Publications by authors named "Yin Chen"

510 Publications

Sterically Wrapped Multiple Resonance Fluorophors for Suppression of Concentration Quenching and Spectrum Broadening.

Angew Chem Int Ed Engl 2021 Oct 11. Epub 2021 Oct 11.

Tsinghua University, Chemistry, HeTian Building Dept. of Chemistry, Tsinghua University, Beijing, P. R. China, 100084, Beijing, CHINA.

Multiple resonance (MR) emitters are promising for highly efficient organic light-emitting diodes (OLEDs) with narrowband emission; however, they still face intractable challenges with concentration-caused emission quenching, exciton annihilation, and spectral broadening. In this study, sterically wrapped MR dopants with a fluorescent MR core sandwiched by bulk substituents were developed to address the intractable challenges by reducing intermolecular interactions. Consequently, high photo-luminance quantum yields of ≥90% and small full width at half maximums (FWHMs) of ≤25 nm over a wide range of dopant concentrations (1 wt%-20 wt%) were recorded. In addition, we demonstrated that the sandwiched MR emitter can effectively suppress Dexter interaction when doped in a thermally activated delayed fluorescence sensitizer, eliminating exciton loss through dopant triplet. Within the above dopant concentration range, the optimal emitter realizes remarkably high maximum external quantum efficiencies of 36.3%-37.2%, identical small FWHMs of 24 nm, and alleviated efficiency roll-offs in OLEDs.
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http://dx.doi.org/10.1002/anie.202113206DOI Listing
October 2021

Lung developmental is altered after inhalation exposure to various concentrations of calcium arsenate.

Toxicol Appl Pharmacol 2021 Oct 8:115754. Epub 2021 Oct 8.

Department of Cellular & Molecular Medicine, University of Arizona College of Medicine, Tucson, AZ 85719, United States of America. Electronic address:

Exposure to dust from active and abandoned mining operations may be a very significant health hazard, especially to sensitive populations. We have previously reported that inhalation of real-world mine tailing dusts during lung development can alter lung function and structure in adult male mice. These real-world dusts contain a mixture of metal(oid)s, including arsenic. To determine whether arsenic in inhaled dust plays a role in altering lung development, we exposed C57Bl/6 mice to a background dust (0 arsenic) or to the background dust containing either 3% or 10% by mass, calcium arsenate. Total level of exposure was kept at 100 μg/m. Calcium arsenate was selected since arsenate is the predominant species found in mine tailings. We found that inhalation exposure during in utero and postnatal lung development led to significant increases in pulmonary baseline resistance, airway hyper-reactivity, and airway collagen and smooth muscle expression in male C57Bl/6 mice. Responses were dependent on the level of calcium arsenate in the simulated dust. These changes were not associated with increased expression of TGF-β1, a marker of epithelial to mesenchymal transition. However, responses were correlated with decreases in the expression of Club cell protein 16 (CC16). Dose dependent decreases in CC16 expression and increases in collagen around airways was seen for animals exposed in utero only (GD), animals exposed postnatally only (PN) and animals continuously exposed throughout development (GDPN). These data suggest that arsenic inhalation during lung development can decrease CC16 expression leading to functional and structural alterations in the adult lung.
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http://dx.doi.org/10.1016/j.taap.2021.115754DOI Listing
October 2021

Structural and Mechanistic Insights Into Dimethylsulfoxide Formation Through Dimethylsulfide Oxidation.

Front Microbiol 2021 24;12:735793. Epub 2021 Sep 24.

Frontiers Science Center for Deep Ocean Multispheres and Earth System, College of Marine Life Sciences, Ocean University of China, Qingdao, China.

Dimethylsulfide (DMS) and dimethylsulfoxide (DMSO) are widespread in marine environment, and are important participants in the global sulfur cycle. Microbiol oxidation of DMS to DMSO represents a major sink of DMS in marine surface waters. The SAR11 clade and the marine clade (MRC) are the most abundant heterotrophic bacteria in the ocean surface seawater. It has been reported that trimethylamine monooxygenase (Tmm, EC 1.14.13.148) from both MRC and SAR11 bacteria likely oxidizes DMS to generate DMSO. However, the structural basis of DMS oxidation has not been explained. Here, we characterized a Tmm homolog from the SAR11 bacterium sp. HTCC7211 (Tmm). Tmm exhibits DMS oxidation activity . We further solved the crystal structures of Tmm and Tmm soaked with DMS, and proposed the catalytic mechanism of Tmm, which comprises a reductive half-reaction and an oxidative half-reaction. FAD and NADPH molecules are essential for the catalysis of Tmm. In the reductive half-reaction, FAD is reduced by NADPH. In the oxidative half-reaction, the reduced FAD reacts with O to form the C4a-(hydro)peroxyflavin. The binding of DMS may repel the nicotinamide ring of NADP, and make NADP generate a conformational change, shutting off the substrate entrance and exposing the active C4a-(hydro)peroxyflavin to DMS to complete the oxidation of DMS. The proposed catalytic mechanism of Tmm may be widely adopted by MRC and SAR11 bacteria. This study provides important insight into the conversion of DMS into DMSO in marine bacteria, leading to a better understanding of the global sulfur cycle.
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http://dx.doi.org/10.3389/fmicb.2021.735793DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8498191PMC
September 2021

Optimization of bifunctional piperidinamide derivatives as σR Antagonists/MOR agonists for treating neuropathic pain.

Eur J Med Chem 2021 Oct 4;226:113879. Epub 2021 Oct 4.

Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address:

Here, we describe the optimization, synthesis, and associated pharmacological analgesic activities of a new series of bifunctional piperidinamide derivatives as sigma-1 receptor (σR) antagonists and mu opioid receptor (MOR) agonists. The new compounds were evaluated in vitro in σR and MOR binding assays. The most promising compound 114 (also called HKC-126), showed superior affinities for σR and MOR and good selectivity to additional receptors related to pain. Compound 114 showed powerful dose-dependent analgesic effects in the acetic acid writhing test, formalin test, hot plate test, and chronic constriction injury (CCI) neuropathic pain model. In contrast to an equianalgesic dose of fentanyl, compound 114 produced fewer opioid-like side effects, such as reward liability, respiratory depression, physical dependence, and sedation. Lastly, the pharmacokinetic properties of this drug were also acceptable, and these results suggest that compound 114, as a mixed σR/MOR ligand, has potential for treating neuropathic pain.
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http://dx.doi.org/10.1016/j.ejmech.2021.113879DOI Listing
October 2021

Midazolam Exposure Impedes Oligodendrocyte Development via the Translocator Protein and Impairs Myelination in Larval Zebrafish.

Mol Neurobiol 2021 Oct 9. Epub 2021 Oct 9.

Department of Anesthesiology, Huashan Hospital, Fudan University, No. 12 Wu lu mu qi Road, Shanghai, 200040, China.

Anesthetics are commonly used in various medical procedures. Accumulating evidence suggests that early-life anesthetics exposure in infants and children affects brain development, causing psychiatric and neurological disorders. However, the underlying mechanisms are poorly understood. Using zebrafish larvae as a model, we found that the proliferation and migration of oligodendrocyte progenitor cells (OPCs) were severely impaired by the exposure of midazolam (MDZ), an anesthetic widely used in pediatric surgery and intensive care medicine, leading to a reduction of oligodendroglial lineage cell in the dorsal spinal cord. This defect was mimicked by the bath application of translocator protein (TSPO) agonists and partially rescued by genetic downregulation of TSPO. Cell transplantation experiments showed that requirement of TSPO for MDZ-induced oligodendroglial lineage cell defects is cell-autonomous. Furthermore, transmission electron microscopy and in vivo electrophysiological recording experiments demonstrated that MDZ exposure caused axon hypomyelination and action potential propagation retardation, resulting in delayed behavior initiation. Thus, our findings reveal that MDZ affects oligodendroglial lineage cell development and myelination in young animals, raising the care about its clinic use in infants and children.
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http://dx.doi.org/10.1007/s12035-021-02559-8DOI Listing
October 2021

Molecular epidemiologic characteristics of hemagglutinin from five waves of avian influenza A (H7N9) virus infection, from 2013 to 2017, in Zhejiang Province, China.

Arch Virol 2021 Sep 30. Epub 2021 Sep 30.

Zhejiang Provincial Center for Disease Control and Prevention, 3399 Binsheng Road, Hangzhou, 310051, Zhejiang, China.

There have been five waves of influenza A (H7N9) epidemics in Zhejiang Province between 2013 and 2017. Although the epidemiological characteristics of the five waves have been reported, the molecular genetics aspects, including the phylogeny, evolution, and mutation of hemagglutinin (HA), have not been systematically investigated. A total of 154 H7N9 samples from Zhejiang Province were collected between 2013 and 2017 and sequenced using an Ion Torrent Personal Genome Machine. The starting dates of the waves were 16 March 2013, 1 July 2013, 1 July 2014, 1 July 2015, and 1 July 2016. Single-nucleotide polymorphisms (SNPs) and amino acid mutations were counted after the HA sequences were aligned. The evolution of H7N9 matched the temporal order of the five waves, among which wave 3 played an important role. The 55 SNPs and 14 amino acid mutations with high frequency identified among the five waves revealed the dynamic occurrence of mutation in the process of viral dissemination. Wave 3 contributed greatly to the subsequent epidemic of waves 4 and 5 of H7N9. Compared with wave 1, wave 5 was characterized by more mutations, including A143V and R148K, two mutations that have been reported to weaken the immune response. In addition, some amino acid mutations were observed in wave 5 that led to more lineages. It is necessary to strengthen the surveillance of subsequent H7N9 influenza outbreaks.
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http://dx.doi.org/10.1007/s00705-021-05233-5DOI Listing
September 2021

Invited Response on: "Letter to the Editor: Proper Skin Management in Breast Augmentation with a Periareolar Incision Prevents Implant Contamination and Biofilm-Related Capsular Contracture".

Aesthetic Plast Surg 2021 Sep 28. Epub 2021 Sep 28.

Department of Plastic and Reconstructive Surgery, Guangdong Second Provincial General Hospital, 466 Middle Xin Gang Road, Guangzhou City, 510317, Guangdong Province, China.

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http://dx.doi.org/10.1007/s00266-021-02587-8DOI Listing
September 2021

circMBOAT2 serves as the sponge of miR-433-3p to promote the progression of bladder cancer.

Pathol Res Pract 2021 Sep 14;227:153613. Epub 2021 Sep 14.

Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, 310007 Hangzhou, China. Electronic address:

Background: Bladder cancer (Bca) is the most common cancer in urinary system. Recent studies revealed that circular RNAs (circRNAs) play vital roles in the development and progression of cancers. circMBOAT2 serves as an oncogenic gene in various kinds of cancer, promoting cell growth and metastasis. Nevertheless, the biological function of circMBOAT2 in Bca has not been reported.

Methods: qRT-PCR was used to measure the mRNA, circRNA and miRNA expression levels in Bca tissues and cells. Loss-of function experiments were carried to investigate the effect of circMBOAT2 on cell proliferation and migration. Nuclear mass separation, RNA pull-down and dual-luciferase reporter were performed to the molecular mechanisms underlying the functions of circMBOAT2.

Results: In this research, we identified that circMBOAT2 expression was increased in Bca tissues and positively corelated with unfavorable prognosis. In vitro assay demonstrated that suppression of circMBOAT2 impaired the proliferation and migration of Bca cells. Mechanically, circMBOAT2 was predominantly spread in cytoplasm and it sponged miR-433-3p to strengthen CREB1 expression.

Conclusion: Hence, our study suggested that circMBOAT2 may serve as an oncogene in the development and progression of Bca and it will be the novel tumor biomarker and therapeutic target for Bca.
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http://dx.doi.org/10.1016/j.prp.2021.153613DOI Listing
September 2021

Status of N-of-1 Trials in Chronic Pain Management: A Narrative Review.

Pain Ther 2021 Sep 16. Epub 2021 Sep 16.

Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, No. 253 Gongye Road, Guangzhou, 510282, China.

N-of-1 trials are randomized controlled clinical trials conducted exclusively on a single patient. The ultimate aim of N-of-1 trials is to optimize a strategy in a particular individual. Chronic pain is a common but refractory clinical problem. Its diverse etiologies and broad variations among patients often lead to the requirement of individualizing medicine. Thus, chronic pain represents a classical condition for N-of-1 clinical trials. Studies have indicated that N-of-1 benefits patients with chronic pain, multiple comorbidities, and uncertain variations during therapies; however, this approach it is not yet adopted as the first choice in pain clinics. To dissect the current status of N-of-1 in chronic pain management, as well as the limitations for its implementation, we herein studied all N-of-1 studies related to chronic pain by searching three major databases (PubMed, ClinicalTrial.gov, Cochrane Library) for publications between 1985 and 2020. Of 35 eligibility papers, 19 were selected for analysis. Results confirmed that N-of-1 trials have solved the refractory cases including osteoarthritis, chronic musculoskeletal pain, and neuropathic pain; however, none of the trials dealt with cancer pain. Longer time and more efforts are needed from investigators when carrying out N-of-1 trials, which inevitably result in implementation difficulties. Of note, all recruited trials were conducted in developed countries. As mobile devices have been introduced and protocols improve, renewed interest in the implementation of N-of-1 trials will occur. Collectively, a previously underestimated conflict between "precision medicine" and "poor implementation" has put N-of-1 in a challenging position for chronic pain management.
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http://dx.doi.org/10.1007/s40122-021-00314-4DOI Listing
September 2021

Novel Mouse Models of Fungal Asthma.

Front Cell Infect Microbiol 2021 16;11:683194. Epub 2021 Aug 16.

Asthma & Airway Disease Research Center, University of Arizona, Tucson, AZ, United States.

is a ubiquitous fungus and a major allergen associated with the development of asthma. Inhalation of intact spores is the primary cause of human exposure to fungal allergen. However, allergen-rich cultured fungal filtrates are oftentimes used in the current models of fungal sensitization that do not fully reflect real-life exposures. Thus, establishing novel spore exposure models is imperative. In this study, we established novel fungal exposure models of both adult and neonate to live spores. We examined pathophysiological changes in the spore models as compared to the non-exposure controls and also to the conventional filtrate models. While both filtrate- and spore-exposed adult BALB/c mice developed elevated airway hyperresponsiveness (AHR), filtrates induced a greater IgE mediated response and higher broncholavage eosinophils than spores. In contrast, the mice exposed to spores had higher numbers of neutrophils. Both exposures induced comparable levels of lung tissue inflammation and mucous cell metaplasia (MCM). In the neonatal model, exposure to spores resulted in a significant increase of AHR in both adult and neonatal mice. Increased levels of IgE in both neonatal and adult mice exposed to spores was associated with increased eosinophilia in the treatment groups. Adult demonstrated increased numbers of lymphocytes that was paralleled by increased IgG1 production. Both adults and neonates demonstrated similarly increased eosinophilia, IgE, tissue inflammation and MCM.
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http://dx.doi.org/10.3389/fcimb.2021.683194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415780PMC
August 2021

Protective function of interleukin-22 in pulmonary fibrosis.

Clin Transl Med 2021 Aug;11(8):e509

Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive scarring disease with unknown etiology. The evidence of a pathogenic role for transforming growth factor-beta (TGF-β) in the development and progression of IPF is overwhelming. In the present study, we investigated the role of interleukin-22 (IL-22) in the pathogenesis of IPF by regulating the TGF-β pathway. We measured parameters and tissue samples from a clinical cohort of IPF. IL-22R knock out (IL-22RA1 ) and IL-22 supplementation mouse models were used to determine if IL-22 is protective in vivo. For the mechanistic study, we tested A549, primary mouse type II alveolar epithelial cell, human embryonic lung fibroblast, and primary fibroblast for their responses to IL-22 and/or TGF-β1. In a clinical cohort, the expression level of IL-22 in the peripheral blood and lung tissues of IPF patients was lower than healthy controls, and the lower IL-22 expression was associated with poorer pulmonary function. IL-22R mice demonstrated exacerbated inflammation and fibrosis. Reciprocally, IL-22 augmentation by intranasal instillation of recombinant IL-22 repressed inflammation and fibrotic phenotype. In vitro, IL-22 treatment repressed TGF-β1 induced gene markers representing epithelial-mesenchymal-transition and fibroblast-myofibroblast-transition, likely via the inhibition of TGF-β receptor expression and subsequent Smad2/3 activation. IL-22 appears to be protective against pulmonary fibrosis by inhibiting TGF-β1 signaling, and IL-22 augmentation may be a promising approach to treat IPF.
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http://dx.doi.org/10.1002/ctm2.509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387792PMC
August 2021

Deep learning-based carotid plaque vulnerability classification with multicentre contrast-enhanced ultrasound video: a comparative diagnostic study.

BMJ Open 2021 08 27;11(8):e047528. Epub 2021 Aug 27.

Department of Ultrasound, Beijing Tiantan Hospital, Beijing, China.

Objectives: The aim of this study was to evaluate the performance of deep learning-based detection and classification of carotid plaque (DL-DCCP) in carotid plaque contrast-enhanced ultrasound (CEUS).

Methods And Analysis: A prospective multicentre study was conducted to assess vulnerability in patients with carotid plaque. Data from 547 potentially eligible patients were prospectively enrolled from 10 hospitals, and 205 patients with CEUS video were finally enrolled for analysis. The area under the receiver operating characteristic curve (AUC) was used to evaluate the effectiveness of DL-DCCP and two experienced radiologists who manually examined the CEUS video (RA-CEUS) in diagnosing and classifying carotid plaque vulnerability. To evaluate the influence of dynamic video input on the performance of the algorithm, a state-of-the-art deep convolutional neural network (CNN) model for static images (Xception) was compared with DL-DCCP for both training and holdout validation cohorts.

Results: The AUCs of DL-DCCP were significantly better than those of the experienced radiologists for both the training and holdout validation cohorts (training, DL-DCCP vs RA-CEUS, AUC: 0.85 vs 0.69, p<0.01; holdout validation, DL-DCCP vs RA-CEUS, AUC: 0.87 vs 0.66, p<0.01), that is, also better than the best deep CNN model Xception we had performed, for both the training and holdout validation cohorts (training, DL-DCCP vs Xception, AUC:0.85 vs 0.82, p<0.01; holdout validation, DL-DCCP vs Xception, AUC: 0.87 vs 0.77, p<0.01).

Conclusion: DL-DCCP shows better overall performance in assessing the vulnerability of carotid atherosclerotic plaques than RA-CEUS. Moreover, with a more powerful network structure and better utilisation of video information, DL-DCCP provided greater diagnostic accuracy than a state-of-the-art static CNN model.

Trial Registration Number: ChiCTR1900021846.
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http://dx.doi.org/10.1136/bmjopen-2020-047528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8404444PMC
August 2021

Generation and Evaluation of Recombinant Thermostable Newcastle Disease Virus Expressing the HA of H9N2 Avian Influenza Virus.

Viruses 2021 Aug 13;13(8). Epub 2021 Aug 13.

Jiangsu Co-Innovation Center for the Prevention and Control of Animal Infectious Disease and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou 225009, China.

H9N2 avian influenza virus (AIV) has become endemic in many countries, causing great economic losses when co-infected with other pathogens. So far, several live vaccines based on Newcastle disease virus (NDV) vectors expressing influenza hemagglutinin (HA) have been developed. However, the thermostable recombinant NDV is rarely reported. In this study, using a thermostable NDV rAHR09 strain as the vector, three recombinant NDVs expressing native HA, chimeric HA ectodomain with transmembrane domain/C-terminal cytoplasmic tail domain from fusion protein of NDV, and HA ectodomain were generated, designated rAHR09-HA, rAHR09-HAF, and rAHR09-HAE. The MDT value of three recombinant NDVs was above 120 h, their ICPI value was about 0.03, and the recombinant NDVs were still infectious when treated for 100 min under 56 °C, which demonstrated that the recombinant NDVs kept the lentogenic and thermostable nature of rAHR09. The immunization data showed that rAHR09-HA and rAHR09-HAF induced a higher HI antibody titer against H9N2 AIV and NDV. After being challenged with H9N2 AIV, the rAHR09-HA and rAHR09-HAF could significantly reduce the virus shedding in cloacal and tracheal swab samples. Our results suggest that rAHR09-HA and rAHR09-HAF might be vaccine candidates against H9N2 AIV.
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http://dx.doi.org/10.3390/v13081606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402907PMC
August 2021

An angiotensin-converting enzyme-2-derived heptapeptide GK-7 for SARS-CoV-2 spike blockade.

Peptides 2021 11 19;145:170638. Epub 2021 Aug 19.

State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Combined Injury of PLA, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing, 400038, China. Electronic address:

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a global concern and necessitates efficient drug antagonists. Angiotensin-converting enzyme-2 (ACE2) is the main receptor of SARS-CoV-2 spike 1 (S1), which mediates viral invasion into host cells. Herein, we designed and prepared short peptide inhibitors containing 4-6 critical residues of ACE2 that contribute to the interaction with SARS-CoV-2 S1. Among the candidates, a peptide termed GK-7 (GKGDFRI), which was designed by extracting residues ranging from Gly353 to Ile359 in the ligand-binding domain of ACE2, exhibited the highest binding affinity (25.1 nM) with the SARS-CoV-2 spike receptor-binding domain (RBD). GK-7 bound to the RBD and decreased SARS-CoV-2 S1 attachment to A549 human alveolar epithelial cells. Owing to spike blockade, GK-7 inhibited SARS-CoV-2 spike pseudovirion infection in a dose-dependent manner, with a half-maximal inhibitory concentration of 2.96 μg/mL. Inspiringly, pulmonary delivery of GK-7 by intranasal administration did not result in toxicity in mice. This study revealed an easy-to-produce peptide inhibitor for SARS-CoV-2 spike blockade, thus providing a promising candidate for COVID-19 treatment.
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http://dx.doi.org/10.1016/j.peptides.2021.170638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375220PMC
November 2021

Simultaneously Enhanced Reverse Intersystem Crossing and Radiative Decay in Thermally Activated Delayed Fluorophors with Multiple Through-space Charge Transfers.

Angew Chem Int Ed Engl 2021 Aug 17. Epub 2021 Aug 17.

Key Laboratory of Organic Optoelectronics & Molecular Engineering of Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084, China.

Thermally activated delayed fluorescence (TADF) materials with through-space charge transfers (CT) have attracted particularly interest recently. However, the slow reverse intersystem crossing (RISC) and radiative decay always limit their electroluminescence performances. Herein, TADF molecules with ortho-linked multiple donors-acceptor (ortho-D -A) motif are developed to create near-degenerate excited states for the reinforcement of spin-orbit coupling. The incorporation of both through-bond and through-space CT enlarges oscillator strength. The optimal ortho-D -A compound exhibits a photoluminescence quantum yield of ca. 100 %, a high RISC rate of 2.57×10  s and a high radiative decay rate of 1.00×10  s simultaneously. With this compound as the sensitizer, a TADF-sensitized-fluorescent organic light-emitting diode shows a maximum external quantum efficiency of 31.6 % with an ultrapure green Commission Internationale de L'Eclairage y coordinate value of 0.69.
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http://dx.doi.org/10.1002/anie.202109041DOI Listing
August 2021

Corrigendum: Large-Area Photoreceptor Degeneration Model in Rabbits by Photocoagulation and Oxidative Stress in the Retina.

Front Neurosci 2021 26;15:738004. Epub 2021 Jul 26.

State Key Laboratory of Medical Neurobiology, Department of Ophthalmology, MOE Frontiers Center for Brain Science, Zhongshan Hospital, Institutes for Brain Science, Fudan University, Shanghai, China.

[This corrects the article DOI: 10.3389/fnins.2021.617175.].
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http://dx.doi.org/10.3389/fnins.2021.738004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350927PMC
July 2021

In vitro and in vivo immunoregulatory activity of sulfated fucan from the sea cucumber A. leucoprocta.

Int J Biol Macromol 2021 Sep 4;187:931-938. Epub 2021 Aug 4.

School of Food Science and Pharmaceutical Engineering, Weifang Medical University, Weifang 261000, People's Republic of China. Electronic address:

The in vitro and in vivo immunoregulatory activity of a water-soluble sulfated fucan AL1-1 from the sea cucumber A. leucoprocta was elucidated. In vitro experiments showed that AL1-1 up-regulated immunostimulatory activities in RAW264.7 cells and that it could successfully promote ROS production and phagocytic activity, increase secretion levels of iNOS, and induce the production of considerable amounts of cytokines (TNF-α, IL-6, IL-1β and IL-12). We found that toll-like receptor 4 (TLR4) was mainly involved in AL1-1 mediated macrophage activation. AL1-1's in vivo immunomodulatory activity on cyclophosphamide (CY)-treated mice was investigated and it was shown that it could strongly enhance Sig A levels, promote the total antioxidant capacity (T-AOC), and reduce malondialdehyde (MDA) level in the intestine. It could also increase activities of superoxidase dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-PX). These results demonstrate that AL1-1 has a significant effect on enhancing in vivo and in vitro immune response.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.008DOI Listing
September 2021

Transporter characterisation reveals aminoethylphosphonate mineralisation as a key step in the marine phosphorus redox cycle.

Nat Commun 2021 07 27;12(1):4554. Epub 2021 Jul 27.

Department of Animal and Plant Sciences, University of Sheffield, Sheffield, UK.

The planktonic synthesis of reduced organophosphorus molecules, such as alkylphosphonates and aminophosphonates, represents one half of a vast global oceanic phosphorus redox cycle. Whilst alkylphosphonates tend to accumulate in recalcitrant dissolved organic matter, aminophosphonates do not. Here, we identify three bacterial 2-aminoethylphosphonate (2AEP) transporters, named AepXVW, AepP and AepSTU, whose synthesis is independent of phosphate concentrations (phosphate-insensitive). AepXVW is found in diverse marine heterotrophs and is ubiquitously distributed in mesopelagic and epipelagic waters. Unlike the archetypal phosphonate binding protein, PhnD, AepX has high affinity and high specificity for 2AEP (Stappia stellulata AepX K 23 ± 4 nM; methylphosphonate K 3.4 ± 0.3 mM). In the global ocean, aepX is heavily transcribed (~100-fold>phnD) independently of phosphate and nitrogen concentrations. Collectively, our data identifies a mechanism responsible for a major oxidation process in the marine phosphorus redox cycle and suggests 2AEP may be an important source of regenerated phosphate and ammonium, which are required for oceanic primary production.
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http://dx.doi.org/10.1038/s41467-021-24646-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316502PMC
July 2021

COVID-19 or treatment associated immunosuppression may trigger hepatitis B virus reactivation: A case report.

World J Clin Cases 2021 Jul;9(19):5266-5269

Department of Infectious Diseases, The Affiliated People's Hospital of Ningbo University, Ningbo 315040, Zhejiang Province, China.

Background: Since the initial recognition of coronavirus disease 2019 (COVID-19) in Wuhan, this infectious disease has spread to most areas of the world. The pathogenesis of COVID-19 is yet unclear. Hepatitis B virus (HBV) reactivation occurring in COVID-19 patients has not yet been reported.

Case Summary: A 45-year-old hepatitis B man with long-term use of adefovir dipivoxil and entecavir for antiviral therapy had HBV reactivation after being treated with methylprednisolone for COVID-19 for 6 d.

Conclusion: COVID-19 or treatment associated immunosuppression may trigger HBV reactivation.
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http://dx.doi.org/10.12998/wjcc.v9.i19.5266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8283611PMC
July 2021

Astrocyte activation imaging with 11C-acetate and amyloid PET in mild cognitive impairment due to Alzheimer pathology.

Nucl Med Commun 2021 Nov;42(11):1261-1269

Division of Nuclear Medicine, Department of Radiology.

Background: Neuroinflammation is a well-known feature of early Alzheimer disease (AD) yet astrocyte activation has not been extensively evaluated with in vivo imaging in mild cognitive impairment (MCI) due to amyloid plaque pathology. Unlike neurons, astrocytes metabolize acetate, which has potential as a glial biomarker in neurodegeneration in response to AD pathologic features. Since the medial temporal lobe (MTL) is a hotspot for AD neurodegeneration and inflammation, we assessed astrocyte activity in the MTL and compared it to amyloid and cognition.

Methods: We evaluate spatial patterns of in vivo astrocyte activation and their relationships to amyloid deposition and cognition in a cross-sectional pilot study of six participants with MCI and five cognitively normal participants. We measure 11C-acetate and 18F-florbetaben amyloid standardized uptake values ratios (SUVRs) and kinetic flux compared to the cerebellum on PET, with MRI and neurocognitive testing.

Results: MTL 11C-acetate SUVR was significantly elevated in MCI compared to cognitively normal participants (P = 0.03; Cohen d = 1.76). Moreover, MTL 11C-acetate SUVR displayed significant associations with global and regional amyloid burden in MCI. Greater MTL 11C-acetate retention was significantly related with worse neurocognitive measures including the Montreal Cognitive Assessment (P = 0.001), word list recall memory (P = 0.03), Boston naming test (P = 0.04) and trails B test (P = 0.04).

Conclusions: While further validation is required, this exploratory pilot study suggests a potential role for 11C-acetate PET as a neuroinflammatory biomarker in MCI and early AD to provide clinical and translational insights into astrocyte activation as a pathological response to amyloid.
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http://dx.doi.org/10.1097/MNM.0000000000001460DOI Listing
November 2021

Large-Area Photoreceptor Degeneration Model in Rabbits by Photocoagulation and Oxidative Stress in the Retina.

Front Neurosci 2021 10;15:617175. Epub 2021 Jun 10.

State Key Laboratory of Medical Neurobiology, Department of Ophthalmology, MOE Frontiers Center for Brain Science, Zhongshan Hospital, Institute for Brain Science, Fudan University, Shanghai, China.

Photocoagulation is used for the treatment of retinal ischemic disease. However, due to the invasive nature of photocoagulation and variety of melanin concentrations between individuals, it is challenging to avoid damaging the adjacent photoreceptors and inducing several side effects. Previous studies indicate the role of laser power, duration, and spot size on retinal lesions, but the effect of interspot distance of the laser pulses needs to be considered in panretinal photocoagulation. In this study, we examine different parameters of photocoagulation on lesions of the retina in rabbit, finding that the lesion level of the outer nuclear layer of the retina depended on the pulse duration and laser spot size, and decreasing interspot distance could completely abolish the photoreceptor layer. The degeneration of the photoreceptor by photocoagulation occurred in 24 h and was not restored afterward. We then conducted panretinal photocoagulation in rabbit and found that oxidative stress was decreased in the inner nuclear layer of the retina, and pupillary light reflex and ERG signals were impaired. Our study could provide a rabbit model to explore the mechanism of photoreceptor degeneration and therapies for the side effects after photocoagulation.
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http://dx.doi.org/10.3389/fnins.2021.617175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222581PMC
June 2021

Bifunctional μ opioid and σ receptor ligands as novel analgesics with reduced side effects.

Eur J Med Chem 2021 Nov 18;223:113658. Epub 2021 Jun 18.

Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address:

Opioid analgesics are highly effective painkillers for the treatment of moderate or severe pain, but they are associated with a number of undesirable adverse effects, including the development of tolerance, addiction, constipation and life-threatening respiratory depression. The development of new and safer analgesics with innovative mechanisms of action, which can enhance the efficacy in comparison to available treatments and reduce their side effects, is urgently needed. The sigma-1 receptor (σR), a unique Ca-sensing chaperone protein, is expressed throughout pain-modulating tissues and affects neurotransmission by interacting with different protein partners, including molecular targets that participate in nociceptive signalling, such as the μ-opioid receptor (MOR), N-methyl-d-aspartate receptor (NMDAR) and cannabinoid 1 receptor (CBR). Overwhelming pharmacological and genetic evidence indicates that σR antagonists induce anti-hypersensitive effects in sensitising pain conditions (e.g. chemically induced, inflammatory and neuropathic pain) and enhance opioid analgesia but not opioid-mediated detrimental effects. It has been suggested that balanced modulation of MORs and σRs may improve both the therapeutic efficacy and safety of opioids. This review summarises the functional profiles of ligands with mixed MOR agonist and σR antagonist activities and highlights their therapeutic potentials for pain management. Dual MOR agonism/σR antagonism represents a promising avenue for the development of potent and safer analgesics.
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http://dx.doi.org/10.1016/j.ejmech.2021.113658DOI Listing
November 2021

Knockdown of TRIM15 inhibits the activation of hepatic stellate cells.

J Mol Histol 2021 Aug 17;52(4):839-848. Epub 2021 Jun 17.

Department of Gastroenterology, Minhang Hospital of Fudan University, 170 Shensong Road, Shanghai, 201100, China.

Liver fibrosis is a global public health problem, and the activation of hepatic stellate cells (HSCs) is the main driving force for liver fibrosis. However, the activation mechanism of HSCs is still not fully understood. In this study, we screened out 854 differentially expressed genes [Log fold change absolute: log2 FC(abs) ≥ 1] in activated LX-2 cells. Subsequently, we performed functional analyses of these differentially expressed genes. Gene Ontology enrichment analysis showed that the target genes were mainly enriched in processes such as positive regulation of cell migration involved in sprouting angiogenesis, negative regulation of keratinocyte proliferation, and nuclear inclusion bodies. Kyoto Encyclopedia of Gene and Genome signaling pathway enrichment analysis revealed that dysregulated genes were involved in signaling pathways such as pantothenate and coenzyme A biosynthesis and riboflavin metabolism. The microarray results were validated by reverse transcription-quantitative polymerase chain reaction, which indicated that the microarray results were reliable and that the tripartite motif containing 15 (TRIM15) had the highest absolute value of LogFC. Additionally, the effect of TRIM15 on the proliferation, migration, and activation of LX-2 cells was assessed using overexpression plasmids and siRNA transfections. TRIM15 promoted the proliferation and migration of LX-2 cells and positively regulated the expression of α-smooth muscle actin and type I collagen. Collectively, the data revealed the gene expression profiles of quiescent and activated LX-2 cells and the involvement of TRIM15 in the activation of LX-2 cells. Hereby, TRIM15 could be a novel target of the HSC activation mechanism.
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http://dx.doi.org/10.1007/s10735-021-09997-7DOI Listing
August 2021

Synergistic photocatalytic activity of a combination of carbon nanotubes-graphene-nickel foam nanocomposites enhanced by dielectric barrier discharge plasma technology for water purification.

Water Sci Technol 2021 Jun;83(11):2762-2777

School of Chemistry and Chemical Engineering, Nantong University, Nantong 226019, China E-mail:

Degradation activity of plasma catalysis between dielectric barrier discharge (DBD) and carbon nanotubes-graphene-nickel foam (CNTs-G-Ni) has been studied in treatment of dye wastewater. CNTs-G-Ni was prepared through a two-step chemical vapor deposition (CVD) approach. The composite has been characterized by different techniques such as X-ray diffraction (XRD), scanning electron microscope (SEM) and Raman spectroscopy. SEM results showed that the Ni as the growth substrate was evenly wrapped by G and then CNTs were successfully grown on G as the support. The growth mechanism of composite was proposed. The possible coupled catalytic mechanism between DBD and CNTs-G-Ni were addressed. In addition, the modification on G-Ni was found by SEM during the discharge process in liquid phase. And the modification mechanism of DBD plasma (DBDP) acting on composites was discussed. Finally, by means of analyses of ultraviolet-visible (UV-Vis) spectroscopy, Fourier transform infrared (FT-IR) spectroscopy, gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), the general degradation pathway and stepwise degradation pathways of alizarin green (AG) were proposed in detail.
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http://dx.doi.org/10.2166/wst.2021.030DOI Listing
June 2021

Productive Infection of Human Breast Cancer Cell Lines with Human Cytomegalovirus (HCMV).

Pathogens 2021 May 23;10(6). Epub 2021 May 23.

Department of Biology, University of San Francisco, San Francisco, CA 94117, USA.

Breast cancer is the leading cause of cancer deaths among women worldwide. There are many known risk factors for breast cancer, but the role of infectious disease remains unclear. Human cytomegalovirus (HCMV) is a widespread herpesvirus that usually causes little disease. Because HCMV has been detected in breast tumor biopsy samples and is frequently transmitted via human breast milk, we investigated HCMV replication in breast tumor cells. Four human breast cancer cell lines with different expression profiles for the key diagnostic markers of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were infected with a bacterial artificial chromosome-derived HCMV clinical strain TB40/E tagged with green fluorescent protein (GFP). Fluorescence microscopy confirmed that all four breast cancer cell lines supported virus entry. RNA was isolated from infected cells and the expression of immediate early (UL123), early (UL54), and late (UL111A) genes was confirmed using PCR. Viral proteins were detected by immunoblotting, and viral progeny were produced during the infection of breast tumor cells, as evidenced by subsequent infection of fibroblasts with culture supernatants. These results demonstrate that breast tumor cells support productive HCMV infection and could indicate that HCMV replication may play a role in breast cancer progression.
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http://dx.doi.org/10.3390/pathogens10060641DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8224681PMC
May 2021

A new family of globally distributed lytic roseophages with unusual deoxythymidine to deoxyuridine substitution.

Curr Biol 2021 Jul 24;31(14):3199-3206.e4. Epub 2021 May 24.

School of Life Sciences, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK. Electronic address:

Marine bacterial viruses (bacteriophages) are abundant biological entities that are vital for shaping microbial diversity, impacting marine ecosystem function, and driving host evolution. The marine roseobacter clade (MRC) is a ubiquitous group of heterotrophic bacteria that are important in the elemental cycling of various nitrogen, sulfur, carbon, and phosphorus compounds. Bacteriophages infecting MRC (roseophages) have thus attracted much attention and more than 30 roseophages have been isolated, the majority of which belong to the N4-like group (Podoviridae family) or the Chi-like group (Siphoviridae family), although ssDNA-containing roseophages are also known. In our attempts to isolate lytic roseophages, we obtained two new phages (DSS3_VP1 and DSS3_PM1) infecting the model MRC strain Ruegeria pomeroyi DSS-3. Here, we show that not only do these phages have unusual substitution of deoxythymidine with deoxyuridine (dU) in their DNA, but they are also phylogenetically distinct from any currently known double-stranded DNA bacteriophages, supporting the establishment of a novel family ("Naomiviridae"). These dU-containing phages possess DNA that is resistant to the commonly used library preparation method for metagenome sequencing, which may have caused significant underestimation of their presence in the environment. Nevertheless, our analysis of Tara Ocean metagenome datasets suggests that these unusual bacteriophages are of global importance and more diverse than other well-known bacteriophages, e.g., the Podoviridae in the oceans, pointing to an overlooked role for these novel phages in the environment.
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http://dx.doi.org/10.1016/j.cub.2021.05.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323127PMC
July 2021

Phosphorus stress induces the synthesis of novel glycolipids in Pseudomonas aeruginosa that confer protection against a last-resort antibiotic.

ISME J 2021 May 24. Epub 2021 May 24.

School of Life Sciences, University of Warwick, CV4 7AL, Coventry, UK.

Pseudomonas aeruginosa is a nosocomial pathogen with a prevalence in immunocompromised individuals and is particularly abundant in the lung microbiome of cystic fibrosis patients. A clinically important adaptation for bacterial pathogens during infection is their ability to survive and proliferate under phosphorus-limited growth conditions. Here, we demonstrate that P. aeruginosa adapts to P-limitation by substituting membrane glycerophospholipids with sugar-containing glycolipids through a lipid renovation pathway involving a phospholipase and two glycosyltransferases. Combining bacterial genetics and multi-omics (proteomics, lipidomics and metatranscriptomic analyses), we show that the surrogate glycolipids monoglucosyldiacylglycerol and glucuronic acid-diacylglycerol are synthesised through the action of a new phospholipase (PA3219) and two glycosyltransferases (PA3218 and PA0842). Comparative genomic analyses revealed that this pathway is strictly conserved in all P. aeruginosa strains isolated from a range of clinical and environmental settings and actively expressed in the metatranscriptome of cystic fibrosis patients. Importantly, this phospholipid-to-glycolipid transition comes with significant ecophysiological consequence in terms of antibiotic sensitivity. Mutants defective in glycolipid synthesis survive poorly when challenged with polymyxin B, a last-resort antibiotic for treating multi-drug resistant P. aeruginosa. Thus, we demonstrate an intriguing link between adaptation to environmental stress (nutrient availability) and antibiotic resistance, mediated through membrane lipid renovation that is an important new facet in our understanding of the ecophysiology of this bacterium in the lung microbiome of cystic fibrosis patients.
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http://dx.doi.org/10.1038/s41396-021-01008-7DOI Listing
May 2021

Multimodality oncologic evaluation of superficial neck and facial lymph nodes.

Radiol Med 2021 Aug 16;126(8):1074-1084. Epub 2021 May 16.

Department of Radiology, Division of Neuroradiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.

Involvement of lymph nodes in patients with head and neck cancers impacts treatment and prognosis. Head and neck lymph nodes are comprised of superficial and deep groups which are interconnected. The deep lymph nodes, predominantly centered along internal jugular veins, are very well-known to radiologists and clinicians. However, superficial lymph nodes that drain lymph from the scalp, face, and neck are much less recognized. Here, we describe the anatomic and imaging features of these superficial lymph nodes on CT, MRI, and PET in oncologic settings.
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http://dx.doi.org/10.1007/s11547-021-01367-3DOI Listing
August 2021

Prolonged release and shelf-life of anticoagulant sulfated polysaccharides encapsulated with ZIF-8.

Int J Biol Macromol 2021 Jul 10;183:1174-1183. Epub 2021 May 10.

Department of Chemistry and Chemical Biology, Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, 12180, USA.

Natural active polysaccharides are attracting increased attention from pharmaceutical industries for their valuable biological activities. However, the application of polysaccharides has been restricted due to their relatively large molecular weight, complex structure, and instability. Metal-organic frameworks (MOFs) have emerged to help deliver cargo to specific locations, achieving the objectives of eliminating the potential damage to the body, protecting the drugs, and improving therapeutic effectiveness. Here, a pH-responsive zeolitic imidazolate framework (ZIF-8) was synthesized to encapsulated three sulfated polysaccharides (heparin, fucan sulfate, fucosylated chondroitin sulfate) and a non-sulfated polysaccharide, hyaluronic acid. The resulting [email protected] biocomposites showed differences in terms of morphology, particle size, encapsulation, and release efficiency. These biocomposites retained antithrombotic activity and the framework ZIF-8 effectively protected these polysaccharides from degradation and prolonged shelf-life of the anticoagulants from the unfavorable environment.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.05.007DOI Listing
July 2021

A sequence analysis of hospitalization patterns and service utilization in patients with major psychiatric disorders in China.

BMC Psychiatry 2021 05 11;21(1):245. Epub 2021 May 11.

Department of Psychiatry and Behavioral Sciences, Emory University, 12 Executive Park Drive NE, Suite 300, Atlanta, GA, USA; Atlanta VA Medical Center, 1670 Clairmont Road, Decatur, GA, USA.

Background: Understanding the long-term inpatient service cost and utilization of psychiatric patients may provide insight into service demand for these patients and guide the design of targeted mental health programs. This study assesses 3-year hospitalization patterns and quantifies service utilization intensity of psychiatric patients in Beijing, China.

Methods: We identified patients admitted for one of three major psychiatric disorders (schizophrenia, bipolar and depressive disorders) between January 1 and December 31, 2013 in Beijing, China. Inpatient admissions during the following 3 years were extracted and analyzed using sequence analysis. Clinical characteristics, psychiatric and non-psychiatric service use of included patients were analyzed.

Results: The study included 3443 patients (7657 hospitalizations). The patient hospitalization sequences were grouped into 4 clusters: short stay (N = 2741 (79.61% of patients), who had 126,911 or 26.82% of the hospital days within the sample), repeated long stay (N = 404 (11.73%), 76,915 (16.26%) days), long-term stay (N = 101 (2.93%), 59,909 (12.66%) days) and permanent stay (N = 197 (5.72%), 209,402 (44.26%) days). Length and frequency of hospitalization, as well as readmission rates were significantly different across the 4 clusters. Over the 3-year period, hospitalization days per year decreased for patients in the short stay and repeated long stay clusters. Patients with schizophrenia (1705 (49.52%)) had 78.4% of cumulative psychiatric stays, with 11.14% of them in the permanent stay cluster. Among patients with depression, 23.11% had non-psychiatric hospitalizations, and on average 46.65% of their total inpatient expenses were for non-psychiatric care, the highest among three diagnostic groups.

Conclusion: Hospitalization patterns varied significantly among psychiatric patients and across diagnostic categories. The high psychiatric care service use of the long-term and permanent stay patients underlines the need for evidence-based interventions to reduce cost and improve care quality.
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http://dx.doi.org/10.1186/s12888-021-03251-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111895PMC
May 2021
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