Publications by authors named "Jing Gao"

1,369 Publications

  • Page 1 of 1

Accumulation, distribution and removal of triazine pesticides by Eichhornia crassipes in water-sediment microcosm.

Ecotoxicol Environ Saf 2021 May 12;219:112236. Epub 2021 May 12.

Institute for the Control of Agrochemicals, Ministry of Agriculture and Rural Affairs (ICAMA), No. 22 Maizidian Street, Chaoyang, Beijing 100125, China. Electronic address:

After application, pesticides remained in the field may contaminate water resources through surface runoff and leaching, posing a threat to aquatic ecosystem. In the current study, the accumulation, translocation, distribution and removal of four triazine pesticides (simazine, atrazine, terbuthylazine and metribuzin) by free floating aquatic plant Eichhornia crassipes (E. crassipes) in water-sediment microcosm were investigated and the removal mechanisms were explored. E. crassipes was exposed to an initial concentration of 50 μg·L and the pesticide levels in water, sediment, roots and shoots of E. crassipes were monitored during 30 days. The results demonstrated that E. crassipes was capable of accumulating triazine pesticides with the bio-concentration factor (BCF) ranging from 0.8 to 18.4. Triazine pesticides were mainly stored in roots, and root accumulation and translocation amount depend on the hydrophobicity of the pesticides. The removal of the pesticides in water were significantly accelerated by the presence of E. crassipes, with the removal efficiency ranging from 66% to 79% after 30 days of treatment. Though phytoaccumulation only constituted 2-18% of the total spiked pesticides in the microcosm, E. crassipes played a vital role in removing simazine, atrazine and metribuzin. However, microbial degradation in sediment was the main pathway for the removal of terbuthylazine in the microcosm. This study demonstrated the potential application of E. crassipes to accelerate removal of contaminants from aquatic environment.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112236DOI Listing
May 2021

Combined effects of volume ratio and nitrate recycling ratio on nutrient removal, sludge characteristic and microbial evolution for DPR optimization.

J Environ Sci (China) 2021 Jun 17;104:69-83. Epub 2020 Dec 17.

College of Environmental Science and Engineering, Yangzhou University, Yangzhou 225127, China. Electronic address:

The optimization of volume ratio (V/V/V) and nitrate recycling ratio (R) in a two-sludge denitrifying phosphorus removal (DPR) process of Anaerobic Anoxic Oxic-Moving Bed Biofilm Reactor (A/O-MBBR) was investigated. The results showed that prolonged anaerobic retention time (HRT: 1.25→3.75 hr) exerted favorable effect on chemical oxygen demand (COD) removal (57.26%→73.54%), poly-β-hydroxyalkanoates (PHA) synthesis (105.70→138.12 mgCOD/L) and PO release (22.3→38.9 mg/L). However, anoxic retention time (HRT) and R exhibited positive correlation with PHA utilization (43.87%-81.34%) and denitrifying phosphorus removal (DPR) potential (ΔNO/ΔPO: 0.57-1.34 mg/mg), leading to dramatical TN removal variations from 68.86% to 81.28%. Under the V/V/V ratio of 2:6:0, sludge loss deteriorated nutrient removals but the sludge bioactivity quickly recovered when the oxic zone was recovered. The sludge characteristic and microstructure gradually transformed under the dissolved oxygen (DO) control (1.0-1.5→1.5-2.0 mg/L), in terms of sludge volume index (SVI: 194→57 mL/gVSS), median-particle-size (D: 99.6→300.5 μm), extracellular polymeric substances (EPS) (105.62→226.18 mg/g VSS) and proteins/polysaccharides (PN/PS) ratio (1.52→3.46). Fluorescence in situ hybridization (FISH) results showed that phosphorus accumulation organisms (PAOs) (mainly Cluster I of Accumulibacter, contribution ratio: 91.79%-94.10%) dominated the superior DPR performance, while glycogen accumulating organisms (GAOs) (mainly Competibacter, contribution ratio: 82.61%-86.89%) was responsible for deteriorative TN and PO removals. The optimal HRT and R assembled around 5-6.5 hr and 300%-400% based on the PHA utilization and DRP performance, and the oxic zones also contributed to PO removal although it showed low dependence on DO concentration and oxic retention time (HRT).
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http://dx.doi.org/10.1016/j.jes.2020.12.003DOI Listing
June 2021

Reliability of Performing Multiparametric Ultrasound in Adult Livers.

J Ultrasound Med 2021 May 13. Epub 2021 May 13.

Rocky Vista University, Ivins, Utah, USA.

Purpose: The aim of the study was to test inter-observer and intra-observer reliability of measuring multiparametric ultrasound in adult livers.

Methods: We prospectively measured shear wave velocity (SWV, m/s), shear wave dispersion slope (SWD, m/s/kHz), attenuation coefficient (ATI, dB/cm/MHz), normalized local variance (NLV), and echo intensity ratio of liver to kidney (L/K ratio) in 21 adults who underwent liver magnetic resonance imaging-proton density fat fraction (MRI-PDFF). Intraclass correlation coefficient and 95% Bland-Altman limits of agreement (95% LOA) were used to analyze intra- and inter-observer reproducibility.

Results: Based on liver MRI-PDFF, 21 participants (8 men and 13 women, mean age 55 years) were divided into group 1 (11 normal livers, MRI-PDFF <5%) and group 2 (10 steatotic livers, MRI-PDFF ≥5%). ICCs for intra-observer repeatability and inter-observer reproducibility in measuring multiple ultrasound parameters in both normal and steatotic livers were above 0.75. However, 95% confidence interval for measuring SWD in all livers and L/K ratio in normal livers was 0.38-0.90 and 0.47-0.91, respectively. Differences in SWV, SWD, ATI, NLV, L/K ratio, and MRI-PDFF between participants with and without hepatic steatosis were significant (p < .05), whereas serum biomarkers and body mass index were not (p > .05), based on a two-tailed t-test.

Conclusions: The results suggest that the repeatability and reproducibility for measuring liver SWV, ATI, and NLV are moderate to excellent, while those for SWD and L/K ratio are poor. Standardized machine settings, scanning protocols, and operator training are suggested in performing multiparametric ultrasound of the liver.
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http://dx.doi.org/10.1002/jum.15751DOI Listing
May 2021

Cannabinoid WIN 55,212-2 Inhibits Human Glioma Cell Growth by Triggering ROS-Mediated Signal Pathways.

Biomed Res Int 2021 22;2021:6612592. Epub 2021 Apr 22.

Postdoctoral Workstation, Taian City Central Hospital, Tai'an, Shandong 271000, China.

Glioblastoma is a highly invasive primary malignant tumor of the central nervous system. Cannabinoid analogue WIN 55,212-2 (WIN) exhibited a novel anticancer effect against human tumors. However, the anticancer potential and underlying mechanism of WIN against human glioma remain unclear. Herein, the anticancer efficiency and mechanism of WIN in U251 human glioma cells were investigated. The results showed that WIN dose-dependently inhibited U251 cell proliferation, migration, and invasion . WIN treatment also effectively suppressed U251 tumor spheroids growth . Further studies found that WIN induced significant apoptosis as convinced by the caspase-3 activation and release of cytochrome C. Mechanism investigation revealed that WIN triggered ROS-mediated DNA damage and caused dysfunction of VEGF-AKT/FAK signal axis. However, ROS inhibition effectively attenuated WIN-induced DNA damage and dysfunction of VEGF-AKT/FAK signal axis and eventually improved U251 cell proliferation, migration, and invasion. Taken together, our findings validated that WIN had the potential to inhibit U251 cell proliferation, migration, and invasion and induce apoptosis by triggering ROS-dependent DNA damage and dysfunction of VEGF-AKT/FAK signal axis.
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http://dx.doi.org/10.1155/2021/6612592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087470PMC
April 2021

Taste Masking Study Based on an Electronic Tongue: the Formulation Design of 3D Printed Levetiracetam Instant-Dissolving Tablets.

Pharm Res 2021 May 11. Epub 2021 May 11.

State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Haidian District, Beijing, 100850, China.

Purpose: Proper taste-masking formulation design is a critical issue for instant-dissolving tablets (IDTs). The purpose of this study is to use the electronic tongue to design the additives of the 3D printed IDTs to improve palatability.

Methods: A binder jet 3D printer was used to prepare IDTs of levetiracetam. A texture analyzer and dissolution apparatus were used to predict the oral dispersion time and in vitro drug release of IDTs, respectively. The palatability of different formulations was investigated using the ASTREE electronic tongue in combination with the design of experiment and a model for masking bitter taste. Human gustatory sensation tests were conducted to further evaluate the credibility of the results.

Results: The 3D printed tablets exhibited rapid dispersion (<30 s) and drug release (2.5 min > 90%). The electronic tongue had an excellent ability of taste discrimination, and levetiracetam had a good linear sensing performance based on a partial least square regression analysis. The principal component analysis was used to analyze the signal intensities of different formulations and showed that 2% sucralose and 0.5% spearmint flavoring masked the bitterness well and resembled the taste of corresponding placebo. The results of human gustatory sensation test were consistent with the trend of the electronic tongue evaluation.

Conclusions: Owing to its objectivity and reproducibility, this technique is suitable for the design and evaluation of palatability in 3D printed IDT development.
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http://dx.doi.org/10.1007/s11095-021-03041-9DOI Listing
May 2021

Increasing prevalence of cerebral palsy among children and adolescents in China 1988-2020: A systematic review and meta-analysis.

J Rehabil Med 2021 May 7. Epub 2021 May 7.

Department of Epidemiology and Biostatistics, School of Public Health, Southeast University, Nanjing, China.

To investigate the pooled prevalence of cerebral palsy in China, analyse the differences between different subgroups, and explore the trend over the 32-year period from 1988 to 2020. All potential studies related to the prevalence of cerebral palsy among children and adoles-cents in China were identified from 3 English- language databases and 4 Chinese-language databases. Pooled prevalence was calculated to estimate the prevalence of cerebral palsy among 0-18 years old and different geographical regions in China, using a random-effects meta-analysis model. Continuous fractional polynomial regression modelling was used to estimate the trend in prevalence of cerebral palsy over time. Subgroup analysis and meta-regression were conducted to investigate heterogeneity. Funnel plots and Egger's test were used to explore potential publication bias. The pooled prevalence of cerebral palsy over the study period among 0-18 years old and different geographical regions in China was 2.07% (95% confidence interval (95% CI) 1.66-2.47%), and the prevalence of cerebral palsy was higher in males compared with females (2.25% vs 1.59%), and in rural residents compared with urban residents (2.54% vs 1.9%), respectively. The prevalence of cerebral palsy varied significantly between different geographical regions. In subjects with birthweights < 2.5 and > 4 kg the prevalence of cerebral palsy was significantly higher than in subjects with birthweights between 2.5 and 4 kg. The trend in pooled prevalence of cerebral palsy increased continuously over the period studied, and could be divided into 3 stages; the mean annual increase in prevalence from 1988 to 1996 and from 2008 to 2019 was more rapid. Multivariate meta-regression found that the year of study was one of the sources of heterogeneity among overall prevalence. (p=0.006). The pooled prevalence of cerebral palsy over the 32-year period from 1988 to 2020 was 2.07%. There was an increasing trend in prevalence of cerebral palsy among children and adolescents in China over this period.
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http://dx.doi.org/10.2340/16501977-2841DOI Listing
May 2021

Amino Acid Reduction Can Help to Improve the Identification of Antimicrobial Peptides and Their Functional Activities.

Front Genet 2021 20;12:669328. Epub 2021 Apr 20.

The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, College of Life Sciences, Inner Mongolia University, Hohhot, China.

Antimicrobial peptides (AMPs) are considered as potential substitutes of antibiotics in the field of new anti-infective drug design. There have been several machine learning algorithms and web servers in identifying AMPs and their functional activities. However, there is still room for improvement in prediction algorithms and feature extraction methods. The reduced amino acid (RAA) alphabet effectively solved the problems of simplifying protein complexity and recognizing the structure conservative region. This article goes into details about evaluating the performances of more than 5,000 amino acid reduced descriptors generated from 74 types of amino acid reduced alphabet in the first stage and the second stage to construct an excellent two-stage classifier, Identification of Antimicrobial Peptides by Reduced Amino Acid Cluster (iAMP-RAAC), for identifying AMPs and their functional activities, respectively. The results show that the first stage AMP classifier is able to achieve the accuracy of 97.21 and 97.11% for the training data set and independent test dataset. In the second stage, our classifier still shows good performance. At least three of the four metrics, sensitivity (SN), specificity (SP), accuracy (ACC), and Matthews correlation coefficient (MCC), exceed the calculation results in the literature. Further, the ANOVA with incremental feature selection (IFS) is used for feature selection to further improve prediction performance. The prediction performance is further improved after the feature selection of each stage. At last, a user-friendly web server, iAMP-RAAC, is established at http://bioinfor.imu.edu. cn/iampraac.
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http://dx.doi.org/10.3389/fgene.2021.669328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093877PMC
April 2021

CAN017, a novel anti-HER3 antibody, exerted great potency in mouse avatars of esophageal squamous cell carcinoma with NRG1 as a biomarker.

Am J Cancer Res 2021 15;11(4):1697-1708. Epub 2021 Apr 15.

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College Shenzhen 518116, China.

CAN017 (AV-203), a novel anti-HER3 antibody, exerts very promising anti-tumor activities in several human tumor models. The aim of this study was to further investigated the efficacy and possible responsive biomarkers of CAN017 in esophageal squamous cell carcinoma (ESCC) with Chinese characteristics. Two separate cohorts of ESCC patient-derived xenograft (PDX) models including 24 (cohort 1 as training models, from Crown Bioscience Inc.) and 22 (cohort 2 as validating models, from Peking University Cancer Hospital) models, respectively, were used to study the efficacy and safety of CAN017, as well as the correlation of NRG1 expression to the response of CAN017. In cohort 1, all PDX models showed good tolerance to CAN017 and 8 out of 24 (33.3%) PDX models responded to CAN017 with tumor growth inhibition (TGI) ≥70% compared to controls. Furthermore, the efficacy of CAN017 was positively correlated with NRG1 expression and the response rates in cohort 1 were 73% (8/11) versus 0% (0/13) in NRG1 high and low expression models, respectively. These results were also validated in PDX models of cohort 2 indicated as the powerful anti-tumor activity of CAN017 in PDX models with NRG1 high expression. In our study, HER3-targeting therapy was first demonstrated to have potency in inhibiting ESCC tumor growth, and NRG1 served as a predictive biomarker to screen patients in future clinical trials.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085865PMC
April 2021

Aerosol Transmission of Coronavirus and Influenza Virus of Animal Origin.

Front Vet Sci 2021 13;8:572012. Epub 2021 Apr 13.

Shandong Provincial Key Laboratory of Animal Biotechnology and Disease Control and Prevention, Sino-German Cooperative Research Center for Zoonosis of Animal Origin Shandong Province, Shandong Provincial Engineering Technology Research Center of Animal Disease Control and Prevention, College of Animal Science and Veterinary Medicine, Shandong Agricultural University, Taian, China.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused great harm to global public health, resulting in a large number of infections among the population. However, the epidemiology of coronavirus has not been fully understood, especially the mechanism of aerosol transmission. Many respiratory viruses can spread via contact and droplet transmission, but increasing epidemiological data have shown that viral aerosol is an essential transmission route of coronavirus and influenza virus due to its ability to spread rapidly and high infectiousness. Aerosols have the characteristics of small particle size, long-time suspension and long-distance transmission, and easy access to the deep respiratory tract, leading to a high infection risk and posing a great threat to public health. In this review, the characteristics of viral aerosol generation, transmission, and infection as well as the current advances in the aerosol transmission of zoonotic coronavirus and influenza virus are summarized. The aim of the review is to strengthen the understanding of viral aerosol transmission and provide a scientific basis for the prevention and control of these diseases.
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http://dx.doi.org/10.3389/fvets.2021.572012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078102PMC
April 2021

The Effects of Exposure to Flupyradifurone on Survival, Development, and Foraging Activity of Honey Bees ( L.) under Field Conditions.

Insects 2021 Apr 16;12(4). Epub 2021 Apr 16.

Key Laboratory of Pollinating Insect Biology, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Ministry of Agriculture, Beijing 100093, China.

Flupyradifurone (FPF) is a novel systemic nAChR agonist that interferes with signal transduction in the central nervous system of sucking pests. Despite claims that FPF is potentially "bee-safe" by risk assessments, laboratory data have suggested that FPF has multiple sub-lethal effects on individual honey bees. Our study aimed to expand the studies to the effects of field-realistic concentration of FPF. We found a statistically significant decrease in the survival rate of honey bees exposed to FPF, whereas there were no significantly negative effects on larvae development durations nor foraging activity. In addition, we found that the exposed foragers showed significantly higher expression of ApidNT, CYP9Q2, CYP9Q3, and AmInR-2 compared to the CK group (control group), but no alteration in the gene expression was observed in larvae. The exposed newly emerged bees showed significantly higher expression of Defensin and ApidNT. These results indicate that the chronic exposure to the field-realistic concentration of FPF has negligible effects, but more important synergistic and behavioral effects that can affect colony fitness should be explored in the future, considering the wide use of FPF on crops pollinated and visited by honey bees.
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http://dx.doi.org/10.3390/insects12040357DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074100PMC
April 2021

Probiotics alleviate depressive behavior in chronic unpredictable mild stress rat models by remodeling intestinal flora.

Neuroreport 2021 May;32(8):686-693

Department of Psychiatry.

Objective: To explore the effects of probiotics on depressive behavior in a chronic unpredictable mild stress (CUMS) rat model by remodeling intestinal flora.

Methods: Twenty-four male SD rats aged 6-8 weeks were randomly divided into four groups: control group, depression group (CUMS), depression+paroxetine group (Paro) and depression+probiotics group (Pro). Sucrose preference, open field and forced swimming tests were used to assess depression-like behavior in rats. ELISA was used to detect the levels of adrenocorticotropic hormone (ACTH), and corticosterone, norepinephrine and 5-hydroxytryptamine in rat serum. Real-time PCR was used to determine the changes of Lactobacillus, Bifidobacterium, Enterococcus faecalis and Escherichia coli in rat cecum.

Results: Compared with the control group, CUMS led to significant decreases of body weight, total traveled distance, duration in central area, immobility time, norepinephrine and 5-hydroxytryptamine contents in hippocampal tissues, as well as Lactobacillus and Bifidobacterium in the cecum. It also resulted in marked increases of the contents of E. faecalis and E. coli in the cecum, ACTH and corticosterone contents in the serum of rats. Paroxetine and probiotic treatment each diminished or prevented these changes.

Conclusion: By remodeling intestinal flora, probiotics can reduce the CUMS-induced depressive behavior of rats, increase the levels of norepinephrine and 5-hydroxytryptamine, and inhibit the expression of ACTH and corticosterone. Significantly, the effect of both paroxetine and probiotic on microorganisms is similar.
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http://dx.doi.org/10.1097/WNR.0000000000001637DOI Listing
May 2021

D-Galactose Induces Chronic Oxidative Stress and Alters Gut Microbiota in Weaned Piglets.

Front Physiol 2021 8;12:634283. Epub 2021 Apr 8.

Key Laboratory of Agro-ecological Processes in Subtropical Region, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, China.

Oxidative stress commonly occurs in pig production, which can severely damage the intestinal function of weaned piglets. This study was conducted to investigate the effects of D-galactose with different levels used to induce chronic oxidative stress on growth performance, intestinal morphology and gut microbiota in weaned piglets. The results showed that addition of 10 and 20 g/kg BW D-galactose reduced average daily gain and average daily feed intake from the first to the third week. 10 g/kg BW D-galactose increased the concentration of serum MDA at the second and third week. 10 g/kg BW D-galactose significantly influenced the jejunal and ileal expressions of , , and . The results of 16S rRNA sequencing showed that compared with the control, 10 and 20 g/kg BW D-galactose significantly decreased the relative abundance of , , , and , while increased the relative abundance of , , and . The results indicated that treatment with 10 g/kg BW/day D-galactose for 3 weeks could induce chronic oxidative stress, reduce the growth performance and alter gut microbiota in weaned piglets.
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http://dx.doi.org/10.3389/fphys.2021.634283DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8060641PMC
April 2021

Pseudomonas stutzeri GF2 augmented the denitrification of low carbon to nitrogen ratio: Possibility for sewage wastewater treatment.

Bioresour Technol 2021 Apr 16;333:125169. Epub 2021 Apr 16.

School of Environmental and Municipal Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China; Shaanxi Key Laboratory of Environmental Engineering, Xi'an University of Architecture and Technology, Xi'an 710055, China.

A denitrifying strain with high efficiency at low carbon to nitrogen (C/N) ratio of 2.0 was isolated and characterized. It belongs to the genus Pseudomonas. Scanning electron microscopy (SEM) showed that GF2 was rod-shaped. The nitrate removal efficiency reached up to 92.41% (1.85 mg L h) with the C/N ratio of 2.0 and the nitrite accumulation eventually decreased to 0.88 mg L. By response surface method (RSM) method, three reaction conditions of strain GF2 were optimized, including pH, C/N ratio, and nitrate concentration. Nitrogen balance and gas detection revealed that 88.03% of nitrogen was removed in gaseous form (included 98.80% nitrogen gas), which confirmed its efficient denitrification ability and pathway. 3D fluorescence spectrum (3D-EEM) manifested that in the absence of organic matter, strain GF2 can utilize extracellular polymeric substance (EPS) as carbon source for efficient denitrification. This research strived to provide new research ideas for low C/N ratio sewage treatment.
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http://dx.doi.org/10.1016/j.biortech.2021.125169DOI Listing
April 2021

A longitudinal observation of brain structure between AD and FTLD.

Clin Neurol Neurosurg 2021 Mar 24;205:106604. Epub 2021 Mar 24.

Department of Neurology, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Introduction: Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) are the leading causes of dementia. To better understand the disease development of cognitive function and anatomical structure in AD and FTLD, we analyzed the changes in brain volume by MRI and the psychological test results. Here, we report a dynamic observation of brain structure.

Methods: Thirteen patients diagnosed with probable AD by the 2011 NIA-AA criteria and eight FTLD patients diagnosed by the FTLD criteria underwent MRI at baseline. All subjects were rescanned after 5 months to 3 years of follow-up. The anatomic changes on T1-weighted imaging of each subject were measured, and the separate changes in the two groups and the differences in the changes between AD and FTLD were analyzed.

Results: In AD patients, the anterior and posterior horns of the lateral ventricle and lateral fissure enlarged progressively (p < 0.001). The volume of the regions, including the medial and lateral temporal lobe, especially the parahippocampal gyrus, and the frontal lobe decreased significantly as the disease progressed (p < 0.001). Additionally, the volume of white matter in the frontal, parietal, temporal lobe and cerebellum decreased in a relatively symmetric pattern (p < 0.001). In FTLD patients, the anterior horn of the lateral ventricle, lateral fissure, cerebral longitudinal fissure, external space of the orbitofrontal cortex, and mesencephalon surrounding the cisterna were enlarged (p < 0.005), while regions including the left frontal lobe, anterior cingulate cortex, basal ganglia (especially the left basal ganglia), left lateral temporal lobe and inferior cerebellar vermis decreased as the disease progressed (p < 0.005). Regarding the differences between AD and FTLD, atrophy of the frontal lobe and bilateral basal ganglia was more significant in FTLD than in AD (p < 0.01). In addition, enlargements of the anterior horn of the lateral ventricle, left lateral fissure and interpeduncular cistern were more significant in FTLD patients than in AD patients (p < 0.01).

Conclusions: These findings suggest that AD and FTLD have distinctly different atrophy patterns: AD patients show diffuse atrophy while FTLD patients show an asymmetrical focal atrophy pattern, which might explain the relatively better and longer preservation of daily living function in FTLD patients.
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http://dx.doi.org/10.1016/j.clineuro.2021.106604DOI Listing
March 2021

Impact of heat stress and a feed supplement on hormonal and inflammatory responses of dairy cows.

J Dairy Sci 2021 Apr 14. Epub 2021 Apr 14.

Department of Animal and Dairy Science, University of Georgia, Tifton 31793. Electronic address:

The aim of this trial was to evaluate the effects of an immunomodulatory supplement (OmniGen AF, OG; Phibro Animal Health Corp.) and heat stress on hormonal, inflammatory, and immunological responses of lactating dairy cows. Sixty multiparous Holstein cows were randomly assigned to 4 treatments in a 2 × 2 factorial arrangement using 2 environments: cooled using fans and misters, or noncooled, and 2 top-dressed feed supplements (56 g/d): OG or a placebo (CTL). Temperature-humidity index averaged 78 during the 8-wk trial. Blood was drawn to analyze cortisol, prolactin, and circulating tumor necrosis factor (TNF)-α and IL10. Peripheral blood mononuclear cells (PBMC) were isolated and stimulated with hydrocortisone, prolactin, or lipopolysaccharide (LPS), individually or in several combinations, to assess induced proliferation and cytokine production. At d 52, 6 cows per treatment were injected i.v. with an LPS bolus (ivLPS) to assess hormone and cytokine responses. For cooled cows, feeding OG increased plasma cortisol concentration relative to CTL. Noncooled cows fed CTL had lower circulating TNF-α concentrations than noncooled-OG and cooled-CTL cows, with cooled-OG intermediate. Hydrocortisone+LPS-stimulated PBMC from OG cows tended to proliferate more than CTL. Relative to cooled cows, PBMC from noncooled cows produced more TNF-α and IL10 when stimulated with LPS. Following ivLPS, cooled-OG cows had a greater cortisol response than the other treatments. In conclusion, OG supplementation enhanced cortisol release under basal condition and induced inflammation with cooling compared with CTL. This suggests that heat stress inhibits OG-mediated cortisol release. Heat stress seemed to enhance the inflammatory responses of PBMC from lactating cows. However, OG supplementation promoted PBMC proliferation under stress, or in the presence of hydrocortisone.
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http://dx.doi.org/10.3168/jds.2021-20162DOI Listing
April 2021

Anti-Cancer Activity Based on the High Docetaxel Loaded Poly(2-Oxazoline)s Micelles.

Int J Nanomedicine 2021 9;16:2735-2749. Epub 2021 Apr 9.

School of Pharmacy, Second Military Medical University, Shanghai, 200433, People's Republic of China.

Purpose: Nanocarriers, with a high drug loading content and good safety, to achieve desirable therapeutic effect are always the goals for industry and research.

Methods And Results: In the present study, we developed a docetaxel loaded poly-2-oxazoline polymer micellar system which employed poly-2-butyl-2 oxazoline and poly-2-methyl-2 oxazoline as the hydrophobic chain and hydrophilic chain, respectively. This micellar system achieves a high load up to 25% against the docetaxel, and further demonstrates an IC50 as low as 40% of the commercialized docetaxel injection in vitro and a double maximum tolerated dose in MCF-7 cells in vivo.

Conclusion: The high drug loading content, superior safety, and considerable anti-cancer activity make this newly developed docetaxel loaded poly(2-oxazoline) micelle go further in future clinical research.
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http://dx.doi.org/10.2147/IJN.S298093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043799PMC
May 2021

Effects of ectomycorrhizal fungi (Suillus variegatus) on the growth, hydraulic function, and non-structural carbohydrates of Pinus tabulaeformis under drought stress.

BMC Plant Biol 2021 Apr 10;21(1):171. Epub 2021 Apr 10.

College of Forestry, Northwest A&F University, Yangling, 712100, People's Republic of China.

Background: A better understanding of non-structural carbohydrate (NSC) dynamics in trees under drought stress is critical to elucidate the mechanisms underlying forest decline and tree mortality from extended periods of drought. This study aimed to assess the contribution of ectomycorrhizal (ECM) fungus (Suillus variegatus) to hydraulic function and NSC in roots, stems, and leaves of Pinus tabulaeformis subjected to different water deficit intensity. We performed a continuous controlled drought pot experiment from July 10 to September 10, 2019 using P. tabulaeformis seedlings under 80, 40, and 20% of the field moisture capacity that represented the absence of non-drought, moderate drought, and severe drought stress, respectively.

Results: Results indicated that S. variegatus decreased the mortality rate and increased height, root biomass, and leaf biomass of P. tabulaeformis seedlings under moderate and severe drought stress. Meanwhile, the photosynthetic rates, stomatal conductance, and transpiration rates of P. tabulaeformis were significantly increased after S. variegatus inoculation. Moreover, the inoculation of S. variegatus also significantly increased the NSC concentrations of all seedling tissues, enhanced the soluble sugars content, and increased the ratios of soluble sugars to starch on all tissues under severe drought. Overall, the inoculation of S. variegatus has great potential for improving the hydraulic function, increasing the NSC storage, and improving the growth of P. tabulaeformis under severe drought.

Conclusions: Therefore, the S. variegatus can be used as a potential application strain for ecological restoration on arid regions of the Loess Plateau, especially in the P. tabulaeformis woodlands.
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http://dx.doi.org/10.1186/s12870-021-02945-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035767PMC
April 2021

Effects of three kinds of head acupuncture therapies on regulation of brain microenvironment and rehabilitation of nerve function in rats with cerebral palsy.

J Tradit Chin Med 2021 04;41(2):276-283

Department of Child Rehabilitation Division, Huai'an maternal and child care hospital Huai'an, Jiangsu 223002, China.

Objective: To compare and observe the effects of three kinds of cephalic acupuncture therapies commonly used in the clinic on promoting nerve function rehabilitation in the brain microenvironment of rats with cerebral palsy.

Methods: A negative control group, positive control group, and three cephalic acupuncture groups based on the administration of three cephalic acupuncture therapies were established. Ten experimental rats were selected from each group at 1, 2, and 3 weeks after modeling. Neuromotor function after treatment was rated according to the Basso, Beattie, and Bresnahan method. White matter fiber bundles were evaluated by head diffusion tensor imaging. The expression levels of neuron-specific enolase, microtubule-associated protein 2, and myelin basic protein in the brain tissue extract were detected by Western blot analysis and the activities of ATPases were determined using a fixed phosphorus method.

Results: The pathological changes in brain tissue were restored and motor function scores were increased in the mice in each cephalic acupuncture group, and the expression of neuronal growth-related proteins in the brain tissue extract was significantly increased. Additionally, the activities of ATPases in the lesion area were significant enhanced (P < 0.05). Diffusion tensor imaging revealed that the white matter fiber bundles of mice in each cephalic acupuncture group gradually increased and recovered. The nervous system structure was significantly improved.

Conclusions: All three acupuncture methods promoted the rehabilitation of nerve function damaged by cerebral palsy. These effects are likely related to the improved expression of nerve growth-related proteins, enhancement of ATPase activities, and regulation of the brain microenvironment.
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April 2021

Comparisons of nitrite accumulation, microbial behavior and nitrification kinetic in continuous stirred tank (ST) and plug flow (PF) moving bed biofilm reactors.

Chemosphere 2021 Mar 29;278:130410. Epub 2021 Mar 29.

College of Environmental Science and Engineering, Yangzhou University, Yangzhou, 225127, PR China. Electronic address:

Two types of continuous stirred tank moving bed biofilm reactors (ST-MBBR) and plug flow MBBR (PF-MBBR) were compared for nitrification. PF-MBBR showed strong shock resistance to temperature, and ammonium oxidation ratio (AOR) was 9.63% higher than that in the ST-MBBR, although the average biomass and biofilm thickness of ST-MBBR were 7.32-18.59%, 9.44-14.06% higher than those in the PF-MBBR. Meanwhile, a lower nitrite accumulation ratio (NAR) was observed (54.88%) in the PF-MBBR than the ST-MBBR (78.92%) due to different operation modes, and the divergence was demonstrated by the microbial quantitative analysis. Nitrification kinetics revealed that the temperature coefficient (θ) in the ST-MBBR (1.068) was much higher than that in the PF-MBBR (1.006-1.015), proving the contrasting nitrification performances caused by temperature shock. According to the Monod equation, the half-saturation coefficient (K) in the ST-MBBR was 0.19 mg/L while it varied around 0.12-0.24 mg/L in the PF-MBBR, revealing various NH affinity owing to different biofilm thickness and microbial composition. Finally, MBBR optimization related to operation mode, temperature, and free ammonium (FA) inhibition for nitrite accumulation was discussed.
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http://dx.doi.org/10.1016/j.chemosphere.2021.130410DOI Listing
March 2021

Loading and Releasing Behavior of Selenium and Doxorubicin Hydrochloride in Hydroxyapatite with Different Morphologies.

ACS Omega 2021 Mar 16;6(12):8365-8375. Epub 2021 Mar 16.

Research Center for Nano Biomaterials, Analytical & Testing Center, Sichuan University, Chengdu 610064, P. R. China.

Doxorubicin (Dox)-loaded or selenium-substituted hydroxyapatite (HA) has been developed to achieve anti-osteosarcoma or bone regeneration in a number of studies. However, currently, there is a lack of studies on the combination of Dox and selenium loading in/on HA and comparative research studies on which form and size of HA are more suitable for drug loading and release in the treatment osteogenesis after osteosarcoma resection. Herein, selenium-doped rod-shaped nano-HA (n-HA) and spherical mesoporous HA (m-HA) were successfully prepared. The doping efficiency of selenium and the Dox loading capacity of selenium-doped HA with different morphologies were studied. The release kinetics of Dox and the selenium element in phosphate-buffered saline with different pH values was also comparatively investigated. The drug loading results showed that n-HA exhibited 3 times higher selenium doping amount than m-HA, and the Dox entrapment efficiency of selenium-doped n-HA (0.1Se-n-HA) presented 20% higher than that of selenium-doped m-HA (0.1Se-m-HA). The Dox release behaviors of HA in two different morphologies showed similar release kinetics, with almost the same Dox releasing ratio but slightly more Dox releasing amount in selenium-doped HA than in HA without selenium. The selenium release from selenium-doped n-HA-D (0.1Se-n-HA-D) particles was 2 times as much as that of selenium-doped m-HA-D (0.1Se-m-HA) particles. Our study indicated that n-HA loaded with Dox and selenium may be a promising drug delivery strategy for inhibition of osteosarcoma recurrence and promoting osteogenesis simultaneously.
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http://dx.doi.org/10.1021/acsomega.1c00092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015115PMC
March 2021

Effectiveness of traditional Chinese medicine music therapy on anxiety and depression emotions of lung cancer patients: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Mar;100(12):e25040

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

Background: Lung cancer patients often accompanied with severe depression and anxiety emotions, and those negative emotions could affects the treatment and recovery of the illness, decrease the patients' quality of life. In recent years, traditional Chinese medicine five-element music therapy (TCM-FEMT) is widely used for psychological problems of lung cancer patients for its unique advantages, TCM-FEMT applied to negative emotions management of lung cancer patients has been reported in many publications, but there is lacks evidence-based medicine, in this study, effectiveness of TCM-FEMT on anxiety and depression emotions of lung cancer patients will be systematically evaluated.

Methods: PubMed, the Cochrane Library, Web of Science, Embase, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, VIP Database, WanFang Database were electronically searched to collect RCTs on the efficacy of TCM-FEMT on anxiety and depression emotions of lung cancer patients from inception to February 2021. In addition, retrospect the references of the included literature to supplement the relevant literature. Research selection, data extraction and quality evaluation of literature will be carried out by 2 researchers, respectively. RevMan 5.3 software will be used for statistical analysis.

Results: This study will comprehensively summarize the current trials to determine the effectiveness of TCM-FEMT on anxiety and depression emotions of lung cancer patients.

Conclusion: This study will provide comprehensive evidence for the efficacy of TCM-FEMT on anxiety and depression emotions of lung cancer patients.
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http://dx.doi.org/10.1097/MD.0000000000025040DOI Listing
March 2021

Deep sparse transfer learning for remote smart tongue diagnosis.

Math Biosci Eng 2021 01;18(2):1169-1186

The School of Software Technology, Dalian University of Technology, Dalian 116620, China.

People are exploring new ideas based on artificial intelligent infrastructures for immediate processing, in which the main obstacles of widely-deploying deep methods are the huge volume of neural network and the lack of training data. To meet the high computing and low latency requirements in modeling remote smart tongue diagnosis with edge computing, an efficient and compact deep neural network design is necessary, while overcoming the vast challenge on modeling its intrinsic diagnosis patterns with the lack of clinical data. To address this challenge, a deep transfer learning model is proposed for the effective tongue diagnosis, based on the proposed similar-sparse domain adaptation (SSDA) scheme. Concretely, a transfer strategy of similar data is introduced to efficiently transfer necessary knowledge, overcoming the insufficiency of clinical tongue images. Then, to generate simplified structure, the network is pruned with transferability remained in domain adaptation. Finally, a compact model combined with two sparse networks is designed to match limited edge device. Extensive experiments are conducted on the real clinical dataset. The proposed model can use fewer training data samples and parameters to produce competitive results with less power and memory consumptions, making it possible to widely run smart tongue diagnosis on low-performance infrastructures.
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http://dx.doi.org/10.3934/mbe.2021063DOI Listing
January 2021

Osthole enhances the immunosuppressive effects of bone marrow-derived mesenchymal stem cells by promoting the Fas/FasL system.

J Cell Mol Med 2021 May 21;25(10):4835-4845. Epub 2021 Mar 21.

Northern Department of Endodontics, Stomatological Hospital of Chongqing Medical University, Chongqing, China.

Thanks to the advantages of easy harvesting and escape from immune rejection, autologous bone marrow-derived mesenchymal stem cells (BMSCs) are promising candidates for immunosuppressive therapy against inflammation and autoimmune diseases. However, the therapy is still challenging because the immunomodulatory properties of BMSCs are always impaired by immunopathogenesis in patients. Because of its reliable and extensive biological activities, osthole has received increased clinical attention. In this study, we found that BMSCs derived from osteoporosis donors were ineffective in cell therapy for experimental inflammatory colitis and osteoporosis. In vivo and in vitro tests showed that because of the down-regulation of Fas and FasL expression, the ability of osteoporotic BMSCs to induce T-cell apoptosis decreased. Through the application of osthole, we successfully restored the immunosuppressive ability of osteoporotic BMSCs and improved their treatment efficacy in experimental inflammatory colitis and osteoporosis. In addition, we found the immunomodulatory properties of BMSCs were enhanced after osthole pre-treatment. In this study, our data highlight a new approach of pharmacological modification (ie osthole) to improve the immune regulatory performance of BMSCs from a healthy or inflammatory microenvironment. The development of targeted strategies to enhance immunosuppressive therapy using BMSCs may be significantly improved by these findings.
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http://dx.doi.org/10.1111/jcmm.16459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107110PMC
May 2021

Quantitative Ultrasound to Assess Skeletal Muscles in Post Stroke Spasticity.

J Cent Nerv Syst Dis 2021 3;13:1179573521996141. Epub 2021 Mar 3.

Rocky Vista University, Ivins, UT, USA.

Quantitative ultrasound (QUS) techniques such as pixel intensity, ultrasound strain, and shear wave elastography have made it possible to identify the echogenicity (brightness) and mechanical properties (stiffness) of normal and pathological tissues. These techniques can be utilized as an alternative diagnosis tool to assess post stroke spasticity. Current clinical assessment methods include the Modified Ashworth Scale (MAS) and the Modified Tardieu Scale (MTS), which can result in inconsistencies due to their subjective nature. QUS provides robust approaches to assessing muscle stiffness associated with post stroke spasticity. Computer-aided pixel count quantifies tissue echogenicity in grayscale image. A strain ratio in ultrasound strain imaging compares the stiffness and movement (lengthening or shortening) of a spastic muscle with nonspecific muscle. In addition, shear wave elastography provides the shear wave velocity of an affected muscle that directly associated with the muscle stiffness before and after treatment for spasticity. This article reviews the theory behind these aforementioned concepts and discuss the relations between QUS and skeletal muscles in post stroke spasticity.
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http://dx.doi.org/10.1177/1179573521996141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940737PMC
March 2021

Effect of Streptococcus anginosus on biological response of tongue squamous cell carcinoma cells.

BMC Oral Health 2021 03 20;21(1):141. Epub 2021 Mar 20.

College of Stomatology, Chongqing Medical University, Songshi Road No. 426, Yubei District, Chongqing, China.

Background: Streptococcus anginosus (S. anginosus) was reported increased in oral squamous cell carcinoma (OSCC) tissue. The aim of this study was to investigate the response of oral cancer cells in the biological characteristics evoked by the S. anginosus and investigate its potential mechanisms.

Methods: The growth curve and concentration standard curve of S. anginosus were determined, and a series of concentrations of S. anginosus supernatant were applied to OSCC cell lines SCC15, then selected an optimal time and concentration by CCK-8 assay. Then autophagic response, proliferative activity, cell cycle and apoptosis, invasion and migration abilities were evaluated in SCC15.

Results: The results showed that when the ratio of S. anginosus supernatant to cell culture medium was 1:1 and the co-culture time was 16 h, the inhibitory effect on SCC15 was the most obvious; Furthermore, the supernatant of Streptococcus upregulated the autophagy activity of SCC15, thus significantly inhibiting its proliferation, migration and invasion ability. Compared with control groups, the cell cycle showed G1 arrest, S and G2/M phases decreased, and the percentage of apoptotic cells relatively increased (P < 0.05).

Conclusion: S. anginosus reduced the proliferation, migration and invasion of SCC15 cells and promoted cell apoptosis; Moreover, autophagy may be one of the mechanisms in this process.
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http://dx.doi.org/10.1186/s12903-021-01505-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7981962PMC
March 2021

Impact of wheat bran micronization on dough properties and bread quality: Part I - Bran functionality and dough properties.

Food Chem 2021 Mar 1;353:129407. Epub 2021 Mar 1.

Department of Food Science and Technology, National University of Singapore, Science Drive 2, Singapore 117542, Singapore; National University of Singapore (Suzhou) Research Institute, 377 Linquan Street, Suzhou Industrial Park, Jiangsu 215123, China. Electronic address:

This study aimed to investigate the effect of wheat bran micronization on its functionality including physicochemical and antioxidant properties, and dough properties. Coarse bran (D = 362.3 ± 20.5 μm) was superfine ground to medium (D = 60.4 ± 10.1 μm) and superfine (D = 11.3 ± 2.6 μm) bran, accompanied with increasing specific surface area and breakdown of aleurone layers. Bran micronization increased its soluble dietary fibre content, ferulic acid liberation, and antioxidant properties including total polyphenol content, ABTS•+ and DPPH• scavenging activities, while decreased its water retention capacity and insoluble dietary fibre content. Moreover, bran micronization impacted dough rheological properties. The dough with superfine bran had higher water absorption and gelatinization temperature, peak viscosity, final viscosity and setback value, lower stability time, resistance to extension, and extensibility than the dough with coarse bran. This dough furthermore exhibited more solid-like properties characterized by decreased loss moduli and frequency dependence (n').
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http://dx.doi.org/10.1016/j.foodchem.2021.129407DOI Listing
March 2021

LncRNA SNHG7 Promotes the HCC Progression Through miR-122-5p/FOXK2 Axis.

Dig Dis Sci 2021 Mar 18. Epub 2021 Mar 18.

Medical College of Northwest Minzu University, Lanzhou, 730030, Gansu, China.

Hepatocellular carcinoma (HCC) is a malignant tumor with high mortality and severe complication in China. Numerous studies have shown that long noncoding RNAs (lncRNAs) are involved in the regulation of various processes in cancer cells. Our research aimed to investigate the underlying mechanism of the lncRNA small nucleolar RNA host gene 7 (SNHG7) in HCC development. The expression of SNHG7, microRNA-122-5p (miR-122-5p), and Forkhead box K2 (FOXK2) was assessed via quantitative real-time polymerase chain reaction. 3-(4,5) -dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) and transwell assays were performed to measure cell viability, migration, and invasion, respectively. The relative protein levels were detected by Western blot. The relationships between miR-122-5p and SNHG7 or FOXK2 were predicted by online software and then confirmed by dual-luciferase reporter assay. Animal experiments were conducted to clarify the effects of SNHG7 on proliferation in vivo. To begin with, SNHG7 was upregulated, while miR-122-5p was downregulated in HCC tissues and cells. Downregulation of SNHG7 inhibited cell growth and metastasis. Interestingly, SNHG7 could abolish the effects of miR-122-5p on HCC cells. Furthermore, miR-122-5p targeted FOXK2 and miR-122-5p recovered the effects of FOXK2 downregulation on cell growth and metastasis in HCC cells. Besides, SNHG7 facilitated HCC tumor growth in vivo through the miR-122-5p/FOXK2 axis. The lncRNA SNHG7 boosted the development of HCC by regulating FOXK2 through sponging miR-122-5p.
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http://dx.doi.org/10.1007/s10620-021-06918-2DOI Listing
March 2021

The effect of age on the clinical and immune characteristics of critically ill patients with COVID-19: A preliminary report.

PLoS One 2021 18;16(3):e0248675. Epub 2021 Mar 18.

Department of Respiratory Intensive Care Unit, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.

Background: In December 2019, a new disease named coronavirus disease 2019 (COVID-19) was occurred. Patients who are critically ill with COVID-19 are more likely to die, especially elderly patients. We aimed to describe the effect of age on the clinical and immune characteristics of critically ill patients with COVID-19.

Methods: We retrospectively included 32 patients with COVID-19 who were confirmed to have COVID-19 by the local health authority and who were admitted to the first affiliated hospital of Zhengzhou University in Zhengzhou, China between January 3 and March 20, 2020. Clinical information and experimental test data were retrospectively collected for the patients. The 32 patients in this study were all in a critical condition and were classified as severe, according to the guidelines of 2019-nCoV infection from the National Health Commission of the People's Republic of China. Data were compared between those <60 years old and ≥60 years old.

Results: Of 32 patients, 13 were under 60 years old, and 19 patients were ≥60 years old. The most common symptom among all patients upon admission was fever (93.8%, 30/32). Compared to younger patients, older patients exhibited increased comorbidities. Among patients who were 60 years and older, platelet count, direct bilirubin (DBIL), indirect bilirubin(IBIL), lactate dehydrogenase (LDH), B-type natriuretic peptide (BNP), C-reactive protein (CRP), procalcitonin (PCT), and interleukin-10 (IL-10) were significantly higher than in younger patients who were less than 60 years old. CD4+ T lymphocytes, CD8+ T lymphocytes, and NKT lymphocytes were decreased, CD4+/CD8+ T lymphocytes were significantly increased in all 32 patients, while there were no evident differences between younger and older patients. The CURB-65 (confusion, urea, respiratory, rate, blood pressure plus age ≥65 years), Acute Physiology and Chronic Health Evaluation (APACHE) II and pH value were significantly higher in older patients than in patients who were under 60 years old. However, the PaO2 and PaO2:FiO2 were lower in older patients than the younger. Compared to patients under 60 years old, patients who were 60 years and older tended to develop ARDS (15 [78.9%] vs 5 [38.5%]), septic shock (7 [36.8%] vs 0 [0.0%]) and were more likely to receive mechanical ventilation (13 [68.4%] vs 3[23.1%]). Dynamic trajectories of seven laboratory parameters were tracked on days 1, 3, 5 and 7, and significant differences in lymphocyte count (P = 0.026), D-dimer (P = 0.010), lactate dehydrogenase (P = 0.000) and C-reactive protein (P = 0.000) were observed between the two age groups.

Conclusions: A high proportion of critically ill patients were 60 or older. Furthermore, rapid disease progression was noted in elderly patients. Therefore, close monitoring and timely treatment should be performed in elderly COVID-19 patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248675PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971498PMC
April 2021

Transcriptional programming drives Ibrutinib-resistance evolution in mantle cell lymphoma.

Cell Rep 2021 Mar;34(11):108870

Chemical Biology and Molecular Medicine Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. Electronic address:

Ibrutinib, a bruton's tyrosine kinase (BTK) inhibitor, provokes robust clinical responses in aggressive mantle cell lymphoma (MCL), yet many patients relapse with lethal Ibrutinib-resistant (IR) disease. Here, using genomic, chemical proteomic, and drug screen profiling, we report that enhancer remodeling-mediated transcriptional activation and adaptive signaling changes drive the aggressive phenotypes of IR. Accordingly, IR MCL cells are vulnerable to inhibitors of the transcriptional machinery and especially so to inhibitors of cyclin-dependent kinase 9 (CDK9), the catalytic subunit of the positive transcription elongation factor b (P-TEFb) of RNA polymerase II (RNAPII). Further, CDK9 inhibition disables reprogrammed signaling circuits and prevents the emergence of IR in MCL. Finally, and importantly, we find that a robust and facile ex vivo image-based functional drug screening platform can predict clinical therapeutic responses of IR MCL and identify vulnerabilities that can be targeted to disable the evolution of IR.
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http://dx.doi.org/10.1016/j.celrep.2021.108870DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8057695PMC
March 2021