Publications by authors named "Rui Li"

3,105 Publications

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Heat/pH-boosted release of 5-fluorouracil and albumin-bound paclitaxel from Cu-doped layered double hydroxide nanomedicine for synergistical chemo-photo-therapy of breast cancer.

J Control Release 2021 May 11. Epub 2021 May 11.

Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia. Electronic address:

Considerable attention has been devoted to nanomedicine development for breast cancer therapy, while the therapeutic efficiency is far from satisfactory owing to non-specific biodistribution-caused side effects and limitation of single modal treatment. In this study, we have developed a novel nanomedicine for efficient combination breast cancer therapy. This nanomedicine was based on copper-doped layered double hydroxide (Cu-LDH) nanoparticles loaded with two FDA-approved anticancer drugs, i.e. 5-fluorouracil (5-FU) and albumin-bound paclitaxel (nAb-PTX) with complementary chemotherapeutic actions. The 5-FU/Cu-LDH@nAb-PTX nanomedicine showed pH-sensitive heat-facilitated therapeutic on-demand release and demonstrated the moderate-to-strong synergy of photothermal therapy and chemotherapy in inducing apoptosis of breast cancer cells (4 T1). This nanomedicine had a high colloidal stability in saline and serum, and efficiently accumulated in the tumor tissue. Remarkably, this nanomedicine nearly eliminated 4 T1 tumors in vivo after a two-course treatment under mild 808 nm laser irradiation (0.75 W/cm, 3 min) at very low doses of 5-FU and nAb-PTX (0.25 and 0.50 mg/kg, 8-50 times less than that used in other nanoformulations), without observable side effects. Therefore, this research provides a novel approach to designing multifunctional nanomedicines for on-demand release of chemotherapeutics to cost-effectively treat breast cancer with minimal side effects in future clinic applications.
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http://dx.doi.org/10.1016/j.jconrel.2021.05.011DOI Listing
May 2021

Venous thromboembolism in non-COVID-19 population during the pandemic: a nationwide multicenter retrospective survey.

J Thromb Thrombolysis 2021 May 14. Epub 2021 May 14.

Department of Interventional Radiology, Nanjing First Hospital, 68 Changle Rd., Nanjing, Jiangsu Province, China.

Impact of pandemic on the incidence of venous thromboembolism (VTE) in non-COVID-19 patients is undetermined. Thus, a nationwide multicenter retrospective survey was conducted to evaluate the disease burden in non-COVID-19 population. This multi-center survey involved 94 hospitals from 24 provinces in the mainland of China, and collected data on non-COVID-19 patients admitted to the radiology departments due to VTE between January 24 and April 16, 2020. Baseline characteristics, VTE risk factors, clinical manifestations and the treatments were compared with those in the same period of 2019. 3,358 patients with VTE from 74 hospitals were included in this study (1,458 in 2020, 1,900 in 2019). Most aged ≥ 50 years (80.6% in the pandemic, 81.2% in 2019). The number of patients aged 30-39 years increased from 3.9% in 2019 period to 5.8% in the pandemic (p = 0.009). Among the VTE risk factors, the rate of decreased activity increased significantly in the pandemic, and was much higher than that in 2019 (30.7% vs 22.6%, p < 0.0001). Under the risk of decreased activity, patients with comorbidities chronic diseases, especially diabetes, showed significantly a higher incidence of VTE (30.4% vs 22.0%, p < 0.0001). In the pandemic period, fewer patients were treated with anticoagulation alone (33.5% vs 36.7%, p = 0.05), and more underwent inferior vena cava filter (IVCF) implantation, compared with those in 2019 (66.5% vs 63.2%, p = 0.046). The pandemic increased the VTE risk of decreased activity among the non-COVID-19 population. Patients with comorbidities, especially diabetes, have a significant higher risk of VTE during the pandemic.
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http://dx.doi.org/10.1007/s11239-021-02442-2DOI Listing
May 2021

Dual mitigation of immunosuppression combined with photothermal inhibition for highly effective primary tumor and metastases therapy.

Biomaterials 2021 May 7;274:120856. Epub 2021 May 7.

Department of Ultrasound, The Third Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, PR China. Electronic address:

T-cell based immune response can attack cancer cells formidably when certain immune checkpoint (e.g., PD-1/PD-L1) is blocked. Unfortunately, PD-1/PD-L1 blockade only provoke limited immune response because the differentiation of tumor-reactive T lymphocytes is often suppressed by TGF-β pathway. Namely, the combating cancer weapon is weakened. In this study, other than employing photothermal therapy (PTT) to eliminate the primary tumor, we also aimed to expose in situ tumor-associated antigens and exert immune response for metastases inhibition. This enhanced immunotherapeutic strategy is achieved by IR780/SB-505124 based nanoliposomes (Nano-IR-SB@Lip). Upon administration, TGF-β pathway is inhibited by SB to drive effector T cells into a responsive state and reduce the infiltration of Treg cells, eventually greatly enhancing the weapon against cancer. In the meantime, the immunosuppressive "protection" of tumor cells is also neutralized by blocking PD-1/PD-L1 immune checkpoint. By virtue of inherent characteristics of IR780, Nano-IR-SB@Lip can selectively accumulate, penetrate deeply in tumor tissues, and preferentially retain in mitochondria. The above features are of critical importance to tumor therapy. Thus, highly effective cancer immunotherapy is implemented via selective accumulation/deep penetration of Nano-IR-SB@Lip in tumor, achieving PTT induced immunogenic cell death and dual mitigation of immunosuppression strategy (TGF-β inhibition/PD-1/PD-L1 blockade), which is a promising therapeutic modality for cancer.
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http://dx.doi.org/10.1016/j.biomaterials.2021.120856DOI Listing
May 2021

Corrigendum: MR-guided 125I seed implantation treatment for maxillofacial malignant tumor.

J Appl Clin Med Phys 2021 May 12. Epub 2021 May 12.

Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.

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http://dx.doi.org/10.1002/acm2.13272DOI Listing
May 2021

Low-dose aspirin can downregulate progesterone resistance and increase the expression of LIF in endometriosis during the implantation window.

Gynecol Endocrinol 2021 May 11:1-5. Epub 2021 May 11.

Department of Obstetrics and Gynaecology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China.

Aim: Study the effect of low-dose aspirin on the endometrial receptivity in endometriosis rat models.

Materials And Methods: This study is to explore the expressions of progesterone receptor and LIF among three groups of endometriosis rat models: control group ( = 12), EMs group ( = 15), and aspirin group ( = 17). The expressions of progesterone receptor (PR), PRA, PRB, and leukemia inhibitory factor receptor (LIFR) in eutopic endometrium were determined using immunohistochemistry technology, western blot, and qRT-PCR. The levels of LIF in eutopic endometrium and serum were detected by western blot, qRT-PCR, and ELISA.

Results: The expressions of PR, PRA, and PRB protein were significantly increased in the eutopic endometrium after low-dose aspirin treatment, and the level of PRB mRNA was also increased while the ratio of PRA/PRB mRNA was decreased in the eutopic endometrium. The levels of LIF in eutopic endometrium and serum were increased compared with the untreated endometriosis rats. However, the expression of LIFR was not statistically different among the three groups.

Conclusions: The results suggest that the low-dose aspirin treatment could downregulate progesterone resistance and increase the expression of LIF of endometriosis rats during the implantation window, which could improve endometrial receptivity and enhance the pregnant rate of endometriosis. It may provide a potential treatment method for endometriosis-related infertility.
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http://dx.doi.org/10.1080/09513590.2021.1918663DOI Listing
May 2021

First Report of Paramyrothecium breviseta Causing Leaf Spot Disease of Coffea canephora in China.

Plant Dis 2021 May 11. Epub 2021 May 11.

Hai Kou , China;

Coffee is a tropical plant with two widely cultivated species, namely Coffea arabica and Coffea canephora. A leaf spot disease causing brownish and necrotic lesions was broken out on the C. canephora coffee seedlings in a nursery in Ruili County, Yunnan Province, China, during 2018 to 2019. The incidence of the disease was 15% ~ 20%. Ten diseased leaf samples from five diseased plants were collected for pathogen isolation by tissue separation method. Leaf pieces were cut from the margin of the necrotic lesions (4 × 6 mm), surface-sterilized for 30 s in 75% ethanol, followed by 0.1% arsenic mercury solution for 15 s, then washed 3~4 times with sterilized distilled water and transferred onto potato dextrose agar (PDA) medium in petri plates. Four morphologically similar isolates were obtained from lesions and cultivated on PDA at 25°C. Initial colonies of isolates were round, neat edge, white, floccose mycelium and developed dark green-to-black concentric rings that were sporodochia bearing viscid spore masses after 5~7 days. Conidia were acetates, hyaline and cylindrical with both rounded ends and 4.8 to 6.4 µm long × 1.6 to 2.6 µm wide. Koch's test were conducted on three healthy plants leaves of original source variety C. canephora No.2 and C.arabica Catimor CIFC7963 (control plants) with spore suspension (1 × 106/mL), respectively. Meanwhile, equal numbers of healthy plants were inoculated with water as controls. After inoculation, the plants were transferred into an incubator at 25℃ with saturated humidity. After 10 days of inoculation, all the tested plants presented similar typical symptoms with the diseased leaves under natural conditions; whereas the controls remained healthy. Koch's postulates were performed by re-isolating the fungus from the inoculated leaves and verifying its colony and morphological characters. Two single spore isolates cultured on PDA medium were selected for DNA extraction. The ribosomal internal transcribed spacer (ITS) was PCR amplified by using primers ITS1 and ITS4 (White et al., 1990), β-tubulin gene by Bt2a and Bt2b (Glass and Donaldson, 1995), the RNA polymerase II second largest subunit (rpb2) by RPB2-5F2 and RPB2-7cR (O'Donnell et al, 2007), calmodulin (cmda) gene by CAL-228F and CAL2Rd (Groenewald et al., 2013). The sequences of ITS (MT853067 ~ MT853068), β-tubulin (MT897899 ~ MT897900), rpb2 (MW256264~ MW286265) and cmda (MT897897~ MT897898) were deposited in GenBank databases. BLAST analysis revealed that the representative isolates sequences shared 99.31%~99.65% similarities to the ITS sequence of Paramyrothecium breviseta (Accession Nos. NR_155670.1), 99.43% similarities to the β-tubulin sequence of P. breviseta (Accession Nos. KU846406.1), 98.98% similarities to the rpb2 sequence of P. breviseta (Accession Nos. KU846351.1), and 98.54%~98.71% similarities to the cmda sequence of P. breviseta (Accession Nos. KU846262.1). As it shown in the phylogenetic tree derived from combined ITS, β-tubulin, rpb2, and cmda gene sequences, the two representative isolates were clustered together with P. breviseta CBS 544.75 with 98% strong bootstrap support, which confirmed that P. breviseta is the causal agent of leaf spot of Coffea canephora. To our knowledge, this is the first report of a leaf spot disease caused by P. breviseta on C. canephora in China, which raised the caution that P. breviseta is also pathogenic to Coffea Arabica.
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http://dx.doi.org/10.1094/PDIS-10-20-2276-PDNDOI Listing
May 2021

Dorsal raphe serotonergic neurons promote arousal from isoflurane anesthesia.

CNS Neurosci Ther 2021 May 11. Epub 2021 May 11.

Department of Anesthesiology and Perioperative Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Aims: General anesthesia has been widely applied in surgical or nonsurgical medical procedures, but the mechanism behind remains elusive. Because of shared neural circuits of sleep and anesthesia, whether serotonergic system, which is highly implicated in modulation of sleep and wakefulness, regulates general anesthesia as well is worth investigating.

Methods: Immunostaining and fiber photometry were used to assess the neuronal activities. Electroencephalography spectra and burst-suppression ratio (BSR) were used to measure anesthetic depth and loss or recovery of righting reflex to indicate the induction or emergence time of general anesthesia. Regulation of serotonergic system was achieved through optogenetic, chemogenetic, or pharmacological methods.

Results: We found that both Fos expression and calcium activity were significantly decreased during general anesthesia. Activation of 5-HT neurons in the dorsal raphe nucleus (DRN) decreased the depth of anesthesia and facilitated the emergence from anesthesia, and inhibition deepened the anesthesia and prolonged the emergence time. Furthermore, agonism or antagonism of 5-HT 1A or 2C receptors mimicked the effect of manipulating DRN serotonergic neurons.

Conclusion: Our results demonstrate that 5-HT neurons in the DRN play a regulative role of general anesthesia, and activation of serotonergic neurons could facilitate emergence from general anesthesia partly through 5-HT 1A and 2C receptors.
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http://dx.doi.org/10.1111/cns.13656DOI Listing
May 2021

Cloning and Heterologous Expression of a Novel Xylanase Gene TAX1 from Trichoderma atroviride and Its Application in the Deconstruction of Corn Stover.

Appl Biochem Biotechnol 2021 May 10. Epub 2021 May 10.

Northeast Agricultural University, Harbin, 150030, People's Republic of China.

Xylanase plays a vital role in the efficient utilization of xylan, which accounts for up to 30% of plant dry matter. However, the production cost of xylanase remains high, and the enzymatic characteristics of xylanases of most microorganisms are not suitable for industrial production. Therefore, it is of great significance to discover and develop new and efficient xylanases. In this study, the xylanase gene TAX1 (672 bp cDNA) was cloned from Trichoderma atroviride 3.3013 and expressed in Pichia pastoris. The TAX1 gene encoded a 223-amino acid protein (TAX1) with a molecular weight of 24.2 kDa which showed high similarity to glycoside hydrolase family 11. Enzyme activity assay verified that the recombinant xylanase TAX1 had optimal activity (215.3 IU/mL) at 50°C and pH 6.0. Stable working conditions were measured as pH 4.0-7.0 and 40-60°C. By adding Zn, the relative enzymatic activity of recombinant TAX1 was enhanced by 26%. The recombinant xylanase showed high activity toward birchwood xylan and corn stover. The K and K for xylan and corn stover were 0.36 mg/mL and 0.204 S and 0.48 mg/mL and 0.149 S, respectively. The enzymatic activity of the TAX1 produced by P. pastoris was about 2.4-4 times higher that directly isolated from T. atroviride, so engineered P. pastoris for xylanase production could be an ideal candidate for industrial enzyme production.
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http://dx.doi.org/10.1007/s12010-021-03582-0DOI Listing
May 2021

Identification and Characterization of a Novel SXT/R391 Integrative and Conjugative Element in a Food Isolate.

Foodborne Pathog Dis 2021 May 7. Epub 2021 May 7.

College of Food Science and Engineering, Wuhan Polytechnic University, Wuhan, China.

is an opportunistic human pathogen. In this study, a novel SXT/R391 integrative and conjugative element (ICE), named ICEChnS012, was identified in the multidrug-resistant strain S012 that was isolated from retail chicken in China. Whole genome sequencing revealed that ICEPChnS012 carried 22 resistance genes including , , , , and . ICEPChnS012 harbored 10 copies of IS and IS-mediated genetic new rearrangements caused variations in HS4 region. To our knowledge, an unusual gene cassette array was found in in this study for the first time. And this is the first report of identification of and in VRIII region in The conjugation experiments proved that ICEChnS012 could be transferred to EC600 through conjugation. These findings demonstrated that ICEChnS012 was a special ICE that carried the largest number of antimicrobial resistance genes in the family of SXT/R391 ICEs. This element could serve as an important vehicle for the dissemination of antibiotic resistance genes and should receive great concern.
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http://dx.doi.org/10.1089/fpd.2020.2886DOI Listing
May 2021

A Robust Circular RNA-Associated Three-Gene Prognostic Signature for Patients with Gastric Cancer.

Biomed Res Int 2021 21;2021:6633289. Epub 2021 Apr 21.

Department of Medical Oncology, Xuzhou Central Hospital, Clinical School of Xuzhou Medical University, Xuzhou 221009, China.

Accumulating evidence has demonstrated that circular RNAs (circRNAs) play vital roles in cancer progression. However, the underlying molecular mechanisms of circRNAs remain poorly elucidated in gastric cancer (GC). The main purpose of present study is to explore the underlying regulatory mechanism by constructing a circRNA-associated competitive endogenous RNA (ceRNA) network and further establish a robust prognostic signature for patients with GC. Based on expression data of circRNA, microRNA, and mRNA derived from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases, a circRNA-associated ceRNA network, containing 15 cirRNAs, 9 microRNAs, and 35 mRNAs, was constructed using the Starbase database. Functional enrichment analysis showed that the ceRNA network might be involved in many cancer-related pathways, such as regulation of transcription from RNA polymerase II promoter, mesodermal cell differentiation, and focal adhesion. A protein-protein interaction network was constructed based on genes within the circRNA-associated ceRNA network. We found that six of ten hub genes within the PPI network were significantly associated with overall survival (OS). Thus, using the LASSO method, we constructed a three-gene prognostic signature based on TCGA-GC cohort, which could classify GC patients into low-risk and high-risk groups with significant difference in OS (HR = 1.9, 95%CI = 1.14-3.2, and log-rank = 0.001). The prognostic performance of the three-gene signature was verified in GSE15459 (HR = 1.9, 95%CI = 1.27-3.0, and log - rank  = 2.2 - 05) and GSE84437 (HR = 1.5, 95%CI = 1.17-2.0, and log - rank  = 6.3 - 04). Multivariate Cox analysis further revealed that the three-gene prognostic signature could serve as an independent risk factor for OS. Taken together, our findings contribute to a better understanding of the underlying mechanisms of circRNAs in GC progression. Furthermore, a robust prognostic signature is meaningful to facilitate individualized treatment for patients with GC.
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http://dx.doi.org/10.1155/2021/6633289DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8084642PMC
April 2021

A patient with metastatic non-small cell lung cancer who received pembrolizumab monotherapy after stereotactic body radiotherapy had progression-free survival of nearly 5 years: a case report.

Ann Palliat Med 2021 Apr;10(4):4999-5009

Department of Cardiothoracic Surgery, Hwa Mei Hospital, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital), Ningbo, China; Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences (Ningbo No. 2 Hospital), Ningbo, China.

Lung cancer is a malignancy with the highest morbidity and mortality in the world. Radiotherapy, chemotherapy, targeted therapy, and immunotherapy have been widely used to treat metastatic non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT), also known as stereotactic ablation radiotherapy (SABR), can precisely deliver a high dose of radiation to a target in a limited area. SBRT has been established as the standard treatment for patients with early NSCLC who are unsuitable for operation or refuse surgery and patients with oligometastatic NSCLC who are not suitable for surgery. As an immunologic agent, pembrolizumab has been approved to treat metastatic NSCLC in certain countries, including China and the United States. Increased tumor proportion score (TPS) can reduce pembrolizumab's immunotherapeutic effect, while SBRT can reduce TPS and enhance immunotherapy efficacy. However, there have been no reports in China on metastatic NSCLC patients who have received pembrolizumab monotherapy after stereotactic body radiotherapy (SBRT). Here, we present a case of progression-free survival (PFS) of nearly 5 years with pembrolizumab monotherapy after SBRT for metastatic NSCLC. This case is the patient with the most prolonged medication duration and who experienced the most efficacious treatment among the patients with metastatic NSCLC reported in the Chinese literature.
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http://dx.doi.org/10.21037/apm-21-860DOI Listing
April 2021

Combined effect of vitamin C and vitamin D on intestinal epithelial barrier by regulating Notch signaling pathway.

Nutr Metab (Lond) 2021 May 8;18(1):49. Epub 2021 May 8.

Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, China.

Background: Tight junction proteins play crucial roles in maintaining the intestinal mucosal barrier. Although previous studies have shown that Notch signaling is closely related to tight junction proteins, the mechanism remains unclear. This study was performed to investigate whether vitamin C combined with vitamin D affects intestinal mucosal barrier stability via the Notch signaling pathway.

Methods: Intestinal epithelial barrier and notch signaling pathway were studied using guinea pig and SW480 cells. The guinea pigs were randomized into four groups (n = 6 in each group): control group (C, 200 IU/kg d VD + 100 mg/kg d VC), low VC group (LVC, 200 IU/kg d VD + 10 mg/kg d VC), medium VC group (MVC, 200 IU/kg d VD + 100 mg/kg d VC), and high VC group (HVC, 200 IU/kg d VD + 200 mg/kg d VC). Except for the control group, the other three groups were freely drinked with 2% dextran sodium sulfate solution for 4 days. And the control group was free to drink distilled water. The following cell groups were used: control group (SW480 cells without intervention); LPS group (100 ng/mL LPS); VD group (0.1 μmol/L VD); VC + VD group (0.1, 1, 5, 10 μmol/mL VC + 0.1 μmol/L VD).

Results: Electron microscopy analysis revealed that both low and high doses of vitamin C combined with vitamin D maintained dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal epithelium tight junction. Compared with the control group, the expression level of ZO-1 mRNA in the colon tissue of the high-dose vitamin C group was significantly increased. In SW480 cell experiments, compared with the control group, cell migration and repair following treatment with different concentrations of vitamin C combined with vitamin D were significantly improved and the protein expression of Notch-1 was increased, whereas the protein expression of claudin-2 was significantly decreased. Thus, our results demonstrate that an appropriate amount of vitamin C combined with vitamin D can regulate the expression of claudin-2 by regulating Notch-1, relieve destruction of the intestinal mucosal barrier, and promote the repair of damage to the cell mucosal barrier.

Conclusions: We found that vitamin C combined with vitamin D protected against dextran sodium sulfate-induced ulcerative colitis in the guinea pig intestinal mucosa.
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http://dx.doi.org/10.1186/s12986-021-00576-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105975PMC
May 2021

Amelioration of diabetic retinopathy in db/db mice by treatment with different proportional three active ingredients from Tibetan medicine Berberis dictyophylla F.

J Ethnopharmacol 2021 May 6;276:114190. Epub 2021 May 6.

Innovative Institute of Chinese Medicine and Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Ethnopharmacological Relevance: Berberis dictyophylla F., a famous Tibetan medicine, has been used to prevent and treat diabetic retinopathy (DR) for thousands of years in clinic. However, its underlying mechanisms remain unclear.

Aim Of The Study: The present study was designed to probe the synergistic protection and involved mechanisms of berberine, magnoflorine and berbamine from Berberis dictyophylla F. on the spontaneous retinal damage of db/db mice.

Materials And Methods: The 14-week spontaneous model of DR in db/db mice were randomly divided into eight groups: model group, calcium dobesilate (CaDob, 0.23 g/kg) group and groups 1-6 (different proportional three active ingredients from Berberis dictyophylla F.). All mice were intragastrically administrated for a continuous 12 weeks. Body weight and fasting blood glucose (FBG) were recorded and measured. Hematoxylin-eosin and periodic acid-Schiff (PAS) stainings were employed to evaluate the pathological changes and abnormal angiogenesis of the retina. ELISA was performed to assess the levels of IL-6, HIF-1α and VEGF in the serum. Immunofluorescent staining was applied to detect the protein levels of CD31, VEGF, p-p38, p-JNK, p-ERK and NF-κB in retina. In addition, mRNA expression levels of VEGF, Bax and Bcl-2 in the retina were monitored by qRT-PCR analysis.

Results: Treatment with different proportional three active ingredients exerted no significant effect on the weight, but decreased the FBG, increased the number of retinal ganglionic cells and restored internal limiting membrane. The results of PAS staining demonstrated that the drug treatment decreased the ratio of endothelial cells to pericytes while thinned the basal membrane of retinal vessels. Moreover, these different proportional active ingredients can markedly downregulate the protein levels of retinal CD31 and VEGF, and serum HIF-1α and VEGF. The gene expression of retinal VEGF was also suppressed. The levels of retinal p-p38, p-JNK and p-ERK proteins were decreased by drug treatment. Finally, drug treatment reversed the proinflammatory factors of retinal NF-κB and serum IL-6, and proapoptotic Bax gene expression, while increased antiapoptotic Bcl-2 gene expression.

Conclusions: These results indicated that DR in db/db mice can be ameliorated by treatment with different proportional three active ingredients from Berberis dictyophylla F. The potential vascular protection mechanisms may be involved in inhibiting the phosphorylation of the MAPK signaling pathway, thus decreasing inflammatory and apoptotic events.
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http://dx.doi.org/10.1016/j.jep.2021.114190DOI Listing
May 2021

3D Multiscale Micro-/Nanofolds by Femtosecond Laser Intermittent Ablation and Constrained Heating on a Shape Memory Polymer.

ACS Appl Mater Interfaces 2021 May 7. Epub 2021 May 7.

CAS Key Laboratory of Mechanical Behavior and Design of Materials, Key Laboratory of Precision Scientific Instrumentation of Anhui Higher Education Institutes, Department of Precision Machinery and Precision Instrumentation, University of Science and Technology of China, Hefei, Anhui 230027, China.

Spontaneous wrinkling of films with a thickness gradient offers a new opportunity for constructing various 3D hierarchical surface morphologies. Unfortunately, accurately and facilely controlling the gradient film thickness to yield multiscale and 3D hierarchical micro-/nanostructures is still difficult. Here, a rapid, facile, and highly controllable fabricating strategy for realizing 3D multiscale hierarchical micro-/nanofolds on a shape memory polymer (SMP) surface is reported. First, the nanoparticle film with gradient thickness is rapidly (100 ms to 4 s) and facilely obtained by laser intermittent ablation on the SMP, termed as laser ablation-induced gradient thickness film. Following one-time constrained heating, the 3D micropillars grow out of the substrate based on the "self-growing effect," and the nanoparticle gradient film on its top shrinks into multiscale micro-/nanofolds simultaneously. Significantly, the evolution process and the underlying mechanism of the 3D micro-/nanofolds are systematically investigated. Fundamental basis enables us to accurately regulate the gradient thickness of nanoparticle films and feature size of folds by varying laser scanning times and scanning path. Finally, desirable patterns on micro-/nanofolds can be readily realized by programmable laser cleaning technology, and the tunable adhesion of the water droplet on the multiscale structured surface is demonstrated, which is promising for microdroplet manipulation.
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http://dx.doi.org/10.1021/acsami.1c04049DOI Listing
May 2021

Drug-induced liver injury: Oltipraz and C2-ceramide intervene HNF-1α/GSTA1 expression via JNK signaling pathway.

J Appl Toxicol 2021 May 6. Epub 2021 May 6.

Department of Basic Veterinary Science, College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.

Drug-induced liver injury (DILI) is a serious and frequently occurring issue in drug development. The c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in many diseases; hepatocyte nuclear factor-1α (HNF-1α) and glutathione S-transferase A1 (GSTA1) are important in regulating liver-specific genes expressions and affecting drug metabolism. Oltipraz is used to treat liver cirrhosis by improving liver function, and C2-ceramide is a pro-apoptotic lipid that regulates multiple signaling pathways. In this study, we investigated the function of the JNK signaling pathway with HNF-1α and GSTA1 in a cellular model of DILI and whether oltipraz and C2-ceramide exert effects via the JNK pathway. The results showed that inhibiting JNK could ameliorate APAP-induced hepatocyte injury, reduced oxidative stress, suppressed JNK and c-Jun activation, and hepatocyte apoptosis. Meanwhile, the mRNA and protein expressions of HNF-1α and GSTA1 were increased significantly compared to control conditions. The effect of oltipraz (8 μmol/L) was similar to a JNK inhibitor and significantly increased HNF-1α/GSTA1 expression, but oltipraz combined with JNK inhibitor did not show a synergistic effect. Although C2-ceramide (8 μmol/L) aggravated hepatocyte injury and apoptosis, exacerbated oxidative stress, increased phosphorylation of JNK and c-Jun, and markedly decreased HNF-1α/GSTA1 expression, C2-ceramide combined with JNK inhibitor could partially alleviate these alterations. These results demonstrated that the JNK signaling pathway with HNF-1α/GSTA1 are involved in the process of DILI. Inhibiting JNK up-regulated HNF-1α and GSTA1 expressions which could attenuate hepatocyte injury. Oltipraz and C2-ceramide might affect the expression of HNF-1α/GSTA1 though JNK signaling.
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http://dx.doi.org/10.1002/jat.4181DOI Listing
May 2021

Glutaredoxin 1 protects neurons from oxygen-glucose deprivation/reoxygenation (OGD/R)-induced apoptosis and oxidative stress via the modulation of GSK-3β/Nrf2 signaling.

J Bioenerg Biomembr 2021 May 6. Epub 2021 May 6.

Department of Anesthesiology, The First Hospital of Yulin, No. 93 Yuxi Street, Yulin, Shaanxi, 719000, China.

Increasing evidence has indicated that glutaredoxin 1 (GRX1) is a potent antioxidant protein that promotes cell survival under conditions of oxidative stress. Oxidative stress-induced neuronal injury contributes to cerebral ischemia/reperfusion injury. However, the role of GRX1-mediated antioxidant defense against neuronal damage during cerebral ischemia/reperfusion injury has not been thoroughly investigated. Thus, the objective of this study was to evaluate whether GRX1 protects neurons against oxygen-glucose deprivation/reoxygenation (OGD/R)-evoked oxidative stress injury in an in vitro model of cerebral ischemia/reperfusion injury. Our data revealed that GRX1 was induced by OGD/R treatment in neurons. Functional assays indicated that loss of GRX1 exacerbated OGD/R-induced apoptosis and the generation of reactive oxygen species (ROS), while GRX1 up-regulation protected against OGD/R-evoked neuronal injury. Further investigation revealed that GRX1 promoted the nuclear expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and enhanced transcription of the Nrf2/antioxidant response element (ARE) in GOD/R-exposed neurons. Furthermore, GRX1 promoted the activation of Nrf2/ARE associated with the modulation of glycogen synthase kinase-3β (GSK-3β). GSK-3β inhibition blocked GRX1 knockdown-mediated suppression of Nrf2 activation. Notably, the suppression of Nrf2 partially reversed GRX1-mediated anti-oxidative stress injury in OGD/R-exposed neurons. In summary, these findings indicate that GRX1 protects neurons against OGD/R-induced oxidative stress injury by enhancing Nrf2 activation via the modulation of GSK-3β. Our study suggests that GRX1 is a potential neuroprotective protein that protects against cerebral ischemia/reperfusion injury.
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http://dx.doi.org/10.1007/s10863-021-09898-0DOI Listing
May 2021

Irisin ameliorates endoplasmic reticulum stress and liver fibrosis through inhibiting PERK-mediated destabilization of HNRNPA1 in hepatic stellate cells.

Biol Chem 2021 May 20;402(6):703-715. Epub 2021 Jan 20.

Department of Pathophysiology, Guizhou Medical University, No. 9 Beijing Road, Yunyan District, Guiyang City550004, Guizhou Province, China.

Liver fibrosis is a common consequence of chronic liver diseases involved with the activation of hepatic stellate cells (HSCs) and endoplasmic reticulum (ER) stress. Irisin is a small polypeptide hormone that shows beneficial effects on metabolic disorders. The current study aimed to investigate the biological function of irisin on hepatic fibrosis. A mouse model of carbon tetrachloride (CCl)-induced hepatic fibrosis was established. CCl-treated mice showed elevated serum levels of AST and ALT, increased collagen accumulation, induced ER stress, and upregulated expressions of pro-fibrotic proteins in the liver compared to the controls. The administration of irisin, however, ameliorated CCl-induced hepatic fibrosis in both cultured HSCs and mice. PKR-like ER kinase (PERK) is a key component of the ER stress-associated signaling pathway. We found that irisin treatment improved the stability of heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) via regulating the phosphorylation of PERK in mouse livers and isolated HSCs. Also, the knockdown of HNRNPA1 eliminated the hepatoprotective effects of irisin on hepatic fibrosis and ER stress. In summary, this study showed that irisin alleviated ER stress and hepatic fibrosis by inhibiting PERK-mediated HNRNPA1 destabilization, suggesting that irisin may represent a promising therapeutic strategy for patients with liver fibrosis.
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http://dx.doi.org/10.1515/hsz-2020-0251DOI Listing
May 2021

HIV-1 Natural Antisense Transcription and Its Role in Viral Persistence.

Viruses 2021 04 29;13(5). Epub 2021 Apr 29.

Department of Molecular and Comparative Pathobiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Natural antisense transcripts (NATs) represent a class of RNA molecules that are transcribed from the opposite strand of a protein-coding gene, and that have the ability to regulate the expression of their cognate protein-coding gene via multiple mechanisms. NATs have been described in many prokaryotic and eukaryotic systems, as well as in the viruses that infect them. The human immunodeficiency virus (HIV-1) is no exception, and produces one or more NAT from a promoter within the 3' long terminal repeat. HIV-1 antisense transcripts have been the focus of several studies spanning over 30 years. However, a complete appreciation of the role that these transcripts play in the virus lifecycle is still lacking. In this review, we cover the current knowledge about HIV-1 NATs, discuss some of the questions that are still open and identify possible areas of future research.
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http://dx.doi.org/10.3390/v13050795DOI Listing
April 2021

Analysis of mutagenic components of oxidative hair dyes with the Ames test.

Hum Exp Toxicol 2021 May 4:9603271211013433. Epub 2021 May 4.

Pharmacology and Toxicology Department, Shanghai Institute for Food and Drug Control, Shanghai, China.

Oxidative hair dyes consist of two components (I and II) that are mixed before use. Aromatic amines in component I and their reaction with hydrogen peroxide after mixing them with component II have been of primary concern. In addition, two genotoxicity assays are still required for the approval of the final products of oxidative hair dyes in China, and the substance in the oxidative hair dye that causes the high rate of positive results in genotoxicity tests, especially the Ames test, has not been fully elucidated. In this study, we analyzed the formulation of 55 different oxidative hair dyes from 7 color series and performed Ames tests in the strain TA98 with the S9 mix (oxidative hair dyes No. 1-30) and in strain TA97a without the S9 mix (oxidative hair dyes No. 31-55). We found that toluene-2,5-diamine sulfate (2,5-diaminotoluene sulfate, DATS) in component I may be the cause of mutagenicity in TA98, and hydrogen peroxide in component II may be the cause of mutagenicity in TA97a, and their positive concentrations were consistent with those that we calculated from Ames tests. The results suggest that the positive results for the oxidative hair dye in the Ames test were inevitable because of the existence of DATS in component I and of hydrogen peroxide in component II. Therefore, we should carry out safety assessments on each raw material and carry out risk assessments on the final products of oxidative hair dyes instead of genotoxicity tests in China.
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http://dx.doi.org/10.1177/09603271211013433DOI Listing
May 2021

Relationship Between Non-contrast Computed Tomography Imaging Markers and Perihemorrhagic Edema Growth in Intracerebral Hemorrhage.

Neurocrit Care 2021 May 3. Epub 2021 May 3.

Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Objectives: Perihemorrhagic edema (PHE) growth has been gradually considered as predictor for outcome of Intracerebral hemorrhage (ICH) patients. The aim of our study was to investigate correlation between non-contrast computed tomography (CT) markers and early PHE growth.

Methods: ICH patients between July 2011 and March 2017 were included in this retrospective analysis. ICH and PHE volumes were measured by using a validated semiautomatic volumetric algorithm. Nonparametric test was used for comparing PHE volume at different time points of non-contrast computed tomography (NCCT) imaging markers. Multivariable linear regression was constructed to study the relationship between NCCT imaging markers and PHE growth over 36 h.

Results: A total of 214 patients were included. Nonparametric test showed that PHE volume was significantly different between patients with and without NCCT imaging markers. (all p < 0.05) In multivariable linear regression analysis adjusted for ICH characteristics, blend sign (p = 0.011), black hole sign (p = 0.002), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001) were correlated with PHE growth. Follow-up PHE volume within 36 h after baseline CT scan was associated with blend sign (p = 0.001), island sign (p < 0.001), and expansion-prone hematoma (p < 0.001).

Conclusion: NCCT imaging markers of hematoma expansion are associated with PHE growth. This suggests that early PHE growth can be predicted using radiology markers on admission CT scan.
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http://dx.doi.org/10.1007/s12028-021-01188-2DOI Listing
May 2021

Alleviative Effects of Exercise on Bone Remodeling in Fluorosis Mice.

Biol Trace Elem Res 2021 May 3. Epub 2021 May 3.

Shanxi Key Laboratory of Ecological Animal Science and Environmental Veterinary Medicine, College of Veterinary Medicine, Shanxi Agricultural University, 030801, Taigu, Shanxi, China.

Fluorine is widely present in nature in the form of fluoride. Prolonged high-dose fluoride exposure can cause skeletal fluorosis, resulting in osteosclerosis, osteoporosis or osteomalacia. It has been proved that exercise is one of the important factors affecting the health of the bone and promoting bone formation. To investigate the effects of exercise on bone remodeling in fluorosis mice, 120 male 3-week-old ICR mice were randomly divided into four groups: control group (C), exercise group (E), fluoride group (F), fluoride plus exercise group (F + E). After 8-week physical exercise and/or fluoride exposure, we evaluated the content of fluorine, the histopathological structure and microstructure of femur, bone metabolism biochemical indexes and oxidative stress related parameters, and the mRNA and protein levels of genes in BMP-2/Smads and OPG/RANKL/RANK signaling pathways. Our results showed that 100 mg/L NaF exposure increased the accumulation of fluoride in bone, altered histology of bone, and enhanced the activities of ALP and TRACP. Meanwhile, excessive fluoride induced oxidative stress in bone tissue by increasing the content of ROS and MDA, and decreasing the activities of antioxidant enzymes. In addition, the results of qRT-PCR suggested that NaF significantly increased the mRNA expression of BMP-2, Smad-5, Col IA1, Col IA2, OPG, RANKL and RANK, as well as the elevated proteins of OPG, RANKL and RANK. However, these fluoride-induced changes were alleviated after moderate exercise. Taken together, these findings indicated that moderate exercise decreased the toxicity of fluoride by reducing the accumulation of fluorine in the body to relieve the bone damage caused by fluorosis.
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http://dx.doi.org/10.1007/s12011-021-02741-yDOI Listing
May 2021

Mechanisms of polymyxin resistance induced by Salmonella typhimurium in vitro.

Vet Microbiol 2021 Apr 1;257:109063. Epub 2021 Apr 1.

Pharmacology and Toxicology Laboratory, College of Animal Science and Technology, Anhui Agricultural University, Hefei, Anhui 230026, PR China; Anhui Province Key Lab of Veterinary Pathobiology and Disease Control, Anhui Agricultural University, Hefei, Anhui 230036, PR China. Electronic address:

The increase incidence of multi-drug resistant (MDR) Salmonella has become a major global health concern. Polymyxin, an ancient polypeptide antibiotic, has been given renewed attention over recent years, resulting in resistance of Gram-negative bacteria to polymyxin, but its resistance mechanism is not completely clear. Thus, it is important to study its resistance mechanisms. In this study, an in vitro induced polymyxin-resistant strain of Salmonella typhimurium in the laboratory were constructed to investigate the mechanism of resistance of Salmonella to polymyxin. Gradual induction of Salmonella typhimurium ATCC13311 (AT) by concentration increment was used to screen for a highly polymyxin-resistant strain AT-P128. The broth dilution technique was used to compare the sensitivity of the two strains to different antimicrobial drugs. Single nucleotide polymorphisms (SNPs) were then identified by whole genome sequencing, and differences in gene expression between the two strains were compared by transcriptome sequencing and reverse transcription-quantitative PCR (RT-qPCR). Finally, for the first time, the CRISPR/Cas9 gene-editing system was used to construct gene deletion mutants in Salmonella to knock out the phoP gene of AT-P128. The results showed that strain AT-P128 was significantly more resistant to amoxicillin, ceftiofur, ampicillin, fluphenazine, and chloramphenicol and significantly less resistant to sulfamethoxazole than the parental strain AT. The growth curve results showed no significant change in the growth rate between AT-P128 and AT. Motility and biofilm formation assays showed a significant decrease in AT-P128. Additionally, the WGS results showed that AT-P128 had mutations in 9 genes involving 14 SNPs. RNA-seq and RT-qPCR results showed increased expression of phoPQ. The loss of the phoP gene decreased AT-P128ΔphoP resistance to polymyxin by 32-fold. These results suggested that polymyxin resistance affected the biology, genome components, and gene expression levels of Salmonella and that the PhoPQ two-component system played a key role in polymyxin resistance in Salmonella, providing insights into the diversity and complexity of polymyxin resistance in Salmonella.
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http://dx.doi.org/10.1016/j.vetmic.2021.109063DOI Listing
April 2021

Porcine reproductive and respiratory syndrome virus increases SOCS3 production via activation of p38/AP-1 signaling pathway to promote viral replication.

Vet Microbiol 2021 Apr 20;257:109075. Epub 2021 Apr 20.

Key Laboratory of Animal Immunology of the Ministry of Agriculture, Henan Provincial Key Laboratory of Animal Immunology, Henan Academy of Agricultural Sciences, Zhengzhou, 450002, China; College of Veterinary Medicine, Northwest A&F University, Yangling, 712100, China; College of Animal Medicine, Henan Agricultural University, Zhengzhou, 450002, China. Electronic address:

SOCS3 belongs to the suppressor of cytokine signaling (SOCS) family, which function as negative factors in host immune responses. Prior studies have noted the importance of SOCS family proteins in immunosuppression induced by some viruses. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most important swine-borne viruses and has threatened the global swine industry with huge economic losses since it was first described in the 1980s. PRRSV is the etiological agent of PRRS, which causes reproductive failure and respiratory disorders. PRRSV causes immunosuppression thus establishing persistent infection. In this study, it was observed that SOCS3 was upregulated in PRRSV-infected primary porcine alveolar macrophages (PAMs) and Marc-145 cells with dose-dependent effects, which depends on virus replication. Deletion of AP-1 binding motif located in SOCS3 promoter inhibited promoter activities, which indicates that AP-1 is essential for PRRSV-induced SOCS3. This result was confirmed by experiments using AP-1 inhibitor, whose pretreatment suppressed SOCS3 mRNA and protein expression. Further research showed that p38 was crucial for PRRSV-induced SOCS3 production. Importantly, SOCS3 enhanced PRRSV replication during infection. Taken together, this study indicates that PRRSV infection induced SOCS3 expression through p38/AP-1 signaling pathway. These results revealed the molecular basis of SOCS3 upregulation and would advance further understanding of the strategy for viral immune evasion.
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http://dx.doi.org/10.1016/j.vetmic.2021.109075DOI Listing
April 2021

Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances.

Authors:
Amit Bar-Or Rui Li

Lancet Neurol 2021 Apr 27. Epub 2021 Apr 27.

Center for Neuroinflammation and Experimental Therapeutics, Department of Neurology, Multiple Sclerosis Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Novel insights from basic and translational studies are reshaping concepts of the immunopathogenesis of multiple sclerosis and understanding of the different inflammatory responses throughout the disease course. Previously, the cellular immunology of relapsing multiple sclerosis was considered to be principally T-cell driven; however, this process is now understood to involve multiple cell types and their functionally distinct subsets. Particularly, relapsing multiple sclerosis appears to involve imbalanced interactions between T cells, myeloid cells, B cells, and their effector and regulatory subpopulations. The major contributors to such imbalances differ across patients. Several emerging techniques enable comprehensive immune cell profiling at the single-cell level, revealing substantial functional heterogeneity and plasticity that could influence disease state and response to treatment. Findings from clinical trials with agents that successfully limit new multiple sclerosis disease activity and trials of agents that inadvertently exacerbate CNS inflammation have helped to elucidate disease mechanisms, better define the relevant modes of action of current immune therapies, and pave the way for new therapeutic strategies.
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http://dx.doi.org/10.1016/S1474-4422(21)00063-6DOI Listing
April 2021

Multiresidue determination of antibiotics in ready-to-eat duck eggs marketed through e-commerce stores in China and subsequent assessment of dietary risks to consumers.

J Food Sci 2021 May 29;86(5):2145-2162. Epub 2021 Apr 29.

Institute of Agro-product Safety and Nutrition, State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products; National Reference Laboratory for Agricultural Testing (Pesticide residues); Agricultural Ministry Key Laboratory for Pesticide Residue Detection; Zhejiang Province Key Laboratory for Food Safety, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang, 310021, China.

In this work, the occurrence of 34 common antibiotic (15 sulfonamides and 19 quinolones) residues were evaluated in 236 ready-to-eat duck eggs (salted and preserved duck eggs) marketed through e-commerce stores by ultra-performance liquid chromatography coupled to tandem mass spectrometry, and subsequent dietary risk assessments for Chinese consumers were conducted. Among violated positives in duck egg samples, 11 analytes were found including sulfamethazine, sulfaquinoxaline, sulfamethoxazole, sulfadiazine, sulfamonomethoxine, ciprofloxacin, enrofloxacin, ofloxacin, flumequine, sarafloxacin, and nalidixic acid. A higher number of antibiotics were detected in salted duck eggs (five sulfonamides and six quinolones) than in preserved duck eggs (one sulfonamide and two quinolones). The maximum contamination of sulfonamides and quniolones was 448.0 µg/kg (sulfaquinoxaline) and 563.7 µg/kg (enrofloxacin) in salted duck eggs, respectively. Dietary exposure was evaluated through the estimated daily intake (EDI) of risky antibiotics (sulfamethazine, ciprofloxacin, and enrofloxacin) and hazard quotients (HQs). The results showed that EDIs and HQs were in the range of 0.0004 to 0.0099 µg/kg bw/day and 0.0009 to 0.1594%, respectively. The risk was low since HQs obtained were less than 100%. However, a special attention should be paid to ready-to-eat duck egg products high percentile consumers with the prosperity of e-commerce market in China. PRACTICAL APPLICATION: The present analytical method could be used for multiresidue determination of antibiotics in ready-to-eat duck eggs, and dietary risk assessments of risky antibiotics provided a support for the work of regulatory bodies to conduct surveillance programs regarding food safety evaluation of ready-to-eat foods.
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http://dx.doi.org/10.1111/1750-3841.15724DOI Listing
May 2021

Auranofin-Mediated NRF2 Induction Attenuates Interleukin 1 Beta Expression in Alveolar Macrophages.

Antioxidants (Basel) 2021 Apr 21;10(5). Epub 2021 Apr 21.

Section of Neonatal-Perinatal Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.

Background: Alveolar macrophages (AMs) are resident inflammatory cells in the lung that serve as early sentinels of infection or injury. We have identified thioredoxin reductase 1 inhibition by gold compounds increases activation of nuclear factor erythroid 2-related factor 2 (NRF2)-dependent pathways to attenuate inflammatory responses. The present studies utilized murine alveolar macrophages (MH-S) to test the hypothesis that the gold compound, auranofin (AFN), decreases interleukin (IL)-1β expression through NRF2-mediated interactions with nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway genes and/or increases in glutathione synthesis.

Methods: MH-S cells were treated with AFN and lipopolysaccharide (LPS) and analyzed at 6 and 24 h. The promoter was analyzed by chromatin immunoprecipitation for direct interaction with NRF2.

Results: Expression of IL-1β, p-IκBα, p-p65 NF-kB, and NOD-, LRR-, and pyrin domain-containing protein 3 were elevated by LPS exposure, but only IL-1β expression was suppressed by AFN treatment. Both AFN and LPS treatments increased cellular glutathione levels, but attenuation of glutathione synthesis by buthionine sulfoximine (BSO) did not alter expression of Il-1β. Analysis revealed direct NRF2 binding to the promoter which was enhanced by AFN and inhibited the transcriptional activity of DNA polymerase II.

Conclusions: Our data demonstrate that AFN-induced NRF2 activation directly suppresses IL-1β synthesis independent of NFκB and glutathione-mediated antioxidant mechanisms. NRF2 binding to the promoter region of directly inhibits transcription of the gene. Collectively, our research suggests that gold compounds elicit NRF2-dependent pulmonary protection by suppressing macrophage-mediated inflammation.
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http://dx.doi.org/10.3390/antiox10050632DOI Listing
April 2021

Acute Ischemic Stroke at High Altitudes in China: Early Onset and Severe Manifestations.

Cells 2021 Apr 5;10(4). Epub 2021 Apr 5.

Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.

The detailed characteristics of strokes at high altitudes in diverse nations have not been extensively studied. We retrospectively enrolled 892 cases of first-ever acute ischemic strokes at altitudes of 20, 2550, and 4200 m in China (697 cases from Penglai, 122 cases from Huzhu, and 73 cases from Yushu). Clinical data and brain images were analyzed. Ischemic strokes at high altitudes were characterized by younger ages (69.14 ± 11.10 vs. 64.44 ± 11.50 vs. 64.45 ± 14.03, < 0.001) and larger infract volumes (8436.37 ± 29,615.07 mm vs. 17,213.16 ± 47,044.74 mm vs. 42,459 ± 84,529.83 mm, < 0.001). The atherosclerotic factors at high altitude, including diabetes mellitus (28.8% vs. 17.2% vs. 9.6%, < 0.001), coronary heart disease (14.3% vs. 1.6% vs. 4.1%, < 0.001), and hyperlipidemia (20.2% vs. 17.2% vs. 8.2%, = 0.031), were significantly fewer than those in plain areas. Polycythemia and hemoglobin levels (138.22 ± 18.04 g/L vs. 172.87 ± 31.57 g/L vs. 171.81 ± 29.55 g/L, < 0.001), diastolic pressure (89.98 ± 12.99 mmHg vs. 93.07 ± 17.79 mmHg vs. 95.44 ± 17.86 mmHg, = 0.016), the percentage of hyperhomocysteinemia (13.6% in Penglai vs. 41.8% in Huzhu, < 0.001), and the percentage of smoking (33.1% in Penglai vs. 50.0% in Huzhu, = 0.023) were significantly elevated at high altitudes. We concluded that ischemic stroke occurred earlier and more severely in the Chinese plateau. While the atherosclerotic factors were not prominent, the primary prevention of strokes at high altitudes should emphasize anticoagulation, reducing diastolic pressure, adopting a healthy diet, and smoking cessation.
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http://dx.doi.org/10.3390/cells10040809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8067425PMC
April 2021

Midday Nap Duration and Hypertension among Middle-Aged and Older Chinese Adults: A Nationwide Retrospective Cohort Study.

Int J Environ Res Public Health 2021 Apr 1;18(7). Epub 2021 Apr 1.

Department of Health Management, School of Health Sciences, Wuhan University, Wuhan 430071, China.

The goal of this study was to investigate the associations of midday nap duration and change in midday nap duration with hypertension in a retrospective cohort using a nationwide representative sample of middle-aged and older Chinese adults. Data were obtained from the China Health and Retirement Longitudinal Study (CHARLS) database during 2011-2015. Information on midday nap duration was collected via a self-reported questionnaire and blood pressure was objectively measured. Hazard ratios (HR) with 95% confidence interval (CI) were estimated using Cox proportional hazards regression models to quantify the associations. A sample of 5729 Chinese adults (≥45 years old) were included in the longitudinal analysis. Relative to non-nappers, participants who napping for ≥90 min/day was associated with significantly larger HR for hypertension at four-year follow-up (HR = 1.18, 95% CI = 1.01-1.40, = 0.048). Compared with people who napped ≥90 min/day both at baseline (2011) and follow-up (2013), hypertension risk at four-year follow-up declined in individuals whose midday nap durations decreased in the 2-year study period from ≥ 90 min/day to 1-59 min/day (HR = 0.59, 95% CI = 0.36-0.97, = 0.037) and 60-89 min/day (HR = 0.68, 95% CI = 0.47-0.99, = 0.044). Among middle-aged and older Chinese adults, relative to non-nappers, people who had longer midday nap duration (≥90 min/day) were associated with significantly larger HR for hypertension and decreased napping duration may confer benefit for hypertension prevention.
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http://dx.doi.org/10.3390/ijerph18073680DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8037516PMC
April 2021

Role of Surfactants Based on Fatty Acids in the Wetting Behavior of Solid-Oil-Aqueous Solution Systems.

Langmuir 2021 May 29;37(18):5682-5690. Epub 2021 Apr 29.

Department of Chemical and Materials Engineering, University of Alberta, Edmonton, Alberta T6G 1H9, Canada.

Surfactants based on fatty acids have attracted extensive attention thanks to their eco-friendly and pH-responsive features. Here, we studied two fatty acid-based surfactants that were paired with the same organic counterion but distinguished by their aliphatic chain lengths (monoethanolamine-oleic acid (MEA-OA) and monoethanolamine-lauric acid (MEA-LA)). Both surfactants exhibited the ability to lower the oil-water interfacial tension but lost their interfacial activity in a low-pH environment. We experimentally investigated their influence on the receding and spreading of oil droplets on solid surfaces. It was found that the interfacial tension reduction could decrease the static contact angle of the aqueous phase and hindered displacement dynamics during the oil droplet receding. Meanwhile, the interfacial activity was more likely to suppress the initiation of the oil droplet spreading due to the more stable thin-film forming prior to the spreading process. Nevertheless, the experimental results also exhibited that MEA-OA was more effective than MEA-LA in suppressing the receding dynamics and the spreading initiation even when they were characterized by similar interfacial tension values. Such an interesting observation could be attributed to the more considerable Marangoni flow in the solution of MEA-OA whose molecules have longer aliphatic chains. The insight from this study is expected to improve the knowledge on the molecular design for more efficient applications of fatty acid-based surfactants.
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http://dx.doi.org/10.1021/acs.langmuir.1c00586DOI Listing
May 2021

Association of Infant Feeding Methods and Excess Weight from Birth to Age 6.

Breastfeed Med 2021 Apr 27. Epub 2021 Apr 27.

Center for Biobehavioral Health, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, Ohio, USA.

To examine the associations between human milk feeding method (at the breast versus bottle) and measures of child adiposity during the first 6 years of life. Women 12 months' postpartum who delivered a singleton, liveborn infant at >24 weeks gestation completed a survey assessing infant feeding methods and sociodemographics. Mothers were recontacted when the child was 6 years old for a follow-up study assessing growth ( = 269). Children were categorized as ever or never having excess weight using weight-for-age z-scores (WAZ), weight-for-height z-scores (WHZ), and body mass index-for-age z-scores (BMIZ) from birth to 6 years. Modified Poisson regression estimated associations between the duration of each feeding method (exclusive and combined) with excess weight status. Mixed-effect models estimated associations between feeding methods and trajectories of the outcomes. For all feeding practices, increasing duration (in months) was unassociated with the risk of ever having excess weight by age 6 years. Based on mixed models, longer duration of feeding human milk by any method was associated with lower BMIZ (adj β for 6-12 months versus 0-3 months = -0.50, 95% CI: -0.99 to -0.01) and also with the shape of the BMIZ trajectory curve. No other associations between feeding methods and excess weight outcomes were observed. Longer duration of feeding human milk was associated with lower average BMIZ in early childhood but feeding at the breast and feeding expressed milk were not clearly associated with the outcomes when considered separately. Larger studies would help clarify the associations between these specific feeding methods and outcomes. IRB17-00876.
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http://dx.doi.org/10.1089/bfm.2020.0261DOI Listing
April 2021