Publications by authors named "Jianmin Zhang"

455 Publications

Competitive activation cross amplification combined with smartphone-based quantification for point-of-care detection of single nucleotide polymorphism.

Biosens Bioelectron 2021 Mar 26;183:113200. Epub 2021 Mar 26.

National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Key Laboratory of Zoonoses, Ministry of Agriculture, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangdong Laboratory for Lingnan Modern Agriculture, College of Veterinary Medicine, South China Agricultural University, Guangzhou, 510642, China. Electronic address:

In this study, we firstly propose a novel smartphone-assisted visualization SNP genotyping method termed competitive activation cross amplification (CACA). The mutation detection strategy depends on the ingenious design of both a start primer and a verification probe with ribonucleotide insertion through competitive combination and perfect matching with the target DNA, Meanwhile, the RNase H2 enzyme was utilized to specifically cleave ribonucleotide insertion and achieve extremely specific dual verification. Simultaneously, the results allow both colorimetric and fluorescence product dual-mode visualization by using self-designed 3D-printed dual function cassette. We validated this novel CACA by analyzing the Salmonella Pullorum rfbS gene at the 237th site, successfully solve the current bottleneck of specific identification and visual detection of this pathogen. The concentration detection limits of the plasmid and genomic DNA were 1500 copies/μL and 3.98 pg/μL, respectively, and as low as the presence of 0.1% mutant-type can be distinguished from 99.9% wild-type. Combined with a powerful hand-warmer, which can provide heating more than 60 °C for 20 h to realize power-free, dual function cassette and smartphone quantitation, our novel CACA platform firstly realizes user-friendly, cost-effective, portable, rapid, and accurate POC detection of SNP.
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http://dx.doi.org/10.1016/j.bios.2021.113200DOI Listing
March 2021

Immune Checkpoint-Associated Locations of Diffuse Gliomas Comparing Pediatric With Adult Patients Based on Voxel-Wise Analysis.

Front Immunol 2021 17;12:582594. Epub 2021 Mar 17.

Department of Neurosurgery, School of Medicine, The Second Affiliated Hospital of Zhejiang University, Hangzhou, China.

Pediatric diffuse gliomas (pDGs) are relatively rare and molecularly distinct from pediatric pilocytic astrocytoma and adult DGs. Immunotherapy is a promising therapeutic strategy, requiring a deep understanding of tumor immune profiles. The spatial locations of brain tumors might be related to the molecular profiles. We aimed to analyze the relationship between the immune checkpoint molecules with the locations of DGs comparing pediatric with adult patients. We studied 20 pDGs patients (age ≤ 21 years old), and 20 paired adult patients according to gender and histological types selected from 641 adult patients with DGs. Immune checkpoint molecules including B7-H3, CD47, and PD-L1, as well as tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs), were manifested by immunohistochemical staining. Expression difference analyses and Spearman's correlation were performed. MRI data were voxel-wise normalized, segmented, and analyzed by Fisher's exact test to construct the tumor frequency and p value heatmaps. Survival analyses were conducted by Log-rank tests. The median age of pediatric patients was 16 years. 55% and 30% of patients were WHO II and III grades, respectively. The left frontal lobe and right cerebellum were the statistically significant locations for pDGs, while the anterior horn of ventricles for adult DGs. A potential association between the expression of PD-L1 and TAMs was found in pDGs (p = 0.002, R = 0.670). The right posterior external capsule and the lateral side of the anterior horn of the left ventricle were predominant locations for the adult patients with high expression of B7-H3 and low expression of PD-L1 compared to pediatric ones, respectively. Pediatric patients showed significantly improved overall survival compared with adults. The prognostic roles of immune checkpoint molecules and TILs/TAMs were not significantly different between the two groups. Immune checkpoint-associated locations of diffuse gliomas comparing pediatric with adult patients could be helpful for the immunotherapy decisions and design of clinical trials.
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http://dx.doi.org/10.3389/fimmu.2021.582594DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010651PMC
March 2021

Prone positioning in intubated and mechanically ventilated patients with SARS-CoV-2.

J Clin Anesth 2021 Mar 29;71:110258. Epub 2021 Mar 29.

Department of Neurosurgery, Southwest Hospital, Third Military Medical University (Army Military Medical University), Chongqing, China; Department of Electrical and Computer Engineering, Faculty of Science and Technology, University of Macau, Macau, China. Electronic address:

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http://dx.doi.org/10.1016/j.jclinane.2021.110258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8006210PMC
March 2021

Enhancing the Stability of Polymer Nanostructures via Ultrathin Oxides Coating for Nanooptics Device Applications.

Nanotechnology 2021 Mar 29. Epub 2021 Mar 29.

School of Physics and Electronics, Hunan University, Changsha, CHINA.

Polymer nanostructures have drawn tremendous attention due to their wide applications in nanotechnology. However, the morphology of the polymer nanostructures is fragile under harsh conditions such as high-power irradiation and organic-solution environment during the fabrication or the measurement processes, significantly limiting their potential applications. In this work, we propose and demonstrate a simple approach to improve the stability of polymer nanostructures by coating a conformal ultrathin oxide film via atomic-layer deposition (ALD). Due to the refractory and dense coating of oxides layer, the stability of polymer structures is enhanced by the prohibition of deformations occurrence from thermal-induced reflow and organic solution. As a proof of concept, PMMA nanostructures coated with sub-10-nm TiO2 layers are demonstrated, and the structures exhibit high-temperature stability at 60℃ and the good resistance of soluble damage from organic solutions. Subsequently, the mechanism of the improved thermal stability is analyzed via mechanical simulations. Such an effective approach is supposed to significantly broaden the application of polymer nanostructures as functional elements for optical structures/devices which require excellent thermal and chemical stability.
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http://dx.doi.org/10.1088/1361-6528/abf300DOI Listing
March 2021

Melatonin Ameliorates Hemorrhagic Transformation via Suppression of ROS-Induced NLRP3 Activation after Cerebral Ischemia in Hyperglycemic Rats.

Oxid Med Cell Longev 2021 11;2021:6659282. Epub 2021 Mar 11.

Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.

Melatonin is a strong antioxidant which beneficially protects against middle cerebral artery occlusion (MCAO) followed by hemorrhagic transformation in rats; protection includes the reduction of neurological deficits, infarction, and hematoma volume. The molecular mechanisms underlying these neuroprotective effects in the MCAO model have not been clearly identified. This study examined the influence and involved mechanism of melatonin on inflammation in hemorrhagic transformation following hyperglycemia MCAO rat model. Compared with the MCAO group, MCAO+dextrose (DX) group showed worse neurological function and higher infarction and hematoma volume. Interestingly, the protein expression of Nod-like receptor protein 3 (NLRP3) inflammasome increased in the MCAO+DX group compared with the MCAO group, which indicated that NLRP3 inflammasome may be involved in the DX-induced hemorrhagic transformation following MCAO. Then, three dosages of melatonin were intraperitoneally injected 2 h after MCAO induction. Melatonin treatment attenuated inflammatory response by inhibiting the reactive oxygen species (ROS) and NLRP3 inflammasome, alleviating neuronal injury, and reducing infarction and hematoma volume, finally improving neurological score. Melatonin also repressed cortical levels of proinflammatory cytokine IL-1, which were increased 24 h after hyperglycemia MCAO. In order to identify the potential mechanisms, we further revealed that nigericin administration reversed the neuroprotective effect of melatonin by promoting NLRP3 inflammasome activation. In general, this present study reveals that melatonin prevents the occurrence of hyperglycemia-enhanced hemorrhagic transformation, and this effect might be beneficial to attenuate neurological dysfunction via suppressing the inflammatory response after MCAO which possibly associated with the inhibition of the ROS/NLRP3 inflammasome pathway.
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http://dx.doi.org/10.1155/2021/6659282DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972845PMC
March 2021

Discovery of LAMP-2A as potential biomarkers for glioblastoma development by modulating apoptosis through N-CoR degradation.

Cell Commun Signal 2021 Mar 24;19(1):40. Epub 2021 Mar 24.

Department of Neurosurgery, 2Nd Affiliated Hospital, School of Medicine, Zhejiang University, 88# Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Background: Lysosome-associated membrane protein type 2A (LAMP-2A) is the key component of chaperone-mediated autophagy (CMA), a cargo-selective lysosomal degradation pathway. Aberrant LAMP-2A expression and CMA activation have been demonstrated in various human malignancies. The study focusing on the intrinsic role of LAMP-2A and CMA in glioblastoma (GBM), and downstream mechanism could provide valuable insight into the pathogenesis and novel therapeutic modality of GBM.

Methods: The levels of LAMP-2A, nuclear receptor co-repressor (N-CoR), unfolded protein response (UPR) and apoptosis were examined in clinical samples. LAMP-2A siRNA and shRNA were constructed to manipulate CMA activation. The role of CMA and downstream mechanism through degradation of N-CoR and arresting UPR mediated apoptosis were explored in GBM cells and nude mouse xenograft model.

Results: Elevated LAMP-2A and associated decreased N-CoR expression were observed in GBM as compared with peritumoral region and low-grade glioma. Inhibited UPR and apoptosis were observed in GBM with high LAMP-2A expression. In vitro study demonstrated co-localization and interaction between LAMP-2A and N-CoR. LAMP-2A silencing up-regulated N-CoR and aroused UPR pathway, leading to apoptosis, while N-CoR silencing led to an opposite result. In vivo study further confirmed that LAMP-2A inhibition arrested tumor growth by promoting apoptosis.

Conclusions: Our results demonstrated the central role of CMA in mediating N-CoR degradation and protecting GBM cells against UPR and apoptosis, and provided evidence of LAMP-2A as potential biomarker. Further research focusing on CMA with other tumorigenic process is needed and selective modulators of LAMP-2A remain to be investigated to provide a novel therapeutic strategy for GBM. Video Abstract.
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http://dx.doi.org/10.1186/s12964-021-00729-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7992845PMC
March 2021

Modulation of untranslated region alternative polyadenylation in glioma tumorigenesis.

Biomed Pharmacother 2021 May 24;137:111416. Epub 2021 Feb 24.

Department of Neurosurgery, Second Affiliated Hospital, School of medicine, Zhejiang University, Hangzhou, 310000, China. Electronic address:

RNA modification is an important form of regulation in cancer biology, that is capable of affecting cell proliferation, migration, other genetic characteristics of tumors, and protein expression. Recent research has shown that dysregulation of RNA modification plays an important role in glioma pathogenesis. A key form of RNA post-transcriptional modification, alternative polyadenylation (APA), may represent a mechanism by which genes escape miRNA-mediated inhibition of cancer. Global shortening of 3' untranslated region (3'-UTR)-mediated APA events have become a potential novel marker of cancer progression. Current treatments in which a single gene or pathway is targeted do not have significant therapeutic benefits for glioma patients, while strategies that are less targeted, in which inhibitors of major regulatory hubs such as APA regulators are utilized, may have superior therapeutic effects. However, the precise mechanisms by which untranslated region-alternative polyadenylation (UTR-APA) regulates glioma are poorly understood. In the present review, we will discuss the important roles of UTR-APA in glioma. In addition to the role of APA in the progression of glioma, we will also explore potential treatment options that target these processes to improve the prognosis of glioma patients.
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http://dx.doi.org/10.1016/j.biopha.2021.111416DOI Listing
May 2021

Construction of competitive endogenous RNA network reveals regulatory role of long non-coding RNAs in intracranial aneurysm.

BMC Neurosci 2021 Mar 9;22(1):15. Epub 2021 Mar 9.

Department of Neurosurgery, School of Medicine, Second Affiliated Hospital, Zhejiang University, NO.88 Jiefang Rd, Hangzhou, 310009, Zhejiang, China.

Background: Rupture of intracranial aneurysm (IA) is the main cause of devastating subarachnoid hemorrhage, which urges our understanding of the pathogenesis and regulatory mechanisms of IA. However, the regulatory roles of long non-coding RNAs (lncRNAs) in IA is less known.

Results: We processed the raw SRR files of 12 superficial temporal artery (STA) samples and 6 IA samples to count files. Then the differentially expressed (DE) mRNAs, miRNAs, and lncRNAs between STAs and IAs were identified. The enrichment analyses were performed using DEmRNAs. Next, a lncRNA-miRNA-mRNA regulatory network was constructed using integrated bioinformatics analysis. In summary, 341 DElncRNAs, 234 DEmiRNAs, and 2914 DEmRNAs between the STA and IA. The lncRNA-miRNA-mRNA regulatory network of IA contains 91 nodes and 146 edges. The subnetwork of hub lncRNA PVT1 was extracted. The expression level of PVT1 was positively correlated with a majority of the mRNAs in its subnetwork. Moreover, we found that several mRNAs (CCND1, HIF1A, E2F1, CDKN1A, VEGFA, COL1A1 and COL5A2) in the PVT1 subnetwork served as essential components in the PI3K-Akt signaling pathway, and that some of the non-coding RNAs (ncRNAs) (PVT1, HOTAIR, hsa-miR-17, hsa-miR-142, hsa-miR-383 and hsa-miR-193b) interacted with these mRNAs.

Conclusion: Our annotations noting ncRNA's role in the pathway may uncover novel regulatory mechanisms of ncRNAs and mRNAs in IA. These findings provide significant insights into the lncRNA regulatory network in IA.
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http://dx.doi.org/10.1186/s12868-021-00622-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945298PMC
March 2021

Characterization of the microbial communities in wheat tissues and rhizosphere soil caused by dwarf bunt of wheat.

Sci Rep 2021 Mar 11;11(1):5773. Epub 2021 Mar 11.

State Key Laboratory for Biology of Plant Disease and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing, China.

Dwarf bunt of wheat, which is caused by Tilletia controversa J.G. Kühn, is a soil-borne disease which may lead up to an 80% loss of yield together with degradation of the quality of the wheat flour by production of a fishy smell. In this study, high-throughput sequencing technology was employed to characterize the microbial composition of wheat tissues (roots, spikes, first stem under the ear, and stem base) and rhizosphere soil of wheat varieties that are resistant and susceptible to T. controversa. We observed that the soil fungal community abundance and diversity were higher in resistant varieties than in susceptible varieties in both inoculated and uninoculated wheat, and the abundances of Sordariomycetes and Mortierellomycetes increased in the resistant varieties infected with T. controversa, while the abundances of Dothideomycetes and Bacteroidia increased in the susceptible varieties. Regarding the bacteria present in wheat tissues, the abundances of Chloroflexi, Bacteroidetes, Gemmatimonadetes, Verrucomicrobia and Acidobacteria in the ear and the first stem under the ear were higher than those in other tissues. Our results indicated that the abundances of Sordariomycetes, Mortierellomycetes, Leotiomycetes, Chryseobacterium and Massilia were higher in T. controversa-infected resistant varieties than in their controls, that Dothideomycetes, Bacteroidia, Nocardioides and Pseudomonas showed higher abundances in T. controversa-infected susceptible varieties, and that Curtobacterium, Exiguobacterium, Planococcus, and Pantoea may have higher abundances in both T. controversa-infected susceptible and resistant varieties than in their own controls.
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http://dx.doi.org/10.1038/s41598-021-85281-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952392PMC
March 2021

An updated review of autophagy in ischemic stroke: From mechanisms to therapies.

Exp Neurol 2021 Mar 5;340:113684. Epub 2021 Mar 5.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China; Brain Research Institute, Zhejiang University, Hangzhou, Zhejiang, China; Collaborative Innovation Center for Brain Science, Zhejiang University, Hangzhou, Zhejiang, China. Electronic address:

Stroke is a leading cause of mortality and morbidity worldwide. Understanding the underlying mechanisms is important for developing effective therapies for treating stroke. Autophagy is a self-eating cellular catabolic pathway, which plays a crucial homeostatic role in the regulation of cell survival. Increasing evidence shows that autophagy, observed in various cell types, plays a critical role in brain pathology after ischemic stroke. Therefore, the regulation of autophagy can be a potential target for ischemic stroke treatment. In the present review, we summarize the recent progress that research has made regarding autophagy and ischemic stroke, including common signaling pathways, the role of autophagic subtypes (e.g. mitophagy, pexophagy, aggrephagy, endoplasmic reticulum-phagy, and lipophagy) in ischemic stroke, as well as the current methods for autophagy detection and potential therapeutic strategy.
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http://dx.doi.org/10.1016/j.expneurol.2021.113684DOI Listing
March 2021

The Changes of Leukocytes in Brain and Blood After Intracerebral Hemorrhage.

Front Immunol 2021 15;12:617163. Epub 2021 Feb 15.

Department of Neurosurgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.

Preclinical and clinical research has demonstrated that inflammation is a critical factor regulating intracerebral hemorrhage (ICH)-induced brain injury. Growing evidence suggests that myeloid cells and lymphocytes have an effect on the pathophysiological processes associated with ICH, such as inflammation, immune responses, perihematomal edema formation, blood-brain barrier (BBB) integrity, and cell death. However, the underlying mechanisms remain largely unknown. We aimed to explore the role immune cells played at different stages of the ICH. To achieve this, novel bioinformatics algorithms were employed to analyze the gene expression profiles and three different analytical tools were utilized to predict the abundances of cell types. In this study, we found that natural killer (NK) cells infiltrated into the brain parenchyma after ICH. Infiltrating NK cells may mediate brain injury through degranulation and recruitment of other cells. Besides, in the acute phase of ICH, monocytes in peripheral blood carried out phagocytosis and secretion of cytokines. On the other hand, in the subacute stage, non-classical monocytes were activated and showed a stronger ability to carry out heme metabolism, wound healing, and antigen processing and presentation. In conclusion, our findings emphasize the significance of intracerebral infiltrating immunocytes in ICH and demonstrate that ICH is a systemic disease affected by peripheral blood. The hub genes identified might be promising therapeutic targets. We also provide a reference on how to use bioinformatics approaches to explore non-neoplastic immune-related diseases.
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http://dx.doi.org/10.3389/fimmu.2021.617163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7917117PMC
February 2021

Hippo signalling maintains ER expression and ER breast cancer growth.

Nature 2021 03 3;591(7848):E1-E10. Epub 2021 Mar 3.

Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.

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http://dx.doi.org/10.1038/s41586-020-03131-5DOI Listing
March 2021

Co-construction of sulfur vacancies and carbon confinement in VS/CNFs to induce an ultra-stable performance for half/full sodium-ion and potassium-ion batteries.

Nanoscale 2021 Mar;13(9):5033-5044

Engineering Research Center of Polymer Green Recycling of Ministry of Education, College of Environmental Science and Engineering, Fujian Normal University, Fuzhou, Fujian 35007, China. and Fujian Key Laboratory of Pollution Control & Resource Reuse, Fuzhou, Fujian 350007, China and Key Laboratory of Advanced Energy Materials Chemistry (Ministry of Education), College of Chemistry, Nankai University, Tianjin 300071, China.

The construction of anode materials for sodium-ion batteries (SIBs) and potassium-ion batteries (PIBs) with a high energy and a long lifespan is significant and still challenging. Here, sulfur-defective vanadium sulfide/carbon fiber composites (D-V5S8/CNFs) are designed and fabricated by a facile electrospinning method, followed by sulfuration treatment. The unique architecture, in which V5S8 nanoparticles are confined inside the carbon fiber, provides a short-range channel and abundant adsorption sites for ion storage. Moreover, enlarged interlayer spacings could also alleviate the volume changes, and offer small vdW interactions and ionic diffusion resistance to store more Na and K ions reversibly and simultaneously. The DFT calculations further demonstrate that sulfur defects can effectively facilitate the adsorption behavior of Na+ and K+ and offer low energy barriers for ion intercalation. Taking advantage of the functional integration of these merits, the D-V5S8/CNF anode exhibits excellent storage performance and long-term cycling stability. It reveals a high capacity of 462 mA h g-1 at a current density of 0.2 A g-1 in SIBs, while it is 350 mA h g-1 at 0.1 A g-1 in PIBs, as well as admirable long-term cycling characteristics (190 mA h g-1/17 000 cycles/5 A g-1 for SIBs and 165 mA h g-1/3000 cycles/1 A g-1 for PIBs). Practically, full SIBs upon pairing with a Na3V2(PO4)3 cathode also exhibit superior performance.
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http://dx.doi.org/10.1039/d0nr08788bDOI Listing
March 2021

Massive Cerebral Infarction Following Facial Injection of Autologous Fat: A Case Report and Review of the Literature.

Front Hum Neurosci 2021 9;15:610945. Epub 2021 Feb 9.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.

Facial fat grafting techniques often offer impressive surgical results. However, fatal complications, such as irreversible cerebral ischemia, blindness, and hemiplegia are associated with them. We have presented a case report of a patient who presented with a massive cerebral infarction, a serious complication of facial autologous fat injection. The patient was a 28-year-old female who experienced motor dysfunction of the left extremities, which was accompanied with loss of consciousness immediately following fat grafting for facial augmentation. Imaging studies suggested that the patient had a large cerebral infarction on the right frontal, temporal, and parietal lobes due to complete occlusion of her right external carotid artery. Emergency decompressive craniectomy was completed in addition to multiple follow-up medical treatments. The patient recovered after 4 months with reduced motor function in her left upper extremity. This report further summarizes published cases of massive cerebral ischemia after facial injection of autologous fat, as well as lists high-risk facial areas and critical warnings.
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http://dx.doi.org/10.3389/fnhum.2021.610945DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900534PMC
February 2021

Research Advances in Protective Effects of Ursolic Acid and Oleanolic Acid Against Gastrointestinal Diseases.

Am J Chin Med 2021 20;49(2):413-435. Epub 2021 Feb 20.

The First Clinical Medical College of Lanzhou University, Lanzhou 730000, P. R. China.

The intestinal tract plays an essential role in protecting tissues from the invasion of external harmful substances due to impaired barrier function. Furthermore, it participates in immunomodulation by intestinal microorganisms, which is important in health. When the intestinal tract is destroyed, it can lose its protective function, resulting in multiple systemic complications. In severe cases, it may lead to systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Thus far, there are no curative therapies for intestinal mucosal barrier injury, other than a few drugs that can relieve symptoms. Thus, the development of novel curative agents for gastrointestinal diseases remains a challenge. Ursolic acid (UA) and its isomer, Oleanolic acid (OA), are pentacyclic triterpene acid compounds. Both their aglycone and glycoside forms have anti-oxidative, anti-inflammatory, anti-ulcer, antibacterial, antiviral, antihypertensive, anti-obesity, anticancer, antidiabetic, cardio protective, hepatoprotective, and anti-neurodegenerative properties in living organisms. In recent years, several studies have shown that UA and OA can reduce the risk of intestinal pathological injury, alleviate intestinal dysfunction, and restore intestinal barrier function. The present study evaluated the beneficial effects of UA and OA on intestinal damage and diseases, including inflammatory bowel disease (IBD) and colorectal cancer (CRC).
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http://dx.doi.org/10.1142/S0192415X21500191DOI Listing
February 2021

Ceria nanoparticles ameliorate white matter injury after intracerebral hemorrhage: microglia-astrocyte involvement in remyelination.

J Neuroinflammation 2021 Feb 15;18(1):43. Epub 2021 Feb 15.

Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Background: Intracerebral hemorrhage (ICH) can induce excessive accumulation of reactive oxygen species (ROS) that may subsequently cause severe white matter injury. The process of oligodendrocyte progenitor cell (OPC) differentiation is orchestrated by microglia and astrocytes, and ROS also drives the activation of microglia and astrocytes. In light of the potent ROS scavenging capacity of ceria nanoparticles (CeNP), we aimed to investigate whether treatment with CeNP ameliorates white matter injury by modulating ROS-induced microglial polarization and astrocyte alteration.

Methods: ICH was induced in vivo by collagenase VII injection. Mice were administered with PLX3397 for depleting microglia. Primary microglia and astrocytes were used for in vitro experiments. Transmission electron microscopy analysis and immunostaining were performed to verify the positive effects of CeNP in remyelination and OPC differentiation. Flow cytometry, real-time polymerase chain reaction, immunofluorescence and western blotting were used to detect microglia polarization, astrocyte alteration, and the underlying molecular mechanisms.

Results: CeNP treatment strongly inhibited ROS-induced NF-κB p65 translocation in both microglia and astrocytes, and significantly decreased the expression of M1 microglia and A1 astrocyte. Furthermore, we found that CeNP treatment promoted remyelination and OPC differentiation after ICH, and such effects were alleviated after microglial depletion. Interestingly, we also found that the number of mature oligodendrocytes was moderately increased in ICH + CeNP + PLX3397-treated mice compared to the ICH + vehicle + PLX3397 group. Therefore, astrocytes might participate in the pathophysiological process. The subsequent phagocytosis assay indicated that A1 astrocyte highly expressed C3, which could bind with microglia C3aR and hinder microglial engulfment of myelin debris. This result further replenished the feedback mechanism from astrocytes to microglia.

Conclusion: The present study reveals a new mechanism in white matter injury after ICH: ICH induces M1 microglia and A1 astrocyte through ROS-induced NF-κB p65 translocation that hinders OPC maturation. Subsequently, A1 astrocytes inhibit microglial phagocytosis of myelin debris via an astrocytic C3-microglial C3aR axis. Polyethylene glycol-CeNP treatment inhibits this pathological process and ultimately promotes remyelination. Such findings enlighten us that astrocytes and microglia should be regarded as a functional unit in future works.
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http://dx.doi.org/10.1186/s12974-021-02101-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7883579PMC
February 2021

Effectiveness of Postoperative Adjuvant Radiotherapy in Atypical Meningioma Patients After Gross Total Resection: A Meta-Analysis Study.

Front Oncol 2020 15;10:556575. Epub 2021 Jan 15.

Department of Neurosurgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China.

Background: It still remains unclear whether patients with atypical meningioma (AM) could benefit from postoperative adjuvant radiotherapy (PORT) after gross-total resection (GTR).

Objective: Exploring the effectiveness of PORT on AM patients after GTR.

Methods: Literatures on PubMed, Embase, Web of science, and Scopus databases published between January 2000 and January 2019 were searched. After the selection based on the certain exclusion criteria, the Newcastle-Ottawa evaluation scale was used to evaluate the quality of the included literatures. Finally, a meta-analysis was conducted to analyze the effectiveness of PORT on local control (LC), progression-free survival (PFS) and overall survival (OS) in atypical meningioma patients after GTR.

Results: A total of 17 articles with 2,008 AM patients were included in the meta-analysis. The 5-year LC, 5-year PFS, and 5-year OS rates were 82.2, 84.1, and 79.0%, respectively, for AM patients receiving PORT after GTR, and they were 71.0, 71.9, and 81.5%, respectively, for those not receiving PORT after GTR. PORT could significantly improve 5-year LC rate (OR [95% Cl] = 2.59 [1.40-4.81], = 0.002) and 5-year PFS rate (OR [95% Cl] = 1.99 [1.35-2.95], = 0.001), but did not significantly improve 5-year OS rate (OR [95% Cl] = 1.07 [0.60-1.91], = 0.828).

Conclusion: PORT could improve the 5-year LC rate and 5-year PFS rate in AM patients after GTR. AM patients might benefit from PORT after GTR.
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http://dx.doi.org/10.3389/fonc.2020.556575DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7873933PMC
January 2021

Bactericidal Permeability Increasing Protein Deficiency Aggravates Acute Colitis in Mice by Increasing the Serum Levels of Lipopolysaccharide.

Front Immunol 2020 21;11:614169. Epub 2021 Jan 21.

Department of Immunology, CAMS Key Laboratory for T cell and Immunotherapy, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, State Key Laboratory of Medical Molecular Biology, Beijing, China.

Objective: The objective of this study was to understand the role of bactericidal permeability increasing protein (BPI) in the pathogenesis of experimental murine colitis.

Methods: We used the Cre-LoxP system to generate BPI knockout (BPI KO) mice. Acute colitis was induced in BPI KO mice and wild-type (WT) mice by subjecting the mice to 5% dextran sulfate sodium (DSS). Mice were observed for symptoms of experimental colitis. The survival of BPI KO mice to infection with , a gram-negative bacterium, was also assessed.

Results: Southern blot, RT-PCR, and western blot results showed that the 2 and 3 exons of the murine gene were knocked out systemically, confirming successful construction of the BPI KO mouse. BPI KO mice subjected to DSS showed increased symptoms of experimental colitis, increased colonic mucosal damage, increased epithelial permeability, elevated levels of serum LPS, and a disrupted fecal microbiome as compared with WT mice. Furthermore, BPI KO mice challenged intraperitoneally with died sooner than WT mice, and the total number of bacteria in the abdominal cavity, spleen, and liver was increased in BPI KO mice as compared to WT mice.

Conclusions: We successfully generated BPI KO mice. The BPI KO mice developed worse colitis than WT mice by increased colitis symptoms and colonic mucosal damage, elevated levels of serum LPS, and a disrupted microbiome. BPI could be a potential target for treatment of ulcerative colitis in humans.
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http://dx.doi.org/10.3389/fimmu.2020.614169DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858664PMC
January 2021

A tunable, rapid, and precise drug control of protein expression by combining transcriptional and post-translational regulation systems.

J Genet Genomics 2020 11 26;47(11):705-712. Epub 2020 Oct 26.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, South China Institute for Stem Cell Biology and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China; School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, 529020, China. Electronic address:

Rapid, precise, and tunable regulation of protein abundance would be significantly useful in a variety of biotechnologies and biomedical applications. Here, we describe a system that allows tunable and rapid drug control of gene expression for either gene activation or inactivation in mammalian cells. We construct the system by coupling Tet-on 3G and small molecule-assisted shutoff systems, which can respectively induce transcriptional activation and protein degradation in the presence of corresponding small molecules. This dual-input drug inducer regulation system facilitates a bidirectional control of gene expression. The gene of interest can be precisely controlled by dual small molecules in a broad dynamic range of expression from overexpression to complete silence, allowing gene function study in a comprehensive expression profile. Our results reveal that the bidirectional control system enables sensitive dosage- and time-dependent regulation for either turn-on or shutoff of gene expression. We also apply this system for inducible genome editing and gene activation mediated by clustered regularly interspaced short palindromic repeats. The system provides an integrated platform for studying multiple biological processes by manipulating gene expression in a more flexible way.
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http://dx.doi.org/10.1016/j.jgg.2020.07.009DOI Listing
November 2020

Comparison of Postoperative Analgesic Effects Between Nalbuphine and Fentanyl in Children Undergoing Adenotonsillectomy: A Prospective, Randomized, Double-Blind, Multicenter Study.

Front Pharmacol 2020 9;11:597550. Epub 2020 Dec 9.

Key Laboratory of Anesthesiology of Zhejiang Province, Department of Anesthesiology, Perioperative and Pain Medicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Zhejiang, China.

There is no universal agreement on optimal pharmacological regimens for pain management during surgeries. The aim of this study to compare the postoperative analgesic effects of nalbuphine with fentanyl in children undergoing adenotonsillectomy. We conducted a prospective, randomized, double-blind, non-inferiority and multicenter trial in 311 patients admitted to four different medical facilities in China from October 2017 to November 2018. The primary outcome was postoperative pain score. The secondary outcomes were as follows: the numbers of patients who developed moderate or severe pain (FLACC ≥4 points); time to first rescue analgesic top up and the actual number of rescue pain medicine given in pain control in post-anesthesia care unit (PACU), and additional analgesics requirement (received ≥2 rescue analgesics or/and other analgesics except study medications administered in PACU and ward); emergence and extubation time; Waking up time; time of PACU stay, and other side effects (desaturation, nausea/vomiting etc.). A total of 356 children were screened and 322 patients were randomized. The mean age was 5.8 (5.5, 6.1) in the nalbuphine group and 5.6 (5.3, 5.8) in the fentanyl group ( = 0.2132). FLACC score of nalbuphine group was lower than that of fentanyl group upon patients' arrival at PACU ( < 0.05). The time to first required rescue dose of pain drug for nalbuphine group was longer than for the fentanyl group (2.5 vs 1.2 h, < 0.0001). Only one patient (0.6%) in nalbuphine group presented a slow respiratory rate (RR) at 9/min while 29 patients (18.5%) in fentanyl group developed slow RR ≤10/min in PACU. Meanwhile, SpO was lower in the fentanyl group at 10 min after patients' arrival in PACU ( < 0.05). The other profiles observed from these two drug groups were similar. Nalbuphine provided better pain relief with minimal respiration depression than fentanyl in children undergoing Adenotonsillectomy.
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http://dx.doi.org/10.3389/fphar.2020.597550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7849154PMC
December 2020

Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden.

Sci Adv 2021 Jan 1;7(1). Epub 2021 Jan 1.

Department of Cell Stress Biology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

In ultraviolet (UV) radiation-exposed skin, mutations fuel clonal cell growth. The relationship between UV exposure and the accumulation of clonal mutations (CMs) and the correlation between CMs and skin cancer risk are largely unexplored. We characterized 450 individual-matched sun-exposed (SE) and non-SE (NE) normal human skin samples. The number and relative contribution of CMs were significantly different between SE and NE areas. Furthermore, we identified hotspots in , , and where mutations were significantly associated with UV exposure. In the normal skin from patients with cutaneous squamous cell carcinoma, we found that the cancer burden was associated with the UV-induced mutations, with the difference mostly conferred by the low-frequency CMs. These findings provide previously unknown information on UV's carcinogenic effect and pave the road for future development of quantitative assessment of subclinical UV damage and skin cancer risk.
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http://dx.doi.org/10.1126/sciadv.abd7703DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775785PMC
January 2021

A one-step closed-tube enzyme-activated blocked probe assay based on SNP for rapid detection of Salmonella Pullorum.

Poult Sci 2021 Feb 18;100(2):1059-1067. Epub 2020 Nov 18.

National and Regional Joint Engineering Laboratory For Medicament of Zoonoses Prevention and Control, Guangzhou 510642, China; Key Laboratory of Zoonoses, Ministry of Agriculture, Guangzhou 510642, China; Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, Guangzhou 510642, China; Key Laboratory of Animal Vaccine Development, Ministry of Agriculture, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture, Guangzhou 510642, China; College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China. Electronic address:

Salmonella enterica serovar Gallinarum biovars Pullorum (S. Pullorum) is an infectious bacterial pathogen in the poultry industry that causes systemic pullorum disease. This disease causes great losses in terms of the clinical production and quality of chicken products in breeding farms. However, an acknowledged usable rapid detection method for its specific identification has not been reported, and it is generally difficult to distinguish from fowl typhoid caused by Salmonella enterica serovar Gallinarum biovars Gallinarum. The development of a specific and rapid detection method for this pathogen is therefore needed. In the present study, we targeted the single-nucleotide mutation position 237 of the S. Pullorum rfbS gene to develop an enzyme-activated blocked probe for its clinical rapid detection. The method displayed robust specificity and reproducibility, and it achieved minimal detection limits of 21 copies/μL of copy number and 4.53 pg/μL of genomic DNA. Compared with traditional identification and PCR methods, this method performed better for the detection of 100 clinical actual samples and without false negative results. The entire process can be accomplished in a 1-step closed-tube operation, overcomes the difficulties currently associated with S. Pullorum detection, and provides a specific and rapid method with broad application potential for SNP detection.
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http://dx.doi.org/10.1016/j.psj.2020.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7858149PMC
February 2021

Tunable thickness of mesoporous ZnO-coated metal nanoparticles for enhanced visible-light driven photoelectrochemical water splitting.

Chemosphere 2021 Jan 19;273:129679. Epub 2021 Jan 19.

School of Materials Science and Engineering, Shijiazhuang Tiedao University, Shijiazhuang, 050043, China; Hebei Key Laboratory of Advanced Materials for Transportation Engineering and Environment, Shijiazhuang, 050043, China.

The insufficient utilization of sunlight of ZnO, due to its broad band gap, results in low efficiency for photocatalytic hydrogen production. In this work, plasmonic noble metal nanoparticles (NPs) with different shapes (spheres and rods) were combined with mesoporous ZnO forming core-shell nanostructure to enhance the photocatalytic efficiency of ZnO in visible-light region. The photoelectrochemical water splitting activities of the metal@ZnO core-shell nanocomposites (NCs) were investigated. The photocurrent response of metal@ZnO NCs was found higher than pure ZnO or the mixture of metal NPs and ZnO ascribed to the effective charge transfer mechanism. It was also found that the photocurrent of metal@ZnO NCs was related to the thickness of ZnO and there was optimized shell for each kind of metal cores. Moreover, the introduction of Ag shell can get a higher photoelectrocatalytic efficiency compared to pure Au NPs core due to lower Schottky barrier between Ag and ZnO and wider extinction range in the visible light of Au@Ag NPs.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129679DOI Listing
January 2021

Immuno-oncology: are TAM receptors in glioblastoma friends or foes?

Cell Commun Signal 2021 Jan 28;19(1):11. Epub 2021 Jan 28.

Department of Neurosurgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, 310009, China.

Tyro3, Axl, and Mertk (TAM) receptors are a subfamily of receptor tyrosine kinases. TAM receptors have been implicated in mediating efferocytosis, regulation of immune cells, secretion of inflammatory factors, and epithelial-to-mesenchymal transition in the tumor microenvironment, thereby serving as a critical player in tumor development and progression. The pro-carcinogenic role of TAM receptors has been widely confirmed, overexpression of TAM receptors is tied to tumor cells growth, metastasis, invasion and treatment resistance. Nonetheless, it is surprising to detect that inhibiting TAM signaling is not all beneficial in the tumor immune microenvironment. The absence of TAM receptors also affects anti-tumor immunity under certain conditions by modulating different immune cells, as the functional diversification of TAM signaling is closely related to tumor immunotherapy. Glioblastoma is the most prevalent and lethal primary brain tumor in adults. Although research regarding the crosstalk between TAM receptors and glioblastoma remains scarce, it appears likely that TAM receptors possess potential anti-tumor effects rather than portraying a total cancer-driving role in the context of glioblastoma. Accordingly, we doubt whether TAM receptors play a double-sided role in glioblastoma, and propose the Janus-faced TAM Hypothesis as a conceptual framework for comprehending the precise underlying mechanisms of TAMs. In this study, we aim to cast a spotlight on the potential multidirectional effects of TAM receptors in glioblastoma and provide a better understanding for TAM receptor-related targeted intervention. Video Abstract.
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http://dx.doi.org/10.1186/s12964-020-00694-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7841914PMC
January 2021

Highly prevalent multidrug resistance and QRDR mutations in Salmonella isolated from chicken, pork and duck meat in Southern China, 2018-2019.

Int J Food Microbiol 2021 Feb 12;340:109055. Epub 2021 Jan 12.

National and Regional Joint Engineering Laboratory for Medicament of Zoonoses Prevention and Control, Guangdong Laboratory for Lingnan Modern Agriculture, Key Laboratory of Zoonoses, Ministry of Agriculture, Key Laboratory of Zoonoses Prevention and Control of Guangdong Province, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, PR China. Electronic address:

This study was undertaken to investigate the prevalence, serotype distribution and antimicrobial resistance in Salmonella isolated from retail meat in Southern China, and to characterize the major mechanisms that mediate the ciprofloxacin resistance of isolates. High levels of Salmonella contamination were detected in pork (67.0%), duck (50.5%) and chicken (46.2%). Thirty different serotypes were identified among 500 detected Salmonella isolates, as well as significant differences in serotypes between different retail meat samples. Notably, 405 (80.1%) isolates exhibited multidrug resistance (MDR). Meanwhile, we also found that 74 (14.8%) Salmonella isolates were resistant to ciprofloxacin and the major mechanisms underlying this resistance were investigated. The commonest mutations in gyrA S83F (40.5%) and D87N (35.1%), and in parC was T57S (71.6%) and S80I (35.1%). Multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE) analysis revealed that the S. Kentucky isolates that were resistant to ciprofloxacin mostly belonged to ST198 (21/23, 91.3%) and PFGE revealed the presence of various genotypes. This study identified a diversity of Salmonella serotypes and a high prevalence of multidrug resistance (MDR) among Salmonella isolated from retail meat in Southern China, which indicates that foodborne Salmonella potentially constitutes a potential food safety risk.
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http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109055DOI Listing
February 2021

Improved sodium storage properties of nickel sulfide nanoparticles decorated on reduced graphene oxide nanosheets as an advanced anode material.

Nanotechnology 2021 May;32(19):195406

College of Chemistry, Zhengzhou University, Zhengzhou, 450001, People's Republic of China. Green Catalysis Center, College of Chemistry, Zhengzhou University, 450001, People's Republic of China.

For sodium ion batteries, the fabrication of nanocrystal anode materials has been identified as a satisfactory strategy to improve electrochemical performance and maintain the structural integrity of electrodes. However, the issues of agglomeration and serious volume variation have always existed within the process of charging/discharging in anode materials. In this work, a series of composites of nickel sulfide nanoparticles decorated on reduced graphene oxide nanosheets (denoted as NiS@rGO) were successfully synthesized via a simple one-step hydrothermal method under different temperatures. The strategy of confining nickel sulfide nanoparticles within the interlayer of graphene nanosheets can not only avoid the agglomeration, but also alleviate the volume change to some extent in electrode materials. For sodium ion storage, the NiS@rGO synthesized at 160 °C exhibited a higher reversible capacity and better rate capability.
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http://dx.doi.org/10.1088/1361-6528/abde04DOI Listing
May 2021

Dissolution process of a single bubble under pressure with a large-density-ratio multicomponent multiphase lattice Boltzmann model.

Phys Rev E 2020 Dec;102(6-1):063306

State Key Laboratory of Hydraulics and Mountain River Engineering, Sichuan University, Chengdu 610065, China.

A large-density-ratio and tunable-viscosity-ratio multicomponent multiphase pseudopotential lattice Boltzmann model is used to study the dissolution process of a bubble under pressure. The multi-relaxation-time collision operator, exact-difference-method external force scheme, and scaling coefficient k are applied to ensure the numerical stability of the model. The influence of k in the equation of state (EOS) and intermolecule interaction strength on the stationary bubble evolution process are discussed, and the effect of k on thermodynamic consistency is also analyzed. The results indicate that adjusting the scaling coefficient in the EOS changes the surface tension and interface thickness, and that the gas-liquid interface width w is proportional to 1/sqrt[k]. Considering the effect of k on the surface tension, interface thickness, and thermodynamic consistency, the scaling coefficient should be between 0.6 and 1. Furthermore, the dissolution process of a single bubble under pressure is studied using the developed model, and it is found that the dissolution mass and concentration of dissolved gas increase linearly with increases in the pressure difference, and that the concentration of dissolved gas is proportional to the gas pressure after the fluid system reaches equilibrium. These results are consistent with Henry's law.
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http://dx.doi.org/10.1103/PhysRevE.102.063306DOI Listing
December 2020

A novel fully immersive virtual reality environment for upper extremity rehabilitation in patients with stroke.

Ann N Y Acad Sci 2021 Jan 14. Epub 2021 Jan 14.

Molecular Imaging and Neuropathology Division, Department of Psychiatry, Columbia University & New York State Psychiatric Institute, New York City, New York.

Given the rising incidence of stroke, several technology-driven methods for rehabilitation have recently been developed. Virtual reality (VR) is a promising therapeutic technology among them. We recently developed a neuroscientifically grounded VR system to aid recovery of motor function poststroke. The developed system provides unilateral and bilateral upper extremity (UE) training in a fully immersive virtual environment that may stimulate and activate mirror neurons (MNs) in the brain necessary for UE rehabilitation. Twenty-three participants were randomized to a VR group (n = 12) to receive VR intervention (8 h within 2 weeks) plus 8-h occupational therapy (OT) or a control group (n = 11) to receive time-matched OT alone. Treatment effects on motor recovery and cortical reorganization were investigated using the Barthel Index (BI), Fugl-Meyer Upper Extremity (FM-UE), and resting-state fMRI. Both groups significantly improved BI (P < 0.05), reflecting the recovery of UE motor function. The VR group revealed significant improvements on FM-UE scores (P < 0.05) than the control group. Neural activity increased after the intervention, particularly in the brain areas implicating MNs, such as in the primary motor cortex. Overall, results suggested that using a neuroscientifically grounded VR system might offer additional benefits for UE rehabilitation in patients receiving OT.
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http://dx.doi.org/10.1111/nyas.14554DOI Listing
January 2021

GNA13 regulates BCL2 expression and the sensitivity of GCB-DLBCL cells to BCL2 inhibitors in a palmitoylation-dependent manner.

Cell Death Dis 2021 Jan 9;12(1):54. Epub 2021 Jan 9.

Shanghai Institute of Hematology, State Key Laboratory for Medical Genomics, Collaborative Innovation Center of Hematology, National Research Center for Translational Medicine, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

GNA13, encoding one of the G protein alpha subunits of heterotrimeric G proteins that transduce signals of G protein-coupled receptors (GPCR), is frequently mutated in germinal center B-cell-like diffuse large B-cell lymphoma (GCB-DLBCL) with poor prognostic outcomes. Due to the "undruggable" nature of GNA13, targeted therapy for these patients is not available. In this study, we found that palmitoylation of GNA13 not only regulates its plasma membrane localization, but also regulates GNA13's stability. It is essential for the tumor suppressor function of GNA13 in GCB-DLBCL cells. Interestingly, GNA13 negatively regulates BCL2 expression in GCB-DLBCL cells in a palmitoylation-dependent manner. Consistently, BCL2 inhibitors were found to be effective in killing GNA13-deficient GCB-DLBCL cells in a cell-based chemical screen. Furthermore, we demonstrate that inactivating GNA13 by targeting its palmitoylation enhanced the sensitivity of GCB-DLBCL to the BCL2 inhibitor. These studies indicate that the loss-of-function mutation of GNA13 is a biomarker for BCL2 inhibitor therapy of GCB-DLBCL and that GNA13 palmitoylation is a potential target for combination therapy with BCL2 inhibitors to treat GCB-DLBCL with wild-type GNA13.
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http://dx.doi.org/10.1038/s41419-020-03311-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797003PMC
January 2021

Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury.

J Neuroinflammation 2021 Jan 5;18(1). Epub 2021 Jan 5.

Department of Neurosurgery, Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, 310009, Zhejiang, China.

Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI.

Methods: The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed.

Results: Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation.

Conclusions: Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.
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http://dx.doi.org/10.1186/s12974-020-02041-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787000PMC
January 2021