Publications by authors named "Juan Zhu"

84 Publications

Attenuation of cerebral edema facilitates recovery of glymphatic system function after status epilepticus.

JCI Insight 2021 Sep 8;6(17). Epub 2021 Sep 8.

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

Status epilepticus (SE) is a neurological emergency usually accompanied by acute cerebral edema and long-term cognitive impairment, and is characterized by neurodegeneration and aberrant hyperphosphorylated tau protein (p-tau) aggregation. The glia-lymphatic (glymphatic) system plays a central role in facilitating the clearance of metabolic waste from the brain, but its relationship with cerebral edema and cognitive dysfunction after SE is unclear. We hypothesized that cerebral edema after SE might impair glymphatic system function through compression, thus leading to impaired removal of metabolic waste, and ultimately affecting long-term cognitive function. Our results showed that glymphatic system function was temporarily impaired, as evidenced by 2-photon imaging, MRI enhancement, imaging of brain sections, and astrocytic water channel aquaporin 4 (AQP4) protein polarization. The severity of cerebral edema on MRI correlated well with glymphatic system dysfunction within 8 days following SE. Moreover, when cerebral edema was alleviated by glibenclamide treatment or genetic deletion of Trpm4, post-SE glymphatic system function recovered earlier, along with fewer p-tau-deposited neurons and neuronal degeneration and better cognitive function. These findings suggest that SE-induced cerebral edema may cause glymphatic system dysfunction and render the post-SE brain vulnerable to p-tau aggregation and neurocognitive impairment.
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http://dx.doi.org/10.1172/jci.insight.151835DOI Listing
September 2021

Dysregulated lncRNAs are Involved in the Progress of Sepsis by Constructing Regulatory Networks in Whole Blood Cells.

Front Pharmacol 2021 17;12:678256. Epub 2021 Aug 17.

Department of Emergency, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, People's Hospital of Henan University, Zhengzhou, China.

Sepsis is a highly heterogeneous syndrome that is caused by an unbalanced host response to an infection. Long noncoding RNAs (lncRNAs) have been reported to exert regulatory roles in a variety of biological processes, and became potential biomarkers and therapeutic targets for diverse diseases. However, current understanding on the roles of lncRNAs in sepsis is extremely limited. Herein, to decipher the underlying functions of lncRNAs, we reexplored the 83 transcriptome datasets from specimens with sepsis, no_sepsis by final diagnosis, and control. The results of differentially expressed genes (DEGs), differentially expressed lncRNA (DElncRNA) analysis, and co-expression analysis of lncRNA-mRNA pairs were obtained. We found that the expression pattern of lncRNAs was significantly activated in sepsis specimens, which was clearly distinguished in sepsis from no_sepsis and control specimens. By performing co-expression analysis, we found DElncRNAs were closely related to T-cell activation and immune response-related terms in sepsis by regulating mRNA expression in the manner. The lncRNA-mRNA network and the qRT-PCR test revealed that lncRNAs , , and were significantly correlated with the pathogenesis of sepsis. In addition, weighted gene co-expression analysis (WGCNA) and -regulation analysis also revealed sepsis-specific lncRNAs were highly associated with important biological processes correlated with sepsis. In summary, the systematic dysregulation of lncRNAs is tightly involved in the remodeling of gene expression regulatory network in sepsis, and the lncRNA-mRNA expression network may be used to refine biomarker predictions for developing novel therapeutic approaches in sepsis.
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http://dx.doi.org/10.3389/fphar.2021.678256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416166PMC
August 2021

Biological correlates before esophageal cancer screening and after diagnosis.

Sci Rep 2021 Aug 23;11(1):17015. Epub 2021 Aug 23.

National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.

Almost 50% of the world's esophageal cancer (EC) cases occur in China, and the impact of cancer screening has long been a controversial topic. The study was designed to evaluate the biological correlates of EC screening and subsequent diagnosis in China. Based on the national cohort of esophageal cancer program, a prospective multicenter study in high-risk regions was conducted from 2017 to 2019. 61 participants received twice esophageal endoscopy screening and pathological biopsy successively (with a mean follow-up of 14.03 months). Box-Cox-power transformation and two-way repeated measures ANOVA were used to evaluate hormone cortisol and immunoglobulin (IgA, IgG, IgM) levels in plasma, reflecting their stress, immune function, and biological correlates before screening and after knowing the diagnosis. The median of cortisol, IgA, IgG, and IgM in pre-screening was 15.46 ug/dL, 1.86 g/L, 12.14 g/L, and 0.91 g/L, corresponding value at post-diagnosis was 15.30 ug/dL, 2.00 g/L, 12.79 g/L, and 0.94 g/L, respectively. No significant differences in biological indicators were found between normal and esophagitis and low-grade intraepithelial neoplasia before screening and after diagnosis. After normality transformation, cortisol, IgA, IgG and IgM levels were (0.25 ± 0.04) U/mL, (0.72 ± 0.13) (g/L), (2.44 ± 0.22) (g/L) and (0.98 ± 0.25) (g/L) before screening, (0.25 ± 0.05) U/mL, (0.70 ± 0.13) (g/L), (2.48 ± 0.21) (g/L) and (1.00 ± 0.25) (g/L) after diagnosis, respectively. Repeated Measures ANOVA showed that the main effects were significant on IgA levels between pre-screening and post-diagnosis (P = 0.019). No interaction effects on biological levels between pre-post screening and esophageal pathology, anxiety states (all P > 0.05). Little biological correlates were found both before screening and after diagnosis. Cortisol and IgA dropped less significantly, while IgM and IgA were increased slightly after diagnosis. Further multi-round longitudinal studies are needed to validate these results.
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http://dx.doi.org/10.1038/s41598-021-96548-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382699PMC
August 2021

Tuning Strain Sensor Performance via Programmed Thin-Film Crack Evolution.

ACS Appl Mater Interfaces 2021 Aug 3;13(32):38105-38113. Epub 2021 Aug 3.

Arias Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, California 94720, United States.

Stretchable strain sensors with well-controlled sensitivity and stretchability are crucial for applications ranging from large deformation monitoring to subtle vibration detection. Here, based on single-metal material on the elastomer and one-pot evaporation fabrication method, we realize controlled strain sensor performance via a novel programable cracking technology. Specifically, through elastomeric substrate surface chemistry modification, the microcrack generation and morphology evolution of the strain sensing layer is controlled. This process allows for fine tunability of the cracked film morphology, resulting in strain sensing devices with a sensitivity gauge factor of over 10 000 and stretchability up to 100%. Devices with a frequency response up to 5.2 Hz and stability higher than 1000 cycles are reported. The reported strain sensors, tracking both subtle and drastic mechanical deformations, are demonstrated in healthcare devices, human-machine interaction, and smart-home applications.
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http://dx.doi.org/10.1021/acsami.1c10975DOI Listing
August 2021

Glycocalyx is critical for blood-brain barrier integrity by suppressing caveolin1-dependent endothelial transcytosis following ischemic stroke.

Brain Pathol 2021 Jul 19:e13006. Epub 2021 Jul 19.

Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, China.

The breakdown of the blood-brain barrier (BBB) is related to the occurrence and deterioration of neurological dysfunction in ischemic stroke, which leads to the extravasation of blood-borne substances, resulting in vasogenic edema and increased mortality. However, a limited understanding of the molecular mechanisms that control the restrictive properties of the BBB hinders the manipulation of the BBB in disease and treatment. Here, we found that the glycocalyx (GCX) is a critical factor in the regulation of brain endothelial barrier integrity. First, endothelial GCX displayed a biphasic change pattern, of which the timescale matched well with the biphasic evolution of BBB permeability to tracers within the first week after t-MCAO. Moreover, GCX destruction with hyaluronidase increased BBB permeability in healthy mice and aggravated BBB leakage in transient middle cerebral artery occlusion (t-MCAO) mice. Surprisingly, ultrastructural observation showed that GCX destruction was accompanied by increased endothelial transcytosis at the ischemic BBB, while the tight junctions remained morphologically and functionally intact. Knockdown of caveolin1 (Cav1) suppressed endothelial transcytosis, leading to reduced BBB permeability, and brain edema. Lastly, a coimmunoprecipitation assay showed that GCX degradation enhanced the interaction between syndecan1 and Src by promoting the binding of phosphorylated syndecan1 to the Src SH2 domain, which led to rapid modulation of cytoskeletal proteins to promote caveolae-mediated endocytosis. Overall, these findings demonstrate that the dynamic degradation and reconstruction of GCX may account for the biphasic changes in BBB permeability in ischemic stroke, and reveal an essential role of GCX in suppressing transcellular transport in brain endothelial cells to maintain BBB integrity. Targeting GCX may provide a novel strategy for managing BBB dysfunction and central nervous system drug delivery.
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http://dx.doi.org/10.1111/bpa.13006DOI Listing
July 2021

Coronary artery calcification and risk of mortality and adverse outcomes in patients with COVID-19: a Chinese multicenter retrospective cohort study.

Chin J Acad Radiol 2021 Jun 28:1-9. Epub 2021 Jun 28.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, 210002 Jiangsu Province People's Republic of China.

Background: Coronary artery calcification (CAC) is an independent risk factor of major adverse cardiovascular events; however, the impact of CAC on in-hospital death and adverse clinical outcomes in patients with coronavirus disease 2019 (COVID-19) remains unclear.

Objective: To explore the association between CAC and in-hospital mortality and adverse events in patients with COVID-19.

Methods: This multicenter retrospective cohort study enrolled 2067 laboratory-confirmed COVID-19 patients with definitive clinical outcomes (death or discharge) admitted from 22 tertiary hospitals in China between January 3, 2020 and April 2, 2020. Demographic, clinical, laboratory results, chest CT findings, and CAC on admission were collected. The primary outcome was in-hospital death and the secondary outcome was composed of in-hospital death, admission to intensive care unit (ICU), and requiring mechanical ventilation. Multivariable Cox regression analysis and Kaplan-Meier plots were used to explore the association between CAC and in-hospital death and adverse clinical outcomes.

Results: The mean age was 50 years (SD,16) and 1097 (53.1%) were male. A total of 177 patients showed high CAC level, and compared with patients with low CAC, these patients were older (mean age: 49 vs. 69 years,  < 0.001) and more likely to be male (52.0% vs. 65.0%,  = 0.001). Comorbidities, including cardiovascular disease (CVD) ([33.3%, 59/177] vs. [4.7%, 89/1890],  < 0.001), presented more often among patients with high CAC, compared with patients with low CAC. As for laboratory results, patients with high CAC had higher rates of increased D-dimer, LDH, as well as CK-MB (all  < 0.05). The mean CT severity score in high CAC group was also higher than low CAC group (12.6 vs. 11.1,  = 0.005). In multivariable Cox regression model, patients with high CAC were at a higher risk of in-hospital death (hazard ratio [HR], 1.731; 95% CI 1.010-2.971,  = 0.046) and adverse clinical outcomes (HR, 1.611; 95% CL 1.087-2.387,  = 0.018).

Conclusion: High CAC is a risk factor associated with in-hospital death and adverse clinical outcomes in patients with confirmed COVID-19, which highlights the importance of calcium load testing for hospitalized COVID-19 patients and calls for attention to patients with high CAC.

Supplementary Information: The online version contains supplementary material available at 10.1007/s42058-021-00072-4.
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http://dx.doi.org/10.1007/s42058-021-00072-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237549PMC
June 2021

Resveratrol Improves Mitochondrial Biogenesis Function and Activates PGC-1α Pathway in a Preclinical Model of Early Brain Injury Following Subarachnoid Hemorrhage.

Front Mol Biosci 2021 22;8:620683. Epub 2021 Apr 22.

Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, China.

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has been shown to play a pivotal role in the regulation of mitochondrial biogenesis in diseases. Resveratrol (RSV), a natural polyphenolic reagent, has powerful antioxidant properties and the ability to scavenge mitochondrial reactive oxygen species (ROS) in a variety of central nervous system diseases. However, the underlying molecular mechanisms of RSV on mitochondrial biogenesis in early brain injury (EBI) following subarachnoid hemorrhage (SAH) remain poorly understood. This study aimed to explore the potential neuroprotective effects of RSV on mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in a prechiasmatic cistern SAH model. PGC-1α expression and related mitochondrial biogenesis were detected. Amounts of nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) were determined to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis after SAH were observed in the temporal cortex. Resveratrol increased the expression of PGC-1α, NRF1, and TFAM, and promoted PGC-1α nuclear translocation. Moreover, RSV could scavenge excess ROS, increase the activity of superoxide dismutase (SOD), enhance the potential of mitochondrial membrane and ATP levels, reduce the number of mitochondrial DNA copy, and decrease the level of malondialdehyde (MDA). RSV significantly ameliorated the release of apoptosis-related cytokines, namely P53, cleaved caspase-3, cytochrome c, and BAX, leading to the amelioration of neuronal apoptosis, brain edema, and neurological impairment 24 h after SAH. These results indicate that resveratrol promotes mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in EBI following SAH.
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http://dx.doi.org/10.3389/fmolb.2021.620683DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8100450PMC
April 2021

Analysis of physiochemical composition and antioxidant properties between hulls of the genetically modified glyphosate-tolerant soybean and northeast soybean.

Food Sci Biotechnol 2021 Apr 27;30(4):505-512. Epub 2021 Mar 27.

Department of Preventive Medicine, Institute of Biomedical Technology, Jiangsu Vocational College of Medicine, Jiangsu, 224005 People's Republic of China.

In this study, the physiochemical and antioxidant properties of the soybean hulls from the genetically modified glyphosate-tolerant soybeans (line 40-3-2) and local cultivar northeast soybeans were investigated. The levels of fat, total phenolic, total extractable pectin and soluble dietary fiber in northeast soybeans hulls were less than that in glyphosate-tolerant soybeans hulls, respectively. The antioxidant capacity of total phenolic, water soluble pectin, and soluble dietary fiber showed that DPPH free radical scavenging activities of glyphosate-tolerant soybeans hulls were 118.23, 57.34 and 197.22 μg AAE/g, which were 2.3, 1.2 and 9.4 times of northeast soybeans hulls, respectively ( < 0.05), and FRAP of glyphosate-tolerant soybeans hulls were 401.67, 747.51 and 328.53 μg AAE/g, which were 1.8, 8.7 and 4.8 times of northeast soybeans hulls ( < 0.05). Glyphosate-tolerant soybeans hulls extract showed the stronger antioxidant activity, which was positively correlated with total phenolic content (r = 0.890,  = 0.001). It provides evidence on developing value-added utilization of hulls, soybean processing by-products, as nutraceuticals or functional food ingredients.
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http://dx.doi.org/10.1007/s10068-021-00894-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050184PMC
April 2021

Downregulated ribosomal protein L39 inhibits trophoblast cell migration and invasion by targeting E-cadherin in the placenta of patients with preeclampsia.

FASEB J 2021 04;35(4):e21322

Department of Hainan Provincial Key Laboratory for human reproductive medicine and Genetic Research, Key Laboratory of Tropical Translational Medicine of Ministry of Education, Reproductive Medicine, the First Affiliated Hospital of Hainan Medical University, Haikou, China.

Early-onset preeclampsia (PE) is a pregnancy complication that can lead to severe adverse maternal and fetal outcomes. However, the mechanisms underlying the development of early-onset PE are not fully understood. Ribosomal protein L39 (RPL39) is a member of the S39E family of ribosomal proteins that plays an important role in stem cell self-renewal, cancer metastasis, and chemoresistance. In this study, we aimed to explore the potential function of RPL39 in placental trophoblast cells. We analyzed the expression of RPL39 in early-onset PE and normal placental tissues using real-time PCR, western blot analysis, and immunohistochemistry. The results showed that RPL39 was markedly downregulated in early-onset PE placental tissues. RPL39 knockdown inhibited trophoblast cell proliferation, migration, and invasion, as well as placental explant outgrowth. Flow cytometry analysis suggested that knockdown of RPL39 resulted in cell cycle arrest at the G0/G1 phase, but had no significant effect on cell apoptosis. We also found that RPL39 knockdown could alter cell morphology. We then measured the expression of the epithelial cell marker E-cadherin following knockdown of RPL39 in Bewo and HTR8/SVneo cells. RPL39 knockdown increased the expression of E-cadherin. Furthermore, E-cadherin expression was upregulated in placental explant outgrowth tissues transfected with RPL39 small interfering RNA. In conclusion, RPL39 plays an essential role in proliferation, invasion, and migration of trophoblast cells by targeting E-cadherin. Our findings provide novel insight into the mechanisms underlying the occurrence of early-onset PE.
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http://dx.doi.org/10.1096/fj.202002061RDOI Listing
April 2021

Identification of Eltrombopag as a Repurposing Drug Against Staphylococcus epidermidis and its Biofilms.

Curr Microbiol 2021 Apr 21;78(4):1159-1167. Epub 2021 Feb 21.

Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, People's Republic of China.

Staphylococcus epidermidis is a common cause of nosocomial infections, and readily adheres to medical apparatus to form biofilms consisting of highly resistant persister cells. Owing to the refractory infections caused by S. epidermidis biofilms and persisters in immunosuppressed patients, it is crucial to develop new antimicrobials. In the present study, we analyzed the antimicrobial effects of the thrombopoietin receptor agonist eltrombopag (EP) against S. epidermidis planktonic cells, biofilms, and persister cells. EP was significantly toxic to S. epidermidis with the minimal inhibitory concentration of 8 μg/ml, and effectively inhibited the biofilms and persisters in a strain-dependent manner. In addition, EP was only mildly toxic to mammalian cells after 12 to 24 h treatment. It also partially synergized with vancomycin against S. epidermidis, which enhanced its antimicrobial effects and reduced its toxicity to mammalian cells. Taken together, EP is a potential antibiotic for treating refractory infections caused by S. epidermidis.
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http://dx.doi.org/10.1007/s00284-021-02386-zDOI Listing
April 2021

Comparison of the analgesic effect of quadratus lumborum block and epidural block in open uterine surgery: a randomized controlled trial.

Minerva Anestesiol 2021 04 16;87(4):414-422. Epub 2021 Feb 16.

Department of Anesthesiology, Affiliated Hospital of Jiangsu University, Zhenjiang, China -

Background: Effective regional analgesia during open surgery could reduce opioid consumption and enhance early recovery. We compared the effects of the newly developed quadratus lumborum block (QLB) and the traditional epidural block (EB) in open uterine surgery.

Methods: In this randomized controlled trial, we included patients scheduled for elective open uterine surgery during May - September 30, 2019. Patients received QLB or EB for perioperative pain relief before general anesthesia. Perioperative opioid consumption, and numeric rating scale (NRS: 0-10) pain scores after surgery, heart rate (HR), mean arterial pressure (MAP), ephedrine and urapidil use during surgery, lower limb muscle strength, timing of first flatus and defecation, nausea, vomiting, and other complications within 24 h post-surgery, were the primary and secondary outcomes, respectively.

Results: Data of 72 (86%; 36/group) of 83 eligible patients were analyzed. Remifentanil consumption during surgery was higher in the QLB than in the EB group, while cumulative sufentanil consumption within 24 h post-surgery was similar between both groups. NRS pain scores at rest and during activity were higher at 1 h post-surgery, and MAP was higher at 5-, 15-, and 30-min postincision in the QLB than in the EB group; HR was similar between groups. Lower ephedrine requirements, higher lower limb muscle strength at 1 h post-surgery, and lower nausea incidence were observed in the QLB group.

Conclusions: QLB produces a less intense but longer block and fewer side effects in the first 24 h after open uterine surgery than those produced by EB.
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http://dx.doi.org/10.23736/S0375-9393.21.14800-XDOI Listing
April 2021

A 14-amino acids deletion in BmShadow results to non-moult on the 2nd instar in the bivoltine silkworm, Bombyx mori.

Gene 2021 Apr 29;777:145450. Epub 2021 Jan 29.

Jiangsu Key Laboratory of Sericutural Biology and Biotechnology, College of Biotechnology, Jiangsu University of Science and Technology, Zhenjiang, Jiangsu 212018, China; Key Laboratory of Silkworm and Mulberry Genetic Improvement, Ministry of Agriculture and Rural Affairs, Sericultural Research Institute, Chinese Academy of Agricultural Sciences, Zhenjiang, Jiangsu 212018, China. Electronic address:

The Bombyx mori Shadow gene (BmShadow) belongs to the superfamily of cytochrome P450 genes. To elucidate the function of the BmShadow gene and its association with diapause, we employed the CRISPR/Cas9 system to knock out the BmShadow gene in the bivoltine strain Qiufeng. The mutant (BmShadow) was obtained in G, exhibiting a 42-base deletion corresponded exactly to the amino acids regions from positions 155 to 168. The larvae of BmShadow cannot moult at the pre-moulting stage of the 2nd instar. When the BmShadow larvae were fed with 20E analogue at the late stage of the 2nd instar, they were rescued and developed into the 3rd instar. Rescue experiments indicated that the 20E concentration of BmShadow larvae was significantly lower than that in WT larvae, and the 20E concentration of BmShadow larvae which fed 20E analogue was restored to normal levels. Interestingly, the BmShadow larvae could not moult on the 1st instar when they hatched from eggs after being stored at 5 °C for 40 days or after hibernation, suggesting that the 20E transported from the mother was partially consumed in the diapause maintenance phase. Our study confirmed that BmShadow is involved in 20E synthesis and a 14-amino acids region from position 155 to 168 was essential for its function, also there appears to be no other compensation pathway in vivo, which offered an important potential target locus for the control of silkworm development and the biological control of agricultural and forestry pests.
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http://dx.doi.org/10.1016/j.gene.2021.145450DOI Listing
April 2021

Mobility-Included DNN Partition Offloading from Mobile Devices to Edge Clouds.

Sensors (Basel) 2021 Jan 1;21(1). Epub 2021 Jan 1.

School of Computer Science and Technology, Zhejiang University of Technology, Hangzhou 310023, China.

The latest results in Deep Neural Networks (DNNs) have greatly improved the accuracy and performance of a variety of intelligent applications. However, running such computation-intensive DNN-based applications on resource-constrained mobile devices definitely leads to long latency and huge energy consumption. The traditional way is performing DNNs in the central cloud, but it requires significant amounts of data to be transferred to the cloud over the wireless network and also results in long latency. To solve this problem, offloading partial DNN computation to edge clouds has been proposed, to realize the collaborative execution between mobile devices and edge clouds. In addition, the mobility of mobile devices is easily to cause the computation offloading failure. In this paper, we develop a mobility-included DNN partition offloading algorithm (MDPO) to adapt to user's mobility. The objective of MDPO is minimizing the total latency of completing a DNN job when the mobile user is moving. The MDPO algorithm is suitable for both DNNs with chain topology and graphic topology. We evaluate the performance of our proposed MDPO compared to local-only execution and edge-only execution, experiments show that MDPO significantly reduces the total latency and improves the performance of DNN, and MDPO can adjust well to different network conditions.
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http://dx.doi.org/10.3390/s21010229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795226PMC
January 2021

Evolutionary legacy of a forest plantation tree species (): Implications for widespread afforestation.

Evol Appl 2020 Dec 27;13(10):2646-2662. Epub 2020 Jul 27.

Key Laboratory of Resource Biology and Biotechnology in Western China Ministry of Education College of Life Sciences Northwest University Xi'an China.

Many natural systems are subject to profound and persistent anthropogenic influence. Human-induced gene movement through afforestation and the selective transportation of genotypes might enhance the potential for intraspecific hybridization, which could lead to outbreeding depression. However, the evolutionary legacy of afforestation on the spatial genetic structure of forest tree species has barely been investigated. To do this properly, the effects of anthropogenic and natural processes must be examined simultaneously. A multidisciplinary approach, integrating phylogeography, population genetics, species distribution modeling, and niche divergence would permit evaluation of potential anthropogenic impacts, such as mass planting near-native material. Here, these approaches were applied to , a Chinese endemic coniferous tree species, that has been mass planted across its native range. Population genetic analyses showed that natural populations of comprised three lineages that diverged around the late Miocene, during a period of massive uplifts of the Hengduan Mountains, and intensification of Asian Summer Monsoon. Only limited gene flow was detected between lineages, indicating that each largely maintained is genetic integrity. Moreover, most or all planted populations were found to have been sourced within the same region, minimizing disruption of large-scale spatial genetic structure within . This might be because each of the three lineages had a distinct climatic niche, according to ecological niche modeling and niche divergence tests. The current study provides empirical genetic and ecological evidence for the site-species matching principle in forestry and will be useful to manage restoration efforts by identifying suitable areas and climates for introducing and planting new forests. Our results also highlight the urgent need to evaluate the genetic impacts of large-scale afforestation in other native tree species.
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http://dx.doi.org/10.1111/eva.13064DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7691453PMC
December 2020

Effects of Heshouwuyin on gene expression of the insulin/IGF signalling pathway in rat testis and spermatogenic cells.

Pharm Biol 2020 Dec;58(1):1199-1210

School of Basic Medical Sciences, Hebei University, Baoding, China.

Context: The Chinese herbal formula Heshouwu decoction (Heshouwuyin) has protective effects on testicular function in aging male rats, but the mechanism is unknown.

Objective: This study investigated whether Heshouwuyin affects the testicular function of aging rats by regulating the insulin/IGF signalling pathway.

Materials And Methods: Sixteen-month-old male Wistar rats in the Heshouwuyin group and the natural-aging group were orally administered Heshouwuyin granules (0.056 g/kg) or equivalent normal saline for 60 d. The testicular tissue of 12-month-old male Wistar rats was removed as a young control group ( = 10). The testicular tissue and spermatogenic cells were studied.

Results: The immunofluorescence results revealed that the insulin receptor (INSR)- (0.056 ± 0.00548), insulin receptor substrate 1(IRS1)- (0.251 ± 0.031), IRS2 (0.230 ± 0.019)- and insulin-like growth factor 1 (IGF1)-positive cell rate (0.33 ± 0.04) in the aging group was higher than that in the young control group (0.116 ± 0.011, 0.401 ± 0.0256, 0.427 ± 0.031, 0.56 ± 0.031;  < 0.01), and the IGF-binding protein 3 (IGFBP3)-positive cell rate (0.42 ± 0.024) was lower than that (0.06 ± 0.027) in the young group ( < 0.01). The intervention of Heshouwuyin reversed the above phenomena. The qPCR and immunoblot results were consistent with those of the immunofluorescence. The same results were obtained in spermatogenic cells.

Conclusions: Our research shows that Heshouwuyin can regulate the insulin/IGF signalling pathway to improve testicular function, and provides an experimental basis for further clinical use.
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http://dx.doi.org/10.1080/13880209.2020.1839511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717869PMC
December 2020

A Single-Mode, Self-Adapting, and Self-Powered Mechanoreceptor Based on a Potentiometric-Triboelectric Hybridized Sensing Mechanism for Resolving Complex Stimuli.

Adv Mater 2020 Dec 12;32(50):e2005970. Epub 2020 Nov 12.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, CA, 94720, USA.

Human skin is equipped with slow adapting (SA) and fast adapting (FA) capabilities simultaneously. To mimic such functionalities, elaborately designed devices have been explored by integrating multiple sensing elements or adopting multimode sensing principles. However, the complicated fabrication, signal mismatch of different modules, complex operation, and high power-consumption hinder their widespread applications. Here, a new type of single-mode and self-powered mechanoreceptor that can mimic both SA and FA via seamless fusion of complementary while compatible potentiometric and triboelectric sensing principles is reported. The resultant potentiometric-triboelectric hybridized mechanoreceptor exhibits distinctive features that are hard to achieve via currently existing methods, including single-mode output (only voltage signal), greatly simplified operation (single-measurement setup), ultralow power-consumption (<1 nW), self-adaptive response behavior, and good capability for resolving complex stimuli. Diverse mechanical characteristics, including magnitude, duration, frequency, applying and releasing speed, can be well interpreted with this single-mode and self-powered mechanoreceptor. Its promising application for monitoring object manipulations with a soft robotic gripper is explored. Furthermore, the versatility of the mechanoreceptor for resolving complex stimuli in diverse daily scenarios is demonstrated. This work presents a new design that will significantly simplify the fabrication/operation and meanwhile boost the functionality/energy-efficiency of future electronic devices and smart systems.
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http://dx.doi.org/10.1002/adma.202005970DOI Listing
December 2020

The association between anxiety and esophageal cancer: A nationwide population-based study.

Psychooncology 2021 03 3;30(3):321-330. Epub 2020 Nov 3.

Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (CAMS & PUMC), Beijing, People's Republic of China.

Objective: Research on generalized anxiety disorder (GAD) and its association with esophageal cancer (EC) is sparse. The study aimed to explore the association between GAD and EC.

Methods: A multicenter, population-based study in high-risk regions for EC (ECHRRs) was conducted from 2017 to 2019. All participants received free endoscopy screening. If the esophageal endoscopy results were suspicious, the pathological biopsy was performed to confirm normal, esophagitis, low-grade intraepithelial neoplasia (LGIN), high-grade intraepithelial neoplasia (HGIN), and EC. Information on participants' exposure to risk factors was collected. GAD was assessed with Generalized Anxiety Disorder Scale-7.

Results: With esophageal endoscopy, 25,650 participants in ECHRRs were examined, 9586 of whom were suspicious and confirmed by esophageal pathology. The detection rate of EC and precancerous lesions was 6.83% (1751/25,650), with 1377 LGIN (5.37%), 272 HGIN (1.06%), and 102 EC (0.40%) cases. The overall mean GAD score (95% CI) and prevalence among 25,650 participants with endoscopy were 1.96 (1.93-1.99) and 16.90%, respectively. The mean GAD score and prevalence among 9586 participants with pathology were 1.96 (1.91-2.02) and 17.98%, respectively. The mean GAD scores of patients confirmed with normal, esophagitis, LGIN, HGIN, and EC were 1.73 (1.62-1.85), 1.91 (1.85-1.97), 1.94 (1.80-2.08), 3.98 (3.73-4.23). and 2.97 (2.49-3.45), respectively (p < 0.001). The corresponding prevalence of GAD were 5.21%, 18.72%, 17.72%, 43.75%, and 36.27%, respectively (p < 0.001). The age- and gender-adjusted odds ratios (ORs) between GAD and each esophageal lesion type were 1.02 (0.99-1.04), 1.01 (0.98-1.04), 1.27 (1.21-1.33), and 1.16 (1.08-1.24), respectively. The ORs (95% CIs) of the positive associations were 1.08 (1.05-1.12), 1.03 (0.99-1.07), 1.35 (1.29-1.42), and 1.19 (1.10-1.29) after further adjustment for potential confounders (all p < 0.001). Sensitivity analysis showed that the positive association persisted.

Conclusions: GAD was significantly higher in patients with EC and precancerous lesions. Focusing on and alleviating anxiety in high-risk groups (including patients with HGIN and EC) may be an effective strategy for EC prevention and control. Further prospective studies are warranted to validate the results.
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http://dx.doi.org/10.1002/pon.5580DOI Listing
March 2021

LncRNA ARFRP1 knockdown inhibits LPS-induced the injury of chondrocytes by regulation of NF-κB pathway through modulating miR-15a-5p/TLR4 axis.

Life Sci 2020 Nov 12;261:118429. Epub 2020 Sep 12.

Department of Orthopedics, Affiliated Hospital of Jiangsu University, Jiangsu, Zhejiang, China. Electronic address:

Aims: Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) have been reported as the important regulators in osteoarthritis (OA). However, the detailed mechanism is implicated. The aim of this study is to reveal the functional mechanism of lncRNA ARFRP1 and miR-15a-5p in osteoarthritis.

Materials And Methods: The expression level of genes was detected by quantitative real time polymerase chain reaction (qRT-PCR) or western blot assay. Cell Counting Kit-8 (CCK-8) was used to assess cell viability. Cell apoptosis rate was analyzed by flow cytometry analysis. Furthermore, Enzyme-linked immunosorbent assay (ELISA) was performed to measure tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1β contents. The interaction between miR-15a-5p and ARFRP1 or Toll-like receptor 4 (TLR4) was predicted by miRcode or PITA, and then confirmed by the dual luciferase reporter assay or pull down assay. Besides, NF-κB-driven luciferase activity was determined using NF-κB luciferase reporter assay.

Key Findings: ARFRP1 and TLR4 levels were increased and miR-15a-5p level was decreased in OA cartilage tissues and lipopolysaccharides (LPS)-induced chondrocytes. ARFRP1 knockdown inhibited LPS-induced the injury of chondrocytes. Interestingly, miR-15a-5p downregulated by ARFRP1 negatively modulated TLR4 expression through interaction. ARFRP1 mediated LPS-induced the injury of chondrocytes via regulating miR-15a-5p/TLR4 axis. Furthermore, ARFRP1 exerted function by modulation of NF-κB pathway.

Significance: Our findings confirmed that ARFRP1 mediated LPS-induced the injury of chondrocytes through regulating NF-κB pathway by modulation of miR-15a-5p/TLR4 axis, providing theoretical basis for the treatment of OA patients.
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http://dx.doi.org/10.1016/j.lfs.2020.118429DOI Listing
November 2020

Comparing EQ-5D-3L and EQ-5D-5L performance in common cancers: suggestions for instrument choosing.

Qual Life Res 2021 Mar 15;30(3):841-854. Epub 2020 Sep 15.

Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer /Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan South Lane, Chaoyang District, Beijing, 100021, People's Republic of China.

Purpose: To compare the performance of three-level EuroQol five-dimensions (EQ-5D-3L) and five-level EuroQol five-dimensions (EQ-5D-5L) among common cancer patients in urban China.

Methods: A hospital-based cross-sectional survey was conducted in three provinces from 2016 to 2018 in urban China. Patients with breast cancer, colorectal cancer, or lung cancer were recruited to complete the EQ-5D-3L and EQ-5D-5L questionnaires. Response distribution, discriminatory power (indicator: Shannon index [H'] and Shannon evenness index [J']), ceiling effect (the proportion of full health state), convergent validity, and health-related quality of life (HRQoL) were compared between the two instruments.

Results: A total of 1802 cancer patients (breast cancer: 601, colorectal cancer: 601, lung cancer: 600) were included, with the mean age of 55.6 years. The average inconsistency rate was 4.4%. Compared with EQ-5D-3L (average: H' = 1.100, J' = 0.696), an improved discriminatory power was observed in EQ-5D-5L (H' = 1.473, J' = 0.932), especially contributing to anxiety/depression dimensions. The ceiling effect was diminished in EQ-5D-5L (26.5%) in comparison with EQ-5D-3L (34.5%) (p < 0.001), mainly reflected in the pain/discomfort and anxiety/depression dimensions. The overall utility score was 0.790 (95% CI 0.778-0.801) for EQ-5D-3L and 0.803 (0.790-0.816) for EQ-5D-5L (p < 0.001). A similar pattern was also observed in the detailed cancer-specific analysis.

Conclusions: With greater discriminatory power, convergent validity and lower ceiling, EQ-5D-5L may be preferable to EQ-5D-3L for the assessment of HRQoL among cancer patients. However, higher utility scores derived form EQ-5D-5L may also lead to lower QALY gains than those of 3L potentially in cost-utility studies and underestimation in the burden of disease.
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http://dx.doi.org/10.1007/s11136-020-02636-wDOI Listing
March 2021

Down-regulated FOXA1 in early-onset pre-eclampsia induces apoptosis, and inhibits migration and invasion of trophoblast cells.

J Gene Med 2020 12 1;22(12):e3273. Epub 2020 Oct 1.

Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, Hainan Provincial Clinical Research Center for Thalassemia, The First Affiliated Hospital of Hainan Medical University, Hainan Medical University, Haikou, Hainan, China.

Background: Pre-eclampsia (PE) is a major cause of maternal and neonatal mortality and morbidity. Abnormal invasion of trophoblast cells is a major pathogenesis observed in PE. In the present study, we aimed to explore the association between forkhead box A1 (FOXA1) and early-onset pre-eclampsia (EOPE) and to determine the effects of FOXA1 on trophoblast cell apoptosis, migration and invasion.

Methods: Clinical data and placentas of patients with EOPE and normal pregnant women were collected in the First Affiliated Hospital of Hainan Medical College. The protein expression levels of FOXA1 in the clinical samples were evaluated by western blotting and immunohistochemistry. The effects of FOXA1 knockdown on HTR-8/SVneo cell apoptosis, migration and invasion were evaluated by flow cytometry, wound healing and transwell invasion assays, respectively.

Results: The western blot and immunohistochemical analysis showed that FOXA1 protein expression in placenta of EOPE group was significantly lower than that of normal group. The expression of FOXA1 in the placentas of EOPE and normal pregnant women was negatively correlated with systolic pressure and diastolic pressure. The expression of FOXA1 in EOPE and normal pregnant women was positively correlated with gestation weeks at delivery and neonatal birthweight. In vitro functional studies showed that silencing FOXA1 increased apoptosis, and inhibited the migration and invasion of HTR-8/SVneo cells.

Conclusions: Down-regulation of FOXA1 in the placentas may indicate poor prognosis of EOPE. Silencing of FOXA1 induced apoptosis in trophoblast cells, and impaired the migratory and invasive capacity of trophoblast cells. FOXA1 may represent a potential therapeutic target for EOPE.
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http://dx.doi.org/10.1002/jgm.3273DOI Listing
December 2020

Biomass-Derived, Water-Induced Self-Recoverable Composite Aerogels with Robust Superwettability for Water Treatment.

Langmuir 2020 09 11;36(37):10960-10969. Epub 2020 Sep 11.

College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, P. R. China.

Polluted water is a worldwide problem; therefore, effective separation of oil/water and removal of dyes, organic micropollutants, and heavy metals in wastewater are the need of the hour. Herein, hydrophilic β-cyclodextrin-grafted carboxymethyl cellulose, biodegradable polyvinyl alcohol, and chitosan were used as main raw materials to construct a multifunctional aerogel framework by simple sol-gel and directional freeze-drying methods. Featuring intrinsic superamphiphilic wettability in air, robust superoleophobic wettability underwater, and excellent shape-recovery characteristics, the biomass-derived aerogel presents durable oil/water separation even after 10 cycles. The aerogels possess prominent adsorption capacity for methyl blue, 1-naphthylamine, and Cu, which was as high as 121.55 mg/g, 33.96 mg/g, and 122.6 mg/g, respectively. In addition, various pollutant mixtures could be effectively adsorbed by the aerogel at the same time with the adsorption capacity of 121.75 mg/g for methyl blue, 0.97 mg/g for bisphenol A, and 20.11 mg/g for Cu.
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http://dx.doi.org/10.1021/acs.langmuir.0c01690DOI Listing
September 2020

A randomized Phase I pharmacokinetic trial comparing the potential biosimilar trastuzumab (SIBP-01) with the reference product (Herceptin®) in healthy Chinese male volunteers.

Expert Opin Drug Metab Toxicol 2020 Oct 26;16(10):997-1003. Epub 2020 Aug 26.

Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University , Nanjing, Jiangsu, China.

Objectives: This study aimed to evaluate the bioequivalence, safety, tolerability and immunogenicity of the biosimilar trastuzumab (SIBP-01) compared to Herceptin®.

Methods: In this Phase I randomized double-blind parallel-group trial, 100 healthy male volunteers were randomized in a1:1 ratio to receive a single 6 mg•kg-1 intravenous dose of SIBP-01 or Herceptin®. Serum concentrationswere analyzed using a validated ELISA.

Results: The two groups had similar baseline characteristics. The geometric mean ratios (90% CI) of C, AUC and AUC between the trial group and the reference group were 93.55%-104.27%, 91.98%-102.35% and 91.88%-102.34%, respectively; the geometric mean ratios (90% CI) of AUC and AUC in the sensitivity analysis were 92.29%-102.63% and 91.81%-102.16%, respectively. These values were within the prespecified equivalence margins, establishing the bioequivalence of SIBP-1 and Herceptin®. AEs were similar across all subjects in the SIBP-01 and Herceptin® arms, with treatment-related AEs reported by 72.00% and 80.00%, respectively. In each group, there was one AE that caused a subject to discontinue the study.

Expert Opinion: Trastuzumab (Herceptin®) is significantly more effective than chemotherapy in reducing exacerbations and tumor cell growth, and its adverse events are far lower than chemotherapy. Herceptin®is very expensive for most patients in China. The protein molecular primary structure of the biosimilar trastuzumab (SIBP-01) is consistent with Herceptin®, with highly similar high level structure, biologocal activity and purity.But there are few studies comparing the bioequivalence of SIBP-01 and Herceptin® in healthy subjects and cancer patients 2.

Conclusions: This study showed the PK similarity of SIBP-01 to Herceptin®. SIBP-01 was safe and well tolerated in healthy male volunteers, with no significant differences from the reference drug in safety or immunogenicity 4.
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http://dx.doi.org/10.1080/17425255.2020.1807935DOI Listing
October 2020

A potentiometric mechanotransduction mechanism for novel electronic skins.

Sci Adv 2020 Jul 24;6(30):eaba1062. Epub 2020 Jul 24.

Department of Electrical Engineering and Computer Sciences, University of California, Berkeley, Berkeley, CA 94720, USA.

Human skin perceives external mechanical stimuli by sensing the variation in the membrane potential of skin sensory cells. Many scientists have attempted to recreate skin functions and develop electronic skins (e-skins) based on active and passive sensing mechanisms. Inspired by the skin sensory behavior, we investigated materials and electronic devices that allow us to encode mechanical stimuli into potential differences measured between two electrodes, resulting in a potentiometric mechanotransduction mechanism. We present here a potentiometric mechanotransducer that is fabricated through an all-solution processing approach. This mechanotransducer shows ultralow-power consumption, highly tunable sensing behavior, and capability to detect both static and low-frequency dynamic mechanical stimuli. Furthermore, we developed two novel classes of sensing devices, including strain-insensitive sensors and single-electrode-mode e-skins, which are challenging to achieve using the existing methods. This mechanotransduction mechanism has broad impact on robotics, prosthetics, and health care by providing a much improved human-machine interface.
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http://dx.doi.org/10.1126/sciadv.aba1062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439546PMC
July 2020

One-step synthesis of Mn-doped MIL-53(Fe) for synergistically enhanced generation of sulfate radicals towards tetracycline degradation.

J Colloid Interface Sci 2020 Nov 15;580:470-479. Epub 2020 Jul 15.

Hunan Xinheng Environmental Technology Co Ltd, Changsha 410005, PR China.

Herein, Mn-doped MIL-53(Fe) were fabricated via one-pot solvothermal method and used for peroxymonosulfate (PMS) activation towards tetracycline (TC) degradation from aqueous solution. The characterizations of SEM, FTIR and XRD were utilized to reveal the morphology and structure of the materials. The results showed that Mn-MIL-53(Fe)-0.3 displayed the optimal catalytic performance, the removal efficiency of TC could reach 93.2%. Moreover, the catalytic activity of Mn-MIL-53(Fe) towards TC under different initial pH values, co-existing anions (Cl,CO and SO) and humic acid (HA) were investigated. The results of thermodynamic experiment suggested that the catalytic process was endothermic. In addition, integrated with capture experiments results and the characterization results of electron paramagnetic resonance (EPR), which revealed that SO and HO were the reactive radicals involving in the reaction. More importantly, the possible activation mechanism was discussed in detail based on the X-ray photoelectron spectroscopy results. The active species were generated by the active sites of Fe(II) and Mn(II) on Mn-MIL-53(Fe) effectively activated PMS. Furthermore, the degradation intermediates and possible degradation pathway were investigated by LC-MS. Finally, the catalyst also showed good performance in actual wastewater and demonstrated good recyclability. The Mn-MIL-53(Fe)/PMS system exhibited a promising application prospect for antibiotic-containing waste water treatment.
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http://dx.doi.org/10.1016/j.jcis.2020.07.045DOI Listing
November 2020

NLRP3 inflammasome-mediated microglial pyroptosis is critically involved in the development of post-cardiac arrest brain injury.

J Neuroinflammation 2020 Jul 23;17(1):219. Epub 2020 Jul 23.

Department of Neurology, Nanfang Hospital, Southern Medical Univerisity, North Avenue 1838#, Guangzhou, Guangzhou, 510515, China.

Background: Brain injury is the leading cause of death and disability in survivors of cardiac arrest, where neuroinflammation is believed to play a pivotal role, but the underlying mechanism remains unclear. Pyroptosis is a pro-inflammatory form of programmed cell death that triggers inflammatory response upon infection or other stimuli. This study aims to understand the role of microglial pyroptosis in post-cardiac arrest brain injury.

Methods: Sprague-Dawley male rats underwent 10-min asphyxial cardiac arrest and cardiopulmonary resuscitation or sham-operation. Flow cytometry analysis, Western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), co-immunoprecipitation, and immunofluorescence were used to evaluate activated microglia and CD11b-positive leukocytes after cardiac arrest and assess inflammasome activation and pyroptosis of specific cellular populations. To further explore the underlying mechanism, MCC950 or Ac-YVAD-cmk was administered to block nod-like receptor family protein 3 (NLRP3) or caspase-1, respectively.

Results: Our results showed that, in a rat model, successful resuscitation from cardiac arrest resulted in microglial pyroptosis and consequential inflammatory infiltration which was mediated by the activation of NLRP3 inflammasome. Targeting NLRP3 and caspase-1, the executor of pyroptosis, with selective inhibitors MCC950 and Ac-YVAD-cmk treatment significantly prevented microglial pyroptosis, reduced infiltration of leukocytes, improved neurologic outcome, and alleviated neuro-pathological damages after cardiac arrest in modeling rats.

Conclusions: This study demonstrates that microglial pyroptosis mediated by NLRP3 inflammasome is critically involved in the pathogenesis of post-cardiac arrest brain injury and provides a new therapeutic strategy.
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http://dx.doi.org/10.1186/s12974-020-01879-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376727PMC
July 2020

Stabilization of an intermolecular RNA triplex by two novel binders Lys- and Arg-rich Ru(II) polypyridyl metallopeptides.

J Inorg Biochem 2020 09 3;210:111171. Epub 2020 Jul 3.

Key Lab of Environment-friendly Chemistry and Application in Ministry of Education, Xiangtan University, Xiangtan 411105, People's Republic of China; Key Laboratory for Green Organic Synthesis and Application of Hunan Province, Xiangtan University, Xiangtan 411105, People's Republic of China. Electronic address:

In this work, using [Ru(bpy)(pip)] (bpy = 2,2'-bipyridine, pip = 2-phenyl-1H-imidazo[4,5-f]-[1,10]-phenanthroline) as chromophores and neutral amino acid glycine as spacers, two novel Arg- and Lys-rich Ru(II) polypyridyl metallopeptides as an intermolecular triplex RNA stabilizers, namely [Ru(bpy)(pic-Lys-Gly-Lys-Gly-Lys)] (Ru1; pic = 2-(4-carboxy-phenyl)imidazo-[4,5-f] [1,10] phenanthroline, Gly = glycine, Lys = lysine) and [Ru(bpy)(pic-Arg-Gly-Arg-Gly-Arg)] (Ru2; Arg = arginine), have been synthesized and characterized. The binding properties of Ru1 and Ru2 with poly(U)·poly(A)∗poly(U) triplex have been studied by UV-Vis spectroscopy, fluorescence spectroscopy, viscosity measurements as well as circular dichroism and thermal denaturation. The obtained results suggest that attaching cationic peptides to a Ru(II) polypyridyl complex can obviously enhance the triplex stabilization. Considering the structure natures of Ru1 and Ru2, conceivably besides electrostatic interaction, the forces stabilizing the triplex should also involve hydrophobic interaction and hydrogen binding. Compared with the Lys-rich metallopeptide (Ru1), however, the third-strand stabilizating effect of the Arg-rich one (Ru2) is slightly more marked, which may be due to differences in the interactions of arginine and lysine residues with the third strand of the triplex. The results obtained here may be useful for understanding the interaction of triplex RNA poly(U)·poly(A)∗poly(U) with small molecule, particularly ruthenium(II) complexes.
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http://dx.doi.org/10.1016/j.jinorgbio.2020.111171DOI Listing
September 2020

A Platform to Study the Effects of Electrical Stimulation on Immune Cell Activation During Wound Healing.

Adv Biosyst 2019 10 21;3(10):e1900106. Epub 2019 Aug 21.

Department of Electrical and Computer Engineering, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.

Wound healing is a complex process involving diverse changes in multiple cell types where the application of electric fields has been shown to accelerate wound closure. To define the efficacy of therapies based on electric fields, it would be valuable to have a platform to systematically study the effects of electrical stimulation (ES) upon the inflammation phase and the activation of signaling mediators. Here, an in vivo ES model in which flexible electrodes are applied to an animal model for monitoring inflammation in a wound is reported on. Subcutaneous implants of polyvinyl alcohol sponges elicit inflammation response as defined by the infiltration of leukocytes. The wound site is subjected to electric fields using two types of additively fabricated flexible electrode arrays. The sponges are then harvested for flow cytometry analysis to identify changes in the phosphorylation state of intracellular targets. This platform enables studies of molecular mechanisms, as it shows that an application of low-frequency ES ≤0.5 Hz increases phosphorylation of Erk proteins in recruited leukocytes, identifying a signaling pathway that is activated during the healing process.
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http://dx.doi.org/10.1002/adbi.201900106DOI Listing
October 2019

Highly Flexible Transparent Micromesh Electrodes via Blade-Coated Polymer Networks for Organic Light-Emitting Diodes.

ACS Appl Mater Interfaces 2020 Jul 29;12(28):31687-31695. Epub 2020 Jun 29.

Department of Electrical Engineering and Computer Sciences, University of California Berkeley, Berkeley, California 94720, United States.

The availability of transparent conductive thin films that exhibit mechanical flexibility and are adapted to low-cost and large-area fabrication is a major obstacle for high-performance flexible thin-film optoelectronics. Here, by combining printing, thin-film deposition, and wet-etching processes, interconnected transparent metal micromesh (TMM) electrodes are reported. Blade-coating is used to generate self-assembled polymer micromesh networks on flexible substrates. The network structures are subsequently converted into conductive metal networks. As-fabricated TMM films display a surface roughness of around 20 nm with thickness down to 50 nm. A transmittance of 86% and a conductance of 80 Ω sq are achieved at the described optimal blade-coating suspension concentration. The electrodes show mechanical flexibility with no conductivity degradation with the smallest bending radius of 1 mm or at repeated bending over 3000 cycles at a bending radius of 15 mm. We successfully demonstrate organic light-emitting diodes (OLEDs) using TMM electrodes via the blade-coating technique. The printed OLEDs have a low turn-on voltage of 3.4 V and can achieve a luminance of over 4000 cd/m at 6.5 V. At a luminance of 100 cd/m, the OLEDs show a current density of 7.6 mA/cm, an external quantum efficiency (EQE) of 3.6%, and a luminous efficacy of 1.4 lm/W.
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http://dx.doi.org/10.1021/acsami.0c07299DOI Listing
July 2020

Mechanism of Heshouwuyin inhibiting the Cyt c/Apaf-1/Caspase-9/Caspase-3 pathway in spermatogenic cell apoptosis.

BMC Complement Med Ther 2020 Jun 11;20(1):180. Epub 2020 Jun 11.

School of Medicine, Hebei University, Baoding, 071002, Hebei Province, China.

Background: The Chinese herbal compound Heshouwuyin has been shown to downregulate the apoptotic rate of testicular tissue cells in Wistar naturally aging rats, and this effect might be related to the mitochondrial pathway [15]. Apoptotic protease activating factor-1 (Apaf-1) is a major component of the apoptotic complex, which is a key element of the mitochondrial endogenous apoptotic pathway [13]. To further clarify the mechanism of Heshouwuyin in the mitochondrial apoptotic pathway, this study used Apaf-1 as a target to explore the mechanism by which Heshouwuyin inhibits the Apaf-1 pathway of spermatogenic cell apoptosis.

Methods: In this study, an aging model of rat spermatogenic cells was established using free radical oxidative damage. Flow cytometry was used to detect the apoptosis rate of germ cells and the inhibitory effect of Heshouwuyin. Apaf-1 was specifically knocked down by siRNA interference technology, and mitochondrial membrane potential was measured. qRT-PCR, Western blotting and immunofluorescence analyses were used to detect the expression of the key genes Cyt c, Caspase-9 and Caspase-3 in the mitochondrial apoptotic pathway of spermatogenic cells.

Results: Heshouwuyin reduced the mRNA and protein expression levels of Cyt c, Caspase-9 and Caspase-3 in senescent spermatogenic cells. In these cells, the mRNA and protein expression levels of Cyt c did not change significantly after specific knockdown of Apaf-1, and the mRNA and protein expression levels of Caspase-9 and Caspase-3 decreased significantly. This finding indicated that knockdown of Apaf-1 could decrease the mRNA and protein expression levels of the downstream pro-apoptotic genes Caspase-9 and Caspase-3. Although Cyt c was an upstream gene of Apaf-1, knockdown of Apaf-1 had no significant effect on Cyt c expression.

Conclusion: The inhibition of spermatogenic cell apoptosis by Heshouwuyin was closely related to the Cyt c/Apaf-1/Caspase-9/Caspase-3 pathway. The inhibition of apoptosis by Heshouwuyin not only involved the Apaf-1 pathway, but other signaling pathways.
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http://dx.doi.org/10.1186/s12906-020-02904-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7291440PMC
June 2020

Risk factors for adverse clinical outcomes with COVID-19 in China: a multicenter, retrospective, observational study.

Theranostics 2020 15;10(14):6372-6383. Epub 2020 May 15.

Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210002, China.

The risk factors for adverse events of Coronavirus Disease-19 (COVID-19) have not been well described. We aimed to explore the predictive value of clinical, laboratory and CT imaging characteristics on admission for short-term outcomes of COVID-19 patients. This multicenter, retrospective, observation study enrolled 703 laboratory-confirmed COVID-19 patients admitted to 16 tertiary hospitals from 8 provinces in China between January 10, 2020 and March 13, 2020. Demographic, clinical, laboratory data, CT imaging findings on admission and clinical outcomes were collected and compared. The primary endpoint was in-hospital death, the secondary endpoints were composite clinical adverse outcomes including in-hospital death, admission to intensive care unit (ICU) and requiring invasive mechanical ventilation support (IMV). Multivariable Cox regression, Kaplan-Meier plots and log-rank test were used to explore risk factors related to in-hospital death and in-hospital adverse outcomes. Of 703 patients, 55 (8%) developed adverse outcomes (including 33 deceased), 648 (92%) discharged without any adverse outcome. Multivariable regression analysis showed risk factors associated with in-hospital death included ≥ 2 comorbidities (hazard ratio [HR], 6.734; 95% CI; 3.239-14.003, p < 0.001), leukocytosis (HR, 9.639; 95% CI, 4.572-20.321, p < 0.001), lymphopenia (HR, 4.579; 95% CI, 1.334-15.715, p = 0.016) and CT severity score > 14 (HR, 2.915; 95% CI, 1.376-6.177, p = 0.005) on admission, while older age (HR, 2.231; 95% CI, 1.124-4.427, p = 0.022), ≥ 2 comorbidities (HR, 4.778; 95% CI; 2.451-9.315, p < 0.001), leukocytosis (HR, 6.349; 95% CI; 3.330-12.108, p < 0.001), lymphopenia (HR, 3.014; 95% CI; 1.356-6.697, p = 0.007) and CT severity score > 14 (HR, 1.946; 95% CI; 1.095-3.459, p = 0.023) were associated with increased odds of composite adverse outcomes. The risk factors of older age, multiple comorbidities, leukocytosis, lymphopenia and higher CT severity score could help clinicians identify patients with potential adverse events.
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http://dx.doi.org/10.7150/thno.46833DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255028PMC
June 2020
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