Publications by authors named "Ting Jiang"

382 Publications

The Downregulation of eIF3a Contributes to Vemurafenib Resistance in Melanoma by Activating ERK via PPP2R1B.

Front Pharmacol 2021 27;12:720619. Epub 2021 Aug 27.

Department of Clinical Pharmacology, Hunan Key Laboratory of Pharmacogenetics, and National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Vemurafenib, a BRAF V600E inhibitor, provides therapeutic benefits for patients with melanoma, but the frequent emergence of drug resistance remains a challenge. An understanding of the mechanisms underlying vemurafenib resistance may generate novel therapeutic strategies for patients with melanoma. Here, we showed that eIF3a, a translational regulatory protein, was an important mediator involved in vemurafenib resistance. eIF3a was expressed at significantly lower levels in vemurafenib-resistant A375 melanoma cells (A375R) than in parental A375 cells. Overexpression of eIF3a enhanced the sensitivity to BRAF inhibitors by reducing p-ERK levels Furthermore, eIF3a controlled ERK activity by regulating the expression of the phosphatase PPP2R1B via a translation mechanism, thus determining the sensitivity of melanoma cells to vemurafenib. In addition, a positive correlation between eIF3a and PPP2R1B expression was also observed in tumor samples from the Human Protein Atlas and TCGA databases. In conclusion, our studies reveal a previously unknown molecular mechanism of BRAF inhibitor resistance, which may provide a new strategy for predicting vemurafenib responses in clinical treatment.
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http://dx.doi.org/10.3389/fphar.2021.720619DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430041PMC
August 2021

Effect of a Virtual Reality-Based Restorative Environment on the Emotional and Cognitive Recovery of Individuals with Mild-to-Moderate Anxiety and Depression.

Int J Environ Res Public Health 2021 Aug 27;18(17). Epub 2021 Aug 27.

Faculty of Psychology, Beijing Normal University, Beijing 100875, China.

In this study, restorative environment theory and virtual reality (VR) technology were combined to build different 3D dynamic VR interactive scenes. We discuss the effects of a VR restorative environment on the emotional and cognitive recovery of individuals with mild-to-moderate anxiety and depression. First, we built a VR restorative garden scene, divided into four areas: forest, lawn, horticultural planting, and water features. The scene was verified to have a good recovery effect in 26 participants. Then, 195 participants with mild-to-moderate anxiety and depression were selected as experimental subjects. Through psychological testing and EMG (Electromyography) and EEG (Electroencephalography) data feedback, we further explored the differences in the sense of presence in VR restorative scenes and their effect on individual emotional and cognitive recovery. The results showed that (1) both the restorative environment images and the VR scenes had a healing effect (the reduction in negative emotions and the recovery of positive emotions and cognition), with no difference in the subjective feeling of recovery among the different scenes, but the recovery score of the VR urban environment was higher than that of the natural environment (differing from the results in real environments); (2) a high sense of presence can be experienced in different VR scenes, and interactive activities in VR scenes can provide a great presence experience; (3) the recovery effects of VR restorative environment on emotion and self-efficacy are realized through the presence of VR scenes; (4) a VR restorative environment is helpful for the emotional improvement and cognitive recovery of individuals with mild-to-moderate anxiety and depression. VR urban scenes also have good recovery effects. In terms of cognitive recovery, self-efficacy improved significantly. In addition, from the perspective of EEG indicators, the VR restorative scene experience activated the prefrontal lobe, which is conducive to cognitive recovery in individuals with mild-to-moderate anxiety and depression. In terms of emotional improvement, negative emotions were significantly reduced in the different VR scene groups. In conclusion, we further explored ways to help individuals with mild-to-moderate anxiety and depression, in order to promote the development and application of mental health.
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http://dx.doi.org/10.3390/ijerph18179053DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430968PMC
August 2021

NMR-Based Metabolomic Analysis on the Protective Effects of Apolipoprotein A-I Mimetic Peptide against Contrast Media-Induced Endothelial Dysfunction.

Molecules 2021 Aug 24;26(17). Epub 2021 Aug 24.

Key Laboratory for Chemical Biology of Fujian Province, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361000, China.

Endothelial dysfunction plays key roles in the pathological process of contrast media (CM)-induced acute kidney injury (CI-AKI) in patients undergoing vascular angiography or intervention treatment. Previously, we have demonstrated that an apolipoprotein A-I (apoA-I) mimetic peptide, D-4F, inhibits oxidative stress and improves endothelial dysfunction caused by CM through the AMPK/PKC pathway. However, it is unclear whether CM induce metabolic impairments in endothelial cells and whether D-4F ameliorates these metabolic impairments. In this work, we evaluated vitalities of human umbilical vein endothelial cells (HUVECs) treated with iodixanol and D-4F and performed nuclear magnetic resonance (NMR)-based metabolomic analysis to assess iodixanol-induced metabolic impairments in HUVECs, and to address the metabolic mechanisms underlying the protective effects of D-4F for ameliorating these metabolic impairments. Our results showed that iodixanol treatment distinctly impaired the vitality of HUVECs, and greatly disordered the metabolic pathways related to energy production and oxidative stress. Iodixanol activated glucose metabolism and the TCA cycle but inhibited choline metabolism and glutathione metabolism. Significantly, D-4F pretreatment could improve the iodixanol-impaired vitality of HUVECs and ameliorate the iodixanol-induced impairments in several metabolic pathways including glycolysis, TCA cycle and choline metabolism in HUVECs. Moreover, D-4F upregulated the glutathione level and hence enhanced antioxidative capacity and increased the levels of tyrosine and nicotinamide adenine dinucleotide in HUVECs. These results provided the mechanistic understanding of CM-induced endothelial impairments and the protective effects of D-4F for improving endothelial cell dysfunction. This work is beneficial to further exploring D-4F as a potential pharmacological agent for preventing CM-induced endothelial impairment and acute kidney injury.
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http://dx.doi.org/10.3390/molecules26175123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433922PMC
August 2021

Deoxyribonucleic acid anchored on cell membranes for biomedical application.

Biomater Sci 2021 Sep 8. Epub 2021 Sep 8.

Department of Pharmaceutics, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, 410013, Hunan Province, P. R. China.

Engineering cellular membranes with functional molecules provides an attractive strategy to manipulate cellular behaviors and functionalities. Currently, synthetic deoxyribonucleic acid (DNA) has emerged as a promising molecular tool to engineer cellular membranes for biomedical applications due to its molecular recognition and programmable properties. In this review, we summarized the recent advances in anchoring DNA on the cellular membranes and their applications. The strategies for anchoring DNA on cell membranes were summarized. Then their applications, such as immune response activation, receptor oligomerization regulation, membrane structure mimicking, cell-surface biosensing, and construction of cell clusters, were listed. The DNA-enabled intelligent systems which were able to sense stimuli such as DNA strands, light, and metal ions were highlighted. Finally, insights regarding the remaining challenges and possible future directions were provided.
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http://dx.doi.org/10.1039/d1bm01057cDOI Listing
September 2021

Lnc-GD2H Promotes Proliferation by Forming a Feedback Loop With c-Myc and Enhances Differentiation Through Interacting With NACA to Upregulate Myog in C2C12 Myoblasts.

Front Cell Dev Biol 2021 18;9:671857. Epub 2021 Aug 18.

Department of Radiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

In the present study, the roles of a novel long non-coding RNA (lncRNA), lnc-GD2H, in promoting C2C12 myoblast proliferation and differentiation and muscle regeneration were investigated by quantitative polymerase chain reaction, western blotting, Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine (EdU), immunofluorescence staining, luciferase reporter, mass spectrometry, pulldown, chromatin immunoprecipitation, RNA immunoprecipitation assay, wound healing assays, and cardiotoxin (CTX)-induced muscle injury assays. It was observed that lnc-GD2H promoted myoblast proliferation as evidenced by the enhancement of the proliferation markers c-Myc, CDK2, CDK4, and CDK6, percentage of EdU-positive cells, and rate of cell survival during C2C12 myoblast proliferation. Additional experiments confirmed that c-Myc bound to the lnc-GD2H promoter and regulated its transcription. lnc-GD2H promoted cell differentiation with enhanced MyHC immunostaining as well as increased expression of the myogenic marker genes myogenin (Myog), Mef2a, and Mef2c during myoblast differentiation. Additional assays indicated that lnc-GD2H interacted with NACA which plays a role of transcriptional regulation in myoblast differentiation, and the enrichment of NACA at the Myog promoter was impaired by lnc-GD2H. Furthermore, inhibition of lnc-GD2H impaired muscle regeneration after CTX-induced injury in mice. lnc-GD2H facilitated the expression of proliferating marker genes and formed a feedback loop with c-Myc during myoblast proliferation. In differentiating myoblasts, lnc-GD2H interacted with NACA to relieve the inhibitory effect of NACA on Myog, facilitating Myog expression to promote differentiation. The results provide evidence for the role of lncRNAs in muscle regeneration and are useful for developing novel therapeutic targets for muscle disorders.
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http://dx.doi.org/10.3389/fcell.2021.671857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416608PMC
August 2021

Metabolomics Reveals the Mechanisms for the Pulmonary Toxicity of L. and the Toxicity-Reducing Effect of Processing.

Front Pharmacol 2021 9;12:630319. Epub 2021 Aug 9.

International Institute for Translational Chinese Medicine, School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, China.

L. (SO) is a commonly used Chinese medicinal herb. It has long been used as a remedy in traditional Chinese medicine (TCM) for symptoms that resemble inflammatory joint disorders. However, it is slightly toxic. According to the TCM theory, processing can reduce the toxicity of the herbs. Here, we performed metabolomics to determine whether processing with rice wine reduces the toxicity of raw SO, and to explore the mechanisms underlying the raw SO-induced toxicity and the toxicity-reducing effect of processing. Our results showed that raw SO has long-term toxicity in rats. It significantly elevated the serum level of LDH and caused histopathological damages in the lung tissues. It is worth noting that the LDH level in the PSO group was lower than that in the raw SO group, and the damages in lung tissues were relatively mild in PSO-treated rats, suggesting that processing reduces the pulmonary toxicity of the raw. Moreover, a total of 32 significantly changed metabolites were identified. Based on the MetaboAnalyst pathway analysis, we found that two characteristic metabolic pathways including alanine, aspartate and glutamate metabolism and glycerophospholipid metabolism were only changed in the raw SO group, while histidine metabolism was only changed in the PSO group, which suggests that induction of oxidative stress contributes to raw SO-induced pulmonary toxicity, and free radical scavenging might be responsible for the toxicity-reducing effect of processing. Our data shed new light on how raw SO induces pulmonary toxicity and how the toxicity can be reduced by processing. This study not only provides scientific justifications for the traditional processing theory of SO, but also helps to optimize the processing protocol and the clinical drug combination of SO.
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http://dx.doi.org/10.3389/fphar.2021.630319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8381750PMC
August 2021

Large-Scale Implementation and Flaw Investigation of Human Serum Suspect Screening Analysis for Industrial Chemicals.

J Am Soc Mass Spectrom 2021 Sep 19;32(9):2425-2435. Epub 2021 Aug 19.

Department of Obstetrics, Gynecology and Reproductive Sciences, University of California, San Francisco, California 94158, United States.

Non-targeted analysis (NTA), including both suspect screening analysis (SSA) and unknown compound analysis, has gained increasing popularity in various fields for its capability in identifying new compounds of interests. Current major challenges for NTA SSA are that (1) tremendous effort and resources are needed for large-scale identification and confirmation of suspect chemicals and (2) suspect chemicals generally show low matching rates during identification and confirmation processes. To narrow the gap between these challenges and smooth implementation of NTA SSA methodology in the biomonitoring field, we present a thorough SSA workflow for the large-scale screen, identification, and confirmation of industrial chemicals that may pose adverse health effects in pregnant women and newborns. The workflow was established in a study of 30 paired maternal and umbilical cord serum samples collected at delivery in the San Francisco Bay area. By analyzing LC-HRMS and MS/MS data, together with the assistance of a combination of resources including online MS/MS spectra libraries, online in silico fragmentation tools, and the EPA CompTox Chemicals Dashboard, we confirmed the identities of 17 chemicals, among which monoethylhexyl phthalate, 4-nitrophenol, tridecanedioic acid, and octadecanedioic acid are especially interesting due to possible toxicities and their high-volume use in industrial manufacturing. Similar to other previous studies in the SSA field, the suspect compounds show relatively low MS/MS identification (16%) and standard confirmation (8%) rates. Therefore, we also investigated origins of false positive features and unidentifiable suspected features, as well as technical obstacles encountered during the confirmation process, which would promote a better understanding of the flaw of low confirmation rate and encourage gaining more effective tools for tackling this issue in NTA SSA.
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http://dx.doi.org/10.1021/jasms.1c00135DOI Listing
September 2021

Outcomes and toxicities of immune checkpoint inhibitors in colorectal cancer: a real-world retrospective analysis.

Cancer Commun (Lond) 2021 Sep 30;41(9):921-924. Epub 2021 Jul 30.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, P. R. China.

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http://dx.doi.org/10.1002/cac2.12199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8441054PMC
September 2021

Knockdown of CNN3 Impairs Myoblast Proliferation, Differentiation, and Protein Synthesis via the mTOR Pathway.

Front Physiol 2021 8;12:659272. Epub 2021 Jul 8.

Guangdong Traditional Medical and Sports Injury Rehabilitation Research Institute, Guangdong Second Provincial General Hospital, Guangzhou, China.

Background: Myogenesis is a complex process that requires optimal outside-in substrate-cell signaling. Calponin 3 (CNN3) plays an important role in regulating myogenic differentiation and muscle regeneration; however, the precise function of CNN3 in myogenesis regulation remains poorly understood. Here, we investigated the role of CNN3 in a knockdown model in the mouse muscle cell line C2C12.

Methods: Myoblast proliferation, migration, differentiation, fusion, and protein synthesis were examined in CNN3 knockdown C2C12 mouse muscle cells. Involvement of the mTOR pathway in CNN3 signaling was explored by treating cells with the mTOR activator MHY1485. The regulatory mechanisms of CNN3 in myogenesis were further examined by RNA sequencing and subsequent gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene set enrichment analysis (GSEA).

Results: During proliferation, CNN3 knockdown caused a decrease in cell proliferation and migration. During differentiation, CNN3 knockdown inhibited myogenic differentiation, fusion, and protein synthesis in C2C12 cells via the AKT/mTOR and AMPK/mTOR pathways; this effect was reversed by MHY1485 treatment. Finally, KEGG and GSEA indicated that the NOD-like receptor signaling pathway is affected in CNN3 knockdown cell lines.

Conclusion: CNN3 may promote C2C12 cell growth by regulating AKT/mTOR and AMPK/mTOR signaling. The KEGG and GSEA indicated that inhibiting CNN3 may activate several pathways, including the NOD-like receptor pathway and pathways involved in necroptosis, apoptosis, and inflammation.
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http://dx.doi.org/10.3389/fphys.2021.659272DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295729PMC
July 2021

A Comprehensive Non-targeted Analysis Study of the Prenatal Exposome.

Environ Sci Technol 2021 08 14;55(15):10542-10557. Epub 2021 Jul 14.

Department of Obstetrics, Gynecology and Reproductive Sciences, Program on Reproductive Health and the Environment, University of California San Francisco, San Francisco 94143, California, United States.

Recent technological advances in mass spectrometry have enabled us to screen biological samples for a very broad spectrum of chemical compounds allowing us to more comprehensively characterize the human exposome in critical periods of development. The goal of this study was three-fold: (1) to analyze 590 matched maternal and cord blood samples (total 295 pairs) using non-targeted analysis (NTA); (2) to examine the differences in chemical abundance between maternal and cord blood samples; and (3) to examine the associations between exogenous chemicals and endogenous metabolites. We analyzed all samples with high-resolution mass spectrometry using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS) in both positive and negative electrospray ionization modes (ESI+ and ESI-) and in soft ionization (MS) and fragmentation (MS/MS) modes for prioritized features. We confirmed 19 unique compounds with analytical standards, we tentatively identified 73 compounds with MS/MS spectra matching, and we annotated 98 compounds using an annotation algorithm. We observed 103 significant associations in maternal and 128 in cord samples between compounds annotated as endogenous and compounds annotated as exogenous. An example of these relationships was an association between three poly and perfluoroalkyl substances (PFASs) and endogenous fatty acids in both the maternal and cord samples indicating potential interactions between PFASs and fatty acid regulating proteins.
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http://dx.doi.org/10.1021/acs.est.1c01010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8338910PMC
August 2021

Effects of exercise on markers of inflammation and indicators of nutrition in patients with chronic kidney disease: a systematic review and meta-analysis.

Int Urol Nephrol 2021 Jul 13. Epub 2021 Jul 13.

Department of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shi-er-qiao Road, Chengdu, 610072, Sichuan Province, People's Republic of China.

Purpose: This meta-analysis aimed to reveal the effects of exercise training on markers of inflammation and indicators of nutrition in non-dialysis-dependent patients with chronic kidney disease (NDD-CKD).

Methods: We searched the MEDLINE, EMBASE, CENTRAL, Web of Science, CINAHL, CNKI, WANFANE, VIP, and CBM databases, from their inception up to October 2020 to identify randomized controlled trials that examined the effects of exercise training on inflammation and nutrition in NDD-CKD patients. A total of 16 trials, comprising 724 patients, were included in the analysis.

Results: The BMI (P = 0.005) and waist circumference (P = 0.004) decreased significantly after exercise training in NDD-CKD patients. Similarly, IL-6 (P = 0.03) decreased after exercise training in NDD-CKD patients. However, serum albumin level, body fat, CRP and hs-CRP were not different between patients who received exercise training and those who received usual care. Furthermore, BMI (P = 0.009), body weight (P = 0.009), and waist circumference (P = 0.010) were decreased in overweight patients (BMI ≧ 25 kg/m). Moreover, BMI (P = 0.003), body weight (P = 0.005), and waist circumference (P = 0.007) reduced when the length of intervention exceeded 48 weeks. Subgroup analyses revealed no significant alteration of serum albumin, body fat, CRP, or hs-CRP, when studies were divided based on BMI or intervention duration.

Conclusion: Overall, these findings suggest that exercise training may improve inflammation status in NDD-CKD patients, and enhance weight loss in obese adult CKD patients. Registration number: INPLASY2020100025.
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http://dx.doi.org/10.1007/s11255-021-02949-wDOI Listing
July 2021

Memristor Based on Inorganic and Organic Two-Dimensional Materials: Mechanisms, Performance, and Synaptic Applications.

ACS Appl Mater Interfaces 2021 Jul 12;13(28):32606-32623. Epub 2021 Jul 12.

Department of Applied Physics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong Kong China.

A memristor is a two-terminal device with nonvolatile resistive switching (RS) behaviors. Recently, memristors have been highly desirable for both fundamental research and technological applications because of their great potential in the development of high-density memory technology and neuromorphic computing. Benefiting from the unique two-dimensional (2D) layered structure and outstanding properties, 2D materials have proven to be good candidates for use in gate-tunable, highly reliable, heterojunction-compatible, and low-power memristive devices. More intriguing, stable and reliable nonvolatile RS behaviors can be achieved in multi- and even monolayer 2D materials, which seems unlikely to be achieved in traditional oxides with thicknesses less than a few nanometers because of the leakage currents. Moreover, such two-terminal devices show a series of synaptic functionalities, suggesting applications in simulating a biological synapse in the neural network. In this review article, we summarize the recent progress in memristors based on inorganic and organic 2D materials, from the material synthesis, device structure and fabrication, and physical mechanism to some versatile memristors based on diverse 2D materials with good RS properties and memristor-based synaptic applications. The development prospects and challenges at the current stage are then highlighted, which is expected to inspire further advancements and new insights into the fields of information storage and neuromorphic computing.
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http://dx.doi.org/10.1021/acsami.1c07665DOI Listing
July 2021

Effects of transjugular intrahepatic portosystemic shunt treatment of patients with liver cirrhosis and portal hypertension: Case series.

Medicine (Baltimore) 2021 Jul;100(27):e26610

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China.

Rationale: Transjugular intrahepatic portosystemic shunt (TIPS) is well established as an effective treatment tool for portal hypertension. However, the effects of TIPS in patients with liver cirrhosis and portal hypertension have not been adequately verified in clinical trials.

Patient Concerns: To evaluate the effects of TIPS in patients with liver cirrhosis and portal hypertension with or without portal vein thrombosis (PVT).

Interventions: A total of 55 patients with liver cirrhosis and portal hypertension received TIPS treatment from December 2014 to April 2018 were enrolled. Clinical data, including portal pressure, Child-Pugh score, and relevant complications were recorded.

Outcomes: TIPS was successfully performed in 54 patients. The overall technical success rate was 98.19% without serious technical complications. After TIPS treatment, portal pressure was significantly reduced from 38.13 ± 4.00 cmH2O to 24.14 ± 3.84 cmH2O (P < 0.05). In addition, symptoms including gastrointestinal bleeding and ascites were improved after TIPS treatment. During the 6 to 21-month follow up, hepatic encephalopathy in 15 patients (27.8%), shunt dysfunction in 5 patients (9.3%), rebleeding in 12 patients (22.2%) and deterioration of liver function in 2 patients (3.7%) were recorded. Moreover, there were no significant differences in the rates of rebleeding and hepatic encephalopathy between patients with PVT and the non-PVT group, whereas the occurrence rate of TIPS dysfunction was higher in the PVT group.

Lessons: TIPS treatment could alleviate the symptoms of liver cirrhosis and portal hypertension in individuals with or without PVT. However, complications during follow-up should be appropriately noted and addressed with corresponding treatments.
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http://dx.doi.org/10.1097/MD.0000000000026610DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270572PMC
July 2021

Different Expressions of HIF-1α and Metabolism in Brain and Major Visceral Organs of Acute Hypoxic Mice.

Int J Mol Sci 2021 Jun 23;22(13). Epub 2021 Jun 23.

Institute of Brain Diseases and Cognition, Medical College of Xiamen University, Xiamen 361102, China.

Hypoxia is associated with clinical diseases. Extreme hypoxia leads to multiple organs failure. However, the different effects of hypoxia on brain and visceral organs still need to be clarified, and moreover, characteristics in vulnerable organs suffering from hypoxia remain elusive. In the present study, we first aimed to figure out the hypoxic sensitivity of organs. Adult male mice were exposed to 6% O or 8% O for 6 h. Control mice were raised under normoxic conditions. In vivo and in vitro imaging of anti-HIF-1α-NMs-cy5.5 nanocomposites showed that the expression level of hypoxia-inducible factor (HIF-1α) was the highest in the liver, followed by kidney and brain. HIF-1α was detected in the hepatocytes of liver, distal convoluted tubules of kidney and neurons of cerebral cortex. The liver, kidney and brain showed distinct metabolic profiles but an identical change in glutamate. Compared with kidney and brain, the liver had more characteristic metabolites and more disturbed metabolic pathways related to glutaminolysis and glycolysis. The level of O-phosphocholine, GTP, NAD and aspartate were upregulated in hypoxic mice brain, which displayed significant positive correlations with the locomotor activity in control mice, but not in hypoxic mice with impaired locomotor activities. Taken together, the liver, kidney and brain are the three main organs of the body that are strongly respond to acute hypoxia, and the liver exhibited the highest hypoxic sensitivity. The metabolic disorders appear to underlie the physiological function changes.
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http://dx.doi.org/10.3390/ijms22136705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268807PMC
June 2021

Single-cell analyses reveal suppressive tumor microenvironment of human colorectal cancer.

Clin Transl Med 2021 06;11(6):e422

Affiliated Cancer Hospital and Institute of Guangzhou Medical University, State Key Laboratory of Respiratory Disease, Guangzhou, China.

Profiling heterologous cell types within tumors is essential to decipher tumor microenvironment that shapes tumor progress and determines the outcome of therapeutic response. Here, we comprehensively characterized transcriptomes of 34,037 single cells obtained from 12 treatment-naïve patients with colorectal cancer. Our comprehensive evaluation revealed attenuated B-cell antigen presentation, distinct regulatory T-cell clusters with different origin and novel polyfunctional tumor associated macrophages associated with CRC. Moreover, we identified expanded XCL1 T-cell clusters associated with tumor mutational burden high status. We further explored the underlying molecular mechanisms by profiling epigenetic landscape and inferring transcription factor motifs using single-cell ATAC-seq. Our dataset and analysis approaches herein provide a rich resource for further study of the impact of immune cells and translational research for human colorectal cancer.
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http://dx.doi.org/10.1002/ctm2.422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181206PMC
June 2021

Epilepsy Associated With Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes.

Front Neurol 2021 11;12:675816. Epub 2021 Jun 11.

Department of Neurology and Neuroscience Center, The First Hospital of Jilin University, Changchun, China.

The present study explored the clinical characteristics and prognostic factors of epilepsy in patients with mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS). Thirty-four MELAS patients were included in the present study. They were diagnosed by clinical characteristics, genetic testing, muscle biopsy, and retrospective analysis of other clinical data. The patients were divided into three groups according to the effects of treatment after at least 2 years of follow-up. Epilepsy was more common in male MELAS patients than in females (20/14). The age of onset ranged from 0.5 to 57 years, with an average of 22.6 years. Patients with epilepsy and MELAS had various forms of seizures. Focal seizures were the most common type affecting 58.82% of patients, and some patients had multiple types of seizures. The abnormal EEG waves were mainly concentrated in the occipital (69.57%), frontal (65.22%) and temporal lobes (47.83%). Overall, the prognosis of patients with epilepsy and MELAS was poor. Poor prognosis was associated with brain atrophy ( = 0.026), status epilepticus ( < 0.001), and use of anti-seizure medications with high mitochondrial toxicity ( = 0.015). Avoiding the application of anti-seizure medications with high mitochondrial toxicity, controlling seizures more actively and effectively, and delaying the occurrence and progression of brain atrophy as much as possible are particularly important to improve the prognosis of patients with MELAS and epilepsy.
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http://dx.doi.org/10.3389/fneur.2021.675816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226157PMC
June 2021

Nomogram to Predict Distant Metastasis Probability for Pathological Complete Response Rectal Cancer Patients After Neoadjuvant Chemoradiotherapy.

Cancer Manag Res 2021 15;13:4751-4761. Epub 2021 Jun 15.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China.

Purpose: This study aimed to predict the risks of distant metastasis (DM) of locally advanced rectal cancer (LARC) patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy (NACRT) and total mesorectal excision (TME), and to find the association between adjuvant chemotherapy (ACT) and their survival outcomes.

Methods And Materials: A total of 242 patients with LARC achieving pCR after NACRT were enrolled in this retrospective study. We developed a nomogram model using logistic regression analyses for predicting risk of DM. The model performance was evaluated by the concordance index and calibration curve. Survival was determined using Kaplan-Meier survival curve.

Results: Age, pre-operative CEA, pre-treatment CEA and distance of tumor to anal verge were identified as significantly associated variables that could be enrolled in the model to predict the risk of DM for pCR patients. The nomogram we created had a bootstrapped-concordance index of 0.731 (95% CI = 0.627 to 0.834) and was well calibrated. The high risk group was more likely to develop DM than low risk group (total score) (95% CI = 1.439 to 6.493, = 0.0036). The 1-year, 3-year, and 5-year distant metastasis-free survival (DMFS) for the low and high risk groups (total score ≤ 90 vs > 90) was 97.8%, 94.2%, 94.2% and 91.3%, 83.4%, 81.8%, respectively ( = 0.0036). DM occurred within 1 and 2 years after TME surgery was 33.3% and 55.6% for the low risk group, and 47.3% and 84.2% for the high risk group. The value of ACT was assessed among the whole cohort, patients with cT, with cN or with either DM risk group, but no significant difference was observed concerning DMFS whether ACT was given or not (all > 0.05). Active treatment after DM was more beneficial than palliative treatment ( < 0.001).

Conclusion: The nomogram model, including age, pre-operative CEA, pre-treatment CEA and distance to anal verge, predicted the probability of DM among LARC patients achieving pCR after NACRT. The effects of ACT were not seen in different subgroups, while closer clinical follow-up may have greater contribution to pCR patients in the first 2 years, especially for patients with relatively higher risk to develop DM. It is suggested that timely active treatment can bring survival benefit for pCR patients developing DM after NACRT.
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http://dx.doi.org/10.2147/CMAR.S313113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8214524PMC
June 2021

5-Aza-2-deoxycytidine alleviates the progression of primary biliary cholangitis by suppressing the FoxP3 methylation and promoting the Treg/Th17 balance.

Int Immunopharmacol 2021 Jul 2;96:107820. Epub 2021 Jun 2.

Digestive Diseases Department, The Second Affiliated Hospital of Kunming Medical University, Kunming, China. Electronic address:

Primary biliary cholangitis (PBC) is a common autoimmune liver disease manifested by the infiltration of CD4 T cells, and the subsequent targeted injury of biliary epithelial cells (BECs). As important components of CD4 subsets, the Treg/Th17 axis maintains an immunological balance between self-tolerance and inflammation in the liver microenvironment. However, the role and regulatory mechanism of the Treg/Th17 axis in PBC remain unclear. In this study, we examined the Treg/Th17 axis in PBC patients and found that the Treg/Th17 axis was imbalanced in PBC at both the transcriptional and cellular levels, with Treg being a weak candidate, which correlates with the PBC progression. This imbalanced Treg/Th17 axis was likely to be affected by the FoxP3 hypermethylation, which was related to the increase of DNA methyltransferase. Furthermore, the effect of 5-Aza-2-deoxycytidine (DAC)-mediated FoxP3 demethylation on PBC mice was investigated. We verified that DAC significantly suppressed the FoxP3 methylation and rebuilt the Treg/Th17 balance, resulting in the alleviation of liver lesions and inflammation. Taken together, our data indicate that DAC plays a positive role in alleviating the progression of PBC through the inhibition of DNA methylation of FoxP3 to rebuild the balanced Treg/Th17 axis. DAC could be considered as a potential candidate for the development of new anti-inflammation strategies in the treatment of PBC.
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http://dx.doi.org/10.1016/j.intimp.2021.107820DOI Listing
July 2021

Genome-wide analysis and functional characterization of the DELLA gene family associated with stress tolerance in B. napus.

BMC Plant Biol 2021 Jun 22;21(1):286. Epub 2021 Jun 22.

Institute of Life Sciences, Jiangsu University, Zhenjiang, China.

Background: Brassica napus is an essential crop for oil and livestock feed. Eventually, this crop's economic interest is at the most risk due to anthropogenic climate change. DELLA proteins constitute a significant repressor of plant growth to facilitate survival under constant stress conditions. DELLA proteins lack DNA binding domain but can interact with various transcription factors or transcription regulators of different hormonal families. Significant progress has been made on Arabidopsis and cereal plants. However, no comprehensive study regarding DELLA proteins has been delineated in rapeseed.

Results: In our study, we have identified 10 BnaDELLA genes. All of the BnaDELLA genes are closely related to five AtDELLA genes, suggesting a relative function and structure. Gene duplication and synteny relationship among Brassica. napus, Arabidopsis. thaliana, Brassica rapa, Brassica oleracea, and Brassica nigra genomes were also predicted to provide valuable insights into the BnaDELLA gene family evolutionary characteristics. Chromosomal mapping revealed the uneven distribution of BnaDELLA genes on eight chromosomes, and site-specific selection assessment proposes BnaDELLA genes purifying selection. The motifs composition in all BnaDELLA genes is inconsistent; however, every BnaDELLA gene contains 12 highly conserved motifs, encoding DELLA and GRAS domains. The two known miRNAs (bna-miR6029 and bna-miR603) targets BnaC07RGA and BnaA09GAI, were also predicted. Furthermore, quantitative real-time PCR (qRT-PCR) analysis has exhibited the BnaDELLA genes diverse expression patterns in the root, mature-silique, leaf, flower, flower-bud, stem, shoot-apex, and seed. Additionally, cis-acting element prediction shows that all BnaDELLA genes contain light, stress, and hormone-responsive elements on their promoters. The gene ontology (GO) enrichment report indicated that the BnaDELLA gene family might regulate stress responses. Combine with transcriptomic data used in this study, we detected the distinct expression patterns of BnaDELLA genes under biotic and abiotic stresses.

Conclusion: In this study, we investigate evolution feature, genomic structure, miRNAs targets, and expression pattern of the BnaDELLA gene family in B. napus, which enrich our understanding of BnaDELLA genes in B. napus and suggests modulating individual BnaDELLA expression is a promising way to intensify rapeseed stress tolerance and harvest index.
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http://dx.doi.org/10.1186/s12870-021-03054-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220683PMC
June 2021

Evaluation of candidate reference genes for gene expression analysis in the brassica leaf beetle, Phaedon brassicae (Coleoptera: Chrysomelidae).

PLoS One 2021 3;16(6):e0251920. Epub 2021 Jun 3.

Institute of Entomology, Jiangxi Agricultural University, Nanchang, China.

The brassica leaf beetle Phaedon brassicae is a notorious defoliator of cruciferous vegetables. However, few molecular studies of this pest have been conducted due to limited sequence data. Recently, RNA sequencing has offered a powerful platform to generate numerous transcriptomic data, which require RT-qPCR to validate target gene expression. The selection of reliable reference genes to normalize RT-qPCR data is a prerequisite for gene expression analysis. In the present study, the expression stabilities of eight candidate reference genes under biotic conditions (development stages and various tissues) and abiotic perturbations (thermal stress and pesticide exposure) were evaluated using four different statistical algorithms. The optimal suites of reference genes were recommended for the respective experimental conditions. For tissue expression analysis, RPL32 and EF-1α were recommended as the suitable reference genes. RPL19 and TBP were the optimal reference genes across different developmental stages. RPL32 and TBP were identified as the most suitable references for thermal stress. Furthermore, RPL32 and RPL19 were ranked as the best references for insecticide exposure. This work provides a systematic exploration of the optimal reference genes for the respective experimental conditions, and our findings would facilitate molecular studies of P. brassicae.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0251920PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174695PMC
June 2021

Prevalence of ultrasound-detected knee synovial abnormalities in a middle-aged and older general population-the Xiangya Osteoarthritis Study.

Arthritis Res Ther 2021 06 2;23(1):156. Epub 2021 Jun 2.

Department of Orthopaedics, Xiangya Hospital, Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, China.

Background: There is paucity of data on the prevalence of ultrasound-detected synovial abnormalities in the general population, and the relationship between synovial changes and knee pain remains unclear. We examined the prevalence of synovial abnormalities on ultrasound and the relationship of these features with knee pain and radiographic osteoarthritis (ROA) in a community sample.

Methods: Participants aged 50 years or over were from the Xiangya Osteoarthritis Study, a community-based cohort study. Participants were questioned about chronic knee pain and underwent (1) ultrasonography of both knees to determine presence of synovial hypertrophy (≥ 4 mm), effusion (≥ 4 mm), and Power Doppler signal [PDS; yes/no]; and (2) standard radiographs of both knees (tibiofemoral and patellofemoral views) to determine ROA.

Results: There were 3755 participants (mean age 64.4 years; women 57.4%). The prevalence of synovial hypertrophy, effusion, and PDS were 18.1% (men 20.2%; women 16.5%), 46.6% (men 49.9%; women 44.2%), and 4.9% (men 4.9%; women 5.0%), respectively, and increased with age (P for trend < 0.05). Synovial abnormalities were associated with knee pain, with adjusted odds ratios (aORs) of 2.39 (95% confidence interval [CI] 2.00-2.86) for synovial hypertrophy, 1.58 (95%CI 1.39-1.80) for effusion, and 4.36 (95%CI 3.09-6.17) for PDS. Similar associations with ROA were observed, the corresponding aORs being 4.03 (95%CI 3.38-4.82), 2.01 (95%CI 1.76-2.29), and 6.49 (95%CI 4.51-9.35), respectively. The associations between synovial hypertrophy and effusion with knee pain were more pronounced among knees with ROA than those without ROA, and the corresponding P for interaction were 0.004 and 0.067, respectively.

Conclusions: Knee synovial hypertrophy and effusion are more common and increase with age, affecting men more than women. All three ultrasound-detected synovial abnormalities associate both with knee pain and ROA, and knee synovial hypertrophy or effusion and ROA may interact to increase the risk of knee pain.
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http://dx.doi.org/10.1186/s13075-021-02539-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8170794PMC
June 2021

Effect of antifoaming agent on benign colorectal tumors in colonoscopy: A meta-analysis.

World J Clin Cases 2021 May;9(15):3607-3622

Department of Gastroenterology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, Hubei Province, China.

Background: Although several trials have shown that the addition of antifoaming agents to polyethylene glycol (PEG) can improve bowel preparation, whether PEG plus antifoaming agents have a beneficial role in the detection of benign tumors during colonoscopy has yet to be confirmed. Our aim was to clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors.

Aim: To clarify whether adding simethicone to PEG solution could improve the detection of benign colorectal tumors.

Methods: The PubMed, EMBASE, and Cochrane Library databases were searched for articles published prior to September 2019. The outcomes included the detection rates of colorectal adenomas and polyps.

Result: Twenty studies were eligible. Although there was no difference in the colorectal adenoma detection rate (ADR), a significant effect of simethicone for diminutive adenomas (< 10 mm) was revealed in the group taking simethicone. We also found that simethicone could significantly improve the ADR in the proximal colon but did not affect the colorectal polyp detection rate. Furthermore, the subgroup analyses revealed a beneficial effect of simethicone on the ADR among Asians ( = 0.005) and those with an ADR < 25% ( = 0.003). Moreover, it was a significant finding that the low dose simethicone was as effective as the high dose one with respect to the detection of benign colorectal tumors.

Conclusion: In summary, the addition of simethicone to PEG might improve the detection of diminutive adenomas in the right colon by colonoscopy in Asia. Low-dose simethicone was recommended for the detection of benign colorectal tumors. However, large clinical trials are necessary to validate our results and determine the ideal dose of simethicone.
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http://dx.doi.org/10.12998/wjcc.v9.i15.3607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130091PMC
May 2021

The current understanding on the impact of KRAS on colorectal cancer.

Biomed Pharmacother 2021 Aug 24;140:111717. Epub 2021 May 24.

Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, International Institute for Translational Chinese Medicine, School of Pharmaceutical Science, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, China. Electronic address:

KRAS (kirsten rat sarcoma viral oncogene) is a member of the RAS family. KRAS mutations are one of most dominant mutations in colorectal cancer (CRC). The impact of KRAS mutations on the prognosis and survival of CRC patients drives many research studies to explore potential therapeutics or target therapy for the KRAS mutant CRC. This review summarizes the current understanding of the pathological consequences of the KRAS mutations in the development of CRC; and the impact of the mutations on the response and the sensitivity to the current front-line chemotherapy. The current therapeutic strategies for treating KRAS mutant CRC, the difficulties and challenges will also be discussed.
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http://dx.doi.org/10.1016/j.biopha.2021.111717DOI Listing
August 2021

Application of digital prosthodontics and connective tissue grafting in the management of peri-implant mucosal recession around a malpositioned 1-piece implant: A clinical report.

J Prosthet Dent 2021 May 21. Epub 2021 May 21.

Professor, Department of Prosthodontics, Peking University School and Hospital of Stomatology & National Center of Stomatology & National Clinical Research Center for Oral Disease & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatlogy & Research Center of Engineering and Technology for Computerized Dentistry Ministry of Health & NMPA Key Laboratory for Dental Materals, Beijing, PR China.

This clinical report describes a conservative approach to improve an unesthetic implant-supported crown and peri-implant mucosal recession around a malpositioned, 1-piece implant in the maxillary right central incisor region by using digital technology. In such clinical situations, the implants are usually removed because of an unpredictable definitive esthetic outcome. However, this clinical report describes the preservation of such a compromised implant by improving the esthetic outcome with a connective-tissue graft, and a digital approach used a 1-step preformed zirconia coping technique with an appropriate emergence profile.
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http://dx.doi.org/10.1016/j.prosdent.2021.03.013DOI Listing
May 2021

Total Neoadjuvant Therapy (TNT) versus Standard Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer: A Systematic Review and Meta-Analysis.

Oncologist 2021 Sep 7;26(9):e1555-e1566. Epub 2021 Jun 7.

Departments of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.

Background: Total neoadjuvant therapy (TNT) is a novel approach for locally advanced rectal cancer (LARC), which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery. However, its efficacy and safety remain controversial in randomized controlled trials (RCTs). We conducted this meta-analysis to assess such concerns.

Materials And Methods: Head-to-head phase II/III RCTs were searched in Embase, PubMed, Web of Science, and the Cochrane Library, as well as other sources. The primary endpoint was pathologic complete response (pCR). Secondary endpoints were disease-free survival (DFS), overall survival (OS), local recurrence-free survival, distant metastasis-free survival, and the R0 resection rate.

Results: Eight phase II/III RCTs involving 2,196 patients with LARC were assessed. The primary analysis demonstrated a statistically significant improvement in the pCR rate for TNT treatment (odds ratio, 1.77; 95% confidence interval [CI], 1.28-2.45; p = .0005). TNT treatment also showed improvements in DFS and OS outcomes compared with standard chemoradiotherapy (hazard ratio [HR], 0.83; 95% CI, 0.72-0.96; p = .03 and HR, 0.88; 95% CI, 0.74-1.05; p = .15). In addition, TNT treatment showed significant efficacy in reducing the risk of distant metastasis (HR, 0.81; 95% CI, 0.68-0.95; p = .012).

Conclusion: The overall pCR rate may be improved with TNT compared with standard treatment. The TNT strategy may also improve DFS and OS and reduce the risk of distant metastasis.

Implications For Practice: Locally advanced rectal cancer (LARC) is a relatively common disease, with a poor prognosis because of its high metastatic potential. The role of total neoadjuvant therapy (TNT) has always been controversial. This meta-analysis found that TNT in LARC is associated with a significant improvement in overall pathologic complete response rate, disease-free survival, overall survival, and distant metastasis-free survival compared with standard treatment. TNT is a promising strategy for LARC, especially for patients who have little desire for surgery.
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http://dx.doi.org/10.1002/onco.13824DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417863PMC
September 2021

BPV associated with imaging features of SSI on MRI.

Brain Behav 2021 06 7;11(6):e02155. Epub 2021 May 7.

Department of Neurology, Weihai Central Hospital Affiliated to Qingdao University, Weihai, China.

Objectives: A retrospective study was performed to investigate the relationship between blood pressure variability (BPV) and imaging features of single small infarction (SSI) on magnetic resonance imaging (MRI).

Materials And Methods: Two hundreds and five patients with SSI and 120 healthy subjects matched with age and sex as the control group were enrolled into this study. All subjects came from the Affiliated Hospital to Qingdao University and Qingdao Municipal Hospital from October 2011 to June 2016. Research subjects were classified into different groups. Blood pressure was measured once a day and recorded during the hospitalization period (7-10 days). The followed up data of patients after discharging from hospital was collected from the follow-up records.

Results: Twenty-four hours BPV (SBP , DSBP , DSBP , NDBP , NDBP and DDBP ), day-to-day, and visit-to-visit BPV (SBP , SBP , DBP and DBP ) in the SSI group were significantly higher than that in control group. Compared with the giant lacunar group, day-to-day BPV (SBP , SBP , SBP , SBP , DBP , DBP , DBP ), and visit-to-visit BPV (SBP , SBP , SBP , DBP , DBP , DBP ) were significantly higher in the small lacunar infarct group (p < .05). The 24 hr BPV (SBP , DDBP , DDBP ), day-to-day BPV (SBP , SBP , SBP ), and visit-to-visit SBP in nonround lesion group were significantly higher than that in round group (p < .05). Compared with nondeep lesion group, some parameters in day-to-day BPV and visit-to-visit BPV were significantly higher in the deep small lesion group (p < .05).

Conclusion: Increased BPV parameters such as day-to-day and visit-to-visit (SBP , SBP , DBP ) were related to the SSI characterized by small lesion in deep brain region.
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http://dx.doi.org/10.1002/brb3.2155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213932PMC
June 2021

Wi-Fi-Based Location-Independent Human Activity Recognition via Meta Learning.

Sensors (Basel) 2021 Apr 9;21(8). Epub 2021 Apr 9.

School of Information and Communication Engineering, Beijing University of Posts and Telecommunications, Beijing 100876, China.

Wi-Fi-based device-free human activity recognition has recently become a vital underpinning for various emerging applications, ranging from the Internet of Things (IoT) to Human-Computer Interaction (HCI). Although this technology has been successfully demonstrated for location-dependent sensing, it relies on sufficient data samples for large-scale sensing, which is enormously labor-intensive and time-consuming. However, in real-world applications, location-independent sensing is crucial and indispensable. Therefore, how to alleviate adverse effects on recognition accuracy caused by location variations with the limited dataset is still an open question. To address this concern, we present a location-independent human activity recognition system based on Wi-Fi named WiLiMetaSensing. Specifically, we first leverage a Convolutional Neural Network and Long Short-Term Memory (CNN-LSTM) feature representation method to focus on location-independent characteristics. Then, in order to well transfer the model across different positions with limited data samples, a metric learning-based activity recognition method is proposed. Consequently, not only the generalization ability but also the transferable capability of the model would be significantly promoted. To fully validate the feasibility of the presented approach, extensive experiments have been conducted in an office with 24 testing locations. The evaluation results demonstrate that our method can achieve more than 90% in location-independent human activity recognition accuracy. More importantly, it can adapt well to the data samples with a small number of subcarriers and a low sampling rate.
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http://dx.doi.org/10.3390/s21082654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069986PMC
April 2021

Caveolae-Mediated Endocytosis Drives Robust siRNA Delivery of Polymeric Nanoparticles to Macrophages.

ACS Nano 2021 05 29;15(5):8267-8282. Epub 2021 Apr 29.

State Key Laboratory of Genetic Engineering, Department of Pharmaceutical Sciences, School of Life Sciences, Fudan University, Shanghai 200438, P.R. China.

Cytosolic delivery of small interfering RNA (siRNA) remains challenging, and a profound understanding of the cellular uptake and intracellular processing of siRNA delivery systems could greatly improve the development of siRNA-based therapeutics. Here, we show that caveolae-mediated endocytosis (CvME) accounts for the robust siRNA delivery of mannose-modified trimethyl chitosan-cysteine/tripolyphosphate nanoparticles (MTC/TPP NPs) to macrophages by circumventing lysosomes. We show that the Golgi complex and ER are key organelles required for the efficient delivery of siRNA to macrophages in which the siRNA accumulation positively correlates with its silencing efficiency ( = 0.94). We also identify syntaxin6 and Niemann-Pick type C1 (NPC1) as indispensable regulators for MTC/TPP NPs-delivered siRNA into macrophages both and . Syntaxin6 and NPC1 knockout substantially decrease the cellular uptake and gene silencing of the siRNA delivered in MTC/TPP NPs in macrophages, which result in poor therapeutic outcomes for mice bearing acute hepatic injury. Our results suggest that highly efficient siRNA delivery can be achieved CvME, which would give ideas for designing optimal delivery vectors to facilitate the clinical translation of siRNA drugs.
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http://dx.doi.org/10.1021/acsnano.0c08596DOI Listing
May 2021

The chromatin remodeling complex imitation of switch controls stamen filament elongation by promoting jasmonic acid biosynthesis in Arabidopsis.

J Genet Genomics 2021 02 4;48(2):123-133. Epub 2021 Mar 4.

State Key Laboratory of Genetic Engineering, Ministry of Education Key Laboratory of Biodiversity Sciences and Ecological Engineering, Institute of Plant Biology, School of Life Sciences, Fudan University, Shanghai 200438, China. Electronic address:

Plant reproduction requires the coordinated development of both male and female reproductive organs. Jasmonic acid (JA) plays an essential role in stamen filament elongation. However, the mechanism by which the JA biosynthesis genes are regulated to promote stamen elongation remains unclear. Here, we show that the chromatin remodeling complex Imitation of Switch (ISWI) promotes stamen filament elongation by regulating JA biosynthesis. We show that AT-Rich Interacting Domain 5 (ARID5) interacts with CHR11, CHR17, and RLT1, several known subunits of ISWI. Mutations in ARID5 and RLTs caused a reduced seed set due to greatly shortened stamen filaments. RNA-seq analyses reveal that the expression of key genes responsible for JA biosynthesis is significantly down-regulated in the arid5 and rlt mutants. Consistently, the JA levels are drastically decreased in both arid5 and rlt mutants. Chromatin immunoprecipitation-quantitative PCR analyses further show that ARID5 is recruited to the chromatin of JA biosynthesis genes. Importantly, exogenous JA treatments can fully rescue the defects of stamen filament elongation in both arid5 and rlt mutants, leading to the partial recovery of fertility. Our results provide a clue how JA biosynthesisis positively regulated by the chromatin remodeling complex ISWI, thereby promoting stamen filament elongation in Arabidopsis.
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http://dx.doi.org/10.1016/j.jgg.2021.02.003DOI Listing
February 2021

Physical exercise modulates the astrocytes polarization, promotes myelin debris clearance and remyelination in chronic cerebral hypoperfusion rats.

Life Sci 2021 Aug 21;278:119526. Epub 2021 Apr 21.

Department of Rehabilitation Medicine, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, China. Electronic address:

Aims: White matter damage is the main pathological feature of chronic cerebral hypoperfusion (CCH) and glial activation is crucial in this process. Physical exercise has protective effects on CCH, but the mechanism is unclear. Therefore, this study focuses on investigating the influence of physical exercise on activated astrocytes polarization and its role in CCH.

Main Methods: Rats were given wheel running 48 h after 2VO (2 vessel occlusion) surgery. The cognitive function was evaluated by Morris water maze and novel object recognition test. Inflammatory cytokines expressions were detected by ELISA. Astrocytes polarization was analyzed by immunofluorescence. Myelin debris clearance and remyelination were detected by immunofluorescence and transmission electron microscopy.

Key Findings: Astrocytes were activated and mainly switched to A1 phenotype in rats 2 and 3 months after 2VO. Myelin debris deposition and limited remyelination can be observed at the corresponding time. Whereas physical exercise can improve the cognitive function of 2VO rats, downregulate the expression of inflammatory factors IL-1α, C1q and TNF, upregulate the release of TGFβ, and promote activated astrocytes transformation from A1 to A2 phenotype. In addition, it can also enhance myelin debris removal and remyelination.

Significance: These findings suggest that the benefits of physical exercise on white matter repair and cognition improvement may be related to its regulation of astrocytes polarization, which contributes to myelin debris clearance and effective remyelination in CCH.
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http://dx.doi.org/10.1016/j.lfs.2021.119526DOI Listing
August 2021
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