Western medicine.
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http://dx.doi.org/10.1016/j.toxlet.2021.06.005DOI Listing
October 2021

Effects of Antihypertensive Drugs on Cognitive Function in Elderly Patients with Hypertension: A Review.

Aging Dis 2021 Jun 1;12(3):841-851. Epub 2021 Jun 1.

Department of Geriatric Medicine, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China.

Hypertension is a common comorbidity that contributes to the development of various cardiovascular disorders in elderly patients. Moreover, hypertension has been associated with cognitive decline and dementia. Cognitive impairment leads to increased morbidity and mortality in elderly patients with hypertension. However, previous studies investigating the association between blood pressure (BP), BP variability (BPV), and antihypertensive drug use and the risk of cognitive impairment in elderly patients with hypertension have reported inconsistent findings. Given the global burden of hypertension, the aging population, and the low quality of life associated with cognitive impairment, a more comprehensive understanding of the association between hypertension and cognitive decline is needed. In this review, we summarized the current preclinical evidence and clinical research regarding the association of BP control, BPV, and antihypertensive drug use and cognitive function. We particularly focused on the differences among categories of antihypertensive drugs. We concluded that the correlation of BP and risk of cognitive function is non-linear and dependent on a patient's age. Intensive BP control is generally not recommended, particularly for the oldest-old. Increased BPV and characteristics of orthostatic hypotension in the elderly also increase the risk of cognitive decline. The current evidence does not support one category of antihypertensive drugs as superior to others for preventing dementia in elderly patients with hypertension.
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http://dx.doi.org/10.14336/AD.2020.1111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8139194PMC
June 2021

Cyclic adenosine monophosphate regulates connective tissue growth factor expression in myocardial fibrosis after myocardial infarction.

J Int Med Res 2021 Jun;49(6):3000605211015586

The First Department of Cardiology, The First Hospital of Hebei Medical University, Shijiazhuang, P.R. China.

Objective: This study aimed to investigate regulation of the cyclic adenosine monophosphate (cAMP) signaling pathway on connective tissue growth factor (CTGF) during myocardial fibrosis (MF) in mice after myocardial infarction (MI).

Methods: An MI mouse model was established and cardiac function indices were detected by ultrasound. Quantitative reverse transcription polymerase chain reaction and western blotting were used to determine CTGF and transforming growth factor β1 (TGF-β1) cardiac expression. Mouse cardiac fibroblasts (MCFs) were used to study the mechanism of MF after MI.

Results: Cardiac function indices were lower after MI. Cardiac function indices were better in the MI + meglumine adenosine cyclophosphate (MAC) group than in the MI group, and CTGF expression in the MI + MAC group was downregulated. TGF-β1 expression was not different among the MI groups. Forskolin increased intracellular cAMP levels and inhibited CTGF expression in MCFs. Expression of p44/42 mitogen-activated protein kinase (MAPK) was significantly lower in the TGF-β1 + forskolin group than in the TGF-β1 group, while protein kinase A was significantly upregulated. CTGF expression was significantly lower in the TGF-β1 + forskolin + PD98509 group than in the TGF-β1 + forskolin group.

Conclusions: This study shows that cAMP upregulates protein kinase A expression through the p44/42MAPK signaling pathway and decreases p44/42MAPK phosphorylation levels, inhibiting CTGF expression.
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http://dx.doi.org/10.1177/03000605211015586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182188PMC
June 2021

Expression profile of a novel glutathione S-transferase gene in the marine polychaete Perinereis aibuhitensis in short-term responses to phenanthrene, fluoranthene, and benzo[α]pyrene.

Mar Pollut Bull 2021 May 31;169:112552. Epub 2021 May 31.

Dalian Ocean University, Dalian 116023, China.

Polychaete worms can eliminate polycyclic aromatic hydrocarbons (PAHs) in environments through a mechanism that increases their water solubility. This detoxification starts with cytochrome P450 enzymes (CYPs) and then with glutathione S-transferases (GSTs). Here, a novel GST gene was identified and characterized from the widespread polychaete Perinereis aibuhitensis. The full-length cDNA of GST is 1544 bp and encodes 256 amino acids, belonging to the omega class. Gene expression patterns in P. aibuhitensis showed that its transcriptional level was positively correlated with the concentration of benzo[α]pyrene (0.5, 2, 4, and 8 μg/L) exposure but was negatively correlated with a PAH benzene ring after it was exposed to the same mass concentrations of fluoranthene (3.2 μg/L), phenanthrene (2.9 μg/L), and benzo[α]pyrene (4.0 μg/L) during the 14-day experimentation. These findings indicate that omega GST may play an important role in the phase II detoxification of PAHs in polychaete worms, and the persistence and bioavailability of PAHs may depend on benzene rings.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112552DOI Listing
May 2021

Trace elements in children with autism spectrum disorder: A meta-analysis based on case-control studies.

J Trace Elem Med Biol 2021 Sep 21;67:126782. Epub 2021 May 21.

School of Public Health, Key Laboratory of Environmental Pollution Monitoring Control Ministry of Education, Guizhou Medical University, 550025, PR China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, 550014, PR China. Electronic address:

Autism spectrum disorder (ASD) is a common childhood neurodevelopmental disorder that may be related to trace elements. However, reports on the relationship between them are still inconsistent. In this article, we conducted a meta-analysis on this issue. We searched the PubMed, EMBASE, and Cochrane databases as of November 15, 2019. A random-effects model was used, and subgroups of studies were analyzed using samples of different measurements. Twenty-two original articles were identified (18 trace elements, including a total of 1014 children with ASD and 999 healthy controls). In autistic children, the overall levels of barium (Ba), mercury (Hg), lithium (Li), and lead (Pb) were higher. There were significant differences in the levels of copper (Cu) in the hair and serum between autistic children and the control group. The levels of Hg, Li, Pb and selenium (Se) in the hair of autistic children were higher than those of healthy children, while the levels of zinc (Zn) in the blood were lower. Excessive exposure to toxic heavy metals and inadequate intake of essential metal elements may be associated with ASD. Preventing excessive exposure to toxic metals and correcting poor dietary behaviors may be beneficial for the prevention and treatment of the disease.
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http://dx.doi.org/10.1016/j.jtemb.2021.126782DOI Listing
September 2021

Diisoprenyl-cyclohexene/ane-Type Meroterpenoids from sp. and Their Anti-inflammatory Activities.

J Org Chem 2021 May 27. Epub 2021 May 27.

Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, Jinan University, Guangzhou 510632, People's Republic of China.

A secondary metabolites investigation on sp. 71-10-1-1 was carried out, which led to the obtention of nine new diisoprenyl-cyclohexene/ane-type meroterpenoids (-) and two new isoprenylbenzoic acid-type meroterpeniods (-). The structures of these isolates were established on the basis of multispectroscopic analyses, ECD, and C chemical shifts calculations, and single-crystal X-ray diffraction. Among them, biscognin A () is the first diisoprenyl-cyclohexene-type meroterpenoid with a unique 2-isopropyl-6'-methyloctahydro-1'-spiro[cyclopropane-1,2'-naphthalene] skeleton. Biscognienyne F () is the first diisoprenyl-cyclohexene-type meroterpenoid with a cyclic carbonate. The anti-inflammatory assays of the majority of compounds were evaluated, which exhibited that compounds and can obviously inhibit pro-inflammatory cytokines TNF-α and IL-6 productions. This is the first report for diisoprenyl-cyclohexene-type meroterpenoids with anti-inflammatory activity. Moreover, the possible biogenetic pathways of the majority of compounds (-) are proposed.
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http://dx.doi.org/10.1021/acs.joc.1c00369DOI Listing
May 2021

Facet-controlled palladium nanocrystalline for enhanced nitrate reduction towards ammonia.

J Colloid Interface Sci 2021 Oct 14;600:620-628. Epub 2021 May 14.

Key Laboratory of Eco-chemical Engineering, Key Laboratory of Optic-electric Sensing and Analytical Chemistry of Life Science, Taishan Scholar Advantage and Characteristic Discipline Team of Eco Chemical Process and Technology, College of Chemistry and Molecular Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China; Shandong Engineering Research Center for Marine Environment Corrosion and Safety Protection, College of Environment and Safety Engineering, Qingdao University of Science and Technology, Qingdao 266042, PR China. Electronic address:

Electrochemical nitrate reduction reaction (NORR) is considered an appealing way for producing ammonia (NH) under ambient conditions and solving environmental problems caused by nitrate, whereas the lack of adequate catalysts hampers the development of NORR. Here, we firstly demonstrate that the Pd nanocrystalline with a well-desired facet can act as a highly efficient NORR electrocatalyst for ambient ammonia synthesis. Pd (1 1 1) exhibits excellent activity and selectivity in reducing NO to NH with a Faradaic efficiency of 79.91% and an NH production of 0.5485 mmol h cm (2.74 mmol h mg) in 0.1 M NaSO (containing 0.1 M NO), which is 1.4 times higher than Pd (1 0 0) and 1.9 times higher than Pd (1 1 0), respectively. Density functional theory (DFT) calculation reveals that the superior NORR activity of Pd (1 1 1) originates from its optimized activity of NO adsorption, smaller free energy change of the rate-limiting step (*NH to NH), and poorer hydrogen evolution reaction activity (HER, competitive reaction). This work not only highlights the potentials of Pd-based nanocatalysts for NORR but also provides new insight for the applications in NORR of other facet-orientation nanomaterials.
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http://dx.doi.org/10.1016/j.jcis.2021.05.061DOI Listing
October 2021

LncRNA GAS5 modulates the progression of non-small cell lung cancer through repressing miR-221-3p and up-regulating IRF2.

Diagn Pathol 2021 May 22;16(1):46. Epub 2021 May 22.

Department of Respiration, The Sixth People's Hospital of Nantong, Yonghe road No.500, 226011, Nantong, Jiangsu, China.

Background: Long non-coding RNA growth arrest specific 5 (GAS5) is a regulator in non-small cell lung cancer (NSCLC) progression. Nonetheless, the mechanism by which GAS5 exerts its biological function in NSCLC cells remains unclear.

Methods: GAS5, miR-221-3p relative expression levels in NSCLC tissues and cells were examined by qPCR. After gain-of-function and loss-of-function models were established, the viability of H1299 and A549 cells were examined by CCK-8 and EdU assays. Cell migration and invasion were examined by the Transwell experiment. The binding sequence of GAS5 for miR-221-3p was confirmed by the dual-luciferase reporter gene experiment. The regulatory function of GAS5 and miR-221-3p on IRF2 was investigated by Western blot.

Results: GAS5 expression was down-modulated in NSCLC tissues and cell lines. GAS5 overexpression restrained the proliferation, migration and invasion of NSCLC cells, while miR-221-3p, which was targeted and negatively modulated by GAS5, worked oppositely. Restoration of miR-221-3p markedly reversed the effects of GAS5 on NSCLC cells. Additionally, GAS5 increased IRF2 expression in NSCLC cells by repressing miR-221-3p.

Conclusions: GAS5 blocks the progression of NSCLC partly via increasing IRF2 expression level via repressing miR-221-3p.
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http://dx.doi.org/10.1186/s13000-021-01108-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140465PMC
May 2021

Genetic fate-mapping reveals surface accumulation but not deep organ invasion of pleural and peritoneal cavity macrophages following injury.

Nat Commun 2021 05 17;12(1):2863. Epub 2021 May 17.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.

During injury, monocytes are recruited from the circulation to inflamed tissues and differentiate locally into mature macrophages, with prior reports showing that cavity macrophages of the peritoneum and pericardium invade deeply into the respective organs to promote repair. Here we report a dual recombinase-mediated genetic system designed to trace cavity macrophages in vivo by intersectional detection of two characteristic markers. Lineage tracing with this method shows accumulation of cavity macrophages during lung and liver injury on the surface of visceral organs without penetration into the parenchyma. Additional data suggest that these peritoneal or pleural cavity macrophages do not contribute to tissue repair and regeneration. Our in vivo genetic targeting approach thus provides a reliable method to identify and characterize cavity macrophages during their development and in tissue repair and regeneration, and distinguishes these cells from other lineages.
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http://dx.doi.org/10.1038/s41467-021-23197-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129080PMC
May 2021

A SCID mouse-human lung xenograft model of SARS-CoV-2 infection.

Theranostics 2021 3;11(13):6607-6615. Epub 2021 May 3.

State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, Fujian, P. R. China.

SARS-CoV-2 infection, which is responsible for the current COVID-19 pandemic, can cause life-threatening pneumonia, respiratory failure and even death. Characterizing SARS-CoV-2 pathogenesis in primary human target cells and tissues is crucial for developing vaccines and therapeutics. However, given the limited access to clinical samples from COVID-19 patients, there is a pressing need for models to investigate authentic SARS-CoV-2 infection in primary human lung cells or tissues with mature structures. The present study was designed to evaluate a humanized mouse model carrying human lung xenografts for SARS-CoV-2 infection . Human fetal lung tissue surgically grafted under the dorsal skin of SCID mice were assessed for growth and development after 8 weeks. Following SARS-CoV-2 inoculation into the differentiated lung xenografts, viral replication, cell-type tropism and histopathology of SARS-CoV-2 infection, and local cytokine/chemokine expression were determined over a 6-day period. The effect of IFN-α treatment against SARS-CoV-2 infection was tested in the lung xenografts. Human lung xenografts expanded and developed mature structures closely resembling normal human lung. SARS-CoV-2 replicated and spread efficiently in the lung xenografts with the epithelial cells as the main target, caused severe lung damage, and induced a robust pro-inflammatory response. IFN-α treatment effectively inhibited SARS-CoV-2 replication in the lung xenografts. These data support the human lung xenograft mouse model as a useful and biological relevant tool that should facilitate studies on the pathogenesis of SARS-CoV-2 lung infection and the evaluation of potential antiviral therapies.
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http://dx.doi.org/10.7150/thno.58321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120224PMC
May 2021

Novel Biallelic Variations Cause Multiple Morphological Abnormalities of the Sperm Flagella.

DNA Cell Biol 2021 Jun 14;40(6):833-840. Epub 2021 May 14.

Department of Ophthalmology, Xiang'an Hospital of Xiamen University; Fujian Provincial Key Laboratory of Ophthalmology and Visual Science; Fujian Engineering and Research Center of Eye Regenerative Medicine; Eye Institute of Xiamen University; School of Medicine, Xiamen University, Xiamen, Fujian, China.

Sperm motility is vital to human reproduction, and malformed sperm flagella can cause male infertility. Individuals with multiple morphological abnormalities of the flagella mostly have absent, short, coiled, bent, and/or irregular-caliber flagella. In this study, a patient with male infertility underwent a physical examination along with his wife. Genetic testing was performed by whole-exome sequencing of the couple, and Sanger sequencing was performed for validation. Novel biallelic variations in the : (NM_015512.4) gene consisting of c.1336G>C (p.E446Q) and c.2912G>A (p.R971H) were identified. structural analysis revealed that the amino acid residues affected by the variation were evolutionarily conserved, and the variant p.R971H influenced the stability of the DNAH1 protein. Morphological studies of the patient's sperm showed defects in its flagella. Results of Papanicolaou staining and scanning electron microscopy demonstrated coiled and short flagella with multiple anomalies. Transmission electron microscopy of the sperm flagella showed that the inner dynein arm and radial spoke were absent, and the dense fiber and microtubule doublets were displaced. Quantitative PCR of the mRNA of the patient's sperm showed that the expression of was dramatically reduced. Collectively, these findings elucidated the genetic cause of the family's infertility and provided insight into the functioning of the gene.
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http://dx.doi.org/10.1089/dna.2021.0097DOI Listing
June 2021

Study on life histroy traits of Stellera chamaejasme provide insights into its control on degraded typical steppe.

J Environ Manage 2021 Aug 3;291:112716. Epub 2021 May 3.

College of Grassland Science and Technology, China Agricultural University, Beijing, 100193, China; GuYuan National Grassland Ecosystem Field Station, Hebei Province, 076550, China. Electronic address:

The increase of unpalatable Stellera chamaejasme plants has become commonplace in degraded grasslands of China, which can hinder the establishment and growth of palatable plants and have an impact on sustainable development of livestock production. Controlling S. chamaejasme is thus a necessary, yet usually problematic step towards the degraded grassland. Various measures have been implemented to control S. chamaejasme but relatively little is known about the growth and development of S. chamaejasme in degraded grassland. Therefore, focusing on the life history traits of S. chamaejasme can provide theoretical support underpinning its management. In this study, different age classes of S. chamaejasme plants were surveyed and studied from a degraded typical steppe in China, and the variation of the phenotypic traits, biomass increasement, biomass allocation, reserves and nutrient content were described. These analyses could be of great importance in identifying the management practices of S. chamaejasme that are most consistent with the development of S. chamaejasme in degraded grasslands. We found that most of the phenotypic traits and biomass of all organs increased by different patterns with age class. Like many other species, there has been three developmental phases in S. chamaejasme, however, previous researches only focus on the S. chamaejasme in the adult reproductive phase, therefore leading to a delay between the time of S. chamaejasme's seedling and the time when it begins to establish. Our findings demonstrate that S. chamaejasme mainly distributes the biomass to belowground part (RMF and SMF), which is conducive to the survival of S. chamaejasme on degraded grasslands, making mowing fail to eradicate S. chamaejasme in practice. Partial least squares path modeling suggested that nutrient content (N) played a key role in flowering of S. chamaejasme, but the indirect effect was greater than direct effect. The results from this study highlight that control efforts and the management of S. chamaejasme should not only focus on the S. chamaejasme individual in unreproductive phase, but also on the belowground part of plant in reproductive phase.
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http://dx.doi.org/10.1016/j.jenvman.2021.112716DOI Listing
August 2021

Antiangiogenic Effect of Platelet P2Y Inhibitor in Ischemia-Induced Angiogenesis in Mice Hindlimb.

Biomed Res Int 2021 8;2021:5529431. Epub 2021 Apr 8.

Clinical Laboratory, People's Hospital Affiliated to Jiangsu University, Zhenjiang 212002, China.

Purpose: Postischemic inflammation induces angiogenesis, while platelet P2Y inhibitors can alleviate this inflammation. Therefore, we studied the potential effects of P2Y inhibitor, ticagrelor, on angiogenesis in a mouse model of hindlimb ischemia.

Methods: Laser Doppler perfusion imaging and capillary density measurement were used for angiogenesis quantified. Immunofluorescence was used to detect the level of CD31. The mice muscle was harvested for enzyme-linked immunosorbent (ELISA) assay of interleukin- (IL) 10 activity and Western blot determination of vascular endothelial growth factor (VEGF) production.

Results: Ischemic hindlimb angiogenesis was sharply decreased in IL-10 mice than IL-10 mice. Ticagrelor inhibited angiogenesis and blood reperfusion recovery significantly elevated the levels of IL-10 and decreased the expression of VEGF in the IL-10 mouse ischemic hindlimb, which were abolished in IL-10-deficient (IL-10) C57BL/6J mice.

Conclusion: The study underscores that the effect of ticagrelor antiangiogenic function is related with the higher IL-10 expression.
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http://dx.doi.org/10.1155/2021/5529431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052144PMC
May 2021

Computer-aided superimposition of the frontal sinus via 3D reconstruction for comparative forensic identification.

Int J Legal Med 2021 Apr 22. Epub 2021 Apr 22.

Department of Forensic Genetics, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, No. 3, 17 South Renmin Road, Wuhou District, Sichuan Province, Chengdu, People's Republic of China.

The anatomical uniqueness of the frontal sinus morphology has been widely used for comparative forensic identification using various techniques, mostly including 2D X-rays or one fixed slice of an axial computed tomography (CT) scan image. However, computer-aided 3D automatic graphical comparison techniques can provide accurate comparisons between two 3D models that allow users to comply with even the strictest deviation standards, avoiding error-prone identification of frontal sinuses with similar morphologies. The study proposes the use of a computer-aided comparative paradigm based on the 3D-3D frontal sinus model superimposition process and further assesses the anatomical uniqueness of frontal sinuses using a large Chinese Han sample. Three hundred thirty-six patients older than 20 years with two multi-slice CT scans were collected. Frontal sinus 3D models were semi-automatically segmented through Dolphin Imaging software. Automatic pairwise comparisons of 336 matched pairs from the same person and 340 mismatched pairs from different individuals with an analysis of average root mean square (RMS) point-to-point distance were performed using Geomagic Studio Qualify software. RMS ranged between 0.005 and 1.032 (mean RMS 0.390 ± 0.25 mm) in the group of matches and between 1.107 and 19.363 (mean RMS 4.49 ± 2.69 mm) in the group of mismatches. On average, the RMS value was over ten-fold greater in mismatches than in matches. Statistically significant differences in RMS between the group of matches and mismatches were assessed using the Mann-Whitney U test (p < 0.05). This study supports the value of the frontal sinus with a 3D computer-aided superimposition method for human identification with large samples when DNA, fingerprints, and dental materials are not accessible.
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http://dx.doi.org/10.1007/s00414-021-02585-0DOI Listing
April 2021

Damage to the central nucleus of the thalamus via atypical Holmes tremor: a case report.

J Int Med Res 2021 Apr;49(4):300060521999567

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, PR China.

Holmes tremor (HT) is a rare symptomatic movement disorder characterized by a combination of resting, postural, and action tremors. HT is usually caused by lesions in the brain stem, thalamus, and cerebellum, and the pathogenesis is believed to be related to the nigrostriatal pathway and/or the cerebello-thalamo-cortical pathway. Many medications have been used to treat HT with various degrees of effectiveness. We herein present a case involving an elderly woman who developed atypical HT 23 months after cerebral hemorrhage. The atypical HT manifested as a tremor of the right limb with involuntary flexion of the distal five fingers of the right upper limb. Imaging findings suggested the existence of an old hemorrhage in the left thalamus. Specifically, diffusion tensor imaging data of the whole brain and multimodal three-dimensional medical imaging revealed significant white matter microstructural changes in the centromedian nucleus of the left thalamus. Treatment with high-dose oral levodopa was not efficient, but the symptoms gradually decreased in severity and disappeared 1 month after switching to oral clonazepam treatment.
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http://dx.doi.org/10.1177/0300060521999567DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024459PMC
April 2021

Sodium Selenite Attenuates Balloon Injury-Induced and Monocrotaline-Induced Vascular Remodeling in Rats.

Front Pharmacol 2021 15;12:618493. Epub 2021 Mar 15.

Department of Cardiology, Lishui Hospital of Zhejiang University, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui Municipal Central Hospital, Lishui, China.

Vascular remodeling (VR), induced by the massive proliferation and reduced apoptosis of vascular smooth muscle cells (VSMCs), is primarily responsible for many cardiovascular conditions, such as restenosis and pulmonary arterial hypertension. Sodium selenite (SSE) is an inorganic selenium, which can block proliferation and stimulate apoptosis of tumor cells; still, its protective effects on VR remains unknown. In this study, we established rat models with carotid artery balloon injury and monocrotaline induced pulmonary arterial hypertension and administered them SSE (0.25, 0.5, or 1 mg/kg/day) orally by feeding tube for 14 consecutive days. We found that SSE treatment greatly ameliorated the development of VR as evidenced by an improvement of its characteristic features, including elevation of the ratio of carotid artery intimal area to medial area, right ventricular hypertrophy, pulmonary arterial wall hypertrophy and right ventricular systolic pressure. Furthermore, PCNA and TUNEL staining of the arteries showed that SSE suppressed proliferation and enhanced apoptosis of VSMCs in both models. Compared with the untreated VR rats, lower expression of PCNA and CyclinD1, but higher levels of Cleaved Caspase-3 and Bax/Bcl-2 were observed in the SSE-treated rats. Moreover, the increased protein expression of MMP2, MMP9, p-AKT, p-ERK, p-GSK3β and β-catenin that occurred in the VR rats were significantly inhibited by SSE. Collectively, treatment with SSE remarkably attenuates the pathogenesis of VR, and this protection may be associated with the inhibition of AKT and ERK signaling and prevention of VSMC's dysfunction. Our study suggest that SSE is a potential agent for treatment of VR-related diseases.
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http://dx.doi.org/10.3389/fphar.2021.618493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005533PMC
March 2021

Pre-existing beta cells but not progenitors contribute to new beta cells in the adult pancreas.

Nat Metab 2021 03 15;3(3):352-365. Epub 2021 Mar 15.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences; University of Chinese Academy of Sciences, Shanghai, China.

It has been suggested that new beta cells can arise from specific populations of adult pancreatic progenitors or facultative stem cells. However, their existence remains controversial, and the conditions under which they would contribute to new beta-cell formation are not clear. Here, we use a suite of mouse models enabling dual-recombinase-mediated genetic tracing to simultaneously fate map insulin-positive and insulin-negative cells in the adult pancreas. We find that the insulin-negative cells, of both endocrine and exocrine origin, do not generate new beta cells in the adult pancreas during homeostasis, pregnancy or injury, including partial pancreatectomy, pancreatic duct ligation or beta-cell ablation with streptozotocin. However, non-beta cells can give rise to insulin-positive cells after extreme genetic ablation of beta cells, consistent with transdifferentiation. Together, our data indicate that pancreatic endocrine and exocrine progenitor cells do not contribute to new beta-cell formation in the adult mouse pancreas under physiological conditions.
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http://dx.doi.org/10.1038/s42255-021-00364-0DOI Listing
March 2021

Retrospective assessment of at-risk myocardium in reperfused acute myocardial infarction patients using contrast-enhanced balanced steady-state free-precession cardiovascular magnetic resonance at 3T with SPECT validation.

J Cardiovasc Magn Reson 2021 03 15;23(1):25. Epub 2021 Mar 15.

Biomedical Imaging Research Institute, Cedars Sinai Medical Center, Los Angeles, CA, 90048, USA.

Background: Contrast-enhanced (CE) steady-state free precession (SSFP) CMR at 1.5T has been shown to be a valuable alternative to T2-based methods for the detection and quantifications of area-at-risk (AAR) in acute myocardial infarction (AMI) patients. However, CE-SSFP's capacity for assessment of AAR at 3T has not been investigated. We examined the clinical utility of CE-SSFP and T2-STIR for the retrospective assessment of AAR at 3T with single-photon-emission-computed tomography (SPECT) validation.

Materials And Methods: A total of 60 AMI patients (ST-elevation AMI, n = 44;  non-ST-elevation AMI, n = 16) were recruited into the CMR study between 3 and 7 days post revascularization. All patients underwent T2-STIR, CE-bSSFP and late-gadolinium-enhancement CMR. For validation, SPECT images were acquired in a subgroup of patients (n = 30).

Results: In 53 of 60 patients (88 %), T2-STIR was of diagnostic quality compared with 54 of 60 (90 %) with CE-SSFP. In a head-to-head per-slice comparison (n = 365), there was no difference in AAR quantified using T2-STIR and CE-SSFP (R = 0.92, p < 0.001; bias:-0.4 ± 0.8 cm, p = 0.46). On a per-patient basis, there was good agreement between CE-SSFP (n = 29) and SPECT (R = 0.86, p < 0.001; bias: - 1.3 ± 7.8 %LV, p = 0.39) for AAR determination. T2-STIR also showed good agreement with SPECT for AAR measurement (R = 0.81, p < 0.001, bias: 0.5 ± 11.1 %LV, p = 0.81). There was also a strong agreement between CE-SSFP and T2-STIR with respect to the assessment of AAR on per-patient analysis (R = 0.84, p < 0.001, bias: - 2.1 ± 10.1 %LV, p = 0.31).

Conclusions: At 3T, both CE-SSFP and T2-STIR can retrospectively quantify the at-risk myocardium with high accuracy.
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http://dx.doi.org/10.1186/s12968-021-00730-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958470PMC
March 2021

The Allocation of Water Resources in the Midstream of Heihe River for the "97 Water Diversion Scheme" and the "Three Red Lines".

Int J Environ Res Public Health 2021 02 16;18(4). Epub 2021 Feb 16.

Shaanxi Key Laboratory of Earth Surface System and Environmental Carrying Capacity, College of Urban and Environmental Sciences, Northwest University, Xi'an 710127, China.

Rapid economic and societal development increases resource consumption. Understanding how to balance the discrepancy between economic and social water use and ecological water use is an urgent problem to be solved, especially in arid areas. The Heihe River is the second-largest inland river in China, and this problem is notable. To ensure the downstream ecological water use, the "Water Distribution Plan for the Mainstream of the Heihe River" (97 Water Diversion Scheme) controls the discharge of Yingluo Gorge and Zhengyi Gorge, while the "Opinions of applying the strictest water resources control system" (Three Red Lines) restricts the water use. With the development of the economy and agriculture in the midstream, Zhengyi Gorge's discharge cannot reach the Heihe River's ecological water downstream. This paper is under the constraints of the "97 Water Diversion Scheme" of Heihe River and the "Three Red Lines" of the total water use control index for Zhangye County. We constructed a water resource allocation model for the midstream of Heihe River to reasonably allocate water resources in the Heihe River's midstream and downstream. This model is divided into three parts: Establish the mathematical equation, simulate the water consumption under the different inflow conditions, and ensure each water user's demand. The result showed that if we fail to confine total water consumption in the midstream, through the reasonable allocation of water resources, the real water use and water consumption of the middle Heihe River will be greater than the "97 Water Diversion Scheme" and the "Three Red Lines." If we confine water consumption, they will be within the "97 Water Diversion Scheme" and the "Three Red Lines," at the same time, they can reach the downstream of the Heihe River's ecological water. Besides, under the premise of satisfying the economic water and ecological water downstream of the Heihe River, returning farmland to wasteland and strengthening water-saving measures will improve water efficiency and be more conducive to allocating water resources.
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http://dx.doi.org/10.3390/ijerph18041887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7919795PMC
February 2021

Electrophysiological characterization of photoreceptor-like cells in human inducible pluripotent stem cell-derived retinal organoids during in vitro maturation.

Stem Cells 2021 Jul 8;39(7):959-974. Epub 2021 Mar 8.

Eye Center, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People's Republic of China.

Retinal organoids (ROs) derived from human inducible pluripotent stem cells (hiPSCs) exhibit considerable therapeutic potential. However, current quality control of ROs during in vitro differentiation is largely limited to the detection of molecular markers, often by immunostaining, polymerase chain reaction (PCR) assays and sequencing, often without proper functional assessments. As such, in the current study, we systemically characterized the physiological maturation of photoreceptor-like cells in hiPSC-derived ROs. By performing patch-clamp recordings from photoreceptor-like cells in ROs at distinct differentiation stages (ie, Differentiation Day [D]90, D150, and D200), we determined the electrophysiological properties of the plasma membrane and several characteristic ion channels closely associated with the physiological functions of the photoreceptors. Ionic hallmarks, such as hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and cyclic nucleotide-gated (CNG) channels, matured progressively during differentiation. After D200 in culture, these characteristic currents closely resembled those in macaque or human native photoreceptors. Furthermore, we demonstrated that the hyperpolarization-activated inward current/depolarization-activated outward current ratio (I /I ), termed as the inward-outward current (IOC) ratio hereon, accurately represented the maturity of photoreceptors and could serve as a sensitive indicator of pathological state. Thus, this study provides a comprehensive dataset describing the electrophysiological maturation of photoreceptor-like cells in hiPSC-derived ROs for precise and sensitive quality control during RO differentiation.
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http://dx.doi.org/10.1002/stem.3363DOI Listing
July 2021

Machine-learning-enhanced time-of-flight mass spectrometry analysis.

Patterns (N Y) 2021 Feb 21;2(2):100192. Epub 2021 Jan 21.

Max-Planck-Institut für Eisenforschung, Max-Planck-Strasse 1, 40237 Düsseldorf, Germany.

Mass spectrometry is a widespread approach used to work out what the constituents of a material are. Atoms and molecules are removed from the material and collected, and subsequently, a critical step is to infer their correct identities based on patterns formed in their mass-to-charge ratios and relative isotopic abundances. However, this identification step still mainly relies on individual users' expertise, making its standardization challenging, and hindering efficient data processing. Here, we introduce an approach that leverages modern machine learning technique to identify peak patterns in time-of-flight mass spectra within microseconds, outperforming human users without loss of accuracy. Our approach is cross-validated on mass spectra generated from different time-of-flight mass spectrometry (ToF-MS) techniques, offering the ToF-MS community an open-source, intelligent mass spectra analysis.
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http://dx.doi.org/10.1016/j.patter.2020.100192DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892357PMC
February 2021

Hypoxic Tumor Radiosensitization Using Engineered Probiotics.

Adv Healthc Mater 2021 05 28;10(10):e2002207. Epub 2021 Feb 28.

Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.

Owing to their ability to rapidly proliferate in specific niches and their amenability to genetic manipulation, bacteria are frequently studied as potential diagnostic or therapeutic bioagents in a range of pathological contexts. A sustained oxygen supply within solid tumors is essential in order to achieve positive radiotherapy (RT) outcomes, as these intratumoral oxygen levels are necessary to facilitate RT-induced reactive oxygen species (ROS) generation. In this study, a genetically engineered variant of the tumor-targeting probiotic E. coli Nissle 1917 bacteria that secret catalase is utilized to alleviate intratumoral hypoxia and to thereby enhance tumor radiosensitivity. These engineered bacteria are able to facilitate robust O evolution and consequent ROS generation in response to X-ray irradiation both in vitro and in vivo, significantly inhibiting tumor growth. Overall, the study highlights a novel and practical approach to enhance the efficacy of tumor RT, underscoring the value of future research in the field of probiotic medicine.
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http://dx.doi.org/10.1002/adhm.202002207DOI Listing
May 2021

A suite of new Dre recombinase drivers markedly expands the ability to perform intersectional genetic targeting.

Cell Stem Cell 2021 06 9;28(6):1160-1176.e7. Epub 2021 Feb 9.

State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, 100 Haike Road, Shanghai 201210, China; School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China; Institute for Stem Cell and Regeneration, Chinese Academy of Sciences, Beijing 100101, China. Electronic address:

The use of the dual recombinase-mediated intersectional genetic approach involving Cre-loxP and Dre-rox has significantly enhanced the precision of in vivo lineage tracing, as well as gene manipulation. However, this approach is limited by the small number of Dre recombinase driver constructs available. Here, we developed more than 70 new intersectional drivers to better target diverse cell lineages. To highlight their applicability, we used these new tools to study the in vivo adipogenic fate of perivascular progenitors, which revealed that PDGFRa but not PDGFRaPDGFRb perivascular cells are the endogenous progenitors of adult adipocytes. In addition to lineage tracing, we used members of this new suite of drivers to more specifically knock out genes in complex tissues, such as white adipocytes and lymphatic vessels, that heretofore cannot be selectively targeted by conventional Cre drivers alone. In summary, these new transgenic tools expand the intersectional genetic approach while enhancing its precision.
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http://dx.doi.org/10.1016/j.stem.2021.01.007DOI Listing
June 2021

Ultrasensitive chemiluminescence immunoassay with enhanced precision for the detection of cTnI amplified by acridinium ester-loaded microspheres and internally calibrated by magnetic fluorescent nanoparticles.

Nanoscale 2021 Feb 3;13(5):3275-3284. Epub 2021 Feb 3.

State Key Laboratory of Bioelectronics, National Demonstration Center for Experimental Biomedical Engineering Education, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

A novel enhanced chemiluminescent immunoassay (CLIA) for ultrasensitive and excellent precisive determination of cardiac troponin I (cTnI) was reported. The method made full use of poly[(N-isopropyl acrylamide)-co-(methacrylic acid)] (P(NIPAM-co-MAA)) microspheres as new potential signal enhancers and magnetic fluorescent nanoparticles as internal standards for better precision. This protocol involved a sandwich format, in which the antigen in the sample was captured by the immobilized antibodies on the surface of magnetic fluorescent beads and recognized by the other antibodies labeled with acridinium ester (AE)-loaded P(NIPAM-co-MAA) microspheres. The combination of the remarkable sensitivity of the enhanced CLIA method and the use of P(NIPAM-co-MAA) microspheres as anti-cTnI carriers for acridinium ester signal amplification provided an extremely sensitive limit of blank (LoB) at 0.097 pg mL, a limit of detection (LoD) at 0.116 pg mL, and a limit of quantitation (LoQ) at 0.606 pg mL, much greater than those achieved by the classical chemiluminescence immunoassay (CLIA, Getein). Moreover, the intra-day variable coefficient can be improved to 1.21-2.12%, and inter-day variability was 2.01-3.49% under the application of magnetic fluorescent beads as an internal standard. The sensitivity and precision have reached a high level, comparable with the current commercial detection kits. The results showed a good correlation with a commercial chemiluminescence assay (CLIA, Abbott), with a correlation coefficient of 0.9883. This proposed method has been successfully applied to the clinical determination of cTnI in the human serum.
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http://dx.doi.org/10.1039/d0nr08008jDOI Listing
February 2021