Publications by authors named "Xin Lin"

643 Publications

The multimodal imaging characteristics of IRVAN syndrome: a case report.

Am J Transl Res 2021 15;13(8):9866-9873. Epub 2021 Aug 15.

School of Clinical Medicine, Weifang Medical University Weifang, Shandong Province, China.

Background: In this case report, we aimed to describe the multimodal imaging characteristics and the successful treatment of idiopathic retinal vasculitis, aneurysms, and neuroretinitis (IRVAN) syndrome in a 39-year-old man.

Case Presentation: His both eyes were diagnosed with IRVAN syndrome via multimodal imaging, including fundus color photograph, multicolor imaging, infrared ray, fundus autofluorescence, fundus fluorescence angiography and optical coherence tomography angiography. Both eyes were treated with vitrectomy and laser photocoagulation. The treatment was effective. Eighteen months after discharge, the patient had visual acuity of 20/20 in both eyes.

Conclusions: This case report demonstrates that vitrectomy and retinal laser photocoagulation can be successful in treating a patient with IRVAN syndrome in both eyes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430155PMC
August 2021

Sono-photo hybrid process for the synergistic degradation of levofloxacin by FeVO/BiVO: Mechanisms and kinetics.

Environ Res 2021 Sep 10;204(Pt A):112032. Epub 2021 Sep 10.

College of Civil Engineering, Fuzhou University, 350116, Fujian, China.

A novel FeVO/BiVO heterojunction photocatalyst was synthesized by hydrothermal method. The FeVO/BiVO nanostructures were characterized by XRD, SEM, XPS, UV-vis, and photoluminescence spectroscopy. The effects of catalyst dosage, contaminant concentration, initial hydrogen peroxide (HO) concentration, and pH value on the degradation of levofloxacin were investigated and several repeated experiments were conducted to evaluate the stability and reproducibility. The optimized process parameters were used for mineralization experiments. Reactive oxygen species, degradation intermediates, and possible catalytic mechanisms were also investigated. The results showed that the sonophotocatalytic performance of the FeVO/BiVO heterojunction catalyst was better than that of sonocatalysis and photocatalysis. In addition, the Type II heterojunction formed by the material still had good stability in the degradation of levofloxacin after 5 cycles. The possible degradation pathway and mechanism of levofloxacin by sonophotocatalysis were put forward. This work develops new sono-photo hybrid process for potential application in the field of wastewater treatment.
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http://dx.doi.org/10.1016/j.envres.2021.112032DOI Listing
September 2021

Transmission dynamics and the effects of non-pharmaceutical interventions in the COVID-19 outbreak resurged in Beijing, China: a descriptive and modelling study.

BMJ Open 2021 09 7;11(9):e047227. Epub 2021 Sep 7.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China

Objective: To evaluate epidemiological characteristics and transmission dynamics of COVID-19 outbreak resurged in Beijing and to assess the effects of three non-pharmaceutical interventions.

Design: Descriptive and modelling study based on surveillance data of COVID-19 in Beijing.

Setting: Outbreak in Beijing.

Participants: The database included 335 confirmed cases of COVID-19.

Methods: To conduct spatiotemporal analyses of the outbreak, we collected individual records on laboratory-confirmed cases of COVID-19 from 11 June 2020 to 5 July 2020 in Beijing, and visitor flow and products transportation data of Xinfadi Wholesale Market. We also built a modified susceptible-exposed-infected-removed model to investigate the effect of interventions deployed in Beijing.

Results: We found that the staff working in the market (52.2%) and the people around 10 km to this epicentre (72.5%) were most affected, and the population mobility entering-exiting Xinfadi Wholesale Market significantly contributed to the spread of COVID-19 (p=0.021), but goods flow of the market had little impact on the virus spread (p=0.184). The prompt identification of Xinfadi Wholesale Market as the infection source could have avoided a total of 25 708 (95% CI 13 657 to 40 625) cases if unnoticed transmission lasted for a month. Based on the model, we found that active screening on targeted population by nucleic acid testing alone had the most significant effect.

Conclusions: The non-pharmaceutical interventions deployed in Beijing, including localised lockdown, close-contact tracing and community-based testing, were proved to be effective enough to contain the outbreak. Beijing has achieved an optimal balance between epidemic containment and economic protection.
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http://dx.doi.org/10.1136/bmjopen-2020-047227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8424429PMC
September 2021

Gate Alignment of Liquid Water Molecules in Electric Double Layer.

Front Chem 2021 17;9:717167. Epub 2021 Aug 17.

Physics Department, State Key Laboratory of Surface Physics, Key Laboratory of Micro and Nano Photonic Structures [Ministry of Education (MOE)], Fudan University, Shanghai, China.

The behavior of liquid water molecules near an electrified interface is important to many disciplines of science and engineering. In this study, we applied an external gate potential to the silica/water interface via an electrolyte-insulator-semiconductor (EIS) junction to control the surface charging state. Without varying the ionic composition in water, the electrical gating allowed an efficient tuning of the interfacial charge density and field. Using the sum-frequency vibrational spectroscopy, we found a drastic enhancement of interfacial OH vibrational signals at high potential in weakly acidic water, which exceeded that from conventional bulk-silica/water interfaces even in strong basic solutions. Analysis of the spectra indicated that it was due to the alignment of liquid water molecules through the electric double layer, where the screening was weak because of the low ion density. Such a combination of strong field and weak screening demonstrates the unique tuning capability of the EIS scheme, and would allow us to investigate a wealth of phenomena at charged oxide/water interfaces.
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http://dx.doi.org/10.3389/fchem.2021.717167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8416066PMC
August 2021

The indole-hydantoin derivative exhibits anti-inflammatory activity by preventing the transactivation of NF-κB through the inhibition of NF-κB p65 phosphorylation at Ser276.

Int Immunopharmacol 2021 Aug 30;100:108092. Epub 2021 Aug 30.

Division of Hygienic Chemistry, Faculty of Pharmacy, Keio University, 1-5-30 Shibakoen, Minato-ku, Tokyo 105-8512, Japan. Electronic address:

Indole- and hydantoin-based derivatives both exhibit anti-inflammatory activity, suggesting that the structures of indole and hydantoin are functional for this activity. In the present study, we synthesized two types of indole-hydantoin derivatives, IH-1 (5-(1H-indole-3-ylmethylene) imidazolidine-2,4-dione) and IH-2 (5-(1H-indole-3-ylmethyl) imidazolidine-2,4-dione) and examined their effects on LPS-induced inflammatory responses in murine macrophage-like RAW264.7 cells. LPS-induced inflammatory responses were not affected by indole, hydantoin, or IH-2. In contrast, IH-1 significantly inhibited the LPS-induced production of nitric oxide (NO) and secretion of CCL2 and CXCL1 by suppressing the mRNA expression of inducible NO synthase (iNOS), CCL2, and CXCL1. IH-1 markedly inhibited the LPS-induced activation of NF-κB without affecting the degradation of IκBα or nuclear translocation of NF-κB. IH-1 markedly attenuated the transcriptional activity of NF-κB by suppressing the LPS-induced phosphorylation of the NF-κB p65 subunit at Ser276. Furthermore, IH-1 prevented the LPS-induced interaction of NF-κB p65 subunit with a transcriptional coactivator, cAMP response element-binding protein (CBP). Collectively, these results revealed the potential of the novel indole-hydantoin derivative, IH-1 as an anti-inflammatory drug.
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http://dx.doi.org/10.1016/j.intimp.2021.108092DOI Listing
August 2021

Characteristics of the Computed Tomography Imaging Findings in 72 Patients with Airway-Invasive Pulmonary Aspergillosis.

Med Sci Monit 2021 Aug 28;27:e931162. Epub 2021 Aug 28.

Department of Respiratory and Critical Care, Beijing Shijitan Hospital, Capital Medical University; Peking University Ninth School of Clinical Medicine; Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China (mainland).

BACKGROUND This multiple-center retrospective study aimed to investigate computed tomography (CT) imaging findings in 72 patients with airway-invasive pulmonary aspergillosis. MATERIAL AND METHODS Seventy-two patients with airway-invasive pulmonary aspergillosis confirmed by pathology results were divided into 3 types according to image characteristics. Type I involved the trachea or the main bronchus. Type II involved the lobular and segmental bronchi, which manifested early as bronchial wall thickening, and later development was divided into types IIa and IIb. Type IIa manifested as bronchiectasis, and type IIb manifested as consolidation around the bronchus. Type III involved the bronchioles and pulmonary parenchyma, with tree-in-bud sign and acinar nodules around. CT signs of the various types and their differentiation were investigated. RESULTS The main clinical manifestations of the 72 patients with airway-invasive pulmonary aspergillosis were shortness of breath (55/72, 76.4%), cough (40/72, 55.6%), expectoration (35/72, 48.6%), dyspnea (8/72, 11.1%), weight loss (2/72, 2.8%), and fever (30/72, 41.7%). CT typing identified 3 types: 2 patients (2.8%) had type I, presenting as thickening of trachea or main bronchial walls; 3 patients (4.2%) had early type II, manifesting as thickening of lobular or segmental bronchial walls; 27 patients (37.5%) developed type IIa, manifesting as bronchiectasis; 22 patients (30.6%) had type IIb, manifesting as consolidation around the bronchus; and 18 patients (25.0%) had type III, presenting as nodules and patchy shadows with small cavities in the periphery of the lung. CONCLUSIONS Airway pulmonary aspergillosis has characteristic imaging findings, which can help early clinical diagnosis through classification according to CT imaging characteristics.
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http://dx.doi.org/10.12659/MSM.931162DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8409142PMC
August 2021

Dysregulated long noncoding RNAs in the brainstem of the DBA/1 mouse model of SUDEP.

BMC Genomics 2021 Aug 17;22(1):621. Epub 2021 Aug 17.

Department of Neurology, West China Hospital, Sichuan University, Wai Nan Guo Xue Lane 37 #, 610041, Chengdu, Sichuan, China.

Background: Long noncoding RNAs (lncRNAs) play an important role in many neurological diseases. This study aimed to investigate differentially expressed lncRNAs and messenger RNAs (mRNAs) in the susceptibility gaining process of primed DBA/1 mice, a sudden unexpected death in epilepsy (SUDEP) model, to illustrate the potential role of lncRNAs in SUDEP.

Methods: The Arraystar mouse lncRNA Microarray V3.0 (Arraystar, Rockville, MD) was applied to identify the aberrantly expressed lncRNAs and mRNAs between primed DBA/1 mice and normal controls. The differences were verified by qRT-PCR. We conducted gene ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and coexpression analyses to explore the possible function of the dysregulated RNAs.

Results: A total of 502 lncRNAs (126 upregulated and 376 downregulated lncRNAs) and 263 mRNAs (141 upregulated and 122 downregulated mRNAs) were dysregulated with P < 0.05 and a fold change over 1.5, among which Adora3 and Gstt4 were possibly related to SUDEP. GO analysis revealed that chaperone cofactor-dependent protein refolding and misfolded protein binding were among the top ten downregulated terms, which pointed to Hspa1a, Hspa2a and their related lncRNAs. KEGG analysis identified 28 upregulated and 10 downregulated pathways. Coexpression analysis showed fifteen dysregulated long intergenic noncoding RNAs (lincRNAs) and three aberrantly expressed antisense lncRNAs, of which AK012034 and NR_040757 are potentially related to SUDEP by regulating LMNB2 and ITPR1, respectively.

Conclusions: LncRNAs and their coexpression mRNAs are dysregulated in the priming process of DBA/1 in the brainstem. Some of these mRNAs and lncRNAs may be related to SUDEP, including Adora3, Lmnb2, Hspa1a, Hspa1b, Itrp1, Gstt4 and their related lncRNAs. Further study on the mechanism of lncRNAs in SUDEP is needed.
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http://dx.doi.org/10.1186/s12864-021-07921-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8369804PMC
August 2021

The Impact of Switching Intention of Telelearning in COVID-19 Epidemic's Era: The Perspective of Push-Pull-Mooring Theory.

Front Psychol 2021 28;12:639589. Epub 2021 Jul 28.

Chulalongkorn Business School, Chulalongkorn University, Bangkok, Thailand.

Under the impact of COVID-19, medical telelearning education is increasingly becoming urgent to resolve the contradiction between the physical isolation of medical students and the need for on-site clinical teaching. In this study, the push-pull-mooring (PPM) theory is integrated into a comprehensive model as a conceptual PPM framework: push factors (information system quality and perceived risk), pull factors [telepresence (TP), trust, etc.], mooring factors (switching costs), and switching intention. The results show that most hypotheses were positive, but perceived risk did not influence user satisfaction significantly, and switching costs did not provide the impact on switching intention. This study provides a comprehensive empirical analysis of key factors influencing the choice of distance education by medical students through the integrated multi-model framework.
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http://dx.doi.org/10.3389/fpsyg.2021.639589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355365PMC
July 2021

Spontaneously Sn-Doped Bi/BiO Core-Shell Nanowires Toward High-Performance CO Electroreduction to Liquid Fuel.

Nano Lett 2021 Aug 9;21(16):6907-6913. Epub 2021 Aug 9.

College of Materials Science and Engineering, State Key Laboratory of Advanced Design and Manufacturing for Vehicle Body, Hunan University, Changsha, Hunan 410082, China.

Electrochemical CO reduction provides a promising strategy to product value-added fuels and chemical feedstocks. However, it remains a grand challenge to further reduce the overpotentials and increase current density for large-scale applications. Here, spontaneously Sn doped Bi/BiOx nanowires (denoted as Bi/Bi(Sn)O NWs) with a core-shell structure were synthesized by an electrochemical dealloying strategy. The Bi/Bi(Sn)O NWs exhibit impressive formate selectivity over 92% from -0.5 to -0.9 V versus reversible hydrogen electrode (RHE) and achieve a current density of 301.4 mA cm at -1.0 V vs RHE. In-situ Raman spectroscopy and theoretical calculations reveal that the introduction of Sn atoms into BiO species can promote the stabilization of the *OCHO intermediate on the Bi(Sn)O surface and suppress the competitive H/CO production. This work provides effective in situ construction of the metal/metal oxide hybrid composites with heteroatom doping and new insights in promoting electrochemical CO conversion into formate for practical applications.
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http://dx.doi.org/10.1021/acs.nanolett.1c02053DOI Listing
August 2021

Significant downtrend of antimicrobial resistance rate and rare β-lactamase genes and plasmid replicons carriage in clinical Pseudomonas aeruginosa in Southern China.

Microb Pathog 2021 Oct 5;159:105124. Epub 2021 Aug 5.

Department of Civil and Environmental Engineering, University of Maryland, College Park, MD, 20742, USA. Electronic address:

Objectives: Pseudomonas aeruginosa is a medically important pathogen showing intrinsic low permeability to various antimicrobial agents and its potential to acquire multiple resistance mechanism. A longitudinal surveillance aimed to investigate the antimicrobial resistance and its determinants of Pseudomonas aeruginosa in Southern China. A total of 2163 P. aeruginosa isolates were obtained from patients in Southern China during 2004-2016.

Methods: The antimicrobial susceptibility of the isolates was performed by disk diffusion and Vitek 2 automated system and interpreted according to the Clinical and Laboratory Standard Institute (CLSI) 2015.

Results: A significant downtrend of resistant rate (>10.0%) was observed for tested antibiotic agents including ciprofloxacin (>30.0%), gentamicin (29.0%), tobramycin (24.2%) and ceftazidime (24.0%) except for aztreonam and amikacin. A total of 269 randomly selected isolates were further studied on the carriage of β-lactam resistance genes by using 7 groups of multiplex PCRs targeting on 20 genes. β-lactam resistance genes were rarely detected with a rate lower than 8%. Among all β-lactam resistance genes, bla acquired the highest identification rate (18/269, 6.7%), followed by bla-like (6/269, 2.2%) and bla (6/269, 2.2%). In addition, 8 different plasmid replicons were amplified using 8 groups of multiplex PCRs including 18 sets of primers. Only five plasmid replicons were identified in 5 different P. aeruginosa isolates. Insignificant clonal relatedness among the positive strains identified by regular PCR were further verified by randomly amplified polymorphic DNA (RAPD)-PCR.

Conclusion: This study has provided comprehensive knowledge on current antimicrobial resistance, β-lactam resistance genes and plasmid replicons carriage in a large scale of clinical P. aeruginosa isolates.
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http://dx.doi.org/10.1016/j.micpath.2021.105124DOI Listing
October 2021

A fusion decision system to identify and grade malnutrition in cancer patients: Machine learning reveals feasible workflow from representative real-world data.

Clin Nutr 2021 08 3;40(8):4958-4970. Epub 2021 Jul 3.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, 400042, China. Electronic address:

Background And Aims: Most nutritional assessment tools are based on pre-defined questionnaires or consensus guidelines. However, it has been postulated that population data can be used directly to develop a solution for assessing malnutrition. This study established a machine learning (ML)-based, individualized decision system to identify and grade malnutrition using large-scale data from cancer patients.

Methods: This was an observational, nationwide, multicenter cohort study that included 14134 cancer patients from five institutions in four different geographic regions of China. Multi-stage K-means clustering was performed to isolate and grade malnutrition based on 17 core nutritional features. The effectiveness of the identified clusters for reflecting clinical characteristics, nutritional status and patient outcomes was comprehensively evaluated. The study population was randomly split for model derivation and validation. Multiple ML algorithms were developed, validated and compared to screen for optimal models to implement the cluster prediction.

Results: A well-nourished cluster (n = 8193, 58.0%) and a malnourished cluster with three phenotype-specific severity levels (mild = 2195, 15.5%; moderate = 2491, 17.6%; severe = 1255, 8.9%) were identified. The clusters showed moderate agreement with the Patient-Generated Subjective Global Assessment and the Global Leadership Initiative on Malnutrition criteria. The severity of malnutrition was negatively associated with the nutritional status, physical status, quality of life, and short-term outcomes, and was monotonically correlated with reduced overall survival. A multinomial logistic regression was found to be the optimal ML algorithm, and models built based on this algorithm showed almost perfect performance to predict the clusters in the validation data.

Conclusions: This study developed a fusion decision system that can be used to facilitate the identification and severity grading of malnutrition in patients with cancer. Moreover, the study workflow is flexible, and might provide a generalizable solution for the artificial intelligence-based assessment of malnutrition in a wider variety of scenarios.
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http://dx.doi.org/10.1016/j.clnu.2021.06.028DOI Listing
August 2021

Characteristics of Fertility Transition Response to the Cumulative Effective Low Temperature in a Two-Line Male Sterile Rice Cultivar.

Rice (N Y) 2021 Aug 3;14(1):71. Epub 2021 Aug 3.

National Engineering Research Center of Plant Space Breeding, South China Agricultural University, Guangzhou, 510642, People's Republic of China.

Background: Photo-thermo-sensitive genic male sterile (PTGMS) rice (Oryza sativa L.) is usually considered two-line male sterile rice because of its dual-purpose in two-line hybrid rice system: under short days and low temperatures, it is fertile and used for self-propagation, but under long days and high temperatures, it is sterile and used for hybrid seed production. Therefore, photoperiod and temperature conditions are extremely important for the fertility transition of two-line male sterile rice. In recent years, there have been frequent occurrences of abnormally low-temperature (ALT) resulting in failure of two-line hybrid rice seed production. The daily average temperature (DAT) during ALT events is sometimes higher than the critical sterility-inducing temperature (CSIT) of two-line male sterile rice, of which the night temperature is lower than the CSIT. DAT has been traditionally used as the single indicator of pollen fertility transition, but it is unknown why the fertility of two-line male sterile rice in seed production restored fertility under ALT conditions.

Results: For Hang93S (H93S), a newly released PTGMS line, we hypothesized fertility transition is determined mainly by the cumulative effective low temperature (ELT) and only a certain duration of low temperature is required every day during the fertility-sensitive period. This study simulated ALTs where the DAT was higher than the CSIT while some segments of night temperature were lower than the CSIT. The results showed H93S exhibited a fertility transition to varying degrees. Moreover, fertility was restored under simulated ALT conditions and pollen fertility increased with increasing cumulative ELT, indicating that the fertility transition was affected primarily by the cumulative ELT. Results also indicated that pollen fertility increased as the number of treatment days increased.

Conclusions: The fertility transition is caused mainly by the cumulative ELT. In two-line male sterile rice breeding, the effects of day length, ALT at night, and continuous response days should be considered together. The present study provides new insight into fertility transition so breeders can more effectively utilize the two-line male sterile rice, H93S, in breeding programs.
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http://dx.doi.org/10.1186/s12284-021-00514-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333178PMC
August 2021

Magnetically separable ZnFeO/AgPO/g-CN photocatalyst for inactivation of Microcystis aeruginosa: Characterization, performance and mechanism.

J Hazard Mater 2021 Jul 21;421:126703. Epub 2021 Jul 21.

Fujian Jinhuang Environmental Sci-Tech Co., Ltd, 350002 Fujian, China.

Water eutrophication leads to increasingly serious harmful algal blooms (HABs), which poses tremendous threats on aquatic environment and human health. In this work, a novel magnetically separable ZnFeO/AgPO/g-CN (ZFO/AP/CN) photocatalyst with double Z-scheme was constructed for Microcystis aeruginosa (M. aeruginosa) inactivation and Microcystin-LR (MC-LR) degradation under visible light. The photocatalyst was characterized by XRD, SEM, EDS, TEM, XPS, FTIR, UV-vis, PL, and VSM. Approximately 96.33% of chlorophyll a was degraded by ZFO/AP/CN (100 mg/L) after 3 h of visible light irradiation. During the photocatalytic process, the malondialdehyde (MDA) of M. aeruginosa increased, the activities of superoxide dismutase (SOD) and catalase (CAT) increased initially and decreased afterwards. Furthermore, the photocatalytic removal efficiency of M. aeruginosa (OD ≈0.732) and MC-LR (0.2 mg/L) reached 94.31% and 76.92%, respectively, in the simultaneous removal of algae and algal toxin experiment. Reactive species scavenging experiments demonstrated that·O and·OH played key roles in inactivating M. aeruginosa and degrading MC-LR. The excellent recoverability and stability of ZFO/AP/CN were proved by cycling photocatalytic experiment which using magnetic recovery method. In summary, the synthesized magnetically separable ZFO/AP/CN photocatalyst has remarkable photocatalytic activity under visible light and shows promising potential for practical application of alleviating HABs.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126703DOI Listing
July 2021

NADPH Oxidase Limits Collaborative Pattern-Recognition Receptor Signaling to Regulate Neutrophil Cytokine Production in Response to Fungal Pathogen-Associated Molecular Patterns.

J Immunol 2021 08 23;207(3):923-937. Epub 2021 Jul 23.

Department of Pediatrics, School of Medicine, Washington University in St. Louis, St. Louis, MO;

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by genetic defects in leukocyte NADPH oxidase, which has both microbicidal and immunomodulatory roles. Hence, CGD is characterized by recurrent bacterial and fungal infections as well as aberrant inflammation. Fungal cell walls induce neutrophilic inflammation in CGD; yet, underlying mechanisms are incompletely understood. This study investigated the receptors and signaling pathways driving aberrant proinflammatory cytokine production in CGD neutrophils activated by fungal cell walls. Although cytokine responses to β-glucan particles were similar in NADPH oxidase-competent and NADPH oxidase-deficient mouse and human neutrophils, stimulation with zymosan, a more complex fungal particle, induced elevated cytokine production in NADPH oxidase-deficient neutrophils. The dectin-1 C-type lectin receptor, which recognizes β-glucans (1-3), and TLRs mediated cytokine responses by wild-type murine neutrophils. In the absence of NADPH oxidase, fungal pathogen-associated molecular patterns engaged additional collaborative signaling with Mac-1 and TLRs to markedly increase cytokine production. Mechanistically, this cytokine overproduction is mediated by enhanced proximal activation of tyrosine phosphatase SHP2-Syk and downstream Card9-dependent NF-κB and Card9-independent JNK-c-Jun. This activation and amplified cytokine production were significantly decreased by exogenous HO treatment, enzymatic generation of exogenous HO, or Mac-1 blockade. Similar to zymosan, conidia induced increased signaling in CGD mouse neutrophils for activation of proinflammatory cytokine production, which also used Mac-1 and was Card9 dependent. This study, to our knowledge, provides new insights into how NADPH oxidase deficiency deregulates neutrophil cytokine production in response to fungal cell walls.
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http://dx.doi.org/10.4049/jimmunol.2001298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425286PMC
August 2021

Sodium Reduction in Traditional Fermented Foods: Challenges, Strategies, and Perspectives.

J Agric Food Chem 2021 Jul 16;69(29):8065-8080. Epub 2021 Jul 16.

College of Biomass Science and Engineering, Healthy Food Evaluation Research Center, Sichuan University, Chengdu 610065, China.

Sodium salt is a pivotal ingredient in traditional fermented foods, but its excessive consumption adversely affects human health, product quality, and production efficiency. Therefore, reducing sodium salt content in traditional fermented foods and developing low-sodium fermented foods have attracted increasing attention. Given the essential role of sodium salt in the safety and quality of fermented foods, appropriate approaches should be applied in the production of low-sodium fermented foods. In this review, the challenges of sodium reduction in traditional fermented foods are presented, including the possible growth of pathogenic bacteria, the formation of hazardous chemicals, flavor deficiency, and texture deterioration. Physical, chemical, and biological strategies are also discussed. This review provides references for improving the quality and safety of low-sodium fermented foods.
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http://dx.doi.org/10.1021/acs.jafc.1c01687DOI Listing
July 2021

Internal dosimetry in F-18 FDG PET examinations based on long-time-measured organ activities using total-body PET/CT: does it make any difference from a short-time measurement?

EJNMMI Phys 2021 Jul 15;8(1):51. Epub 2021 Jul 15.

Institute of Radiation Medicine, Fudan University, 2094 Xietu Road, Shanghai, 200032, China.

Purpose: A 2-m axial field-of-view, total-body PET/CT scanner (uEXPLORER) has been recently developed to provide total-body coverage and ultra-high sensitivity, which together, enables opportunities for in vivo time-activity curve (TAC) measurement of all investigated organs simultaneously with high temporal resolution. This study aims at quantifying the cumulated activity and patient dose of 2-[F-18]fluoro-2-deoxy-D-glucose (F-18 FDG ) imaging by using delayed time-activity curves (TACs), measured out to 8-h post-injection, for different organs so that the comparison between quantifying approaches using short-time method (up to 75 min post-injection) or long-time method (up to 8 h post-injection) could be performed.

Methods: Organ TACs of 10 healthy volunteers were collected using total-body PET/CT in 4 periods after the intravenous injection of F-18 FDG. The 8-h post-injection TACs of 6 source organs were fitted using a spline method (based on Origin (version 8.1)). To compare with cumulated activity estimated from spline-fitted curves, the cumulated activity estimated from multi-exponential curve was also calculated. Exponential curve was fitted with shorter series of data consistent with clinical procedure and previous dosimetry works. An 8-h dynamic bladder wall dose model considering 2 voiding were employed to illustrate the differences in bladder wall dose caused by the different measurement durations. Organ absorbed doses were further estimated using Medical Internal Radiation Dose (MIRD) method and voxel phantoms.

Results: A short-time measurement could lead to significant bias in estimated cumulated activity for liver compared with long-time-measured spline fitted method, and the differences of cumulated activity were 18.38% on average. For the myocardium, the estimated cumulated activity difference was not statistically significant due to large variation in metabolism among individuals. The average residence time differences of brain, heart, kidney, liver, and lungs were 8.38%, 15.13%, 25.02%, 23.94%, and 16.50% between short-time and long-time methods. Regarding effective dose, the maximum differences of residence time between long-time-measured spline fitted curve and short-time-measured multi-exponential fitted curve was 9.93%. When using spline method, the bladder revealed the most difference in the effective dose among all the investigated organs with a bias up to 21.18%. The bladder wall dose calculated using a long-time dynamic model was 13.79% larger than the two-voiding dynamic model, and at least 50.17% lower than previous studies based on fixed bladder content volume.

Conclusions: Long-time measurement of multi-organ TACs with high temporal resolution enabled by a total-body PET/CT demonstrated that the clinical procedure with 20 min PET scan at 1 h after injection could be used for retrospective dosimetry analysis in most organs. As the bladder content contributed the most to the effective dose, a long-time dynamic model was recommended for the bladder wall dose estimation.
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http://dx.doi.org/10.1186/s40658-021-00395-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8282883PMC
July 2021

MyD88-Dependent Signaling Is Required for HOIP Deficiency-Induced Autoinflammation.

J Immunol 2021 Jul 12. Epub 2021 Jul 12.

Institute for Immunology, Tsinghua University School of Medicine, Beijing, China; and

The linear ubiquitin chain assembly complex (LUBAC) plays pivotal roles in regulating lymphocyte activation, inflammation, and cell death. This is highlighted by the fact that patients with mutations in LUBAC catalytic subunit HOIP suffer from autoinflammation combined with immunodeficiency. Although defective development of T and B cells resulting from HOIP deficiency in adaptive immunity can explain immunodeficiency, the pathogenesis of autoinflammation is not clear. In this study, we found that dendritic cell (DC)-specific deletion of HOIP resulted in spontaneous inflammation, indicating the essential role of HOIP in maintaining DC homeostasis. Although HOIP deficiency in DCs did not affect TNF-α-induced NF-κB activation, it enhanced TNF-α-induced apoptosis and necroptosis. However, crossing mice with TNFR1-knockout mice surprisingly could not rescue the systematic inflammation, suggesting that the autoinflammation is not due to the effect of HOIP on TNF-α signaling. In contrast, treatment of mice with antibiotics reduced the inflammation, implying that TLR signaling may contribute to the inflammatory phenotype found in mice. Consistently, we found that LPS induced more cell death and significantly higher levels of IL-1α and IL-1β in cells. Importantly, MyD88 deficiency rescued the inflammatory phenotype in mice. Together, these findings reveal the indispensable function of HOIP in maintaining DC homeostasis, and MyD88-dependent proinflammatory signal plays a substantial role in the pathogenesis of human autoinflammation associated with HOIP mutations.
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http://dx.doi.org/10.4049/jimmunol.2100173DOI Listing
July 2021

Integrating 13 Microarrays to Construct a 6 RNA-binding proteins Prognostic Signature for Gastric Cancer patients.

J Cancer 2021 11;12(16):4971-4984. Epub 2021 Jun 11.

Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, China.

It has been confirmed in many tumors that RNA-binding proteins (RBPs) will affect the progress of cancer, but there is still a lack of large-scale research in gastric cancer (GC). We obtained 13 microarray mRNA expression profiles of the GPL570 platform, and extracted expression from them after integration to analyze the expression differences of RBPs. Enrichment analysis studies the role of these RBPs in GC. Univariate, Lasso and multivariate Cox regression analysis are used to identify independent prognostic hub RBPs, thereby constructing and verifying a prognostic signature. External data and rt-PCR verified the expression of hub RBPs. We have identified 51 dysregulated RBPs in GC. Enrichment analysis shows that it can mainly participate in RNA decomposition, modification, processing, etc. and affect the progress of GC. After multiple statistical analysis, six independent prognostic RBPs of GC were determined and a prognostic signature was developed. According to the median risk value, the training cohort was divided into high-risk and low-risk groups. Considering the clinical characteristics, in training, testing, and complete cohorts, the overall survival rate of the high-risk group was significantly lower than that of the low-risk group, which was confirmed by the time-dependent receiver operating characteristic curve. Univariate and multivariate Cox regression analysis of independent prognostic ability of risk score. In addition, we constructed and verified a nomogram based on the prognostic signature, showing accurate prediction performance. rt-PCR and external data verification are consistent with our conclusions. This study analyzed the overall expression of RPBs in GC and explored its mechanism. A new prognostic signature was developed and verified. A nomogram has also been established and verified, which helps to improve the treatment strategy for GC.
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http://dx.doi.org/10.7150/jca.57225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8247375PMC
June 2021

Prognostic signature composed of transcription factors accurately predicts the prognosis of gastric cancer patients.

Cancer Cell Int 2021 Jul 7;21(1):357. Epub 2021 Jul 7.

Department of General Surgery, The Second Affiliated Hospital of Nanchang University, 1 Minde Road, Donghu District, Nanchang, 330006, Jiangxi, China.

Background: Transcription factors (TFs) are involved in important molecular biological processes of tumor cells and play an essential role in the occurrence and development of gastric cancer (GC).

Methods: Combined The Cancer Genome Atlas Program and Genotype-Tissue Expression database to extract the expression of TFs in GC, analyzed the differences, and weighted gene co-expression network analysis to extract TFs related to GC. The cohort including the training and validation cohort. Univariate Cox, least absolute contraction and selection operator (LASSO) regression, and multivariate Cox analysis was used for screening hub TFs to construct the prognostic signature in the training cohort. The Kaplan-Meier (K-M) and the receiver operating characteristic curve (ROC) was drawn to evaluate the predictive ability of the prognostic signature. A nomogram combining clinical information and prognostic signatures of TFs was constructed and its prediction accuracy was evaluated through various methods. The target genes of the hub TFs was predicted and enrichment analysis was performed to understand its molecular biological mechanism. Clinical samples and public data of GC was collected to verify its expression and prognosis. 5-Ethynyl-2'-deoxyuridine and Acridine Orange/Ethidium Bromide staining, flow cytometry and Western-Blot detection were used to analyze the effects of hub-TF ELK3 on the proliferation and apoptosis of gastric cancer in vitro.

Results: A total of 511 misaligned TFs were obtained and 200 GC-related TFs were exposed from them. After systematic analysis, a prognostic signature composed of 4 TFs (ZNF300, ELK3, SP6, MEF2B) were constructed. The KM and ROC curves demonstrated the good predictive ability in training, verification, and complete cohort. The areas under the ROC curve are respectively 0.737, 0.705, 0.700. The calibration chart verified that the predictive ability of the nomogram constructed by combining the prognostic signature of TFs and clinical information was accurate, with a C-index of 0.714. Enriching the target genes of hub TFs showed that it plays an vital role in tumor progression, and its expression and prognostic verification were consistent with the previous analysis. Among them, ELK3 was proved in vitro, and downregulation of its expression inhibited the proliferation of gastric cancer cells, induced proliferation, and exerted anti-tumor effects.

Conclusions: The 4-TFs prognostic signature accurately predicted the overall survival of GC, and ELK3 may be potential therapeutic targets for GC.
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http://dx.doi.org/10.1186/s12935-021-02008-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8261954PMC
July 2021

Tempo-spatial regulation of the Wnt pathway by FAM13A modulates the stemness of alveolar epithelial progenitors.

EBioMedicine 2021 Jul 3;69:103463. Epub 2021 Jul 3.

Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Background: Family with Sequence Similarity 13, Member A (FAM13A) gene has been consistently associated with COPD by Genome-wide association studies (GWAS). Our previous study demonstrated that FAM13A was mainly expressed in the lung epithelial progenitors including Club cells and alveolar type II epithelial (ATII) cells. Fam13a mice were resistant to cigarette smoke (CS)-induced emphysema through promoting β-catenin/Wnt activation. Given the important roles of β-catenin/Wnt activation in alveolar regeneration during injury, it is unclear when and where FAM13A regulates the Wnt pathway, the requisite pathway for alveolar epithelial repair, in vivo during CS exposure in lung epithelial progenitors.

Methods: Fam13a or Fam13a mice were crossed with TCF/Lef:H2B-GFP Wnt-signaling reporter mouse line to indicate β-catenin/Wnt-activated cells labeled with GFP followed by acute (1 month) or chronic (7 months) CS exposure. Fluorescence-activated flow cytometry analysis, immunofluorescence and organoid culture system were performed to identify the β-catenin/Wnt-activated cells in Fam13a or Fam13a mice exposed to CS. Fam13a;SftpcCreERT2;Rosa26RmTmG mouse line, where GFP labels ATII cells, was generated for alveolar organoid culture followed by analyses of organoid number, immunofluorescence and gene expression. Single cell RNA-seq data from COPD ever smokers and nonsmoker control lungs were further analyzed.

Findings: We found that FAM13A-deficiency significantly increased Wnt activation mainly in lung epithelial cells. Consistently, after long-term CS exposure in vivo, FAM13A deficiency bestows alveolar epithelial progenitor cells with enhanced proliferation and differentiation in the ex vivo organoid model. Importantly, expression of FAM13A is significantly increased in human COPD-derived ATII cells compared to healthy ATII cells as suggested by single cell RNA-sequencing data.

Interpretation: Our findings suggest that FAM13A-deficiency promotes the Wnt pathway-mediated ATII cell repair/regeneration, and thereby possibly mitigating CS-induced alveolar destruction. FUND: This project is funded by the National Institutes of Health of United States of America (NIH) grants R01HL127200, R01HL137927, R01HL148667 and R01HL147148 (XZ).
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http://dx.doi.org/10.1016/j.ebiom.2021.103463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264115PMC
July 2021

Fat mass assessment using the triceps skinfold thickness enhances the prognostic value of the Global Leadership Initiative on Malnutrition criteria in patients with lung cancer.

Br J Nutr 2021 Jul 5:1-11. Epub 2021 Jul 5.

Department of Clinical Nutrition, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing400042, People's Republic of China.

The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
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http://dx.doi.org/10.1017/S0007114521002531DOI Listing
July 2021

Salt-Inducible Kinase 3 Promotes Vascular Smooth Muscle Cell Proliferation and Arterial Restenosis by Regulating AKT and PKA-CREB Signaling.

Arterioscler Thromb Vasc Biol 2021 09 1;41(9):2431-2451. Epub 2021 Jul 1.

Division of Vascular Surgery and Endovascular Therapy, Department of Surgery, Yale University School of Medicine, New Haven, CT (Y.C., R.J.G.).

Objective: Arterial restenosis is the pathological narrowing of arteries after endovascular procedures, and it is an adverse event that causes patients to experience recurrent occlusive symptoms. Following angioplasty, vascular smooth muscle cells (SMCs) change their phenotype, migrate, and proliferate, resulting in neointima formation, a hallmark of arterial restenosis. SIKs (salt-inducible kinases) are a subfamily of the AMP-activated protein kinase family that play a critical role in metabolic diseases including hepatic lipogenesis and glucose metabolism. Their role in vascular pathological remodeling, however, has not been explored. In this study, we aimed to understand the role and regulation of SIK3 in vascular SMC migration, proliferation, and neointima formation.

Approach And Results: We observed that SIK3 expression was low in contractile aortic SMCs but high in proliferating SMCs. It was also highly induced by growth medium in vitro and in neointimal lesions in vivo. Inactivation of SIKs significantly attenuated vascular SMC proliferation and up-regulated p21CIP1 and p27KIP1. SIK inhibition also suppressed SMC migration and modulated actin polymerization. Importantly, we found that inhibition of SIKs reduced neointima formation and vascular inflammation in a femoral artery wire injury model. In mechanistic studies, we demonstrated that inactivation of SIKs mainly suppressed SMC proliferation by down-regulating AKT (protein kinase B) and PKA (protein kinase A)-CREB (cAMP response element-binding protein) signaling. CRTC3 (CREB-regulated transcriptional coactivator 3) signaling likely contributed to SIK inactivation-mediated antiproliferative effects.

Conclusions: These findings suggest that SIK3 may play a critical role in regulating SMC proliferation, migration, and arterial restenosis. This study provides insights into SIK inhibition as a potential therapeutic strategy for treating restenosis in patients with peripheral arterial disease.
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http://dx.doi.org/10.1161/ATVBAHA.121.316219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8411910PMC
September 2021

Predictive Indicators for Necrotizing Enterocolitis With the Presence of Portal Venous Gas and Outcomes of Surgical Interventions.

Front Pediatr 2021 14;9:683510. Epub 2021 Jun 14.

Department of Neonatology, Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, China.

Portal venous gas (PVG) was an important clinical sign in stage II or III necrotizing enterocolitis (NEC) in preterm neonates. Not a proper predictive indicator was found to predict the diseases (NEC with the presence of PVG) up to now. There is a need to put forward predictive indicators and compare the predictive effects among them. We conducted a retrospective study of preterm neonates with NEC-PVG ( = 61) or NEC-non PVG ( = 62) from 2014 to 2021. Predictive indicators were put forward and determined by receiver operating characteristic curve analysis. An analysis of the surgical interventions and their outcomes was performed. The incidence rate of NEC among preterm neonates was 4.99%; surgical and conservative interventions accounted for 20.47 and 75.07%, and the mortality rate was 0.03%. The composition ratio of shock in the NEC-PVG group increased 13.2% ( = 0.029). C-reactive protein, fibrinogen degradation product, and blood glucose had better predictive effects in the predictive indicators ( < 0.05). Intestinal necrosis and subependymal hemorrhage in the outcomes of surgical interventions had a strong relationship with the presence of PVG in NEC II/III ( < 0.05). Early and reasonable use of antibiotics, improvement of coagulation function, rectification of acidosis, and decreased blood glucose could cut down the occurrence of the disease (NEC with the presence of PVG). Except for subependymal hemorrhage and intestinal necrosis, NEC with the presence of PVG did not increase the occurrence of other outcomes after surgery.
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http://dx.doi.org/10.3389/fped.2021.683510DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238085PMC
June 2021

Linear Ubiquitination of RIPK1 on Lys 612 Regulates Systemic Inflammation via Preventing Cell Death.

J Immunol 2021 Jun 23. Epub 2021 Jun 23.

Institute for Immunology, School of Medicine, Tsinghua University, Beijing, China;

Receptor-interacting protein kinase-1 (RIPK1) is a master regulator of the TNF-α-induced cell death program. The function of RIPK1 is tightly controlled by posttranslational modifications, including linear ubiquitin chain assembly complex-mediated linear ubiquitination. However, the physiological function and molecular mechanism by which linear ubiquitination of RIPK1 regulates TNF-α-induced intracellular signaling remain unclear. In this article, we identified Lys627 residue as a major linear ubiquitination site in human RIPK1 (or Lys612 in murine RIPK1) and generated mice, which spontaneously develop systemic inflammation triggered by sustained emergency hematopoiesis. Mechanistically, without affecting NF-κB activation, mutation enhances apoptosis and necroptosis activation and promotes TNF-α-induced cell death. The systemic inflammation and hematopoietic disorders in mice are completely abolished by deleting TNF receptor 1 or both RIPK3 and Caspase-8. These data suggest the critical role of TNF-α-induced cell death in the resulting phenotype in mice. Together, our results demonstrate that linear ubiquitination of RIPK1 on K612 is essential for limiting TNF-α-induced cell death to further prevent systemic inflammation.
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http://dx.doi.org/10.4049/jimmunol.2100299DOI Listing
June 2021

Constructing a new prognostic signature of gastric cancer based on multiple data sets.

Bioengineered 2021 12;12(1):2820-2835

Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, P.R China.

In order to explore new prediction methods and key genes for gastric cancer. Firstly, we downloaded the 6 original sequencing data of gastric cancer on the Illumina HumanHT-12 platform from Array Expression and Gene Expression Omnibus, and used bioinformatics methods to identify 109 up-regulated genes and 271 down-regulated genes. Further, we performed univariate Cox regression analysis of prognostic-related genes, then used Lasso regression to remove collinearity, and finally used multivariate Cox regression to analyze independent prognostic genes (MT1M, AKR1C2, HEYL, KLK11, EEF1A2, MMP7, THBS1, KRT17, RPESP, CMTM4, UGT2B17, CGNL1, TNFRSF17, REG1A). Based on these, we constructed a prognostic risk proportion signature, and found that patients with high-risk gastric cancer have a high degree of malignancy. Subsequently, we used the GSE15459 data set to verify the signature. By calculating the area under the recipient operator characteristic curve of 5-year survival rate, the test set and verification set are 0.739 and 0.681, respectively, suggesting that the prognostic signature has a moderate prognostic ability. The nomogram is used to visualize the prognostic sig-nature, and the calibration curve verification showed that the prediction accuracy is higher. Finally, we verified the expression and prognosis of the hub gene, and suggested that HEYL, MMP7, THBS1, and KRT17 may be potential prognostic biomarkers.
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http://dx.doi.org/10.1080/21655979.2021.1940030DOI Listing
December 2021

Metal-organic framework/3,3',5,5'-tetramethylbenzidine based multidimensional spectral array platform for sensitive discrimination of protein phosphorylation.

J Colloid Interface Sci 2021 Nov 6;602:513-519. Epub 2021 Jun 6.

Research Center for Analytical Sciences, Department of Chemistry, College of Sciences, Northeastern University, Box332, Shenyang 110819, Liaoning, China. Electronic address:

A multifunctional metal-organic framework (MOF) hybrid Zr-FeTCPP-MOF is fabricated with 2-aminoterephthalic acid (NH-BDC) and Fe (III) meso-Tetra (4-carboxyphenyl) porphine chloride (FeTCPPCl) participating in the coordination to Zr clusters via one-pot hydrothermal method. The adsorption of phosphoproteins on the surface of Zr-FeTCPP-MOF hybrid cause the chances on the absorbance (Abs), fluorescence (FL) and resonance light scattering (RLS) signals of Zr-FeTCPP-MOF/3,3',5,5'-Tetramethylbenzidine (TMB) system, and an array sensing platform is successfully built for sensitive identification of protein phosphorylation based on the three-dimensional spectral changes of MOF/TMB sensing system induced by the variations on the structure, size, and phosphorylation site of phosphoproteins. This array sensing system is robust in recognizing different phosphoprotein species, and shows high sensitivity in discriminating similar phosphoproteins of different phosphorylation distribution, i.e., caseins (α-, β- and κ-cas). The detection limit of this array sensing platform to individual phosphoprotein is low down to 5 nM. The practical application of this MOF/TMB-base sensing system is substantially demonstrated by identifying tau peptides with different phosphorylation distribution, and distinguishing cancer cells of abnormal phosphorylations from normal cells. This work proves the reliability, sensitivity, and practicality of the MOF/TMB-base sensing system platform for the diagnosis of phosphorylation-related diseases in clinical trials.
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http://dx.doi.org/10.1016/j.jcis.2021.06.025DOI Listing
November 2021

Mussel-Inspired Immobilization of Photocatalysts with Synergistic Photocatalytic-Photothermal Performance for Water Remediation.

ACS Appl Mater Interfaces 2021 Jul 17;13(26):31066-31076. Epub 2021 Jun 17.

Shanghai Urban Construction Design and Research Institute Co., Ltd., 200125 Shanghai, China.

The serious problem of pharmaceutical and personal care product pollution places great pressure on aquatic environments and human health. Herein, a novel coating photocatalyst was synthesized by adhering Ag-AgCl/WO/g-CN (AWC) nanoparticles on a polydopamine (PDA)-modified melamine sponge (MS) through a facile layer-by-layer assembly method to degrade trimethoprim (TMP). The formed PDA coating was used for the anchoring of nanoparticles, photothermal conversion, and hydrophilic modification. TMP (99.9%; 4 mg/L) was removed in 90 min by the photocatalyst coating (AWC/PDA/MS) under visible light via a synergistic photocatalytic-photothermal performance route. The stability and reusability of the AWC/PDA/MS have been proved by cyclic experiments, in which the removal efficiency of TMP was still more than 90% after five consecutive cycles with a very little mass loss. Quantitative structure-activity relationship analysis revealed that the ecotoxicities of the generated intermediates were lower than those of TMP. Furthermore, the solution matrix effects on the photocatalytic removal efficiency were investigated, and the results revealed that the AWC/PDA/MS still maintained excellent photocatalytic degradation efficiency in several actual water and simulated water matrices. This work develops recyclable photocatalysts for the potential application in the field of water remediation.
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http://dx.doi.org/10.1021/acsami.1c02973DOI Listing
July 2021

A novel HBsAg-based model for predicting significant liver fibrosis among Chinese patients with immune-tolerant phase chronic hepatitis B: a multicenter retrospective study.

Therap Adv Gastroenterol 2021 29;14:17562848211010675. Epub 2021 May 29.

Department of Hepatology, Hepatology Research Institute, The First Affiliated Hospital, Fujian Medical University, No. 20 Chazhong Road, Taijiang District, Fuzhou, Fujian 350005, China.

Background: Hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) in the immune-tolerant (IT) phase is significantly associated with high risk for hepatocellular carcinoma, suggesting requirement for antiviral therapy, particularly for those with histological liver injury. This study aimed to establish a non-invasive panel to assess significant liver fibrosis in IT chronic hepatitis B.

Patients And Methods: One hundred and thirteen IT-phase CHB patients were retrospectively recruited and divided into two histopathological groups according to their histological profiles: necroinflammatory score <4 (N <4)/fibrosis score ⩽1 (F0-1), and necroinflammatory score ⩾4 (N ⩾4)/fibrosis score ⩾2 (F2-4). Multivariate analysis was conducted to assess the predictive value of the non-invasive model for significant liver fibrosis.

Results: IT-phase CHB patients with N <4/F0-1 had significantly higher HBsAg levels than those with N ⩾4/F2-4. The optimal HBsAg level of log 4.44 IU/mL for significant liver fibrosis (F ⩾2) gave an area under the curve (AUC) of 0.83, sensitivity of 81.1%, specificity of 81.6%, positive predictive value (PPV) of 68.2%, and negative predictive value (NPV) of 89.9%. An IT model with HBsAg and gamma glutamyl transpeptidase (GGT) in combination was established, and it had an AUC of 0.86, sensitivity of 86.5%, specificity of 81.6%, PPV of 69.6, NPV of 92.5, and accuracy of 83.2% to predict F ⩾2 in the IT-phase CHB patients. Notably, the IT model exhibited higher predictive value than the existing aspartate aminotransferase-to-platelet ratio index, Fibrosis-4 score, and GGT to platelet ratio.

Conclusion: The established IT model combining HBsAg and GGT has good performance in predicting significant liver fibrosis in IT-phase CHB patients.
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http://dx.doi.org/10.1177/17562848211010675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165523PMC
May 2021

Discovery of an orally active VHL-recruiting PROTAC that achieves robust HMGCR degradation and potent hypolipidemic activity .

Acta Pharm Sin B 2021 May 6;11(5):1300-1314. Epub 2020 Nov 6.

State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, China.

HMG-CoA reductase (HMGCR) protein is usually upregulated after statin (HMGCR inhibitor) treatment, which inevitably diminishes its therapeutic efficacy, provoking the need for higher doses associated with adverse effects. The proteolysis targeting chimera (PROTAC) technology has recently emerged as a powerful approach for inducing protein degradation. Nonetheless, due to their bifunctional nature, developing orally bioavailable PROTACs remains a great challenge. Herein, we identified a powerful HMGCR-targeted PROTAC () comprising a VHL ligand conjugated to lovastatin acid that potently degrades HMGCR in Insig-silenced HepG2 cells (DC = 120 nmol/L) and forms a stable ternary complex, as predicated by a holistic modeling protocol. Most importantly, oral administration of the corresponding lactone reveled favorable plasma exposures referring to both the parent and the conversed acid . Further studies of demonstrated robust HMGCR degradation and potent cholesterol reduction in mice with diet-induced hypercholesterolemia, highlighting a promising strategy for treating hyperlipidemia and associated diseases.
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http://dx.doi.org/10.1016/j.apsb.2020.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148065PMC
May 2021

Reference intervals for preterm thyroid function during the fifth to seventh day of life.

Clin Biochem 2021 Sep 30;95:54-59. Epub 2021 May 30.

Fujian Maternity and Child Health Hospital, Affiliated Hospital of Fujian Medical University, China. Electronic address:

Background: Due to the lack of reference intervals for serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone (TSH) in preterm neonates during the 5th to 7th day of life, we performed a retrospective study using the chemiluminescence immunoassay system.

Methods: A total of 2040 preterm neonates with a gestational age (GA) of 26-35 weeks in the neonatal intensive care unit from 2014 to 2019 were included. Their serum FT3, FT4 and TSH values were calculated and analyzed to establish reference intervals for preterm neonates stratified by GA. The comparisons of FT3, FT4 and TSH were made by sex (males and females) and gestational age (26-28 weeks; 29-32 weeks; 33-35 weeks).

Results: The reference intervals for FT3, FT4 and TSH in preterm neonates with a GA of 26-35 weeks were (1.65~5.21) pmol/L, (8.64~25.41) pmol/L, and (0.406~12.468) mlU/L, respectively. There were significant differences between serum FT3 and FT4 values and GA, while TSH levels were not significantly different (P < 0.01). The serum FT3 values of males were lower than those of females, especially in the 29-32 weeks group. No significant differences in serum values between sexes were found in FT4 or TSH (P > 0.05).

Conclusion: Reference intervals of thyroid function tests were established to determine the early diagnostic criteria of thyroid diseases for neonates with a GA of 26-35 weeks and to avoid unnecessary retesting and interventions. The reference intervals of FT4 can be used as an indicator to regulate the doses of thyroid hormone supplement in the treatments of congenital hypothyroidism.
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http://dx.doi.org/10.1016/j.clinbiochem.2021.05.014DOI Listing
September 2021
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