Publications by authors named "Yu Gu"

434 Publications

A Scalable Framework for Map Matching Based Cooperative Localization.

Sensors (Basel) 2021 Sep 25;21(19). Epub 2021 Sep 25.

Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, WV 26506, USA.

Localization based on scalar field map matching (e.g., using gravity anomaly, magnetic anomaly, topographics, or olfaction maps) is a potential solution for navigating in Global Navigation Satellite System (GNSS)-denied environments. In this paper, a scalable framework is presented for cooperatively localizing a group of agents based on map matching given a prior map modeling the scalar field. In order to satisfy the communication constraints, each agent in the group is assigned to different subgroups. A locally centralized cooperative localization method is performed in each subgroup to estimate the poses and covariances of all agents inside the subgroup. Each agent in the group, at the same time, could belong to multiple subgroups, which means multiple pose and covariance estimates from different subgroups exist for each agent. The improved pose estimate for each agent at each time step is then solved through an information fusion algorithm. The proposed algorithm is evaluated with two different types of scalar field based simulations. The simulation results show that the proposed algorithm is able to deal with large group sizes (e.g., 128 agents), achieve 10-m level localization performance with 180 km traveling distance, while under restrictive communication constraints.
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http://dx.doi.org/10.3390/s21196400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512796PMC
September 2021

Clinical features of cryptococcosis in patients with different immune statuses: a multicenter study in Jiangsu Province-China.

BMC Infect Dis 2021 Oct 8;21(1):1043. Epub 2021 Oct 8.

Department of Respiratory and Critical Care Medicine, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China.

Background: Current guidelines support different management of cryptococcosis between severely immunodeficient and immunocompetent populations. However, few studies have focused on cryptococcosis patients with mild-to-moderate immunodeficiency. We performed this study to determine the clinical features of pulmonary (PC) and extrapulmonary cryptococcosis (EPC) and compared them among populations with different immune statuses to support appropriate clinical management of this public health threat.

Methods: All cases were reported by 14 tertiary teaching hospitals in Jiangsu Province, China from January 2013 to December 2018. The trends in incidence, demographic data, medical history, clinical symptoms, laboratory test indicators, imaging characteristics and diagnostic method of these patients were then stratified by immune status, namely immunocompetent (IC, patients with no recognized underlying disease or those with an underlying disease that does not influence immunity, such as hypertension), mild-to-moderate immunodeficiency (MID, patients with diabetes mellitus, end-stage liver or kidney disease, autoimmune diseases treated with low-dose glucocorticoid therapy, and cancer treated with chemotherapy) and severe immunodeficiency (SID, patients with acquired immunodeficiency syndrome, haematologic malignancies, solid organ transplantation or haematologic stem cell transplantation, idiopathic CD4 lymphocytosis, agranulocytosis, aggressive glucocorticoid or immunosuppressive therapy and other conditions or treatments that result in severe immunosuppression).

Results: The clinical data of 255 cryptococcosis patients were collected. In total, 66.3% of patients (169) were IC, 16.9% (43) had MID, and 16.9% (43) had SID. 10.1% of the patients (17) with IC were EPC, 18.6% of the patients (8) with MID were EPC, and 74.4% of patients (32) were EPC (IC/MID vs. SID, p < 0.001). Fever was more common in the SID group than in the IC and MID groups (69.8% vs. 14.8% vs. 37.2%, p < 0.001). Of chest CT scan, most lesions were distributed under the pleura (72.7%), presenting as nodules/lumps (90.3%) or consolidations (10.7%). Pleural effusion was more common in SID group compared to IC group (33.3% vs. 2.4%, p < 0.001). Positivity rate on the serum capsular polysaccharide antigen detection (CrAg) test was higher in the SID group than in the other two groups [100.0% vs. 84.4% (MID) vs. 78.2% (IC), p = 0.013]. Positivity rate on the serum CrAg test was also higher in cryptococcal meningitis patients than in PC patients (100.0% vs. 79.5%, p = 0.015).

Conclusions: The clinical presentation of MID patients is intermediate between SID and IC patients and is similar to that of IC patients. The serum CrAg test is more sensitive for the identification of SID or EPC patients.
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http://dx.doi.org/10.1186/s12879-021-06752-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8499499PMC
October 2021

Camrelizumab plus apatinib in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia (CAP 01): a single-arm, open-label, phase 2 trial.

Lancet Oncol 2021 Oct 5. Epub 2021 Oct 5.

Department of Obstetrics and Gynecology, National Clinical Research Centre for Obstetric and Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address:

Background: Treatment options for patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia are scarce. The synergistic antitumour effect of immunotherapy and antiangiogenic drugs has been shown in many solid tumours. This phase 2 trial evaluated the activity and safety of camrelizumab (PD-1 inhibitor) plus apatinib (VEGF receptor inhibitor) in patients with high-risk chemorefractory or relapsed gestational trophoblastic neoplasia.

Methods: This was a single-arm, open-label, phase 2 trial, done at a single tertiary health-care centre in Beijing, China. Women (18-70 years) with high-risk (International Federation of Gynecology and Obstetrics score ≥7) chemorefractory or relapsed gestational trophoblastic neoplasia who had received at least two lines of previously unsuccessful multidrug chemotherapy regimens and had an Eastern Cooperative Oncology Group performance status of 0-2 were eligible for inclusion. Patients received 4-week cycles of intravenous camrelizumab 200 mg every 2 weeks plus oral apatinib 250 mg once per day until disease progression or unacceptable toxicity. The primary endpoint was objective response rate assessed according to serum human chorionic gonadotrophin concentration. Activity and safety were analysed in all patients who received at least one dose of study drug. The study is ongoing, but recruitment is complete. The study is registered with ClinicalTrials.gov, NCT04047017.

Findings: Between Aug 7, 2019, and March 18, 2020, 20 patients enrolled; 19 (95%) were diagnosed with choriocarcinoma and one (5%) had placental site trophoblastic tumour. The median follow-up duration was 18·5 months (IQR 14·6-20·9). The objective response rate was 55% (95% CI 32-77); ten (50%; 95% CI 27-73) patients had complete response. The most common grade 3 treatment-related adverse events were hypertension (five [25%] patients), rash (four [20%] patients), neutropenia (two [10%]), leukocytopenia (two [10%]), and aspartate aminotransferase increase (two [10%]). One patient had a treatment-related serious adverse event (aspartate aminotransferase 19-times higher than the upper limit of normal). No grade 4 or 5 treatment-related adverse events were reported.

Interpretation: Camrelizumab plus apatinib showed promising antitumour activity and acceptable toxicity and could be a salvage therapy option for the treatment of high-risk chemorefractory or relapsed gestational trophoblastic neoplasia. Immune checkpoint inhibitors combined with chemotherapy for heavily-treated patients and upfront use of camrelizumab plus apatinib for patients with high-risk gestational trophoblastic neoplasia are under investigation in phase 2 trials.

Funding: National Natural Science Foundation of China, Jiangsu Hengrui Pharmaceuticals.
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http://dx.doi.org/10.1016/S1470-2045(21)00460-5DOI Listing
October 2021

MOrPH-PhD: A Phage Display System for the Functional Selection of Genetically Encoded Macrocyclic Peptides.

Methods Mol Biol 2022 ;2371:261-286

Department of Chemistry, University of Rochester, Rochester, NY, USA.

Macrocyclic peptides represent promising scaffolds for targeting biomolecules with high affinity and selectivity, making methods for the diversification and functional selection of these macrocycles highly valuable for drug discovery purposes. We recently reported a novel phage display platform (called MOrPH-PhD) for the creation and functional exploration of combinatorial libraries of genetically encoded cyclic peptides. In this system, spontaneous, posttranslational peptide cyclization by means of a cysteine-reactive non-canonical amino acid is integrated with M13 bacteriophage display, enabling the creation of genetically encoded macrocyclic peptide libraries displayed on phage particles. Using this system, it is possible to rapidly generate and screen large libraries of phage-displayed macrocyclic peptides (up to 10 to 10 members) in order to identify high-affinity binders of a target protein of interest. Herein, we describe step-by-step protocols for the production of MOrPH-PhD libraries, the screening of these libraries against an immobilized protein target, and the isolation and characterization of functional macrocyclic peptides from these genetically encoded libraries.
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http://dx.doi.org/10.1007/978-1-0716-1689-5_14DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493807PMC
January 2022

Consecutive severe immune-related adverse events after PD-1 inhibitor induction and surgery in locally advanced non-small cell lung cancer: a case report.

Transl Lung Cancer Res 2021 Aug;10(8):3682-3688

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Neoadjuvant PD-(L)1 inhibitors may be promising for locally advanced non-small cell lung cancer (NSCLC) with potential pathological and survival benefits. But severe immune-related adverse events (irAEs) may cause fatal consequences which require early identification and timely intervention. The basis for most of these adverse events is a reactive hyperactivated T-cell response to normal tissues that results in the production of high levels of CD4 T-helper cell cytokines or increased migration of cytolytic CD8 T cells in normal tissues. It is recommended that all patients receiving PD-(L)1 inhibitors routinely have thyroid function studies, complete blood counts, and liver function and metabolic panels at each treatment and at intervals of 6 to 12 weeks for the first 6 months after finishing treatment. Herein, we report a rare case who had two grade 3-4 irAEs consecutively occurring after PD-1 induction therapy and surgery. A 59-year-old man with stage IIIA squamous cell lung cancer receiving 3 cycles of neoadjuvant nab-paclitaxel, carboplatin, and nivolumab was reevaluated for resectability. The patient experienced acute serum transaminase elevation right after induction therapy. Seven days after surgery he had severe pneumonia. These two serious complications were both eventually relieved by a month long treatment of corticosteroids but not regular medicine which verified the diagnosis of irAEs. Although results of clinical trials of neoadjuvant immunotherapy are worth expecting, our case calls attention to careful surveillance and timely management of irAEs during the perioperative use of PD-(L)1 inhibitors. We also further discuss the standard use of corticosteroids for irAEs based on a review of literature.
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http://dx.doi.org/10.21037/tlcr-21-603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8435383PMC
August 2021

Root canals shaped by nickel-titanium instrumentation with automated computerized numerical control systems.

BMC Oral Health 2021 09 28;21(1):482. Epub 2021 Sep 28.

Department of Endodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, No. 44-1 Wenhua Road West, Jinan, 250012, Shandong, People's Republic of China.

Background: To investigate the efficacy of a nickel-titanium (NiTi) file with an automated computerized numerical control (CNC) system for root canal shaping.

Methods: The movement of the automated device and the insertion angle were investigated. In Experiment 1, simulated resin root canals were randomly divided into four groups (n = 20): manual downward movement using a handpiece (Group 1), vertical downward movement by CNC (Group 2), reciprocating up and down movement by CNC (Group 3), and spiral up and down movement by CNC (Group 4). In Experiment 2, five different insertion angles of the NiTi file were evaluated (n = 20). Four parameters were used to evaluate the shaping ability: change in the working length, central axis offset, curvature variation, and preparation time. Groups were compared using one-way analysis of variance (ANOVA) with significance was set at P < 0.05.

Results: The change in central axis position in the curved part of the root canal was found to be smaller in Group 4 than in other groups (P < 0.05). The curvature changes and preparation time of Groups 1 and 4 were significantly reduced compared with Groups 2 and 3 (P < 0.05). The variation in working length and curvature in the 5° insertion angle group was significantly smaller than in the other groups (P < 0.05).

Conclusions: A spiral up and down movement, controlled by the CNC machine, and 5° insertion angle, maintained original root canal shape more precisely than other methods.
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http://dx.doi.org/10.1186/s12903-021-01841-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8480065PMC
September 2021

Bile Acid-Gut Microbiota Axis in Inflammatory Bowel Disease: From Bench to Bedside.

Nutrients 2021 Sep 9;13(9). Epub 2021 Sep 9.

Department of Gastroenterology and Hepatology, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin Medical University General Hospital, Tianjin 300052, China.

Inflammatory bowel disease (IBD) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract, with increasing prevalence, and its pathogenesis remains unclear. Accumulating evidence suggested that gut microbiota and bile acids play pivotal roles in intestinal homeostasis and inflammation. Patients with IBD exhibit decreased microbial diversity and abnormal microbial composition marked by the depletion of phylum (including bacteria involved in bile acid metabolism) and the enrichment of phylum . Dysbiosis leads to blocked bile acid transformation. Thus, the concentration of primary and conjugated bile acids is elevated at the expense of secondary bile acids in IBD. In turn, bile acids could modulate the microbial community. Gut dysbiosis and disturbed bile acids impair the gut barrier and immunity. Several therapies, such as diets, probiotics, prebiotics, engineered bacteria, fecal microbiota transplantation and ursodeoxycholic acid, may alleviate IBD by restoring gut microbiota and bile acids. Thus, the bile acid-gut microbiota axis is closely connected with IBD pathogenesis. Regulation of this axis may be a novel option for treating IBD.
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http://dx.doi.org/10.3390/nu13093143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8467364PMC
September 2021

Effect of Bainite to Ferrite Yield Strength Ratio on the Deformability of Mesostructures for Ferrite/Bainite Dual-Phase Steels.

Materials (Basel) 2021 Sep 16;14(18). Epub 2021 Sep 16.

Key Lab of Metastable Materials Science&Technology, Hebei Key Lab for Optimizing Metal Product Technology and Performance, College of Materials Science Engineering, Yanshan University, Qinhuangdao 066004, China.

The strength and plasticity balance of F/B dual-phase X80 pipeline steels strongly depends on deformation compatibility between the soft phase of ferrite and the hard phase of bainite; thus, the tensile strength of ferrite and bainite, as non-negligible factors affecting the deformation compatibility, should be considered first. In this purely theoretical paper, an abstract representative volume elements (RVE) model was developed, based on the mesostructure of an F/B dual-phase X80 pipeline steel. The effect of the yield strength difference between bainite and ferrite on tensile properties and the strain hardening behaviors of the mesostructure was studied. The results show that deformation first occurs in ferrite, and strain and stress localize in ferrite prior to bainite. In the modified Crussard-Jaoul (C-J) analysis, as the yield strength ratio of bainite to ferrite (σy,B/σy,F) increases, the transition strain associated with the deformation transformation from ferrite soft phase deformation to uniform deformation of ferrite and bainite increases. Meanwhile, as the uncoordinated deformation of ferrite and bainite is enhanced, the strain localization factor (SLF) increases, especially the local strain concentration. Consequently, the yield, tensile strength, and yield ratio (yield strength/tensile strength) increase with the increase in σy,B/σy,F. Inversely, the strain hardening exponent and uniform elongation decrease.
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http://dx.doi.org/10.3390/ma14185352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8465738PMC
September 2021

Quinolone Resistance of Revealed through Genome and Transcriptome Analyses.

Int J Mol Sci 2021 Sep 17;22(18). Epub 2021 Sep 17.

College of Life Sciences, Sichuan Agricultural University, Chengdu 611130, China.

is a pathogen that infects pigs and poses a serious threat to the pig industry. The emergence of quinolone-resistant strains of further limits the choice of treatment. However, the mechanisms behind quinolone resistance in remain unclear. The genomes of a ciprofloxacin-resistant strain, SC1810 and its isogenic drug-sensitive counterpart were sequenced and analyzed using various bioinformatics tools, revealing 559 differentially expressed genes. The biological membrane, plasmid-mediated quinolone resistance genes and quinolone resistance-determining region were detected. Upregulated expression of efflux pump genes led to ciprofloxacin resistance. The expression of two porins, OmpP2B and LamB, was significantly downregulated in the mutant. Three nonsynonymous mutations in the mutant strain disrupted the water-metal ion bridge, subsequently reducing the affinity of the quinolone-enzyme complex for metal ions and leading to cross-resistance to multiple quinolones. The mechanism of quinolone resistance in may involve inhibition of expression of the outer membrane protein genes and to decrease drug influx, overexpression of AcrB in the efflux pump to enhance its drug-pumping ability, and mutation in the quinolone resistance-determining region to weaken the binding of the remaining drugs. These findings will provide new potential targets for treatment.
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http://dx.doi.org/10.3390/ijms221810036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472844PMC
September 2021

Systematic Lymph Node Dissection May Be Abolished in Patients With Apparent Early-Stage Low-Grade Mucinous and Endometrioid Epithelial Ovarian Cancer.

Front Oncol 2021 6;11:705720. Epub 2021 Sep 6.

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Objective: To investigate whether systematic lymph node dissection can confer clinical benefits in patients with apparent early-stage low-grade epithelial ovarian cancer.

Methods: Patients with apparent early-stage low-grade epithelial ovarian cancer seen at Peking Union Medical College Hospital from January 1, 2005, to December 31, 2015, were retrospectively enrolled. Patients with other histological types and those who did not receive necessary adjuvant chemotherapy were excluded. Data collection and long-term follow-up were performed. According to the removed lymph node number, three groups based on surgical methods were used: abnormal lymph node resection, pelvic lymphadenectomy, and systematic lymph node dissection to control surgical quality. Their effects on prognosis were analyzed in pathological subgroups.

Results: A total of 196 patients were enrolled; 30.1% of patients had serous, 42.3% of patients had mucinous, and 27.6% of patients had endometrioid carcinoma, of which 51 (26.0%), 96 (49.0), and 49 (25.0%) patients were treated with the above surgical methods, respectively. The occult lymph node metastasis rate was 14 (7.1%), and only five (2.6%) of apparent early-stage patients were upstaged due to lymph node metastasis alone. Systematic lymph node dissection did not benefit progression-free survival or disease-specific overall survival of apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but prolonged progression-free survival of apparent early-stage low-grade serous patients (OR, 0.231, 95% CI, 0.080, 0.668, p = 0.007).

Conclusions: Systematic lymph node dissection may be abolished in patients with apparent early-stage low-grade mucinous and endometrioid epithelial ovarian cancer but may be considered for apparent early-stage low-grade serous patients.
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http://dx.doi.org/10.3389/fonc.2021.705720DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450513PMC
September 2021

Molecularly assembled graphdiyne with atomic sites for ultrafast and real-time detection of nitric oxide in cell assays.

Biosens Bioelectron 2021 Sep 12;195:113630. Epub 2021 Sep 12.

School of Materials Science and Engineering, Suzhou University of Science and Technology, Suzhou, 215011, China; Jiangsu Laboratory for Biochemical Sensing and Biochip, Suzhou, 215011, China. Electronic address:

Nitric oxide as a signal molecule participates in a variety of physiological and pathological processes but its real-time detection in cell assays still faces challenging because of the trace amount, short half-life and easy conversion to other substances. We report here a rational design by assembling highly π-conjugated and small capacitive gaphdiyne (GDY) with a coordination complex of hemin (HEM) into a molecularly assembled material of GDY/HEM to achieve ultrafast and real-time monitoring of nitric oxide in cell assays. GDY comprising alkynyl C atoms can hybridize with the HEM to enable strong π-π interaction and atomic dispersion of iron sites while avoiding the formation of catalytically inactive dimer for the HEM. These characteristics make the GDY/HEM an excellent sensing material towards nitric oxide, which has an ultrafast response time of 0.95 s, a low detection limit of 7 nM and long linear range up to 151.38 μΜ. The GDY/HEM realizes real-time monitoring nitric oxide released from cancer and normal cells, demonstrating its capability for cell analysis.
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http://dx.doi.org/10.1016/j.bios.2021.113630DOI Listing
September 2021

Value of shear wave elastography in predicting hepatorenal syndrome in patients with liver cirrhosis and ascites.

Int J Clin Pract 2021 Sep 7:e14811. Epub 2021 Sep 7.

Department of Ultrasound, The 2nd Affiliated Hospital of Guizhou University of TCM, Guizhou, China.

Background: Early detection of renal damage in cirrhosis is critical to prevent hepatorenal syndrome (HRS). Although shear wave elastography (SWE) is useful for the assessment of kidney stiffness, no study has yet investigated the clinical feasibility of SWE for predicting HRS.

Objective: The aim of this study was to evaluate the value of SWE in predicting HRS in patients with cirrhosis and ascites.

Methods: A total of 131 patients with liver cirrhosis and ascites were recruited and followed them for 30 days for the development of AKI. Ultrasonographic examination was performed on all patients at hospital admission. The baseline clinical characteristics, renal biomarkers, renal resistive index (RI) and Young's modulus (YM) were recorded, and their relationship with development HRS was investigated.

Results: Sixty-eight patients developed AKI, 23 of them were HRS. Compared with patients in the non-AKI group and non-HRS group, the values of serum cystatin C (CystC), urine neutrophil gelatinase-associated lipocalin (NGAL) and renal RI were significantly increased, while the YM value was significantly decreased in the AKI group and HRS group. Correlation analysis showed that YM was significantly and negatively associated with serum creatinine, serum CystC, urinary NGAL and renal RI in addition to the significant association with the AKI stage. Logistic regression and ROC analysis showed that urine NGAL, renal RI and YM were closely related to the development of HRS. Among them, YM had a good predictive ability in predicting the occurrence of HRS, and the predictive value (AUC = 0.894) was improved when combined with renal RI.

Conclusion: SWE can indicate renal injury in patients with cirrhosis and ascites. The combination of YM and RI has a good predictive value for the occurrence of HRS.
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http://dx.doi.org/10.1111/ijcp.14811DOI Listing
September 2021

The protective effect of harpagoside on angiotensin II (Ang II)-induced blood-brain barrier leakage in vitro.

Phytother Res 2021 Sep 5. Epub 2021 Sep 5.

Department of Neurology, Jiangsu Province Hospital of Chinese Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China.

Hypertension and its associated dysfunction of the blood-brain barrier (BBB) contribute to cerebral small vessel disease (cSVD). Angiotensin II (Ang II), a vasoactive peptide of the renin-angiotensin system (RAS), is not only a pivotal molecular signal in hypertension but also causes BBB leakage, cSVD, and cognitive impair. Harpagoside, the major bioactive constituent of Scrophulariae Radix, has been commonly used for the treatment of multiple diseases including hypertension in China. The effect of harpagoside on Ang II-induced BBB damage is unclear. We employed an immortalized endothelial cell line (bEnd.3) to mimic a BBB monolayer model in vitro and investigated the effect of harpagoside on BBB and found that harpagoside alleviated Ang II-induced BBB destruction, inhibited Ang II-associated cytotoxicity in a concentration-dependent manner and attenuated Ang II-induced reactive oxygen species (ROS) impair by downregulation of Nox2, Nox4, and COX-2. Harpagoside prevented Ang II-induced apoptosis via keeping Bax/Bcl-2 balance, decreasing cytochrome c release, and inactivation of caspase-8, caspase-9, and caspase-3 (the mitochondria-dependent and death receptor-mediated apoptosis pathways). Moreover, harpagoside can alleviate Ang II-induced BBB damage through upregulation of tight junction proteins and decrease of caveolae-mediated endocytosis. Thus, harpagoside might be a potential drug to treat Ang II-induced cSVD.
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http://dx.doi.org/10.1002/ptr.7269DOI Listing
September 2021

GPER and IGF-1R mediate the anti-inflammatory effect of genistein against lipopolysaccharide (LPS)-induced nigrostriatal injury in rats.

J Steroid Biochem Mol Biol 2021 Aug 31;214:105989. Epub 2021 Aug 31.

Department of Physiology, Shandong Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines: Physiology, School of Basic Medicine, Qingdao University, Qingdao, 266071, China. Electronic address:

Neuroinflammation plays an important role in the pathogenesis of Parkinson's disease (PD). Genistein is an estrogen-like phytoestrogen that can exert biological effects via the crosstalk of estrogen receptor and insulin-like growth factor 1 receptor (IGF-1R). The present study aimed to evaluate the involvement of G protein-coupled estrogen receptor (GPER) and IGF-1R in the anti-inflammatory effects of genistein against lipopolysaccharide (LPS)-induced nigrostriatal injury in ovariectomized rats. Our results showed that genistein treatment could ameliorate the apomorphine-induced rotational behavior in LPS-induced inflammatory PD rat model. Genistein attenuated LPS-induced decrease of the contents of dopamine (DA) and its metabolites in striatum as well as the loss of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantia nigra (SN) of the lesioned side, which could be blocked by GPER antagonist G15 or IGF-1R antagonist JB1. Meanwhile, G15 or JB1 could attenuate the anti-inflammatory effects of genistein in LPS-induced microglial activation and production of tumor necrosis factor-α (TNF-α), interleukin 1β (IL-1β), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Moreover, genistein could inhibit the LPS-induced phosphorylation of p38, JNK, ERK and IκB in the lesioned side of SN and these effects could also be blocked by G15 or JB1. Taken together, our data provide the first evidence that genistein can inhibit the increase of microglia and protect dopaminergic neurons at least in part via GPER and IGF-1R signaling pathways in ovariectomized PD rat model.
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http://dx.doi.org/10.1016/j.jsbmb.2021.105989DOI Listing
August 2021

A survey of computer-aided diagnosis of lung nodules from CT scans using deep learning.

Comput Biol Med 2021 10 25;137:104806. Epub 2021 Aug 25.

Inner Mongolia Key Laboratory of Pattern Recognition and Intelligent Image Processing, School of Information Engineering, Inner Mongolia University of Science and Technology, Baotou, 014010, China; College of Information Engineering, Inner Mongolia University of Technology, Hohhot, 010051, China.

Lung cancer has one of the highest mortalities of all cancers. According to the National Lung Screening Trial, patients who underwent low-dose computed tomography (CT) scanning once a year for 3 years showed a 20% decline in lung cancer mortality. To further improve the survival rate of lung cancer patients, computer-aided diagnosis (CAD) technology shows great potential. In this paper, we summarize existing CAD approaches applying deep learning to CT scan data for pre-processing, lung segmentation, false positive reduction, lung nodule detection, segmentation, classification and retrieval. Selected papers are drawn from academic journals and conferences up to November 2020. We discuss the development of deep learning, describe several important aspects of lung nodule CAD systems and assess the performance of the selected studies on various datasets, which include LIDC-IDRI, LUNA16, LIDC, DSB2017, NLST, TianChi, and ELCAP. Overall, in the detection studies reviewed, the sensitivity of these techniques is found to range from 61.61% to 98.10%, and the value of the FPs per scan is between 0.125 and 32. In the selected classification studies, the accuracy ranges from 75.01% to 97.58%. The precision of the selected retrieval studies is between 71.43% and 87.29%. Based on performance, deep learning based CAD technologies for detection and classification of pulmonary nodules achieve satisfactory results. However, there are still many challenges and limitations remaining including over-fitting, lack of interpretability and insufficient annotated data. This review helps researchers and radiologists to better understand CAD technology for pulmonary nodule detection, segmentation, classification and retrieval. We summarize the performance of current techniques, consider the challenges, and propose directions for future high-impact research.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104806DOI Listing
October 2021

Assessing the protective effects of cryptotanshinone on CoCl‑induced hypoxia in RPE cells.

Mol Med Rep 2021 Oct 26;24(4). Epub 2021 Aug 26.

Department of Ophthalmology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.

The development of several retinal diseases is closely related to hypoxia. As a component of the Traditional Chinese medicine , the effects of cryptotanshinone (CT) on retinal cells under hypoxic conditions are not well understood. The aim of the present study was to explore how CT exerted its protective effects on retinal pigment epithelium (RPE) cells under hypoxic conditions induced by cobalt chloride (CoCl). The effects of CT were investigated using a Cell Counting Kit‑8 assay, Annexin V‑FITC/PI staining, reverse transcription‑quantitative PCR and western blotting in ARPE‑19 cells. CT (10 and 20 µM) reduced the CoCl‑induced increase in vascular endothelial growth factor expression and hypoxia‑inducible transcription factor‑1α expression in ARPE‑19 cells. Additionally, CT alleviated hypoxia‑induced apoptosis by regulating Bcl‑2 and Bax protein expression. CT treatment also reduced the increase in the mRNA levels of IL‑6, IL‑1β and TNF‑α induced by CoCl. In summary, CT may protect RPE cells against apoptosis and inflammation in CoCl‑induced hypoxia, and these results warrant further study into its value as a drug for treating hypoxic eye diseases.
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http://dx.doi.org/10.3892/mmr.2021.12379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404095PMC
October 2021

Identification of Jmjd3 as an Essential Epigenetic Regulator of Gene Temporal Collinear Activation for Body Axial Patterning in Mice.

Front Cell Dev Biol 2021 21;9:642931. Epub 2021 Jul 21.

Department of Otolaryngology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Body axial patterning develops a rostral-to-caudal sequence and relies on the temporal colinear activation of genes. However, the underlying mechanism of gene temporal colinear activation remains largely elusive. Here, with small-molecule inhibitors and conditional gene knockout mice, we identified Jmjd3, a subunit of TrxG, as an essential regulator of temporal colinear activation of genes with its H3K27me3 demethylase activity. We demonstrated that Jmjd3 not only initiates but also maintains the temporal collinear expression of genes. However, we detected no antagonistic roles between Jmjd3 and Ezh2, a core subunit of PcG repressive complex 2, during the processes of axial skeletal patterning. Our findings provide new insights into the regulation of gene temporal collinear activation for body axial patterning in mice.
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http://dx.doi.org/10.3389/fcell.2021.642931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333871PMC
July 2021

Gut Microbiota in NSAID Enteropathy: New Insights From Inside.

Front Cell Infect Microbiol 2021 6;11:679396. Epub 2021 Jul 6.

Department of Gastroenterology and Hepatology, General Hospital, Tianjin Medical University, Tianjin Institute of Digestive Diseases, Tianjin Key Laboratory of Digestive Diseases, Tianjin, China.

As a class of the commonly used drugs in clinical practice, non-steroidal anti-inflammatory drugs (NSAIDs) can cause a series of adverse events including gastrointestinal injuries. Besides upper gastrointestinal injuries, NSAID enteropathy also attracts attention with the introduction of capsule endoscopy and double balloon enteroscopy. However, the pathogenesis of NSAID enteropathy remains to be entirely clarified. Growing evidence from basic and clinical studies presents that gut microbiota is a critical factor in NSAID enteropathy progress. We have reviewed the recent data about the interplay between gut microbiota dysbiosis and NSAID enteropathy. The chronic medication of NSAIDs could change the composition of the intestinal bacteria and aggravate bile acids cytotoxicity. Meanwhile, NSAIDs impair the intestinal barrier by inhibiting cyclooxygenase and destroying mitochondria. Subsequently, intestinal bacteria translocate into the mucosa, and then lipopolysaccharide released from gut microbiota combines to Toll-like receptor 4 and induce excessive production of nitric oxide and pro-inflammatory cytokines. Intestinal injuries present in the condition of intestinal inflammation and oxidative stress. In this paper, we also have reviewed the possible strategies of regulating gut microbiota for the management of NSAID enteropathy, including antibiotics, probiotics, prebiotics, mucosal protective agents, and fecal microbiota transplant, and we emphasized the adverse effects of proton pump inhibitors on NSAID enteropathy. Therefore, this review will provide new insights into a better understanding of gut microbiota in NSAID enteropathy.
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http://dx.doi.org/10.3389/fcimb.2021.679396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290187PMC
July 2021

Skin Microbiota of the Captive Giant Panda () and the Distribution of Opportunistic Skin Disease-Associated Bacteria in Different Seasons.

Front Vet Sci 2021 5;8:666486. Epub 2021 Jul 5.

Key Laboratory of Animal Disease and Human Health of Sichuan Province, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

The giant panda is one of the rarest animals in the world. Skin diseases seriously endanger the health of giant panda and are considered the second major cause of its morbidity. Skin microbiota is a complex ecosystem, and the community structure and the pathogenic potential of bacteria on giant panda skin remain largely unclear. In order to understand the skin bacterial flora of captive giant pandas, the microbiota in giant panda skin samples collected during different seasons was profiled 16S gene sequencing. In total, 522 genera from 53 bacterial phyla were detected, with Proteobacteria (40.5%), Actinobacteria (23.1%), Firmicutes (21.1%), Bacteroidetes (9.5%), Cyanobacteria (2.1%), and Thermi (1.2%) as the predominant phyla and (13.9%), (9.2%), (2.9%), (5.9%), (4.8%), (2.9%), (2.7%), (2.1%), (1.6%), (1.5%), (1.2%), (1.1%), and (1.1%) as the predominant genera. The results indicated that the diversity was lower in winter than in other seasons and higher in autumn than in other seasons, and the abundance in spring was significantly higher than that in other seasons. Several skin disease-associated bacteria were detected as opportunists in the skin microbiota of healthy giant pandas. In this study, the results indicated that the high diversity and abundance of the skin bacteria may have enhanced the occurrence of skin disease in autumn and spring and that skin disease-associated bacteria are the normal components of the skin microbiota.
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http://dx.doi.org/10.3389/fvets.2021.666486DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8286994PMC
July 2021

Evaluating Vaccine Efficacy Against SARS-CoV-2 Infection.

Clin Infect Dis 2021 Jul 14. Epub 2021 Jul 14.

Vaccine and Infectious Disease Division, Fred Hutch, Seattle, Washington, USA.

Although interim results from several large placebo-controlled phase 3 trials demonstrated high vaccine efficacy (VE) against symptomatic COVID-19, it is unknown how effective the vaccines are in preventing people from becoming asymptomatically in- fected and potentially spreading the virus unwittingly. It is more difficult to evaluate VE against SARS-CoV-2 infection than against symptomatic COVID-19 because infection is not observed directly but rather is known to occur between two antibody or RT-PCR tests. Ad- ditional challenges arise as community transmission changes over time and as participants are vaccinated on different dates because of staggered enrollment of participants or crossover of placebo recipients to the vaccine arm before the end of the study. Here, we provide valid and efficient statistical methods for estimating potentially waning VE against SARS-CoV-2 infection with blood or nasal samples under time-varying community transmission, stag- gered enrollment, and blinded or unblinded crossover. We demonstrate the usefulness of the proposed methods through numerical studies mimicking the BNT162b2 phase 3 trial and the Prevent COVID U study. In addition, we assess how crossover and the frequency of diagnostic tests affect the precision of VE estimates.
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http://dx.doi.org/10.1093/cid/ciab630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8406869PMC
July 2021

Exploratory Analysis of Electronic Cigarette-Related Videos on YouTube: Observational Study.

Interact J Med Res 2021 Jul 6;10(3):e27302. Epub 2021 Jul 6.

Department of Clinical & Translational Research, University of Rochester Medical Center, Rochester, NY, United States.

Background: Electronic cigarette (e-cigarette) use has become more popular than cigarette smoking, especially among youth. Social media platforms, including YouTube, are a popular means of sharing information about e-cigarette use (vaping).

Objective: This study aimed to characterize the content and user engagement of e-cigarette-related YouTube videos.

Methods: The top 400 YouTube search videos related to e-cigarettes were collected in January 2020. Among them, 340 valid videos were classified into provaping, vaping-warning, and neutral categories by hand coding. Additionally, the content of e-cigarette videos and their user engagement (including average views and likes) were analyzed and compared.

Results: While provaping videos were dominant among e-cigarette-related YouTube videos from 2007 to 2017, vaping-warning videos started to emerge in 2013 and became dominant between 2018 and 2019. Compared to vaping-warning videos, provaping videos had higher average daily views (1077 vs 822) but lower average daily likes (12 vs 15). Among 161 provaping videos, videos on user demonstration (n=100, 62.11%) were dominant, and videos on comparison with smoking had the highest user engagement (2522 average daily views and 28 average daily likes). Conversely, among 141 vaping-warning videos, videos on potential health risks were the most popular topic (n=57, 40.42%) with the highest user engagement (1609 average daily views and 33 average daily likes).

Conclusions: YouTube was dominated by provaping videos, with the majority of videos on user demonstrations before 2018. The vaping-warning videos became dominant between 2018 and 2019, with videos on potential health risks being the most popular topic. This study provides updated surveillance on e-cigarette-related YouTube videos and some important guidance on associated social media regulations.
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http://dx.doi.org/10.2196/27302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292940PMC
July 2021

Socially Aware Robot Obstacle Avoidance Considering Human Intention and Preferences.

Int J Soc Robot 2021 Jul 5:1-18. Epub 2021 Jul 5.

Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, WV USA.

In order to navigate safely and effectively with humans in close proximity, robots must be capable of predicting the future motions of humans. This study first consolidates human studies in motion, intention, and preference into a discretized human model that can readily be used in robotics decision making algorithms. Cooperative Markov Decision Process (Co-MDP), a novel framework that improves upon Multiagent MDPs, is then proposed for enabling socially aware robot obstacle avoidance. Utilizing the consolidated and discretized human model, Co-MDP allows the system to (1) approximate rational human behavior and intention, (2) generate socially-aware robotic obstacle avoidance behavior, and (3) remain robust to the uncertainty of human intention and motion variance. Simulations of a human-robot co-populated environment verify Co-MDP as a feasible obstacle avoidance algorithm. In addition, the anthropomorphic behavior of Co-MDP was assessed and confirmed with a human-in-the-loop experiment. Results reveal that participants can not directly differentiate agents that were controlled by human operators from Co-MDP, and the reported confidences of their choices indicates that the predictions from participants were backed by behavioral evidence rather than random guesses. Thus the main contributions for this paper are: consolidating past human studies of rational human behavior and intention into a simple, discretized model; the development of Co-MDP: a robotic decision framework that can utilize this human model and maximize the joint utility between the human and robot; and an experimental design for evaluation of the human acceptance of obstacle avoidance algorithms.
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http://dx.doi.org/10.1007/s12369-021-00795-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8256236PMC
July 2021

Abnormal expression and methylation of PRR34-AS1 are associated with adverse outcomes in acute myeloid leukemia.

Cancer Med 2021 Aug 5;10(15):5283-5296. Epub 2021 Jul 5.

Department of Hematology, Affiliated People's Hospital of Jiangsu University, Zhenjiang, Jiangsu, People's Republic of China.

It was previously reported that PRR34-AS1 was overexpressed in some solid tumors. PRR34-AS1 promoter was shown to have a differential methylation region (DMR), and was hypomethylated in acute myeloid leukemia (AML). Therefore, the present study used real-time quantitative PCR (RQ-PCR) to explore the expression characteristics of PRR34-AS1 in AML. In addition, the correlation between the expression of PRR34-AS1 and clinical prognosis of AML was determined. The findings of this study indicated that high PRR34-AS1 expression was bound up with shorter overall survival (OS) in AML patients (p = 0.002). Moreover, patients with high expression of PRR34-AS1 had significantly lower complete remission (CR) rate compared with those with low expression of PRR34-AS1 after induction chemotherapy. Furthermore, multivariate analysis confirmed that PRR34-AS1 expression was an independent factor affecting CR in whole-AML, non-APL-AML, and CN-AML patients (p = 0.032, 0.039, and 0.036, respectively). Methylation-specific PCR (MSP) and bisulfite sequencing PCR (BSP) were used to explore the methylation status of PRR34-AS1. PRR34-AS1 promoter showed a pattern of hypomethylation in AML patients compared with normal controls (p = 0.122). Notably, of whole-AML and non-APL-AML patients, PRR34-AS1 hypomethylated patients presented a significantly shorter OS than those with a hypermethylated PRR34-AS1 (p = 0.010 and 0.037, respectively). Multivariate analysis confirmed that the hypomethylation of PRR34-AS1 served as an independent prognostic indicator in both whole-cohort AML and non-APL-AML categories (p = 0.057 and 0.018, respectively). In summary, the findings of this study showed that abnormalities in PRR34-AS1 are associated with poor prognosis in AML. Therefore, monitoring this index may be important in the prognosis of AML and can provide information on effective chemotherapy against the disease.
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http://dx.doi.org/10.1002/cam4.4085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335806PMC
August 2021

Integrated Metagenomic and Transcriptomic Analyses Reveal the Dietary Dependent Recovery of Host Metabolism From Antibiotic Exposure.

Front Cell Dev Biol 2021 18;9:680174. Epub 2021 Jun 18.

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, China.

The balance of gut microbiome is essential for maintaining host metabolism homeostasis. Despite widespread antibiotic use, the potential long-term detrimental consequences of antibiotics for host health are getting more and more attention. However, it remains unclear whether diet affects the post-antibiotic recovery of gut microbiome and host metabolism. In this study, through metagenomic sequencing and hepatic transcriptome analysis, we investigated the divergent impacts of short-term vancomycin (Vac), or combination of ciprofloxacin and metronidazole (CM) treatment on gut microbiome and host metabolism, as well as their recovery extent from antibiotic exposure on chow diet (CD) and high-fat diet (HFD). Our results showed that short-term Vac intervention affected insulin signaling, while CM induced more functional changes in the microbiome. However, Vac-induced long-term (45 days) changes of species were more apparent when recovered on CD than HFD. The effects of antibiotic intervention on host metabolism were long-lasting, antibiotic-specific, and diet-dependent. The number of differentially expressed gene was doubled by Vac than CM, but was comparable after recovery on CD as revealed by the hepatic transcriptomic analysis. In contrast, HFD intake during recovery could worsen the extent of post-antibiotic recovery by altering infection, immunity, and cancer-related pathways in short-term Vac-exposed rats and by shifting endocrine system-associated pathways in CM-exposed rats. Together, the presented data demonstrated the long-term recovery extent after different antibiotic exposure was diet-related, highlighting the importance of dietary management during post-antibiotic recovery.
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http://dx.doi.org/10.3389/fcell.2021.680174DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250461PMC
June 2021

Brain-Specific Gene Expression and Quantitative Traits Association Analysis for Mild Cognitive Impairment.

Biomedicines 2021 Jun 8;9(6). Epub 2021 Jun 8.

State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096, China.

Transcriptome-wide association studies (TWAS) have identified several genes that are associated with qualitative traits. In this work, we performed TWAS using quantitative traits and predicted gene expressions in six brain subcortical structures in 286 mild cognitive impairment (MCI) samples from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The six brain subcortical structures were in the limbic region, basal ganglia region, and cerebellum region. We identified 9, 15, and 6 genes that were stably correlated longitudinally with quantitative traits in these three regions, of which 3, 8, and 6 genes have not been reported in previous Alzheimer's disease (AD) or MCI studies. These genes are potential drug targets for the treatment of early-stage AD. Single-Nucleotide Polymorphism (SNP) analysis results indicated that cis-expression Quantitative Trait Loci (cis-eQTL) SNPs with gene expression predictive abilities may affect the expression of their corresponding genes by specific binding to transcription factors or by modulating promoter and enhancer activities. Further, baseline structure volumes and cis-eQTL SNPs from correlated genes in each region were used to predict the conversion risk of MCI patients. Our results showed that limbic volumes and cis-eQTL SNPs of correlated genes in the limbic region have effective predictive abilities.
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http://dx.doi.org/10.3390/biomedicines9060658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229744PMC
June 2021

Disruption of Jmjd3/p16 Signaling Pathway Causes Bizarre Parosteal Osteochondromatous Proliferation (BPOP)-like Lesion in Mice.

J Bone Miner Res 2021 Jun 25. Epub 2021 Jun 25.

Department of Oncology, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.

Bizarre parosteal osteochondromatous proliferation (BPOP), or Nora's lesion, is a rare benign osteochondromatous lesion. At present, the molecular etiology of BPOP remains unclear. JMJD3(KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. Previously, Jmjd3 was shown to be critical for bone development and osteoarthritis. Here, we report that conditional deletion of Jmjd3 in chondrogenic cells unexpectedly resulted in BPOP-like lesion in mice. Biochemical investigations revealed that Jmjd3 inhibited BPOP-like lesion through p16 . Immunohistochemistry and RT-qPCR assays indicated JMJD3 and p16 level were significantly reduced in human BPOP lesion compared with normal subjects. This was further confirmed by Jmjd3/Ink4a double-gene knockout mice experiments. Therefore, our results indicated the pathway of Jmjd3/p16 may be essential for the development of BPOP in human. © 2021 American Society for Bone and Mineral Research (ASBMR).
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http://dx.doi.org/10.1002/jbmr.4401DOI Listing
June 2021

Direct analysis of metabolites in the liver tissue of zebrafish exposed to fiproles by internal extractive electrospray ionization mass spectrometry.

Analyst 2021 Jul 23;146(14):4480-4486. Epub 2021 Jun 23.

Key Laboratory of Groundwater Resources and Environment of Ministry of Education, Changchun, 130012, PR China. and College of New Energy and Environment, Jilin University, Changchun, 130012, PR China.

Exploring the metabolic disturbance of fipronil and its derivatives in aquatic organisms may provide a more comprehensive understanding of the impact of fipronil on the ecological environment. In this work, internal extractive electrospray ionization mass spectrometry (iEESI-MS) was used to directly analyze metabolites in the liver tissue of zebrafish exposed to fipronil and its three derivatives. Partial least squares-discriminant analysis (PLS-DA) revealed that 32 signals were considered as differential signals in zebrafish after the exposure treatment of fipronil and its derivatives, including phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), phosphatidylethanolamines (PEs), fatty acids and so on. The pathway analysis result showed that both fipronil and its derivatives have a significant impact on the glycerophospholipid metabolism of zebrafish. Besides, the intensities of PC signals in the liver samples of each group showed such a trend: mixed fiprole exposed group > fipronil sulfone exposed group ≈ fipronil sulfide exposed group > fipronil exposed group > fipronil desulfinyl exposed group > control group, indicating that mixed exposure of fipronil and its derivatives exhibited more significant metabolic disturbance in zebrafish. Taken together, iEESI-MS is applied to environmental toxicology and investigating the metabolic disturbance induced by fipronil and its derivatives in aquatic organisms, providing a new analytical method for this field.
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http://dx.doi.org/10.1039/d1an00490eDOI Listing
July 2021

Electric signals counterbalanced posterior vs anterior PTEN signaling in directed migration of Dictyostelium.

Cell Biosci 2021 Jun 14;11(1):111. Epub 2021 Jun 14.

Department of Ophthalmology & Vision Science, UC Davis, School of Medicine, Davis, CA, 95618, USA.

Background: Cells show directed migration response to electric signals, namely electrotaxis or galvanotaxis. PI3K and PTEN jointly play counterbalancing roles in this event via a bilateral regulation of PIP3 signaling. PI3K has been proved essential in anterior signaling of electrotaxing cells, whilst the role of PTEN remains elusive.

Methods: Dictyostelium cells with different genetic backgrounds were treated with direct current electric signals to investigate the genetic regulation of electrotaxis.

Results: We demonstrated that electric signals promoted PTEN phosphatase activity and asymmetrical translocation to the posterior plasma membrane of the electrotaxing cells. Electric stimulation produced a similar but delayed rear redistribution of myosin II, immediately before electrotaxis started. Actin polymerization is required for the asymmetric membrane translocation of PTEN and myosin. PTEN signaling is also responsible for the asymmetric anterior redistribution of PIP3/F-actin, and a biased redistribution of pseudopod protrusion in the forwarding direction of electrotaxing cells.

Conclusions: PTEN controls electrotaxis by coordinately regulating asymmetric redistribution of myosin to the posterior, and PIP3/F-actin to the anterior region of the directed migration cells.
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http://dx.doi.org/10.1186/s13578-021-00580-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201722PMC
June 2021

Light-intensity switch enabled nonsynchronous growth of fluorinated raspberry-like nanoparticles.

Chem Sci 2020 Sep 10;11(38):10431-10436. Epub 2020 Sep 10.

State Key Laboratory of Molecular Engineering of Polymers, Department of Macromolecular Science, Fudan University Shanghai 200433 China http://polymaolab.com/.

Raspberry-like (RB) nanoparticles hold potential for diverse applications due to their hierarchical morphology. Here we developed a novel tandem synthetic approach of nonsynchronous growth based on photo-mediated reversible-deactivation radical polymerization, enabling simple, efficient and bottom-up synthesis of RB nanoparticles of uniform sizes at quantitative conversions of fluorinated monomers. Chain transfer agents of different chain lengths, concentrations and chemical compositions were varied to tune the diameter of RB particles. Importantly, fluorinated RB nanoparticles obtained with this method allow facile post modifications both covalent bond formation and intermolecular physical interactions without disrupting the RB morphology. The facile nature of this method and versatility of the obtained fluorinated RB materials open new opportunities for the development of functional materials using nanoparticles.
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http://dx.doi.org/10.1039/d0sc04141fDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162262PMC
September 2020
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