Publications by authors named "Li Zhou"

2,878 Publications

  • Page 1 of 1

A systematic review and meta-analysis of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC).

Transl Androl Urol 2021 Aug;10(8):3476-3485

Urology Surgery, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.

Background: A meta-analysis was conducted to evaluate the curative effect of radical cystectomy in the treatment of muscular invasive bladder cancer (MIBC).

Methods: Chinese and English databases were searched using free combinations of the terms "bladder cancer," "radical cystectomy," "muscle invasive bladder cancer," and "bladder preservation." Review Manager 5.3 software was used for the meta-analysis.

Results: A total of 12 articles were included in the meta-analysis, most of which had low-bias risk and were of medium and high quality. A funnel chart showed that the circles of some studies were basically symmetrical with the midline, suggesting that the research accuracy was high, the publications were not biased, and the final conclusions were credible. Twelve articles analyzed patients' 5-year survival rate in randomized controlled trials (RCTs). In these RCTs, the experimental group (expt group) comprised 775 cases and the control group (ctrl group) comprised 766 cases. A heterogeneity test using the fixed-effects model (FEM) showed Chi =2.19, df =11, I=0%, P=1.00>0.1, Z =2.57, odds ratio (OR) =1.30, 95% confidence interval (CI): 1.06-1.59, and P=0.01<0.05. 3 articles analyzed patients' 10-year survival rates in RCTs. These trials comprised a total of 417 patients (209 in the expt group and 208 in the ctrl group). The overall heterogeneity test showed Chi =0.40, df =2, I=0%, P=0.82>0.1, Z =1.42, OR =1.32, 95% CI: 0.90-1.94, and P=0.16>0.05. 6 articles analyzed 5-year distant metastasis rates (DMRs) in RCTs. The overall heterogeneity test showed Chi =1.68, df =5, I=0%, P=0.89>0.1, Z =1.70, OR =1.28, 95% CI: 0.96-1.71, and P=0.09>0.05).

Discussion: Our meta-analysis confirmed that radical cystectomy is effective in the treatment of MIBC and is worthy of clinical promotion.
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http://dx.doi.org/10.21037/tau-21-564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421829PMC
August 2021

Divergent Antiviral Mechanisms of Two Homeologs in a Recurrent Polyploid Fish.

Front Immunol 2021 31;12:702971. Epub 2021 Aug 31.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, The Innovative Academy of Seed Design, Chinese Academy of Sciences, Wuhan, China.

Polyploidy and subsequent diploidization provide genomic opportunities for evolutionary innovations and adaptation. The researches on duplicated gene evolutionary fates in recurrent polyploids have seriously lagged behind that in paleopolyploids with diploidized genomes. Moreover, the antiviral mechanisms of Viperin remain largely unclear in fish. Here, we elaborate the distinct antiviral mechanisms of two homeologs ( and ) in auto-allo-hexaploid gibel carp (). First, and showed differential and biased expression patterns in gibel carp adult tissues. Subsequently, using co-immunoprecipitation (Co-IP) screening analysis, both Viperin-A and Viperin-B were found to interact with crucian carp () herpesvirus (HV) open reading frame 46 right (ORF46R) protein, a negative herpesvirus regulator of host interferon (IFN) production, and to promote the proteasomal degradation of ORF46R decreasing K63-linked ubiquitination. Additionally, Viperin-B also mediated ORF46R degradation through autophagosome pathway, which was absent in Viperin-A. Moreover, we found that the N-terminal α-helix domain was necessary for the localization of Viperin-A and Viperin-B at the endoplasmic reticulum (ER), and the C-terminal domain of Viperin-A and Viperin-B was indispensable for the interaction with degradation of ORF46R. Therefore, the current findings clarify the divergent antiviral mechanisms of the duplicated homeologs in a recurrent polyploid fish, which will shed light on the evolution of teleost duplicated genes.
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http://dx.doi.org/10.3389/fimmu.2021.702971DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438203PMC
August 2021

A Novel Scoring System for Predicting the Metastases of Posterior Right Recurrent Laryngeal Nerve Lymph Node Involvement in Patients With Papillary Thyroid Carcinoma by Preoperative Ultrasound.

Front Endocrinol (Lausanne) 2021 31;12:738138. Epub 2021 Aug 31.

Department of Oncological Surgery, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Objective: Our goal was to investigate the correlation between papillary thyroid carcinoma (PTC) characteristics on ultrasonography and metastases of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN). There is still no good method for clinicians to judge whether a patient needs LN-prRLN resection before surgery, and we also wanted to establish a new scoring system to determine whether patients with papillary thyroid carcinoma require LN-prRLN resection before surgery.

Patients And Methods: There were 482 patients with right or bilateral PTC who underwent thyroid gland resection from December 2015 to December 2017 recruited as study subjects. The relationship between the PTC characteristics on ultrasonography and the metastases of LN-prRLN was analyzed by univariate and logistic regression analyses. Based on the risk factors identified in univariate and logistic regression analysis, a nomogram-based LN-prRLN prediction model was established.

Result: LN-prRLN were removed from all patients, of which 79 had LN-prRLN metastasis, with a metastasis rate of 16.39%. Multivariate logistic regression analysis revealed that LN-prRLN metastasis was closely related to sex, age, blood supply, larger tumors (> 1 cm) and capsular invasion. A risk prediction model has been established and fully verified. The calibration curve used to evaluate the nomogram shows that the consistency index was 0.75 ± 0.065.

Conclusion: Preoperative clinical data, such as sex, age, abundant blood supply, larger tumor (> 1 cm) and capsular invasion, are positively correlated with LN-prRLN metastasis. Our scoring system can help surgeons non-invasively determine which patients should undergo LN-prRLN resection before surgery. We recommend that LN-prRLN resection should be performed when the score is above 103.1.
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http://dx.doi.org/10.3389/fendo.2021.738138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8439577PMC
August 2021

Magnetic solid-phase extraction based on zirconium-based metal-organic frameworks for simultaneous enantiomeric determination of eight chiral pesticides in water and fruit juices.

Food Chem 2021 Sep 4;370:131056. Epub 2021 Sep 4.

School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang, Liaoning 110016, PR China. Electronic address:

A novel multi-residue method, magnetic solid-phase extraction combined with LC-MS/MS, was proposed for simultaneous enantiomeric determination of eight chiral pesticides in water and fruit juices. [email protected]@UiO-66 was firstly used to extract and enrich pesticides, showing excellent adsorption capacity, which was proved by adsorption kinetic and thermodynamic experiments. Multiple extraction parameters were optimized by Plackett-Burman and Box-Behnken design. Under optimized conditions, good linearity (1.0-200 ng L, R ≥ 0.9953) for all analytes, detection limits (0.10 to 0.35 ng L), quantitation limits (0.35 to 1.00 ng L), recoveries (83.68-95.99%), and precision (intra-day RSD ≤ 7.06%, inter-day RSD ≤ 9.40%) were obtained, meeting the requirements of pesticides residues analysis. It is worth mentioning that eight chiral pesticides can be separated quickly within 19 min. The above results indicate that the proposed method with satisfactory sensitivity and accuracy has the potential for routine analysis of chiral pesticide residues in aqueous samples.
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http://dx.doi.org/10.1016/j.foodchem.2021.131056DOI Listing
September 2021

Radiomics analysis of EPID measurements for patient positioning error detection in thyroid associated ophthalmopathy radiotherapy.

Phys Med 2021 Sep 11;90:1-5. Epub 2021 Sep 11.

Department of Radiation Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China. Electronic address:

Purpose: Electronic portal imaging detector (EPID)-based patient positioning verification is an important component of safe radiotherapy treatment delivery. In computer simulation studies, learning-based approaches have proven to be superior to conventional gamma analysis in the detection of positioning errors. To approximate a clinical scenario, the detectability of positioning errors via EPID measurements was assessed using radiomics analysis for patients with thyroid-associated ophthalmopathy.

Methods: Treatment plans of 40 patients with thyroid-associated ophthalmopathy were delivered to a solid anthropomorphic head phantom. To simulate positioning errors, combinations of 0-, 2-, and 4-mm translation errors in the left-right (LR), superior-inferior (SI), and anterior-posterior (AP) directions were introduced to the phantom. The positioning errors-induced dose differences between measured portal dose images were used to predict the magnitude and direction of positioning errors. The detectability of positioning errors was assessed via radiomics analysis of the dose differences. Three classification models-support vector machine (SVM), k-nearest neighbors (KNN), and XGBoost-were used for the detection of positioning errors (positioning errors larger or smaller than 3 mm in an arbitrary direction) and direction classification (positioning errors larger or smaller than 3 mm in a specific direction). The receiver operating characteristic curve and the area under the ROC curve (AUC) were used to evaluate the performance of classification models.

Results: For the detection of positioning errors, the AUC values of SVM, KNN, and XGBoost models were all above 0.90. For LR, SI, and AP direction classification, the highest AUC values were 0.76, 0.91, and 0.80, respectively.

Conclusions: Combined radiomics and machine learning approaches are capable of detecting the magnitude and direction of positioning errors from EPID measurements. This study is a further step toward machine learning-based positioning error detection during treatment delivery with EPID measurements.
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http://dx.doi.org/10.1016/j.ejmp.2021.08.014DOI Listing
September 2021

The nonlinear optical transition bleaching in tellurene.

Nanoscale 2021 Sep 14. Epub 2021 Sep 14.

Hunan Key Laboratory of Nanophotonics and Devices, School of Physics and Electronics, Central South University, 932 South Lushan Road, Changsha, Hunan 410083, P. R. China.

To date, outstanding linear and nonlinear optical properties of tellurene, caused by multiple two-dimensional (2D) phases and optical anisotropy, have attracted considerable interest for potential nanophotonics applications. In this work, the ultrafast nonlinear optical (NLO) properties of α-tellurene have been studied -scan and pump-probe techniques at a broadband spectral region. Typical saturable absorption and band filling effects are observed in tellurene due to the Pauli exclusion principle. Analysis using density functional theory (DFT) computation shows the enhancements in NLO response within the ultraviolet-visible absorption spectral region are owing to the increased optical intraband transition in tellurene. Moreover, the effects of varying the photon energy of the probe pulse were explored. Our results indicated that probe pulses with higher photon energies can make smaller differential transmission signal, this effect is found to be negatively correlated with calculated joint density of states (JDOS). These results offer insights into the intrinsic photophysics of 2D tellurene, driving its applications in photonic and optoelectronic fields.
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http://dx.doi.org/10.1039/d1nr03639dDOI Listing
September 2021

Adaption to hydrogen sulfide-rich environments: Strategies for active detoxification in deep-sea symbiotic mussels, Gigantidas platifrons.

Sci Total Environ 2021 Sep 1;804:150054. Epub 2021 Sep 1.

CAS Key Laboratory of Marine Ecology and Environmental Sciences, and Center of Deep Sea Research, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China; Laboratory for Marine Ecology and Environmental Science, Qingdao National Laboratory for Marine Science and Technology, Qingdao 266071, China; Center for Ocean Mega-Science, Chinese Academy of Sciences, Qingdao 266071, China; University of Chinese Academy of Sciences, Beijing 10049, China. Electronic address:

The deep-sea mussel Gigantidas platifrons is a representative species that relies on nutrition provided by chemoautotrophic endosymbiotic bacteria to survive in both hydrothermal vent and methane seep environments. However, vent and seep habitats have distinct geochemical features, with vents being more harsh than seeps because of abundant toxic chemical substances, particularly hydrogen sulfide (HS). Until now, the adaptive strategies of G. platifrons in a heterogeneous environment and their sulfide detoxification mechanisms are still unclear. Herein, we conducted 16S rDNA sequencing and metatranscriptome sequencing of G. platifrons collected from a methane seep at Formosa Ridge in the South China Sea and a hydrothermal vent at Iheya North Knoll in the Mid-Okinawa Trough to provide a model for understanding environmental adaption and sulfide detoxification mechanisms, and a three-day laboratory controlled NaS stress experiment to test the transcriptomic responses under sulfide stress. The results revealed the active detoxification of sulfide in G. platifrons gills. First, epibiotic Campylobacterota bacteria were more abundant in vent mussels and contributed to environmental adaptation by active oxidation of extracellular HS. Notably, a key sulfide-oxidizing gene, sulfide:quinone oxidoreductase (sqr), derived from the methanotrophic endosymbiont, was significantly upregulated in vent mussels, indicating the oxidization of intracellular sulfide by the endosymbiont. In addition, transcriptomic comparison further suggested that genes involved in oxidative phosphorylation and mitochondrial sulfide oxidization pathway played important roles in the sulfide tolerance of the host mussels. Moreover, transcriptomic analysis of NaS stressed mussels confirmed the upregulation of oxidative phosphorylation and sulfide oxidization genes in response to sulfide exposure. Overall, this study provided a systematic transcriptional analysis of both the active bacterial community members and the host mussels, suggesting that the epibionts, endosymbionts, and mussel host collaborated on sulfide detoxification from extracellular to intracellular space to adapt to harsh HS-rich environments.
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http://dx.doi.org/10.1016/j.scitotenv.2021.150054DOI Listing
September 2021

Recent progress of self-powered respiration monitoring systems.

Biosens Bioelectron 2021 Sep 7;194:113609. Epub 2021 Sep 7.

College of Chemistry and Chemical Engineering, Center on Nanoenergy Research, Guangxi University, 530004, Nanning, China; Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, 101400, Beijing, China. Electronic address:

Wearable and implantable medical devices are playing more and more key roles in disease diagnosis and health management. Various biosensors and systems have been used for respiration monitoring. Among them, self-powered sensors have some special characteristics such as low-cost, easy preparation, highly designable, and diversified. The respiratory airflow can drive the self-powered sensors directly to convert mechanical energy of the airflow into electricity. One of the major goals of the self-powered sensors and systems is realizing health monitoring and diagnosis. The relationship between the output signals and the models of respiratory diseases has not been studied deeply and clearly. Therefore, how to find an accurate relationship between them is a challenging and significant research topic. This review summarized the recent progress of the self-powered respiratory sensors and systems from aspects of device principle, output property, detecting index and so on. The challenges and perspectives have also been discussed for reference to the researchers who are interested in the field of self-powered sensors.
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http://dx.doi.org/10.1016/j.bios.2021.113609DOI Listing
September 2021

The Intersection of Big Data and Epidemiology for Epidemiologic Research: The Impact of the COVID-19 Pandemic.

Int J Qual Health Care 2021 Sep 11. Epub 2021 Sep 11.

Division of General Medicine and Primary Care, Brigham and Women's Hospital, Boston, MA, USA.

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http://dx.doi.org/10.1093/intqhc/mzab134DOI Listing
September 2021

Overall Survival of Patients With Unresectable or Metastatic BRAF V600-Mutant Acral/Cutaneous Melanoma Administered Dabrafenib Plus Trametinib: Long-Term Follow-Up of a Multicenter, Single-Arm Phase IIa Trial.

Front Oncol 2021 24;11:720044. Epub 2021 Aug 24.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma, Peking University Cancer Hospital & Institute, Beijing, China.

Objectives: To examine the long-term survival outcome of dabrafenib in combination with trametinib in Chinese patients with unresectable or metastatic acral/cutaneous melanoma with BRAF-V600 mutation and to explore potential predictors of effectiveness.

Methods: This was a long-term follow-up of Chinese patients with unresectable or metastatic BRAF V600-mutant acral/cutaneous melanoma administered dabrafenib (150 mg twice daily) plus trametinib (2 mg once daily) in an open-label, multicenter, single-arm, phase IIa study (NCT02083354). Efficacy endpoints included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). The impacts of baseline characteristics on PFS and OS were analyzed.

Results: A total of sixty patients were included. The median age was 48 years, and 24 patients (40.0%) were male. Totally 12 individuals (20.0%) had acral melanoma, and 45 (75.0%) had failed previous systemic therapy. Up to July 2020, the median duration of follow-up was 37.0 (95% confidence interval [CI] 29.1-44.9) months. The updated ORR was 71.7% (95%CI 60.3%-83.1%). The 3-year OS rate was 28.8% (95%CI 19.1-43.6%) in the overall population, and 35.7% (95%CI 15.5-82.4%) in acral melanoma patients. The median DOR was 7.5 months (95%CI 4.5 to 10.5). Baseline normal lactic dehydrogenase (LDH), metastatic organ sites<3 and complete response to combination therapy with dabrafenib plus trametinib were associated with improved PFS and OS.

Conclusion: Dabrafenib combined with trametinib confer long-term survival in Chinese patients with BRAF V600-mutant, unresectable or metastatic acral/cutaneous melanoma.

Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02083354, identifier NCT02083354.
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http://dx.doi.org/10.3389/fonc.2021.720044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422804PMC
August 2021

Chitosan (CTS) Alleviates Heat-Induced Leaf Senescence in Creeping Bentgrass by Regulating Chlorophyll Metabolism, Antioxidant Defense, and the Heat Shock Pathway.

Molecules 2021 Sep 2;26(17). Epub 2021 Sep 2.

Soil and Fertilizer Research Institute, Sichuan Academy of Agricultural Sciences, Chengdu 610066, China.

Chitosan (CTS) is a deacetylated derivative of chitin that is involved in adaptive response to abiotic stresses. However, the regulatory role of CTS in heat tolerance is still not fully understood in plants, especially in grass species. The aim of this study was to investigate whether the CTS could reduce heat-induced senescence and damage to creeping bentgrass associated with alterations in antioxidant defense, chlorophyll (Chl) metabolism, and the heat shock pathway. Plants were pretreated exogenously with or without CTS (0.1 g L) before being exposed to normal (23/18 °C) or high-temperature (38/33 °C) conditions for 15 days. Heat stress induced detrimental effects, including declines in leaf relative water content and photochemical efficiency, but significantly increased reactive oxygen species (ROS) accumulation, membrane lipid peroxidation, and Chl loss in leaves. The exogenous application of CTS significantly alleviated heat-induced damage in creeping bentgrass leaves by ameliorating water balance, ROS scavenging, the maintenance of Chl metabolism, and photosynthesis. Compared to untreated plants under heat stress, CTS-treated creeping bentgrass exhibited a significantly higher transcription level of genes involved in Chl biosynthesis ( and ), as well as a lower expression level of Chl degradation-related gene () and senescence-associated genes (, , , and ), thus reducing leaf senescence and enhancing photosynthetic performance under heat stress. In addition, the foliar application of CTS significantly improved antioxidant enzyme activities (SOD, CAT, POD, and APX), thereby effectively reducing heat-induced oxidative damage. Furthermore, heat tolerance regulated by the CTS in creeping bentgrass was also associated with the heat shock pathway, since and were significantly up-regulated by the CTS during heat stress. The potential mechanisms of CTS-regulated thermotolerance associated with other metabolic pathways still need to be further studied in grass species.
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http://dx.doi.org/10.3390/molecules26175337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434246PMC
September 2021

Genomic anatomy of male-specific microchromosomes in a gynogenetic fish.

PLoS Genet 2021 Sep 7;17(9):e1009760. Epub 2021 Sep 7.

State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, The Innovative Academy of Seed Design, Hubei Hongshan Laboratory, Chinese Academy of Sciences, Wuhan, China.

Unisexual taxa are commonly considered short-lived as the absence of meiotic recombination is supposed to accumulate deleterious mutations and hinder the creation of genetic diversity. However, the gynogenetic gibel carp (Carassius gibelio) with high genetic diversity and wide ecological distribution has outlived its predicted extinction time of a strict unisexual reproduction population. Unlike other unisexual vertebrates, males associated with supernumerary microchromosomes have been observed in gibel carp, which provides a unique system to explore the rationales underlying male occurrence in unisexual lineage and evolution of unisexual reproduction. Here, we identified a massively expanded satellite DNA cluster on microchromosomes of hexaploid gibel carp via comparing with the ancestral tetraploid crucian carp (Carassius auratus). Based on the satellite cluster, we developed a method for single chromosomal fluorescence microdissection and isolated three male-specific microchromosomes in a male metaphase cell. Genomic anatomy revealed that these male-specific microchromosomes contained homologous sequences of autosomes and abundant repetitive elements. Significantly, several potential male-specific genes with transcriptional activity were identified, among which four and five genes displayed male-specific and male-biased expression in gonads, respectively, during the developmental period of sex determination. Therefore, the male-specific microchromosomes resembling common features of sex chromosomes may be the main driving force for male occurrence in gynogenetic gibel carp, which sheds new light on the evolution of unisexual reproduction.
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http://dx.doi.org/10.1371/journal.pgen.1009760DOI Listing
September 2021

Correction to: Differentiating total from subtotal arterial occlusion in lower extremities by using reverse attenuation gradient sign in CT angiography.

Eur Radiol 2021 Sep 7. Epub 2021 Sep 7.

Department of Radiology, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710061, Shaanxi Province, People's Republic of China.

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http://dx.doi.org/10.1007/s00330-021-08219-8DOI Listing
September 2021

SARS-CoV-2 crosses the blood-brain barrier accompanied with basement membrane disruption without tight junctions alteration.

Signal Transduct Target Ther 2021 09 6;6(1):337. Epub 2021 Sep 6.

NHC Key Laboratory of Human Disease Comparative Medicine, Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, China.

SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.
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http://dx.doi.org/10.1038/s41392-021-00719-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419672PMC
September 2021

Variations of Phyllosphere and Rhizosphere Microbial Communities of Pinus koraiensis Infected by Bursaphelenchus xylophilus.

Microb Ecol 2021 Sep 6. Epub 2021 Sep 6.

College of Forestry, Shenyang Agricultural University, Shenyang, 110866, China.

Pine wood nematode, Bursaphelenchus xylophilus, as one of the greatest threats to pine trees, is spreading all over the world. Plant microorganisms play an important role in the pathogenesis of nematodes. The phyllosphere and rhizosphere bacterial and fungal communities associated with healthy Pinus koraiensis (PKa) and P. koraiensis infected by B. xylophilus at the early (PKb) and last (PKc) stages were analyzed. Our results demonstrated that pine wood nematode (PWD) could increase the phyllosphere bacterial Pielou_e, Shannon, and Simpson index; phyllosphere fungal Chao 1 index, as well as rhizosphere bacterial Pielou_e, Shannon, and Simpson index; and rhizosphere fungal Pielou_e, Shannon, and Simpson index. What's more, slight shifts of the microbial diversity were observed at the early stage of infection, and the microbial diversity increased significantly as the symptoms of infection worsened. With the infection of B. xylophilus in P. koraiensis, Bradyrhizobium (rhizosphere bacteria), Massilia (phyllosphere bacteria), and Phaeosphaeriaceae (phyllosphere fungi) were the major contributors to the differences in community compositions among different treatments. With the infection of PWD, most of the bacterial groups tended to be co-excluding rather than co-occurring. These changes would correlate with microbial ability to suppress plant pathogen, enhancing the understanding of disease development and providing guidelines to pave the way for its possible management.
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http://dx.doi.org/10.1007/s00248-021-01850-4DOI Listing
September 2021

: A Dietary Supplement as an Immune-Modulator on the Basis of Bioactive Components.

Front Nutr 2021 17;8:722813. Epub 2021 Aug 17.

National R&D Center for Edible Fungus Processing Technology, Henan University, Kaifeng, China.

Nutrients can be considered as functional foods, which exert physiological benefits on immune system. The seeds of , which have many active constituents, are mainly used for medicine, food spice, and nutritional supplements in Egypt. Much attention has been paid to seeds for their anticancer, antibacterial, anti-inflammatory, and immune properties. However, their active constituents and mechanisms underlying functions from seeds is unclear. Thus, the bioactive constituents with immune regulation in seeds were systematically studied. A new compound (3-methoxythymol-6--β-D-apiofuranosyl-(1→6)-β-D-glucopyranoside ) and 11 known compounds () were separated from the seeds by chromatographic methods. Their structures were then elucidated by spectroscopic analysis of MS, UV, IR, H-, and C-NMR. Furthermore, immunomodulatory effects of those compounds in RAW 264.7 cells were evaluated by phagocytosis, nitric oxide (NO) and cytokine release, related mRNA transcription, and key proteins expression . Monosaccharide derivatives, Ethyl-α-D-furaarabinose (), and Ethyl-β-D-fructofuranoside () were shown to played bidirectional regulatory roles in immunity and anti-inflammation through the regulation of nuclear factor-κB (NF-κB) signaling pathways. The results showed the active compounds and mechanisms of immune regulation in , thus indicating that seeds could be used as dietary supplements in immunomodulation.
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http://dx.doi.org/10.3389/fnut.2021.722813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415885PMC
August 2021

Expression Characteristics and Clinical Correlations of BRD1 in Colorectal Cancer Samples.

Technol Cancer Res Treat 2021 Jan-Dec;20:15330338211039678

Molecular Medicine and Tumor Research Center, 12550Chongqing Medical University, Chongqing, China.

The incidence of colorectal cancer (CRC), as well as subsequent patient mortality, has increased in the last decade; an unhealthy diet is considered to be the leading cause. Previous studies have shown the potential of the bromodomain containing 1 () gene as a therapeutic target for CRC based on its specificity; however, the genetic mode of action and expression in CRC cells are yet to be investigated. In this study, target genes were screened from single-cell transcriptome sequencing data, and the collected clinical specimens were subjected to immunohistochemistry (IHC) to identify the protein expression of target genes; the results were verified in the GSE17536 array set. Receiver operating characteristic curves (ROC) and overall survival (OS) were used to test target genes as biomarkers and independent predictive markers for CRC. Based on these results, was screened as a target gene, and IHC results showed that BRD1 protein expression in CRC was higher than that in normal tissues and was significantly upregulated in poorly differentiated (PD) CRC. ROC analysis showed that the area under the curve in the collected clinical specimens and GSE17536 were 0.6062 and 0.6094, respectively. OS analysis showed that higher BRD1 protein expression was associated with a significantly shorter survival time. In conclusion, BRD1 expression was positively correlated with PD CRC and negatively correlated with OS, indicating that could predict the differentiation state of CRC and may be a novel predictive biomarker.
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http://dx.doi.org/10.1177/15330338211039678DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422826PMC
September 2021

Ultrathin Stretchable Triboelectric Nanogenerators Improved by Postcharging Electrode Material.

ACS Appl Mater Interfaces 2021 Sep 2;13(36):42966-42976. Epub 2021 Sep 2.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, No. 8 Yangyandongyi Road, Beijing 101400, People's Republic of China.

Sustainable ultrathin stretchable power sources have emerged with the development of wearable electronics. They obtain energy from living organisms and the environment to drive these wearable electronics. Here, an ultrathin stretchable and triboelectric nanogenerator (TENG) improved by chargeable carbon black (CB)/thermoplastic polyurethane (TPU) composite material (CT-TENG) is proposed for mechanical energy harvesting and physiological signal sensing. The CB/TPU composite can act as both a stretchable electrode and a triboelectric layer due to the coexistence of conductive CB and dielectric TPU. The CT-TENG demonstrates good stretchability (≈646%), ultrathin thickness (≈50 μm), and a lightweight (≈62 mg). The triboelectric electrode material can be improved by postcharging treatment. With the corona charging process, the output performance of the CT-TENG was improved eightfold and reached 41 V. Moreover, the CT-TENG with a self-powered sensing capability can inspect the amplitude and frequency of different physiological movements. Consequently, the CT-TENG is promising in promoting the development of electronic skins, wearable systems of self-powered sensors, human-machine interactions, soft robotics, and artificial intelligence applications.
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http://dx.doi.org/10.1021/acsami.1c13840DOI Listing
September 2021

Construction of high internal phase Pickering emulsions stabilized by bamboo fungus protein gels with the effect of pH.

Food Chem 2021 Aug 24;369:130954. Epub 2021 Aug 24.

School of Pharmaceutical Sciences, South-Central University for Nationalities, Wuhan 430074, PR China; National Demonstration Center for Experimental Ethnopharmacology Education, South-Central University for Nationalities, Wuhan 430074, PR China. Electronic address:

This study is a contribution to explore natural protein sources as high internal phase Pickering emulsions (HIPPEs) stabilizers and to achieve full utilization of biological resources. Bamboo fungus proteins were obtained by alkaline extraction and subsequently transformed into protein gels by enzymatic cross-linking method. 1% (w/v) of bamboo protein gel particles (BGPs) were used to stabilize high HIPPEs (φ = 80%) using a one-step homogenization method. At pH 3, 9 and 11, BGPs could produce stable, gel-like oil/water HIPPEs with excellent storage stability. In contrast, at pH 5 and 7, stable HIPPEs could not be formed, which might be attributed to the variation of contact angle and electrostatic repulsion of BGPs. Structure analysis indicated that HIPPEs with gel-like structures were mainly stabilized by physical barriers and electrostatic repulsion. The present study is expected to provide new insight on comprehensive utilization of fungi sources.
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http://dx.doi.org/10.1016/j.foodchem.2021.130954DOI Listing
August 2021

Introduction of cation vacancies and iron doping into TiO enabling efficient uranium photoreduction.

J Hazard Mater 2021 Aug 17;423(Pt A):126935. Epub 2021 Aug 17.

State Key Laboratory of Environment-friendly Energy Materials, National Co-innovation Center for Nuclear Waste Disposal and Environmental Safety, Sichuan Co-Innovation Center for New Energetic Materials, Nuclear Waste and Environmental Safety Key Laboratory of Defense, School of National Defence Science & Technology, Southwest University of Science and Technology, Mianyang, Sichuan 621010, PR China. Electronic address:

The reduction of U(VI) to U(IV) in wastewater by semiconductor photocatalysis has become a new highly efficient and low-cost method for U(VI) removal. However, due to the weak absorption of visible light led by wide band gap and low carrier utilization rate resulted from the severe electron-holes recombination, the photoreduction performance of U(VI) is limited. Herein, the Ti vacancies and doped Fe atoms were simultaneously introduced into TiO nanosheet (labeled as 4%Fe-TiO) as a highly active and stable catalysis for U(VI) photoreduction. Without adding any hole sacrifice agent, 4%Fe-TiO nanosheets achieved 99.7% removal efficiency for U(VI) within 120 min. And the 92.1% removal efficiency of U(VI) via 4%Fe-TiO nanosheets was still maintained after 5 cycles. Moreover, 4%Fe-TiO exhibited dramatic removal rate, 81.6% U(VI) in the solution was removed in 10 min. Further study on the mechanism showed that simultaneously introducing the Ti vacancies and doped Fe atoms in 4%Fe-TiO nanosheets improved the visible light utilization and decreased the recombination of photogenerated electron-hole pairs, contributing to the highly efficiency removal of U(VI).
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http://dx.doi.org/10.1016/j.jhazmat.2021.126935DOI Listing
August 2021

Non-linear dose-response relation between urinary levels of nicotine and its metabolites and cognitive impairment among an elderly population in China.

Ecotoxicol Environ Saf 2021 Aug 27;224:112706. Epub 2021 Aug 27.

Key Laboratory of Environment & Health (Huazhong University of Science and Technology), Ministry of Education, State Environmental Protection Key Laboratory of Environment and Health (Wuhan) and State Key Laboratory of Environment Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Hangkong Road 13, Wuhan 430030, Hubei, China. Electronic address:

Background: Active smoking and exposure to environmental tobacco smoke may be related to cognitive function decline. We assessed the associations of urinary levels of nicotine and its metabolites with cognitive function.

Methods: A total of 553 elder adults at high risk of cognitive impairment and 2212 gender- and age-matched individuals at low risk of cognitive impairment were selected at a ratio of 1: 4 from the remained individuals (n = 6771) who completed the baseline survey of the Shenzhen Ageing-Related Disorder Cohort, after excluding those with either Alzheimer's disease, Parkinson's syndrome or stroke as well as those with missing data on variables (including active and passive smoking status, Mini-Cog score). Urinary levels of nicotine and its metabolites and cognitive function for all individuals were measured by high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) and assessed using the Mini-Cog test, respectively. Associations of urinary levels of nicotine and its metabolites with cognitive function were analyzed by conditional logistic regression models.

Results: Individuals in the highest tertile of urinary OHCotGluc (OR: 1.52, 95%CI: 1.19-1.93) or NNO (OR: 1.50, 95%CI: 1.16-1.93) levels as well as in the second tertile of urinary ∑Nic level (OR: 1.43, 95%CI: 1.13-1.82) were at higher risk of cognitive impairment compared with those in the corresponding lowest tertile. Restricted cubic spline models revealed the non-linear dose-response relationships between urinary levels of OHCotGluc, NNO or ∑Nic and the risk of cognitive impairment.

Conclusions: Urinary levels of OHCotGluc, NNO or ∑Nic exhibited a non-linear dose-response relationship with cognitive function in the urban elderly.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112706DOI Listing
August 2021

A non-clinical comparative study of IL-23 antibodies in psoriasis.

MAbs 2021 Jan-Dec;13(1):1964420

Abbvie Bioresearch Center, Worcester.

Four antibodies that inhibit interleukin (IL)-23 are approved for the treatment of moderate-to-severe plaque psoriasis. Here, we present non-clinical data comparing ustekinumab, guselkumab, tildrakizumab and risankizumab with regard to thermostability, IL-23 binding affinity, inhibitory-binding mode, potency and efficacy. Risankizumab and guselkumab exhibited 5-fold higher affinity for IL-23 and showed more potent inhibition of IL-23 signaling than ustekinumab and tildrakizumab. Risankizumab and guselkumab completely blocked the binding of IL-23 to IL-23Rα as expected, whereas tildrakizumab did not. , risankizumab and guselkumab blocked the terminal differentiation of T17 cells in a similar manner, while tildrakizumab had minimal impact on T17 differentiation. In a human IL-23-induced ear-swelling mouse model, risankizumab and guselkumab were more effective than ustekinumab and tildrakizumab at reducing IL-17, IL-22, and keratinocyte gene expression. Our results indicate that the four clinically approved antibodies targeting IL-23 differ in affinity and binding epitope. These attributes contribute to differences in potency, receptor interaction inhibition mode and efficacy in preclinical studies as described in this report, and similarly may affect the clinical performance of these drugs.
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http://dx.doi.org/10.1080/19420862.2021.1964420DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409790PMC
August 2021

Visual detection of perchlorate in aqueous solution using alkali methylene blue.

Anal Sci 2021 Aug 27. Epub 2021 Aug 27.

Tea Research Institute, Chinese Academy of Agricultural Sciences.

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http://dx.doi.org/10.2116/analsci.21P174DOI Listing
August 2021

Dopamine receptor 2 downregulation and brain-derived neurotrophic factor upregulation in the paraventricular nucleus are correlated with brown adipose tissue thermogenesis in rats with bilateral substantia nigra lesions.

J Chem Neuroanat 2021 Aug 26;117:102016. Epub 2021 Aug 26.

Department of Human Anatomy and Histoembrology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang 453003, China; Xinxiang Key Laboratory of Molecular Neurology, Xinxiang Medical University, Xinxiang 453003, China; Henan International Joint Laboratory of Noninvasive Neuromodulation, Xinxiang Medical University, Xinxiang 453003, China. Electronic address:

The thermogenesis resulting from brown adipose tissue (BAT)-induced energy consumption is an important method of energy regulation. It has been reported that brain-derived neurotrophic factor (BDNF)-positive neurons in the paraventricular nucleus (PVN) can regulate adaptive thermogenesis in interscapular brown adipose tissue (IBAT), but the upstream regulatory mechanism is still unclear. Our previous studies have found that a large number of dopamine (DA) receptors (DRs) are expressed on BDNF-positive neurons in the PVN and that the substantia nigra (SN) can directly project to the PVN (forming the SN-PVN pathway). Therefore, we speculate that DA in the SN can regulate the expression of BDNF via DRs and then affect IBAT thermogenesis. In this study, bilateral SN lesions were induced in rats with 6-hydroxydopamine (6-OHDA), and the altered expression of DRs and BDNF in the PVN and the metabolic changes in IBAT were studied via double immunofluorescence and western blotting. The results showed that BDNF-positive neurons in the PVN expressed DR 1 (D1) and DR 2 (D2) and were surrounded by a large number of tyrosine hydroxylase (TH)-positive nerve fibers. Compared with the control group, the 6-OHDA group exhibited significantly fewer TH-positive neurons and significantly lower TH expression in the SN, but body weight, IBAT weight and food consumption did not differ between the groups. In the PVN, BDNF expression was upregulated in the 6-OHDA group, while D2 and TH expression was downregulated. In IBAT, the expression of uncoupling protein-1 (UCP-1), phosphorylated hormone-sensitive lipase (p-HSL), TH and β3-adrenergic receptor (β3-AR) was increased, while the expression of fatty acid synthase (FAS) was decreased. The IBAT cell diameter was also decreased in the 6-OHDA group. The results suggest that the SN-PVN pathway may be an upstream neural pathway that can affect BDNF expression in the PVN and that DRs may mediate its regulatory effects. This study expands our understanding of the relationship between DA and obesity.
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http://dx.doi.org/10.1016/j.jchemneu.2021.102016DOI Listing
August 2021

Pain relief and cartilage repair by Nanofat against osteoarthritis: preclinical and clinical evidence.

Stem Cell Res Ther 2021 Aug 26;12(1):477. Epub 2021 Aug 26.

The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China.

Background: Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode.

Methods: Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients.

Results: The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events.

Conclusion: In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.
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http://dx.doi.org/10.1186/s13287-021-02538-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390235PMC
August 2021

Metabolic Changes in Maternal and Cord Blood in One Case of Pregnancy-Associated Breast Cancer Seen by Fluorescence Lifetime Imaging Microscopy.

Diagnostics (Basel) 2021 Aug 19;11(8). Epub 2021 Aug 19.

Shanghai Engineering Research Center of Ultra-Precision Optical Manufacturing, Key Laboratory of Micro and Nano Photonic Structures (Ministry of Education), Department of Optical Science and Engineering, School of Information Science and Technology, Fudan University, 220 Handan Road, Shanghai 200433, China.

Pregnancy-associated breast cancer (PABC) is a rare disease, which is frequently diagnosed at an advanced stage due to limitations in current diagnostic methods. In this study, fluorescence lifetime imaging microscopy (FLIM) was used to study the metabolic changes by measuring maternal blood and umbilical cord blood via the autofluorescence of coenzymes, reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H), and flavin adenine dinucleotide (FAD). The NAD(P)H data showed that a PABC case had significant differences compared with normal cases, which may indicate increased glycolysis. The FAD data showed that both maternal and cord blood of PABC had shorter mean lifetimes and higher bound-FAD ratios. The significant differences suggested that FLIM testing of blood samples may be a potential method to assist in PABC non-radiative screening.
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http://dx.doi.org/10.3390/diagnostics11081494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8392038PMC
August 2021

Anthocyanin from purple sweet potato attenuates lead-induced reproductive toxicity mediated by JNK signaling pathway in male mice.

Ecotoxicol Environ Saf 2021 Aug 24;224:112683. Epub 2021 Aug 24.

Department of Hygiene, School of Public Health, Xuzhou Medical University, Xuzhou, China.

The present work aimed to explore the protective effect of APSP on Pb-induced reproductive toxicity and possible mechanism. APSP (100 mg/kg) was administered to Pb-intoxicated (0.2% lead acetate) male Kunming mice once daily by oral gavage for 6 weeks. Our results showed that APSP exerted male reproductive protection effects as showed by attenuated Pb-induced testicular injury, improved sperm count and motility, and reduced sperm abnormality rate. APSP also restored Pb-induced decrease in both enzymatic and non-enzymatic antioxidants, and GSH/GSSG ratio, but inhibited lipid peroxidation in serum and testes. Moreover, APSP downregulated Pb-induced Bax mRNA and protein expressions, suppressed activation of caspase-3, upregulated Bcl-2 protein expression, and prevented Pb-induced DNA damage. APSP treatment also interfered with Pb-induced testicular JNK signaling through inhibition of JNK mRNA expression and phosphorylation, resulting in inhibition of c-Jun expression. These effects of APSP were abolished by Pb. In conclusion, APSP represents a potential therapeutic agent for preventing Pb-caused reproductive toxicity, which is attributed to its antioxidant and anti-apoptotic properties, as well as, modulation of JNK signaling pathway.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112683DOI Listing
August 2021

Using Shattered Assumption Theory to Understand How Cyberbullying Victimization is Linked With Perceived Control Among Chinese College Students.

J Interpers Violence 2021 Aug 26:8862605211042572. Epub 2021 Aug 26.

Renmin University of China, Beijing, China.

Perceived control (PC) is considered as one of the most basic psychological needs of human beings, and it is also an important index to measure individual mental health. Previous studies have shown that negative life experience is an important risk factor for predicting PC. With the prevalence of cyberbullying among college students, this study explored how cybervictimization (CV) was related to the PC, mediated through the personal belief in a just world (PBJW). Besides, this study examined the moderating role of interpersonal forgiveness (IF) in the direct relationship between CV and PC and the indirect connection through PBJW. It was expected that CV would negatively predict the PC, and the PBJW would mediate this relationship. The direct and indirect effects were stronger in individuals with low IF than those with high IF. In this study, 837 Chinese college students were invited to conduct an online survey using a convenient sampling method. Participants were asked to complete the measurement of CV, PBJW, IF, and PC. After controlling gender and age, the results revealed that CV could directly and negatively predict college students' PC and indirectly predict the PC through the mediation of PBJW. Additionally, IF moderated the effect of CV on PBJW and PC. Unlike what we expected, the effect of CV on PBJW was stronger for low IF individuals than those with high IF, while the effect of CV on PC was stronger for high IF individuals than those with low IF. The unexpected orientation and other results were discussed.
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http://dx.doi.org/10.1177/08862605211042572DOI Listing
August 2021

Variations in the insulin receptor substrate 1 (IRS1) and its association with growth traits in Chinese black Tibetan sheep ().

Anim Biotechnol 2021 Aug 25:1-6. Epub 2021 Aug 25.

College of Agriculture and Animal Husbandry, Qinghai University, Xining, Qinghai Province, People's Republic of China.

This paper presented the results on the study of insulin receptor substrate 1 (IRS1) polymorphisms in Chinese black Tibetan sheep. Via DNA direct sequencing, four variations within 3' untranslated region (UTR) of IRS1, including g.9382T > G, g.9569T > G, g.9572C > T and g.9695A > C were detected in the black Tibetan sheep population. Based on the test, those four loci deviated from Hardy-Weinberg equilibrium ( < 0.05). In g.9569T > G locus, genotype of GG possessed advantage on body weight ( < 0.05). In g.9572C > T locus, individuals with genotype of TT homozygous mutation decreased significantly on body weight, withers height, body length and chest circumference ( < 0.05 or  < 0.01). In g.9695A > C locus, the body weight and chest circumference were also higher in AA carriers than in CC carriers ( < 0.05). Our results provided evidence that polymorphisms in IRS1 were associated with growth efficiency traits by quantitative genetic analysis, and may be used for marker-assisted selection in Chinese indigenous sheep.
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http://dx.doi.org/10.1080/10495398.2021.1957687DOI Listing
August 2021

Peroxiredoxin 1 is essential for natamycin-triggered apoptosis and protective autophagy in hepatocellular carcinoma.

Cancer Lett 2021 Aug 21;521:210-223. Epub 2021 Aug 21.

West China School of Basic Medical Sciences & Forensic Medicine, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, And Collaborative Innovation Center for Biotherapy, Chengdu, China; Institute of Cancer Research, Shenzhen Bay Laboratory, Shenzhen, China. Electronic address:

Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide and lacks effective treatment. Herein, we found that the antifungal Natamycin (NAT) exhibits antitumor activity by inducing apoptosis both in vitro and in vivo. Mechanistically, NAT downregulates the expression of Peroxiredoxin 1 (PRDX1) by promoting ubiquitination-mediated degradation, thereby leading to increased reactive oxygen species (ROS) accumulation and subsequent apoptosis. Exogenous overexpression of PRDX1 or N-acetyl-l-cysteine (NAC) pretreatment abrogates NAT-induced cytotoxicity in PLC/PRF/5 and Huh7 cells, suggesting the vital role of ROS in the antitumor properties of NAT. Of note, downregulation of PRDX1 decreases the phosphorylation of AKT, thereby inducing cytoprotective autophagy and combinational use of NAT and chloroquine (CQ) achieves better anti-tumor efficacy. Moreover, NAT acts synergistically with sorafenib (SOR) in HCC suppression. Collectively, our study provides an important molecular basis for NAT-induced cell death and suggests that the antifungal NAT holds the potential to be repurposed as an anticancer drug for HCC treatment.
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http://dx.doi.org/10.1016/j.canlet.2021.08.023DOI Listing
August 2021
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