Publications by authors named "Xiaowen Hu"

201 Publications

Correction to: Birt-Hogg-Dubé syndrome encountered at rare lung disease clinic in Anhui province, China.

Orphanet J Rare Dis 2022 Aug 11;17(1):312. Epub 2022 Aug 11.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.

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http://dx.doi.org/10.1186/s13023-022-02438-yDOI Listing
August 2022

Hetero-bivalent nanobodies provide broad-spectrum protection against SARS-CoV-2 variants of concern including Omicron.

Cell Res 2022 Jul 29. Epub 2022 Jul 29.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.

SARS-CoV-2 variants with adaptive mutations have continued to emerge, causing fresh waves of infection even amongst vaccinated population. The development of broad-spectrum antivirals is thus urgently needed. We previously developed two hetero-bivalent nanobodies (Nbs), aRBD-2-5 and aRBD-2-7, with potent neutralization activity against the wild-type (WT) Wuhan isolated SARS-CoV-2, by fusing aRBD-2 with aRBD-5 and aRBD-7, respectively. Here, we resolved the crystal structures of these Nbs in complex with the receptor-binding domain (RBD) of the spike protein, and found that aRBD-2 contacts with highly-conserved RBD residues and retains binding to the RBD of the Alpha, Beta, Gamma, Delta, Delta plus, Kappa, Lambda, Omicron BA.1, and BA.2 variants. In contrast, aRBD-5 and aRBD-7 bind to less-conserved RBD epitopes non-overlapping with the epitope of aRBD-2, and do not show apparent binding to the RBD of some variants. However, when fused with aRBD-2, they effectively enhance the overall binding affinity. Consistently, aRBD-2-5-Fc and aRBD-2-7-Fc potently neutralized all of the tested authentic or pseudotyped viruses, including WT, Alpha, Beta, Gamma, Delta, and Omicron BA.1, BA.1.1 and BA.2. Furthermore, aRBD-2-5-Fc provided prophylactic protection against the WT and mouse-adapted SARS-CoV-2 in mice, and conferred protection against the Omicron BA.1 variant in hamsters prophylactically and therapeutically, indicating that aRBD-2-5-Fc could potentially benefit the prevention and treatment of COVID-19 caused by the emerging variants of concern. Our strategy provides new solutions in the development of broad-spectrum therapeutic antibodies for COVID-19.
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http://dx.doi.org/10.1038/s41422-022-00700-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9334538PMC
July 2022

Pharmacogenomics of Leukotriene Modifiers: A Systematic Review and Meta-Analysis.

J Pers Med 2022 Jun 29;12(7). Epub 2022 Jun 29.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China.

Pharmacogenetics research on leukotriene modifiers (LTMs) for asthma has been developing rapidly, although pharmacogenetic testing for LTMs is not yet used in clinical practice. We performed a systematic review and meta-analysis on the impact of pharmacogenomics on LTMs response. Studies published until May 2022 were searched using PubMed, EMBASE, and Cochrane databases. Pharmacogenomics/genetics studies of patients with asthma using LTMs with or without other anti-asthmatic drugs were included. Statistical tests of the meta-analysis were performed with Review Manager (Revman, version 5.4, The Cochrane Collaboration, Copenhagen, Denmark) and R language and environment for statistical computing (version 4.1.0 for Windows, R Core Team, Vienna, Austria) software. In total, 31 studies with 8084 participants were included in the systematic review and five studies were also used to perform the meta-analysis. Two included studies were genome-wide association studies (GWAS), which showed different results. Furthermore, none of the SNPs investigated in candidate gene studies were identified in GWAS. In candidate gene studies, the most widely studied SNPs were ALOX5 (tandem repeats of the Sp1-binding domain and rs2115819), LTC4S-444A/C (rs730012), and SLCO2B1 (rs12422149), with relatively inconsistent conclusions. LTC4S-444A/C polymorphism did not show a significant effect in our meta-analysis (AA vs. AC (or AC + CC): -0.06, 95%CI: -0.16 to 0.05, = 0.31). AA homozygotes had smaller improvements in parameters pertaining to lung functions (-0.14, 95%CI: -0.23 to -0.05, = 0.002) in a subgroup of patients with non-selective CysLT receptor antagonists and patients without inhaled corticosteroids (ICS) (-0.11, 95%CI: -0.14 to -0.08, < 0.00001), but not in other subgroups. Variability exists in the pharmacogenomics of LTMs treatment response. Our meta-analysis and systematic review found that LTC4S-444A/C may influence the treatment response of patients taking non-selective CysLT receptor antagonists for asthma, and patients taking LTMs not in combination with ICS for asthma. Future studies are needed to validate the pharmacogenomic influence on LTMs response.
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http://dx.doi.org/10.3390/jpm12071068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9316609PMC
June 2022

Systematic Review and Meta-Analysis of Vortioxetine for the Treatment of Major Depressive Disorder in Adults.

Front Psychiatry 2022 24;13:922648. Epub 2022 Jun 24.

Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China.

Objective: We aimed to compare the efficacy, acceptability, and tolerability of vortioxetine in the treatment of Major Depressive Disorder (MDD) in adults.

Method: We searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Clinical Trials (CENTRAL), and www.ClinicalTrials.gov for randomized controlled trials that examined vortioxetine vs. placebo or other antidepressants for the treatment of MDD from database inception to August 30, 2021, using keywords Vortioxetine, Brintellix, Trintellix, LuAA21004, major depressive disorder, mood disorder, affective disorder, and MDD. We identified 789 publications after removing duplicates. After screening, 20 eligible randomized controlled trials were identified, of which 19 were included in the final meta-analysis. We included adults (aged 18 years and older) with a primary diagnosis of MDD. Two review authors independently selected the studies and extracted data. We extracted data on study characteristics, participant characteristics, intervention details and outcome measures in terms of efficacy, acceptability, and tolerability. Analyses were performed using random-effects models, and outcomes were pooled as risk ratios (RRs) and standardized mean differences (SMDs).

Results: In total, 20 studies (8,547 participants) met the inclusion criteria. Vortioxetine outperformed the placebo in efficacy outcomes, including response (RR 1.35, 95% CI 1.23-1.48; < 0.001), remission (RR 1.33, 95% CI 1.17-1.52; < 0.001), and cognitive function (SMD 0.34, 95% CI 0.16-0.52; = 0.0003). Compared with the serotonin noradrenaline reuptake inhibitors (SNRIs), vortioxetine had better tolerability (RR 0.90, 95% CI 0.86-0.94; < 0.001) but no significant difference in response (RR 0.91, 95%CI 0.82-1.00; = 0.06) or remission (RR: 0.99, 95% CI 0.81-1.20, = 0.88). Vortioxetine had no difference in response (RR 1.08, 95% CI 0.88-1.32; = 0.46), remission (RR 1.00, 95% CI 0.41-2.44; = 1.00) comparing with selective serotonin reuptake inhibitors (SSRIs).

Conclusions: Vortioxetine is more advantageous over placebo in treating MDD among adults, but no significant difference compared to SNRIs and SSRIs in general.

Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?ID=CRD42021278355, identifier: CRD42021278355.
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http://dx.doi.org/10.3389/fpsyt.2022.922648DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9263295PMC
June 2022

Metagenomic Next-Generation Sequencing Is Highly Efficient in Diagnosing Pneumocystis Jirovecii Pneumonia in the Immunocompromised Patients.

Front Microbiol 2022 17;13:913405. Epub 2022 Jun 17.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China.

Purposes: To explore the value of metagenomic next-generation sequencing (mNGS) in diagnosing pneumocystis jiroveciipneumonia (PJP) in the immunocompromised patients.

Methods: Data of 122 patients with PJP in an immunosuppressed state and 67 non-PJP patients were collected. The diagnostic efficacy of mNGS was compared with the conventional methods, including Gomori methenamine silver (GMS) staining and serum (1,3)-β-D-glucan (BDG). Changes of anti-microbial therapy for patients with PJP based on mNGS results were also reviewed.

Results: The diagnostic sensitivity of mNGS to PJP was higher than that of GMS and BDG (100% vs. 15 and 74.5%, < 0.001). The diagnostic specificity (91.%) was lower than that of GMS (100%), and similar with BDG (89.6%). In addition to P. jirovecii, mNGS revealed co-pathogens like human β-herpesvirus 5, human γ-pesvirus 4, and some other opportunistic pathogens. The reads of mNGS were remarkably higher in BALF than in blood samples. Initial antimicrobial treatment was modified in 89.3% patients based on the mNGS results, and 74 cases (60.7%) were treated with anti- jirovecii therapy.

Conclusion: mNGS is highly efficient in diagnosing PJP and good at identifying pathogens in mixed infections.
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http://dx.doi.org/10.3389/fmicb.2022.913405DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9247511PMC
June 2022

Impaired Membrane Lipid Homeostasis in Schizophrenia.

Schizophr Bull 2022 Jun 25. Epub 2022 Jun 25.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

Background And Hypothesis: Multiple lines of clinical, biochemical, and genetic evidence suggest that disturbances of membrane lipids and their metabolism are probably involved in the etiology of schizophrenia (SCZ). Lipids in the membrane are essential to neural development and brain function, however, their role in SCZ remains largely unexplored.

Study Design: Here we investigated the lipidome of the erythrocyte membrane of 80 patients with SCZ and 40 healthy controls using ultra-performance liquid chromatography-mass spectrometry. Based on the membrane lipids profiling, we explored the potential mechanism of membrane phospholipids metabolism.

Study Results: By comparing 812 quantified lipids, we found that in SCZ, membrane phosphatidylcholines and phosphatidylethanolamines, especially the plasmalogen, were significantly decreased. In addition, the total polyunsaturated fatty acids (PUFAs) in the membrane of SCZ were significantly reduced, resulting in a decrease in membrane fluidity. The accumulation of membrane oxidized lipids and the level of peripheral lipid peroxides increased, suggesting an elevated level of oxidative stress in SCZ. Further study of membrane-phospholipid-remodeling genes showed that activation of PLA2s and LPCATs expression in patients, supporting the imbalance of unsaturated and saturated fatty acyl remodeling in phospholipids of SCZ patients.

Conclusions: Our results suggest that the mechanism of impaired membrane lipid homeostasis is related to the activated phospholipid remodeling caused by excessive oxidative stress in SCZ. Disordered membrane lipids found in this study may reflect the membrane dysfunction in the central nervous system and impact neurotransmitter transmission in patients with SCZ, providing new evidence for the membrane lipids hypothesis of SCZ.
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http://dx.doi.org/10.1093/schbul/sbac011DOI Listing
June 2022

Application of Multiple-Source Data Fusion for the Discrimination of Two Botanical Origins of Magnolia Officinalis Cortex Based on E-Nose Measurements, E-Tongue Measurements, and Chemical Analysis.

Molecules 2022 Jun 17;27(12). Epub 2022 Jun 17.

National Institutes for Food and Drug Control, Beijing 100050, China.

Rehd. et Wils. and Rehd. et Wils. var. Rehd. et Wils, as the legal botanical origins of Magnoliae Officinalis Cortex, are almost impossible to distinguish according to their appearance traits with respect to medicinal bark. The application of AFLP molecular markers for differentiating the two origins has not yet been successful. In this study, a combination of e-nose measurements, e-tongue measurements, and chemical analyses coupled with multiple-source data fusion was used to differentiate the two origins. Linear discriminant analysis (LDA) and quadratic discriminant analysis (QDA) were applied to compare the discrimination results. It was shown that the e-nose system presented a good discriminant ability with a low classification error for both LDA and QDA compared with e-tongue measurements and chemical analyses. In addition, the discriminating capacity of LDA for low-level fusion with original data, similar to a combined system, was superior or equal to that acquired individually with the three approaches. For mid-level fusion, the combination of different principals extracted by PCA and variables obtained on the basis of PLS-VIP exhibited an analogous discrimination ability for LDA (classification error 0.0%) and was significantly superior to QDA (classification error 1.67-3.33%). As a result, the combined e-nose, e-tongue, and chemical analysis approach proved to be a powerful tool for differentiating the two origins of Magnoliae Officinalis Cortex.
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http://dx.doi.org/10.3390/molecules27123892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9229508PMC
June 2022

Photothermal Dual Passively Driven Liquid Crystal Smart Window.

ACS Appl Mater Interfaces 2022 Jun 12;14(24):28301-28309. Epub 2022 Jun 12.

CAS Key Laboratory of Bio-inspired Materials and Interfaces Sciences, Technique Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.

Photochromic or thermochromic liquid crystal (LC) smart windows have attracted wide attention due to their spontaneous transmittance modulation under different environments. There remains a challenge for the LC smart windows that can be modulated with light and temperature simultaneously owing to the difficulty in selecting photothermal molecules. Herein, we selected a photothermal molecule, isobutyl-substituted diimmonium borate (IDI), which shows excellent characteristics of a photothermal material used in smart windows, such as transparency in the visible light range with a slight brown color, good compatibility with the LC system, and excellent photothermal effect compared with common photothermal materials. Thus, a photothermal dual-driven smart window is developed by doping IDI into chiral LC mixtures, which can efficiently modulate the transmittance at different temperatures (or light intensities) by varying the phase state from the homeotropically oriented smectic phase (transparent) to the focal conic cholesteric phase (opaque). The transmittance is high (70%) when the ambient temperature is low and the light intensity is weak, allowing more sunlight to enter the room. The transmittance is low (20%) when the ambient temperature is high and the light intensity is strong, which prevents sunlight from entering the room. The proposed smart window will have a promising application in terms of energy saving and personalized privacy protection.
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http://dx.doi.org/10.1021/acsami.2c07462DOI Listing
June 2022

Ferulic acid attenuates high glucose-induced apoptosis in retinal pigment epithelium cells and protects retina in db/db mice.

PeerJ 2022 31;10:e13375. Epub 2022 May 31.

Department of Ophthalmology, Ning Xia Eye Hospital, People's Hospital of Ningxia Hui Autonomous Region (First Affiliated Hospital of Northwest University for Nationalities, Ningxia Clinical Research Center on Diseases of Blindness in Eye), Yinchuan, Ningxia, China.

Background: Herein, we aimed to present evidence that Ferulic acid (FA), a phenolic acid, can alleviate high glucose (HG)-induced retinal pigment epithelium (RPE) cell apoptosis and protect retina in db/db mice.

Methods: ARPE-19 cells (a human RPE cell line) were divided into four groups: control group; HG group (30 mmol/L glucose); HG+FA group (30 mmol/L glucose and 10 mmol/L FA). Cell viability and apoptosis were detected using CCK-8 and Annexin-5 staining, respectively. Apoptosis-related markers including P53, BAX and Bcl2 were examined by RT-qPCR, western blot and immunohistochemistry. Totally, 30 male db/db mice were randomly divided into db/db group (5 ml/kg saline) and FA group (0.05 g/kg FA). After treatment for 2 months, retinal samples were subjected to hematoxylin and eosin (H&E) and Masson staining. Moreover, immunofluorescence was used to detect apoptosis-related markers. Blood samples were collected for measuring cholesterol, triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL) levels.

Results: FA treatment markedly increased cell viability and suppressed cell apoptosis of ARPE-19 cells compared to the HG-exposed group. Furthermore, FA ameliorated the abnormal expression levels of P53, BAX and Bcl2 in HG-induced ARPE-19 cells. In animal models, FA attenuated pathological changes in the retina tissues of diabetic mice. Consistent with models, FA significantly ameliorated the expression of apoptosis-related markers in retina tissues. Biochemical test results showed that FA reduced hyperlipidemia in diabetic mice.

Conclusion: Our findings suggest that FA alleviates HG-induced apoptosis in RPE cells and protects retina in db/db mice, which can be associated with P53 and BAX inactivation and Bcl2 activation.
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http://dx.doi.org/10.7717/peerj.13375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9165606PMC
May 2022

Birt-Hogg-Dubé syndrome encountered at rare lung disease clinic in Anhui province, China.

Orphanet J Rare Dis 2022 05 16;17(1):203. Epub 2022 May 16.

Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, 230001, China.

Background: Diagnosis of rare diseases remains a challenge in China. We describe our experience with Birt-Hogg-Dubé syndrome (BHDS) encountered at a Rare Lung Disease Clinic recently established in China.

Methods: After the first patient with BHDS was recognized in 2017, a Rare Lung Disease Clinic with a multidisciplinary team of specialists was established. We retrospectively analyzed the data of consecutive patients with BHDS encountered from inception to December 2021.

Results: There were 1, 1, 15, 12 and 21 cases with BHDS diagnosed from year 2017 to 2021, respectively. All 50 patients (34 women) were of Han race with a mean age of 47.4 years. The common manifestations were pulmonary cysts (98%), pneumothorax (54%) and skin lesions (68%). Renal cancer was detected in two patients and renal angiomyolipoma in four other patients. The main presentations leading to diagnosis were pneumothorax (42%), family screening (36%), and lung cysts identified on radiologic imaging (20%). The average delay in diagnosis was 8.3 years, and 4.7 years in patients with only pulmonary cysts. The most frequent pathogenic variant was c.1285del/dup on exon 11 (23%) among 44 patients confirmed by genetic testing. Renal cancer has not been found on follow-up surveillance thus far.

Conclusions: Increasing number of patients with BHDS are being recognized in China, facilitated by establishment of a Rare Lung Disease Clinic. Pulmonary cysts and pneumothorax were commonly encountered features, but skin lesions appeared to be more prevalent in Chinese subjects than previously reported in other Asian countries.
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http://dx.doi.org/10.1186/s13023-022-02362-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9112470PMC
May 2022

Base water potential but not hydrotime predicts seedling emergence of under water stress conditions.

PeerJ 2022 10;10:e13206. Epub 2022 May 10.

State Key Laboratory of Grassland Agro-Ecosystems; Key Laboratory of Grassland Livestock Industry Innovation, Ministry of Agriculture and Rural Affairs; Engineering Research Center of Grassland Industry, Ministry of Education; College of Pastoral Agricult, Lanzhou, China.

We determined the hydrotime model parameters of 10 alfalfa seed lots by incubating seeds at various water potentials in the laboratory. Meanwhile, seedling emergence under drought and salinity conditions in a greenhouse pot experiment, and seedling establishment in the field were determined. Correlation analysis was utilized to detect the relationship between hydrotime model parameters and seedling emergence under water stress conditions. The germination percentage did not differ significantly among seed lots when seeds were incubated at -0.1 MPa, while it differed significantly among seed lots at water potentials of -0.3 and -0.6 MPa. Compared to control conditions, drought and salinity decreased seedling emergence to different extents, depending on seed lots. Seedling emergence in the field differed significantly among seed lots and ranged from 30% to 80%. showed a significant correlation with seedling emergence under various conditions and with seedling establishment in the field, while no correlation was observed between , and seedling emergence and establishment. These results suggest that can be used to rank the vigor of alfalfa seed lots and thus predict seedling emergence and establishment under water stress conditions.
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http://dx.doi.org/10.7717/peerj.13206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9104092PMC
May 2022

Designable Layer Edge States in Quasi-2D Perovskites Induced by Femtosecond Pulse Laser.

Adv Sci (Weinh) 2022 Jul 12;9(20):e2201046. Epub 2022 May 12.

Laboratory of Quantum Engineering and Quantum Material, School of Physics and Telecommunication Engineering, South China Normal University, Guangzhou, 510006, P. R. China.

The low-energy layer edge states (LESs) from quasi 2D hybrid perovskite single crystals have shown great potential because of their nontrivial photoelectrical properties. However, the underlying formation mechanism of the LESs still remains controversial. Also, the presence or creation of the LESs is of high randomness due to the lack of proper techniques to manually generate these LESs. Herein, using a single crystals platform of quasi-2D (BA) (MA) Pb I (n > 1) perovskites, the femtosecond laser ablation approach to design and write the LESs with a high spatial resolution is reported. Fundamentally, these LESs are of smaller bandgap 3D MAPbI nanocrystals which are formed by the laser-induced BA escaping from the lattice and thus the lattice shrinkage from quasi-2D to 3D structures. Furthermore, by covering the crystal with tape, an additional high-energy emission state corresponding to the reformation of (BA) PbI (n = 1) within the irradiation region is generated. This work presents a simple and efficient protocol to manually write LESs on single crystals and thus lays the foundation for utilizing these LESs to further enhance the performance of future photoelectronic devices.
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http://dx.doi.org/10.1002/advs.202201046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9284193PMC
July 2022

The effect of ambient temperature on hand, foot and mouth disease in Qingdao, China, 2014-2018.

Int J Environ Health Res 2022 May 4:1-10. Epub 2022 May 4.

Department of Acute Infectious Diseases, Qingdao Municipal Centre of Disease Control and Prevention, Qingdao Institute of Prevention Medicine, Qingdao City, Shandong Province, People's Republic of China.

Hand, foot, and mouth disease (HFMD) is a kind of infection gastrointestinal disease. The present study aims to explore the association between ambient temperature and HFMD in Qingdao. A distributed lag nonlinear model with Poisson distribution was adopted to explore the effects of daily mean temperature on HFMD incidence. Our results found that the high temperature had acute and short-term effects and then declined rapidly along the lag days, with the maximum risk occurring 0 day of exposure. Compared with low temperature, higher effects were observed for high-temperature exposure. Overall, we found that the association between temperature and HFMD incidence was non-linear, exhibiting an approximate "J" shape, with peak value occurring at 30.5℃ (RR = 2.208, 95% CI: 1.995-2.444). Our findings suggest that ambient temperature is significantly associated with the incidence of HFMD in Qingdao. Monitoring ambient temperature changes is an appropriate recommendation to prevent HFMD.
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http://dx.doi.org/10.1080/09603123.2022.2072818DOI Listing
May 2022

Laboratory investigation of pollutant emissions and PM toxicity of underground coal fires.

Sci Total Environ 2022 Sep 27;837:155537. Epub 2022 Apr 27.

State Key Laboratory of Fire Science (SKLFS), University of Science and Technology of China, Hefei 230026, China.

Widespread underground coal fires (UCFs) release large amounts of pollutants, thus leading to air pollution and health impacts. However, this topic has not been widely investigated, especially regarding the potential health hazards. We quantified the pollutant emissions and analyzed the physicochemical properties of UCF PM in a laboratory study of coal smoldering under a simulated UCF background. The emission factors of CO, CO, and PM were 2489 ± 35, 122 ± 9, 12.90 ± 1.79 g/kg, respectively. UCF PM are carbonaceous particles with varied morphology and complex composition, including heavy metals, silica and polycyclic aromatic hydrocarbons (PAHs). The main PAHs components were those with 2-4 rings. Benzoapyrene (BaP) and indeno[1,2, 3-cd]pyrene (IcdP) were important contributors to the carcinogenesis of these PAHs. We quantitatively evaluate the toxicity of inhaled UCF PM using a nasal inhalation exposure system. The target organs of UCF PM are lungs, liver, and kidneys. UCF PM presented an enriched chemical composition and induced inflammation and oxidative stress, which together mediated multiple organ injury. Long-term PM metabolism is the main cause of persistent toxicity, which might lead to long-term chronic diseases. Therefore, local authorities should recognize the importance and effects of UCF emissions, especially PM, to establish control and mitigation measures.
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http://dx.doi.org/10.1016/j.scitotenv.2022.155537DOI Listing
September 2022

Exploring noncoding RNAs in thyroid cancer using a graph convolutional network approach.

Comput Biol Med 2022 06 8;145:105447. Epub 2022 Apr 8.

Beidahuang Industry Group General Hospital, Harbin, China. Electronic address:

Noncoding RNAs (ncRNAs) are crucial regulators in initiating and promoting thyroid cancer. Exploring the relationship between ncRNAs and thyroid cancer is essential for the diagnosis and treatment of thyroid cancer. Wet-lab experiments are costly and are difficult to conduct on a large scale. Although there are several ncRNA and cancer-related databases, there are few data related to thyroid cancer. There is a lack of computational approaches for predicting ncRNA-thyroid cancer associations. This work describes TCGCN, a linear residual graph convolution network to predict ncRNA-thyroid cancer associations. We collected a large amount of ncRNA-disease association data and constructed a bipartite graph. We use a simple linear embedding propagation at each convolutional layer and use the weighted sum of the embeddings on all graph convolutional layers to make the final prediction. In 5-fold cross-validation on the ncRNA-thyroid cancer dataset, TCGCN obtained significantly better performances with an AUC of 0.8162 and an AUPR of 0.8049, which are considerably better than those of other state-of-the-art approaches. We also demonstrate the usability of our method in the case studies.
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http://dx.doi.org/10.1016/j.compbiomed.2022.105447DOI Listing
June 2022

DNA methylation age acceleration is associated with age of onset in Chinese spinocerebellar ataxia type 3 patients.

Neurobiol Aging 2022 05 9;113:1-6. Epub 2022 Feb 9.

The First Rehabilitation Hospital of Shanghai, Department of Medical Genetics, School of Medicine, Tongji University, Shanghai, China; Clinical Center for Brain and Spinal Cord Research, Tongji University, Shanghai, China; Institute for Advanced Study, Tongji University, Shanghai, China. Electronic address:

Spinocerebellar ataxia type 3 (SCA3), also known as Machado Joseph disease (MJD), is a common dominantly inherited ataxia, and has heterogeneous clinical features and variable age of onset, ranging from 10 to 78 years. Repeats variability of ATXN3, HTT, ATN1 and ATXN2 can explain partially but not fully SCA3 age of onset heterogeneity. Aging is a reported modifier of SCA3 severity and closely linked to DNA methylation (DNAm). DNAm age acceleration was associated with disease risk and/or variable disease phenotypes in several repeat associated neurodegenerative diseases (such as Huntington's disease and Amyotrophic lateral sclerosis). To understand if DNAm age acceleration is associated with SCA3 age of onset, we performed a genome-wide DNAm study of a Chinese SCA3 family with variable age of onset and clinical presentations. All patients showed unsteady gait, deterioration of extremities coordination, speech (dysarthria) and swallowing problems (dysphagia, choking on eating and/or drinking) and oculomotor abnormalities, with variable age of onset ranging from 27 to 52 years. We found that DNAm age acceleration is associated with age of onset (p-value = 0.0023, B = -1.26), suggesting that every 5 year increase in DNAm-age acceleration is corresponding to a 6.3 year earlier disease onset. This association remains significant after the adjustment to ATXN3 CAG repeats (adjusted p-value = 0.037, adjusted B = -1.0). In an independent SCA3 cohort (n = 40), we also observed the association between DNAm age acceleration and age of onset (adjusted p-value = 0.007, adjusted B = -0.69). Of note, we found no significant association between DNAm of single-CpG locus and/or CpG-SNPs and SCA3 age of onset in the current family or the SCA3 cohort. Our findings suggested that DNAm age acceleration might be a SCA3 age of onset modifier, and encourage further investigations in extended SCA3 cohorts to clarify the role of epigenetic aging in modifying disease onset.
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http://dx.doi.org/10.1016/j.neurobiolaging.2022.02.002DOI Listing
May 2022

Systematic illumination of druggable genes in cancer genomes.

Cell Rep 2022 02;38(8):110400

Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address:

By combining 6 druggable genome resources, we identify 6,083 genes as potential druggable genes (PDGs). We characterize their expression, recurrent genomic alterations, cancer dependencies, and therapeutic potentials by integrating genome, functionome, and druggome profiles across cancers. 81.5% of PDGs are reliably expressed in major adult cancers, 46.9% show selective expression patterns, and 39.1% exhibit at least one recurrent genomic alteration. We annotate a total of 784 PDGs as dependent genes for cancer cell growth. We further quantify 16 cancer-related features and estimate a PDG cancer drug target score (PCDT score). PDGs with higher PCDT scores are significantly enriched for genes encoding kinases and histone modification enzymes. Importantly, we find that a considerable portion of high PCDT score PDGs are understudied genes, providing unexplored opportunities for drug development in oncology. By integrating the druggable genome and the cancer genome, our study thus generates a comprehensive blueprint of potential druggable genes across cancers.
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http://dx.doi.org/10.1016/j.celrep.2022.110400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8919705PMC
February 2022

Correlative analysis of lung CT findings in patients with Birt-Hogg-Dubé Syndrome and the occurrence of spontaneous pneumothorax: a preliminary study.

BMC Med Imaging 2022 02 7;22(1):22. Epub 2022 Feb 7.

Department of Radiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China.

Background: The diagnosis of patients with Birt-Hogg-Dubé (BHD) syndrome is always delayed (even for more than 10 years). Improving the understanding and diagnosis of this disease is vital for clinicians and radiologists. In this study we presented the chest computed tomography (CT) findings of BHD syndrome and offered suggestions for BHD cases with spontaneous pneumothorax.

Methods: Twenty-six BHD patients from 11 families (10 men, 16 women; mean age: 46 ± 12 years, 20-68 years) were included. The clinical features of the patients included pneumothorax, renal lesions, and skin lesions. Twenty-three patients underwent chest CT imaging. The cyst condition of each patient derived from reconstructed chest CT imaging was recorded, including the cyst number, size, volume, pattern, and distribution.

Results: Pneumothorax occurred in 54% (14/26) of patients. Among them, 43% (6/14) had pneumothorax more than twice. However, typical skin and renal lesions were absent. Four patients had renal hamartoma. CT showed that 23 (100%) patients had lung cysts. Pulmonary cysts were bilateral and multiple, round, irregular, or willow-like. And 93.6% of the large cysts (long-axis diameter ≥ 20 mm) were under the pleura, and near the mediastinum and spine. The long-axis diameter, short-axis diameter and volume of the largest cysts were associated with the occurrence of pneumothorax (all P < 0.05).

Conclusions: Chest CT imaging can reveal some characteristic features of BHD syndrome. The occurrence of pneumothorax in BHD patients is closely related to their pulmonary cystic lesions.
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http://dx.doi.org/10.1186/s12880-022-00743-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8819866PMC
February 2022

The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets.

Nat Cancer 2021 12 13;2(12):1406-1422. Epub 2021 Dec 13.

Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, PA, USA.

Cell-surface proteins (SPs) are a rich source of immune and targeted therapies. By systematically integrating single-cell and bulk genomics, functional studies and target actionability, in the present study we comprehensively identify and annotate genes encoding SPs (GESPs) pan-cancer. We characterize GESP expression patterns, recurrent genomic alterations, essentiality, receptor-ligand interactions and therapeutic potential. We also find that mRNA expression of GESPs is cancer-type specific and positively correlates with protein expression, and that certain GESP subgroups function as common or specific essential genes for tumor cell growth. We also predict receptor-ligand interactions substantially deregulated in cancer and, using systems biology approaches, we identify cancer-specific GESPs with therapeutic potential. We have made this resource available through the Cancer Surfaceome Atlas ( http://fcgportal.org/TCSA ) within the Functional Cancer Genome data portal.
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http://dx.doi.org/10.1038/s43018-021-00282-wDOI Listing
December 2021

Assessment of predicted aircraft engine non-volatile particulate matter emissions at Hangzhou Xiaoshan International Airport using an integrated method.

J Air Waste Manag Assoc 2022 Apr 9;72(4):370-382. Epub 2022 Mar 9.

Department of Aeronautics and Astronautics, Fudan University, Shanghai, People's Republic of China.

Assessing the aircraft engine nonvolatile particulate matter (nvPM) emissions during landing and take-off (LTO) cycles is significant for airport air quality management. However, presently few prior studies have examined aircraft engine nvPM emissions on a daily basis for optimizing flight operations at airports. Therefore, based on the latest first-order approximation method of engine nvPM emissions, we introduce the engine emission data and aircraft flight data to establish an integrated method for estimating daily aircraft engine nvPM emissions at airports. This method can be applied to obtain different engine nvPM mass and number emissions in each phase of the LTO cycle, and therefore the total nvPM mass and number emissions in different time periods can be estimated for the analysis of the sources and trends of daily aircraft engine nvPM emissions during LTO cycles at Hangzhou Xiaoshan International Airport. Results show that the highest aircraft engine nvPM mass and number emissions are generally predicted to occur in the climb and taxi/ground idle phase, respectively. The proportion of total engine nvPM mass and number emissions in each phase of the LTO cycle could also be estimated, specifically the take-off phase (21% & 6%), climb phase (52% &15%), approach phase (8% & 27%), and taxi/ground idle phase (19% & 52%). In addition, the trends of hourly engine nvPM mass and number emissions during LTO cycles within a day are similar, but the predicted highest total hourly engine nvPM mass and number emissions occur in different time periods (7:00-8:00 a.m. & 11:00-12:00 a.m.) at the airport, and the total hourly engine nvPM mass and number emissions at 6:00 a.m. to 17:00 p.m. are generally higher than those of the rest periods. These results are valuable for optimizing flight operations for mitigating the environmental impact of aircraft engine nvPM emissions.: The integrated method for estimating engine nvPM mass and number emissions in the LTO cycle based on FOA4.0 method reported in this study is effective to assess the sources and trends of daily aircraft engine nvPM emissions during LTO cycles at airports, which is valuable for optimizing flight operations considering the environmental impact of aircraft engine nvPM emissions. When the relevant aircraft flights, engine parameters, and engine nvPM emission databases embedded in the integrated method for any airport are established, the method is feasible to assess the sources and trends of aircraft engine nvPM emissions during LTO cycles at any time period in the airport.
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http://dx.doi.org/10.1080/10962247.2022.2029617DOI Listing
April 2022

Extracellular vesicles from adipose-derived stem cells promote microglia M2 polarization and neurological recovery in a mouse model of transient middle cerebral artery occlusion.

Stem Cell Res Ther 2022 01 20;13(1):21. Epub 2022 Jan 20.

Shanghai Sixth People's Hospital and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, 200030, China.

Background: Adipose-derived stem cells (ADSCs) and their extracellular vesicles (EVs) have therapeutic potential in ischemic brain injury, but the underlying mechanism is poorly understood. The current study aimed to explore the contribution of miRNAs in ADSC-EVs to the treatment of cerebral ischemia.

Methods: After the intravenous injection of ADSC-EVs, therapeutic efficacy was evaluated by neurobehavioral tests and brain atrophy volume. The polarization of microglia was assessed by immunostaining and qPCR. We further performed miRNA sequencing of ADSC-EVs and analyzed the relationship between the upregulated miRNAs in ADSC-EVs and microglial polarization-related proteins using Ingenuity Pathway Analysis (IPA).

Results: The results showed that ADSC-EVs reduced brain atrophy volume, improved neuromotor and cognitive functions after mouse ischemic stroke. The loss of oligodendrocytes was attenuated after ADSC-EVs injection. The number of blood vessels, as well as newly proliferated endothelial cells in the peri-ischemia area were higher in the ADSC-EVs treated group than that in the PBS group. In addition, ADSC-EVs regulated the polarization of microglia, resulting in increased repair-promoting M2 phenotype and decreased pro-inflammatory M1 phenotype. Finally, STAT1 and PTEN were highlighted as two downstream targets of up-regulated miRNAs in ADSC-EVs among 85 microglia/macrophage polarization related proteins by IPA. The inhibition of STAT1 and PTEN by ADSC-EVs were confirmed in cultured microglia.

Conclusions: In summary, ADSC-EVs reduced ischemic brain injury, which was associated with the regulation of microglial polarization. miRNAs in ADSC-EVs partly contributed to their function in regulating microglial polarization by targeting PTEN and STAT1.
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http://dx.doi.org/10.1186/s13287-021-02668-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8772170PMC
January 2022

In silico identification of sugarcane (Saccharum officinarum L.) genome encoded microRNAs targeting sugarcane bacilliform virus.

PLoS One 2022 20;17(1):e0261807. Epub 2022 Jan 20.

Institute of Tropical Bioscience and Biotechnology, Sugarcane Research Centre of Chinese Academy of Tropical Agricultural Sciences, Haikou, China.

Sugarcane bacilliform virus (SCBV) is considered one of the most economically damaging pathogens for sugarcane production worldwide. Three open reading frames (ORFs) are characterized in the circular, ds-DNA genome of the SCBV; these encode for a hypothetical protein (ORF1), a DNA binding protein (ORF2), and a polyprotein (ORF3). A comprehensive evaluation of sugarcane (Saccharum officinarum L.) miRNAs for the silencing of the SCBV genome using in silico algorithms were carried out in the present study using mature sugarcane miRNAs. miRNAs of sugarcane are retrieved from the miRBase database and assessed in terms of hybridization with the SCBV genome. A total of 14 potential candidate miRNAs from sugarcane were screened out by all used algorithms used for the silencing of SCBV. The consensus of three algorithms predicted the hybridization site of sof-miR159e at common locus 5534. miRNA-mRNA interactions were estimated by computing the free-energy of the miRNA-mRNA duplex using the RNAcofold algorithm. A regulatory network of predicted candidate miRNAs of sugarcane with SCBV-ORFs, generated using Circos-is used to identify novel targets. The predicted data provide useful information for the development of SCBV-resistant sugarcane plants.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0261807PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8775236PMC
February 2022

How do microalgae in response to biological pollution treat in cultivation? A case study investigating microalgal defense against ciliate predator Euplotes vannus.

Environ Sci Pollut Res Int 2022 May 11;29(21):32171-32179. Epub 2022 Jan 11.

College of Marine Life Sciences & Institute of Evolution and Marine Biodiversity, Ocean University of China, Qingdao, China.

Microalgae have significant amounts of proteins, lipids, carotenoids, vitamins, minerals, and unique pigments. However, with the gradual expansion of microalgae cultivation, hostile biological pollution seriously restricted the large-scale microalgae cultivation and limited the exploitation of its biological resources. Moreover, protozoan poses the greatest threat to microalgae cultivation. Here, the relationship between six marine economic microalgae populations and their ciliate predator Euplotes vannus was examined. And four concentrations were designed for each type of microalgae to carry out the experiment. It was revealed that four species of microalgae inhibit the ciliate population growth at high density. Furthermore, the experiment which was the influence of microalgae at three different growth stages on the growth of the ciliates for these four kinds of high-density inhibitory microalgae was designed. The microalgae inhibitory effects were already exhibited at the end of the exponential growth phase, and it was significantly inhibited during the stationary growth phase. As the microalgae concentration increased, the inhibitory effect became more pronounced. This study provides fundamental data for screening protozoan-inhibiting microalgae and shows potential to be used in algae cultivation.
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http://dx.doi.org/10.1007/s11356-021-18123-9DOI Listing
May 2022

Photo-Embossed Surface Relief Structures with Improved Aspect Ratios and Their Applications in Liquid Crystal Devices.

Polymers (Basel) 2022 Jan 2;14(1). Epub 2022 Jan 2.

SCNU-TUE Joint Lab of Device Integrated Responsive Materials (DIRM), National Center for International Research on Green Optoelectronics, South China Normal University, No. 378, West Waihuan Road, Guangzhou Higher Education Mega Center, Guangzhou 510006, China.

Photo-embossing has been developed as a convenient and economical method for creating complex surface relief structures in polymer films. The pursuit for large aspect ratios of the photo-embossed structures has never stopped. Here, we demonstrate a simple strategy to obtain improved aspect ratios by adding a quick solvent developing step into the photo-embossing process. A good solvent for the monomer is used to remove unreacted monomers from the unexposed region, resulting in deepened valleys of the surface reliefs. In a polymer film as thin as 2.5 µm, the height of the surface reliefs can be increased by a factor of three to around 1.0 µm. This strategy is also shown to be compatible with other methods used to improve the aspect ratios of the photo-embossed structures. Lastly, we employ these surface relief structures in the fabrication of liquid crystal (LC) devices and investigate their performances for visible light regulation.
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http://dx.doi.org/10.3390/polym14010171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8747292PMC
January 2022

Cluster randomised controlled trial to assess a tailored intervention to reduce antibiotic prescribing in rural China: study protocol.

BMJ Open 2022 Jan 3;12(1):e048267. Epub 2022 Jan 3.

School of Health Services Management, Anhui Medical University, Hefei, Anhui, China

Introduction: Up to 80% of patients with respiratory tract infections (RTI) attending healthcare facilities in rural areas of China are prescribed antibiotics, many of which are unnecessary. Since 2009, China has implemented several policies to try to reduce inappropriate antibiotic use; however, antibiotic prescribing remains high in rural health facilities.

Methods And Analysis: A cluster randomised controlled trial will be carried out to estimate the effectiveness and cost effectiveness of a complex intervention in reducing antibiotic prescribing at township health centres in Anhui Province, China. 40 Township health centres will be randomised at a 1:1 ratio to the intervention or usual care arms. In the intervention group, practitioners will receive an intervention comprising: (1) training to support appropriate antibiotic prescribing for RTI, (2) a computer-based treatment decision support system, (3) virtual peer support, (4) a leaflet for patients and (5) a letter of commitment to optimise antibiotic use to display in their clinic. The primary outcome is the percentage of antibiotics (intravenous and oral) prescribed for RTI patients. Secondary outcomes include patient symptom severity and duration, recovery status, satisfaction, antibiotic consumption. A full economic evaluation will be conducted within the trial period. Costs and savings for both clinics and patients will be considered and quality of life will be measured by EuroQoL (EQ-5D-5L). A qualitative process evaluation will explore practitioner and patient views and experiences of trial processes, intervention fidelity and acceptability, and barriers and facilitators to implementation.

Ethics And Dissemination: Ethical approval was obtained from the Biomedical Research Ethics Committee of Anhui Medical University (Ref: 20180259); the study has undergone due diligence checks and is registered at the University of Bristol (Ref: 2020-3137). Research findings will be disseminated to stakeholders through conferences and peer-reviewed journals in China, the UK and internationally.

Trial Registration Number: ISRCTN30652037.
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http://dx.doi.org/10.1136/bmjopen-2020-048267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724711PMC
January 2022

A comprehensive review on immuno-nanomedicine for breast cancer therapy: Technical challenges and troubleshooting measures.

Int Immunopharmacol 2022 Feb 16;103:108433. Epub 2021 Dec 16.

Department of Bio-Health convergence, Kangwon National University, Chuncheon 200-701, Republic of Korea. Electronic address:

Nanosized drug carriers have received a major attention in cancer therapeutics and theranostics. The immuno-nanomedicine is a combination of monoclonal antibody (mAb)/mAb-drug-nanoparticles. The immuno-nanomedicine offers a promising strategy to target cancer cells. However, the understating of nanotechnology, cancer biology, immunomedicine, and nanoparticle surface chemistry has provided a better clue to prepare the effective immuno-nanomedicine for cancer therapy. Moreover, the selection of nanoparticles type and its composition is essential for development of efficient drug delivery system (DDS) to target the cancer cell site. Immuno-nanomedicine works in the ligand-receptor binding mechanism through the interaction of mAb conjugated nanoparticles and specific antigen over expressed on target cancer cells. Therefore, the selection of specific receptors in the cancer cell and their ligand is important to prepare the active immuno-nanomedicines. Moreover, the factors such as drug loading, entrapment efficiency, size, shape, and ligand conjugation of a nanocarrier are considered as major factors for a better cancer cell, internalization, drug release, and cancer cell ablation. The target-based over-expression of antigen, mAb is engineered and conjugated with nanoparticles for successful targeting of the cancer cells without causing adverse effects to normal cells. Therefore, this review analyzed the fundamental factors in the immuno-nanomedicine for breast cancer and its technical challenges in the fabrication of the antibody alone/and drug conjugated nanoparticles.
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http://dx.doi.org/10.1016/j.intimp.2021.108433DOI Listing
February 2022

Lattice B-doping evolved ferromagnetic perovskite-like catalyst for enhancing persulfate-based degradation of norfloxacin.

J Hazard Mater 2022 03 29;425:127949. Epub 2021 Nov 29.

Gansu Key Laboratory for Environmental Pollution Prediction and Control, College of Earth and Environmental Sciences, Lanzhou University, Lanzhou 730000, China. Electronic address:

Series of B-doped perovskite-like materials CeCuCoO (B-CO) were fabricated with unique ferromagnetic property due to partial substitution of non-magnetic 2p-impurities boron in the lattice. Then, B-CO was used for activating peroxymonosulfate (PMS) for the degradation of norfloxacin (NOR), one kind of emerging pollutants with the concentration level up to mg/L in wastewaters. The results indicated that 5.0% B-CO exhibited stable catalytic ability at pH 3.0-9.0 and high degradation efficiency in co-existing inorganic Cl, SO, NO, HPO and organic humic acid. Non-radical O, radicals •OH and SO, as well as ClO were detected with synergy effect for NOR degradation. By quantifying free radicals, •OH with 0.52 µM and SO with 10.91 µM were obtained at 180 min, verifying the leading role of SO. The degradation process involved the defluorination and decarboxylation, as well as opening of quinolone and piperazinyl rings. Adopting alfalfa as the model plant, the toxicity effect before and after NOR degradation was finally evaluated with seed germination rate and chlorophyll content as the physiological indicators. In summary, non-metal B-doping not only provides a creative strategy for the development of ferromagnetic perovskite-like materials, but also affords excellent catalysts for aiding the advanced oxidation technology for removal of emerging pollutants in wastewaters.
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http://dx.doi.org/10.1016/j.jhazmat.2021.127949DOI Listing
March 2022

Systematic Pan-Cancer Characterization of Nuclear Receptors Identifies Potential Cancer Biomarkers and Therapeutic Targets.

Cancer Res 2022 01 8;82(1):46-59. Epub 2021 Nov 8.

Center for Research on Reproduction & Women's Health, University of Pennsylvania, Philadelphia, Pennsylvania.

The nuclear receptor (NR) superfamily is one of the major druggable gene families, representing targets of approximately 13.5% of approved drugs. Certain NRs, such as estrogen receptor and androgen receptor, have been well demonstrated to be functionally involved in cancer and serve as informative biomarkers and therapeutic targets in oncology. However, the spectrum of NR dysregulation across cancers remains to be comprehensively characterized. Through computational integration of genetic, genomic, and pharmacologic profiles, we characterized the expression, recurrent genomic alterations, and cancer dependency of NRs at a large scale across primary tumor specimens and cancer cell lines. Expression levels of NRs were highly cancer-type specific and globally downregulated in tumors compared with corresponding normal tissue. Although the majority of NRs showed copy-number losses in cancer, both recurrent focal gains and losses were identified in select NRs. Recurrent mutations and transcript fusions of NRs were observed in a small portion of cancers, serving as actionable genomic alterations. Analysis of large-scale CRISPR and RNAi screening datasets identified 10 NRs as strongly selective essential genes for cancer cell growth. In a subpopulation of tumor cells, growth dependencies correlated significantly with expression or genomic alterations. Overall, our comprehensive characterization of NRs across cancers may facilitate the identification and prioritization of potential biomarkers and therapeutic targets, as well as the selection of patients for precision cancer treatment. SIGNIFICANCE: Computational analysis of nuclear receptors across multiple cancer types provides a series of biomarkers and therapeutic targets within this protein family.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8732309PMC
January 2022

Salivary microbiome profiling reveals a dysbiotic schizophrenia-associated microbiota.

NPJ Schizophr 2021 Oct 28;7(1):51. Epub 2021 Oct 28.

Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.

Schizophrenia is a debilitating mental disorder and often has a prodromal period, referred to as clinical high risk (CHR) for psychosis, prior to the first episode. The etiology and pathogenesis of schizophrenia remain unclear. Despite the human gut microbiome being associated with schizophrenia, the role of the oral microbiome, which is a vital player in the mouth-body connection, is not well understood. To address this, we performed 16S rRNA gene sequencing to investigate the salivary microbiome in 85 patients with drug-naïve first-episode schizophrenia (FES), 43 individuals at CHR, and 80 healthy controls (HCs). The salivary microbiome of FES patients was characterized by higher α-diversity and lower β-diversity heterogeneity than those of CHR subjects and HCs. Proteobacteria, the predominant phylum, was depleted, while Firmicutes and the Firmicutes/Proteobacteria ratio was enriched, in a stepwise manner from HC to CHR to FES. HS-producing bacteria exhibited disease-stage-specific enrichment and could be potential diagnostic biomarkers for FES and CHR. Certain salivary microbiota exhibited disease-specific correlation patterns with symptomatic severities, peripheral pro-inflammatory cytokines, thioredoxin, and S100B in FES. Furthermore, the metabolic functions from inferred metagenomes of the salivary microbiome were disrupted in FES, especially amino acid metabolism, carbohydrate metabolism, and xenobiotic degradation. This study has established a link between salivary microbiome alterations and disease initiation and provided the hypothesis of how the oral microbiota could influence schizophrenia.
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http://dx.doi.org/10.1038/s41537-021-00180-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8553823PMC
October 2021

Machine learning methods to predict the cultivation age of Panacis Quinquefolii Radix.

Chin Med 2021 Oct 9;16(1):100. Epub 2021 Oct 9.

National Institutes for Food and Drug Control, Institute for Control of Chinese Traditional Medicine and Ethnic Medicine, Beijing, 100050, China.

Background: American ginseng (AG) is a valuable medicine widely consumed as a herbal remedy throughout the world. Huge price difference among AG with different growth years leads to intentional adulteration for higher profits. Thus, developing reliable approaches to authenticate the cultivation ages of AG products is of great use in preventing age falsification.

Methods: A total of 106 batches of AG samples along with their 9 physicochemical features were collected and measured from experiments, which was then split into a training set and two test sets (test set 1 and 2) according to the cultivation regions. Principle component analysis (PCA) was carried out to examine the distribution of the three data sets. Four machine learning (ML) algorithms, namely elastic net, k-nearest neighbors, support vector machine and multi-layer perception (MLP) were employed to construct predictive models using the features as inputs and their growth years as outputs. In addition, a similarity-based applicability domain (AD) was defined for these models to ensure the reliability of the predictive results for AG samples produced in different regions.

Results: A positive correlation was observed between the several features and the growth years. PCA revealed diverse distributions among different cultivation regions. The most accurate model derived from MLP shows good prediction power for the fivefold cross validation and the test set 1 with mean square error (MSE) of 0.017 and 0.016 respectively, but a higher MSE value of 1.260 for the test set 2. After applying the AD, all models showed much lower prediction errors for the test samples within AD (IDs) than those outside the AD (ODs). MLP remains the best predictive model with an MSE value of 0.030 for the IDs.

Conclusion: Cultivation years have a close relationship with bioactive components of AG. The constructed models and AD are also able to predict the cultivation years and discriminate samples that have inaccurate prediction results. The AD-equipped models used in this study provide useful tools for determining the age of AG in the market and are freely available at https://github.com/dreadlesss/Panax_age_predictor .
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http://dx.doi.org/10.1186/s13020-021-00511-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501543PMC
October 2021
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