Publications by authors named "Yue Yang"

1,434 Publications

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Safety and Efficacy Study of Neoadjuvant Radiohormonal Therapy for Oligometastatic Prostate Cancer: Protocol of an Open-Label, Dose-Escalation, Single-Centre Phase I/II Clinical Trial.

Cancer Control 2022 Jan-Dec;29:10732748221120462

Department of Radiation Oncology, Shanghai Changhai Hospital, 12520Naval Medical University, Shanghai, China.

Background: The optimal treatment for oligometastatic prostate cancer (OMPC) is still on its way. Accumulating evidence has proven the safety and feasibility of radical prostatectomy and local or metastasis-directed radiotherapy for oligometastatic patients. The aim of this trial is to demonstrate the safety and feasibility outcomes of metastasis-directed neoadjuvant radiotherapy (naRT) and neoadjuvant androgen deprivation therapy (naADT) followed by robotic-assisted radical prostatectomy (RARP) for treating OMPC.

Methods: The present study will be conducted as a prospective, open-label, dose-escalation, phase I/II clinical trial. The patients with oligometastatic PCa will receive 1 month of naADT, followed by metastasis-directed radiation and abdominal or pelvic radiotherapy. Then, radical prostatectomy will be performed at intervals of 4-8 weeks after radiotherapy, and ADT will be continued for 2 years. The primary endpoints of the study are safety profiles, assessed by the Common Terminology Criteria for Adverse Events (CTCAE) 5.0 grading scale, and perioperativemorbidities, assessed by the Clavien-Dindo classification system. The secondary endpoints include positive surgical margin (pSM), biochemical recurrence-free survival (bPFS), radiological progression-free survival (RPFS), postoperative continence, and quality of life (QoL) parameters.

Discussion: The optimal treatment for OMPC is still on its way, prompting investigation for novel multimodality treatment protocol for this patient population. Traditionally, radical prostatectomy has been recommended as one of the standard therapies for localized prostate cancer, but indications have expanded over the years as recommended by NCCN and EAU guidelines. RP has been carried out in some centres for OMPC patients, but its value has been inconclusive, showing elevated complication risks and limited survival benefit. Neoadjuvant radiotherapy has been proven safe and effective in colorectal cancer, breast cancer and other various types of malignant tumors, showing potential advantages in terms of reducing metastatic stem-cell activity, providing clinical downstaging, and reducing potential intraoperative risks. Existing trials have shown that naRT is well tolerated for high-risk and locally-advanced prostate cancer. In this study, we hope to further determine the optimal irradiation dose and patient tolerance for genitourinary, gastrointestinal and systemic toxicities with the design of 3+3 dose escalation; also, final pathology can be obtained following RP to further determine treatment response and follow-up treatment plans.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1900025743. http://www.chictr.org.cn/showprojen.aspx?proj=43065.
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http://dx.doi.org/10.1177/10732748221120462DOI Listing
August 2022

Effect and Related Mechanism of Platelet-Rich Plasma on the Osteogenic Differentiation of Human Adipose-Derived Stem Cells.

Biomed Res Int 2022 8;2022:1256002. Epub 2022 Aug 8.

Department of Orthodontics, School and Hospital of Stomatology, China Medical University, Liaoning Provincial Key Laboratory of Oral Diseases, No. 117 Nanjing North Street, Heping District, Shenyang, 110000 Liaoning Province, China.

Objective: Human adipose-derived stem cells (hADSCs) are ideal seed cells for the regeneration of alveolar bone defects. Platelet-rich plasma (PRP), which is rich in growth factors, promotes tissue repair. The purpose of the present study was to investigate whether PRP promotes the osteogenic differentiation of hADSCs and to perform high-throughput sequencing to explore the possible mechanism.

Methods: hADSCs were divided into the three following groups: CON group, OM group, and PRP group. Osteogenesis was detected by Alizarin Red staining on day 14. Total RNA was extracted from the OM and PRP groups for high-throughput sequencing. The target genes of the differentially expressed osteogenic-related miRNAs were predicted, and combined miRNA/mRNA analysis was then performed. The mRNA and protein expression levels of hsa-miR-212-5p, type 1 cannabinoid receptor (CNR1), alkaline phosphatase (ALP), Runx2, osteocalcin (OCN), and collagen 1 A1 (COL1A1) in the OM and PRP groups were detected by qRT-PCR and Western blot analyses. The binding between hsa-miR-212-5p and CNR1 was detected by a dual-luciferase reporter assay.

Results: Both the OM and PRP groups exhibited enhanced proliferation of hADSCs, and the differences at 48 h and 72 h were statistically significant ( < 0.05). The PRP group had significantly more calcium nodules than the CON group ( < 0.05). Through high-throughput sequencing analysis, differential miRNA and mRNA expression profiles were obtained. During hADSC osteogenesis, the expression of hsa-miR-212-5p was downregulated, and the expression of CNR1 was upregulated. hsa-miR-212-5p was found to bind directly to the 3' UTR of CNR1.

Conclusions: The present findings indicated that downregulation of hsa-miR-212-5p and upregulation of CNR1 may be involved in the process by which PRP promotes the osteogenic differentiation of hADSCs.
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http://dx.doi.org/10.1155/2022/1256002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377928PMC
August 2022

Heat-shock protein 90α is a potential prognostic and predictive biomarker in hepatocellular carcinoma: a large-scale and multicenter study.

Hepatol Int 2022 Aug 16. Epub 2022 Aug 16.

Department of Medical Inspection Technology, Southwest Medical University, Luzhou, 646000, China.

Background: Although the diagnostic value of plasma heat-shock protein 90α (HSP90α) in hepatocellular carcinoma (HCC) has been previously reported, the causal effect of the plasma HSP90α levels on HCC prognosis remains largely unclear. To this extent, we sought to assess whether the plasma HSP90α acts as a prognostic factor for HCC patients.

Methods: A total of 2150 HCC patients were included in this retrospective study between August 2016 and July 2021. Plasma HSP90α levels were tested within a week before treatment and their association with prognosis was assessed.

Results: An optimal cutoff value of 143.5 for the HSP90α based on the overall survival (OS) was determined using the X-tile software. HCC patients with HSP90α < 143.5 ng/mL (low HSP90α) before and after propensity score matching (PSM) indicated longer median OS (mOS) relative to those with HSP90α ≥ 143.5 ng/mL (high HSP90α) (37.0 vs. 9.0 months, p < 0.001; 19.2 vs. 9.6 months, p < 0.001; respectively). In addition, the high HSP90α plasma level is an independent poor prognostic factor for OS in HCC patients. In our subgroup analysis, including the supportive care group, surgery group, transarterial chemoembolization (TACE) group, adjuvant TACE group, an immune checkpoint inhibitor (ICI) plus targeted therapy group, and TACE plus ICI group, the high HSP90α group demonstrated better OS compared to the low HSP90α group. Moreover, in the supportive care, TACE, ICI plus targeted therapy, TACE plus ICI groups, and high HSP90α levels were also an independent poor prognostic factors for OS.

Conclusions: Our study confirmed that the plasma HSP90α level can be used as a prognostic biomarker for HCC.
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http://dx.doi.org/10.1007/s12072-022-10391-yDOI Listing
August 2022

Photocatalytic performance of an α-FeO electrode and its effects on the growth and metabolism of Citrobacter freundii.

Appl Microbiol Biotechnol 2022 Aug 15. Epub 2022 Aug 15.

College of Life Science, Northeast Forestry University, Harbin, China.

Electronic exchanges occur between semiconductor minerals and microorganisms. However, researchers have focused on the photocatalytic degradation of pollutants by semiconductor minerals, and there is a limited amount of studies on semiconductor photogenerated electrons that influence the growth and energetic mechanisms of bacteria. Bioelectrochemical systems (BES) are important new bioengineering technologies for investigating the mechanisms by which bacteria absorb electrons. In this work, we built a BES that used α-FeO nanorods as a photoanode and Citrobacter freundii as bio-cathode bacteria to explore the effect of photoelectrons on C. freundii growth and metabolism. The photoanode was prepared by a hydrothermal synthesis method. As confirmed by X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), the photoanode was made of α-FeO. Corresponding scanning electron microscope (SEM) images showed that α-FeO nanorod arrays formed with a diameter of 50 nm, and the band gap was 2.03 eV, as indicated by UV-vis diffuse reflectance spectroscopy (UV-vis DRS). The C. freundii growth metabolism changed significantly because of photoelectrons; under light conditions, the growth rate of C. freundii significantly accelerated, and as inferred from the three-dimensional fluorescence spectrum, the protein, humic acid, and NADH concentrations were significantly higher at 72 h. According to the changes in the organic acid content, photoelectrons participated in the reductive tricarboxylic acid cycle (rTCA) to enhance growth and metabolism. The results of the study have broad implications for advancing fields that study the effects of semiconductor minerals on electroactive microorganisms and the semiconductor-photoelectronic transport mechanisms of electroautotrophic microorganisms. KEY POINTS: • For the first time, A BES was built that used α-Fe2O3 nanorods as a photoanode and C. freundii as a bio-cathode bacteria. • Photoelectrons produced by α-Fe2O3 photoelectrode promote the growth of C. freundii. • Effects of photoelectrons on C. freundii metabolism were conjectured by the changes of organic acids and NADH.
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http://dx.doi.org/10.1007/s00253-022-12120-9DOI Listing
August 2022

Intramedullary Nail or Primary Arthroplasty? A System Review and Meta-Analysis on the Prognosis of Intertrochanteric Femoral Fractures Based on Randomized Controlled Trials.

Geriatr Orthop Surg Rehabil 2022 6;13:21514593221118212. Epub 2022 Aug 6.

Department of Orthopedic Surgery, Lianyungang No. 2 People's Hospital, Lianyungang, Jiangsu, China.

Introduction: There is no consensus regarding the superiority between intramedullary nailing and primary arthroplasty in the management of intertrochanteric femoral fractures. This systematic review was performed to investigate and compare the clinical efficacy of intertrochanteric femoral fractures treated with these 2 methods.

Materials And Methods: We systematically searched PubMed, Embase, Cochrane, Web of science core collection and ClinicalTrials.gov for randomized controlled trials which compared the clinical outcomes of intertrochanteric fractures treated with either intramedullary nails or primary arthroplasty. Relevant data of the postoperative complications, reoperations, mortality and functional assessment, were pooled and presented graphically.

Results: A total of 6 trials with 427 participants were identified and included in the analyses. The pooled estimates suggested these 2 techniques have comparable risks in terms of overall complications (pooled risk ratio [RR] .80; 95% confidence interval [CI] .43 to 1.43; I = 79.94%), the rate of patients with orthopedic complications (RR .71, 95% CI .40 to 1.27; I = .00%), reoperations (RR 1.33, 95% CI .48 to 3.71; I = .00%), the overall mortality (RR .52; 95%CI .26 to 1.02; I = 31.35%) and 1-year mortality (RR .67; 95%CI .38 to 1.19; I = .00%). Primary arthroplasty associated with higher HHS at 3 months postoperatively (MD -21.95, 95% CI -28.29 to -15.60; I = 70.44%). While the difference was not significant at 6 months (MD 2.32, 95% CI -1.55 to 6.18; I = .00%), and even reversed at 12 months postoperatively (MD 13.02, 95% CI 8.14 to 17.90; I = 73.42%).

Conclusions: Meta-analytic pooling of current evidences demonstrated that primary arthroplasty is related to a better early functional recovery at the early stage postoperatively, but the long-term result tends to favor to intramedullary nailing. The differences in overall complications, the rate of patients with orthopedic complications, reoperations, overall and 1-year mortality did not reach a significant level.
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http://dx.doi.org/10.1177/21514593221118212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9364206PMC
August 2022

Predicting acupuncture efficacy for functional dyspepsia based on functional brain network features: a machine learning study.

Cereb Cortex 2022 Aug 13. Epub 2022 Aug 13.

Acupuncture and Tuina School, Acupuncture and Brain Science Research Center, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan 611137, China.

Acupuncture is effective in treating functional dyspepsia (FD), while its efficacy varies significantly from different patients. Predicting the responsiveness of different patients to acupuncture treatment based on the objective biomarkers would assist physicians to identify the candidates for acupuncture therapy. One hundred FD patients were enrolled, and their clinical characteristics and functional brain MRI data were collected before and after treatment. Taking the pre-treatment functional brain network as features, we constructed the support vector machine models to predict the responsiveness of FD patients to acupuncture treatment. These features contributing critically to the accurate prediction were identified, and the longitudinal analyses of these features were performed on acupuncture responders and non-responders. Results demonstrated that prediction models achieved an accuracy of 0.76 ± 0.03 in predicting acupuncture responders and non-responders, and a R2 of 0.24 ± 0.02 in predicting dyspeptic symptoms relief. Thirty-eight functional brain network features associated with the orbitofrontal cortex, caudate, hippocampus, and anterior insula were identified as the critical predictive features. Changes in these predictive features were more pronounced in responders than in non-responders. In conclusion, this study provided a promising approach to predicting acupuncture efficacy for FD patients and is expected to facilitate the optimization of personalized acupuncture treatment plans for FD.
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http://dx.doi.org/10.1093/cercor/bhac288DOI Listing
August 2022

EML2-S constitutes a new class of proteins that recognizes and regulates the dynamics of tyrosinated microtubules.

Curr Biol 2022 Aug 6. Epub 2022 Aug 6.

Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MI, USA. Electronic address:

Tubulin post-translational modifications (PTMs) alter microtubule properties by affecting the binding of microtubule-associated proteins (MAPs). Microtubule detyrosination, which occurs by proteolytic removal of the C-terminal tyrosine from ɑ-tubulin, generates the oldest known tubulin PTM, but we lack comprehensive knowledge of MAPs that are regulated by this PTM. We developed a screening pipeline to identify proteins that discriminate between Y- and ΔY-microtubules and found that echinoderm microtubule-associated protein-like 2 (EML2) preferentially interacts with Y-microtubules. This activity depends on a Y-microtubule interaction motif built from WD40 repeats. We show that EML2 tracks the tips of shortening microtubules, a behavior not previously seen among human MAPs in vivo, and influences dynamics to increase microtubule stability. Our screening pipeline is readily adapted to identify proteins that specifically recognize a wide range of microtubule PTMs.
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http://dx.doi.org/10.1016/j.cub.2022.07.027DOI Listing
August 2022

Cancer-associated fibroblast-like fibroblasts in vocal fold leukoplakia suppress CD8T cell functions by inducing IL-6 autocrine loop and interacting with Th17 cells.

Cancer Lett 2022 Aug 10;546:215839. Epub 2022 Aug 10.

ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, China; Shanghai Key Clinical Disciplines of Otorhinolaryngology, Shanghai, 200031, China. Electronic address:

The characteristics of fibroblast cells in head and neck precancerous lesion and its ability to secrete inflammatory cytokines and affect CD8T cell functions remain unclear. Herein, we reported the existence of fibroblasts in human-derived vocal fold leukoplakia (VFL) with positive staining of fibroblast activation protein (FAP) and α-smooth muscle actin (α-SMA). The fibroblasts from VFL and cancer-associated fibroblasts (CAFs) from head and neck squamous cell carcinoma (HNSCC) displayed similar cellular functions and robust inflammatory cytokine secretions. The effects of fibroblasts from VFL in inducing the apoptosis, depletion of CD8 T cells and recruitment of regulatory T cells (Treg cells) were observed. We further assessed the autocrine loop within VFL fibroblasts to self-stimulate by secreting IL-6, TGF-β through the IL-6/JAK2/STAT3 pathway. The synergistic stimulation of IL-6 and TGF-β promoted Th17 cell differentiation and IL-17A secretion, which could result in fibroblast activation in another positive loop. Tocilizumab (TOC), a monoclonal antibody targeting IL-6R, managed to suppress the overexpression of both IL-6 and TGF-β in VFL fibroblasts, and thus blocking IL-6 autocrine loop and CAF-Th17 loop in vitro. In a murine model of oral leukoplakia (OL), local injection of TOC inhibited the outgrowth of lesions and showed notable effect in control of OL progression in vivo. Our findings establish a novel rationale for blocking the IL-6/JAK2/STAT3 pathway to inhibit vocal fold (oral) leukoplakia progression and postpone HNSCC tumorigenesis.
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http://dx.doi.org/10.1016/j.canlet.2022.215839DOI Listing
August 2022

Isolation, identification and antihypertensive effect of novel angiotensin I-converting enzyme (ACE) inhibitory peptides from protein hydrolysate.

Food Funct 2022 Aug 10. Epub 2022 Aug 10.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China.

The side effects of traditional antihypertensive drugs have driven people's interest in the discovery of novel angiotensin-I converting enzyme (ACE) inhibitory peptides with efficiency and safety. possesses abundant proteins and is considered as a good source of bioactive peptides. To identify ACE inhibitory peptides, protein was hydrolyzed by protease K, and the hydrolysate was separated by gel permeation chromatography and reverse phase HPLC. Thirty peptide sequences were identified from the ACE inhibitory fractions by LC-MS/MS, and 15 potential ACE inhibitory peptides were further selected by combined virtual screening and experimental investigation. Among the identified peptides, TVLYEH (SpH-6, IC = 2.88 μM) and LQAGGLF (SpH-7, IC = 66.83 μM) were found to possess potent ACE inhibitory activity. The inhibition patterns of SpH-6 and SpH-7 were characterized as competitive inhibition. Molecular docking indicated that SpH-6 and SpH-7 could bind to the active pockets of ACE by forming hydrogen bonds, salt bridges and pi-pi stacking. Both SpH-6 and SpH-7 exhibited stable ACE inhibitory activity under different pH (2, 4, 6, 8, 10, 12) and temperature (0, 20, 40, 60, 80, 100 °C) conditions. The ACE inhibitory activity of SpH-6 decreased slightly after simulated gastrointestinal digestion, and SpH-7 was unstable against digestive enzymes. The antihypertensive effect demonstrated that oral administration of SpH-6 significantly reduced the systolic blood pressure and diastolic blood pressure of spontaneously hypertensive rats. The present study revealed the potential antihypertensive effects of SpH-6 and indicated that SpH-6 and protein hydrolysate could be applied as nutritional supplements for blood pressure control.
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http://dx.doi.org/10.1039/d2fo01207cDOI Listing
August 2022

Impact of Marital Status on Prognosis of Patients With Invasive Breast Cancer: A Population-Based Study Using SEER Database.

Front Oncol 2022 22;12:913929. Epub 2022 Jul 22.

Department of Breast Disease, Henan Breast Cancer Center, Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.

Objective: This study aimed to investigate the prognostic roles of marital status in patients with invasive breast cancer. Method: We extracted the data of patients with invasive breast cancer who were diagnosed during 2010-2015 and had complete staging and molecular typing from the Surveillance, Epidemiology, and End Results (SEER)-18 database. Kaplan-Meier curve method and Cox regression analysis were performed to investigate the differences in breast cancer-specific survival (BCSS) and overall survival (OS) in the total population and various subgroups with different marital statuses.

Results: Among the 324,062 patients with breast cancer in this study, 55.0%, 40.0%, and 5.0% were married, unmarried, and unknown, respectively; 51.8%, 32.2%, 10.5%, and 5.5% were patients with Stages I, II, III, and IV breast cancer, respectively. The 5-year BCSS and OS of married patients were 92.6% and 88.1%, respectively, higher than those of unmarried patients (88.3% and 78.1%, < 0.001). After adjustment for sex, age, T and N stages, histological grade, insurance status, race, year of diagnosis, and molecular subtypes, married status was an independent predictor of better BCSS [hazard ratio (HR) = 0.775, 95% confidence interval (CI) = 0.753-0.797, < 0.001) and OS (HR = 0.667, 95% CI = 0.653-0.681, < 0.001). After multivariate analysis of various subgroups of sex, age, stage, histological grade, insurance status, race, and molecular subtype, married status was an independent predictor of better BCSS in all subgroups except for Grade IV, age < 35 years, and uninsured subgroups. Marital status was an independent predictor of better OS in all subgroups except the subgroup with age <35 years.

Conclusions: In conclusion, marital status was an independent prognostic factor for breast cancer. The unmarried patients with breast cancer had a worse prognosis, except for the subgroup with age <35 years. Hence, unmarried patients with breast cancer and age ≥35 years may need additional psychosocial and emotional support to achieve more prolonged survival, besides active treatment of primary disease.
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http://dx.doi.org/10.3389/fonc.2022.913929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9355857PMC
July 2022

PPISB: A Novel Network-Based Algorithm of Predicting Protein-Protein Interactions With Mixed Membership Stochastic Blockmodel.

IEEE/ACM Trans Comput Biol Bioinform 2022 Aug 8;PP. Epub 2022 Aug 8.

Protein-protein interactions (PPIs) play an essential role for most of biological processes in cells. Many computational algorithms have thus been proposed to predict PPIs. However, most of them heavily rest on the biological information of proteins while ignoring the latent structural features of proteins presented in a PPI network. In this paper, we propose an efficient network-based prediction algorithm, namely PPISB, based on a mixed membership stochastic blockmodel. By simulating the generative process of a PPI network, PPISB is able to capture the latent community structures. The inference procedure adopted by PPISB further optimizes the membership distributions of proteins over different complexes. After that, a distance measure is designed to compute the similarity between two proteins in terms of their likelihoods of being in the same complex, thus verifying whether they interact with each other or not. To evaluate the performance of PPISB, a series of extensive experiments have been conducted with five PPI networks collected from different species and the results demonstrate that PPISB has a promising performance when applied to predict PPIs in terms of several evaluation metrics. Hence, we reason that PPISB is preferred over state-of-the-art network-based prediction algorithms especially for predicting potential PPIs.
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http://dx.doi.org/10.1109/TCBB.2022.3196336DOI Listing
August 2022

Development and validation of a liquid chromatography coupled with tandem mass spectrometry method for determining total and unbound pamiparib in human plasma and brain tumors.

Biomed Chromatogr 2022 Aug 8:e5478. Epub 2022 Aug 8.

Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI, USA.

Pamiparib (BGB-290) is an orally bioavailable, small molecule inhibitor of poly (ADP-ribose) polymerase 1 (PARP1) and PARP2. A reversed-phase LC with tandem mass spectrometry method was developed and fully validated for determining total and unbound pamiparib concentrations in human plasma and brain tumor tissue. Plasma and tissue homogenate samples were prepared by methanol protein precipitation. Pamiparib and the internal standard [ C , N ]pamiparib were separated on a Waters BEH C (50 × 2.1 mm, 1.7 μm) column, with a gradient elution consisting of mobile phases A (0.1% formic acid in water) and B (0.1% formic acid in acetonitrile) at a flow rate of 0.25 mL/min. The analytes were monitored with multiple reaction monitoring mode under positive electrospray ionization. The method was fully validated for specificity, linearity, accuracy and precision, matrix effect and recovery, and short- and long-term stability. The lower limit of quantitation was 0.5 nM of pamiparib in plasma or tissue homogenate. The calibration curve was linear over the pamiparib concentration range of 0.5-1000 nM in plasma. The intra- and inter-day precision and accuracy were within the generally accepted criteria for bioanalytical method. Pamiparib was stable in plasma at -80°C for at least 6 months. The method was successfully applied to assess the plasma and tumor pharmacokinetics of total and unbound pamiparib in patients with glioma.
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http://dx.doi.org/10.1002/bmc.5478DOI Listing
August 2022

Upregulation of CCNB2 and Its Perspective Mechanisms in Cerebral Ischemic Stroke and All Subtypes of Lung Cancer: A Comprehensive Study.

Front Integr Neurosci 2022 19;16:854540. Epub 2022 Jul 19.

Department of Pathology/Forensic Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.

Cyclin B2 (CCNB2) belongs to type B cell cycle family protein, which is located on chromosome 15q22, and it binds to cyclin-dependent kinases (CDKs) to regulate their activities. In this study, 103 high-throughput datasets related to all subtypes of lung cancer (LC) and cerebral ischemic stroke (CIS) with the data of CCNB2 expression were collected. The analysis of standard mean deviation (SMD) and summary receiver operating characteristic (SROC) reflecting expression status demonstrated significant up-regulation of CCNB2 in LC and CIS (Lung adenocarcinoma: SMD = 1.40, 95%CI [0.98-1.83], SROC = 0.92, 95%CI [0.89-0.94]. Lung squamous cell carcinoma: SMD = 2.56, 95%CI [1.64-3.48]. SROC = 0.97, 95%CI [0.95-0.98]. Lung small cell carcinoma: SMD = 3.01, 95%CI [2.01-4.01]. SROC = 0.98, 95%CI [0.97-0.99]. CIS: SMD = 0.29, 95%CI [0.05-0.53], SROC = 0.68, 95%CI [0.63-0.71]). Simultaneously, protein-protein interaction (PPI) analysis indicated that CCNB2 is the hub molecule of crossed high-expressed genes in CIS and LC. Through Multiscale embedded gene co-expression network analysis (MEGENA), a gene module of CIS including 76 genes was obtained and function enrichment analysis of the CCNB2 module genes implied that CCNB2 may participate in the processes in the formation of CIS and tissue damage caused by CIS, such as "cell cycle," "protein kinase activity," and "glycosphingolipid biosynthesis." Afterward, single-cell RNA-seq analysis, CCNB2 was found up-regulated on GABAergic neurons in brain organoids as well as T cells expressing proliferative molecules in LUAD. Concurrently, the expression of CCNB2 distributed similarly to TOP2A as a module marker of cell proliferation in cell cluster. These findings can help in the field of the pathogenesis of LC-related CIS and neuron repair after CIS damage.
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http://dx.doi.org/10.3389/fnint.2022.854540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9344069PMC
July 2022

Prevalence of Post-traumatic Stress Disorder Status Among Healthcare Workers and Its Impact on Their Mental Health During the Crisis of COVID-19: A Cross-Sectional Study.

Front Public Health 2022 19;10:904550. Epub 2022 Jul 19.

School of Health Management, Southern Medical University, Guangzhou, China.

Objective: After the unprecedented coronavirus disease 2019 (COVID-19) outbreak, the health status of the general population has suffered a huge threat, and the mental health of front-line healthcare providers has also encountered great challenges. Therefore, this study aims to: (1) investigate the prevalence and influencing factors of post-traumatic stress disorder (PTSD) among healthcare providers, and (2) verify the moderating role of self-efficacy in the influence of PTSD on mental health.

Methods: A cross-sectional study was conducted using an online survey of 1993 participants. The presence of depression, anxiety, self-efficacy, and PTSD was evaluated using screening tests from March 1. Sociodemographic and COVID-19-related data were also collected. A data analysis was performed using descriptive statistics, Pearson's correlation coefficient, and multiple linear regression.

Results: The prevalence of PTSD among healthcare providers was 9.3%. PTSD was negatively correlated with self-efficacy (r = -0.265, < 0.01), anxiety (r = -0.453, < 0.01), and depression (r = 0.708, < 0.01). Profession, daily working hours, maximum continuous working days, and daily sleep time were influencing factors of PTSD. A binary logistic regression analysis showed that physicians (OR = 2.254, 95% CI = 1.298, 3.914) and nurses (OR = 2.176, 95% CI = 1.337, 3.541) were more likely to experience PTSD than other healthcare providers.

Conclusion: Self-efficacy has a moderating effect on the influence of PTSD on anxiety and depression. This suggests that health managers need to respond to the current psychological crisis of healthcare providers, implement appropriate psychological interventions, and minimize the psychological harm caused by COVID-19.
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http://dx.doi.org/10.3389/fpubh.2022.904550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9343759PMC
August 2022

Reveal of free radicals in manganese-based catalysts and their roles during selective catalytic reduction of nitrogen oxide.

J Colloid Interface Sci 2022 Jul 18;628(Pt A):193-204. Epub 2022 Jul 18.

Materials Genome Institute, Shanghai University, 333 Nanchen Road, Shanghai 200444, China.

Hypothesis: Manganese-based catalysts attract extensive attentions in low-temperature selective catalytic reduction (SCR) of nitrogen oxide (NO). However, seldom work focuses on the existence of free radicals and their roles in SCR.

Experiments: In this work, electron paramagnetic resonance spectrometer and density functional theory are combined to reveal surface characterizations of manganese oxide and Ce/La-doped manganese oxides.

Findings: As a result, superoxide radical (O*) exists on manganese-oxide surface, produces nitrogen-containing free radical, and functions as electron transfer between NO and NH at 100 °C, resulting in good NO conversion as well as N selectivity at the same time. The O* is born of accepting electrons on adsorbed oxygen through overlapped orbits of Mn-d and O-p. Additional metal doping increases the percentage of O* among all oxygen species from 2.9 % to 6.9 % (Ce doping) and 5.1 % (La doping). The order of O* percentage is consistent with the NO-conversion order at 100 °C, i.e., Ce doping (91.6 %) > La doping (55.7 %) > catalyst without doping (27.5 %). Above result helps to understand interface behaviors of manganese-based catalyst in SCR. This work is also in favor of developing more effective low-temperature catalysts.
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http://dx.doi.org/10.1016/j.jcis.2022.07.093DOI Listing
July 2022

Novel strategy for primary epithelial cell isolation: Combination of hyaluronidase and collagenase I.

Cell Prolif 2022 Aug 3:e13320. Epub 2022 Aug 3.

Department of Geriatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, People's Republic of China.

Objective: Different strategies for epithelial cell isolation significantly affect the viability and physiological properties of primary cells. Trypsin digestion, a conventional method, causes collateral damage owing to its strong digestive potential. To better preserve the physiological properties of epithelial tissues, we aimed to develop a modified method (hyaluronidase and collagenase I combination) for primary cell isolation.

Method: We used conventional and modified methods to compare cell viability, morphology and stemness. Additionally, we investigated the passaging stability of epithelial cells and their capacity for organoid formation. Finally, we compared the two methods for isolating urothelial, oesophageal, lingual, and epidermal epithelial cells.

Result: Gingival epithelial cells obtained using the modified method had higher viability, better morphology and stronger stemness than those obtained using the conventional method. Additionally, primary cells obtained using the modified method were stably passaged. Regarding organoid culture, adopting the modified method led to a significant increase in the growth rate and expression of the stem cell markers cytokeratin (CK)-19 and Ki-67. Furthermore, the modified method outperformed the conventional method for isolating urothelial, epidermal, oesophageal and lingual epithelial cells.

Conclusion: We demonstrated that the combination of hyaluronidase and collagenase I outperformed trypsin in preserving the physiological properties of primary cells and organoid formation. The modified method could be broadly applied to isolate different types of epithelial cells and facilitate studies on organoids and tissue engineering.
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http://dx.doi.org/10.1111/cpr.13320DOI Listing
August 2022

Dao-Chi Powder Ameliorates Pancreatitis-Induced Intestinal and Cardiac Injuries Regulating the Nrf2-HO-1-HMGB1 Signaling Pathway in Rats.

Front Pharmacol 2022 11;13:922130. Epub 2022 Jul 11.

Department of Integrated Traditional Chinese and Western Medicine, West China Hospital, Sichuan University, Chengdu, China.

Dao-Chi powder (DCP) has been widely used in the treatment of inflammatory diseases in the clinical practice of traditional Chinese medicine, but has not been used in acute pancreatitis (AP). This study aimed to evaluate the effect of DCP on severe AP (SAP) and SAP-associated intestinal and cardiac injuries. To this end, an SAP animal model was established by retrograde injection of 3.5% taurocholic acid sodium salt into the biliopancreatic ducts of rats. Intragastric DCP (9.6 g/kg.BW) was administered 12 h after modeling. The pancreas, duodenum, colon, heart and blood samples were collected 36 h after the operation for histological and biochemical detection. The tissue distributions of the DCP components were determined and compared between the sham and the SAP groups. Moreover, molecular docking analysis was employed to investigate the interactions between the potential active components of DCP and its targets (Nrf2, HO-1, and HMGB1). Consequently, DCP treatment decreased the serum levels of amylase and the markers of gastrointestinal and cardiac injury, further alleviating the pathological damage in the pancreas, duodenum, colon, and heart of rats with SAP. Mechanistically, DCP rebalanced the pro-/anti-inflammatory cytokines and inhibited MPO activity and MDA levels in these tissues. Furthermore, Western blot and RT-PCR results showed that DCP intervention enhanced the expression of Nrf2 and HO-1 in the duodenum and colon of rats with SAP, while inhibiting the expression of HMGB1 in the duodenum and heart. HPLC-MS/MS analysis revealed that SAP promoted the distribution of ajugol and oleanolic acid to the duodenum, whereas it inhibited the distribution of liquiritigenin to the heart and ajugol to the colon. Molecular docking analysis confirmed that the six screened components of DCP had relatively good binding affinity with Nrf2, HO-1, and HMGB1. Among these, oleanolic acid had the highest affinity for HO-1. Altogether, DCP could alleviated SAP-induced intestinal and cardiac injuries inhibiting the inflammatory responses and oxidative stress partially through regulating the Nrf2/HO-1/HMGB1 signaling pathway, thereby providing additional supportive evidence for the clinical treatment of SAP.
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http://dx.doi.org/10.3389/fphar.2022.922130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9310041PMC
July 2022

Triphenylamine, Carbazole or Tetraphenylethylene-Functionalized Benzothiadiazole Derivatives: Aggregation-Induced Emission (AIE), Solvatochromic and Different Mechanoresponsive Fluorescence Characteristics.

Molecules 2022 Jul 25;27(15). Epub 2022 Jul 25.

Jiangxi Key Laboratory of Organic Chemistry, Jiangxi Science and Technology Normal University, Nanchang 330013, China.

The development of mechanochromic fluorophors with high-brightness, solid-state fluorescence is very significant and challenging. Herein, highly solid-state emissive triphenylamine, carbazole and tetraphenylethylene-functionalized benzothiadiazole derivatives were developed. These compounds showed remarkable aggregation-induced emission and solvatochromic fluorescence characteristics. Furthermore, these fluorogenic compounds also displayed different mechanically triggering fluorescence responses.
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http://dx.doi.org/10.3390/molecules27154740DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9331885PMC
July 2022

Spectral fiber photometry derives hemoglobin concentration changes for accurate measurement of fluorescent sensor activity.

Cell Rep Methods 2022 Jul 29;2(7):100243. Epub 2022 Jun 29.

Center for Animal MRI, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.

Fiber photometry is an emerging technique for recording fluorescent sensor activity in the brain. However, significant hemoglobin absorption artifacts in fiber photometry data may be misinterpreted as sensor activity changes. Because hemoglobin exists widely in the brain, and its concentration varies temporally, such artifacts could impede the accuracy of photometry recordings. Here we present use of spectral photometry and computational methods to quantify photon absorption effects by using activity-independent fluorescence signals, which can be used to derive oxy- and deoxy-hemoglobin concentration changes. Although these changes are often temporally delayed compared with the fast-responding fluorescence spikes, we found that erroneous interpretation may occur when examining pharmacology-induced sustained changes and that sometimes hemoglobin absorption could flip the GCaMP signal polarity. We provide hemoglobin-based correction methods to restore fluorescence signals and compare our results with other commonly used approaches. We also demonstrated the utility of spectral fiber photometry for delineating regional differences in hemodynamic response functions.
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http://dx.doi.org/10.1016/j.crmeth.2022.100243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308135PMC
July 2022

Absorbable Artificial Dura Versus Nonabsorbable Artificial Dura in Decompressive Craniectomy for Severe Traumatic Brain Injury: A Retrospective Cohort Study in Two Centers.

Front Surg 2022 1;9:877038. Epub 2022 Jul 1.

Department of Neurosurgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Severe traumatic brain injury (TBI) patients usually need decompressive craniectomy (DC) to decrease intracranial pressure. Duraplasty is an important step in DC with various dura substitute choices. This study aims to compare absorbable dura with nonabsorbable dura in duraplasty for severe TBI patients.

Methods: One hundred and three severe TBI patients who underwent DC and dura repair were included in this study. Thirty-nine cases used absorbable artificial dura (DuraMax) and 64 cases used nonabsorbable artificial dura (NormalGEN). Postoperative complications, mortality and Karnofsky Performance Scale (KPS) score in one year were compared in both groups.

Results: Absorbable dura group had higher complication rates in transcalvarial cerebral herniation (TCH) (43.59% in absorbable dura group vs. 17.19% in nonabsorbable dura group,  = 0.003) and CSF leakage (15.38% in absorbable dura group vs. 1.56% in nonabsorbable dura group,  = 0.021). But severity of TCH described with hernial distance and herniation volume demonstrated no difference in both groups. There was no statistically significant difference in rates of postoperative intracranial infection, hematoma progression, secondary operation, hydrocephalus, subdural hygroma and seizure in both groups. KPS score in absorbable dura group (37.95 ± 28.58) was statistically higher than nonabsorbable dura group (49.05 ± 24.85) in one year after operation ( = 0.040), while no difference was found in the rate of functional independence (KPS ≥ 70). Besides, among all patients in this study, TCH patients had a higher mortality rate ( = 0.008), lower KPS scores ( < 0.001) and lower functionally independent rate ( = 0.049) in one year after surgery than patients without TCH.

Conclusions: In terms of artificial biological dura, nonabsorbable dura is superior to absorbable dura in treatment of severe TBI patients with DC. Suturable nonabsorbable dura has fewer complications of TCH and CFS leakage, and manifest lower mortality and better prognosis. Postoperative TCH is an important complication in severe TBI which usually leads to a poor prognosis.
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http://dx.doi.org/10.3389/fsurg.2022.877038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9295144PMC
July 2022

Ferroelectric Single-Molecule Magnet with Toroidal Magnetic Moments.

Adv Sci (Weinh) 2022 Jul 20:e2202979. Epub 2022 Jul 20.

Key Laboratory of Advanced Energy Materials Chemistry (MOE), Haihe Laboratory of Sustainable Chemical Transformations (Tianjin), Renewable Energy Conversion and Storage Center, College of Chemistry, Nankai University, Tianjin, 300071, P. R. China.

Materials that coexist magnetic and electric properties on the molecular scale in single-molecule magnets (SMMs) with peculiar quantum behaviors have promise in molecular electronics and spintronics. Nevertheless, such molecular materials are limited in potentials because their magnetic signal cannot be transformed into an electrical signal through magnetoresistance or Hall effects for their high insulativity. The discovery of an entirely new material, ferroelectric SMMs (FE SMMs) is reported. This FE SMM also shows single-molecule magnetic behaviors, toroidal magnetic moments, and room-temperature ferroelectricity. The toroidal moment is formed by a vortex distribution of magnetic dipoles in triangular Dy clusters. The analysis of ac magnetic susceptibility reveals the coexistence of three distinct magnetic relaxation processes at low temperatures. The ferroelectricity is introduced by incorporating polar alcohol molecules in the structure, which is confirmed by the X-ray diffraction and optical second harmonic generation (SHG) measurements. Moreover, the dielectric measurements reveal a ferroelectric-to-ferroelectric phase transition around 150 K due to the symmetry change from Pc to Pna2 . The coexistence of toroidal moment and ferroelectricity along with quantum magnetism in the rare-earth single-molecule magnets yields a unique class of multiferroics.
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http://dx.doi.org/10.1002/advs.202202979DOI Listing
July 2022

Selective generation of narrow-band harmonics by a relativistic laser pulse interaction with a detuned plasma grating.

Phys Rev E 2022 Jun;105(6-2):065207

Research Center of Laser Fusion, CAEP, P. O. Box 919 986, Mianyang 621900, China.

The spectral characteristics of high-order harmonics generated by the interaction of a linearly polarized relativistic laser pulse with a plasma grating target are investigated. Through particle-in-cell simulations and an analytical model, it is shown that a plasma grating target with periodic structure can select special harmonics with integer multiples of the grating frequency, and that low-order harmonics with frequencies being integer times of the laser frequency are generated nearly parallel to the target surface from a Fresnel zone plate target with an aperiodic structure. Spectral control of the harmonics can be achieved by introducing a correction factor β to the radius formula of the Fresnel zone plate, which can create a slightly detuned plasma grating, and then only the narrow-band harmonics can be selected nearly parallel to the target surface. The center order of the narrow-band harmonics can be tuned by adjusting the correction factor β, while the bandwidth of the harmonics can be selected by adjusting the other parameter λ_{f} of the detuned plasma grating.
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http://dx.doi.org/10.1103/PhysRevE.105.065207DOI Listing
June 2022

Ginsenoside Rg1 improved diabetes through regulating the intestinal microbiota in high-fat diet and streptozotocin-induced type 2 diabetes rats.

J Food Biochem 2022 Jul 19:e14321. Epub 2022 Jul 19.

Faculty of Basic Medical Science, Kunming Medical University, Kunming, China.

Ginsenoside Rg1 is the active ingredient of the plant named genus Panax (ginseng), which exhibited significant bioactivities, including anti-inflammatory, antioxidation, and anti-diabetic effects. Herein, 4-week treatment of ginsenoside Rg1 remarkably decreased blood glucose levels and improved the resistance of insulin, oxidative stress, and inflammation along with lipid profile in T2D rats triggered via high-fat diet and streptozotocin (STZ). Ginsenoside Rg1 supplementation improved the intestinal microbial composition induced by type 2 diabetes (T2D), which increased the proportions of Lachnospiraceae_NK4A136_group and Lachnoclostridium and decreased the proportions of Lactobacillus. Additionally, Spearman's correlation test between the gut microflora and biomedical assays (|r| > .5) revealed that the Lachnospiraceae_NK4A136_group, Roseburia, and Romboutsia greatly affect intestinal microbiota, which may play pivotal roles in preventing T2D. Our findings illustrate the use of ginsenoside Rg1 as a dietary supplement along with prospective prebiotics due to its ability to alter the gut microflora and alleviate T2D-linked biochemical abnormalities. PRACTICAL APPLICATIONS: This was the first study to elucidate the influences of ginsenosides Rg1 in improving the intestinal microbiota of T2D in SD rats. The data illustrated that the ginsenosides Rg1 remarkably increased the proportions of SCFAs producing bacteria. Hence, ginsenoside Rg1 could be used as a potential prebiotic in the treatment of T2D through alteration of intestinal microbiota.
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http://dx.doi.org/10.1111/jfbc.14321DOI Listing
July 2022

Low molecular weight fucoidan alleviates cerebrovascular damage by promoting angiogenesis in type 2 diabetes mice.

Int J Biol Macromol 2022 Jul 13;217:345-355. Epub 2022 Jul 13.

CAS and Shandong Province Key Laboratory of Experimental Marine Biology, Center for Ocean Mega-Science, Institute of Oceanology, Chinese Academy of Sciences, Qingdao, China; Laboratory for Marine Biology and Biotechnology, Pilot Pilot National Laboratory for Marine Science and Technology, Qingdao, China. Electronic address:

Diabetes leading to brain glucose metabolism disorders and cerebrovascular complications. Fucoidan is a kind of sulfated polysaccharides which found in brown algae, has multiply bioactivities and considered to be a promising therapeutic agent. Despite the increasing amount of evidence suggesting the diabetes protective role of fucoidans, the effect of fucoidan on brain abnormalities in type 2 diabetes mellitus patients remains unclear. In this study a low molecular weight fucoidan (LMWF) was obtained from Saccharina japonica and its effect on the cerebrovascular damage in db/db mice was investigated. Results were shown after LMWF treatment, the degree of cerebrovascular damage, the number of apoptotic neuronal cells and the inflammation were all decreased in db/db mice. Moreover, LMWF could up-regulates CD34 and VEGFA expression in db/db mice brain, and the subintestinal vessel angiogenesis in zebrafish was also promoted by LMWF. Moreover, the lumen formation of HUVEC endothelial cells was rescued by LMWF which was destroyed in high glucose treated endothelial cells. Further study found, LMWF alleviates vascular injury by up-regulating the expression level of phosphorylated PI3K and phosphorylated AKT. Our study indicates that LMWF has the potential to develop a cerebrovascular protection agent for type 2 diabetes patients.
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http://dx.doi.org/10.1016/j.ijbiomac.2022.07.053DOI Listing
July 2022

Comprehensive transcriptomic and co-expression analysis of ABL1 gene and molecularly targeted drugs in hepatocellular carcinoma based on multi-database mining.

Med Oncol 2022 Jul 14;39(10):146. Epub 2022 Jul 14.

Zhu's Team, Guangdong Medical University, Zhanjiang, China.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death worldwide. Consequently, it is essential to identify biomarkers for treatment response and the prognosis prediction. We investigated whether ABL1 can function as a biomarker or a drug target for HCC. We assessed the ABL1 expression, genetic alterations and patients' survival from LinkedOmics, GEO, TCGA and Human Protein Atlas. We analyzed PPI, GO and KEGG pathways. GSEA was analyzed for functional comparison. The current drugs targeting ABL1 were statistically analyzed using DRUGSURV and DGIdb database. We found ABL1 is overexpressed in HCC and its higher expression reduces survival probability. Genetic changes of ABL1 are not frequent. We screened out 25 differentially expressed genes correlated with ABL1. The top functions of ABL1 are biological regulation, metabolic process, protein-containing, and protein binding. KEGG pathways showed that ABL1 and correlated with ABL1 significantly genes markedly enriched in the ErbB signaling pathway, and pathways in cancer. We counted the existing drugs targeting ABL1, which indicates that inhibiting ABL1 expression may improve the survival probability of HCC. In conclusion, ABL1 plays a crucial role in the development and progression of this cancerization and is a potential drug target.
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http://dx.doi.org/10.1007/s12032-022-01730-yDOI Listing
July 2022

Safety-Related Drug Withdrawals in China Between 1999 and 2021: A Systematic Investigation and Analysis.

Drug Saf 2022 Jul 12;45(7):737-745. Epub 2022 Jul 12.

School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.

Introduction: The Chinese National Medical Products Administration (NMPA) has emphasized proactive pharmacovigilance throughout the product life cycle in recent years. However, the safety-related withdrawal of drugs from the Chinese market has received less attention.

Objectives: The primary aim of the study was to investigate the context of withdrawing a drug for safety reasons in China (between 1999 and 2021).

Methods: Withdrawn drugs were first identified from the Chinese NMPA and United States (US) Food and Drug Administration websites and the World Health Organization's (WHO's) consolidated list of products, WHO Drug Information, and WHO Pharmaceuticals Newsletter. We then searched the China National Knowledge Internet database, Chongqing VIP information database, Wanfang database, PubMed, and Google Scholar for drug withdrawal details. We used the Oxford Centre for Evidence-Based Medicine criteria to assess the levels of evidence that support withdrawing a drug.

Results: A total of 30 drugs were withdrawn from the Chinese market between 1999 and 2021. The number of withdrawals increased during the stable Chinese drug surveillance period (2012-2021). Evidence from case-series or case-control studies was primarily used to determine the withdrawals of 16 drugs (53.3%). Fifteen drugs were withdrawn from the markets of China and the US, including five drugs (5/15, 33.3%) that were withdrawn in the same year in China and the US.

Conclusions: The promulgation of regulations and development of advanced passive and active systems have enhanced pharmacovigilance in China. High-quality evidence, coordination with other regulatory authorities, and communication and information sharing should be strengthened to optimize drug safety surveillance and risk management.
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http://dx.doi.org/10.1007/s40264-022-01185-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9296427PMC
July 2022

Structural insight into apelin receptor-G protein stoichiometry.

Nat Struct Mol Biol 2022 Jul 11;29(7):688-697. Epub 2022 Jul 11.

iHuman Institute, ShanghaiTech University, Shanghai, China.

The technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report describes the structural characterization of a fully active human apelin receptor (APJR) complexed with heterotrimeric G protein observed in both 2:1 and 1:1 stoichiometric ratios. We use cryo-EM single-particle analysis to determine the structural details of both species from the same sample preparation. Protein preparations, in the presence of the endogenous peptide ligand ELA or a synthetic small molecule, both demonstrate these mixed stoichiometric states. Structural differences in G protein engagement between dimeric and monomeric APJR suggest a role for the stoichiometry of G protein-coupled receptor- (GPCR-)G protein coupling on downstream signaling and receptor pharmacology. Furthermore, a small, hydrophobic dimer interface provides a starting framework for additional class A GPCR dimerization studies. Together, these findings uncover a mechanism of versatile regulation through oligomerization by which GPCRs can modulate their signaling.
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http://dx.doi.org/10.1038/s41594-022-00797-5DOI Listing
July 2022

Nitrate pollution source apportionment, uncertainty and sensitivity analysis across a rural-urban river network based on δN/δO-NO isotopes and SIAR modeling.

J Hazard Mater 2022 Jun 28;438:129480. Epub 2022 Jun 28.

Key Laboratory of Watershed Science and Health of Zhejiang Province, School of Public Health and Management, Wenzhou Medical University, Wenzhou 325035, China; Southern Zhejiang Water Research Institute, Wenzhou 325035, China; Department of Land, Air and Water Resources, University of California, Davis, CA 95616, USA. Electronic address:

Nitrate pollution is of considerable global concern as a threat to human health and aquatic ecosystems. Nowadays, δN/δO-NO combined with a Bayesian-based SIAR model are widely used to identify riverine nitrate sources. However, little is known regarding the effect of variations in pollution source isotopic composition on nitrate source contributions. Herein, we used δN/δO-NO, SIAR modeling, probability statistical analysis and a perturbing method to quantify the contributions and uncertainties of riverine nitrate sources in the Wen-Rui Tang River of China and to further investigate the model sensitivity of each nitrate source. The SIAR model confirmed municipal sewage (MS) as the major nitrate source (58.5-75.7%). Nitrogen fertilizer (NF, 8.6-20.9%) and soil nitrogen (SN, 7.8-20.1%) were also identified as secondary nitrate sources, while atmospheric deposition (AD, <0.1-7.9%) was a minor source. Uncertainties associated with NF (UI = 0.32) and SN (UI = 0.30) were high, whereas those associated with MS (UI = 0.14) were moderate and AD low (UI = 0.0087). A sensitivity analysis was performed for the SIAR modeling and indicated that the isotopic composition of the predominant source (i.e., MS in this study) had the strongest effect on the overall riverine nitrate source apportionment results.
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http://dx.doi.org/10.1016/j.jhazmat.2022.129480DOI Listing
June 2022

The powerful brain: Neural correlates of sense of power and hope.

Neuropsychologia 2022 Jul 8;174:108317. Epub 2022 Jul 8.

Key Laboratory of Cognition and Personality, Ministry of Education, Faculty of Psychology, Southwest University, Chongqing, China. Electronic address:

A sense of power refers to the perception that one can control and influence others' states by providing or withholding valued resources in an asymmetrical way, and which has been associated with greater hope. However, little is known about the neural bases underlying this association. The present study aimed to examine these phenomena in 261 healthy adolescent students by assessing resting-state brain activity (i.e., the amplitude of low-frequency fluctuations, ALFF) and connectivity (i.e., resting-state functional connectivity, RSFC). Whole-brain correlation analyses revealed that higher levels of perceived power were linked with reduced ALFF in the left thalamus and increased RSFC between the left thalamus and left superior temporal gyrus. Mediation analyses further showed that perceived power mediated the influence of the left thalamus activity on hope. Our results remained significant even after controlling for the head motion, age, and gender. Our findings contribute to the neurobiological basis of a sense of power and the neural mechanism underlying the relationship between a sense of power and hope.
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http://dx.doi.org/10.1016/j.neuropsychologia.2022.108317DOI Listing
July 2022

Neurexin and frizzled intercept axonal transport at microtubule minus ends to control synapse formation.

Dev Cell 2022 Aug 8;57(15):1802-1816.e4. Epub 2022 Jul 8.

Department of Neuroscience, Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06510, USA. Electronic address:

Synapse formation is locally determined by transmembrane proteins, yet synaptic material is synthesized remotely and undergoes processive transport in axons. How local synaptogenic signals intercept synaptic cargo in transport to promote its delivery and synapse formation is unknown. We found that the control of synaptic cargo delivery at microtubule (MT) minus ends mediates pro- and anti-synaptogenic activities of presynaptic neurexin and frizzled in C. elegans and identified the atypical kinesin VAB-8/KIF26 as a key molecule in this process. VAB-8/KIF26 levels at synaptic MT minus ends are controlled by frizzled and neurexin; loss of VAB-8 mimics neurexin mutants or frizzled hyperactivation, and its overexpression can rescue synapse loss in these backgrounds. VAB-8/KIF26 is required for the synaptic localization of other minus-end proteins and promotes the pausing of retrograde transport to allow delivery to synapses. Consistently, reducing retrograde transport rescues synapse loss in vab-8 and neurexin mutants. These results uncover a mechanistic link between synaptogenic signaling and axonal transport.
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http://dx.doi.org/10.1016/j.devcel.2022.06.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9378695PMC
August 2022
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