Publications by authors named "Zhou Zhu"

232 Publications

Artificial neural network and decision tree models of post-stroke depression at 3 months after stroke in patients with BMI ≥ 24.

J Psychosom Res 2021 Nov 2;150:110632. Epub 2021 Oct 2.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei 430030, China. Electronic address:

Objective: Previous studies have shown that excess weight (including obesity and overweight) can increase the risk of cardiovascular, cerebrovascular and other diseases, but there is no study on the incidence of post-stroke depression (PSD) and related factors in patients with excessive weight. The main purpose of this study was to find related factors of PSD at 3 months after stroke in patients with excessive weight and construct artificial neural network (ANN) and decision tree (DT) models.

Methods: This is a prospective multicenter cohort study (Registration number: ChiCTR-ROC-17013993). Five hundred and three stroke patients with Body Mass Index(BMI) ≥ 24 were included in this study. The diagnostic criteria of PSD is according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-V) diagnostic criteria for depression due to other medical conditions and the HAMD-17 scores > 7 at 3 months after stroke was used as the primary endpoint. The χ test, Mann-Whitney U test or t-test were used to check for statistical significance.

Results: Our study found that sleeping time < 5 h, CHD, physical exercise, BI score, N dimension(EPQ) and subjective support(SSRS) were associated with PSD in patients with excessive weight. Physical exercise(odd ratio [OR] = 0.49, p = 0.001, 95%CI [confidence interval]: 0.32-0.75) and BI score(OR = 0.99, p < 0.001, 95%CI: 0.98-0.99) were protective factors; sleeping time < 5 h(OR = 2.86, p < 0.001, 95%CI: 1.62-5.04), CHD(OR = 2.18, p = 0.018, 95%CI: 1.14-4.15), N dimension(OR = 1.08, p = 0.001, 95%CI: 1.03-1.13) and subjective support(OR = 1.04, p = 0.022, 95%CI: 1.01-1.07) were risk factors.

Conclusion: This study found several factors related to the occurrence of PSD at 3 months in patients with excessive weight. Meanwhile, ANN and DT models were constructed for clinicians to use.
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http://dx.doi.org/10.1016/j.jpsychores.2021.110632DOI Listing
November 2021

Higher fasting C-peptide is associated with post-stroke depression: a multicenter prospective cohort study.

BMC Neurol 2021 Oct 4;21(1):383. Epub 2021 Oct 4.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, Hubei, China.

Background: Fasting C-peptide (FCP) has been shown to play an important role in the pathophysiology of mood disorders including depression and schizophrenia, but it is unknown whether it also predicts post-stroke depression (PSD). This study examined the association between FCP and PSD at 6 months after acute ischemic-stroke onset among Chinese subjects.

Methods: A total of 656 stroke patients were consecutively recruited from three hospitals of Wuhan city, Hubei province. Clinical and laboratory data were collected on admission. PSD status was evaluated by DSM-V criteria and 17-item Hamilton Rating Scale for Depression (HAMD-17) at 6 months after acute ischemic stroke. The χ2-test, Mann-Whitney U-test, and t-test were used to check for statistical significance. Multivariate logistic regression model was used to explore independent predictor of PSD.

Results: In the univariate analysis, significant differences were found between the PSD and non-PSD groups in terms of FCP level (p = 0.009). After multivariate adjustments, FCP remained a significant independent predictor of PSD, with an adjusted odds ratio of 1.179 (95%CI: 1.040-1.337, p = 0.010).

Conclusions: Higher FCP levels on admission were found to be associated with PSD at 6 months after acute ischemic-stroke onset. For stroke patients, doctors should pay attention to the baseline FCP for screening high-risk PSD in clinical practice.
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http://dx.doi.org/10.1186/s12883-021-02413-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489065PMC
October 2021

Soluble epoxide hydrolase inhibitor attenuates BBB disruption and neuroinflammation after intracerebral hemorrhage in mice.

Neurochem Int 2021 Nov 27;150:105197. Epub 2021 Sep 27.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, PR China. Electronic address:

Intracerebral hemorrhage (ICH) is a devastating disease with high mortality and morbidity. Soluble epoxide hydrolase (sEH) is the key enzyme in the epoxyeicosatrienoic acids (EETs) signaling. sEH inhibition has been demonstrated to have neuroprotective effects against multiple brain injuries. However, its role in the secondary injuries after ICH has not been fully elucidated. Here we tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and the secondary injuries after ICH. Adult male C57BL/6 mice were subjected to a collagenase-induced ICH model. TPPU alleviated blood-brain barrier damage, inhibited inflammatory response, increased M2 polarization of microglial cells, reduced the infiltration of peripheral neutrophils. In addition, TPPU attenuated neuronal injury and promoted functional recovery. The results suggest that sEH may represent a potential therapeutic target for the treatment of ICH.
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http://dx.doi.org/10.1016/j.neuint.2021.105197DOI Listing
November 2021

Time effect of rutaecarpine on caffeine pharmacokinetics in rats.

Biochem Biophys Rep 2021 Dec 6;28:101121. Epub 2021 Sep 6.

Department of Chemistry, York College, City University of New York, NY, USA.

Rutaecarpine is reported as a potent inducer of CYP1A2 enzyme in rats. There are natural herbal supplements containing rutaecarpine that are designed to enhance the CYP1A2-dependent removal of caffeine from blood so that people can have coffee later in the day without causing sleep interference. This study aimed to determine the minimum amount of time needed from oral rutaecarpine administration until the observed effect of rutaecarpine on caffeine pharmacokinetics (PK) in 15 male Sprague-Dawley rats. PK parameters for caffeine and its metabolites in the control and rutaecarpine groups were calculated using WinNonlin®. Results showed that orally administered rutaecarpine at 100 mg/kg dose as early as 3 h before oral caffeine administration significantly decreased the oral systemic exposure and mean residence time of caffeine and its metabolites due to decreased caffeine bioavailability (by up to 75%) and increased clearance. The systemic exposure of caffeine and its metabolites were also decreased when caffeine was given intravenously, though this effect was less pronounced than when caffeine was given orally. Although plasma level of rutaecarpine was undetectable (less than 10 ng/mL), rutaecarpine still induced hepatic CYP1A2 activity. Results from 7-methoxyresorufin O-demethylation activity, which is specific to CYP1A2, showed that 3 h after one rutaecarpine oral dose, CYP1A2 activity in rat liver tissue was increased by 3- fold. This finding suggested that rutaecarpine effectively induced CYP1A2 activity in the liver.
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http://dx.doi.org/10.1016/j.bbrep.2021.101121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429912PMC
December 2021

Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor.

Cancer Cell 2021 Oct 13;39(10):1404-1421.e11. Epub 2021 Sep 13.

Pfizer Global Research and Development La Jolla, 10770 Science Center Drive, San Diego, CA 92121, USA.

The CDK4/6 inhibitor, palbociclib (PAL), significantly improves progression-free survival in HR/HER2 breast cancer when combined with anti-hormonals. We sought to discover PAL resistance mechanisms in preclinical models and through analysis of clinical transcriptome specimens, which coalesced on induction of MYC oncogene and Cyclin E/CDK2 activity. We propose that targeting the G kinases CDK2, CDK4, and CDK6 with a small-molecule overcomes resistance to CDK4/6 inhibition. We describe the pharmacodynamics and efficacy of PF-06873600 (PF3600), a pyridopyrimidine with potent inhibition of CDK2/4/6 activity and efficacy in multiple in vivo tumor models. Together with the clinical analysis, MYC activity predicts (PF3600) efficacy across multiple cell lineages. Finally, we find that CDK2/4/6 inhibition does not compromise tumor-specific immune checkpoint blockade responses in syngeneic models. We anticipate that (PF3600), currently in phase 1 clinical trials, offers a therapeutic option to cancer patients in whom CDK4/6 inhibition is insufficient to alter disease progression.
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http://dx.doi.org/10.1016/j.ccell.2021.08.009DOI Listing
October 2021

Ilexsaponin A1: In vitro metabolites identification and evaluation of inhibitory drug-drug interactions.

Drug Metab Pharmacokinet 2021 Oct 2;40:100415. Epub 2021 Aug 2.

Department of Chemistry, York College, City University of New York, New York, 11451, USA. Electronic address:

As a triterpene saponin, ilexsaponin A1 is one of the most abundant, representative and active components in plants of Ilex pubescens, used in the treatment of cardiovascular diseases. This study aimed to identify the metabolites of ilexsaponin A1 and evaluate its in vitro inhibitory drug-drug interaction (DDI) potential by using human liver microsomes (HLM) and cytochrome P450 enzymes (CYPs)-specific probes, with all the qualitative and quantitative analysis performed by LC-MS/MS. As a result, two metabolites generated through the metabolic pathways of glucuronic acid conjugation and glucose conjugation were first time detected in the HLM. An inhibitory DDI evaluating system consisting of 7 major CYP enzymes involving 8 CYP-catalyzed reactions was established, validated and then used for the DDI evaluation. Our data suggested ilexsaponin A1 and its metabolite, ilexgenin A, are not direct or mechanism-based inhibitors of CYP1A2, 2B6, 2C8, 2C9, 2D6, 2E1 or 3A4/5 at 0.05-10 μM. A significant decreased remaining activity of CYP2B6 (from 77.89 % to 23.19 %) was observed in a dose-dependent manner when increased the concentration of ilexsaponin A1 from 50 to 500 μM. Collectively, our data demonstrate ilexsaponin A1 is unlikely to cause DDIs by inhibiting co-administered drugs metabolized by these CYP enzymes.
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http://dx.doi.org/10.1016/j.dmpk.2021.100415DOI Listing
October 2021

TFEB, a master regulator of autophagy and biogenesis, unexpectedly promotes apoptosis in response to the cyclopentenone prostaglandin 15d-PGJ2.

Acta Pharmacol Sin 2021 Aug 20. Epub 2021 Aug 20.

Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China.

Transcriptional factor EB (TFEB), a master regulator of autophagy and lysosomal biogenesis, is generally regarded as a pro-survival factor. Here, we identify that besides its effect on autophagy induction, TFEB exerts a pro-apoptotic effect in response to the cyclopentenone prostaglandin 15-deoxy-∆--prostaglandin J2 (15d-PGJ2). Specifically, 15d-PGJ2 promotes TFEB translocation from the cytoplasm into the nucleus to induce autophagy and lysosome biogenesis via reactive oxygen species (ROS) production rather than mTORC1 inactivation. Surprisingly, TFEB promotes rather than inhibits apoptosis in response to 15d-PGJ2. Mechanistically, ROS-mediated TFEB translocation into the nucleus transcriptionally upregulates the expression of ATF4, which is required for apoptosis elicited by 15d-PGJ2. Additionally, inhibition of TFEB activation by ROS scavenger N-acetyl cysteine or inhibition of protein synthesis by cycloheximide effectively compromises ATF4 upregulation and apoptosis in response to 15d-PGJ2. Collectively, these results indicate that ROS-induced TFEB activation exerts a novel role in promoting apoptosis besides its role in regulating autophagy in response to 15d-PGJ2. This work not only evidences how TFEB is activated by 15d-PGJ2, but also unveils a previously unexplored role of ROS-dependent activation of TFEB in modulating cell apoptosis in response to 15d-PGJ2.
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http://dx.doi.org/10.1038/s41401-021-00711-7DOI Listing
August 2021

Cytoplasmic and nuclear genome variations of rice hybrids and their parents inform the trajectory and strategy of hybrid rice breeding.

Mol Plant 2021 Aug 11. Epub 2021 Aug 11.

National Center for Gene Research, State Key Laboratory of Plant Molecular Genetics, Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200233, China. Electronic address:

The male sterility (MS) line is a prerequisite for efficient production of hybrid seeds in rice, a self-pollinating species. MS line breeding is pivotal for hybrid rice improvement. Understanding the historical breeding trajectory will help to improve hybrid rice breeding strategies. Maternally inherited cytoplasm is an appropriate tool for phylogenetic reconstruction and pedigree tracing in rice hybrids. In this study, we analyzed the cytoplasmic genomes of 1495 elite hybrid rice varieties and identified five major types of cytoplasm, which correspond to different hybrid production systems. As the cytoplasm donors for hybrids, 461 MS lines were also divided into five major types based on cytoplasmic and nuclear genomic architecture. Specific core accessions cooperating with different fertility-associated genes drove the sequence divergence of MS lines. Dozens to hundreds of convergent and divergent selective sweeps spanning several agronomic trait-associated genes were identified among different types of MS lines. We further analyzed the cross patterns between different types of MS lines and their corresponding restorers. This study systematically analyzed the cytoplasmic genomes of rice hybrids revealed their relationships with nuclear genomes of MS lines, and illustrated the trajectory of hybrid rice breeding and the strategies for breeding different types of MS lines providing new insights for future improvement of hybrid rice.
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http://dx.doi.org/10.1016/j.molp.2021.08.007DOI Listing
August 2021

Identification of four gastric cancer subtypes based on genetic analysis of cholesterogenic and glycolytic pathways.

Bioengineered 2021 12;12(1):4780-4793

Department of Gastrointestinal Surgery, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China.

Warburg phenomenon refers to the development of unique metabolic patterns during the growth of tumor cells. This study stratified gastric cancer into prognostic metabolic subgroups according to changes in gene expressions related to glycolysis and cholesterol synthesis. The RNA-seq expression data, single nucleotide variants (SNV), short insertions and deletions (InDel) mutation data, copy number variation (CNV) data and clinical follow-up information data of gastric cancer tissues were downloaded from The Cancer Genome Atlas (TCGA) database. ConsensusClusterPlus was used to stratify the metabolic subtypes of gastric cancer. Four metabolic subtypes (Cholesterogenic, Glycolytic, Mixed and Quiescent) of gastric cancer were identified, and patients with cholesterogenic tumors had the longest disease-specific survival (DSS). Genome-wide analysis showed that aberrant amplification of TP53 and MYC in gastric cancer was associated with abnormal cholesterol anabolic metabolism. The mRNA levels of mitochondrial pyruvate carriers 1 and 2 (MPC1/2) differed among the four subtypes. Tumors in the glycolytic group showed a higher PDCD1. A genomic signature based on tumor metabolism of different cancer types was established. This study showed that genes related to glucose and lipid metabolism play an important role in gastric cancer and facilitate a personalized treatment of gastric cancer.
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http://dx.doi.org/10.1080/21655979.2021.1956247DOI Listing
December 2021

Development and Validation of 3-Month Major Post-Stroke Depression Prediction Nomogram After Acute Ischemic Stroke Onset.

Clin Interv Aging 2021 24;16:1439-1447. Epub 2021 Jul 24.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People's Republic of China.

Purpose: The early detection of major post-stroke depression (PSD) is essential to optimize patient care. A major PSD prediction tool needs to be developed and validated for early screening of major PSD patients.

Patients And Methods: A total of 639 acute ischemic stroke (AIS) patients from three hospitals were consecutively recruited and completed a 3-month follow-up. Sociodemographic, clinical and laboratory test data were collected on admission. With major depression criteria being met in the DSM-V, 17-item Hamilton Rating Scale For Depression (HRSD) score ≥17 at 3 months after stroke onset was regarded as the primary endpoint. Multiple imputation was used to substitute the missing values and multivariable logistic regression model was fitted to determine associated factors with a bootstrap backward selection process. The nomogram was constructed based on the regression coefficients of the associated factors. Performance of the nomogram was assessed by discrimination (C-statistics) and calibration curve.

Results: A total of 7.04% (45/639) of patients were diagnosed with major PSD at 3 months. The final logistic regression model included age, baseline NIHSS and mRS scores, educational level, calcium-phosphorus product, history of hypertension and atrial fibrillation. The model had acceptable discrimination, based on a C-statistic of 0.81 (95% CI, 0.791-0.829), with 71.1% sensitivity and 78.6% specificity. We also transformed the model to a nomogram, an easy-to-use clinical tool which could be used to facilitate the early screening of major PSD patients at 3 months.

Conclusion: We identified several associated factors of major PSD at 3 months and constructed a convenient nomogram to guide follow-up and aid accurate prognostic assessment.
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http://dx.doi.org/10.2147/CIA.S318857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8318664PMC
October 2021

Qingyangshen mitigates amyloid-β and Tau aggregate defects involving PPARα-TFEB activation in transgenic mice of Alzheimer's disease.

Phytomedicine 2021 Oct 12;91:153648. Epub 2021 Jul 12.

Mr. & Mrs. Ko Chi-Ming Centre for Parkinson's Disease Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, China. Electronic address:

Background: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid β plaques (Aβ) and neurofibrillary tangles (NFTs) is the key pathological hallmark of AD. Accumulating evidence suggest that impairment of autophagy-lysosomal pathway (ALP) plays key roles in AD pathology.

Purpose: The present study aims to assess the neuroprotective effects of Qingyangshen (QYS), a Chinese herbal medicine, in AD cellular and animal models and to determine its underlying mechanisms involving ALP regulation.

Methods: QYS extract was prepared and its chemical components were characterized by LC/MS. Then the pharmacokinetics and acute toxicity of QYS extract were evaluated. The neuroprotective effects of QYS extract were determined in 3XTg AD mice, by using a series of behavioral tests and biochemical assays, and the mechanisms were examined in vitro.

Results: Oral administration of QYS extract improved learning and spatial memory, reduced carboxy-terminal fragments (CTFs), amyloid precursor protein (APP), Aβ and Tau aggregates, and inhibited microgliosis and astrocytosis in the brains of 3XTg mice. Mechanistically, QYS extract increased the expression of PPARα and TFEB, and promoted ALP both in vivo and in vitro.

Conclusion: QYS attenuates AD pathology, and improves cognitive function in 3XTg mice, which may be mediated by activation of PPARα-TFEB pathway and the subsequent ALP enhancement. Therefore, QYS may be a promising herbal material for further anti-AD drug discovery.
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http://dx.doi.org/10.1016/j.phymed.2021.153648DOI Listing
October 2021

Lysosomal TPCN (two pore segment channel) inhibition ameliorates beta-amyloid pathology and mitigates memory impairment in Alzheimer disease.

Autophagy 2021 Jul 27:1-19. Epub 2021 Jul 27.

School of Chinese Medicine and Mr. And Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, Hong Kong Baptist University, Hong Kong, China.

Abbreviations: Aβ: β-amyloid; AD: Alzheimer disease; AIF1/IBA1: allograft inflammatory factor 1; ALP: autophagy-lysosomal pathway; APP: amyloid beta precursor protein; ATP6V1B1/V-ATPase V1b1: ATPase H+ transporting V1 subunit B1; AVs: autophagy vacuoles; BAF: bafilomycin A; CFC: contextual/cued fear conditioning assay; CHX: Ca/H exchanger; CTF-β: carboxy-terminal fragment derived from β-secretase; CTSD: cathepsin D; fAD: familial Alzheimer disease; GFAP: glial fibrillary acidic protein; LAMP1: lysosomal associated membrane protein 1; LTP: long-term potentiation; MCOLN1/TRPML1: mucolipin 1; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MAPT: microtubule associated protein tau; MWM: Morris water maze; NFT: neurofibrillary tangles; PFC: prefrontal cortex; PSEN1: presenilin 1; SQSTM1/p62: sequestosome 1; TBS: theta burst stimulation; TEM: transmission electronic microscopy; TPCN2/TPC2: two pore segment channel 2; WT: wild-type; V-ATPase: vacuolar type H-ATPase.
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http://dx.doi.org/10.1080/15548627.2021.1945220DOI Listing
July 2021

A pilot behavioural and neuroimaging investigation on photothrombotic stroke models in rhesus monkeys.

J Neurosci Methods 2021 10 20;362:109291. Epub 2021 Jul 20.

National Resource Center for Non-Human Primates, Kunming Primate Research Center, and National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan, China. Electronic address:

Background: Ischemic stroke leads to a long-term disability in humans and no efficient clinical therapy exists to date. The middle cerebral artery occlusion (MCAO) model in non-human primates has shown to be of value for translational stroke research. New method In the current study, a photothrombotic (PT) stroke model was established in rhesus monkeys with either a proximal or distal segment of middle cerebral artery (MCA) thrombosis. This study is the first that compares the two approaches of PT stroke in monkeys using behavioral and physiological measurements and MRI scans.

Results: The experiment found that infarct occurred in the MCA target regions, with all monkeys having impaired behavior reflected by deficits in neurologic function, and motor and cognition in object retrieval detour (ORD) task. The monkeys with distal MCA thrombosis developed with sequential photo-irritations of the Sylvian fissure zone, adjacent central anterior gyrus and central posterior gyrus, had similar impairments with respect to behavior and showed a tendency of a small edema volume with proximal MCA thrombosis at days 4 and 7 post PT stroke.

Comparison With Existing Methods: The distal MCA thrombosis developed with sequential photo-irritations might provide a consistent and well-tolerated focal ischemia in rhesus monkeys, compared with other PT stroke models which usually were singly conducted on the animal's motor cortex and had a temporal effect.

Conclusions: The sequentially photo-irritated PT stroke model is a promising ischemic stroke model in rhesus monkey for studying human stroke pathology and physiology and for new therapies development.
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http://dx.doi.org/10.1016/j.jneumeth.2021.109291DOI Listing
October 2021

Ciliopathy genes are required for apical secretion of Cochlin, an otolith crystallization factor.

Proc Natl Acad Sci U S A 2021 Jul;118(28)

Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, United Kingdom.

Here, we report that important regulators of cilia formation and ciliary compartment-directed protein transport function in secretion polarity. Mutations in cilia genes and , involved in human ciliopathies, affect apical secretion of Cochlin, a major otolith component and a determinant of calcium carbonate crystallization form. We show that Cochlin, defective in human auditory and vestibular disorder, DFNA9, is secreted from small specialized regions of vestibular system epithelia. Cells of these regions secrete Cochlin both apically into the ear lumen and basally into the basal lamina. Basally secreted Cochlin diffuses along the basal surface of vestibular epithelia, while apically secreted Cochlin is incorporated into the otolith. Mutations in a subset of ciliopathy genes lead to defects in Cochlin apical secretion, causing abnormal otolith crystallization and behavioral defects. This study reveals a class of ciliary proteins that are important for the polarity of secretion and delineate a secretory pathway that regulates biomineralization.
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http://dx.doi.org/10.1073/pnas.2102562118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285972PMC
July 2021

A Comparative Study on the Psychological Health of Frontline Health Workers in Wuhan Under and After the Lockdown.

Front Psychiatry 2021 21;12:701032. Epub 2021 Jun 21.

Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

The coronavirus disease-2019 (COVID-19) outbreak and a 3-month lockdown of Wuhan may have had a long-term impact on the mental health of frontline healthcare workers (HWs). However, there is still a lack of comparative studies on the mental health of front-line HWs in the initial phase of the lockdown and 1 month after the lifting of the lockdown. We recruited 1717 HWs during the initial phase of the lockdown and 2214 HWs 1 month after the lifting of the lockdown, and their baseline characteristics and psychiatric health in these two phases were compared. Furthermore, Pearson's Chi-square test and multivariate logistic regression analysis were used to determine the possible risk factors associated with depressive symptoms in the front-line HWs. Compared with the initial phase of the lockdown, the proportion of HWs with anxiety symptoms and stress decreased, while the proportion of HWs with depressive symptoms increased a month after the lifting of the lockdown. Male sex, exercise habit, comorbidities, and having family members or relatives with suspected or confirmed COVID-19 infection were significantly related to the increased incidence of depressive symptoms during the initial phase of the lockdown. Comorbidities, negative effect of media coverage, working >4 days a week, lower annual household income, and deteriorating relationships with family members were associated with depressive symptoms a month after the lifting of the lockdown. The increased proportion of HWs with depressive symptoms 1 month after the lifting of the lockdown suggested that mental health of front-line HWs should be a top-priority issue, not only during, but also after the pandemic.
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http://dx.doi.org/10.3389/fpsyt.2021.701032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255471PMC
June 2021

Perchlorate in shellfish from South China Sea and implications for human exposure.

Mar Pollut Bull 2021 Sep 1;170:112672. Epub 2021 Jul 1.

School of Public Health (Shenzhen), Sun Yat-sen University, Guangzhou 510275, China. Electronic address:

Shellfish can absorb and accumulate contaminants. The consumption of shellfish could expose humans to pollutants and increase related health risk. Perchlorate (ClO) is a ubiquitous pollutant and could affect thyroid functions, especially for children and pregnant women. However, knowledge on the contamination of perchlorate in aquatic food such as shellfish remains limited. This study aimed to investigate the abundances of perchlorate in shellfish from South China Sea and to assess human exposure risks. A total of 178 shellfish samples from eight species were collected from offshore aquaculture waters in South China Sea. Perchlorate was detected in 99.4% of them, suggesting widespread pollution in coastal waters. Concentrations of perchlorate ranged from not detected (N.D.) to 71.5 μg kg, with a median value of 4.33 μg kg. Estimated daily intake (EDI) and hazard quotient (HQ) were used to assess human exposure dose and health risks, respectively. The HQ values were determined to be less than 1, indicating no significant health risks to local residents via shellfish consumption. To our knowledge, this is the first study to investigate perchlorate contamination in South China shellfish and assess potential human risks.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112672DOI Listing
September 2021

Selective deletion of SHIP-1 in hematopoietic cells in mice leads to severe lung inflammation involving ILC2 cells.

Sci Rep 2021 04 28;11(1):9220. Epub 2021 Apr 28.

Section of Allergy and Clinical Immunology, Yale University School of Medicine, 333 Cedar Street, TAC S469C, New Haven, CT, 06510, USA.

Src homology 2 domain-containing inositol 5-phosphatase 1 (SHIP-1) regulates the intracellular levels of phosphotidylinositol-3, 4, 5-trisphosphate, a phosphoinositide 3-kinase (PI3K) product. Emerging evidence suggests that the PI3K pathway is involved in allergic inflammation in the lung. Germline or induced whole-body deletion of SHIP-1 in mice led to spontaneous type 2-dominated pulmonary inflammation, demonstrating that SHIP-1 is essential for lung homeostasis. However, the mechanisms by which SHIP-1 regulates lung inflammation and the responsible cell types are still unclear. Deletion of SHIP-1 selectively in B cells, T cells, dendritic cells (DC) or macrophages did not lead to spontaneous allergic inflammation in mice, suggesting that innate immune cells, particularly group 2 innate lymphoid cells (ILC2 cells) may play an important role in this process. We tested this idea using mice with deletion of SHIP-1 in the hematopoietic cell lineage and examined the changes in ILC2 cells. Conditional deletion of SHIP-1 in hematopoietic cells in Tek-Cre/SHIP-1 mice resulted in spontaneous pulmonary inflammation with features of type 2 immune responses and airway remodeling like those seen in mice with global deletion of SHIP-1. Furthermore, when compared to wild-type control mice, Tek-Cre/SHIP-1 mice displayed a significant increase in the number of IL-5/IL-13 producing ILC2 cells in the lung at baseline and after stimulation by allergen Papain. These findings provide some hints that PI3K signaling may play a role in ILC2 cell development at baseline and in response to allergen stimulation. SHIP-1 is required for maintaining lung homeostasis potentially by restraining ILC2 cells and type 2 inflammation.
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http://dx.doi.org/10.1038/s41598-021-88677-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8080607PMC
April 2021

Nanoparticles Displaying Allergen and Siglec-8 Ligands Suppress IgE-FcεRI-Mediated Anaphylaxis and Desensitize Mast Cells to Subsequent Antigen Challenge.

J Immunol 2021 05 28;206(10):2290-2300. Epub 2021 Apr 28.

Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA

Siglec-8 is an inhibitory receptor expressed on eosinophils and mast cells. In this study, we took advantage of a novel Siglec-8 transgenic mouse model to assess the impact of modulating IgE-dependent mast cell degranulation and anaphylaxis using a liposomal platform to display an allergen with or without a synthetic glycan ligand for Siglec-8 (Sig8L). The hypothesis is that recruitment of Siglec-8 to the IgE-FcεRI receptor complex will inhibit allergen-induced mast cell degranulation. Codisplay of both allergen and Sig8L on liposomes profoundly suppresses IgE-mediated degranulation of mouse bone marrow-derived mast cells or rat basophilic leukemia cells expressing Siglec-8. In contrast, liposomes displaying only Sig8L have no significant suppression of antigenic liposome-induced degranulation, demonstrating that the inhibitory activity by Siglec-8 occurs only when Ag and Sig8L are on the same particle. In mouse models of anaphylaxis, display of Sig8L on antigenic liposomes completely suppresses IgE-mediated anaphylaxis in transgenic mice with mast cells expressing Siglec-8 but has no protection in mice that do not express Siglec-8. Furthermore, mice protected from anaphylaxis remain desensitized to subsequent allergen challenge because of loss of Ag-specific IgE from the cell surface and accelerated clearance of IgE from the blood. Thus, although expression of human Siglec-8 on murine mast cells does not by itself modulate IgE-FcεRI-mediated cell activation, the enforced recruitment of Siglec-8 to the FcεRI receptor by Sig8L-decorated antigenic liposomes results in inhibition of degranulation and desensitization to subsequent Ag exposure.
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http://dx.doi.org/10.4049/jimmunol.1901212DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113104PMC
May 2021

STORM imaging reveals the spatial arrangement of transition zone components and IFT particles at the ciliary base in Tetrahymena.

Sci Rep 2021 04 12;11(1):7899. Epub 2021 Apr 12.

Bateson Centre and the Department of Biomedical Science, University of Sheffield, Western Bank, Sheffield, S10 2TN, UK.

The base of the cilium comprising the transition zone (TZ) and transition fibers (TF) acts as a selecting gate to regulate the intraflagellar transport (IFT)-dependent trafficking of proteins to and from cilia. Before entering the ciliary compartment, IFT complexes and transported cargoes accumulate at or near the base of the cilium. The spatial organization of IFT proteins at the cilia base is key for understanding cilia formation and function. Using stochastic optical reconstruction microscopy (STORM) and computational averaging, we show that seven TZ, nine IFT, three Bardet-Biedl syndrome (BBS), and one centrosomal protein, form 9-clustered rings at the cilium base of a ciliate Tetrahymena thermophila. In the axial dimension, analyzed TZ proteins localize to a narrow region of about 30 nm while IFT proteins dock approximately 80 nm proximal to TZ. Moreover, the IFT-A subcomplex is positioned peripheral to the IFT-B subcomplex and the investigated BBS proteins localize near the ciliary membrane. The positioning of the HA-tagged N- and C-termini of the selected proteins enabled the prediction of the spatial orientation of protein particles and likely cargo interaction sites. Based on the obtained data, we built a comprehensive 3D-model showing the arrangement of the investigated ciliary proteins.
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http://dx.doi.org/10.1038/s41598-021-86909-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041816PMC
April 2021

Psycho-social factors associated with high depressive symptomatology in female adolescents and gender difference in adolescent depression: an epidemiological survey in China's Hubei Province.

BMC Psychiatry 2021 03 26;21(1):168. Epub 2021 Mar 26.

Department of Plastic surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.

Background: Exploring etiological clues to adolescent depression, especially in female adolescents, might be helpful to improve the social environment of female adolescents. The aim at this study is to explore psycho-social factors of female adolescents with high depressive symptomatology and gender differences in depressive symptoms among Chinese adolescents.

Method: We examined 4100 adolescents from Wuhan city and Jianli county via a cross-sectional study. Depressive symptomatology was screened through the Chinese version of Center for Epidemiology Studies Depression Scale. Multivariate logistic regression was performed to explore the factors related to high depressive symptomatology in female and male adolescents, respectively.

Results: The prevalence of high depressive symptomatology in female and male were 38.9 and 30.2% respectively. The psycho-social factors of high depressive symptomatology in female adolescents were age (Adjusted odds ratio [aOR] = 1.201, 95% confidence interval [CI], 1.076 ~ 1.341), single parent family (aOR = 2.004, 95%CI, 1.448 ~ 2.772) and fathers' education level (compared to primary school and below, [Junior middle school, aOR = 0.641, 95%CI, 0.439 ~ 0.934; Senior middle school, aOR = 0.603, 95%CI, 0.410 ~ 0.888; College degree and above, aOR = 0.639, 95%CI, 0.437 ~ 0.936]).

Conclusion: Fathers' education level was associated with high depressive symptomatology in female adolescents. Female adolescents whose father with primary school education or below deserves more attention. Further epidemiologic researches need to be conducted to explore the different risk factors between female and male adolescents in China.
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http://dx.doi.org/10.1186/s12888-021-03165-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995784PMC
March 2021

Effects of exposure to urban particulate matter SRM 1648a during pregnancy on the neurobehavioral development of offspring mice.

Ecotoxicol Environ Saf 2021 Jun 17;215:112142. Epub 2021 Mar 17.

State Key Laboratory of Reproductive Medicine, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing 211166, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China. Electronic address:

The development of the nervous system is crucial to a child's health. However, the nervous system is also susceptible to a variety of factors during development. To date, epidemiological studies have reported controversial results on the relationship between prenatal exposure to particulate matter (PM) and neurobehavioral development. Thus, we investigated the effect of PM exposure during pregnancy on the neurobehavioral development of offsprings. Adult C57BL/6 mice were exposed to PM from gestation day (GD) 0.5-21 by the intratracheal instillation. The daily exposure doses were 250 µg/kg.b.w and 2500 µg/kg.b.w respectively. The offspring mice began behavioral tests at the 5th week. We assessed neurobehavioral development, and the gene expression level changes in the mouse hippocampus using RNA-seq. In the open field test, the movement distance in the central area was significantly decreased in the high-dose group. Serum free triiodothyronine (FT3) levels were significantly increased in male offspring mice with prenatal high-dose PM exposure. The RNA-seq results suggested that the Prkca, Med12l, Ep300, and Slc16a10 in the thyroid hormone signaling pathway were significantly decreased in offspring mice in the high-dose group. Our data showed that prenatal PM exposure caused the offspring mice's anxiety-like behaviors and increased serum FT3 levels. The changes in thyroid hormone pathway-related genes might be the causes of the above series of changes.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112142DOI Listing
June 2021

A mussel-inspired film for adhesion to wet buccal tissue and efficient buccal drug delivery.

Nat Commun 2021 03 16;12(1):1689. Epub 2021 Mar 16.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

Administration of drugs via the buccal route has attracted much attention in recent years. However, developing systems with satisfactory adhesion under wet conditions and adequate drug bioavailability still remains a challenge. Here, we propose a mussel-inspired mucoadhesive film. Ex vivo models show that this film can achieve strong adhesion to wet buccal tissues (up to 38.72 ± 10.94 kPa). We also demonstrate that the adhesion mechanism of this film relies on both physical association and covalent bonding between the film and mucus. Additionally, the film with incorporated polydopamine nanoparticles shows superior advantages for transport across the mucosal barrier, with improved drug bioavailability (~3.5-fold greater than observed with oral delivery) and therapeutic efficacy in oral mucositis models (~6.0-fold improvement in wound closure at day 5 compared with that observed with no treatment). We anticipate that this platform might aid the development of tissue adhesives and inspire the design of nanoparticle-based buccal delivery systems.
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http://dx.doi.org/10.1038/s41467-021-21989-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7966365PMC
March 2021

A Massive Right Hemisphere Infarction After Autologous Fat Grafting for Facial Filling.

J Craniofac Surg 2021 Mar-Apr 01;32(2):e215-e217

Department of Plastic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Abstract: Cerebral fat embolism following facial autologous fat injection is a rare and serious complication. There are limited long-term follow-up data on the motion, cognitive and mental outcomes of surviving patients with cerebral fat embolism following facial autologous fat injection. In this study, the authors reported a patient with a 22-year-old woman with a massive right hemisphere infarction following facial autologous fat injection had normal cognitive function, independent living ability, and social function at 5 years follow-up visit, even though computed tomography showed her entire right cerebral hemisphere had atrophied with softening lesions.
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http://dx.doi.org/10.1097/SCS.0000000000006898DOI Listing
June 2021

Sialic acid-binding immunoglobulin-like lectin 9 as a potential therapeutic target for chronic obstructive pulmonary disease.

Chin Med J (Engl) 2021 Feb 16;134(7):757-764. Epub 2021 Feb 16.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

Abstract: Chronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.
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http://dx.doi.org/10.1097/CM9.0000000000001381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8104259PMC
February 2021

Effectiveness and safety of different doses of tenecteplase in the treatment of acute ischemic stroke: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Jan;100(3):e23805

XiXi Hospital of Hangzhou, Hangzhou, Zhejiang Province, China.

Background: Tenecteplase is a modified recombinant tissue-plasminogen activator, which is effective and safe in the treatment of acute ischemic stroke. However, the therapeutic dose of tenecteplase has been controversial. The purpose of this study is to systematically investigate the efficacy and safety of different doses of tenecteplase thrombolytic therapy for acute ischemic stroke.

Methods: Computer retrieval of English databases (PubMed, EMBASE, Web of Science, the Cochrane Library) and Chinese databases (CNKI, Wanfang, Viper, and Chinese Biomedical Database) is conducted for a randomized controlled clinical study on thrombolytic treatment of acute ischemic stroke with different doses of tenecteplase from the establishment of the database to October 2020. Two researchers independently conduct data extraction and literature quality evaluation on the quality of the included studies, and meta-analysis is conducted on the included literatures using RevMan5.3 software.

Outcome: In this study, National Institute of Health Stroke Scale (NIHSS) score, Modified Rankin Scale (mRS) score scale, symptomatic intracranial hemorrhage (SICH) incidence, All-cause mortality, and so on are used to evaluate the efficacy and safety of tenecteplase thrombolytic therapy in acute ischemic stroke with different doses.

Conclusion: This study will provide reliable evidence-based evidence for the clinical application of different doses of tenecteplase in thrombolytic therapy for acute ischemic stroke.

Osf Registration Number: DOI 10.17605/OSF.IO/2MPCW.
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http://dx.doi.org/10.1097/MD.0000000000023805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837936PMC
January 2021

Rectifying Attenuated Store-Operated Calcium Entry as a Therapeutic Approach for Alzheimer's Disease.

Curr Alzheimer Res 2020 ;17(12):1072-1087

School of Chinese Medicine and Mr. and Mrs. Ko Chi Ming Centre for Parkinson's Disease Research, Hong Kong Baptist University, 7 Baptist University Road, Kowloon Tong, Kowloon, Hong Kong, China.

Alzheimer's disease (AD) is the most common neurodegenerative disorder. Although the pathological hallmarks of AD have been identified, the derived therapies cannot effectively slow down or stop disease progression; hence, it is likely that other pathogenic mechanisms are involved in AD pathogenesis. Intracellular calcium (Ca) dyshomeostasis has been consistently observed in AD patients and numerous AD models and may emerge prior to the development of amyloid plaques and neurofibrillary tangles. Thus, intracellular Ca disruptions are believed to play an important role in AD development and could serve as promising therapeutic intervention targets. One of the disrupted intracellular Ca signaling pathways manifested in AD is attenuated storeoperated Ca entry (SOCE). SOCE is an extracellular Ca entry mechanism mainly triggered by intracellular Ca store depletion. Maintaining normal SOCE function not only provides a means for the cell to replenish ER Ca stores but also serves as a cellular signal that maintains normal neuronal functions, including excitability, neurogenesis, neurotransmission, synaptic plasticity, and gene expression. However, normal SOCE function is diminished in AD, resulting in disrupted neuronal spine stability and synaptic plasticity and the promotion of amyloidogenesis. Mounting evidence suggests that rectifying diminished SOCE in neurons may intervene with the progression of AD. In this review, the mechanisms of SOCE disruption and the associated pathogenic impacts on AD will be discussed. We will also highlight the potential therapeutic targets or approaches that may help ameliorate SOCE deficits for AD treatment.
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http://dx.doi.org/10.2174/1567205018666210119150613DOI Listing
January 2020

Zeolitic Imidazolate Framework-8 Encapsulating Risedronate Synergistically Enhances Osteogenic and Antiresorptive Properties for Bone Regeneration.

ACS Biomater Sci Eng 2020 04 24;6(4):2186-2197. Epub 2020 Mar 24.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.

Bisphosphonates (BPs) are routinely administered for the treatment of turnover bone diseases. To avoid the undesirable adverse effects of long-term usage of bisphosphonates and improve their bioavailability in the bone microenvironment, we initially encapsulated risedronate (RIS) molecules inside nanoscale zeolitic imidazolate framework-8 particles (nZIF-8) by a one-step synthesis method to generate [email protected] nanoparticles. [email protected] nanoparticles displayed high loading encapsulation efficiency (64.21 ± 2.48%), good biocompatibility, controlled drug release capacity, and dual effects for bone regeneration. This work explored the potential of [email protected] nanoparticles, which could not only enhance ATP production, induce extracellular matrix (ECM) mineralization, and upregulate the expression levels of osteogenic genes but also effectively inhibit the formation of multinucleated giant osteocasts and decrease the Rankl/Opg ratio. Overall, [email protected] nanoparticles could be a very promising approach to synergistically enhance osteogenic and antiresorptive properties for bone regeneration, which could be utilized for the local treatment of bone defects.
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http://dx.doi.org/10.1021/acsbiomaterials.0c00195DOI Listing
April 2020

Accelerated Bone Regeneration by MOF Modified Multifunctional Membranes through Enhancement of Osteogenic and Angiogenic Performance.

Adv Healthc Mater 2021 03 14;10(6):e2001369. Epub 2021 Jan 14.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, P. R. China.

Owing to the insufficient guidance of new bone formation in orthopedic and craniomaxillofacial surgery, construction of a guided bone regeneration membrane to support vascularized bone regeneration remains a challenge. Herein, an electrospun asymmetric double-layer polycaprolactone/collagen (PCL/Col) membrane modified by metal-organic framework (MOF) crystals is developed. The optimization of the PCL/Col weight ratio (1:1 and 1:1.5) enables the composite membrane with a balanced tensile strength (only fell by 49.9% in wet conditions) and a controlled degradation rate (completely degraded at 12 weeks). The MOF crystals can provide a pH-responsive release of Zn ions. In vitro experiments indicate that the barrier layer functions to prevent the infiltration of fibrous connective tissue. The MOF crystal layer functions to enhance osteogenesis and angiogenesis in vitro. Using a rat calvarial defect model, the MOF crystals exhibit a sign of osteoinductivity along with blood vessel formation after 8 weeks post-surgery. Strikingly, when assessed in a chick chorioallantoic membrane model, the MOF modified membrane demonstrates a significant angiogenic response, which can be envisaged as its outstanding merits over the commercially Col membrane. Therefore, the MOF crystals represent an exciting biomaterial option, with neovascularization capacity for bone tissue engineering and regenerative medicine.
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http://dx.doi.org/10.1002/adhm.202001369DOI Listing
March 2021

Nanoscale Zeolitic Imidazolate Framework-8 Activator of Canonical MAPK Signaling for Bone Repair.

ACS Appl Mater Interfaces 2021 Jan 23;13(1):97-111. Epub 2020 Dec 23.

State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu 610041, PR China.

Zeolitic imidazolate framework-8 (ZIF-8) is an important type of metal organic framework and has found numerous applications in the biomedical field. Our previous studies have demonstrated that nano ZIF-8-based titanium implants could promote osseointegration; however, its osteogenic capacity and the related mechanisms in bone regeneration have not been fully clarified. Presented here is a nanoscale ZIF-8 that could drive rat bone mesenchymal stem cell (rBMSC) differentiation into osteoblasts both in vitro and in vivo, and interestingly, nano ZIF-8 exhibited a better osteogenic effect compared with ionic conditions of Zn at the same concentration of Zn. Moreover, the cellular uptake mechanisms of the nanoparticles were thoroughly clarified. Specifically, nano ZIF-8 could enter the rBMSC cytoplasm probably via caveolae-mediated endocytosis and macropinocytosis. The intracellular and extracellular Zn released from nano ZIF-8 and the receptors involved in the endocytosis may play a role in inducing activation of key osteogenic pathways. Furthermore, through transcriptome sequencing, multiple osteogenic pathways were found to be upregulated, among which nano ZIF-8 primarily phosphorylated ERK, thus activating the canonical mitogen-activated protein kinase pathway and promoting the osteogenesis of rBMSCs. Taken together, this study helps to elucidate the mechanism by which nano ZIF-8 regulates osteogenesis and suggests it to be a potential biomaterial for constructing multifunctional composites in bone tissue engineering.
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http://dx.doi.org/10.1021/acsami.0c15945DOI Listing
January 2021

Association of Cerebral Artery Stenosis With Post-stroke Depression at Discharge and 3 Months After Ischemic Stroke Onset.

Front Psychiatry 2020 25;11:585201. Epub 2020 Nov 25.

Department of Neurology, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Post-stroke depression (PSD) is one of the most common complications after stroke, which seriously affects patients' recovery outcome. Although vascular depression has been extensively studied, the relationship between cerebral artery stenosis and PSD has not been clarified so far. Two hundred ninety-eight patients with ischemic stroke (72 women, 226 men) with computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were included in this study. Cerebral artery stenosis ≥50% was used as the cut-off value. The DSM-V diagnostic criteria of PSD was met and the 17-item Hamilton Rating Scale for Depression (HAMD-17) score over 7 at discharge and 3 months after stroke onset was regarded as the primary outcome. The χ-test, Mann-Whitney -test, and -test were used to check for statistical significance. At discharge, Barthel index ( < 0.001), left middle cerebral artery stenosis ( = 0.019), drinking history ( = 0.048), basilar artery stenosis ( = 0.037) were significantly associated with PSD. At 3 months after ischemic stroke onset, Barthel index ( = 0.011), left middle cerebral artery stenosis ( = 0.012), female gender ( = 0.001) were significantly associated with PSD. The findings demonstrated that left middle cerebral artery and basilar artery stenosis are associated with PSD. It was suggested that cerebral artery stenosis was a risk factor of PSD and should be recognized and intervened early. ChiCTR-ROC-17013993.
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http://dx.doi.org/10.3389/fpsyt.2020.585201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7723904PMC
November 2020
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